Poster Presentation Abstracts

...

12 downloads 975 Views 5MB Size

Osteoporos Int (2006) 17 (Suppl 2): S143–S355 DOI 10.1007/s00198-006-0097-y

Poster Presentation Abstracts

International Osteoporosis Foundation and National Osteoporosis Foundation 2006

P100SA. EPIDEMIOLOGY OF HIP FRACTURES IN THE UNITED STATES Orces CH, Ramirez J, Goel N; South Texas Bone and Joint Institute, Laredo, TX, USA Aims: Hip fracture represents the most serious complication of osteoporosis and is associated with considerable morbidity and mortality in the elderly. The purpose of this study was to analyze hip fracture trends from 1980 to 2003 in the U.S. population. Methods: Estimates of hip fracture hospitalization were obtained from the National Hospital Discharge Survey database. Hospital discharges with the principal diagnosis of hip fracture (ICD-9-CM 820) were included in this study. Hip fractures discharges associated with pathologic fractures (n= 19,751) were excluded. Age-specific hip fracture rates for ages 65 years and older were calculated using the U.S population estimates by age and sex for each year. Age-adjusted rates per 100,000 (105) population were calculated by the direct method using the U.S. 2000 population as the standard. Results: An estimated of 1,348,489 men and 4,589,286 women were hospitalized with a diagnosis of hip fracture during the study period. Following a hip fracture, 41% of men and 45% of women were discharged to a long-term care facility. The overall in-hospital mortality rate was 6% and 3% for men and women, respectively. The mean annual percent change of hip fractures from 1980–2003 was 0.34% (p = 0.17) in men and 0.96% (p = 0.60) in women. Hip fracture age-adjusted rates in men increased 1.3% from 539.7 per 105 in 1980–83 to 547.2 per 105 in 2000–03. However, the rates in women decreased 3.2% from 1027.3 per 105 in 1980–83 to 993.9 per 105 in 2000–03 (Fig 1).

Epidemiology of Hip Fracture in U.S. 1980–2003 Conclusions: Hip fracture incidence in women decreased from 1980 to 2003. These findings may reflect improvement in the diagnosis and treatment of osteoporosis in U.S for the past decade.

Further research is needed to explain increasing hip fracture rates in men.

P101SU. PERSISTENCE, GENERALIZABILITY, AND COST-EFFECTIVENESS OF AN INTERVENTION TO IMPROVE QUALITY OF OSTEOPOROSIS CARE AFTER A FRACTURE OF THE WRIST: RESULTS OF A CONTROLLED TRIAL Majumdar SR1,2, Johnson JA1,2, Lier DA2, Russell AS1, Hanley DA3, Blitz S1, Steiner IP1, Maksymowych WP1, Morrish DW1, Holroyd BR1, Rowe BH1,2; 1University of Alberta, Edmonton, Alberta, Canada, 2Institute of Health Economics, Edmonton, Alberta, Canada, 3University of Calgary, Calgary, Alberta, Canada Aims: Older patients with fragility fractures are at high risk of recurrent fractures, but are not commonly treated for osteoporosis. Compared to usual care, a previously reported intervention led to 30% increases in osteoporosis treatment within 6 months of a wrist fracture. Our aim was to examine longer-term outcomes, generalizability, and cost eﬀectiveness of this intervention. Methods: This was an extended analysis of a controlled trial with blinded ascertainment of outcomes, comparing intervention to controls. PatientsR50 years with a wrist fracture treated in Emergency Departments in Alberta, Canada were included; those already treated for osteoporosis were excluded. Overall, 102 patients (55 intervention, 47 controls) participated. The intervention consisted of faxed physician reminders containing treatment guidelines endorsed by local opinion leaders and patient counseling. Controls received usual care; at 6 months, when the original study finished, all controls received the intervention. The main study outcomes were rates of BMD testing and osteoporosis treatment within 6 months (original study) and 1-year (delayed intervention) of fracture, and 1-year persistence with osteoporosis treatments. In addition, from the payer’s perspective and over the lifetime of the patient, a cost-eﬀectiveness analysis (using a Markov decision-analytic model) of the intervention was conducted. Results: Median patient age was 66 years, and 78% were women. Overall, 40% of intervention patients (vs 10% of controls) started osteoporosis treatment within 6 months of fracture, and 82% (95%CI: 67–96) persisted with it at 1 year. Delaying the intervention to controls for 6 months led to equivalent rates of BMD testing (64% vs 60% in the original study, p=0.72) and treatment (43% vs 40%, p=0.77) as previously reported. Compared with usual care, the intervention strategy was dominant: per patient, it led to a 13-dollar Canadian (9-dollar US) cost savings and a gain of 0.012 quality-adjusted life years. Results were most sensitive to costs of osteoporosis treatment. Conclusions: A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment, even when delivered 6 months post-fracture. From the payer’s perspective, the intervention appeared to lead to both cost-savings and gains in life expectancy.

S144

P102MO. A GENERAL PRACTICE AUDIT OF POSTMENOPAUSAL WOMEN AT HIGH FRACTURE RISK AND ITS INFLUENCE ON FALLS BURDEN: THE OSTEOPOROSIS NURSE INITIATIVE PROGRAMME (ONI) Preedy D1, Masud T2, Torgerson D3, Stone M4, Selby P5, Sutcliﬀe A6, Hodson J7, Cooper C8; 1National Osteoporosis Society, Bath, UK, 2Nottingham City Hospital, UK, 3University of York, UK, 4 Llandough Hospital, Cardiﬀ, UK, 5Manchester Royal Infirmary, UK, 6Freeman Hospital, Newcastle, UK, 7Bridge House Medical Centre, Stratford-upon-Avon, UK, 8Southampton General Hospital, UK Aims: The ONI programme was a primary care audit run by the UK National Osteoporosis Society (NOS) involving 71 General Practitioner (GP) surgeries. The aim of this analysis was to evaluate whether assessment in clinics can reduce the falls burden. Methods: 5 specialist osteoporosis nurses audited general practice databases. Female patients aged over 74 years were sent a questionnaire which included questions related to fracture risk and falls history. Fracture risk was calculated for each patient using a validated assessment tool (Black et al., 2001). Patients at low/ moderate risk of fracture were sent general lifestyle advice that aimed to minimise future falls and fracture risk. GPs were contacted with the results of each patient’s risk assessment and advised to re-assess patients at moderate risk annually. High risk patients were invited to attend assessments, organised by the specialist nurses, where they received specific lifestyle advice aimed at preventing falls and fractures. GPs were advised of treatment options and referred to the NOS medical management plan. Approximately 12 months post-assessment, patients were sent a review questionnaire that identified whether they had fallen since assessment. Results: 17481 patients, average age 81.6 (5.2) years, returned questionnaires. 31.0% of patients were identified at high, 57.4% at moderate and 11.6% at low risk of fracture. Of the high risk patients, 2965 (54.7%) attended the osteoporosis clinic, 893 (16.5%) did not arrive at their appointment and 335 (6.2%) had died/moved. Of the patients who attended the clinic, 1571 (53.0%) completed the review questionnaire (3.5% had died/moved). 789 subjects completed reviews 9–15 months post-assessment [mean 363 days (53)]. In these patients total number of falls was 718 in the 12 months prior to questionnaire and 366 in the period following assessment. Mean number of falls per person decreased from 0.91 to 0.46 (CI95% 0.341–0.552, p<0.001). The proportion of patients who were fallers decreased from 45% to 27% (2=99.1, df=1, p<0.001) and the proportion that were recurrent fallers reduced from 23% to 12% (2=57.6, df=1, p<0.001). Conclusions: Specialist osteoporosis nurse assessments of selected patients can significantly reduce the falls burden in older women identified in primary care.

P103SA. INCIDENT FRACTURES, RECURRENT TRAUMA AND LONG-TERM SURVIVAL AFTER HIP FRACTURE: AN 18-YEAR FOLLOW-UP IN 768 WOMEN von Friesendorﬀ M1,3, Besjakov J2, Åkesson K3; 1Department of Orthopedics Hässleholm-Kristianstad Hospital, 2Department of Radiology, 3Department of Orthopedics, Malmö University Hospital, Malmö, Lund University, Sweden Aims: Hip fracture is the most devastating outcome of osteoporosis with high early mortality. Less is known about those surviving beyond a year with regard to new fractures, recurrent trauma and survival. This information is of outmost importance in terms of strategies for fracture prevention in this group. The aim of this study was to evaluate new fractures, significant low trauma events and long-term survival in a cohort of women with hip fracture. Methods: All patients suﬀering a hip fracture 1984–1985 in the city of Malmö were identified. Because of a single radiology unit, virtually all, prevalent and future, fractures were captured. Follow-up in 2002 included mortality, incident fractures and skeletal radiographs as indicators of potential fracture occasions. Results: 768 women (79.6 yrs (range 32–99) with an index hip fracture due to low energy trauma was identified. 6.4% had concomitant fractures and 10.9% had suﬀered a previous hip fracture. After 18 years, 88% were dead; 21% within 12 months,

29% within 24 months and 52% at 5 years. Mean age at death was 86.3 years (range 48–102), equal to 6.7 years above mean age for fracture. Mortality according to 5-year age-bands, shows that 73% of those 85–89 years were dead at 5 years, and 40% of those below 65 years at 18-years. During follow-up, 421 (55%) were referred to x-ray on 1155 occasions (2.1 (range 0–23) x-rays/woman) because of significant trauma. 336 (44%) of all women suﬀered a total of 718 new fractures (2.1 (range 1–12) fractures/woman) during 670 trauma occasions. 15% (n=105) of the fractures occurred within the first year, 27% within 2 years. 20% with significant trauma (falls) did not fracture. Survival curves indicate that patients in the oldest and youngest groups have high early mortality and that those with further falls and fracture have a longer life expectancy. Conclusion: In this first study combining long-term mortality and fracture incidence in women with hip fracture, a majority above 80 years were dead within 5 years. Incident fractures occurred in half of the women below age 80, suggesting that these patients should be the focus of preventive measures.

P104SU. SECOND-HAND SMOKING INCREASES THE RISKS OF OSTEOPOROSIS AND OSTEOPOROTIC FRACTURES IN CHINESE MEN AND WOMEN Hsu YH1, Bouxsein ML2, Venners SA1, Terwedow H1, Feng Y1, Rosen CJ3, Xu X4, Brain J1; 1Program for Population Genetics, Harvard School of Public Health, Boston, MA, USA, 2Beth Israel Deaconess Medical Center, Boston, MA, USA, 3Maine Center for Osteoporosis Research and Education, St. Joseph Hospital, Bangor, ME, USA, 4Center for Population Genetics, School of Public Health, University of Illinois, Chicago, IL, USA A recent meta-analysis confirmed that smoking is a risk factor for fracture (Kanis, 2005). However, skeletal health in those exposed to second-hand smoking has not been studied. Importantly, non-smoking women exposed to passive smoking have significantly lower urinary estrone conjugates. The purpose of this study was to determine the contribution of second-hand smoking to osteoporosis and fracture risk. Methods: 7095 men, 4259 premenopausal and 2022 postmenopausal women aged 25–64 years participated in a communitybased cross-sectional study in rural China. Hip BMD was measured by DXA, and osteoporosis was defined as hip BMD of more than 2.5 SDs below the average peak BMD of young healthy Chinese. Self-reported non-spine fractures, occurring within two years of the BMD measurements, were recorded. Second-hand smoking was defined as subject’s spouse or other family members smoking daily. Gender and menopause-specific multiple generalized linear models were applied. Results: 153 (2.2%) men, 78 (1.8%) premenopausal and 242 (12.0%) postmenopausal women had osteoporosis. 82 (1.2%) men, 54 (1.3%) premenopausal and 46 (2.3%) postmenopausal women reported at least one non-spine fracture. 87.3% men, 4.4% premenopausal, and 9.4% of postmenopausal women were current smokers. The risks of low BMDs increased with second-hand Table Adjusted ORs (95%CI) of osteoporosis and non-spine fractures by current smoking and second-hand smoking status in strata of men and premenopausal women Non-smokers Second-hand smoking

0

Men Osteoporosis

n=737 1.0 b

a

Fracture

1.0

Premenopausal women Osteoporosis

n=664

Fracture

1.0

1.0

Smokers

1

2+

0

1

2+

n=144 1.2 (0.3–4.3) 1.0 (0.7–1.5) n=2971

n=20 n.a

n=4365 1.4 (0.7–2.5) 1.1 (0.9–1.4) n=9

n=1351 1.6 (0.8–3.1) 1.1 (0.9–1.4) n=179

n=478 2.4 (1.1–5.1)* 1.1 (0.8–1.5) n.a

n.a

3.6 (1.9–13.3)* 3.8 (1.1–13.3)*

2.6 (1.1–6.5) * 1.9 (0.6–6.1) *

n.a n=436 3.0 (1.2–9.1)* 2.6 (1.1–6.6)*

n.a

n.a n.a

a: Number of family members smoking daily b: Non-smokers without second-hand smoking exposure as the reference group Adjusted ORs: Adjusted for age, height, weight, occupation, physical activities, education and hip BMD (for fracture only) * p < 0.05

S145 smoking exposure in men and premenopausal women (0.05
P105MO. RIB FRACTURES AS INDICATORS OF FUTURE FRACTURE RISK IN POSTMENOPAUSAL WOMEN 50–99 YEARS OF AGE: RESULTS FROM NATIONAL OSTEOPOROSIS RISK ASSESSMENT SURVEY (NORA) Barrett-Connor E1, Sajjan SG4, Miller PD2, Siris ES3, Weiss TW4, McHorney CA4; 1University of California, San Diego, CA, 2Colorado Center for Bone Research, Lakewood, CO, 3Columbia University, New York, NY, 4Merck & Co., Inc., West Point, PA, USA We studied the association between rib fracture history and self-reported future osteoporotic fractures in postmenopausal women (PMW) using NORA data. Eligible women were at least 50 years of age with no previous diagnosis of osteoporosis who were not taking bone-specific medication at baseline. This analysis included 155,031 PMW who responded to either year 1, year 2, or year 5 year post-baseline follow-up surveys and who had baseline yes/no information on rib fracture history after age 45. Future fracture rates (see Table) were calculated by person-years of follow-up. Relative risk (RR) (see Table) for future fractures was calculated using Cox regression models for women with rib fractures history (N=4658) compared to those with no history of any fractures (N=150,273), and was only slightly reduced after adjusting for age, BMD, ethnicity, health status, maternal history of fracture, education, smoking status, use of hormone therapy, cortisone, menopause before 40 years, alcohol use, and weight. A total of 6,300 women reported 6,830 future fractures. The RR of future fractures for women with rib fracture history compared to women with no fracture history was highest in women aged 50–59. Relative risk of future fracture among women with rib fracture history compared to women with no fracture history Future fracture rate (95% CI) per 1,000 person-year follow-up

Relative risk of future fracture (95% CI) for women with rib fracture history vs. no fracture history

Age

Rib Fracture Hx

No Fracture Hx

Unadjusted

Multivariate Adjusted

50–59

33.3 (28.1, 38.4) 28.6 (24.4 32.8) 36.6 (31.8, 41.4) 53.1 (42.0, 64.2)

7.6 (7.3, 8.0) 9.4 (8.9, 9.8) 15.1 (14.5, 15.8) 24.0 (21.9, 26.1)

4.4 (3.7, 3.1 (2.6, 2.4 (2.1, 2.2 (1.7,

3.4 (2.8, 2.5 (2.1, 2.0 (1.7, 2.0 (1.6,

60–69 70–79 80 +

5.3) 3.6) 2.8) 2.9)

4.0) 3.0) 2.3) 2.6)

The data suggest that previous rib fracture is an important risk factor for future osteoporotic fracture in women of all age groups. Women presenting with a rib fracture should be evaluated for appropriate management to prevent future fractures.

P106SA. ADJUSTED MORTALITY AFTER HIP FRACTURE: FROM THE CARDIOVASCULAR HEALTH STUDY

Methods: Data from the Cardiovascular Health Study, a 16+ year longitudinal study of 5,888 older individuals from 4 US sites were used to compare mortality in participants who fractured their hips (n=379) with control participants (n=1,134) matched for sex, age, race, recruitment period and time since enrollment. Extended Cox models were used to estimate mortality hazard ratios for diﬀerent periods following fracture, adjusting for multiple characteristics known to be related to mortality in the elderly. Results: (See table) Hazards ratios for mortality post hip fracture at various time periods, adjusted for age and race* and age, race, frailty, Mini Mental State Exam score, Digit Symbol Substitution score, body mass index, and congestive heart failure** in fracture participants vs controls are shown. Women (n=1,125) Hazard ratio 1*

Hazard ratio 2**

0 – 1 mo.

4/16

2 – 6 mo.

19/16

12.2 (4.1–36.6) 2.7 (1.4–5.3) 2.0 (1.5–2.8) 1.1 (0.7–1.8)

7.1 (2.3–21.5) 2.1 (1.0–4.1) 1.4 (1.1–2.0) 1.0 (0.6–1.5)

Time after fx.

7 mo. – 4 yrs.

119/69

5 yrs. – 8 yrs.

86/28

#deaths, no fx/fx

Hazard ratio 1*

Hazard ratio 2**

1/14

44.7 (5.9–340.1) 5.9 (2.3–15.3) 1.5 (1.0–2.4) 1.1 (0.4–3.0)

39.9 (5.2–308.7) 3.8 (1.4–10.3) 1.1 (0.7–1.8) 1.0 (0.3–2.7)

8/11 70/26 23/5

Conclusions: The risk of mortality in elderly individuals with hip fracture is highest in the first 6 months following the fracture. A meaningful percentage of this increased mortality can be explained by poor pre-fracture health. Treating osteoporosis to prevent hip fractures will decrease mortality, but not to the degree frequently quoted in the literature.

P107SU. DOES THE RATE OF BONE LOSS INCREASE WITH AGE IN OLDER MEN? Cauley JA1, Lui L2, Ensrud KE3, Fink HA3, Zmuda JM1, Bauer DC4, Orwoll E5, for the Osteoporotic Fractures in Men (MrOS) Study (MrOS)1,2,3,4,5; 1Univ. Pittsburgh, Pittsburgh, PA, USA, 2 California Pacific Medical Center, San Francisco, CA, USA, 3VA Medical Center & Univ. Minnesota, Minneapolis, MN, USA, 4 UCSF, San Francisco, CA, USA, 5OHSU, Portland, OR, USA Objectives: Longitudinal rates of bone loss increase with advancing age in older women and the proportionate increase may be greater in black compared to white women. Whether rates of bone loss increase with age in older men, especially non-white men is less well established. The objective of current analysis is to examine the rate of hip bone loss with age in MrOS. Materials and Methods: We enrolled 5,995 men age 65+ into MrOS at six US clinical centers. A subset of these men (n=2969) had hip BMD measured twice by DXA (Hologic 4500W, Bedford, MA), 3.4 years apart. Linear regression models with tests of trend were used to compare least square mean (95% Confidence Interval, CI) annualized percent change in BMD by age. We adjusted for clinic, weight, initial BMD, weight change and health status. Results: The annualized percent loss (95% CI) in total hip and femoral neck BMD increased with age (Table), even after adjustment for covariates listed above. There was no evidence that the increase in the rate of bone loss with age diﬀered in white (n=2672) and non-white men (n =297): the annualized percent loss in total Mean (95% CI) Annual % Loss in BMD by Age)

Robbins J1, Biggs ML2, Cauley J3; 1Univeristy of California, Davis Medical Center, Sacramento, CA, USA, 2University of Washington, Seattle, Washington, USA, 3University of Pittsburgh, Pittsburgh, PA, USA Aims: One-year mortality after hip fracture is in the range of 20%. We addressed the question of how much of this mortality is related to the fracture and how much is explained by the underlying health conditions which may also have predisposed the individuals to risk of fracture.

Men (n=388)

#deaths, no fx/fx

64 – 69 70 – 74 75 – 79 80+ (p-trend)

Total Hip

Femoral Neck

Mean -0.37 -0.46 -0.57 -0.83

Mean -0.39 -0.31 -0.45 -0.54

(95% CI) (-0.43 to -0.31) (-0.52 to -0.40) (-0.64 to -0.50) (-0.92 to -0.73) (<0.0001)

(95% CI) (-0.48 to -0.30) (-0.40 to -0.22) (-0.55 to -0.35) (-0.67 to -0.41) (0.04)

S146 hip BMD in white and non-white men, respectively was -0.42 and -0.42 in men 75. Conclusions: The mean rate of total hip bone loss increases with age in both white and non-white men.

P108MO. GROWTH IN INFANCY AND CHILDHOOD PREDICTS HIP FRACTURE RISK IN LATE ADULTHOOD IN WOMEN Javaid MK1, Eriksson JG2, Valimaki M2, Kgjantie E2, Forsen T1, Osmond C1, Barker DJ1, Cooper C1; 1MRC Epidemiology Resource Centre, Southampton, UK, 2The National Public Health Institute, Helsinki, Finland Peak bone mass accounts for up to 60% of the variation in adult bone mass, however it is not known whether this variation in bone mass leads to an increased fracture risk in later life. We have previously demonstrated that poor growth in late childhood was associated with an increase in fracture risk in later life. Using a second cohort, we have investigated the relationship between growth in early childhood and later fracture risk and possible mechanisms involving femoral bone mass. Maternity, school and welfare records were electronically linked with hospitalization and mortality records in Helsinki, Finland, and 13, 345 individuals (6,370 women) born in Helsinki between 1934–1944 were identified. These individuals had weight and

length recorded at birth and at varying intervals during infancy and childhood. Hip fractures were identified using hospitalization and mortality records. A sub-sample of 190 women underwent proxmial femoral DXA using a Hologic QDR 4500 DXA instrument. From the 13,345 individuals identified, 106 hip fractures were identified. Of the childhood predictors of fracture risk, the z score changes in body build (BMI) from years 1 to 12 were strongly associated with adult hip fracture risk. Those in the lowest quarter of BMI gain had a 2.2 fold increase in hip fracture risk (p=0.05) compared with those in the highest quarter of this distribution. The increased risk was present only in women and in a sub-sample of 190 women, who underwent bone mineral measurement, an equivalent change in childhood BMI z-score was associated with a 0.11 SD decrease in proximal femoral aBMD. We have been able to demonstrate that poor growth during childhood is associated with an increased risk in hip fracture and the mechanism is explained only in part by the association between measures of early growth and adult bone size and areal density.

P109SA. COST-EFFECTIVENESS OF UNIVERSAL BONE DENSITOMETRY FOLLOWED BY TREATMENT OF THOSE WITH OSTEOPOROSIS (FEMORAL NECK T-SCORE , -2.5) COMPARED TO NO DENSITOMETRY OR TREATMENT IN ELDERLY CAUCASIAN MEN Schousboe JT1,2, Taylor BC3, Fink HA3,4,5, Bauer DC6, Kane RL2,7, Orwoll ES8, Melton LJ9, Ensrud KE3,4,5; 1Park Nicollet Health Services, Minneapolis, MN, USA, 2Division of Health Services Research and Policy, University of Minnesota, Minneapolis, MN, USA, 3CCDOR, Minneapolis VAMC, Minneapolis, MN, USA, 4Department of Medicine, Minneapolis VAMC, Minneapolis, MN, USA, 5Division of Epidemiology, University of Minnesota, Minneapolis, MN, USA, 6UCSF, San Francisco, CA, USA, 7Clinical Outcomes Research Center, University of Minnesota, Minneapolis, MN, USA, 8Department of Medicine, Oregon Health & Science University, Portland, OR, USA, 9Department of Health Sciences Research, Mayo Clinic, Rochester, MN USA

Relationship between childhood growth from 1 to 12 years and HR for adult hip fracture (n=13,345)

Aims: Cost-eﬀective strategies for bone densitometry screening and treatment to prevent fracture in elderly men are not established. Our primary aim was to estimate the cost-eﬀectiveness of universal bone densitometry combined with five years of alendronate therapy for those found to have osteoporosis (femoral neck bone mineral density [BMD] T-score % -2.5 based on Caucasian female norms) in Caucasian men age 65, 70, 75, 80, or 85 years. Our secondary aim was to estimate the cost-eﬀectiveness of strategies restricting densitometry and treatment to those with risk factors for osteoporosis by BMD criteria. Methods: Fracture rates, fracture costs, and long-term care costs following hip fractures were estimated from population-based data of Rochester, MN. The age-adjusted relative risk of incident fractures in those with compared to those without osteoporosis were estimated from the Osteoporotic Fractures in Men (MrOS) study. We assumed a 50% reduction in risk of all fractures on alendronate. We used a Markov model with a lifetime horizon and 8 health states (including wrist, hip, vertebral, and other fractures), and ran all analyses as Monte Carlo simulations with 40,000 trials. Results: Estimated costs (2004 U.S. dollars) per quality-adjusted life year (QALY) gained for the universal screen and treat strategy compared to no screening or treatment for each age were 191,000 (age 65), 106,000 (age 70), 51,000 (age 75), and 16,000 (age 80). The universal screen and treat strategy was cost-saving for those age 85. For those age 65 or 70, threshold analyses showed that costs per QALY gained were < 50,000 U.S dollars if the screen and treat strategy was restricted to those with a pre-test probability of osteoporosis R20% or R12.5%, respectively. Results were sensitive to drug cost, assumed reduction of non-vertebral fractures on alendronate, and cost of densitometry per person. Conclusions: Assuming a societal willingness to pay of 50,000 U.S. dollars per QALY gained, universal bone densitometry with treatment for those with osteoporosis is cost-eﬀective for Caucasian men age > 75. Caucasian men age %75 should be selected for bone densitometry based on clinical risk factors for low BMD.

S147

P110SU. VALIDATION OF A NOVEL METHOD TO PREDICT LONG-TERM EFFECTS OF TREATMENT USING SHORT-TERM PLACEBO CONTROLLED TRIALS Shinoﬀ CW1, McCulloch CE2, Cummings SR1; 1SF Coordinating Center, San Francisco, USA, 2University of California, San Francisco, USA Aims: Because long-term (> 3 year) placebo-controlled trials are not feasible, methods are needed for estimating long-term eﬀects of treatment when only the treatment group continues. We previously developed a method of predicting long-term fracture rates for placebo groups from short-term placebo controlled trials. We used data from the Multiple Outcomes of Raloxifene Evaluation study to validate this method and estimate the treatment eﬀects. Methods: We predicted the non-vertebral fracture rate for those randomized to raloxifene as though they had never received treatment (created a ‘‘placebo virtual twin’’ for each individual – a hypothetical subject with the same key characteristics). We used data from the placebo group to develop a model to estimate the non-vertebral fractures expected during years 1–2, and years 3–4, and to predict rates in years 3–4 for the raloxifene group who continued beyond 2 years. These were compared to actual rates. Bootstrap procedures were used to estimate the variation and provide confidence limits. For validation we used a split-sample approach. To build the model we used data from a random sample of placebo participants who continued beyond 2 years, and predicted the values in remaining placebo participants. Results: There were 5129 participants randomized to raloxifene and 2576 to placebo. Of these, 4326 raloxifene and 2187 placebo participants continued beyond year 2. The observed and predicted rates of fracture were not diﬀerent between the MORE placebo group and its ‘virtual placebo twins’ (see TABLE). Table. Predicted and observed non-vertebral fracture risk

RAL Virtual twin— Predicted RAL—Observed PBO Virtual twin— Predicted PBO—Observed

MORE (years 1–2) Rate ratio 95% CI

MORE (years 3–4) Rate ratio 95% CI

MORE (years 1–4) Rate ratio 95% CI

1.0

Ref

1.0

1.0

0.95 1.0

0.77, 1.18 0.94 Ref 1.0

0.74, 1.16 0.94 Ref 1.0

0.79, 1.13 Ref

1.05

0.81, 1.38 0.96

0.69, 1.26 1.0

0.78, 1.21

Ref

Ref

Using the split-sample approach, the predicted non-vertebral fracture rate during years 3–4 was 0.10 per 1000 p-y, the same as that observed in the MORE placebo group. Conclusions: We validated this method by demonstrating the lack of diﬀerence in rates between the placebo and virtual twin groups. The projected 4 year eﬀect of raloxifene is a 6% reduction in non-vertebral fracture risk.

P111MO. EFFECTS OF FOODS HIGH IN PROTEIN ON RISK OF WRIST FRACTURE OVER 25 YEARS AMONG PERI- AND POSTMENOPAUSAL WOMEN Thorpe DL, Knutsen SF, Rajaram S, Beeson WL, Fraser GE; Loma Linda University, Loma Linda, CA, USA Aims: Current research suggests that a diet high in fruits and vegetables and moderate in protein intake, such as a vegetarian diet, may be ideal for bone health. The aim of this study was to take a whole foods approach in examining the eﬀects of foods high in protein from both animal and plant sources on the risk of a wrist fracture (WF) in a subset of women who had completed a recent questionnaire and who had also participated in an 8-year cohort study 25 years earlier. Methods: A total of 1865 peri- and postmenopausal women completed two lifestyle questionnaires 25 years apart. The first questionnaire, completed in 1976–77, contained 65 food frequency items. The second captured the occurrence of low trauma fractures during the intervening 25 years. Cox regression with estimated age at time of fracture as the time variable was used to assess the eﬀect of high protein foods on fracture risk. Models were adjusted for hormone use, physcial activity, any fracture since age 35, time since

menopause, parity, comorbidities, smoking, alcohol consumption, BMI, education, fruits and vegetable intake. Results: Cheese consumption more than 3x/week and meat intake more than 4x/week were associated with a 58% (HR 0.42, 95% CI 0.18, 0.99) and 54% (HR 0.46, 95% CI 0.24, 0.88) decreased risk of WF, respectively, in multivariate adjusted analysis without interaction terms. When an interaction between meat consumption and high vegetable protein foods (nuts, beans and grain or soy protein-based meat-like products) was considered, high intake of vegetable protein foods decreased risk of WF among non-meat consumers (HR 0.34, 95% CI 0.14, 0.84). Cheese continued to be protective among these vegetarians. Among meat eaters, increasing use of foods high in vegetable protein attenuated the protective of eﬀect of meat intake. Conclusions: The protective eﬀect of foods high in protein from both plant and animal sources suggests the importance of adequate levels of high protein foods in the diet, especially among vegetarians and those with very low meat intake. Further research is needed to validate the existence of an interaction between meat and vegetable protein foods.

P112SA. BICARBONATE FROM MINERAL WATER ACTS POSITIVELY ON BONE METABOLISM IN THE ABSENCE OF CALCIUM DEFICIENCY Wynn Dumartheray E1, Krieg MA1, Burckhardt P2; 1Outpatient Clinic, Lausanne University Hospital, Lausanne, Switzerland, 2 Clinique Bois-Cerf, Osteoporosis Consultation, Lausanne, Switzerland A normal diet produces a daily acid charge to the organism which participates to bone loss. Studies have documented a decrease in bone resorption, after introducing bicarbonate or an alkali diet. The aim of our study was to assess the eﬀect on bone markers of a daily intake of mineral water rich in bicarbonate (HCO3-) in a sample of young healthy women on a relatively high calcium (Ca) intake. This open controlled study compared two mineral waters, one rich in calcium (Water A, 520 Ca mg/l, 291 HCO3- mg/l) and the other rich in calcium and bicarbonate (Water B, 547 Ca mg/l, 2172 HCO3- mg/l). Concentration of other minerals was very similar between the two waters. Thirty young female dieticians (mean age 25.8, mean BMI 20.9) were randomized into two equal groups and followed an identical weighed, balanced daily diet plan (1875 kcal, 965 mg Ca, 75 g proteins) and drank 1.5 litres of the randomly assigned mineral water. The follow-up period was 4 weeks with laboratory examinations including electrolytes, etc. at baseline and after 2 and 4 weeks. In addition, urinary pH and bicarbonate, S-PTH and S-C-telopeptides (CTX) were measured after 12 hours fasting. There was no significant diﬀerence between the two groups for the diﬀerent assessed variables at baseline. The table represents the absolute variations after 4 weeks compared to baseline (*p<0.05, **p<0.02). The pH remained stable under Water A. It increased from 5.5 to 6.2 (p<0.01) under Water B, while S-PTH and S-C-telopeptides decreased significantly. Even when calcium intakes are high, a mineral water rich in bicarbonate led to a decrease by 16% of PTH and by 15% of bone resorption (CTX) in a sample of young women on a normal diet. This could be of major interest for long-term prevention of bone loss and osteoporosis. Absolute variations after 4 weeks compared to baseline Mean (SEM)

Bicarbonate/ Creatinine Fasting urine mmol / mmol

Calcium/ Creatinine Fasting urine mmol/mmol

S-PTH ng/l

S-CTelopeptides mg/l

Water A Water B

-0.06 (0.05) +0.47 (0.22)**

-0.03 -0.05

+0.5 (1.9) -5.3 (1.7)*

+0.01 (0.08) -0.07 (0.12)*

P113SU. MEASURES OF RENAL FUNCTION, BONE MINERAL DENSITY, BONE LOSS AND OSTEOPOROTIC FRACTURE IN OLDER ADULTS: THE RANCHO BERNARDO STUDY Jassal SK1,2, von Muhlen D3, Barrett-Connor E3; 1Department of Medicine, University of California, San Diego, La Jolla, CA,

S148 USA, 2VA San Diego Healthcare System, San Diego, CA, USA, 3 Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, CA, La Jolla, CA, USA Aims: To investigate the cross-sectional and longitudinal association between measures of renal function and bone mineral density, bone loss, and osteoporotic fracture in older adults. To determine which measure of renal function—creatininine clearance by the Cockcroft-Gault (CG) equation, estimated glomerular filtration rate by the Modification of Diet in Renal Disease (MDRD) equation, or serum creatinine—is most strongly associated with bone mineral density (BMD) and fracture. Methods: We report a cross-sectional and prospective study in 1713 older community-dwelling men and women (average age 71.3 +/- 11.1 years). Between 1992 and 1995, participants completed standardized questionnaires, physical examinations, laboratory testing and bone densitometry. Participants returned for a follow-up visit in 1997–1999 (n=1021) an average of 4.1 (+/-0.9) years later. Results: Calculated renal function declined with age (p<0.001). By the CG equation, at baseline, 19% of participants were normal (glomerular filtration rate >90mL/min/1.73m2), 32% mildly abnormal (60–89mL/min/1.73m2), 43% moderately abnormal (30–59mL/ min/1.73m2), and 6% severely abnormal (<30 mL/min/1.73m2). Using the MDRD equation, these percents were 7%, 62%, 31%, and 0.5%. In cross-sectional analyses, there was a significant linear association between creatinine clearance by CG or glomerular filtration rate by MDRD and hip BMD. These diﬀerences were most compelling at lower levels of renal function. In prospective analyses, there was an average annual bone loss of 0.6% in both sexes, and a significant association between baseline CG and four-year hip bone loss. There was no association between baseline MDRD or serum creatinine and bone loss. At baseline, 180 of 1713 participants (11%) reported at least one clinical fracture of the hip, femur, forearm or wrist; there were 83 new clinical fractures during follow-up. Baseline renal function was not significantly associated with prevalent or new clinical fractures. Conclusions: Renal function by both the CG and MDRD equations was associated with hip BMD in cross-sectional analyses, but only creatininine clearance by CG predicted 4-year bone loss. Baseline renal function was not associated with prevalent or incident clinical fractures, perhaps reflecting the multifactorial etiology of fractures beyond BMD.

P114MO. A COMPARISON OF FRACTURE RISK CLASSIFICATION SYSTEMS AND ESTIMATED RATES OF TREATABLE OSTEOPOROSIS Richards JB1,2, Leslie WD3, Joseph L2, Adachi JD4, Brown JP5, Hanley DA6, Josse RG11, Papaioannou A7, Prior JC8, Siminoski K9, Tenenhouse AT10, Goltzman D1; 1Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, Quebec, Canada, 2Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada, 3Department of Medicine, University of Manitoba, Winnipeg, Canada, 4Department of Medicine, St. Joseph’s Healthcare, McMaster University, Hamilton, Ontario, Canada, 5CHUL Research Centre, Laval University, Sante-Foy, Quebec, Canada, 6Division of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Alberta, Canada, 7Health Sciences, McMaster University, Hamilton, Ontario, Canada, 8CaMOS Research Group, Vancouver, British Columbia, Canada, 9 Department of Radiology and Diagnostic Imaging & Division of Endocrinology, Department of Internal Medicine, University of Alberta, Edmonton, Alberta, Canada, 10McGill University, Montreal, Quebec, Canada, 11Department of Medicine, University of Toronto, Toronto, Ontario, Canada Aims: We compared the prevalence of treatable osteoporosis in a population-based cohort using BMD and clinical risk factors identified by the World Health Organization (WHO) and Osteoporosis Canada (OC). The WHO identified seven clinical risk factors (WHO Collaborating Centre, 2005) that augment fracture risk independent of age and BMD. OC has proposed the use of 10-year osteoporotic fracture risk based on age, sex, minimum

T-score and two additional clinical risk factors (OC Guidelines, 2005). Methods: We determined the prevalence of treatable osteoporosis in 4,701 women and 1,901 men aged 50 years and over in the Canadian Multi-Centre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort. For each subject we contrasted 10-year osteoporotic fracture risk using four diﬀerent intervention criteria. These included: 1: minimum T-score %-2.5, 2: age, sex, femoral neck T-score and WHO clinical risk factors using risk factor weightings from CaMos (odds ratios from logistic regression) 3: age, sex, femoral neck T-scores and WHO risk factors with weightings from WHO publications (metaanalyses) and 4: age, sex, minimum T-score, fragility fracture over age 40 and systemic glucocorticoid therapy >3 months in accordance with OC guidelines. For all estimations incorporating clinical risk factors, a 20% 10-year fracture risk threshold (high risk group) was applied. Results: The prevalence of treatable osteoporosis using minimum T-score %-2.5 was 22.4% in women and 8.8% in men. When WHO clinical risk factors were considered, the predicted prevalence of treatable osteoporosis in women was 28.6% using CaMosderived weights and 18.2% for WHO weights. Corresponding figures in men were 6.3% and 2.4%. When OC guidelines were applied, 36.1% of women and 6.3% of men exceeded a 20% 10-year fracture risk. Compared with minimum T-score %-2.5 SD, absolute fracture risk approaches diminished prevalence in younger women and substantially increased prevalence in older women. Conclusions: The combination of clinical risk factors and BMD to determine absolute fracture risk can dramatically aﬀect estimated rates of treatable osteoporosis. Some of these approaches increase the apparent prevalence of treatable osteoporosis, especially among older women, and decrease this prevalence in men. This may significantly impact on patterns and costs of osteoporosis treatment.

P115SA. ALCOHOL USE AND ABUSE BY OLDER MEN AND BONE MINERAL DENSITY, FALLS AND FRACTURES: THE OSTEOPOROTIC FRACTURES IN MEN (MROS) STUDY Cawthon PM1, Litwack SL1, Barrett-Connor E2, Cauley J3, Lewis C4, Fink H5, Orwoll E6, Cummings SR1; 1California Pacific Medical Center Research Institute, San Francisco, CA, USA, 2 University of California, San Diego, CA, USA, 3University of Pittsburgh, PA, USA, 4University of Alabama at Birmingham, AL, USA, 5University of Minnesota, Minneapolis, MN, USA, 6 Oregon Health and Science University, Portland, OR, USA Background: In men, BMD has been reported to be low in alcoholics, whereas moderate alcohol intake has been associated with increased BMD. There have been no prospective studies of the relationship of alcohol use on the outcomes of BMD, falling, and risk of non-spine fractures in a single cohort of older men. Methods: We assessed average alcohol intake and ever having problems with drinking (2+ positive answers to CAGE questions) in a cohort of 5,794 men aged R 65. Height, weight, hip and spine BMD were measured. All results are adjusted for confounding variables such as smoking. Results: During 3.6 years of 99% complete follow-up, we confirmed 256 non-spine (including 46 hip) fractures. 705 (12.0%) participants reported R2 falls during the first year. 1,001 men (16.7%) were classified as ever having problems with drinking. For alcohol intake in the past year, 2,121 (35.5%) men reported no or very infrequent intake (<12 drinks/year); 3,156 (52.8%) reported light intake (up to 13 drinks/week) and 697 (11.7%) reported moderate/heavy intake (R14 drinks/week.) Increasing alcohol intake was associated with higher hip and spine BMD. Moderate/high users had 3.7% higher total hip BMD, and 3.8% higher lumbar spine BMD compared with non-drinkers. Men reporting light alcohol intake had a lower risk of R2 falls (RR = 0.77; 95% CI: 0.65, 0.92) compared to abstainers. Moderate/heavy intake was borderline protective for R2 falls. (RR = 0.78, 95% CI: 0.60, 1.02). Alcohol intake did not influence the risk of non-spine or hip fractures. Compared to men without drinking problems, men with a history of problematic drinking had similar total hip BMD and

S149 higher spine BMD (+1.5%), yet also had a substantially higher risk of 2+ falls (1.59; 95% CI: 1.30, 1.95). A history of problematic drinking increased fall risk even among current abstainers. Problematic drinking was not associated with non-spine or hip fracture risk. Conclusion: Among older men, alcohol use, including a history of problematic drinking, is associated with greater BMD. Problem drinking increases falling risk while light intake decreases fall risk. Neither alcohol intake nor problematic drinking influence the risk of non-spine fractures.

P116SU. OSTEOPOROSIS CARE GAPS AMONG NURSING HOME RESIDENTS IN CANADA Kendler DL1, Dian L1, Manness L-J2, Li W1; 1University of British Columbia, Vancouver, BC, Canada, 2Merck Frosst Canada, Pointe Claire, QC, Canada The Osteoporosis Society of Canada (OSC) has established clear, evidence-based guidelines for the diagnosis and management of osteoporosis (OP) in Canada (CMAJ Nov 2002). The guidelines were meant to include elderly persons who are at the highest risk of fragility fracture and in whom there is the best evidence of eﬀectiveness of diagnosis and therapy. Our study evaluates the quality of OP care delivered in Long Term Care (LTC) facilities. We investigated the prevalence of OP risk factors, the frequency of OP diagnosis, and the utilization of OP interventions according to the OSC guidelines. Facilities had no aﬃliation to academic centres representing usual community LTC settings. We reviewed charts of 67 female residents at 2 LTC facilities in cities at populations of 77,000 and 27,000 in BC. Informed consent was obtained from all participants or their legal caregiver. Our findings indicate deficiencies in the diagnosis and clinical management of OP in the LTC setting. We discovered full guideline-based care in only 1 of 67 (3.6%) residents after the diagnosis of OP. The frequency of care after hip or spine fracture (5%), in 65–84 year olds (3.1%), and in those with 3 or more risk factors (1.6%) was similarly low. Calcium and vitamin D intakes were insuﬃcient according to guidelines in 90% and 97.3% of residents at each of the 2 facilities surveyed and did not diﬀer according to the above categories. Mean elemental calcium intake was 800 and 827 mg daily for residents at the two facilities. Medications were infrequently prescribed for OP with 5.4% and 10% of such patients receiving ‘‘first-line therapies’’ (alendronate, risedronate, raloxifene) and 8.1% and 16.7% receiving ‘‘second-line therapies’’ (estrogen, etidronate, calcitonin) at each of the facilities. Age, prior fracture, OP diagnosis, and the presence of more than 3 risk factors did not increase the frequency of prescription of OP medications. We conclude that among BC care facility residents there is low adherence to OP management guidelines. The high prevalence of OP in this population, poor access to bone density testing, and obstacles to accessing evidence-based eﬀective therapies may account for this large care gap.

P117MO. SMOKING IS AN INDEPENDENT PREDICTOR OF LOW BONE MINERAL DENSITY AND PREVALENT VERTEBRAL FRACTURES IN ELDERLY MEN: MR OS SWEDEN Mellström D1, Ljunggren Ö2, Holmberg A3, Lorentzon M1, Mallmin H2, Orwoll E4, Ohlsson C1, Johnell O3; 1Center for Bone Research at the Sahlgrenska Academy, Department of Geriatrics and Endocrinology, University of Göteborg, Sweden., 2Medical Sciences, University of Uppsala, Uppsala, Sweden, 3Orthopaedics Malmö General Hospital, Malmö, Sweden, 4Bone and Mineral Unit, Oregon Health and sciences University, Portland, OR, USA Aims: Smoking is regarded as a major risk factor for osteoporosis and fractures in women. The aim of the present study was to investigate the predictive role of smoking for bone mineral density (BMD) and prevalent fractures in elderly men. Methods: In the Swedish part of the MR OS-study, 3000 men, aged 69–80, were examined in Göteborg, Malmö and Uppsala. BMD was measured with LUNAR Prodigy in Malmö and Upp-

sala and with Hologic 4500 A in Göteborg. The BMD scanners have been calibrated and standardized BMD (sBMD) was calculated. The international MR OS questionnaire was used. In Malmö and Göteborg, 1369 men had an X-ray of the thoracic and lumbar spine at baseline. Results: 8.4 per cent were current smokers, 56 per cent were ex-smokers and 36 per cent were never smokers. 226 men, 16.6 per cent, had one or more X-ray verified vertebral fractures. Smoking was an independent (adjusted for age, physical activity, calcium intake and BMI) positive predictor of prevalent X-ray verified vertebral fractures (OR 1.80; 95% confidence interval 1.20 - 2.73). Linear regression models including lean mass, fat mass, body height, physical activity, calcium intake and age demonstrated that current smoking was an independent negative predictor of sBMD in total hip ( -0.061, p< 0.001), femoral neck ( -0.049, p= 0.007), trochanter ( -0.047, p< 0.010), and lumbar spine ( -0.041, p< 0.025). When calculating the total amount of smoking during life (Kg-tobacco) not only current smokers but also ex-smokers had significantly lower BMD at all hip-sites and increased risk for prevalent vertebral fracture. Conclusions: Smoking is an independent predictor for low BMD and prevalent vertebral fractures in elderly Swedish men.

P118SA. INCREMENTAL PROGNOSTIC VALUES OF RISK FACTORS-BASED MODEL FOR THE PREDICTION OF FRACTURE Nguyen ND, Eisman JA, Center JR, Nguyen TV; Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia Aim: Apart from bone mineral density (BMD), clinical risk factors such as age, weight, a history of fall and a prior fracture are individually associated with fracture risk. The present study sought to assess the incremental prognostic values of risk factors-based models in the prediction of fracture risk in osteoporotic and non-osteoporotic (i.e., ‘‘normal BMD’’) individuals. Methods: Participants in the Dubbo Osteoporosis Epidemiology Study were randomly divided into two groups: a development cohort (n=405 men, 632 women) and a validate cohort (n=418 men, 667 women), all aged 60+ years as at 1989. Femoral neck BMD (GE Lunar Corp, WI), body weight, and clinical history were assessed at baseline (1989). Subsequent fracture incidence was ascertained by X-ray report between 1989 and 2004. In the development cohort, three models for predicting fracture were developed: model I included only FNBMD; model II included age and weight; and model III utilized age, weight, fall and prior fracture as predictors. The positive predictive value (PPV) and AUC value of the three models were then assessed in the validation cohort. Results: In the validation cohort, 209 women and 71 men had sustained a fracture during the 15-year follow-up period. Risk estimate based on model I correctly identified 52% and 45% fractures in women and men, respectively. Risk estimates from models II and III had a slightly higher predictive values than model I; however, the concordance between model I and model II (or model III) was between 50% and 66%. Thus, when risk derived from model II was combined with model I, the predictive value increased to 77% in women and 70% in men, representing an absolute increase of 25% in both sexes. Comparable improvement was also observed in model III. The AUC values for the three models ranged between 0.61 to 0.68 in both sexes. Conclusion: These data indicate that the PPV of risk factorsbased model was slightly higher than that of BMD-based model, and that the incorporation of clinical risk factors can significantly increase the prognostic value of fracture prediction over and above of BMD alone.

P119SU. VARIATION IN 3’ REGION OF THE WNT10B GENE IS ASSOCIATED WITH PQCT MEASURES OF BONE SIZE AND STRENGTH IN AFRO-CARIBBEAN MEN Moﬀett SP1, Oakley JI1, Yerges LY1, Nestlerode CS1, Wheeler VW2, Patrick AL2, Bunker CH1, Zmuda JM1; 1University of

S150 Pittsburgh, Pittsburgh, USA, Scarborough, Tobago

2

Tobago Health Studies Oﬃce,

Activation of the Wnt signaling pathway by Wnt10b has been shown to stimulate osteoblastogenesis and bone formation in transgenic mice. Previously, we reported an association between a G to T polymorphism in the 3’ untranslated region (UTR) of WNT10B and measures of areal bone density (BMD) in Caucasian and Afro-Caribbean men. We have extended our study by genotyping 12 single nucleotide polymorphisms (SNPs) that span a 98kb region including the entire WNT10B gene in 400 AfroCaribbean men over the age of 40. We then assessed the relationship between these 12 SNPs and high resolution pQCT measures of bone mass, structural geometry and indices of biomechanical strength at 4% (T4), 33% (T33) and 66% (T66) of the tibia and 4% (R4) and 33% (R33) of the radius. Two SNPs in the 3’ UTR of WNT10B and a SNP in the 3’ intergenic region were associated with multiple pQCT measures in the tibia including cortical area and bone mineral content (BMC) at T33, total area and BMC at T33 and T66. For example, men with the 3’ UTR T allele had 16% higher cortical area (p=0.006) and BMC (p=0.009) than the GG homozygotes at the T33 site. As both bone area and BMC were increased in the T allele carriers, no association was observed with cortical or total volumetric BMD at any of the tibia sites. The same 3 SNPs also showed strong associations with both polar strength strain index (SSI) at all tibia sites and axial SSI at T4 and T66. Carriers of the T allele showed 44% higher polar SSI (p=0.004) and 40% higher axial SSI (p=0.009) at the T4 site compared to the GG homozygotes. However, these SNPs showed no association with pQCT measures at either of the radius sites and they were not associated with trabecular measures in the tibia or radius. In addition, none of the other SNPs in the WNT10B gene region showed significant associations with these pQCT measures at the tibia. These results suggest that genetic variation in Wnt10B may influence cortical bone mass, structural geometry and biomechanical strength especially in weight bearing skeletal regions.

P120MO. USE OF PROTON PUMP INHIBITORS AND BONE MASS, BONE LOSS AND FRACTURE IN OLDER MEN: THE MROS STUDY Bauer DC1,2, Blackwell T2, Shinoﬀ C2, Chang L1,2, Ensrud K3, Lane N1,4, Orwoll E5; 1UCSF, San Francisco, USA, 2SF Coordinating Center, San Francisco, USA, 3University of Minnesota, Minneapolis, USA, 4University of California, Davis, Sacramento, USA, 5Oregon Health Sciences Center, Portland, USA Proton pump inhibitors (PPIs) are frequently prescribed to reduce gastric acid secretion, and a recent study found that short-term use was associated with impaired intestinal absorption of calcium (O’Connell, 2005). We tested the hypothesis that PPI use was associated with adverse skeletal outcomes in older men enrolled in the Osteoporosis in Men Study (MrOS). At the baseline visit we measured hip BMD (Hologic QDR4500), BMI and PPI use in the previous 2 weeks in 5688 men R65. Repeat BMD was obtained in 3104 men (99% of those invited) after a mean follow-up of 3.4 yr. Low trauma hip and other non-spine fractures occurring after the baseline visit were documented by central adjudication of x-ray reports over a mean follow-up of 4.1 yr. PPI use and BMD, bone loss and fracture risk were analyzed with regression and hazard models adjusted for age, ethnicity, clinic, BMI, smoking, alcohol, health status, history of stomach surgery, and use of corticosteroids. Men who reported use of bisphosphonates or other osteoporosis medications (N=118), and those taking H2 blockers (N=348) were excluded. PPI users were older, in poorer health, more likely to be Caucasian, and more likely to use corticosteroids (p<0.05 for each). After adjustment for potential confounding eﬀects, PPI users had lower baseline spine BMD (Table), and there was a trend towards lower baseline hip BMD, greater hip bone loss and an increased risk of non-spine fracture during follow-up, but these relationships did not reach statistical significance (p=0.06 for each). PPI was not associated with hip fracture, but there were few events. We conclude that among independent living older men, PPI use is associated with reduced spine BMD, and potentially an in-

creased risk of bone loss and fracture. Further studies of the possible skeletal adverse consequences of PPI use are warranted.

No PPI Use (N=4775)

Outcome Baseline Spine BMD,g/cm2+/-SD Baseline Total Hip BMD, g/cm2+/-SD Total Hip Absolute Bone Loss, g/cm2/yr+/-SD Non-spine Fracture, Hip Fracture, N

PPI User (N=467)

Diﬀerence (95% CI)*

1.076 +/- 0.183 1.055 +/- 0.181 -0.024 (-0.041, -0.007) p=0.01 0.961 +/- 0.138 0.946 +/- 0.142 -0.012 (-0.024, 0.0004) p=0.06 -0.016+/-0.031 -0.021+/-0.035 -0.004 (-0.008, 0.0001) p=0.06 Relative Hazard PPI User (95% CI)* No PPI Use N 161 (3.4%) 25 (5.4%) 1.50 (0.98, 2.30) p=0.06 34 (0.7%) 2 (0.4%) 0.55 (0.13, 2.31) p=0.41

*multiply adjusted

P121SA. VITAMIN D DEFICIENCY AND PHYSICAL PERFORMANCE IN THE LONGITUDINAL AGING STUDY AMSTERDAM (LASA) Wicherts IS1, Van Schoor NM1, Boeke AJP1, Knol D2, Lips P2; 1 EMGO, VU University Medical Center, Amsterdam, The Netherlands, 2Endocrinology, VU University Medical Center, Amsterdam, The Netherlands Recently vitamin D deficiency has been implicated as a cause of decreased muscle strength and falls. In LASA, vitamin D deficiency was associated with low physical performance. Physical performance was assessed by the sum of three tests: chair stands(0– 4), walking test (0–4) and tandem stand (0–4), representing muscle strength and balance. The aim of this study was to assess which aspect of physical performance is strongest related to vitamin D deficiency. The study was done within the framework of LASA, a follow-up study in a representative sample of the older Dutch population. Subjects were 602 men and 638 women aged 65 years or older on January 1, 1996 (mean ageSD: 75.36.5 yr). In 1995–1996, data were collected on physical performance and vitamin D status. Multivariate regression analysis, adjusted for age, gender, body mass index, smoking status, alcohol use, physical activity, number of chronic diseases, season and education level was used to examine the association between vitamin D status and physical performance. Ordinal regression was used to determine which test was most strongly influenced by vitamin D. In table 1, cumulative Odd’s ratios are shown after adjustment for confounding. Persons having a serum 25(OH)D level below 25nmol/l had a significantly increased risk of 2.4 to have a 1-point lower score on the chair stand, 1.6 higher risk to have a 1 point lower score on the tandem stand and a 2.8 higher risk to have a 1 point lower score on the walk test, respectively, as compared with persons having a serum 25(OH)D level above 75 nmol/l. Odd’s ratio

Chair

0–25 (n=134)

25–50 (n=455)

50–75 (n=422)

2.38***

1.30

1.03

1.14

0.88

1.52**

1.23

**

Tandem

1.69

Walk

2.86***

*** p<0.001

** p< 0.05

75+ (n=227) Reference group Reference group Reference group

S151 In conclusion, low serum 25(OH)D was significantly associated with poor performance on the chair stand, tandem stand and walk test. Serum 25(OH)D was most strongly related with the walk test.

P122SU. COHORT EFFECTS ON BONE MINERAL DENSITY (BMD) AND CHANGES IN BMD IN A 10-YEAR FOLLOW-UP STUDY Fujiwara S1, Furukawa K1, Fukunaga M2; 1Radiation Eﬀects Research Foundation, 2Kawasaki Medical College, Hiroshima, Japan Purposes: Our previous report showed decreased incidence of vertebral fracture in younger birth cohorts in Japan. The objectives of our research are to study whether bone mineral density (BMD) and longitudinal change patterns in BMD vary by generation when people reach the same age, and to investigate any possible predictive factors for such change patterns. Methods: The research was conducted among 3,614 subjects (1,195 males and 2,419 females, born between 1894 and 1946) who had their bone mineral density (BMD, lumbar and femoral neck) measured by DXA (QDR 2000, Hologic) in biennial health examinations from 1994 to 2005. A growth curve statistical model by age was used for analysis. Results: Regarding BMD of those reaching the same age, BMD in the youngest 10-year generation was about 6% higher in the spine and about 2% higher in the femoral neck. After adjusting for body weight, the diﬀerences in spine BMD by cohort disappeared, but the diﬀerences in femoral neck BMD by generation remained. There was no diﬀerence in patterns of decrease in BMD with age between generations. The baseline BMD at both sites indicated that the heavier the body weight, the higher the BMD for both men and women, and the higher the age at menopause, the higher the BMD. The rate of changes in BMD were not aﬀected by either body weight or age at menopause. The higher the baseline spine BMD was, the smaller the decrease in BMD, for both men and women, while the decrease in femoral neck BMD did not show any association with the baseline BMD. Conclusions: Younger Japanese generations showed higher BMD compared to the older generation, and diﬀerences in lumber BMD among generations could be explained by intergenerational body weight diﬀerences. Patterns of change in BMD with age did not diﬀer by generation. In Japan, improvement of dietary habits in recent years might have induced increased BMD, resulting in decreased incidence of vertebral fracture in recent years.

P123MO. TREATMENT PATTERNS WITH DAILY AND WEEKLY BISPHOSPHONATE REGIMENS IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS van den Boogaard CHA1, Penning-van Beest FJA1, Erkens JA1, Engbersen AMT2, Herings RMC1; 1PHARMO Institute, Utrecht, Netherlands, 2Novartis Pharma AG, Basel, Switzerland Aim: To determine treatment patterns with daily and weekly bisphosphonate regimens in women with postmenopausal osteoporosis. Methods: Data were obtained from the PHARMO database, which includes linked drug dispensing records and hospital records of more than two million individuals in defined areas in the Netherlands. New female users of daily or weekly alendronate or risedronate therapies, aged 45 years and older or with diagnosed postmenopausal osteoporosis in the period 1 January 1999 – 30 June 2004, were included in the study cohort. One-year persistence of treatment was determined by using episodes of bisphosphonate treatment, using the method of Catalan. For non-persistent patients, the first change in osteoporosis treatment pattern (switch, discontinuation or stop) in the one-year period after starting treatment was determined. Treatment patterns were analyzed separately for new users of daily and weekly bisphosphonate regimens. Results: The study cohort included 4,222 new users of daily bisphosphonates and 4,600 new users of weekly bisphosphonates. One-year continuation rates with bisphosphonates were low: only 1,257 (30%) of daily bisphosphonate users and 2,099 (46%) of weekly bisphosphonate users remained on their initial therapy after one year. Nonpersistent users of daily bisphosphonates

mostly discontinued (27%) or definitely stopped (27%) their initial treatment during the first year. Likewise, most nonpersistent users of weekly bisphosphonates discontinued (29%) or definitely stopped (20%) treatment during this period. For patients discontinuing treatment, the median length of time to restart treatment was 22 days. Treatment was resumed with the original drug regimen in 86% and 96% of daily and weekly bisphosphonate users, respectively. Conclusions: The results of this study indicate that bisphosphonates are not used as recommended. Fewer than half of daily as well as weekly bisphosphonate users remain on their treatment after one year. However, about 30% of nonpersistent bisphosphonate users resume treatment in the first year. It is likely that this pattern of bisphosphonate use has a detrimental impact on treatment eﬃcacy.

P124SA. FRAGILITY FRACTURE PREVALENCE IN WOMEN AND MEN ACCORDING TO T-SCORE VALUES: THE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY (CAMOS) Papaioannou A1, Ioannidis G1, Tenenhouse A2, Gao Y2, Berger C2, Prior JC3, Josse RG4, Hanley DA5, Brown JP6, Olszynski WP7, Kaiser SM8, Murray TM4, Anastassiades T9, Kirkland S4, Joyce C10, Poliquin S2, Kreiger N4, Davison KS7, Kennedy CC1, Siminoski K11, Leslie WD12, Cranney A13, Goltzman D2, Adachi JD1; 1McMaster University, Hamilton, Canada, 2McGill University, Montreal, Canada, 3University of British Columbia, Vancouver, Canada, 4University of Toronto, Toronto, Canada, 5 University of Calgary, Calgary, Canada, 6Laval University, SteFoy, Canada, 7University of Saskatchewan, Saskatoon, Canada, 8 Dalhousie University, Halifax, Canada, 9Queen’s University, Kingston, Canada, 10Memorial University, St. John’s, Canada, 11 University of Alberta, Edmonton, Canada, 12University of Manitoba, Winnipeg, Canada, 13University of Ottawa, Ottawa, Ontario, Canada Aims: Utilizing participants from CaMos, a random sample of the Canadian population, we performed a baseline analysis to determine the number of community dwelling women and men R50 years that report past fragility fractures according to their t-score values. Methods: A total of 5566 women and 2187 men from nine CaMos centres formed the base cohort. At study entry, subjects completed a questionnaire. Bone mineral density (BMD) of the lumbar spine and hip, were measured by dual-energy x-ray absorptiometry. T-scores were classified as osteoporotic (%-2.5), osteopenic (-1% to >-2.5) and normal (>-1). Spinal radiographs were used to confirm prevalent vertebral fractures. Vertebral fractures were defined as either grade 1 (vertebral ratio of 3 standard deviations (SD) below the normal group) or grade 2 (R 4 SD). Spine fractures were divided into two groups: all (clinical and subclinical), and clinical deformities. Clinically recognized hip, ribs, and wrist fragility fractures were based on self-reports. Table 1: Prevalence of fragility fractures in women and men according to BMD t-score values Fracture Women: # (%) Hip Ribs Wrist Clinical Spine All Spine Men: # (%) Hip Ribs Wrist Clinical Spine All Spine

Osteoporosis

Osteopenia

Normal

28 (3.0) 35 (3.8) 132 (14.2) 26 (2.8) 333 (45.6)

26 (1.0) 45 (1.7) 258 (9.9) 14 (0.5) 542 (25.9)

0 (0.0) 14 (1.1) 78 (6.1) 5 (0.4) 165 (16.4)

4 (3.3) 7 (5.7) 5 (4.1) 1 (0.8) 39 (41.1)

3 (0.3) 28 (3.0) 77 (8.3) 3 (0.3) 200 (28.1)

2 (0.2) 14 (1.6) 33 (3.8) 1 (0.1) 131 (20.3)

Results: BMD baseline values showed osteoporosis, osteopenia and normal results respectively in 19.4% (n=930), 54.2% (n=2602),

S152 and 26.5%(n=1273) of women and in 6.4% (n=122), 48.2% (n=925), and 45.5 % (n=873) of men R50 years. The percentage with fractures was highest in patients with osteoporosis by BMD. More patients had vertebral fractures, as compared with nonvertebral fractures (table 1). Women and men had a similar percentage of vertebral fractures. Men had a slightly greater percentage of fragility rib fractures; however, more women had wrist and hip fractures. Conclusion: A large number of fractures occur in both men and women with osteoporosis by BMD. Although most vertebral fractures go unnoticed in a clinical setting, this fracture type has the highest prevalence. Osteoporotic fractures are associated with increased mortality and morbidity, and patients with fractures should be treated aggressively to reduce the likelihood of subsequent fracture.

P125SU. ASSOCIATIONS BETWEEN OBESITY, THE METABOLIC SYNDROME AND BONE MINERAL DENSITY IN OLDER MEN AND WOMEN FROM THE RANCHO BERNARDO STUDY von Muhlen D1, Safii S1, Jassal S2, Barrett-Connor E1; 1Department of Family and Preventive Medicine, 2Department of Medicine, University of California San Diego, USA Aim: The Metabolic Syndrome (MS) is a cluster of risk factors associated with excess CVD morbidity among overweight and obese patients. The association between components of the MS and bone mineral density (BMD) has been extensively researched. Overweight has been associated with better BMD and hypertension has been associated with poorer BMD. The results of studies of the association between high blood glucose levels, high triglycerides or lower HDL levels with BMD have been contradictory, with strong evidence for either positive or negative associations. We examined the cross-sectional association between MS and BMD among 420 men and 676 women aged 38 to 97 (mean=74, SD=9.7) from the Rancho Bernardo Study. Methods: We determined whether MS defined by NCEPATPIII criteria is associated with BMD and prevalence of osteoporosis by WHO criteria, and whether these associations are independent of age, body mass index (BMI), lifestyle, and medication use. Multivariate regression models were used to examine the association of MS with BMD before and after adjustment for covariates. All analyses were repeated after stratification by diabetes mellitus and obesity status. Results: Prevalence of MS was 23.5% in men and 18.2% in women. In both sexes, participants with MS had lower prevalence of osteoporosis at the hip (11% vs. 15%, p=0.005) or femoral neck (37% vs. 45%, p=0.01) when compared with participants without MS. In age adjusted and sex specific analyses, both men and women with metabolic syndrome had higher BMD at total hip when compared to men and women without the MS (p<0.001 and p=0.01, respectively). Men but not women with MS also had higher BMD at the femoral neck (p=0.05). After adjustment for BMI, the significant association between neck BMD and MS in men was reversed, presence of MS was associated with lower and not higher BMD (p=0.02). There were no significant associations after stratification by obesity (BMD>=30) or diabetes status. Conclusions: The association of MS with higher BMD in men and women was entirely explained by the higher BMI in individuals with MS.

P126MO. SERUM CALCIDIOL IS A NEGATIVE PREDICTOR OF PROSTATE VOLUME AND A POSITIVE PREDICTOR OF BONE DENSITY AT CORTICAL SITES IN ELDERLY MEN: MR OS SWEDEN Waern E1, Damber J-E2, Johnell O4, Haug E6, Knutsson T2, Ljunggren Ö5, Orwoll E7, Ohlsson C3, Mellström D1; 1Center for Bone Research at the Sahlgrenska Academy, Department of Geriatrics, University of Göteborg, Sweden, 2Department of Urology, University of Göteborg, Sweden, 3Department of Endocrinology, Univeristy of Göteborg, Sweden, 4Department of Orthopaedics, Malmö University, Sweden, 5Department of medical Sciences, University of Uppsala, Sweden, 6Hormonlaboratory,

Aker University Hospital, Oslo, Norway, 7Bone and Mineral Unit, Oregon Health and Sciences University, Portland, OR, USA Aims: Vitamin D deficiency has been related to increased risk for osteoporosis and prostate cancer. In this study we investigate the influence of serum Calcidiol and PTH on prostate volume and bone density. Methods: Bone density and body composition were determined in 1000 men aged 69–80 years with Hologic 4500 A, MR OS Göteborg. Prostate volume was examined with trans-rectal ultra sound in a subsample of 164 men. Men with prostate cancer and earlier prostate operations were excluded. Blood sample was drawn from an antecubital vein after 10 hours fasting and nonsmoking, at eight in the morning, and placed in -80(C freezer. Calcidiol was analysed with a RIA method, Diasorin, Stillwater, MN, USA and intact PTH was analysed with Immunolite 2000, Diagnostic Products Corporation (DPC), Los Angeles, CA, USA. Results: Prostate volume correlated inversely to serum Calcidiol r=-0.28, p=0.0003 but not to PTH, r=0.11 NS. A multivariate model with body composition, free, estrogen, insulin, free testosteron, age, Calcidiol and PTH showed that calcidiol was an independent strong negative predictor for prostate volume,0.287, p=0.0008. The model explained 18.3 percent of the variation in prostate volume. PTH correlated inverely to Calcidiol r=-0.18, p=0.0001. In multivariate models Calcidiol correlated significantly to BMD in femur neck, trochanter and total body while PTH correlated inversely to BMD in femur neck, trochanter and total hip. Conclusion: The main novel finding, in this study, is that Calcidiol was an independent negative predictor of prostate volume. Furthermore, high serum Calcidiol was a predictor for high bone density in the hip and total body while PTH was a negative predictor for bone density in the hip area in elderly men, MR OS, Göteborg.

P127SA. IMPACT OF PREVALENT AND INCIDENT VERTEBRAL FRACTURES ON UTILITY: RESULTS FROM A PATIENT-BASED AND A POPULATION-BASED SAMPLE Van Schoor NM1, Ewing SK2, O’Neill TW3, Lunt M3, Smit JH4,5, Lips P6; 1EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands, 2Prevention Sciences Group, UCSF, San Francisco, USA, 3ARC Epidemiology Unit, University of Manchester, Manchester, United Kingdom, 4Department of Sociology and Social Gerontology, Vrije Universiteit, Amsterdam, The Netherlands, 5Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands, 6Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands Aims: Vertebral fractures (VFX) are known to influence quality of life as assessed by generic and specific quality of life questionnaires. However, scarce data are available on the impact of VFX on utility, i.e. the value attached to a specific health state, which can be used to calculate loss of quality-adjusted life years. The objective of this study was to assess the impact of prevalent and incident vertebral fractures on utility in both a patient-based and a population-based sample. Methods: Data from the Multiple Outcomes of Raloxifene Evaluation (MORE) study (n=550 for prevalent VFX analysis, and n=178 for incident VFX analysis) and the European Prospective Osteoporosis Study (EPOS) (n=236) were used. Utility was assessed by the index score of the EQ-5D (EuroQol). The estimated time interval between the incident VFX and utility was 1.5 years for the MORE study and 3.8 years for EPOS. Results: In the MORE study, highly statistically significant associations were found between utility and the presence of prevalent VFX (p<0.001), number of prevalent VFX (p<0.001), severity of prevalent VFX (p<0.001), the combination of number and severity of prevalent VFX (p=0.001) and location of prevalent VFX (0.019). Furthermore, the mean utility was significantly lower among women who suﬀered an incident VFX (utility=0.66) than among women who did not (utility=0.77) (p=0.004). In EPOS, a trend towards a significantly lower utility was found for cases with incident VFX (utility=0.77) as compared with controls (utility=0.82) (p=0.065). In addition, the combination score of number

S153 and severity of incident VFX was significantly related to utility (p=0.030). In both study, utility was especially low in persons with incident VFX who already had prevalent VFX (utility=0.66 in the MORE study; utility=0.71 in EPOS). Conclusions: Utility as assessed by the index score of the EQ-5D is lower among persons with prevalent and incident VFX in both a patient-based and a population-based sample. In both studies, utility was especially low in persons with incident VFX who already had prevalent VFX.

P128SU. CALCIUM AND VITAMIN D INTAKE IN A CANADIAN POPULATION: RESULTS FROM THE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY Polqiuin S1, Joseph L2, Gray-Donald K3; 1McGill University Health Centre- Research Institute, 2McGill University, Epidemiology and Biostatistics, 3McGill University, School of Dietetics and Human Nutrition, Montreal, Canada Background: Calcium and vitamin D are essential nutrients for increasing peak bone mass and for minimizing age related bone loss, thereby decreasing the risk of osteoporosis and low trauma fractures. Little is known about intake in Canadians throughout life. Objectives: To report on the calcium and vitamin D intake in a Canadian population of men and women, 25 years of age and older. Methods: In the Canadian Multicentre Osteoporosis Study (CaMos), we estimated the intake of calcium from food and supplements and vitamin D from milk and supplements using baseline cross-sectional data from 9,423 participants who completed an interviewer administered abbreviated food frequency questionnaire. The participants were recruited from July 1995 to September 1997 in nine cities: Vancouver, Calgary, Saskatoon, Toronto, Hamilton, Kingston, Quebec City, Halifax and StJohn’s. Results: See table below. The recommended daily adequate intake for calcium is 1000 mg, 1000 mg and 1200 mg for the three age groups respectively. For vitamin D these values are 5 µg, 10 µg and 15 µg for the three age groups, respectively. Conclusions: The highest intake of total calcium, from food and supplements was found to be in women aged 51–70. This group was the only one that met the adequate intake level for calcium. Women aged 51 to 70 and those aged more than 70 tended to report higher intakes of vitamin D than the corresponding groups of men. Women below the age of 71 met adequate intake levels for vitamin D, while men met adequate intakes only if aged less than 51 years of age. Based on these results, nutrition education campaigns and programs should be targeting women older than 70 years of age and men older than 50 years of age regarding calcium and vitamin D intake. Results: Mean and Median Calcium and Vitamin D Intake Calcium mg/day Men Mean Age Group (SD) 25–50 years of age 51–70 years of age >70 years of age

Median (IQR)

*Vitamin D mcg/day Women Mean (SD)

Median (IQR)

Men Women Mean Median Mean Median (SD) (IQR) (SD) (IQR)

N= 754 N=1068 N= 754 918 (610) 771 (646) 961 (581) 840 (683) 9 (25) 5 (9) N=1380 N=3508 N=1380 908 (581) 783 (646) 1063 (631) 949 (772) 8 (9) 5 (10) N=750 N=1963 N=750 884 (557) 762 (649) 1035 (598) 944 (800) 8 (11) 5 (10)

N=1068 8 (12) 5 (10) N=3508 10 (18) 6 (11) N=1963 12 (45) 6 (10)

* 1 mcg = 40 IU

P129MO. ASSOCIATION BETWEEN OSTEOPOROSIS AND HYPERTENSION: PATHOGENETIC ROLE OF LOW DIETARY CALCIUM INTAKE Varenna M, Casari S, Binelli L, Lurati A, Sinigaglia L; Department and Chair of Rheumatology, Gaetano Pini Institute, Milan, Italy Aims: Epidemiological studies reported an association between hypertension (HP) and related diseases with a low bone mass. The main pathogenetic hypothesis points to an increased PTH level depending to the urinary calcium leak as reported in subjects with

HP. Recently, a low dietary calcium intake has been demonstrated to be related to a metabolic syndrome in which HP frequently occurs. Aim of this study was to verify if a low dietary calcium intake could play a role as a pathogenetic link between HP and osteoporosis (OP). Methods: Cases were recruited from 9898 postmenopausal women referred to the Osteometabolic Unit of our hospital in the last 12 years. From this sample, 825 subjects with HP never treated with thiazide diuretics or other drugs known to aﬀect bone metabolism were selected. For each case three controls were randomly selected matching for age ( 1 year) among healthy postmenopausal women. Results: Univariate analysis showed that HP subjects had a significantly higher body mass index, a higher prevalence of overweight and obesity, a lower dietary calcium intake and a higher prevalence of OP (32.5% vs 23.3%; p<0.001). Multiple logistic analyses demonstrated an inverse correlation between the levels of calcium intake and the HP odd ratio (p for trend = 0.003). By considering in the same models the variable OP risk and after adjusting for confounder variables, OP acts as independent predictive variable toward HP risk. Nevertheless, OP was no longer predictive for HP risk by comparing the extreme quartiles of calcium intake (<400 mg/day vs >750 mg/day) showing that the diﬀerence in calcium intake acts as the only variable linking OP and HP in women with a very low calcium intake. Similar results were observed when HP was considered as predictive variable toward OP risk. Conclusions: Among postmenopausal women a very low dietary calcium intake can be viewed as the main pathogenetic factor linking HP and OP.

P130SA. HIP AXIS LENGTH PREDICTS BONE STRENGTH IN THE PROXIMAL FEMUR INDEPENDENT OF BMD: A HUMAN AUTOPSY STUDY Nissen N1,2, Hauge EM3, Melsen F3, Abrahamsen B4, Brixen K1, Jensen JEB5; 1Department of Endocrinology, Odense University Hospital, Odense, Denmark, 2Department of Orthopdics, Kolding Sygehus, Denmark, 3Department of Rheumatology, Aarhus Sygehus, Aarhus University Hospital, Aarhus, Denmark, 4Department of Endocrinology, Roskilde Amts Sygehus, Koge, Denmark, 5 Osteoporosis Research Clinic, Hvidovre University Hospital, Hvidovre, Denmark Bone mineral density (BMD) predicts the risk of fracture of the proximal hip, however, clinical studies have suggested that geometrical parameters of the hip such as hip axis length (HAL) may predict the risk of hip fractures independent of BMD. Few experimental data, however, has been published to substantiate this. Aim: The aim of this study was to investigate the relationship between BMD, geometrical parameters of the hip, and the maximal bone strength in the human proximal femur in vitro. Methods: 37 proximal femurs without any bone diseases (3 females, 34 males) from forensic autopsies (aged 30–68 years) were studied. BMD of the femoral neck was measured using dualenergy X-ray absorptiometry (DXA) and HAL, neck width (NW), neck shaft angle (NSA), and femoral head radius (HR) were measured on DXA screen images acquired with a Hologict QDR-2000 densitometer. We measured maximal strength of the bone in a position simulating a sideways fall by help of Instron test machine with a load-speed of 2 mm/min and an increasing load. Results: The relationships between hip geometry, age, height, weight, BMD, and bone strength are shown in Table 1. By multiple Table 1. Bivariate correlation analysis. Data are shown as correlation coeﬃcients (R). **: p

HAL NSA NW HR Strength

Age

Height

Weight

BMD-neck

Strength

-0.13 -0.38* 0.11 0.00 -0.38*

0.80** 0.30 0.64** 0.82** 0.46**

0.36* 0.19 0.40* 0.36* 0.12

0.30 0.01 -0.10 0.05 0.71**

0.54** 0.04 0.19 0.37* -

S154 regression analysis (backwards) with height, weight, age, BMD, HAL and NW as independent variables and bone strength as dependent variable, only BMD (R=0.68, p<0.001) and HAL (R=0.49, p<0.001) were significant predictors of bone strength. The overall model explained 62% (p<0.005) of the variation in bone strength. Conclusions: HAL predicts the strength of the proximal femur independently of BMD. In vitro increased HAL is related with increased bone strength. This is at variance with clinical studies. The use of variable load and constant speed during the testing may be important for the results. Further studies are necessary to clarify this.

P131SU. ASIAN WOMEN HAVE A 3-FOLD HIGHER BONE LOSS RATE THAN IN ASIAN MEN, WHY IS THAT SO? RESULTS FROM MR AND MS OS (HONG KONG), THE FIRST OSTEOPOROSIS COHORT STUDY IN ASIA Lau E1, Leung PC2, Kwok T2, Woo J2, Orwoll E3, Cumming S4; 1 Hong Kong Orthopaedic and Osteoporosis Center for Treatment and Research, Hong Kong, China, 2The Chinese University of Hong Kong, Hong Kong, China, 3Oregon University of Health Sciences, Oregon, USA, 4CPMC Research Institute, California, USA Aims: Mr and Ms Os (Hong Kong) is the first cohort study on osteoporosis in Asia. The aims are to compare the incidence of and factors aﬀecting fracture and rate of bone loss in elderly Asian men and women. Methods: A total of 2000 men and 2000 women aged 65 years and above were followed up for 2 years. Bone mineral density (BMD) was measured by the Hologic QDR machine, and life style factors were measured by a standardized structural questionnaire. Rate of bone loss and factors aﬀecting them were studied by regression analysis. Only data for total hip is described in this abstract. The following risk factors were significantly (p<0.05) associated with more rapid bone loss in Asian women and men.

Variable Age (75 years / 65 years) COPD (yes / no) Cancer (yes / no) 5 or more drinks a day (yes / no) Inhaled steroid (yes / no) Diuretic use (yes / no) Underweight (BMI < 18.5 / BMI 18.5) Cigarette smoking (yes / no)

Diﬀerence in women (% bone loss)

Diﬀerence in men (% bone loss)

1.06 0.89 1.06 6.93

0.72 Not Associated Not Associated Not Associated

2.7 2.27 0.24

Not Associated 1.4 0.66

Not Associated

0.73

Results: Over 2 years, the rate of bone loss at the total hip for women were -1.24% (SD = 3.35%, N=1299); while that for men were -0.38% (SD = 2.58%, N = 1744; p<0.005). Conclusions: The rate of bone loss at the hip was around 3-fold higher in women than in men; and this could be partially attributed to the larger number of adverse factors adversely aﬀecting bone loss in women.

P132MO. INFLUENCE OF CALCIUM INTAKE ON BONE RESORPTION DURING PREGNANCY Avendaño-Badillo D1, Téllez-Rojo MM2, Hernández-Cadena L2, Mercado-García A2, Solano-González M2, Koplan K2, Hu H3, Hernández-Ávila M2; 1Instituto Nacional de Rehabilitación, Mexico, 2Instituto Nacional de Salud Pública, Mexico, 3Harvard School of Public Health, USA Aims: Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetal skeleton. The objective of this study was to evaluate the association of calcium intake and bone demineralization process during pregnancy. Methods: At each pregnancy trimester a food frequency intake questionnaire was applied in order to assess the daily calcium intake in a cohort of 206 pregnant women living in Mexico City. Samples of the second morning urine were recollected in order to analyze cross linked N-telopeptides (NTx) of type I collagen, which is a specific biomarker of bone resorption. The relationship between calcium ingestion and bone resorption was analyzed using aleatory eﬀects models; nonlinear associations were explored using Generalized Additive Models. Results: The mean of age was 27 years in a range of 15–43 years, it was observed as a progressive increase of NTx during pregnancy with means and standard deviations (SD) of 76.50 (SD 38), 101.02 (SD 48.86) and 144.83 (SD 61.33) nmol BCE/mmol creatinine during the first, second and first trimester. After adjusting by maternal age, gestational age and height, the results suggest that calcium ingestion during this period is significantly associated with a lower bone resorption (=-0.15; p<0.05). The relationship between age and NTx show a nonlinear behavior with an inflexion point around 33 years, the increase in the age in women under that inflexion point was associated with a decrease in bone resorption; while in older women, the increase was associated with an increased resorption.

The following risk factors were significantly (p<0.05) associated with less rapid bone loss in men and women.

Variable Higher grip strength (>35 kg / < 27kg) Walking more daily (>11 streets / < 5 streets) Higher isoflavone intake (highest quartile / lowest quartile) Calcium supplements (yes / no)

Diﬀerence in % bone loss in women

Diﬀerence in % bone loss in men

0.74

0.6

0.52

0.35

Not Associated

0.41

0.56

Not Associated

Multivariate additive model of NTX among pregnant women (dairy calcium). Mexico City 1997–2000

Conclusions: The results of this study suggest that calcium ingestion, specifically of dairy products have significant influence on bone resorption during pregnancy: for each 300mg (a glass of milk) of calcium there is a diminution of 4.8 nmol BCE/mmol of creatinin from NTx (p<0.05).

S155

P133SA. BONE MINERAL DENSITY AS A PREDICTOR FOR FRACTURES IN ELDERLY MEN: MR. OS SWEDEN Ljunggren O1, Mellstrom D2, Mallmin H1, Ohlsson C2, Orwoll E3, Holmberg A4, Johnell O4; 1Department of Medical Sciences, University of Uppsala, Sweden, 2Department of Geriatrics, University of Gothenburg, Sweden, 3Univerity of Portland, OR, USA, 4 Department of Orthopaedics, University of Malmo, Sweden Bone mineral density (BMD) is a good predictor for fragility fractures in elderly women. This is known from several large prospective cohorts, and from metaanalysis of risk factors for fracture. In men, however, the impact of low BMD as a risk factor for future fractures is less validated since few prospective fracture studies have been performed in men. The Mr. OS trial is a multinational prospective study aiming at identifying risk factors for fractures in men. In this abstract we present prospective data from the Swedish part of Mr. OS, in which 3000 men age 70–80 are included. The men were selected from the population registers and baseline data were collected at three centres, Gothenburg, Malmo, and Uppsala. The DXA scanners were calibrated and standardised, BMD were calculated from previous algorithms. Information of incident fractures were collected by questionnaires and from hospital files. All prospective fractures after baseline have been recorded. A total of 77 fractures were recorded. Of these 54 were considered as osteoporotic, and 20 of these were hip fractures. In this abstract we have investigated the impact of baseline BMD as an independent predictor for fracture. A Cox proportional hazard model adjusted for age was used in the calculation. Results: BMD at all sites measured was a strong independent predictor for fracture. All Fractures Lumbar spine BMD: RR for 1 SD decrease in BMD at baseline = 1.6 (1.3–2.1) Femoral neck BMD: RR = 1.8 (1.3–2.4), All Osteoporotic fractures Lumbar spine BMD: RR = 1.5 (1.1–1.9) Femoral neck BMD: RR = 2.2 (1.7–2.8) Hip fractures Only the hip measurements were significant, possibly due to low power. Femoral neck BMD: RR= 3.0 (2.0–4.6) Conclusion: BMD is a strong predictor for fractures also in elderly men. Hip BMD is the best predictor for hip fractures.

P134SU. MILK INTAKE IN EARLY AND LATE ADULTHOOD AND RISK OF OSTEOPOROTIC HIP FRACTURES IN UTAH Slavens MJ, Munger R, Wengreen H, Cutler R, Corcoran C; Utah State University, Logan, UT, USA Aims: Milk intake may improve overall nutrition among elderly persons and may decrease the risk of osteoporotic fractures. We examined associations between milk intake and avoidance and risk of osteoporotic hip fracture in a statewide case-control study in Utah. Methods: Cases were ascertained at Utah hospitals treating 98% of hip fractures in the state during 1997–2001 and included 1188 men and women aged 50–89 years. Age- and gender-matched controls were randomly selected from Utah driver’s license and Medicare databases (N= 1324). Participants reported frequency of milk intake at age eighteen, during pregnancy among women, and in the one-year period before fracture (cases) or the interview (controls). Diet and supplement intakes were assessed with a food frequency questionnaire and participants reported their history of milk avoidance. Total calcium intake was categorized into quintiles (Q) of distribution of intake. Logistic regression models were used to examine associations between milk intake and risk of hip fracture and included terms for gender, age, body mass index, alcohol use, smoking, physical activity, estrogen use, total calorie intake, total calcium intake and total vitamin D intake. Results: Milk intake was not associated with risk of hip fracture at any of the life stages. Milk avoidance for a year or more was associated with an increased risk of hip fracture compared to those who did not avoid milk (odds ratio (OR): 1.38, 95 percent confidence interval (CI): 1.06, 1.78). A significant interaction was

found between milk avoidance and total calcium intake (p= < 0.04). Milk avoidance was associated with a 1.8 times greater risk (95 percent CI = 1.02, 3.17) of hip fracture compared to nonavoiders among participants with low calcium intake (Q1, Q2) but was not associated with elevated risk among those with higher calcium intake (Q3-Q5). Conclusions: Level of milk intake at age eighteen, during pregnancy for women, and in the year before hip fracture was not associated with risk of hip fracture. Elderly persons who avoided milk for a year or more were at increased risk of hip fracture but only among those within the lower quintiles of calcium intake.

P135MO. PROGRESSIVE HIP BONE LOSS WITH AGE AMONG AFROCARIBBEAN MEN: LONGITUDINAL RESULTS FROM THE TOBAGO BONE HEALTH STUDY Sheu YT1, Wheeler VW2, Cauley JA1, Bunker CH1, Patrick AL2, Zmuda JM1; 1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, 2 Tobago Health Studies Oﬃce, Scarborough, Tobago, West Indies Although men do not experience the rapid bone loss that occurs with the onset of menopause in women, bone loss occurs with aging in men and women. However, very little is known the natural history and magnitude bone loss among non-white men, particularly among those of African descent. Thus, we examined the rate of hip bone loss in relation to age and body mass index (BMI) in an ongoing longitudinal study of Afro-Caribbean men. A total of 2,700 men aged 40 and older were first recruited regardless of their health status for a population-based prostate survey. Bone mineral density (BMD) was measured at the proximal femur at study entry and after an average of 4.3 years later on a Hologic QDR-4500 scanner. A total of 912 men (mean age, 57.110.3; range, 40–88yrs) were included in the analysis. We compared the annualized rate of change in BMD across 10-yr age groups and BMI quartiles. After adjustment for baseline BMD and BMI, the rate of decline in hip BMD accelerated with increasing age. For example, the rate of decline in total hip BMD was -0.51%/yr among men aged 70 and older compared to -0.08 %/yr among men aged 40–49 yrs. Similar patterns were observed at the hip sub-regions. The rate of decline in BMD was greatest among men with the lowest, compared to the highest, BMI quartile. Obese men (BMI>=30kg/m2) experienced the smallest decline whereas underweight men (BMI<18.5kg/m2) experienced the highest rate of decline in BMD (e.g., femoral neck: -0.15%/yr vs -0.77%/yr; p=0.006). Men of African descent appear to experience a progressive and substantial rate of hip bone loss with aging and low body mass. More studies are needed to determine additional factors contributing to the decline in BMD with aging among men of African descent.

P136SA. ADIPONECTIN AND TRABECULAR VOLUMETRIC BONE DENSITY ARE GENETICALLY LINKED: NOVEL FINDINGS FROM THE TOBAGO FAMILY HEALTH STUDY Zmuda JM1, Wang XJ1, Miljkovic-Gacic I1, Wheeler VW2, Evans R1, Bunker CH1, Patrick AL2, Kammerer CM1; 1Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, 2 Tobago Health Studies Oﬃce, Scarborough, Tobago, Trinidad & Tobago, West Indies Adiponectin is a circulating peptide of adipocyte origin. Adiponectin is present within the normal bone marrow compartment, can inhibit fat cell formation by marrow-derived stromal cells, and may regulate pre-adipocyte diﬀerentiation in hematopoietic tissue. Further, human osteoblasts secrete adiponectin and express adiponectin receptors raising the possibility that adiponectin may regulate both adipocyte and bone cell metabolism. In the current study, we examined the relationship between fasting serum adiponectin levels and peripheral quantitative computed tomography (pQCT) measures of bone mass and structure at the tibia and radius in 401 Afro-Caribbeans aged 18 and older (mean, 43 years; 61% women) from 7 large, multigenerational

S156 families with a mean family size >50 individuals (range, 21 to 112). All analyses were adjusted for age, gender and body mass index. Residual heritability of adiponectin was 0.430.11 (P<0.01). Higher adiponectin levels were associated with lower trabecular volumetric BMD at the distal tibia (r = -0.12) and radius (r = -0.25; P<0.01 for both). Higher adiponectin levels were also associated with lower cortical thickness at the proximal radius (r = -0.16) and tibia (r = -0.12; P<0.05 for both), due to greater endocortical circumference at these anatomic sites (r = 0.11–0.12; P<0.05). The phenotypic correlation between adiponectin and bone related traits was then partitioned into genetic and environmental components using bivariate variance-components methods. Significant (p<0.05) negative genetic correlations (rG) were found between serum adiponectin levels and total (-0.49 0.15) and trabecular (-0.39 0.16) BMD at the distal radius. Our results confirm that genes are an important contributor to the normal variation in serum adiponectin levels. Between 15% and 24% of the shared variation between circulating adiponectin and volumetric BMD at the radius may be due to a common set of genes. Adiponectin may be an important element in the regulation of bone metabolism.

P137SU. EFFECT OF VIGOROUS PHYSICAL ACTIVITY ON RISK OF WRIST FRACTURE OVER A 25 YEAR PERIOD IN PERI- AND POSTMENOPAUSAL WOMEN Thorpe DL, Knutsen SF, Beeson WL, Fraser GE; Loma Linda University, Loma Linda, CA, USA Aims: Studies have suggested that a high level of recent physical activity increases the risk of a wrist fracture in postmenopausal women. The relationship of more distant past physical activity to wrist fracture is less clear, and most studies have relied on recall of physical activity much earlier in life. The aim of this study was to assess the risk of wrist fracture in a subset of women who had completed a recent questionnaire and who also had participated in an 8-year cohort study 25 years earlier. Methods: A total of 1865 women who completed the 2002 Adventist Health Study lifestyle questionnaire had also participated in an earlier lifestyle survey in 1976 and were peri- or postmenopausal at that time. Data on risk factors including physical activity were collected from the 1976 survey. Wrist fractures occurring since 1976 and the approximate time of fracture were captured in the 2002 questionnaire. Cox regression with estimated age at time of fracture as the time variable was used to assess the eﬀect of physical activity on the risk of wrist fracture. Results: Period incidence of wrist fracture was 3.7/1000 person years of follow up. There was an inverse dose response relationship between level of physical activity and wrist fracture with a 37% reduction of risk for the highest level of physical activity compared to the lowest level (HR 0.63, 95% CI 0.45, 0.89). The eﬀect of physical activity strengthened somewhat in the final multivariable model (HR 0.59, 95% CI 0.41, 0.84), which was adjusted for hormone use, any fracture since age 35, time since menopause, parity, presence of seven comorbidities, smoking, alcohol consumption, BMI and education. A sensitivity analysis which excluded subjects with any comorbidity reported in 1976, did not substantially alter the results. Conclusions: In this cohort of women with relatively low incidence of wrist fracture, higher levels of physical activity at baseline was protective against risk of fracture over a 25-year period.

P138MO. THE ROLE OF ETHNICITY AND CHRONIC DISEASE AS RISK FACTORS FOR FRACTURE IN CANADIAN ABORIGINALS AND NON-ABORIGINALS Leslie WD1, Derksen S2, Prior HJ2, Metge CM2, Lix L2, O’Neil J3; 1 University of Manitoba, 2Manitoba Centre for Health Policy, 3 Centre for Aboriginal Health Research, Winnipeg, Canada Aim: Eﬀorts to develop global methods for absolute fracture risk prediction are currently limited by uncertainty over the validity of these models in non-White populations. Aboriginal Canadians have recently been reported to be at high fracture risk. This

analysis examined the interaction of ethnicity with diabetes mellitus, disease comorbidity, and substance abuse as possible explanatory variables. Methods: A retrospective, population-based matched cohort study of fracture rates was performed using Manitoba administrative health data (1984–2003). The study cohort consisted of 27,952 registered Aboriginal adults (aged 20 years or older) and 83,856 controls (matched three to one for year of birth and gender). Diabetes mellitus, number of ambulatory disease groups (ADGs), substance abuse and incident fractures were based upon validated definitions. Poisson regression analyses of fracture rates modelled the candidate variables both as main and two-way interaction eﬀects. Results: Fracture rates were significantly higher in the Aboriginal cohort (all p<0.0001). Diabetes, greater number of ADGs, and substance abuse were all more common in the Aboriginal cohort (all p<0.0001). These factors were associated with increased fracture rates in both populations (p<0.0001) and significantly higher population attributable risk percent in the Aboriginal cohort (p<0.0001). Rate ratios for osteoporotic fracture were similar for Aboriginals and controls (see Figure). No significant interaction between the risk factors and ethnicity were seen in Poisson regression models (p-for-interaction >0.1). Conclusions: Greater prevalence of diabetes, comorbidity and substance abuse among Aboriginals contributes to the higher rates of fracture. The relative risk of fracture for these factors is similar for both populations despite large diﬀerences in absolute fracture risk and risk factor prevalence.

Relative osteoporotic fracture rates (Aboriginals vs Controls)

P139SA. THE EFFECT OF SOCIOECONOMIC STATUS ON BONE DENSITY TESTING IN A PUBLIC HEALTH CARE SYSTEM Leslie WD1, Demeter S1, Reed M1, Lix L2, MacWilliam L2, Finlayson G2; 1University of Manitoba, 2Manitoba Centre for Health Policy, Winnipeg, Canada Aim: An inverse relationship between socio-economic status (SES) and osteoporotic fractures has been demonstrated. In publicly funded health care systems there should be no barriers to accessing bone mineral density (BMD) testing, especially for those at increased fracture risk. We hypothesized that SES would be negatively correlated to BMD utilization rates resulting in disparities that disadvantaged lower SES women. Methods: A population-based BMD database from the Manitoba Bone Density Program was utilized to assess the association between indicators of SES and BMD utilization rates in 2001–2002 for older women (108,274 urban resident women aged 50 and older). SES was defined by income quintile and by the socioeconomic factor index (SEFI). Analyses were stratified by age (50–64 year old and 65 years or older) and a morbidity index (low, medium and high). Results: Crude BMD utilization rates by age and income strata showed increased utilization by higher SES groups (ANOVA

S157 p-for-trend <.00001). Regression models demonstrated significantly higher BMD utilization rates among high SES women in all age and morbidity strata, whether SES was defined by income quintile or SEFI. Statistical significance was demonstrated in 5 of 6 strata. Eﬀect sizes varied from a rate ratio of 1.33 (95% CI 1.01–1.75) for low morbidity women age 50–64 years old) to 2.6 (95% CI 1.87–3.6) for high morbidity women age 65 or older. Conclusions: In the context of a publicly funded health care system significant associations are demonstrated between SES and BMD utilization rates. Further research is needed to better understand the nature of these associations and how they may contribute to health outcomes.

Bone density testing rate by income quintile (95% CI bars)

P140SU. HOW CAN WE IDENTIFY AND PLAN INTERVENTION AGAINST HIP FRACTURES IN THE POPULATION? Johnell O1, Lundgren H2, Noreen D2, Weibull H2, Lithman T2; 1 Dept of Orthopaedics, UMAS, Malmo Sweden, 2Region Scania, Lund, Sweden The true risk factors for hip fractures are hard to establish since most cohort studies have only included mentally healthy individuals. We identified all hip fractures 45 years of age occurring January to September 2005 in the Scania (southern) Region of Sweden (n=1.572). All hospital and primary care visits both outpatients and inpatients were analysed one year before the hip fracture. Within the year before the hip fracture, 10.5% (65 years) had visited the health care system with a diagnosis of dementia compared to 1.2% in the general population standardized to the age and sex distribution of the hip fractures. 10.9% of patients had other psychiatric diagnoses compared to 1.5%. Anaemia had 3.1% compared to 0.6%, dizziness and fainting 7.3% to 1.4%, diabetes 9.1% to 2.4%, hypertension 18.2% to 6.1%, other injuries 26% to 3.2%, stroke 13.3% to 1.8% in the general population. To find out the risk of hip fracture we then identified in 2004/2005 all with these diﬀerent diagnoses and identified those who had a hip fracture prospectively January to September 2005 in the time span of one year. 3% of those with dementia had a hip fracture within 1 year and the RR (Relative Risk) for men and women compared to the general population was 13.1 (1.8–94.0) at the age of 45–64 and 2.1 (1.7–2.7) at the age of 85. For those with other psychiatric diagnoses the corresponding figures were RR 4.5 (2.8–7.3) and 1.7 (1.3–2.3), anaemia 8.1 (2.0–32.9) and 0.9 (NS), dizziness and fainting 1.6 and 1.5, diabetes 2.5 and 0.8 (NS), hypertension 2.5 and 1.1 (NS), other injuries 6.5 and 2.3, stroke 17.2 and 1.5 and for alcohol abuse 11.2 and 2.6 (75–84 years). Thus individuals with dementia, other psychiatric diagnosis (including depression) and alcohol have a high increased risk of having a hip fracture within the next year, high enough to warrant an intervention. For many diagnoses, such as hypertension, diabetes, etc., a similar pattern was also observed for having a

myocardial infarction, stroke, etc. Therefore, also strategies can be implemented for several diseases. The main exception was dementia.

P141MO. OVULATORY FUNCTION AND BONE MINERAL DENSITY IN THE EARLY MENOPAUSAL TRANSITION Sowers MF, Grewal J; University of Michigan, Ann Arbor, Michigan, USA Aims: The aim was to determine if luteal abnormalities or urinary measures of sex steroid hormones collected across a menstrual cycle during the menopausal transition were associated with total hip or lumbar spine bone mineral density (BMD). Methods: We studied BMD in 643 pre- and perimenopausal women, aged 43–53 years, in the Daily Hormone Study, a substudy of the Study of Women’s Health Across the Nation (SWAN), a longitudinal, community-based study of the menopause transition. BMD was measured at the lumbar spine and total hip using dual-energy x-ray densitometry. Daily first-voided urine samples from one complete menstrual cycle (up to a maximum of 50 days) were assayed for estrone conjugates (uE1C), pregnanediol glucuronide (uPdG), luteinizing hormone (uLH), and follicle-stimulating hormone (uFSH). Three menstrual cycle attributes evaluated were: (1) absence or presence of ovulation; (2) ratio of the luteal phase to menstrual cycle length; and (3) ovulatory disturbances, defined as anovulatory cycles or cycles with short luteal phases (<10 days). Results: Lower uE1C concentrations (area under the curve) and higher uFSH concentrations (area under the curve) were significantly associated with lower BMD at lumbar spine and total hip bone sites. Measures based on menstrual cycle characteristics including absence or presence of ovulation; ratio of the luteal phase to menstrual cycle length; and ovulatory disturbances, defined as anovulatory cycles or cycles with short luteal phases (<10 days) were not significantly associated with BMD at the total hip or lumbar spine, following adjustment for age, BMI, urinary hormone concentrations, menstrual cycle length, menopausal status, and race/ethnicity. Conclusions: We concluded that direct measures of variation in endogenous hormones as approximated in the assay of daily urine samples collected throughout a menstrual cycle rather than menstrual cycle characteristics were associated with BMD levels in women during the early menopause transition.

P142SA. HIGH PREVALENCE OF INADEQUATE SERUM VITAMIN D LEVELS IN OSTEOPOROTIC EUROPEAN POSTMENOPAUSAL WOMEN Bruyere O, Malaise O, Neuprez A, Reginster J-Y; WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders and Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium Aims: Inadequate vitamin D level is associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. There are no clear international agreements on what constitute a level of vitamin D inadequacy. Recent publications suggest that the circulating level of vitamin D should be over 80 nmol/L or at least between 50 nmol/L and 80 nmol/L. The objective of this study is to assess the prevalence of inadequate serum vitamin D levels in postmenopausal European women. Methods: Assessment of 25-Hydroxyvitamin D [25(OH)D] was performed with a commercial radioimmunoassay (DiaSorin) in 8532 osteoporotic European postmenopausal women. European countries included France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-oﬀs of 25(OH)D inadequacy were fixed : <80nmol/L and <50 nmol/L. Results: Mean (SD) age of the patients was 74.2 (7.1) years, body mass index was 25.7 (4.1) kg/m_. Level of 25(OH)D was 61.0 (27.2) nmol/L. There was a highly significant diﬀerence of vitamin D level across European countries (p<0.0001). The lowest level of vitamin D was found in France [51.5 (26.1 nmol/L)] and the highest in Spain [85.2 (33.3) nmol/L]. In the whole study population, the prevalence of 25(OH)D inadequacy was 79.6% and 32.1% when considering cut-oﬀs of 80 and 50 nmol/L, respectively.

S158 The prevalence of low 25(OH)D (<80 nmol/L) reaches 90.4% in France and 45.8% in Spain. Conclusion: This study confirms the high prevalence of vitamin D inadequacy in osteoporotic European postmenopausal women. The prevalence could be even higher in some particular countries. We believe that a greater awareness of the importance of vitamin D inadequacy is needed to address this public health problem.

P143SU. BONE MINERAL DENSITY IN CANADIAN ADULTS: UPDATED DISTRIBUTION AND DEMOGRAPHIC AND GEOGRAPHIC VARIATION FROM THE CAMOS STUDY Langsetmo L1, Gao Y1, Hanley D2, Prior J3, Goltzman D4, Kreiger N5, Tenenhouse A4; 1CaMos National Coordinating Centre, McGill University, Montreal, Quebec, Canada, 2University of Calgary, Calgary, Alberta, Canada, 3Department of Medicine/Endocrinology, University of British Columbia, Vancouver, British Columbia, Canada, 4Department of Medicine, McGill University, Montreal, Quebec, Canada, 5Cancer Care Ontario, Toronto, Ontario, Canada Aims: To determine the age and sex specific cross-sectional distribution of bone mineral density of the lumbar spine, total hip, trochanter, Ward’s triangle, and femoral neck and to assess heterogeneity of age-adjusted bone mineral density within Canada by geographic location, ethnic/racial group, birth country, and education. Methods: The study sample consists of members of a population-based cross-sectional study of community-dwelling Canadian men and women with available bone density measurements (2590 men, 5740 women). Subjects were recruited by random selection from telephone listings within regions surrounding nine cities across Canada. Sample weights were used to generate population estimates. The Bayesian information criterion was used to identify demographic variables that are important for BMD. Results: Among all age groups and skeletal sites men had a higher median bone mineral density than women and the diﬀerences between men and women were largest in the oldest age category. The diﬀerence in medians between the youngest (25–29) and oldest (80+) age groups varied according to sex and skeletal site with relative diﬀerences for men (respectively women) as follows: lumbar spine 4% (17%), femoral neck 24% (33%), trochanter 10% (24%), total hip 17% (27%), Ward’s triangle 44% (52%). The distribution of BMD of the lumbar spine is substantially wider in the older age groups for both men and women. The age-adjusted mean BMD for men and women and at all skeletal sites was highest in Toronto and Kingston. For women, it was lowest in Quebec (lumbar spine) and in St John’s and Halifax (femoral neck). For men, it was lowest in Quebec and Calgary (lumbar spine) and in Quebec (femoral neck). The subgroups with age-adjusted BMD higher than the rest of the population were women of black, Ukranian, North American Indian, German and Dutch origins and men of black, Ukranian and North American Indian origins. The subgroups with ageadjusted BMD lower than the rest of the population were women of Chinese and South Asian origins and men of Chinese and Jewish origins. There were no systematic diﬀerences by education. Conclusions: Age, sex, ethnicity, and geographic location are important correlates of bone mineral density among Canadian adults.

P144MO. RELATIONSHIP BETWEEN PAP SMEARS, ESTRADIOL LEVELS, BODY WEIGHT AND BONE MINERAL DENSITY IN PERI- AND YOUNG POSTMENOPAUSAL WOMEN Repše-Fokter A1, Fokter SK2, Komadina R3; 1Dept. of Pathmorphology and Cytology, 2Dept. of Orthopaedic Surgery and Sports Trauma, 3Dept. of Traumatology, Celje General Hospital, Celje, Slovenia Aims: Women with low bone mineral density have a high risk for future fractures. However, BMD measurements are not widely available for screening. So it is important to determine other

factors that identify at risk patients who should have a DXA scan. The present study attempted to evaluate a possible relationship between morphologic characteristics in Pap smears, serum estradiol concentrations, anthropometric characteristics and bone mineral density. Methods: DXA measurement was performed in 136 women in whom Pap smears for routine cervical cancer screening were obtained. Also, serum concentrations of estradiol were determinated. The smears were grouped into atrophic and mature cell patterns. Using astereological analysis, the mean areas of squamous cells, their nuclei and cytoplasm were estimated. Results: There was a significant positive correlation between the cell area and t-score (p<0.001) as well as between the cytoplasm area and t-score (p<0.001). There was no significant relationship between the nucleus area and t-score (p>0.40). The mean t-scores of patients with atrophic cells were significantly lower than the mean t-scores of patients with mature cell patterns (p<0.001). The study group that included patients with atrophic or mature cells had a sensitivity of 61.4% and specificity of 86.4%, with positive predictive value of 95.9% in detecting patients with osteopenia or osteoporosis. There was a correlation between estradiol levels and t-scores at lumbar spine (p<0.05), but there was no correlation between estradiol levels and t-scores at femoral neck, with exception of Ward’s triangle. In a multiple linear regression model atrophic smear pattern was the most significant predictor of t-scores of total hip, followed by weight and age, and cytoplasm area was the most significant predictor of t- scores of total spine. Conclusions: These results suggest that a significant number of women with atrophic cells identified during routine Pap test for cervical cancer screening are at greater risk to have either osteopenia or osteoporosis as well and these women should be reﬀered to bone densitometry with DXA.

P145SA. RISK FACTORS FOR FRACTURE IN NON-OSTEOPOROTIC MEN AND WOMEN Nguyen TV, Nguyen ND, Center JR, Eisman JA; Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia Aim: More than 50% of all fractures occurred in women and men without osteoporosis (T-scores>-2.5). The aim of this study was to examine the contribution of non-BMD risk factors on fracture risk in non-osteoporotic men and women. Methods: Among women aged 60+ years who participated in the Dubbo Osteoporosis Epidemiology Study, 1647 (924 women) were classified as non-osteoporosis (femoral neck BMD T-scores>2.5). Apart from femoral neck BMD, postural stability, quadriceps strength, fall history and prior fracture were assessed at baseline in 1989. The incidence of fracture was ascertained during the follow-up period (1989–2004). Results: During the follow-up period, 221 women and 105 men had sustained any fracture. The incidence of fracture (per 1000 person-years) was 23.6 for women and 14.4 for men. In the multivariate Cox’s proportional hazards model with backward elimination, in both men and women the following risk factors were significantly associated with fracture risk: age (+5y) (HR: 1.2, 95% CI: 1.1–1.3) in women and (HR: 1.4, 95% CI: 1.1–1.6) in men; postural sway (HR: 1.1; 95% CI: 1.0–1.2) in women and (HR: 1.2; 95% CI: 1.1–1.3) in men; baseline femoral neck BMD (HR: 1.6, 95% CI: 1.3–1.9) and (HR: 1.2; 95% CI: 1.0–1.5) in men; and fall during the last 12 months (HR: 2.1; 95% CI: 1.6–2.8) in women and (HR: 1.9; 95% CI: 1.2–3.0) in men. Analysis of individual fracture sites in both sexes indicated that the eﬀect of age and baseline BMD on fracture risk were more pronounced at the hip, vertebral and wrist/forearm fractures. In women, the population attributable risk fraction (PARF) of combination of the presence of three risk factors (age, BMD and fall) were 13%, 32% and 20% for any fracture, hip fracture and vertebral fracture, respectively. In men, the PARF was lower: any fracture: 11%, hip fracture: 30%, and vertebral fracture: 14%. Conclusion: These data indicate that in non-osteoporotic elderly, the combination of low BMD, advancing age and a fall history or prior fracture could identify a subgroup of individuals with high risk of fracture.

S159

P146SU. LACTATION-RELATED BONE CHANGES IN UNDERNOURISHED INDIAN WOMEN MAY BE RELATED TO THE NUTRITIONAL STATUS OF THE MOTHER Kulkarni B, Shatrugna V, Balakrishna N; National Institute of Nutrition, Hyderabad, India Aims: Western studies in well nourished women have indicated that transient maternal bone loss occurs during 3–6 months of lactation to meet the increased demand of calcium. This study investigated bone mineral density (BMD) changes during lactation in undernourished women consuming low calcium diets. Methods: Forty postpartum women were recruited for the study. Their baseline BMD measurements were carried out by dual-energy x-ray absorptiometry at lumbar spine (LS), hip, forearm and whole body (WB) within one month after delivery. These measurements were repeated at 6 months, 1 year and 1.5 years. Dietary intakes were measured by 24 hrs recall. Results: All women were breastfeeding at 1.5 years. Their meanSD age, weight and body mass index (BMI) were 23.43.75 years, 46.35.39 kg, 20.42.65, respectively, at baseline. Dietary intakes of all the nutrients were below Recommended Daily Allowance and calcium intake was 449223.7 mg/day. BMDs at all skeletal sites were much lower than in Western women. BMD at forearm and WB-BMD did not change during the study period. Loss of BMD at femoral neck (FN) was 4.75.06% at 6 months postpartum with partial recovery at 1.5 years. Mean LS-BMD did not change at 6 months after which it increased by 6.76.16% at 1.5 years. When women were divided into two groups (see figure), those who lost LS-BMD at 6 months (n=24) had significantly lower BMI as compared to women who did not have any bone loss (n=16) (19.61.94 vs 21.32.64) (P<0.05). Resumption of menstruation was delayed in the group with bone loss. Conclusions: The pattern of postpartum BMD changes was diﬀerent when compared to Western studies. LS-BMD changes exhibited opposing eﬀects of lactation related bone loss and accrual of bone mass to attain peak bone mass. Nutritional status appears to be an important determinant of lactation related bone changes.

Aims of this study are determination of normative values of vitamin D and prevalence of vitamin D deficiency in Iranian population. Methods: We chose 5 cities with diﬀerent climates; individuals were selected with random cluster sampling. Blood samples were drawn at their home and serum was extracted in place and sent to EMRC laboratory for evaluation for Vit D and PTH. Healthy people aged 20–69 without any medical diseases, immobility, recent Vit D use were entered into the study. We stratified subjects based on their Vit D levels in 7 groups and compared mean PTH levels of adjacent groups. Groups with nonsignificant diﬀerences in their mean PTH levels are aggregated and regarded homogenous and boundaries between homogenous groups were regarded cutoﬀ levels between normal vit D and mild, moderate and severe vit D deficiency. Then we evaluated prevalence of vit D deficiency in five cities of Iran. Results: We evaluated 5329 blood samples for Vit D and PTH and found three steps of PTH elevation with decreasing vitamin D levels for women (40, 25 and 12 nmol/L) and two (35 and 25 nmol/L) for men. These concentrations were regarded as cutoﬀ levels for stages of Vit D deficiency. Based on these cutoﬀs, we assessed prevalence of Vit D deficiency in the population of study cities. Prevalence of all stages of Vit D deficiency was unexpectedly high in all cities. Vit D deficiency state was seen in 75.1% of women and 72.1% of men.

Mean PTH levels in diﬀerent Vitamin D levels among Iranian women Conclusion: Our results were in concert with other studies for determination of normal and stages of low Vit D level. High prevalence of Vit D deficiency in Iran is similar to results of other studies in Middle East area and indicates careful search for determination of cause and need for regular fortification program.

P148SA. THE IMPORTANCE OF SPECTRUM BIAS ON BONE DENSITY MONITORING IN CLINICAL PRACTICE Leslie WD; University of Manitoba, Winnipeg, Canada

P147MO. NORMATIVE VALUES OF VITAMIN D AND PREVALENCE OF VITAMIN D DEFICIENCY AMONG IRANIAN POPULATION Moradzadeh K1, Larijani B1, Keshtkar AA1, Hossein-Nezhad A1, Rajabian R2, Nabipour I3, Omrani GH4, Bahrami A5, Gooya MM6, Delavari AR6; 1Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran, 2 Mashhad University of Medical Sciences, Mashhad, Iran, 3Bushehr University of Medical Sciences, Bushehr, Iran, 4Shiraz University of Medical Sciences, Shiraz, Iran, 5Tabriz University of Medical Sciences, Tabriz, Iran, 6Disease Control Department, Ministry of Health, Tehran, Iran

Aim: Spectrum bias can occur if a diagnostic test is applied to a patient population of diﬀerent disease severity than was used in the original test validation. There is uncertainty over whether test precision and follow up assessment should be based upon absolute bone density measurements (in g/cm2) or relative change (in percent). The current study was undertaken to compare absolute and relative precision and change in bone mineral density (BMD) categorization for lower and higher BMD ranges. Methods: Patients with baseline and follow-up BMD measurements (1,317 spine pairs and 1,259 hip scan pairs) were identified in the population-based Manitoba Bone Density Program database (1994–2002). Relative (percent) and absolute (g/cm2) least significant change (LSC) limits were from a convenience sample from the same population (198 spine scan pairs and 193 hip scan

S160 pairs). The main outcome measure was the fraction with BMD change exceeding LSC limits. Results: BMD range strongly aﬀected spine change category using a pooled relative LSC (lower 33.5% vs. higher 20.0%, P<0.0001) but a range-concordant LSC eliminated this diﬀerence (lower 28.3% vs. higher 27.1%, P>0.2). Spine categorization according to absolute LSC showed no significant diﬀerence between lower and higher BMD range patients (27.8% vs. 23.4%, P=0.13). Similar results were seen for the total hip. Disagreement in categorizing spine change occurred in 13.6% (95% CI 11.7–15.4%) using relative LSC but only 1.7% (95% CI 1.0–2.4, P<0.00001) using absolute LSC. Similar disagreement was seen for the hip (relative LSC 14.0% [95% CI 12.1–15.9%] vs. absolute LSC 3.1% [95% CI 2.1–4.1%]; P<0.00001). Conclusions: We observed spectrum bias when BMD monitoring was based upon relative change (in percent) rather than absolute measurements (g/cm2). Categorization of change based upon absolute change in BMD is strongly preferred in the routine clinical setting.

Percent likelihood of spine bone density change exceeding LSC

P149SU. MENARCHE OLDER THAN 12 IS ASSOCIATED WITH OSTEOPOROTIC FRACTURES AND LOW BONE MASS IN A COHORT OF POSTMENOPAUSAL WOMEN Nogues X, Peña MJ, Checa MA, Aymar I, Mellibovsky L, Garrido A, Blanch J, Benito P, Monllau JC, Caceres E, Carreras R, Diez-Perez A; URFOA-IMIM Hospital del Mar Barcelona, Autonomous University of Barcelona, Barcelona, Spain Aim: Estrogens are related with postmenopausal osteoporosis. Years since menopause and fertile years are strong predictors of low bone mass. However, studies on age at menarche by itself are controversial. We studied this variable in a cohort of Spanish postmenopausal women. Patients and methods: 1727 consecutive unselected Spanish postmenopausal women, aged 53.57.6 years (meanSD) from a Menopausal Unit. Medical record, including gynecological data, history of fractures and risk factors for osteoporosis, was collected. Bone mineral density (BMD) was measured in lumbar spine (L-BMD) and femoral neck (Fn-BMD) using dual-energy x-ray absorptiometry (Hologic QDR 4500 SL). Women with surgical menopause and secondary osteoporosis were excluded. Data were analyzed using SPSS 12.01 and t-test, ANCOVA and multiple regression analysis were performed. Results: Age of menopause was 48.64.3 and menarche 12.81.6. 55.1% of women had menarche > 12. L-BMD in women with menarche < 12 was 0.9020.14 g/cm2 and in women with menarche at 13 or older 0.8670.14 (p<0.0001, weight-adjusted). Fn-BMD was also significantly diﬀerent 0.7240.11 vs. 0.6940.11, respectively (p<0.000, weight-adjusted). Prevalent osteoporotic fracture was present in 11% of women with menarche < 12 vs. 15.6% in those > 12 (RR 1.43; CI 95% 1.02–2.01;p=0.03). Age of menarche in women without fractures was 12.81.6 and in women with fractures was 13.41.8; p=0.001. By multiple regression analysis age of menarche and body weight remained significantly associated with L-BMD and Fn-BMD. Conclusion: Age of menarche is a strong predictor of low bone mass and fractures in a cohort of Spanish postmenopausal women.

Preventive measures before menopause could be recommended in women with menarche older than 12 in the Spanish population.

P150MO. FACTORS ASSOCIATED WITH MORTALITY FOLLOWING HIP FRACTURE Oka H1, Muraki S2, Yoshimura N1, Yamamoto S3, Kawaguchi H2, Nakamura K2; 1Department of Joint Disease Research, Graduate School of Medicine, The University of Tokyo, 2Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 3Department of Orthopaedic Surgery, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan Aim: Various factors were reported to increase risk of death following hip fracture. However, our review of the literature indicates that previous studies were mostly performed based on rough classification of comorbidities. In this study, comorbidities were classified in detail and the risk of death following hip fracture was investigated. Methods: Four hundred and eighty patients with hip fracture were enrolled. Patients’ comorbidities and walking ability before injury were investigated by oneself or their family’s or medical reports, and residences where subjects were taken after discharge were recorded. Subsequently, patients or their family were interviewed about whether they were alive or dead on January 1, 2002 by mail or telephone. A survival curve was drawn based on the Kaplan-Meier method. Cox proportional hazards regression models were used to determine risk factors for death. An expected mortality rate was obtained from a life table published by Ministry of Health, Labor, and Welfare for the Japanese population from 1991 to 2002, and compared to observed mortality. Results: One-year survival rate following hip fracture were 88.5%, which was a little lower than the expected survival rate. In subsequent years, the survival rate was lower than expected survival rate. Being male, trochanteric fractures were risk factors for death. Patients who walk with a walker or support or were nonambulatory before injury had increased risk for death. Among comorbidities, dementia, diabetes mellitus and a history of gastrectomy or colonectomy were risk factors for death. Among complications, pneumonia during hospitalization was a risk factor for death. Conclusions: Being male, trochanteric fracture, decreased walking ability before injury, dementia, chronic heart failure, pneumonia during treatment for hip fracture, a history of gastrectomy or colonectomy, DM were found to be significant risk factors for death. Patients with pneumonia, in particular, had a high risk of death.

Observed and expected survival curves for 480 patients with hip fracture. Observed survival curves were drawn using KaplanMeier method. Expected survival curves were drawn based on a life table developed by Ministry of Health, Labor, and Welfa

P151SA. POOR BONE HEALTH OF INDIAN WOMEN FROM LOW INCOME GROUP Shatrugna V, Kulkarni B, Balakrishna N; National Institute of Nutrition, Hyderabad, India

S161 Aims: Studies from India show that women from the low income group (LIG) have osteoporotic hip fractures 10–15 years earlier than women from the middle and high income group. This study investigated the bone parameters of women from low and middle income (MIG) groups. Methods: A hundred women from LIG and 86 women from MIG in the age group of 30–60 years were recruited for this study. Their height and weight were measured using standard procedures and bone parameters at lumbar spine (LS), hip and whole body were measured using DXA. Dietary intake of calcium was measured using food frequency questionnaire. Results: The mean age of the women in the two groups was similar, but LIG women were poorly nourished. They were shorter and lighter than the MIG women and their dietary intake of calcium was also significantly lower when compared to the MIG. A higher proportion of LIG women were postmenopausal and mean age at menopause was significantly lower in post menopausal LIG women when compared to the MIG. Bone area, bone mineral content, bone mineral density and T-scores at all skeletal sites as well as whole body were significantly lower in the LIG women when compared to the MIG women (P<0.01). The mean T-scores at femoral neck, hip as well as LS of LIG women were in the osteopenic range indicating high prevalence of osteoporosis, whereas they were close to normal, i.e., > -1 in the MIG. There was a deficit of 400 g of mineral content in the skeleton of the LIG women. Mean SD values of anthropometric and bone parameters in women in relation to incomes Parameter

MIG Women (86)

LIG Women (100)

Total (186)

Height (cm) Weight (kg) Age (yrs) BMI Neck BMC Neck BA Neck BMD Neck T-Score Hip – BMC Hip – BA Hip- BMD Hip T-Score Spine BMC Spine BA Spine BMD Spine T-Score WB-BMC WB- BA WB-BMD

155.05.49 *** 62.910.09*** 43.57.70 NS 26.23.73 *** 3.610.845 *** 4.560.813 *** 0.790.114 *** -1.041.141 *** 26.235.282 *** 29.402.948 *** 0.890.120 *** -0.731.002 *** 45.889.018 *** 49.115.424 ** 0.930.117 *** -1.091.064 *** 1914.7277.77 *** 1741.6155.61 *** 1.100.098 ***

149.25.97 49.110.10 41.47.68 22.03.81 2.870.671 3.970.763 0.720.105 -1.701.037 21.634.328 27.632.912 0.780.119 -1.620.990 37.7910.209 47.044.591 0.800.147 -2.171.402 1568.4276.43 1559.7169.33 1.000.094

151.96.44 55.512.21 42.47.74 23.94.31 3.220.840 4.240.838 0.760.114 -1.391.133 23.785.309 28.463.052 0.830.130 -1.211.089 41.5510.460 48.005.088 0.860.147 -1.671.364 1709.8324.58 1833.9186.35 1.040.106

*** - P< 0.001 ; ** - P < 0.01 ; NS – not significant ; ( ) - Number MIG - Middle Income Group , LIG - Low Income Group BMI - Body Mass Index ; BMC - Bone Mineral Content in gms BA - Bone Area in cm2 ; BMD - Bone Mineral Density gm/ cm2 , WB - Whole Body

Conclusions: This study highlights poor bone health of Indian women from LIG which may explain early onset of fractures in this group. Poor calcium intake, low body weights and early menopause may be the factors responsible for poor bone health of LIG women.

P152SU. INTERVENTIONS DECREASING OBESITY RISK TEND TO BE BENEFICIAL FOR DECREASING RISK TO OSTEOPOROSIS: A CHALLENGE TO THE CURRENT DOGMA Zhao LJ1, Liu YJ1, Hamilton J2, Recker RR1, Deng HW2,3,4; 1 Osteoporosis Research Center, Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE, USA, 2 Departments of Orthopedic Surgery and Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA, 3Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, P. R. China, 4The Key Laboratory of Biomedical

Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, P.R.China Aims: It is a widely held dogma that interventions lowering risk for obesity may generally result in higher risk for osteoporosis, as increasing body weight is related to higher bone mass and thus lower risk for osteoporosis. However, previous analyses generally confounded total body weight, of which the majority is muscle, with fat mass measurement for obesity, or did not duly control for increased mechanic loading due to larger total body weight in increasing bone mass. In the present study, we attempt to address what is the correlation between obesity per se and osteoporosis, particularly, when the mechanical loading eﬀects due to total body weight is controlled, in large samples of Chinese and Caucasians. Methods: We measured whole body fat mass, lean mass, BMI (body mass index), and bone mass in two samples: 1,988 unrelated Chinese subjects and 4,489 subjects from 512 Caucasian pedigrees. We first evaluated the Pearson correlation, then dissected the phenotypic correlations into genetic and environmental components, with bone mass unadjusted or adjusted for body weight (to control for its mechanical loading eﬀects on bone mass). Results: In both Chinese and Caucasians, fat mass and BMI were, phenotypically, positively correlated with weight-unadjusted bone mass, in agreement with the dogma. However, when bone mass was adjusted for body weight, the phenotypic correlation (including its genetic and environmental components) between fat mass and bone mass turned out to be negative. Our results indicate that, when the mechanical loading eﬀect of body weight on bone mass is adjusted for, increased fat mass is actually associated with decreased bone mass. Conclusions: In contrast to the dogma, for the first time, we show that both genetic and environmental factors that tend to decrease risk for obesity may also decrease risk for osteoporosis. Hence, interventions, based on genetic molecular pathways or nongenetic factors, decreasing obesity risk tend to be beneficial for decreasing risk to osteoporosis.

P153MO. SOY INTAKE IS ASSOCIATED WITH LESS DECLINE IN TOTAL HIP BONE MINERAL DENSITY IN OLDER CHINESE MEN Kwok T, Woo J, Leung PC; Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong, China Aim: Higher soy intakes have been associated with decreased bone loss and less fractures in Chinese postmenopausal women. This study examines the potential association between soy food intake and the rate of bone loss in older Chinese men. Methods: 2,000 men aged between 65 – 92 years were recruited into a cohort study of osteoporosis – Mr Os (Hong Kong) in 2001. They had bone mineral density (BMD) of total hip and lumbar spine measured by dual-energy X-ray absorptiometry (Hologic QDR-4500W). A locally validated food frequency questionnaire was administered to estimate the usual dietary pattern. Nutrient analysis was performed by locally developed computer software. Demographic characteristics, medical and medication history and smoking history were recorded. Amount of physical activities was estimated by a validated questionnaire. Body weight was measured. 1744 subjects (87%) returned for follow-up after 2 years. They all had BMD repeated. Results: At baseline, soy intake was negatively associated with total hip BMD after adjustment for dietary intake of no-soy protein and calcium, and risk factors of osteoporosis which included age, weight, previous fracture, current smoking, physical activities, history of diabetes mellitus, chronic obstructive airway disease, gastrectomy and thyroid disease, use of thiazide, steroids and calcium supplement (mean diﬀerence per SD -0.7%, 95% CI -1.2 to -0.1). But soy food intake was positively associated with the change in total hip BMD over two years, after adjustment for confounders including weight change (mean diﬀerence per SD 0.13%, 95% CI 0.001, 0.25). Soy intake was not associated with lumbar spine BMD either at baseline or in the change of BMD over two

S162 years. Conclusions: Higher soy intake may have a mild protective eﬀect on the decline in hip bone mineral density in older Chinese men.

P154SA. A COMPARISON OF BONE MINERAL MEASUREMENTS FOR FRACTURE PREDICTION: A META-ANALYSIS Johnell O1, Kanis JA2, Johansson A3, Oden A3, Delmas PD4, Eisman JA5, Fujiwara S6, Gluer C7, Kroger H8, McCloskey EV2, Mellstrom D9, Melton LJ III10, Pols HA11, Reeve J12, Silman A13, Tenenhouse A14; 1Malmo General Hospital, Malmo, Sweden, 2 University of Sheﬃeld, UK, 3Consulting Statistician, Gothenburg, Sweden, 4Hopital Edouard Herriot, Lyon, France, 5Garvan Institute of Medical Research, Sydney, Australia, 6Radiation Eﬀects Research Foundation, Hiroshima, Japan, 7Universitas Klinikum Schleswig-Hostein, Keil, Germany, 8Kuopio University Hospital, Kuopio, Finland, 9Goteborg University, Sweden, 10 Mayo Clinic, Rochester, USA, 11Erasmus Medical Centre, Rotterdam, The Netherlands, 12Strangeway’s Research Laboratory, Cambridge, UK, 13University of Manchester, UK, 14Montreal General Hospital, Canada The aim of this study was to compare the performance characteristics of bone mineral measurements for fracture prediction. We used the primary data of up to 9 population-based cohorts in which BMD or heel QUS had been measured at base-line. 30,238 men and women were followed for up to 125,600 person-years. The eﬀect of BMD on fracture risk was examined using a Poisson model for each cohort separately, and the results of the diﬀerent studies were then merged using weighted coeﬃcients. Gradients of risk for fracture prediction (RR/SD decrease in Z-score) were computed for the age of 70 years and are shown in the table below. Outcome fracture Technique/ site Hip

Vertebral clinical

DXA TH DXA FN DXA LS SoS Heel BUA Heel

1.6 (1.4–1.8) -a 1.4 (1.4–1.5) 1.7 (1.5–1.9) 1.5 (1.4–1.7) 1.6 (1.4–1.9) -a -a -a -a

a

2.5 2.8 1.7 2.4 2.6

(1.8–3.5) (2.4–3.2) (1.4–2.1) (1.6–3.6) (1.8–3.8)

only 1 cohort available,

b

Vertebral Any osteoporotic morphometricb fracture 1.4 1.5 1.4 1.6 1.4

(1.2–1.5) (1.4–1.6) (1.3–1.5) (1.3–2.0) (1.2–1.7)

computed with logistic regression

There were no significant diﬀerences in gradients of risk between men and women. BMD at the femoral neck (FN) provided the highest gradient of risk for hip fracture prediction, which was significantly higher (p<0.001) than BMD at the lumbar spine (LS). For vertebral or all osteoporotic fracture prediction, there was no diﬀerence between techniques. Quantitative ultrasound at the heel performed similarly to DXA for hip and all fracture outcomes. We conclude that there is no advantage in measuring lumbar spine over femoral neck or total hip (TH), and that heel ultrasound may perform similarly to central DXA in the assessment of fracture risk.

women and 612 men were included (age 65–88). Physical performance was measured by summing the scores on standardized chair stands, tandem stand and walk test (range 0–12). Hand grip strength was measured using a strain-gauged dynamometer. Blood samples were taken to determine serum total and free cortisol levels. Regression analyses (stratified for sex and adjusted for age, body mass index, alcohol use, physical activity, incontinence and number of chronic diseases) were conducted to examine the relationship between cortisol and physical performance. Results: In women, physical performance decreased with increasing total cortisol (=-0.23 per SD increase in total cortisol, p=0.037) or free cortisol (=-0.36 per SD increase in free cortisol, p=0.001). This relationship was for the greater part explained by the relationship between cortisol and the tandem stand test, a measure for balance (OR=0.70, p<0.001 and OR=0.65, p<0.001 per SD increase in total and free cortisol, respectively). Analysis with maximum grip strength as dependent variable revealed no significant relationship with cortisol (p=0.578) or free cortisol (p=0.412). No significant relationships were found in men. Conclusions: It was concluded that balance is negatively related to both total and free cortisol in older women.

P156MO. CHANGES IN FOOD SOURCES OF CALCIUM FROM CHILDHOOD TO EARLY ADULTHOOD IN THE UNIVERSITY OF SASKATCHEWAN PEDIATRIC BONE MINERAL ACCRUAL STUDY Vatanparast HV, Whiting SW; University of Saskatchewan, Saskatoon, Canada Aims: To determine changes in intake and food sources of calcium of males and females from childhood through adolescence to early adulthood. Methods: Six-year longitudinal (1991–96) and three-year follow up data (2002–04) from the University of Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS) were used. Subjects’ dietary intakes were compared in three age groups: periadolescents, 8–14y (130 M, 126 F); late adolescents, 15–19y (79 M, 96 F); and young adults 19–27y (67 M, 87 F). Dietary intake from serial 24-hour recalls and a food frequency questionnaire were used in PBMAS (ages 8–19 y) and follow up study (ages 19–27y), respectively. One-way ANOVA was used to investigate diﬀerences in food sources of calcium among age groups. Results: Mean calcium intake of young adults was 1140 mg/d and 824 mg/d in males and females respectively, with 46% of males and 79% of females not meeting the AI (1000 mg). Table 1 presents the percent contribution of food groups to total dietary calcium intake by gender and age group. Fluid milk was the major source of dietary calcium from childhood to early adulthood in both genders. The contribution of cheese to calcium intake increased in both genders (p<0.05). The intake of calcium from vegetables in young adult males and females was the lowest among the three age groups (p<0.05). In young adults, 51% of females and 38% of males did not meet the AI value (5 µg) for dietary vitamin D; milk was the main food source of dietary vitamin D. Table 1. Percent Contribution of food groups (SD) to total dietary calcium intake by gender and age group

P155SU. RELATIONSHIP BETWEEN SERUM CORTISOL AND PHYSICAL PERFORMANCE IN OLDER PERSONS Peeters GMEE1, van Schoor NM1, Visser M1,2, Knol DL1,3, Eekhoﬀ EMW4, Lips P4; 1EMGO, 2Department of Nutrition and Health, Faculty of Earth and Life Sciences, 3Department of Clinical Epidemiology and Biostatistics, 4Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands Aims: During aging, muscle tissue is gradually lost, resulting in reduced muscle mass, strength and consequently physical function. One of the hormones controlling muscle mass is cortisol. This study investigates the relation between cortisol and physical performance in older persons. Methods: The study was conducted within the Longitudinal Aging Study Amsterdam (LASA), a follow-up study in a representative sample of older persons in the Netherlands. In total, 640

Milk Products — Fluid milk — Cheese — Yogurt — Other Fruits Vegetables Meat & Alternatives Grain Products Other Foods (Only combined dishes) Total

Male Group 1 Group 2 Group 3 (n= 130) (n=79) (n= 67)

Female Group 1 Group 2 (n=126) (n=96)

Group 3 (n=87)

63.3 49.6(26) 10.0(17) 0.9(5) 2.8(8) 2.9(5) 3.6(5) 2.5 9.0(9) 11.7(18)

62.3 48.2(27) 11.7(18) 0.4(3) 2(7) 2.2(3.8) 3.8(6) 3.0 8.6(9) 12.0(18)

67.7 38.8(20)a 21.8(14) a,b 4.0(5) a,b 3.1(6) 6.2(12) a,b 1.3(1) a,b 2.4 4.6(6) a,b 17.7(11)

62.1 48.4(24) 9.5(16) 0.9(6) 3.3(9) 3.1(5) 3.6(6) 2.0 8.9(9) 12.7(19)

57.2 39.5(29)c 14.6(21.2) 0.7(8) 2.4(7) 2.8(4) 4.8(7) 2.1 8.5(9) 14.7(21)

68.6 41.0(20) 17.9(12)d 7.7(8) d,e 1.8(4)d 3.4(3) 1.7(1) d,e 1.8 3.9(3) d,e 20.5(14)d

93

92

100

92

90

100

Group 1: Peri-adolescents (8–14 y). Group 2: Late adolescents (15–19 y). Group 3: Young adults (19–27 y). Results of multiple comparisons between groups are presented as a: between groups

S163 1&3 in males, b: between groups 2&3 in males, c: between groups 1&2 in females, d: between groups 1&3 in females, e: between groups 2&3 in female (P < 0.05 Bonferroni comparison test). Conclusions: There were significant changes in dietary behavior of subjects from childhood to adulthood, especially in females. The substitution of fluid milk by cheese, the decrease in vegetable and fruit intake, and the low intake of vitamin D may put young adult females more at risk of osteoporosis later in life.

P157SA. OSTEOPOROSIS INCREASES COMPLICATION RATES OF PERIPHERAL FRAGILITY FRACTURES Goldhahn J1, Suhm N2, Blauth M3, Goldhahn S4, Hanson B4; 1 Schulthess Clinic, Zurich, Switzerland, 2AO Development Institute, Davos, Switzerland, 3University Hospital Innsbruck, Innsbruck, Austria, 4AO Clinical Investigation and Documentation, Davos, Switzerland Aims: Osteoporosis does not only predispose for metaphyseal fractures, it also aﬀects their treatment and challenge any implant anchorage. The diminished trabecular network (e.g. decreased trabecular number and thickness) and the thinned out cortical shell lead to an increased rate of implant ‘‘cutout’’ or ‘‘cutting through’’ in biomechanical tests. However, no study is available addressing specifically the influence of osteoporosis on complication rate and outcome after surgical treatment. We performed a systematic literature review to find out whether osteoporosis leads to increased rates of complications during fracture healing in metaphyseal fractures and to estimate their magnitude and patterns. Materials and methods: A Medline search was performed to identify studies reporting on the treatment of patients for distal radius, proximal femur and proximal humerus fractures. The studies were classified according to their evidence level. The highest ranked studies were reviewed with respect to information about osteoporosis evaluation (e.g., DXA) or surrogates of osteoporosis (high age, low energy trauma) and reported mechanical complications (implant failure, malalignment, etc.). Studies with similar treatment were pooled to form summary statistics including relative risk (RR) of complication. Results: Three studies and one Cochrane meta-analysis on the distal radius, 16 studies on the proximal humerus and 18 on the proximal femur met the necessary evidence level. For distal radius fracture the overall rate of complications associated with osteoporosis or its surrogates was 39.5% (95% CI: 36.9–42.1), for proximal extracapsular femur fractures 6.9 (95% CI: 6.4–7.5) and for proximal humerus fractures 19.3 (95% CI 14.6–24.7). The most frequent failure patterns were malunion and loss of length at the radius, cutout and fixation failure at the proximal femur and fixation failure and dislocation at the proximal humerus. The complication rates vary tremendously between diﬀerent fixation methods. Conclusions: Osteoporosis has a significant influence on the orthopaedic treatment and outcome of metaphyseal fractures. Implants adapted to the diminished bone structure should be used and the fracture treatment has to be embedded in an adequate pharmacological regime to treat the underlying osteoporosis and to avoid new fractures.

P158SU. IMPACT OF DEGENERATIVE SPINAL DISEASES ON BONE MINERAL DENSITY OF THE LUMBAR SPINE IN ELDERLY WOMEN Muraki S1, Yamamoto S2, Oka H3, Yoshimura N3, Kawaguchi H1, Orimo H4, Nakamura K1; 1Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 2Department of Orthopaedic Surgery, Tokyo Metropolitan Geriatric Medical Center, 3Department of Joint Disease Research, Graduate School of Medicine, The University of Tokyo, 4Department of Endocrinology, Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan Aim: Most of the elderly have degenerative diseases of lumbar spine which can aﬀect the accuracy of bone mineral density (BMD) of lumbar spine. The aim of this study is to determine whether BMD of lumbar spine is related to the degree of degenerative diseases.

Methds: This study included six hundred and thirty women aged 60 or above (mean age: 73.3 plus/minus 6.9 years) visiting the Osteoporosis Outpatient Clinic in Tokyo Metropolitan Geriatric Medical Center. At entry into this study, subjects had undergone anteroposterior and lateral X-ray of the lumbar spine including L1 to L5. Radiographs were read for the presence and severity of osteophyte (Nathan classification), osteoarthritis (Kellgren method), bone sclerosis, joint space narrowing and spondylolisthesis (Meyerding method) involving L1–2 through L4–5 interspaces. Within one month after taking X-ray, BMD of L2-L4 anteroposterior lumbar spine and femoral neck were measured. The relation between BMD and the score of each item was assessed by regression analysis. Results: Among 630 subjects, 619 (98.3%) had degenerative diseases of lumbar spine. BMD of femoral neck was correlated with age; however, BMD of lumbar spine was not correlated with age. The score of osteophyte, osteoarthritis, bone sclerosis, joint space narrowing and spondylolisthesis correlated positively with BMD of lumbar spine; however, they had no correlation with BMD of femoral neck. In multiple regression analysis including age, BMI and all items of degenerative diseases, only BMI, osteophyte, bone sclerosis and joint space narrowing were independently correlated with BMD of lumbar spine. According to the result of the multiple regression analysis, adjusted lumbar spine BMD of the subject with mean score of degenerative diseases was 0.122 g/cm2 less than observed BMD. Unlike observed BMD of lumbar spine, adjusted BMD of lumbar spine was correlated with age. Conclusions: This study suggests that degenerative diseases of lumbar spine are important sources of BMD overestimation at this site, thus leading to clinical errors. We conclude that BMD of lumbar spine was related to the degree of degenerative diseases.

P159MO. KYPHOSIS DOES NOT PREDICT RISK OF SPINAL FRACTURE Prince RL1,2, Devine A1,2,3, Dick IM1,2; 1School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia, 2Dept of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia, 3School of Exercise, Biomedical and Health Science, Edith Cowan University, WA, Australia Aim: Spinal fracture is associated with decreased quality of life and increased mortality, and is preventable with modern therapy. Therefore a simple method of determining spinal fracture risk is required. The aim of this study was to determine if the degree of kyphosis of the spine in elderly women was associated with the subsequent risk of clinical spine fracture. Methods: Baseline kyphosis was measured in 554 women, mean age 753, enrolled in the Calcium Intake Fracture Outcome (CAIFOS) study. A flexirule was pressed against the subject’s back with the top end placed on the seventh cervical spine in the midline. The ruler was moulded into the shape of the subject’s spine in the midline to the level of the lumbosacral joint. The flexicurve ruler was removed and the shape of the spine was then traced onto paper. The kyphosis index (KI) was calculated as the ratio of B (maximum dorsal displacement from the midline) to E (length from the lumbosacral joint to the seventh cervical spine) multiplied by 100. The larger the KI the more marked the kyphosis. The KI was stratified into tertiles, <12.8, 12.8 to 15.5 and >15.5. The coeﬃcient of variation for KI was 6.6%. Radiographically verified clinical spine fractures over five years were determined. Cox regression analysis of time to first event was used to calculate Hazards Ratios (HR) for incident fracture risk, after adjustment for calcium supplementation. Results: Twenty five spine fractures were reported. Age was a significant predictor of spine fracture risk (HR for a 1 year increase 1.20, 95% CI 1.03–1.39). The KI was not a significant predictor of spine fracture risk, (HR middle compared to lowest tertile 1.54, 95% CI 0.58–4.16), (HR highest compared to lowest tertile 1.46, 95% CI 0.54–3.92). This was not significantly modified by adjustment for age and body mass index. Conclusions: The results from this study do not support the commonly held belief that a more kyphotic spine is associated with

S164 increased risk of spinal fracture. This indicates that more sophisticated techniques, such as DXA BMD must be used to determine spinal fracture risk.

P160SA. LEISURE TIME PHYSICAL ACTIVITY AND RISK OF FRACTURES IN 9857 PERI- AND POSTMENOPAUSAL WOMEN: OSTPRE STUDY 10 YEAR FOLLOW-UP Rikkonen TP1, Sirola J1,5, Kröger H2, Tuppurainen M1,3, Jurvelin J4, Honkanen R1; 1Bone and Cartilage Research Unit, University of Kuopio, 2Department of Orthopaedics and Traumatology, Kuopio University Hospital, 3Department of Obstetrics and Gynecology, Kuopio University Hospital, 4Department of Physics, University of Kuopio, 5Mikkeli Central Hospital, Department of Surgery, Mikkeli, Finland Aims: Some studies indicate elevated risk of fractures among physically active persons. The aim of the study was to investigate a long-term association between self-reported physical activity (PA) and the risk of fractures and falls among peri- and early postmenopausal women. Methods: The association between PA and the risk of fractures and falls was examined in a population-based OSTPRE study of 9857 women (mean age 52.2 years at baseline, range 47–57) during the period of 1989–1999. The amount and type of PA and falls were registered with self-administered questionnaires in 1989, 1994 and 1999. Fractures were confirmed in hospital records. In total 2065 fractures were verified from 1690 (17.1%) women between June 1989 and June 1999. Groups were divided by 1 hour PA per week criteria into Active (42.4%), Semi-active (35.0%, status changed during study) and Inactive (22.6%) groups. Results: At baseline, 5094 (51.7%) of women reported at least one hour of regular PA per week. In 1999 number was increased to 6716 (68.1%). Constantly less than one hour of PA per week, throughout 10 year period was reported by 1867 (22.6%) women. Risk for wrist fracture was increased among Active group in Cox hazard model (Exp 1.402, p=0.002), but not for Semi-active group (Exp 1.192, p=0.123). There were no associations between distribution of any other fracture types or their relative risks between the groups. Women with constant 10 year PA reported similar number of falls and trauma mechanisms (falling, traﬃc, etc.) than their inactive counterparts. Most of the fractures were reported as a result of a slip-fall (81.6%) and occurred during spring (FebMay). Active group had greater fracture incidence in March and June (p<0.05), which are popular holiday seasons in Finland. Conclusions: Higher PA level caused a moderate rise in wrist fracture risk. Regular, at least one hour per week, PA does not seem to significantly increase other types of fractures or falls among peri-and postmenopausal women. Wrist fractures might be partly explained by higher kinetic energy during slip-fall in Active group.

P161SU. VARIATION IN THE TRANSFORMING GROWTH FACTOR BETA 1 INDUCED THRANSCRIPT 1 (TGFB1I1) GENE REGION IS ASSOCIATED WITH BODY SIZE, BONE DENSITY AND BODY COMPOSITION IN AFRO-CARIBBEAN MEN Kuipers AL2, Moﬀett SP1, Nestlerode CS1, Wheeler VW4, Patrick AL4, Bunker CH1, Cauley JA1, Ferrell RE3, Zmuda JM1; 1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA, 2Department of Biology, University of Pittsburgh, Pittsburgh, USA, 3Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA, 4The Tobago Health Studies Oﬃce, Scarborough, West Indies Transforming growth factor beta 1 induced transcript 1 (TGFB1I1) is a coactivator of nuclear receptors including the androgen receptor and PPARgamma. We previously identified a SNP (rs10596) in the 3’ untranslated region (UTR) of TGFB1I1 which is associated with multiple body composition measures. We extended this work by performing genetic association analysis of six tagging SNPs spanning a 34kb region encompassing the gene TGFB1I1 and several body size and composition related phenotypes. The population sample comprised 925 Afro-Caribbean men

aged 40 years and older from Tobago. Body composition was measured with dual-energy X-ray absorptiometry (Hologic QDR 4500). From 5’ to 3’, the minor allele frequencies were 0.24 for rs13338548 located in an intron of the flanking gene ARMC5, 0.38 for rs7188278 located 2kb 5’ upstream of TGFB1I1, 0.05 for rs10596 located in the 3’ UTR of TGFB1I1, 0.18 for rs13143 located in the 3’UTR of TGFB1I1, 0.04 for rs3116150 located in an intron of the 3’ flanking gene SLC5A2 and 0.18 for rs9927250 located in the intron of FLJ13868 even further downstream. In age-adjusted, stepwise regression, rs10596 showed statistically significant associations with body weight (R2=0.019, p=0.001), height (R2=0.013, p=0.005), whole body BMC (R2=0.025, p=0.0002) and whole body lean mass (R2=0.018, p=0.001). Also, rs3116150 showed statistically significant associations with whole body BMD (R2=0.018, p=0.001), total hip BMD (R2=0.014, p=0.005) and femoral neck BMD (R2=0.010, p=0.017). Two 3’ UTR SNPs were also associated with whole body fat mass (rs13143: R2=0.015, p=0.004; rs10596: R2=0.008, p=0.037). The SNPs in this genomic interval are all in moderate linkage disequilibrium, but rs10596 and rs3116150 are in higher LD with D’=0.96.The furthest SNPs flanking the TGFB1I1 gene region, rs13338548 and rs9927250, revealed no association for any of the whole body composition phenotypes analyzed. This study supports a role for TGFB1I1 in controlling several body size related phenotypes and body composition. Further studies in other population samples are required to confirm and extend this hypothesis and to identify the underlying causal variant(s).

P162MO. MAXIMUM PREVENTIVE EFFECT OF HIP PROTECTORS GIVEN TO A HIGH-RISK POPULATION Van Schoor NM1, Asma GB2, Smit JH3,4, Bouter LM1, Lips P2; 1 EMGO Instititute, VU University Medical Center, 2Department of Endocrinology, VU University Medical Center, 3Department of Sociology and Social Gerontology, Vrije Universiteit, 4Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands Aims: The preventive eﬀect of hip protectors may be influenced by the circumstances of hip fractures, and by criteria used to define a high-risk population eligible for hip fracture prevention. The objectives of this study are: (1) To describe the circumstances of hip fractures that preclude the use of hip protectors; and (2) To estimate how many hip fractures can not be prevented when providing hip protectors to a high-risk population. Methods: During one year, all hip fracture patients aged 70 years and over who entered the emergency room of five diﬀerent hospitals in the Netherlands were registered. Patients living in the community or in a home for the elderly before the fracture were approached for an interview. A questionnaire on the circumstances of the hip fracture was administered, and the risk for hip fractures was retrospectively assessed using both a risk profile for fractures [1] and for recurrent falling [2]. Results: Of all hip fractures (n=330), 1.5% was not the consequence of a fall, 7.6% occurred during the night, and 14.3% during activities in which a hip protector usually is not worn (dressing/ undressing, toileting, going in/out of bed). According to the risk profile for fractures, 62.7% of the female hip fracture patients and 7.6% of the male hip fracture patients aged 70 years and over was at high risk. Using the risk profile for recurrent falling, 61.0% of the total population was at high risk. When providing hip protectors to persons having a high risk, it was estimated that about 50% of the hip fractures could not be prevented because they occurred in the low risk group or under circumstances that preclude the use of hip protectors. Conclusion: Many hip fractures occur in the low-risk population or under circumstances that preclude the use of hip protectors. It was estimated that the maximum preventive eﬀect of hip protectors is about 50%. 1 CBO. Osteoporose. Tweede herziene richtlijn. Van Zuiden Communications BV, 2002. 2 Pluijm SMF et al. Identifying community-dwelling elderly at high risk for recurrent falling: results of a three year prospective study. Osteoporos Int: In press.

S165

P163SA. REGULAR EXERCISE HAS DIFFERENT EFFECTS ON THE RISK OF INTERTROCHANTERIC AND FEMORAL NECK FRACTURES Mackey DC1,2,3, Lui LY1,2, Cummings SR1,2; 1California Pacific Medical Center Research Institute, San Francisco Coordinating Center, San Francisco, CA, USA, 2University of California, San Francisco, Department of Epidemiology and Biostatistics, San Francisco, CA, USA, 3University of California, Berkeley, School of Public Health, Division of Epidemiology, Berkeley, CA, USA Aims: Exercise is associated with a decreased risk of hip fracture, but it is unknown whether it reduces risk of both intertrochanteric and femoral neck fractures. Methods: We asked 9,704 women aged 65 years and older in the Study of Osteoporotic Fractures (SOF) whether they walked for exercise and assessed their average weekly exercise with the Paﬀenbarger questionnaire. Self-reported hip fractures were validated and classified as intertrochanteric or femoral neck fractures by radiologist review of preoperative films. Results: During 10 years of 98% follow-up, 276 women suﬀered femoral neck and 195 suﬀered intertrochanteric hip fractures. In age-adjusted models, women who walked for exercise had a 28% (RR = 0.72; 95% C.I. = 0.54 to 0.97) lower risk for intertrochanteric fractures but no decreased risk of femoral neck fractures (1.04; 0.82 to 1.31). Women in the highest quartile of weekly exercise had a 47% (RR = 0.53; 0.34 to 0.83) lower age-adjusted risk for intertrochanteric fractures but no significantly reduced risk for femoral neck fractures (0.83; 0.58 to 1.19). Conclusions: Regular physical activity, such as walking for exercise, may reduce the risk of intertrochanteric but not femoral neck fracture. Interventions that reduce the risk of hip fracture may have diﬀerent eﬀects on the risk of intertrochanteric and femoral neck fractures.

P164SU. THE EPIDEMIOLOGY OF PAGET’S DISEASE IN EUROPE: THE PREVALENCE IS DECREASING Poór G1,2,3, Donáth J1,3, Fornet B2, Cooper C4; 1National Institute of Rheumatology and Physiotherapy Budapest, Hungary, 2 Semmelweis University, Medical School, Budapest, Hungary, 3 Musculoskeletal Research Group, Hungarian Academy of Sciences, Hungary, 4MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom To estimate secular changes in the age-and gender-specific prevalence of Paget’s disease of bone in Europe, we conducted a second radiographic survey, using identical sampling and methods in 6 European towns where a basic study was performed in 1978–1979. In addition to these towns the survey was carried out in two Hungarian centers where the study was not conducted previously. In each center, a sample of abdominal radiographs of people aged 55 years and over was taken from stored films within the radiology department of the principal general hospital. The radiographs showing the entire pelvis, sacrum, femoral heads and lumbar vertebrae were studied for the period of 2000–2001. The films were evaluated by a trained observer and a consultant radiologist. A total of 6935 radiographs (3512 women, 3423 men) were assessed in the 8 towns. The overall age – and gender - standardized prevalence rate was 0.3 % with a male/female ratio of 1.5. Prevalence increased with age among men and women rising to 0.8% of men and 0.9% of women aged 85 years and over. The diﬀerences in prevalence rate among the European centers were relatively small especially in females. The vast majority of the rates in 2000–2001 compared to the 1978–1979 values declined steeply in both sexes, in males from 40% to 85.7%, in females from 33.3% to 89.5%. Our European data confirm the decrease in the frequency of the disorder described in Britain. These declines favor an environmental contribution to the causation of the disease that requires further research.

P165MO. ASSOCIATION OF VITAMIN D AND LATITUDE AMONG POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS LIVING IN NON-EQUATORIAL REGIONS Sahota O1, Krishnarajah G2, Yaghi Y3, Poor G4, Kneer W5, Casi-Casenellas A6, Norquist J2, Chandler J2; 1Queen’s Medical Centre NHS Trust, Nottingham, UK, 2Merck & Co. Inc., West Point, PA, USA, 3Hammoud Hospital, Saida, Lebanon, 4Országos Reumatológiai és Fizioterápiás Intézet, Budapest, Hungary, 5Facharzt für Orthopädie, Stockach, Germany, 6C.S. Lakuabizkarra, Vitoria-Gasteiz, Spain Aim: Previously, we reported a 64% global prevalence of vitamin D inadequacy among osteoporotic women, with a higher risk of inadequacy among women living in non-equatorial countries compared to those in equatorial regions (OR 3.5, 95% CI 2.7, 4.5). Since vitamin D3 is synthesized in the skin under the influence of UV irradiation, vitamin D levels are thought to depend on latitude. We examined the influence of latitude on serum 25(OH)D among women in non-equatorial countries, >23(from the equator. Methods: This was a cross-sectional study of a communitybased convenience sample of 2587 osteoporotic postmenopausal women in 18 countries (North, Central and Southern Europe, Middle East, Latin America, Asia and Pacific Rim). Correlations and regression models were used to assess the relationship between serum 25(OH)D and latitude in 14 non-equatorial countries. Results: 2039 (78.8%) women were enrolled from non-equatorial countries; mean age was 67.2 years, compared to 67.1 years, for the overall sample. Mean serum 25(OH)D level among the group was 26.8ng/mL. In women in non-equatorial countries mean serum 25(OH)D was 26.0ng/mL (SD=13.6), compared 29.8ng/mL (SD=11.0) in the equatorial sample. A weak positive correlation (r=0.2, p<0.0001) was observed between serum 25(OH)D levels and latitude; higher serum 25(OH)D was found among women at higher latitudes. The positive relationship remained significant after adjusting for other risk factors (BMI, travel to sunny areas, race, general health, vitamin D supplementation and education; p=0.016). Conclusions: Since sunshine exposure is a critical source of vitamin D, geographic location from the equator should influence serum 25(OH)D levels. Results from this study suggest that the expected relationship between lower vitamin D levels and greater distance from the equator is not apparent; factors other than latitude (i.e., environmental conditions, dietary habits, vitamin supplementation, sun exposure or cultural factors) significantly influence low serum vitamin D levels among women with osteoporosis.

Mean Serum 25(OH)D and latitude

P166SA. CORRELATIONS BETWEEN BONE MINERAL DENSITY AND DEMOGRAPHIC, LIFESTYLE AND BIOCHEMICAL VARIABLES IN ELDERLY JAPANESE WOMEN Nakamura K1, Saito T2, Nishiwaki T3, Ueno K3, Nashimoto M4, Tsuchiya Y1, Oshiki R2, Yamamoto M1; 1Niigata University Graduate School of Medical and Dental Sciences, 2Niigata University of Health and Welfare, 3Niigata University, Niigata, Japan, 4 Nagaoka Nursing School, Nagaoka, Japan

S166 Few epidemiologic studies have comprehensively attempted to identify risk factors for low bone mineral density (BMD) in elderly Asian women. The purpose of this study was to identify demographic, lifestyle, and biochemical factors correlated with BMD in elderly Japanese women 69 years of age and over. The study design was cross-sectional. The subjects were 583 ambulatory women aged 69 years and over, and their average age was 74.5 (SD 4.5) years. Predictor variables were age, reproductive history, anthropometric indices, grip strength, calcium intake, lifestyle information, and serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), osteocalcin (OC), and undercarboxylated osteocalcin (ucOC) values. The outcome variable was forearm BMD measured with a DTX-200 Osteometer. Single linear regression analyses showed that BMD was significantly positively associated with height, weight, BMI, grip strength, serum albumin concentration, and ‘‘housework’’, and negatively associated with age, years since menopause, menarcheal age, number of children, serum 1,25(OH)2D concentration, serum OC concentration and ucOC concentration. The stepwise multiple regression analysis showed that weight (R2=0.221, P<0.0001), serum OC (R2=0.058, P<0.0001), serum 1,25(OH)2D (R2=0.036, P<0.0001), age (R2=0.028, P=0.0251), grip strength (R2=0.020, P=0.0005), and ‘‘farmwork’’ (R2=0.007, P=0.0097) were independently associated with BMD. It was concluded that body weight is the major predictor of forearm BMD in independent Japanese women 69 years of age and over, and that the serum 1,25(OH)2D concentration may be associated with cortical BMD. Maintenance of body weight is very important to maintaining BMD in this population. A follow-up study is needed to confirm these findings.

P167SU. A COMPARISON OF VISUAL AND AUTOMATED METHODS OF VERTEBRAL EXCLUSION IN DUAL-ENERGY X-RAY ABSORPTIOMETRY Tsang J, Leslie WD; University of Manitoba, Winnipeg, Canada Aim: Spine bone densitometry measurements obtained with dualenergy x-ray absorptiometry (DXA) are often confounded by age-related degenerative artifacts which can overestimate the true value. Typically, vertebral levels containing these artifacts are visually identified and excluded by human interpreters. Recently, one manufacturer of DXA equipment (GE Lunar, Madison, WI) proposed two automated computer algorithms to identify and exclude vertebrae that are confounded by structural defects (Barden H, J Clin Densitom 2003;6:401). Methods: We sought to establish the degree of concordance between the human vertebral level exclusion and two published automated methods for flagging abnormal spines (referred to as ‘‘unusual’’). We studied N=30,542 spine scans from the Manitoba Bone Density Database acquired with GE Lunar DPX or Prodigy scanners. Scans with incomplete spine information (N=1,856) were excluded leaving a final total of N=28,686 scans for analysis. Cohen’s was calculated to determine the level of agreement between human visual and two automated algorithms for scan classification (no exclusions vs. unusual). ROC area under the curve (AUC) was determined to assess the test accuracy of the automated methods in the identification of unusual scans. Results: Mean spine T-Score (SD) without any exclusions (-1.171.54) was signficiantly greater than when there were vertebral exclusions defined visually by human readers (-1.341.55, p<.00001) or automatically by Algorithm 1 (-1.351.53, p<.00001) and Algorithm 2 (-1.291.50, p<.00001). ROC analyses yielded AUC values of 0.724 (95% CI [0.717–0.730], p < 0.0005) for human vs. algoruthm 1 and 0.769 (95% CI [0.763–0.775], p < 0.0005) for human vs. algorithm 2. Unadjusted Cohen’s values were 0.281 and 0.358, respectively, while prevalence adjusted values were 0.336 and 0.526, respectively. Conclusions: Automated methods gave mean spine T-scores similar to human readers and significantly greater than T-Scores without any exclusions, consistent with exclusion of artifact. We observed a fair level of agreement between each of the automated and visual methods of exclusion. Automated methods of vertebral exclusion can be a useful adjunct to human interpretation to alert the reader about potentially troublesome scans.

P168MO. ACCUMULATED BREAST-FEEDING OF 6 OR MORE MONTHS IS ASSOCIATED WITH OSTEOPOROTIC FRACTURES AND LOW BONE MASS IN A COHORT OF POSTMENOPAUSAL WOMEN Nogues X, Peña MJ, Checa MA, Aymar I, Mellibovsky L, Supervia A, Garrido A, Carbonell J, Perez-Edo L, Monllau JC, Caceres E, Carreras R, Diez-Perez A; URFOA-IMIM Hospital del Mar Barcelona, Autonomous University of Barcelona, Barcelona, Spain Aim: Breast-feeding is related with hormonal alterations and increased calcium expenditure in the mother to provide suﬃcient calcium to the neonate. Therefore, some bone loss occurs in this period although their relationship with osteoporosis in postmenopausal women is controversial. We analyzed this subject in a cohort of Spanish postmenopausal women. Patients and methods: 1738 consecutive unselected Spanish postmenopausal women with at least one pregnancy, aged 53.17.4 years (meanSD) from a Menopausal Unit were recruited in a prospective observational study. Medical record, including gynecological data, history of bone fracture and risk factors for osteoporosis, was collected. Bone mineral density (BMD) was measured at the lumbar spine (L-BMD) and femoral neck (Fn-BMD) using dual-energy x-ray absorptiometry (Hologic QDR 4500 SL). Women with secondary osteoporosis were excluded. Data were analyzed using SPSS 12.01. T-test and ANCOVA were performed. Results: Age at menopause was 47.84.9, menarche 12.81.6 and accumulated breast-feeding months (ABF) 11.913.7. In 69.3% of women ABF was six or more. L-BMD was 0.9010.14 g/cm2 in women with less than 6 months ABF vs. 0.8620.14 in those with 6 or more (p=0.004). Fn-BMD was also significantly diﬀerent (0.7200.11 vs. 0.7090.11, p=0.018, respectively). Previous osteoporotic fracture was present in 7.8% of women with ABF < 6 months vs. 17.5 in those with 6 or more (RR 1.98; 95% CI 1.42–2.76; p<0.0001). ABF in women without fractures was 7.1910.2 and in women with fractures was 12.822.8; p=0.0001. Conclusion: ABF is relevant for the development of osteoporosis after menopause. Six or more months of ABF are associated with decreased lumbar spine and femoral neck BMD as well as with increased prevalent fractures in a cohort of Spanish postmenopausal women.

P169SA. A SIMPLE INDEX TO IDENTIFY HISPANIC WOMEN AT HIGH RISK OF OSTEOPOROSIS USING BONE DENSITOMETRY Balderramo DC, Douthat WG; Bone and Mineral Metabolism Section, Renal Service. Hospital Privado Centro Medico de Cordoba. Postgraduate School of Nephrology, Catholic University of Cordoba. Argentina Aim: To develop and validate a clinical prediction index to identify Hispanic women at high risk of osteoporosis using bone mineral density (BMD) testing. Methods: We analysed data from ambulatory Hispanic women evaluated in our Section who had undergone dual-energy x-ray absorptiometry testing at the femoral neck and/or at the lumbar spine (L1-L4). Secondary osteoporosis patients were excluded. The main outcome measure was osteoporosis defined as BMD T-score %2.5 standard deviations below the mean for young Argentinian women at either the femoral neck or the lumbar spine. Regression models and receiver operating characteristic (ROC) analysis were used to asses the risk factors associated with osteoporosis, to identify the threshold value of the index, and to evaluate its discriminatory performance. Results: The study population comprised 298 Hispanic women aged 45 years or more (mean age 58.3 years). All patients were from Cordoba, a central region of Argentina. A total of 191 women were randomly allocated to the development cohort of the index and 107 women to the validation cohort. A simple index using the most strong risk factors associated with osteoporosis was developed. To calculate the index, 0.6 point was added for each kilogram of weight, 18 points were subtracted if wrist fracture history after 45 years of age was present, and 1 additional point was subtracted for each postmenopausal year. An index value %

S167 20 points was established as the threshold value. Using this value, the index showed a sensitivity of 94.5% [95% confidence interval (CI) 82.2%-98.3%] and specificity of 44.1% (95% CI 36.6%-51.9%) in the development cohort, and a sensitivity of 92.7% (95% CI 80.1%-98.9%] and specificity of 42.8% (95% CI 34.6%-51.3%) in the validation cohort for selecting women with osteoporosis for testing with bone densitometry. Discriminatory performance was similar in both cohorts (area under ROC curve: 0.81 and 0.78 in the development and validation cohorts, respectively). Conclusions: A simple clinical prediction index identifies the majority of Hispanic women likely to have osteoporosis in an Argentinian population. Further clinical research is necessary to establish the applicability of the present index.

Results: After a mean of 3.02.1 (1.0–9.1) years, 115 subjects were lost to follow up and 27 died. Data from 1,293 women were analyzed. 51 non-traumatic new fractures were reported during follow-up (5 vertebral, 11 hip, 7 humerus, 9 distal forearm fractures). The risk factors in the table below were significant predictors of hip fracture. The rate of osteoporotic fractures for women aged 45–54 years was 7/1000 woman-year while for women aged 75–84 years was 30/1000 woman-year. The fracture rate for postmenopausal women with hip BMD T score>-2.5 was 8/1000 woman-year while for women with 2 or more risk factors was 33/1000 woman-year. Risk factors significantly associated with hip fractures

P170SU. EPIDEMIOLOGY OF FRACTURE IN CHILDREN: A COHORT STUDY FOR SEX- AND AGE-SPECIFIC INCIDENCE RATES AND RELATED FACTORS Iki M1, Tamaki J1, Ikeda Y1, Sato Y2, Naka H3; 1Kinki University School of Medicine, Osaka-Sayama, Japan, 2Tenshi College, Sapporo, Japan, 3Kyoto University of Education, Kyoto, Japan Aims: To estimate sex- and age-specific incidence rates of fracture and risk factors for it in children. Methods: We selected randomly 50 boys and 50 girls from 4th to 9th grade children (9 to 15 years old) in compulsory schools in a town of Japan for the baseline study. Among them, healthy 579 children were invited for the follow-up study conducted 3 years after the baseline and 427 (200 boys and 227 girls, 73.7%, 12.41.7 years old) completed it. We obtained lifestyle factors including exercise habits through in-person interviews, and measured height, weight and bone mineral density (BMD) at the spine and hip by DXA at baseline and at follow-up. Fracture was defined as the one which caused a hospital visit for pain and was diagnosed as a fracture by a physician with X-ray film. It was determined through detailed interviews with the subjects and a questionnaire filled by their guardians whether the subjects had had a fracture. Results: The boys had suﬀered 54 fractures in their lifetime (2.1 per 100 person-years) and 37 fractures (3.9) during the follow-up period. The girls had had 31 (1.1) and 19 fractures (1.7), respectively. The highest age-specific rate in boys was around 5% at age 12–14, and that in girls was about 2.5% at age 11–13. The logistic regression showed that age, height, weight or BMD at any skeletal site at baseline did not relate univariately to the risk for fracture during the follow-up in boys. A combination of height, weight and BMD at the hip significantly predicted the risk and 1 SD increase in BMD increased the risk by 68% (OR: 1.68, 95% CI: 1.05–2.68). When adding indices for exercise to the model, the eﬀect of BMD turned to be insignificant and annual hours of exercise during 4th to 6th school grades were significant (OR:1.26 per 100 hours, 95% CI: 1.01–1.57). Conclusions: Boys run a twofold greater risk for fracture than girls, and boys aged 12–14 and girls aged 11–13 had a twofold greater risk than children of other ages. Physically active boys had an increased risk for fracture independently of BMD.

P171MO. RISK FACTORS FOR HIP FRACTURES IN CHINESE POSTMENOPAUSAL WOMEN: A PROSPECTIVE STUDY Kung AWC, Chan WM, Lee KK; Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China Aim: To evaluate the risk factors for osteoporotic fractures and to determine the fracture rate in postmenopausal Chinese women. Methods: 1,435 postmenopausal treatment naive Chinese women aged 63.48.3(range 45–91) years were recruited from the community. Baseline demographic information and clinical risk factors were determined using a structured questionnaire and bone mineral density (BMD) was measured at the spine and hip using dual-energy X-ray absorptiometry. Periodic assessment by telephone interview was performed and the clinical outcome was ascertained from the computerized record system of the Hospital Authority of Hong Kong. Proportional-hazards analysis was used to identify independent risk factors of hip fracture.

Living alone Use of walking aid L1–4 Spine BMD T(per SD reduction) Femoral neck BMD (per SD reduction) Trochanter BMD (per SD reduction)

Age-adjusted Relative Risk (95% C.I.)

p-value

9.6 (1.2 - 78) 22.4 (2.8 - 178) 2.0 (1.1 - 3.5) 2.5 (1.2 - 5.4) 2.0 (1.1 - 3.6)

0.034 0.003 0.021 0.018 0.021

Conclusion: Osteoporotic fracture is a major public health problem in Chinese and preventive programme should be oﬀered to target subjects at high risks of fracture.

P172SA. DETERMINANTS OF NON-COMPLIANCE WITH BISPHOSPHONATE THERAPY IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS van den Boogaard CHA1, Penning-van Beest FJA1, Erkens JA1, Engbersen AMT2, Herings RMC1; 1PHARMO Institute, Utrecht, Netherlands, 2Novartis Pharma AG, Basel, Switzerland Aim: To identify determinants of non-compliance with bisphosphonate therapy in women with postmenopausal osteoporosis. Methods: Data were obtained from the PHARMO database, which includes linked drug-dispensing records and hospital records of more than two million individuals in defined areas in the Netherlands. New female users of alendronate or risedronate therapies, aged R 45 years or with diagnosed postmenopausal osteoporosis from 1 January 1999 until 30 June 2004, were included in the study. One-year compliance was measured using the Medication Possession Ratio (MPR) and defined as the sum of days’ supply for all prescriptions of the initial drug in the first year after starting treatment. To identify determinants of noncompliance, non-compliant patients (MPR < 50%) were compared to compliant patients (MPR R 80%). The eﬀect of type of initial drug, patient age, prescriber, co-medication and fractures on non-compliance with bisphosphonates was investigated. For those independent factors increasing non-compliance, the impact on the patient population was determined by the Population Attributable Risk percentage (PAR%), taking into account the proportion of non-compliant patients and the odds ratio. Results: The study cohort included 8,822 new users of bisphosphonates, of whom 4,699 (53%) were compliant and 3,089 (35%) were non-compliant with their initial therapy after one year. 1,034 (12%) patients had a MPR R 50% and <80%. Use of daily bisphosphonates, number of diﬀerent co-medications used preceding bisphosphonate therapy, and use of gastrointestinal medication during the first year were associated with an increased risk of non-compliance (OR 3.1, 95% CI 2.7–3.5; OR 1.8, 95% CI 1.3–2.3 for >10 diﬀerent co-medications; and OR 1.2; 95% CI 1.1–1.4, respectively). Corresponding PAR% values were 42%, 14% and 6%, respectively. In contrast, higher age, first prescription from a specialist, hospitalization for osteoporosis or osteoporotic fracture in the year preceding bisphosphonate therapy, and use of NSAIDs in the year prior to bisphosphonate therapy independently decreased the risk of non-compliance with bisphosphonates.

S168 Conclusions: These results indicate that daily, rather than a weekly, dosing regimen is the most important independent determinant of non-compliance with bisphosphonates. However, compliance for both regimens can be considered to be suboptimal and leaves room for improvement.

P173SU. RIGID MORPHOMETRIC CRITERA IMPROVE ITS DIAGNOSTIC ACCURACY IN DETECTION OF PREVALENT VERTEBRAL FRACTURES Wu C, Fuerst T, Genant HK; Synarc Incorporation, California, USA Aims: Quantitative Morphomety (QM) assessment of vertebral prevalent fracture with popular utilized criteria demonstrated higher fracture rate with extensive false prediction to radiological judgment. We studied if more strict QM thresholds can enhance their performance in comparing to radiological reading. Materials and Methods: Vertebral body dimensions (T4-L4) from standardized lateral radiographs of 253 postmenopausal women were measured using the 6 point QM technique to obtain vertebral heights and relevant ratios. Vertebral fracture prevalence was determined by experienced readers with radiological visual Semi-Quantitative (SQ) method. QM measured vertebral height ratio, e.g., anteria/posteria; middle/posterior; posterior/posterior of above vertebral and posterior/posterior of below vertebra were used to identify the spine fracture. Four QM criteria using diﬀerent cut-oﬀ thresholds for these ratios were taken to define the fracture prevalence: (1) Commonly accepted height ratio reduction 3 standard deviation (SD) from normal references (3SD); (2) Height ratio reduction 3.5 SD from normal reference (3.5 SD); (3) Height ratio reduction 4.0 SD from normal reference (4.0 SD); and (4) Height ratios reduction 25% at the same vertebra in a given patient of the study. QM prevalent fracture determined by these four diﬀerent criteria were all matched up with SQ reading to search their agreements. Results: Compared with the frequent used 3SD criterion, the three stiﬀer QM thresholds for spine prevalent fracture had higher agreement to SQ method with improved performances in various aspects. QM performance in comparing to SQ for spine prevalent fracture QM Criteria 3 SD (Fixed ratio reduction for all levels) 3.5 SD (Fixed ratio reduction for all levels) 4 SD (Fixed ratio reduction for all levels) 25% (Fixed ratio reduction for all levels)

Kappa Score

Accuracy %

Sensitivity %

Specificity %

0.61

94.10

56.17

98.02

0.71

96.56

81.82

97.36

0.70

96.72

91.33

96.97

0.69

96.62

92.90

96.79

Conclusion: The study validated that QM accuracy was significantly improved by using these more strict criteria to reach a higher predictive consistence with radiological judgment of spine prevalent fracture.

P174MO. PERFORMANCE OF SEVERAL RISK INDICES FOR PREDICTION OF OSTEOPOROSIS IN PERI- AND POSTMENOPAUSAL WOMEN Gunaydin R, Kaya T, Goksel Karatepe A, Karlibas U, Ozbek G; Izmir Research and Training Hospital, Department of Physical Medicine and Rehabilitation, Izmir, Turkey Aim: This study was performed to evaluate the performance of four risk indices developed to identify peri- and postmenopausal women with an increased likelihood of osteoporosis. Patients and Method: One-hundred eighty-six women ages R45 with mean age of 62.338.13 were recruited in the study. Lumbar spine (L2-L4) and proximal femur bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DXA). Osteoporosis Self-Assessment Tool for Asians (OSTA), Osteoporosis Index of Risk (OSIRIS), Simple Calculated Osteoporosis

Risk Evaluation (SCORE) and Osteoporosis Risk Assessment Instrument (ORAI) were applied to all women. We evaluated the performance of these indices in prediction the women with lumbar spine and femoral neck T-score %-2.5 by Receiver Operating Characteristic (ROC) analysis. Results: Among participants, 26.9% had T-score % -2.5 at the femoral neck and 58.1% had at the lumbar spine. While the sensitivity of SCORE, ORAI, OSIRIS, and OSTA in identifying women with T-score % -2.5 in lumbar spine were 67%, 73%, 58%, 70%, respectively, the specificity of these scores were 38%, 38%, 55%, 42%, respectively. While the sensitivity of SCORE, ORAI, OSIRIS and OSTA in identifying women with T-score % -2.5 in femoral neck were 84%, 86%, 72%, 82%, respectively, the specificity of these scores were 41%, 38%, 54%, 41%, respectively. The performance of SCORE, ORAI, OSIRIS and OSTA indices in identify the women with osteoporosis in femoral neck (AUC were 0.724, 0.733, 0.724, 0.718, respectively) were higher than those with osteoporosis in lumbar spine (AUC were 0.541, 0.573, 0.579, 0.568, respectively). Conclusion: SCORE, ORAI, OSIRIS and OSTA are useful clinical tools for assessing the risk of osteoporosis in femoral neck and eﬀective in decreasing the need to undergo DXA testing for peri- and postmenopausal women.

P175SA. USING AGE AND WEIGHT DATA FROM THE U.S. BEHAVIORAL RISK FACTOR SURVEILLANCE SYSTEM TO ASSESS POPULATION RISK FOR OSTEOPOROSIS IN WOMEN Schneyer CR1, Lopez H2, Concannon M2, Hochberg MC3; 1Division of Endocrinology, Johns Hopkins University School of Medicine, 2Maryland Department of Health & Mental Hygiene, 3 Division of Rheumatology, University of Maryland School of Medicine, Baltimore, USA Aims: Osteoporosis is a major public health problem lacking national intervention programs, partly due to the inability to mass screen at-risk populations. Bone mineral density (BMD), used for diagnosing osteoporosis, is impractical for mass screening. The Osteoporosis Self-Assessment Tool (OST index, calculated from age and weight) is a simple strategy with sensitivity w90% for identifying high-risk individuals requiring BMD testing. Our objective was to use OST to estimate state-specific osteoporosis prevalence. Methods: We calculated OST scores using 2002 Behavioral Risk Factor Surveillance System (BRFSS) data. BRFSS is the world’s largest telephone health survey and the chief information source for states, territories, and the nation on adult preventable health practices and risk behaviors. The BRFSS is conducted annually by state health departments in collaboration with the Center for Disease Control and Prevention (CDC). BRFSS data are weighted to state-specific census data to generate prevalence estimates. To determine osteoporosis prevalence from OST scores, we used well-documented correlations (e.g. 57–58% and 18–23% of women with high- and moderate-risk OST scores, respectively, have BMD-confirmed osteoporosis). Results: State-specific prevalence of high-risk OST scores for women R50 ranged from 2.7% (Alaska) to 14% (Hawaii), median 8.8% (New York), interquartile range (IQR) 7.9–9.8% (North Carolina and Wyoming). Similarly, the state prevalence of moderate-risk scores in these women ranged from 40.7% (Virgin Islands) to 69% (Guam), median 51.2% (Kentucky), IQR 48.8– 53.4% (Utah and Nevada). Estimates of state and national osteoporosis prevalence for women age 50+ using our data are comparable to National Osteoporosis Foundation figures, which are based on femoral neck BMD values from the National Health and Nutrition Examination Survey III, 1988–94. (http:// www.nof.org/advocacy/prevalence/index.htm) Conclusions: We suggest that the OST index (calculated using BRFSS data) reliably estimates state-specific osteoporosis prevalence, a parameter essential for designing and monitoring individual state prevention/treatment programs. Explanations for stateto-state diﬀerences may be revealed by examination of BRFSS data for demographic characteristics, life-style behaviors, healthcare access, and utilization factors. Furthermore, review of historical BRFSS data may facilitate investigation of temporal changes in

S169

P176SU. ASSOCIATION OF A SYNONOMOUS POLYMORPHISM (RS315952) IN THE INTERLEUKIN 1 RECEPTOR ANTAGONIST GENE WITH PQCT MEASURES OF BONE STRUCTURAL GEOMETRY AND BIOMECHANICAL STRENGTH INDICES

women. 73.2% and 89.2% of these numbers, respectively, were fall-related fractures. Female-to-male ratio for fall-induced and total hip fracture rates were 1.2 and 1.0, respectively. The incidence rates increased exponentially after the age of 60 in both genders and nearly tripled after each decade. Comparing to other studies, Iranian age-standardized incidence rates (127.3 and 164.6 per 100000 person-years for men and women, respectively) were considerably lower than all of western countries when standardized to the US population in 2000.

Moﬀett SP1, Wheeler VW2, Patrick AL2, Bunker CH1, Cauley JA1, Ferrell RE1, Zmuda JM1; 1University of Pittsburgh, Pittsburgh, USA, 2Tobago Health Studies Oﬃce, Scarborough, Tobago

Age-standardized annual incidence rates of hip fracture per 100,000 in males and females aged R50 years in diﬀerent populations (standardized to US population in 2000)

prevalence. Future BRFSS data, beginning 2005, will be enhanced because of an osteoporosis optional module developed by our state Task Force.

Interleukin 1 (IL1) is a proinflammatory cytokine which stimulates osteoclastogenesis and bone remodeling. The IL1 receptor antagonist (IL1RN) is a soluble receptor that blocks IL1 signaling by sequestering IL1 away from its receptor. We have examined the associations of genetic variation in the IL1RN gene on high resolution pQCT measures of bone mass, structural geometry and indices of biomechanical strength in 396 AfroCaribbean men over the age of 40. We genotyped 3 polymorphisms in the IL1RN gene region: rs315952 a synonomous C to T polymorphism in exon 6; rs2229235, an intronic G to A substitution; and rs895495, an A to G polymorphism in the 3’ untranslated region. Using age-adjusted analysis of variance models, we found that individuals homozygous for the C allele of IL1RN rs315952 have significantly higher cortical area and bone mineral content in the tibia and radius compared to T/T homozygotes. For example, at the proximal radius, C/C individuals had a higher cortical area (meanSD: C/C=120.315.4; C/T=115.613.0, T/T=115.014.5; p=0.012) and bone mineral content (C/C=145.118.7; C/T=139.616.2, T/T=138.718.0; p=0.013) than either the T/C or T/T individuals. As both bone area and mineral content were increased in the C/C individuals, no association was observed with cortical volumetric density (p=0.87). In addition, both the polar and axial strength strain indices (SSI) at the proximal radius were significantly increased in C/C individuals compared to the other genotypes (polar SSI: C/C=445.089.0; C/T=419.677.4, T/T=419.282.5; p=0.04; axial SSI: C/C=344.551.5; C/T=327.743.1, T/T=322.448.0; p=0.01). These associations were independent of height and weight. The other SNPs in this gene were not significantly associated with these pQCT measures. Our results suggest that alterations in the IL1 signaling pathway could lead to diﬀerential bone modeling/remodeling patterns that influence bone mass, structural geometry and biomechanical strength.

P177MO. EPIDEMIOLOGY OF HIP FRACTURE IN IRAN: RESULTS FROM THE IRANIAN MULTICENTER STUDY ON ACCIDENTAL INJURIES (IMSAI) Moayyeri A1, Abolhassani F1, Soltani A1, Naghavi M2, Larijani B1, Tavakoli Shalmani H1; 1Endocrinology & Metabolism Research Centre, Shariati Hospital, Tehran University of Medical Sciences, 2Undersecretary for Health, Ministry of Health and Medical Education, Tehran, Iran Aims: Incidence of hip fracture varies substantially between countries. As a result of improving life expectancy, the number of elderly people susceptible to hip fractures is increasing rapidly in the developing world. We aimed to estimate incidence of hip fracture in Iran and compare it with other populations. Methods: Data used were obtained from the Iranian Multicenter Study on Accidental Injuries, a large scale population-based study conducted in 9 provinces across the country. All the hospitals serving about 9.5 million people in the study area were prospectively surveyed for any incident injury resulted from accidental events for a period of 135 days (4.5 months). Two databases of falls and traﬃc accidents were considered for this study. All patients aged R50 with radiographically confirmed proximal femur fractures were included. Results: A total of 555 new cases of hip fracture (284 males, 271 females) were recorded during the study period. The annual incidence of hip fracture per 100000 person-years was 115.2 (95% CI: 107.2–123.7) in men and 115.6 (95% CI: 107.4–124.3) in

Age-standardize rate Place and time of the study [reference] Africa Morocco, Rabat; 2002 Asia China, Beijing; 1996 China, Shenyang; 1994 Iran; 2003 [current study] Malaysia; 1997–1998 Thailand; 1997–1998 Japan, Tottori; 1994 Kuwait: Kuwaitis; 1992–1995 Kuwait: Non-Kuwaitis; 1992–1995 Singapore; 1997–1998 Hong Kong;1997–1998 Taiwan; 1996–2000 South America Brazil, Sobral; 1996–2000 Europe Switzerland; 1992 Former East Germany; 1996 Former West Germany; 1996 England, 1997–1998 Greece; 1992 Sweden; 1991 Norway, Trøndelag; 1997–1998 Norway, Oslo; 1996–1997 North America United States, Minnesota; 1989–1991 United States; 1988–1989 Oceania New South Wales; 1999–2000 Australia; 1994–1996

Female: Male ratio

Male

Female

57.7

79.9

1.4

80.5 101.3 127.3 87.4 112.6 107.3 216.6 236.2 162.9 193.0 233.4

85.7 87.8 164.6 212.5 261.6 297.3 316.0 401.6 431.7 484.3 496.8

1.1 0.9 1.3 2.4 2.3 2.8 1.5 1.7 2.7 2.5 2.1

59.3

168.4

2.8

137.8 127.4 154.5 143.6 201.7 302.7 352.0 399.3

346.0 354.7 399.4 418.2 469.9 709.5 763.6 920.7

2.5 2.8 2.6 2.9 2.3 2.3 2.2 2.3

201.6 197.2

511.5 553.5

2.5 2.8

191.8 187.8

475.1 504.2

2.5 2.7

Conclusions: When compared with the rates from other Asian countries, Iranian females had the lowest rates after China. This could be the result of several potential factors related to genetic or lifestyle diﬀerences between Iranians and people of other countries. Further studies to reveal these factors are necessary.

P178SA. SELF-REPORTED VERSUS MEASURED PREVALENCE OF OSTEOPOROSIS: AN AGE-STRATIFIED ANALYSIS OF ITS DIAGNOSTIC COVERAGE Richy F1, Bruyere O1, Maassen P2, Pire G3, Reginster JY1; 1 University of Liège (Belgium), Faculty of Medicine, Public Health, Epidemiology and Health Economics; WHO collaborating center for public health aspects of osteoarticular disorders, 2General Director, Health and Environment, Province of Liège, Belgium, 3Representative in charge of Health, Environment and Quality of life, Province of Liège, Belgium Introduction: The eﬃcacy and eﬃciency of prophylactic and therapeutic treatments for osteoporosis are limited by the lack of awareness of the patients and the physicians about this condition and by the lack of reimbursement of diagnostic procedures. There is a lack of data regarding what percentage of the osteoporotic population receives diagnosis.

S170 Methods: Two databases were crossed to link 1) the age-specific prevalence of the diagnosis of osteoporosis at the total hip, femoral neck and L2-L4 (n=609) assessed during an independent, free osteoporosis-screening campaign and 2) the self-reported prevalence of osteoporosis in a representative sample of postmenopausal women (n=2726). Records were matched on age in a 4 to 1 fashion. Results: The age-specific prevalence of osteoporosis (considered at any measurement site) presented an exponential increase and ranged from 16.8 to 59.1%. The percentage of awareness of osteoporosis among the osteoporotic subjects ranged from 20 to 69% and increased steadily with age groups. The positive impact of the free screening campaigns organised for 4 years now in the Province of Liège could be observed on the basis of higher awareness rates compared to global Belgium values. Implications: Even in a country like Belgium, were the availability of densitometers is one of the highest in Europe, the percentage of diagnosed osteoporosis remains critically poor in the general population. Our data show that up to 59% to 80% of the osteoporotic subjects remain undiagnosed, placing them at risk of fractures and weighting down the community with the increasing burden of direct and indirect costs. These data accurately document the need for a better access and reimbursement of densitometry. 1) Richy, F., et al., Development and validation of the ORACLE score to predict risk of osteoporosis. Mayo Clin Proc 2004; 79: 1402–8. 2) The Belgian Health Interview Survey. Web-based interractive analysis.

determine the incidence of hip fractures and their associated factors in elderly individuals residing in an urban center located on the northeast coast of Brazil. An open cohort was used, composed of both sexes, aged 60 years or over and residing in the city of Natal-RN who suﬀered hip fracture between 2001 and 2002. A multidimensional assessment questionnaire was used containing information on sociodemographic aspects, health condition, trauma circumstances and prefracture functional capacity. Global risk fracture and incidence density according to associated potential risk factors were calculated. The verification of the association magnitude between the distinct factors studied and fracture rate was estimated using the density ratio, with a confidence interval of 95% and p-value < 0.05. The number of hip fractures observed was 196, with 151 (77%) in females and 45 (23%) in males, a male/ female proportion of 1:3.3. The mean age of the cohort was 80.6 9.2 years, 80.5 9.6 for men and 80.7 (SD = 8.7) for women (p = 0.864). A predominance of fractures was verified in spouseless Caucasian individuals. Intertrochanteric fracture was the most common type. The annual incidence of proximal femur fractures was 33.78/10,000 inhabitants, 19.61/10,000 inhabitants for males and 43.04/10,000 inhabitants for females. The factors associated with fractures were: Caucasian race (OR = 2.25; CI 95% = 1.67–3.03), diminished visual acuity (OR = 1.59; CI 95% = 1.19 -2.15), arterial hypertension (OR = 2.21; CI 95% = 1.63–3.01) and previous osteoporosis diagnosis (OR = 1.99; CI 95% = 1.41–2.81).

P180MO. INCIDENCE AND CHANGE OF PREVALENCE OF VERTEBRAL FRACTURES IN A RURAL JAPANESE COMMUNITY: A 10-YEAR FOLLOW-UP OF THE MIYAMA COHORT Yoshimura N1, Kinoshita H2, Oka H1, Muraki S3, Kawaguchi H3, Nakamura K3; 1Department of Joint Disease Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 2 Department of Orthopaedic Surgery, Wakayama Medical University Kihoku Hospital, Wakayama, Japan, 3Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

P179SU. INCIDENCE AND FACTORS ASSOCIATED WITH HIP FRACTURES IN THE ELDERLY IN AN URBAN CENTER IN NORTHEAST BRAZIL Guerra RO1,2, Guerra GCB1,3, Viana AS1,4; 1University Federal of Rio Grande do Norte, 2Physical Therapy Departament, 3Department of Pharmacology, 4Onofre Lopes University Hospital, Natal - RN, Brazil In the coming years Latin America will experience the largest increase in osteoporotic fractures of any region in the world. It is known that the world hip fracture incidence in the elderly varies according to the socioeconomic characteristics of the regions studied. In Brazil, a country of continental dimensions and with great socioeconomic diversity among its regions, a low incidence of hip fractures is found in the elderly. The aim of this study was to

Aim: To clarify the change of prevalence and the cumulative incidence of vertebral fractures (VFx) among general inhabitants of a rural Japanese community. Method: A cohort of 1543 inhabitants aged 40–79 years was established using resident registration in 1989. Four hundred subjects were selected by sex and age decade from the full list of residents born between 1910 and 1949, with 50 men and 50 women in each age decade. Anteroposterior and lateral x-ray examinations of the thoracolumbar spine were performed on the participants in 1990 and 2000 and VFx were diagnosed by an experienced orthopaedic surgeon. Results: The 10-year follow-up by x-ray examination was completed for 299 of the 400 initial participants (74.8%: 137 men, 162 women). The baseline prevalence of VFx for men in their 40s, 50s, 60s, and 70s were 4.3%, 14.6%, 22.0%, and 24.5%, respectively, and those for women were 2.1%, 10.2%, 14.0%, and 44.9%, respectively. The prevalence of VFx at the follow-up survey in 2000 for men in their 50s, 60s, 70s, and 80s were 2.9%, 10.3%, 13.2%, and 25.0%, respectively, and those for women were 2.1%, 9.1%, 20.5%, and 54.2%, respectively. Incident cases were defined as new cases and subjects who had suﬀered from prevalent fractures and showed an increased number of VFx during the observed 10 years. The cumulative incidence was calculated by dividing the number of cases by the number of all participants at the baseline study. As a result, the observed cumulative incidence for men in their 40s, 50s, 60s, and 70s were 2.1%, 8.3%, 10.0% and 12.2%, respectively, and those for women were 2.1%, 6.1%, 18.0%, and 22.4%, respectively. Conclusions: The present study clarified the gender and age diﬀerences in the prevalence and incidence of VFx in a rural Japanese population. Furthermore, we found evidence of diﬀerences in prevalence of VFx for given age strata between birth cohorts. The comparison of data collected in 1990 and 2000 showed improvements over time for men and women in their 50s, 60s, and 70s, suggesting that future problems with osteoporotic fractures might be less severe than has previously been predicted in Japan.

S171

P181SA. ARE COSTS OF FRACTURE PROPORTIONAL TO THEIR MORBIDITY? 1,5

2

3

4

1

Borgström F , Johnell O , Jönsson B , Kanis JA ; Stockholm Health Economics, Stockholm, Sweden, 2Department of Orthopaedics, Malmö General Hospital, Sweden, 3Stockholm School of Economics, Stockholm, Sweden, 4Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheﬃeld Medical School, Sheﬃeld, UK, 5Medical Management Centre, Karolinska Institutet, Stockholm, Sweden Aims: Intervention thresholds (IT) for osteoporosis can be defined as the 10 year absolute hip fracture risk at which an intervention becomes acceptable. To account for the total burden of osteoporosis the excess morbidity of all fractures compared to hip fracture (a.k.a. hip fracture equivalents) have been calculated and used in intervention threshold estimations. One assumption underlying these calculations is that the fracture costs are proportional to fracture disutility. The aim is to investigate whether the assumption of proportionality between disutility and fracture costs by estimating the excess costs of all osteoporotic fractures compared to hip fracture. Methods: An approach similar to what was used to assess the excess morbidity of fractures was adapted for costs. A Markov cohort model was built that could measure the downstream of costs related to osteoporotic fracture types for diﬀerent ages of fracture occurrence. The estimated lifetime related fracture costs were related to age diﬀerentiated fracture incidence making it possible to create a hip fracture cost equivalent index. The cost data used in the model was the most recent and appropriate for a Swedish setting. Results: The estimated hip fracture cost equivalent index varied from 2.33 at the ages 50–54 to 1.36 for ages 85–89. This can be compared to the previously calculated hip fracture morbidity equivalents that vary from 6.07 (50–54 year olds) to 1.60 (85–89 years olds). This indicate that, with available fracture cost data, hip fractures is related to a higher proportion of the total fracture costs compared to the proportion of disutility related to hip fractures. Conclusions: The results show that the assumption of proportionality between cost and disutility might not be entirely appropriate. Not taking this into account might have the potential to skew the results in intervention threshold calculations. One solution could be to down adjust the fracture related costs by the ratio between the morbidity and the cost index when estimating the intervention thresholds.

P182SU. OSTEOPOROSIS TREATMENT FOR STROKE PATIENTS Greenberg JA1, Wuermser LA1,2, Roth EJ1,2, Schnitzer TJ1,2; 1 Northwestern University, Feinberg School of Medicine, Chicago, USA, 2Rehabilitation Institute of Chicago, Chicago, USA Aims: Stroke patients are at increased risk of fracture due to a heightened risk of falling coupled with decreased bone strength. In this population, bone mass can be better maintained by the appropriate use of pharmacologic interventions. This study was undertaken at a single center that specializes in rehabilitation medicine to determine the prevalence of use of agents which could aﬀect bone loss. Methods: A clinical database at the Rehabilitation Institute of Chicago was searched for stroke patients (ICD-9 codes #430–438 excluding 435). All stroke patients 18 years old and over were included. The sample included 1219 stroke inpatients (11/1/01 to present) and 3129 stroke outpatients (1/29/99 to present). 599 of the inpatients continued as outpatients. Medications and demographic information (age, gender, and race) were obtained for each patient. Results: The percentages of patients receiving osteoporosis medications (bisphosphonates, calcitonin, or hormone replacement therapy) or common osteoporosis supplements are displayed in the table below. When the results were further analyzed, older patients, females, and white patients were found to be more frequently treated with osteoporosis medications in both the inpatient and outpatient samples. The median age, percent female, and percent Caucasian for the total stroke inpatient population was 65, 48.1, and 57.5 respectively. The median age, percent female, and percent Caucasian for the stroke inpatient population on osteoporosis medication was 73, 72.4, and 66.7 respectively. However, the use of supplements, particularly multivitamins, was

closer demographically to the overall stroke inpatient and outpatient populations. The percentages of stroke inpatients and outpatients on osteoporosis medication and supplements

Inpatients (N=1219) Outpatients (N=3129)

Osteoporosis Medication

Calcium

Vitamin D

Multivitamin

7.14% (N=87) 5.50% (N=172)

11.3% (N=138) 5.7% (N=180)

5.9% (N=72) 2.0% (N=64)

45.1% (N=550) 15.1% (N=472)

Conclusions: Overall, relatively few stroke patients were taking osteoporosis medications or supplements, either as inpatients or outpatients. Those patients being treated with specific osteoporosis therapies were older, more likely to be female and Caucasian. There is a need to increase the recognition and treatment of bone loss in this high-risk population.

P183MO. TIME TO MEDICATION GAP, DISCONTINUATION AND RESTART BEHAVIOR WITH ORAL BISPHOSPHONATES IN A LARGE U.S. PHYSICIAN GROUP Nichol MB1, Omar MA2, Dow T1, Bamford S3; 1JMRG Consulting, Encino, CA, USA, 2Novartis Pharmaceuticals, East Hanover, NJ, USA, 3Physician Associates, Pasadena, CA, USA Objectives: Clinical studies have demonstrated that women at risk of osteoporotic fracture reduce the risk of new osteoporotic fracture risk with bisphosphonate treatment. However, observational studies have also shown high discontinuation rates with these oral medications. This study investigated the persistence rates, discontinuation, and restart behavior among women started on one of two oral bisphosponates: alendronate or risedrenate. Methods: The patient population was selected from a large Western US physician group with access to integrated administrative data from 2003–2004. Female patients older than 40 were selected with at least three months of eligibility prior to the index bisphosphonate, and 12 months post-index. Time to discontinuation (60 or 90 days without medication), time to gap (15 days without medication), and time to restart (first fill after discontinuation) were analyzed using chi-square and proportional hazards. Results: 1,203 patients were included, with 875 patients initiating therapy on alendronate and 328 on risedronate. Patients started on alendronate average 41.5 days between fills, while those on risedronate averaged 43.5 days (p = 0.58), although alendronate patients experienced gaps in therapy quicker than risedronate users (see Figure). Approximately 25.6% of the alendronate users and 22.5% of the risedronate users who discontinued therapy for at least 60 days restarted therapy (p = 0.059). Risedronate users averaged 138.9 days to restarting therapy, and alendronate users restarted an average of 121.3 days after discontinuation (p = 0.05). Conclusions: These data demonstrate lack of persistence with oral bisphosphonates. It is also demonstrated that many patients are intermittent users who may experience discontinuation and restart episodes. Supported by Novartis Pharmaceuticals.

Time to Gap by Index Medication

S172

P184SA. THYROID HORMONES BONE MINERAL DENSITY AND BODY COMPOSITION IN 683 70 YEAR OLD WOMEN: THE NORDOS STUDY Stenstrom M1, Nystrom E2, Jansson S3, Johnell O4, Åkesson K4, Ohlsson C5, Mellstrom D5; 1Sahlgrenska University Hospital, dept of Geriatric Medicine, Gothenburg, Sweden, 2Sahlgrenska University Hospital, dept of Internal Medicine, Gothenburg, Sweden, 3 Sahlgrenska University Hospital, dept of Surgery, Gothenburg, Sweden, 4Malmoe University Hospital, dept of Orthopeadics, Malmoe, Sweden, 5Center for Bone Research at the Sahlgrenska Academy, Gothenburg, Sweden Aim: Thyroid hormones are known to aﬄict bone mineral density with increased bone turnover and subsequent bone loss. In this study our aim was to investigate the relation of thyroid hormones within the reference range to bone mineral density and body composition. Methods: A random sample of 70-year-old women in Gothenburg and Malmoe, Sweden were asked to participate. 683 participated, 482 from Gothenburg. All women were measured with DXA technique, Hologic 4500 A. Blood samples were collected in the morning under similar conditions after 10 hours fasting. Body composition was measured in subjects from Gothenburg. All participants were interviewed and information was collected about concomitant medication, fracture history, lifestyle factors, present and earlier medical conditions. Weight and height was obtained. Thyroid status was analysed in all subjects, with TSH, FT4 and T3. All subjects with thyroxin treatment were excluded, and those women with values outside reference range were also excluded. Results: Multiple regression models controlling for height weight and smoking showed no correlation between TSH and BMD at any site. T3 was negatively correlated to spine BMD p=0.008. FT4 negatively related to hip total BMD p=0.0004, neck BMD p=0.001, troch BMD p=0.001, spine BMD p=0.007. FT4 correlated to fat mass r 0.125 p<0.01 and indirectly to lean mass r -0.100 p<0.02 and indirectly to whole body BMD r -0.095 p<0.02. FT4 was related to s-calcium r 0.18 p<0.01 and s-alkaline phosphatase activity r 0.15 p<0.01. Conclusion: This study indicated a negative relationship between FT4 and bone mineral density in lumbar spine total hip and whole body after exclusion for subjects on thyroxin treatment and subjects with thyroid hormones levels outside the reference range. We found no correlation between TSH and bone mineral density.

P185SU. THE RISK OF FOREARM FRACTURE AMONG 6801 POSTMENOPAUSAL WOMEN Olsson JO1, Odén A2, Mellström D1; 1Department of Geriatrics, Center for Bone Research at the Sahlgrenska Academy University of Göteborg, Sweden, 2Department of Statistics, Chalmers University of Technology, Sweden Aims: In general the prediction of fractures among younger women is poorer than among older, where hip fractures are more common. In this study we investigated a set of risk variables with respect to their ability to predict forearm fractures among women. Methods: 6801 women from Gothenburg, Sweden mean age 59.0 participated in a prospective study of simultaneous screening of breast cancer and osteoporosis. Bone mineral density was measured in the nondominant forearm with DXA technique (Osteometer 2000). Fracture data was collected from hospital files and x-ray archives. Health questionnaires were obtained. Material contributing to the analysis: 6801 women from Gothenburg, 44893 patient years, 198 forearm fractures, mean age at entry 59.0 years (SD 7.02, range 40.6–88.8 years). Results: Age, BMD and previous fracture were the only variables contributing significantly to the prediction of forearm fracture. The gradient of risk per 1SD was 1.41 for BMD and the corresponding gradient was 1.49 when BMD and previous fracture were combined. The risk ratio of forarm fracture for a woman with previos fracture versus a woman without previous fracture was 1.77 (95% CI 1.30–2.41) provided that age and BMD were equal.The increase of forearm fracture risk was 5.6% per year of age (95% CI 3.5–7.9%). Conclusion: The gradient of risk for forearm fracture in early postmenopausal women was per 1SD 1.41. The risk ratio of forearm

fracture adjusted to BMD and age was 1.77 for a woman with previous osteoporotic fracture versis a woman without previous fracture.

P186MO. INCIDENCE AND CHARACTERISTICS OF FALLS LEADING TO HIP FRACTURE IN IRANIAN POPULATION Moayyeri A1, Abolhassani F1, Naghavi M2, Soltani A1, Larijani B1, Tavakoli Shalmani H2; 1Endocrinology & Metabolism Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, 2Undersecretary for Health, Ministry of Health and Medical Education, Tehran, Iran Aims: Hip fractures are the most serious consequences of falls in elderly people. Identifying the characteristics of falls leading to hip fracture may provide information about high risk individuals, environment, and activities useful for the development of intervention strategies. Methods: We are presenting data from the Iranian Multicenter Study on Accidental Injuries (IMSAI), a prospective populationbased study conducted in 9 provinces of Iran in 2003. In a period of 135 days, all the hospitals serving about 9.5 million people in the study area were prospectively surveyed for any incident injury resulting from accidental events. Results: A total of 3557 patients (2438 male, 1119 female) were admitted due to any injurious fall events, where 672 (18.9%) of them suﬀered a hip fracture. Annual incidence rates of injurious fall events and related hip fractures were 100.9 and 19.1 per 100,000 person-years, respectively. These figures were 237.1 and 93.6 per 100,000 person-years for people over the age of 50 years, respectively. 69.1% of fall injuries and 77% of hip fractures occurred indoors. Among 450 patients with hip fractures R 50 years of age, 61.8% arose from a fall from standing height or less. Only one in these 450 hip fractures occurred at the time of recreational activity. In multivariate logistic regression analysis, marriage was the only protective factor against hip fractures comparing to other fall-related injuries among younger participants < 50 years (odds ratio [OR] = 0.31). For older patients, falls from standing height or loss (OR= 2.67), falls during walking (OR = 1.71), and falls on stairs (OR = 1.73) were detected as risk factors of hip fracture. Married persons and those falling from a ladder or other elevations were less likely to fracture their hip in this age group. Conclusions: Incidence of injurious falls and related hip fractures is lower in Iran comparing to Western populations. Our data suggests that modification of the factors external to the homes is less likely to prevent more than a small proportion of fall-related hip fractures in Iran. Further studies on this topic have potential applications for developing preventive strategies.

P187SA. GREEN TEA DRINKING IS ASSOCIATED WITH INCREASED BONE MINERAL DENSITY IN ELDERLY WOMEN Muraki S1, Yamamoto S2, Oka H3, Yoshimura N3, Kawaguchi H1, Orimo H4, Nakamura K1; 1Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan, 2Department of Orthopaedic Surgery, Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan, 3Department of Joint Disease Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 4Department of Endocrinology, Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan Aim: Tea drinking is associated with increased bone mineral density (BMD), as demonstrated by previous studies, suggesting that flavonoids, contained in tea, may partly account for it. However, to our knowledge, this study serves as the first to investigate the relationship between consumption of green tea, which also contains flavonoids, and BMD. The aim of this study is to determine whether green tea drinking is associated with increased BMD. Methods: This study included 655 women aged 60 years and above (mean age 71.67.6 years) visiting the Osteoporosis Outpatient Clinic in Tokyo Metropolitan Geriatric Medical Center. At entry to the study, body height and weight were measured. Subjects were interviewed their lifestyles by means of a questionnaire which includes consumption of 10 dietary items such as green tea, milk, cheese, yogurt, fish, vegetable, tofu, natto, meat and coﬀee, smoking, consumption of alcohol, physical activity and use

S173 of drug for osteoporosis. For each dietary item, subjects were divided into two groups: consuming five or more days per week, and less than five days per week. BMD of lumbar spine, serum calcium, serum phosphorus, serum parathyroid hormone, serum alkaline phosphatase, serum osteocalcin, serum 1,25dihydroxyvitamin D and urine deoxypyridinoline were measured. Statistical analysis was performed using a non-paired t test and multiple regression analysis. Results: Among six hundred and fifty-five subjects, six hundred (91.6%) consume green tea five days or more per week and their mean BMD was 0.8080.199 g/cm2, and fifty-five (8.4%) consume green tea less than five days per week and their mean BMD was 0.7380.174 g/cm2. The BMD of the former subjects was significantly higher than the latter. The same result was achieved after adjustment for age, BMI, other dietary items, smoking, alcohol, physical activity and use of drug for osteoporosis. No significant correlation was observed between green tea drinking and any serum or urinary levels. Conclusions: We conclude that green tea drinking is associated with increased BMD among elderly women. Estrogenic eﬀect induced by flavonoids or apoptosis of osteoclasts induced by (-)-epigallocatechin-3-gallate, one of flavonoids, may account for the significant increase of the BMD.

P188SU. COSTS OF FRAGILITY FRACTURES AMONG MEN ARE CONSIDERABLE IN MANAGED CARE Adachi JD1, Magowan SH2, Borisov NN2, Lange JL2, Ohsfeldt RL3; 1Saint Joseph’s Hospital, McMaster University, Hamilton, Ontario, Canada, 2Procter and Gamble Pharmaceuticals, Mason, OH, USA, 3School of Rural Public Health, Texas A&M University, Bryan, TX, USA Aims: 1 in 5 males over the age of 50 years will sustain a clinical fragility fracture. The objective was to estimate the percent of total fragility fracture costs within managed care that are attributable to men ages 50+ years in managed care. Methods: The data source was Medstat Marketscan (comprised of approximately 45 private and public health plans in the US) for inpatient and outpatient medical claims of vertebral and nonvertebral fractures among both sexes ages 50 to 89 (n = 1,857,339) enrolled in managed care during the year 2003. Fracture rates were calculated for each of the anatomical sites (wrist, leg, arm, hip, pelvis, clavicle, spine). Fragility fractures were estimated by the fracture rate for ages 50 and over minus the fracture rate of the 40–49 year age group (assumed to be the baseline traumatic fracture rate). These fragility fracture rates were multiplied by the fracture-related direct medical costs, based upon 2003 Medicare fee schedule, over the first year after fracture. Results: Men are responsible for 30% of the total costs of fragility fractures in a managed care. Nonvertebral fractures account for over 90% of the costs associated with male fragility fractures. Conclusion: Fragility fractures in men pose a considerable clinical and economic burden within the managed care setting.

Aims: Kyphoplasty is now a widely performed procedure to treat vertebral body compression fractures (VCFs). In selecting appropriate patients for kyphoplasty, it is important to distinguish the pain caused by VCFs from the other numerous causes of back pain. The diﬀerential diagnosis must include not only osteoporosis, but also various causes of osteomalacia, endocrinopathy, and malignancy. It has recently been demonstrated that a biopsy taken during kyphoplasty confers no increased morbidity, and that even in the setting of normal laboratory values can identify patients with multiple myeloma. In this prospective study, we identified 3 unsuspected cases of lymphoma during routine biopsy during kyphoplasty. Methods: A prospective histological evaluation of biopsies from presumed osteoporotic VCFs was performed to confirm latent hematopoetic dyscrasia. From August 2001 to September 2005, we performed vertebral body biopsies in 238 patients for 525 levels. We additionally performed a simultaneous iliac crest bone marrow aspiration. Vertebral body biopsies were taken using a KyphXt Bone Biopsy Device during the kyphoplasty procedure. Results: All specimens demonstrated signs of bone remodeling and/or fracture healing; woven bone and cartilaginous tissue were often found representing callus formation. In three patients (1.3%), both the bone biopsy and the bone marrow showed evidence of B-cell lymphoma. Conclusions: Bone biopsy before kyphoplasty is advocated as a screening test for occult malignancy. Three patients in this series were diagnosed with unsuspected malignancy and were referred to an oncologist for further evaluation and treatment. Lymphoma has been an uncommon cause of VCFs, but based on our experience in this series, we recommend that biopsies be taken and followed-up on all kyphoplasty patients in order to rule out unsuspected malignancies.

Annual rates & cost of fragility fractures in men and women over 50 years of age per 1,000 in a managed care population Women

Type of fracture hip vertebral leg arm pelvis clavicle wrist Total

Men

Annual fracture Annual cost ($) per rate per 1,000 fracture 26,856 19.0

Annual fracture costs per 1,000 510,264

Annual fracture rate per 1,000 9.5

Annual fracture costs per 1,000 255,132

% of total fracture costs occurring in men 33%

907 12,174 5567 10,198 1373 2688

25,124 141,218 69,031 100,960 2,471 40,051 889,120

13.6 4.5 4.1 3.0 0.4 2.9

12,335 54,783 22,825 30,594 549 7,795 384,013

33% 28% 25% 23% 19% 16% 30%

27.7 11.6 12.4 9.9 1.8 14.9

P189MO. UNSUSPECTED LYMPHOMA DIAGNOSED USING BIOPSY DURING KYPHOPLASTY Edobor-Osula OF, Shindle MK, Tyler W, Shindle L, Gardner MJ, Lane JM; Hospital for Special Surgery, New York, USA

Frequency of Kyphoplasty by Level

P190SA. RISK FACTORS OF FRACTURES AMONG OLDER PERSONS IN FINLAND: A POPULATION BASED 12 YEAR FOLLOW-UP Piirtola M1,2,3, Vahlberg T1, Isoaho R1,4, Aarnio P2, Kivelä S-L1,2,5; 1University of Turku, Turku, Finland, 2Satakunta Central Hospital, Pori, Finland, 3Härkätie Health Centre, Lieto, Finland, 4 Pori Health Centre, Pori, Finland, 5Turku University Hospital, Turku, Finland Aims: The number of fractures is assumed to increase. Information about the risk factors of fractures exists. There is, however, little information about the strength of risk factors to predict fractures in time. The aim of this study is to describe risk factors of all types of fractures in 5 and 12 year follow-up periods in aged population. Methods: The study is a part of the larger ‘‘Lieto Study’’, a clinical population based longitudinal survey of subjects aged 65

S174 years or over in the municipality of Lieto, Finland, started in 1990–1991. The fractures occurred from year 1991 until 2002 in Table 1. Baseline risk factors of all fractures, relative risks (RR) with their 95 percent confidence intervals (95% CI) and p-values in age-adjusted multivariate Poisson Regression analyses among men and women sustained at least one fracture during the five and 12 year of follow-up. Men

Risk factor

5 year follow -up RR (95% CI) #

Women 12 year follow-up RR (95% CI) #

Number of medication 0–5 1 6+ 1.0 (0.4 – 2.6) Ability to walk stairs alone yes, without 1 diﬃculties yes, with 0.8 diﬃculties (0.3 – 2.0) no one self 0.7 (0.1 – 5.8) Ability to wash alone yes, without 1 diﬃculties yes, with 0.4 diﬃculties (0.0 – 3.1) no one self 4.4 (0.6 – 31.0) Zung score 20 -44 1 1 45 -80 3.6 2.0 (1.7 – (1.2 7.6)*** A compressed thoracic vertebra no 1 1 yes 4.1 3.4 (1.8 – 9.6) (1.8 *** *** MMSE score 24–30 1 18–23 1.6 (0.8 0–17 5.0 (0.7 Hand Grip Strength (Kpa) 76 + 48 -75

#

5 year follow -up RR (95% CI) §

12 year follow-up RR (95% CI) §§

1177 subjects (482 men, 695 women, and mean age 73 years) were derived individually from medical records. Baseline risk factors for all types of fractures were analysed for both five and 12 year follow-up periods by gender. First age adjusted and then ageadjusted multivariate Poisson regression methods were used in analyses. Results were presented using Relative Risks (RR) with their 95% confidential intervals (95% CI). Here we present the results of age-adjusted multivariate Poisson regression analyses for persons sustained at least one fracture during the follow-up periods. Results: During five and 12 year of follow-ups 178 persons sustained altogether 221 fractures (45 in men; 176 in women), and 307 persons sustained 425 fractures (97 in men; 328 in women), respectively. The risk factors for persons sustained at least one fracture during the follow-up periods are presented in table 1. Conclusion: Risk factors of fractures vary by gender. Low hand grip strength, low BMI and a compressed thoracic vertebra in women and depression symptoms (Zung) and a compressed thoracic vertebra in men were independent risk factors both in five and 12 year follow-ups. As the number of older people is increasing, to screen risk factors, and implement preventive

P191SU. LONGITUDINAL ASSOCIATIONS BETWEEN PHYSICAL ACTIVITY AND BONE MASS DURING CHILDHOOD: THE FELS LONGITUDINAL STUDY Lee M, Remsberg KE, Wurzbacher K, Choh AC, Demerath EW, Chumlea WC, Sun SS, Towne B, Siervogel RM, Czerwinski SA; Lifespan Health Research Center, Wright State University School of Medicine, Dayton, OH, USA

– 3.4)*

– 6.2)

1 2.3 (1.4 – 3.8) ***

– 3.2)

1 1.4 (0.8 – 2.3) 2.4 (1.1 – 5.7) *

– 37.5)

%47 BMI score 30 + 25 -29.9 0.1 – 24.9

1 1.3 (0.8 – 2.3) 2.2 (1.2 – 4.0) *

Ability to move in familiar surrounding yes no

1 1.5 (1.0 – 2.2) * 2.1 (1.4 – 3.4) ***

1 1.5 (0.9 – 2.3)

1 1.8 (1.3 - 2.6) *** 2.1 1.9 (1.3 – 3.4) ** (1.3 - 2.7) ***

Diastolic blood pressure (mmHg) 78 + %77 Binocular sight 0.3 + < 0.3

1 2.0 (1.3 – 2.9) ***

1 1.2 (0.9 – 1.7) 1 1.4 (0.7 -2.6) 1 8.0 (1.1 – 59.8)*

* p % 0.05, ** p%0.01, *** p%0.001 # Adjusted for age, number of medication, ability to walk stairs alone, ability to wash alone, depressive symptoms (Zung) and a compressed thoracic vertebra. ## Adjusted for age, MMSE, depressive symptoms (Zung) and a compressed thoracic vertebra. § Adjusted for age, a compressed thoracic vertebra, MMSE, hand grip strength, BMI and sight. §§ Adjusted for age, a compressed thoracic vertebra, hand grip strength, BMI, diastolic blood pressure and ability to move in familiar surrounding.

Introduction: Bone mass during growth is an important predictor of osteoporosis risk. Recent studies of children have shown the importance of physical activity on bone growth; however, few studies have examined longitudinal eﬀects of physical activity on bone mass. Study aims: We examined the concurrent eﬀects of changes in children’s physical activity over time on changes in bone mass. Methods: The study sample consisted of participants in the Fels Longitudinal Study. A total of 99 white children (54 males and 45 females, 8 to 18 years of age) had 413 serial observations with both physical activity and bone mass data. Leisure and sport activity level was determined using the Baecke questionnaire modified for children. Dual-energy X-ray absorptiometry (Hologic, Waltham, MA, USA) was used to measure bone mineral content (BMC) and bone density (BMD) in the total body (TB), femoral neck (FN) and lumbar spine (LS). Mixed models for serial data were used to estimate the eﬀects of physical activity on bone mass. Results: The pattern of eﬀects of physical activity on bone mass diﬀers by sex. For males, leisure activity has significant eﬀects on the initial values of TB-BMC, TB-BMD, LS-BMC and LS-BMD (p < 0.05). In addition, the rates of change in all four bone measures over time diﬀer significantly according to concurrent leisure activity level (p < 0.05). Sport activity has no eﬀect on bone mass in males. In females, leisure activity has significant eﬀects on the initial values and the rates of change of TB-BMC and TB-BMD (p < 0.01). Sport activity has significant eﬀects on the initial values in FN-BMC and FN-BMD (p < 0.01). The rates of change in TB-BMC, TB-BMD, FN-BMC, and FN-BMD diﬀer significantly by sport activity level (p < 0.05). The relationship between physical activity and bone mass remains significant even after adjusting for BMI. Conclusions: Our serial data shows that physical activity is a strong predictor of bone mass during childhood. Furthermore, there are sex diﬀerences in the eﬀect of changing physical activity level on changes in bone mass.

P192MO. PEAK BONE MASS OF IRANIAN POPULATION: THE IRANIAN MULTICENTER OSTEOPOROSIS STUDY (IMOS) Moayyeri A1, Larijani B1, Keshtkar AA1, Hossein-nezhad A1, Bahrami A2, Omrani GH3, Rajabian R4, Nabipour I5, Soltani A1; 1 Endocrinology & Metabolism Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, 2Tabriz University of Medical Sciences, Tabriz, Iran, 3Shiraz University of Medical Sciences, Shiraz, Iran, 4Mashhad University of Medical Sciences, Mashhad, Iran, 5Bushehr University of Medical Sciences, Bushehr, Iran

S175 Aims: Osteoporosis is a major public health problem in Western countries and is projected to have a similar impact in the Middle East. It has been suggested that peak bone mineral density (BMD) may be lower in this part of the world compared with the Western world. The purpose of the Iranian Multicenter Osteoporosis Study (IMOS) was to determine reference values of BMD in a randomly chosen sample of healthy Iranian subjects. Methods: 5201 participants (2340 males, mean age 42.7 13.8) were recruited based on randomized clustered sampling from all regions of five major cities across the country. Bone mass was determined using dual-energy X-ray absorptiometry (DXA) on Lunar bone densitometers. To explore the relationship between age and BMD, a hierarchical approach (from cubic to quadratic to linear models) was used to find the best-fitted model for each densitometric site. Results: In women, peak lumbar BMD (1.182 0.127 g/cm2) occurred in the 29 to 33-year age group (cubic model fitted), whereas peak total femur BMD (1.006 0.126 g/cm2) occurred in the 32 to 36-year age group (quadratic model fitted). In men, peak lumbar BMD (1.181 0.153 g/cm2) and femoral BMD (1.096 0.159 g/cm2) both occurred in the 20 to 24-year age group (linear model fitted for both). The subject classification according to the WHO criteria was similar using the IMOS and NHANES reference values for the femur; for the spine, the Lunar reference values classified a larger proportion of men as osteoporotic (14.2% vs. 3.5%) compared to IMOS. Conclusions: There is no evidence of low peak BMD in Iran. When standardized to mg/cm2 units using established formulas, Iranian peak bone mass values are comparable to that of Western and Middle Eastern countries and generally higher than Eastern Asian countries (Table). Mean values of standardized bone mineral density (sBMD) in mg/cm2 for the peak bone mass of lumbar and femoral regions in diﬀerent countries Male

Iran (current study) USA Canada Sweden Italia China Taiwan Japan Lebanon Saudi Arabia Kuwait Qatar Turkey

Female

Lumbar spine

Total femur

Lumbar spine

Total femur

1264

1042

1265

954

1134 1141 1132 1173 1263 1079 1073

1055 1008 1076 1003 1036 1044 1034

1150 1117 1143 1117 1046 1155 1127 1263 1059 1177 1106 1010

955 951 934 928 888 886 921 928 940 970 988 863

P193SA. MISLEADING HISTORY OF PAIN LOCATION IN 51 PATIENTS WITH OSTEOPOROTIC VERTEBRAL FRACTURES Friedrich MF1,2, Gittler GG3, Pieler-Bruha EP1; 1Department of Orthopaedic Pain Management, Orthopaedic Hospital Vienna, 2 CEOPS- Center of Excellence of Orthopaedic Pain Management Vienna, 3University of Vienna, Department of Psychology, Vienna, Austria The aim of this study was to investigate associations between the location of osteoporotic vertebral fractures and the patient’s localization of pain. 51 consecutive patients (m: 6, f: 45; average age: 74.8 years) with diagnosed osteoporotic vertebral fractures between T8 and L2 were included in the study. Exclusion criteria were: fractures above T8 and below L2, spondylolysthesis, disc herniations, tumors, infections and instability. Pain location was assessed by pain drawing, subdivided into thoracic, lumbar and thoracic plus lumbar pain areas, and pain intensity using a 101 numeric rating

scale. Furthermore, the onset of back pain and the lack or the indication of a trigger event at the onset of pain were documented. Only 4 of 20 patients with thoracic fractures reported thoracic pain, while the other 16 (80%) reported only lumbar pain. The location of the fracture and the patient’s pain report were not related. Cohens Kappa=0.046; p=0.438). Patients with thoracic or lumbar osteoporotic fractures reported pain mainly in the lumbosacrogluteal area. Therefore, the complaint of low back pain in persons at risk for osteoporotic fractures may require both thoracic and lumbar x-rays. Low back pain patients with a suspect history of an osteoporotic vertebral fracture should also be given an x-ray of the thoracic and lumbar spine. Patients with a thoracic vertebral fracture had more severe pain than patients with a lumbar vertebral fracture. Onset not related to a fall or a false movement related to a significantly longer pain duration.

P194SU. A MILK-FREE DIET DOES NOT CONTRIBUTE TO THE HIGH PREVALENCE OF FRACTURES IN CHILDHOOD Konstantynowicz J1, Kaczmarski M2, Jamiolkowski J3, PiotrowskaJastrzebska J3, Zielinska A2, Seeman E4; 1Pediatrics & Auxology, 2 Third Department of Pediatrics, 3Public Health and Biostatistics, Medical University of Bialystok, Poland, 4University of Melbourne, Endocrinology, Melbourne, Australia Aims: A low calcium intake during growth is regarded as a risk factor for bone fragility despite the lack of evidence for higher fracture rates associated with a consumption of calcium below the recommended daily intake (RDI) of 800–1200 mg. As the lack of evidence may be due to many participants consuming amounts of calcium equivalent to or higher than the RDI, we studied a group of children with intakes well below the RDI due to life long cow’s milk allergy (CMA). Methods: We compared fracture prevalence and bone mineral density (BMD), measured using dual-energy x-ray absorptiometry, in 144 boys and 86 girls aged 2–20 yr with CMA given a milk-free diet for 3.6 years (range 2.5–14) and 745 controls (422 boys, 323 girls) consuming a customary milk intake. Multiple and logistic regression analyses were used to assess trait associations. Results: In the females, a greater proportion of cases (11.6%) than controls (7.4%) had fractures [Odds Ratio: 3.01, 95% confidence intervals (CI): 1.14 - 7.95; p = 0.03] but the milk-free diet accounted for less than 1% of diﬀerence in fracture prevalence. BMD was not reduced in female cases. In males, fractures were no more common in cases (9%) than controls (10.4%). The male cases had lower arm BMD (P = 0.003) but the milk-free diet accounted for 0.1% of the BMD deficit. Conclusion: Fractures are common in children and adolescents. Little of the fracture burden is explained by an intake of calcium below the RDI.

P195MO. FEAR OF FALLING IN PATIENTS NEWLY DIAGNOSED WITH OSTEOPOROSIS Wetherell CE1, Thornton EW1,2, Davies ADM1,2, Poll L3, Siddiqi M3; 1University of Liverpool, Liverpool, UK, 2Mersey Care National Health Service Trust, Liverpool, UK, 3Aintree University Hospital National Health Service Trust, Liverpool, UK Aims: To measure levels of fear of falling (FOF) in fracture patients newly diagnosed with osteoporosis and to see if any measured eﬀects are stable over time. Method: The study was a three-phase longitudinal design. 84 post-fracture patients (mean age 63; sd=9.83) were recruited from a hospital bone density clinic and interviewed before their DXA scan. FOF was measured using the SAFFE (Lachman et al., 1998); the FES (Tinetti et al., 1990) and the FHI (Markson et al., 1995). Personality was measured using the N (neuroticism) scale of the NEO-PI (Costa & McRae 1992b). The FOF questionnaires were sent out by post to the patients immediately after diagnosis and again at six months post-diagnosis. A total of 54 patients completed all three sets of questionnaires correctly and these data were analysed. Analysis showed there was no significant diﬀerences between those who did return questionnaires and those who did not.

S176 Results: Repeated measures design analysis showed that there was an increase in FOF in patients newly diagnosed with osteoporosis, as measured by two scales: the FES (Chi sq = 9.71; p=.008) and the SAFFE Worry subscale (Chi sq = 20.31; p=%.001) and this increase in FOF was maintained over time. Factor analysis revealed that the FES and SAFFE Worry subscale loaded onto the same factor with the SAFFE Restriction subscale and the FHI loading onto separate factors. A median cutoﬀ point was established for the N scale and analysis carried out to compare those with a high and low score. All FOF questionnaires’ baseline scores were significantly higher in those with above median N scores. This eﬀect was maintained on diagnosis of osteoporosis, though no significant extra increase in FOF was found. Conclusions: FOF increased significantly in those patients newly diagnosed with osteoporosis and this did not depend on levels of N. Those with higher N scores had higher baseline scores for all FOF scales, including those measuring activity restriction. These results suggest FOF may not be a unitary construct and furthermore levels of FOF may be influenced by personality type.

P196SA. ASSOCIATIONS BETWEEN BONE HEALTH NUTRIENTS AND ULTRASOUND IN THE SWISS ELDERLY POPULATION: PRELIMINARY ANALYSIS OF EVANIBUS Wynn Dumartheray E1, New SA3, Whittamore DR3, Krieg MA1, Burckhardt P2; 1Outpatient Clinic, Lausanne University Hospital, Lausanne, Switzerland, 2Clinique Bois-Cerf, Osteoporosis Consultation, Lausanne, Switzerland, 3Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK Osteoporosis is a major health problem; fracture prevention depends on eﬃcient screening procedures and knowledge of reversible risk factors such as nutrition. Whilst optimum diet for osteoporosis prevention remains unknown, a variety of nutrients are important to the ageing skeleton including protein, calcium, vitamin K, potassium and micronutrients. There is growing interest that the Western diet may be a risk factor for osteoporosis through excess protein supply. Fruit and vegetable intake may balance the excess acidity by providing potassium. The aim of this study was to examine for preliminary associations between key bone nutrients and indices of bone health (as measured by ultrasound) in the Swiss elderly population. As part of on going study in elderly Swiss women (n=401) (mean age 80.4 yrs, body mass index (BMI) 25.2, broad-band ultrasound attenuation (BUA) 98.5, speed of sound (SOS) 1528.8, stiﬀness index (SI) 68) on nutrition and bone health, we identified a sub-group of 217 women (mean age 80.64 yrs, BMI 24.8, BUA 97.4, SOS 1524.9, SI 66.1) who had reported a fracture in their life-time but who were not on osteoporosis treatment. Dietary intake was assessed with a validated food frequency questionnaire. Bone evaluation was done with a quantitative heel ultrasound (BUA-Achilles, Lunar Corporation) as this approach was predictive of fracture risk in elderly women. Pearson correlations between bone ultrasound indices and nutrients

Pearson Correlation Energy Protein energy adjusted Magnesium energy adjusted Calcium energy adjusted Potassium energy adjusted PRAL NEAP * p < 0.05 ** p < 0.01

Speed of sound (SOS)

Broad-band ultrasound attenuation (BUA)

Stiﬀness index (SI)

ns ns

ns 0.138*

ns ns

0.167*

ns

0.140*

0.190**

0.151*

0.165*

0.170*

0.153*

0.161*

ns ns

-0.137* ns

ns ns

Higher intakes of protein, magnesium, potassium and calcium and lower PRAL estimates (a measure of dietary acidity) were found to be correlated to higher bone ultrasound results. Correlations were relatively weak but likely to be biologically relevant and were on the whole consistent amongst the ultrasound measurements. These findings suggest that protein and suﬃcient alkali supplied in the diet are beneficial to bone in these elderly subjects with previous fractures. Further analysis of the data will determine if the findings apply to the entire study group.

P197SU. IS FEAR WORSE THAN FACT? HEALTH RELATED QUALITY OF LIFE ASSOCIATED WITH FEAR OF FALLING, FALLS AND FRACTURES Iglesias CP1,2, Manca A2, Torgerson DJ1; 1Department of Health Sciences, 2Centre for Health Economics, University of York, York, UK Aims: To investigate the impact of falls, fractures and ‘‘fear of falling’’ on the health related quality of life (HRQoL) of elderly women in the UK. Methods: HRQoL was measured using the EQ5D and SF12 generic questionnaires in three UK-based large prospective clinical studies (two RCTs and one cohort study). Additionally, data on risk factors for fracture and fear of falling measured using a six-level Likert scale (0=none of the time to 5=all of the time) were collected on more than 7,000 women aged 70+ living in the community. The analyses focussed on an 18-month follow-up period common to all three studies, with participants assessed at 6-month intervals. To appropriately represent the complex nature of the data, Bayesian multivariate hierarchical models were used to analyse HRQoL scores. This modelling technique allowed us to capture the longitudinal nature of the data (i.e. repeated measures for each participant); facilitated the estimation of the correlation between the various HRQoL instruments; and aided the identification of trends in HRQoL scores overtime. Results: In all three studies falls and fractures were related to a statistically significant reduction in HRQoL. Overtime EQ-5D scores were reduced by –0.02 (SE0.005) and –0.08 (SE0.013), in the event of a fall or a fracture, respectively. The physical (PSC) and mental scores (MSC) of the SF-12 were also negatively aﬀected by falls and/or fractures, reductions were in the range [–1.5 to -0.5], for the PSC and MSC, respectively. The level of anxiety associated with a fear of falling was the variable with the strongest statistically significant influence on the HRQoL scores measured here. The higher the level of anxiety, the larger the decrement in HRQoL. Other covariates associated with statistically significant reductions in HRQoL were, smoking status, weight and age. Conclusions: Falls and fractures have a significant impact on individuals’ HRQoL. Similarly, anxiety related to fear of falling has a strong negative eﬀect on HRQoL. This study can significantly contribute to clinical and economic evaluations of the treatment/prevention of falls and fractures by facilitating the estimation of quality adjusted life years loss related to these events in the UK population.

P198MO. EVALUATION OF QUALITY OF LIFE IN MEN WITH VERTEBRAL FRACTURES ATTRIBUTABLE TO OSTEOPOROSIS Ramirez E1, Clark P2, Wacher N2; 1National Institute of Rehabilitation, SSA, México, 2Clinical Epidemiology Unit CMN Siglo XXI, IMSS, México Osteoporosis (OP) in men is well recognized and studied in developed countries but not in developing countries like Mexico. It is estimated that 1 of every 4 men over 50 years old will sustain a fracture attributable to osteoporosis. In Mexico, the impact of OP and its fractures has been evaluated. The prevalence of vertebral fractures is 19.5% and 9.7% in women and men, respectively, over 50 years of age. In the health context, the studies for LQ in people with vertebral factures attributable to OP are insuﬃcient. Vertebral fractures have severe eﬀects in the individual such as decline in functionality and dependence. Mental as well as physical aspects of life are impaired.

S177 The aim was to evaluate the quality of life in Mexican men with vertebral fractures using the QUALEFFO to define the impact of vertebral fractures in pain, physical function, mental function, social function and perception of health. Method: In a cross sectional study, the QUALEFFO was applied to a randomized sample of 407 men over 50 years in Puebla, Mexico. The instrument was applied through a home interview and SF36 was applied concurrently. OP diagnosis and/or vertebral fractures (3 months old) was defined morphometrically using a modified Eastell criteria. Osteoporosis was diagnosed using the WHO criteria. Results: 70 men were analyzed for the purpose of this analysis, 34 with vertebral fractures and 36 without fracture, 7611.53 years average age, 64.3% married. Significant results were found between the groups with and without fractures in: physical function (p=0.01), social function (p=0.03), health perception (0.001) and mental function (p=0.05) using the specific instrument (QUALEFFO). QUALEFFO Domains results Qualeﬀo Domain

With Fractures

Pain 10.505.10 Physical function 43.2620.78 Social function 20.154.67 Health perception 10.532.39 Mental function 22.187.29 Global 107.0933.11

Without fractures ‘’p’’ value 9.335.14 32.2813.57 17.884.03 8.502.49 19.085.77 87.0823.41

0.34 0..01 0.03 0.001 0.05 0.005

Conclusion: Our results demonstrate that quality of life in men with vertebral fractures is aﬀected and the QUALEFFO questionnaire has good specific properties to be used in patients with vertebral fractures.

P199SA. IDENTIFYING WRIST FRACTURE PATIENTS WITH HIGH ACCURACY BY AUTOMATIC CATEGORIZATION OF X-RAY REPORTS Cranney A1,2, deBruijn B3, O’Donnell S1, Martin J3, Forster A1,2; 1 Clinical Epidemiology Program, Ottawa Health Research Institute, 2Faculty of Medicine, University of Ottawa, 3National Research Council Canada, Institute for Information Technology, Ottawa, Canada Aims: Despite eﬀective interventions, the majority of low-trauma fracture patients do not receive secondary prevention for osteoporosis. To prevent recurrent fractures, a systematic method to identify this high risk population is critical. Natural language processing methods, including text classification, translate free text reports into coded data and have been utilized previously in clinical medicine. We performed this study to determine the accuracy of several text classification (TC) methods for categorizing wrist x-ray reports into those with and without an acute fracture. Methods: Retrospective chart review at a tertiary academic hospital. We randomly sampled patients older than 40 years who had a wrist x-ray between 2003 and 2004. Two expert reviewers examined 751 x-ray reports to determine the presence of an acute fracture. Using these ratings as the gold standard, we then evaluated three text classification methods, including two information retrieval methods using key word searches (IR-1, IR-2) and a machine learning method using a support vector machine (TC-1), on a derivation set of 493 reports. We validated the accuracy of TC-1 using a validation set of the remaining 258 reports. We measured the accuracy, sensitivity, specificity, and positive predictive value of the three text categorization methods for correctly classifying the presence of a wrist fracture. Results: Of the 751 reports, 301 were classified as having evidence of a wrist fracture by the expert reviewers. Accuracies for IR-1, IR-2 and TC-1 on the derivation set were 78%, 89%, and 94% respectively. In the validation set, the accuracy, sensitivity, specificity, and positive predictive value of TC-1 were respectively, 94%, 96%, 93%, and 88%. Conclusions: TC-1 accurately classified wrist x-ray reports into those with and without a fracture. Future work will include the

validation of TC-1 in another fracture population and the development of decision support tools using support vector machinebased applications to trigger electronic reminders to the both patients, and treating physician to improve access to osteoporosis testing and therapies. Research supported by CIHR

P200SU. ASSOCIATION OF ESTROGEN RECEPTOR ALPHA GENE POLYMORPHISMS WITH BONE MINERAL DENSITY: STUDY IN POSTMENOPAUSAL WOMEN OF DIFFERENT ETHNICITIES Mitra S1, Desai M1, Ahuja M2, Khatkhatay I1; 1National Institute for Research in Reproductive Health, 2Mahatma Gandhi Memorial Hospital, Parel, Mumbai, India Aim: Various genes have been implicated to account for genetic basis of osteoporosis that include genes for steroid hormone receptors, cytokines and bone associated proteins. The role of estrogen is vast in bone physiology, from sexual dimorphism of skeleton to maintenance of balance in bone metabolism through several proteins regulated by it. Thus, estrogen receptor alpha (ER) gene polymorphisms in the intron I (Xba I and Pvu II), known to be associated with osteoporosis, menarche age and breast and endometrium cancers, have been studied in diﬀerent populations. These polymorphisms are likely to aﬀect total tissue estrogen exposure as P-allele (loss of Pvu II site) results in the binding site for transcription factor myb b. Polymorphism Xba I is reported to be in linkage disequilibrium with Pvu II, which varies with population ancestry. We compared the relationship of ER polymorphisms with BMD and vitamin D receptor (VDR) gene polymorphisms in two ethnic groups. Further, we compared the population diﬀerentiation at these loci. Methods: Postmenopausal women of Indian-ethnic (n=350) and Indian-Parsee (n=100) were genotyped followed by BMD measurements. Parsees constitute diﬀerent ethnic group as the gene pool is originally from Iran. Results: Genotype XX and PP (homozygous for absence of polymorphism) were associated with higher BMD at spine and hip in both the groups; however the average BMD of Indian-Parsee cohort was significantly higher. Observed and expected heterozygosity was low in Parsees (0.480, 0.350). Genotypes XX and PP were significantly (p=0.001) prevalent in Parsee cohort than Indian-ethnic, whereas genotypes Xx and Pp were prevalent in Indian-ethnic. ER polymorphic alleles showed stronger linkage disequilibrium in Parsees. Haplotype PX (46.3%) was prevalent in Parsee women whereas px (33.3%) in Indian-ethnic women. PX carriers with VDR T (Taq I) and b (Bsm I) allele had significantly higher BMD than px-T/px-b in both groups. Conclusion: The genetic variation at the ER locus singly or in relation to VDR gene may influence interethnic BMD variation. The studies on interpopulation diﬀerentiation at these loci may help in gene mapping eﬀorts in search of unanimous genetic marker for osteoporosis and giving insights into evolutionary history of complex diseases.

P201MO. THE ECONOMICS OF TARGETING FRAGILITY FRACTURES IN AN ORTHOPEDIC TREATMENT UNIT Sander B1,2, Elliot-Gibson V3, Beaton DE3, Bogoch ER3, Maetzel A4; 1University of Toronto, Department of Health Policy, Management and Evaluation, Toronto, ON, Canada, 2University Health Network, Division of Clinical Decision Making and Health Care Research, Toronto, ON, Canada, 3St. Michael’s Hospital, Mobility Program Clinical Research Unit, Toronto, ON, Canada, 4 Amgen Europe GmbH, Lucerne, Switzerland Objective: The orthopedic unit at a university teaching hospital hired an osteoporosis (OP) coordinator to manage a collaborative program to identify fragility fracture patients and arrange for investigation and treatment of OP and patient education. This study evaluates the cost-eﬀectiveness for an academic hospital to hire a coordinator and identifies areas for future research. Methods: Using patient-level data from the first year of the program and data from the literature, a 1-year decision analytic

S178 model was developed. The model calculates the annual incidence of a further hip fracture dependent on type of index fracture (hip, wrist, humerus, other), attribution to OP, age and gender. Referral uptake, initiation of OP treatment and compliance modified the incidence of further hip fractures in the presence of a coordinator. Deterministic and Bayesian modeling techniques were used to evaluate the cost-eﬀectiveness and its consequences for decision making. An expected value of perfect information (EVPI) analysis was performed to identify areas where more research would be most valuable. Results: A coordinator who manages 500 patients yearly would reduce further hip fractures from 35 to 25, a net cost saving to the hospital of C138,450. A coordinator was cost-saving: 1) if the costs of treating a further hip fracture are greater than C8,000, 2) if only half of patients initiated treatment and only half of these complied, 3) if treatment eﬃcacy reduced fractures by as low as 20% and 4) if only 190 patients were seen annually. The probability of the coordinator being a cost-eﬀective intervention exceeds 80% if willingness to pay (WTP) is C16,000 per hip fracture avoided or greater. More research is most valuable for the treatment costs of further hip fractures (C90,000 at a WTP threshold of C15,000). Conclusion: Employment of a coordinator to manage fragility fracture patients may reduce further hip fractures and was a dominant strategy in the deterministic analysis. The Bayesian analysis showed a high probability of cost-eﬀectiveness for this intervention from the hospital’s perspective if WTP exceeds C16,000 per hip fracture avoided. However, if WTP is low, more research on treatment costs of further hip fractures is warranted.

P202SA. CLINICAL CHARACTERISTICS OF PATIENTS WITH FRAGILITY FRACTURES WITHIN OSTEOPENIC RANK Riera F1, Riera-Espinoza G1,2; 1Unilime UC, Hospital Universitario ‘‘Dr. Angel Larralde’’, Universidad de Carabobo, 2 Unidad Metabolica del Centro Policilinico Valencia, Valencia, Venezuela Fracture risk is associate with diverse risk factors, one of them being bone mineral density. A high incidence of fractures in patients not only within the osteoporotic rank but also within osteopenic rank of BMD has been recently reported. Our objective is to compare clinical characteristics of patients with fractures by bone fragility with osteopenia or osteoporosis in femoral neck or lumbar spine. 86 fractures in 49 patients were evaluated, clinical history and risk factors were obtained at admission, as well as BMD measured by DXA at femoral neck or lumbar spine, L1-l4 (LUNAR DPX, VC 1.5%) and measurement of mineral metabolism parameters. The results obtained are shown in the table below (Fig.1). Clinical Characteristics of Patient with Fragility Fractures Osteopenia Osteoporosis Osteopenia Osteoporosis CF CF CL CL n Age Menopause Age No of Fractures Weight Height BMI BMD gr/cm2 FN BMD T-score FN BMD gr/cm2 LS BMD T-score LS Serum Ca mg/dl Cal/creat u Serum CTx ng/ml

33 62.2 10 47.44 1.581.03 64.+-9 1.540.06 274 0.780.05 -1.720.47 0.900.1 -2.451.06 9.310.6 0.160.1 0.30.2

16 60.7511 505 2.131.4 5711 1.490.05 242 0.640.08 -3.360.73 0.740.1 -3.071.0 9.20.4 0.20.1 0.30.1

20 58.211 47.25 1.421.12 669 1.560.04 273 0.780.03 -1.870.7 0.980.07 -1.680.62 9.340.56 0.150.1 0.30.2

29 64.28.6 49.15 1.961.20 6010 1.500.06 264.1 0.710.09 -2.571.0 0.770.09 -3.310.72 9.240.6 0.20.1 0.30.2

In conclusion, there are no significant diﬀerences between osteopenic and osteoporotic patients, independently of the place of measurement, femoral neck or lumbar spine regarding age, age of menopause, number of fractures, being this 1.58 and 2.13 fract/ pacient in osteopenia/osteoporosis, respectively, at femoral neck.

Similarly, the number of frac/pac was 1.42 and 1.96 in osteopenic and osteoporotic subjects according to BMD at lumbar spine.

P203SU. POST-FRACTURE CARE AND OSTEOPOROSIS IN FIVE COMMUNITIES IN ONTARIO, CANADA Jaglal SB1,4,5, Bogoch E2, Carroll J3, Hawker G1,4, Jaakkimainen L4,5, Kreder H3,4, Zwarenstein M5; 1University of Toronto, 2St. Michael’s Hospital, 3Mount Sinai Hospital, 4Sunnybrook and Women’s College Health Sciences Centre, 5Institute for Clinical Evaluative Sciences, Toronto, ON, Canada Aims: The overall purpose of this project was to implement an integrated post-fracture care model in five communities in Ontario, Canada. The aim of the first phase was to determine baseline rates of post-fracture care for osteoporosis within these communities. Methods: A telephone survey was conducted with patients 40 years and older who had experienced a minimal trauma wrist, hip, spine or shoulder fracture in 2003. The survey examined postfracture care and osteoporosis management (pharmacological and non-pharmacological); health behaviours (exercise, calcium and vitamin D, fall prevention); and knowledge. Results: 44% (125/285) of eligible fracture patients responded of which 78% were female, with a median age of 71. 45% had experienced a wrist fracture, 34% hip, 17% shoulder and 4% vertebral fracture. Sixty-five percent of respondents indicated that this was their first fracture since age 40. Twenty-six percent of respondents were diagnosed with osteoporosis or osteopenia before their 2003 fracture, 11% were diagnosed after their fracture, and 63% had no known diagnosis. Of those who had been diagnosed, 85% had been prescribed osteoporosis medications. 61% of fracture patients with no known diagnosis of osteoporosis had not had a BMD test within the last two years. The majority of respondents also indicated that they had not received any information about osteoporosis and its management from their family physician or other health care professionals. Respondents had not increased their calcium and vitamin D intake and exercise since their fracture. However, respondents indicated that they had made a number of changes including walking slower (49.6%), not going outside as much in the winter (44.8%) and changing the types of activities they participate in (29.6%). Knowledge of osteoporosis was low in this sample. Conclusions: The findings from this survey indicate that there are gaps in post-fracture care for individuals at high risk for future fractures. These data highlight the need to improve fracture patient and health care professional awareness about the need to address osteoporosis in individuals who have experienced a low trauma fracture.

P204MO. BURDEN OF HIP FRACTURE IN IRAN Ahmadi-Abhari S1, Moayyeri A1, Soltani A1, Larijani B1, Naghavi M2, Abolhassani F1,2; 1Endocrinology & Metabolism Research Centre, Shariati Hospital, Tehran University of Medical Sciences, 2 Ministry of Health and Medical Education, Tehran, Iran Aims: The burden of hip fracture has not previously been studied in Iran. We applied the Global Burden of Disease (GBD) methodology created by the World Health Organization to compare the burden of hip fractures in Iran with other countries. Methods: Incidence of hip fracture was obtained from the Iranian Multicenter Study on Accidental Injuries(IMSAI), a largescale nationwide prospective study conducted in 9 provinces of Iran. Disability-adjusted life years (DALY) as a measure of burden of disease is the result of adding years of life lost due to premature death (YLL) and years lost due to disability (YLD). YLD is calculated from the number of incident cases in a year, times the duration of disability, times the disability weight. To compute YLL, relative risk of mortality from hip fracture used data from Sweden. We assumed that 25% of hip fracture associated mortality is causally related to hip fracture. Discount rate of 3% and age weighting were applied. GBD template was utilized for analyses. Results: In Iran, hip fracture generated 19,379 DALYs, comprising 8,812 (45%) YLLs and 10,567 (55%) YLDs. Results of

S179 Table: YLL, YLD, DALY and DALY per 1000 population over 50 years with changes in assumptions on age weighting and excess mortality

Age weight

Excess mortality (%)

+ + + -

25 25 100 100 0 0

Men

Women

Total

YLD

YLL

DALY

DALY (per 1000)

YLD

YLL

DALY

DALY (per 1000)

YLD

YLL

DALY

DALY (per 1000)

4382 5396 4382 5396 4382 5396

4141 7397 16565 29588 0 0

8523 12793 20947 34984 4382 5396

1.95 2.93 4.80 8.02 1.00 1.24

6185 8209 6185 8209 6185 8209

4671 8794 18684 35177 0 0

10856 17003 24869 43386 6185 8209

2.42 3.79 5.55 9.67 1.38 1.83

10567 13605 10567 13605 10567 13605

8812 16191 35249 64765 0 0

19379 29796 45816 78370 10567 13605

2.19 3.37 5.18 8.86 1.19 1.54

sensitivity analysis removing age weighting and considering diﬀerent fractions of deaths as causally related to hip fracture are summarized in the Table. Iran accounted for 1% of the global burden of hip fracture and 15% of burden of hip fracture in the Middle East. The female to male ratio in Iran (1.3) was lower than that of the world (2.1), similar to that of Middle East, and higher than that of other Asian countries (1.0). Conclusions: Burden of hip fractures in Iran is considerably lower than that of countries with established market economy. We recommend utilization of standardized methodology of GBD project to calculate burden of osteoporosis in diﬀerent countries and set the local priorities according to these measures.

P205SA. RELATIONSHIP BETWEEN THE EXPERIENCE OF FALLS AND FRACTURE AND THE STATE OF SOCIAL PARTICIPATION IN FEMALE ELDERLY PEOPLE LIVING IN THE LOCAL COMMUNITY Kajita E1, Nakatani Y2, Matsubara I3, Komatsu M1, Takeuchi S1, Kagamimori S4; 1Nagoya University School of Health Sciences, Nagoya, Japan, 2Hamamatsu University School of Medicine, Hamamatsu, Japan, 3Ishikawa Prefectural Nursing University, Kanazawa, Japan, 4Toyama University School of Medicine, Toyama, Japan Aims: The relationship between the experience of falls and fracture and the state of participation in social activities and QOL was evaluated in females aged 65 years and above and living in the local community to devise measures for the prevention of a bedridden state and isolation. Methods: The subjects were 1,407 who consented to be subjects in the study among all females aged 65 years and above selected from the resident registration book. The items investigated were the age, degree of independence in daily living (ADL), history of outpatient and inpatient treatments, whether the subject had fallen during the past year, whether the subject had sustained fracture after the age 60, state of participation in social activities, and QOL. Results: The mean age of the subjects was 75.17.1 years. Falls were observed in 31.6% of the subjects, and the percentage was significantly higher in the older subjects (aged 75 years or above) than in the younger subjects (aged 65–74 years). Fracture after the age 60 was observed in 193 subjects (17.9%); 14.0% of the younger subjects and 22.9% of the older subjects. As for the relationship between fracture and participation in social activities, the scores of all items of participation in social activities such as mixing with friends and participating in social activities were significantly lower in those who experienced fracture than those who did not. The relationship between falls and the state of participation of social activities was similar. The general score, satisfaction score, physical score, psychological score, social score, and environmental score of the WHO-QOL scores were all significantly lower in those who fell than in those who did not. The results were similar also when the younger and older subjects were evaluated separately. Conclusion: Thus, the scores of participation in social activities and the QOL scores were lower in those who had experience falls and fracture. These results suggest the necessity to intensify measures for the prevention of falls and to devise measures to attract elderly people to social activities and to improve their QOL.

P206SU. PEAK BONE DENSITY IN CHINESE AND CAUCASIAN WOMEN: EFFECTS OF BODY SIZE Pocock NA1, Nicholson G2, Nguyen TV3, Henry MJ2, Yu W4, Pasco JA2, Xu L4; 1Nuclear Medicine Department, St Vincents Hospital, Sydney, Australia, 2University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, Australia, 3Garvan Institute of Medical Research, Sydney, Australia, 4Peking Union Medical College, Beijing, Peoples Republic of China Low peak bone mass accumulated during the second decade of life is considered an important risk factor of fracture in late decades of life. Areal bone mineral density (BMD) in Asian women is lower than in Caucasian women, probably due to smaller body frame and bone size. It is not well established whether peak bone mass in Asians is lower than in Caucasians. This study was designed to address these questions. Bone area and BMD of the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy x-ray absorptiometry (DXA) in 205 Chinese women in Beijing, China (Lunar Prodigy) and 221 Caucasian women in Geelong, Australia (Lunar DPXL). The instruments were cross calibrated using a GE-Lunar Bar Phantom and the BMD results appropriately standardized. The two ethnic groups were comparable in terms of age (mean: 26, SD: 3.9 years); however, Chinese women had lower weight (56.28.2 vs 66.313.7 kg) and shorter height (162.45.9 vs 164.06.0 cm) than Caucasian women. In unadjusted analysis, Caucasian women had significantly higher BMD than Chinese women at both the lumbar spine (4.2% higher) and femoral neck (7.3%). However, after adjusting for age, weight and height in an analysis of covariance model, the diﬀerences were not statistically significant for the lumbar spine BMD (1.210.12 vs 1.200.11 g/cm2; p=0.11), and reduced for femoral neck BMD (0.990.11 vs 0.970.11 g/cm2; p=0.05). These results suggest that peak lumbar spine and femoral neck BMD in Chinese women is lower than in Caucasian women, but this diﬀerence is likely to be due to diﬀerence in body size. The results also imply that diﬀerence in peak bone density is unlikely to account for the lower risk of fracture in the Chinese population. This study was supported by Fonterra Brands, New Zealand.

P207MO. PREVALENCE OF FEMORAL OSTEOPOROSIS IN MEDIEVAL HUMANS FROM DUBOVANY CEMETERY (WESTERN SLOVAKIA): MACROSCOPIC AND MICROSCOPIC EXAMINATION Martiniakova M1, Omelka R2, Grosskopf B3, Vondrakova M1, Bauerova M2; 1Department of Zoology and Anthropology, 2Department of Botany and Genetics, Constantine the Philosopher University, Nitra, Slovakia, 3Institute of Zoology and Anthropology, Georg-August University, Gottingen, Germany Osteoporosis and its clinical manifestation is a major medical and societal problem in the modern world. However, many studies have demonstrated bone loss with aging also in archaeological populations from diverse geographic regions with a variety of methodologies. Archaeological samples have the advantages of being (usually) more genetically and behaviorally homogeneous

S180 than most modern clinical or autopsy samples, conversely however, they present problems associated with inaccurate age assignments and uncertain dietary and other environmental factors. In our study we analyzed a prevalence of femoral osteoporosis in medieval humans from Dubovany cemetery (western Slovakia) dated from 8th-9th centuries A.D. Investigated skeletal material consisted of the remains of 39 adults (22 females and 17 males) aged from 20 to 60 years. The standard methods were employed in aging and sexing population (Workshop of European Anthropologists JHE 1980; 9:517–549). Radiographs of the femora were performed in a specialized x-ray laboratory. Patterns of cortical growth and maintenance were determined from histological analysis of femoral sections. The bones were embedded, sectioned and examined according to procedures described by Martiniakova et al. (AJPA 2005; Supplement 40:146). Both macroscopic and microscopic examinations were employed in an assessment of cortical dynamics. Age-related bone loss has been observed in femora of medieval individuals. The diﬀerence in bone loss was not statistically significant between females and males. According to radiological examination the frequency of femoral osteoporosis was 10.25%. However, no osteoporotic fractures were found. Histomorphometrical analysis revealed that the area and diameter of the Haversian canals disposed higher values in osteoporotic individuals as compared to non-osteoporotic ones (P<0.05). On the other hand, higher values for the perimeter and diameter of the secondary osteons were recorded in non-osteoporotic humans (P<0.05). For the microstructure of osteoporotic femora, higher frequencies of resorption cavities and forming osteons were identified. In conclusion, osteoporotic changes in the femora of medieval individuals from the territory of Slovakia influence the microstructure of the bone tissue. On the other hand, these changes are not associated with increased risk to fractures. Acknowledgement: This study was supported from grants KEGA 3/3181/05 and CGA VI/6/2004.

P208SA. BONE MINERAL DENSITY AND DISEASE ACTIVITY IN YOUNG ADULTS WITH JUVENILE IDIOPATHIC ARTHRITIS Hamalainen H1, Arkela-Kautiainen M1, Haapasaari J1, Kautiainen H1, Kotaniemi A1, Leirisalo-Repo M2; 1Rheumatism Foundation Hospital, Heinola, Finland, 2Helsinki University Hospital, Helsinki, Finland Aims: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease emerging in childhood. Diminished bone mineral density (BMD) in JIA patients have been connected with high inflammatory activity and long duration of JIA, delay of pubertal maturation and treatment with corticosteroids. Some patients with JIA may not reach enough peak bone mass during their growth. Therefore to obtain information of bone mineral content (BMC) development in late JIA, we measured axial BMD in a cohort of 116 adults diagnosed to have JIA during the years 1976–1995. They had 68 aged matched controls. Methods: Patients with JIA were divided into two groups: Active disease (N=73) and in-active (N=43). A patient was considered to be in remission if ESR was < 20 mm/h, morning stiﬀness lasted < 15minutes, there were no tender or swollen joints, and the patient had been oﬀ DMARD or corticosteroid for at least the past two years. BMD measurement was performed at the lumbar spine and the femoral neck by dual-energy X-ray absorptiometry. Results: The mean age was 23 (SD 2) years in JIA and control groups. The mean weight was 67 (SD 15) kg in JIA patients and 66 (SD 12) kg in controls. The proportion of females was 72% in JIA patients and 70% in controls. The mean age at the diagnosis of JIA was 8 (SD 4) years and the mean disease duration was 15 (SD 5) years. JIA patients considered to have active disease have inferior axial BMC to patients with JIA in remission and to controls. Patients with JIA in remission and the controls did not statistically diﬀer from each other according to axial BMC and area (Table). Conclusions: Those patients with JIA, who have their disease in remission, thrive better with their axial BMC, which should be taken in consideration at clinical work.

Table 1. Bone mineral density in 116 patients with JIA and in 68 controls Disease activity of JI Aat follow up Inactive (N=43) Mean (SD)

Controls (N=68) Mean (SD) P-value

0.97 (0.12) 4.79 (0.84) 4.91 (0.50)

1.04 (0.13) 5.24 (0.99) 5.04 (0.57)

1.07 (0.14) 5.38 (1.13) 5.00 (0.55)

<0.001 <0.001 0.55

1.18 (0.15) 49.6 (10.3) 42.0 (5.2)

1.21 (0.13) 54.5 (10.3) 44.9 (5.7)

1.23 (0.14) 54.4 (11.5) 43.9 (5.9)

0.053 0.037 0.16

Measurement Active (N=73) site Mean (SD) Femoral neck BMD, g/cm2 BMC, g Area, cm2 Lumbar spine BMD, g/cm2 BMC, g Area, cm2

P209SU. YOUNG POSTMENOPAUSAL WOMEN HAVE HIGH PREVALENCE OF INADEQUATE SERUM VITAMIN D LEVELS: RESULTS OF A EUROPEAN STUDY Bruyere O, Malaise O, Neuprez A, Reginster J-Y; WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders and Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium Aims. A high prevalence of vitamin D Inadequacy has been widely documented in elderly women. Low vitamin D level is associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. The objective of this study is to assess the prevalence of inadequate serum vitamin D levels in women aged less than 70 years old. Methods. Postmenopausal osteoporotic women were recruited from 9 European countries (France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany). Assessment of 25-Hydroxyvitamin D [25(OH)D] was performed with a commercial radioimmunoassay (DiaSorin) in all patients. There are no clear international agreements on what constitute a level of vitamin D inadequacy. However, recent publications suggest that the circulating level of vitamin D should be over 80 nmol/L or at least between 50 nmol/L and 80 nmol/L. We used, in the present study, two cut-oﬀs of 25(OH)D fixed according to these publications (<80 nmol/L and <50 nmol/L). Results. A total of 8532 women with a mean (range) age of 74.2 (45–100) years were included in this study. The mean (SD) level of 25(OH)D was 61.0 (27.2) nmol/L. There was a slight, not clinically significant, correlation between the age of the patients and the level of 25(OH)D (r=-0.10; p<0.0001). In the whole study population (n=8532) the prevalence of vitamin D inadequacy was 79.6% and 32.1% when considering cut-oﬀ of 80 and 50 nmol/L, respectively. In women aged less than 70 years old (n=1631), the prevalence was 80.3% and 37.6%, respectively. The prevalence of vitamin D inadequacy reaches 78.9% (cut-oﬀ of 80 nmol/L) and 38.2% (cut-oﬀ of 50 nmol/L) in patients aged less than 60 years old (n=285). Conclusion: This study confirms the high prevalence of vitamin D inadequacy in osteoporotic European postmenopausal women. However, age does not seem to substantially influence this prevalence.

P210MO. DO PATIENTS WITH FRAGILITY FRACTURES PERCEIVE THEMSELVES TO BE AT RISK OF FUTURE FRACTURE? Giangregorio LM1,2,3, Papaioannou A2,8, deBeer J2,8, Dolovich L2,4,5, Cranney A6,7, Thabane L2,4, Nixon M8, Adachi JD2,4; 1 University of Waterloo, Waterloo, Canada, 2McMaster University, Hamilton, Canada, 3Toronto Rehabilitation Institute, Toronto, Canada, 4St. Joseph’s Healthcare, Hamilton, Canada, 5 University of Toronto, Toronto, Canada, 6Ottawa Health Research Institute, Ottawa, Canada, 7University of Ottawa, Ottawa, Canada, 8Hamilton Health Sciences, Hamilton, Canada To engage fragility fracture patients in osteoporosis management, it is important for them to be aware they are at risk of fracture. Whether or not patients link fragility fracture with increased risk of future fracture is unknown.

S181 Aims: To explore whether fracture patients associate having a fracture with osteoporosis and increased risk of future fracture. Methods: In this cross-sectional study, patients seen by orthopedic surgeons at Hamilton Health Sciences for fragility fracture in 2004–2005 were asked to participate in a structured telephone interview. Patient responses and demographics were summarized using mean (standard deviation [SD]) for continuous variables and count (percent) for categorical variables. Results: Of 162 approached, 64 (40%) agreed to participate; 13 males and 51 females average (SD) age 69 (12) years; average (SD) months post fracture 11 (5). Respondents reported having the following fractures: wrist (23), hip (16), pelvis (1) or other (20). Seventeen (27%) patients reported a history of fracture prior to the most recent fracture. Bone density tests prior to fracture were reported in 61% of patients. Eighty percent were not advised to go for a bone density test after their fracture. A total of 30 patients (47%) reported a diagnosis of osteoporosis and 90% of these had been diagnosed before their fracture. Although over 40% of patients had been previously diagnosed with osteoporosis, only 17% thought their fracture was related to osteoporosis, 22% were unsure, and 61% said they did not think their fracture was osteoporosis-related. Similarly, 45% of patients did not believe they were at risk of future fracture, 9% were unsure, and the remaining 45% said they thought they were at risk. Of patients that had received an osteoporosis diagnosis, only 40% were specifically told that they were at risk of future fracture. Conclusions: Many patients who suﬀer fragility fracture do not make the link between their fracture and osteoporosis. Further, many patients are not aware that they may be at risk of future fracture. Eﬀorts to ensure that fracture patients are informed of their risk are necessary.

P211SA. OSTEOPOROSIS INFORMATION NEEDS AND PREFERENCES IN FRAGILITY FRACTURE PATIENTS Nixon M1, Giangregorio L2,3,4, Cranney A5,6, deBeer J1,3, Dolovich L3,7,8, Papaioannou A1,3, Thabane T3,7, Adachi JD3,7; 1 Hamilton Health Sciences, Hamilton, Canada, 2University of Waterloo, Waterloo, Canada, 3McMaster University, Hamilton, Canada, 4Toronto Rehabilitation Institute, Toronto, Canada, 5 Ottawa Health Research Institute, Ottawa, Canada, 6University of Ottawa, Ottawa, Canada, 7St. Joseph’s Healthcare, Toronto, Canada, 8University of Toronto, Toronto, Canada Self-management is an important component of fracture prevention, however patient preferences regarding osteoporosis information and resources are not known. Aims: To assess patients’ unmet needs and preferences with respect to osteoporosis information and resources. Methods: In this cross-sectional study, patients seen by orthopedic surgeons at Hamilton Health Sciences for a fragility fracture in 2004 or 2005 were asked to participate in a structured telephone interview. Interviewers were trained and the survey was pilot tested. The responses and demographics of the respondents are summarized using mean (standard deviation [SD]) for continuous variables and count (percent) for categorical variables. Results: Of 162 approached, 64 (40%) agreed to participate; 13 males and 51 females average (SD) age 69 (12) years; average (SD) months post fracture 11 (5). Respondents reported having the following fractures: wrist (23), hip (16), pelvis (1) or other (20). A total of 30 patients (47%) reported a diagnosis of osteoporosis. Most patients (80%) want to make decisions about osteoporosis therapy in cooperation with physicians. Furthermore, 44 (69%) patients want to read or learn more before making the decision, while 24 (38%) would consult a friend or relative. When asked how much osteoporosis information they would want after diagnosis, 39 (61%) patients want as much information as possible and 21 (33%) want only the information needed to care for themselves properly. Patients reported using pamphlets (50%), magazines (45%), newspaper (38%), a health care provider (25%), books (20%), a friend/relative (22%), and the internet (16%) to learn about osteoporosis. Their most preferred source of information about osteoporosis was a health care provider (39%), followed by pamphlets (17%), the internet (13%) and books (11%). The topic they would most like to learn more about was osteoporosis

prevention (28%), medication information (20%) and how to live with osteoporosis (17%). Conclusions: A large percentage of fracture patients are interested in osteoporosis management, and are taking an active role in self-education and decision-making. Patient preferences identify the need for health care providers to participate in patient education.

P212SU. TIME TRENDS OF MORTALITY AFTER FIRST HIP FRACTURES Giversen IM; National Board of Health, Denmark, Viborg Hospital, Department of Ortopedic Surgery, Viborg, Denmark A retrospective cohort study was performed to investigate, if the mortality of first hip fractures in a Danish County was associated with time trend and fracture type. Study material was obtained by record linkage of excerpts from two computerized national health registers. First hip fractures were identified indirectly by searching the files ten years prior to the date of admission. The period from 1987 through 1996 saw inclusion of 2687 (average follow-up 2.6 years) patients. Data from 1978 collected for comparison revealed 122 patients with first and recurrent hip fractures (average follow-up 6.3 years). All patients were aged 50 years and older. Data were analyzed using weighted regression analysis and 2 test. The cumulative mortality of first hip fracture patients did not change significantly during the investigation period (P > .05). A weighted average for both sexes combined was 9% (95% CI, 7.9–10.1) at 1 month, 15.5% (95% CI, 14.1–16.8) at 3 months, 26.5% (95% CI, 24.7–28.3) at 1 year, and 36.2% (95% CI, 34.1–38.3) at 2 years after admission. Cervical and pertrochanteric first hip fracture patients did not experience significantly diﬀerent mortality rates (P > .05). The corrected mortality for both sexes combined was 13.6% (95% CI, 12.2–15.0) at 3 months, 19.6% (95% CI, 17.7–21.5) at 1 year, and 23.8% (95% CI, 21.5–26.1) at 2 years after admission. In conclusion, no changing time trend of mortality after first hip fracture was observed despite increasing age at admission, nor was the mortality linked to the kind of fracture suﬀered.

P213MO. ADHERENCE WITH OSTEOPOROSIS ASSESSMENT AND TREATMENT AFTER FRAGILITY FRACTURE IN AN INNER CITY ORTHOPAEDIC UNIT Bogoch ER1,2, Elliot-Gibson V2, Beaton DE2, Baburam A3, Jamal SA4, Josse RG4, Murray TM4; 1Department of Surgery, 2Mobility Program Clinical Research Unit, 3Former Fellow, Department of Surgery, 4Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Canada Aims: To evaluate the adherence with osteoporosis (OP) assessment and treatment after fragility fracture in an inner city university hospital orthopaedic unit in Toronto, Ontario. Methods: Inclusion criteria: male R50; female R40; low trauma fracture of the wrist, humerus, hip, vertebrae; plus any nontargeted patients referred by the orthopaedic surgeons. A chart audit to measure adherence, at a minimum of one year, was conducted on patients screened from December 1, 2002 to November 30, 2003 (n = 430). Results: There were 184 hip, 125 wrist, 8 vertebrae, 72 humerus, and 41 other fractures. Bone density tests (BMD) were ordered for 208 patients and 158 complied. Eighteen patients had normal BMD, 139 were either osteoporotic (n = 58) or osteopenic (n = 81); one result unknown. Inpatient results (n = 154): 10 inpatients died, six refused intervention, 43 were already on appropriate OP care, and 16 were referred back to family physician (FP). Sixty-one inpatients were referred to OP Clinic or inpatient consult; 47 (77%) attended. All 47 inpatients were prescribed appropriate care. Chart audit revealed that at least 24 (55%) were still on treatment, 1 (2%) was non-adherent and 19 (43%) followed up with community physician or not at all (no chart data). Outpatient Results (n = 276): Thirteen patients with normal BMD were not referred, nine refused intervention, 87 were already on appropriate care, and 28 were referred back to FP. One hundred and thirty-six patients were referred to the OP Clinic and 100 (74%) attended. Ninety-four patients receive appropriate care including no treatment for six patients; six patients refused medication. Chart audit revealed at

S182 least 48 (52%) were adherent to prescribed medication, nine (10%) were non-adherent and 34 (38%) followed up with family physician or not at all (no chart data). No referral for 23 patients due to physical and mental health issues, although vitamin D and calcium were initiated or recommended. Conclusions: This program was able to identify and refer fragility fracture patients for OP assessment and treatment. Adherence was over 50% at one year, which is likely underestimated through the chart audit methodology.

P214SA. RECOGNIZING OSTEOPOROSIS AND ITS CONSEQUENCES IN QUÉBEC (ROCQ): THE CARE GAP FOLLOWING A FRAGLITY FRACTURE Bessette L1, Brown JP1, Beaulieu M2, Baranci M3, Jean S1, Davison KS1, Ste-Marie L-G4; 1Laval University, Ste-Foy, Canada, 2Merck Frosst Canada, Montreal, Canada, 3SanofiAventis Pharma, Montreal, Canada, 4University of Montreal, Montreal, Canada The objective of this analysis is to evaluate the diagnostic and treatment rates of osteoporosis six months following a fragility fracture in women 50 years and over participating in the ROCQ programme, an ongoing patient health-management programme. At phase 1, women with fragility and traumatic fractures were recruited at a cast or outpatient clinic or by mail using a list of names provided by the Quebec provincial health administrative database. Upon receipt of an authorization form, the patients are contacted by phone to answer a short questionnaire that identifies their fracture circumstances. The possible association between their fracture and osteoporosis is not mentioned and no investigation or intervention is proposed. Six months following the fracture, women are contacted again by phone (phase 2) to determine the diagnostic (informed of osteoporosis and/or BMD measurement with diagnosis of osteoporosis) and treatment (bisphosphonates, raloxifene, nasal calcitonin or teriparatide) rates of osteoporosis. After 24 months, 2 414 women (mean age: 65.9 years) completed phase 1. A total of 1,864 (81%) sustained a fragility fracture and 430 (19%) sustained a traumatic fracture. One-third of the participants reported a previous fracture after 40 years of age. Of those not treated for osteoporosis at phase 1, 17% initiated pharmacological therapy within the six-month period following their fracture. At phase 2, only 26% of participants either received a diagnosis of osteoporosis or were on treatment despite 72% consulting a physician during the six to eight months between phases 1 and 2. Women over 65 years of age and those who had a BMD measurement between phases 1 and 2 with a diagnosis of osteoporosis were more likely to be treated. Education level, history of fracture, and level of knowledge were not associated with a higher probability of initiating treatment. Despite the availability of diagnostic modalities, eﬀective treatments, and adequate health care assessments, there is a substantial care gap in the management of osteoporosis. The decision to initiate treatment is primarily influenced by the BMD measurement result and not by fracture type. The proportion of fragility fractures is higher than expected and the management of osteoporosis is suboptimal.

P215SU. PREVALENCE OF LUMBAR SPINE AND HIP OSTEOPOROSIS IN AFRO-CARIBBEAN MEN Sheu YT1, Wheeler VW2, Cauley JA1, Bunker CH1, Patrick AL2, Zmuda JM1; 1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, 2 Tobago Health Studies Oﬃce, Scarborough, Tobago, West Indies Osteoporosis is an increasingly important clinical and public health problem among older men. The prevalence of osteoporosis among men of African descent is less well defined. Thus, we determined the prevalence of osteoporosis in a large, ongoing prospective cohort study of Afro-Caribbean men who were recruited without regard to their health status for a population-based prostate screening survey. Bone mineral density (BMD) was measured on the L2-L4 lumbar spine and proximal femur (Hologic QDR-4500). The

device normative data for lumbar spine BMD and NHANES III study for femur BMD in African Americans were used as reference values. The prevalence of osteoporosis and osteopenia were defined according to World Health Organization T-score criteria. We also determined the degree of osteoporosis diagnostic discordance. A major discordance was considered when one skeletal site was osteoporotic and the other was normal. A total of 914 Afro-Caribbean men (mean age, 61.510.3; range, 43–91 yrs) with complete BMD data were included in the analysis. The prevalence of osteoporosis and osteopenia was 13.1% and 32.0% at the lumbar spine, compared with 1.3% and 34.6% at the femoral neck. Among the 120 men with osteoporosis at the spine, 7.5% and 22.5% were classified as being osteoporotic or normal at the femoral neck, respectively. Among the 12 men considered osteoporotic at the femoral neck, 75.0% and 16.7% were classified as osteoporotic and normal at the lumbar spine, respectively. A total of 3.2% of the men had major T-score discordance. We conclude that Afro-Caribbean men have a considerably higher prevalence of osteoporosis at the lumbar spine than femoral neck. Additional work is needed to understand the factors (e.g., physiologic, pathophysiologic, anatomic) contributing to the higher prevalence of osteoporosis at the lumbar spine than femoral neck and to test if the current observations extend to African American men.

P216MO. KAP STUDY AND HOW THE COMMUNITY PEOPLE RESPOND TO OSTEOPOROSIS IN A DEVELOPING COUNTRY Joshi SD1, Bk S1, Bhandari R2, Pandit N1; 1Nepal Medical College and Teaching Hospital, 2Community Health and Environmental Society, Nepal Objectives: Nepal is a developing country where quality of healthcare is very poor. Osteoporosis is one of the challenging subjects for the management of healthcare professions in the community. Methods: We evaluated awareness, knowledge, practice, risk factors and current treatment of osteoporosis from hospital-based, nursing home, community health camps and healthcare centres, 2002–2004. Subjects included were 86 women and 23 men with an average age of 68 years. All participants answered an interviewadministered questionnaire regarding osteoporosis awareness, risk factors and treatment. Data were edited, coded and entered into the EPI info programme. They were given health education about osteoporosis. Results: Most of the subjects from the nursing home (15%) are literate, while the majority of seniors attending the educational program (85%) are illiterate. 96(%) of all subjects were aware of osteoporosis and 49% gave the correct information. Television, friends and physicians were identified as the main source of information, especially among women. In all, 80% knew that osteoporosis could be prevented and this was less in healthcare centres (p<0.001). Women believed that they could get osteoporosis more than men (p< 0.001). Besides old age and estrogen deficiency association with menopause, the most prevalent risk factors included FHF 19%, past smoking 30%, and previous fracture 13%. FHF and previous fracture were both more common among seniors attending an educational program than between subjects from the nursing home, (p< 0.05). Only 25% of the subjects were using specific treatment of osteoporosis and had high level of awareness and accurate definition of osteoporosis in community. Conclusion: The study shows that educational programs, specific therapy and prevention measures for osteoporosis were inappropriately low for this group of subjects at high risk of osteoporosis. Parents, families, communities and national policy are critical in guiding and supporting old people to make safe healthcare choices about their health and well-being. Studies have shown from mass media that consistent, positive, emotional connection with caring elder people help old people feel safe and secure, allowing them to develop the resiliency needed to manage the changes in their lives without social stigma, denial and discrimination.

S183

P217SA. VITAMIN D STATUS IN POSTMENOPAUSAL WOMEN OF MOSCOW REGION, RUSSIA Toroptsova NV, Benevolenskaya LI, Nikitinskaya OA, Demin NV; Institute of Rheumatology RAMS, Moscow, Russia Vitamin D is an important determinant of bone health, its deficiency leads to decrease of calcium absorption and secondary hyperparathyroidism that results in bone loss, mineralization defect and increasing fracture risk. Aim: To determine the vitamin D status and its seasonal variation in postmenopausal women. Material and methods: 256 postmenopausal women (mean age 64.07.5 years) were enrolled into the study. Bone mass measurements at lumbar spine (L1-L4) and hip were performed by DXA (Hologic 4500A device), fasting blood samples were collected for serum 25(OH)D, PTH, total calcium, phosphorus and alkaline phosphatase. Vitamin D deficiency was defined as 25(OH)D < 25 nmol/l and insuﬃciency as 25(OH)D < 50 nmol/l. No women had vitamin D supplements before the study. Results: The mean level of serum 25(OH)D was 45.522.9 nmol/l; however, it was 41.417.4 nmol/l in winter and early spring and significantly increased in autumn (60.630.8 nmol/l, p<0,0001). In 17.6% cases, serum 25(OH)D was below 25 nmol/l, and 64.8% of women had vitamin D below 50 nmol/l. A positive correlation was observed between serum 25(OH)D and bone mineral density (BMD) of the femoral neck (r=0.14; p=0.03), no correlation between BMD L1-L4 and 25(OH)D. Negative correlation was found between 25(OH)D and PTH (r=-0.27; p=0.012). No correlation was found with total calcium, phosphorus and alkaline phosphatase. In early spring, 80 postmenopausal women with osteoporosis (mean 25(OH)D level 38.5616.3 nmol/l) were given supplements of calcium 1000 mg and vitamin D 800 IU during 1 month and after that blood samples were collected. Serum 25(OH)D significantly increased till 68.35+16.77 nmol/l (p<0.0001), only in 10% cases we found its insuﬃciency. Conclusion: We determined that 64.8% postmenopausal women in Moscow have vitamin D insuﬃciency, there is a seasonal variation of 25(OH)D level: the values were lower in winter and early spring and higher in autumn. Additional vitamin D supplements increase serum 25(OH)D level and this may be the first step in prevention of osteoporosis and fractures.

P218SU. EXERCISE AND CALCIUM INTAKE ACT SYNERGISTICALLY ON BONE IN POSTMENOPAUSAL WOMEN? Dionyssiotis Y, Trovas G, Charopoulos I, Katsalira A, Papakitsou E, Tournis S, Samdanis B, Economopoulos D, Galanos A, Lyritis GP; Laboratory for Research Musculoskeletal System, University of Athens, KAT Hospital, Kifissia, Greece Aims: To study the synergistic action of exercise and calcium intake on bone in postmenopausal women. Methods: During the years 2004 and 2005, 1319 randomly selectedcommunity dwelling postmenopausal women participated in a control program for osteoporosis which was organised by the Hellenic Foundation of Osteoporosis in cooperation with the Hellenic Patient Osteoporosis Society. Exercise and calcium intake were assessed by answering a questionnaire by interview about weekly exercise activity and duration including walking, dancing, aerobics, muscle strengthening, gardening and about daily calcium intake. In the same session all women performed quantitative ultrasound of the heel with an osteometer ultrasound Achilles Express GE Lunar on the left heel. None of the women were taking bone acting drugs and/or calcium supplementation. Women were separated according to weekly exercise, in 1219 women who never exercised, 67 women who exercised less than two hours and 33 women who exercised more than two hours weekly and according to daily calcium in women with less than 800 mg intake (n=942, mean age 64.88.8(SD)) and in women with more than 800 mg calcium intake (n=377, mean age 63.88.9(SD)). Results: Estimation of mean T-score between women who exercised, according to more or less than 800 mg daily calcium intake, revealed an increased significant result (p=0.05),in women who exercised more than two hours weekly and received more than 800 mg calcium daily. Contrarily, in women with less than 800 mg

daily calcium intake, we did not observe any diﬀerence in mean T-score between women, independently of weekly duration of exercise. Conclusions: These results suggest the importance of adequate calcium consumption as a synergistic factor with the proper exercise to induce gains in bone mass.

P219MO. THE EFFECTS OF TRANSFORMING GROWTH FACTOR BETA1 GENE POLYMORPHISMS AND LIFESTYLE FACTORS ON BONE MINERAL DENSITY IN REPRESENTATIVE SAMPLE OF JAPANESE WOMEN: JPOS STUDY Morita A1, Iki M1, Dohi Y2, Ikeda Y1, Kagamimori S3, Kagawa Y4, Yoneshima H5; 1Kinki University School of Medicine, OsakaSayama, Japan, 2Nara Medical University, Kashihara, Japan, 3 University of Toyama, Toyama, Japan, 4Kagawa Nutrition University, Tokyo, Japan, 5Shuwa General Hospital, Kasukabe, Japan Aims: To evaluate the associations of the two previous reported transforming growth factor beta1 (TGF1) gene polymorphisms with bone mineral density (BMD), and to clarify the interactions between these polymorphisms and lifestyle factors on BMD in a large-scale representative study for the Japanese female population. Methods: Fifty women were randomly selected from each of the 5-year age stratified populations (15–79 years) in each of 3 municipalities as a part of Japanese population–based osteoporosis (JPOS) baseline study in 1996. BMD at the lumbar spine, hip and distal forearm were measured using DXA, and information on medical history and various lifestyle factors were obtained by the detailed interviews. Genotypes were determined in the signal sequence region of the exon 1 in the TGF1 gene by an allelic discrimination method with fluorogenic probes (T29C polymorphism) and in the promoter region of the TGF1 gene identified by PCR-RFLP method with endonuclease Eco81I (C-1348T polymorphism). Changes in BMD were determined 3 years after the baseline. Results: After the exclusion of women who had medical and menstrual history aﬀecting BMD, we included in our study only women 20 years of age and older from the remaining women. Finally, 1177 women were analyzed. The T29C and C-1348T genotypes showed a significant association indicating strong linkage disequilibrium. The T29C and C-1348T genotypes were found to be associated with baseline BMD at the lumbar spine in postmenopausal women. The subjects with CC at T29C or TT at C-1348T showed lower spine BMD than the subjects with heterozygote. These associations, however, were inconsistent over the diﬀerent skeletal sites. We found some significant links between lifestyle factors and BMD, such as the fact that sports activities during childhood and adolescence had an eﬀect on BMD at the femoral neck and ultradistal forearm only in the subjects with heterozygote. However, these relationships were inconsistent across the skeletal sites. Conclusions: Neither of the two TGF1 gene polymorphisms showed consistent association with BMD and interaction with lifestyle factors on BMD in our representative study. The TGF1 genotype did not have a substantial eﬀect on bone mass in Japanese women.

P220SA. INTEROBSERVER VARIABILITY OF GENANT’S METHOD IN OSTEOPOROTIC VERTEBRAL FRACTURE ASSESSMENT Kaya T1, Goksel Karatepe A1, Gunaydin R1, Oztekin O2, Cengiz A2, Adibelli Z2, Ozbek G1; 1Department of Physical Medicine and Rehabilitation, 2Department of Radiology, Izmir Training and Research Hospital, Izmir, Turkey Aims: The objective of this study is to evaluate the interobserver variability between two radiologists and one physiatrist in the assessment of osteoporotic vertebral fracture by using semiquantitative Genant’s method. Method: Thirty-nine postmenopausal osteoporotic (L2–4 T-score %-2.5) women with a mean age of 63.25 7.19 years were included in the study. Lateral radiographs of thoracic (T4–12) and

S184 lumbar spine (L1–4) were evaluated in all patients. Genant’s method was used to define vertebral fractures. Scoring was made by three observers. Two radiologists and one physiatrist evaluated all radiographs independently. Interobserver agreement between two radiologists and also between one radiologist and physiatrist was calculated using the kappa statistic. Results were compared for all vertebrae. Results: Interobserver agreement between radiologist and physiatrist for all vertebrae was poor with a kappa score of 0.289. Interobserver agreement between two radiologists was moderate with a kappa score of 0.539. Conclusion: We observed a moderate agreement for Genant’s method in vertebral fracture assessment between radiologists and a poor agreement between radiologist and physiatrist. These results are probably due to the use of an evaluation method which is based on a fracture/nonfracture dichotomy. Only two vertebrae were assigned as 2 and 3 by a radiologist. Except for these, all scores of vertebrae were assigned as 0 or 1 by observers. So it was diﬃcult to separate fracture from normal vertebrae. Besides, the radiologists and clinicians who interpreted radiographs did not have specific training, standardization and they have only reference to a diagram about Genant’s method. The visual interpretation when done by the expert eye and trained observer will also separate true fractures from normal or anomalous vertebrae.

P221SU. PRESCRIPTION AND COPRESCRIPTION PATTERNS OF BONEACTIVE SUBSTANCES AMONG POSTMENOPAUSAL WOMEN Richy F, Bruyere O, Mawet A, Reginster J.-Y.; University of Liège, Faculty of Medicine, Dept of Public Health, Epidemiology and Health Economics, CHU B23, Sart-Tilman, Belgium; WHO Collaborating Center for the Public Health Aspects of Osteoarticular Disorders, Belgium Setting: In a balanced clinical and health economics perspective, the accurate prescription and coprescription rates of the numerous substances and drugs aﬀecting bone are essential. We designed this study to investigate the rate of prescription and coprescription of vitamin D and calcium among women aged 60 to 80 years. Methods: Cross-sectional data from 1733 postmenopausal women collected between 1996 and 1999 in an outpatient clinic located in Liège, Belgium. The following classifications were made,

according to the presence or absence of osteoporosis at various anatomical sites (hip, femoral neck, lumbar spine, measured by DXA-Hologic QDR 2000): use of calcium, vitamin D, hormone replacement therapy, biphosphonates, calcitonin, SERMS alone or in combination. Results: The mean age (SD) of the subjects was 68.5 (5.2) years. 26% of the subjects had osteoporosis at the hip, femoral neck, or lumbar level. 69% of the subjects with osteoporosis received a treatment while 64% of the subjects free of osteoporosis did. Calcium and vitamin D were the most often prescribed substances for osteoporotic subjects, hence their combination was only seen among 34% of the patients. Biphosphonates in conjunction with vitamin D, and in conjunction with calcium, were prescribed among 21% and 7% of the subjects with osteoporosis, respectively. Among healthy subjects, hormone replacement therapy was most prevalent (41%), followed by calcium (33%), vitamin D (13%), vitamin D and calcium (11%), and biphosphonates (4%). Interpretation: This pragmatic study has shown that few osteoporotic women receive adequate treatment, and that currently accepted preventive measures, i.e. calcium and vitamin D, are seen in less than 1 patient at risk out of three. Our preliminary data also provide and insight on the lack of coprescription rates of vitamin D and calcium, especially regarding biphosphonates. Coprescription of these drugs, together with biphosphonates should be reinforced, or combined therapies should be promoted.

P222MO. WHAT IS THE RISK OF INSTITUTIONALIZATION AFTER HIP FRACTURE? Zethraeus N1,2, Ström OE2, Borgström F2,3; 1Centre for Health Economics, Stockholm School of Economics, 2Stockholm Health Economics, 3Medical Management Centre, Karolinska Institute, Stockholm, Sweden Objective: In health economic evaluations of osteoporosis the long-term costs of hip fractures are usually based on the proportion of patients going into long term care (LTC). The aim of this study was to quantify these age-specific proportions and also to consider whether increased fracture related costs are incurred. Material and Methods: Data was collected for 2 747 patients that were admitted for hip fracture surgery during the year 1990 in the Stockholm county council in Sweden. The patient sample included both male and female patients. The patient’s accommodation status was registered before and 1 year after the hip fracture. About 25% of the patient’s died within the first and were thus excluded from the estimates. Also, the risk of being institutionalized due to hip fracture had to be adjusted down by the proportion of patients having special accommodation before the fracture. The calculations are based on the assumption that already institutionalized patients not will incur additional accommodation costs when going to LTC. Results: results are presented in the table below. Conclusions: The results from this study indicate the risk of being institutionalized after a hip fracture to be constant in patients between 50 and 70 years of age. In older patients the risk seems to increase exponentially with age. Table 1. Accommodation before and after hip fracture in Sweden

Age

Proportion going from own home to LTC after 1 year

Proportion initially living at home

Adjusted proportion going to LTC*

50–59 60–69 70–79 80–89 90all

7.2% 7.1% 12.8% 19.0% 30.8% 15.6%

92.6% 92.4% 79.7% 77.5% 73.3% 79.7%

6.7% 6.5% 10.2% 14.7% 22.6% 12.4%

* proportion of all surviving hip fracture patients going to LTC and also incurring additional accommodation costs due to fracture.

S185

P223SA. COMPARISON OF ASSOCIATIONS BETWEEN NUTRIENT INTAKES AND BONE MINERAL DENSITY ESTIMATED BY 2 DIETARY ASSESSMENT METHODS IN POSTMENOPAUSAL WOMEN IN THE B.E.S.T. EXERCISE STUDY Stanford V1, Harris M2, Lohman T1, Going S1, Thomson C1, Weber J2, Houtkooper L1; 1University of Arizona, 2University of Arkansas for Medical Sciences, Tucson, USA Aims: To compare the associations of mean nutrient intake and their association with bone mineral density (BMD) using two dietary assessment methods over one year. Methods: The Bone Estrogen Strength Training (BEST) study was a partially randomized clinical trial of the eﬀects of 12 months of progressive resistance exercise on BMD in healthy, nonsmoking, postmenopausal women (n=244; ages 55.74.6 years). BMD was measured at the lumbar spine L2-L4, trochanter, femur neck, Ward’s triangle and total body using dual-energy X-ray absorptiometry. Subjects were randomized to either exercise or no exercise conditions within groups stratified by hormone replacement therapy (HRT) use. Subjects received 800 mg of calcium citrate supplement daily. Mean nutrient intakes were assessed using 8-days of diet records (DR) collected over one year and one Arizona Food Frequency Questionnaire (AFFQ) administered at one year. Linear regression was used to test the association of 17 nutrients on BMD at every bone site (dependent variables) measured at 1 year. All regression analysis were adjusted for the eﬀects of exercise, HRT use, body weight at 1 year, years post menopause and total energy intake. Results: Significant (p<0.05) correlations were found for mean intake of all nutrients between both methods (r=0.3–0.7). Regression analyses of nutrient associations on BMD by bone site, showed associations varied by nutrient and bone site between the two dietary assessment methods. Vitamin E, vitamin D, iron, magnesium, potassium, sodium and alcohol were consistently significantly associated with each of the same bone sites regardless of the dietary method. AFFQ regression coeﬃcients for potassium and magnesium were slightly attenuated when compared to the DR (by w0.1 unit). Fiber, calcium plus calcium supplement, calcium, phosphorus, fat and carbohydrate had fewer numbers of significant associations (50–80%) with BMD at similar bone sites. Vitamin C, caﬀeine and protein were not able to assess similar associations with BMD between the two methods. Conclusion: The magnitude and significance of the associations between nutrient intake and BMD are somewhat dependent on the dietary method. Depending on the nutrient of interest, DR or AFFQ may be used to assess significant nutrient associations with BMD in postmenopausal women.

P224SU. CORRELATION BETWEEN HEMOGLOBIN LEVELS AND BONE STATUS OF POSTMENOPAUSAL RURAL WOMEN IN KOREA Choe JS1, Kwon SO1, Paik HY2; 1National Rural Resource Development Institute, RDA, Suwon, Republic of Korea, 2Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea Hypoxemia can aﬀect bone mineral density and might be a risk factor for bone loss. Several studies have directly or indirectly suggested an association of hemoglobin levels with bone density in specific populations such as thalassemia and hemodialysis patients. However, this topic has not yet been profoundly studied in the general Korean older population. Therefore, we assessed to the relationship of anemia and hemoglobin levels with bone status at radius, tibia and phalanx of 379 postmenopausal women aged 50–93 years in Korea. Bone status was assessed by quantitative ultrasound device (Sunlight Omnisense 7000S) at radius, tibia and phalanx. Anemia has been defined by the WHO criteria as hemoglobin levels lower than 12 g/dl for women. The mean age of subjects was 68.9 (SD 8.9) years. The prevalence of anemia according to the WHO criteria was 42.2% (n=160). In unadjusted analyses, a significant diﬀerence, according to anemia status was reported for bone status at tibia. Anemic women were also more likely to present lower levels of bone status at the other two sites, but not significantly. In diet, iron intake was lower in anemic women, but not significant. The bone status at

tibia was positively correlated with hemoglobin (r = 0.20, P=<0.0001). After adjusted for age, the positive correlation between hemoglobin and bone status at tibia remained significant. Coeﬃcients from adjusted linear regression analyses evaluating the association between bone status and hemoglobin levels showed significantly positive association of hemoglobin with bone status at tibia (=18.248, SE=7.322; P=0.013). Significantly negative association was reported between anemia and bone status at tibia. Subjects with hemoglobin levels R2 g/dl above the anemia cut-oﬀ point were significantly higher bone measurements at tibia than anemic subjects. However, this tendency never showed a significant diﬀerence after adjusted analyses of covariance (age, height, weight, albumin, calcium and mental health). These results showed that anemia and hemoglobin levels are negatively associated with bone status at tibia in postmenopausal women older than 50 years. There is the need for further studies to explore the relationship of bone status and hemoglobin levels.

P225MO. BASELINE EVALUATION OF HEALTH-RELATED QUALITY OF LIFE IN GREEK POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS AND AN INADEQUATE RESPONSE TO ANTIRESORPTIVE MEDICATION Ginis A1, Thalassinos N2, Charalampidou E1, Hellenic OSSO Study Group GR3; 1Department of Medical Research, Pharmaserve – Lilly Greece, 2Diabetes and Metabolism Department, General Hospital ‘‘Evangelismos’’, 3Hellenic OSSOStudy Group Investigators, Greece Aim: The Observational Study of Severe Osteoporosis (OSSO) is a 12-month, European, prospective study aiming to assess the changes in Health Related Quality of Life (HRQoL) of women with osteoporosis and an inadequate clinical response to antiresorptive (AR) medications. Methods: The study population was assigned in 2 groups according to the following criteria: a) Patients(pts) who sustain a new clinical fragility fracture, despite an AR treatment at least 12 months prior to this fracture (Group A); b)Pts who discontinue AR therapy due to noncompliance and/or side eﬀects (Group B). HRQoL is assessed at baseline using a generic HRQoL questionnaire: EQ-5D (EuroQoL), and an osteoporosis-specific HRQoL questionnaire: QUALEFFO In Greece, data were obtained from 271 pts with severe osteoporosis. 263 (97%) met the inclusion criteria. After applying a Bonferroni correction, p-values less than 0.003 were considered statistically significant, giving an overall significance level of 0.10 across all tests. Results: Group A consisted of 143 pts (54.4%) with mean age 71.4 years. Group B consisted of 120 pts (45.6%) with mean age 64.7 years. Regarding QUALEFFO questionnaire , group A has statistically significant higher QUALEFFO mean [standard deviation] score for all domains except pain (49.3 [26.0] vs 39.9 [26.3] p=0.004) , than group B (physical function 46.3 [21.5] vs 27.4 [21.2] p<0.001 , social function 72.3 [22.7] vs 47.6 [23.7] p<0.001, general health perception 73.1 [19.0] vs 58.4 [21.0] p<0.001, mental function 51.4 [18.4] vs 41.9 [18.9] p<0.001). With reference to the evaluation of HRQoL assessed by EuroQoL questionnaire, diﬀerences were observed beetween groups A and B concerning the percentage of patients who experienced some or extreme problems regarding the usual activities (74 vs 51.6% p<0.001), mobility (73.9 vs 50.0% p<0.001), and self-care (43.7 vs 20.0% p<0.001). Conclusions: Women with several clinical risk factors for fracture and inadequate response to antiresorptive medications as observed have poor health related quality of life assessed by a EuroQoL (EQ-5D) generic HRQoL questionnaire and QUALEFFO an osteoporosis-specific HRQoL questionnaire.

P226SA. PARTICULARITIES OF OSTEOPOROSIS AND RISK FACTORS AFFECTING POSTMENOPAUSAL WOMEN IN BLACK SEA COASTLINE IN ROMANIA Circo E1, Circo S2, Chirca I2, Shavazo D1; 1Ovidius University, Constanta, Romania, 2Carol Davila University, Bucharest, Romania

S186 Aims: Evaluating the incidence of osteoporosis and risk factors in postmenopausal women living in an area with maximal annual sun exposure. Methods: We surveyed 1032 Caucasian postmenopausal women using dual-energy x-ray absorptiometry (DXA) with T- and Z-scores using WHO criteria. We have also assesed the physiological and pathological background, lifestyle habits, and secondary causes of osteoporosis. Screening for 25(OH)vitD was performed in September on 56 osteoporotic women (p%0.001). Results: Osteoporosis was diagnosed in 503(48.7%) women, osteopenia in 491(38%). Mean age 61.58.2yrs. First menses at 12.41.3 yrs, menopause at 44.11.8 yrs. Early menopause was seen in 9.1% of osteoporotic women mostly due to ovarectomy (8.6%). A significant negative corelation between Z-score and time duration till menopause was seen. Menopausal disturbances were noted in 12% of osteoporotic and 8% in osteopenic women. Nulliparity was met in 13.4% of osteoporotic and 11% in osteopenic women. Maternal osteoporosis: 58% of osteoporotic and 27% of osteopenic women (p%0.001). Fragile farctures 12.5% (65.1% had a single fracture, 34.8% had 2 fractures). Milk products were constant in 14% and intermitent in 6.8%. Voluntary sun exposure was 18%, occupational sun exposure 41%. Physical activity after menopause 36%, 4.8% continued exercises. Consumption of alcohol, coﬀee, smoking (0.8%,19.6%,2.5%, respectively). Mean BMI 30.18.3 in osteoporotic and 32.811.3% in osteopenic women. Secondary causes of osteoporis/osteopenia were: prolonged corticotherapy R6 weeks in 3.8%, hypercortisism 0.2%, hyperthyroidism 4.6%, hyperarathyroidism 0.08%,chronic renal insuﬃciency 5.3%. Mean serum level of 25(OH)vitD on 56 women age range 48.42.1 yrs was 26.616.7 ng/ml. Conclusions: The prevalence of osteoporosis and osteopenia is significantly elevated and probably underestimated in coastal area in Romania. Mean age of menopause is lower compared to other EU countries, diﬀerences existing between urban and rural areas. Fragile fracture prevalence known is high. Heredity is significant in a number of cases. Smoking, alcohol, coﬀee, BMI showed a poor correlation. A moderate consumption of milk products or calcium preparations was noted, physical exercise in postmenopausal women with osteoporosis is modest. Secondary causes leading to osteoporosis were low. It is surprising the mean serum level of 25(OH)vitD in a population living in a high annual sun exposure area.

P227SU. THE INCIDENCE OF SECONDARY HYPERPARATHYROIDISM AMONG ‘HEALTHY’ POSTMENOPAUSAL WOMEN SUFFERING FROM PRIMARY OSTEOARTHRITIS OF THE KNEE Papavasiliou KA1,2, Kirkos JM1, Potoupnis M1, Sarris IK1, Sayegh F1, Dimitriou C2, Kapetanos GA1; 13rd Orthopaedic Department, Aristotle University of Thessaloniki Medical School, 2 Orthopaedic Department, ‘‘Hippokrateion’’ General Hospital, Thessaloniki, Greece Aims: The assessment of the incidence of secondary hyperparathyroidism among otherwise ‘healthy’, symptom-free postmenopausal women suﬀering from primary osteoarthritis of the knee who did not receive any medication for the treatment of osteoporosis. Methods: This is a prospective cohort study. Between November 2004 and November 2005, 148 postmenopausal female patients suﬀering from primary osteoarthritis of the knee were admitted to our department in order to undergo primary total knee replacement. None of them had suﬀered any osteoporotic fracture, received any antiosteoporosis treatment or suﬀered from any other disease that could interfere with their bone mass or quality. None of them had previously assessed their bone mass index. All necessary anthropometric and statistic data (height, weight, age, years since menopause and aﬀected knee) was registered and the serum levels of intact parathyroid hormone (PTH), Calcium and phosphorus were evaluated. The patients’ mean age was 68.8 years (range: 58–81). The years that had passed since their menopause ranged from 7 to 30 (mean of 19.4 years). The patients were divided into three groups according to their age: Group A (n=21) age 55–64 years, Group B (n=88) age 65–74 years and Group C (n=39) age >75. The increased number of Group B patients (when

compared to Group A & C) was inevitable as most patients suﬀering from knee osteoarthritis decided to be operated at around that age. Results: The overall incidence of secondary hyperparathyroidism in all three groups was found to be 42.56% (63 out of 148 patients). Group A patients were most likely to suﬀer from secondary hyperparathyroidism (11 out of 21 in total patients). PTH values of Group B patients were normal in 52 out of 88 patients (59.09%) and of Group C in 23 out of 39 (58.98%). Conclusions: Secondary hyperparathyroidism seems to be a ‘silent’ epidemic among elderly postmenopausal women. According to our results women during their late fifties or early sixties are most likely to suﬀer from secondary hyperparathyroidism, mainly due to insuﬃcient calcium and/or vitamin D intake. It is our belief that antiosteoporosis diagnosis and treatment modalities should be focused on this group of patients too.

P228MO. ONE YEAR ACCIDENT AND INJURY PROFILE AMONG AGED IN SOUTHEASTERN FINLAND IN AN AREA OF 100 000 INHABITANTS Nurmi-Lüthje IS1, Lüthje PM2, Hinkkurinen J2, Lundell L2, Salmio K2, Karjalainen K2, Kajander A1; 1Health Centre of Kouvola Region, 2Kuusankoski Regional Hospital, Kuusankoski, Finland Aim: To investigate prospectively accidents and injuries and accident related factors among elderly 65 years and older. Methods: All first visits due to an injury from June 1, 2004 to May 31, 2005 were registered in ER in acute hospital using data base developed for this purpose. The following data were gathered: age, sex, time of injury, external cause of accident (ICD-10), type of accident (ICD-10), breath alcohol, use of hip protectors and type of injury (ICD-10). Preliminary results: Of a total of 523 accidents in 505 patients (193 males and 312 females), 62% occurred in women. The median age was 80 yr in women and 74 yr in men. The accidents distributed evenly throughout the year. Most accidents were falls on the same level (73%), 4% were falls from ladders or stairs, 1% falls from high level (>1 m) and 5% were unidentified falls. 6% were traﬃc accidents and 3% collisions. 42% of accidents took place in home or residential home, 46% during leisure time, 7% in institutional care, and 5% in other circumstances. A total of 561 injuries occurred. Most common injuries were fractures: 43% (n=244) and head and face injuries: 22% (n=125, of which 25% were severe). Distribution of fractures was: hip 31% (75% in women), wrist 17% (83% in women), proximal humerus 13%, ankle 7%, elbow 5%, tibia 4%, pelvis 2%, knee 2%, vertebrae 1%. Hip protectors were worn in 2% of the falls. Ethylalcohol was positive in 15% of men and in 3% of women (p<0.05). In 11% of men ethylalcohol level was over 1.5‰. Conclusion: Fall on the same level was the most typical accident. Nearly half of the accidents led to fractures and one fourth led to head or face injuries. Half of the fractures were those of hip or wrist. Rate of positive ethylalcohol result was high in men.

P229SA. VALIDITY OF SELF-REPORTED DXA TESTING AND DXA RESULTS Cadarette SM1,2, Beaton DE1,3, Dickson L1,2, Gignac MAM1,4, Jaglal SB1,2, Hawker GA1,2; 1University of Toronto, 2Sunnybrook and Women’s College Health Sciences Centre, 3St. Michael’s Hospital, 4University Health Network, Toronto, Canada Aims: To examine the validity of self-reported bone mineral density (BMD) testing by dual-energy X-ray absorptiometry (DXA) compared to physician records, and the validity of selfreported DXA results compared to actual DXA reports. Methods: Participants were recruited from a population-based study of women aged 65 or more years examining osteoporosis management in Ontario, Canada (N=871). Women reporting to have had a DXA were eligible, and asked to report the results of their most recent test as: high or normal bone density, low without osteoporosis (borderline or osteopenia), or osteoporosis. BMD was categorized by actual DXA reports obtained from physician records using WHO criteria.

S187 Results: Of 510 women reporting DXA testing, 413 (81%) physician records were obtained. Of these, 27 (7%) had no evidence of ever having had a DXA, giving a positive predictive value for self-reported DXA testing of 93%. A total of 332 women had a DXA report and self-reported results. The DXA report identified 24% with normal BMD, 43% with osteopenia and 33% with osteoporosis. This compared to the following self-reported results: 46% normal, 22% osteopenic and 32% osteoporotic. The weighted kappa statistic for the agreement between actual DXA results and self-report was 0.42 (95%CI=0.34, 0.49). Although 84% of those with normal BMD by DXA self-reported as such, only 29% of those with osteopenia by DXA and 62% with osteoporosis by DXA self-reported their results correctly (figure). Sensitivity, specificity, positive predictive value and negative predictive value for self-reported osteoporosis by DXA to indicate true osteoporosis by DXA were 62%, 83%, 65% and 82% respectfully. Conclusions: These data suggest minimal measurement error with respect to self-report of having had a DXA. However, the validity of self-reported DXA results was poor, misclassifying 38% of women with osteoporosis by DXA. Therefore caution is warranted in interpreting self-report of DXA results.

Proportion of self-reported DXA results by actual DXA results, N=332; solid: self-report high or normal bone density, n=153; stripped: self-report low without osteoporosis (borderline or osteopenia), n=74; dotted: self-report osteoporosis, n=105

P230SU. IS URINARY INCONTINENCE ASSOCIATED WITH FRACTURE RISK IN EARLY POSTMENOPAUSAL COMMUNITY DWELLING WOMEN? Dionyssiotis Y, Tournis S, Papakitsou E, Trovas G, Katsalira A, Economopoulos D, Samdanis B, Galanos A, Lyritis GP; Laboratory for Research Musculoskeletal System, University of Athens, KAT Hospital, Kifissia, Greece Aims: Urinary incontinence is a common problem and a chronic medical condition. Little importance has been attributed to the association of urinary incontinence and fractures, especially in community dwelling women. The aim was to study the influence of urinary incontinence as a risk factor for fracture in a postmenopausal female population. Methods: During the years 2004 and 2005, 1055 randomly selected community dwelling women participated in a control program for osteoporosis which was organised by the Hellenic Foundation of Osteoporosis in cooperation with the Hellenic Patient Osteoporosis Society. Incontinence episodes and fractures were assessed by answering a questionnaire about risk factors for low energy fractures by interview. None of the women took any antiosteoporotic drug including calcium supplementation. Women were separated into group A: 331 women with incontinence and group B: 724 women without incontinence episodes. The mean age of the participants included in the study was 64.88.8(SD) in group A and 63.88.9(SD) in group B. Women were also separated into subgroups according to age decade. Subgroup 1 (n=340): 50–59 years, subgroup 2 (n=363): 60–69 years and subgroup 3(n=346): 70+ years. In each subgroup we calculated the prevalence of fractures according to the presence of urinary

incontinence. Fisher’s test and regression analysis were used to estimate the association between urinary incontinence and fractures (OR, CI). Results: From group A 97 women (29.3%) had fractures vs 193 women (26.7%) from group B, a nonsignificant (N.S.) result (OR:1.14, CI:0.85–1.52, p=0.373). Subgroups’ analysis was given a significant result according to fractures only in subgroup 1: 23.4% vs 15.6% (p=0.05, OR:1.74, CI:1.1–3.05) between women with incontinence and without incontinence, respectively. In subgroups 2 and 3 the results were N.S. Conclusions: Urinary incontinence was associated with increased risk of fracture in early postmenopausal women. The results suggest that these community dwelling women should be considered as a special target group in order to prevent fractures.

P231MO. IS SCOLIOSIS ASSOCIATED WITH POSTMENOPAUSAL OSTEOPOROSIS Papadokostakis G1, Damilakis J2, Kontakis G1, Perisinakis K2, Hadjipavlou A1; 1Orthopaedic Department, 2Department of Medical Physics, University Hospital Crete, Crete, Greece Aim: The present study was undertaken to determine the incidence of scoliosis in a population of postmenopausal women with osteoporosis. Methods: Four groups were included in this study: (a) Sixty postmenopausal osteoporotic women aged from 48 to 75 years (mean 63.6 years). (b) Sixty osteoporotic postmenopausal women aged from 57 to 78 years (mean 67.3 years) with at least one vertebral fracture. (c) Sixty healthy postmenopausal women without osteoporosis aged from 49 to 68 years (mean 58.1 years). (d) Sixty non-osteoporotic postmenopausal women with degenerative disorders at the lumbar spine, aged from 51 to 67 years (mean 59 years). Osteoporosis was defined according the WHO criteria (T-score< - 2.5SD of the normal mean at the lumbar spine or femoral neck). BMD was measured at the lumbar spine and femoral neck with dual-energy X-ray absorptiometry (Hologic QDR 1000 plus). The Cobb method was used to measure the scoliotic curve at the lumbar spine. Results: Thirty patients from group A (50%), 33 patients from group B (55%), 11 patients from group C (18%) and 15 patients from group D (25%) had scoliotic curve at the lumbar spine greater than 10 degrees. A positive correlation was found between age and degree of curvature. However this correlation was not statistically significant(p>0.05). Age-adjusted data showed that osteoporotic women had a significantly higher incidence of lumbar scoliosis as compared with healthy women or those with degenerative disorders (p<0.01). Conclusions: Lumbar scoliosis is associated with postmenopausal bone loss and should be a radiological indicator for low bone mineral density.

P232SA. USING WEIGHT CUT-OFFS TO PREDICT OSTEOPOROSIS RISK Whelan BR1, Falvey EC1, Daly M1, Crowley M1, Shanahan F2, Harney S1, Molloy MG1; 1Dept of Rheumatology and Sports Medicine, CUH, 2Dept. of Medicine, UCC, Cork, Ireland Weight is known to influence bone mineral density at all skeletal sites and low body weight is a risk factor for fracture. Aim: To determine the relative influence of body weight on T-score in pre- and postmenopausal women and men at a number of diﬀerent skeletal sites. Method: DXA scan results from 22029 subjects (16623 postmenopausal, 4235 premenopausal women and 1171 men) were analysed. Correlation of body weight with T-score at lumbar spine (L1–4, L2–4) as well as left and right total hip (TH), femoral neck (FN) and trochanter (TR) were calculated using a Pearson correlation test. Where a significant correlation existed linear regression was carried out to establish the relative contribution of weight to T-score at each site in each of the diﬀerent groups. ROC curves were then plotted and optimal cut oﬀs for osteoporosis risk were chosen from these.

S188 Results: There was significant correlation between weight and T-score at all sites in all groups(p<0.001 for all). R2 values ranged from 0.270 for L2–4 in men to 0.468 for Left TR in postmenopausal women. R2 values were highest across all groups for trochanteric T score (0.380–0.468) and were greater in the postmenopausal group than in the other two groups. AUC values ranged from 0.775 to 0.871 and optimal cut-oﬀs for osteoporosis ranged from 69 kg in premenopausal women to 81 kg in men over 50 y.o. Conclusion: Weight has a greater influence on trochanteric T-score than at any other site. Weight has the greatest influence on postmenopausal T-score and this emphasises the importance of adequate nutrition in postmenopausal women. Simple weight cut-oﬀs can be used to reliably predict osteoporosis risk.

P233SU. ASSESSMENT OF PREVALENCE OF VITAMIN D IN POSTMENOPAUSAL WOMEN IN THE CITY OF BUENOS AIRES, ARGENTINA (LAVOS SUBSTUDY) Zanchetta JR1,2, Massari FE1,2, Agüero RG1,2, Silveira FD1,2, Cachizumba MO1,2, Fradinger E1,2, Messina OD3,4, Bogado CE1,2, LAVOS Study Group5; 1Instituto de Investigaciones Metabólicas, 2School of Medicine, USAL University, 3Argerich Hospital, 4CIRO Medical Center, Buenos Aires, Argentina, 5 LAVOS Study Group In spite of seasonal or technical diﬀerences, vitamin D status in adults living in great cities is usually insuﬃcient or deficient as shown in diﬀerent studies. Aim: To assess vitamin D nutritional status measuring serum levels of 25-hydroxyvitamin D (25-(OH)D) in postmenopausal women. Methods: A sample of 420 postmenopausal ambulatory women older than 50, participating in a Latin American osteoporosis prevalence study, were selected (Argentina‘s 2001 National Census). The groups were stratified according to censal segments within each geographical area (north, south, east, west, center) of the city of Buenos Aires (34( southern latitude). A blood sample for 25-(OH)D analysis (RIA), a bone densitometry of lumbar spine (AP) and proximal femur (Hologic Discovery A, USA), and a lateral radiography of thoracic and lumbar spine (GBA, Argentina) were performed to all subjects on the same day. To prevent seasonal bias, we measured 287 blood samples collected in winter time (May 18th - September 20th 2004) . The population selected was divided into 2 groups considering a deficit of 25-(OH)D equals to or below 12ng/ml (Lips P, 2001). Results: Prevalence of Vitamin D deficit was 26.8%. The group with deficit of 25-(OH)D was significantly older and with an increased BMI (Table 1). The percentage of deficit increased in every decile of age over 50 years (from 19.8% to 41.4%); BMI was not related with age deciles (p = NS). Osteoporosis (WHO criteria) in diﬀerent scanned regions showed no diﬀerences between groups (%12 ng/dl: 31.2% vs 28.6%, p=NS). The same occurred with vertebral fractures (%12 ng/dl: 14.3% vs 12.9%, p=NS). Table 1: Demographic characteristics of both groups

Characteristics Age (years) Weight (kg) Height (m) BMI (kg/m2)

Vit. D %12 ng/dl

Vit. D > 12 ng/dl

n=77 68.6510.00 70.6714.39 1.5390.059 29.785.42

n=210 65.899.26 67.9011.93 1.5580.062 27.984.74

P 0.0298 0.1339 0.0165 0.0065

Values are meansSD Two-sample T Test pR0.05 NS Conclusions: 1- In spite of the latitude, the prevalence of vitamin D deficit in the city Buenos Aires is slightly higher than in other international reports. 2- We confirm that older age and higher BMI are risk factors for vitamin D deficit.

P234MO. A PREVALENCE ASSESSMENT OF FRAGILITY FRACTURES IN THE PHILIPPINES delaRosa MT, Bonifacio LR, Canete AC; Philippine Orthopedic Association, Quezon City, Philippines Current figures on the prevalence of osteoporosis in the Philippines are not known. Aims: To determine prevalence of age, sex and site specific fragility fractures in the country. Methods: The source of information is the ICD 10 based data system of the Philippine Health Insurance Corporation (PhilHealth). PhilHealth covers three quarters of the Philippine population. The authors reviewed all data entries for 2004, involving fractures of the hip, spine and distal radius. Summary statistics include count and percentage, prevalence proportion, standard error (SE) and 95% confidence limits (95% CI; lower limit and upper limit). Results: A total of 4670 records of patients of all age groups with reported fractures of the spine (11.7%; 545 of 4670), distal radius (48.8%; 2280 of 4670) and proximal femur (39.5%; 1845 of 4670) are considered in the estimation of the prevalence proportion of osteoporosis in 2004. There were 2385 females and 2285 males. In the % 50 age group, 22% are females and 78% males, whereas in the more than 50, 76% are females and 24% males. About 80% of the total population are 50 years and above. Of these data, 51.1% (2385 of 4670) are that of female patients with reported fractures of the spine (294 of 545), distal radius (785 of 2280) and femur (1306 of 1845). Of the female patients, majority of them (75.8%; 1917 of 2385) are more than 50 years old. Relative to the female population, more than 50 years old, prevalence proportion for fracture of spine and proximal femur peaks at 71 to 80 years age bracket; whereas, distal radial fractures are maximum at sixth decade. For site specific fractures, fracture of proximal femur is highest, followed by spine and distal radius. Conclusions: Osteoporosis-related fractures are a significant public health problem in the country. Even if the majority of those aﬀected are economically nonproductive, osteoporosis and subsequent fractures are associated with significant costs relating to hospitalization, outpatient care, disability and premature death. A burden of illness study can further define the magnitude of the problem and detect areas where information is lacking.

P235SA. QUANTITATIVE CALCANEAL ULTRASONOMETRY: NORMATIVE DATA FOR THE TURKISH POPULATION AND AGE RELATED VARIATION IN STIFFNESS INDEX Durmaz B, Oncel S, Kirazli Y, Alper S, Ozlen P, Saridogan M, Kutsal YG, Dincer G, Atalay F, Eskiyurt N; Turkish Osteoporosis Society, Turkey The aim of the present study was to establish a normative data for calcaneal stiﬀness index (SI) as a quantitative ultrasound measurement in healty Turkish population and to evaluate the age related changes in this value. This was a cross-sectional, epidemiological study. The subjects with medical conditions aﬀecting bone metabolism (chronic diseases or medications) were excluded. A total number of 10435 subjects were measured with Achilles devices; 8156 subjects (1389 males and 6767 females) in the age range 18–89 years from both rural and urban area were included in the study. Normative data was expressed using two statistical models mean and 95% percentile, and regression analysis. The peak value for SI in female subjects was achieved in the 30–39 years age group. The total age related decrease was 24.26% for SI in female subjects. For SI measurements in male subjects, the peak value was obsered in the age range 18–29 years. The total age related reduction in SI values of male subjects was 17.8%. There was a statistically significant reduction in male SI data between 40–49 and 50–59 years. The female SI data showed significant decrease between the age groups 40–49 and 50–59; 50–59 and 60–69; and 60–69 and 70–79. In 4401 women from 40 years to 59 years of age, the mean SI was significantly higher in premenopausal women (N=2002) than in postmenopausal women (N=2399).

S189 The curve representing the SI change according to age is best fitted by the regression analyses of cubic model. The results of this study could be useful as a guide for comparing the data of individual studies.

P236SU. SELECTED INDICES OF SOMATIC DEVELOPMENT IN CHILDREN WITH OSTEOPOROSIS Loba-Jakubowska E, Chlebna-Sokol D, Frasunkiewicz J, Rusinska A; Department of Paediatric Propedeutics and Bone Metabolic Diseases Medical University, Lodz, Poland Developmental age osteoporosis can lead to somatic development disorders in children and adolescents. Physical development abnormalities are also conducive to bone mineralisation disorders. The aim of the study was to evaluate the somatic development in children with osteoporosis diagnosed on the basis of complex clinical, biochemical and densitometric examination. Patients and methods: The examination included 82 children aged 5–18 years. 29 of them were diagnosed with primary osteoporosis and 53 with secondary. The following anthropometric measurements were taken: body height, length of the lower limb, upper limb and trunk; width of shoulder, chest, pelvic, elbow epiphysis and knee epiphysis, chest depth and body weight, according to the commonly recommended methods. The BMI index was evaluated. Value normalization was carried out for the given somatic features in relation to the reference group. The correlation between bone mineral density and anthropometric measurements was evaluated by means of Statistica 5.0 program. Results: Somatic development disorders were found predominantly in children with secondary osteoporosis – in 11/53 there was body height deficiency, and in 6 body weight deficiency was detected. Only in 2/29 children with primary osteoporosis negative (below -2.0) normalized values of these features were found. For the most part the negative normalized values were related to: trunk length and lower limb length (in 15/82), the upper limb length (18/82), shoulder width (24/82) and elbow epiphysis width (15/82). Positive statistically significant correlation between bone mineral density and limb length measurements as well as between bone mineral density and trunk, elbow and knee width measurements were found. Conclusions: 1. Infrequent abnormalities within the range of somatic development indices in children with primary osteoporosis are not causally linked to the disease. 2. Physical development disorders predominantly related to body proportions in children with secondary osteoporosis are caused by the course and the manner of treatment of the primary disease.

P237MO. ECONOMIC EVALUATION OF ACLASTAT (ZOLEDRONIC ACID 5 MG) VERSUS ACTONELT (RISEDRONATE) IN TREATMENT OF PAGET’S DISEASE Mittmann N1,2, Isogai PK1, Adachi JD3, Kindundu CM4, Barbeau M4; 1HOPE Research Centre, Division of Clinical Pharmacology, Department of Medicine, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada, 2Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada, 3St. Joseph’s Healthcare, McMaster University, Hamilton, Ontario, Canada, 4Novartis Pharmaceuticals Canada Inc., Dorval, Quebec, Canada Aims: Aclastat (zoledronic acid 5 mg) is a new agent available for the treatment of Paget’s disease of the bone (PDB). The objective of this evaluation is to conduct an economic evaluation of Aclastat and Actonelt (risedronate) in a PDB population. Actonelt is the standard of care in Canada. Methods: Perspective of the study was from the publicly funded Canadian provincial health care system. Target population was PDB patients with serum alkaline phosphatase levels at least twice the upper limit normal, symptomatic, or at risk of PDB complications. Treatment cost (2005 CAN$) was determined using eﬃcacy and safety data obtained from the pooled analysis of two comparative trials recently published. Direct medical costs included drug, physician, remission, laboratory, diagnostic and adverse event costs. Frequency of physician visits, laboratory and diagnostic tests were based on published treatment guidelines. No

infusion costs for Aclastat were included since Novartis will fund the infusions. A 5% discount rate was used after one-year. The acquisition cost of Aclastat was equivalent to Actonelt. Results: A single 5-mg IV dose of Aclastat was shown clinically to have superior eﬃcacy, faster onset and longer-lasting eﬀect, compared to 30 mg of daily Actonelt for 60 days. Overall PDB treatment costs were 2,051.69 for Aclastat and 2,498.96 for Actonelt. Based on remission rates, drug costs over two-years was 867.80 for Aclastat and 1,277.02 for Actonelt. A breakdown of costs is shown in Table 1. No incremental cost-eﬀectiveness ratio was calculated as treatment with Aclastat was clinically more eﬀective and cost less than Actonelt. Cost breakdown of PDB treatment with Aclastat and Actonelt over 2-years

Initial drug cost Drug cost due to relapse Additional drug cost (antipyretic and opiate agonist) Infusion cost Physician cost Laboratory cost Diagnostic cost Adverse event cost (flu like symptoms) Total treatment cost

Aclastat

Actonelt

$716.04 $151.76 $679.42

$716.04 $560.98 $679.42

Supported by Novartis $404.80 $77.94 $19.76 $1.97 $2,051.69

None $404.80 $107.49 $29.08 $1.15 $2,498.96

Conclusions: Aclastat for PDB treatment was clinically and economically superior over a two-year time period compared to Actonelt.

P238SA. QUANTITATIVE ULTRASOUND REFERENCE AND FRACTURE DATA FOR MEN Glueer CC, Wolter J; Medical Physics, Diagnostic Radiology, University Clinic Schleswig-Holstein, Kiel, Germany Aims: Bone mineral density (BMD) reference data show substantial diﬀerences for men and women but fracture risk appears to be fairly similar at the same level of BMD. Quantitative ultrasound (QUS) methods are widely used but gender-related diﬀerences have received little attention. The fact that several diﬀerent QUS methods have been introduced further complicates the assessment. In order to be able to interpret QUS findings in men, we reviewed reference and fracture data available. Methods: In the EU project NEMO (Network in Europe on Male Osteoporosis) we have reviewed published QUS reference ranges and fracture data in men. We included the following QUS techniques: transverse transmission techniques at the calcaneus (two devices: GE Lunar Achilles, Hologic Sahara), transverse transmission at the finger phalanges (one device: IGEA DBM Sonic), and axial transmission (one device: Sunlight Omnisense). QUS variables included speed of sound (SOS), broadband ultrasound attenuation (BUA), stiﬀness index and quantitative ultrasound index (QUI) for transverse transmission techniques at the calcaneus, amplitude-dependent speed of sound (AD-SoS) for transverse transmission at the finger phalanges, and SOS for axial transmission techniques at several sites. Results. 10 studies on reference data (8437 men) were included in the survey. SOS decreased by -0.02 to -0.22 % p.a. and BUA decreased by -0.12 to -0.13 % p.a for transverse transmission techniques. SOS decreased by -0.02 to -0.08 % p.a. for axial transmission methods. When standardized by the population standard deviation the decrease p.a. was similar for transverse transmission techniques at the calcaneus (both SOS and BUA) and axial transmission techniques (SOS), ranging from - 0.01 to - 0.04 SD p.a. (all variables) but it was larger for transverse transmission techniques at the finger phalanges, ranging from 0.06 to -0.1 SD p.a. for AD-SoS. The sample sizes of the fracture studies were too small to judge gender-associated diﬀerences in QUS.

S190 Conclusions. Age related decreases were observed for all QUS techniques and variables studied but the magnitudes of the annual decreases diﬀer among techniques. Fracture data are too limited to judge whether fracture risk is similar for men and women at given levels of QUS variables.

P239SU. DIETARY AND LIFE HABITS AND BONE HEALTH IN URUGUAYAN SCHOOL CHILDREN: NATIONAL SURVEY Hernández J1, Chijani V1, Alemán A2, Calegari M1, Lima S1, Vaglio V1; 1Osteopathy Study Group from Society of Rheumatology of Uruguay, 2School of Medicine, Montevideo, Uruguay Aim: to study dietary, genetic and life habits that influence bone health among school children from public and private primary schools in Uruguay. Methodology: A sample of 573 third and fourth graders from schools from five Departments of Uruguay which represented diﬀerent areas and socioeconomic status were selected for the study. A descriptive exploratory study was performed. Data was obtained using a questionnaire applied to the children and filled in by the teachers of the selected schools. Some data were obtained from parents‘ reports. Teachers were trained for data collection by members of Osteopathy Study Group from Society of Rheumatology of Uruguay. Results: About 45% of school children do less than two hours of physical activity per week. In relation to dietary habits: 16% reported never taking any kind of milk, and only 26% satisfy calcium requirements with the intake of milk (the most cheap and available dairy product in the country). About 14% of participants had a bone fracture once in their lives and 10.6% had relatives with hip fracture. More than 50% reported intake of other drinks (soft drinks, juice, tea) as substitutes of milk. Conclusions: Dairy consumption and physical activity in most of the school children is not enough for an optimal bone development. This fact is alarming since some other studies in the country have shown that dairy intake decreases when children become adolescents. It is necessary to design a preventive intervention to increase calcium intake and physical activity in this stage of life to improve bone health in this population.

P240MO. PREFERRED SKELETAL SITE FOR OSTEOPOROSIS SCREENING IN HIGH-RISK POPULATIONS Moayyeri A1, Soltani A1, Bahrami H2, Tavakoli Shalmani H3, Ahmadi Abhari S3, Larijani B1; 1Endocrinology & Metabolism Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, 2Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3Research Development Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Aims: The current World Health Organization (WHO) definition of osteoporosis, which is based on densitometry of lumbar and femoral regions, is extensively used for decision-making in clinical practice. Discordance in diagnosis of osteoporosis using this definition is a known phenomenon. The aim of this study was to evaluate the impact of such discordance and to assess the diagnostic value of using one skeletal site for screening purposes as opposed to the two sites required in the WHO criteria. Methods: Data was collected from 4188 individuals (3848 female, mean age 53.4 11.8) referred to a community-based outpatient osteoporosis testing center in Tehran, Iran. Dualenergy X-ray absorptiometry (DXA) using a Lunar DPX-MD densitometer (Lunar 7164, GE, Madison, WI) was performed on L2-L4 lumbar spine and total hip for all cases. The DXA results were categorized according to WHO criteria. Sensitivity for each site was calculated as number of cases with T-score < -2.5 at that site divided by the total number of cases with T-score < -2.5 at any site. Results: Prevalence of osteoporosis diagnosis using lumbar DXA, femoral DXA, and WHO criteria (either of the sites) were 24.7%, 12.4%, and 27.8%, respectively. Sensitivity of lumbar DXA for diagnosis of osteoporosis (88.9%) was significantly higher than femoral DXA (44.6%, p < 0.000); but this diﬀerence became

non-significant for men R60 and women R 70 (p = 0.615 and p = 0.077, respectively). Agreement of the procedures in diﬀerent sites (kappa) was 0.40 (0.37 to 0.43). When proximal femur was considered as the reference, positive likelihood ratios of lumbar DXA to detect cases were 4.8 and 2.2 in younger and older groups, respectively. Conclusions: Concerning high rate of discordance and low agreement between DXA results, the data obtained from each anatomical site cannot predict the condition of the other site. However, if use of a single assessment is intended for screening programs, public health authorities can develop diﬀerent strategies for diﬀerent age groups of their population. We propose lumbar DXA for the younger group (men < 60 and women < 70) and femoral densitometry for the older.

P241SA. DIET AND OSTEOPOROSIS IN POSTMENOPAUSAL IRANIAN AND INDIAN WOMEN: A MULTICENTER BASED STUDY Keramat A1, Patwardhan B1, Chopra A2, Larijani B3, Mithal A4, Chakravarty D5, Adibi H3, Hossainnezhad A3; 1School of Health Sciences,Pune University, India, 2Center of Rheumatoid Diseases, Pune, India, 3Endocrinology and Metabolism Research Center, Tehran, Iran, 4Endocrinology Department of Appolo Hospital, New Delhi, India, 5Radiology Department of Max Medical Center, New Delhi, India Aim: In this study we aimed to assess the association of nutrition factors and osteoporosis in postmenopausal women from selected BMD centers of two developing Asian countries (Iran and India). Methods: This study is a multicenter interview-based study conducted in selected hospitals and health centers from urban areas in Iran and India. The case group included postmenopausal osteoporotic women who were identified as patients with bone density higher than 2.5 SD below average of young normal bone density (in L1-L4) spine region interest and/or total femoral region) by using DXA method. The controls were chosen from postmenopausal women with normal bone density (in L1-L4 spine and total femoral regions using DXA method) matched in age group with cases. The sample sizes included from Iran a total of 363 subjects (178 osteoporotic and 185 normal) and from India a total of 354 subjects (203 osteoporotic and 151 normal). Data collected included filling food frequency questionnaires through personal interviews, use of case records, files and documents. Estimation association of risk factors with osteoporosis has been calculated by odds ratio, and multiple logistic regression analysis has been used for adjustment of the most relevant factors like: age, weight, height, education level, duration of menopause, menarche and menopause age, etc. Results: Pure vegetarianism (2.2)and red meat consumption more than 4 times per week (1.02) were found to be significant risk factors in Indian and Iranian subjects, respectively. Regular consumption of soya (0.32), almond (0.46), yogurt (0.59), fish (0.54), fruits (0.50) and milk/tea 4 cups per day and more (0.39) appeared to be significant protective factors in India. Regular consumption of cheese (0.55), milk (0.61), yogurt (0.42), chicken (0.48), egg (0.56), fruit (0.43), tea 7 cups per day and more (0.29) and limitation in use of salt (0.51) and oil (0.54) were found to be significant protective factors in Iran. Conclusions: Osteoporosis in Iranian and Indian subjects (that were rather diﬀerent in diet pattern) appears to be associated with several nutrition factors. It can be exploited in preventive educational strategies on osteoporosis in these populations.

P242SU. APPROPRIATENESS OF CARE IN OSTEOPOROTIC AND ELEVATED RISK PATIENTS IN CANADA: THE EXPERTMD IN OSTEOPOROSIS PROJECT Adachi JD1,2, Meilleur MC3, Sénécal M3, Nemis-White J3, Trasler T3, Choquette D4,5; 1Department of Medicine, McMaster University, Hamilton, Ontario, Canada, 2St. Joseph’s Healthcare, Hamilton, Ontario, Canada, 3Merck Frosst Canada Ltd, Montréal, Quebec, Canada, 4Université de Montréal, Montréal, Québec, Canada, 5Hôpital Notre-Dame, Montréal, Québec, Canada

S191 Aims: To assess the appropriateness of osteoporosis care provided to high risk Canadians according to risk profile. Methods: ExpertMD in Osteoporosis is an educational program designed for family physicians and aimed at enhancing the care provided to patients at risk of osteoporotic fractures. Patients at high risk for osteoporosis, based on validated clinical and medical risk factors shown to predict low BMD and fractures, were recruited by family physicians voluntarily participating in the program. Gathered data include individual clinical and medical risk factors, osteoporosis screening (X-ray, DXA, QUS), and osteoporosis-related drugs or dietary supplements use (bisphosphonates, hormone replacement therapy, selective estrogenreceptor modulators, calcitonin, PTH analogs; calcium, vitamin D). Prior to educational activities, osteoporosis-related state of care was assessed at entry and exit of medical visit to establish whether recommended care was provided. According to risk status, patients were classified as osteoporotic (OP) or elevated risk (ER). For OP patients, recommended care was defined as being currently treated with an OP-related drug, and for ER patients as having been referred for BMD testing within the last 3 years or being treated with OP-related drug or supplements. Post-educational program data will follow. Results: See Table. State of care at visit entry OP patients (N=342)

1

Elevated risk patients 2 (N=588)

63.5% 64.8% (381/588) Under recommended (217/342) care 3 Not under 36.5% 35.2% (207/588) recommended care (125/342) State of care at visit exit in patient requiring care at visit entry OP patients Elevated risk patients (N=125) (N=207) 11.2% (14/125) 72.0% (149/207) Under recommended care 3 Not under 88.8% 28.0% (58/207) recommended care (111/125)

P-value

Methods: Conducted from March to August 2003, 200 subjects were recruited from a community in the eastern part of Singapore. The sample was representative of the socio-economic status of Singaporeans and had a wide range of BMI (<18.5 kg/m2: 20%, 18.5–22.9 kg/m2: 50%, >23 kg/m2: 30%). Dropouts were replaced by matching the gender, housing type and BMI of subjects. BMD measurement of the lumbar spine was performed by dual-energy x-ray absorptiometry (DXA) using a Hologic QDR 4500W densitometer (S/N 49088). Multiple ordered logistic regression was used to ascertain if the identified factors (age, gender, osteoporotic status) were associated with the risk of falls. Performed with Stata 7.0, all statistical analyses were carried out at 5% level of significance. Results: Among the subjects (68% female, age: 57–82 years) 24.5% were osteoporotic. Among the subjects, 86.5% were at risk of falling (low risk: 26.5%; low-moderate: 31.0%, moderate: 19.0%and high risk: 10.0%). The multiple ordered logistic regression model showed that female subjects had a higher risk of falling when compared with their male counterparts (OR: 2.4; 95% C.I.: 1.2—4.7). In addition, the risk of fall also increased with age (OR: 1.1; 95% C.I.: 1.0—1.2). Discussion/Conclusion: Singapore has one of the fastest ageing populations in the world. It is predicted that by 2030, 18% of the population will be 65 years and above. In addition, the speed of ageing is very rapid at 3.1% per annum. A better understanding of diseases/conditions contributing to disability in old age would help ensure the development of appropriate services to address growing needs. This study has indicated that Singapore’s community dwelling population is at high risk of falls and has a significant prevalence of osteoporosis. A nation wide programme is underway to proactively identify elderly at risk of falls, osteoporosis as well as primary, secondary and tertiary intervention programmes.

0.6796

<0.0001

1-Patients with prior osteoporotic fracture or low BMD test result (hip or spine T-score < -2.5); 2-Patients with elevated clinical risk for osteoporosis or with systemic corticosteroid therapy, premature menopause, abnormal menstrual cycles, or surgically induced menopause; 3-For OP patients, being currently treated with an OP-related drug. For ER patients, having been referred for BMD testing within the last 3 years or being treated with OP-related drug or dietary supplement.

Conclusions: At visit entry, appropriateness of care was similar for OP and ER patients, with 35% of patients not receiving recommended care. During visit, physicians were significantly less likely to adjust care for OP patients compared to ER patients. Participating physicians were eﬀective at screening osteoporosis, but fracture preventive therapy in OP patients remained underused. Our results indicate that risks evaluation tools may help recognition of patient at high risk for osteoporotic fracture. As these physician and patient populations are not randomly selected and as physician behavior is under self-reported study settings, the rate of appropriate care may be an overestimate of the prevalent care in Canada.

P243MO. THE BURDEN OF FALLS AND OSTEOPOROSIS IN SINGAPORE Goh C1,3, Chan SP2, Jumala J3, Deurenberg-Yap M2,4; 1Ministry of Health, 2Health Promotion Board, 3Changi General Hospital, 4 National University of Singapore, Republic of Singapore Aims: Osteoporosis, an age-related illness, is becoming an increasing problem in Singapore. Older persons with osteoporosis are at much greater risk for developing hip fractures from falls. This study aimed to identify the factors for explaining the risk of falls among elderly Chinese subjects in Singapore.

P244SA. LYCOPENE IN THE SERUM OF POSTMENOPAUSAL WOMEN HAS INTERACTIVE EFFECTS WITH THE DIETARY COMPONENTS CALCIUM AND VITAMIN C ON OXIDATIVE STRESS AND BONE TURNOVER MARKERS Mackinnon ES1, Rao AV2, Josse RG1, Murray TM1, Rao LG1; 1 St. Michael’s Hospital, Toronto, Canada, 2University of Toronto, Toronto, Canada Aims: Oxidative stress has been associated with the risk of osteoporosis. We have recently shown that in postmenopausal women serum lycopene correlates with lower bone resorption and lower protein oxidation. A diet high in calcium and antioxidants, such as vitamin C, is known to improve bone mineral density in postmenopausal women. Our objective was to conduct a crosssectional study to determine whether there is an interactive eﬀect between lycopene and the dietary components calcium and vitamin C, on bone turnover markers and oxidative stress parameters in postmenopausal women. Methods: We recruited 33 postmenopausal women between the ages of 50–60, who provided fasting blood samples and dietary records from the preceding seven days. We measured serum lycopene, the oxidative stress markers, lipid peroxidation and protein thiols, and the turnover markers, bone alkaline phosphatase (BAP) and cross-linked N-telopeptides of Type I Collagen (NTx). Participants were grouped according to their calcium and vitamin C intake, as determined by dietary records, and correlations made between serum lycopene and NTx, BAP, lipid peroxidation and protein thiols. Results: There was a significant, positive correlation between serum lycopene per kilogram body weight and protein thiols (r = 0.67, p<0.01) in participants who consumed R1200 mg per day of calcium. No eﬀect was seen in participants who consumed <1200 mg per day. These results suggest an interactive eﬀect between calcium and serum lycopene on protein thiols. There was a significant, negative correlation between serum lycopene per kilogram body weight and NTx (r = -0.68, p<0.05) in participants who consumed R 500 mg/day of vitamin C, suggesting an interactive eﬀect between vitamin C and serum lycopene on bone resorption. No eﬀect was seen in participants who consumed <500 mg per day of vitamin C.

S192 Conclusions: These results support our hypothesis that in postmenopausal women serum lycopene interacts with the dietary factors calcium and vitamin C to decrease protein oxidation and bone resorption. Our results suggest that the incorporation of tomato lycopene into the daily diet of postmenopausal women who are at elevated risk for osteoporosis reduces the risk of developing this debilitating disease.

P245SU. PRELIMINARY STUDY OF SPATIO-TEMPORAL GAIT PARAMETERS OF A GERIATRIC MEXICAN FEMALE SAMPLE Núñez CL, Ramírez PE, Rodríguez RG, Quiñones UI, Alessi MA, Pérez SPI; Instituto Nacional de Rehabilitación, México, D.F. México Literature reports behavior of gait parameters in elderly population, however these do not adapt to Mexican women’s anthropometric characteristics. The aim of the study was to generate a gait parameters database of elderly Mexican female population and to assess its agreement with reported data. This database is intended to be used to compare gait parameters between healthy and osteoporotic women in a future study. 250 healthy Mexican women between 60 and 89 years of age, without history of lower extremity fractures, osteoporosis or any musculoskeletal pathology participated in the study. Volunteers walked through an instrumented walkway and spatial and temporal gait parameters were recorded. Ambulation time, velocity, stride and step length, toe in/out angle and the Functional Ambulation Profile score (FAP) were considered for the analysis. FAP is a numerical expression that reflects gait proficiency and was calculated by the software provided with the instrumented walkway. A score of 100 represents optimal performance, 0 represents no walking ability. Population’s mean age, height and weight were 69.16.5 years, 151 6.2 cm and 63.59.73 kg, respectively. Table I shows mean (SD) and limit values for a 95% confidence interval of the measured parameters distributed by groups of age. Cadence values remained similar to those reported in literature; however, mean values of number of steps and ambulation time increased while velocity stride and step length decreased. These diﬀerences tended to increase with age. Table I. Spatial and Temporal Gait Parameters of a Healthy, Geriatric Mexican Female Sample Age (years)

60–69

70–79

80–89

FAP 95% CI Ambulation time (s) 95% CI velocity (cm/s) 95% CI Number of Steps 95% CI Cadence (steps/min) 95% CI Stride length Left 95%CI (cm) Right 95% CI

92.65( 6.63) (91.52 – 93.79) 3.31 (0.84) (3.16 – 3.45) 95.59 (16.31) (92.79 – 987.39) 6 (5.80 – 6.18) 110.38 (10.63) (108.56 - 112.20) 104.06(12.36) (101.94 - 106.18) 103.94 (12.14) (101.81 - 106.07) 51.75(6.33) (50.66 - 52.84) 51.84(6.29) (50.76 - 52.92) 8.61(6.04) (7.58 - 9.65) 11.21(6.12) (10.15 - 12.26)

90.43 ( 8.87) (88.67 – 92.19) 3.57(0.92) (3.39 – 3.76) 90.72 (17.07) (87.33 – 94.11) 7 (6.18- 6.66) 109.78(11.36) (107.52 - 112.04) 98.91 (12.96) (96.34 - 101.48) 99.33 (13.08) (96.73 - 101.93) 49.27(6.59) (47.96 - 50.57) 49.47(6.71) (48.14 - 50.80) 7.89(5.90) (6.72 - 9.06) 10.85(5.63) (9.73 - 11.97)

85.82 (10.43) (80.82 – 91.19) 4.18(1.24) (3.55 – 4.82) 80.51 (18.43) (71.03- 89.98) 8 (6.62 – 7.67) 107.49 (12.73) (100.94 - 114.04) 89.71 (13.91) (82.56 – 96.86) 89.45 (13.60) (82.46 - 96.45) 44.82(6.51) (41.47 - 48.17) 44.36(7.61) (40.45 - 48.28) 8.90(7.33) (5.13 - 12.67) 11.42(8.86) (6.88 - 15.97)

Step length (cm)

Left 95%CI Right 95%CI

toe in/ toe out (()

left 95%CI Right95%CI

The diﬀerences observed, and its progression, may be explained in part by Mexican women population’s anthropometry and by a general decrease in muscle strength associated with aging, which induces a new adaptation of gait attempting maximal security and stability. This study supports the idea that comparing gait parameters of pathological populations with those of a healthy population, but of diﬀerent extraction (i.e. Caucasian vs. Asian), may induce errors in results.

P246MO. NATIONAL NUTRITION AND HEALTH SURVEY 2003: PREVALENCE OF FRACTURES AND OSTEOPOROSIS AMONG FILIPINOS Li-Yu J; Osteoporosis Society of the Philippines Foundation, Inc. Objective: The objectives of this study are: 1) to determine the prevalence of fracture and osteoporosis among individuals 50 years and above in the Philippines; 2) to determine the risk factors for osteoporosis; 3) to determine the prevalence of low bone mass using peripheral bone density measurement; and 4) to determine the prevalence of patients at risk for osteoporosis using the Osteoporosis Risk Assessment Tool for Asians. Methodology: Using a multi-staged cluster sampling methodology, a total of 2,850 adults, 50 years and over out of 4,753 adults aged 20 and over that were covered in the National Nutrition and Health Survey in 2003 were examined. A valid questionnaire was administered to the survey respondents to determine the prevalence of fractures and osteoporosis. Random screening of peripheral bone density using the LUNAR pixi was conducted in 284 adults, 50 years and above in the National Capital Region (NCR) only. These respondents were also asked to accomplish a risk assessment profile using the OSPFI-IOF millennium one-minute osteoporosis risk test. Results: The overall prevalence rate of osteoporosis in adult Filipinos 60–69 years of age was 0.8% while those beyond 70 years old was 2.5%. There was no report of osteoporosis among 50–59 year old individuals. The overall prevalence of fractures was 11.3% in females and 9.0% in males. The overall prevalence of low bone mass using the heel pixi was 65.2% in females and 70.0% in males. Using the OSTA, 44.8% females and 41.9% males were identified to be at intermediate risk while 17.6% females and 12.9% males were at high risk for osteoporosis. Of the factors considered in the one-minute osteoporosis risk test that put patients at risk for osteoporosis, coﬀee intake, menopause at age 45, and presence of fractures after age 45 were identified as the most prevalent among the respondents. Discussion: The result of this survey maybe used in considering osteoporosis as an emerging health problem among our elderly population. The data presented here can also serve as recommendations for the health policy makers in prioritizing primary as well as secondary preventive health care programs for the Filipino elderly.

P247SA. FREQUENCY ASSESSMENT OF OSTEOPOROSIS RISK FACTORS IN A SAMPLE OF ADULT TURKISH POPULATION OVER 16 YEARS OF AGE: A PRELIMINARY REPORT Tuncer T, Durmaz B, Akarimak U, Kuran B, Akyuz G, Altan L, Butun B, Canturk F, Celik R, Gilgil E, Gulbahar S, Kacar C, Kayhan O, Kozanoglu F, Kutlay S, Kurtais Y, Oncel S, Sarpel T, Sindel D, Sener K, Yalcin P; Turkish RASPA-OP Epidemiological Study Group, Turkey Aim: To determine the frequency of generally accepted risk factors in a sample of adult Turkish population aged over 16 years. Method: A two stage stratified sampling method was used to select a sample of the population over 16 years of age. The study was carried out in 9 cities from diﬀerent regions of Turkey. The study population (approx. 25 million) represented 39.2% of the total Turkish population. 10 interviewers worked face to face with the subjects during the field survey. The generally accepted risk factors for osteoporosis (OP) used in this survey were risks related to lifestyle (physical activity, Ca intake, sun exposure, smoking, coﬀe and alcohol consumption), previous fracture, family history of fracture. Medications, hormonal profile and comorbidity were also assessed. The awareness of the population about OP was evaluated by the percentage of the population previously screened besides questionnaire. Chi square test was used for statistical analysis, data were weighted with respect to Turkish population. Results: A total of 2579 subjects (1048 men mean age 41.896.70 and 1284 women mean age 41.136.53) were included in the analysis. 567 (22%) of them were over 50 years of age. 19 subjects (0.7%) reported previous fracture, 4 were over 50 and 11 were women. Family history of fracture was found in 32 subjects (1.2%). The frequency of secondary causes of OP as medications

S193 and comorbid diseases were very low. Sun exposure, Ca intake, smoking, alcohol and coﬀee consumption were significantly low for the female gender. Level of daily physical activity was higher in female subjects, but sporting activity level was quite low in both genders. The awareness of the population about OP was low (9.9%), 5.7% applied to physician for OP while 4.3% had been screened previously by DXA (64.8% were detected as OP). Conclusion: Fragility fracture which is the main endpoint of OP was detected to be quite low in this survey. In the population evaluated the major risk factors were found to be related particularly to lifestyle. Educating the population against risk factors for OP seems to be important for prevention of OP in Turkey.

P248SU. IDENTIFYING THE ASSOCIATED RISK FACTORS FOR OSTEOPOROSIS AND DEVICE A SCORING SYSTEM IN MALAYSIAN WOMEN Lim PS, Seri Suniza S, Adeeb N, Ong FB; Department Obstetrics & Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lampur, Malaysia Introduction: Osteoporosis is a silent epidemic amongst women in the perimenopausal age group. In the first phase, healthy women above 45 years who attended the Department of Obstetrics & Gynaecology, Hospital Universiti Kebangsaan Malaysia (HUKM) were recruited over 3 years from November 1999 to November 2002. A health assessment with investigations and a set of questionnaire was filled including DXA testing at both femoral neck and lumbar spine (L1-L4). This phase aimed to identify the risk factors associated with osteoporosis in women above 45 years in order to devise a scoring system to predict women at risk of low BMD. The second phase was to validate the scoring system devised from analysis of data collected in the first phase. The main outcome measured was low BMD (T-score of R2 SD below the mean for young Malaysian women) at either the femoral neck or the lumbar spine. Results: The first phase comprised of 514 healthy women above 45 years old who had a baseline BMD and general health assessment. Risk factors of age and years of menopause were significantly associated with lower spine and hip BMD. Whereas higher BMI, income, waist-circumference, hip-circumference were significantly associated with higher BMD. A simple algorithm based on years of menopause, BMI and hip circumference was formulated for screening. This screening formula when tested on 514 sample size had a sensitivity of 66.2%, a specificity of 72.86%, and a positive predictive value of 63.2% for selecting women with low BMD. The sensitivity of selecting women with osteoporosis was 75.8%. This initial screening identified a 56.6% reduction of DXA testing compared to screening the total study smaple of 514. A validation population of 72 healthy women was recruited and this screening formula when applied had a sensitivity of 87.5%, a specificity of 75.0% and a negative predicitive value of 98.0% Conclusion: The screening formula devised enables to identify 63% of women who were likely to have low BMD. It was eﬀective in reducing the number of women requiring DXA, an expensive test only available at tertiary centres in Malaysia. The rate of underdiagnosis was negligible.

P249MO. EARLY MORTALITY RATE OF FEMUR NECK FRACTURES IN MALES OVER 65 IN HUNGARY Sebestyen A1, Boncz I2,3, Ghodratollah N4, Ember I4, Nyarady J5, Pentek M6, Gulacsi L6; 1County Baranya Health Insurance Fund, Pecs, Hungary, 2Department of Health Policy, National Health Insurance Fund Administration(OEP), Budapest, Hungary, 3Institute of Diagnostics and Management, University of Pecs, Pecs, Hungary, 4Institute of Public Health and Preventive Medicine, University of Pecs, Pecs, Hungary, 5Department of Traumatology, University of Pecs, Pecs, Hungary, 6Corvinus University Budapest, Hungary Aim: The aim of the study is to analyze the early mortality rate after femur neck fractures in males over 65 age. The study includes the analysis of age groups, progressivity levels, regional diﬀerences and surgical techniques. The mortality can be aﬀected by several other factors that are out of the scope of this study.

Materials and methods: In this retrospective study the data derive from the financial database of the National Health Insurance Fund of Hungary. For the analysis we used code S7200 of the International Classification of Diseases (ICD) tenth revision. The patients included into the study had femur neck fracture and being discharged from the hospital after the primary treatment in 2000. The patients with polytrauma or complications were excluded from the study. In course of the calculations the patients were categorized according to the place of the primary treatment (institution and progressivity level) and primary surgical technique. We analyzed the early mortality rate within 45 days after treatment of primary femur neck fracture. For the analysis of geographical regional mortality rates we used the permanent address of patients. Results: Altogether 985 patients were included into the study. The national average of mortality was 18.5%. According to age groups: Age 65–69: 4.2%, Age 70–74: 11.9%, Age 75–79: 19%, Age 80–84: 20.7%, over 85 age: 30.5%. According to progressivity levels: national health institutes:17.2%, universities: 13.2%, city hospitals of Budapest: 26.1 %, county hospitals: 18.7%, city hospitals: 16.4%. According to surgical techniques: arthroplasty: 11.3%, screw fixation: 18.1 %, Dinamic hip screw: 28.1%, femoral neck nailing: 5.6%, ender nailing: 41.2%. According to geographical regions: Central-Hungary: 21%, Central-Transdanubia: 11.8%, Western-Transdanubia: 26.9%, Southern-Transdanubia: 16.1%, Northern-Hungary: 17.2%, Northern-Greatplane: 14.7%, Southern-Greatplane: 17.6%. Conclusion: The early mortality rate increased significantly with the age of patients. The early mortality rate was the highest in Budapest both according to both progressivity level and regional analysis. Many other factors can influence this mortality, which will be analyzed in our further studies.

P250SA. FREQUENCY AND DISTRIBUTION OF FEMUR NECK FRACTURES IN MALES OVER 65 IN HUNGARY Sebestyen A1, Boncz I2,3, Ghodratollah N4, Ember I4, Nyarady J5; 1 County Baranya Health Insurance Fund, Pecs, Hungary, 2Department of Health Policy, National Health Insurance Fund Administration(OEP), Budapest, Hungary, 3Institute of Diagnostics and Management, University of Pecs, Pecs, Hungary, 4Institute of Public Health and Preventive Medicine, University of Pecs, Pecs, Hungary, 5Department of Traumatology, University of Pecs, Pecs, Hungary Aim: The aim of the study to analyse the frequency of fresh femur neck fractures in males over 65 in Hungary according to geographical regions and age groups. Data and methods: This retrospective study includes male patients with femur neck fractue in 2000. Data derive from the financial database of the National Health Insurance Fund of Hungary and the database of the Hungarian Central Statistical Oﬃce. For the analysis we used the International Classification of Diseases (ICD) tenth revision (S7200 code) and the surgical codes (371 A,B,C,H,K, 374 A,B,C, 375 A,B,C) of the Hungarian Homogenous Disease Groups related to femur neck fracture. The patients with polytrauma or comorbidities were excluded from the study. Results: Total number of femur neck fractures over 65 was 4144. The female/male ratio was 23.8%/76.2%. Altogether 985 male patients met the inclusion criteria. Distribution of femur neck fractures according to age groups: Age 65–69: 14.6%; Age 70–74: 19.6%; Age 75–79: 27.8%; Age 80–84: 13.7%; Age 85–89: 15.3%; over 90: 8.1%. Number of femur neck fractures per 10,000 male population according to age groups: age 65–69: 7.3, Age 70–74: 12.1, Age 75–79: 24.4, over 80: 50.2. Distribution of femur neck fractures according to regions: Central-Hungary: 29.9%, CentralTransdanubia: 7.7%, Western-Transdanubia: 9.4%, SouthernTransdanubia: 8.9%, Northern-Hungary: 13%, NorthernGreatplane: 13.8%, Southern-Greatplane: 17.3%. Number of femur neck fractures per 10,000 male population according to regions: Central-Hungary: 19.1, Central-Transdanubia: 13.6, Western-Transdanubia: 16.8, Southern-Transdanubia: 16.4,

S194 Northern-Hungary: 18.5, Northern-Greatplane: 17.4, SouthernGreatplane: 21.6. Conclusion: The frequency of femur neck fractures over 65 per 10,000 male population almost doubled from one age group to the other. We found the highest frequency of femur neck fractures in the Southern-Greatplane region laying in South-East Hungary. A further study is needed to analyze the reasons behind the large diﬀerences in the frequency of femur neck fractures.

P251SU. EFFECTS OF SERUM HOMOCYSTEINE AND MTHFR C677T POLYMORPHISM ON BONE MINERAL DENSITIES IN KOREANS Nam HS1, Shin MH2, Kweon SS2, Park KS2, Lee TY1, Cui LH3,4, Choi JS3; 1Department of Preventive Medicine and Public Health, Chungnam National University College of Medicine, Daejeon, Republic of South Korea, 2Department of Preventive Medicine, Seonam University College of Medicine, Namwon, Republic of South Korea, 3Department of Preventive Medicine, Chonnam National University School of Medicine, Gwangju, Republic of South Korea, 4Department of Preventive Medicine, YanBian University College of Medicine, Yanji, China The objectives of this population-based study were to investigate the potential eﬀects of serum homocysteine and the genotype MTFHR C677T on bone mineral density (BMD) in men and postmenopausal women, aged 45–74 years. In January and February 2005, BMD (g/cm2) was measured at peripheral (distal forearm and calcaneus) and central (lumbar spine at L1–4, femoral neck, Ward’s triangle, trochanter and shaft) skeletal sites by dual-energy X-ray absorptiometry, using PIXI and DPX Bravo (GE Lunar, Madison, WI, USA) in a South Korean populationbased sample of 1046 men and 1070 post-menopausal women. The raw BMD values were adjusted by regression for covariates of age, height, weight. The men with higher level of serum homocysteine (R9µmol/L) had significantly (p<0.05) lower BMDs at femoral neck, Ward’s triangle, trochanter, shaft and distal forearm. But postmenopausal women did not have any diﬀerences in BMDs between both groups with higher and lower homocysteine level. There were no significant diﬀerences in terms of BMDs among the genotypes MTFHR C677T (CC, CT, TT).

P252MO. RISK FACTORS FOR INCIDENCE OF OSTEOPOROTIC FRACTURES IN HUNGARIAN POPULATION Kiss C1, Felsenberg D2, Reeve J3, O’Neill TW4, Silman A4, Poór G1; 1National Institute of Rheumatology and Phisiotherapy, Budapest, Hungary, 2Freie Universitat Berlin, Germany, 3University Department of Medicine, Cambridge, UK, 4Epidemiology Research Unit Manchester Universíty, UK Better knowledge of modifiable and non-modifiable factors could aid prevention in subjects at high risk of fracture. To evaluate the association between gynecological, reproductive factors and family history of hip fracture with the incidence of vertebral and nonvertebral osteoporotic fractures in women older than 50 years. We studied 253 women aged 50 and over, randomly selected from a Hungarian population that had participated in the EVOS study. This cohort was prospectively followed for 8 years by means of four postal questionnaires in order to find out the incidence of nonvertebral fractures. Concerning the incidence of vertebral fractures, participants were invited to repeat the lumbar spine X-rays 4 years after the initial study. A total of 28 women had incident osteoporotic fractures. The analysis of gynecological variables showed that an increase in the age at menarche was a risk factor for all incident osteoporostic fractures /OR=1.49 (C.I. 1.03–2.46)/. The presence of amenorrhoea at any age during the fertile period was associated with higher incidence of all osteoporotic fractures /OR=4.20 (C.I. 1.53–27.61)/. Pregnancy, number of live birth, breast feeding were not associated with osteoporotic fractures. Family history of hip fracture was associated with a higher incidence of all osteoporotic fractures /OR=2.91(C.I. 1.01–13.65)/.

A late age at menarche, the presence of amenorrhoea and having close relatives with hip fracture were all risk factors which independently of bone mineral density and age, were associated with higher incidence of all osteoporotic fractures.

P253SA. EFFECTIVENESS OF A STANDARDIZED ALGORITHM IN FRAGILITY FRACTURE CARE Dobler T1, Vogel T1, Bitterling H2, Weber C2, Kirchhoﬀ C1, Buerklein D1, Boehm H2, Kampmann P1, Ockert B1, Pfeifer KJ2, Mutschler W1; 1Dept. of Traumatology, 2Dept. of Radiology, University Munich, Munich, Germany Fragility fractures aﬀect up to one-half of women and one-third of men over the age of fifty, and are associated with low bone mineral density (BMD). Trials have demonstrated that specific treatment of patients with diminished BMD can reduce the risk of future fractures by up to 50%. Although the proceedings to diagnose and treat those patients are widely available, their implementation remains discontenting. Therefore, a clinical algorithm was implemented to identify and treat patients with fragility fractures in a Level I trauma center. All patients presenting to our emergency department for operative fracture treatment, women older than 50 and men older than 75 years of age, were investigated prospectively. Dual-energy X-ray absorptiometry (DXA) measurement of the lumbar spine and the femoral neck were performed to determine the BMD. Data were recorded including age, gender, T-scores, fracture site and therapy resumption during initial hospital stay. In case of reduced BMD therapy was induced according to evidence-based international guidelines. Furthermore, diagnosis and therapy advice was pointed out in the final report, to ensure therapy conduction during rehabilitation and beyond. During May 2003–July 2005, 393 patients of the defined age groups underwent surgery for diﬀerent types of osteosynthesis due to an acute fracture at our institution. Of these patients 318 (80.9%) were tested for diminished BMD (297 women and 21 men). 214 patients (67.3%) showed reduced BMD in terms of osteoporosis, 82 patients (25.8%) in terms of osteopenia. Only 22 patients (6.9%) had normal BMD according to the WHO definition. The mean T-score in the osteoporosis group was -2.7 (SD 1.1) at the lumbar spine and -3.3 (SD 0.8) at the femoral neck, respectively. Therapy with calcium, vitamin D3 and alendronate was induced in 183 patients (85.5%) with osteoporosis. These data demonstrate that diminished BMD in terms of osteopenia/osteoporosis is a finding in 93% of the elderly fracture patients. Even with standardized clinical pathways 75 patients (19.1%) were not investigated and of the investigated 31 (14.5%) did not receive specific therapy. Clinical algorithms are necessary to identify and treat patients with fragility fractures, but its acceptance by orthopaedic trauma surgeons is nonsatisfying.

P254SU. INCIDENCE OF OSTEOPOROSIS RELATED FRACTURES IN HUNGARY BETWEEN 1999–2003, BASED ON ROUTINELY COLLECTED HEALTHCARE DATA Horvath C1, Boncz I2, Pentek M3, Falusi Z2, Toth E3, Sebestyen A4, Gulacsi L5; 11st Department of Internal Medicine, Semmelweis University Budapest, Hungary, 2National Health Insurance Fund Administration, Budapest, Hungary, 3Flor Ferenc County Hospital, Kistarcsa, Hungary, 4Baranya County Health Insurance Fund Administration, Pécs, Hungary, 5Health Economics and Health Technology Assessment, Corvinus University of Budapest, Budapest, Hungary Aims: Healthcare in Hungary is based on a social insurance system covering the entire population. Patient level data of all healthcare utilisation are routinely collected by the National Health Insurance Fund. The aim of our study was to assess the incidence of the main osteoporosis related fractures on the national level between 1999– 2003 in Hungary. Our results should serve comparable data for intervention threshold analysis and adaptation of osteoporosis cost-eﬀectiveness models.

S195 Methods: We performed a systematic search in the Hungarian National Health Insurance Fund database for the 50–100 years old population in the time period observed. We analysed the incidence of hip, wrist and proximal humerus fractures in women, their distribution by age and their variation in a five years period. Occurrence of consecutive fractures was also detected. Results: 9178 hip, 27530 wrist and 8266 proximal humerus fractures occurred in women in 2003 and there was no significant diﬀerence comparing with the previous years. 16.3% of the hip fratures occurred under the age 70, and there was an increase over in age groups of 5 years (13.1%, 19.4%, 26.2% respectively), 25% occurred in women elder than 85 years. 85% of wrist fractures was detected in the 50–80 years female population with a homogenous distribution between age groups (mean 14% in each). We found similar results regarding proximal humerus fractures, with highest incidence (16%) in the group of 75–79 years. In 2003, 9.3% of hip fracture cases had antecedent fracture in the previous year: wrist 2.5%, humerus 1.9%, vertebral fracture with in-patient care 0.1% and other fractures (4.8%). Conclusions: Burden of illness and fracture risk assessment are keypoints in osteoporosis cost-eﬀectiveness studies. Country specific, population based data are unevitable to assess the applicability of international results. Our study serve comprehensive epidemiological data for further clinical investigations and economic evaluations of new drugs in Hungary.

P255MO. MORPHOMETRIC X-RAY ABSORPTIOMETRY OF THE SPINE: IDENTIFICATION OF PREVALENT VERTEBRAL DEFORMITY IN POLISH ADULT POPULATION OF LODZ REGION – PART OF THE EPOLOS STUDY Skowronska-Jozwiak E1, Pludowski P2, Karczmarewicz E2, Lewinski A1, Lorenc R2; 1Department of Endocrinology & Metabolic Diseases, The Medical University of Lodz, Poland, 2Department of Biochemistry and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw, Poland Vertebral fractures are hallmarks of osteoporosis. Knowledge about previous fractures is important because the prevalence of vertebral fractures increases the risk of subsequent fractures with a positive correlation with their number, especially that the majority of them are clinically asymptomatic. The aim of the study was the evaluation of vertebral deformities in adult population of Lodz region, as a part of the Polish population studied within the EPOLOS Programme. Patients and Methods: 362 subjects without history of osteoporosis were examined (244 women, their mean age: 53 16 years and 97 men, their mean age: 53 14 years). Morphometric X-ray absorptiometry (MXA) lateral scans were performed using a DXA system Expert-XL. Six point digitization was used to calculate the anterior (Ha), central (Hc), and posterior (Hp) height of the vertebral bodies T4-L4. The vertebra was classified as having prevalent deformity if, at least, one ratio (Ha/Hp, Hc/Hp, Hp/Hp up, or Hp/Hp low) was below its threshold value (20% for grade 1, 30% for grade 2), according to the classification of vertebral fractures by Genant. Results: three 3969 vertebrae were analyzed. 112 (2.81%) vertebrae in 81 subjects (22.4% of the examined individuals) were classified as deformed. In 56 subjects (69.13%), one deformity and in 25 subjects, multiple deformities were identified. In 86%, mild deformity (grade 1) was observed. The prevalence of vertebral fractures was higher in women, rising with age. Th8 and Th12 were the most frequently deformed. Conclusions: Bone studies indicated that, as in other regions of Poland, also in Lodz, vertebral osteoporotic fractures are common. MXA seems to be useful and safe tool in the diagnosis of vertebral fractures. Low dose of radiation, fan-beam system and the centerline scan technique are the most important advantages comparing to the classical MRX.

P256SA. INVESTIGATION OF THE RELATIONSHIP OF TYPE 2 DIABETES AND OSTEOPOROSIS USING BAYESIAN INFERENCE Sta. Romana M1, Li-Yu J2; 1UP College of Public Health, Manila, Philippines, 2Faculty of Medicine & Surgery, University of Santo Tomas, Espana, Manila, Philippines Objective: The study aims to determine prevalence of type 2 diabetes with osteoporosis and estimate the odds ratio of osteoporosis with type 2 diabetes using Bayesian inference. Methodology: This is a case-control study design where women R30 years of age had their BMD measured in the lumbar spine and femoral neck using DXA at a tertiary referral center in Manila, Philippines. Results: There were 582 with normal BMD and 598 with osteoporosis. Prevalence of type 2 diabetes with osteoporosis is 22.41% while 19.07% of subjects with normal BMD had diabetes. Without considering confounders, the odds of osteoporosis is 22.5% higher for type 2 diabetic subjects. When physical activity and BMI are controlled singly, the odds of osteoporosis for type 2 diabetics was 21.73% and 53.89% higher, respectively. Patients with osteoporosis were older by 10 years. 44.78% of diabetic osteoporotic patients were physically active. 60.36% with normal BMD had BMI > 25 kg/m2. Less than 10% of patients were ever user of HRT. 20.74% had severe osteoporosis. Considering all possible confounders and eﬀect modifiers in the model with a diﬀuse normal prior distribution, the estimate for odds ratio (Model 1) is 0.67. A separate analysis excluding confounders (Model 2) gave the measure of association which significantly identified diabetes to be a protective factor for osteoporosis. Table: Estimates of the Odds Ratio for Type 2 Diabetes and Osteoporosis (Controlling for Age, Physical Activity, BMI, and HRT in [Model 1] Age and HRT in [Model 2]) Model

Prior for Logit Model

Log OR

Odds Ratio

95% CI for OR

Model 1 Model 2

N(0.0,1000000) N(0.0,1000000)

-0.4006 -0.4159

0.670 0.660

0.464 0.455

0.970 0.946

Discussion: The crude OR indicated that type 2 diabetes is a risk factor for osteoporosis. However, when confounders were included in the model, the direction of the relationship changed. Results cannot be generalized since all patients were referred by primary care givers. Conclusion: Diabetes is a significant protective factor for osteoporosis in this referred population of women. However, with the well known diabetes-related complications, one should still strongly consider assessing and screening for osteoporosis as well as fracture risk in diabetic patients.

P257SU. RISK FACTORS FOR FRACTURE IN PREMENOPAUSAL WOMEN Pilipovic N, Brankovic S, Vujasinovic-Stupar N, Palic-Obradovic D; Institute of Rheumatology, Belgrade, Serbia and Montenegro Objective was to examine risk factors for fracture in premenopausal women. Methods: We examined 566 women aged 20–79 (48.70), from urban part of Belgrade randomly selected from population register. 292 (51.59%) were premenopausal and 28 (9.59%) of them had fracture. BMD of spine was measured by dual-energy x-ray absorptiometry, using a Lunar DPX-L device. We investigated risk factors for fracture in 28 premenopausal women with fracture and in 264 premenopausal women without fracture. Results: See table. Conclusion: In premenopausal women with fracture concomitant diseases, family history of osteoporosis and fracture and loss of height are siginificantly more frequent than in premenopausal women without fracture.

S196 Factors for fracture in premenopausal women

Risk factors Age Sedentary type of work Decreased physical activity Cigarette smoking Alcohol abuse Coﬀein abuse Low Ca intake Low Ca intake in childhood Low sun exposure Concomitant diseases relevant for OP Family history of OP or fracture Late menarcha Irregular cycles Nullipare Long breast feeding Loss of height Low BMI Low BMD

Women with fracture (28)

Women without fracture (264)

Statistical signific.

42,89 21 (75,00%) 19 (67,86%)

39,53 166 (62,88%) 171 (64,77%)

-

14 (50,00%) 2 (7,14%) 18 (64,29%) 9 (32,14%) 1 (3,57%)

124 (46,99%) 5 (1,89%) 161 (60,99%) 109 (41,29%) 32 (12,12%)

-

12 (42,86%) 7 (25,00%)

124 (46.97%) 15 (5,68%)

p<0.02

12 (42,86%)

45 (17,05%)

p<0.01

4 (14,29%) 5 (17,86%) 3 (10,71%) 9 (32,14%) 16 (57,14%) 2 (7,14%) 5 (17,86%)

61 31 65 90 99 28 40

p<0.05 -

(23,11%) (11,74%) (26,42%) (34,09%) (37,50%) (11,38%) (15,15%)

Conclusions: All groups of women had poor QOL. Group I (up to 3 months after fracture) had significantly lower values of OQLQ, especialy pain, physical function, ADL and emotional function. Group II (3–12 months after fracture) and Group III (osteoporosis without fracture) had better and similar QOL – the worst in domains of pain and physical function.

P259SA. PREVALENCE OF RISK OF FRACTURES ESTIMATED BY QUANTITATIVE ULTRASOUND OF THE CALCANEUS IN A POPULATION OF POSTMENOPAUSAL WOMEN

P258MO. QUALITY OF LIFE IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN AFTER VERTEBRAL FRACTURE DEPENDING ON TIME OF FRACTURE Brankovic S, Pilipovic N, Stanisic D; Institute of Rheumatology, Belgrade, Serbia and Montenegro The aim of this study was to assess quality of life (QOL) in postmenopausal (PM) osteoporotic women with fracture, considering the time of fracture. Method: We examined 68 PM women and divided them into three groups: Group I (12 pts) up to 3 months after fracture; Group II (24 pts) 3–12 months after fracture; and Group III (32 pts) with osteodensitometric diagnosis of osteoporosis without fracture. Bone mineral density (BMD) was measured on lumbar spine by DXA method, using Lunar DPX-L device. We assessed QOL by a specific questionnaire for osteoporosis .Osteoporosis Quality of Life QuestionnaireZ (OQLQ) with 30 questions, which were grouped into five domains: symptoms, emotional function, physical function, activities of daily living (ADL), leisure and social activities with a score between 1 and 7. Higher scores reflect better QOL. Spearman‘s rank test was used to analyse the strength of relationships between variables. Results presented in Table 1. Women with fracture had higher T-score because 11% of them had normal BMD, 47% of them had osteopenia and only 42% of them had osteoporosis. The worst T-score was in the group of women without fracture. Patients and OQLQ Groups

I

II

III

No Age Menopausis Duration MP T-score OQLQ Symptoms Emotional function Physical function ADL Social activities

12 65,20 45,82 18,01 -2,54

24 64,35 46,24 17,81 -3,01

32 63,12 46,11 15,45 -3,29

2,14 3.01 2,79 2,41 2,80

2,91 3,42 3,24 3,28 3,65

3,14 3,82 3,40 3,50 3,85

Oliveira PP1, Klumb EM2, Marinheiro LPF1,2; 1Fernandes Figueira Institute / Oswaldo Cruz Fundation, 2Rio de Janeiro State University, Rio de Janeiro, Brazil The strong propensity of an aging world population induces a rise in the prevalence of such sicknesses as osteoporosis and fractures. Quantitative ultrasound of the calcaneus has emerged as a possibility of tracking large populations in the public health sector. Aim: To determine the prevalence of the risk of fractures estimated by QUS of the calcaneus in a population of menopausal women who reside on the island of Paqueta/RJ. We did a crossover study. Methods: With the apparatus Sonost 2000, we carried out anthropometric measurements and quantitative ultrasound of the calcaneus on 385 menopausal women. Results: The average age was 64.63 9.93 years, with the time of menopause averaging 17.00 10.76 years. We observed that 59.22% of the test group displayed T-score%1, while 16.88% displayed T-score%2.5. There were variations in all of the parameters of the exam due to the age increase and the statistically significant diﬀerence (p < 0.05) between the risk groups for fracture by age, time of menopause, weight, bone mass index, and percentage of body fat. There was a correlation between SOS and bone mass index (r = 0.155; p = 0.002). The women at highest risk (T-score < –2.5) were older, with a higher weight and bone mass index than the other groups. Conclusions: An important portion of the female population shows some degree of risk for fractures according to evaluation of the QUS. This alteration was significantly related to clinical and anthropometric factors.

P260SU. THE ROLE OF ADOLESCENT PHYSICAL ACTIVITY ON OSTEOPOROSIS IN LATER LIFE Siqueira FV, Facchini LA, Reichert FF, Azevedo MR, Bastos JP, Hallal PC; Programa de Pós-graduação em Epidemiologia, Universidade Federal de Pelotas, Pelatos, Brazil Aims: Physical activity in adolescence has previously been linked to lower incidence of osteoporosis in later life. However, few studies have evaluated the role of adolescent physical activity on osteoporosis after adjusting for adult activity levels. The aim of the present study was to assess the eﬀect of adolescent physical activity on the risk of osteoporosis in adulthood. Methods: A population-based cross-sectional study including 1,016 individuals aged 50 years or more was carried out in Pelotas, Southern Brazil. The sample was selected in multiple stages. Self-reported osteoporosis was the outcome variable. Adult leisure time physical activity was assessed using the International Physical Activity Questionnaire (long version). Individuals were defined as active in adolescence if engaged in physical activity between 10 and 19 years for at least six consecutive months. Confounding factors included were sex, age, socioeconomic level, skin color, smoking status and body mass index. Results: Individuals classified as active in adolescence were 67% less likely than inactive ones to present osteoporosis in adulthood (P<0.001). After adjustment for confounding factors, this protection was reduced to 45% (P=0.005), and further adjustment for adult physical activity level did not aﬀect this result (P=0.007). Therefore, adolescent physical activity reduces the risk of osteoporosis in later life regardless of physical activity level in adulthood.

S197 Conclusions: Based on these findings, it is possible to conclude that adolescence is a crucial period of life for improvements in bone health, and thus, encouragement to physical activity should start early in life.

P261MO. FAILURE OF INTERVENTION IN PATIENTS WITH HIGH RISK OF FRACTURES

across all groups for FN T-score (0.153–0.467) and were greater in the postmenopausal group than in the other two groups. Optimal age cut-oﬀs for osteoporosis risk were 56 years and 58 years for postmenopausal women and men, respectively Conclusion: Age has a greater influence on femoral neck T-score than at any other site. Simple age cut-oﬀs can be used for the prediction of osteoporosis risk in women and men over 50.

Garces S, Cravo AR, Tavares V, Canas-Silva J; Hospital Garcia de Orta, Almada, Portugal

P263SU. VERTEBRAL FRACTURES IN POSTMENOPAUSAL WOMEN WITH NORMAL BONE MINERAL DENSITY VALUES

Aims: Hip fractures are one of the main consequences of osteoporosis, a major cause of morbidity and mortality and an important public health issue. Patients with hip fractures represent a high risk population where therapeutic intervention is mandatory. Our aim was to evaluate if any intervention was taken in this high risk group following a recent hip fracture. Methods: We selected all patients with hip fractures (transcervical) admitted to the trauma unit during a one-year period (September 2004 to August 2005). A questionnaire to evaluate medications at time of discharge or on the following period, history of previous fractures and knowledge of the disease by the patients, was conducted through telephone contact to patients or close family or caregivers. Results: Over a 1-yr period a total of 140 patients (82 women, mean age total population 7717) were hospitalized with transcervical hip fractures. Almost 21% of patients died during hospital stay or the following year. Fourteen patients were lost to followup. Eighteen of the 97 patients interviewed had already suﬀered a non-vertebral fracture and of those only 27.7% were receiving treatment. At time of discharge orthopedic surgeons prescribed pharmacological treatment for osteoporosis to 14.4% of the patients. Treatment was later instituted by general practitioners or physiatrists to a minority and presently 16.6% of the patients are receiving treatment. Relation between fracture and osteoporosis was established by only 13.4% of the patients. Conclusions: Although patients with osteoporotic fractures represent a well established high risk population that should receive treatment to prevent further complications, several studies have shown that there is a failure to recognize the importance of this intervention among orthopedic surgeons. Our results are in accordance with these studies. Moreover the same problem was found among primary care physicians where pharmacologic treatment is sometimes oﬀered to low risk younger patients but forgotten in older high risk populations, where intervention is more cost-eﬀective and with a higher impact in quality of life.

Mesci E1, Sendinc B2; 1Haseki Education and Research Hospital, 2 Okmeydani Education and Research Hospital, Istanbul, Turkey

P262SA. SETTING AGE CUT-OFFS FOR OSTEOPOROSIS RISK Whelan BR1, Falvey EC1, Daly M1, Crowley M1, Shanahan F2, Harney S1, Molloy MG1; 1Dept of Rheumatology and Sports Medicine, CUH, 2Dept. of Medicine, UCC, Cork, Ireland Age is known to influence Bone Mineral Density at all skeletal sites and older age is a major risk for osteoporotic fracture. The ISCD has stated that osteoporosis can be define for both postmenopausal women and men based on T-score. Aim: To determine the relative influence of age on t-score in preand postmenopausal women and men at a number of diﬀerent skeletal sites. Method: DXA scan results from 17794 subjects (16623 postmenopausal women and 1171 men) were analysed. Age range 25–99 Correlation of age with T-score at lumbar spine (L1–4, L2–4) as well as left and right total hip (TH) , femoral neck (FN) and Trochanter (TR) were calculated using a Pearson correlation test. Linear regression was carried out where a significant correlation existed to establish the relative contribution of age to T-score at each site in each of the diﬀerent groups. ROC curves were plotted and used to set optimal age cut-oﬀs for osteoporosis risk. Results: There was no significant correlation between age and T-score at lumbar spine or trochanter for men. All other sites in all groups showed significant correlation with age (p<0.001–0.011). R2 values ranged from 0.069 for TH in premenopausal women to 0.467 for FN in postmenopausal women. R2 values were highest

In this study we aimed to assess the probability of vertebral fractures in postmenopausal women with normal bone mineral density values and distinctive characteristics of women with fractures. The study enrolled 150 postmenopausal women with lumbar vertebra and proximal femur bone mineral density (BMD) measurements below 1 standard deviation as obtained by dualenergy X-Ray absorbtiometry (DXA) method. Serum Ca, P, alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OC), urine calcium and type I collagen C telopeptide (CTx) measurements were obtained from all cases. Lateral thoracic and lumbar radiographies were evaluated by the Kleerekoper method and spinal deformity index (SDI) was calculated. Patients who were diagnosed with vertebral fractures were evaluated for newly generated fractures after 1 year. Statistical analyses were performed by using student t-test and Pearson correlation test. Mean age of 150 cases was 59.3 6.5 years and 20 of them (13.3%) had vertebral deformity. The most frequent deformity was wedge vertebrae which predominated in central and lower thoracic regions (65%). No significant diﬀerence was found between mean ages of fractured cases and the other women but menopause period was longer in fractured cases (p<0.05). Also, there was no significant diﬀerence between the two groups with respect to serum Ca, P, OC, ALP, 24-hours urine calcium, body mass index, L2-L4 vertebral and femoral (trochanter and neck) BMD values (p>0.05 for all parameters). Urinary CTx (p<0.01) and BAP (p<0.05) levels of fractured cases were significantly higher compared to the cases without fractures. A positive correlation was found between CTx (p<0.01) and serum BAP (p<0.001) levels and SDI among fractured cases. In these cases, increased frequency of kyphosis, height loss, back pain and scoliosis was remarkable. One-year follow-up of cases with vertebral fractures showed that 3 cases (15%) had newly developed fractures. As DXA measurements are associated with inaccuracies resulting from incorrect technique or misuse, it might be helpful to evaluate bone turnover markers and vertebral morphology in addition to bone mineral density measurements especially in cases with longer time since menopause.

P264MO. SURVEY OF OSTEOPOROSIS PREVENTIVE CARE IN COMMUNITY FAMILY MEDICINE SETTINGS Gourlay ML, Preisser JS, Callahan LF, Linville JC, Sloane PD; University of North Carolina, Chapel Hill, USA Aims: Despite the availability of evidence-based guidelines, osteoporosis preventive care has not been widely incorporated into standard primary care practice. Our purpose was to document and describe osteoporosis preventive care for women aged 45 years and older in community family medicine settings. Methods: We conducted a cross-sectional mailed survey of 400 women aged 45 years and older enrolled in a community-based family medicine research network. Participants responded to 42 items regarding osteoporosis screening and prevention during primary care visits. We compared patterns of osteoporosis preventive care in women aged 45 to 64 vs. 65 and older. Results: 275 respondents returned the survey (adjusted response rate 71.4%), including 162 women (58.9% of the sample) aged 45 to 64 and 113 women (41.1%) aged 65 and older. Rates of counseling on calcium intake, exercise, falls and bone density testing were similar in the two age groups. Half of women aged 65 and older

S198 and 43.8% of women under 65 had received bone density testing. Ninety two percent of the respondents rated the discussion of osteoporosis and fracture prevention with their primary care provider as ’’very’’, ‘’moderately’’ or ‘’somewhat’’ important, but only 44% actually had such a discussion. Conclusion: Most women aged 45 and older considered osteoporosis preventive care to be important. However, fewer than half discussed this topic with their primary care provider, and only half of women aged 65 and older underwent bone density screening.

P265SA. PEAK BONE MASS, BMD AND BMC IN NORMAL GIRLS AND TEENAGERS FROM BARRANQUILLA: JUNE 2003 – APRIL 2005 Jaller JJ1, Navarro E2, Vargas RF2, Del Toro K1; 1Centro de Reumatologia y Ortopedia, 2Universidad del Norte, Barranquilla, Colombia Introduction: The process of acquisition of bone mass begins in childhood, although during adolescence bone mineral content experiences an increment of great magnitude. This complex process involves decisive genetic, hormonal, nutritional and environmental factors. Aim: To establish the normal values of (DMO and CMO) for children and adolescent in Barranquilla from 5 to 20 years, for complete body (DC) and in the antero-later lumbar column (CL) in L1-L4, to establish the influence of the puberty in the bone mass. To observe the peak bone mass before the age of 20 years. Methods: 350 girls were studied and recruited previously in the neighborhoods of the city of Barranquilla through a systematic sampling, bietápico. Those girls and adolescents who were below the percentile 75 vo and for up of the 25 vo as much in the weight as in the size were applied a questionnaire and the development puberal was evaluated according to the parameters of Chiming. Results: The peak bone mass was observed at the age of 17 years old. The average of DMO in the studied population was of 0.94 mg/cm2 (DE+/-0.10) and that of CMO 1464.7 mg (DE+/-520.96). It was found that as much the weight as the size show a directly proportional behavior with regard to the DMO and the CMO. Bone mass correlated with the development puberal in positive and upward form. Conclusions: according to the results, peak bone mass was reached to the 17 years, that which encourages us to carry out measures of prevention and of bone gain from early ages. The development pubertal it is directly proportional to the bone mass, for what to maintain a good level of steroids gonadales allows an appropriate bone development.

P266SU. ASSOCIATION OF BODY MASS INDEX AND OSTEOPENIA IN HEALTHY POSTMENOPAUSAL FILIPINO WOMEN Li-Yu J1, Angeles N2, Rosales G3, Sunga J4; 1UST Faculty of Medicine & Surgery, Dept. of Medicine, Manila, Philippines, 2 Dept. of Obstetrics & Gynecology, St. Martin de Porres Charity Hospital, Manila, Philippines, 3Research Development Oﬃce, Manila Central University Filemon D. Tanchoco Medical Foundation, Kalookan City, Philippines, 4Dept. of Pediatrics, Capitol Medical Center, Quezon City, Philippines Osteopenia, defined by WHO, is BMD that lies between 1 and 2.5 standard deviation below young adult mean value. There has been a paucity of studies that have focused on osteopenia. From the public health standpoint, measures need to be directed before one reaches osteoporosis where there will be more economic implication as well as psychosocial burden. This study aimed to determine association of BMI, a potentially modifiable risk factor, with osteopenia among healthy postmenopausal women. Methodology: This is a cross-sectional study conducted between 1999 to 2002 in a tertiary referral center in Manila, Philippines. Review of medical records with lifestyle habits and bone mineral density in the lumbar spine and femoral neck of healthy Filipino postmenopausal women was done. Results: There were 542 patients with mean weight of 59.87 9.41 kg, height of 1.54 0.05 m, body mass index of 25.4 3.89

kg/m2, average years since menopause of 11.93 8.72 years, lumbar spine BMD of 0.89 0.16 g/cm2, and femoral neck BMD of 0.73 0.14 g/cm2. Almost three quarters (74.5%) of subjects were osteopenic. More than half of them have BMI %23 k/m2, had family history of osteoporosis, were smokers, did not have calcium or vitamin D supplements, were not physically fit, and had longer periods of menopausal state. Using logistic regression modeling, the odds for low bone mass among women with BMI %23 kg/m2 was almost 2-fold, controlling for vitamin D supplementation and number of years since menopause. Logistic Model Factors

Odds Ratio

p-value

BMI Actual YSM Vitamin D

1.78 0.30 0.42

0.021 0.000 0.024

Conclusion: BMI together with vitamin D supplementation and length of time since menopause were the ones found to identify individuals at risk for low bone mass. Absence of vitamin D supplement serendipitously showed a protective eﬀect in our study. Further studies need to be undertaken in considering determination of vitamin D levels in postmenopausal women.

P267MO. HEALTH-RELATED QUALITY OF LIFE AFTER HIP FRACTURE IN COMMUNITY-DWELLING ELDERLY Jithathai J; Division of Physical Therapy, Department of Rehabilitation Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Hip fracture occurs commonly in older individuals and can have a considerable impact on the functional independence and quality of life for older patients living in the community. In a populationbased case-control study six months after hip fracture, we investigated the association between functionality and quality of life. The Functional Independence Measure (FIM), the Frenchay Activities of Daily Living Index (FAI), and the Berg Balance Scale (BBS) were used to measure physical function, and quality of life was measured by completing a Short Form-36 (SF-36). With age and gender match, the hip fracture group scores were significantly lower (p%0.05) than the control group in all measurements of physical function (FIM 95.54 vs 103.5; FAI 23.68 vs 30.76; BBS 46.21 vs 54.25). The quality of life was assessed by SF-36, which has eight domains: physical function, physical role, bodily pain, mental health, emotional role, social function, general health and vitality. All eight domains were significantly lower in the hip fracture group compared with the controls (p<0.05). The reduction in function was reflected in a reduction in the quality of life. Thus, clinically reported hip fracture impairs both the functionality and quality of life of these subjects. The adverse impact of hip fracture on quality of life and functionality needs to be recognized by health personnel in the community, so that adequate health resources can be devoted to preventing and treating this debilitating condition.

P268SA. MUNICIPALITES’ COOPERATION FOR PREVENTING OSTEOPOROSIS IN JAPAN Satomura K, Nakahara T, Iwanaga S, Noami M, Sakamoto R, Takahashi T; Dept. of Public Health, Faculty of Medicine, Kyoto University, Kyoto, Japan Aim: In Japan one of the main causes of osteoporosis is law calcium intake. There is a screening test for osteoporosis in forty and fifty years old female by the law and also health education by municipalities are endeavored by it. Disseminating knowledge of osteoporosis and its prevention are very important to decrease numbers of osteoporosis patients. We surveyed cooperation between municipalities and other organizations for its health education for preventing osteoporosis.

S199 Method: A questionnaire sent to all municipalities in Japan. It was asking their cooperation with other organizations for health education of preventing osteoporosis. Result: 33.4% of municipalities replied to the questionnaire. 2% of them targeted osteoporosis as most important issue for prevention. Only two to five percent of them cooperated for health education with hospitals, schools, enterprises, public health centers and NGO/NPOs. Three to thirty percent of them knew health education in other organizations. Three to fifteen percent of them diﬀused public relations of their health education to other organizations. Fewer than twenty five percent of them exchanged information about health education of osteoporosis prevention with other organizations. The cooperation between municipalities and public health centers was higher than that with hospitals and so on. Discussion: There are little relations between municipalities and other organizations for health education of preventing osteoporosis. Also they have little information of its health education by other organizations. Without cooperation of other organizations disseminating knowledge of osteoporosis is limited and it is diﬃcult to increase calcium intake or other preventive activities by inhabitants. Conclusion: New strategies to cooperate between municipalities and other organizations and to diﬀuse information of preventing osteoporosis should be developed to decrease numbers of patients with osteoporosis.

P269SU. ECONOMICAL IMPACT OF OSTEOPOROSIS AND FRAGILITY FRACTURES IN MEXICO Clark P1, Guzman G1, Carlos F1, Barrera C1, Lavielle P1, Ramirez E2, Tamayo J3, Maetzel A4, Robinson V5, Tugwell P5; 1Clinical Epidemiology Unit CMN Siglo XXI-Faculty of Medicine UNAM, 2 Instituto Nacional de Rehabilitacion, 3COMMOP Mexico, 4Amgen Lab, 5Intitute of Global Health, University of Ottawa, Canada Osteoporosis related costs are considered a major burden for health authorities in most developed countries. The information about costs in developing countries is scarce. The aim of this study was to estimate the total direct costs involved in Osteoporosis and fragility fractures in a sample of governmental and private institutions from the Mexican Health System (Ministry of Health (SS), Social Security (IMSS) and Private Sector (PS). Methods: A cross sectional study was conducted to patients aged 50 and over attending diﬀerent Osteoporosis outpatient’s clinics and hip surgery departments from selected institutions. Information was gathered from clinical charts and direct interviews with the patients regarding the costs involved in their diagnosis and treatment. Micro costing for governmental institutions and lists of prices from private institutions were used to estimate the costs per case. The institutional perspective is presented. Results: A total sample of 275 OP and 187 hip fracture patients were included, 85.9% of the total sample were women. The estimated cost for OP diagnoses included Central DXA, consultation fee, X-rays and lab tests. The lowest cost found was at SS and the highest in the private sector. For hip fracture, similar cost figures were found, with the lowest prices at SS and the highest at IMSS and PS. Important diﬀerences were found in average hospitalization days (6.6 days at the IMSS to 2.7 days at the private institutions) as well as costs charged per surgery intervention.

ITEM OP Diagnoses Hip Fracture Total Costs Surgery Cost bed/day

SSUSA Dollars

IMSSUSA Dollars

PS (range)*

$102.00 $1,515.00

$187.00 $4,596.00

$103.00–155.00 $3,834.00–5,751.00

$859.00 $28.60

$1,755.00 $254.00

$3,100.00–4,650.00** $106.00–159.00

* A 50% of diﬀerence was estimated between clinics and hospitals attending diﬀerent SES (low vs. upper middle and high) ** not including medical fees

Conclusions: Our results reflect the variability between the diﬀerent health systems in Mexico. Careful attention is needed for the governmental institutions where the majority of patients are attended since higher costs are influenced by longer stay at the hospital. Since hip fractures are expected to increase in the near future, the burden and expenditures will increase exponentially for this condition.

P270MO. CROSS COUNTRY SURVEY OF OSTEOPOROTIC FRACTURE CARE IN GERMANY Vogel T1, Bitterling H2, Dobler T1, Weber C2, Buerklein D1, Boehm H2, Kampmann PH1, Kirchhoﬀ CH1, Pfeifer KJ2, Mutschler W1; 1Dept. of Traumatology, 2Dept. of Radiology, University Munich, Munich, Germany Clinical trials have demonstrated that specific treatment of patients with fragility fractures can reduce the risk of future fractures by up to 50%. Although the proceedings to diagnose and treat those patients are widely available and simple, their implementation remains discontenting. To evaluate the current status of osteoporotic fracture care in Germany, a cross-country survey of Departments of Traumatology was carried out. During March and July 2004, specific Questionnaires were mailed to 409 Departments of Traumatology throughout Germany. Matters of interest were the existence of standardized clinical pathways in osteoporotic fracture care, diagnostic tools used and therapy advice given to patients who were treated as inpatients for a fragility fracture. Of the 409 sent Questionnaires 328 (80.2%) were returned and analyzed. Only 115 Hospitals (35.1%) reported to have a standardized proceeding to diagnose and treat patients with fragility fractures. Of those Departments 19 (16.5%) reported to use X-ray and DXA to diagnose reduced BMD. Adequate drug therapy, as recommended by national and international guidelines, was available in 68 departments (59.1%). According to recent national guidelines, adequate diagnostics and therapie after a fragility fracture is carried out by 11 (9.6%) Departments of Traumatology. The vast majority of older patients’ shows reduced BMD as a substantial underlying cause of their fracture. Still, the awareness throughout Traumatologists in Germany remains discontenting. Eﬀorts have to be undertaken to show that prevention of fractures is as important as their operative management.

P271SA. FREQUENCY OF LOW ENERGY FRACTURES IN GREEK POSTMENOPAUSAL WOMEN Papakitsou E, Galanos A, Dionyssiotis Y, Katsalira A, Charopoulos J, Samdanis B, Economopoulos D, Lyritis GP; Laboratory for the Research of the Musculoskeletal System, KAT Hospital, Kifisia, Greece Aim of this epidemiologic study was to estimate the frequency of prevalent low energy fractures in Greek postmenopausal women and the modifiable risk factors for fractures. For this purpose 1740 postmenopausal women randomly selected, completed by interview a questionnaire history of previous low energy fractures, previous bone mineral density measurement, co-morbidities and treatment with antihypertensive or sedative drugs, anthropometric variables (BMI), lifestyle risk factors for fractures (smoking and exposure to sunlight), and active treatment with antiresorptives. About 47.8% of the women had been measured by one or serial DXA measurements. About 27.7% of the women reported that they had sustained at least one low energy fracture. The frequency of self reported hip, Colles’ and vertebral fractures were respectively 1.8 %, 7.5%, and 1.8%. The frequency of the use of antihyperthensive (43.2% vs 34.7%, p<0,0001) or sedative agents (24.7% vs 16.6%, p<0,0001), avoidance of sunlight during summertime (66.4% vs 55.8%, x2 P<0.0001) and smoking (23% vs 19%, P=0.028) was significantly higher in women with fractures compared to women with no fracture, while BMI was not significantly associated with the fracture incidence. 23.5% of all the women were actively receiving

S200 calcium and vitamin D supplementation and/or antiresorptives by the time of the interview. This study estimates the prevalence of osteoporosis in Greek postmenopausal women by a population–screening method, and shows concordance between therapy and fracture distribution.

P272SU. OSTEOPORSIS AND RISK FACTORS IN A LATIN MALE POPULATION Jaller JJ1, Navarro E2, Vargas RF2; 1Centro de Reumatologia y Ortopedia, 2Universidad del Norte, Barranquilla, Colombia Osteoporosis is a leading cause of morbidity and mortality in elderly people. While less common in men than women, about 1.5 million men over age 65 years in the United States have osteoporosis, and another 3.5 million men are at risk. In the last few years the burden of osteoporosis in men has been recognized as an important public health issue. Aim: To determine the prevalence and the risk factors associated to osteoporosis in a group of male outpatients assisting to the Centro de Reumtaología y Ortopedia, in Barranquilla, Colombia, during 2002–2005. Methods: We performed a descriptive, transversal survey, including all males older than 20 years in our ambulatory clinic (n=401), who don’t knew they have osteoporosis. We apply a test focused on risk factors related to osteoporosis, and each patient was invited to do a central densitometry measure, in spine and femur. Results: The mean age was 57.65 years (SD+/-: 14.7); 71.4% were older than 49 years. The general prevalence of osteoporosis was 17.96%, and osteopenia: 34.41%. The highest prevalence of osteoporosis was found in the age group of 70 to 79 years, and in the group of 40 to 49 years with 20.9%. Primary osteoporosis was present in 46.62% from all cases. In patients with secondary osteoprorosis, 18.06% are smokers, 13.9% have used corticoids for at least 3 years, 11.1% have prostatic disease, 11.1% have rheumatoid arthritis, and when we compare thus risk factors between osteoporotic with none osteoporotic men, the diﬀerence was statistically significance (p<0.05) in all of them. Conclusions: The prevalence of osteoporosis and osteopenia were similar to those found by other groups. A high proportion of men had primary osteoporosis. An important number of men with osteoporosis had risk factors for this disease. Aditionally, we found two osteoprotic peaks by age, in the groups of 40 to 49 and 70 to 79, probably due to secondary cause.

P273MO. EPIDEMIOLOGY OF OSTEOARTHRITIS OF THE KNEE IN A RURAL JAPANESE POPULATION Oka H1, Yoshimura N1, Suzuki T2, Yoshida H2, Muraki S3, Mabuchi A3, Matsudaira K3, Kawaguchi H3, Nakamura K3; 1 Department of Joint Disease Research, Graduate School of Medicine, The University of Tokyo, 2Tokyo Metropolitan Institute of Gerontology, 3Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan Aim: To investigate the prevalence of knee osteoarthritis(OA) and to measure the impact of knee OA on quality of life(QOL) in a rural Japanese population. Method: We studied 1154 subjects between the ages of 69–88 years who participated in the Comprehensive Health Examination(‘‘Otasha-Kenshin’’). Data were collected by questionnaire, physical examination, and anteroposterior standing radiographs of both knees. Radiographs were graded from 0 to 4 according to Kellgren and Lawrence scale. OA was defined as being present in a knee if radiographic grades of 2 or higher were detected. Severe OA was defined as being present in a knee if radiographic grades of 3 or higher were detected. The 8-item Medical Outcomes Study Short-Form Health Survey (SF-8) and Western Ontario and McMaster Universities (WOMAC) OA Index were used in QOL measurements. Results: Radiographic grade according to Kellgren and Lawrence scale of 0–1, 2, 3–4 were 33.9%, 55.3%, 10.8%, respectively. In other words, the prevalence of radiographic OA of the knee were 66.1%. The prevalence of radiographic OA of the knee increased with age, and was significantly higher in women than in

men (77.8% vs. 47.5%, respectively). Almost all of the knees with radiographic OA exhibited a varus deformity due to the loss of cartilage in the medial tibiofemoral compartment. Patients with severe OA had lower mean scores in all SF-8 domains and higher mean scores in all WOMAC domains, indicating poorer QOL. Women with OA had poorer scores compared to men for bodily pain, general health after adjusting for age. Conclusions: The prevalence of radiographic OA of the knee were 66.1%. OA has a significant impact on QOL, as assessed by the SF-8 and WOMAC in this population.

P274SA. THE DURATION OF STAY IN TREATMENT IN GREEK POSTMENOPAUSAL OSTEOPOROTIC WOMEN Economopoulos D, Tournis S, Dionyssiotis Y, Papakitsou E, Katsalira A, Samdanis B, Lyritis GP; Laboratory of Research for the Musculoskeletal System, University of Athens, KAT Hospital, Kifissia, Greece Osteoporosis treatment is crucial for the maintenance of a good quality of life by reducing the risk of potential complications, such as fractures and immobilization. Compliance to treatment is an important issue, essential for the preservation of an acceptable therapeutic result. Aim: To examine retrospectively the compliance of osteoporotic women, undergoing treatment for a time period of 2 years. Materials and Methods: From 783 community dwelling women, who expressed an interest in osteoporosis, 460 patients suﬀered from osteoporosis and were undergoing treatment. They were asked to fill a questionnaire regarding their duration of stay in treatment. Information about the participant’s therapy adaptation, over a 6 month, 1 year, 2 years and more than 2 years period, were collected, as well as information about the probable reasons leading to an early therapy discontinuation. Results: 349 (75.9%) women received treatment for a time period of at least 6 months, 323 (70.2%) for a year, 298 (64.7%) for 2 years, whilst 221 (48%) complied to treatment for more than 2 years. Regarding the cause of early discontinuation, 26 (7.4%) stopped their treatment following doctor’s orders, 95 (27.2%) because they had diﬃculties receiving their treatment, 15 (4.3%) because they feared of future medication side eﬀects, 40 (11.5%) interrupted on their own decision, 30 (8.6%) due to inconvenience in receiving treatment, 2 (0.6%) ceased treatment for no reason, whereas 141 (40.4) continued their therapeutic scheme. Conclusion: The documented compliance to any osteoporosis treatment was better, compared to other studies, but still rather low. A constant decrease of therapy uptake has been documented amongst the time periods. Furthermore, a diﬃculty in receiving treatment seems to be the primary cause for early discontinuation.

P275SU. VALIDATION OF THE GREEK VERSION OF THE QUALITY OF LIFE QUESTIONNAIRE OF THE EUROPEAN FOUNDATION FOR OSTEOPOROSIS (QUALEFFO-41) Kakavelakis KN1, Papadokostakis GM1, Damilakis J2, Hadjipavlou AG1; 1Department of Orthopaedics and Traumatology, University of Crete, University Hospital of Heraklion, 2Department of Medical Physics, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece Background – Aim: The Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) is a selfadministered questionnaire and one of the most widely used and validated instrument for measuring the quality of life in vertebral fractures patients. However, no validated Greek version was available at the time our study was initiated. The aim of this study was to adapt, and assess internal consistency and validity of adapted Greek version of QUALEFFO. Methods: Translation/back-translation of the English version of the QUALEFFO was done blindly and independently by 4 diﬀerent individuals. All steps for cross-cultural adaptation process were performed properly by an expert committee. The Greek version was tested on 134 women. Sixty-five female patients from our outpatient clinic with osteoporotic spinal fractures, aged 55–82

S201 years, were invited to participate. The control group was composed by 67 healthy women, age-matched to patients. Participants were requested to complete the QUALEFFO twice within 14 days to assess retest reliability, while cconcurrent validity was measured by comparing with an already validated questionnaire (SF-36). Measurement was made using the Pearson correlation coeﬃcient (r). Reliability, validity and reproducibility of the Greek version of the index were assessed. Results: The internal consistency of the Greek version of the QUALEFFO was high (Cronbach alpha = 0.96) and the test-retest reliability was satisfactory (intraclass correlation coeﬃcient = 0.9). The Pearson correlation coeﬃcients of the QUALEFFO to the SF-36 showed a correlation with physical component summary scores rather than mental component summary scores. Bodily pain, physical function and role-physical scores among the SF-36 subscales were most significantly correlated with QUALEFFO disability/symptom scores. Conclusions: The results of this study indicate that the Greek version of QUALEFFO has good comprehensibility, internal consistency, and reliability. The QUALEFFO is applicable for use among osteoporotic spinal fractures patients in Greece.

P276MO. PREVALENCE OF POSTMENOPAUSAL OTEOPOROSIS IN JORDAN: THE FIJONOR STUDY Masri BK1,2, Azar ES1,2, Faqih AM2,3, Sornay-Rendu E4,5, Duboeuf F4,5, Delmas PD4,5; 1Jordan Osteoporosis Centre, Jordan Hospital, Amman, Jordan, 2Jordanian Osteoporsis Prevention Society, Amman, Jordan, 3Jordan University, Amman, Jordan, 4 INSERM Research Unit 403, Lyon, France, 5Université Claude Bernard, Lyon, France In order to determine the prevalence of postmenopausal osteoporosis in Jordanian females, a representative random sample of 1241 females aged 20 to 89 years were interviewed in their homes, using a stratified three-stage cluster sample covering urban and rural regions in the entire country as drawn by the Jordanian Department of Statistics. 821 women met the study criteria and underwent dual-energy X-Ray absorptiometry (DXA) measurement (Hologic Delphi A) as well as other laboratory investigations. Peak bone mass (PBM) was calculated at the regions of interest (L1-L4 spine, total hip, trochanter and femur neck) in the 483 women who were premenopausal. 333 women were postmenopausal (43 to 89 years old). Osteoporosis was defined as a T-score < -2.5. Using the Jordanian PBM data, the study revealed a prevalence of osteoporosis of 23.4%. This proportion is lower than what would be obtained using the reference data supplied by Hologic and lower than the published prevalence data from North America and Europe but close to what has been reported from Lebanon.

P277SA. PREVALENCE OF OSTEOPENIA IN SPANISH POSTMENOPAUSAL WOMEN Marí Solivellas B, Cabanes Martín T; FHOEMO Fundación Hispana de Osteoporosis y Enfermedades Metabólicas Óseas, Palma de Mallorca, Spain Aims: To analyse the prevalence of densitometric diagnoses, bone mineral density (BMD) in lumbar spine/femoral neck, in ambulatory postmenopausal women. Methods: Descriptive, cross-sectional study. On a database of 5847 women, 4000 were chosen for the study, divided into groups of age with an interval of 10 years each group (50–59, 60–69, 70–79 and >80 years). Diagnoses were been based on the determination of BMD in lumbar spine/femoral neck using the WHO criteria. Osteopenia was classified into moderate (T-score -1.0 to -1.99) and severe (T-score -2.0 to -2.49). The average age of the population studied is 68.38.8 years, menoage 18.510.2 years, body mass index 29.42, weight 67.0210.1 kg, height 1520.10 cm, nonsmoker 95.57%, physical activity in their group 83.66% and exposure to the sun 83.47%. Results: Total results in all the groups: Moderate Osteopenia 27.32%

Severe Osteopenia 19.46% Osteoporosis 20.88% Conclusions: – The prevalence of osteopenia is similar to the one defined in other international studies in the mediterranean area. – The fracture risk is higher in severe osteopenia that in moderate osteopenia, therefore it is important to classify osteopenia into groups. – Although the incidence of fractures in moderate osteopenia is more low, this group is very important since in this group we can develop therapeutic prevention to avoid the degree of bone fragility increases in the future. Results RESULTS BY GROUPS OF AGES AND PREVALENCE IN % GROUP

50–59 years 60–69 years 70–79 years >80 years TOTAL

Moderate 18,22 % Osteopenia Severe 12,03 % Osteopenia Osteoporosis 16,33 %

23,36 %

29,68 %

38,02 %

27,32 %

16,42 %

23,28 %

26,10 %

19,46 %

18,02 %

24,13 %

25,03 %

20,88 %

P278SU. ‘‘ARCHITECTURAL DEFECTS’’ IN THE ITALIAN NATIONAL HEALTH SYSTEM: HOW MANY OSTEOPOROTIC PATIENTS ESCAPE THE NET? Tarantino U1,2, Andreoli A1,3, Cerocchi I1,2, Celi M1,2, Lecce D1,2, Iundusi R1,2; 1University ‘‘Tor Vergata’’ Faculty of Medicine and Surgery, 2‘‘Policlinico Tor Vergata’’ Department of Orthopaedics and Traumatology, 3Human Nutrition Unit University ‘‘Tor Vergata’’, Rome, Italy Aims: Individuals who sustain a low energy fracture are at increased risk of sustaining another fracture. The incidence of refractures can be reduced by secondary preventive measures, although ensuring such interventions and evaluating their impact is diﬃcult due to the problems encountered in conducting epidemiological studies in Italy. The aim of this study is to compare the data about the incidence of femoral neck fractures among the elderly, derived from the Hospital Discharge Reports supplied by the Italian National Health Service, with the data we obtained thanks to the national ‘‘Femur Fractures Project’’ and those we collected in main trauma units in Rome and Lazio. We intended to estimate the real size of the problem in Italy and to bring up the discrepancies we found between our data and the oﬃcial ones. Methods: 1) We consulted data published by the Italian Ministry of Health based on the ICD-9 codes which refer to ‘‘pathologic femoral neck fractures’’. We considered the number of female patients older than 65 years who were discharged with a diagnosis of ‘‘pathologic femoral neck fracture’’ during a 1-year period in Italy and Lazio. 2) We processed national and regional data based on anamnestic forms compiled for 3579 femoral neck fracture patients by 115 trauma units in Italy over a 1-year period (from March 2004 to March 2005), evaluating several risk factors, prior investigation and treatment for osteoporosis, fracture type and surgical intervention, treatment given at discharge. 3) We are directly collecting the number of female patients older than 65 years admitted for a fragility femoral neck fracture in the main trauma units in Rome and Lazio during the year 2004. Results: Among the femoral neck fracture patients directly collected approximately 10% are registered in the anamnestic forms in trauma units and only 0.5% are discharged with a diagnosis of ‘‘pathologic femoral neck fracture’’. Many interesting aspects on diagnosis and treatment emerged from the ‘‘Femur Fractures Project’’ forms. Conclusions: According to the problems evidenced we have developed some initiatives to improve epidemiological data collection and consultation, and to optimize treatment and secondary prevention of osteoporotic fractures in Italy.

S202

P279MO. MEN LACK AWARENESS OF MALE OSTEOPOROSIS 1

2

2

1

Gold DT , Patel A , Jones MA ; Duke University Center for Aging and Human Development, Durham, NC, USA, 2Procter & Gamble Pharmaceuticals, Mason, OH, USA Aims: Osteoporosis, often considered a women’s disease, is serious and debilitating in men as well. One in 5 men over age 50 will experience an osteoporotic fracture in his lifetime. Additionally, men have a 70–100% higher mortality rate than women after a hip fracture. Nevertheless, most available information on osteoporosis focuses only on postmenopausal women. We conducted qualitative research on men in order to better understand their perceptions and awareness of osteoporosis. Methods: Seven men diagnosed with osteoporosis and 11 men not diagnosed with osteoporosis were recruited into focus groups. The mean age was 62 years (range 52–70). The men without osteoporosis had a first degree relative (sister, mother) with osteoporosis. Men were interviewed in small groups of 2 or 3 at a time. An independent moderator led discussions to determine their understanding and perceptions of osteoporosis. Results: All men said that osteoporosis is a woman’s disease. None were aware that osteoporosis aﬀected men until their diagnosis or until they attended this session. In the undiagnosed group, 6 of 9 men indicated they believed osteoporosis might be due to inactivity or not taking care of oneself properly (2 did not indicate a cause). None of these men had been screened or had ever asked his physician about osteoporosis. When given general information about the disease, men were motivated and receptive to learning about osteoporosis and indicated they planned to discuss the topic with their physician. For those who had been diagnosed, 4 of 7 were screened via a health fair heel scan and a follow-up diagnostic DXA. Upon learning that men can develop osteoporosis, all men expressed concern and frustration regarding the lack of readily available information about the condition. Conclusion: Although men seem receptive to learning about osteoporosis, only limited information is available. More educational information about osteoporosis needs to be developed for men to increase their awareness of and understanding about the disease. Men who have greater knowledge may be more willing to seek appropriate screening and treatment. This could ultimately reduce risk of fracture and improve quality of life in later years.

P280SA. PREFERENCE TO THE THERAPEUTIC SCHEME IN OSTEOPOROTIC PATIENTS WITH INDICATION TO START BISPHOSPHONATE TREATMENT Samdanis B, Dionyssiotis Y, Tournis S, Papakitsou E, Katsalira A, Economopoulos D, Lyritis GP; Laboratory of Research for the Musculoskeletal System, University of Athens, KAT Hospital, Kifissia, Greece Osteoporosis is a metabolic disease that decreases the mechanical strength of bone tissue, thus increasing the risk of fragility fractures. Therapeutic schemes for osteoporosis are divided in daily, weekly and monthly. Aim: To examine the preference to the therapeutic scheme in osteoporotic patients with indication to start bisphosphonate treatment. Materials and Methods: 349 postmenopausal women, receiving osteoporosis treatment for more than 6 months, were asked to complete a questionnaire regarding: (a) Their intention to begin an alternative therapeutic scheme. (b) Their preference to weekly or monthly therapeutic scheme. Results: 284 (81.4%) would rather change their treatment, whilst 45 (12.9%) stated their intention to continue their recurrent treatment. Furthermore 286 (81.9%) answered that they would definitely prefer a monthly applied treatment, 41 (11.7%) would probably take up such a scheme, 1 (0.3%) was uncertain, 4 (1.1%) were probably not keen on changing their weekly therapy and 2 (0.6%) answered that they would definitely not change their weekly scheme. Conclusion: 81.4% of the population would rather change their current treatment. Moreover the monthly treatment seems to be more attractive to osteoporotic patients, since 93.6% stated that

they would definitely or probably prefer such a scheme, compared to the weekly one.

P281SU. DIETARY AND LIFE HABITS AND BONE HEALTH IN URUGUAYAN TEENAGERS: NATIONAL SURVEY Hernández J, Chijani V, Alemán A, Calegari M, Lima S, Vaglio A; Uruguayan Society of Reumathology, Uruguay Aim: to study the relation between dietary, genetic and life habits and bone health among teenagers from secondary schools in Uruguay. Methods: This is a descriptive study. A representative sample of 1052 high school adolescents from diﬀerent areas and social classes of the country were surveyed. A self administered questionnaire was given to each teenager. This form was developed by the Osteopathy Study Group from Society of Rheumatology of Uruguay. A brief explanation in relation to some of the questions of the survey was given to the students before filling the form. Results: About 51% of the teenagers reported doing only 2 h per week of extracurricular physical activity. No extra sports were practiced by more than 500 of teenagers surveyed. About 12.4% of participants reported not consuming any dairy in their daily diet and minimum calcium daily requirements were not consumed by 48% of participants (assuming 60% of requirements should come from dairy sources). About 24% reported not consuming any portion of milk daily and only 17.6% reached calcium needs through milk consumption (the most available and cheap calcium source in the country). Otherwise there is a high daily consumption of ‘‘milk’’ substitutes like cola drinks (48%). In relation to alimentary habits, 76% reported having a daily breakfast but not in all cases dairy food is a component of this meal. Conclusions: Dairy intake is low in high school teenagers in Uruguay. It is a priority to develop and implement programs targeted to this population to stimulate healthy habits including dairy intake and increase of physical activity. These programs should include families and educators and should be evaluated.

P282MO. WITH WHAT BONE DENSITY DO MY PATIENTS FRACTURE? A LATIN AMERICAN CLINICAL EXPERIENCE Riera-Espinoza G, Riera F; Unilime UC, Hospital Universitario ‘‘Dr. Angel Larralde’’, Universidad de Carabobo, Valencia, Venezuela, Unidad Metabolica del Centro Policilinico Valencia, Valencia, Venezuela Most of fractures caused by a minor trauma in people over 45 years are due to osteoporosis (BMD % -2.5). The present work of clinical nature tries to establish the relationship between the values of BMD and fractures in patients who attend a general osteoporosis consultation. 49 fractured patients were evaluated with 61.69 10.37 average age, of which 95.9% were female and 4.1% male; age of menopause (women) 48.2 4.82 years; weight 62.49 10.0 kg; height 1.52 6.43 cm; and BMI 26.43 3.74. BMD were femoral neck T-score -2.2 and L1-l4 Tscore -2.6 1.05. Of the patients evaluated 20.4% had secondary causes for osteoporosis. Among risk factors were 14.3% had smoking habits, alcoholic 6.1%, 49% were sedentaries, 51% were breast fed, 18.4% did not consume milk products, 6.1% had a relative with osteoporosis fracture and 22.4% had a previous fracture (86 fractures in 49 patients). As far as types of fracture 26.5% had femur fracture, 34.7% vertebrae fracture and 65.3% another type of osteoporotic fracture; requiring orthopedical treatment 79.6% and surgical treatment 20,4%; in addition it was found that only 34% of the patients received specific treatment for osteoporosis at the time of fracture. Regarding the values of BMD, osteopenia was present in 67.3% and 40.5% at femoral beck or lumbar spine, respectively. Conclusion: In a specialized osteoporosis and mineral metabolism consultation, two thirds (67.3%) of the patients who presented and or displayed some type of osteoporoitic fracture had density values within the osteopenic rank at femoral neck and 40.4% at lumbar spine. T-score mean values were -2.2 at femoral neck and -2.6 at lumbar spine. These findings in Venezuelan

S203 patients still suggest a high incidence of fractures in subjects with low bone mass within osteopenic rank.

P283SA. REGIONAL OSTEOPOROSIS IN SPINAL CORD DISABLED VETERANS Sojaei H, Soroush MR, Modirian E; Janbazan Medical and Engineering Research Center (LMERC), Tehran, Iran Introduction: Osteoporosis the result of an imbalance between bone resorption and bone formation and is a potential problem for individuals with a spinal cord injury because of immobility commonly associated with this impairment. Bone mineral content decreases by 25 to 50% and the magnitude of reduction is dependent on the level, completeness and duration of SCI. Methods: In this cross-sectional study, by use of a cluster sampling frame, 115 SCI veterans undergone dual-energy X-ray absorbtiometery (DXA), to define bone mineral density (BMD) in 2nd to 4th lumbar vertebrae and the neck of right femur (g/cm_). Results: The study on the femoral neck showed that 94.6% of subjects suﬀered from abnormal BMD (84.9% osteoporosis and 15.1% osteopenia). Evaluation of lumbar spines also showed that 34.9% of veterans suﬀered from low BMD (52.2% osteoporosis and 47.8% osteopenia). A significant diﬀerence was observed between vertebral bone density (mean 1.23 g/cm_) and the neck of right femur (mean 0.66 g/cm_). Comparing the results in paraplegics and quadriplegics reveals that there is no significant diﬀerence between bone densities in the femoral neck and lumbar spines. It was also shown that there is no significant relationship between bone density and age, level of injury, and post–injury period and exercise. There was a slight correlation between weight and BMD. Discussion: During spinal cord injury, BMD in the lumbar vertebrae is significantly reserved better than the femoral neck.

P284SU. FRACTURE OCCURENCE IN PATIENTS WITH OSTEOPENIA: THE SEARCH FOR A NEW TREATMENT THRESHOLD Muschitz C1, Patsch J1, Woegerbauer T1, Pascher N1, Buchinger E1, Edlmayr E1, Nirnberger G2, Resch H1; 1St. Vincent Hospital, Medical Department II, Vienna, Austria, 2Bioconsult Ltd., Perchtoldsdorf, Austria Aims: According to current guidelines pharmacological intervention to prevent osteoporotic fractures should start at a T-Score less than -2.5 SD. Our retrospective analysis focussed on the prevalence of fractures in patients with osteopenic T-scores. Methods: We retrospectively analysed 1180 DXA-scans (lumbar spine or hip) over a period of eight months at our outpatient clinic. 57.1% were considered as osteoporotic, 35.6% had osteopenic values and 7.3% were within normal range. In our analysis we included 188 Caucasian pre- and postmenopausal women and men aged 20 to 92 years from the osteopenic subgroup. Vertebral fractures were identified by lateral x-ray examinations of the lumbar spine. Previous peripheral fractures were patient self-reported. Statistical analysis was performed using Mann-Whitney U-tests or chi-square tests, respectively. A p-value %0.05 was considered statistically significant. Results: Gender distribution within the subgroup was 85% female and 15% male. Mean age was 64.9 17.05 years. The mean T-score showed moderate osteopenic values at lumbar spine (-1.26 0.95) and total hip (-1.66 0.36). 34% had oral calcium substitution, 28% had bisphosphonates while 22% percent had no osteotropic medication. Fracture analysis revealed 27% vertebral and 8.5% peripheral fractures. 6.4% had fractures at both sites. Vertebral fractures most significantly occurred in the sixth and seventh decade of life (p=0.0006). The mean age of patients with vertebral fractures was 72.0 9.99 vs 61.4 18.7 years (p=0.0004). Primary diseases such as chronic inflammatory bowel disease, eating disorder (e.g. anorexia or bulimia) or chronic back pain (p=0.0008) and increased BMI (26.37 vs 23.06; p=0.000022) had significant influence on the occurrence of vertebral fractures. Conclusions: Co-existing risk factors such as age, sex and prevalent adult fractures must be assessed to estimate the fracture

risk of individual osteopenic patients. The influence of BMI on fractures still remains controversial. Taking into account the above mentioned results the redefinition of the intervention threshold to prevent the occurrence of an osteoportic fracture will be a major target for the future.

P285MO. DIABETES AND RISK OF HIP FRACTURES IN AGEING POPULATION: THE ITALIAN CASE STUDY Piscitelli P1, Iolascon G2, Muratore M3, Camboa P1, Avitto F4, Termini G5, Rini G5, Rossini M6, Adami S6, Angeli A7, Guida G2, and the SIOMMS Study Group; 1Health Economics, LUM Jean Monnet University, Bari, Italy, 2Second University of Naples, Naples, Italy, 3ASL Lecce/1, Lecce, Italy, 4La Sapienza University, Rome, Italy, 5University of Palermo, Palermo, Italy, 6University of Verona, Verona, Italy, 7University of Turin, Turin, Italy Objective: This study was aimed to analyze incidence and costs of hip fractures in people suﬀering from diabetes mellitus (both types I and II) in the Italian population, which represents an interesting case-study of ageing population among western countries. Methods: We analyzed the incidence of hip fractures (major diagnosis of hip fr.) in people aﬀected by diabetes (associated secondary diagnosis of diabetes) in people aged >65. The study examined data from national hospitalisation database concerning year 2002 (the latest available), allowing us to get real values rather than estimations. We considered ICD-9CM codes 820.0 and 820.1 (cervical hip fr.), 820.2 and 820.3 (intertrochanteric fr.), 820.8, 820.9, 821.1 (other hip fr.) as major diagnosis and ICD-9CM codes from 250.0 to 250.9 (diabetes mellitus, all types) as concomitant diagnosis. Results: 8.8% of male patients and 9.1% of females experiencing hip fr. were suﬀering from diabetes at the time of fracture; 94.6% of diabetic patients experiencing hip fr. were >65 y.o. and 78.6% of them were women (according to the higher incidence of osteoporosis in this sex and age group). Diabetic patients accounted for 9.0% of global costs sustained for treatment and rehabilitation of hip fractures. Table 1. Incidence and costs (Euros) of hip fr. occurred in diabetic patients aged R65 y.o. (Italy, year 2002). YEAR 2002 No. of hip fr. >65 y.o. (overall) No. of hip fr. >65 y.o. occurred in diabetic patients Overall direct costs >65 y.o. (hospitalisation + 1 month rehabilitation) Direct costs for diabetic patients >65 y.o. (hospitalisation + 1 month rehabilitation) Overall indirect costs >65 y.o. Indirect costs for diabetic patients >65 y.o.

17,910 (M) + 63,490 (F) 1,580 (M) + 5,820 (F) 854,400,000 Eur 77,670,000 Eur 170,900,000 Eur 15,527,000 Eur

P286SA. DEVELOPMENT OF AN ASSESSMENT FORM AND TEACHING TOOL FOR USE BY STAFF WORKING IN AN OSTEOPOROSIS SCREENING AND HEALTH PROMOTION CLINIC IN JAPAN Kitazawa M1, Maeda J1, Takayama S2, Nakamura S2, Stanley G1, Nosaka T1, Tanaka T1, Miyama T1, Yoshizawa K3, Fisher A4, Konishi E5; 1Nagano College of Nursing, Nagano, Japan, 2Health Promotion Division of Ueda City, Ueda, Japan, 3General Aﬀairs Division of Ueda City, Ueda, Japan, 4McMaster University, Canada, 5Oita University of Nursing and Health Sciences, Oita, Japan Japanese women’s life expectancy is the highest in the world, and the population of elderly women is increasing. Orimo et al (1998) estimated that there were about 10 million individuals with osteoporosis (80% were women) in Japan. Japanese municipalities have developed community-based programs in which women

S204 attend clinics for bone mineral density measurement and lifestyle assessment and counseling by public health nurses and dietitians. Exercise information is also oﬀered by non-licensed exercise instructors. This report focuses on the development of an assessment form and teaching tools for use by staﬀ who work in these clinics. An initial assessment form was developed based on the literature. This form included 38 items related to clients’ medical history and lifestyle. This was used during three osteoporosis screening and health promotion clinics in which one thousand women participated. However, the form was found by staﬀ and clients to be too complex, and revision was undertaken. Two focus group interviews were held with staﬀ who worked in the clinics. The interviews were recorded and analyzed using key words. Based on the analysis, the assessment form was revised. The number of items was decreased to 20, some items were changed and the layout was simplified. In addition, two types of instruction manuals were developed as teaching tools, one for staﬀ and another for clients. The new assessment form and instruction manuals were used in a subsequent clinic with 500 clients. Clinic staﬀ (n=32) were then surveyed by means of a questionnaire to determine their response to the new form and manuals. Twenty-five (78%) responded. All respondents described the new form as more satisfactory. Most respondents (88%) found the instruction manual for staﬀ useful as it provided consistent guidelines for teaching. Because the form and manuals were synchronized, respondents found they could answer clients’ questions more easily. In addition 48% of respondents described clients as ‘‘being interested in the instruction manual designed for them’’. This process was eﬀective for development of an assessment form and teaching tool for use by staﬀ in osteoporosis screening and health promotion clinics in Japan. Further testing and evaluation is ongoing.

P287SU. RISK FACTORS ASSOCIATED WITH OSTEOPOROTIC FRACTURES IN A LATINOAMERICAN POPULATION Jaller JJ1, Navarro E2, Vargas RF2, Jaller AJ1, Uribe J1; 1Centro de Reumatologia y Ortopedia, 2Universidad del Norte, Barranquilla, Colombia Osteoporotic fractures are widely recognized as a common and important cause of disability and death among postmenopausal women. The risk for having fracture in a woman starting from 50 years old is 15.6%, and in men is the half. Many factors are related to osteoporosis fracture. Aim: to determine risk factors associated to osteoporotic fractures in a population older than 49 years from Latin America (Colombia), during 2003–2005. Methods: we studied 467 outpatients having a osteoporotic clinic fracture From January 2003 to June 2005, assisting to our clinic. With informed consent, we performed a test for risk factors and a bone densitometry in femur and spine. Data were registered in a Microsoft Access database and migrated to Excel. Results: The mean age was 67.07 years (SD+/-: 9.7). We found that fractures in forearm were: 44.1%, hip: 17.13%, and spine: 4.71%. The mean age for hip fracture was: 68.28 years, spine: 67.29, and forearm: 63.86. In the other hand, risk factors for fractures were: low BMD (osteoporosis 49.6% and osteopenia 37.47%), low calcium intake: 19%, familiar antecedent of osteoporosis: 15.6%, smoking: 15.1%, Thyroid disease: 9.61%, Rheumatoid arthritis: 8.92%, Lithiasis: 6.41%, and corticoid intake by at least 3 years. 2.97%. When we compare fractured with not fractured woman, the diﬀerence was statistically significance (p<0.05) in all of them. Concussions: Many fractures are not dependent of osteoporosis. We found a important group of fracture having osteopenia. Hip fractures are prevalent in elderly women, and forearm fracture in women with 50 to 60 years. Identifying factors of risk for osteoporotic fractures is important to establish programs of prevention.

P288MO. THE CHARACTERISTICS OF MALE PATIENTS DIAGNOSED WITH OSTEOPOROSIS Aktas I1, Esen S2, Saridogan M2, Tuzun S2, Akarirmak U2; 1Saygi Hospital, 2IU Cerrahpasa Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey Aims: Evaluating the characteristics of male osteoporosis cases followed up in our polyclinic. Methods: The age, education status, alcohol, cigarette and coﬀee consumption, and nutritive habits of the male cases followed up in our osteoporosis polyclinic between 2004–2005 were evaluated. Secondary disease presence was confirmed by consultations carried out by the related units and by examination of the previous diagnoses. Usage of toxic drugs (against bone) and low energy fracture presence in the patient and his family were recorded. Sexual function was evaluated. Total blood count, comprehensive biochemical analyses, and bone mineral density (BMD) measurement (DXA Hologic) were applied. Results: The mean age of the 55 study subjects was 61.7 14.69 (age range: 22–85). 49.09% of the cases graduated from university, 29.09% high school, and 21.81% primary school. 78.2% were not consuming alcohol at all, 5.5% one glass a day, and 3.6% a few glasses a week. While the nonsmokers were 89%, 7.3% were smoking up to 5 cigarettes a day, and 3.7% were consuming above that level. The percentage of cases consuming more than 3 cup of coﬀees a day was 3.6%, the percentage of people consuming calcium-rich food was 69.1%, and the percentage of cases regularly exercising was 49%. 40% of the cases manifested sexual dysfunction. Secondary diseases were determined in 67.3% of cases and 29.1% of them had a history of toxic drug usage. The percentages pertaining to presence of fracture history in patients and their families were, respectively, 16.4% and 10.9%. Mean total hip densitometry value T-score was -2.19 0.89, and Lumbar 1–4 T-score was -2.63 0.80. Conclusions: We can aﬃrm about osteoporosis that it should be considered in men at advanced ages, secondary diseases and sexual hormones play significant roles as etiologic causes, and it eﬀects especially lumbar region (due to low mean T-score results at the lumbar region in our study).

P289SA. FACTORS ASSOCIATED TO COSTS, HOSPITALIZATION DAYS AND IMMEDIATE COMPLICATIONS OF PROXIMAL FEMUR FRACTURES IN THE ELDERLY: A BRAZILIAN STUDY Guerra RO1,2, Maranhão EV2, Coutinho LD2, Viana AS1,3, Campos TF1,2; 1University Federal of Rio Grande do Norte, 2 Physical Therapy Department, 3Onofre Lopes Hospital, NatalRN, Brazil Proximal femur fractures, besides being a serious and incapacitating infirmity in the elderly, incur high financial costs to health services. The aim of the present study was to identify the main factors associated to costs and hospitalization days of this type of fracture. The sample consisted of 208 cases of individuals over the age of 60 years treated at the main traumatology hospitals in Natal-RN, Brazil (77.9% female, mean age = 79.1 years). The femoral shaft fracture was the most frequent encountered (46.6%) and DHS Plate Fixation was the most frequently used surgical technique (59.1%). The mean number of hospitalization days was 7.4. The factors associated to costs and hospitalization days were the type of surgery employed and the occurrence of immediate postoperative complications. The development of new preventive and therapeutic measures could reduce immediate complications, hospital costs and consequently provide better functional conditions for elderly patients after proximal third femur fractures.

P290SU. HIGH PREVALENCE OF VITAMIN D INSUFFICIENCY IN ELDERLY WOMEN WITH A RECENT DIAGNOSIS OF OSTEOPOROSIS Genaro PS1, Pereira GAP1, Pinheiro MM2, Szejnfeld VL2, Martini LA1; 1São Paulo University, 2São Paulo Federal University, São Paulo, Brazil

S205 Vitamin D status is counted among the changeable factors involved in the pathophysiology of osteoporosis as it plays a key role in bone mineralization. Numerous reports recently attest vitamin D deficiency is a universal occurrence, not only in childhood, but particularly in the elderly. Aim: the aim of the present study was evaluate vitamin D status in postmenopausal women with osteoporosis, living in a sunny country. Methods: Forty-five free-living postmenopausal women, mean age 63.3 (8.2)y assisted at São Paulo Hospital osteoporosis outpatients clinic were invited to participate. Vitamin D status was evaluated by serum 25(OH)D3 and dietary vitamin D intake. Bone and mineral metabolism was evaluated by DXA and calcemic biomarkers such as serum calcium, ionized calcium, phosphorus, parathyroid hormone (PTH) and 1,25(OH)2D3. Results: The mean L1-L4 BMD T-score was -3.01(0.88) and femoral neck BMD T-score -2.10(0.89). Hypovitaminosis D was present in 71.2% and insuﬃciency in 24.4% of the women. Mean serum calcium, phosphorus, PTH and 1,25(OH)2D3were in accordance to the reference values. PTH however, was above the upper limit in 51% of the participants, indicating hypersecretion of the hormone. A positive correlation was observed between PTH and 1,25(OH)2D3(r=0.365 p=0.014). Vitamin D intake was under recommended levels in all participants, the mean dietary intake was 4.2 (2.0) µg/d. Moreover, none of them were taking vitamin D supplements. The mean calcium intake, 723.80 (263.96) mg/d was also lower than recommended levels for age. Conclusion: These results indicate a poor vitamin D status and an imbalance in bone and mineral metabolism in elderly women with osteoporosis and encourage the increase in vitamin D and calcium intake from foods and supplements to maximize their bone health.

P291MO. THE IMPORTANCE OF DIFFERENCE BETWEEN ARM SPAN AND STANDING HEIGHT IN ELDERLY POSTMENOPAUSAL OSTEOPOROTIC WOMEN Vural M, Esmaeilzadeh S, Basat H, Aki S, Eskiyurt N; Istanbul University, Istanbul Faculty of Medicine, Physical Medicine and Rehabilitation Department, Istanbul, Turkey Objectives: Deformities due to vertebral compression fractures cause thoracic kyphosis and shortness of height. As it is equal for normal individuals, in patients with osteoporotic compression fractures the height is shorter than the arm span. Since the measurement of height in standing position is aﬀected from compression fracture induced kyphosis, it is preferable to use arm span in osteoporotic elderly patients instead of standing height measurement. The aim of this study is to compare the diﬀerence between arm span and height measurements in elderly postmenopausal women with vertebral compression fractures and without these fractures, correlated with radiologic signs. Materials & Methods: Retrospectively, 106 women with known osteoporosis were included in our study. All patients were more than 65 years old. The patients were sorted into two groups, the study group had 47 patients with compression fractures in their vertebral radiography and the control group had 59 patients without these radiologic signs. Results: The mean age was 73.30 5.65 for the study group and 70.24 4.76 for the control group. There was no significant diﬀerence between the mean ages of two groups (p>0.05). The diﬀerences between arm span and height was calculated. The diﬀerences were statistically greater in the study group (p<0.05). Conclusions: Arm span – height diﬀerence although seems to be a simple measurement method but it is very useful in evaluating of osteoporotic patients with vertebral compression. It is recommended that it be used as a first step in screening for osteoporosis and its complications.

P292SA. THE RELATIONSHIP OF OSTEOPOROSIS KNOWLEDGE TO CLINICAL AND FALL RISK FACTORS IN INDEPENDENT COMMUNITY DWELLING ELDERS Burke-Doe A1,2, Hudson AL1,2, Werth HM1; 1California State University Fresno, 2Central California Center for Health and Human Services, Fresno, California, USA

Aims: Many seniors are not aware of osteoporosis risk factors despite the available evidence and the public awareness programs on prevention and treatment. The purpose of this study was to identify the prevalence and knowledge of risk factors for OP, fractures, and falls in an independent community-dwelling elderly population. It was hypothesized that seniors who had knowledge of OP and its risk factors would have adopted lifestyle changes that promote bone health and prevent fractures. Methods: Forty nine seniors participated in the study from a sample of connivence. Participants were aﬄuent and the community provided onsite wellness programs. Participants completed a series of questionnaires and physical testing procedures including health history, Osteoporosis Self-assessment Tool (OST), Balance Eﬃcacy Scale (BES), Medical Outcome Study (SF-36), Senior Fitness Test (SFT), Physical Activity Scale for Elderly (PASE), 3-day food frequency (Calcium and Vitamin D intake), home safety questionnaire (HSQ) and Osteoporosis Knowledge Assessment Tool (OKAT). Results: Forty-one females, 8 males with a mean age of 84.4 years participated. Participants were primarily Caucasian (98%) and 63% scored below 50% on the twenty item OP knowledge questionnaire (OKAT) with an average score of 8.2. The average number of risk factors present was 5.5 but only 57% had received bone density testing. Thirty-eight percent of the participants had limitations in agility, dynamic balance and strength in the upper and lower extremities. Forty-four percent had poor endurance, 75% and 53% had reduced upper and lower extremity flexibility, respectively. Eighty-three percent had inadequate calcium intake and 95% had inadequate vitamin D intake with only 48% reporting calcium supplementation. Weak but significant correlations were found between knowledge and the BES r = 0.294, P = 0.043 and moderate correlations between knowledge and the BERG r = 0.472, P = 0.001. Conclusions: Despite an increase in eﬀective identification and treatment techniques for OP in the last decade, participants in the study demonstrated gaps in knowledge and limited change in behaviors. This study identified participants at risk for OP in multiple areas related to knowledge, endurance, balance, exercise and diet demonstrating the need for individualized intervention programs.

P293SU. ASSESSMENT OF RISK FACTORS FOR OSTEOPOROSIS AND BONE MINERAL DENSITY IN SERBIA Prodanovic N1, Bozic B2, Dimic A3; 1Military Medical Academy, Belgrade, 2Faculty of Biology, University of Belgrade, 3Faculty of Medicine, University of Nis, Serbia and Montenegro Introduction: Osteoporosis (OP) is a skeletal disorder characterized by decreased bone density and increased risk for bone fractures. Main problem in OP are bone fractures due to bone fragility. It is essential to prevent them in order to decrease morbidity and mortality, and increase quality of life. Aim: The aim of this study was assessment of risk factors (RF) for osteoporosis, osteoporotic fractures frequency, and bone mineral density (BMD), through examining population by portable ultrasound device. Material and methods: This study conducted during a period of six months and included 1049 persons, average age 57, from three towns in Serbia (Belgrade – urban zone, Pancevo – industrial zone, and Zajecar – rural zone). Questionnaires, including questions related to RF (early menopause, consummation of more than three cups of coﬀee a day, smoking more than five cigarettes daily, physical inactivity, history of previous fractures), were filled by each examinee during our research. BMD was measured by ultrasound ‘‘Sahara’’ – Hologic device, on hill of our examinees. We measured BMD by Lunar DXA DPX 2000 device on the level of lumbal spine (L1 – L4) and/or femur, to all persons whose ultrasound finding showed osteopenia and who had one of the important RF, and to all persons whose ultrasound finding showed osteoporosis. Results: Out of 405 examined persons in Belgrade, 36 (8.8%) had osteopenia, and 22 (5.4%) osteoporosis. Out of 464 examined persons in Pancevo, 44 (9.4%) had osteopenia, and 29 (6.3%) osteoporosis. Out of 180 examined persons in Zajecar, 14 (7.8%)

S206 had osteopenia, and 8 (4.4%) osteoporosis. The most common RF in Belgrade and Pancevo was consuming of coﬀee, in Zajecar smoking. The most frequent occurrence of osteoporotic fractures was noted in Pancevo (10.3%); in Belgrade it was 7.2%, in Zajecar 6.8%. Conclusion: Based on results of our study, we concluded that decreased BMD and higher number of osteoporotic fractures are occurring in industrial areas in comparison to urban and rural area. The highest number of early menopause in Pancevo could be one of reasons for BMD decrease.

P294MO. BONE MINERAL DENSITY IN WOMEN OVER 70 YEARS IN RIO DE JANEIRO Rocha FBS1,2, Silva RO1, Russo LAT1,2, Gregorio LH2, Melazzi AC2, Lacativa PGS2, Oliveira FV1, Pinheiro RAC1,2, Argentina D2, Dornellas M2; 1Hospital Pro Matre, 2Center for Clinical and Basic Research – CCBR Brasil, Rio de Janeiro, Brazil Osteoporosis is a common disease that increases with aging. The aim of this study was to evaluate the bone mineral density in a group of women of 70 years and over. Methods: 415 women were selected from a database of a women’s health reference center in Rio de Janeiro, Brazil. The patients were divided into four groups: 70–74, 75–79, 80–84 and over 84 years. Age, body mass index (BMD) and BMD were analysed. Hologic densitometer was used to assess BMD. Statistics was performed by SPSS. Results: Prevalence of osteoporosis was 68.7% (lumbar spine) and 54.5% (femoral neck). Osteopenia was found in 23.2% and 29.7%. A concordance of 47.3% for the osteoporosis group and 11.9% for osteopenia was seen when both sites were analised. Average BMI was: 27.48.3 (first group), 25.87.2, 24.76.9 and 24.58.4, respectively. A positive correlation was observed between BMI and BMD. Conclusion: Osteoporosis is a public healthy problem especially in elderly women, needing actions to prevent and treat, to avoid its complications.

P295SA. OSTEOPOROTIC FRACTURES IN VETERANS WITH SPINAL CORD INJURY: IS BONE MARROW DENSITY A GOOD PREDICTIVE VALUE? Modirian E, Soroush MR, Shojaei H; Janbazan Medical and Engineering Research Center (LMERC), Tehran, Iran Aims: Prospective studies have shown that in adult women the risk of fractures increases progressively with decreasing bone mineral density (BMD); approximately 1.5 to 3 fold for each standard deviation decrease in BMD, and below 2 SD, it increases exponentially. In SCI patients, there are no standard criteria to predict fracture risk and usually BMD is used for this reason. We planned this study to evaluate the relation between BMD and the frequency of fractures in SCI patients; meanwhile detecting osteoporosis progression during 4 years. Methods: Following 127 SCI veterans for 4 years, we assessed bone density of the right femoral neck (hip) and 2nd to 4th vertebrae by DXA method (LUNAR, Madison, WI), at the beginning and the end of the study. Using a comprehensive form, we recorded all confounding factors as gender, age, body mass index (BMI), level of injury, length of time since injury, patient’s daily exercise and diet, and their medications along with number and sites of osteoporotic fractures. Results: Preliminary results revealed that in the femoral neck (hip), more than 80% of our study population suﬀers from osteoporosis; in some of them T-score was as low as -6 SD bellow the normal range. Statistical analysis showed that every unit (SD) decrease in BMD of the femoral neck increases the fracture risk up to 1.43 times. But during 4 year follow up, we discovered less fractures in osteoporotic category than predicted. Conclusions: Since underlying factors as sedentary position and strong care support play important roles in prevention of fractures in SCI veterans, BMD may not be a good predictive value to assess fracture risk in these patients.

P296SU. EVALUATION OF THE PREVALENCE OF OSTEOPOROSIS AND ITS RISK FACTORS IN A WOMEN’S HEALTH CENTER IN RIO DE JANEIRO Rocha FBS1,2, Silva RO1, Russo LAT1,2, Gregorio LH2, Lacativa PGS2, Melazzi ACM2, Vasconcelos FO1; 1Hospital PRO MATRE, 2Center for Clinical and Basic Research-CCBR Brazil, Rio de Janeiro, Brazil Introduction: Osteoporosis is a common skeletal disease characterized by a decrease in bone mineral density (BMD) and microarchitectural deterioration of bone tissue with an increase in susceptibility to fracture risk. Studies of Brazilian population showed a similar prevalence to other countries. The aim is to evaluate the prevalence of densitometric diagnosis in ambulatory postmenopausal women and its relation with risk factors to osteoporosis in a center in Rio de Janeiro. Melhods: Descriptive, cross-sectional, 1148 women attended by free-demand underwent a bone density test in a period of six months. Diagnosis was based on the region with lowest T-score (WHO criteria). Risk factors evaluated were: low body weight (<20), low calcium intake (less than 2 glasses of milk/day), excess of caﬀeine comsuption (more than 300ml/day), inadequate physical activity and past of fracture after age of 35. BMD measurements were done with Hologic 4500 DW densitometer. In data analysis the Chi square test was used. Results: Average age was 61.58.4 years. Osteoporosis was found in 45.23% and osteopenia in 37.19%. A significant relation between osteoporosis and low body weight (p=0.001) and past fracture (p=0.02) was observed. Lifestyle factors evaluated had no impact on BMD. Conclusion: The authors concluded that the prevalence of osteoporosis among the population examined was higher than expected. This shows that osteoporosis is a public health problem, needing actions to prevent, diagnosis and treat, in order to obtain a better quality of life.

P297MO. NONVERTEBRAL FRACTURES IN ELDERLY PEOPLE Zotkin EG1, Kosulnikova EN2, Ivanova LI3; 1Medical Academy of Postgraduate Study, 2Municipal Osteoporosis Center, 3Municipal Geriatric Center, St. Petersburg, Russia Aims: It is well known that approximately one-third to one-half of women will sustain at least one osteoporotic fracture during their lifetime. Fractures among old people are the main cause of mobility loss and high mortality. This study assessed the frequency of nonvertebral fractures among elderly people. Materials and Methods: This retrospective study enrolled 122 women and 87 men at the age of R90 (95.44.1).The information about fractures was collected by caregivers/nurses 4 times per year. Nonosteoporotic fractures were excluded from analyses. Results: A total of 98 women (in 80.3% cases) suﬀered at least one nonvertebral fracture during their life. The incidence of clinical nonvertebral fractures in men was low (10.3%). More than two nonvertebral fractures were observed in 30 women (24.6%) and 2 men (2.3%). Femur fractures occurred in 45 women (36.9%) and 5 men (5.7%). At the age of 90–99 years old the number of femur fractures was estimated to be 28.7% in women and 5.7% in men. Conclusions: The rate of nonvertebral fractures among elderly women compared with men was 7.8 timeshigher. One-half of all femur fractures in elderly women occurred at the age R90 years old.

P298SA. MEASURING THE MARKET SHARE OF OSTEOPOROSIS CENTERS FROM OUTPATIENT CARE FINANCING IN HUNGARY Boncz I1,2, Sebestyen A3, Ghodratollah N4, Fodor B5, Borzsei L5, Ember I4, Nyarady J5, Pentek M6, Gulácsi L6; 1Department of Health Policy, National Health Insurance Fund Administration (OEP), Budapest, Hungary, 2Institute of Diagnostics and Management, University of Pecs, Hungary, 3County Baranya Health Insurance Fund, Pecs, Hungary, 4Institute of Public Health and

S207 Preventive Medicine, University of Pecs, Hungary, 5Department of Traumatology and Hand Surgery, University of Pecs, Hungary, 6 Corvinus University Budapest, Hungary Aim: Hungarian outpatient care is financed through a fee-forservice point system. Medical procedures are listed according to the ICPM (International Classification of Procedures in Medicine) code system of the WHO (World Health Organization). It allows us to carry out detailed analyses of specific parameters of health care financing. The aim of this study is to analyze the market share of outpatient osteoporosis centers from the total outpatient care in Hungary. Data and methods: Data derive from the financial database of the National Health Insurance Fund Administration (OEP), the one and only health care financing agency in Hungary. The year 2004 is covered. At the time of analysis, there were 73 osteoporosis centers in Hungary in outpatient care. For the analysis the following performance indicators were used: number of contact hours, number of financial cases (patients), number of medical procedures, health insurance reimbursement (money). Results: Altogether 274,202 patients visited any osteoporosis centers in Hungary in 2004. National Health Insurance Fund Administration (OEP) spent more than 5 million US dollars (1 billion Hungarian forints) on financing osteoporosis centers. The market share of osteoporosis outpatient centers varied significantly depending on the indicators used for calculating the market share. The market share of osteoporosis centers was as follows: 0.65% from the number of contact hours, 0.76% from the number of financial cases (patients), 0.43% from the number of medical procedures, 1.21% from the health insurance reimbursement (money). Conclusions: Our results showed that the relative financial position of osteoporosis care in Hungary is stable. The market share measured by health insurance reimbursement (money) was by fare higher than measured by any other indicator. The relatively higher market share of osteoporosis centers from health insurance reimbursement might indicate a cost intensive care. A further study is needed to analyze the reasons behind these values.

P300MO. ACTION ‘‘ARE YOU IN THE RISK GROUP FOR OSTOPOROSIS’’, INDJIJA, JULY 18– 25, 2005 Iriski VS; Health Center, Indjija, Serbia Goal: detection of a problem of low bone density in work-active women in the territorial of community of Indjija, located in the north of Serbia. Material and methodology: study of a section of the bone density state with 202 patients and analysis of potential risk factors. From July 18–25, 2005 there has been an campaign .A week of fight against osteoporosisZ at Health Center Indjija. This was a unique action for prevention of ostoporosis carried out at some health centers of primary health care in Serbia. Public was informed through posters, local television and newspapers about campaign as well as about this illness. Visiting diﬀerent administrative institutions, through immediate interview and filling out the IOF One Minute Risk Test for ostoporosis has recruited 202 work-active women at the age between 25–55. To all of them bone density has been measured by QUISS densitometry, and before measuring, they all filled out the test for risk factors for this illness. Women with low bone density and at least 2 ostoporosis risk factors were sent to DXA measuring of bone density, after which they had plan for prevention or osteoporosis treatments made. Results: Total of 31% of women had osteoporosis, and even 49.8% had osteopenia according to QUISS measurement. After DXA measuring, result changed but they haven’t cross the limits of statistical importance (p>0.05). 24.2% of women had osteoporosis and 55.5% had osteopenia. Presence of 2 risk factors was detected in 82.2% of women with low bone density, 53% had 3 risk factors, and 47% had more than 3 risk factors. Interesting data are that even 4.95% of women with ostoporosis didn’t have any risk factor. Conclusion: with this action, first in our area, has been touched the top of a low bone density problem in women population of this territory. Proportions of this problem were detected, which nobody paid any atention before and knowledge about this illness is very small among population and health workers too. Action should be widened to total female population that is work-active to prevent ostoporosis which is much cheaper and more eﬀective than ostoporosis therapy.

P299SU. MEASUREMENT OF BONE MINERAL DENSITY BY ULTRASOUND AND FOREARM DXA IN CLINICAL PRACTICE Fait T, Zivny J; General Faculty Hospital and 1st Faculty of Medicine Charles University Prague, Czech Republic

P301SA. SOMATOTYPE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN: A PILOT STUDY

We examined 190 women with average age 56 years by both methods - Lunar PIXI (dual photon absorptiometry) on forearm and CUBA Clinical (broadband ultrasound attenuation) on heel. We took personal history for menopause status, hormone replacement therapy, smoking, sport activity and age. The incidence of T-scores was the same for both methods, there were diﬀerences in Z-scores. In both methods we have seen the same tendencies of interaction with risk factors. Bone mineral density (BMD) respective T-score significantly decreased with age. There were no significant connections between BMD and body mass index (lineary regression test), hormone replacement therapy (paired t-test), smoking and physical exercise (Mann-Whitney U test). T-score was significantly (p<0.003) lower in women with history of fracture (Mann-Vhitney U test). In spite of totally diﬀerent principles of measurement both methods are able to screen BMD.

Ronco AR, Miranda CM, Wiluzanski DW; Centroseo Diagnostic Clinic, Montevideo, Uruguay

Frequency of osteoporosis and osteopenia Lunar

CUBA

T-score

n

%

n

%

normal -1,5 – -2,5 < -2,5 Total

107 64 19 190

56,4 33,6 10 100

121 60 9 190

63,4 31,7 4,9 100

Aim: To explore possible associations among bone mineralization and fat and muscular distribution in postmenopausal women. Methodology: A bone densitometry study and a somatotype evaluation was performed in 44 postmenopausal women (26 osteopenic and 18 normal ones), all proceeding from the pre-paid healthcare system and resident in Montevideo, who consulted at a medical center specialized in bone densitometry. They were administered a brief questionnaire on menstrual and reproductive history, family history and other variables of interest. Several skinfolds, girths and diameters were measured, specifically in order to estimate somatotype of each patient. Results: The analysis of somatotype revealed a highly mesoendomorphic pattern in the studied group. Osteopenic women tended to be slightly less endo- and mesomorphic and more ectomorphic than controls, particularly in the subset of menopause under age 45. The endo- and mesomorphic components were positively correlated with bone mineral density of lower limbs (r=0.40), trunk (r=0.42) and total (r=0.39), whereas the ectomorphic component displayed a negative correlation (r=-0.34, -0.26 and –0.24, respectively). Conclusions: This report on body shape quantification in the study of osteoporosis is, to our knowledge, the first one communicated in the specialized literature. Modifying somatotype through nutrition and exercise could enable to expand primary prevention in a risk population subset like the analyzed herewith, if results were confirmed in larger samples.

S208

P302SU. BODY COMPOSITION AND BONE MINERALIZATION: PRELIMINARY RESULTS OF A CASE-CONTROL STUDY IN EARLY POSTMENOPAUSAL WOMEN Wiluzanski DW, Ronco AR, Miranda CM; Centroseo Diagnostic Clinic, Montevideo, Uruguay Aim: To analyze possible associations between body composition and risk of osteopenia in early postmenopausal Uruguayan women. Methodology: 37 patients proceeding from the pre-paid medical healthcare system in Montevideo, whose menopause occurred at ages %45, 23 of them recent osteopenic cases and 14 controls having a normal bone densitometry, were interviewed on menstrual and reproductive history, family history, medication received, and a series of 18 skinfolds, circumferences and anatomic girths were measured, together with weight and height. Densitometry allowed us to assess 25 anthropometric variables at upper limbs, lower limbs, trunk and total. Results: A negative association between several body measures and the risk of osteopenia was found. Women with higher absolute adipose and muscular weights were found as low-risk ones, although their proportionality was similar to that one found among osteopenic patients. Broader girths and diameters in limbs and a higher adipose load in the upper part of the body were also positively associated with bone mineralization. Conclusions: Albeit findings are preliminary and based on a small sample, they suggest that a larger skeletal structure with larger adipose and muscle masses can be a possible protection for bone mineralization in early postmenopausal women. New studies at a larger scale are required to confirm these results.

In bone densitometry it is appraised that T-SCORE more low in lumbar spine they appear in L4 with 65.24%. The prevalence of detected vertebral fractures in this group is 17.6% of all women studied. By age groups, the 40–60 years represent 14% of the detected fractures and the group of 60–80 years an 86%. 71.13% of the fractures are thoracic, 28.87% lumbar and 11.34% of the group present both thoracic and lumbar fractures. 48.69% of the fractures are degree I, 30.45% are degree II and 28.86% are degree III. Most of the detected fractures, 54.13% are of the average wall, and the rest, 45.87%, of the previous wall. Fractures of the later wall in this study have not been detected. 47.73% of women with fractures had two or more vertebral fractures. Conclusions: X-ray of the pine is a useful and cheap method for the measurement and detection of vertebral fractures in primary care programs. The method can be used by trained sanitary personnel using direct visual measurement or from computer programs scanning the X-rays. This method is useful to restore treatments, but definitive diagnosis should always take control of bone densitometry.

P305SU. INHIBITION OF FPP-SYNTHASE IN OSTEOBLASTS MAY EXPLAIN THE BLUNTING OF THE BONE ANABOLIC RESPONSE TO PTH OBSERVED AFTER CHRONIC EXPOSURE OF RATS TO BISPHOSPHONATES

P303MO. PREVALENCE OF OSTEOPOROSIS AMONG ELDERLY WOMEN LIVING IN DELHI AND RURAL HARYANA

Gasser JA, Ingold P, Rebmann A, Susa M, Green JR; Novartis Institutes for BioMedical Research, Basel, Switzerland

Roy R, Chibber G, Marumudi E, Srivasta M, Ammini AC; AllIndia Institute of Medical Sciences, New Delhi, India

Chronic exposure to the bisphosphonate (BP) alendronate (ALN) was shown to blunt the bone anabolic response to parathyroid hormone (PTH) in rats (Gasser J, J Musculoskel Neuron Interact 2000;1:53) and humans (Finkelstein JA, NEJM 2003;349:1216). We investigated the potential mechanism behind the BP–PTH interaction. Skeletally mature Wistar rats were treated with ALN (28µg/kg s.c. twice per week) or vehicle for 16 weeks before starting daily s.c. injections of 100µg/kg hPTH(1–38) 5 times per week. The anabolic response was monitored by serial quantitative computed tomography (pQCT) and mechanical testing. The response to PTH was significantly blunted in ALNpretreated rats. pQCT measurements indicated a 2-week delay in the anabolic action of PTH. Also, ALN-pretreated rats did not develop the full anabolic response observed in vehicle-pretreated rats over time. A second study investigated equipotent therapeutic doses of the BPs ALN (200µg/kg) and zoledronic acid (ZOL; 32µg/kg or 322µg/kg) administered as single i.v. injections. Daily s.c. PTH(1–34) treatment (40µg/kg, 5x/week) was initiated 24h later and continued for 6 weeks. Serial measurements of BMD, cortical and trabecular architecture in the proximal tibia metaphysis by pQCT and in vivo microCT indicated a normal bone anabolic response in all structural parameters in ALN and ZOL treated animals, including those given the supra-pharmacological dose of ZOL. Although osteoblasts (Obs) are not generally considered to be a target for BP inhibition, in vitro experiments provided direct evidence that BPs reduce protein prenylation in MC3T3–1b cells as measured by Rap1A immunoblotting. Since small G proteins, such as Rap1 participate in cytoskeletal reorganization, BPs may thus aﬀect the cytoskeleton in osteoblasts. PTH is able to activate flat bone lining cells into cuboid, collagen-synthesizing osteoblasts within 6h after administration. Our data suggest that chronic BP exposure may reduce the ability of PTH to activate bone lining cells into matrix-secreting Obs, a crucial step in the early bone anabolic response to PTH. Due to the ineﬃcient uptake of BPs into Obs, this mechanism is only observed after chronic treatment in vivo and may explain the blunting of the anabolic response to PTH observed after chronic exposure of patients and rats to BPs.

Apparently healthy women living in 5 residential areas of Delhi and 10 villages of rural Haryana were invited for bone mineral density assessment at AIIMS hospital after a team of doctors and social workers spoke to them about osteoporosis and role of BMD in osteoporosis screening. BMD was done with a Hologic QDR4500A machine. 429 women (311 from Delhi and 118 from Haryana) in the age group of 60 to 83 years underwent BMD assessment. 224 (52%; 45% from Delhi and 69% from Haryana) were osteoporotic by WHO criteria. Mean height of women with osteoporosis was not significantly diﬀerent from those without osteoporosis, however osteoporotic women had lower bodyweight (51 kg vs 63 kg). 7% of osteoporotic women had suﬀered one or more fractures, forearm constituting 5% followed by hip fracture.

P304SA. PREVALENCE AND IDENTIFICATION OF VERTEBRAL FRACTURES: COMPARISON OF RX VIRTUAL INSPECTION AND DENSITOMETRY IN SPINE (T4-L4) Marí Solivellas B1, Cabanes Martín T1, López A2; 1Servicio de Medicina del Deporte, 2Medicina del Trabajo Gesma, Palma de Mallorca, Spain Aims: We analyzed 500 women, postmenopausal women or with precocious menopause, aged between 40 and 80 years and with two or more factors of osteoporosis risk. The results obtained are compared by age groups (40–60 and 60–80 years). The X-rays are analyzed by visual radiological inspection and they were compared with bone densitometry in the spine for the evaluation of vertebral fractures. Methods: Spinal X-rays of spine of all women are made in lateral position of thoracic and lumbar spine. The measurement is taken from the previous, average and later vertebral wall in lateral position. Vertebral fracture is considered by diminution of 20% of the normal height, according to the recommendations of the International Osteoporosis Foundation (IOF). Results: Of the women studied 43.2% have T-SCORE of spine < -1.0, 30,2% have it between -1.0 and 2.5, and 26,61% have osteoporosis with T-SCORE > -2.5.

S209

P306MO. CONCOMITANT ADMINISTRATION OF ALENDRONATE BLUNTS THE ACUTE CALCEMIC RESPONSE TO RECOMBINANT HUMAN PARATHYROID HORMONE 1–84: RESULTS FROM A PATH SUBSTUDY Bilezikian JP1, Greenspan SL2, Black DM3, Sellmeyer DE3, Ensrud K4, Rosen CJ5, Fox J6; 1Columbia University, New York City, NY, 2University of Pittsburgh, Pittsburgh, PA, 3Univeristy of California, San Francisco, San Francisco, CA, 4VA Medical Center, Minneapolis, MN, 5St. Joseph’s Hospital, Bangor, ME, 6 NPS, Salt Lake City, UT, USA Aim: The PaTH study demonstrated that concomitant administration of alendronate (ALN) with PTH (1–84), significantly blunts the increases in bone turnover and in volumetric trabecular bone mineral density at the lumbar spine induced by 12-months of daily PTH monotherapy. The physiological role of PTH is to increase plasma calcium levels by increasing calcium eﬄux from bone, enhancing renal calcium reabsorption and renal 1,25(OH)2D production, the latter of which increases intestinal calcium absorption. This study investigated whether ALN also influences the acute calcemic response to PTH. Methods: This study was performed in a subset of subjects at Month 12 of PaTH. Blood and 2-hour urine samples were collected before and for 8-hours after PTH injection (100 mg) and/or oral ALN administration (10 mg). PTH was measured using the Scantibodies Whole PTH IRMA. Results: Mean predose serum calcium levels were 9.5, 9.4, and 9.1 mg/dL and PTH levels were 27, 40, and 47 pg/mL in the PTH (n=20), PTH+ALN (n=9), and ALN (n=12) groups, respectively. There was no significant eﬀect of ALN on the pharmacokinetic profile of PTH; mean baseline-corrected maximum PTH concentrations achieved were 346 and 377 pg/mL in the PTH and PTH+ALN groups, respectively. Serum total and plasma ionized calcium (Ca2+) increased progressively starting at about 2-hours after PTH injection. At 8-hours, the mean changes in serum total calcium were +0.51, +0.24, and -0.08 mg/dL and in Ca2+, +0.46, +0.24, and -0.04 mg/dL, in the PTH, PTH+ALN, and ALN groups, respectively. The increase in serum 1,25(OH)2D levels at 8-hours was significantly greater in the PTH+ALN than in the PTH group (23 vs. 11 pg/mL). ALN administration had no eﬀect on the nonsignificant tendency for urinary fractional excretion of calcium (FECa) to decrease following PTH injection. At 6-hours FECa decreased from 1.4%>1.0% in the PTH alone group and from 1.6%>1.0% in the PTH+ALN group. Conclusions: Concomitant ALN with PTH administration blunted the acute calcemic response to PTH monotherapy by w50%, but did not inhibit the renal response. This suggests that the eﬀect of ALN is predominantly through inhibition of acute PTH-induced calcium eﬄux from bone, possibly by inhibiting bone turnover.

P307SA. STRONTIUM RANELATE REDUCES THE RISK OF VERTEBRAL FRACTURE IN PATIENTS WITH OSTEOPENIA Seeman E1, Sawicki A2, Reginster JY3, Roux C4, Rubinacci A5, Diaz-Curiel M6, Kaufman JM7, De Vernejoul MC8, Aquino JP9, Meunier PJ10; 1Endocrine Unit, Augustine Hospital, Melbourne, Australia, 2Warszawskie Centrum Osteoporozy, Warsaw, Poland, 3 Dept of Epidemiology and Public Health, University of Liège, Liège, Belgium, 4Hopital Cochin, Paris, France, 5Bone Metabolic Unit, Scientific Inst. H. San Raﬀael, Milano, Italy, 6Servicio de Medicina Interna, Fundacion Jimenez Diaz, Madrid, Spain, 7Polyclinique d’Endocrinologie, Gent Universiy Hospital, Belgium, 8 Hôpital Lariboisière, Paris, France, 9Clinique Médicale de la Porte Verte, Versailles, France, 10Dept of Rheumatology and Bone Diseases, Edouard Herriot Hospital, Lyon, France Objective: There is little evidence to demonstrate that any of the available anti-resorptive or anabolic drugs reduce the risk of vertebral fractures in patients with osteopenia. In part, this may reflect the low incidence of fractures in this population rather than lack of anti-fracture eﬃcacy of the drugs. Materials and methods: To address this question, we analysed the pooled data from SOTI (n = 1649) and TROPOS (n = 5091) in which postmenopausal women received strontium ranelate 2g/d

orally or placebo for 3 years in a randomized double blind fashion. Each patient received calcium and vitamin D supplementation according to baseline nutritional status. In this sample, 409 patients with lumbar and/or femoral neck T-score between –1 and –2.5 and both T-scores > –2.5, with or without prevalent fractures were included. Vertebral X-rays were performed yearly. Results: No relevant diﬀerences between groups were detected for the main baseline characteristics: mean(SD) age: 73(6) years; time since menopause: 25(8) years; mean(SD) Lumbar T-score: –1.20(1.15); mean(SD) Femoral Neck T-score: –2.06(0.44). In the intent-to-treat population, strontium ranelate was associated with a 62% reduction in the relative risk of vertebral fracture over 3 years (as assessed through semi-quantitative method by a central reading centre) (RR=0.38, 95%CI[0.21;0.70], p=0.001). Amongst the 409 described patients 57% of patients had a prevalent fracture. In this subgroup, strontium ranelate reduced the risk of vertebral fracture by 56% over 3 years (RR=0.44; 95% CI [0.22–0.87], p=0.015). The other 43% of patients presented an osteopenia according to their BMD values (described above) and had no prevalent fracture. In this subgroup, strontium ranelate reduced the risk of vertebral fracture by 72% over 3 years (RR=0.28; 95% CI [0.07; 0.99], p=0.045). Conclusion: We infer that strontium ranelate, a new antiosteoporotic agent, reduces the risk of vertebral fractures in women with osteopenic range of BMD with and without any prevalent fracture.

P308SU. STRONTIUM RANELATE REDUCES THE RISK OF FRACTURE IN ELDERLY WOMEN WITH OSTEOPOROSIS IN THE FIRST YEAR OF TREATMENT Seeman E1, Vellas B2, Benhamou CL3, Aquino JP4, Semler J5, Kaufman JM6, Hoszowski K7, Roces-Varela A8, Fiore CE9, Brixen K10, Reginster JY11, Boonen S12; 1Austin Hospital, University of Melbourne, Melbourne, Australia, 2CHU Purpan, Toulouse, France, 3Hôpital de la Madeleine, Orléans, France, 4 Clinique Médicale de la Porte Verte, Versailles, France, 5Immanuel Krankenhaus Rheumaklinik, Berlin, Germany, 6U.Z. Gent Dept of Internal Medicine, Gent, Belgium, 7Centrum Medyczyne, Warsaw, Poland, 8Hospital Universitario N. S. de Candelaria, Dept of Rheumatology, Tenerife, Canary Islands, Spain, 9 Clinica Medica Ove, University of Catania, Italy, 10Odense University Hospital, Odense, Denmark, 11University of Liège, Liège, Belgium, 12Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Leuven, Belgium Objective: Over 80 year old women are often left untreated because it is believed to be ‘too late’. However, women 80 years and over contribute 30% of the burden of all fragility fractures and 60% of the burden of all hip fracture because of high prevalence of osteoporosis and high incidence of falls. Despite this, few antifractures studies have focussed on the elderly. Materials and methods: Strontium ranelate is a new antiosteoporotic treatment which reduces bone resorption while allowing continued bone formation. The results of the phase III program including 2 international, double-blind, placebocontrolled studies (SOTI and TROPOS trials), support the eﬃcacy and safety of strontium ranelate 2g/day orally in reducing the risk of vertebral and non vertebral fractures including hip fractures in postmenopausal women with osteoporosis. A preplanned analysis of the pooled data from these 2 studies was performed to investigate the eﬃcacy of strontium ranelate in women aged 80 years or more (n=1488). Results: The baseline characteristics of patients were similar in both groups (age 83.53.0 years; lumbar BMD T-score –2.71.7; femoral neck BMD T-score -3.30.7). From the first year of treatment, in the intent-to-treat population, strontium ranelate reduced the risk of vertebral fracture by 59% (RR=0.41; 95%CI[0.22;0.75], p=0.002), of clinical fractures by 37% (RR=0.63; 95%CI[0.44;0.91], p=0.012) and of non-vertebral fracture by 41% (RR=0.59; 95%CI[0.37;0.95], p=0.027), compared to placebo. These reductions were confirmed over 3 years: -32% (RR=0.68; 95%CI[0.50;0.92], p=0.013) for vertebral fracture, -22% (RR=0.78; 95%CI[0.61;0.99], p=0.040) for clinical fracture and -31% (RR=0.69; 95%CI[0.52;0.92], p=0.011) for non-vertebral

S210 fracture. The drug had a good safety profile, similar to that in younger patients. Conclusion: Strontium ranelate is the first anti-osteoporotic treatment to demonstrate an early and sustained reduction for vertebral and non-vertebral fractures in patients aged 80 years and more. This early eﬃcacy is of great consequence in elderly.

P309MO. THE RELATIONSHIP BETWEEN ADHERENCE TO BISPHOSPHONATE THERAPY AND VERTEBRAL AND NON-VERTEBRAL FRACTURE RATES IN OSTEOPOROTIC WOMEN Siris ES1, Silverman SL2, Harris ST3, Barr CE4; 1Columbia University Medical Center, New York, USA, 2Osteoporosis Medical Center, Beverly Hills, USA, 3University of California, San Francisco, USA, 4Roche Laboratories, Nutley, USA This study was designed to determine the relationships between adherence to bisphosphonate therapy and the risk of vertebral and non-vertebral fractures. Medstat MarketScan Commercial and Medicare databases were retrospectively analyzed to determine patient adherence with bisphosphonate therapy and fracture risk. The databases included medical and pharmaceutical claims data collected from 1999 to 2003 from 6 million individuals. This study examined claims from 35,537 women R45 years of age with an index prescription for a bisphosphonate and data for 6-month baseline and 24-month follow-up periods. Adherence was measured by compliance (Medication Possession Ratio, calculated as the sum of days supply divided by follow-up time) and persistence (no gap in refills >30 days). During the 24 month study period, 43% of women were refill compliant (MPR R80%) and 20% were persistent with bisphosphonate therapy. Relative risk reductions of 37% and 40% for vertebral fractures and 20% and 29% for non-vertebral fractures were observed in the compliant (vs noncompliant) and persistent (vs nonpersistent) cohorts, respectively. Adjustment for baseline factors such as age, concomitant medications, and history of previous fracture did not aﬀect the significance of the relationship between adherence and fracture risk. In addition to analyses using an MPR cut-oﬀ point of 80%, the eﬀect of compliance on fracture risk across the full range of MPR values (0% to 100%) was analyzed. There was a positive correlation between refill compliance and fracture risk reduction which was first evident at refill compliance rates of approximately 50% and became progressively more robust as compliance increased (Figure).

P310SA. BONE STRONTIUM DISTRIBUTION AND DEGREE OF MINERALIZATION OF BONE IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN TREATED WITH STRONTIUM RANELATE FOR 2 AND 3 YEARS Boivin G1,2, Farlay D1,2, Simi C1, Meunier PJ1; 1INSERM Unité 403, Faculté de Médecine R. Laennec, Université Claude Bernard Lyon1, Lyon, France, 2Centre Technologique des Microstructures, Université Claude Bernard-Lyon1, Villeurbanne, France Strontium ranelate (Protelost) is a new eﬀective treatment for postmenopausal osteoporosis which provides early and sustained antifracture eﬃcacy and increases the bone mineral density (BMD) 1,2. Here, strontium (Sr) interactions with bone mineral were investigated in iliac bone biopsies from postmenopausal osteoporotic women. Samples were obtained at the end of 2 sets of studies: a 2-year placebo-controlled (PLA) phase II study (STRATOS 3) with 3 diﬀerent doses of Protelos (0.5 g/day n=6; 1 g/day n=6; 2 g/day n=8) or PLA (n=7); and the 3-year phase III studies (SOTI and TROPOS 1,2) with PLA (n=15) or Protelos (2g/day n=15). All patients received daily calcium and vitamin D supplements according to their needs. Bone samples were quantified by X-ray microanalysis for Sr uptake and distribution and by microradiography to measure the degree of mineralization of bone (DMB) 4. In Protelos-treated women, Sr is deposited dependently of dose in bone (p%0.0002 vs PLA), with significantly (p=0.0001) higher content in newly formed bone structure units (BSUs) than in old BSUs which are constantly devoid of Sr even after 3 years of treatment. At 2g/day, bone Sr content (BSC) is only slightly higher after 3 years of treatment than after 2 (NS) confirming the chemical analysis showing that a plateau in BSC is reached after 3 years. In new BSUs containing Sr, the maximal Sr content is similar after a 2 or 3-year treatment, suggesting that Sr is adsorbed onto the mineral surface rather than substituting calcium ions. Such a situation is in favor of rapid Sr clearance from bone. DMB is not diﬀerent in Protelos and PLA groups regardless of the dose used in STRATOS or the treatment duration. Heterogeneity index of mineralization does not change after a 2- or 3-year treatment. To conclude, these data suggest that the increased BMD observed during Protelos treatment could be due to increased bone mass, as BSC reaches a plateau between 2 and 3 years of treatment and DMB is not modified. (1) (2) (3) (4)

Meunier et al. 2004 NEJM 350:459–68 Reginster et al. 2005 JCEM 90:2816–22 Meunier et al. 2002 JCEM 87:2060–6 Farlay et al. 2005 JBMR 20:1569–78

P311SU. ONCE-A-MONTH 150 MG ORAL RISEDRONATE IS AS EFFECTIVE AS ORAL DAILY 5 MG RISEDRONATE IN POSTMENOPAUSAL OSTEOPOROSIS: PHASE II STUDY RESULTS Ste-Marie LG1, Brown JP2, Beary JF3, Darbie L3, Burgio DE3, Racewicz A4; 1Centre de recherche du CHUM, Hôpital Saint-Luc, Montreal, Quebec, Canada, 2Centre de recherche du CHUL, Laval University, Quebec City, Quebec, Canada, 3Procter & Gamble Pharmaceuticals, Mason, Ohio, USA, 4Centrum Medyczne Specjalistyczny Gabinet Lekarski, Bialystok, Poland

Probability of fracture over 24 months for bisphosphonate-treated subjects (95% CIs shown by dashed lines) This study demonstrated that women who were refill compliant and persistent with therapy had a reduced risk of both vertebral and non-vertebral fractures. Women with an MPR R80% experienced a 21% reduction in overall fracture risk and those who persisted with therapy had 29% lower overall fracture rates.

This was a randomized, multi-center, active-control, double-blind, sequential escalating dose study in postmenopausal women with low bone mineral density. Three-hundred and seventy women were randomly assigned to receive one of four treatments for six months, risedronate once-a-month of 100 mg, 150 mg, and 200 mg or 5 mg daily. Overall, risedronate was shown to be well tolerated across all doses, and assessment of clinical laboratory results showed no clinically relevant diﬀerences among the treatment groups. The primary eﬃcacy endpoint was the percent change in lumbar spine BMD at 6-months, results are summarized in the Table 1 below: Both the 150 mg and 200 mg monthly dose groups had a similar increase in lumbar spine BMD when compared to the 5 mg daily group at Month 6, Day 30. The 150 mg dose was shown to be most similar to 5 mg daily with respect to percent change in lumbar spine BMD with a LS mean diﬀerence of 0.06%. In addition, the lumbar spine BMD changes between the 150 mg and 200 mg were not statistically diﬀerent (p=0.520). Dosing risedronate 150 mg

S211 Table 1. Percent Change in Lumbar Spine BMD at Month 6 (ITT Pop) Statistic N LS Mean (SE)

5 mg Daily

100 mg Monthly

85 81 3.05 2.10 (0.472) (0.470) 0.95 Daily-Monthly (-0.04, 1.93) LS Mean Diﬀ (95% CI)

150 mg Monthly

200 mg Monthly

70 2.99 (0.527) 0.06 (-1.02, 1.13)

75 3.38 (0.558) -0.33 (-1.46, 0.79)

ITT = Intent to Treat, CI=Confidence Interval, LS=least squares, SE=standard error once-a-month significantly increased lumbar spine BMD after six months of treatment, and was shown to be as eﬃcacious as the 5 mg daily regimen. Unlike some other bisphosphonates, risedronate when dosed at a monthly interval, does not require the dose to be greater than 30 times the daily equivalent to provide comparable eﬃcacy.

vertebral fracture risk reduction with TPTD treatment. We sought to determine whether increases in BMD are associated with improvements in cortical and trabecular microarchitecture. Paired iliac crest biopsies were obtained at study baseline and after a mean treatment duration of 22 2 months (range, 19 - 24 months) in a subset (n=36) of postmenopausal women with osteoporosis who participated in the Fracture Prevention Trial (placebo [n=13], TPTD 20 mg/day [n=13], TPTD 40 mg/day [n=10]). The biopsy samples were analyzed by 2-D histomorphometry and 3-D microcomputed tomography (µCT). LS and femoral neck (FN) BMD were measured at baseline and 12 months. Pearson correlation was performed to assess the relationship between actual changes in BMD and actual changes in microarchitectural parameters. Changes in LS and FN BMD correlated with changes in trabecular, but not cortical microarchitecture, suggesting that BMD increases are associated with improvements in trabecular bone microarchitecture. Improvements in trabecular bone microarchitecture may contribute to BMD-associated increases in bone strength during TPTD treatment. Change in BMD (12 months)

P312MO. EXCESS MORTALITY AFTER HIP FRACTURE AMONG POSTMENOPAUSAL WOMEN: A META-ANALYSIS Haentjens P1, Vanderschueren D2, Venken K2, Boonen S2; 1Department of Orthopaedics and Traumatology, Vrije Universiteit Brussel, Brussels, Belgium, 2Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium Purpose: To determine the magnitude and duration of excess mortality after hip fracture among postmenopausal women. Methods: We conducted a systematic review and meta-analysis of the literature to estimate the pooled relative risk of death after hip fracture by time since fracture. We selected only controlled studies that reported data on postmenaupausal women aged 50 years or older, carried out a life-table analysis, and displayed the survival curves of the hip-fracture group and an age- and sexmatched control group. Using random-eﬀects models we calculated the pooled relative risk of death with 95% confidence intervals (95%CI) by time since fracture. Results: Twenty-three studies contributed to this meta-analysis. The pooled relative risk of dying within three, six, twelve, and twenty-four months following hip fracture was 5.06 (95%CI: 4.31, 5.93), 3.92 (95%CI: 3.11, 4.94), 2.71 (95%CI: 2.33, 3.14), and 2.02 (95%CI: 1.83, 2.23), respectively. Thereafter, excess mortality remained relatively constant. The relative risk of mortality at five years, ten years, and fifteen years post-fracture was 1.44 (95%CI: 1.29, 1.62), 1.40 (95%CI: 1.35, 1.45), and 1.36 (95%CI, 1.31, 1.41), respectively. Conclusions: Excess mortality among postmenopausal women having suﬀered a hip fracture was most apparent immediately after the event, declined steeply during the first years post-fracture, but did not return to that of age- and sex-matched controls, even at the longest duration of follow-up. The impact of a hip fracture on excess mortality among postmenopausal women continued for up to 15 years.

P313SA. RELATIONSHIP BETWEEN TERIPARATIDE-MEDIATED CHANGES IN BMD AND MICROARCHITECTURE IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS Recker R1, Resch H2, Chen P3, Misurski D3, Pavo I3, Sipos A3; 1 Creighton University Medical Center, Osteoporosis Research Center, Omaha, NE, USA, 22nd Department of Internal Medicine, St. Vincent Hospital, Vienna, Austria, 3Eli Lilly and Company, Indianapolis, IN, USA Bone strength is determined by bone mineral density (BMD) and other elements of bone quality, including bone microarchitecture. Teriparatide (TPTD) treatment increases BMD and improves both cortical and trabecular bone microarchitecture. Increases in lumbar spine(LS) BMD account for approximately 30 to 41% of the

Change in Microarchitectural Parameters (22 months) 2-D Histomorphometry Trabecular volume Cortical thickness Wall thickness Marrow star volume 3-D CT Connectivity density Bone volume/total volume Trabecular number Trabecular separation Trabecular thickness Structure model index Degree of anisotropy Cortical porosity Cortical thickness

Lumbar Spine

Femoral Neck

0.45 (n=26, p=0.02) 0.02 (n=26, p=0.92) 0.41 (n=29, p=0.03) -0.09 (n=24, p=0.67)

0.35 (n=25, p=0.09) -0.07 (n=25, p=0.75) 0.56 (n=28, p=0.002) -0.14 (n=23, p=0.52)

0.41 (n=32, p=0.02) 0.48 (n=32, p=0.006) 0.44 (n=32, p=0.01) -0.37 (n=32, p=0.04) 0.22 (n=32, p=0.22) -0.54 (n=32, p=0.001) -0.01 (n=32, p=0.94) 0.03 (n=28, p=0.88) 0.20 (n=28, p=0.30)

0.32 (n=31, p=0.08) 0.51 (n=31, p=0.004) 0.44 (n=31, p=0.01) -0.46 (n=31, p=0.01) 0.34 (n=0.06, p=0.02) -0.55 (n=31,p=0.001) -0.02 (n=31, p=0.92) 0.10 (n=27, p=0.63) 0.14 (n=27,p=0.50)

P314SU. ONCE-MONTHLY ORAL IBANDRONATE (150MG) PROVIDES SUPERIOR EFFICACY VERSUS DAILY DOSING: 2-YEAR RESULTS FROM MOBILE Felsenberg D1, Greenwald M2, Need A3, Elizondo-Alanis L-J4, Hughes C5, Mairon N5, Coutant K5, Radominski S6; 1CharitéUniversity Medicine Berlin, Berlin, Germany, 2Desert Medical Advances, Palm Desert, CA, USA, 3Institute of Medical and Veterinary Science, University of Adelaide, Adelaide, Australia, 4 Clínica San José, Obregón, Mexico, 5F. Hoﬀmann-La Roche Ltd, Basel, Switzerland, 6Universidade Federal do Paraná, Curitiba, Brazil Aims: With oral bisphosphonates in postmenopausal osteoporosis, patient adherence to current daily and weekly administration schedules is suboptimal, compromising treatment outcomes. Less frequent dosing may help to overcome this issue, especially as a strong patient preference exists. Ibandronate (Bonviva), a new bisphosphonate that can be administered less frequently than weekly, was recently shown to be highly eﬃcacious and well tolerated in the MOBILE study when administered oncemonthly.1 Two-year eﬃcacy results from this study are presented below. Methods: MOBILE, a randomized and double-blind study, compared the eﬃcacy of oral ibandronate when taken monthly (50+50mg [single doses on consecutive days], 100mg [single day] and 150mg [single day]) or daily (2.5mg; 3-year vertebral fracture risk reduction: 62%2). All participants were postmenopausal osteoporotic women (baseline lumbar spine BMD T-score <–2.5, 55–80 years old, R5 postmenopause). Daily oral calcium (500mg) and vitamin D (400IU) supplements were taken. Results: In MOBILE, 1,609 women were randomized. In all treatment arms, sizeable gains in spinal BMD were obtained at 2 years: 5.0% in the daily arm, 5.3% in the 50+50mg arm, 5.6% in the 100mg arm and 6.6% in the 150mg arm. By statistical test, all monthly regimens were proven non-inferior to the daily regimen for spinal BMD gain, corroborating the 1-year findings.1 At the

S212 150mg dose, superiority versus the daily regimen was also prospectively proven (as at 1 year; p<0.001). Sizeable gains in proximal femur (total hip, femoral neck and hip trochanter) BMD were obtained in all treatment arms. At all sites, greatest gains were obtained with the 150mg dose. For serum CTX, the pronounced reductions observed at the 3 month time point1 were maintained for the duration of treatment (61.5% in the daily arm, 56.1% in the 50+50mg arm, 60.5% in the 100mg arm and 67.7% in the 150mg arm at 2 years). Conclusions: In postmenopausal osteoporosis, once-monthly oral ibandronate is an eﬀective treatment option. Versus the daily regimen, additional clinical benefits may be associated with the increased eﬃcacy provided by the 150mg regimen. 1. Miller PD, et al. J Bone Miner Res 2005;20:1315–22. 2. Chesnut CH, et al. J Bone Miner Res 2004;19:1241–9.

P315MO. EFFECTS OF VITAMIN D AND CALCIUM SUPPLEMENTATION ON FALLS AND PARAMETERS OF MUSCLE FUNCTION: A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND MULTICENTER STUDY Minne HW1, Dobnig H2, Pfeifer M1, Suppan K2; 1Institute of Clinical Osteology and Clinic der Fuerstenhof, Bad Pyrmont, Germany, 2Dept. of Endocrinology, University of Graz, Graz, Austria The eﬀects of calcium and vitamin D supplements on falls, falls-related fractures and functional measures are well-known (Pfeifer et al. 2000, Bischoﬀ et al. 2003, Dukas et al. 2004, Larsen et al. 2004). This prospective study was undertaken to test the influence of latitude, seasonal variations, possible threshold eﬀects and duration of vitamin D eﬃcacy after cessation of therapy. 242 healthy male and female subjects over 70 years of age and a 25-OH-D3 serum level below 78 nmol/l were recruited in Bad Pyrmont (52(N) and Graz (48(N) and were randomly assigned to two treatment groups: one receiving 1000 mg Calcium/day (Ca) and the other 1000 mg Calcium and 800 I.U. Vitamin D (Ca+D) over 12 months. This double blind intervention phase was followed by a treatment free observation phase over another 8 months. Falls as the primary eﬃcacy parameter were recorded by diaries and phone calls every two months. Parameters of muscle function such as quadriceps strength, body sway and timed up and go test were measured every four months. Statistical evaluation was carried out using the statistics software of IDV, Gauting (Test + Estimation, Version 5.2, CRO; Dr. Heinz, Vienna, Austria). Baseline parameters did not diﬀer between groups. TABLE 1 shows intention-to-treat analysis after 12 months of treatment and 8 months of follow-up: (Ca) versus (Ca+D) Falls per group (N) Falls per subject (N) Body sway (mm) Quadr.str.(Newton) TUG-Test (Sec.) 25-OH-D3(nmol/l)

0.69 vs 0.45; p<0.01 1.61 vs 0.95; p<0.01 12.9 9.1 vs 9.2 7.9; p<0.01 175 65 vs 210 65; p<0.01 8.1 3.4 vs 7.3 3.8; p<0.01 38 13 vs 48 16; p<0.01

Despite a relatively high inclusion criterion for vitamin D (78 nmol/l) and independent of latitude, we observed a significant reduction of falls and parameters of muscle function after supplementation with vitamin D and calcium. So far, we did not find any evidence for a threshold phenomenon or an eﬀect of latitude.

P316SA. INTERMITTENT INTRAVENOUS IBANDRONATE INJECTIONS ARE AN EFFECTIVE TREATMENT OPTION IN POSTMENOPAUSAL OSTEOPOROSIS: 2-YEAR RESULTS FROM DIVA Eisman JA1, Garcia-Hernandez PA2, Ortiz-Luna G3, Ste-Marie LG4, Hughes C5, Mairon N5, Masanauskaite D5, Delmas PD6; 1 Garvan Institute of Medical Research, St Vincent’s Campus & UNSW, Sydney, Australia, 2Hospital Universitario, Monterrey, Mexico, 3Instituto Nacional de Perinatologia, Mexico City, Mexico, 4CHUM Hopital Saint-Luc, Montreal, Canada, 5F.

Hoﬀmann-La Roche Ltd, Basel, Switzerland, 6Claude Bernard University and INSERM Research Unit 403, Lyon, France Aims: An eﬀective and well tolerated intravenous (i.v.) bisphosphonate could be an attractive treatment option for women with postmenopausal osteoporosis for whom oral bisphosphonates are contraindicated or unsuitable. Ibandronate (Bonviva), a potent, nitrogen-containing bisphosphonate, can be administered as a rapid (15–30 second) i.v. injection with extended dosing intervals. At 1 year in the DIVA study, superior spinal BMD gains were obtained with 2- or 3-monthly i.v. ibandronate injections versus daily oral dosing.1 Here, we present the 2-year eﬃcacy data from this study. Methods: DIVA is a randomized, double-blind, non-inferiority study. In total, 1,395 osteoporotic (lumbar spine [L2-L4] BMD T-score <-2.5) women (aged 55–80 years and R5 years postmenopause) were enrolled. Medication consisted of 2mg every 2 months (q2mo) or 3mg every 3 months (q3mo) i.v. ibandronate injections plus daily oral placebo, or 2.5mg daily oral ibandronate plus q2mo or q3mo i.v. placebo injections. Supplemental vitamin D (400IU) and calcium (500mg) were provided. Results: At 2 years, similar increases in lumbar spine BMD were obtained, with the q2mo (6.4%) and q3mo (6.3%) regimens statistically non-inferior (margin: 1.3%) to the daily regimen (4.8%; Figure). In fact, both i.v. regimens were superior to daily (p<0.001). Compared with daily, consistently greater increases were obtained in proximal femur BMD in the i.v. groups (Figure). In all treatment arms, clinically meaningful reductions in serum CTX concentrations were observed (53.4–59.9%). Conclusions: I.v. ibandronate injections, administered 2 or 3 monthly, provided superior bone density eﬃcacy to an established daily oral ibandronate regimen in postmenopausal osteoporosis. Although not a fracture study, these data suggest that intermittent i.v. injections may be of utility for those diﬃcult to treat patients that are unable or unwilling to take an oral bisphosphonate. 1. Recker RR, et al. Arthritis Rheum 2004;50(Suppl.):4095.

Change (%) from baseline BMD at 2 years (per-protocol population).

P317SU. A SYSTEMATIC REVIEW OF CALCIUM SUPPLEMENTATION AND BONE MASS IN CHILDREN Winzenberg TM, Shaw K, Fryer J, Jones G; Menzies Research Institute, Hobart, Australia Trials of calcium supplementation in children have given inconsistent results particularly as to whether any benefit persists after supplementation is ceased. We performed a systematic review of randomised placebo-controlled trials of calcium supplementation in healthy children with measurement of bone mass at any site as an outcome. We searched multiple databases including Medline and Embase and used hand-searching to identify 233 potential studies. Assessment by 2 independent reviewers, yielded 35 references to 19 studies. Of these, 18 provided data which could be used in meta-analysis. Results are given in the table below. There was no significant heterogeneity at any site. In conclusion, calcium supplementation has little eﬀect on BMD at the hip or lumbar spine. Total body bone mass increased during

S213 Eﬀect of calcium supplementation of bone mass Site

No. studies

No. participants

Eﬀect size1 at end trial

No. studies

No. participants

Eﬀect size after supplement ceased

Femoral neck BMD (g/cm2) Lumbar spine BMD (g/cm2) Total body BMC (g) Upper limb BMD (g/cm2)

10 11 9 12

1073 1164 953 1579

+0.07 +0.08 +0.14 +0.14

5 5 1 6

617 617 96 840

+0.10 (-0.06, +0.26) -0.01 (-0.16, +0.17) 0.00 (-0.40, +0.40)2 +0.14 (+0.01, 0.28)

1 2

(-0.05, +0.19) (-0.04, +0.20) (+0.01, +0.27) (+0.04, +0.24)

standardised mean diﬀerence (SMD) (95% CI); an SMD of 0.3 is regarded as small. single study only

supplementation but this eﬀect does not persist. Upper limb bone mass increases with supplementation and this eﬀect persists after cessation but is likely to have little eﬀect on fracture risk in children or later life. The diﬀerences between the sites are diﬃcult to explain biologically. Taken as a whole, this overview suggests calcium supplementation in childhood as a measure for improving long-term bone density is of marginal benefit at best.

P318MO. ZOLEDRONIC ACID SAFETY AND EFFICACY OVER 5 YEARS IN POSTMENOPAUSAL OSTEOPOROSIS Devogelaer JP1, Burckhardt P2, Meunier P3, Kaufman JM4, Lippuner K5, Body JJ6, Samsioe G7, Felsenberg D8, Brown J9, Garnero P3, Sanna L10, Ortmann CE10, Krasnow J11, Eriksen EF10, Fashola T10, Trechsel U10; 1Cliniques Universitaires St Luc, Brussels, Belgium, 2Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 3Hôpital Edouard Herriot, INSERM, Lyon, France, 4University Hospital of Ghent, Ghent, Belgium, 5 Leiter Einheit fur Osteoporose, Inselspital, Bern, Switzerland, 6 Institut Jules Border, Brussels, Belgium, 7Kvinnokliniken, Universitets sjukhuset, Lund, Sweden, 8Universitätsklinikum Benjamin Franklin, Berlin, Germany, 9Centre Hospitalier Universitaire de Québec, Sainte-Foy, Québec, Canada, 10Novartis Pharma AG, Basel, Switzerland, 11Novartis Pharmaceuticals Inc, US Aims: Zoledronic acid (ZOL) administered as a single intravenous dose has been shown to increase BMD and decrease biochemical markers of bone turnover similar in magnitude to that observed with oral bisphosphonates in post-menopausal osteoporosis (PMO)(1). To explore the long term safety and eﬃcacy of ZOL, the results from an open label extension to the study of Reid et al (1) with total annual dose of 4 mg up to 5 years are presented. Methods: ZOL doses administered in the core and extension phases are: Treatment Groups Group 1: 2 years of ZOL treatment N = 19 Core study (1 Placebo year treatment or placebo)* 4x1 mg E1 study (2-year treatment for all patients)* Calcium E2 study (2-year treatment or calcium only)*

Group 2: 3 years of ZOL treatment N = 78

Group 3: 5 years of ZOL treatment N = 22

4x0.25 mg

4x0.5 mg

4x1 mg

2x2 mg

1x4 mg

4x1 mg

4x1 mg

4x1 mg

4x1 mg

4x1 mg

Calcium

Calcium

Calcium

1x4 mg

1x4 mg

* all patients received 1g calcium daily during the 5 years

Results: After 5 years, the lumbar spine BMD increased 8.5 5.80% (mean SD) in group 1, 9.0 4.97% in group 2 and 6.3 6.60% in group 3, while total hip BMD increased 5.5 3.70% , 4.9 4.04% and 5.2 4.53% respectively over baseline. Bone turnover markers (CTX and BSAP) following the first year of treatment were within the premenopausal range in all 3 groups. Repeated dosing of ZOL did not result in further suppression of bone turnover and no patient revealed sustained suppression below the premenopausal range over the 5 years. During the 2 year

oﬀset period in group 1, bone markers revealed an upward trend within the premenopausal range. No clinically significant renal safety issues were identified and no cases of osteonecrosis of the jaw reported. Conclusions: In the limited number of PMO patients, the use of iv ZOL 4 mg for up to 5 years was generally safe and well tolerated. Continuing treatment resulted in maintenance of bone turnover within the premenopausal range. After discontinuation of treatment, bone turnover increased over time, showing preservation of remodeling capacity. The anti-fracture eﬃcacy of annual i.v ZOL 5mg, is currently being investigated in large Phase III trials in Osteoporosis. 1) Reid I et al. NEJM Feb 2002, 346:653–661

P319SA. ZOLEDRONIC ACID 5 MG IV PRODUCES MORE RAPID REDUCTION IN BONE RESORPTION MARKERS COMPARED TO WEEKLY 70 MG ORAL ALENDRONATE IN POST-MENOPAUSAL WOMEN WITH OSTEOPOROSIS/ OSTEOPENIA Saag K1, Lindsay R2, Kriegman A3, Davis J3, Zhou W3; 1Division of Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA, 2Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Aims: To assess the rapidity of zoledronic acid (ZOL) 5 mg IV versus oral alendronate (ALN) 70 mg weekly in reducing bone resorption markers in post-menopausal women with osteoporosis/ osteopenia. Methods: Multi-center, randomized, double-blind, activecontrolled trial to assess rapidity of onset of action of a single infusion of ZOL 5 mg ( =69) versus oral weekly ALN 70 mg (N=59) over 24 weeks. The primary eﬃcacy variable was relative change from baseline of urine N-telopeptide of type 1 collagen (NTx) at 1 week. Secondary variables included relative change from baseline of NTx at weeks 2, 4, 8, 12, and 24 and bone-specific alkaline phosphatase (BSAP) at baseline and 4, 12, and 24 weeks. Safety assessments were evaluated over 24 weeks. Results: ZOL demonstrated significantly greater reduction in NTx at week 1 versus ALN (P<.0001). Compared to ALN, ZOL significantly reduced NTx levels at all timepoints (P<.05 for weeks 2, 4, 8, 12, 24). Consistent with IV bisphosphonates, reduction in NTx with ZOL was greatest at week 1 post-infusion, then levels gradually increased. BSAP, which was elevated at baseline, slowly decreased for both ZOL and ALN, and achieved levels within the normal premenopausal reference range from week 12 onward. There were no significant BSAP diﬀerences between groups at week 24. As expected, during the first 3 days post-dose, more patients reported adverse experiences with ZOL versus ALN, including flu-like symptoms (18.8 vs 5.1%), myalgia (11.6% vs 1.7%), and/or nausea (11.6% vs 5.1%). Post-infusion symptoms were transient and usually resolved within 4 days. There were no diﬀerences in overall incidence of adverse events between groups after 3 days (79.7% vs 78.0%). Conclusions: A single infusion of ZOL 5 mg achieved more rapid and greater reductions in biochemical markers of bone resorption with similar eﬀects on bone formation versus weekly oral ALN.

S214

P320SU. THE EFFECT OF VITAMIN D SUPPLEMENTATION ON FALLS IN OLDER INDIVIDUALS ODonnell S1, Cranney A1,2, Armour T2,3, Weiler H4, Ooi D5, Hanley D6; 1Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada, 2Faculty of Medicine, University of Ottawa, Ottawa, Canada., 3Chalmers Research Group, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada, 4School of Dietetics and Human Nutrition, McGill University, Montreal, Canada, 5Department of Laboratory Medicine, The Ottawa Hospital, Ottawa, Canada, 6Department of Medicine, Division of Endocrinology and Metabolism, University of Calgary, Calgary, Canada Aims: To systematically review the eﬃcacy of vitamin D supplementation on the prevention of falls in postmenopausal women and elderly men. Methods: We searched PreMEDLINE, MEDLINE, Embase, CINAHL and Cochrane Library for published RCTs that evaluated the eﬀect of supplemental vitamin D2 or D3 (+/- calcium) versus placebo or calcium on falls in postmenopausal women (R 50 years) and elderly men (R 65 years). Those trials that investigated the eﬀects of active preparations (e.g. 1,25-hydroxyvitamin D) were excluded. Two reviewers independently determined study eligibility and abstracted the relevant data. Methodological quality was assessed using the Jadad scale. RCTs were grouped by vitamin D preparation and +/- calcium. Meta-analysis was conducted using the random eﬀects model. Results: Nine RCTs (8 parallel and one factorial design) were included in the meta-analysis. A pooled estimate from four trials (n = 5,958) of oral vitamin D3 versus placebo to assess the eﬀect of vitamin D3 alone did not demonstrate a statistically significant reduction in the risk of falls in older individuals (OR 1.03, 95% CI 0.91–1.17). A pooled estimate from three trials (n = 3,297) of oral vitamin D3 + calcium versus placebo demonstrated a reduction in the risk of falls however, this reduction was not significant (OR 0.86, 95% CI 0.62–1.18). Furthermore, a pooled estimate from seven trials (n = 9,261) of oral vitamin D3 +/- calcium versus placebo or calcium did not demonstrate a significant reduction in the risk of falls (OR 0.96, 95% CI 0.85–1.07). Separate sensitivity analyses to investigate the eﬀect of including trials that: (1) administered oral vitamin D3 of dosages > 700 IU daily; (2) clearly defined the ascertainment of falls or; (3) received a quality assessment rating (Jadad score) > 3 also did not show a significant reduction in falls. Chi square tests for heterogeneity of treatment eﬀect were not significant in any of the aforementioned analyses. Conclusions: Evidence suggests that oral vitamin D3 supplementation +/- calcium does not reduce the risk of falls in older community-dwelling or institutionalized individuals. This finding remains consistent across subgroup analyses including diﬀerent doses, fall ascertainment and methodological quality.

P321MO. RECOMBINANT HUMAN PARATHYROID HORMONE 1–84 (PTH) REDUCES THE INCIDENCE OF MULTIPLE NEW VERTEBRAL FRACTURES AND NEW FRACTURE SEVERITY IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN Ettinger MP1, Marriott TB2; 1Regional Osteoporosis Center and Radiant Research, Stuart, USA, 2NPS Pharmaceuticals, Salt Lake City, USA Aim: The 18-month, randomized, double-blind, placebocontrolled Treatment of Osteoporosis with PTH (TOP) Study

assessed the eﬀect of PTH on vertebral fracture incidence in 2532 postmenopausal osteoporotic (PMO) women. Compared with placebo, PTH treatment resulted in a 61% reduction in the risk of new vertebral fractures in these women (P=0.001) and 68% and 53% reductions in women without (P=0.006) and with (P=0.040) a pre-existing vertebral fracture, respectively. This preplanned analysis evaluated the eﬀect of PTH on the number of women with R2 new vertebral fractures and with moderate or severe new fractures. Methods: Women were included in the study as follows: R1 year postmenopausal; R55 years of age; spine, femoral neck, or total hip BMD T-score %-2.5 (or %-2.0 with a prevalent vertebral fracture), or 45–54 years of age with a T-score %-3.0 (or %-2.5 with fracture). All women received 700 mg calcium and 400 IU vitamin D supplements daily and were randomized to placebo or PTH 100 µg/day. The primary endpoint was the occurrence of new or worsened vertebral fractures, identified semi-quantitatively from X-rays. This evaluation includes women in the intent-to-treat population who had R1 new vertebral fracture during the study. Results: Of the 2532 women in the intent-to-treat population, 42 placebo-treated patents and 17 PTH-treated patients had R1 new vertebral fracture. Only one woman in the PTH group had R2 new vertebral fractures versus eight in the placebo group. Three times more women in the placebo group had moderate or severe new vertebral fractures compared with the PTH group. Conclusion: Treatment with PTH resulted in a significant reduction in the relative risk of new vertebral fractures in PMO women with or without a pre-existing fracture, and reduced both the incidence of multiple new fractures and of new fracture severity in these women.

Number (%) of subjects

Placebo (n =1246)

PTH (n = 1286)

With any new vertebral fracturea with no pre-existing vertebral fractureb with a pre-existing vertebral fracturec

42 (3.37) 21 (2.08) 21 (8.94)

17 (1.32) 7 (0.67) 10 (4.24)

With 1 or 2 new vertebral fractures 1 2

34 (2.73) 8 (0.64)

16 (1.24) 1 (0.08)

With new vertebral fracture severity Grade 1, 2, or 3d Mild (Grade 1) 18 (1.44) Moderate (Grade 2) 23 (1.85) Severe (Grade 3) 1 (0.08)

9 (0.70) 8 (0.62) 0

a PTH vs placebo, relative risk (95% CI): 0.39 (0.22, 0.69) b PTH (n=1049) vs placebo (n=1010), relative risk (95% CI): 0.32 (0.14, 0.75) c PTH (n=236) vs placebo (n=235), relative risk (95% CI): 0.47 (0.23, 0.98) d For subjects with more than 1 new vertebral fracture, only the highest fracture severity grade is shown

P322SA. WHO AND WHEN SHOULD WE TREAT FOR OSTEOPOROSIS? Ström OE1, Borgström F1,2; 1Stockholm Health Economics, Stockholm Sweden, 2Medical Management Centre, Karolinska Institutet, Stockholm, Sweden Objective: In health economic evaluations of therapies for osteoporosis the results are often highly dependant on what population in terms of age, T-score and prevalence of prior fractures is targeted. The choice of when to initiate therapy will aﬀect all these factors. The aim of this study was to, in a societal perspective, estimate the cost-eﬀectiveness of initiating osteoporosis therapy in unfractured female patients with low BMD compared to waiting and initiate therapy after a fracture occurs. Material and methods: In an individual state transition model we examined the eﬀects of an intervention costing V600/year given for 5 years that decreased the risk of osteoporotic fractures (hip, vertebral, wrist) by 35% followed by an oﬀset time of 5 years. In the base case, patients started simulations 70 years old and with a

S215 T-score of -2.5. Since prior fracture is an important risk factor for subsequent fractures, elevated risks were programmed to take eﬀect directly after a fracture event. In one arm all patients were treated from the start and could not receive any additional treatment eﬀect after the first 5+5 years. In the other arm, treatment was only initiated when and if a fracture occurred. The model was populated with data relevant for a Swedish setting. Results: The cost per QALY (quality adjusted life year) gained of treating a base case-patient without knowing if they were to sustain any fractures was V32 000 while for treating a low risk patient (age=60 and T-score -2) it was V117 000 compared to waiting for a fracture to occur. It was found cost-saving to directly treat a high risk patient (age=80 and T-score -3). If a screening cost of V300 was added for the directly treated arm the cost per QALY increased to V40 000. Conclusion: These results indicate that high risk patients in Sweden should receive treatment regardless of prevalent fracture status while the decision regarding treatment of patients with lower fracture risks and without prior fracture is dependant on the societal willingness to pay for a QALY gained.

P323SU. OSTABOLIN-CY: A PHASE I TRIAL TO ASSESS ITS SAFETY, TOLERABILITY AND PHARMACOKINETICS IN HEALTHY OLDER ADULTS Barclay CL1, Anderson R1, Champoux-Knott L2, Morelli G2, Morley P1; 1Zelos Therapeutics Inc., Ottawa, Canada, 2MDS Pharma Services, Montreal, Canada Aims: The biological activity, safety, tolerability and pharmacokinetic profile of subcutaneously (SC) administered Ostabolin-C (cyclized hPTH –(1–31)NH2; 10–160 µg) was assessed in a randomized, double blind, placebo-controlled single escalating dose study in healthy older volunteers. Methods: Forty subjects (20 males and 20 females; 45–96 kg; 45–73 years of age) in 5 cohorts received a single subcutaneous injection of Ostabolin-C 10, 20, 40, 80 or 160 µg or placebo. Each cohort contained 6 active (3 males and 3 females) and 2 placebo (1 male and 1 female) treated subjects. Pre- and post-dose urinary and plasma cyclic AMP levels, serial serum calcium (0.25–24 hours post-dose), ECG, vital signs, plasma Ostabolin-C levels using a validated ELISA, and Adverse Events (AEs) were recorded. Results: Following SC administration Cmax increased proportionally with dose (26 pg/ml at 10 µg up to 319 pg/ml at 160 µg). The mean Tmax ranged from 0.25–0.75 hours and the tY was consistent across dose groups (0.83–1.12 hours). Biological activity, measured by urinary and plasma cyclic AMP, showed significant increases from pre- to post-dose at all doses for urinary cyclic AMP and for 80 and 160 µg for plasma cyclic AMP. AEs were rare with 10 and 20 µg doses. The most frequently reported AEs were nausea, headache, vomiting, back pain, and dizziness. Tolerability was poor in women receiving 160 µg. Serial total and ionized serum calcium testing revealed only one subject (a woman treated with 160 µg) with a single total serum calcium value (2.65 mmol/L) marginally above the normal ranges (total 2.11–2.60 mmol/L; ionized 0.91–1.13 mmol/L). A dose-dependent increase in heart rate was recorded but no clinically significant ECG changes were observed. Conclusions: Ostabolin-C was biologically active at all doses tested. It was safe and well tolerated as a single injection in healthy older adults at doses up to 80 µg. Elevated serum calcium values were rare (1/30 Ostabolin-C treated subjects: 3.3%), occurring only once and only at the maximum dose tested. The safety profile was otherwise as expected for a drug of this class.

P324MO. EFFECT OF LIGUSTILIDE ON BONE MINERAL DENSITY, MUSCLE MASS, AND HEMOGLOBIN LEVELS IN ELDERLY WOMEN WITH OSTEOPOROSIS Li GS1,2, Li BF1, Tian JW2; 1College of Life Science,Ocean University of China, 2School of Pharmacy, Yantai University, China Aims: To investigate the eﬀect of ligustilide on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis.

Methods: In a randomized, double-blind, placebo-controlled clinical trial, we evaluated the eﬀect of a 2-year treatment with ligustilide on bone mineral density of lumbar spine, femoral neck, and trochanter and on vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five osteoporotic women older than 70 years were studied. Thirty-two patients received injections of 50 mg ligustilide, and 33 received placebos every 3 weeks. All patients received 500 mg calcium tablets daily. Results: Compared to baseline, ligustilide increased the bone mineral density of the lumbar spine (3.4% 6.0 and 3.7% 7.4; P <0.05) and femoral neck (4.1% 7.3 and 4.7% 8.0; P < 0.05) after 1 and 2 years, respectively. The bone mineral density of trochanter increased significantly only after the first year (4.8% 9.3, P < 0.05). Compared to the placebo group, the ligustilide group presented with significantly increased bone mineral density of the trochanter and neck. Ligustilide significantly reduced incidence of new vertebral fractures (21% vs 43% in the placebo group; P < 0.05). Ligustilide showed a significant statistical increase in lean body mass after the first (6.2% 5.8; P < 0.01) and second years (11.9% 29.2; P < 0.01). In addition, a 2-year treatment with ligustilide significantly increased hemoglobin levels compared to baseline (14.3%; P < 0.01) and placebo (P < 0.01). Conclusions: Ligustilide increased bone mineral density, hemoglobin levels, and muscle mass, and reduced the vertebral fracture rate of elderly osteoporotic women.

P325SA. EFFECTS OF CALCIUM SUPPLEMENTATION ON BONE MINERAL DENSITY AND FRACTURES IN NORMAL OLDER WOMEN - A RANDOMIZED CONTROLLED TRIAL Reid IR, Mason B, Horne A, Ames R, Reid HE, Bava U, Bolland MJ, Gamble GD; Department of Medicine, University of Auckland, Auckland, New Zealand Purpose: Calcium has been shown to have positive eﬀects on bone mineral density (BMD) in postmenopausal women. However, these eﬀects are small, it is unknown whether they are sustained with long-term use, they have not been shown with intention-totreat (ITT) analyses, and the evidence for fracture prevention with calcium monotherapy is inconsistent. Thus, the quality of the evidence for prevention of osteoporosis by calcium is poor by currently accepted standards. Methods: A randomized controlled trial of calcium supplementation (1g daily as the citrate) in 1471 normal postmenopausal women (aged 74 4 years), assessing the eﬀects of calcium on BMD and fracture incidence over a period of 5 years. Results: Follow-up was complete in 90% of subjects, and average medication compliance was 55–58%. Calcium supplementation had a significant beneficial eﬀect on BMD throughout the skeleton by intention-to-treat analysis (ITT), with between-groups diﬀerences at 5 years of 1.8% (spine), 1.6% (total hip) and 1.2% (total body). Eﬀects were greater in a per-protocol analysis, with 5-year diﬀerences of 2.3%, 2.8% and 1.8%, respectively, and a linear reduction in bone loss at the hip and total body by about 60%. 425 fractures occurred in 281 women. Hazards ratios, based on time to first fracture were 0.90 (95% CI, 0.71,1.16) for any symptomatic fracture, 0.72 (0.44,1.18) for vertebral, 3.55 (1.31,9.63) for hip, and 0.65 (0.41,1.04) for forearm fracture. Per-protocol analysis found respective hazard ratios of 0.86 (0.64, 1.17), 0.62 (0.33, 1.16), 3.24 (0.65, 16.1), and 0.45 (0.24, 0.87). Height loss was similar in both groups by ITT (P=0.46) but reduced by calcium in the per-protocol population (P = 0.03). Serum alkaline phosphatase activity decreased more in the calcium group than in placebo (11% versus 6%, P<0.0001), and serum PINP concentrations were 22% lower in the calcium group at year 5 (P=0.03). Falls, tooth loss, urinary calculi, and iron studies were not diﬀerent between groups. Constipation was more common in the calcium group. Conclusions: Calcium supplementation results in a sustained reduction in bone turnover and rate of bone loss, but its eﬀect on fracture remains uncertain. Poor long-term compliance limits its eﬀectiveness.

S216

P326SU. VERTEBRAL FRACTURE RISK REDUCTION WITH STRONTIUM RANELATE IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS IS INDEPENDENT OF BASELINE RISK FACTORS Roux C1, Reginster JY2, Fechtenbaum J1, Kolta S1, Sawicki A3, Tulassay Z4, Luisetto G5, Padrino JM6, Doyle D7, Prince R8, Fardellone P9, Sorensen OH10, Meunier PJ11; 1Dept of Rheumatology, Cochin Hospital, René Descartes University, Paris, France, 2Dept of Epidemiology, Public Health and Health Economics, University of Liège, Liège, Belgium, 3Warsawian Center of Osteoporosis and Calcium Metabolism, Warsaw, Poland, 42nd Dept of Internal Medicine, Semmelweis Medical University, Budapest, Hungary, 5Dipartimento Scienze Mediche e Chirurgiche, Universita degli Studi Padova, Padova, Italy, 6Servicio de Reumatologia, Hospital 12 de Octubre, Madrid, Spain, 7Consultant and Hon Reader in Rheumatology, Whipps Cross University Hospital, UK, 8Dept of Medicine, Sir Charles Gairdner Hospital, Perth, Australia, 9Dept of Rheumatology, Nord Hospital, Amiens, France, 10The Osteoporosis Research Center, Department 545, Hvidovre University Hospital, Hvidovre, Denmark, 11Dept of Rheumatology and Bone Diseases, Edouard Herriot Hospital, Lyon, France Objective: Strontium ranelate is an orally active treatment able to decrease the risk of vertebral and hip fractures in osteoporotic post menopausal women. The aim of this study was to assess the eﬃcacy of strontium ranelate according to the main determinants of vertebral fracture risk: age, baseline BMD, prevalent fractures, familial history of osteoporosis, baseline BMI and addiction to smoking. Materials and methods: A population of 5082 women from the pooled analysis of SOTI and TROPOS made of patients with a baseline and at least one post baseline assessment for vertebral fracture risk (2536 receiving strontium ranelate 2g/d and 2546 receiving a placebo), 74 years on average, was followed for 3 years. Results: Over this period the treatment decreased the risk of both vertebral (RR=0.60 [0.53–0.69], p<0.001) and non-vertebral (RR= 0.85 [0.74–0.99], p=0.03) fractures. The decrease in risk of vertebral fractures was significant whatever the class of age considered: 37% (RR=0.63 [0.46–0.85], p=0.003) in women <70 years, 42% (RR=0.58 [0.48–0.68], p<0.001) in women aged 70–80 years, and 32% (RR=0.58 [0.50–0.92], p=0.013) in women >80 years. The relative risk of vertebral fracture was 0.28 [0.07–0.99] in osteopenic and 0.61 [0.53–0.70] in osteoporotic women, and baseline BMD was not a determinant of eﬃcacy. The incidence of vertebral fractures in the placebo group increased with the number of prevalent vertebral fractures, but this was not a determinant of the eﬀect of strontium ranelate. In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (RR=0.52 [0.40–0.67], p<0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (RR=0.55 [0.41–0.74], p<0.001) (1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (RR=0.67 [0.55–0.81], p<0.001) (1365 patients). Familial history of osteoporosis, baseline BMI and addiction to smoking were not a determinant of eﬃcacy as well. Conclusion: This study demonstrates that a 3-year treatment with strontium ranelate leads to anti-vertebral fracture eﬃcacy in post menopausal women independently of age, initial BMD, prevalent vertebral fractures, familial history of osteoporosis, initial BMI and addiction to smoking.

P327MO. THE ANNUAL COST OF FRACTURES ASSOCIATED WITH LOW MEDICATION COMPLIANCE AMONG POSTMENOPAUSAL WOMEN TREATED FOR OSTEOPOROSIS Wenten M, Badamgarav E, Macarios D; Amgen Inc., Thousand Oaks, CA, USA Aims: Among the 8 million women in the US with postmenopausal osteoporosis (PMO) in 2004, 12% to 17.5% received treatment and less than half of treated women complied with treatment regimens. Low compliance increases fracture risk by 35%; however, the economic burden of osteoporotic fractures among patients with low compliance is not known. We used the current literature to

develop an estimate of the cost of osteoporotic fractures among patients with low medication compliance. Methods: English language articles evaluating compliance with osteoporosis treatment, fracture rates, and costs were identified through a Medline search for the period of 1999–2005, by a manual search of bibliographies from relevant reviews and conference proceedings, and through guidance from expert researchers. We used the standard definition of poor compliance of a medication possession ratio [MPR] < 80%. Total cost (including direct and indirect costs) of osteoporotic fractures among those with low compliance was estimated using low and high estimates of compliance and fracture rates over a 12-month period. The Medline search yielded 445 relevant citations. Articles were rejected if fracture rates were not specified by compliance status, if 12-month MPR was not utilized to measure compliance, and if the study was conducted outside the US or did not involve PMO patients. Ten publications met our inclusion criteria and provided data for cost estimation. Results: The total cost of osteoporotic fractures among those with low medication compliance is estimated to range from 4M to 2M, while the total cost of fractures in compliant patients is 0M to 8M. Similarly the direct cost of fractures among patients with low compliance was also higher than for compliant patients (range 2M-1M, range 2M-9M, respectively). Conclusion: Adherence with osteoporosis treatment is less than 50%, and low compliance appears to increase healthcare costs of osteoporotic fractures. In PMO patients, low compliance is associated a > 90% increase in total annual cost compared with compliant patients. Given the central importance of medication compliance in osteoporosis, interventions leading to increased medication compliance among PMO women may decrease the overall economic burden resulting from osteoporosis.

P328SA. PHARMACOKINETICS AND PHARMACODYNAMIC EFFECT OF AAE581, A NOVEL CATHEPSIN K INHIBITOR, IN JAPANESE POSTMENOPAUSAL WOMEN Itabashi A1, Kurata N2, Sugita Y2, Nakamichi N3, Kawai R2; 1 Saitama Medical School, Saitama, Japan, 2Novartis Pharma K.K, Tokyo, Japan, 3Minoru Clinic, Yokohama, Japan AAE581 is a novel compound which potently, specifically, and directly inhibits human cathepsin K, a cysteine protease highly expressed by osteoclasts, and is currently under global development for the treatment of osteoporosis. Aims: The aim of this study was to assess the safety, tolerability, pharmacokinetics and pharmacodynamic eﬀect on bone turnover markers of this compound in Japanese postmenopausal women and to compare it to a similar study in a Caucasian population. Methods: A total of 40 subjects were randomized to receive AAE581 single oral doses of 10 mg, 25 mg, 50 mg, 100 mg or matching placebo (30 active/10 placebo). Eﬀect of food was also evaluated in this study. Results: AAE581 was safe and well tolerated in this study. AAE581 was rapidly absorbed with mean Tmax ranging from 1.3 to 2.1 hours postdose under fasting condition. The mean Cmax and AUC increased in a dose-dependent manner. The elimination half-life averaged from 13.7 to 18.6 hours postdose. Apparent clearance (CL/f) ranged from 36.7 4.6 L/h at 10 mg to 20.6 2.5 L/h at 100 mg. There was no remarkable food eﬀect on AAE581 pharmacokinetics. AAE581 dose-dependently decreased bone resorption biomarkers, serum CTx and NTx, with maximal decrease at 8–24 hours postdose (see Figure). The pharmacokinetic and pharmacodynamic pattern of this Japanese study is almost similar to the Caucasian study. Conclusion: AAE581 was well tolerated and potently decreased bone resorption biomarkers. These results suggest AAE581 may be an eﬀective therapeutic agent for osteoporosis as a potent bone resorption inhibitor, by a diﬀerent mechanism from bisphosphonates and a similar PK-PD relationship in Japanese and Caucasian postmenopausal women makes the global development easier including Japan.

S217

Serum Ctx after AAE581 administration

P329SU. STRONTIUM RANELATE REDUCES NEW VERTEBRAL FRACTURES IN A SEVERE OSTEOPOROTIC MICE MODEL WITH SPONTANEOUS FRACTURES BY IMPROVING BONE MICROARCHITECTURE Geoﬀroy V1, Lalande A2, Marty C1, de Vernejoul1 MC1; 1INSERM U606, Hospital Lariboisiere, Paris, France, 2Groupe Servier, Courbevoie, France Strontium ranelate is a novel therapy which has demonstrated its eﬃcacy to reduce the risk of vertebral and hip fractures in post-menopausal osteoporotic women. However, the mechanism underlying this anti-fracture eﬀect needs further investigations. We therefore used a murine model of severe osteoporosis to go into the mechanism of strontium ranelate eﬃcacy in preventing vertebral fracture. Mice overexpressing Cbfa1/runx2 (Cbfa1) in osteoblastic lineage exhibit an increase in bone remodelling with bone resorption exceeding bone formation leading to a severe osteoporosis and spontaneous vertebral fractures after 4-week of age (Geoﬀroy et al, MCB, 2002). These mice (7-week-old) were randomized to receive either strontium ranelate (1800 mg/kg/d) or vehicle (VEH) for 9 weeks once daily by gavage. At the end of treatment, strontium ranelate -treated mice had a plasmatic strontium concentration in the same range than the one observed in patients receiving the therapeutic dose. The fractures number at the caudal vertebrae was measured (X-ray; FAXITRON) before and after 5 and 9 weeks of dosing. At baseline, fractures number (meanSD) was 2.751.49 and 3.632.00 in the VEH and strontium ranelate therapeutic groups respectively (n=8/group). The number of new fractures per mice was reduced in strontium ranelate group by 47% and 60% at 5 and 9 weeks respectively (VEH, 2.13 vs strontium ranelate, 1.13; p=0.021 and VEH, 3.13 vs strontium ranelate, 1.25; p<0.005). At the end of the experiment, bone histomorphometry showed a significant strontium ranelate eﬀect on trabecular architecture at the lumbar vertebrae with a markedly higher BV/TV (VEH, 10.50.3% vs strontium ranelate, 16.83.9%; p<0.005) and Tb.N (VEH, 2.710.71 vs strontium ranelate, 4.070.86; p<0.005), and a lower Tb.Sp (VEH, 356.899.7µm vs strontium ranelate, 216.962.9µm; p<0.005). Vertebrae cortical thickness increased also significantly (VEH, 60.24.0µm vs strontium ranelate, 70.54.7µm; p<0.001). In conclusion: this study shows that when bone remodelling is high, strontium ranelate decreases the number of new vertebral fracture per mice by preventing disconnection of trabeculae and thinning of the cortices. Therefore, strontium ranelate prevents fractures in increasing bone mass and improving microarchitecture.

P330MO. STRONTIUM RANELATE PREVENTS ALTERATION OF BONE STRENGTH IN OVX RATS BY IMPROVING INTRINSIC BONE TISSUE QUALITY Ammann P1, Badoud I1, Shen V2, Bain S2, Dupin-Roger I3, Rizzoli R1; 1Division of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospital, Geneva, Switzerland, 2 MDS Pharma Services/SkeleTech, Bothell, USA, 3Groupe Servier, Courbevoie, France

Strontium ranelate (SR) reduces the risk of vertebral and hip fracture in women with postmenopausal osteoporosis. It has been proposed that SR influences both bone formation and resorption resulting in a positive balance of bone turnover. To better appreciate the eﬀect of SR on the diﬀerent determinants of bone strength, we treated adult ovariectomized (OVX) rats with diﬀerent doses of SR (125, 250 or 625 mg/kg.day) for one year. By the end of the study, bone mechanical properties (ultimate strength N/mm2, energy mJ) were evaluated by an axial compression of the vertebral body. The eﬀects on microarchitecture parameters were determined using histomorphometry (trabecular bone volume BV/TV %). Intrinsic bone tissue quality (Modulus GPa, Hardness GPa and Working Energy mN*nm) was evaluated with a nanoindentation test performed at the level of the trabecular nodes in physiological conditions. Values are means SEM, * and ** indicate p<0.05 and p<0.01 vs OVX control respectively, ( p<0.05 vs non OVX control by Anova. Ovariectomy decreased bone strength by altering microarchitecture and intrinsic bone tissue quality. Administration of SR prevented the alteration of bone strength (ultimate strength and energy). A partial prevention of microarchitecture deteriorations occurred with SR treatments which could not explain the full prevention of bone strength decrease observed. This might be due to the higher intrinsic bone tissue quality in OVX rats treated with SR. These results indicate that the load and energy required to induce a given deformation at the lamellar level were markedly increased by SR. The bone formed under SR treatment shows improved intrinsic quality properties and is able to withstand greater damage before fracture. This could contribute to the antifracture eﬃcacy of strontium ranelate. Biomechanics, histomorphometry and nanoindentation results Sham (n=20) Ultimate Strength Energy BV/TV Modulus Hardness Working Energy

OVX (n=20)

OVX SR 125 (n=27)

OVX SR250 (n=26)

OVX SR625 (n=27)

25.671.35**

16.701.12

17.350.98

18.450.74

21.110.85**

24.153.98* 31.82.62** 14.070.38 56227 3268135

13.521.34 16.21.79 13.230.38 48723( 3069175

19.561.90 22.01.81* 14.400.51 59028* 3596110*

19.762.23 24.21.91** 15.330.44 66025*( 363470*(

23.592.08** 22.71.6* 14.350.48 56621* 3508103*

P331SA. THE SKELETAL EFFECTS OF A GROWTH HORMONE-DERIVED PEPTIDE (AOD9604) ORALLY ADMINISTERED IN THE OVARIECTOMIZED RAT MODEL OF OSTEOPOROSIS Rowe EJ, Grynpas MD; Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Canada A synthetic human Growth Hormone (hGH) 16AA C-terminus peptide, AOD9604 (AOD, Tyr-hGH177–191), has been shown to modulate fat metabolism and is currently being developed as a novel weight-loss drug. However, hGH is known to eﬀect both adipocytes and osteoblasts, which suggests that AOD may also aﬀect bone. Therefore, this study focuses on the skeletal eﬀect of AOD in the ovariectomized (OVX) rat model of osteoporosis. Sham and OVX models were examined. Each model had untreated controls and rats treated with AOD 0.5 mg/kg/day (AOD 0.5) and AOD 0.25 mg/kg/day (AOD 0.25). AOD was administered orally by gavages for 12-weeks. Rats were weighed before and after this period. Following sacrifice, dual-energy x-ray absorptiometry was used to determine femoral and vertebral Bone mineral density (BMD) and three-point bending and femoral neck fracture tests were used to evaluate femoral mechanical properties. Minor weight-reduction was seen in the sham model with AOD 0.5 while AOD 0.25 had no weight-eﬀect. Contrarily, in the OVX model, both AOD 0.5 and AOD 0.25 caused significant reduction in weight gain. This indicates more pronounced weight-reduction eﬀects of AOD in the estrogen deficient obesity state and also implies a diﬀerent drug-dose dependency in the sham and OVX models. In terms of skeletal eﬀects, in the sham model, AOD 0.5 increased cortical (femoral) and trabecular (vertebral) BMD although the cortical eﬀect was more pronounced. Meanwhile, in the

S218 sham model AOD 0.25 had no BMD eﬀect. Conversely, in the OVX skeleton both doses caused a BMD increase although, as in the sham model, AOD was more eﬀective in cortical bone than in trabecular bone. Mechanical tests on the sham skeleton showed improved structural and material properties with AOD 0.5 but not AOD 0.25. In OVX bone, three-point bending tests demonstrated that both AOD 0.5 and AOD 0.25 enhance structural and material bone properties. Therefore, this study points out a relationship between fat and bone metabolism and demonstrates that sham and OVX bone respond to AOD doses diﬀerently and also that AOD reverses the eﬀect of ovariectomy in cortical bone.

P332SU. PARATHYROID HORMONE 1–84 (PTH) IS EFFECTIVE IN PATIENTS WITH A WIDE RANGE OF CLINICAL RISK FACTORS Silverman S1, Miller P2, Gallwitz W3; 1Osteoporosis Medical Center, Beverly Hills, USA, 2Colorado Center for Bone Research, Lakewood, USA, 3NPS Pharmaceuticals, Parsippany, USA Aim: Bone mineral density (BMD) measurement is important in diagnosing postmenopausal women with osteoporosis. However, identification of clinical risk factors (CRF) as the basis for diagnosing women who may benefit from therapy, but would not be considered on the basis of BMD criteria alone, may be supportive. In this exploratory analysis, new vertebral fracture incidence as a function of CRF was determined in the Treatment of Osteoporosis with PTH (TOP) clinical study, designed to determine the eﬀectiveness of PTH in preventing vertebral fractures in osteoporotic woman during 18 months of treatment. Methods: CRFs captured at baseline were as follows: femoral neck BMD T-score <-3.0; age; prior fracture; current smoker; alcohol intake; family history of osteoporosis; glucocorticoid use. Results: A total of 2532 subjects were enrolled, 1246 received placebo and 1286 received PTH (100 µg daily). At baseline, the distribution of CRFs was similar for both the PTH-treated and placebo groups; 8% of the baseline population had no CRFs, 28% had 1, 31% had 2, 20% had 3, 9% had 4, 3% had 5, and 1% of the subjects had 6 CRFs. In the intent-to-treat population, PTH reduced the risk of new vertebral fractures by 61% (95% CI, 22%, 69%) compared with placebo at 18 months. The number of unweighted CRFs increased in parallel with the percentage of subjects with new vertebral fractures. In the placebo group, 1.1% of subjects with 0–1 CRF had a new vertebral fracture, 3.8% of subjects with 2–3 CRFs had a new vertebral fracture and 8.3% of subjects with R4 CRFs had a new vertebral fracture. PTH reduced the risk of new vertebral fractures by 59% (95% CI, -112%, 92%) compared with placebo in the 0–1 CRF subgroup, by 68% (95% CI, 31%, 86%) in the 2–3 CRF group and by 48% (95% CI, -6%, 79%) in the R4 CRF group. Conclusion: The findings of this exploratory analysis demonstrate that the TOP clinical study included a wide range of subjects with CRFs, and suggest that PTH is eﬀective in reducing new vertebral fracture in subjects chosen on the basis of number of CRFs.

P333MO. INDIRECT COMPARISON OF ANTI-VERTEBRAL FRACTURE EFFICACY AMONG AVAILABLE THERAPIES: A BAYESIAN ANALYSIS Nguyen ND, Eisman JA, Nguyen TV; Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia Aim: Clinicians sometimes have to make decision on treatment selection based on eﬃcacy and cost consideration. Several antifracture drugs with diﬀerent magnitudes of treatment eﬀect are currently available for the treatment of osteoporosis. In the absence of a comparative head-to-head clinical trial, the selection of an optimal treatment is diﬃcult. The present analysis was undertaken to indirectly compare the anti-vertebral fracture eﬃcacies among therapies by using a Bayesian approach. Methods: Published data from placebo-controlled clinical trials (RCT) evaluating the anti-fracture eﬃcacy of alendronate (n=4 trials), residronate (n=5), calcitonin (n=8), calcium (n=3), fluoride (n=6), raloxifene, (n=4) and HRT (n=13) were included in the

analysis. A random-eﬀects Bayesian meta-analysis model was utilized to estimate the eﬀect size (log relative risk) and its variance for an individual therapy. The index of superiority was defined as the probability that a drug’s eﬀect size is 20% greater than another drug. This superiority index was computed by the Bayesian hierachical models using Markov chain Monte Carlo implemented in WinBUGS. Results: When compared to placebo, most active therapies significantly reduced the risk of vertebral fracture, with variable magnitudes: alendronate (RR; 95% credible interval-CrI: 0.52; 0.34–0.79), risedronate (0.59; 0.40–0.71), raloxifene (0.60; 0.37– 0.99) and HRT (0.60; 0.37–0.99). However, the evidence of eﬀect was uncertain for calcitonin (0.79; 0.53–1.21), calcium (0.71; 0.35–1.39) and fluoride (0.72; 0.44–1.36). More importantly, pairwise comparison of active therapies by the index of superiority revealed no strong evidence of superiority among the drugs. The probabilities that alendronate is superior to risedronate was 0.42, to HRT: 0.47, raloxifene: 0.48, calcitonin: 0.82, fluoride: 0.68, and calcium: 0.65. Conclusion: These results indicate that while alendronate, risedronate, raloxifene and HRT were eﬃcacious in reducing vertebral fracture risk, their eﬀect sizes were comparable. There is no evidence for the superiority of one drug to another among the currently available drugs.

P334SA. RESULTS OF A 3-MONTH RANDOMIZED TRIAL TO EXAMINE WEEKBY-WEEK EFFECTS OF MONTHLY IBANDRONATE ON BIOCHEMICAL MARKERS OF BONE RESORPTION Kung AWC1, Rovayo R2, Geusens P3, Walliser J4, Verbruggen N5, Shivaprakash M6, Wehren LE7, Melton ME6; 1Queen Mary Hospital, Hong Kong, China, 2Central University of Ecuador, Eloy Alfaro, Ecuador, 3Universitaire Campus Gebouw C, Diepenbeek, Belgium, 4Hospial Angeles del Pedregal, Padierna, Mexico, 5Merck & Co., Inc., Brussels, Belgium, 6Merck & Co., Inc., Whitehouse Station, NJ, USA, 7Merck Research Laboratories, Rahway, NJ, USA Aims: Bisphosphonates (BPs) bind preferentially to active bone remodeling sites where they decrease bone resorption through direct eﬀects on osteoclasts. The number and depth of active bone resorption sites are considered important determinants of bone strength and fracture risk. Because resorption at a remodeling site is typically completed within 2–3 weeks, some resorption sites may proceed to completion if BPs are given at intervals greater than 1–2 weeks. We examined the pattern of urinary and serum resorption marker levels with monthly dosing of oral ibandronate, since no data are available on the eﬀect of a monthly regimen on bone markers in the interval between doses. Methods: After a 4-week run-in of calcium and vitamin D, 203 postmenopausal osteoporotic women were randomized to receive 3 once-monthly doses of ibandronate 100 mg or 150 mg, or matching placebo. Patients and all study staﬀ remained blinded to treatment allocation throughout the study. Serum CTx and urine NTx were measured at baseline (Week 0, just prior to first dose), one and 4 weeks after each dose and weekly after the third dose (Weeks 9–12). Geometric mean percent change from baseline was determined. Results: In each cycle, sCTx and uNTx decreases were less 4 weeks post-dose of ibandronate than at one week post-dose. Mean marker levels in ibandronate groups increased progressively

Percent change from baseline in sCTx (left) and uNTx (right)

S219 throughout the 4 weeks following the third dose of ibandronate, but remained below placebo at all time points. Conclusions: Both sCTx and uNTx exhibited cyclic reductions with monthly dosing of oral ibandronate. The clinical implications of this eﬀect are unknown and merit further investigation.

P335SU. THE EFFECT OF A ONCE-WEEKLY TABLET CONTAINING ALENDRONATE AND VITAMIN D3 FOR THE TREATMENT OF OSTEOPOROSIS Binkley N1, Lippuner K2, Recker R3, Bianchi G4, Minisola S5, Ljunggren O6, Benevolenskaya L7, Liu M8, Lamotta A8, Santora A8; 1University of Wisconsin, Madison, WI, USA, 2University Hospital, Berne, Switzerland, 3Creighton University Osteoporosis Research Center, Omaha, NE, USA, 4Ospedale La Colletta Azienda Sanitaria Genovese, Genova, Italy, 5Department of Clinical Sciences, University of Rome ’’La Sapienza,’’ Rome, Italy, 6 Dept. Medicin, Institutionen för Medicinska Vetenskaper, Uppsala Universitet, Sweden, 7Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russia, 8Merck Research Laboratories, Rahway, NJ, USA Aims: A 15-week, randomized double-blind, multi-center controlled study conducted in winter/early spring to evaluate eﬃcacy, safety and tolerability of a once-weekly tablet containing alendronate 70 mg with cholecalciferol (vitamin D3) 2800 IU (ALN+D) was previously reported. Results of an extension with additional vitamin D3 are described here. Methods: In the 15 week base study, postmenopausal women and men with osteoporosis (T<-2.5) were randomized to onceweekly ALN+D (n=360) or ALN alone (n=357). Patients with baseline serum 25-hydroxyvitamin D (25OHD) <9 ng/mL were excluded. Sunlight and supplements containing vitamin D were to be avoided. The 24-week extension was conducted in summer/fall; all patients received ALN+D and randomly received either 2800 IU of additional D3 or matching placebo once weekly. Vitamin D supplements up to 1000 IU/day (in addition to study therapy) were permitted and sunlight exposure was not restricted. The primary focus of the extension was hypercalciuria (24-hour urine calcium >300 mg in women and >350 mg in men and >25% higher than baseline). Serum 25OHD was the primary endpoint in the base study and secondary in the extension. Results: Hypercalciuria was present in 4.2% of those in the ALN+D5600 and 2.8% in the ALN+D2800 groups upon conclusion of the extension [RR, 1.48 (95% CI: 0.64–3.40); not significant], similar to the w4% at the end of the base study (week 15). There were no reports of hypercalcemia. Serum 25OHD averaged 22 ng/mL at baseline and declined in the ALN only group, but was 26% higher in the ALN+D group (p<0.001 vs ALN only) at week 15. At extension completion, mean 25OHD levels were 27.9 and 25.6 ng/ml, and serum 25OHD was <15 ng/mL in 3.1% and 5.6%, in the ALN+D5600 and ALN+D2800 groups, respectively. Reductions in NTx were similar in both groups at week 15, and remained stable during the extension. Conclusions: During the 24-week extension the safety and tolerability profile was maintained when some patients were randomized to receive 5600 IU weekly and all patients were permitted sunlight and additional vitamin D. Additionally, further increases in serum 25OHD were observed, and the proportion of patients with low 25OHD was further reduced.

P336MO. MORE PATIENTS GAIN BMD WITH ALENDRONATE THAN RISEDRONATE AFTER 24 MONTHS: RESULTS OF THE US AND INTERNATIONAL FOSAMAXT ACTONELT COMPARISON TRIALS (FACTS) Reid DM1, Hosking D2, Saag K3, Sebba A4, Rosenberg E5, Chen E5, Verbruggen N5, Melton M5, de Papp AE5; 1University of Aberdeen, Aberdeen, UK, 2Nottingham City Hospital, Nottingham, UK, 3University of Alabama, Birmingham, AL, USA, 4 Arthritis Associates, Palm Harbor, FL, USA, 5Merck & Co., Inc., West Point, PA, USA Aims: To compare the percentage of patients achieving predefined changes in bone mineral density (BMD) with once-weekly (OW) alendronate (ALN) 70 mg versus BMD achieved with OW rise-

dronate (RIS) 35 mg in 12-month extensions of the randomized, double-blind, 1-year FACT-US and FACT-International studies. Methods: Of the original cohorts, 833 (US) and 798 (international) postmenopausal women with low bone mineral density (BMD) entered the 12-month extensions of the FACT-US and FACT-International trials. Patients continued their original treatment allocations (OW ALN 70mg or OW RIS 35mg). Results: In both trials, after 24 months, significantly more ALN than RIS patients had measured BMD increases of R0% at all BMD sites examined. Similarly, in both trials after 24 months, significantly more ALN than RIS patients had BMD increases of R3% at all BMD sites. In contrast, after 24 months, significantly more RIS than ALN patients had measured BMD declines of R3% at all BMD sites in FACT-US and at 2 of the 4 sites in FACT-International (see table). There were no diﬀerences in overall or upper gastrointestinal adverse experiences between treatment groups in either trial. 24-month Change in BMD Location R3%

%3%

Hip Trochanter Femoral Neck Total Hip Lumbar Spine Hip Trochanter Femoral Neck Total Hip Lumbar Spine

FACT-US

FACT-International

ALN RIS Diﬀerence(95% CI) ALN RIS Diﬀerence(95% CI) 66.9 48.0 49.1 73.4 5.3 6.1 2.4 2.7

45.3 28.5 27.5 51.2 10.4 17.3 7.5 6.9

21.6*(14.7, 28.5) 19.5*(12.7, 26.3) 21.6*(14.8, 28.4) 22.2*(15.5, 28.9) -5.1#(-8.9, -1.2) -11.2*(-15.7, -6.7) -5.1†(-8.2, -2.0) -4.2#(-7.2, -1.1)

70.2 51.6 61.9 77.0 3.6 5.5 1.9 1.4

53.1 39.3 41.6 60.6 8.0 8.0 4.3 4.8

17.1*(10.1, 24.1) 12.3*(5.1, 19.6) 20.3*(13.2, 27.5) 16.4*(9.7, 23.0) -4.4†(-7.9, -1.0) -2.5(-6.2, 1.2) -2.4(-4.9, 0.2) -3.4†(-6.0, -0.9)

*P%0.001 for treatment comparison, †P% 0.006 for treatment comparison, # P=0.012 for treatment comparison, CI=Confidence Interval

Conclusion: In two studies with a combined total of more than 1600 women, greater percentages of patients maintained or gained BMD with OW ALN 70 mg than with OW RIS 35 mg and greater percentages lost BMD with OW RIS than with OW ALN after 24 months, with no diﬀerences in overall or upper gastrointestinal tolerability.

P337SA. SAFETY AND TOLERABILITY PROFILE OF INTRAVENOUS IBANDRONATE INJECTION IS SIMILAR TO DAILY ORAL DOSING: DIVA 2-YEAR ANALYSIS Zaidi M1, Recknor C2, Olszynski WP3, Leigh C4, Jonkanski I4, Masanauskaite D4, Sambrook PN5; 1Mount Sinai Medical Center, New York, NY, USA, 2United Osteoporosis Centers, Gainsville, GA, USA, 3Midtown Medical Centre, Saskatoon, Canada, 4F. Hoﬀmann-La Roche Ltd, Basel, Switzerland, 5University of Sydney, Sydney, Australia Aims: In osteoporotic patients for whom oral bisphosphonates are unsuitable or contraindicated, an eﬃcacious and well tolerated intravenous (i.v.) bisphosphonate could be advantageous. Ibandronate (Bonviva), a potent, nitrogen-containing bisphosphonate, can be intravenously administered as a rapid (15–30 seconds) injection with extended intervals. In the DIVA study, the safety and tolerability of two novel intermittent i.v. ibandronate injection schedules were compared with a conventional daily oral regimen. Methods: All participants in this randomized, double-blind, double-dummy study were osteoporotic (lumbar spine [L2-L4] BMD T-score <-2.5 and R-5.0) postmenopausal women (R5 years since menopause and aged 55–80 years). In addition to daily calcium (500mg) and vitamin D (400IU), participants also received either i.v. (2mg every 2 months [q2mo] or 3mg every 3 months [q3mo]) or oral (2.5mg daily) ibandronate, plus placebo medication. Safety parameters were continuously assessed. Results: A total of 1,395 women participated. At 2 years, a comparable rate of adverse events (AEs; 85–89%) was reported in the i.v. and oral treatment arms. Although drug-related AEs occurred with a slightly higher incidence in the i.v. arms (46% in q2mo, 42% in q3mo and 37% in daily), diﬀerences were generally attributed to symptoms commonly associated with i.v. dosing, such as flu-like illness and transient musculoskeletal symptoms (e.g. myalgia and arthralgia). For flu-like illness, rates were higher in the i.v. arms than oral arm (4.5–4.7% vs 0.9%, respectively), but were generally associated with the initial administrations only,

S220 mild to moderate in intensity and transient. Despite these imbalances, withdrawals were comparable across treatment arms (10– 12%). Most serious AEs were considered unrelated to treatment, with a low and similar incidence of treatment-related cases (0.4– 1.1%, n=11). In all arms, a low and similar rate of clinical fracture was reported (6–7%). No cases of osteonecrosis of the jaw were reported. Conclusions: I.v. ibandronate injections, administered every 2 or 3 months, are well tolerated over a 2-year treatment period. Apart from symptoms commonly associated with i.v. bisphosphonate administration, both schedules show a safety profile similar to daily oral dosing. Intermittent i.v. dosing may be particularly beneficial for patients who cannot tolerate oral bisphosphonates.

P338SU. ABSOLUTE FRACTURE RISK BASED DECISION FOR DRUG TREATMENT IN OSTEOPOROSIS: DOES IT HELP TO REDUCE CLINICAL FRACTURE INCIDENCE IN ELDERLY OSTEOPOROTIC WOMEN? Bock O, Boerst H, Felsenberg D; Centre for Muscle and Bone Research, Charité – Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany Objectives: To examine whether or not the incidence of clinical fractures is reduced in elderly osteoporotic women getting drug treatment for osteoporosis acc.to guidelines based on absolute fracture risk calculation. Patients and Methods: 1197 elderly women (60 to 95 yrs) were examined in the ‘‘Osteoporosis Risk Factor Survey’’ in 2002 and contacted quarterly (questionnaire, telephone) for follow-up to evaluate their actual health and medical supply status with special consideration of falls, clinical fractures and drug treatment for osteoporosis. Patients were categorized retrospectively whether or not they fulfilled criteria for a drug treatment based on absolute fracture risk (acc.to a published draft version of the German guidelines 2006). Results: Complete follow-up data sets were available for 795 women (baseline mean age 70.9 yrs +/- 7.2 SD). Among those were 247 women with osteoporosis (31.1%) who fulfilled treatment indication criteria based on absolute fracture risk calculation. A total of 93 (11.7 %) experienced at least one clinical fracture, 77 of them sustained a fall related fracture. The percentage of osteoporotic women with clinical fractures was just 40.4% higher (14.6 vs. 10.4%) for all clinical fractures and 33.0% higher (11.7 vs. 8.8%) for fall related fractures as compared to non-osteoporotic women, whereas the relative number of fallers was the same in both groups (41.5%). Out of 247 women in need for drug treatment 129 patients (52.2%) were treated, 118 patients (47.8%) were not. Surprisingly, as compared to untreated patients the fracture incidence was higher in the treated group for clinical fractures in general (21.7 vs. 6.8%) and for fall related fractures (17.8 vs. 5.1%) in particular. Otherwise patients under treatment had a more severe osteoporosis. Therefore, no conclusions on drug treatment eﬃcacy should be made from the data. Conclusions: The absolute majority of all clinical fractures in the age group of 60 years and older was fall related. Whereas the eﬃcacy of drug treatment in elderly osteoporotic women could not be evaluated suﬃciently in this study, the findings emphasise on the importance of fall prevention to reduce clinical fracture incidence in elderly women in general and in osteoporotic women in particular.

P339MO. A 4-WEEK, DOUBLE-BLIND, RANDOMIZED, CONTROLLED MULTICENTER CLINICAL TRIAL TO EXAMINE THE EFFECT OF ONCE-WEEKLY ALENDRONATE 70 MG AND VITAMIN D3 2800 IU ON FRACTIONAL CALCIUM ABSORPTION IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN Kendler D1, Robson R2, Handel M3, Shapses S4, Yang Z5, Wilson T5, Liu M5, Mantz A5, Wehren L5, Santora A5; 1Osteoporosis Research Centre, Vancouver, BC, Canada, 2Christchurch Clinical Trials, Christchurch, New Zealand, 3Prince of Wales Hospital, Randwick, NSW, Australia, 4Rutgers University, New Brunswick, NJ, USA, 5Merck Research Laboratories, Rahway, NJ, USA

Aims: Recent studies have shown that a large minority of patients do not regularly take vitamin D supplements, although vitamin D is essential for eﬃcient calcium absorption and is important in osteoporosis management. The majority of patients being treated for osteoporosis have serum vitamin D levels <30 ng/mL (75 nmol/L). This study was designed to examine the eﬀect of a once-weekly tablet containing 70 mg of alendronate and vitamin D3 2800 IU (ALN D2800) on fractional calcium absorption (FCA). Methods: After a 4-week placebo run-in and dietary stabilization period, 56 postmenopausal women with osteoporosis (T-score % -2 at lumbar spine, total hip, femoral neck, or trochanter) were randomized to receive drug or matching placebo for 4 weeks. FCA was measured, using mass spectrometry, at baseline and at treatment Week 4 from urines collected for 10 hours following IV and oral administration of stable isotopes of calcium. ANCOVA was used to evaluate change in FCA, with treatment as a model factor and baseline FCA and 25-hydroxyvitamin D as covariates. Results: After 4 weeks of treatment, FCA absorption was significantly increased from baseline with once-weekly ALN D2800 compared to placebo (p <0.001). The absolute LS mean increase with ALN D2800 was 7.0% from a baseline of 30.8% (22.7% relative increase); FCA decreased 1.6% in the placebo group from a baseline value of 31.6% (5.1% relative decrease). Conclusions: A relative increase in FCA of approximately 23% was associated with four weeks of treatment with once-weekly alendronate 70 mg vitamin D3 2800 IU. The absolute increase of 7.0% is likely to be clinically meaningful and would support the increase in BMD observed during the first year of treatment with alendronate.

Mean FCA, at baseline and after 4 weeks of treatment

P340SA. COSTING FRACTURES FOR USE IN HEALTH ECONOMIC MODELLING Borgström F1,5, Johnell O2, Jönsson B3, Kanis JA4; 1Stockholm Health Economics, Stockholm, Sweden, 2Department of Orthopaedics, Malmö General Hospital, Sweden, 3Stockholm School of Economics, Stockholm, Sweden, 4Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheﬃeld Medical School, Sheﬃeld, UK, 5Medical Management Centre, Karolinska Institutet, Stockholm, Sweden Aims: Intervention thresholds for osteoporosis can be defined as the 10-year absolute hip fracture risk at which an intervention becomes acceptable. To account for the total burden of osteoporosis an index of the excess morbidity of all fractures compared to hip fracture (hip fracture equivalents) have been calculated. One assumption underlying these calculations is that the fracture costs are proportional to fracture disutility. The objective was to investigate how accurately cost-eﬀectiveness is estimated when using hip fracture equivalents compared to a model including all

S221 fractures explicitly and to examine whether a downadjustment of fracture costs lead to a better fit. Methods: A Markov cohort model was built to be able to estimate the cost per QALY gained based on fracture specific health states explicitly and by the use of hip fracture equivalents and thereby implicitly taking all fractures into account. All fracture types that were used in the calculation of excess morbidity of hip fracture were included. The model was populated with Swedish data. The cost-eﬀectiveness was estimated for a 5-year long intervention that was assumed to reduce the fracture risk by 35%. Results: The cost per QALY gained was estimated for women at population risk of fracture with increasing starting age of intervention. On average, the cost-eﬀectiveness ratio was 180 lower when using hip fracture equivalents compared to all fractures explicitly. The incremental QALY was found to be very similar between the two approaches (average diﬀerence of 0.002 units or 6%) but the incremental cost diﬀered somewhat more (on average 9 or 30%). When down adjusting the fracture related costs by the excess fracture cost of all osteoporotic fractures compared to hip fracture the average diﬀerence in cost per QALY gained decreased to 29. Conclusions: The results show that the estimated QALYs using hip fracture equivalents compare well with an all fracture model but less so in terms of fracture costs. This might indicate that the assumption of proportionality between costs and utility loss needs some modification. When down adjusting the fracture costs a better congruence was achieved between the hip fracture equivalent and the all fracture approach.

P341SU. CALCITIONIN DIRECTLY MODULATES CHONDROCYTE ACTIVITY THROUGH THE CALCITONIN RECEPTOR AND INDUCTION OF CAMP: EX VIVO AND IN VIVO EVIDENCE Karsdal MA, Sondergaard BC, Henriksen K, Qvist P, Oestergaard S, Wulf H, Sumer E, Olsen AK, Christiansen C; Nordic Bioscience, Denmark Purpose: To investigate the expression of the calcitonin resorption in articular chondrocytes and evaluate possible direct eﬀects of calcitonin ex vivo. Secondly, to investigate a novel formulation of oral calcitonin on cartilage turnover, in a non-traumatic model of osteoarthritis (OA). Methods: Localisation and expression of the calcitonin receptor on articular chondrocytes were investigated by immunhistochemistry, RT-PCR and stimulation of cAMP levels by salmon calcitonin (0.0001–1 µM). Osteoclasts were used as positive control. Anti-catabolic eﬀects of calcitonin were evaluated in articular cartilage explants. Cartilage degradation was induced by cytokine stimulation of TNF- (20 ng/ml) + oncostatin M (OSM) (10 ng/ml), in the presence or absence of calcitonin. Chondroanabolic actions of calcitonin were evaluated in articular cartilage explants in the presence of (0.0001–1 µM) sCT, followed by investigation of collagen synthesis by [3H]-proline and proteoglycan synthesis by 35S-sulfate incorporation. In vivo, the eﬀects of calcitonin were evaluated in 7 months rats that underwent ovariectomy (OVX) for 9 weeks. Sham, OVX+estrogen, OVX+2mg/kg calcitonin and 150 mg/kg 5-CNAC. Fasting blood samples for biochemical marker analysis were taken at baseline, week 1, 2, 4, 6, 9. Cartilage degradation was both assessed by measurement of collagen type II degradation resulting in the release of C-terminal telopeptides of collagen type II (CTX II ELISA) and histological scoring of articular cartilage erosion in rat knees. Results: The calcitonin receptor was identified by RT-PCR and immunohistochemistry. Calcitoinn dose dependently induced cAMP level in chondrocytes. Ex vivo, calcitonin dose dependently inhibited cartilage degradation induced by OSM and TNF, and stimulated collagen and proteoglycan syntheis. In vivo, as measured by CTX-II, calcitonin completely abrogated cartilage degradation. Similar chondroprotective eﬀects were obtained from histological scoring of articular cartilage in the rat OVX experiment. Conclusion: Calcitonin might both exert direct chondroprotective and chondroanabolic eﬀects on chondrocytes, thereby being

an important mediator of chondrocyte metabolism. These results may promise chondroprotective eﬀects of calcitonin in a clinical setting, albeit this still remains to be investigated.

P342MO. A NEW STRONTIUM SALT AVAILABLE IN TABLET FORM WITH IMPROVED BIOAVAILABLITY OF STRONTIUM COMPARED TO STRONTIUM RANELATE Krogsgaard K1, Weis M2, Christgau S2; 1PhaseOneTrials A/S, Hvidovre University Hospital, Hvidovre, Denmark, 2Osteologix A/S, Copenhagen, Denmark Aim: Strontium ranelate (SR) has recently been approved by the European Medical Agency for the treatment of postmenopausal osteoporosis. SR is available in a sachet formulation delivering a 2 g dose (Protelost). We assessed pharmacokinetic properties of strontium malonate (NB-S101) formulated in tablets and compared the bioavailability from a single oral dose of strontium from this salt with that of SR. Methods: 60 healthy male volunteers were randomized into five groups to receive either NB-S101 in doses of 0.6, 1.2 and 2.4 g (containing 277, 554 and 1108 mg ionic strontium) or 2 g SR in sachets containing 680 mg ionic strontium or placebo. The study subjects were fasting from 1p.m. and given a single oral dose at 7p.m. They had frequent blood samples drawn for strontium determinations in the following 24 h, and at 1, 3 and 5 weeks post-dosing. Results: The pharmacokinetic profiles of strontium uptake from tablet formulated NB-S101 and sachet formulated SR were similar, but SR had a lower Tmax (3.750.37 h, Mean standard error) than NB-S101 (5.920.53; 5.000.55; 5.670.41 h, respectively for the three NB-S101 groups, p<0.05), indicative of a faster uptake of strontium. Analysis of the total strontium uptake in the four treated groups by area under the curve (AUC) analysis, revealed a good bioavailability of strontium from NB-S101 tablets. The SR group had an AUC5weeks of 356.324.4 µg*h/ml compared with 275.324.3; 386.939.5; 654.663.7 µg*h/ml in the three groups treated with 0.6, 1.2 and 2.4 g NB-S101. Elimination rates were similar for both strontium salts, with TY for SR of 116.18.3 h compared with 140.411.7; 125.26.6, 130.75.3 h for the three NB-S101 groups. Conclusions: In this pharmacokinetic study we demonstrate that NB-S101 (strontium malonate) tablets containing less than 555 mg ionic strontium delivers more strontium than a 2 g strontium ranelate sachet formulation containing 680 mg ionic strontium. This suggests that the tablet formulated NB-S101 provides better bioavailability. Tablet formulated NB-S101 may oﬀer a more clinically advantageous and convenient dosage form of strontium. Further studies are ongoing to characterize the eﬀect of NB-S101 on skeletal metabolism and bone strength.

P343SA. ELEVATIONS IN SERUM AND URINARY CALCIUM WITH PARATHYROID HORMONE (1–84): THE PATH (PARATHYROID HORMONE AND ALENDRONATE FOR OSTEOPOROSIS) STUDY Antoniucci DM1, Bilezikian JP2, Sellmeyer DE1, Greenspan SL3, Palermo L4, Black DM4; 1Division of Endocrinology, Department of Medicine, University of California, San Francisco, CA, USA, 2 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 3Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA, 4Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA The extent to which PTH therapy for osteoporosis increases serum and urinary calcium levels and results in clinically relevant hypercalcemia or hypercalciuria is controversial. To address this question, we examined increments in serum and urinary calcium levels associated with PTH(1–84) therapy in the PaTH trial and the extent to which a defined algorithm resolved the increases. In PaTH, 238 postmenopausal women with low hip or spine BMD and normal calcium concentrations were randomized to daily PTH, alendronate, or both and followed for 12 months. All participants received daily calcium and vitamin D supplements.

S222 This analysis includes 178 women assigned to PTH alone or in combination with alendronate. Fasting serum calcium was measured at baseline, 1, 3, and 12 months; 24-hour urinary calcium was measured at baseline and 3 months. During the study, 24 (13%) participants developed serum calcium >10.5 mg/dl on at least one occasion; 7 values were >11 mg/dL. Following the defined algorithm, 58% of elevated measurements were normal on repeat testing; 38% resolved after discontinuation of calcium and vitamin D supplementation. In one participant, hypercalcemia resolved when PTH injection frequency was decreased. No cases required discontinuation of PTH. One participant had normal serum calcium concentrations at all visits, but developed transient hypercalcemia requiring hospitalization. The episode resolved with intravenous hydration. Baseline characteristics that aﬀected the odds of developing hypercalcemia were serum calcium (odds ratio[OR]=1.9 per 0.5 mg/dl; 95% confidence interval[95%CI]=1.1–3.2), and serum 1,25-dihydroxyvitamin D (OR=1.9 per 10 pg/ml; 95%CI=1.2–3.1). Fifteen women (8%) developed hypercalciuria (24-hour urinary calcium>400 mg or calcium/creatinine ratio>0.4). 80% of cases resolved after discontinuation of calcium and vitamin D supplementation, 13% without intervention, and one after PTH injection frequency was decreased. Hypercalciuria did not recur when daily PTH frequency was restored. Higher baseline urinary calcium excretion doubled the odds of hypercalciuria on PTH therapy, with OR=2.2 per 50 mg/day (95%CI=1.2–4.0). Proportions of patients with elevated serum and urinary calcium were similar on single and combination therapy. In summary, the frequency of episodic hypercalcemia or hypercalciuria in the PaTH trial was low, and episodes readily resolved spontaneously or with discontinuation of calcium and vitamin D supplementation.

P344SU. ROLE OF PROSTAGLANDINS IN THE ANABOLIC EFFECTS OF STRONTIUM RANELATE Choudhary S1, Halbout P2, Alander C1, Raisz L1, Pilbeam C1; 1 UConn Center for Osteoporosis, University of Connecticut Health Center, Farmington, USA, 2Groupe Servier, Courbevoie, France Strontium ranelate is a new agent for the treatment of postmenopausal osteoporosis that increases bone formation and decreases bone resorption. Although its anti-fracture eﬃcacy has been demonstrated, its mechanism of action at the cellular level is still under investigation. We have assessed the involvement of prostaglandins (PGE2) in the eﬀects of strontium ranelate on osteoblasts. Osteoblastic precursors from bone marrow (MSC) or primary osteoblasts isolated from murine calvariae (POB) were cultured for 7 to 14 days, and treated with strontium ranelate (1 and 3 mM strontium, Sr2+) for various times. Eﬀects on proliferation, alkaline phosphatase (ALP) activity, PGE2 production and mineralization were assessed. Strontium ranelate (1 mM and 3 mM Sr2+) increased the proliferation of POB 1.53 fold (p<0.01) and 1.35 fold (p<0.01), respectively, after a 7-day treatment. ALP activity of POB assessed at the end of a 14-d culture was significantly increased by strontium ranelate (3 mM Sr2+) after a 0–3 d (186%, p<0.01), 0–7 d (95%, p<0.05) and 0–14 d (92%, p<0.05) treatment. Similarly, ALP activity was increased in MSC by 92% (p<0.01) and 63% (p<0.01) after a continuous treatment with strontium ranelate (3 mM Sr2+) for 10 and 14 days, respectively. This eﬀect was completely blocked by NS-398, a selective cyclooxygenase (COX)-2 inhibitor. A 14-day culture was used to assess the strontium ranelate eﬀects on PGE2 production by MSC. After 7-days of treatment with strontium ranelate (1 mM and 3 mM Sr2+), cumulative PGE2 levels were increased 2.4 fold (p<0.01) and 11.0 fold (p<0.01), respectively. COX-2 was involved in the strontium ranelate-induced PGE2 production, as demonstrated by the inhibition of this eﬀect by NS-398. Osteoblasts diﬀerentiated in presence of strontium ranelate were functional as illustrated by the increased mineralization observed when MSC were continuously treated for 14 days with strontium ranelate (3 mM Sr2+). These results confirm the stimulatory eﬀects of strontium ranelate on proliferation, diﬀerentiation and mineralization of murine osteoblasts. These eﬀects, which were coupled to a

COX-2 dependent increase in PGE2 production, are consistent with a possible involvement of prostaglandins in the anabolic eﬀect of strontium ranelate.

P345MO. OSTABOLIN-C: A NOVEL PARATHYROID HORMONE ANALOGUE INCREASES BONE FORMATION AND STRENGTH IN RATS TREATED FOR 26 WEEKS Morley P1, Jolette J2, Smith SY2, Turner CH3, Moreau I2, Mayer J2; 1Zelos Therapeutics, Ottawa, ON, Canada, 2Charles River Laboratories Preclinical Services, Montreal, QC, Canada, 3Indiana University, Indianapolis, IN, USA Aims: Ostabolin-C, (Leu27, Cyclo[Glu22Lys26]-hPTH[1–31]amide), a novel parathyroid hormone (PTH) analogue being developed for the treatment of osteoporosis, was administered daily by subcutaneous injection to gonad-intact crl:Wistar rats (20/sex/group) at dose levels of 0, 2, 10 or 25 µg/kg for 26 weeks to evaluate toxicity. Methods: Rats were 11–13 weeks of age at start of treatment. Blood and urine samples were collected to measure biochemical markers of bone turnover. Femurs, tibiae and lumbar vertebral bodies, labeled with calcein green 10 and 3 days prior to euthanasia, were retained for densitometry, biomechanical testing and histomorphometry. Results: Ostabolin-C was well tolerated with no antibody formation and no hypercalcemia (total or ionized) observed in blood samples collected at weeks 13 and 26 approximately 24 hours post-dose. Treatment with Ostabolin-C increased the bone formation marker osteocalcin. For bone resorption markers, urinary DPD values were comparable to controls and C-telopeptide values were increased in the 25 µg/kg group only. Bone mass, as measured by DXA and/or pQCT, was increased at the femur and/or lumbar spine at all dose levels. Ostabolin-C increased femur diaphysis cortical area and cortical thickness, with decreases in endocortical circumference, significant for high dose females. Changes in bone geometry were associated with non-significant increases in femur bone strength at the diaphysis and femoral neck. Increases in lumbar vertebral bone mass translated into significant increases in bone strength, work to failure and toughness. Increases in bone mass were generally positively correlated with increases in bone strength at sites evaluated. Tibial cancellous bone volume was increased along with the mineralizing surfaces and surface referent bone formation rates. A clear eﬀect on resorption as measured with osteoclast surface was not observed with Ostabolin-C treatment. Conclusions: The results of this study are consistent with the anticipated anabolic eﬀects of Ostabolin-C as a PTH analogue. Increases in bone mass, attributed to increases in bone formation with no significant increases in indices of bone resorption, were associated with increased bone strength at the femur and spine. Ostabolin-C may have significant therapeutic value in the treatment of osteoporosis.

P346SA. DIFFERING EFFECTS ON HIP AND NONSPINE FRACTURE RISK REDUCTION AMONG N-CONTAINING BISPHOSPHONATES: REVIEW AND META-ANALYSIS Liberman UA1, Hochberg MC2, Geusens P3, Ross PD4; 1Felsenstein Medical Research Center, Department of Physiology & Pharmacology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 2Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA, 3Biomedical Research Institute – LUC, Universitaire Campus, Diepenbeek, Belgium and Maastricht, The Netherlands, 4Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA Objectives: N-containing bisphosphonates reduce the risk of vertebral fractures (VFx); however, results have not shown consistent eﬀects on hip and other nonspine fractures. Systematic reviews are useful to summarize eﬀects that often vary among individual trials, and meta-analysis provides a more precise estimate when results are consistent across pooled trials.1

S223 Methods: We surveyed earlier systematic reviews and metaanalyses1 together with subsequent reports2–4 of randomized, placebo-controlled trials with data on nonspine and/or hip fractures, and used meta-analysis where appropriate to test for heterogeneity and derive pooled estimates. Results: For risedronate (RIS) (n=12958 subjects in trials), the relative risk (RR) reduction was 27% for nonspine fracture (RR=0.73; 95% CI= 0.61, 0.87)1 and 26% for hip fracture (RR=0.74; 0.58, 0.94); there was no significant interaction of treatment and age >80 and there was no heterogeneity by dose (2.5 or 5 mg/day). For alendronate (ALN), heterogeneity existed; doses >10 mg/day were significantly more eﬀective for reduction of nonspine and hip fracture. The RR reduction with ALN >10 mg (n=3723) was 49% for nonspine fractures (RR=0.51; 0.38, 0.69).1 The RR reduction for hip fracture was 55% (RR=0.45; 0.28, 0.71) when osteoporotic women in FIT (ALN 5 mg/day in years 1–2 then 10 mg/day for remainder of trial) were included (n=6804), and 55% (RR=0.45; 0.18, 1.13) for doses >10 mg/day (n=3723).1 One post-hoc analysis suggested an eﬀect of ibandronate (IBN) on non-spine fractures in patients with severe osteoporosis, but the limited fracture data and diﬀerences in dosing precluded pooling studies for meta-analysis. No data are available on the eﬀect of IBN on hip fracture. Consequently, there is no consistent evidence of hip or nonspine fracture risk reduction available for metaanalysis with IBN at a dose of 2.5 mg/day.4 Conclusions: The magnitude of eﬀect on hip fracture appears to diﬀer among drugs. Based on current data, ALN reduces the risk of hip and nonspine fracture by 49–55% and RIS by 26–27%. There is insuﬃcient and/or inconsistent evidence of an eﬀect on these fractures for ibandronate.4 1. 2. 3. 4.

Cranney et al. Endocr Rev 2002;23:570–8. Papapoulos Osteoporos Int 2005;16:468–74. McClung et al. NEJM 2001;344:333–40. Chesnut et al. JBMR 2004;19:1241–9.

P347SU. THE PREFER-US STUDY: AN EVALUATION OF PATIENT PREFERENCES FOR OSTEOPOROSIS MEDICATIONS AND THEIR ATTRIBUTES Silverman SL1, Weiss TW2, Gold DT3, McHorney CA2; 1CedarsSinai/UCLA, Los Angeles, CA, USA, 2Merck & Co., Inc, West Point, PA , USA, 3Duke University Medical Center, Durham, NC, USA Aims: To assess patient preferences for eight medication attributes that patients may consider when evaluating prescription osteoporosis medications. Methods: Eligible sample was 3,368 women age 50+ who responded to the 2003 or 2004 internet-based National Health and Wellness Survey as being diagnosed with osteoporosis, considered themselves at-risk, or had a family history of osteoporosis. In this internet survey, respondents were asked to: (1) force-rank order, from one to eight, the eight attributes according to their preference and (2) separately rate the importance of each attribute on a Likert scale from 1 (extremely unimportant) to 7 (extremely important). Bivariate subgroup analyses performed by demographics, osteoporosis diagnosis, osteoporosis treatment status, fracture status, and selected comorbidities. Ranking comparisons made by ChiSquare and mean importance comparisons made by t-test for nominal variables and by ANOVA for categorical variables. Results: We collected 999 responses on three days and stopped compiling responses after achieving sample size targets. Mean age was 65. Drug eﬀectiveness (e.g., ability to reduce the risk of fractures) was force ranked as the most important attribute (37% ranked as #1). The other seven attributes were force ranked #1 as follows: side eﬀects (36%), out-of-pocket costs (10%), drug interactions (10%), time on market (3%), dosing frequency (2%), formulation (1%), and dosing procedure (1%). Drug eﬀectiveness had the highest mean importance rating (6.1, S.D. 1.6); dosing frequency had the lowest (4.7, S.D. 1.8). Respondents with more education and larger incomes tended to rank eﬀectiveness higher than dosing frequency. Diﬀerences in mean importance ratings found for drug eﬀectiveness by 5-year age groups (range 6.0 to 5.3 with no trends). Dosing frequency diﬀered by treatment status (4.7 vs. 4.4; treated vs. untreated), race (4.8 vs. 4.5; non-white vs.

white), and education (4.9 vs. 4.4; high school vs. post-graduate). Conclusions: Drug eﬀectiveness was both the highest ranked and highest rated osteoporosis medication attribute that patients seek in an osteoporosis therapy. The side eﬀects attribute was also of high importance, while dosing frequency was of lower importance. These findings were largely invariant across subgroups. These findings may be useful for clinicians initiating discussions with women about osteoporosis medications.

P348MO. POTENTIAL ANTIOSTEOARTHRITIC EFFECTS OF A 12-MONTH THERAPY WITH RALOXIFENE IN WOMEN WITH KNEE OSTEOARTHRITIS Badurski JE1, Daniluk S1, Dobrenko A1, Jeziernicka EZ1, Nowak NA1, Buslowska J2, Holiczer W3; 1Centre of Osteoporosis & Osteoarticular Diseases, 2Sniadecki Hospital, 3Technical University, Bialystok, Poland The aim of this study was to evaluate the eﬀect of a 12-month therapy with raloxifene (RLX) in women with osteoarthritis of knees (OAK) on WOMAC and Lequesne indexes and on cartilage degradation and bone remodeling markers. The study was conducted in 65 women aged 52–79, mean 65.5 years, with OAK diagnosed according to ACR criteria and rated on a 3-point Kellgren-Lawrence scale, with low bone mass (BMD of Hip Neck and/or L1-L4 LS T-score between –1.0 and 2.5) without contraindication to be treated with RLX. Patients were randomly assigned in ratio 1:2 to the control(C), or to group (E) being treated for 12 months with 60 mg of RLX p.o./day. All the participants took calcium up to 1200 mg/day plus 800 IU Vit. D, and in the case of pain, Tramadol 1–2 x 50 mg/day. Evaluation of RLX eﬀect was based on WOMAC and Lequesne indices, and on cartilage-specific C-terminal tetrapeptide of type II collagen CTX-II/Cr, and oligometric matrix protein COMP with ELISA method. The bone metabolism was monitored by bonespecific alkaline phosphatase b-ALP, osteoprotegerin OP, bone specific C-terminal tetrapeptide of type I collagen CTX-I, and soluble NF-kappa-B receptor activator sRANKL with ELISA method. The patients and markers were examined before and after 3, 6 and 12 months of treatment with RLX. The results pointed to a significant improvement of WOMAC index (p=0.002), Lequesne’s test results were on the border of significance (p=0.05) and testing level of probability for CTX-II/Cr and WOMAC marker correlation was p=0.058. Regressive analysis of time changes showed statistically significant decrease in OP, CTX-II, CTX-II/Cr in the group E and lack of any marker changes in the C one. The drop of CTX-II and CTX-II/Cr after 12 months in the group E was 30% and 40%, respectively, with regard to the values before treatment. There were neither diﬀerences in time and between the groups E and C as for markers of bone metabolism nor their correlation with markers of cartilage degeneration nor COMP changes. Conclusion: It seems that RLX may display a curative eﬀect on cartilage degradation with improvement of clinical outcomes of OAK.

P349SA. CONSISTENT 61% RISK REDUCTION OF NEW VERTEBRAL FRACTURES IN MEN WITH OSTEOPOROSIS AFTER THE FIRST AND SECOND YEAR OF RISEDRONATE THERAPY Ringe JD, Dorst A, Faber H; Medizinische Klinik IV, Klinikum Leverkusen, University of Cologne, Leverkusen, Germany Objective: To examine the eﬀects of risedronate on vertebral fractures and mean changes in lumbar spine, femoral neck and total hip BMD only in men with primary and secondary osteoporosis. Patients and methods: In this single center, open label, controlled prospective two year trial we enrolled 316 male patients with T-score values of lower than -2.5 SD at lumbar spine (LS) and lower than -2.0 SD at the femoral neck (FN) with or without prevalent vertebral fractures (vert.-fx). Patients in group A (n=158; 81 with, 77 without prevalent vert.-fx) received risedronate 5 mg plus calcium 1000 mg and 800 IU Vit. D daily. Group B comprised equally 158 men. Those with a prevalent vert-fx (subgroup B1

S224 n=81) were treated with alfacalcidol 1 µg plus calcium 500 mg daily, whereas patients without prevalent vert.-fx (subgroup B2, n=77) were treated with 800 IU plain vitamin D plus calcium 1000 mg daily. BMD measurements and x-rays were performed at baseline and 12 and 24 months thereafter. Results: The LS-BMD increase after 12 and 24 months amounted to 4.7% and 6.5% resp. in risedronate patients compared with a mean resp. increases of 1.0% and 2.2% in controls (p<0.001). The mean changes at the total hip site were 2.7% and 4.4% for group A after the first and second year. For group B an average change of 0.4% was documented after one year and unchanged after the second (p<0.001). In the first year 8 patients of group A and 20 of group B sustained new vert.-fx (risk reduction 61%). The cumulative patient numbers with new vert-fx after 2 years were 14 and 35 in the resp. groups, i.e. an unchanged fracture reduction of 61% (Fisher’s exact test 0.0026). Reduction of back pain after one and two year was significantly more pronounced in risedronate versus control patients (p<0.0001). All therapies were well tolerated. Conclusion: Risedronate therapy in men with established primary or secondary osteoporosis consistently reduces the risk of new vertebral fractures by 61% over two years and significantly increases BMD at the lumbar spine and proximal femur.

P350SU. PREDICTORS OF ESTROGEN DISCONTINUATION POST WOMEN’S HEALTH INITIATIVE: RESULTS FROM THE NATIONAL OSTEOPOROSIS RISK ASSESSMENT PROGRAM (NORA) Siris ES1, McHorney CA2, Miller PD3, Barrett-Conor E4; 1Columbia University College of Physicians and Surgeons, NY, NY, 2 Merck & Co. Inc., West Point, PA, 3University of Colorado Health Scences Center, Lakewood, CO, 4University of California, San Diego, La Jolla, CA, USA Aims: The Women’s Health Initiative (WHI) demonstrated that the health risks of using estrogen plus progestin in postmenopausal women (PMW) exceeded health benefits. We use a longitudinal registry of PMW to study HRT discontinuation post-WHI. Methods: From 1997–1999, NORA enrolled over 200,000 women from 49 states and DC in a longitudinal registry of PMW. Eligibility criteria were: at least 50 years old, at least six months post last menses, no prior diagnosis of osteoporosis, no BMD testing in the preceding year, and no specific osteoporosis medication use (HRT use was permitted). At the Year-5 survey, women reported change in HRT since the WHI(two-year recall). The sample was limited to women eligible to discontinue HRT (recent users). Logistic regression modeled predictors of HRT discontinuation in the total sample as well as samples diﬀerentiated by WHI HRT health risks (CHD, hypertension, stroke, breast cancer) and age (< 60 vs. 60+). Results: At the Year-5 survey, 56% of participants had discontinued HRT. Variables which increased the odds of HRT discontinuation were: (1) Asian (vs. white) (OR:1.54 CI:1.12- 2.11); (2) age greater than 55 (e.g., OR:1.36, CI:1.27–1.46 for age 60–64); (3) CHD history (OR: 1.17; CI: 1.04–1.32); (4) hypertension history (OR:1.10, CI:1.04–1.16); and (5) baseline T-score <-2.50 (OR:1.22, CI:1.01–1.48). Variables which decreased odds of HRT discontinuation were: (1) baseline estrogen use (OR:0.56, CI: 0.52–0.60); (2) Native American (vs. white) (OR:0.64, CI: 0.47–0.89); (3) less than a high school education (vs. college graduate) (OR:0.64, CI:0.57– 0.72); and (4) African American (vs. white) (OR:0.83, CI: 0.73– 0.95). In patients with HRT health risks, results for Native American (OR:0.49;CI: 0.28–0.87), African American (OR:0.77, CI: 0.64–0.92), and low education (OR:0.66, CI: 0.54–0.79) were replicated. Subgroup analyses within age (< 60 vs. 60+) and WHI HRT health risks replicated the low education results. Conclusions: The WHI recommendations that HRT should not be initiated/continued for prevention of CHD was not equally adopted across NORA racial and education subgroups. These disparities persisted among women with risk factors for poor outcome for continued HRT use. Such disparities in the processes of care can contribute to disparities in health outcomes and should be ameliorated.

P351MO. A PEPTIDE DERIVED FROM CHEMOKINE CXCL7 RESTORES BONE STRENGTH IN OVX RATS Squires D1, Varela A2, Smith SY2, Peel SAF1, Ramirez Yañez GO1, Gu Y1, Malek LT1; 1Osteopharm Inc., Oakville, ON, Canada, 2Charles River Laboratories Preclinical Services Montreal, Senneville, PQ, Canada It was reported that fragments of the human CXC chemokine neutrophil activating peptide-2 (NAP-2, CXCL7) stimulated bone mineral apposition in rats (Tam 2004, US Pat. No. 6,693,081). The purpose of this study was to determine whether the modified 8 amino acid peptide Ac-TTSGIHPK-amide (OSB) derived from CXCL7 would aﬀect bone composition and strength in ovariectomized (OVX) rats. Virgin SD rats were OVX or sham operated at 23 weeks of age and placed into groups (N=12) on the basis of DEXA measurements of bone and body composition. Eight weeks after surgery the rats received injections of OSB (300 nmoles/kg) or vehicle (sham and OVX controls) for 5 days per week. After 26 weeks of treatment the rats were sacrificed and bones were collected for pQCT and micro-CT analyses. Each femur was further subjected to a 3-point bending test, followed by a femoral neck shearing test on the proximal fragment. Results of the 3-point bending tests indicate that femora from the OSB group were significantly stronger than from the OVX control, based upon higher peak load (11%, p=0.008) and stiﬀness (14%, p=0.04), which were both comparable to Sham. This result was anticipated from pQCT analysis, showing that femora and tibiae from the OSB-treated OVX rats had significantly higher cortical bone in a favorable geometric arrangement, indicative of enhanced biomechanical strength. The shearing tests on the proximal femora demonstrated that the OSB-treated OVX rats were significantly stronger at the femoral neck, based upon higher peak load (21%, p=0.003), work to failure (38%, p=0.006), and maximum displacement (20%, p=0.02), which were all similar to Sham. This was consistent with pQCT results, indicating that the total BMC and BMD at the femoral neck was significantly higher in OSB-treated OVX rats. In summary, OSB treatment of OVX rats significantly enhanced the biomechanical strength at the femoral neck and diaphysis, restoring both to Sham levels. This result combined with the pQCT results indicates that OSB improved both bone density and strength at the proximal femur, which may be clinically important for lowering the risk of osteoporotic hip fracture.

P352SA. PYRMONT ASSESSMENT OF COMPLAINTS AND QUALITY OF LIFE IN PATIENTS WITH OSTEOPOROSIS (PACO) Minne HW1, Hinz C1, Pfeifer M1, Schmitt S2, Lazarescu D1; 1 Institute of Clinical Osteology and Clinic ’’Der Fuerstenhof’’, Bad Pyrmont, Germany, 2Procter & Gamble Pharmaceuticals, Weiterstadt, Germany Introduction: So far, several questionnaires to assess quality of life in patients with osteoporosis are available. These include generic instruments such as the Nottigham Health Profile (NHP) or the Short Form 36 (SF-36) as well as disease specific instruments such as QUALEFFO-41 and OPTOQol. Clinical experience, however, indicate that the degree of disease specificity is not high enough to reveal the whole picture of osteoporosis and to reflect the burden of disease in its complexity and various appearances in diﬀerent patients. Materials and Methods: In the first step, 104 questions were selected out of clinical experience of the investigators. In its first and crude version, this new instrument entered a validation phase to test for within-subject reproducibility, internal consistency and construct validity. Finally, 24 items with a significant Odds Ratio >10 were identified in a case-control study comparing patients with back pain due to spinal degenerative disease and patients with back pain due to osteoporotic vertebral fractures. These 24 items were included into the final version of PACO. The items of PACO will now be randomly mixed with QUALEFFO-41 and SF-36 in order to compare reproducibility, consistency, and validity. Results: Especially, items such as to carry home shoppings (OR = 19.7; 95%C.I.: 5.4 to 71.4), to move a vacuum cleaner (OR =

S225 21.3; 95%C.I.: 2.6 to 170.6), to drive a car (OR = 13.1; 95%C.I.: 3.4 to 51.1), to go to a movie theater (OR = 19.8; 95%C.I.: 2.5 to 158.9), to retreat from circle of acquaintances (OR = 48.4; 95%C.I.: 5.9 to 293.3), or gardening (OR = 11.5; 95%C.I.: 2.4 to 54.7) were highly specific for osteoporosis. In a ROC-analysis, PACO-24 showed a sensitivity of 0.88 with a specificity of 0.70. Conclusion: The newly developed PACO-24 discriminates between cases and controls and diﬀerentiates between pain caused by osteoporotic vertebral fractures and pain caused by spinal degenerative disease. Furthermore, PACO-24 demonstrates a good sensitivity and specificity and reveals severe impairments of activities in daily living in patients suﬀering from postmenopausal osteoporosis resulting in vertebral fractures.

P353SU. ALENDRONATE IMPROVES SCREW FIXATION IN OSTEOPOROTIC BONE: A CLINICAL STUDY OF PERTROCHANTERIC FRACTURES Hoang-Kim AM, Faldini C, Pegreﬃ F, Moroni A; Rizzoli Orthopaedic Institute, Bologna, Italy Recently, animal studies have demonstrated the eﬃcacy of using antiresorptive agents such as alendronate ALN)as a fixation augmentation technique. In this study, we used the systemic administration of bisphosphonates to investigate osteointegrative properties of hydroxyapatite-coated implants in osteoporotic patients treated with external fixation. Methods: Sixteen consecutive patients with pertrochanteric fractures were selected. Inclusion criteria were: female, age R 65 years, BMD T-score < -2.5 SD. Exclusion criteria included pin insertion torque %1000 N/mm and bisphosphonate treatment during the two-year period prior to fracture. Fractures were fixed with a pertrochanteric fixator and 4 HA-coated pins. Two pins were implanted in the femoral head (pin positions 1 and 2) and two in the femoral diaphysis (pin positions 3 and 4). Patients were randomized to therapy with either ALN (Group A) or control (Group B) for a three-month post-operative period. Group A patients received an oral dose of 70mg of ALN per week. Fixators were removed at 3 months post-op in all patients. Results: All the fractures healed. No pin loosening or infection occurred in either group and no diﬀerences between femoral neck-shaft angle at 6 months versus post-op were observed. There was no significant diﬀerence in pin insertion torque between the two groups. The combined mean extraction torque of the pins implanted at positions 1 and 2 (cancellous bone of the femoral head) was 3181 1385 N/mm in Group A and 1890 813N/mm in Group B (p < 0.001). The combined mean extraction torque of the pins implanted at positions 3 and 4 (cortical bone of the femoral diaphysis) was 4327 1720 N/mm in Group A and 3785 1181N/mm in Group B (ns). Conclusions: These data show that weekly systemic administration of ALN improves fixation in elderly patients with osteoporosis. We observed a two-fold fixation increase in the pins implanted in cancellous bone. With cortical bone, the diﬀerence in pin fixation was less marked. We believe that the eﬀect of ALN on implant fixation could be even more pronounced with standard metal screws which have a lower osteointegrative ability than HA-coated screws.

The aim of our study is not only to examine the patient’s compliance with daily doses of alendronate or risedronate but also to find the causes of noncompliance through the questionnaire survey. The treatment duration of each patient was obtained from a database for the prescriptions in pharmacies. The diﬀerence in compliance rates between the two treatment groups was analyzed by Kaplan-Meier method and Log-rank test. Factors aﬀecting compliance were analyzed by Cox’s proportional hazards model or logistic regression. Overall compliance rate was approximately 60% for 179 days after the initial dose, and decreased in 40% after one year. No significant diﬀerence was obtained between the alendronate group (569 patients) and the risedronate group (445 patients). The compliance rate was higher in the female group than the male group, and that of patients with rheumatism was higher than those with other diseases. A total of 208 patients answered the questionnaire, in which 16 patients among noncompliant group (45 patients) indicated to have some side eﬀects, and other noncompliant patients stopped to take bisphosphonates in spite of having no side eﬀects. In the noncompliant group, 6 patients stopped to take bisphosphonate because the pain from osteoporosis had dissipated. These patients are considered to misunderstand that the treatment by the drug intake had finished or they bothered to visit medical facility when the pain was removed by the treatment with NSAIDs. From these results, it is indicated that understanding of the disease, the purpose of the therapy to prevent the bone fracturing and bedridden, and necessity of long-term medication by the patients themselves are the most important factors to achieve better compliance.

P355SA. ASSESSMENT OF PATIENTS’ PREFERENCE FOR OSTEOPOROSIS MEDICATIONS Walliser J1, Bolge S2, Sen SS3; 1Clinical de Metabolismo Oseo y Mineral del Hospital Angeles del Pedregal, 2Consumer Health Sciences, Princeton, NJ, USA, 3Merck & Co., Whitehouse, NJ, USA Objective: To evaluate patients’ preferences for two diﬀerent osteoporosis medication profiles and the reasons for their preferences. Methods: Physicians were randomly selected in France, Germany, Mexico, Spain and UK, and asked to refer the next 4 osteoporotic women aged 50 years or older seen in their practices. These patients were asked over telephone or face-to-face (Mexico) to indicate their preference between two hypothetical osteoporosis medication profiles, A and B which varied on 4 parameters, eﬃcacy, time on market, dosing frequency and dosing procedure. They were also asked to indicate the most importance reason for their medication preference among these 4 parameters. Results: A total of 3000 patients were interviewed of whom 1500 were on prescription treatment for osteoporosis while the rest were not. The majority of patients (78%) preferred drug A over drug B. Eﬀectiveness in reducing risk of fracture was most frequently (72%) ranked as the most important reason for their preference Drug A

P354MO. FACTORS AFFECTING LONG-TERM COMPLIANCE OF OSTEOPOROTIC PATIENTS WITH BISPHOSPHONATE TREATMENT 1,3

2

1

Kamatari M , Koto S ; Kyoto Pharmaceutical University, Kyoto, Japan, 2Koto Orthopedics, Osaka, Japan, 3Maruzen Pharmacy, Osaka, Japan Bisphosphonates are a group of major drugs for osteoporotic treatment, which potently inhibit bone resorption. However, the ingestion of bisphosphonates is limited because bisphosphonates easily form metal complexes in digestive systems, and thus the bioavailability is low. For better ingestion, patients need to take the drug immediately after getting up in the morning with a glass of water. After the administration, patients must not eat anything except water and stay in an upright position for 30 minutes.

Description proven to reduce risk of spine and hip fracture 10 year in regular practice once a week 30 minutes wait Results Preferred by 78% (0.4) of all patients 79% (0.4) of patients on treatment 76% (0.4) of patients not on treatment

Drug B

proven to reduce only spine fracture recently introduced once a month 60 minutes wait 22% (0.4) of all patients 21% (0.4) of patients on treatment 24% (0.4) of patients not on treatment

S226 followed by time on market (13%), dosing frequency (9%) and dosing procedure (6%). Conclusion: The drug profile A with proven hip fracture reduction was chosen over drug B by the majority of the patients regardless of their treatment status. Eﬀectiveness in reducing risk of fracture was the most important reason for selection of a drug profile.

P356SU. A COMPARISON OF THE EFFECT OF ALENDRONATE AND RISEDRONATE ON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS OVER 24 MONTHS (FOSAMAXT ACTONELT COMPARISON TRIALS - INTERNATIONAL: FACTS - INTERNATIONAL) Reid DM1, Hosking D2, Kendler D3, Brandi ML4, Wark JD5, Weryha G6, Marques-Neto JF7, Verbruggen N8, Hustad CM8, Melton ME8; 1University of Aberdeen, Aberdeen, UK, 2Nottingham City Hospital, Nottingham, UK, 3Providence Health Care, Vancouver, BC, Canada, 4University of Florence, Florence, Italy, 5 Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia, 6Hôpital de Brabois, Nancy, France, 7State University (Unicamp), Campinas, São Paulo, Brazil, 8Merck & Co., Inc., Whitehouse Station, New Jersey, USA Aims: To compare alendronate 70 mg once weekly to risedronate 35 mg once weekly with respect to change in bone mineral density (BMD), biochemical markers, and upper gastrointestinal tolerability over 24 months. Methods: The study was a 12-month extension to the randomized, double-blind, 12-month FACTs-international study. Postmenopausal women with osteoporosis were randomly assigned to treatment with either alendronate 70 mg once weekly or risedronate 35 mg once weekly for 12 months in a 1:1 ratio for the base study. All patients who completed the base study and met all extension entry criteria were enrolled. Patients continued the same double-blind study medication during the extension study. Eﬃcacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck at 24 months. Other assessments included levels of four bone turnover markers at 24 months. Tolerability was assessed by adverse experience reporting. The primary hypothesis was that treatment with alendronate would produce a greater mean percent increase from baseline in hip trochanter BMD at 24 months than that observed with risedronate. Results: Of 936 patients randomized into the base study, 854 patients completed the 12-month visit, and 798 patients entered the extension (403 alendronate and 395 risedronate patients). Trochanter BMD increased significantly from baseline to Month 24 in both treatment groups, with a significantly larger increase with alendronate: adjusted mean treatment diﬀerence of 1.50% (95% CI: 0.74%, 2.26%; p<0.001). This between-group diﬀerence was numerically larger than that seen at Month 12. Similar results were seen at all other BMD sites. Significant geometric mean percent decreases (p<0.001) from baseline were seen for all four markers of bone turnover in both the alendronate and risedronate groups, with a significantly larger decreases (p<0.001) with alendronate: adjusted mean treatment diﬀerences ranged from 8.9% to 25.3%. No significant diﬀerences were seen between groups in the incidence of upper gastrointestinal adverse events. Conclusions: Patients taking alendronate 70 mg once weekly had significantly greater gains in BMD and larger decreases in levels of bone turnover markers than those taking risedronate 35 mg once weekly over 24 months of treatment, with no diﬀerence in upper gastrointestinal tolerability.

P357MO. THE BISPHOSPHONATE TREATMENT CARE GAP IN COMMUNITY DWELLING MEN WHO HAVE INCIDENT FRAGILITY FRACTURES: THE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY (CAMOS) Ioannidis G1, Papaioannou A1, Tenenhouse A2, Gao Y2, Berger C2, Prior JC3, Kaiser SM4, Hanley DA5, Brown JP6, Olszynski WP7, Josse RG8, Murray TM8, Anastassiades T9; 1McMaster University, Hamilton, Canada, 2McGill University, Montreal, Canada, 3University of British Columbia, Vancouver, Canada, 4 Dalhousie University, Halifax, Canada, 5University of Calgary,

Calgary, Canada, 6Laval University, Ste-Foy, Canada, 7University of Saskatchewan, Saskatoon, Canada, 8University of Toronto, Toronto, Canada, 9Queen’s University, Kingston, Canada, 10 Memorial University, St. John’s, Canada, 11University of Alberta, Edmonton, Canada Aims: A large number of osteoporotic fractures occur in men. To reduce the likelihood of subsequent fractures, these individuals should be treated with a bisphosphonate. Utilizing participants from CaMos, a prospective population-based cohort study that involves an age- sex-, and region- stratified random sample of the Canadian population we performed a 5-year analysis to determine the number of men 50 years of age and older who had an incident fracture and were administered a bisphosphonate. Methods: All fractures were a result of minimal trauma, clinically recognized and were assessed cumulatively over the 5-year observational period (i.e. fractures at year 5 occurred during that year and before). The fracture locations that were examined included the hip, wrist, rib and spine. Bisphosphonate use was evaluated by patients’ self-reports from the CaMos baseline and annual follow-up questionnaires. Results: Data are available at baseline (n=2187), year one (n=2134), and year five (n=1656) for men R 50 years. Results indicated that there was an approximately 6-fold increase in the number of men being treated who had a hip fracture during the course of the study. In addition, there was about a 2-fold increase in the number of men being treated who had other non-vertebral or vertebral fractures (table 1). Table 1: The distribution for men who have incident fragility fractures and are administered bisphosphonate therapy over a 5-year period Obs. Period

Year Year Year Year Year

One Two Three Four Five

Hip Fracture

Wrist Fracture

Rib Fracture

Spine fracture

total #

treated N (%)

total #

treated N (%)

total #

treated N (%)

total #

treated N (%)

17 16 14 12 8

1 1 4 3 3

123 128 128 127 115

5 (4.1) 6 (4.7) 9 (7.0) 8 (6.3) 10 (8.7)

62 69 67 66 62

5 (8.1) 8 (11.6) 12 (17.9) 10 (15.2) 11 (17.7)

7 9 9 8 8

1 1 4 1 2

(5.9) (6.3) (28.6) (25) (37.5)

(14.3) (11.1) (44.4) (12.5) (25)

Conclusion: Although the number of men treated with a bisphosphonate following a fracture increased over the 5-year observational period, there is still a large treatment gap and is most likely larger than in women with incident fragility fractures. Given the large therapeutic care gap in treating men with fractures, particularly men with wrist fractures, future research should focus on increasing recognition of incident fragility fractures, their association with osteoporosis and appropriate treatment.

P358SA. PARTIAL RESTORATION OF SKELETAL STRENGTH IN OVARIECTOMIZED RATS BY TREATMENT WITH STRONTIUM SALTS Christgau S.1, Høegh-Andersen P.2, Andersen J.E.T.3; 1Osteologix A/S, Copenhagen Denmark, 2Nordic Bioscience A/S, Herlev, Denmark, 3Institute of Analytical Chemistry, Technical University of Denmark, Denmark Aim: Ovariectomy of female rats induces significant bone-loss by depriving endogenous estrogen production. We assessed whether administration of strontium salts had a therapeutic benefit in this animal model of postmenopausal osteoporosis. Methods: The study was performed in 48 female 5 months old Sprague-Dawley rats. After 4 weeks acclimatization, 12 rats were subjected to sham operation and the remaining 36 were ovariectomized (OVX). After 4 weeks, the 36 OVX rats were randomized into three groups and subjected to treatment by oral gavage with vehicle alone or vehicle + 533 mg/kg/day strontium glutamate (S-G) or 300 mg/kg/day strontium malonate (S-M)(both doses correspond to 137 mg ionic strontium/kg/day). The treatment period was five weeks, and at the end we analyzed circulating strontium levels, as well as bone strength analysis by indentation testing and BMD measurement by pQCT.

S227

Results: Strontium content at the end of the 5 week treatment period showed relatively large inter-individual variation with average levels in S-G treated animals of 76404606 ppm and 59641969 ppm. Calcium levels were not aﬀected by strontium treatment (28.2 and 28.7 mg/l in S-G and S-M animals compared to 27.9 mg/l in vehicle treated rats). pQCT analysis of the distal femur revealed only a relatively modest eﬀect of strontium treatment on BMD (693 and 703 mg/cm3 in S-M and S-G respectively compared to 671 mg/cm3 in vehicle treated OVX and 750 mg/cm3 SHAM rats). Bone strength analysis revealed a significant increase (p<0.05) in bone strength in S-M and S-G treated OVX rats compared to the vehicle treated group (see table). Bone Strength Analysis Group

Maximum Load

Energy to fracture

Ultimate Strength

SHAM OVX S-G S-M

N 9,39 2,78 3,42 4,11*

mJ 0,86 0,17 0,36* 0,37*

N/mm2 4,99 1,48 1,82* 2,18*

Conclusion: Treatment of OVX rats with strontium over a five week period was able to partly correct the bone loss sustained in vehicle treated OVX rats. However, bone strength and BMD was only partly normalized indicating that increased doses or longer treatment duration may be required.

P359SU. STRONTIUM RANELATE NORMALIZES BONE MINERAL DENSITY IN OSTEOPENIC PATIENTS Malaise O, Bruyere O, Deroisy R, Jupsin I, Reginster J-Y; WHO Collaborating Center for Public Health Aspects of Osteoarticular Disorders University of Liege, Belgium Aims: Recent epidemiological studies have shown that a substantial fraction of fractures occurs in patients with osteopenia. Strontium ranelate was shown to reduce the incidence of vertebral and nonvertebral fractures in postmenopausal osteoporosis. The objective of this study is to assess the capacity of strontium ranelate to restore normal BMD (WHO definition: T-score R-1) in postmenopausal osteopenic women (T-score between -1 and -2.5). Methods: In the SOTI study (Spinal Osteoporosis Therapeutic Intervention) focused on vertebral fracture eﬃcacy of strontium ranelate, the patients included were osteoporotic at vertebral level and in the TROPOS study (Treatment of Peripheral Osteoporosis) focused on nonvertebral eﬃcacy, the patients included were osteoporotic at femoral neck level. Among these osteoporotic patients,

4240 were also osteopenic at the nonosteoporotic site. A post hoc analysis from the SOTI and TROPOS studies including these 4240 patients was performed. The patients received either 2 g a day of strontium ranelate or placebo for three years. BMD was measured at baseline and each year during three years. The results were analyzed on an intention-to-treat basis. Results: At lumbar spine, after one, two and three years of treatment with strontium ranelate, 28.4, 45.4 and 58.7%, respectively, of the osteopenic patients normalized their BMD compared to 4.9, 6.7 and 11.2% in the placebo group (all p <0.001). At the total hip, the percentage of patients normalizing their BMD was 7.3, 12.6 and 21.1% in the strontium ranelate group and 1.8, 1.5 and 2.0% in the placebo one (all p<0.001). Conclusion: Strontium ranelate is able to normalize BMD in a significant proportion of osteopenic patients.

P360MO. PROGESTINS WITH NO GLUCOCORTICOID ACTIVITY MAY BE A BETTER CHOICE FOR HORMONE REPLACEMENT THERAPY TO ACHIEVE MORE BENEFICIAL EFFECTS ON BONE METABOLISM Ishida Y, Taguchi T; Yamaguchi University School of Medicine, Yamaguchi, Japan This randomized controlled trial was conducted to test the hypothesis that progestins with no glucocorticoid (GC) activity may be a better choice for hormone replacement therapy (HRT) to achieve more beneficial eﬀects on bone metabolism. A total of 104 postmenopausal women aged 50–75 with osteoporosis were randomly allocated into three groups: 1) HRT- medroxyprogesterone acetate (MPA, with significant GC activity) (conjugated estrogen 0.625 mg/day plus MPA 2.5 mg/day); 2) HRT- norethisterone (NET, with no significant GC activity) (conjugated estrogen 0.625 mg/day plus NET 5 mg/day); or 3) control (no treatment). Thoracic and lumbar spine radiographs and bone mineral density (BMD) at distal 1/3 radius were assessed at baseline and at every 6 months during the 2-year study period, along with markers of bone turnover [serum bone specific alkaline phosphatase (BAP) and urinary N-telopeptide of type I collagen (NTX)]. Mean changes in BMD relative to baseline after the 2-year treatment in HRT-MPA, HRT-NET, and control was 1.6%, 2.7%, and -2.6%, respectively. Importantly, the rate of increase in BMD in HRTNET was significantly greater than that in HRT-MPA (p=0.019). In control, the incidence of new vertebral fractures during the 2-year treatment was 21% (7/34). The relative risk of a vertebral fracture compared with control was 0.13 (95% CI: 0.02- 1.07, p=0.06) for HRT-NET and 0.40 (95% CI: 0.10- 1.56, p=0.18) for HRT-MPA (HRT-NET versus HRT-MPA, p=0.34). There were significant decreases in BAP from baseline after the 2-year treatment in HRT-MPA (-23.8%, p<0.01) and HRT-NET (-19.2%, p<0.01) (4.6% diﬀerence, p=0.17). A significant reduction in NTX was seen in HRT-MPA (-45.4%, p<0.001) and HRT-NET (-47.9%, p<0.001) (2.5% diﬀerence, p=0.58). This study showed significant increase in BMD for HRT-MPA and HRT-NET, as compared to control, in which the rate was significantly higher in HRT-NET than that in HRT-MAP. The data suggest that progestins with no significant GC activity may be a better choice for the HRT treatment to achieve more beneficial eﬀects on bone metabolism than progestins with strong GC activity.

P361SA. OSTEOPOROSIS INTERVENTION IN AMBULATORY PATIENTS WITH PREVIOUS HIP FRACTURE Minisola S1, Romagnoli E1, Colapietro F1, Di Nicola C2, Scillitani A3, Carnevale V3; 1Università di Roma ’’La Sapienza’’, Rome, Italy, 2Associazione Italiana Donne Medico, Rome, Italy, 3Ospedale ’’Casa Sollievo della Soﬀerenza’’ S. Giovanni Rotondo, Italy We investigated the patterns of treatment and adherence to therapies in 2191 ambulatory patients with previous hip osteoporotic fractures, at 207 orthopedic centers throughout Italy. All patients were administered a questionnaire (investigating: age, sex, height, weight, date of admission and length of hospital stay, previous clinical fractures, bone density or biochemical

S228 testing concerning mineral metabolism, treatment with bone active drugs in the 6 months before fracture, treatment after discharge from the hospital, continuous use of prescribed drugs, pain at the site of hip surgery, comorbidity) by the involved orthopaedic surgeons. A multivariate logistic regression model tested a subset of the investigated variables, to determine which factors significantly influenced discontinuation of treatment after hip fracture. Among patients, 88.1 % were female and 86.2% were older than 65. The mean length of stay in the hospital for hip fracture was 19.0 25.3 days. At the time of interview, the mean time since hospitalization was 542.9 1197.3 days. 20.2% of patients referred a previous clinical fracture. Before hip fracture, 52.8% of patients had never received any treatment (73% if we included those who had taken only calcium and/or vitamin D). Corresponding proportions after fracture were 22% and 31.3%, respectively. Finally, 52% of patients had stopped osteoporosis treatment after a mean period of 1.4 years. Dropout curves with time of patients stopping therapies showed that the suspension of therapy (mostly noticed in the immediate period following fracture) was most common in the oldest (R82 yrs) with respect to youngest(%73 yrs) patients (2=39.985; p=0.00). According to the results of the logistic regression, increasing age, pain (OR: 1.36; 95% CI 1.21– 1.65) and no use of diagnostic tests (OR: 2.46; CI: 1.79–3.37) showed a positive eﬀect on the probability of quitting the medication. On the other hand, being female reduces by half (OR: 0.49; CI: 0.37–0.45) the probability of quitting medication. Our data showed a low rate of primary prevention, a still insuﬃcient post-fracture therapy, along with a high rate of early discontinuation of osteoporosis medication in patients with previous hip fracture.

P362SU. THE IMPACT OF HABITUAL VERSUS STRENGTH TRAINING EXERCISE ON REGIONAL BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN: GROUND VERSUS JOINT REACTION FORCES Cussler EC, Going SB, Metcalfe LL, Houtkooper LB, Blew RB, Lohman TG; University of Arizona, Tucson, Arizona, USA The aim of this study was to examine the role of habitual exercise in the change in bone mineral density (BMD) in calcium-replete postmenopausal women randomized to a strength training program or control. Twenty-three controls were matched with 23 of the most compliant exercisers (mean 4-year exercise frequency R 50%) by hormone use, baseline body weight/BMI, and age. BMD was measured by dual x-ray absorptiometry at baseline and 4 years. Habitual exercise (excluding prescribed weight training) was assessed annually with the 7-day physical activity recall questionnaire. Primarily walking/running (32.4%), routine housework (31.0%) and light yard-work (14.3%), and other ground-reaction (e.g., dancing and hiking) activities were reported. Percent attendance at strength training sessions was used to measure exercise frequency among exercisers. Controls gained significant body weight over 4 years (2.24.5 kg; p<0.05) while exercisers gained a significant quantity of lean soft tissue (LST: 0.81.2 kg; p<0.01). Exercisers gained lumbar spine (LS) BMD (0.0190.042 gccm-2; p<0.01) while controls lost femur neck (FN) BMD (-0.0190.051 gccm-2; p<0.01). Exercisers gained more LST (p<0.10), more LS BMD (p<0.01), and more femur trochanter (FT) BMD (p<0.01) than controls. Four-year mean total calcium intake and habitual exercise energy expenditure (EEE) were similar for the two groups. Among the controls, mean EEE was significantly correlated with the residuals of 4-year FN and LS BMD regressed on baseline values (r=0.42; p<0.05). EEE was not correlated with FT BMD residuals among controls and with no BMD measure at any site among exercisers. Multiple linear regression, controlling for change in body weight, confirmed these associations. The positive relationship between 4-year habitual exercise and BMD among controls and strength training exercise and BMD among weight lifters suggested that diﬀerent types of long-term exercise influenced BMD at diﬀerent skeletal sites. Specifically, while habitual exercise (ground reaction forces) appeared to impact FN BMD, weight lifting (joint reaction forces) was associ-

ated with increases in FT BMD. The LS BMD responded to both forms of exercise.

P363MO. POSSIBLE ROLE OF PTH IN THE ANABOLIC EFFECT OF PAMIDRONATE IN ADULT RATS FED A LOW PROTEIN DIET Ammann P, Dayer R, Rizzoli R; Division of Bone Diseases, University Hospital, Geneva, Switzerland Isocaloric low protein intakes decrease bone mass and bone strength in adult rats. This is associated with increased bone resorption and decreased bone formation. We previously reported that bisphosphonate administration not only prevented bone quality alteration but also significatively improved bone microarchitecture as compared with pretreatment values (JBMR 2005,20:1365). In order to better understand the mechanism underlining this potential anabolic eﬀect of bisphosphonates, we investigated the eﬀects of pamidronate in 6-month-old female pair-fed a control (15% casein) or an isocaloric low-protein (2.5% casein) diet. Pamidronate (0.6 mg/kg.day) was given subcutaneously during 5 days at the beginning of the study. Bone and serum samples were collected 6 weeks later. Serum PTH, IGF-I and osteocalcin were measured. Microarchitecture (trabecular bone volume: BV/TV; trabecular thickness: Tb.Th) and bone strength were also measured at the level of vertebrae. Values are meansSEM, *p<0.05 vs control, (p<0.05 vs low casein as evaluated by ANOVA.The increase in trabecular thickness and bone strength could be the reflection of a positive bone balance. Isocaloric low protein intake increased PTH secretion despite identical calcium and vitamin D intakes. The administration of pamidronate accentuated secondary hyperparathyroidism. The increased PTH together with an inhibition of bone resorption by pamidronate could possibly explain the bone anabolic eﬀect observed in rats fed a low protein diet and treated with a bisphosphonate. In conclusion, secondary hyperparathyroidism induced by a low protein intake and the inhibition of bone resorption by pamidronate were associated with an anabolic bone response and an increase in bone strength.

PTH (pg/ml) IGF-I (ng/ml) Osteocalcin (µg/l) Maximal load (N) BV/TV (%) Tb.Th (mm)

Control

Low protein

Low protein+ pamidronate

1699 68153 12.30.5 19821 25.81.8 0.0800.003

26456* 52537* 11.90.7* 18425 18.42.9* 0.0710.002*

45269*( 51827* 8.60.4* 27022*( 27.02.2( 0.0890.002*(

P364SA. VITAMIN D STATUS AND SECONDARY HYPERPARATHYROIDISM IN THE ELDERLY: EFFECT OF TREATMENT Crilly RG, Kloseck M, Nassur R, DeAngelis D; University of Western Ontario, London, Canada Aim: This study describes the vitamin D status of our elderly clinical population, determines the 25 hydroxy vitamin D (25 OHD) level needed to suppress parathyroid hormone (PTH) levels (and thus minimize bone loss), and explores the oral intake needed to achieve that level and the additional impact of calcium supplementation. Methods: A convenience sample of 150 patients, (100 women), age 73.4 14 SD, with spinal and/or hip fracture or attending the geriatric day hospital, were studied. Data collected included vitamin D intake as supplementation, blood levels of 25 OHD, PTH, urea and creatinine. Those with abnormal urea or creatinine were excluded. Results: 12.6% of patients not on vitamin D supplements fell into the accepted deficiency range (<25 nmol/L), 54% were between 25 and 60 (the new lower level of normal proposed recently) and 21% above 60 nmol/L. PTH levels correlated in inverse curvilinear fashion with 25 OHD levels. In patients on vitamin D supplements, PTH levels reached a minimum at 25 OHD levels of 80 to 100 nmol/L.

S229 In patients not on vitamin D supplements, PTH level correlated with dose of calcium supplementation (r = -.35 p < .001) but in all patients on vitamin D supplements of 400 I.U./day or over for three months or more, no such correlation was found. Although vitamin D level correlated with D supplementation dose (r = .312 p < .001) only 59% of those on 1000 I.U./day have levels of 80 nmol/L or more, the level associated with maximum suppression of PTH. Conclusions: The elderly population needs a D level of 80 – 100 I.U./day to achieve maximum suppression of PTH and thus minimize the contribution of secondary hyperparathyroidism to age-related bone loss. However, many on a supplementary dose of 1000 I.U. do not reach that level either because the dose is insuﬃcient or compliance is poor. The additional role of calcium supplements in those on vitamin D supplements is unclear, but may be small.

P365SU. PATIENTS TAKE CALCIUM WITHIN 30 MINUTES OF THEIR BISPHOSPHONATES Dawson-Hughes B1, Heitmeyer S2; 1Tufts University, Bone Metabolism Lab, Boston, MA, USA, 2Procter & Gamble Pharmaceuticals, Mason, OH, USA Aims: Calcium consumption close to an oral bisphosphonate treatment can undermine the eﬀectiveness of an osteoporosis therapy. By binding to bisphosphonates, calcium interferes with the absorption of oral bisphosphonates. Thus, correct timing of bisphosphonate and calcium doses is important for patients to receive full benefits of their osteoporosis treatment regimen. The Alliance for Better Bone Health commissioned Harris Interactivet to conduct an online and telephone survey to ascertain the calcium consumption habits of U.S. women aged 50+. Methods: A total of 1,004 women were interviewed (703 online, 301 phone) in February 2005. Of this total, 372 were currently taking a bisphosphonate. Data were weighted to be representative of US population of women >50 years of age. Sampling error for the overall results is +/- 3 percentage points. The 372 survey participants currently taking a bisphosphonate (Actonelt or Fosamaxt) were asked for a yes/no response to the following questions: -Do you ever take a calcium supplement at the same time you take (Actonelt/Fosamaxt Daily/Weekly)? -Do you ever take a calcium supplement within 30 minutes of taking (Actonelt/Fosamaxt Daily/Weekly)? Results: A total of 338 calcium users responded to these two questions; of these, 26% answered ’’yes’’ to both questions. [Figure 1.] Conclusions: Calcium intake for osteoporotic women taking bisphosphonates is an important part of their overall therapy.

About 1 in 4 patients take calcium incorrectly with their bisphosphonate, undermining the eﬀectiveness of the bisphosphonate. Following the Surgeon General’s Report on Bone Health recommendation to simplify and organize treatment regimens may increase the percentage of patients who take calcium correctly with their bisphosphonate. This potentially can maximize the fracture risk reduction benefits of their osteoporosis therapy.

P366MO. LOW RATES OF VITAMIN D SUPPLEMENTATION IN CANADIANS WITH LOW BONE MASS OR FRACTURES Sawka AM1, Papaioannou A2, Josse RG1, Murray TM1, Thabane L2, Hanley DA3, Ioannidis G2, Olszynski WP4, Brown JP5, Sebaldt RJ2, Petrie A2, Tenenhouse A6, Goldsmith CH2, Boulos P2, Adachi JD2; 1University of Toronto, Toronto, Canada, 2McMaster University, Hamilton, Canada, 3University of Calgary, Calgary, Canada, 4University of Saskatchewan, Saskatoon, Canada, 5Centre Hospitalier Universitaire de Quebec, Ste-Foy , Canada, 6McGill University, Montreal, Canada Aims: Out aim was to determine the baseline patterns of calcium and vitamin D consumption among Canadians referred to osteoporosis specialists for evaluation of low bone mass or fracture. Methods: We performed a cross-sectional analysis of baseline characteristics of patients referred to specialists for evaluation of low bone mass or fractures. Univariate analyses were performed using chi-squared analysis for categorical variables and Student’s t-test for continuous variables. Results: We examined data from 5604 women and 561 men of a mean age 64 years (standard deviation [SD] 9). The percentages of individuals who had suﬀered one or more prevalent fracture at respective sites were: vertebra 15% (893), hip 4% (219), wrist 15% (922), and rib 7% (429). The mean T-scores for measured baseline bone mineral densities were: -2.16 (standard deviation [SD] 1.37) at L2-L4 (in 3399 individuals), and -2.08 (SD 0.99) at the femoral neck (in 4295 individuals). Overall, 59% of individuals reported current consumption of a calcium supplement (3636/6165) but only 27% (1653/6165) reported current consumption of a vitamin D supplement. Women were more likely than men to consume supplementary calcium (p<0.001) and vitamin D (p<0.001), respectively. Among, 4827 individuals reporting their dietary calcium consumption, the mean number of 250-mg dietary calcium servings consumed per day was 2.0 (SD 1.4). Consumption of dietary calcium was higher in men (2.1, SD 1.6), than women (2.0, SD 1.4) (p=0.039). Individuals weighing more than 80 kg were less likely to consume calcium and vitamin D supplements compared to leaner individuals (respective p<0.001); consumption of dietary calcium was similar between the heavier and leaner groups (p=0.63). Of particular concern, less than one daily serving of dietary calcium was reported by 23% individuals (1091/4827); among individuals consuming less than one serving of dietary calcium per day, 40% did not take any calcium supplement (437/1091) and 75% did not take any vitamin D supplement (814/1091). Conclusions: Vitamin D supplementation is underused by the majority of Canadians referred to osteoporosis specialists for evaluation of low bone mass or fracture. Calcium supplementation may be particularly underused by men and overweight individuals.

P367SA. CHOLECALCIFEROL SUPPLEMENTATION REVERTS 25HYDROXYVITAMIN D (25OHD) INSUFFICIENCY AND INCREASES LOWER LIMB MUSCLE STRENGTH (LLMS) IN ELDERLY PEOPLE LIVING IN LONG-STAY GERIATRIC CARE (LSGC) Pedrosa MAC, Moreira LDF, Barros ER, Kunii I, LazarettiCastro M; Division of Endocrinology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil Aims: Assess the security and eﬃcacy of a cholecalciferol supplementation on 25OHD and PTH serum levels, LLMS and number of fallers in elderly population living in LSGC. Methods: In a double-blind, placebo-controlled study, 56 elderly were randomized in G1 for placebo and G2 for cholecalciferol. All participants received 1000 mg/day of elemental calcium. Serum

S230 25OHD, PTH and calcium were measured at baseline(M1), 2 months(M2) and 6 months(M3) after treatment with placebo or cholecalciferol. G2 received 150.000 IU/month during the first 2 months(summer) and 90.000 IU/month in the 4 subsequent months(autumn). Falls were recorded in a diary. LLMS was assessed by a muscle strength index, including hip flexors and knee extensors, measured by a hand-held dynamometer. Panel data for gamma distribution and Chi-square test were used for statistical analysis. Level of significance was set at 0.05. Results: At baseline, the groups were similar with relation to all variables investigated. 25OHD serum levels increased at M2 and decreased at M3 in both groups (table), but cholecalciferol supplementation was associated with higher levels of 25OHD at M2 (G2/G1:OR=1.4, 95%CI=1.17–1.6, p<0.0001) and moreover at M3(G2/G1:OR=1.52, 95%CI=1.3–1.8, p<0.0001); it was also related with a 20% augment in LLMS (OR=1.20,95%IC=1.12–1.29). Before treatment, 25OHD insuﬃciency(<50 nmol/L) aﬀected 64.3% of the subjects in G1 and 71.5% in G2. After treatment, 40% of G1 patients remained insuﬃcient whereas no patient in G2. The number of fallers after supplementation was lower in G2(4 fallers14.3%) than in G1(9 fallers-33.3%), but it was not statically significant. PTH levels declined at M2 equally in both groups. Conclusions: Cholecalciferol supplementation was safe and effective in enhancing 25OHD levels and reducing the prevalence of 25OHD insuﬃciency. Although there was no significant diﬀerence between the groups in relation to PTH levels, there was an important improvement in lower limb muscle strength of the treated group. Table: Variation in the serum levels of 25OHD (nmol/L), PTH (pg/mL) and Total Calcium (ng/mL) in G1 (calcium-placebo) and in G2 (calcium-cholecalciferol) between the three assessed moments Variables

Groups

M1

M2

M3

25OHD

G1

39.5 (20.3–68–8) 45.9 (20.3–84.8) 45.0 (20.7–162.7) 48.5 (24.3–158.1) 9.0 (7.4–9.4) 8.85 (7.9–9.9)

73.9 (27.5–167) 99,8 (62.0–146.3) 35.6 (8.03–66.49) 30.1 (2.0–101.6) 9.7 (8.9–10.6) 9.8 (8.9–10.5)

51.8 (23.5–107.8) 86.6 (52.3–106.5) 47.47 (6.58–101.50 41.42 (21.6–151.6) 8.9 (7.3–10.0) 9.1 (8.3–9.8)

G2 PTH

G1 G2

Total Calcium

G1 G2

Values are expressed as median and minimum-maximum

P368SU. ON THE ASSOCIATION BETWEEN STATIN AND FRACTURE: A BAYESIAN CONSIDERATION Wang CY, Nguyen ND, Eisman JA, Nguyen TV; Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, Australia Aim: Despite observational studies have suggested that statin use may be associated with reduced fracture risk, the association is controversial, due to conflicting findings from published studies, probably due to publication bias. This study utilized the Bayesian approach to combine existing evidence and update the association with consideration of potential publication bias. Methods: Data on the association between statin use and fracture incidence from 11 observational studies and 3 secondary analyses of randomized clinical trials (RCTs) were synthesized by both Empirical Bayesian analysis and fully Bayesian randomeﬀects meta-analysis models. Sensitivity analyses were carried out to estimate the eﬀect of potential bias on the observed association. The heterogeneity of eﬀect sizes was assessed by the coeﬃcient of inconsistency. Results: Empirical Bayesian analysis showed that statin use was associated with a reduction in hip fracture risk with odds ratio (OR) being 0.56 and 95% credible interval (CrI) ranging from 0.44 to 0.70. The OR for non-vertebral fracture was 0.62 (95% CrI,

0.56–0.68). These results were comparable with the fully Bayesian random-eﬀects meta-analysis’. The probability that statin use reduces fracture risk by at least 20% was 0.99 for hip fracture and 0.85 for non-vertebral fracture. Smaller studies tended to produce larger eﬀect sizes, raising the possibility of publication bias. Under the assumption that the bias over-estimates the true OR by 10%, there is still a probability of 0.975 that statin use reduces hip fracture risk; however, the eﬀect on non-vertebral fracture was less robust with a probability of 0.86. If bias over-estimates the true OR by 30%, the probability that statin is associated with reduced hip fracture and vertebral fracture is 0.95 and 0.45, respectively. Conclusion: These findings suggest statin use can reduce hip fracture risk; however, there is considerable uncertainty on the association between statin use and vertebral fracture. The Bayesian approach presented here can help researchers update existing evidence when new data becomes available and take into account potential bias.

P369MO. PRESCRIPTION VITAMIN D USE AMONG PATIENTS TAKING ANTIRESORPTIVE AGENTS IN CANADA Hanley DA1, Zhang Q2, Meilleur MC3, Mavros P2, Sen SS2; 1 University of Calgary, Calgary, Alberta, Canada, 2Outcomes Research, Merck & Co., Whitehouse Station, NJ, 3Health Economics, Merck & Co., Kirkland Quebec, Canada Objective: Although vitamin D is recommended as a part of osteoporosis management, recent studies suggest many patients with osteoporosis are not taking vitamin D. This study evaluated the rate of use of prescription vitamin D among patients who were taking anti-resorptive agents (ARAs) for their osteoporosis in Quebec, Canada. Methods: We examined reimbursed pharmacy claims in a random patient sample from the public insurance plan Régie d’Assurance Médicament du Québec who were 65 or older with at least one prescription (Rx) for alendronate, risedronate or raloxifene between January 1st 1996 and December 31, 2004. Pattern of use of prescription vitamin D and ARAs was assessed by reviewing pharmacy claims during the 1-year observation period following the patient’s first (index) Rx for ARA between January 1st, 1996 and December 31, 2003 (index period). A vitamin D and ARA possession ratio was computed as ratio of total number of days of prescription vitamin D supply to total number of days of ARAs supply during the observation period. Results: A total of 50,225 patients were reviewed of whom 90.5% were female. Approximately 28%, 28%, 22%, 14% and 8% of patients were 65–69 years, 70–74 years, 75–79 years, 80–84 years and 85 years or over, respectively. Only 38.25% of these patients had any use of prescription vitamin D during the observation period. Higher age groups were associated with higher proportion of prescription vitamin D use, with 32%, 36%, 40%, 45%, and 47% of patients in the 65–69 years, 70–74 years, 75–79 years, 80–84 years and 85 years or older age groups respectively. The vitamin D and ARA possession ratio was 0.55 (2.9) indicating that patientdays taking prescription vitamin D were only about half of the days taking ARAs. Similar observations were made for a sub-set of patients who did not change ARAs from their index ARA Rx during the observation period. Conclusion: Prior studies have shown high prevalence of inadequate vitamin D nutrition in Canada, and a need for vitamin D supplementation. However, even with a diagnosis of osteoporosis requiring the use of ARAs, a majority of patients are not taking vitamin.

P370SA. RISEDRONATE SHOWN TO BE SAFE AND EFFECTIVE IN MEN WITH OSTEOPOROSIS IN A 2-YEAR, DOUBLE-BLIND, RANDOMIZED, PLACEBOCONTROLLED, MULTICENTER STUDY Boonen S1, Delmas PD2, Wenderoth D3, Stoner KJ4, Eusebio R5, Orwoll ES6; 1University Hospital Leuven, Leuven, Belgium, 2INSERM Research Unit 403, Lyon, France, 3Procter and Gamble Pharmaceuticals, Schwalbach a. Ts., Germany, 4Procter and Gamble Pharmaceuticals, Egham, UK, 5Procter and Gamble Pharmaceuticals, Mason, OH, USA, 6Oregon Health Sciences University, Portland, OR, USA

S231 Aims: The objectives of this 2-year, double-blind, randomized, placebo-controlled, parallel group, multicenter study were to determine the eﬃcacy and safety of risedronate 35 mg once a week compared to placebo in men with osteoporosis. Methods: 284 men (95% Caucasian) between the ages of 36 and 84 years, inclusive, who had osteoporosis (lumbar spine T-score %2.5 and femoral neck T-score %-1 SD or lumbar spine T-score %-1 and femoral neck T-score % -2 SD) were randomized (2:1) to either risedronate 35 mg once a week (N=191) or placebo (N=93) and received daily supplementation of calcium (1000 mg) and vitamin D (400–500 IU) for 2 years. Eﬃcacy was assessed by percent change from baseline in lumbar spine and total proximal femur, femoral neck, and femoral trochanter bone mineral density (BMD) and bone turnover markers (BTMs) including type I collagen C-telopeptide (CTx), type I collagen N-telopeptide/ creatinine (NTx/cr), and bone-specific alkaline phosphatase (BAP). BMD was measured at Months 6, 12, 24, and endpoint (last observation carried forward); BTMs were measured at Months 3, 6, 12, 24, and endpoint. Results: The primary endpoint showed a statistically significant diﬀerence between risedronate and placebo groups in mean percent change from Baseline to endpoint in lumbar spine BMD [4.53% (95% CI: 3.46%, 5.60%)]. The risedronate group had statistically significant increases compared to placebo in mean percent change from Baseline for lumbar spine BMD at Months 6, 12, and 24, total proximal femur and femoral trochanter BMD at Months 12, 24, and endpoint, and femoral neck BMD at Month 24 and endpoint. The mean percent change values for all BTMs (CTx, NTx/cr, and BAP) were statistically significantly reduced in the risedronate group compared to baseline and to placebo at all time points measured. The 2 treatment groups were comparable in overall percentages of patients with adverse events (AEs) (73% placebo, 70% risedronate), serious AEs (16% placebo, 15% risedronate), moderate-to-severe upper GI AEs (4% placebo, 3% risedronate), and overall musculoskeletal AEs (11% placebo, 12% risedronate). Conclusions: In this 2-year study, risedronate 35 mg once a week was safe and eﬀective for the treatment of osteoporosis in men.

P371SU. HIP PROTECTOR BIOMECHANICAL EFFECTIVENESS: THE INFLUENCE OF SOFT TISSUE STIFFNESS Laing AC, Gillan CP, Robinovitch SN; Injury Prevention and Mobility Laboratory, School of Kinesiology, Simon Fraser University, Burnaby, BC, Canada Aims: Wearable hip protectors may reduce hip fracture risk in the event of a fall. However, there are no accepted standards for measuring the biomechanical eﬀectiveness of these devices. One factor that should aﬀect force attenuation (and therefore needs to be simulated accurately) is the spring stiﬀness of the skin, fat, and muscle overlying the hip region, which acts in-series with the spring stiﬀness of the hip protector. Our aim was to determine how the stiﬀness of these tissues aﬀects the force attenuation provided by hip protectors. Methods: Our test system, which consists of an impact pendulum and surrogate pelvis, measures the peak force applied to the proximal femur (Fmax) during a simulated sideways fall. The system matches the eﬀective mass and pelvic stiﬀness of the body during impact to the hip, pelvis surface geometry, and the impact velocity of the body during a fall (2.6 m/s). We used this system to determine how soft tissue stiﬀness (simulated with closed-cell polyethelene foam) aﬀects the attenuation in Fmax provided by rigid and soft shell hip protectors. We varied the soft tissue stiﬀness (measured by indentation testing) between ‘‘stiﬀ’’ (183 kN/m), ‘‘physiologic’’ (23 kN/m, matching the average stiﬀness measured in 15 elderly women), and ‘‘compliant’’ (10 kN/m). Results: The force attenuation provided by hip protectors increased with increasing soft tissue stiﬀness (p<0.001). In the physiologic condition, the rigid and soft protectors attenuated peak force by 19% and 22%, respectively. In the stiﬀ condition, force attenuation increased to 32% and 47% for the rigid and soft protectors, respectively. In the compliant condition, force attenuation decreased to 2% and 14% for the rigid and soft protectors, respectively.

Conclusions: These results indicate the need for impact testing systems to accurately simulate soft tissue stiﬀness in order to provide valid estimates of the biomechanical eﬀectiveness of hip protectors. For soft protectors, the eﬀect is simply of springs acting in series. For rigid hip protectors, tissue stiﬀness influences the amount the hip protector intrudes into the soft tissues, which aﬀects its ability to form an energy-shunting bridge. Funded by grants from NSERC, CIHR, MSFHR, and Tytex, Inc.

P372MO. VERTEBRAL FRACTURES AFFECT SPINE LOADS IN VIVO Briggs AM1, Wrigely TV1, Dieen JHv2, Phillips B3, Lo SK4, Greig AM1, Bennell KL1; 1Centre for Health, Exercise and Sports Medicine, School of Physiotherapy, University of Melbourne, Melbourne, Australia, 2Institute for Fundamental and Clinical Human Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands, 3Rehabilitation Sciences Research Centre, School of Physiotherapy, University of Melbourne, Melbourne, Australia, 4 Faculty of Health and Behavioural Sciences, Deakin University, Melbourne, Australia Aims: The aetiology of osteoporotic vertebral fractures is multifactorial and complex, and cannot be explained solely by low bone mineral density. Examination of physiologic loading of vertebral bodies in vivo may help to explain mechanisms underlying fracture and recurrent fracture. The aim of this study was to model physiologic load parameters in individuals with and without osteoporotic vertebral fractures in upright stance, to determine if spinal loading profiles diﬀer between these groups. Methods: Gravitational flexion moments and compression and shear forces due to gravity and trunk muscle force were calculated from T2-L5 in 12 participants with fractures (66.46.4yrs, 162.25.1cm, 69.111.2kg) and 32 without fractures (60.76.8yrs, 160.25.4cm, 63.310.3kg). Gravitational loading estimates were solved using static analysis for each vertebral level, while muscle forces were calculated using a detailed trunk muscle model driven by mathematical optimisation, with a cost function minimising muscle fatigue. Least squares regression was used to derive polynomial functions to describe normalised load profiles over vertebral levels. Non-linear regression co-eﬃcients were compared between the 2 groups using t-tests to examine diﬀerences in load profiles. Loads parameters were also compared between groups at the level of fracture and the vertebral level inferior. Results: Results are presented as normalised data. Fractures were most common in the mid-thoracic spine at T6 and T8. The fracture group demonstrated signficantly greater flexion moments across vertebral levels (9–82%, p=0.033). Significantly greater compression force (p<0.0001) and shear force (p=0.002) profiles (1–17% and 13–162%, respectively) were observed in the fracture group. The fracture group had significantly greater flexion moments (p<0.001) and shear forces (p<0.001) at the level of fracture and greater flexion moments (p=0.001) and compression force (p=0.004) at the level below the fracture, compared to the equivalent level in the non-fracture group. Conclusion: The diﬀerences observed in multilevel spinal loading between the groups may partly explain the reasons for increased risk of subsequent vertebral fractures. Force profiles are likely to diﬀer due to subtle changes in spinal curvature as a result of fracture. These results may provide valuable insight into interventions to improve posture and/or restore normal vertebral morphology in order to normalise spine force profiles.

P373SA. OSTEOPOROSIS MEDICATION PROFILE PREFERENCE: RESULTS FROM THE PREFER-US STUDY Weiss TW, Sen SS, McHorney CA; Merck & Co., Inc. West Point, PA and Whitehouse Station, PA, USA Aims: Assess patient preferences for osteoporosis medication profiles. Methods: 3,368 women age 50+ diagnosed or at risk for osteoporosis based on the 2003/2004 internet-based National Health and Wellness Survey responses received the PREFER survey via internet. Preferences assessed by comparing Drug A vs.

S232 Drug B with the same out-of-pocket costs, side eﬀects, potential for drug interaction, and spine fracture eﬃcacy. The two drugs diﬀered by the following attributes: time on market (recently vs. 10 years); dosing frequency (monthly vs. weekly); drug eﬀectiveness (not proven vs. proven to reduce non-spine or hip fracture after three years); and dosing procedure (60 vs. 30 minute wait). Patients (1) force-rank ordered, from 1–4, the four attributes according to their preference and (2) separately rated the importance of each attribute from 1 (extremely unimportant) to 7 (extremely important). Subgroup analyses were performed by demographics, osteoporosis diagnosis, treatment status, fracture status, and selected comorbidities. Comparisons were made by Chi-Square. Results: We collected 999 responses after three days and stopped compiling responses after achieving sample size targets. Mean age was 65. Drug B was chosen by 96% of respondents. Drug eﬀectiveness was ranked as the most important determinant of their preference (80% ranked as #1 reason for their choice) compared to time on market (14%), dosing procedure (4%), and dosing frequency (2%). Eﬀectiveness had the highest mean importance rating (6.1, S.D. 1.8), followed by time on market (4.7, S.D. 1.7), dosing procedure (4.6, S.D 1.4), and dosing frequency (4.5, S.D. 1.4). No subgroups showed any significant diﬀerences in choice of Drug A vs. Drug B. Conclusions: The drug profile with proven data on fracture risk reduction was chosen by almost all respondents. Drug eﬀectiveness was the most important determinant of preference, while dosing frequency was a weaker determinant of preference. These findings were largely invariant across subgroups.

P374SU. AN EVALUATION OF CONVENIENCE AMONG PATIENTS TAKING OSTEOPOROSIS MEDICATIONS: RESULTS FROM THE PREFER-US STUDY Gold DT1, McHorney CA2, Weiss TW2, Silverman SL3; 1Duke University Medical Center, Durham, NC, USA, 2Merck & Co., Inc, West Point, PA , USA, 3Ceders Sinai/UCLA, Los Angeles, CA, USA Aims: Adherence to osteoporosis medication is not optimal. Dosing convenience has been suggested as one reason for poor adherence. We evaluated attitudes towards dosing convenience among patients reporting current use of osteoporosis medication. Methods: Sample included 3,368 women age 50+ who responded to the 2003 or 2004 internet-based National Health and Wellness Survey, had been diagnosed with osteoporosis, considered themselves at-risk, or had a family history of osteoporosis. Respondents were re-contacted to complete the PREFER survey on-line. Responses provided by 999 women during a three-day period: 351 reported current use of a single prescription osteoporosis medication and were asked six questions regarding dosing convenience. An osteoporosis medication convenience score was derived from all six questions, ranging from 0 (convenient none of the time) to 100 (convenient all of the time). Bivariate subgroup analyses of the convenience score were performed for demographics, osteoporosis diagnosis, fracture status, dosing frequency, and selected comorbidities by t-test for nominal variables or by ANOVA for categorical variables. A multivariate model was developed to examine predictors of convenience. Results: 80% of respondents were taking a bisphosphonate, of whom 90% took weekly dosing. 85% reported that it was easy to take their prescription osteoporosis medication (i.e., ‘all of the time’ or ‘quite a bit of the time’). 80% reported that the frequency of taking their medication is acceptable, 79% reported that remembering to take their medication was easy, while 90% reported exactly following their doctor’s suggestions for taking their medications most or all of the time. Only 19% wanted to take their medication less often, and only 5% reported forgetting to take their medication often. Based on the overall convenience score, 75% of respondents had minor or no convenience issues. Respondents taking calcium and/or vitamin D supplementation had higher convenience scores as did those with more education or better health status. A multivariate model failed to demonstrate any significant predictors of convenience. Conclusions: Three in four women in this study currently taking osteoporosis medication had little or no convenience concerns. More research is needed to better understand how convenience

influences medication adherence relative to other medication attributes.

P375MO. THE RATE THAT FAMILY PHYSICIANS PRESCRIBE BISPHOSPHONATES TO THEIR PATIENTS: CANADIAN QUALITY CIRCLES (CQC) NATIONAL PROJECT Hodsman A1, Ioannidis G2, Papaioannou A2, Kvern B3, Thabane L2, Gafni A2, Johnstone D4, Crowley C4, Plumley N4, Adachi JD2; 1 University of Western Ontario, London, Canada, 2McMaster University, Hamilton, Canada, 3University of Manitoba, Winnipeg, Canada, 4Procter and Gamble Pharmaceuticals, Toronto, Canada Aim: The CQC Project was designed to improve family physicians’ (FPs) adherence with the new Canadian osteoporosis (OP) guidelines (2002). Methods: The project consists of five phases: wave I data collection, 1st educational intervention, wave II data collection, 2nd educational intervention, and wave III data collection. This interim analysis (wave I & II) examined the rate that FPs prescribed bisphosphonates to their patients. Patients were classified into two groups: all patients, and the sub-group with prior fractures. Patients were further subdivided according to their bone density (BMD). The guidelines recommend that therapy should be administered in patients with osteoporosis (t-score <-2.5) or those with low BMD (-1 to -2.5) plus a fracture. The available bisphosphonates were alendronate, etidronate, and risedronate. The results are summarized using counts (percent). A total of 340 (wave I) and 289 (wave II) FPs formed 34 Quality Circles (QC). FPs collected data using a standardized collection form. A total of 8376 (wave I) and 6972 (wave II) separate patient records were analyzed. All patients were women 55 years and older. During the educational intervention QC’s met to discuss profiles (snapshots of the physician’s management of osteoporosis) and to participate in an OP workshop. Results: A total of 883/8376 (10.5%) and 867/6972 (12.4%) patients had a prior fracture at the hip, wrist, or spine during wave I and II, respectively. Furthermore, 2547/8376 (30.4%) and 2295/ 6972 (32.9%) patients were administered a bisphosphonate. Table 1 shows the number of patients taking a bisphosphonate according to their BMD and prior fracture status. Table 1: The rate that FPs prescribe bisphosphonate therapy to their patients according to their BMD and prior fracture status. Wave I

T-score BMD not tested >-1.0 -1 to -2.5 <-2.5

Wave II

All: On therapy Count (%)

With fractures: On therapy Count (%)

All: On therapy Count (%)

With fractures: On therapy Count (%)

199 (7.1)

77 (43.5)

143 (8.01)

75 (45.2)

73 (4.9) 703 (34.7) 1545 (87.1)

13 (25.0) 95 (56.2) 399 (87.7)

56 (4.6) 935 (43.0) 1091 (90.3)

9 (23.1) 208 (74.8) 302 (92.6)

Conclusions: Most patients with a t-score <-2.5 were given a bisphosphonate. Following the educational intervention more high risk patients were on a bisphosphonate. This is particularly true in patients with moderately low BMD (-1 to -2.5) and a fracture. The QC intervention appeared to modify FPs behaviour.

P376SA. KYPHOPLASTY VERSUS CONSERVATIVE TREATMENT IN OSTEOPOROTIC VERTEBRAL FRACTURES: PROSPECTIVE 12-MONTH RESULTS OF A COMPARATIVE STUDY Lienert A, Komp M, Ruetten S, Godolias G; Department Spine Surgery and Pain Therapy, Center for Orthopaedics and Traumatology, Department of Radiology and Microtherapy University of Witten/Herdecke, St. Anna-Hospital, Herne, Germany

S233 Vertebral compression fractures (VCF) are the most common fractures in patients with osteoporosis. Osteoporotic vertebral fractures may induce severe acute pain. An increase of the kyphotic vertebral angle can result in chronic pain. Recurrent fractures lead to progressive kyphosis, which impacts pulmonary and gastrointestinal function and increase mortality. The negative consequences of vertebral fractures increase with the number of fractures and the degree of spinal deformation. Conservative treatment, consisting of pharmacological pain therapy, back bracing and exercise may result in pain reduction, but has no influence on the spinal deformation. Open surgery is only indicated in a small part of the patients. Balloon kyphoplasty is a minimal invasive percutaneous technique involving insertion of an inflatable balloon into the aﬀected vertebral body via a transpedicular, percutaneous approach, creation of an intravertebral bone void and fracture reduction via balloon inflation, with subsequent filling with bone cement. Methods: 36 patients with monosegmental vertebral compression fractures, proven on AP lateral radiograph, received balloon kyphoplasty (n=19) or conservative treatment (n=17) after informed patient selection of the treatment option. They were followed over a total period of 12 months. Evaluation points were 6 weeks, 6 and 12 months after intake. The visual analogue scale for back pain, the German version of the North-American-SpineSociety-Instrument and Oswestry-Low-Back-Pain-Disability Questionnaire and radiographs were evaluated. Results: In the group treated by balloon kyphoplasty there was a rapid and constant pain reduction. During the 12 months follow-up, 13 of 17 (76%) receiving conservative management experienced in total 23 subsequent fractures of which 19 were at a level adjacent to the index fracture. In contrast, 8 of 19 (42%) balloon kyphoplasty-treated patients experienced in total 10 subsequent fractures, 6 at adjacent levels. In the balloon kyphoplasty group all subsequent fractures except 1 were detected during radiological follow-up control and did not cause clinical discomfort. Conclusion: Balloon kyphoplasty is a more eﬀective and safe alternative for conservative management of recent painful osteoporotic vertebral fractures. In the balloon kyphoplasty group the incidence of subsequent vertebral compression fractures is significantly lower than in the group treated conservatively.

P377SU. NEGATIVE ATTITUDES TOWARD MEDICATIONS AMONG THOSE WITH OSTEOPOROSIS Schousboe JT1,2, Kind EA1, Adlis SA1, Kane RL2,3, Davidson ML4; 1Park Nicollet Health Services, 2Division of Health Services Research and Policy, University of Minnesota, 3Clinical Outomes Research Center, University of Minnesota, 4Department of Educational Psychology, University of Minnesota, Minneapolis, MN, USA Aims: Long-term adherence to oral bisphosphonate therapy to treat osteoporosis is poor and is largely unexplained. Negative attitudes regarding medications may play a role in medication non-adherence. The primary aim of this study was to develop a survey instrument to assess attitudes toward medications among adults diagnosed with osteoporosis. Methods: The study survey was sent to 503 patients with osteoporosis diagnosed by bone densitometry (T-score % -2.5 at the spine and/or femoral neck) at the Park Nicollet Osteoporosis Center, the sole provider of bone densitometry services at a large multispecialty clinic servicing 400,000 patients. Eligible participants were age 80 or younger. The survey included 18 questions regarding perceptions that medications are intrinsically harmful and/or are overused. Questions to assess socioeconomic status, co-morbidity, and past experiences of side eﬀects with medications were also included. Results: Four hundred forty one (87%) of those surveyed responded, and complete responses to all of the medication attitudes questions were recorded in 391 (77%). Exploratory factor analysis showed that 17 of the 18 questions regarding potential harm or overuse of medications loaded onto one factor. A reduced Medications Concerns Scale (MCS) using 12 of these items showed excellent fit to a generalized partial credit item-response theory

model (overall goodness of fit chi-square p-value 0.74), with good coverage of the breadth of the latent construct. The internal consistency reliability (Cronbach’s alpha) of the MCS was 0.83. The proportion of individuals answering ‘‘somewhat agree’’, ‘‘agree’’, or ‘‘strongly agree’’ on items indicating a concern regarding medications ranged from a low of 16% (for ‘‘Medicines do more harm than good’’) to 40% (for ‘‘I sometimes worry about becoming too dependent on my medications’’), to a high of 57% (for ‘‘Doctors in general use too many medicines’’). Twenty two percent had a raw total score indicating more agreement than disagreement with the items of the MCS. Conclusions: A substantial proportion of those with osteoporosis have ambivalent or negative attitudes regarding medications. Further studies are planned to validate the MCS survey instrument and to estimate the degree to which these attitudes explain non-adherence to medications to prevent osteoporotic fracture.

P378MO. PHYTOESTROGENIC FRACTION FROM HERBAL EPIMEDIUM PREVENTS BONE LOSS IN POSTMENOPAUSAL CHINESE WOMEN: A RANDOMIZED CONTROLLED CLINICAL TRIAL OF TWO YEARS Zhang G1, Qin L1, Shi Y2; 1Department of Orthopedics & Traumatology, Chinese University of Hong Kong, 2Institute of Orthopedics & Traumatology, Shanghai University of Chinese Medicine, China Aims: Information from the ‘Women’s Health Initiative’ implied a need to develop a safe alternative to HRT for preventing postmenopausal osteoporosis. Herbal Epimedium is a kind of ‘Bone Strengthening’ medicinal herb in traditional Chinese medicine without documenting any notable side eﬀects. Recently, we have successfully isolated phytoestrogenic fraction from herbal Epimedium (PFE; 10 mg PFE containing 5000 µg icariin, 250 µg genistein, 1250 µg daidzein and 3500 µg vehicle; prepared by Tong Ji Tang Pharmacal Company, Gui Zhou, China), and confirmed its prevention eﬀect on OVX-induced osteoporosis in a rat model. However, there is still lack of well-controlled clinical evidence on PFE. Especially, a long term prevention eﬀect of PFE on postmenopausal osteoporosis has not been established. We accordingly performed a two-year randomized controlled clinical trial to examine its eﬀects in prevention of postmenopausal osteoporosis. Methods: A total of 60 Chinese women within 10 years of onset of menopause were randomly assigned to PFE group (n=30, treated with PFE 120 mg/d and element calcium 300 mg/d) and control group (n=30, treated with placebo and element calcium 300 mg/d). Lumbar spine and proximal femur bone mineral density (BMD) and biochemical bone formation/bone resorption indices were measured at baseline, 1 year and 2 years after treatment. Results: BMD at all measurement sites in the PFE group did not change significantly (1.5% and 1.8% mean increase from baseline for lumbar and femoral neck, P>0,05 for both), whereas those decreased significantly in the control group (2.4% and 2.1% mean decrease form baseline for lumbar and femoral neck, P<0.05 for both). General Linear Model (GLM)-based repeated measure multivariate analysis of variance (MANOVA) showed significant diﬀerence in BMD at all sites between the PFE group and the control group (P<0.05). Urine DPD/Cr level was found significantly lower in the PFE group than that in the control group (P<0.05), whereas no diﬀerence was found in serum OC between the PFE and the control group (P>0.05). Conclusion: Two-year oral administration of phytoestrogenic fraction from herbal Epimedium is able to prevent bone loss at least through inhibition of bone resorption in postmenopausal Chinese women.

P379SA. THE RESPONSE OF BACK PAIN TO 12 MONTHS OF TERIPARATIDE (RHPTH1–34)IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS DEPENDS ON THE DEGREE OF BASELINE PAIN: SUBGROUP ANALYSES FROM THE EUROFORS STUDY Lyritis G1, Minne H2, Farrerons J3, Brixen K4, Ochs P5, Ginis A5, Skytte Jensen M5, Nickelsen T5; 1University of Athens, Athens,

S234 Greece, 2Klinik Der Fuerstenhof, Bad Pyrmont, Germany, 3Hospital Santa Creu i Sant Pau, Barcelona, Spain, 4Odense University Hospital, Odense, Denmark, 5Eli Lilly & Company Europe, Windlesham, UK The EUROFORS trial was designed to compare 3 sequential treatments of teriparatide (TPTD) over two years in women with established postmenopausal osteoporosis. In year 1, all subjects received open-label treatment with TPTD 20 µg/d with calcium and vitamin D supplements. This 12-month interim analysis investigates the changes in subjective back pain, assessed on a 100-mm visual analog scale. Subjects self-administered the instrument at baseline (BL) and after 1, 6, and 12 months of TPTD. Of the 865 subjects, 864 had a BL value, and 840 had R1 follow-up assessment and were included in the statistical analysis, which used the ’’last observation carried forward (LOCF)’’ approach. After 12 months, the mean back pain score had decreased by 11.523.3 mm from a BL score of 48.924.2 mm (p<0.001). The individual degree of back pain at BL was highly variable: 129 women had no back pain at BL (defined as %20 mm), while 276 suﬀered from severe pain (>60 mm). The results of further subgroup analyses comparing the changes in back pain among groups with diﬀerent BL pain levels are shown in the Table. Patients with a vertebral fracture in the 2 years prior to BL (N=506) had a higher BL level of pain (54.122.2) than those without a recent vertebral fracture (N=103; 50.023.9), but also had a greater decline in back pain, so that both groups reached a mean score of 39.6 (LOCF). The interindividual variability of pain response within each subgrop was high. In conclusion, in this uncontrolled cohort of postmenopausal women with advanced osteoporosis, 12 months of TPTD were associated with a stistically significant decrease in back pain; the highest decreases were observed in women with severe pain at BL or with a history of recent vertebral fractures. Change in back pain after 12 months of treatment with TPTD

Back painat BL (mm)

N

Change (mm) (mean + SD)

>30 to 50 >50 to 60 >60 to 70 >70

210 125 123 199

-6.3 + 20.8 -13.3 + 20.0 -17.2 + 24.3 -24.7 + 24.5

Number (%) of women with decrease by 30 to 50 mm

>50 mm

30 25 27 40

N.A. 3 (2.4) 14 (11.4) 33 (16.6)

(14.3) (20.0) (22.0) (20.1)

P380SU. ONCE-MONTHLY AND DAILY ORAL IBANDRONATE ARE SIMILARLY WELL TOLERATED IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS: 2-YEAR RESULTS FROM MOBILE Luckey M1, Stepan J2, Kendler DL3, Feldman D4, Lipschitz S5, Leigh C6, Burdeska A6, Hiltbrunner V6, Morales-Torres J7; 1Saint Barnabas Ambulatory Care Center, Livingston, NJ, USA, 2 Charles University, Prague, Czech Republic, 3Osteoporosis Research Center, University of British Columbia, Vancouver, Canada, 4Federal University of São Paulo, São Paulo, Brazil, 5The Osteoporosis Clinic, Johannesburg, South Africa, 6F. HoﬀmannLa Roche Ltd, Basel, Switzerland, 7Hospital Aranda de la Parra, Hidalgo, Mexico Aims: In postmenopausal osteoporosis, premature withdrawal from oral bisphosphonate treatment can significantly compromise therapeutic outcomes. Adverse events (AEs) are a leading cause of treatment discontinuation. Extending the dosing interval may help to improve therapeutic adherence. Ibandronate (Bonviva) is a potent, nitrogen-containing bisphosphonate that can be administered as a once-monthly oral regimen.1 At 1 year, once-monthly ibandronate dosing was well tolerated in the MOBILE study. We present the 2-year safety and tolerability findings from this study. Methods: In MOBILE, a randomized and double-blind study, women (aged 55–80 years and R5 years postmenopause) with osteoporosis (lumbar spine BMD T-score <-2.5, but R-5) received 2-years’ treatment with either once-monthly (50+50mg, 100mg or

150mg) or daily (2.5mg) oral ibandronate. Vitamin D (400IU/day) and calcium (500mg/day) were also provided. All recorded AEs, including symptomatic fractures, were included in the safety analysis. Results: Over the 2-year treatment period, once-monthly dosing was well tolerated, independent of the administered dose. Specifically, and as at 1 year, no imbalance in the overall incidence of AEs (76.5–80.3%), including drug-related AEs (30.1–36.9%) and drugrelated AEs leading to withdrawal (5.1–7.6%), was reported across the treatment groups. In all analyses, no safety disadvantage was observed in the 150mg arm. Drug-related serious AEs were reported with a low incidence (0.3–0.8%; n=8). At 2 years, the frequency of upper gastrointestinal AEs was well balanced across the treatment arms (monthly: 19.9–25.8%; daily: 22.8%). A low and balanced rate of clinical fractures was also obtained (6.3– 8.1%). No cases of osteonecrosis of the jaw were reported. Conclusions: Once-monthly oral ibandronate administrations are as well tolerated as a daily schedule that has previously shown tolerability similar to placebo. With improved adherence to therapy, once-monthly dosing may further improve the overall therapeutic eﬀectiveness of oral bisphosphonates. 1. Miller PD, et al. J Bone Miner Res 2005;20:1315–22.

P381MO. RALOXIFENE DOES NOT INFLUENCE FAT TISSUE MASS IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS Franek E1,2, Bulanowski M2, Czerwienska B2, Haczynski J3, Kokot F2, Wiecek A2; 1Dept of Int Dis, Endocrinology and Diabetology CSK MSWiA, Warszawa, 2Dept of Nephrology, Endocrinology and Metabolic Dis, Silesian Univ School of Med, Katowice, 3Dept of Gynaecology, Medical Academy in Lublin, Poland Introduction: It is not clear whether hormone replacement therapy (HRT) may influence body mass, but it seems that at least in part of these patients body weight increases under such treatment. It is known that increase of body weight, and especially increase of fat mass is associated with potential risk of many complications (eg, increase of cardiovascular risk). This study aimed to answer the question whether treatment with selective estrogen receptor modulator, raloxifene, may cause an increase of fat mass in patients with postmenopausal osteoporosis. Material and methods: 48 women were examined (mean age 61.44.9 y). Postmenopausal osteoporosis was defined as T-score of femoral neck or lumbar spine (L2-L4) lower than -2.5. Women with secondary osteoporosis, diabetes mellitus or smokers were excluded from the study. In all the patients body fat mass (using DXA method) were assessed and treatment with raloxifene (60 mg/d) with calcium carbonate (1 g/d) and vitamin D (500 UI/d) was started. The protocol was repeated after 12 months of treatment. The control group consisted of 35 women with postmenopausal osteoporosis, appropriately matched with regard to age and body mass, treated with calcium carbonate and vitamin D only. Results: In patients from the control group body mass increased slightly and not significantly after 12 months of treatment (62.99.8 vs. 66.811.6 kg, NS), whereas in the patients treated with raloxifene body weight (63.99.7 vs. 63.89.5 kg, NS) was stable. Trunk fat mass (117493052 vs. 119233851 g, NS), arms fat mass (2638985 vs. 27221088 g, NS), legs fat mass (88332150 vs. 92242960 g, NS) and total body fat mass (246785631 vs. 254407686 g, NS) before and after the treatment were also similar. Conclusion: Raloxifene does not increase body weight or fat tissue mass in women with postmenopausal osteoporosis.

P382SA. WOMEN PREFER ONCE-MONTHLY ORAL IBANDRONATE TO WEEKLY ORAL ALENDRONATE AS POSTMENOPAUSAL OSTEOPOROSIS TREATMENT: RESULTS OF BALTO II Barrett-Connor E1, Bourgeois P2, Devas V3, Masanauskaite D4, Minne H5; 1University of California, San Diego, CA, USA,

S235 2 Pitie-Salpetriere Hospital, Paris, France, 3GlaxoSmithKline, Collegeville, PA, USA, 4F. Hoﬀmann-La Roche Ltd, Basel, Switzerland, 5Klinik der Furstenhot, Bad Pyrmont, Germany

Aims: Despite replacement of daily dosing with weekly dosing, long-term non-adherence to oral bisphosphonates remains a considerable problem in postmenopausal osteoporosis (PMO). Less frequent dosing schedules may improve adherence. The US BALTO I and US/European BALTO II studies used identical designs to compare once-monthly oral ibandronate dosing with weekly oral alendronate dosing in terms of patient preference and convenience. BALTO I showed a strong patient preference for monthly ibandronate over weekly alendronate. We report results from BALTO II. Methods: In this two-sequence, two-period, crossover, openlabel study, 350 women with PMO were enrolled and randomized. In sequence A, 176 women received 3 calendar months of once-monthly oral ibandronate (150mg), immediately followed by 12 weeks of weekly oral alendronate (70mg). Sequence B reversed this order (n=174). At the final study visit, a questionnaire was used to assess patient preference. Results are reported for 321 women who received at least one dose of each medication and completed the questionnaire (modified intent-to-treat [mITT] population). Results: The majority of women in the mITT population expressed a preference (n=299; 93.1%). Most of these women preferred monthly ibandronate (70.6%) over weekly alendronate (29.4%; Figure). The preference rate for monthly dosing was statistically significant (p<0.0001). Reasons given for preferring ibandronate included the ability to facilitate long-term adherence (81.5% of women) and a better lifestyle fit (75.4% of women). In addition, 273 women (85.0%) expressed an opinion on convenience, with 76.6% favoring monthly ibandronate and 23.4% weekly alendronate (Figure). The convenience rate for the monthly regimen was statistically significant (p<0.0001). The safety profiles of both regimens were similar.

Aims: Once-monthly oral ibandronate does not maintain stable reduction in bone resorption, suggesting that some persons taking the drug may have little reduction in turnover for at least part of the dosing interval. Because the extent of reduction in turnover is correlated with clinical eﬃcacy of bisphosphonates, this may have important clinical consequences. To explore this question, we examined the proportion of participants who reached specified threshold levels of resorption marker reduction. Methods: Postmenopausal osteoporotic women participated in a 3-month, randomized, double-blind, placebo-controlled clinical trial. Enrolled participants were randomized to receive ibandronate 150 mg or 100 mg or matching placebo every 4 weeks for 3 doses. Serum CTx was measured just prior to each dose, one week after each dose, and weekly for 4 weeks after the final dose. Geometric mean percent change from baseline was calculated, as was the proportion of participants who had marker reductions of at least 40%, 50%, and 60% at each time point after the third dose (Weeks 9–12). Results: At each week after dosing a progressively smaller proportion of women met the defined sCTx reduction thresholds. Fewer than half of women taking 150 mg of ibandronate had sCTx reductions of at least 60% at all 4 weeks after the third dose (Weeks 9–12) and fewer than three-quarters (71.9%) of women had reductions of at least 40% at all four weeks. Conclusions: With once-monthly dosing of oral ibandronate, the proportion of women who attain specified reductions in sCTx declines progressively with time between doses. Because the observed cyclic changes in bone resorption might aﬀect eﬃcacy, the possible clinical implications of intermittent dosing deserve further study.

Proportion attaining specified reductions each week after Dose 3

Preference and convenience rates in BALTO II (mITT population; patients expressing a preference and opinion on convenience). Conclusions: The majority of women in BALTO II preferred once-monthly oral ibandronate to weekly oral alendronate for convenience and ease of use. Consistent with results from the US BALTO I study, once-monthly bisphosphonate dosing shows a strong potential to increase adherence.

P383SU. EFFECTS OF ONCE-MONTHLY ORAL IBANDRONATE ON SERUM CTX LEVELS: RESULTS OF A 3-MONTH RANDOMIZED TRIAL Kung AWC1, Geusens P2, Walliser J3, Rovayo R4, Shivaprakash M5, Verbruggen N6, Wehren LE7, Melton ME5; 1Queen Mary Hospital, Hong Kong, China, 2Universitaire Campus Gebouw C, Diepenbeek, Belgium, 3Hospial Angeles del Pedregal, Padierna, Mexico, 4Central University of Ecuador, Eloy Alfaro, Ecuador, 5 Merck & Co., Inc., Whitehouse Station, NJ, USA, 6Merck & Co., Inc., Brussels, Belgium, 7Merck Research Laboratories, Rahway, NJ, USA

P384MO. THE ORTHOSES SPINOMED AND SPINOMED ACTIVE IMPROVE POSTURE, TRUNK MUSCLE STRENGTH, AND QUALITY OF LIFE IN POSTMENOPAUSAL WOMEN WITH VERTEBRAL FRACTURES: A CONTROLLED, RANDOMIZED, AND PROSPECTIVE CLINICAL TRIAL Minne HW, Pfeifer M, Kohlwey L; Institute of Clinical Osteology and Clinic ’’Der Fuerstenhof’’, Bad Pyrmont, Germany Introduction: Spinal orthoses may play an important role in the treatment of spinal fractures due to osteoporosis. So far, however, clinical trials addressing eﬃcacy according to evidencebased medicine are rare. In a first pivotal study, an improvement in posture, trunk muscle strength, and quality of life after wearing the orthosis Spinomed has been demonstrated (Pfeifer M et al. 2004). Materials and Methods: In this study, 110 patients suﬀering from vertebral fractures and an angle of kyphosis of 60( and above were recruited in this randomized, prospective clinical trial with the angle of kyphosis being the primary endpoint. Secondary endpoints include body height, trunk muscle strength, body sway, pain and limitations of daily living using standardized questionnaires.

S236 Results: Table 1 presents results after six months of treatment (*:p<0.01; #:p<0.05; vs Controls): Spinomed active (N=48) vs Spinomed (N=31) vs Controls (N=31): Age (Years):

68.510.6 vs 72.87.1 vs 72.36.7

Vertebral fractures (Number): Angle of kyphosis (Change in Degrees): Body height (Change in mm): Back ext. strength (Change in N): Abd. flex. strength (Change in N): Body sway (Change in mm): Vital capacity (Change in %): Pain (Change in ScorePoints): ADL (Change in ScorePoints):

1.52.4 vs 2.02.7 vs 2.12.8 -6.25.3* vs -7.94.9* vs -1.65.5 +4.85.7* vs +5.36.3* vs -0.44.7 +178135* vs +189152* vs +755 +131117* vs +9471* vs +2346 -16.231.2* vs -20.440.2* vs -1.735.6 +5.618.9# vs +6.120.5# vs -9.916.1 -1.31,0* vs -1.51.2* vs +0.10.9 -1.41.5* vs -2.11.6* vs +0.20.8

Conclusion: Both orthoses Spinomed and Spinomed active led to an improvement in posture, trunk muscle strength, and quality of life in patients suﬀering from osteoporotic vertebral fractures. Especially Spinomed active, which is completely invisible below normal clothes is characterized by a very high compliance and acceptance among patients and thus comes very close to an ideal orthosis for the treatment of osteoporosis.

P385SA. COMPLIANCE, ACCEPTANCE, AND SAFETY OF TERIPARATIDE INJECTION OVER 18 MONTHS IN PATIENTS WITH SEVERE OSTEOPOROSIS Adachi JD1, Hanley DA2, Lorraine JK3, Tam F3, Boudreau T3; 1 McMaster University, Hamilton, Canada, 2University of Calgary, Calgary, Canada, 3Eli Lilly Canada Inc., Toronto, Canada Aims: Assessment of compliance, acceptance, and safety of teriparatide injection therapy over 6 and 18 months. Materials and Methods: 116 patients with severe osteoporosis, and inadequate response or intolerance to previous therapy, were enrolled and received teriparatide 20 µg/day as open label study drug. ‘‘Inadequate response’’ was defined as a significant loss of BMD, or fracture on antiresorptive therapy. Compliance (selfreported; >80% of study drug taken) and pen acceptance (using detailed questionnaires), were documented at baseline, 3 and 6 months, and end of study. Adverse events were elicited every 3 months. Results: 109 subjects (94%) completed the 6-month main study and 98 (84%) completed the 12-month extension. 94% were compliant at month 6. 89% of those entering the extension were compliant during this study period. Median duration of therapy was 549 days. As previously reported, patients became more comfortable with self-injection over the initial six months of therapy. At baseline, 50% were somewhat or quite concerned about the daily injection, but by month 6, most patients felt no concern (42%), or much less concerned (49%). By month 18, 44% reported no concern and 48% reported much less concerned. At baseline, 58% anticipated that the injection would be somewhat or very comfortable; however, 89% at 6 months and 91% at 18 months felt it was somewhat to very comfortable. At both 6 and 18 months, at least 95% felt that both performing the injection and holding the pen was somewhat to very easy. 73% and 78% felt very to very much satisfied with teriparatide treatment at 6 and 18 months respectively. Five patients had elevated trough serum calcium levels at 3 months (maximum value 2.8 mmol/L); none were elevated on repeat testing. Fourteen patients experienced 20 serious adverse events during the study; none were believed related to study drug. Conclusions: In this group of severely osteoporotic patients, acceptance of the teriparatide pen injection increased over the first 6 months of therapy, and then remained constant. Generally, compliance and acceptance were very high, as was overall treatment satisfaction. The safety profile was consistent with previous trial and postmarketing reports.

P386SU. FRAGILITY FRACTURES AND OSTEOPOROSIS TREATMENT IN LONG TERM CARE: RETROSPECTIVE COHORT STUDY Borisov NN1, Steinbuch M1,2; 1Procter & Gamble Pharmaceuticals, Mason, USA, 2Ohio State University, Columbus, USA Aims: To describe a long term care (LTC) population within a claims database in terms of their fragility fractures and fracturepreventing treatments. Methods: A retrospective cohort study was conducted among 27,566 women and men who received long term care service (the index date) between July 1, 2000, and December 31, 2002. All patients in the study had continuous enrollment throughout their individual study period including 6 months prior to and 12 months following the index date. Patients were followed during their LTC stay to identify their fragility fractures (vertebral or non-vertebral) and fracture-prevention treatment (risedronate, alendronate, or nasal calcitonin). Patients with a record of a fracture or an osteoporosis treatments during 6 months prior to the index date were excluded from the analysis. Results: The mean age of the study population was 69 years; women comprised 64% of the cohort. Mean length of stay in a LTC facility was 105 days per patient (median, 27 days). During the LTC stay, 3,837 (14%) patients experienced a fracture; 1,896 (7%) patients received an osteoporosis treatment. Of the patients who fractured, 80% (3,072) did not receive osteoporosis therapy, 2% (68) received osteoporosis treatment before and 18% (697) after their fracture. Conclusions: This study suggests that a LTC population may be under-treated for osteoporosis and associated fragility fractures. Approximately one in seven LTC patients sustained fragility fracture and the majority of these patients did not receive osteoporosis treatment before or after their fracture.

P387MO. PERSISTENCE AND ITS DETERMINANTS AMONG ELDERLY WOMEN INITIATING OSTEOPOROSIS THERAPIES FOR SECONDARY PREVENTION Blouin J1, Dragomir A1, Ste-Marie LG2, Fernandès JC2, Perreault S1; 1Faculty of Pharmacy, 2Faculty of Medicine, University of Montreal, Quebec, Canada Aims: The impact of the introduction of new antiresorptive therapies (ART) and dosing regimens on persistence rate and its determinants is not clearly known. Methods: A cohort of 12,933 women was reconstructed from the Régie de l’assurance maladie du Québec (RAMQ) administrative database (1998–2004). Our population consisted of women R 70 years who started ART for secondary prevention of osteoporosis, defined by ICD-9 code of osteoporosis or fracture, or medical procedure code for fracture in the 5 years preceding index date (date of first prescription). Impact of new ART and dosing regimens was assessed by separating the follow-up in two periods: Jan1998-Dec2001 and Jan2002-Jun2004. Minimum and maximum follow-up was 6 months and 4 years, respectively. Persistence was defined as no lapse of R 60 days after completion of a refill.Cumulative persistence rates were estimated using Kaplan-Meier analysis. Cox regression models were used to estimate the adjusted rate ratio (RR) of ceasing treatment. Results: Mean age was 77.2 years; 67.3% of women had had bone mineral density (BMD) testing before index date. During follow-up, 13.0% underwent BMD testing and 6.5% had a fracture. After controlling for demographic and clinical characteristics, starting ART in 2002–2004 had no impact on RR of cessation (RR: 0.96; 0.90–1.02). The RR was lower among women who started on alendronate or risedronate versus other agents (RR: 0.87; 0.83–0.92), and among those who had undergone BMD testing prior to index date (RR: 0.76; 0.72–0.80). During followup, women who had BMD testing (RR: 0.30; 0.28–0.34) and those who developed a fracture (RR: 0.51; 0.45–0.57) had lower RR of cessation. Women using the greatest number of pharmacies and physicians had a high cessation rate. Conclusions: Even after the introduction of new agents and dosing regimens, persistence rate with ART remains low. BMD testing and fracture are important determinants.

S237 1. Not available (follow-up was shorter than 2 years in the 1998–2001 period for risedronate, raloxifene and nasal calcitonin since they were listed on RAMQ drug formulary in 2000) Persistence rate after 6 months (%)

Persistence rate after 2 years (%)

Antiresorptive Therapies

1998–2001

2002–2004

p-value

1998–2001

2002–2004

p-value

Alendronate Risedronate Cyclic etidronate Raloxifene Nasal calcitonin

64.4 68.7 66.7 68.3 48.1

73.7 71.2 57.4 63.9 49.6

<0.01 0.54 0.52 0.32 0.52

43.7 n/a1 37.3 n/a n/a

53.0 49.8 27.4 46.4 26.7

<0.01 n/a 0.05 n/a n/a

P388SA. PERSISTENCE RATE AND ADHERENCE LEVEL TO OSTEOPOROSIS THERAPIES FOR PRIMARY AND SECONDARY PREVENTION AMONG ELDERLY WOMEN Blouin J1, Dragomir A1, Ste-Marie LG2, Fernandès JC2, Perreault S1; 1Faculty of Pharmacy, 2Faculty of Medicine, University of Montreal, Quebec, Canada Aims: Few data on both persistence rate and adherence level with antiresorptive therapies (ART) are available. We assessed persistence rate and adherence level among elderly women initiating ART for primary or secondary prevention. Methods: A cohort of 8,221 women was reconstructed from the Régie de l’assurance maladie du Québec administrative database (2002–2004). Women were aged 70 years and older and had started ART for primary (n=3,016) or secondary (n=5,205) prevention of osteoporosis. The primary and secondary prevention cohorts were respectively defined according to the absence or presence of ICD-9 code of osteoporosis or fracture or a medical procedure code for fracture in the 5 years preceding the index date (date of the first prescription). The minimum and maximum follow-up was 6 months and 2.5 years, respectively. Persistence was defined as no lapse of R60 days after completion of a refill. Cumulative persistence rates after 1 year were evaluated with a Kaplan-Meier analysis. Adherence level was calculated only among women having at least 1 year of follow-up (n=5,546) and was defined as the proportion of days exposed to therapy (<80% or R80%). Results: Mean age was 78.5 and 77.8 years for the primary and secondary prevention cohorts, respectively. Compared to other ART, once-weekly regimens of alendronate and risedronate showed the highest persistence rates in both primary and secondary prevention cohorts. We also noted a trend towards higher adherence level among once-weekly regimens for both primary and secondary prevention cohorts. Conclusions: The introduction of once-weekly regimens of bisphosphonates did not result in an important increase of persistence rate or adherence level. Non optimal use of ART may significantly modify their real benefit on fracture risk reduction. 1. Reference used for comparisons *Denotes significance of p<=0.05 Primary Prevention

Secondary Prevention

Antiresorptive Therapies

Persistence Rate

Adherence LevelR80%

Persistence Rate

Adherence Level R80%

Alendronate daily1 Alendronate once-weekly Risedronate daily Risedronate once-weekly Cyclic etidronate Raloxifene Nasal calcitonin

54.7 62.7 53.0 61.0 45.6 46.8 30.2

57.9 62.6 55.0 64.0 53.3 50.0 23.4

60.6 % 66.2 %* 57.3 % 61.8 % 44.7 %* 56.6 % 38.4%*

61.2 67.9 59.8 64.5 51.9 54.7 31.1

% %* % % % % %*

% % % % % % %*

% %* % % % % %*

P389SU. TREATMENT OF OVARIECTOMIZED SKELETALLY-MATURE RHESUS MONKEYS WITH RECOMBINANT HUMAN PARATHYROID HORMONE 1–84 (PTH) FOR 16 MONTHS INCREASES BONE DENSITY AND STRENGTH AT THE LUMBAR SPINE Fox J1, Miller MA1, Turner CH2, Smith SY3; 1NPS Pharmaceuticals, Salt Lake City, USA, 2Indiana University, Indianapolis, USA, 3Charles River Preclinical Services, CTBR, Montreal Canada

Aim: Osteoporosis is characterized by impaired bone quality leading to increased susceptibility to fracture. However, direct assessment of the eﬀects of treatments for osteoporosis on bone strength can only be determined by biomechanical testing in preclinical species. We investigated the eﬀects of PTH treatment on bone density and strength at the lumbar spine of ovariectomized (OVX) monkeys, the best model of human postmenopausal bone loss. Methods: Skeletally-mature rhesus monkeys (n=8–10/group) were OVX and, following a bone depletion period of 9-months, treated daily for 16-months with PTH (5, 10, or 25 µg/kg). BMD was quantified by DXA at L2-L4 during the study (region of interest positioned laterally over the middle of each vertebral body) and by pQCT ex vivo after 16 months. The vertebral bodies of L2 and L4 were subjected to compression testing and the results averaged. Results: At baseline, DXA BMD was 11% lower in OVX than in sham animals. All PTH doses increased BMD such that sham levels were achieved by approximately 3, 7 and 12 months with the 25, 10, and 5 µg/kg doses, respectively. The increases in BMD above baseline levels at Month 16 were 18%, 24%, and 24% with the 5, 10, and 25 µg/kg doses, respectively. By pQCT, volumetric trabecular BMD (vTbBMD) at Month 16 was, respectively, 28%, 36%, and 49% higher than in OVX controls. Despite the greater increase in vTbBMD in the 25 µg/kg group, yield load and yield stress were highest in the 10 µg/kg group. Yield load was 18%, 25% and 23% higher, and yield stress 7%, 23% and 7% higher in the 5, 10 and 25 µg/kg groups, respectively, than in OVX controls. Stiﬀness was 21%, 18% and 30% higher and modulus 9%, 14% and 13% higher in the three dose-groups versus OVX controls. Bone strength in all PTH groups was similar to or significantly greater than sham levels. Conclusion: PTH treatment of OVX rhesus monkeys increased vTbBMD and bone strength at the lumbar spine. The 10 µg/kg dose produced the greatest eﬀect on vertebral strength possibly because the highest dose resulted in an excessive stimulation of remodeling.

P390MO. 15 YEARS OF PERCUTANEOUS VERTEBROPLASTY: A CRITICAL REVIEW Proschek D1,2, Hochmuth K2, Kurth AA2, Mack MG1, Vogl TJ1; 1 Dep. of Interventional and Diagnostic Radiology, University Hospital, 2Dep. of Orthopaedic Surgery, University Hospital Friedricjsheim, Frankfurt, Germany Purpose: To review and analyze 15 years of percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures. Methods and Materials: Between 1989 and 2004, 30 studies and a total of 2086 treated patients have been found in literature. A review of these studies has been performed. We assessed number and age of the patients, number of treated vertebrae, pre- and postoperative outcome of pain results and complications of the diﬀerent studies and carried out a statistical analysis of the diﬀerent parameters. Results: Most of studies found in literature presented retrospective findings. Still there is no prospective randomized controlled trial existent. A total of 2086 patients and 5849 treated vertebrae have been analyzed. The medium age of the treated patients between 1989 and 2004 was 68.9 years. The mean female ratio was 67.4%. Before treatment, mean pain score VAS (visual-analoguescale) was 8.1, with a range from 6.4 to 9.7. After percutaneous vertebroplasty, pain has been reduced significantly down to VAS 2.6, with a range from 1.7 to 3.9. Technical complications have been found in less than 2% of the treated patients. The mean extravasation rate was 41% with 98% of the extravasation having been asymptomatic. Conclusion: Results of all evaluated studies show a significant reduction of pain, a minor complication rate and a fast, easy to learn and favourable technique. But there is no explicit proof in terms of evidence based medicine, that percutaneous vertebroplasty is really better than conservative treatment or other techniques. Especially long-term results regarding stability of the

S238 cement and the adjacent vertebrae is still absent in most of the studies.

P391SA. THE EFFECT OF RALOXIFENE ON GONADOTROPHINS, PROLACTIN AND LIPIDS IN POSTMENOPAUSAL WOMEN Izol Torun AN1, Emral R2, Corapcioglu D1, Uysal AR1, Kamel N1, Tonyukuk Gedik V1; 1Ankara University Faculty of Medicine, Ankara, Turkey, 2Baskent University Faculty of Medicine, Ankara, Turkey Aims: To evaluate the eﬀect of raloxifene administration for one month on gonadotrophins, prolactin and lipid metabolism in postmenopausal women who were treated for osteoporosis. Methods: Thirteen postmenopausal women who have osteoporosis were included in this cross over study. 60 mg/day raloxifene was started and the FSH, LH, PRL, estradiol(E2), lipids and fasting plasma glucose measurements were taken before and after the first month of the medication and one month after the withdrawal of the drug. Results: On the first month of the medication, LH was increased when compared with the initial (p=0.008). After the withdrawal of raloxifene, LH decreased significantly to its initial levels (p=0.043). FSH and E2 levels did not diﬀer with raloxifene, while PRL significantly decreased (p=0.017), and this eﬀect on PRL disappeared after the withdrawal of raloxifene. HDL decreased significantly with raloxifene and increased after its withdrawal. LDL also decreased in the first month of the medication (p=0.003) and increased with its withdrawal. Raloxifene did not exert any eﬀect on fasting plasma glucose, while its decremental eﬀect on trigycerides was not significant. Conclusions: The data from the previous studies are controversial about the eﬀect of raloxifene on the anterior pituitary. Our study indicated a decrease in PRL, increase in LH and no eﬀect on FSH with raloxifene administered for one month. The decremental eﬀect that we observed on PRL was similar with previous studies, while its eﬀect on LH diﬀers from other studies which were conducted on women but similar to the animal studies. Animal studies showed that the eﬀect of raloxifene on gonadotrophins depends on the duration of the medication. It is not clear that the estrogen receptors are the main mediators of its decremental eﬀect on PRL, but the antiproliferative eﬀect of raloxifene and mediation of beta-endorphin tonus are supposed to be a factor. The eﬀect of raloxifene on lipids mimics estrogen. Our study indicated that raloxifene exerts a central antiestrogenic eﬀect on gonadotrophins and an estrogenic eﬀect on lipids.

P392SU. ASSESMENT OF THERAPY CONCORDANCE IN POST FRACTURE PATIENTS ASSESSED IN THE OSTEOPOROSIS NURSE LED CLINIC Hind SP1, Summers GD2; 1Derby City General Hospital, 2Derbyshire Royal Infirmary, Derby, UK The purpose of the audit was to determine what percentage of patients attending the Osteoporosis Nurse Led clinic were still on their therapy after one year. This was a retrospective audit identifying consecutive patients attending between 1 January to 31 December 2003. For those patients in whom treatment was recommended a letter explaining the purpose of the audit was written to their GP with a spreadsheet enclosed. The spreadsheet identified the name and date of birth of their patient, treatment recommended and two blank columns headed date of first and last prescription (at time of completing form) to be entered by GP or a designated person who could access the practice prescribing data. A total of 55 practices were contacted, 40 (73%) practices responded and returned completed spreadsheets, 13 (24%) did not respond and 2 (3%) declined to provide information. Appointments were oﬀered to 190 patients over the period specified. 170 attended the clinic, 17 did not attend and 3 cancelled due to ill health and did not take up the oﬀer of a further appointment. Of those that attended 129 (76%) had some form of treatment recommended based on risk factors, bone density measurements,

and guidelines from Royal College of Physicians 1999 for secondary fracture prevention which were in use at the time. Treatments recommended were weekly bisphosphonates, Raloxifene, HRT, +/- calcium and vitamin D supplementation or supplementation alone. Treatment was not required by 41 (24%) of those seen. Prescribing information was returned on 66% of patients who had been recommended treatment. Of this group 76% had been taking the medication for more than 12 months, 24% did not reach this level of concordance. Information was not received on 34% of patients. Reasons for not continuing with treatment included 1 patient leaving practice, 5 patients dying within 12 months of treatment initiation, drug side eﬀects, and concerns about ongoing treatment with HRT. The audit confirmed that GPs are prescribing medication recommended by the nurse specialist and 76% of patients had continued treatment beyond 12 months.

P393MO. SUPERIORITY OF A COMBINED TREATMENT OF ALFACALCIDOL AND ALENDRONATE COMPARED TO THE RESPECTIVE MONOTHERAPIES IN ESTABLISHED OSTEOPOROSIS Ringe JD1, Farahmand P1, Schacht E2; 1Medical Clinic 4, Leverkusen Clinic, Leverkusen, Germany, 2University Clinic Balgrist, Zurich, Switzerland The objectives of the study were to compare the eﬃcacy and safety of the treatment with Alfacalcidol and Alendronate combined to the treatment with either Alfacalcidol or Alendronate alone in patients with established postmenopausal or male osteoporosis. 90 patients included as matched pairs received randomly either 1 µg Alfacalcidol daily + 70 mg Alendronate weekly + 500 mg Calcium daily (group A, n=30) or 1 µg Alfacalcidol + 500 mg Calcium daily (group B, n=30) or 70 mg Alendronate weekly + 1000 mg Calcium + 1000 IU Vitamin D daily (group C, n=30). The three groups were well matched in terms of sex, mean age, height, weight, baseline mean BMD at lumbar spine and femoral neck, the prevalence rates of falls, vertebral and non-vertebral fractures. In all patients BMD was measured at lumbar spine and at femoral neck with DXA at baseline, 12 and 24 months. We observed significant increases of BMD compared to baseline at the lumbar spine of 9.6%, 3.0% and 5.4% in group A, B and C respectively. The diﬀerences between combination therapy and Alfacalcidol (6.6%) and Alendronate (4.2%) were highly significant (p< 0.001). We also observed significant increases of BMD at the femoral neck of 3.8%, 1.5% and 2.4% in group A, B and C respectively. Diﬀerences between combination therapy and Alfacalcidol (2.3%) and Alendronate (1.4%) were again significant. The 2-year number of patients with vertebral fractures were 1 in group A, 5 in group B and 4 in group C. 2-year incidences of nonvertebral fractures were 1 in group A, 4 in group B and 6 in group C, i.e. the fracture data support the view of a relevant superiority of Alfacalcidol and Alendronate combined versus either Alfacalcidol or Alendronate alone. At month 24, 80% of the patients on combination therapy were free from back pain, compared to 43.3% in the Alfacalcidol group and 30.0% in the Alendronate group. In conclusion, the combination therapy of Alfacalcidol and Alendronate exhibited superiority over either Alfacalcidol or Alendronate alone. In addition the overall safety profiles of the three treatment regimens were found to be similar in this study.

P394SA. PROSPECTIVE RANDOMIZED CLINICAL TRIAL COMPARING HEMIARTHROPLASTY TO TOTAL HIP ARTHROPLASTY: FUNCTIONAL OUTCOMES IN THE TREATMENT OF DISPLACED FEMORAL NECK FRACTURES Macaulay W1, Nellans K1, Garvin K2, Iorio R3, Healy W3, Teeny S4, Yoon RSH1, Geller J1, Rosenwasser MP1, DFACTO CONSORTIUM; 1Center for Hip & Knee Replacement, Columbia University, New York, NY, USA, 2University of Nebraska Medical Center, Omaha, NE, USA, 3Lahey Clinic, Burlington, MA, USA, 4NorthWest Orthopaedic Institute, Tacoma, WA, USA

S239 Aim: With 300,000 hip fractures annually in the US, most of which are due to bone fragility, the loss of functional independence and quality of life for previously active individuals following a hip fracture is a prime area to optimize outcomes. The Displaced Femoral (neck fracture) Arthroplasty Consortium for Treatment and Outcomes (DFACTO) study is a prospective, multi-center randomized clinical trial comparing hemiarthroplasty to total hip arthroplasty (THA) in the treatment of displaced femoral neck fractures. Methods: Primary outcomes have been measured at 6, 12, and 24 months using the following validated patient-reported measures: the SF-36, WOMAC, and the Harris Hip Score. The Timed ‘‘Up & Go’’ Test (TUG) is used as an objective performance measure. Results: Forty subjects were enrolled in this pilot. To date, we have collected 6-month data for 39 subjects, 12-month data on 36 subjects, and 24-month data on 11 subjects. Using an intentionto-treat analysis, 6-month data shows mean SF-36 results favoring THA over hemiarthroplasty in bodily pain sub-scores (39.3 vs. 27.0), physical component summary (31.6 vs. 23.1), and mental component summary (39.7 vs. 28.1). Additionally, the stiﬀness component of the WOMAC index suggests THA subjects had less post-operative stiﬀness than hemiarthroplasty subjects (57.8 vs. 44.3). Average TUG results also favor THA over hemiarthroplasty (14.2 sec vs. 20.7 sec). Twelve month data demonstrates mean diﬀerences favoring THA over hemiarthroplasty in the SF-36 bodily pain sub-scores (32.7 vs. 20.1), physical component summary (24.1 vs. 18.0), and mental component summary (34.5 vs. 24.8). Additionally, we found 57% of THA subjects walked independently or with a cane occasionally at one year, while compared to only 41% of the subjects in the hemiarthroplasty group. Due to the pilot nature of our study, statistically significant results have yet to be achieved. Conclusions: These results suggest a possible sustained, superior result in terms of pain, stiﬀness, and functional results for subjects receiving a THA for the treatment of a displaced femoral neck fracture. Following these subjects through 2 years will be important to fully assess the risks and benefits of THA vs. hemiarthroplasty and best define the criteria for treatment decisions.

P395SU. COST IMPLICATIONS OF PARATHYROID HORMONE (TERIPARATIDE) THERAPY IN THE TREATMENT OF OSTEOPOROSIS Binymin K1,2, Pradeep Y1; 1Rheumatology Department, Southport DGH, 2Liverpool University, Mersyside, UK Objective: Teriparatide [rhPTH (1–34)] increases bone mass and reduces the risk of vertebral and other osteoporotic fractures. The National Institute of Clinical Excellence (NICE) in the UK set the guidelines for use of teriparatide in postmenopausal osteoporosis. Teriparatide carries a cost implications at around £5250 for 18 months treatment of a single patient. Method: Patients attending the DXA scan unit who are between 65–80 years of age with a lumbar spine T-score of -3 SD or lower were studied between September 2003 and September 2004. Results: Out of a total of 72 patients, 6 (8.33%) were eligible for treatment with teriparatide, 2 of them had extremely low bone mineral density (T scores < -4) (group one) and 4 had very low bone mineral density (T scores < -3) (group two). The average duration of osteoporosis was 152.3 years for group one and 122.2 years for group two. All patients from group two had two or more new fractures while on bisphosphonate therapy for 363.6 months. Group one patients sustained one further fracture while on bisphosphonate treatment for an average of 273.6 months. Both groups have more than two (average 30.3) age independent risk factors for osteoporosis. Conclusions: In a secondary care setting (District General Hospital) catering for a population of 120,000 for osteoporosis services, 6 patients are expected to be eligible for teriparatide treatment in the 65–80 year age group. In this cohort of patients the costs of treatment will escalate by an extra £30000 compared with an average of £3000 if bisphosphonate or alternative oral therapy were to be used. The average total cost of treatment with teriparatide will be higher if patients over the age of 80 who did not have scan (based on our hospital policy) are included.

NICE guidelines for teriparatide use in the secondary prevention of postmenopausal osteoporosis NICE ‘‘Technology Appraisal No. 87 / 2005’’ Guidelines for selecting patient with postmenopausal osteoporosis suitable for treatment with Teriparatide — Teriparatide is recommended as a treatment option for the secondary prevention of osteoporotic fragility fractures in women aged 65 years and older who have had an unsatisfactory response to bisphosphonates or intolerance to bisphosphonates — who have an extremely low BMD (with a T-score of approximately –4 SD or below, or — who have a very low BMD (with a T-score of approximately –3 SD or below) plus multiple fractures (that is, more than two) plus one or more age independent risk factors: (a) low body mass index (< 19 kg/m2) (b) family history of maternal hip fracture before the age of 75 years (c) untreated premature menopause (d) certain medical disorders independently associated with bone loss (such as chronic inflammatory bowel disease, rheumatoid arthritis, hyperthyroidism or coeliac disease) (e) conditions associated with prolonged immobility.

P396MO. BISPHOSPHONATE USE IN ELDERLY NURSING HOME RESIDENTS Papaioannou A1,2, Kennedy CC1, Campbell G3, Garg AX4, Dolovich L1,5, Adachi JD1,5; 1McMaster University, Hamilton, Canada, 2Hamilton Health Sciences, Hamilton, Canada, 3Medical Pharmacies Group Inc., Hamilton, Canada, 4London Health Sciences Centre, London, Canada, 5St. Joseph’s Healthcare, Hamilton, Canada Aims: The oral bisphosphonates alendronate and risedronate have proven anti-fracture eﬃcacy, however, due to ‘‘lack of clinical experience’ they are not recommended in patients with renal insuﬃciency. This presents a challenge for treating nursing home residents: an estimated 50% of men and 80% of women have osteoporosis, and 10% of men and 24% of women have severe renal impairment [creatinine clearance (CrCl) < 30 ml/min]. The purpose of this study was to examine the level of renal impairment in nursing home residents prescribed a bisphosphonate. Methods: In this descriptive study we reviewed information from 7 nursing homes in Ontario, Canada. In November 2005, the centralized pharmacy provider initiated a ‘‘CrCl Alert program’’ which identified residents with severe renal impairment and printed a prescribing alert for potentially inappropriate medications (and includes recommendations developed by an expert panel). An alert was generated for alendronate or risedronate if the CrCl was < 30 ml/min (calculated using the Cockcroft-Gault equation). Results: Twenty percent of residents (279/1390 patients) were prescribed a bisphosphonate (alendronate 25%; etidronate 47%; risedronate 28%; calcium/vitamin D regularly prescribed); CrCl data were available for 254 of these patients. Of the patients prescribed a bisphosphonate, 89% were female, mean age was 83.8 (SD 7.7) years, and mean CrCl (ml/min) was 48.1 (SD 22.3). Of the 133 patients taking alendronate or risedronate, an alert was generated for 17% (23/133) due to a CrCl < 30 ml/min. A further 13.5% (18/133) of patients had a CrCl between 30 – 35 ml/min (just above the alert limit). If the criteria of >15ml/min were used, only 2 patients would have been excluded from taking a bisphosphonate. Conclusion: A substantial proportion of patients taking alendronate or risedronate had CrCl <30. A recent study suggested bisphosphonates may be safe for patients with a CrCl >15 ml/min, however further studies are needed. The risk benefit of using this drug class in nursing home elderly is uncertain, as many residents have a CrCl < 30. Given the high prevalence of osteoporosis and the serious consequences of hip/other fractures in the elderly, further studies should address this issue.

S240

P397SA. A SINGLE ZOLEDRONIC ACID 5MG INFUSION IS PREFERRED OVER WEEKLY 70MG ORAL ALENDRONATE IN A CLINICAL TRIAL OF POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS/OSTEOPENIA Lindsay R1, Saag K2, Kriegman A3, Davis J3, Beamer E3, Zhou W3; 1Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA, 2Division of Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Aims: To assess patient preference for annual IV infusion therapy compared to weekly oral therapy in a clinical trial. Methods: This multi-center, randomized, double-blind, doubledummy trial assessed the onset of action of a single 15-minute infusion of zoledronic acid [ZOL] 5 mg (N = 69) compared to oral weekly alendronate [ALN] 70 mg (N = 59) over a 24-week period. At the end of the study, patients were asked to respond to four questions to determine their preference for the diﬀerent treatment modalities. While still blinded to therapy, patients were asked which treatment was 1) more convenient, 2) more satisfying, 3) they would be more willing to take for a long period of time, and 4) was preferred. Safety assessments were evaluated over the duration of the 24-week study. Results: Overall, 66.4% of the patients who completed the questionnaire (N = 122) expressed a preference for a once-a-year IV infusion, compared to 19.7% who preferred a once-weekly pill; 13.9% indicated that both treatment modalitiesThe percentage of patients who reported an adverse event was similar in the ZOL (91%) and ALN (86%) groups. However, more patients in the ZOL treatment group reported transient post-infusion adverse experiences (AE), mostly ‘‘flu-like’’ symptoms (n = 13, 18.8%), nausea (n = 8, 11.6%), and/or myalgia (n = 8, 11.6%), during the first 3 days after infusion compared to the ALN group. After 3 days, there were no significant diﬀerences between groups. Even among patients who reported an AE within the first 3 days and completed the questionnaire (n = 61), 73.8% expressed an overall preference for once-a-year IV therapy. Conclusions: A once-a-year IV infusion was preferred over a once-weekly pill by 66.4% of postmenopausal women with osteoporosis/osteopenia participating in ZOL vs ALN comparative trial. Patient Preference Questionnaire (% of responders)

More convenient (N=122) More satisfying (N=121) More willing to take a long time (N=122) Overall preference (N=122)

Once-a-Year IV

Once-a-Week Pill

Both Are Equal

66.4 59.8 68.0

15.6 18.9 15.6

18.0 20.5 16.4

66.4

19.7

13.9

P398SU. STATIC BALANCE CHARACTERISTICS ARE ALTERED IN INDIVIDUALS WITH OSTEOPOROTIC VERTEBRAL FRACTURE Greig AM1,2, Bennell KL1, Briggs AM1,2, Wark JD2, Hodges PW3; 1Centre for Health, Exercise and Ports Medicine, School of Physiotherapy, University of Melbourne, Melbourne, Australia, 2 Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne Australia, 3School of Health and Rehabilitation Sciences, School of Physiotherapy, University of Queensland, Brisbane, Australia Aims: The leading mechanism of osteoporotic vertebral fractures is a fall; therefore, understanding balance in the osteoporotic population is important. Altered balance strategies and fall impact may impose forces on osteoporotic vertebrae that exceed their compressive strength, leading to fracture. It is also possible that balance deficits manifest secondary to factors associated with fracture (pain, postural changes, fear). The purpose of this study was to compare balance characteristics in individuals with and without osteoporotic vertebral fractures. Individuals were also compared based on magnitude of thoracic kyphosis. Methods: 22 postmenopausal females with osteoporosis participated: 10 with vertebral fracture (68 7.1 years, 160.2 6.0 cm, 67.4 11.3 kg); 12 without fracture (64 9.0 years, 157.1 3.9

cm, 58.5 9.5 kg). Participants were also grouped into low (26.6 4.9 () and high (39.5 4.3 () thoracic kyphosis groups measured by centroid angle. Pain was less than 3/10 (visual analogue scale) for all participants during data collection. Force plate centre of pressure (COP) (range and standard deviation (SD) of displacement, velocity, shear forces) in the antero-posterior (AP) and medio-lateral (ML) directions were compared. Participants performed three quiet standing tasks: flat surface, eyes open; flat surface, eyes closed; and short base, eyes open. A 2 x 3 repeated measures ANOVA assessed diﬀerences between conditions based on fracture and thoracic kyphosis groups. Results: Individuals with fracture had higher range in AP COP displacement (p = 0.05), and higher range and SD in AP shear forces (p = 0.048 and p = 0.032 respectively). There was no diﬀerence in magnitude of kyphosis between fracture groups (p = 0.913). There were no balance diﬀerences between low and high kyphosis groups. Conclusions: The results suggest that individuals with vertebral fracture have altered balance characteristics compared with individuals without fracture, including less constraint of AP COP displacement and increased use of hip strategy (indicated by greater shear forces). These findings also suggest that the altered balance characteristics in this population are not due to diﬀerences in kyphosis. These findings provide further rationale for balance retraining in individuals with osteoporotic vertebral fracture.

P399MO. PERSISTENCE AND ITS DETERMINANTS AMONG ELDERLY WOMEN INITIATING OSTEOPOROSIS THERAPIES FOR PRIMARY PREVENTION Blouin J1, Dragomir A1, Ste-Marie LG2, Fernandès JC2, Perreault S1; 1Faculty of Pharmacy, 2Faculty of Medicine, University of Montreal, Quebec, Canada Aims: The eﬃcacy of antiresorptive therapies (ART) in primary prevention of osteoporosis is controversial. We evaluated persistence and its determinants among elderly women initiating ART. Methods: A cohort of 8,880 women was reconstructed from the Régie de l’assurance maladie du Québec (RAMQ) database (1998– 2004). Our population consisted of women R70 years who started ART and did not have ICD-9 code of osteoporosis or fracture, or medical procedure code for fracture in the 5 years preceding index date (date of first prescription). Impact of new ART and new dosing regimens was assessed by separating follow-up in two periods: Jan1998-Dec2001 and Jan2002-Jun2004. Minimum and maximum follow-up was 6 months and 4 years, respectively. Persistence was defined as no lapse of R 60 days after completion of a refill. Cumulative persistence rates were estimated using Kaplan-Meier analysis. Cox regression models were used to estimate the adjusted rate ratio (RR) of ceasing treatment. Results: Mean age was 77.3 years; 46.9% of women had had bone mineral density (BMD) testing before the index date. During follow-up, 11.9% underwent BMD testing, 3.5% suﬀered a fracture and 13.5% had ICD-9 code for osteoporosis. After adjustment for demographic and clinical characteristics, starting ART in the 2002–2004 period had minimal impact on RR of cessation (RR: 1.11; 1.04–1.19).RR of ceasing agents was lower among women who started on alendronate or risedronate versus other ART (RR: 0.84; 0.79–0.90), and among women who had undergone BMD testing before the index date (RR: 0.71; 0.66–0.75). During followup, women who had BMD testing (RR: 0.43; 0.38–0.48), a fracture 1. Not available (follow-up was shorter than 2 years in the 1998–2001 period for risedronate, raloxifene and nasal calcitonin since they were listed on RAMQ drug formulary in 2000) Persistence rate after 6 months (%)

Persistence rateafter 2 years (%)

Antiresorptive Therapies

1998–2001 2002–2004 p-value 1998–2001

Alendronate Risedronate Cyclic etidronate Raloxifene Nasal calcitonin

62.5 64.3 62.5 66.8 39.2

70.0 65.7 58.7 57.0 40.0

<0.01 0.88 0.58 0.06 0.92

40.9 n/a1 33.4 n/a n/a

2002–2004

p-value

52.2 49.0 33.4 30.7 21.3

<0.01 n/a 0.87 n/a n/a

S241 (RR: 0.50; 0.42–0.61) or a diagnosis of osteoporosis (RR: 0.54; 0.48–0.60) had lower cessation rates. Conclusions: Given their low persistence rates and few evidences supporting their eﬃcacy in primary prevention, it is worthed to explore the reasons for initiating ART in this population.

P400SA. BISPHOSPHONATE THERAPY AND THE THERAPEUTIC CARE GAP IN WOMEN WHO HAVE FRAGILITY FRACTURES: THE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY (CAMOS) Ioannidis G1, Papaioannou A1, Tenenhouse A2, Gao Y2, Berger C2, Prior JC3, Kaiser SM4, Hanley DA5, Josse RG6, Brown JP7, Olszynski WP8, Murray TM6, Anastassiades T9; 1McMaster University, Hamilton, Canada, 2McGill University, Montreal, Canada, 3University of British Columbia, Vancouver, Canada, 4 Dalhousie University, Halifax, Canada, 5University of Calgary, Calgary, Canada, 6University of Toronto, Toronto, Canada, 7 Laval University, Ste-Foy, Canada, 8University of Saskatchewan, Saskatoon, Canada, 9Queen’s University, Kingston, Canada, 10 Memorial University, St. John’s, Canada, 11University of Alberta, Edmonton, Canada Aims: Given that osteoporotic fractures are associated with increased mortality and morbidity, patients with fractures should be treated with a first-line therapy, such as a bisphosphonate, to reduce the likelihood of an additional fracture. Utilizing participants from CaMos, a nation-wide, random sample of the Canadian population, we performed a 5-year prospective analysis to determine the number of community dwelling women 50 years of age and older who had a fracture and were administered a bisphosphonate. Methods: Hip, wrist, rib and spine fractures were evaluated. All fractures were a result of minimal trauma, clinically recognized and were assessed cumulatively over the 5-year observational period (i.e. fractures at year 5 occurred during that year and before). Bisphosphonate use was based on self-reports from CaMos questionnaires. Results: Results indicated that approximately, one third of women who had non-vertebral fractures were treated with a bisphosphonate. This percentage modestly improved over the course of the study. Approximately 50 to 60% of women who had vertebral fracture were treated with a bisphosphonate. This percentage did not appear to change during the study (table 1).

Method: A 3 year clinical trial study from Sep 2002-Nov 2005; 63 male pensioners with osteopenia (T-score<-1.5) over 55 years with no sign of wedging or compress fracture in radiographic studies was designed. All participants were recomended adequate calcium and vitD intake ,back straightening and pelvic tilt exercise based on Sinaki back extention exercise program of osteoporosis,walking 30 minute twice a week and swimming 20 min twice a week. Patients were voluntary allocated to 3 group based type of swimming: — frog swimmers (group 1 = 19 ones) — back swimmers (group 2 = 21 ones)and — mix swimmers (breast, butterfly, frog): (group 3 = 23 ones). Musculoskeletal complains were registered in PM&R clinic during the study. After 3 years the back kyphosis degree , bone minneral densitometry(based on DXA- dual-energy X-ray absorptiometry) and functional rating index was reassesed. We used paired T-test to determine the eﬀect of intervention in each group and ANOVA to compare 3 diﬀerent groups. Results: Mean T-score of participants was (-2.2 0.3) at the begining and (-1.9 0.4) at the end of trial. Incidence of osteoporosis was 11.1%. No significant diﬀerence between 3 group in mean BMD and frequency of osteoporosis was found. The frequency of muscloskletal complains was higher in frog swimmers than the others.In back swimmers ,improvment in functional rating index was 42% and the mean change in thoracic kyphosis was (-4.6 0.4) degree (P<0.05). Conclusion: Back swimming has better outcme in functional improvement, reduction of kyphosis and compression fracture in comparison with frog and other types of swimming. on recommendation of frog swiiming must be careful because of high frequency of cervical pain.

P402MO. ADDITIVE EFFECTS OF 1,25(OH)2 VITAMIN D3 AND ALENDRONATE ON BONE METABOLISM IN OVARIECTOMIZED MICE Zhang ZL, Li BY, Tong J; Radiation Medical and Public School of Soochow University, Suzhou, China

P401SU. EFFECTIVENESS OF DIFFERENT TYPES OF SWIMMING ON POSTURE AND MUSCULOSKELETAL PROBLEMS IN PERSONS WITH OSTEOPENIA

Vitamin D is commonly used in elderly people, especially by postmenopausal women with osteoporosis. Alendronate is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate and 1,25(OH)2 Vitamin D3 are used concurrently. In this study, we examined the eﬀect of 1,25(OH)2 Vitamin D3 combined with alendronate on bone loss in ovariectomized (OVX) mice. Eight-week old female mice were assigned to five groups; ovariectomized (OVX; n = 8), sham control (sham; n = 8). ovariectomized supplemented with 1,25(OH)2D3 (OVX+ D3; n = 8), ovariectomized supplemented with alendronate (OVX+ ALN; n = 8) and ovariectomized supplemented with 1,25(OH)2D3 and alendronate(OVX+D3+ ALN; n = 8). We administered 1,25(OH)2D3, 0.0625 µg per mouse once daily and alendronate 25 µg per mouse once a week subcutaneously. Administration was begun after operation and continued for six weeks. Bone mineral density (BMD, mg/cm2) of the femur was measured by PIXImus II bone densitometer (GE Lunar). Mineral content in the tibia, femur and histomorphometric parameters of the tibia (width of osteoid, periosteal and endosteal transverse growth) and femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Ovariectomy induced osteopenic changes in murine skeleton. Alendronate inhibited the development of changes induced by ovariectomy in the skeletal system. Combination of 1,25(OH)2D3 and alendronate demonstrated additive eﬀects on bone metabolism in ovariectomized mice.

Reis-sadat A1,2, Rezae moghaddam F1, Azma K1, Markazi moghaddam N1; 1PMR Researh Center, Army University of medical Science, Tehran, Iran, 2Iranian Young Research Club, Tehran, Iran

P403SA. BONE LOSS ASSOCIATED WITH SPACEFLIGHT OR BOTOX INDUCED MUSCLE PARALYSIS IS AMELIORATED BY RANKL INHIBITION

Aim: The aim of the study is to determine and compare the eﬀect of diﬀerent types of swimming on osteopenic persons.

Warner SE1, Bateman TA3, Morony S2, Ferguson VL3, Simske SJ3, Lacey DL2, Warmington KS2, Geng Z2, Tan HL3, Shalhoub

Table 1: The distribution for women who have fragility fractures and are administered bisphosphonate therapy over a 5-year period. Hip Fracture

Wrist Fracture

Rib Fracture

Spine fracture

Obs.Period

total #

treated N (%)

total #

treated N (%)

total #

treated N (%)

total #

treated N (%)

Year Year Year Year Year

65 79 81 80 71

22 25 26 29 35

430 571 574 566 530

111 133 133 159 172

100 137 139 141 134

31 40 42 52 56

50 76 80 79 74

30 36 47 43 43

One Two Three Four Five

(33.9) (31.7) (32.1) (36.3) (49.3)

(25.8) (23.3) (25.6) (28.1) (32.5)

(31.0) (29.2) (30.2) (36.9) (41.8)

(60.0) (47.4) (58.8) (54.4) (58.1)

Conclusion: A large number of women over the age of 50 years who had a fragility fracture were not given bisphosphonate therapy. More women with vertebral fractures were administered therapy as compared with women with non-vertebral fractures. Given the large therapeutic care gap in treating patients with fractures, initiatives should be taken to reduce the gap and to improve patient management.

S242 V3, Dunstan CR2, Kostenuik PJ2, Gross TS1; 1Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, USA, 2Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA, 3BioServe Space Technologies, University of Colorado, Boulder, CO, USA Aim: To compare the eﬀectiveness of RANKL inhibition (by OPG) in preventing bone loss induced by either spaceflight or when hindlimb muscles are unilaterally paralyzed by a Botox injection. Methods: All animals were female C57B6 mice. Thirty-six 10 week old mice were randomized into 3 groups (n=12/group) for the 12 day spaceflight study (SF): 1) ground control (GC), 2) SF age-matched vehicle (SFC), and 3) SF with OPG (SF+OPG). Thirty-six 16 week old mice were randomized into 3 groups (n=12/group) for the 21 day Botox study (BTX): 1) age-matched saline controls (S), 2) BTX (B), and 3) BTX with OPG (B+OPG). Recombinant human OPG (OPGFc) was injected once (20 mg/kg) 24h prior for SF+OPG group and twice weekly (5 mg/kg) for B+OPG. Alterations in proximal tibia bone volume fraction (BV/TV) were assessed in all mice (via pQCT for SF and µCT for BTX). Serum osteocalcin was assessed in terminal collections. Results: Compared to respective control mice, SF and BTX both significantly reduced tibia BV/TV (-35 and -52%). Treatment with OPG inhibited bone loss and increased BV/TV compared to control mice for both SF (+35%) and BTX (+33%). While SF significantly decreased osteocalcin compared to controls (-14%), BTX did not (+11%). OPG significantly reduced osteocalcin in both SF and BTX mice (-64 and -46%). Conclusions: Both SF and BTX induced rapid bone loss in mice. Despite variations in the initial age of the mice, study duration, and OPG regimen, OPG prevented bone loss in both models. Though both models induced significant bone resorption, reduced osteoblast activity due to SF is known to contribute to decreased bone mass. In contrast, BTX induced muscle paralysis appears to minimally alter osteoblast function while significantly increasing osteoclast function. As in the Botox model, SF is known to reduce muscle mass which may also contribute through currently unknown pathways to observed bone loss in both conditions. Together, these data suggest that Botox induced transient muscle paralysis may serve as a particularly useful model to study skeletal alterations associated with space flight. RANKL inhibition may be a promising therapy to inhibit various forms of disuse osteopenia.

(n=9). There was no case of cement failure, when PMMA had been used. Currently in kyphoplasty, a routine use of CaP cannot be recommended. Due to its minor resistance to bending, extension, and shear forces compared to PMMA, there is a high risk for cement failure and subsequent loss of correction in the well defined clinical setting of osteoporotic vertebral body fractures type A3.

P405MO. RESPONSE TO THERAPY WITH ONCE-MONTHLY IBANDRONATE 150 MG: POST-HOC ANALYSIS OF BMD RESPONDERS FROM THE MOBILE STUDY Silverman SL1, Hochberg MC2, Cole RE3, Barr CE4, Genant HK5; 1Osteoporosis Medical Center, Beverly Hills, 2University of Maryland, Baltimore, 3Michigan State University, Brooklyn, 4Roche Laboratories, Nutley, 5UCSF Medical Center, San Francisco, USA This post-hoc analysis of MOBILE study data evaluated the proportion of responders (women with BMD gains R3% and R5%) and non-responders (women with BMD losses R3%) at the spine and hip following 1 year of treatment with once-monthly oral ibandronate (150 mg). MOBILE (Monthly Oral iBandronate In LadiEs) was a multicenter, Phase III, randomized, double-blind, non-inferiority trial. Women (n=1609) aged 55–80 years with lumbar spine BMD T-scores between –2.5 and –5.0 received once-monthly (50+50 mg [50 mg dose for 2 consecutive days], 100 mg, or 150 mg) or daily (2.5 mg) oral ibandronate. The present analysis evaluated the response to therapy in patients randomized to the 150 mg monthly dose. Responder cut-points were established previously1,2 based on the premise that BMD changes of this magnitude can be determined accurately by dual-energy X-ray absorptiometry (DXA) and can predict antifracture eﬃcacy of bisphosphonates. BMD measurements at four sites were compared: lumbar spine, total hip, femoral neck, and hip trochanter. As seen in the Table, 33%-67% of women randomized to the 150 mg once-monthly ibandronate regimen had BMD increases R3% in the lumbar spine, total hip, femoral neck, and hip trochanter. Using a cut-point of R5%, 17%-42% of women were classified as responders at the four sites. A small percentage of women in the study (2.4%-5.7%) were non-responders (BMD losses R3%). Table. Responders defined by relative BMD change BMD change from baseline

P404SU. CALCIUM PHOSPHATE VERSUS POLYMETHYLMETHACRYLATE: A PROSPECTIVE, RANDOMIZED, CLINICAL TRIAL OF PERCUTANEOUS BALLOON KYPHOPLASTY Blattert TR; Trauma, Reconstructive & Plastic Surgery, Leipzig University, Leipzig, Germany In kyphoplasty and vertebroplasty, polymethylmethacrylate (PMMA) currently represents the standard augmentation material. It is characterized, however, by a lack of osteointegration and its limited biocompatibility. This prospective, randomized trial investigated the feasibility of calcium phosphate (CaP) for augmentation of osteoporotic vertebral body fractures by means of percutaneous balloon kyphoplasty in comparison to PMMA. Inclusion criteria were osteoporotic fractures of vertebral bodies in the thorocolumbar spine, patient age R65 years, and fracture age %4 months. Exclusion criteria were tumor lesions and additional posterior instrumentation. A total of 60 osteoporotic vertebral body fractures in 56 patients were included. CaP and PMMA were randomly applied in 30 cases each. All 60 fractures were classified type A (acc. to Magerl et al.). Of these, 19 were classified type A3. 52/56 patients experienced p.op. pain relief (2.1 1.9 to 8.2 1.5 on a Visual Analogue Scale from 0 ‘‘worst’’ to 10 ‘‘best’’). Endplate angles were restored by 6.2( 2.9 on average. For both parameters (pain relief and restoration of endplate angle), no statistically significant diﬀerence was found between the groups. Cement-specific complications were vascular embolism using PMMA (n=2); subtotal ‘‘cement-washout’’ using CaP (n=1); and substantial loss of correction on radiographs 6 weeks p.op. due to cement failure in all fractures type A3, if CaP had been applied

Site Lumbar spine (n=368) Total hip (n=369) Femoral neck (n=369) Hip trochanter (n=369)

< -3% n(%)

> 0% n(%)

> 3% n(%)

> 5% n(%)

10 (2.7%)

331 (89.9%)

247 (67.1%)

154 (41.8%)

9 (2.4%)

327 (88.6%)

167 (45.3%)

70 (19.0%)

21 (5.7%)

271 (73.4%)

123 (33.3%)

61 (16.5%)

10 (2.7%)

333 (90.2%)

236 (64.0%)

142 (38.5%)

Using R3% BMD gain as a responder cut-point, approximately two out of three women were classified as responders to oncemonthly 150 mg ibandronate treatment at the lumbar spine and hip trochanter, while large numbers responded at the femoral neck and total hip. Relatively few patients were classified as nonresponders based on BMD declines at the four sites measured. 1. Sebba A. et al. (2004) Curr Med Res Opin 20,2031–2041. 2. Hochberg, MC. et al. (2002) J Clin Endocrinol Metab 87,1586– 1592.

P406SA. A DEDICATED COORDINATOR AND AWARENESS PROGRAM IMPROVE THE DOCUMENTATION OF OSTEOPOROSIS IDENTIFICATION AND CARE IN AN ACUTE CARE FRACTURE CLINIC Laughren JJ, Beaton DE, Ward SE, Elliot-Gibson V, Bogoch ER; Mobility Program, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

S243 Aims: To evaluate osteoporosis (OP) documentation and follow-up in fragility fracture patients following implementation of an Osteoporosis Exemplary Care Program (OECP). Methods: A case control study using chart audit was performed on 166 patients with fragility fractures. Patients in the post-OECP group (cases, n=83) were selected from a registry of patients identified as having fragility fractures of the hip or wrist during the first four months of the program. Age, sex and fracture type matched controls (n=83) who had their fracture prior to program implementation were obtained through medical records. Group characteristics were compared using -square tests. Results: Following OECP implementation, chart documentation of OP risk/diagnosis improved from 20.5% (17/83) to 36.1% (30/83) (unadjusted OR 2.20; 95% CI 1.1–4.4). Documentation of referral for OP follow-up increased from 19.3% (16/83) to 42.2% (35/83) (unadjusted OR 3.05; 95% CI 1.5–6.1) and documentation of appropriate OP treatment increased from 25.3% (21/83) to 67.5% (56/83) (unadjusted OR 6.12; 95% CI 3.1–12.0). All patients in the database had been contacted by the coordinator and 97% received appropriate osteoporosis education and referral or treatment, so we are confident that the documented treatment rate was lower than the actual care. Conclusions: Being in the OECP program significantly improved the odds of having a diagnosis of OP in the chart, or having care for the probable OP. Documentation of OP treatment or referral is less common on charts than in our registry. Since the chart remains the avenue of communication and is critical for continuity of care, we have changed our protocol to include the coordinator’s notes in the medical chart.

P407SU. ASSESSMENT OF RELATIVE IMPORTANCE OF DIFFERENT ATTRIBUTES OF OSTEOPOROSIS FROM THE PATIENTS’ PERSEPECTIVE Walliser J1, Bolge S2, Sen SS3; 1Clinical de Metabolismo Oseo y Mineral del Hospital Angeles del Pedregal, 2Consumer Health Sciences, Princeton, NJ, USA, 3Merck & Co., Whitehouse, NJ, USA Background: As per Anderson’s health belief model, a patient’s decision to take action is dependent upon the patient’s perception of advantages and disadvantages of the treatment itself. A better understanding of patients’ preference for diﬀerent attributes of osteoporosis medication may indicate what would be the driving factor for enhancing their adherence to therapy. Objective: To evaluate patients’ attitudes towards diﬀerent attributes of osteoporosis medication. Methods: Physicians were randomly selected in France, Germany, Mexico, Spain and UK and asked to recruit consecutive 4 osteoporotic women aged 50 years or older seen in their practices. These patients were contacted and those who consented to an interview were asked to rank and rate importance of eﬃcacy in reducing risk of fracture, side eﬀects, out-of-pocket costs, dosing frequency, formulation (oral, vs. IV), time on market and dosing procedure on a scale of 1 to 5 (1=not important at all and 5=extremely important). The correlation between patient’s ranking for each attribute and importance rating for that attribute was evaluated to assess the consistency in patients’ response. Results: A total of 3000 patients were interviewed of whom 1500 were on prescription treatment for osteoporosis while rest were not. A majority (57%) of the patients ranked eﬀectiveness in reducing risk of fracture as the most important reason for their preference for osteoporosis prescription medication, while sideeﬀects (20%), and out-of-pocket costs (7%) were the second and third most frequently cited most important reason among all the 7 attributes of osteoporosis medication. Eﬀectiveness in reducing risk of fracture also had significantly (P%0.05) higher mean importance rating (4.6) than side-eﬀects, out-of-pocket costs, dosing frequency, formulation, time on market or dosing procedure. There were significant correlations (P%0.05) between patients’ ranking of each attribute and their importance rating. Conclusion: A majority of patients ranked and rated eﬀectiveness in reducing risk of fracture as the most important reason and of highest importance of all attributes in preferring an osteoporosis medication. Patients ranking of attributes as per their importance

were consistent with their importance rating of each of these attributes indicating internal consistency of the questionnaire used.

P408MO. CORRELATION BETWEEN THE BONE MINERAL DENSITY AND TSH IN PATIENTS ON LEVOTHYROXIN TREATMENT Giorgadze E, Chachibaia V, Tsagareli M, Jikurauli N, Tsagareli N; N4 Clinical Hospital, Department of Endocrine Disorders, Tbilisi, Georgia It is controversial whether the long term treatment with thyroid hormones has a negative eﬀect on bone mass. Most patients receiving hormone replacement therapy with thyroid hormones have a decreased level of TSH, which is regarded as subclinical hyperthyreosis. A number of studies reveal higher bone turnover and greater calcium excretion in patients who are receiving thyroid hormones. Objective: The aim of our study was to reveal the correlation between the bone mineral density (BMD) and TSH in patients on Levothyroxin treatment. Materials and methods: We studied 269 patients (112 males, 157 females) under age 45 on hormone replacement therapy with Levothyroxine at a dose of 75–100 µg (mean duration of treatment was 27 months) after near total thyroidectomy. Patients with history of hyperthyroidism were excluded. We measured ionized calcium, phosphorus values, thyrotropin (TSH), free thyroxine (FT4), parathyroid hormone (PTH), osteocalcin (OC), BMD with ultrasound bone densitometry. Results: The mean value of BMD was (-1.7 0.12), Ca++ values were at the lower level of the norm (1.03 0.01 mmol/l), PTH values varied within the normal range, OC was insignificantly elevated (30.7 0.2 ng/ml). The mean value of TSH was 0.9 0.01. Statistical analyses revealed a correlation between BMD and TSH levels (r=0.45, p<0.01). Conclusion: Long term treatment with thyroid hormones aﬀects bone mass.

P409SA. THE MINIMAL-INVASIVE TREATMENT OF OSTEONECROSIS IN OSTEOPOROTIC VERTEBRAL FRACTURES WITH KYPHOPLASTY Becker SWJ, Tuschel A, Meissner J, Chavanne A, Ogon M; Spine Center, Orthopaedic Hospital Vienna – Speising, Vienna, Austria A complete collapse of osteoporotic vertebral fractures is diﬃcult to treat. Restoration of the vertebral height is very diﬃcult, if ever possible. Kyphoplasty has been shown to restore vertebral compression fractures; however, the best results are achieved in fractures without total collapse. Some fractures develop osteonecrosis and pseudarthrosis which can be easily seen on x-rays. We performed a retrospective study in order to evaluate the capacity of kyphoplasty in vertebra plana with osteonecrosis. Materials and methods: We analyzed the pre- and postoperative x-rays of vertebra plana treated between 2002 and 2005. Vertebral height (vh - anterior, middle and posterior) and kyphotic angle were measured with a digital imaging system. 2 independent examiners classified the preoperative x-rays into fractures with osteonecrosis/pseudarthrosis (group 1) and without osteonecrosis (group 2). Statistical analysis with the non-parametric MannWhitney test. Results: Between 2002 and 2005 we performed 315 kyphoplasties, 15 cases with vertebra plana (mean age 76 years, SD 5.2 years, average time of treatment after fracture 4 months). Osteonecrosis was prevalent in 8 cases. The osteonecrosis group 1 showed a statistically significant higher degree of vertebral reconstruction (p < 0.013 - group 1: anterior vh 33%, middle vh 37.8%, posterior vh 19.1%; group 2: anterior vh 4.9%, middle vh 17.5%, posterior vh 1.8%). No significant diﬀerence was found regarding pre- and postop. kyphotic angle (p = 0.146, group 1: restoration mean 9.1( - maximum 18(; group 2: restoration mean 3.5( - maximum 13(). No statistical diﬀerence was found in the clinical outcome of both groups, all patients showed a significant reduction of the pain level and could be discharged one day postop. Conclusion: Osteonecrosis is a positive predictive sign for the potential of vertebral reconstruction. Vertebral height can be

S244 significantly improved in those patients and the major changes of the kyphotic angle are possible. Even after 4 months, correction of the deformity is possible with kyphoplasty. However, without this sign, restoration of the vertebral height and correction of kyphosis is limited to rare cases. Nevertheless all our patients showed a significant improvement of back pain, which supports the indication for this intervention.

P410SU. KYPHOPLASTY PERSISTENTLY REDUCES PAIN IN PATIENTS WITH OSTEOPOROTIC VERTEBRAL FRACTURES: 3 YEAR OUTCOME OF A PROSPECTIVE CONTROLLED COHORT STUDY Grafe I1, Da Fonseca K2, Hillmeier J2, Meeder PJ2, Libicher M3, Noeldge G3, Sommer U1, Hilscher U1, Nawroth P1, Kasperk C1; 1 Internal Medicine I, Endocrinology, 2Orthopedic Surgery, 3Radiology, University of Heidelberg, Heidelberg, Germany Introduction: Recently we have shown reduction of pain and improvement of morphological parameters after kyphoplasty in patients with painful osteoporotic vertebral fractures compared to a conservatively treated control group. To evaluate long-term eﬀectiveness of the kyphoplasty procedure we reassessed the patients of this trial in a 3 year follow-up. Methods: Kyphoplasty was performed in 40 of 60 consecutive patients with primary osteoporosis and painful vertebral fractures, 20 patients served as controls. All patients received a pharmacological osteoporosis treatment (1000 mg calcium, 1000 IU vitamin D3, oral aminobisphosphonate), pain medication and physiotherapy. Pain (visual analog scale (VAS), range 0–100) and radiomorphological measures were assessed at baseline, after 6, 12 and after 36 months. Results: After initial improvement of the pain score (VAS) from 26.2 to 44.4 during the first year in the kyphoplasty group, there was almost no further change in the VAS-score (46.1) after a 3 year follow-up period. The pain score of the conservatively treated control group changed from 33.6 to 37.9 during the follow-up period. Clinically asymptomatic cement leakages were observed in 9.7 % of the vertebral bodies, which is comparable to previous reports. No complications of neurological, embolic or cardiovascular symptoms occurred after kyphoplasty. Conclusions: Kyphoplasty is a safe method for a sustained pain reduction in patients with painful osteoporotic vertebral fractures in addition to medical treatment, if performed in appropriately selected patients by an interdisciplinary team.

P411MO. MR-DETECTED BONE EDEMA IS NOT A PREREQUISITE FOR LONG TERM BENEFIT BY KYPHOPLASTY Grafe I1, Noeldge G2, Da Fonseca K3, Hillmeier J3, Meeder PJ3, Libicher M2, Sommer U1, Hilscher U1, Nawroth P1, Kasperk C1; 1 Internal Medicine I, Endocrinology, 2Radiology, 3Orthopedic Surgery, University of Heidelberg, Heidelberg, Germany Introduction: Kyphoplasty has been shown to be a safe and eﬀective method for reducing pain in patients with painful osteoporotic vertebral fractures. In fractured vertebral bodies, bone edema detected by MRI are a radiological finding in acute fracture cases which is usually not discernable after 3 months. This study investigates the possibility that only patients with acute vertebral fractures as indicated by MR-detected bone edema benefit from kyphoplasty in terms of pain reduction. Methods: Preoperative MR-Images are available from 35 patients with primary osteoporosis and painful vertebral fractures who were treated by kyphoplasty. MR-Images were evaluated with regard to the presence or absence of a bone edema. All patients received a pharmacological osteoporosis treatment (1000 mg calcium, 1000 IU vitamin D3, oral aminobisphosphonate), pain medication and physiotherapy. Pain (visual analog scale (VAS), range 0–100) and radiomorphological measures were assessed at baseline, after 1 and 12 months. Results: In 20 patients with MR-detected bone edema the pain score (VAS) changed from 23.4 (preoperative) to 55.8 (postoperative) and to 49.1 after 12 months. In 15 patients with no preop-

erative bone edema the pain score improved from 29.9 (preoperative) to 39.5 (postoperative) and to 50.9 after 12 months. Conclusions: In patients with new vertebral fractures, confirmed by bone edema in MR-Images, kyphoplasty is an eﬀective method for an immediate and sustained pain reduction. After 12 months there was comparable pain reduction in patients with and without preoperative bone edema. We conclude that MR-detected bone edema is not a prerequisite for the long-term benefit of kyphoplasty in patients with painful osteoporotic vertebral fractures, provided that kyphoplasty was performed at the vertebral bodies which were truly responsible for the back pain.

P412SA. THE EFFECT OF UVB FROM SUN EXPOSURE ON VITAMIN D AND PTH LEVEL IN INDONESIAN ELDERLY WOMEN Setiati SS; Division of Geriatric, Department of Internal Medicine, Faculty of Medicine University of Indonesia, Jakarta, Indonesia Vitamin D deficiency in elderly was thought to occur rarely, especially in Asia as those countries are rich in sunlight exposure. The question is whether the UVB from sunlight exposure can be used as the main source of vitamin D for Indonesian elderly women since there are some characteristics of this population which will reduce vitamin D production in the body, such as old age, dark skin, less skin fat and BMI. There is no study using sunlight exposure to improve vitamin D and parathyroid hormone (PTH) level. Instead, most studies used artificial UVB irradiation as the source. The aim of this study was to compare the eﬀect of UVB from sunlight exposure and control on the vitamin D status and PTH concentration in Indonesian elderly women. The design of this study was a randomized clinical trial. Subjects included 74 elderly women in institutionalized care with a mean age 71 years. Exclusion criteria were having abnormalities in liver and kidney function, pre-cancer and cancer skin lesion. Intervention was random allocation of UVB from sunlight exposure at 0.5 MED/hour noted in UV meter on the face and two arms and calcium 1000 mg three times per week during 6 weeks, or no treatment (calcium 1000 mg only). Main outcome measures were fasting serum levels of 25(OH) D and PTH at 0 and 6 weeks in the treatment and control groups. Baseline serum of 25(OH) D was less than 50 nmol/L of in 35.1% of subjects, and the rest were normal. Baseline mean serum 25(OH) D of intervention and control group were more than 50 nmol/L. In the treatment group, 25(OH) D increased from 59.1 nmol/L to mean value of 84.3 nmol/L (42.6%) after 6 weeks of sunlight exposure. There was only a slight increase of 25(OH) D in the control group. No change in PTH level in both groups. In additional analysis, it was found that in the subgroup of sunlight exposure group with mean serum of 25(OH) D less than 50 nmol/L, the level of 25(OH) D increased 51.1% from 38.7 nmol/L to 58.5 nmol/L.

P413SU. DIAGNOSTIC AND THERAPEUTIC CARE GAP IN BOTH WOMEN AND MEN WHO HAVE BEEN TOLD THEY HAVE OSTEOPOROSIS: THE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY (CAMOS). Papaioannou A1, Ioannidis G1, Tenenhouse A2, Gao Y2, Berger C2, Prior JC3, Kaiser SM4, Hanley DA5, Brown JP6, Olszynski WP7, Josse RG8, Murray TM8, Anastassiades T9; 1McMaster University, Hamilton, Canada, 2McGill University, Montreal, Canada, 3University of British Columbia, Vancouver, Canada, 4 Dalhousie University, Halifax, Canada, 5University of Calgary, Calgary, Canada, 6Laval University, Ste-Foy, Canada, 7University of Saskatchewan, Saskatoon, Canada, 8University of Toronto, Toronto, Canada, 9Queen’s University, Kingston, Canada, 10 Memorial University, St. John’s, Canada, 11University of Alberta, Edmonton, Canada Aims: Although there are proven benefits to pharmacologic therapies many individuals with osteoporosis do not receive treatment. Utilizing participants from CaMos, a nation-wide, random sample of the Canadian population, we performed a cross-sectional analysis to determine the number of community dwelling women

S245 and men 50 years of age and older who have osteoporosis and are on treatment. Methods: A total of 5566 women and 2187 men from nine CaMos centres formed the base cohort of the study. At study entry, subjects completed a questionnaire. Participants were classified as having osteoporosis if they answered yes to the question: Has a doctor ever told you that you have osteoporosis? Participants that answered no were deemed not to have the disease. All treatment options were self-reported. Results: Results indicated that a total of 12.1% (674/5566) of women and 1.3% (29/2187) of men R50 years had osteoporosis. Among these individuals, 6.2, 11.9, 15.2, and 18.4% of women and 1.2, 0.8, 2.1, and 1.5% of men between the ages of 50–59, 60–69, 70–79, 80+ years indicated that they had osteoporosis. Approximately 9 times as many women were told they had osteoporosis as compared with men. Nonetheless, a similar percentage of women and men who had the disease were given therapy, Unfortunately, a majority of osteoporotic subjects were not administered therapy. Given the similar percentages of women on hormone therapy (HRT) who had and did not have osteoporosis, it is likely that HRT was not prescribed specifically for osteoporosis (table 1). Table 1: Treatment distribution for women and men in CaMos with and without osteoporosis

Women: n (%) HRT Bisphosphonates Calcitonin/Fluoride Men: n (%) Bisphosphonates Calcitonin/Fluoride

Osteoporosis

Without Osteoporosis

205 (30.4) 161 (23.9) 21 (3.1)

1209 (25.4) 22 (0.5) 15 (0.3)

6 (20.7) 1 (3.5)

1 (0.1) 1 (0.1)

Conclusion: In this population-based study, the percentage of patients who self-reported osteoporosis is lower than the CaMos prevalence estimates based on bone mineral density testing (19.4% women; 6.4% men). Given the low number of women and men with the condition and on therapy, future initiatives should involve reducing the diagnostic and therapeutic care gap.

P414MO. BONEMARKER AND COMPLIANCE IN PATIENTS WITH OSTEOPOROSIS Günther C1, Kapner A1, Arnold-Dahmen D1, Schultis H-W2, Günther O3, Günther S4; 1Deutsches Zentrum für Osteoporose Prävention, -Therapie und -Rehabilitation, Bad Füssing, Germany, 2Gemeinschaftspraxis für Laboratoriumsmedizin und Mikrobiologie, Weiden, Germany, 3Bundeswehrkrankenhaus Berlin, Abt. X (Anästhesie), Berlin, Germany, 4Kinderklinik des Klinikums Aschaﬀenburg, Germany Introduction: More than 50% of osteoporotic patients under bisphosphonates discontinue treatment within one year. Therefore the question arises if the use of a valid bone resorption marker can improve the compliance during a three weeks osteologic-orientated rehabilitation stay. Methods: In the first step the qualification of two degradation markers (-CTX i. S. from Roche and NTX i. U. from OCD) for a short time monitoring under diﬀerent antiresorptive drugs plus calcium vitamin D was tested. The second step covered 31 patients with osteoporosis (T-score < -2.5), and a therapy with solely Actonel 35 mg weekly plus Calcium (1200mg) and vitamin D (800I.E.). In the third step telephone interviews exactly one year after therapy start investigated the compliance. Results: Both NTX i. U. and -CTX i. S. indicated the eﬃcacy of the used therapies after 14 days. -CTX i. S. (decrease 48.6 %) seemed to be more eﬃcient than NTX i. U. (decrease 30.7 %). That’s why in the second step only -CTX i. S. was used. Patients taking Actonel 35mg showed a high significant (p < 0.001) decrease of 42.1 % after two weeks. 26 out of 31 patients could be reached through telephone interview. 5 (19.2 %) of them stopped taking the medication after consulting their doctor 4 weeks after start of

therapy. 21 patients (80.8 %) continued taking medication regularly for one year. Conclusion: A proved compliance of 80.8 % after one year shows, that a detailed discussion about the course of bone resorption marker -CTX under therapy, is an eﬀective instrument to improve compliance. The recommended intervals for biomarker controls (3 to 6 months) should be shortened, so that biomarker can complete or even replace bone density measurement in eﬃciency judgement of therapy.

P415SA. PATIENTS INTOLERANT TO ORAL ALENDRONATE OR RISEDRONATE PREFER INTRAVENOUS IBANDRONATE OVER ORAL DOSING Lewiecki EM1, Koltun W2, Kornowski A3; 1New Mexico Clinical Research & Osteoporosis Center, Alburquerque, USA, 2Medical Center For Clinical Research, San Diego, USA, 3Roche Laboratories, Nutley, USA PRIOR is a 12 month, open label, multi-center study designed to compare adherence to 150 mg once-monthly oral or 3 mg quarterly intravenous ibandronate dosing in postmenopausal women with osteoporosis or osteopenia who discontinued prior oral bisphosphonate (BP) therapy because of gastrointestinal (GI) adverse events. Subjects included in this study were postmenopausal women (mean age 66, range 31–90 years) with osteoporosis (68%; 365/537) or osteopenia (32%; 172/537), who were previously treated with alendronate or risedronate and had discontinued treatment due to GI intolerance a minimum of 3 months prior to enrollment. Patients were oﬀered two treatment options: ibandronate 150 mg orally once-monthly or ibandronate 3 mg intravenously (IV) every 3 months with the possibility to switch treatment route once during the study. The primary endpoint is the proportion of patients who achieve R75% adherence with therapy. Patients were also asked to complete the GI Experience Survey, capturing the severity and duration of GI symptoms while on BP therapy at screening and months 1, 4, 7, and 10.The duration and severity of GI events in the two treatment groups will be compared. Data on patient selections and early switches in route of administration are presented here. Enrollment in this study was completed ahead of schedule and baseline data (N=537 as of November 1, 2005) have been analyzed. Approximately 72.5% (n=389) of women chose intravenous ibandronate. From among patients with a history of fracture, 81% chose IV over oral ibandronate (p=.0022). As of November 5, 2005, 15 (2.8%) patients had switched administration routes from IV to oral or oral to IV. Based on these findings, it appears that patients who had previously discontinued weekly or daily oral BPs because of GI intolerance prefer IV dosing over oral dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture.

P416SU. ACCEPTANCE AND EFFECTIVENESS OF INJECTABLE ARACHITOL IN PATIENTS OF OSTEOMALACIA IN AN UNDERPRIVILEGED AREA Kalra S, Kalra B, Batra P, Bhatia K, Kumar S; Bharti Hospital, Karnal, Haryana, India Osteomalacia and rickets are common morbidities in northern India, in spite of abundant sunshine. Many patients find it diﬃcult to take adequate dairy products and appropriate medicines because of the cost involved. This study was designed as a randomized open–label trial to assess the acceptance, eﬀectiveness and compliance with therapy of a stat dose of injectable Arachitol (cholecalciferol 600000 U [15mg] in Arachis oil) versus daily dose of 0.25 mg calcitriol capsules. 36 patients of osteomalacia formed the oral vitamin D3 cohort while 36 patients were administered one intramuscular injection of Arachitol monthly. Both groups received calcium preparations in appropriate doses. The Arachitol group had 100% compliance, the cost of therapy was Rs 57 (USD 1.40), and no side eﬀects were reported.

S246 Pain levels, measured on a visual analog scale, reduced from 6.20 1.20 at baseline to 2.20 0.20 at 3 months while serum calcium rose from 7.79 0.30 to 8.74 0.33 mg% in the Arachitol group. Serum alkaline phosphatase fell from 454.8 163.4 to 240.0 50.7 IU/ml at 3 months. Reductions of similar magnitude were observed in the calcitrol group (6.80 1.20 to 2.20 0.20 for pain, 8.29 0.31 to 8.94 0.21 mg% calcium) and 468.3 162.3 to 242.7 48.8 IU/ml alkaline phosphatase). The cost of therapy was Rs 1170 (USD 24) per 3 months. Side eﬀects experienced included epigastric burning in 4/36 patients. Self–reported compliance was poor (more than 50% capsules missed) in 4/36 and good (less than 10% capsules missed) in 22/36. This study demonstrates the equal eﬃcacy of injectable Arachitol vis-a-vis oral calcitrol, with no adverse eﬀects, good patient compliance and significantly better cost-eﬀectiveness (1/60th cost). Injectable Arachitol can thus be used as an economical, safe and eﬀective therapy for osteomalacia.

P417MO. CHANGES IN BODY COMPOSITION ARE THE PRIMARY PREDICTORS OF FOUR-YEAR BONE MINERAL DENSITY CHANGES IN POSTMENOPAUSAL WOMEN Milliken LA1, Cussler EC2, Zeller RA3, Choi JE2, Metcalfe L2, Going SB2, Lohman TG2; 1University of Massachusetts Boston, Boston, MA, USA, 2University of Arizona, Tucson, AZ, USA, 3 Kent State University, Kent, OH, USA Aims: The purpose of this study was to examine the relationship between body weight and changes in body weight or composition and changes in 4-year bone mineral density (BMD) after accounting for age, 4-year exercise frequency (EX), and 4-year calcium intake (CA) in postmenopausal women with or without hormone therapy (HT). Methods: Sedentary postmenopausal women (40–65 years) with HT (1–3.9 years) or without HT (R1 year) were recruited to participate in the Bone Estrogen Strength Training study which was designed to determine the eﬀects of strength and weightbearing exercise training on BMD in calcium-supplemented postmenopausal women. After year 1, women randomized to control were invited to self-select exercise or control. One hundred and sixty-seven women completed 4 years of the study (all pre-WHI). Regional BMD and body composition were measured using dual-energy x-ray absorptiometry at baseline and yearly thereafter. EX, CA and HT use were monitored throughout the study. Hierarchical multiple regression analyses were used to predict 4-year BMD changes from EX, CA compliance, age, baseline and 4-year changes in body weight and composition. Analyses were conducted separately for HT users (n = 115, 55.3 4.3 yrs) and non-users (n = 52, 57.5 4.7 yrs). Results: The adjusted R2’s for the models predicting 4-year changes in femoral neck (FN), greater trochanter (TR), and spine (SP) BMD were 12.9% to 22.6% (HT users) and 15.1% to 37.2% (non-HT users). EX and CA alone explained more variance for non-HT users versus HT users (33.7% vs. 7.3%). For women on HT, EX, baseline body weight and changes in lean and fat mass were consistent significant predictors of FN and TR 4-year changes while EX consistently predicted SP changes. For non-HT users, change in lean mass was a consistent predictor of FN and TR changes, while CA, EX and age predicted SP changes. Conclusion: Body weight and composition changes are important predictors of BMD changes independent of EX and CA supplementation but their contribution varies by bone site and with HT use. While long-term EX and CA aﬀect SP, hip sites tend to respond to 4-year changes in body composition.

P418SA. EVIDENCE OF AN EDUCATION PROGRAM FOR THE PREVENTION AND MANAGEMENT OF OSTEOPOROSIS Woo K1,2,3, Weldon M1, Chan G1,2, Soever L1; 1North York General Hospital, 2University of Toronto, 3Univeristy of Ryerson, Toronto, ON, Canada

Aims: The purpose of this presentation is to discuss and highlight outcome indicators for the evaluation of an osteoporosis program. Self-eﬃcacy in the management of the disease, knowledge acquisition, and behavioural changes after participating in the program will be presented. Methods: Osteoporosis is a common problem in the elderly. However, many patients suﬀer from osteoporosis are unknown to the fact that they have the disease until significant and disabling symptoms emerge. Recognizing the enormity and chronicity of the disease, an education program is developed to meet the learning needs of older adults in the management of osteoporosis. The Building Bridges to Better Bone (BBBB) program is designed to meet the learning needs of people who are age 45 and above in the Toronto area. The program provides education and practical information to participants over two 2-hour sessions led by a nurse and a physiotherapist. It is our goal that appropriate education and resources will empower participants to engage in the self-management of their disease, to make healthy lifestyle choices and to optimize their overall quality of life. Based on a comprehensive review of the literature, tools are selected to evaluate the eﬀectiveness of the program. Each participant was asked to respond to questionnaires related to self-eﬃcacy in the management of the disease, knowledge level, and behavioural changes after participating in the programs. Conclusions: Participants of a short education program reported increased knowledge level and self-eﬃcacy in the prevention and management of osteoporosis. Psychometric properties of the tools are acceptable. Behavioural changes as they related to diet and exercise were inconsistent. Long term follow-up of the participants is instituted to determine if some of those changes are sustained overtime.

P419SU. TESTING OF MECHANICAL PROPERTIES OF NEW MATERIALS COMPARED TO COMMERCIALLY AVAILABLE HIP-PROTECTORS Holzer G, Holzer L; Department of Orthopaedics, Medical University of Vienna, Vienna, Austria Aims: Osteoporosis and falls are the main reasons for hip fractures in elderly. To prevent hip-fractures three steps were recommended: (1) Treatment of osteoporosis, (2) prevention of falls, (3) mechanical prevention of fractures using protectors at the fracture site (Kannus 2005). Due to their design compliance and adherence to wear hip-protectors is poor. The objective of this study was to compare diﬀerent available hip-protectors and new materials with improved mechanical properties. Methods: Two hip-protectors using new materials and five commercially available hip-protectors (AHIP, Astrosorb; AHF Hip pant, Hips, KPH, Safehip, Safety Pants) were mechanically tested using an mechanical testing maschine according to European Norm EN 1621–1, an impact testing with 50 Joule. Results are peak (max) expressed in kiloNewton. Results: The results of impact testing of the two hip-protectors using new materials were superior (AHIP 9.10 kN, Astrosorb 12.65 kN) to the other commercially available hip-protectors (21.97 – 50.62 kN), which diﬀer in the performance to mechanical testing. Conclusion: Compliance and adherence of currently available hip-protectors are poor. Reasons might be design and wearing comfort. New materials with improved mechanical properties will allow more appealing design and increased wearing comfort. This can be reached by the use of thinner elements, more flexibility, less skin contact to reduce sweating. The results of this study shows that new available materials with improved mechanical properties are superior to currently available hipprotectors from the mechanical point of view. Using these materials designing new hip-protectors with increased compliance and adherence is possible. AHIP, a hip-protector using new material, implements modern design, improved wearing comfort and best mechanical properties. Kannus P, et al. Non-pharmacological means to prevent fractures among older adults. Ann Med. 2005;37:303–10.

S247

P420MO. MANAGEMENT OF PATIENTS PRESENTING TO THE EMERGENCY ROOM WITH LOW-TRAUMA FRACTURES: RESULT OF A MULTIDISCIPLINARY INTERVENTION. Reynaud Levy O, Seux V, Nouvelet S, Flecher X, Dumas J, Guenat R, Alazia M, Argenson JN, Soubeyrand J, Retornaz F; Hopital Sainte Marguerite, Marseilles, France Aims: Despite the high frequency, morbidity and mortality of osteoporosis, the proportion of patients who receive appropriate diagnostic and therapeutic measures remains very low. We set up a project to implement a specific intervention for patients with low-trauma fractures seen in the emergency room (ER). The intervention consisted of a complete assessment in order to improve the diagnosis and subsequent treatment of osteoporosis and prevent the risk of new falls. Methods: All patients admitted to the ER with a low-trauma fracture received a letter from the ER physician indicating that they were at risk for osteoporosis. This letter explained that patients discharged home directly could subsequently be assessed as outpatients in the department of Internal and Geriatric Medicine. Those admitted to the Orthopaedic department were evaluated as inpatients. The assessment was performed over 2 visits and included a physical examination, collection of biological parameters, evaluation of risk factors for osteoporosis and falls, and Dual-energy X-ray absorptiometry (if necessary) in order to propose eﬀective interventions and treatment plans for osteoporosis. A geriatric assessment was also performed for patients older than 65 years. Results: Over a 6-month period, 344 patients were admitted to the ER for a low-trauma fracture. 67 patients (mean age = 77.8) were evaluated (hip fracture 51, humerus 5, spine 4, distal forearm 3, other sites 4). 58 patients were assessed during their stay in the Orthopaedic department and 9 were assessed as outpatients. Specific antiosteoporotic therapy was proposed for 60% of patients in addition to calcium and vitamin D supplements (96%). All patients received falls prevention counselling. Conclusion: This study demonstrates that a systematic approach to the evaluation of osteoporosis after low-trauma fracture increased the percentage of patients in whom the diagnosis of osteoporosis is made, particularly when they are inpatients rather than outpatients. In this high risk population, medical management of patients with low-trauma fracture in the orthopaedic department increases the rates of osteoporosis diagnosis and treatment. Simply informing patients about osteoporosis directly in the ER is not suﬃcient to change patients’ attitudes towards the disease.

P421SA. INULIN ENHANCES BOTH THE BMD AND THE MUCOSAL LEVELS OF CALCIUM BINDING PROTEINS IN RATS Manicourt DH, Nzeusseu Toukap A, Devogelaer JP; Rheumatology Unit, St-Luc University Hospital, Brussels, Belgium Increase in BMD observed in growing rats fed with chicory fructans can be related to an improved colonic calcium absorption. Colonic fermentation of fructans increases the solubility of calcium salts by lowering the pH and by inducing hypertrophy of cecal walls. An increase in the levels of calcium binding proteins (CaBPs) in the mucosal cells of the large bowel cannot be excluded. In a 3-month time period, 3 groups of 13 six-week-old male rats each received either the standard AO4 diet (CTL group), the standard diet containing 5% inulin (INU group) or the standard containing 5% chicory oligofructose (OLF group). At sacrifice, rats of the 2 fructan groups both had a similar median cecal wall weight (1.5 g), significantly higher than that of the CTL group (0.9 g; p < 0.001). Mucosal proteins were subjected to Western blots and semiquantification of blots probed with anti-9-kDa-Calbindin antibodies showed that the levels of this CaBP was increased by a factor of 2 in the OLF group and by a factor of 3 in the INU group. Surprisingly, a monoclonal anti-28-kDa-Calbindin antibody detected a signal at the expected molecular weight in all specimens; further, when compared to the CTL group, the signal intensity was increased by a factor of 3 in the OLF group and by a factor of 5 in the INU group. In both L3 and proximal tibia, the

BMD measured by pQCT of cancellous bone was significantly increased by INU (0.27 vs 0.23 and 0.33 vs 0.22 g/cm3, respectively; p<0.001) and to a lower extent by OLF (0.26 and 0.28 g/cm3; p<0.05). Further, inulin but not OLF enhanced the BMD of cortical bone in both L-3 (0.98 vs 0.93 g/cm3; p < 0.01) and tibia (0.88 vs 0.83 g/cm3; p<0.01). In conclusion, the stronger eﬀet of inulin is likely to be related, at least partly, to a strong increase in the mucosal levels of the 9 kDa and 28 kDa calcium binding proteins which both contribute to intestinal calcium absorption. Disclosure: work supported by an institutional grant of Cosucra Group, Warcoing, Belgium.

P422SU. CALCIBON COMPARED TO PMMA-CEMENT IN KYPHOPLASTY OF PAINFUL OSTEOPOROTIC VERTEBRAL FRACTURES: 3 YEAR OUTCOME OF A PROSPECTIVE COHORT STUDY Noeldge G1, Grafe I2, Da Fonseca K3, Hillmeier J3, Meeder PJ3, Libicher M1, Sommer U1, Hilscher U1, Nawroth P1, Kasperk C1; 1 Radiology, 2Internal Medicine I, Endocrinology, 3Orthopedic Surgery, University of Heidelberg, Heidelberg, Germany Introduction: Calcium-phosphate cements have been developed for the use in kyphoplasty of vertebral fractures. These cements are replaceable by newly formed bone after implantation into bone tissue, e.g. into vertebral bodies. Previously available calciumphosphate cements showed early cement resorption which resulted in instability and pain due to ongoing vertebral fracturing. Calcibon is a new calcium-phosphate cement which exhibited satisfying stability in short term observations. Here we report the 3 year outcome compared to conventional PMMA-cement. Methods: Kyphoplasty was performed in 40 consecutive patients with primary osteoporosis and painful vertebral fractures, 20 received Calcibon cement, 20 were treated with PMMA-cement. All patients received a pharmacological osteoporosis treatment (1000 mg calcium, 1000 IU vitamin D3, oral aminobisphosphonate), pain medication and physiotherapy. Pain (visual analog scale (VAS), range 0–100) and radiomorphological measures were assessed at baseline, after 6 and 36 months. Results: The pain score (VAS) improved from 26.9 (preoperative) to 41.5 after 6 months and to 41.9 after 3 years after kyphoplasty with Calcibon cement. In the PMMA-cement group the pain score changed from 25.5 (preoperative) to 46.9 after 6 months and to 47.3 after 3 years. Diﬀerences between both groups were not statistically significant at any time point. Conclusions: Calcibon calcium-phosphate cement is as eﬀective as conventional PMMA-cement in immediate and sustained pain reduction in patients with painful vertebral fractures. Since Calcibon has the potential of being resorbed and replaced by newly formed bone tissue, it conceivably may be used in younger patients with type A.1.1 (AO) traumatic fractures.

P423MO. EFFICACY OF ALFACALCIDOL TREATMENT FOR SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH CHRONIC RENAL FAILURE BEFORE DIALYSIS Rozhinskaya LY1, Il’ina AN1, Borisov AV2; 1National Research Center for Endocrinology, 2Center for Extracorporal therapy ‘‘Fesfarm’’, Moscow, Russia Aims: Secondary hyperparathyroidism (SHP) is observed in some patients with end-stage renal disease (ESRD) as the glomerular filtration rate (GFR) falls below 60 ml/minute and is a severe complication of uraemia. To determine the eﬀective doses of Alfacalcidol for SHP in patients with ESRD before dialysis. Methods: 57 patients (42 women and 15 men) with creatinine level from 150 to 450 unit/l and GFR from 58 to 13 ml/minute were examined. 55% of these patients were with diabetes mellitus. The basic level of parathyroid hormone (PTH) was from 43 to 1032 pg/ml. 38 patients (66%) suﬀered from SHP with mean PTH level 417 pg/ml. Alfacalcidol was prescribed individually in doses from 0.5 to 3.75 µg per week in patients with PTH level more than 200 pg/ml. Patients were treated during one year and it was possible to correct dose during the treatment. PTH, calcium, phosphorous, creatinine, bone resorption marker CTx levels were measured in

S248 serum several times during the treatment. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA) (Lunar) at the lumbar spine, femoral neck, total hip and radius. Results: PTH was 50% lower from basic level in patients who received more than 1.75 µg Alfacalcidol per week. When Alfacalcidol was prescribed in dose less than 1.75 µg PTH level decreased insignificantly or even increased. The treatment was ineﬀective in 9 (24%) patients. The creatinine level increases in average at 21% among patients with Alfacalcidol treatment; however, it was independent of Alfacalcidole dose. There were no significant diﬀerences in calcium, phosphorous levels and BMD in all regions of the skeleton. The CTx level did not significantly change during the treatment and was 1.7660.877 (meanstandard deviation) before and 1.7240.735 after treatment. Conclusions: Thus Alfacalcidol is eﬀective for SHP treatment in patients with ESRD before dialysis if it is received in dose more than 1.75 µg per week. Treatment with Alfacalcidol leads to BMD stabilization. There were no diﬀerences in CTx level apparently due to progress of main disease and relatively low doses of Alfacalcidol.

Veneto. In particular, in 2003 the timing of surgery after hospital admission varied from 2.2 2.4 days in Padua to 6.2 4.0 (mean standard deviation) days in other Health Units and the percentage of patients undergoing surgery varies from about 94% in Padova to less than 70% in other Health Units. The risk of death after 3 months from discharge for those who did not undergo surgery was double compared to those undergoing surgery (HR. 1.96, CI=1.26–3.04) after adjusting for age, sex and co-morbidity. The SISAV Study underlines also that the pharmacological treatment after hip fracture is inadequate: antithrombotic drugs for a period of time of at least 28 days and antiresorptive drugs are prescribed with a large variability across centers and generally do not reflect international guidelines: only 58.6% seem to be treated optimally with antithrombotic drugs and only 8.1% with antiresorptive drugs. The follow up of the patients, showed a re-fracture rate of 4% among those who are not treated, versus 0% of those adequately treated with antiresorptive drugs. Moreover, the 2 year mortality rates were significantly higher among those not treated with antithrombotic and with antiresorptive drugs, after adjusting for co-morbidity, age and sex.

P424SA. QUANTITATIVE STUDY ON THE EFFECT OF LIGUSTILIDE ON PROXIMAL TIBIAE IN OVARIECTOMIZED RATS Tian JW, Li GS; School of Pharmacy, Yantai University, China Aims: To investigate the possible protective eﬀect of ligustilide on proximal tibiae in ovariectomized rats. Methods: Thirty-one 3-month-old female Sprague-Dawley rats were randomly divided into 5 groups, basal control (group 1, killed at the begining), aging control (group 2), ovariectomized (OVX, group 3 ), OVX with nilestriol treatment group (group 4) and OVX with ligustilide treatment group (group 5). Group 2 and group 3 ig with water 5 mlckg-1 and group 5 ig with ligustilide 10 mgckg-1, all once a day for 6 d; group 9 ig with nilestriol 1 mgckg-1, once a week. After 12 weeks, all rats were killed. The proximal tibiae of rats were processed into undecalcified sections at 20 um thickness for histomorphometric analysis. Results: OVX was shown to reduce markedly the trabecular bone mass (%TbcArw59%)due to increase of bone turnover with the result that bone resorption exceeded bone formation, as compared with aging controls. In contrast, treatment of OVX rats with ligustilide and nilestriol increased significantly the trabecular area (increased 68% and 274% compared with that of OVX, respectively). Conclusions: ligustilide and nilestriol treatment provides protection against osteoporosis in OVX rats. The protective mechanism of ligustilide and nilestriol involves supression of bone turnover, but the eﬀects of ligustilide is lower than that of nilestriol (trabecular area decreased 55% more in ligustilide group than that with nilestriol treatment). Our finding may provide theoretical evidence for the clinical use of ligustilide or nilestriol for treatment and prevention of osteoporosis.

P425SU. PROFILE OF CARE FOR HIP FRACTURE IN ITALY Maggi S1, Grion AM2, Giannini S1, Saugo M3, Crepaldi G1; 1 CNR Center on Aging, Padua, Italy, 2Teaching Hospital, Padua, Italy, 3Health Unit 4, Schio (VI), Italy Hip fracture is one of the most important causes of death and disability among older people. The SISAV project (Sistema di Indicatori della Salute dell’Anziano nel Veneto), is an ongoing research program, supported by a grant from the National Health Department since 2003. The main aim of the study is to ascertain the profile of care for hip fractures in the teaching Hospital of the university of Padua and in the Veneto Region (Italy). Patients with pathological fractures were excluded from the study, as well as multiple hospital discharges for the same event. The frequency of hip fractures is about 65/10.000 individuals aged 65+/year. The accuracy of neck of femur fractures using ICD9 codes is high, and the coding mistakes irrelevant. The profile of care and the availability of community services present a high variability among the diﬀerent Health Units in

P426MO. TRUNK MUSCLE RESPONSE TO PERTURBATION IS AFFECTED BY OSTEOPOROTIC VERTEBRAL FRACTURE AND THORACIC KYPHOSIS Greig AM1,2, Bennell KL1, Briggs AM1,2, Hodges PW3; 1Centre for Health, Exercise and Sports Medicine, School of Physiotherapy, University of Melbourne, Melbourne, Australia, 2Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne Australia, 3School of Health and Rehabilitation Sciences, School of Physiotherapy, University of Queensland, Brisbane, Australia Aims: The relationship between vertebral fracture, osteoporosis, and falls is complex; it may be primarily related to vertebral fragility and fall-related impact forces, or the potential balance deficits secondary to factors associated with the fracture (pain, postural changes, fear of falling). Given the role of trunk muscles in postural control, balance maintenance and production of spinal compressive loads, the aim of this study was to investigate diﬀerences in the anticipatory trunk muscle activity in individuals with and without osteoporotic vertebral fracture. Individuals were also compared based on magnitude of thoracic kyphosis. Methods: 35 participants with and without osteoporotic vertebral fracture participated: 11 with fracture (68.2 6.7 years); 24 without fracture (61.2 7.7 years). Participants were also grouped into tertiles according to the magnitude of thoracic kyphosis using centroid angle: low (23.4 2.7(), intermediate (30.9 2.7(), high (40.6 4.1(). Trunk muscle electromyography (EMG) during voluntary arm movements on two support surfaces (flat and short base) was recorded. Raw EMG amplitude was compared between groups using parametric tests. Normalized EMG compared eﬀects of surface (flat, short) using a 2 way repeated measures ANOVA. Results: A novel finding was co-contraction of trunk flexors and extensors (150 to 50 ms prior to deltoid activation) during forwards arm movements; this was most pronounced in the fracture and high kyphosis groups. During backwards arm movements, the fracture group demonstrated a reduction in paraspinal activity from baseline compared with no activity change in the no-fracture group. During forwards arm movements on the short base, the group with greatest kyphosis demonstrated increased paraspinal activity. There was no diﬀerence in magnitude of kyphosis between fracture groups. Conclusions: Results demonstrated that in this elderly population, arm flexion is associated with co-contraction of the trunk flexors and extensors. Co-contraction was most evident in the fracture group, and the group with greatest kyphosis. This trunk stiﬀening response may have several consequences, including a compromised balance response and the potential creation of increased compressive loads through the spine. Both of these outcomes may have serious consequences in a population with fragile vertebrae that are susceptible to fracture.

S249

P427SA. WHICH EXERCISES TO CHOOSE FOR OSTEOPOROTIC PATIENTS WITH VERTEBRAL FRACTURES? Urosevic Lj.1, Jovanovic V.1, Ilic-Stojanovic O.2; 1Institute for Orthopedic Surgery Banjica, 2Institute for Rehabilitation, Belgrade, Serbia Exercise is not a common activity for elderly people, especially if they have a health problem that causes pain. Aims: The goal of our research is to establish patient’s compliance regarding the oﬀered exercise program. Method: We studied 86 osteoporotic women with 2 or more vertebral fractures. Mean age was 64 (ranging from 48–72). Medications were included in treatment, with obligatory vitamin D. Patients were separated in two groups, A (44) and B (38 patients). Within its program, group A had exercises for back extensors and exercises for abdominal flexors strengthening. Exercise duration was 20–30 minutes. Group B’s exercises included all body joints, and lasted for 90 minutes. Patients exercised within the institute for three weeks, five days a week, and after that continued exercising at home. Patients were controlled after 6 months, 1 and 3 years. Results: In group A, all patients continued with exercises beyond 1st year. After 3 years, 36 patients (82%) still continued to exercise. In group B, after 6 months, 30 patients (79%) quit, after 1 year, another 4 (11%)quit, and remaining 4 transferred to the group A program. Conclusion: Elderly persons hardly accept exercise as regular life activity. Their concentration falters and they have other diseases. They are only willing to accept exercises that bring relief, that are not exhausting, and do not worsen their condition.

P428SU. ORTHOPAEDIC SURGEONS AND FRAGILITY FRACTURES TREATMENT: RESULTS OF 980 SURVEYS BY SIOT, BJD AND IOF Panarella L, Tarantino U; University of Rome ’’Tor Vergata’’, Rome, Italy Aims: Current treatment of fragility fractures often does not include full osteoporosis management. An international osteoporosis survey was conducted by the Italian Society of Orthopaedics and Traumatology (SIOT), the Bone and Joint Decade (BJD) and the International Osteoporosis Foundation (IOF) to evaluate and to diﬀuse the international guidelines. Methods: The study included 4580 surveys distributed by the Italian Society of Orthopaedics and Traumatology from August to September 2002. Nine-hundred-eighty (21%) answers returned. The results were processed in Lund, Sweden by the Bone and Joint Decade secretariat and evaluated to diﬀuse communications and publications plans in each country participating in the study. We are thus presenting the Italian results. Results: Most orthopaedic surgeons have one or two subspecialties and about 60% work in a hospital. Only 10% work on osteoporosis. Most of the units operate more than 20 patients per month for fragility fractures. Young doctors have the largest amount of fragility fractures. Both peripheral and total body densitometry are largely diﬀuse but quantitative CT is not currently available. Orthopaedic surgeons often identify osteoporosis and initiate investigation or treatment. A bone density test is frequently prescribed to patients that have been treated for a fragility fracture. Those patients are then referred to primary care physicians. Alendronate/risedronate and calcium/vitamin D drugs are mainly used for treating osteoporosis. Formal training in osteoporosis is evaluated as important by the surgeons who replied to the survey. Nevertheless, most of them would like to learn more about osteoporosis, especially in high quality courses and in self-instructional computer tools. Journals and textbooks are less appreciated. Conclusions: Orthopaedic surgeons feel generally comfortable in osteoporosis patient management. However, there is a general request of technical support from the institutional experts. Therefore, it has been organised at the University of Rome ‘‘Tor

Vergata’’ a fellowship in ‘‘osteoporosis, matrix metalloproteinases and bone metabolism in low gravity force conditions and on the ground’’ financed by the Italian Spatial Agency; a retrospective study on fragility fractures including all second level DEA in Rome; a prospective study on surgical management evaluating functional outcome, rehabilitative and pharmacological treatment and a national register project.

P429MO. DETERMINATION OF FRACTIONAL CALCIUM ABSORPTION USING STABLE CALCIUM ISOTOPES IN A DUAL TRACER METHOD Sherrell R1, Shapses S1, Field P1, Robson R2, Bayne W3, Woolf E3, Liu M3, Wehren L3, Santora A3; 1Rutgers University, New Brunswick, NJ, USA, 2Christchurch Clinical Trials, Christchurch, New Zealand, 3Merck Research Laboratories, Rahway, NJ, USA Aims: Optimal calcium absorption from the gut depends on vitamin D adequacy, so vitamin D is important for skeletal metabolism. Measurement of fractional calcium absorption (FCA) is, therefore, a means of assessing the eﬀectiveness of orallyadministered vitamin D. Methods: FCA was measured by dual tracer method at baseline and after 4 weeks of treatment in 56 participants in a randomized, controlled clinical trial comparing a once-weekly tablet containing alendronate 70 mg and vitamin D3 2800 IU to matching placebo. Dietary calcium intake was stabilized prior to and during treatment to a target of 1100 to 1300 mg/day, by use of 3-day food diaries, dietary counseling, and calcium supplements. The IV and oral calcium formulations were enriched with stable isotopic forms of calcium, 42Ca and 43Ca, respectively, and were administered simultaneously. Isotope doses were chosen to achieve approximately 10% enrichment of urine over the natural abundance. Ten hour urine samples were collected; calcium was precipitated as the oxalate salt and ashed to remove organics. Isotopic composition of calcium was determined by mass spectrometry. 44Ca was used as the internal standard, and baseline (pre-dose) 42Ca and 43Ca used in determinations of FCA were the actual natural abundances of these isotopes in urines collected at baseline. Power/sample size calculations were based on 7.7% variability in FCA estimates previously reported by Ensrud et al. (Ann Intern Med 2000), and on an estimated correlation between baseline and on-treatment values of 0.50. A sample size of 25 patients per group had 90% power to detect a 7.2% between-group diﬀerence and 80% power to detect a 6.3% change from baseline. Blinded interim variability estimates confirmed these assumptions, with an observed variance of 6.3%, based on the first 24 patients enrolled. Results: Observed variability at study end was 6.5%. The dual tracer method of estimating FCA using mass spectrometry was shown to be an excellent means for assessing treatment eﬀects. Conclusions: The observed variability of FCA supports the power/sample size calculations for the study. This method, using stable calcium isotopes, avoids the use of radioisotopes, sparing patient exposure and eliminating the need to handle radioactive substances.

P430SA. ORAL DELIVERY OF PEPTIDES IN ENTERIC-COATED AND NONCOATED FORMULATIONS Gilligan JP, Stern W, Sturmer AM, Bolat A, Philip S, Hakimi T, Picininno K, Mehta N; Unigene Laboratories Inc, Fairfield, NJ, USA A solid dosage formulation has been developed for the oral delivery of intact, biologically active peptides. The excipients include an organic acid for the inhibition of proteolytic activity and an acylcarnitine as an enhancer of paracellular transport. In order to target the absorption of the peptide and excipients to the upper intestine and hence maximize peptide absorption, the solid dosage form (ie., capsule or tablet) was sealed with an enteric coating. The oral delivery of several peptide hormones, including Salmon Calcitonin(sCT) and Parathyroid Hormone (PTH) analogs, has been demonstrated in dogs and humans. Dose ranging studies in a dog model showed that the concentration of the peptide in the systemic circulation was linear with dose. Additional studies in the dog model with non-enteric coated capsules have

S250 unexpectedly shown that intact, biologically active peptide can also be absorbed into the circulation with this formulation. The Tmax for non-enteric coated peptide was less than 30 minutes whereas that for enteric coated peptide was greater than 90 minutes. Both excipients are required for maximal bioavailability since the absence of either citric acid or the acylcarnitine results in a dramatic reduction in the Cmax of a peptide such as sCT. These results show that for therapeutic peptides requiring a faster acting mode of action, the formulation that was originally developed to deliver peptides in enteric-coated solid dosage form can also be used without an enteric coating to deliver intact, therapeutically eﬀective peptides.

P431SU. QUALITY OF LIFE AFTER BALLON KYPHOPLASTY FOR THE TREATMENT OF OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES Massari L, Caruso G, Paganelli M, Kiokia E; University of Ferrara, Department of Orthopaedics, Italy Aims: To measure improvements in quality of life, psycho-physical and social function and back pain after kyphoplasty for treatment of osteoporotic vertebral compression fractures (VCFs). Materials and methods: Osteoporosis is an increasing burden of an aging society, resulting in R 400,000 vertebral fractures in the United Staes and R1 million vertebral fractures in Europe per year. Painful osteoporotic VCFs can be a significant burden for patients and their families, impairing physical function and quality of life. VCFs lead to progressive sagittal spine deformity, changes in spinal biomechanics and are believed to contribute to a fivefold increased risk of further fracture by virtue of force transmission to weak vertebrae above or below. Kyphoplasty is a technique treating collapsed VCFs. These thecnique is very eﬀective for achieving rapid pain relief, restoring bone height, and consequent vertebral realignment, and thus stabilization of the vertebra. Forty-two osteoporotic VCFs were treated by kyphoplasty in twenty-eight patients who did not respond to medical therapy. The indication included painful prymary or secondary osteoporotic VCFs. Symptomatic levels were identified by correlating clinical data with radiographs and, in presence of two adjacent collapses vertebral body, with MRI findings demonstrating edema in symptomatic levels. Outcome data were obtained by comparing preoperative and latest postoperative SF-36 and visual analogic scale (VAS) data and statistical analyses wer done using Wilcoxon signed-rank tests and Mann-Whithney test. Results: Patient surveys revealed significant pain reduction within the first week after surgery and improved activity levels for a majority of patients. The SF-36 scores showed a significant improvement and the VAS score showed a significant reduction. Cement extravasation was seen at 7.6% of patients without clinical complications. Conclusions: Kyphoplasty, performed in appropriately selected osteoporotic patients with painful vertebral fractures, is a promising addition to current medical treatment. It improves physical function, reduces pain, and may correct kyphotic deformity if it is carried out within six-eight weeks from the collapse.

P432MO. THE REASON FOR PROPHYLACTIC MULTISEGMENTAL STABILISATION OF OSTEOPOROTIC VERTEBRAL FRACTURES WITH KYPHOPLASTY Becker SWJ, Tuschel A, Meissner J, Chavanne A, Ogon M; Spine Center, Orthopaedic Hospital Vienna – Speising, Vienna, Austria The recurrent fracture risk after osteoporotic vertebral fractures remains a problem for our patients. Minimal-invasive stabilisation strategies such as vertebroplasty and kyphoplasty treat the fractured vertebra but recurrent fractures still occur at other levels. We investigated the indication of a prophylactic kyphoplasty of adjacent levels to the fracture in order to decrease the postoperative refracture risk. Study design: Prospective randomized clinical study with 2 treatment groups (30 patients each): Monosegmental kyphoplasty versus bi- or multisegmental kyphoplasty with prophylactic level depending on the fractured endplate. In cases with damaged superior and inferior endplates, the superior adjacent level was

treated prophylactically. F/U over 12 months with x-rays, statistical analysis with Fisher exact test. Results: Group 1: monosegmental stabilisation, 23 patients (4 males, 19 females, 26 levels, 7 drop-outs). 5 refractures; 3 refractures adjacent to the kyphoplasty and 2 cases not related to the primary stabilisation. In 2 cases cement leakage was seen as direct cause of the refracture. Group 2: prophylactic stabilisation, 27 patients (5 males, 22 females, 60 levels, 27 prophylactic levels, 3 drop-outs). 7 refractures which were all adjacent to the treated levels. In 4 cases cement leakage was seen as cause of recurrent fracture. 6 out of 12 recurrent fractures showed intradiscal cement leakage as the direct cause of the fracture. The statistical analysis did not show a significant diﬀerence of the fracture risk (p=1). No statistical diﬀerence could be shown regarding the intradisc leakage (p<0.5), the percentage of fractures due to leakage (50% of the cases) was higher than leakage without fractures (31%). Conclusion: Refracture rates are similar in both groups (group 1: 22% refracture risk, group 2: 26% refracture risk, no statistical significant diﬀerence). Therefore, we do not see the need for a generalised prophylactic stabilisation of adjacent levels with kyphoplasty following our approach. However, it is crucial to avoid any leakage, which has a direct impact on the fracture rate. In cases with leakage into the disc we advise a prophylactic stabilisation of the vertebra at the leakage site. This approach also limits drastically the costs of the procedure and limits reoperation rates and costs.

P433SA. FRACTURE PREVENTION IN PATIENTS WITH A RECENT CLINICAL FRACTURE: THE APPROACH OF SURGEONS IN THE NETHERLANDS Telgenkamp B1, van Helden S1, Brink P1, Geusens P2; 1Department of General Surgery, 2Department of Rheumatology, Academic Hospital Maastricht, Maastricht, The Netherlands Objective: Patients with a history of fragility fracture have an increased risk for new fractures. Patients older than 50 years that present to the hospital with a clinical fracture have a risk of about 11% to develop a new clinical fracture within 2 years (1). We analysed the current approach of surgeons towards systematic evaluation of patients older than 50 years with a recent clinical fracture for underlying osteoporosis and fall risk, taking into account the availability in the Netherlands of guidelines for osteoporosis (2,3) and fall risk (4). Methods: Two questionnaires were send to all hospitals in the Netherlands (n=100), one to a trauma surgeon and one to an orthopaedic surgeon in each clinic, inquiring about the application of the two above mentioned guidelines. Results: The response rate was 76%, 57% by trauma surgeons and 43% by orthopaedic surgeons. In 58% of the hospitals, some evaluation for osteoporosis was performed, based on the guidelines (24%) or own criteria (34%). In 28% no evaluation for osteoporosis was performed and in 14% the answers within the hospital were contradictory For further evaluation of osteoporosis by dual-energy x-ray absorptiometry was done in 74% and quantitative computertomography in 5% of the hospitals. Some evaluation for fall risk was performed by 34% of the hospitals, based on guidelines (14%) or own criteria (20%). In 50% no evaluation for fall risk was performed and in 16% the answers within the hospital were contradictory. Conclusion: Some screening for osteoporosis was performed in 58% of responding hospitals and for fall risk in 34% of responding hospitals. However systematic application according to guidelines was only 24% for osteoporosis and 14 % for fall risk. These data indicate low adherence to local guidelines for osteoporosis and fall risk evaluation in patients of 50 years and older presenting in the hospital for a clinical fracture. References 1. van Helden et al, Osteoporosis Int., in press 2. Osteoporosis guidelines in the Netherlands, www.CBO.nl 3. Geusens et al, J Eval Clin Practice, 2005, in press 4. Fall risk guidelines in the Netherlands, www.CBO.nl

S251

P434SU. EFFICACY OF EXERCISE AND VERTEBROPLASTY IN REDUCING RISK OF RECURRENT VERTEBRAL FRACTURES IN THE OSTEOPOROTIC PATIENT

P436SA. SKY BONE EXPANDER KYPHOPLASTY VERSUS VERTEBROPLASTY FOR OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES: EARLY EXPERIENCE AND RESULTS

Schmidt CK, Huntoon EA, Sinaki M; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA

Foo LSS, Yeo W, Fook-Chong MC, Guo CM, Yue YM, Chen J, Tan SB; Department of Orthopaedic Surgery, Singapore General Hospital, Republic of Singapore

Aims: Of this study were to compare refracture rates in patients who had at least one prior osteoporotic compression fracture and then were treated using either vertebroplasty (VP), RehabilitationOsteoporosis Program of Exercise (ROPE) or both. Methods: Subjects were retrospectively obtained from a large data base of an academic medical center by computer search. Inclusion criteria were: age greater than 60, at least one radiologically confirmed compression fracture and participation in either or both interventions. Exclusion criteria were: secondary causes of osteoporosis or death less than 24 months after treatment initiation unless a refracture had occurred prior to death. Patients receiving VP had a pre-intervention MRI confirming an acute compression fracture and a physician examination demonstrating severe pain localizing to the same level. Patients receiving ROPE were evaluated by a physical medicine physician, counselled in osteoporosis management, and instructed in a posture training program if appropriate. They participated in a physical therapy instruction session for back extensor strengthening and posture correction. Patients receiving both interventions had ROPE at variable points in the course of their management. Results: Of 342 records reviewed, 55 met the inclusion criteria for the study and 40 received VP or ROPE. Refracture rates in the 20 patients treated with VP were 60% which occurred an average of 7.7 months after VP. Refracture rates in 20 patients treated with ROPE were 20% and occurred an average of 37.8 months after initial diagnosis. Patients (n=15) receiving both interventions had a refracture rate of 40% with variable onset of refracture. These fractures frequently occurred prior to the ROPE component of the treatment. Conclusions: In this preliminary study, the ROPE intervention groups had lower refracture rates when compared to the group not receiving ROPE intervention. If VP is combined with ROPE we can expect decreased refracture rates.

P435MO. THE EFFECTIVENESS OF LIGUSTILIDE ON CHRONIC BACK PAIN AND DAILY ACTIVITIES IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS Li GS1,2, Li BF1, Tian JW2; 1College of Life Science, Ocean University of China, 2School of Pharmacy, Yantai University, China Aims: To investigate the eﬀect of oral icariin on chronic back pain and disability attributed to osteoporosis. Methods: The study design involved three groups of osteoporotic postmenopausal women suﬀering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with nonspecific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a numerical rating scale and disability due to back pain was measured using the Oswestry disability questionnaire. The patients were randomly assigned to receive, for three months, either 200 mg oral salmon icariin and 1,000 mg of oral calcium daily (groups IA, IIA, IIIA) or 1,000 mg of oral calcium daily (groups IB, IIB, IIIB). Results: Repeated measures ANOVA showed that there were no significant time, group or interaction eﬀects for pain intensity and disability in any of the groups studied. Mean Oswestry and numerical rating scale scores were reduced during the follow-up period in the groups IA, IIIA, but the diﬀerences between the two time points were not statistically significant. Oral icariin has no eﬀect on chronic back pain intensity and functional capacity of osteoporotic women regardless of the presence of fractures, degenerative disorders or chronic back pain of non-specific etiology.

Aims: Painful osteoporotic vertebral compression fractures (VCF) cause disability and morbidity. Kyphoplasty and vertebroplasty may provide pain relief and expedite functional recovery. Kyphoplasty may also increase vertebral body height, correct kyphosis and reduce cement extravasation. In this prospective study, we compare radiological and functional outcomes between kyphoplasty and vertebroplasty for osteoporotic VCF. Methods: 40 consecutive patients with painful osteoporotic T12 or L1 VCF who failed 3 months conservative treatment were recruited. Each received standardised medical treatment with calcium supplements, analgesia and physiotherapy. 20 single-level kyphoplasties and 20 single-level vertebroplasties were performed. Kyphoplasties were performed using Sky Bone Expander System (Disc-O-Tech Medical Technologies Ltd). Pre and 6 month postprocedure radiological (wedge angle & vertebral body heights) and functional outcomes [Visual Analogue Score (VAS), North American Spine Society (NASS) & Short Form–36 Item (SF-36)] were recorded by 2 independent researchers. Statistical analysis was by Wilcoxon Signed Ranks Test and Mann-Whitney U Test. Results: Mean percentage wedge angle decrease after kyphoplasty and vertebroplasty was 34.3% (SD 20.1) and 36.9% (SD22.2) respectively. Mean percentage anterior, middle and posterior vertebral body height increases were 40.6% (SD 31.6), 76.7% (SD 81.1) & 10.6% (SD 9.8) for kyphoplasties, and 42.8% (SD 37.1), 50.5% (SD 28.3) & 8.1% (SD 8.2) for vertebroplasties respectively. VAS, NASS and SF-36 scores for physical functioning and bodily pain improved significantly in both study arms. However when kyphoplasties were compared against vertebroplasties, no statistical diﬀerence was found for any of the outcomes, radiological or functional (all p values >0.05). 3 cases of cement extravasation (2 kyphoplasties and 1 vertebroplasty) were documented. 1 case of the Sky Bone Expander System being unable to be contracted and withdrawn from the vertebral body occurred. It had to be left in-situ. This is the first reported incidence of such a complication. Conclusions: Both Sky kyphoplasty and vertebroplasty reduce pain, improve function, wedge angle and vertebral body height. However our study suggests no significant radiological or functional advantage of Sky kyphoplasty over vertebroplasty. Cement extravasation is seen in both procedures. For Sky kyphoplasties, there may be additional instrumentation problems. Possible reasons are discussed and suggestions made.

P437SU. THE FALLS, FRACTURE AND OSTEOPOROSIS RISK CONTROL AND EVALUATION (FORCE) STUDY Ciaschini PM; Group Health Centre, Sault Ste. Marie, ON, Canada The Falls, Fractures and Osteoporosis Risk Control & Evaluation (FORCE) Study is a Northern Ontario, community-based, multidisciplinary collaboration of the Group Health Centre, with the Algoma Health Unit, Sault Area Hospital, Algoma Community Care Access Centre, Algoma District Slips, Trips and Falls Committee, Pharma Alliance (Aventis, Lilly, Merck Frosst, Proctor and Gamble), and Greenshield Foundation. In 2003, FORCE was conceived by the late Dr. Hui Lee in Sault Ste. Marie, following audits of the hospital fracture clinic and emergency department visits for falls, osteoporosis assessments and treatment. District population projections were also reviewed. Objectives of the FORCE Study are to determine if a community-based implementation of a multi-disciplinary, integrated protocol improves evidence-based interventions in Falls and Osteoporosis risk management; and, to determine barriers and solutions to implementation of a sustainable protocol. FORCE includes community-dwelling patients over 55, recruited from four pre-defined high risk groups: Hospital fracture

S252 clinic and Emergency Department; bone mineral density T-score less than –2.0 in previous year; self or care provider referred; and screened as high risk for future falls. 201 patients are randomized into immediate or delayed intervention protocol groups. Patient data were collected using electronic medical records from Group Health Centre and Sault Area Hospital. Immediate intervention protocol consists of osteoporosis risk management including BMD testing, health education, and recommended prescriptions, if necessary. Falls risk management includes screening, medication review, home nurse visit, and referral to physiotherapy and/or occupational therapy, as required. After 6 months, the delayed intervention protocol group receives the intervention protocol. Primary outcomes of the FORCE Study will be appropriate fall and osteoporosis risk management, evaluated at 6 months. Secondary outcomes will assess falls, fractures, compliance, quality of life and healthcare resource utilization at study end, 2005. An additional economic sub-study will determine patient costs and economic consequences of the FORCE program for the healthcare system. Preliminary findings of the FORCE Study will be presented at the IOF World Congress.

P438MO. EFFECTS OF HORMONE THERAPY, CALCIUM INTAKE, AND STRENGTH TRAINING EXERCISE ON SIX-YEAR BONE CHANGES IN POSTMENOPAUSAL WOMEN Zuzuarregui RP1, Cussler EC2, Lohman TG2; 1Stanford University, Palo Alto, CA, USA, 2University of Arizona, Tucson, AZ, USA The purpose of this study was to examine the association of various biological and psychosocial factors with significant changes (2.0%; p<0.05) in bone mineral density (BMD) in a subset of postmenopausal women from the Bone, Estrogen and Strength Training (BEST) study followed over a six-year period. This study looked at 58 calcium-supplemented women randomized initially to a strength training program or control. At baseline, 57% were on hormone therapy (HT). Women who gained (n=33) or lost (n=25) 2.0% BMD over six years at at least two of three sites were included. BMD was measured at baseline and annually thereafter using dual-energy x-ray absorptiometry. Six-year calcium intake was recorded using diet records, food frequency questionnaires, and pill counts. The exercisers recorded exercise weights lifted and repetitions from which exercise frequency was calculated as the percent of sessions attended. The baseline Dishman self-motivation score, Medical Outcome Survey Short Form (SF36) Health Survey vitality score, and Beck Depression Index were assessed through questionnaires. At baseline, both groups displayed similar age and body composition. Women who increased BMD were on HT longer prior to the study and gained significantly more lean soft tissue (LST) than women who lost BMD (p<0.01). Women currently taking HT were more likely to have gained BMD than those not on HT (p<0.05). Women taking >1700 mg⋅d-1 calcium (dietary and supplemental) were more likely to have gained BMD than those taking <1700 mg⋅d-1 (p<0.05). In multiple linear regression using the dependent variable residuals from the regression of 6-year BMD measures on baseline values and covariates of age and baseline body weight, mean percent exercise frequency (36.026.0%) was most strongly associated with change in lumbar spine BMD (p<0.01). Change in body weight was the best predictor of change in BMD at both femur neck and trochanter (FT) sites (p<0.05). The baseline SF-36 vitality score was positively related to change in FT BMD (p<0.05). Evidence of the long-term (six-year) positive eﬀects of HT, calcium intake, and exercise on BMD supports the eﬃcacy of these therapies for women at risk of osteoporosis.

P439SA. ONCE-MONTHLY ORAL IBANDRONATE VERSUS WEEKLY ORAL ALENDRONATE IN POSTMENOPAUSAL OSTEOPOROSIS: RATIONALE AND DESIGN OF MOTION Epstein S1, Borges JLC2, Mautalen C3, Gonzalez Macias J4, Mahoney P5, El Azzouzi B5, Masanauskaite D5, Cosman F6;

1 Doylestown Hospital, Doyleston, PA, USA, 2Universidade Catolica de Brasilia, Brazil, 3Centro de Osteopatias Médicas, Buenos Aires, Argentina, 4Hospital Universitario Marques de Valdecilla, Santander, Spain, 5F. Hoﬀmann-La Roche Ltd, Basel, Switzerland, 6Helen Hayes Hospital, West Haverstraw, NY, USA

Aims: The relative eﬃcacy of alternative treatment options can be assessed by active comparator study. However, as it is not feasible to assess antifracture eﬃcacy as an endpoint, validated surrogate markers need to be used. Previously, change (%) in the surrogate marker bone mineral density (BMD) was used to establish the relative eﬃcacy of two oral bisphosphonates when administered weekly,1 given its predictive value for antifracture eﬃcacy within the class. Here, we describe the design and conduct of a similar comparative study (MOTION) that will establish the relative eﬃcacy of once-monthly oral ibandronate versus weekly oral alendronate. Methods: MOTION is a randomized, double-blind, doubledummy, non-inferiority study that will enroll approximately 1,800 women (aged 55–84 years) with postmenopausal osteoporosis (R5 years since menopause and a lumbar spine [L2-L4] BMD T-score <-2.5, but R-5.0). Participants will be randomized to daily calcium (500–1,500mg) and vitamin D (400IU) plus either 150mg monthly oral ibandronate and weekly placebo, or 70mg weekly oral alendronate and monthly placebo. Co-primary study endpoints are changes (%) from baseline in lumbar spine and total hip BMD at 1 year. Non-inferiority tests will then be performed to establish the relative eﬃcacy of the investigational regimens, with margins of 1.14% and 0.87% employed at the lumbar spine and total hip, respectively. Change (%) in hip trochanter BMD at 1 year will also be assessed. To explore eﬀects on bone turnover, biochemical markers of bone resorption (serum CTX) and formation (P1NP) will also be measured in a subset of patients (30%). Safety parameters will be continuously monitored, and will include clinical vertebral and non-vertebral fractures assessed as adverse events. Conclusions: MOTION will explore the relative eﬃcacy and safety of once-monthly oral ibandronate and weekly oral alendronate. Study outcomes will assist physicians in identifying the optimal treatment option for their patients. 1. Rosen C, et al. J Bone Miner Res 2005;20:141–51.

P440SU. ANALYSIS OF PATIENT AND PHYSICIAN COMMUNICATION CONCERNING OSTEOPOROSIS TREATMENT Cole RE1, Wright WL2, Dore RK3, Gold DT4; 1Michigan State University, Brooklyn, USA, 2Partners in Healthcare Education, Bedford, USA, 3David Geﬀen School of Medicine at UCLA, Los Angeles, USA, 4Duke University Medical Center, Durham, USA This study was designed to explore and better understand the dialogue pertaining to osteoporosis treatment that occurs between patients and physicians in the physician’s oﬃce. Patients included in the study were new or existing bisphosphonate users. Observations were conducted in 2 phases with both phases video-taped for linguistic and kinesic analyses. The first phase involved in-oﬃce observations of 7 physicians and 18 patients. In the second phase, simulated oﬃce visits with 47 physicians and 86 patients were observed. For this phase, patients and physicians were given separate 10 minute pre-briefings before the face-to-face meetings. Patients and physicians were instructed to think of this as an actual appointment to review the results of a bone density scan and discuss potential treatment options. The patient and physician engaged in a 10 minute consultation and were then debriefed separately to discuss their opinions about the consultation (15 minutes). Consults in both phases tended to focus on osteoporosis lifestyle issues associated with osteoporosis, such as steps that could be taken to avoid falling and the need for calcium supplementation, vitamin D, and exercise. The physician/patient dialogue centered more on these non-pharmacologic issues than on the progression of osteoporosis or pharmacologic treatment possibilities. When pharmacologic treatment options were presented, physicians often used ‘scare tactics’ to encourage patients to initiate or continue with treatment, and placed less emphasis on the health benefits of

S253 treatment adherence. Physicians described the potential side eﬀects of bisphosphonate therapy as avoidable if patients follow the specific dosing requirements. Upon careful analysis of the videotapes of physician communication styles, several conclusions may be drawn. Consultations may be improved by having physicians discuss osteoporosis treatment and the consequences of forgoing treatment as it aﬀects the individual patient’s life. To be more eﬀective in promoting osteoporosis treatment, physicians might further emphasize and explain that treatment may prevent further bone loss associated with osteoporosis, build stronger bone, and thereby decrease the risk of fractures. Physicians might additionally emphasize how a fracture can dramatically aﬀect quality of life. More eﬀective communication between patients and physicians may lead to increased adherence to therapy.

P441MO. THE ACTION OF TREADMILL GAIT USING NEUROMUSCULAR ELECTRICAL STIMULATION AND PARTIAL BODY WEIGHT SUPPORT ON BONE MARKERS AND BONE MINERAL DENSITY IN QUADRIPLEGIC SUBJECTS Carvalho DCL1, Garlipp CR2, Bottini PV3, Afaz SH3, Moda MA3, Cliquet Jr A1,4; 1Orthopaedics Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil, 2Department of Clinical Pathology, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil, 3Division of Clinical Pathology, University Hospital – UNICAMP, Campinas, Brazil, 4Department of Electrical Engineering, University of São Paulo (USP at São Carlos), Brazil After a spinal cord injury (SCI), lack of muscle contraction and mechanical load results in decrease of bone mineral density (BMD) below the lesion level, which increases bone fragility and risk of fractures. Many studies have analyzed the eﬀect of short periods of treatment on bone density in SCI subjects using bone densitometry, although the literature has suggested that the interval between the exams should be within 1–2 years.

Treadmill gait training associated to NMES and body weight support.

To evaluate the eﬀect of treadmill gait training using neuromuscular electrical stimulation (NMES), with 30–50% weight relief, on bone mass comparing individual responses of dual-energy X ray absorptiometry (DXA) and biochemical markers of bone metabolism, 21 quadriplegics with incomplete motor loss were divided into gait group (11), which performed the training for six months, twice a week, 20 minutes (Figure 1) and control group (10), which did not perform gait. BMD of lumbar spine, femoral neck and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline and deoxipyridinoline) were measured, at the beginning and after six months. In the gait group 81.8% presented a significant increase of bone formation; 66.7% also presented a significant decrease of bone resorption markers. In the control group 30% did not present any change of markers and 20% presented an increase of bone formation. Results have shown that many individuals who presented bone formation increase, presented a decrease of BMD. Since DXA technique has a precision error associated to exams in SCI persons (spasticity and diﬃculty to reproduce the same lower limb position) and biochemical markers have been extensively used towards analyzing bone changes after short periods of treatment, the lack of correlation between biochemical markers and BMD suggests that data obtained by DXA should be carefully interpreted in rehabilitation centers, for assessing risks of fractures and monitoring the bone mass in injured subjects.

P442SA. INHIBITION OF PRO-INFLAMMATORY MEDIATORS ACTIVATION IN HUMAN SYNOVIOCYTES Yatsyshyn NG, Yatsyshyn RI; Medical University, IvanoFrankivsk, Ukraine Background: The potential role of dietary supplements such as glucosamine as chondroprotective agents has prompted studies on their mechanism of action. Glucosamine and related compounds have been reported to enhance proteoglycan synthesis in cartilage. These agents have also been proposed to suppress inflammation by inhibiting pro-inflammatory mediators including TNF;, IL-1;, COX-2, and chemokines. More recently, plant-derived dietary supplements exemplified by ginger extract have been documented to exert anti-inflammatory activity. Objectives: The present study aims to define the mode of action of glucosamine and ginger extract using human synoviocyte and chondrocyte microcarrier bioreactor culture models. We evaluated the eﬀect of glucosamine and ginger extract on the expression of pro-inflammatory mediators and aggrecan expression. Methods: Human synoviocytes and chondrocytes propagated in microcarrier bioreactor culture system were incubated with: a) 100 µg/ml of Zinaxin (‘‘Ferrosan’’, Danmark) (combination of Alpinia galanga and Zingiber oﬃcinale), b) 2 mg/ml glucosamine hydrochloride, c) combined ginger extract and glucosamine or, d) control media alone. The cultures were incubated in the presence or absence of 10 ng/ml of TNF for 4 days at 37(C, 5% CO2. The cells were frozen for RNA extraction and subsequent Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis of inflammatory mediators and aggrecan. Results: RT-PCR analysis verified that IL-1 activated expression of pro-inflammatory mediators in synoviocyte and chondrocyte cultures. Glucosamine suppressed MCP-1 expression in synoviocytes whereas ginger extract inhibited MIP-1, TNF and IL-1. Both glucosamine and ginger extract decreased TNF and IL-1 expression in chondrocytes. Moreover, ginger extract enhanced expression of aggrecan in TNF and IL-1 activated chondrocyte cultures. In contrast, glucosamine had a negligible eﬀect on aggrecan expression. Conclusion: We discovered that ginger extract is eﬀective in blocking activation of pro-inflammatory mediators in synoviocytes and promotes aggrecan expression in inflamed chondrocytes. This observation suggests that ginger extract may play a dual role as an anti-inflammatory and as a chondroprotective agent by promoting the expression of aggrecan. Ginger extract may complement the reported chondroprotective eﬀect of glucosamine. Their combined activity may result in more potent inhibition of pro-inflammatory mediators and degradative enzymes while enhancing cartilage matrix-aggrecan expression.

S254

P443SU. MINIMALLY INVASIVE SPINAL SURGERY (MISS) IN THE TREATMENT OF OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES Massari F, Fiori R, Ursone A, Simonetti G, Masala S; University of Rome ‘‘Tor Vergata’’, Rome, Italy Aims: Vertebral compression fracture (VCF) is defined as a reduction in height, which must be at least 20% beyond its initial dimensions. Primary osteoporosis is responsible for about 85% of VCF, while secondary osteoporosis and neoplasty determine the remaining 15%. The presence of a vertebral fracture puts the individual in the following years at a 5 times greater risk of having a second VCF, which in almost 20% of the cases occurs within a one-year period. It is associated with a loss of height and a reduction of volumes in the thoracic and abdominal cavities. In consequence to this it generates pulmonary compression, with a reduction of vital capacity (VC) to 9% for each level fractured and of ‘‘ forced expiratory volume to 1 second ’’ (FEV1), as well as gastrointestinal dysfunction. Moreover, there is a major risk of death compared to the age-matched controls (adjusted mortality risk 1.6). Methods: From January 2002 to September 2005 we have treated with these new techniques 212 patients ( F=143, M=69; ages ranged from 63 to 82, mean age 72,3) with 342 osteoporotic vertebral collapses suﬀering of severe motion pain in the back; refractory to bed rest, corset therapy and use of analgesics, in absence of neurological signs. Percutaneous vertebroplasty and kyphoplasty are Radiological Interventional procedures, consisting in percutaneous injection of bone cement within vertebral body. Only latter throught inflation of two bone tamp in both hemivertebras is able to increase vertebral height and minimize spinal kyphosis. Results: Both procedures were successfully performed in our patients, whose pain relief was swift and persistent, decreasing from an average of 8,2 points of VAS to 2,4 (Visual analogic scale, pain score range between 0 No to 10 Maximum pain). Somatic resistance was considerably increased. We did not observe extravasations of PMMA in epidural or foraminal sites with marrow or radicular compression. Conclusion: Both, Percutaneous Vertebroplasty and Kyphoplasty, provided a precocious and long lasting pain relief (90 % of patients) with an evident increase in vertebral body resistance. Nevertheless only Kyphoplasty revealed itself able to increase vertebral height in order to diminish the spinal kyphosis.

P444MO. EFFECT OF MULTI-DISCIPLINARY THERAPY ON HEALTH-RELATED BEHAVIOUR OF POSTMENOPAUSAL OSTEOPOROTIC WOMEN Kalra B, Kalra S, Chawla K, Baweja J, Kumar N; Bharti Hospital, Karnal, Haryana, India This study was designed as a nonrandomized, prospective, single centre intervention trial to assess the eﬀect of team-based endocrine care (consisting of endocrinologist, gynaecologist, physiotherapist and clinical psychologist) on the quality of life of postmenopausal women with osteoporosis. 150 postmenopausal women presenting to endocrine OPD with radiological or biochemical evidence of osteoporosis were oﬀered a comprehensive package of gynecologic and endocrine care, physiotherapy and clinical psychology sessions. Various validated scales of the Stanford Patient Education Research Centre were used to assess eﬀect of therapy. 126 patients completed 3 months treatment. Communication with physicians improved from 1.43 1.19 to 3.93 0.86 (p<0.05). Time spent in stretching/strengthening exercises increased from 00to 15 0 minutes/week. Time spent in aerobic exercise improved from 15 0 to 45 0 minutes/week. Social/role activities limitations reduced from 2.25 0.63 to 1.08 0.39. Cognitive symptom management improved from 1.3 0.63 to 2 0.67. At the same time, health distress score fell from 3.20 0.82 to 1.35 0.47 (p<0.01) and energy/fatigue levels rose significantly from 2.52 0.51 to 3.30 0.50(p<0.01). Depression levels reduced from 6.01 2.46 to 4.66 1.66. Biochemical assessment of the patients revealed a rise in serum calcium from 8.29 0.28 mg% to 8.98 0.23 mg% and alkaline phosphate levels from 50.5 14.7 IU/ml to 62.8 13.67 IU/ml.

This study demonstrates the multiple beneficial eﬀects of teambased therapy on various health parameters in postmenopausal women with osteoporosis.

P445SA. WHY PATIENTS WITH OSTEOPOROSIS IN BULGARIA ARE NOT TREATED Borissova AM, Kovatcheva RD, Shinkov AD; University Hospital of Endocrinology, Sofia, Bulgaria According to the IOF information bulletin, many patients discontinue their treatment before the first year after its start and thus the fracture risks return to initial levels. The reasons for stopping therapy are as follows: 23% do not want to stay upright for half an hour after the pill, 20% experience adverse events, 17% do not agree to fast before and after the pill intake; 13% forget to take the pills. What is the situation in Bulgaria? Between August and September 2005 the Bulgarian League for the Prevention of Osteoporosis conducted a questionnaire among 150 physicians (endocrinologists, rheumatologists, gynecologists and orthopedists), 50 from the capital Sofia and 100 from the country, on their attitudes and approach with osteoporosis. The preferred medication was as follows: bisphosphonates 48%, calcitonins 30%, HRT 12%, raloxifene 6% and phytoestrogens 4%. One year after commencing therapy 42% in the capital and 7% in the country were still continuing treatment. The primary cause of drug discontinuation cited by 96% of specialists in Sofia and 88% of those in the country, respectively, was the high cost of the medication. Adverse eﬀects were cited as a cause for premature discontinuation of therapy by only 265 and 10% of physicians, respectively. The questionnaire among patients (100 in the capital and 200 in the country) showed that 23% of the subjects never started the prescribed drug due to financial reasons. Only 20% were still on the medication more than one year after its commencement. The patient’s need for information on osteoporosis was rated in the following order: 55% of subjects needed more information on the available therapy, 50% wanted to know more about the disorder and 42% needed information about exercise and diet in osteoporosis. The current trends in the work in Bulgaria are towards: (1) Improved communication between patients and physicians, (2) Improved communication with the health authorities for better reimbursement of antiosteoporotic medication. The latter will allow access to eﬀective treatment for a larger proportion of patients with osteoporosis at the current economic state in the country.

P446SU. PHYSIOTHERAPEUTIC INTERVENTIONS IN OSTEOPOROSIS PATIENTS: UTILIZATION AND BENEFITS Kalra B, Baweja J, Kalra S; Bharti Hospital, Karnal, Haryana, India This study was a prospective analysis designed to assess the frequency of musculoskeletal complaints, and the improvement noted with physiotherapeutic therapies in osteoporosis patients attending an endocrine clinic. Benefits were noted by using previously validated scales of the Stanford Patient Education Centre. 247 patients (121 males, 126 females) were analyzed. 34.89% were aged 51–60 years while 28.83% were 61–70 years. The commonest presentations were neuropathic pain (43.39%), cervical symptoms (13.21%), low backache (11.05%), and knee pain (7.55%). 4.58% persons requested advice for weight and waist loss. Neuropathy was more common in males (49.72% vs. 37.50%), while females experienced more cervical spondylosis (18.75% vs. 7.26%), low backache (13.54% vs. 8.38%) and frozen shoulder (5.73% vs. 1.68%). The physiotherapeutic interventions used most often were TENS/ IFT (43.39%), ultrasonic therapy (16.97%), and shortwave diathermy (13.05%). Physician communication improved from 1.43 1.19 to 3.93 0.86 over two months of therapy. Time spent in stretching/ strengthening exercises increased from 0 0 to 15 0 while aerobic exercise improved from 15 0 to 45 0 minutes/week.

S255 Social/role activities limitations reduced from 2.25 0.63 to 1.08 0.39. Health distress score fell from 3.20 0.82 to 1.35 0.47 and energy/fatigue levels rose from 2.52 0.51 to 3.30 0.50. Pain scores reduced from 6.01 2.46 to 4.66 0.66. This study demonstrates the multiple beneficial eﬀects of physiotherapy interventions in patients of osteoporosis.

P447MO. EARLY EFFICACY OF TERIPARATIDE IN MULTILEVEL OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES TREATED BY PERCUTANEOUS VERTEBROPLASTY Doria C1, Lisai P1, Milia F1, Tidu L1, Tranquilli Leali P1, Meloni GB2; 1Orthopaedic Department, 2Institute of Radiological Sciences, University of Sassari, Sassari, Italy Aims: Teriparatide [rhPTH(1–34)] has been shown to increase bone mineral density (BMD) and reduce the risk of fracture in postmenopausal women with osteoporosis. The purpose of this study was to investigate the skeletal eﬀects of 9 months of treatment with teriparatide in women with osteoporotic vertebral compression fractures treated previously by percutaneous vertebroplasty and antiresorptive therapy for at least two years. Methods: Daily subcutaneous injections of 20 µg teriparatide were administered for 9 months to 30 postmenopausal women previously submitted to percutaneous vertebroplasty for multilevel vertebral compression fractures. Mean age was 71.3 years (range 59–83). All patients had previously received alendronate therapy administered 70 mg/once weekly for 24–36 months. Before teriparatide therapy the median baseline BMD T-score was %-2.5 and the median baseline bone turnover markers levels were 24 µg of osteocalcin, 87 µg of N-propeptide of type I pro-collagen, 15 µg of bone-specific alkaline phosphatase and 13 nMolBCE/L of N-telopeptide of collagen. All patients received daily calcium (1000 mg) and vitamin D (500 IU) supplementation. The primary study outcome was change in lumbar spine BMD measured by DXA. Secondary outcomes included changes in bone turnover markers, pain and incidence of new vertebral fractures detected by magnetic resonance imaging (MRI) and quantitative and semiquantitative morphometry. Results: At 9 months of follow-up, lumbar spine BMD increased 6.4% relative to baseline data. Bone turnover markers had statistically significant increases. New vertebral fractures were observed in only three patients. Clinical data showed significant pain relief. No adverse treatment eﬀects were observed during teriparatide therapy period. Conclusions: Vertebral fracture risk reduction is a primary outcome measure in many studies of osteoporosis treatments. Because teriparatide improves bone density and bone quality and reduces the increasing risk of future fracture associated with a history of fractures, this therapy may reduce the expensive and disabling consequences of osteoporosis in women with a history of fracture.

P448SA. TERIPARATIDE RELIEF OF PAIN IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROTIC VERTEBRAL FRACTURES Hwang JS1, Chen JF1,2; 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, 2Kaohsiung, Chang Gung University, Taiwan, Republic of China Objective: Osteoporotic vertebral fractures occasionally lead to collapse of vertebral body, kyphosis, persistent back pain, and disability. The aim of this study was to obtain the pain relief of postmenopausal women with established osteoporosis in teriparatide treatment. Material and Methods: We performed a prospective study of patients with a painful osteoporotic vertebral compression fractures. At the time of enrollment, back pain were evaluated using a visual analog scale (VAS) (ranging from 1 to 10), and at 1 and 3 months after teriparatide 20 ug daily injection. The minimal, clinically important change of the VAS is 2. Results: Twelve patients with vertebral compression fractures were evaluated. The mean age was 74.3 years (range: 64 to 88

years), and the mean BMI was 22.2 kg/m2 (16 to 28). The mean spine, femoral neck and total hip BMD were 0.705, 0.470, and 0.561 g/cm2, respectively. Based on VAS scores, pain was decreased in 83% patients after teriparatide treatment. The mean pain rating score decreased from 6.7 to 4.2, and 3.7 at 1, and 3 month after the teriparatide treatment respectively (p < 0.001). Conclusion: We conclude that teriparatide provides positive eﬀects on relief of pain in patients with osteoporotic vertebral fractures.

P449SU. SELECTION OF TREATMENT FOR OSTEOPOROTIC DISTAL RADIUS FRACTURES Zeng B; Department of Orthopaedic Surgery, Shanghai No.6 People’s Hospital, Shanghai Jiaotong University, China Objective: To summarize the priciples for selection of treatment for osteoporotic distal radius fractures by retrograde study. Methods: Two hundred and fifteen cases of the distal radius fractures treated in the period from Jan. 2004 to Dec. 2004 were followed up to analyze the relationship between the functional results and the therapeutic methods applied. All the patients were aged over 50 years with an average of 62.3 years, among them 145 were women. Close reduction and immobilization with plaster sprint was employed in 74 cases of extra-articular fractures and 25 cases of intra-articular fractures. Close reduction and percutaneous pinning with external immobilization were done in 11 extra- and 21 intra-articular fractures, while close reduction and immobilization with external fixater were performed in 6 extraand 14 intra-articular fractures. In the rest 64 cases of intraarticular fractures, 19 cases had limited open reduction and immobilization with external fixater and 45 were treated by open reduction and internal fixation with plate, either buttress or locking compression plate. Results: The 99 patients having had close reduction and immobilization with plaster brace got acceptable functional recovery although with light or moderate loss of reduction in 24 of them and with some extents of rotation limitation of the forearm in 31, while 6 of them finally had open reduction and internal fixation because of redisplacement of the fragments. The 68 patients treated with either close or limited open reduction and immobilization with external fixater showed no losses of reduction and fairly good functional recovery of the aﬀected limbs. The 45 patients who underwent open reduction and internal fixation with plate all got bone healing with no or mild limitation of wrist motion and forearm rotation. Conclusions: The treatment of the distal radius fractures in elderly osteoporotic patients needs individualization, not only a careful study of the fracture must be done, but also the needs of the patients be considered.

P450MO. A SINGLE DOSE OF ZOLEDRONIC ACID 5 MG ACHIEVES MORE SUSTAINED BIOCHEMICAL REMISSION VERSUS DAILY 30MG RISEDRONATE IN PATIENTS WITH PAGET’S DISEASE Brown J1, Lyles K2, Fraser W3, Reid I4, Hosking D5, Devogelaer JP6, Moniz C7, Hooper M8, Saidi Y9, Su G10, Pak J10, Davis J10, Fashola T9, Krasnow J10, Zelenakas K10, Miller P11; 1Le Centre Hospitalier Universitaire de Quebec, Sainte-Foy, Quebec, Canada, 2 Duke University and VA Medical Centers, Durham, NC, USA, 3 Royal Liverpool University Hospital, Liverpool, UK, 4University of Auckland, Auckland, New Zealand, 5Nottingham City Hospital, Nottingham, UK, 6Cliniques Universitaires St Luc, Brussels, Belgium, 7Kings College Hospital, London, UK, 8Repatriation General Hospital, Concord, Australia, 9Novartis Pharma AG, Basel, Switzerland, 10Novartis Pharmaceuticals Corporation, NJ, USA, 11Colorado Center for Bone Research, Lakewood, CO, USA Aims: Zoledronic acid (ZOL) was shown to have superior eﬃcacy and faster time to onset than risedronate (RIS) in Paget’s disease from pooled data of the 6-month core period of two identical, randomized controlled trials comparing a single ZOL 5mg 15minute infusion with oral RIS 30mg/day for 60 days(1), suggesting

S256 potential for longer and more sustained biochemical remission by ZOL. To assess this, the results from the extended observation period (EOP) are presented. Methods: The primary eﬃcacy endpoint of the core study was therapeutic response at 6 months, defined as a R75% reduction in serum alkaline phosphatase (ALP) excess or its normalization. Of 169 ZOL and 125 RIS patients eligible for entry, 152 ZOL and 115 RIS responders entered the EOP and had ALP tested every 6 months. Time to first loss of therapeutic response, time to first partial disease relapse (defined as a R50% increase from the ALP measurement at month 6 and at least 1.25 times the upper normal limit) and complete disease relapse (defined as ALP level returned within 20% of baseline ALP value) were evaluated. Results: As of October 21, 2005, 57/115 RIS patients have lost therapeutic response compared to 3/152 ZOL patients (P<.0001). Furthermore, 49/115 and 9/115 RIS patients experienced partial and complete disease relapse compared to only 3/152 and 0/152 ZOL patients (P<.0001 and P<.001, respectively). Within the first 3 days of drug administration, ZOL patients experienced 2-fold higher rate of post-dose symptoms than RIS patients. Symptoms were mild to moderate in severity and mostly resolved after 4 days of onset. After 3 days of drug administration, side eﬀects rate was similar between treatment groups. Conclusions: A single ZOL 5mg infusion shows longer duration of eﬀect relative to the reduction in ALP than RIS. Treatment eﬃcacy was sustained in the majority of ZOL patients compared to the substantial number of RIS patients who either lost their therapeutic response or experienced partial or complete disease relapse. Hence, a single ZOL 5mg dose oﬀers the potential for multi-year biochemical remission in patients with Paget’s disease.

P452SU. PROPHYLACTIC AUGMENTATION OF THE CONTRALATERAL FEMUR: A FINITE ELEMENT STUDY de Bakker PM1, Guy P2, Fernlund G3, Oxland TR1; 1Division of Orthopaedic Engineering Research, UBC, 2Orthopaedics, Vancouver Coastal Health, 3Metals and Materials Engineering, UBC, Vancouver, Canada Purpose: Hip fracture patients are associated with an increased risk of a future contralateral hip fractures. There is currently no procedure that instantly strengthens the contralateral femur in hip fracture patients. To address this need, three new surgical procedures were tested. The goal of this study was to assess, using a finite element analysis, the ability of three new surgical reinforcements to strengthen the proximal femur. Methods: A finite element model of the proximal femur was developed using a QCT scan of a femur from a 73-year-old female donor with a BMD of -2.2. The model was made in ANSYS 8.1 and was validated through mechanical testing with strain gauges. The model was modified to include three diﬀerent implants

(1) Reid I et al. N Engl JMed 2005; 353:898–90

P451SA. AN OBSERVATIONAL STUDY TO EVALUATE TOLERABILITY, SAFETY AND TREATMENT SATISFACTION ASSOCIATED WITH RALOXIFENE AFTER HORMONE REPLACEMENT THERAPY IN POSTMENOPAUSAL WOMEN Oliveira J1, Escander M2, Beltrame PA2, Bertazzo RV2, Weissheimer WA2, Rossi J1, Basso P1, Bracco OL1; 1Eli Lilly, São Paulo, Brazil, 2SHE study Investigators, São Paulo, Brazil Raloxifene is an option to prevent and treat osteoporosis in women with postmenopausal osteoporosis. This was an observational study designed to evaluate tolerability and treatment satisfaction associated with raloxifene treatment after hormone replacement therapy in postmenopausal women in a naturalistic setting in Brazil during a twelve-month follow-up period. The study included two groups of patients, both previously on HRT: one group maintained HRT to prevent or treat osteoporosis (Group 1, n=115), while the second group (Group 2, n=219) switched from HRT to raloxifene after a 4–8 week washout period, each according to the gynecologist’s recommendation. Student t-test or Mann-Whitney U test were used for statistical analyses, and results are expressed as mean SE. Statistical significance was set at p%0.05. Results: Patients advised to maintain HRT were younger than patients who switched to raloxifene (59.4 0.5 vs 63.3 0.4 years, respectively, p<0.001). Time since menopause was shorter among patient on raloxifene (10.4 0.6 years vs 13.3 0.5 years, respectively, p<0.001). A percentage of 1.2% of patients who stopped HRT presented vasomotor symptoms during the ‘‘washout’’ period. After twelve months, treatment satisfaction related to raloxifene and HRT had improved in both groups in visits 2 and 3 compared with visit 1. However, there was no diﬀerence regarding satisfaction between raloxifene and HRT but were not statistically diﬀerent between each treatment group, when evaluated with the EQ5D. The compliance with medications was similar in both groups (96.3% with raloxifene and 97.5 with HRT; p=0.23). Therefore there was no diﬀerence related neither to compliance nor to treatment satisfaction in both groups when HRT and raloxifene were compared in the treatment of osteoporosis in postmenopausal women. In conclusion, postmenopausal women taking either raloxifene or HRT did not present diﬀerences regarding compliance and treatment satisfaction in a naturalistic setting in a Brazilian population.

Figure 1 - Implant models (Figure 1): a Gamma Nail (Howmedica/Osteonics, Mahwah, NJ), a carbon sleeve set in bone cement that contours the cortex in the femoral neck and extends into the trochanteric region, and a two-part construct consisting of a carbon sleeve set in bone cement placed in the superior neck and a wire which is anchored in the femoral head and runs through the inferior neck. Strength testing was performed by loading the models in a simulated fall. Results: The model predicted that the intact femur would fail at the base of the neck at a load of 3618 N. The strength was increased 100% by the first implant, 80% by the second and 15% by the third. Conclusions: In this study the ability of three implants to strengthen the proximal femur was assessed in the hope of preventing a second hip fracture in hip fracture patients. The study suggests that the first and second implants significantly strengthened the femur.

P453MO. THE CARE GAP BETWEEN OPTIMAL AND ACTUAL OSTEOPOROSIS DIAGNOSIS AND TREATMENT FOLLOWING A FRAGILITY FRACTURE: THE SASKATOON ATRAUMATIC FRACTURE ELIMINATION (SAFE) PROGRAM Olszynski WP1,2, Davison KS2,3; 1University of Saskatchewan, Saskatoon, Canada, 2Saskatoon Osteoporosis Centre, Saskatoon, Canada, 3University of Laval, Ste Foy, Canada The clinical manifestation of osteoporosis is the occurrence of fragility fractures. Fragility fractures are associated with losses in health-related quality of life, mobility and personal independence, and increases in morbidity and premature mortality. The direct and indirect financial burden of fragility fractures for the individual, as well as society, is substantial. Individuals who have had a prior fragility fracture may represent the population at greatest risk for a future fragility fracture and those that would benefit most from anti-fracture therapy. Despite the recognition that prior fragility fractures are a significant risk of subsequent fractures, there is a disturbing care gap between those who need osteoporosis diagnosis and therapy and those who receive it. It is estimated that only 20–25% of people who sustain a fragility fracture are ever

S257 diagnosed as osteoporotic, and less than half receive adequate treatment. Therefore, it is probable that only one in ten patients who require anti-fracture therapy receive it. The Saskatoon Atraumatic Fracture Elimination (SAFE) Program has retrospective and prospective arms and aims to first establish and then diminish the osteoporosis care gap after fragility fracture. The retrospective arm is designed to document the rate of osteoporosis diagnosis and the prescription of anti-fracture treatment in the Saskatchewan population who suﬀered a fragility fracture between the years 2001–2004 (three years of data). The prospective arm of the investigation is designed to minimally double the rates of both diagnosis and treatment in the Saskatoon Health Region population who suﬀer a fragility fracture in the period September 2006 through September 2009. This increase in diagnosis and treatment rates will be attained through an integrated approach of fracture identification, specialist referral, patient education, and physician education. By decreasing fragility fracture, health-related quality of life and longevity should be increased and morbidity and premature mortality reduced. Financially, it is hypothesized that the expenditure utilized in preventing the re-occurrence of fragility fractures would be less than that used to treat the complications of, and indirect financial losses consequent from, fragility fractures. The results of the retrospective arm of the program will be reported at the meeting.

P454SA. EXTENSION OF THE INDICATION FOR BALLOON KYPHOPLASTY IN ADVANCED OSTEOPOROTIC VERTEBRAL BODY FRACTURES Boehm B, Drees P, Wagner N, Klonschinski T, Eckardt A, Heine J; Orthopaedic Clinic, Johannes Gutenberg University, Mainz, Germany Introduction: The management of osteoporotic vertebral body fractures (VBF) with posterior wall involvement is problematic. Besides open surgery, new procedures as minimally invasive balloon kyphoplasty can be considered. Materials and methods: Between 01/2003 and 07/2005, 184 patients with symptomatic osteoporotic fractures were admitted for surgical treatment via the emergency of the orthopaedic University Clinic Mainz. 166 patients were managed with a minimally invasive procedure. In 10 patients with an advanced osteoporotic VBF with posterior wall involvement we performed balloon kyphoplasty. The mean patient age was 71.1 years; the median follow-up period was 11.6 months (3.5–16.5). In 8 of the 10 patients the fracture occurred after a trauma. Preoperatively 6 of the 10 patients reported leg pain, neurological deficit was present in 2 of these cases. In two cases a spinal decompression was done during the same operation session. Results: Two of the 10 patients were lost for follow-up, 1 woman died and 1 man was not available for follow-up control. The back pain improved from 8.1 preoperatively to 2.3 immediately post intervention (n=10, VAS). Leg pain resolved completely in 1/3 patients and was reduced in 2/3. During the follow-up period the leg pain was reduced from 3.9 to 2.2 (n=8, VAS). Quadriceps weakness KG 4 remained unchanged in one case. X-ray and CT control showed in the 8 patients available for follow-up a reconstruction in vertebral body height from 26 % (15.0–30.8%) to 71% (56.6–72.4%) of the initial vertebral body height. The kyphotic angle was corrected from 17( kyphosis to 2( lordosis. Conclusions: When critically analyzed, the pain reduction obtained in patients with VBF with posterior wall involvement is lower than in patients with uncomplicated VBF. In this patient group we noted 75% (6/8) of the patients with ostoporotic VBF with posterior wall involvement indicate a reduction of back and leg pain. They returned to their normal domestic environment. Clinically unsatisfactory results were only seen in the patients with a dislocated fracture (n=2/8). In patients with an increased surgical risk, the outcome of balloon kyphoplasty treatment is good, even in VBF with posterior wall involvement.

P455SU. OPERATIVE THERAPEUTIC STRATEGIES FOR OSTEOPOROTIC VERTEBRAL FRACTURES WITH NEUROLOGICAL DYSFUNCTION Boehm B, Meinig H, Meurer A, Heine J; Clinic of Orthopaedics, Johannes Gutenberg University, Mainz, Germany

Problem: Whereas the majority of osteoporotic vertebral fractures can be treated suﬃciently using minimally invasive therapeutic measures, the treatment of an osteoporotic vertebral fracture, with the involvement of the posterior edges and neurological dysfunction is problematic and harbours the risk of numerous complications. Material and methods: During the period of 01/2003 to 09/2005, the Outpatient Ward at the Clinic of Orthopaedics in Mainz referred 184 symptomatic patients with an osteoporotic fracture to undergo operative therapy. 166 patients underwent minimally invasive therapy (vertebroplasty/kyphoplasty). 18 patients required open surgery. 12 of the 18 patients were immobile, and 8 had neurological deficits. The average age was 67.3 years. As a standard measure, we conducted a combined procedure using ventro-dorsal spondylodesis, ventral decompression and vertebral body replacement in 17 cases, as well as vertebroplasty of the adjacent vertebral bodies. The treatment was performed using either the MOSSt Miami Spine System or the ExpediumTM Spine System (DePuy Spine, Kirkel-Limbach); in all these cases a 4-mm rod was used. Results: Directly following the operation we detected one deep infection and one case cage subsidence. In both cases revision surgery was necessary. It was possible to re-examine 16/17 patients at an average of 9 months after the operation. 4 of the 8 patients with neurological dysfunctions showed a complete absence of the symptoms; in three cases, sensory disturbances were observed, and in one case a motor disturbance. Only 2 patients complained about postoperative leg pain. Back pain improved from 8.9 to 2.3 (VAS). The kyphosis angle could be improved from 32( preoperatively to 7( postoperatively. 1 patient suﬀered an adjacent fracture 8 months after the operation. 5/17 patients take pain medication when needed, and 4/17 patients take them continually. All the patients are fully mobile in their home environment. Conclusion: The ventral decompression of unstable vertebral body fractures, combined with multi-segmental, dorsal spondylodesis is operatively demanding, but produces good results. As opposed to the usual traumatic vertebral fractures, osteoporosis requires an augmentation of the adjacent vertebral bodies, the application of a cage covering a large surface area and a 4-mm rod for dorsal spondylodesis.

P456MO. DIFFERENT INTRAVERTEBRAL PRESSURES IN VERTEBROPLASTY AND KYPHOPLASTY? Weisskopf M, Wirtz DC, Ohnsorge JAK, Niethard FU; Dept. of Orthopaedics RWTH University Hospital, Aachen, Germany Aims: High intravertebral pressures during PMMA injection have frequently been proposed as the reason for a higher cement leakage rate of vertebroplasty (VP) in contrast to kyphoplasty (KP). It has been shown that the intravertebral pressure measured in the shell of the vertebral body is much lower than the pressure applied to the injection syringe. However, the pressure relations in the center of the vertebral body are not known. This in vitro study investigates the diﬀerent intravertebral pressures measured in close proximity to the injection cannula during VP and KP. Methods: Vertebroplasty and kyphoplasty was performed in 10 lumbar cadaver spines. A pressure sensor (Cole Parmer, Vernon Hills, IL) was placed close to the tip of the injection cannula. In the VP subgroup a total volume of 6 cc of PMMA cement was delivered in 1.5 cc increments. In the KP subgroup balloon dilation up to a volume of 4 cc was made prior to cement injection of 6 cc (1.5 cc increments). Room temperature, cement mixing time and constant volume flow during cement injection were recorded. Results: During the administration of the first 1.5cc of PMMA the average intravertebral pressure for the VP was 58 versus 6 KPa for KP. For the 2nd filling an average pressure of 92 KPa (VP) and 19 KPa (KP) was recorded. The average intravertebral pressure during the 3rd injection was 134 KPa (VP) and 51 KPa (KP). The pressure of the last 1.5 cc averaged in 175 KPa (VP) and 105 KPa(KP). Conclusions: The intravertebral pressure measured during the PMMA filling of the vertebrae of cadaver spines was lower in kyphoplasty than in vertebroplasty. In the kyphoplasty group a

S258 sharp increase of the intravertebral pressure was registered at the end state of cement augmentation.

P457SA. HIP PROTECTOR PAD STYLE: WOULD THIS IMPROVE UTILITY? Juby AG1, Davis SR1, Manca D2, Nelson T3,4, Thompson B2, Nam M4; 1University of Alberta, Department of Medicine, Division of Geriatrics, 2University of Alberta, Department of Family Medicine, 3University of Alberta, Department of Psychology, 4 Always Hip Safety Wear Mfg, Edmonton, Alberta, Canada Aim: To evaluate the preferences and uptake of hip protector pads in a group of individuals attending an osteoporosis educational session. Methods: Prospective evaluation of all the attendees at an Osteoporosis Society sponsored osteoporosis educational session, (held at an acute care hospital) using a questionnaire. Prior to the educational session, attendees were shown two types of hip protector pads undergarments: Safehip (Sahvatex) – inbuilt hard shell style, and Insider Health Undergarment ( Always Hip Safety Wear) – removable soft shell (gel) style. The products could be examined, but were not tried on. Each attendee then completed a 14 item questionnaire. Results: 37 questionnaires were completed. All were community dwelling and independently mobile. The average age was 64 years (range 43–82) and all were women. 57% had a diagnosis of osteoporosis and 32% had osteopenia. Only 48% said they would wear hip pads. Reasons cited for not using hip pads were a sense of not needing them yet, or not wanting to look fat. But, had they already fractured their hip, 75% said they would consider hip pads. The majority said they preferred the soft pad style (94%). 53% said cost was not a factor in deciding on whether or not to wear a pad, or on the type of pad preferred. Even if they were given free hip pads, 23% said they would not wear them, and 13% were unsure. 83% said they would recommend hip pad wear to someone else. Availability in outer wear (such as trousers or a coat) was said by 88% to make the hip pad wear more likely. 69% believed that hip pads prevent hip fracture. Conclusions: Participants in this study were motivated and interested in osteoporosis as evidenced by their attendance at an osteoporosis educational program. Nonetheless, even though a significant number had a diagnosis of osteoporosis or osteopenia the majority would still not consider wearing hip protector pads, even though they believed that they prevented hip fractures. This study highlights the need for developing a hip protector pad that is not only eﬀective, but also aesthetically acceptable to community dwelling patients.

P458SU. PATIENT PREFERENCES WITH A ONCE-MONTHLY BISPHOSPHONATE Dore RK; David Geﬀen School of Medicine at UCLA, Los Angeles, USA Aim: Ibandronate 150 mg once monthly has been available in the United States for over six months. The other two bisphosphonates approved in the US for treatment of osteoporosis, risedronate and alendronate, are almost always prescribed on a weekly basis; they were first available as daily treatment. Most patients changed to weekly from daily dosing for convenience. For others, it was due to a desire to experience fewer GI symptoms. Ibandronate is the first monthly oral agent for osteoporosis. The objective of the study was to determine why patients preferred once-monthly therapy. Methods: Fifty consecutive patients who were oﬀered and accepted once-monthly bisphosphonate therapy were asked why they selected monthly instead of weekly therapy. The reason for therapy change and prior therapy were recorded. For treatment naïve patients, the reason for selecting a monthly bisphosphonate was recorded. Results: Tolerability, convenience and compliance appear to explain patient preference for monthly treatment. For example, patients experiencing GI upset weekly state that anticipated GI discomfort once monthly would be tolerable (n=16). Some patients (n=13) feel that taking 3 fewer pills a month will greatly reduce their ‘‘pill burden’’ while others (n=10) simply want the convenience of a monthly bisphosphonate; these patients are not

having adverse events. Other patients (n=6) say they will be more compliant with a monthly medication than a weekly one they weren’t taking faithfully, although they did not admit to this non-compliance until an alternative was available. Five patients changed for other reasons. Of note, patients have not objected to waiting 60 minutes after taking ibandronate before eating rather than 30 minutes required for other bisphosphonates. Prior therapy discontinued included risedronate (n=17), alendronate (n=13), teriparatide (7) [completing therapy (n=5), discontinuing therapy (n=2)], raloxifene (n=4), calcitonin (n=1) and etidronate (n=1). Seven patients initiating ibandronate were not discontinuing (or completing) a prior osteoporosis therapy. Patient self-reported compliance has been high (48/50), with most patients taking therapy the first day of the month or on the day of their birthday. Four patients discontinued ibandronate due to adverse events. Conclusion: Physicians should ask patients their preferences when treatment options oﬀer diﬀerent dosing regimens.

P459MO. THE CHALLENGE OF IDENTIFYING PATIENTS WITH LOW TRAUMA FRACTURE Nixon J1, Karlsen A1,2, Allen D1, Summers G1,2; 1Department of Rheumatology, Derbyshire Royal Infirmary, UK, 2Osteoporosis Clinic, Derby City General Hospital, UK A Fracture Liaison Service was setup at Derbyshire Royal Infirmary in November 2002. The aim is to identify all patients age 50 years or more presenting with a low trauma fracture. Since January 2004 the Orthopaedic Clinic secretaries have sent all Fracture Clinic letters to the Fracture Liaison Service so that patients with low trauma fracture of the distal forearm, ribs, humerus, hip, other major long bone, pelvis or spine can be identified. The purpose of this audit was to check the eﬃciency of identifying female patients with a low trauma fracture of a distal radius during 2004. The A&E database was searched for females over the age of 50 with ‘‘wrist fracture’’. 445 patients were identified and the casualty cards of all patients were extracted from the A&E archives to check the diagnosis and mechanism of injury. 56 patients with open fracture due to high trauma were excluded as well as 17 patients with fracture of the small bones of the wrist. There were 372 patients with a closed low trauma fracture of the distal radius. Where there was a query about the diagnosis the x-rays were checked. Data extracted from the fracture liaison database for patients with distal forearm fracture for the time period of 2004 as well as the first six months of 2005 showed 264 female patients who matched the Accident and Emergency database. 108 patients were recorded in the A&E database but not in the fracture liaison database. The fracture liaison process using Fracture Clinic letters to identify women with low trauma fracture was successful in identifying only 71% of patients who originally came to Accident and Emergency. This represents an improvement from before the introduction of the Fracture Liaison Service. An audit of 350 women aged 40–70 years who attended the A&E Department between March 1996 and February 1997 with a distal forearm fracture showed that only 20% consulted a medical professional regarding possible osteoporosis. The women identified who have not been contacted by the Fracture Liaison Service will receive letters to make sure that they have an assessment for osteoporosis.

P460SA. ADJUVANT THERAPY WITH TERIPARATIDE AFTER HIP ARTHROPLASTY IN OSTEOPOROTIC FRACTURE: FIRST REPORT OF THREE CASES Corradini C1, Ulivieri FM2, Macchia M1, Occhipinti V1, Verdoia CA1; 1Orthopaedic Clinic, Studies’ University of Milan, Milan, Italy, 2U.O. Nuclear Medicine; Fondazione IRCCS, Milan, Italy Introduction: Even if the highest risk of a second fracture exists after femoral neck fracture, there is still poor consideration of adjuvant therapy for osteoporosis in elderly people. Recently

S259 two-dimensional and three-dimensional assessments of cancellous bone structure have shown that parathormone (PTH) can reestablish lost trabecular connectivity and improve biomechanical competence. In randomized controlled clinical trials of intermittent PTH treatment, the incidence of osteoporotic fractures in postmenopausal women is decreased. We present the first report of adjuvant treatment with teriparatide [rhPTH(1–34), TPTD] after hip arthroplasty in osteoporotic fracture. Materials and Methods: Three in women of 82 years old with postmenopausal osteoporosis after 6 months by hip arthroplasty for a femoral neck fracture. Parathormone (PTH), alkaline phosphate (ALP), calcium (Ca), phosphorus (P) and 25hydroxyvitamin D (25OHD) serum levels and calcium (Ca), phosphorus (P) on urine of 24 hours were measured at the beginning and 1, 6 months later. Bone mineral density (BMD) measurements at the lumbar spine and non-injured hip were obtained at baseline and after 6 months. The pain symptoms and quality of life through respectively on a self-reported Visual Analogue Scale (VAS) and QUALEFFO 41 were collected at 0, 1, 6 months. All the women after signature on informed consent received daily subcutaneous TPTD injection of 400 U (25 microg) in association with 880 U.I. of colecalciferol and 1g of calcium carbonate per os for 6 months. Results: Haematochemical values in the six month demonstrated normal values of PTH that decreased not significantly; low levels of 25 OHD that increased significantly (p < 0.001); high levels of ALP that decreased significantly (p < 0.004); normal serum and of calcium and phosphate remained unchanged. Normal urinary levels of calcium and phosphate remained unchanged from baseline to endpoint. BMD significantly increased (p < 0.02). Also the quality of life improved in term of pain relief, mobility, autonomy and prevention of new fracture in relative short time from baseline. Neither adverse eﬀect was registered nor any modification of therapeutic program was requested. Conclusions: This preliminary study suggests a clinical significance of adjuvant therapy with teriparatide after a femoral neck fracture.

P461SU. COST-EFFECTIVENESS OF FOSAVANCET IN THE TREATMENT OF OSTEOPOROSIS IN THE NETHERLANDS Jansen JP1, Shavit O2, Bergman G1, Sen SS3; 1Mapi Values, Houten, The Netherlands, 2Temple University, Philadelphia, PA, USA, 3Merck & Co., Inc., Whitehouse Stations, NJ, USA Objective: To evaluate the cost-eﬀectiveness of Fosavancet (alendronate plus vitamin D3) versus Ibandronate in the treatment of post-menopausal osteoporotic women with history of vertebral fracture in the Netherlands. Methods: A lifetime patient simulation model depicting the osteoporosis disease progression was developed adopting a previously published model (Kanis et al. 2000) to estimate the cost-eﬀectiveness of Fosavancet versus comparators using cost estimates from the Netherlands. This discrete state transition model using a 1-year cycle included health states related to hip, vertebral, wrist and proximal humerus fractures, as well as health states for death due to hip fractures and death due to other causes. The model estimated outcomes including number of fractures, quality-adjusted life years (QALYs), direct medical costs, cost per QALY gained and cost per fracture avoided. The impact of 5 years of treatment on the occurrence of fractures and other associated outcomes was modeled with relative risks observed in Vertebral Fracture Arm of the Fracture Intervention Trial (FIT) for Fosavancet and data from Chesnut et al (2004) for ibandronate. Direct medical costs, utilities associated with diﬀerent health states were derived from existing literature. Analyses were performed for women with a history of vertebral fracture aged 50, 60, 70 and 80 years. Probabilistic sensitivity analyses using Monte Carlo simulation were undertaken to estimate the uncertainty of the model outcomes. Results: Fosavancet was projected to be dominant over ibandronate (cost saving and more eﬀective) in women with a history of vertebral fracture, aged 50 years and older The base case

projected that on average there was a incremental cost savings of 790 to 2,593 euros, QALY gain of 0.006 to 0.12 and 0.07 to 0.1 fractures avoided with Fosavancet as compared to Ibandroante for women with history of vertebral fracture aged 50 years and older. Conclusions: In the Netherlands, Fosavancet was projected to be a dominant therapy over Ibandronate for post-menopausal women with a history of vertebral fracture aged 50 years and over.

P462MO. TERIPARATIDE PERFORMANCE IN WOMEN’S BONE FORMATION Bazarra-Fernandez A1, Bazarra-Castro MA2; 1Juan Canalejo University Hospital, 2Santiago University, Chile Background: It has been reported that elderly women with osteoporosis can significantly and safely improve their bone mass with a combination therapy of hormone replacement and bisphosphonates. After three years at the lumbar spine the mean increases in BMD were 10.4% with combination of therapy of hormone replacement plus alendronate. Bisphosphonates can yeld side eﬀects in the long term and conjugated estrogen with or without medroxyprogesterone are not beta-estradiol and progesterone. So its eﬀects and risks can not be extrapolated. Aim: looking into new possibilities as treatment to osteoporosis. Material and method: 16 women who were 45–80 years old were recruited. They were assigned to two groups according to age: 45–65 and 66–80. Bone density was determined by DXA. They were given subcutaneous teriparatide injection of 20 µg/d for three months. Fasting blood and urine samples were collected at baseline, at three and six months. Biochemistry: Serum calcium, PTH, 25-hydroxyvitamin D, osteocalcin, alkaline phosphatase, bonespecific alkaline phosphatase. 24-hour urine collection: PYD, calcium without and with calcium intake. Calcium supplement was 1500 mg/d with 0.266 mg vitamin D twice a week. Results: In 45–65, 66–80 groups the mean BMD was T-score –1.8 and –3.20, respectively. At baseline fasting blood and urine sample mean: Serum calcium 9.1; 8.9 mg/dl, 25-hydroxyvitamin D 16; 12 ng/ml, alkaline phosphatase173; 162 U/L bone-specific alkaline phosphatase 26.3%; 23%. PID 9;15 nM PYD/mM creatinine, urinary calcium 64;240. At three months: Serum calcium 9.9; 9.3 mg/dl, 25-hydroxyvitamin D 68; 88 ng/ml, alkaline phosphatase193; 180 U/L bone-specific alkaline phosphatase 45.3%; 32%. PID 4.8; 8.7 nM PYD/mM creatinine, urinary calcium 189; 309. At six months with seven and six cases the results are similar in relation to both groups. Conclusions: Increasing of bone formation is given but is diﬀerent in both groups. The bone development is not continuous but in cycle basis because we think one cycle basis approach is needed to be found with teriparatide and inhibitors of osteoclastmediated bone resorption of short action without deposit for long in bones. So, proposal of study is made with estradiol and progesterone plus teriparatide.

P463SA. RELATIVE RISK FOR DEVELOPING DEPRESSION IN COMPLICATED OSTEOPOROSIS (CLINICAL STUDY) Wendlova J; University Hospital and Policlinic, Bratislava, Slovakia Patients and methods: In a prospective study we observed which female patients developed depression following an acute and painful vertebral fracture. On the day of diagnosing the vertebral fracture the patients filled questionnaires 1 and 2. The aim of the study: To verify the hypothesis that the patients with more traumatic experience in the anamnesis (Ques. 1) are more depression prone following the osteoporotic vertebrae fractures and their character features are typical for subjects with higher emotional vulnerability (Ques. 2). Statistical analysis: Questionnaires 1 and 2 were evaluated by two statistical methods: (1) automatization of mathematical and statistical estimates and tests based on binomial distribution; (2) ADALINE Programme. Results:

S260 (1) Ques. 1 completed by depressed patients contained statistically significant higher number of positive answers to questions defining experienced stress situations. (2) Ques. 2 completed by depressed patients contained statistically significant higher number of positive answers by more depression prone subjects in comparison with nondepressed patients. (3) Proposed questionnaires are according to validity criteria (sensitivity, specificity, prediction value of positive test, prediction values of negative test, test eﬀectiveness) indicated for identification of persons risking the onset of depression following osteoporotic fracture of vertebrae. Conclusion: We recommend to use questionnaires 1 and 2 in female patients with acute painful vertebrae fractures to select patients with risk of depression development. Early therapy of depression enables to accelerate the mobilisation, rehabilitation and resocialisation and reduce the costs of analgetic treatment of pain, sedatives and rehabilitation.

P464SU. LONG TERM FOLLOW UP AND RESULTS USING PERCUTANEOUS KYPHOPLASTY FOR VERTEBRAL FRACTURES Cesaroni A, Nardi PV, Cabezas D; Policlinico Casilino, Neurochirurgia, Rome, Italy Long-term eﬀects of kyphoplasty have not yet been reported in the literature. 305 consecutive patients underwent kyphoplasty for the treatment of vertebral compression fractures: 108 single level, 197 two or more levels. Cases were divided into acute fractures (under 10 weeks) and chronic (over 10 weeks). Follow up ranged from 12 to 28 months. All operations were performed with local anaesthesia and one level at a time in case of multiple fractures. Mean operation time duration was 20 minutes. Results were evaluated in terms of kyphosis correction, vertebral height changes, pain relief (VAS), global wellness referring to back pain and overall improvement as quality of life (Oswestry Disability Questionnaire). In case of single level the kyphosis correction was strictly correlated with the time passed from fracture and is firmly related to the grade of vertebral collapse. Best surgical correction was reached when time was under 10 weeks (6 mm mean), cases operated on in a latter period had a lower increase in vertebral height (2 mm mean). Pain relief in these patients was a superb result where response reached almost 97% of complete healing 10 days from operation. Mean VAS reduction was near 6.3 and daily activities were, in all cases, improved; at long term follow up it was of 67% (ODQ mean drop 26 points 18). All these results were statistically significant (P<0.001). In cases of multiple levels involved by fractures, kyphosis was slightly improved with a decreased kyphosis of 5 degrees. In 88% of these cases the vertebral height did not change after intervention, in 12% a poor increase (2 mm mean 1) was observed. Pain amelioration after procedures was slightly less successful than in single level pathologies (76%). The pain relief (mean pre-op VAS 6.9, post-op 3.5) and quality of life (ODQ mean drop 17 point 12) was in all patients reduced significantly (P<0.010). Daily activities and personal wellness were improved in a high percentage of cases (60%) at long term follow up, more reduced at short term follow up (25%).

P465MO. EFFECT OF TWO-YEAR DISCONTINUATION AFTER FIVE YEARS OF ALENDRONATE TREATMENT IN PATIENTS WITH POSTMENOPAUSAL OSTEOPOROSIS AND IMPAIRED FASTING GLUCOSE Cokolic M1, Hren R2; 1Department of Endocrinology and Diabetology, Internal Clinic, Teaching Hospital, Maribor, Slovenia, 2 Institute of Mathematics, Physics, and Mechanics, University of Ljubljana, Ljubljana, Slovenia Background and Aims: In our previous reports, we have shown that postmenopausal osteoporosis can be eﬀectively and safely treated in patients with impaired fasting glucose (IFG; serum levels of fasting glucose > 6.1 and < 6.9mmol/l) for up to five years. In this study, we evaluated the remaining eﬀects of a 5-year treatment with alendronate in 24-month follow-up after withdrawal of alendronate treatment.

Material and Methods: Eleven women with postmenopausal osteoporosis (T-score below -2.5 SD) and IFG were enrolled in a seven-year prospective study. At the enrollment, patients were 55 to 73 years old (mean: 65) and 5 to 19 years (mean: 12.6years) after the menopause. They were treated with alendronate (10 mg/d in Years 1–4 and 70 mg/w during Year 5) in combination with 500 mg/d elemental calcium; in Years 6–7 alendronate treatment was discontinued. During the seven-year follow-up, the BMD in the lumbar spine (L1-L4) and left hip was measured in all patients using DXA (Hologic QDR2000+). The serum levels of glucose, HbA1c, Ca, ALP and creatinine were measured every 6 months. All patients were treated for IFG with diabetic diet only. Results: In Years 1–5, BMD increased on average by 11.1% in the lumbar spine (L1-L4) and by 6.4% in the left hip. In Years 6–7, BMD increased in the lumbar spine by additional 1.1%, but decreased on hip by 4%. Levels of Ca, ALP and creatinine were within normal limits, while serum levels of fasting glucose and the average level of HbA1c showed no statistically significant changes during the entire period of 7-year follow-up; also, no clinical side eﬀects were observed. Conclusions: Results of our study indicate that residual eﬀects of alendronate treatment are seen in the lumbar spine region, but not in the hip region. Moreover, more than 60% of improvement observed during the 5-year treatment with alendronate was lost in just 2 years after cessation of the treatment. As the risk for hip fractures markedly increases with the decline in BMD of the hip, alendronate treatment should be continued to maintain its benefits.

P466SA. EFFECTS OF COMBINED THERAPY (HORMONE REPLACEMENT THERAPY AND ALENDRONATE) ON BONE MINERAL DENSITY OF ELDERLY WOMEN WITH OSTEOPOROSIS Karzewnik EK1, Sewerynek ES2; 1Outpatients Clinic of Endocrinology in Piotrkow Trybunalski, 2Department of Bone Metabolism, Medical University of Lodz, Poland Hormone replacement therapy (HRT) alone as well as bisphosphanates alone are eﬀective treatment for postmenopausal osteoporosis but the eﬀect of multidrug treatment is not well recognized. The aim of the study was to compare HRT, and its combination with alendronate (ALE) on bone mineral density (BMD) in postmenopausal women with osteoporosis. Materials and Methods: A total of 90 patients with osteoporosis, who had not been receiving HRT for at least 1 year were randomized to receive 1 mg 17b-estradiol plus 0.5 mg 19norethisterone acetate daily, per os (n=45; Group I), or in combination with ALE in a dose 10 mg/d (HRT+ALE; n=45; Group II), for 1 year. Changes of the bone mineral density of the lumbar spine was measured using QCT at baseline and after 1 year of treatment. Each group were divided into 2 subgroups depend on the T-score values: A – 2.5 or less at the lumbar spine (osteoporosis; n=37); B – higher than –2.5 in patients with additional risk factors (osteopenia; n=8). Results: At the end of one year treatment, increases in spinal BMD were found in all examined groups but statistically significant on combined therapy. Compared with HRT alone, ALE+HRT produced significantly greater increases in BMD of the lumbar spine [T-score ALE+HRT vs HRT - Group A 8.26% vs 5.78% (NS); Group B 13.8% vs 10.18% (NS) or BMD - Group A 3,24% vs 1.40% (NS); Grupa B 3.35% vs 0.74% (NS)]. Addition of ALE to ongoing HRT was well tolerated without gastrointestinal site eﬀects. Conclusion: The combination of HRT and ALE, in erderly postmenopausal women with osteoporosis, did not oﬀer an extra gain of bone mineral density over treatment of HRT alone.

P467SU. INCREASING THE TREATMENT OF OSTEOPOROSIS IN A HIP FRACTURE POPULATION Crilly RG1,4, Overend T1,4, Speechley M1,4, Simon S2,4, Mackenzie R3,4, Cremer S1,4; 1University of Western Ontario, 2London

S261 Health Sciences Centre, 3St. Joseph’s Health Centre, 4Hip Fracture Interest Group, London, ON, Canada Aims: Failure to assess and treat osteoporosis after a hip fracture is a universally recognized problem. As part of the development of a hip fracture pathway in orthopedic units, the Hip Fracture Interest Group sought the insertion of standing orders in an attempt to have patients started (at least) on calcium (1000 mg) and vitamin D (1000 IU). This audit was undertaken to evaluate the success of the initiative. At the time of the audit, the pathway had not been implemented in all orthopedic units, permitting a comparison of those on its pathway and those not. Methods: An audit of 50% of hip fracture patients admitted in one year (2002) to three acute care hospitals was conducted. 230 cases, 55 males and 175 females were reviewed and data on a wide range of demographic characteristics, bone related information, living arrangements, treatment, comorbidities etc were collected. Results: 23% were male. Overall, men were younger, contrary to expectations (81 8 (SD) vs. 83.3 7.4 yrs for women) but this was due to an older subpopulation from long term care who were predominantly female. Men and women admitted from their own home were of similar age (81 7 yrs for both). 22% came from long term care, 9.5% from retirement home, 58% from their own home. Implementation of the pathway varied from site to site. Overall, 42% of patients were started on vitamin D and calcium in hospital and subsequently discharged on treatment. For those on the pathway it was 72% vs. 13% for those not on the pathway (P<.01). There was no gender bias in this decision, such a bias having been noted in other studies. Conclusions: The audit shows that if a pathway contains automatic instructions for the initiation of treatment with calcium and vitamin D, it is relatively eﬀective. Continuation of treatment after discharge is, of course, another matter. An interesting observation is that hip fractures appear to be occurring at an older age, particularly in women, and the age diﬀerence between women and men, who used to fracture later, was not observed in this study.

P468MO. EXERCISE TRAINING PROGRAM INFLUENCES ON ANKLE MUSCLE STRENGTH, BALANCE PERFORMANCE AND QUALITY OF LIFE TO WOMEN SUFFERING FROM OSTEOPOROSIS Aveiro MC1, Granito RN1, Navega MT1, Driusso P2, Oishi J3; 1 Physical Therapy Department, São Carlos Federal University (UFSCar), São Carlos/SP, Brazil, 2Physical Therapy Department, City of São Paulo University (UNICID), São Paulo/SP, Brazil, 3 Statistics Department, São Carlos Federal University (UFSCar), São Carlos/SP, Brazil Aims: This study proposed to apply and to analyze the eﬀects of an exercise training program in ankle muscle strength, balance performance and quality of life in women suﬀering from osteoporosis. Methods: Twenty volunteers with densitometric diagnosis of osteoporosis at the lumbar spine or femoral neck were submitted to a physical evaluation, but only twelve (age 68.7 2.7) finished the study. A control group was not included in this study because it would be not ethic to maintain some people without performing the exercise program, if it is known the benefits of physical exercise for human health. Isometric peak torque was assessed through an isokinetic dynamometer BIODEX II, a balance performance index was assessed through subject’s performance in some postures, according to established criterion and the quality of life was assessment through OPAQ – Osteoporosis Assessment Questionnaire. The physical activity program was guided by a physical therapist, who worked 60 minutes, 3 times a week for twelve weeks. Each session included some stretching exercises; twentyminute walking, exercises to strengthen ankle dorsiflexors and plantar-flexors muscles, with 50% of 10-repetition maximum (10RM) and balance training. The data were statistically analyzed by Wilcoxon non-parametric test. Results: The variables analyzed regarding to balance performance, plantar flexors peak torque and dorsiflexors peak torque showed significant improvement (p % 0.05). The questions with reference to flexibility, activities of daily living and level of pain, in

OPAQ, presented a significant improvement; however those with reference to level of tension/anxiety and family support did not present a significant improvement. Conclusions: It can be concluded from the obtained results that the physical activity program was eﬃcient to improve balance performance, ankle muscle strength and some aspects of quality of life, suggesting that the program has been an eﬀective and safe training to women suﬀering from osteoporosis.

The eﬀects of the exercise training program.

Right plantar flexor peak torque Left plantar flexor peak torque Right dorsiflexor peak torque Left dorsiflexor peak torque Balance performance Index Flexibility Activities of daily living Family support Level of pain Level of tension/ anxiety

Baseline

After 12 weeks

p-value

50.8315.78

61.1418.20

0.0037 *

51.8015.29

59.5815.43

0.0029 *

16.584.16

20.494.25

0.0022 *

16.853.91

20.813.92

0.0022 *

23.176.25

19.928.52

0.0178 *

3.690.19 3.870.16

3.780.15 3.970.07

0.0277 * 0.0277 *

3.140.38 0.760.50 1.160.52

3.190.34 0.350.31 0.970.38

NS 0.0068 * NS

Data are expressed as mean standard deviation. p-value based on Wilcoxon test. * Significant (p 0.05) NS= not significant

P469SA. EFFECTS OF 2-YEAR TREATMENT WITH CALCITONIN IN POSTMENOPAUSAL OSTEOPOROSIS Gurer G, Sendur OF, Tastaban E, Aydemir AH; Department of Physical Medicine and Rehabilitation, Adnan Menderes University Medical Faculty, Aydin, Turkey Introduction: Osteoporosis is a disease that is characterized by low bone mass and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. Randomized clinical studies indicate that prolonged administration of salmon calcitonin prevents bone loss, increases spine bone mass, and decreases fracture risk in postmenopausal women. Objective: This study was performed to research the eﬀects of calcitonin treatment with 2 years duration in women with postmenopausal osteoporosis. Methods: One hundred four women with postmenopausal osteoporosis were enrolled in this study. Calcitonin at one dose of 200 IU daily was gived to all of these patients. Bone mineral density (BMD) in the lumbar spine and left proximal femur was measured by dual-energy X-ray absorptiometry (DXA) three times at before treatment, first and second year. Results: Significant improvement was found in the lumbar spine (p<0.001) and femur BMD (p<0.05) at the end of treatment. However, increasing of lumbar spine was more significant than femur measures with treatment. In conclusion, calcitonin in the treatment of postmenopausal osteoporosis by 2 years produced an increase in BMD of trabecular and cortical bone. Reference 1. Chesnut CH 3d, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence of Osteoporotic Fractures Study. PROOF Study Group. Am J Med 2000;109:267–76.

S262

P470SU. EFFECT OF WEIGHT-BEARING TRAINING IN WOMEN WITH ESTABLISHED OSTEOPOROSIS ON QUALITY OF LIFE, BALANCE AND USE OF PAIN KILLERS Möller M1, Grahn Kronhed AC2, Hallberg I3, Toss G3, Ödkvist L4; 1Institute of Community Medicine, Department of Primary Health Care, Gothenburg University, Sweden, 2Primary Health Care Center, Vadstena, Sweden, 3Osteoporosis Unit, Department of Endocrinology, University Hospital of Linköping, Sweden, 4 Department of Audiology, University Hospital of Linköping, Sweden Osteoporosis is a common chronic disease in Swedish women with a strong impact on quality of life. Aims: To evaluate if weight-bearing training in a group would improve quality of life, balance and muscle strength in women with established osteoporosis. Methods: Women aged 60–80 years were invited to the study. 73 persons were randomised to exercise (E-) and control (C-) groups. A health-related quality of life questionnaire ‘‘Qualeﬀo-41’’, balance tests etc. were used prior to the study, at four-month and one-year follow-ups. Balance performance was measured by dynamic posturography and bone mineral density by DXA. Physical activity levels, use of analgesics and falls were reported each week. The four-month weight-bearing training was conducted by a physiotherapist. After the group-training period the E-group was encouraged to continue training. Results: 31 persons participated in the E-group and 34 persons in the C-group. Three persons in each group did not take drugs against osteoporosis. The E-group carried out 24 sessions on average. The reported physical activity wearing track-clothes decreased in the E-group after the group-training period. At the four-month follow-up the E-group performed better than the C-group in tandem standing with eyes closed (p<0.05), standing on the right and on the left leg with eyes open (p<0.05), walking backwards on a line (p<0.05), and in a strategy condition (p<0.05). At the one-year follow-up these diﬀerences were equalised. There were no diﬀerences between the groups in BMD-values at the one-year follow-up. Prior to the study the E-group scored better than the C-group in most Qualeﬀo-41 domains. The E-group also scored better in the mental domain than the C-group at both follow-ups (p<0.01 and p<0.05). There was no fracture reported in the groups for the study period. 22 persons in the E-group (71%) and 18 persons in the C-group (53%) did not use analgesics at the inclusion of the study. During the one-year study the E-group used analgesics for 14 weeks and the C-group for 24 weeks. Conclusions: The study implies that coaching is important to encourage frequent training, to achieve and retain positive eﬀects on the use of analgesics and on balance performance.

P471MO. A PHASE I SAFETY, DOSE-ESCALATION STUDY OF VITAMIN D3 WITH CALCIUM IN PATIENTS WITH MULTIPLE SCLEROSIS Kimball S1, Vieth R1, Ursell M2, O’Connor PG2, Gray B2; 1Mount Sinai Hospital, 2St. Michael’s Hospital, Toronto, ON, Canada Background: Although vitamin D3 is often used in the treatment of osteoporosis, a Phase I, dose-finding study has never been undertaken to our knowledge. Vitamin D3 may play a role in the development and/or progression of multiple sclerosis (MS). Objective: To perform a dose-finding study, characterizing the therapeutic safety of vitamin D3 with calcium supplements in patients with MS. DESIGN: In a Phase I, escalating-dose design, vitamin D3 (100 to 1,000 mcg/day) was given orally over 28 weeks to 12 patients with clinically definite MS. Calcium was also given orally at the current recommended daily intake (1000 mg/day). Every 6 weeks, serum and urine calcium, serum liver enzymes, creatinine, protein and electrolytes were monitored, and the vitamin D3 dose increased incrementally, ending after 4 weeks of supplementation at 1,000 mcg/day. Disease activity was monitored based on annualized relapse rates and magnetic resonance imaging (MRI) scans of the brain. Results: Mean serum 25-hydroxyvitamin D (25(OH)D) concentrations increased from 79.4 nmol/L at baseline to 452.6 nmol/L

(p<0.001). At the end of the protocol the highest individual 25(OH)D value was 810 nmol/L. Serum calcium levels and urine calcium:creatinine remained within normal ranges (2.2–2.6 mmol/L and <1.0 respectively) for all participants, and did not change significantly (paired t-test). Liver enzymes, serum creatinine, electrolytes and serum protein all remained unchanged and within reference ranges. In terms of MS, there was no significant change in annualized relapse rates or the number of lesions on MRI scans (indicators of active disease). Conclusions: Despite attaining serum 25(OH)D concentrations much higher than physiologic levels (>230 nmol/L), no participant developed hypercalcemia, hypercalciuria or adverse clinical eﬀects. These data support the safety of higher vitamin D3 intakes, and will help to define serum 25(OH)D concentrations that could be evaluated for the treatment of disease such as MS or osteoporosis.

P472SA. AN INTERPROFESSIONAL MODEL FOR PREVENTION AND TREATMENT OF OSTEOPOROSIS: BUILDING THE BRIDGE TO BETTER BONES Weldon M, Woo K, Chan G, Soever L; Ambulatory Geriatric Services, North York General Hospital, Toronto, ON, Canada Aims: The aim of the Building the Bridge to Better Bones (BBBB) program is to facilitate knowledge transfer about topics related to osteoporosis for men and women over 45 years of age, including risk factors, prevention, exercise, diet, treatments, and local community resources. Methods: Development of the program utilized a best practice approach and was based on needs identified within a local hospital as well as the surrounding community. Based on the fact that the majority of patients who suﬀer from a first fracture are not evaluated for osteoporosis, a partnership was developed with the volunteer department and staﬀ from the fracture clinic in the hospital. Women and men with fractures, especially wrist fractures, are actively recruited from the fracture clinic in the hospital for the BBBB program. From the community, women and men aged 45 and over who would benefit from early participation in healthy bone lifestyles are also the targets of the BBBB program. This program therefore addresses those with either diagnosed or undiagnosed osteoporosis as well as those interested in preventing osteoporosis. The education module for the BBBB program incorporates principles of adult education and is delivered by an interprofessional team which includes a nurse and a physiotherapist. Results: The model for the Building the Bridge to Better Bones program is grounded in a framework that encompasses health promotion, disease prevention, self referral, self management, interprofessional education, and community partnerships. The program also utilizes outcome measures to continually monitor its eﬃcacy. Conclusions: Utilization of the BBBB program and its’ interprofessional model has contributed to increased knowledge about osteoporosis and changes in behaviours regarding healthy bone lifestyles, among those who attended the program.

P473SU. TREATMENT OF BONE LOSS AFTER RENAL TRANSPLANTATION IN CHILDREN: ALFACALCIDOL VERSUS CALCITONIN THERAPY El-Husseini A, El-Agroudy A, El-Sayed M, Sobh M; Mansoura Urology & Nephrology Center, Mansoura, Egypt Background: Osteoporosis is a well known complication of renal transplantation in children. We conducted a randomized trial comparing alfacalcidol with calcitonin for the treatment of bone loss. Methods: Among 59 young patients who received live related renal transplant and were subjected to dual-energy x-ray absorptiometry (DXA), 30 patients had low bone mineral density (BMD) (Z-score < -1) were enrolled into the study. Their mean age at time of transplantation was 13.5 3.4 years and the mean duration after transplantation was 46 32 months. Patients with low BMD were randomized into two equal homogeneous groups: group 1 received daily alfacalcidol 0.25 µg by mouth and group 2 received 200 IU/day nasal spray calcitonin. Every patient in both groups received daily 500 mg calcium carbonate supplements. Parameters

S263 of bone metabolism (intact parathyroid hormone, serum osteocalcin and urinary deoxypyridinoline) and BMD were assessed before and after the study period. Estimates of bone loss and the incidence of fractures among untreated patients were obtained from a reference group of 15 prospectively recruited patients who received renal transplants within the same period as the intervention groups. Results: At one year, the BMD at the lumbar spine had increased from -2.3 to -0.5 in the alfacalcidol group and from -2.3 to -1.0 in the calcitonin group while it was decrease from -2.2 to -2.5 in the reference group. Incidence of vertebral fractures did not diﬀer significantly among the groups (13.3 percent in the calcitriol group, 6.7 percent in the calcitonin and the reference groups). Serum intact parathyroid hormone level decreased significantly in the alfacalcidol group compared with the calcitonin group (P = 0.042). Apart from transient hypercalcemia in 1 patient in the alfacalcidol group, no other significant adverse eﬀects were noted. Conclusion: This study suggested the value of alfacalcidol and calcitonin agents in the treatment of osteopenia and osteoporosis in young renal transplant recipients. These therapies were safe, tolerable, simple to administer and potentially applicable to other renal transplant patients.

x-ray radiogrammetry (Pronosco X-posure System Version 2) to estimate bone mineral density (DXR-BMD). Confirmation of osteoporosis by DXR-BMD was obtained in 28 cases. Idiopathic osteoporosis was diagnosed in 21 cases. From them 12 were treated with ALN 10 mg/day or 70 mg/week for 3 years. The changes in BMD under treatment were appraised every 12 months. Biochemical screening included renal and liver function, protein electrophoresis, PTH, TSH, testosterone measurements, glucocorticoids and alcohol consumption. Results: Age of patients ranged from 26 to 79 years (mean 58.9 years). At start of treatment the mean BMD was 0.3150.02 g/cm2 representing a mean T-score of -2.890.30. After a year of ALN, BMD increased at 0.3210.02 g/cm2(+1.8%); after 2 years at 0.3250.02 g/cm2 (+3.2%), and after 3 years 0.3270.02 g/cm2(+3.8%) representing a mean T-score of -2.780.30. In the control group (6 men) the BMD at start was 0.3390.02 g/cm2 and after 3 years 0.3390.02 g/cm2, a decrease of 1.8%. Conclusion: In our study of male patients with idiopathic osteoporosis the ALN treatment increased BMD by 3.8% after 3 years and suggested clinical benefits in male patients. DXR-BMD, largely used by us in diagnosis and follow up of therapy in osteoporosis, is a good method in clinical practice.

P474MO. THE ETHICS OF GENERICS: MEDICAL AND ECONOMIC ADVANTAGES OF A GENERIC ALENDRONATE IN TREATING OSTEOPOROSIS PATIENTS

P476SU. THE EFFECTS OF ANGELICA SINENSIS OIL ON SERUM ESTRADIOL AND OTHER BIOCHEMICAL ITEMS IN OSTEOPOROSIS RATS

Halperin M; Teva Pharmaceutical Industries, Israel

Liu Z1,2, Li C1, Li G1, Li M2, G Y2, Liu K1; 1School of Pharmacy, Yantai University, 2Shandong Engineering Research Center for Natural Drugs, Yantai, Shandong Province, China

Since Hippocrates (460–377 B.C.) first formulated the basic ethical precept ’’First, Do no harm’’, there have been ongoing additions to the ethical imperatives. In 2001, the American Medical Association adopted a 9 points Code of Ethics, containing the following imperatives: A physician shall, while caring for a patient, regard responsibility to the patient as paramount. A physician shall support access to medical care for all people. (AMA’s House of Delegates June 17, 2001.) Cost containment in the health system is a high priority for governments all over the world. In Israel, it is implemented by a strict policy of reimbursement for medications. This puts limitations on the use of Alendronate, which is reimbursed, according to the Government Health Basket, for patients with a T-Score of < 2.5 standard deviations or an existing fracture. A generic Alendronate has been approved by the Israeli Ministry of Health based on Bioequivalence Studies. Since 2001, hundreds of thousands of packs have been marketed with an excellent eﬃcacy and safety profile. The cost reduction of the generic product compared to the innovative drug is about 60%. We postulate that a wide adoption of generic Alendronate by doctors and patients will lessen the need for cost containement in the osteoporosis segment and lead to the widening of reimbursement indications, thus aﬀording access to medical care to all osteoporosis patients according to the ethical imperative of the medical profession.

P475SA. ALENDRONATE TREATMENT IN IDIOPATHIC OSTEOPOROSIS IN MEN: DIAGNOSIS AND FOLLOW UP BY DIGITAL X-RAY RADIOGRAMMETRY Galesanu C1, Ciubotariu C2, Galesanu RG2, Melnic G2; 1University of Medicine and Pharmacy, Department of Endocrinology, 2 Center of Radiology and Imaging Diagnosis, Iasi, Romania Aims: Osteoporosis is an increasingly disorder in men associated with fractures and significant morbidity and mortality. The pathogenesis of bone loss in men remains unexplained; 40% of disease is classified as idiopathic. To reduce male osteoporotic fracture burden, diagnosis of asymptomatic state by BMD is constrainted, but are not consensus in densitometric definition of male osteoporosis. The aim of the study was to assess the eﬀectiveness of alendronate (ALN) therapy in idiopathic male osteoporosis. Materials and Methods: We evaluated 12 male with osteoporosis according to the WHO criteria for osteoporosis in postmenopausal women. Between 2001–2005 a total 156 healthy men referred to our bone densitometry department where we use digital

Aims: To study the eﬀects of Angelica sinensis oil on serum biochemistry items in osteoporosis rats. Methods: 60 SD rats were randomly divided into 6 groups, which included control group (CON), model group (MOD), high dose group (HDG; 80 mg/day/kg body weight of Angelica sinensis oil), middle dose group (MDG; 40 mg/day/kg body weight of Angelica sinensis oil), low dose group (LDG; 20 mg/day/kg body weight of Angelica sinensis oil), and positive drug control group (PCON; Long mu zhuang gu granule, 5 g/kg). After 3 months of ovariectomy, the osteoporosis rat model was prepared. Then the rats were administered Angelica sinensis oil by ig once daily for 3 months. After 12 hours of the last drug administration, serum bone alkaline phosphotase(BALP), estradiol(E2), osteocalcin (BGP)and parathyroid hormone(PTH) were measured by electric radiation immunologic method. Results: The serum level of E2 increased markedly in HDG, MDG, and LDG (P < 0.05). The serum level of BGP and BALP only increased in HDG (P < 0.05). The serum level of PTH decreased significantly in HDG and MDG(P < 0.05). Conclusions: Those results indicated that Angelica sinensis oil might be used to treat osteoporosis, especially the menopause osteoporosis.

P477MO. PAMIDRONATE IN OSTEOPOROSIS TREATMENT Sousa M, Simões ME, Ribeiro JS, Cortes S, Figueiredo R, Barcelos F, Santos HC, Coelho P; Rheumatology Portuguese Institut, Lisboa, Portugal Introduction: There are studies referring to the use of Pamidronate in patients intolerant or non-responders to other anti-reabsorptive therapies. Objective: To test the eﬃcacy of intravenous Pamidronate in increasing BMD and preventing new osteoporotic fractures in a group of patients with established osteoporosis. Methods: We included, prospectively, patients with osteoporosis non-responders or intolerant to oral biphosphonates. Pamidronate was administered intravenously (30 mg, each three months). The participants were evaluated at the beginning of the study and each year with thoracic and lumbar x-ray, lumbar and hip DXA and we registered occurrence of clinical and radiological fractures. A complete analytical study was performed each three months (including PTH, osteocalcin and urinary NTX). Results: We included 74 patients: 53 with postmenopausal osteoporosis, 10 with rheumatoid arthritis and 3 with ankylosing

S264 spondylitis. The radiological and clinical evaluation of fractures at the end of 12 months was only carried out in 17 patients. In 9 patients there were no new fractures. In 2 patients without new fractures we found a 10% increase in the height of a vertebral body. We discovered the occurrence of new fractures in 8 patients: 1 new fracture in two cases; 2 new fractures in three cases and 3 new fractures in two cases. We also found a significant increase in BMD at L1-L4 bettween 0 and 12 months (p=0.01), and observed a significant reduction of urinary NTX between 0 and 6 months (p=0.046). The reported adverse eﬀects were vitreous dislocation in one patient, muscle cramps (5.4%) and bone pain (2.7%). Discussion: We carried out an uncontrolled longitudinal study in patients with a very high risk of fracture (elder patients, low BMD, multiple vertebral fractures). We also demonstrated therapeutic eﬃcacy in increasing BMD at the end of 12 months. We found a significant decrease at the levels of one marker of bone reabsorption (urinary NTX). These results suggest that this therapy could be a valid option in patients with osteoporosis intolerant or non-responders to oral biphosphonates.

P478SA. AN OVERVIEW OF OSTEOPOROSIS TREATMENT AND COMPLIANCE IN A PUBLIC HOSPITAL IN RIO DE JANEIRO 1,2

1

1,2

2

Rocha FBS , Silva RO , Russo LAT , Gregorio LH , Lacativa PGS2, Melazzi AC2, Oliveira FV1, Pinheiro RAC1,2, Argentina D2, Dornellas M2; 1Hospital Pro Matre, 2Center for Clinical and Basuc Research – CCBR Brasil, Rio de Janeiro, Brazil Osteoporosis is a chronic and progressive disease, very common nowadays, especially in postmenopausal women. Aim: Evaluate the frequency of osteoporosis in postmenopausal women in a reference center and analyse the compliance of diﬀerent kinds of treatments. Methods: Cross-sectional, descriptive study, 915 women were submitted to a bone density test (DXA), using a Hologic 4500 densitometer for 7 months. Diagnosis was based on the region with lowest T-score (WHO). Distribution of frequency by age, diagnosis and treatment were evaluated using Chi-square test. To compare proportions between diagnosis and treatment the Z-test was used. Results: Average age was 63.59.4 years. 39.43% had osteoporosis and 46.92% had osteopenia. Among the osteopenia group, 55.1% were using some pharmacology therapy. In the osteoporosis group, 49.6% were under treatment, 78.1% with alendronate (weekly), 7.6% with raloxifene and 3.2% with hormonal therapy. All patients evaluated were asked about dificulties of treatment: 89.31% pointed to the cost as the major problem, followed by the duration of treatment. Conclusion: The authors believe that although DXA is an available test in our public health system, only a small part of the population is under an adequate treatment probably because of the costs of treatment.

P479SU. PRELIMINARY RESULTS FROM THE USE OF TERIPARATIDE IN PATIENTS WITH ESTABLISHED OSTOPOROSIS Sokorelos SM, Tiliakos TM, Tsibidakis TH, Nikolaou NH, Dimitriadis DM, Dimitrakopoulos DV; Department of Orthopaedics, General Hospital, Rhodes, Greece Aim: The aim of this study is to present the preliminary results of treatment with teriparatide in elderly patients with established osteoporosis. Patients and Methods: During the last 2 years we administered teriparatide to 46 patients (40F, 6M) with mean age 75 years R(65–80). The indication for teriparatide administration was established senile osteoporosis as documented by DXA. At initial evaluation of osteoporosis using this method, mean measurement of loss of bone density was 25% R(19–28) before commencement of therapy. T-score L3 was 3.7 R(3.2–4.2), Z-score L3 2.6 R(1.9–2.6). All patients were submitted to a complete laboratory, biochemical and radiological investigation including complete blood picture, serum calcium, 24 hour urinary calcium,

thyroid function tests (T3, T4, TSH), phosphate, magnesium, calcitonin, and x-rays of pelvis, hips and lumbar spine to confirm the presence of osteoporotic fractures. The duration of treatment was 18 months with concurrent administration of calcium and vitamin D3. Two patients dropped out of the study because of failure to comply and one patient died of other causes. Results: Repeated assessment of bone density with DXA and laboratory investigations at the end of this treatment period revealed a significant increase in bone mass and a definite improvement in biochemical parameters in all patients. 12 months after initiation of therapy, mean loss of bone density was 19% (R17– 24%), T-score L3 3.4 (R3.2–3.9), Z-score L3 1.6 (R1.4–2.0). At the end of therapy (18 months duration) mean loss of bone density was 8%(R7.14) T-score L3 3.2(R3.9–2.5), Z-score L3 1.3(R1.1–1.4). We believe that the overall results are impressive on the basis of the data to date. Conclusion: The use of teriparatide in patients with established osteoporosis appears to be promising in the future treatment and management of this condition resulting in a possible reduction in the risk of fracture, reduction of pain and improvement in the quality of life in elderly people.

P480MO. PERSISTENCE OF WEEKLY ADMINISTERED ALENDRONATE IN CROATIA Grazio S1, Curkovic B2, Babic-Naglic D2, Kehler T3, Jajic Z1, Nemcic T1, Grubisic F1, Peric P2; 1Department of Rheumatology, Physical Medicine and Rehabilitation, Sisters of Mercy University Hospital, Zagreb, Croatia, 2Department of Rheumatology and Rehabilitation, University Clinical Center, Zagreb, Croatia, 3Department of Rheumatology, Thalassotherapia Hospital, Opatija, Croatia Aim: To discover what is the persistence of weekly administered alendronate in patients with a recorded diagnosis of osteoporosis (according to the WHO criteria) in Croatia. Patients and methods: The data on the persistence (missed tablets of ALN 70/week) regarding last month and last year were collected in 100 consecutive patients (6 men, 94 women), of mean age 67.25 7.89 years, who came to the three outpatient clinics of the departments of rheumatology in Croatia. Descriptive statistics and non-parametric tests were used to analyze the results. Results: The diagnosis of osteoporosis was established 3.21 1.83 years ago. Co-morbidity mostly included hypertension (n=38) and rheumatoid arthritis (n=35). Eighty-one percent of patients had co-therapy ranging from 1–7 diﬀerent drugs taken every day. Only 2 patients missed 1–2 tablets of ALN 70 last month. During the previous year 86 patients did not miss any tablets, whereas among the remaining patients 2 of them missed 1 tablet, 5 missed 2 tablets, 3 patients missed 3 tablets, 2 patients missed 4 tablets, 1 patient missed 12 tablets and 1 patient missed 15 tablets. Cotherapy was associated with more missed tablets of ALN 70 (p=0.044), while the occurrence or number of fractures (spine, hip, other) were not associated with persistence. Antiresorptive therapy has been reimbursed in Croatia for patients with established osteoporosis, therefore it could not have influenced the results. Conclusions: In Croatia, patients with osteoporosis have better persistence with weekly administered alendronate than the persistence recorded in other countries. Co-medication was associated with poorer persistence.

P481SA. CT-GUIDED VERTEBRO- AND KYPHOPLASTY: COMPARING TECHNICAL SUCCESS- AND COMPLICATION RATE IN 116 CASES Weber C H1, Kroetz M1, Hoﬀmann R T1, Euler E2, Heining S2, Pfeifer K J1, Reiser M1, Linsenmaier U1; 1Institute of Clinical Radiology, 2Dept. of Surgery – Trauma and Orthopedic Surgery, LMU Munich, Munich, Germany Purpose: To compare technical success and complication rate in CT-guided vertebro- and kyphoplasty Materials and Methods: From 2002–2005 we treated 80 patients (116 vertebrae) with vertebroplasty (n=97) or kyphoplasty (n=19) using 4-slice MSCT with CT-fluoroscopy as the only guidance for

S265 the procedure. The underlying lesions were osteoporotic fractures in 91 vertebral bodies and 25 vertebral metastases. Results: We achieved technical success in all 116 procedures. Post-interventional CT demonstrated asymptomatic minor cement leakage in 57/116 (49.1%) vertebrae. Kyphoplasty resulted in leakage in 11/19 (57.9%) and vertebroplasty in 46/97 (47.4%) procedures. With p = 0.48 (Mann-Whitney Test) we found no significant diﬀerence between kyphoplasty and vertebroplasty concerning the incidence of cement leakage. There was one minor complication of an L5 root irritation following radiofrequency ablation and vertebroplasty of a sarcoma metastasis which subsided without treatment after 8 weeks. There was one major complication of intraspinal cement leakage during tumour vertebroplasty causing T5 root compression and requiring laminectomy for cement removal. The overall rate of major complications requiring treatment was 0.86%. Conclusion: Vertebro- and kyphoplasty can be safely performed under MSCT-fluoroscopy guidance. The rate of major complications is very low. We saw a high rate of small asymptomatic cement leakages which may likely have remained undetected with conventional fluoroscopy (CF). There was no statistically significant advantage for kyphoplasty concerning cement leakage and technical success rate.

P482SU. ADDRESSSING THE OSTEOPOROSIS TREATMENT CARE GAP IN OUTPATIENTS SUFFERING A FRAGILITY FRACTURE Juby AG1, Bayne P2, Yuksel N3, Hanley D4, Kline G4, Wirzba B2, Hagen S2, Letourneau S5, Shemanchuk C5; 1University of Alberta, Department of Medicine, Division of Geriatrics, Edmonton, Canada, 2Womens Wellness Program, Menopause and Osteoporosis Clinics, Grey Nuns Community Hospital, Edmonton, 3University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, 4University of Calgary, Department of Medicine and Oncology, Division of Endocrinology and Metabolism, Calgary, 5 Capital Health Link, Capital Health Authority, Edmonton, Alberta, Canada Aim: To enhance identification of fracture patients at risk for osteoporosis. Method: In Edmonton, Alberta, Canada a 24 hour consumer telephone information service (Capital Healthlink) provides an opportunity for an innovative, low-cost opportunity for targeted follow up and screening of all patients, over 50 years, with an ICD code indicating fracture. In this study, the usual call-in service for clients with health questions has been modified to provide call-out screening and education about osteoporosis by registered nurses. All patients presenting to an emergency room or cast clinic were identified electronically by ICD code and followed up by telephone by a Healthlink nurse within eight weeks of their fracture. Additional follow up calls were scheduled for three, six and twelve months post initial call. Wrist fractures were excluded for the first three months of the study as another intervention was occurring for these patients. In those identified as having a fragility fracture, the patient received telephone education and a mail out package of information about osteoporosis and the patient’s physician was sent a letter which included an osteoporosis assessment and treatment algorithm. Results: The initial screening telephone call took up to 20 minutes per patient, including evaluation and education. Initial data for a 5 month period, identified 408 out-patient fractures. 46% patients were unable to be contacted (over 4 consecutive attempts). Of the 222 contacted, 47% had suﬀered a fragility fracture (74 women and 31 men), with 42% in the 56–70 year age range. The majority were secondary to falls (83%). 47% of these had a pre-existing diagnosis of osteoporosis. 55% were taking calcium supplements and 45% supplemental vitamin D (dosages were not evaluated). 61% of the fragility fracture group were not on any anti-resorptive therapy. Conclusions: Use of an existing 24 hour Healthlink telephone service allowed further evaluation of fracture patients. It was able to identify those in whom the fracture was a fragility fracture and so are at risk for osteoporosis. Patient education and physician information was also provided. Follow-up evaluation will establish

whether this resulted in appropriate investigation and treatment for osteoporosis.

P483MO. A NOVEL METHODOLOGY TO IMPROVE DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS USING AN EXISTING TELEPHONE HEALTH INFORMATION SERVICE Juby AG1, Bayne P2, Yuksel N3, Hanley D4, Kline G4, Wirzba B2, Hagen S2, Letourneau S5, Shemanchuk C5; 1University of Alberta, Department of Medicine, Division of Geriatrics, Edmonton, Canada, 2Womens Wellness Program, Menopause and Osteoporosis Clinics, Grey Nuns Community Hospital, Edmonton, 3University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, 4University of Calgary, Department of Medicine and Oncology, Division of Endocrinology and Metabolism, Calgary, 5 Capital Health Link, Capital Health Authority, Edmonton, Alberta, Canada Aim: Use of a novel methodology to improve the diagnosis and treatment of osteoporosis with an existing telephone Health Information Service. Method: Capturing patients with a fragility fracture for screening for osteoporosis is particularly challenging. Studies consistently report diagnosis and treatment rates well below 50%, whether in-patient treatment is required or not. The opportunity for osteoporosis identification and treatment is also influenced by the geographical location of the treatment facility. Presently, fewer than 30% of patients receive assessment for osteoporosis postfracture and less than 15% receive treatment. In Edmonton, Canada, an innovative fracture intervention project is underway that uses existing health system infrastructure and technology to deliver sustainable and cost-eﬀective follow up of patients (over 50 years) who present to a hospital emergency room or cast clinic with a fracture. Using the existing consumer telephone information service (Capital Healthlink) and electronic health record system, fracture patients are identified and then phoned by a registered nurse to determine if the fracture might be attributable to osteoporosis. If so, the patient receives immediate education and advice. In addition the patient’s physician receives a letter which includes an osteoporosis assessment and treatment algorithm. Information is gathered as to fracture cause, pre-existing osteoporosis diagnosis, bone mineral density evaluation, and current medical therapy. Patients are called again at 3, 6 and 12 months to ensure recommended assessment has occurred. Results: Project commencement was June 2005. To date, 408 patients have been identified of whom 242 are women and 166 are men. The age range is 50–96 years with 25% being in the 56–65 age range. The initial telephone evaluation took a maximum of 20 minutes. Four contact attempts were made over 2 days, but 46% could not be contacted. Of the 222 contacted, 47% had had fragility fractures. Conclusions: This model is noteworthy in that: it utilizes a telephone advice service in a new way, to do call-out for the purposes of health screening for chronic disease; it is cost-eﬀective, delivering screening and education to the highest risk patients and their physicians through existing health service delivery technologies; and it is readily transferable.

P484SA. PROSPECTIVE STUDY OF 4 YEARS CONTINUOUS TREATMENT WITH RISEDRONATE AND ITS EFFECT ON BONE MARKERS AND QUALITY OF LIFE OF POSTMENOPAUSAL WOMEN Koulouris I, Skarantavos Gr, Anadiotis L, Koulouris G; Orthopaedics, 1st Ika Egaleo, Reumatology, Attikon University Hospital, Biochemistry Lab, Evangelismos Hospital, Psychiatry, Aeginition University Hospital, Athens, Greece Objectives: Eﬀect of daily administration of risedronate to early postmenopausal women for 48 months by measuring serum CTX changes, urine Crosslaps, urine Pyrilinks, serum osteocalcin and 25(OH)D and by assessing their quality of life. Methods: 40 early postmenopausal women 48–53 yrs old (mean 50), 6 mo-1yr after menopause,with T-score%2SD on lumbar spine DXA, without any prior metabolic disorders or fractures

S266 were separated into 2 groups: Group A (n=30) received 5 mg risedronate,1 µg alphacalcidol and 1000 mg calcium carbonate daily for 12 mo and alphacalcidol and calcium for the rest of the study period, while Group B (n=10) received the same doses of alphacalcidol and calcium for the first 12 mo and only calcium thereafter. Serum and urine bone turnover markers were measured at 0, 6, 12, 24, 26, 48 mo intervals. A questionnaire by Roberto KA, Zimmermann and Cook as well as VAS score and PPI score concerning mood swings, pain, anxiety, fear of falling and fracture, loss of role and isolation was completed and reevaluated at the above intervals by all patients. Results: Group A showed a statistically important decrease in sCTX, Pyrilinks D, urine crosslaps. In Group B sCTX was increased while the rest of the markers showed a statistically important decrease as well. A statistically important improvement (70.2% vs 29.8%) in quality of life scores was observed favoring Group A. Conclusions: Changes in the measured markers demonstrate that risedronate eﬀectively decreases them as early as 6 mo after treatment and the eﬀect is maintained until the end of 48 mo without any values falling bellow normal which would imply the presence of frozen bone. Patients receiving the drug showed an improvement compared to controls as far as fear of falling, insecurity, restriction of mobility and alteration of their role in the family and society are concerned.

P485SU. THE EFFECTS OF COUMESTROL ON NEONATAL AND ADULT MICE OSTEOBLASTS ACTIVITIES Sun Js1, Li Yy2, Liu Mh2, Chen Lt3, Sheu Sy1; 1National YangMing University, 2Taipei Medical University, 3Healthbanks Biotechnology Corporation Ltd, Taipei, Taiwan, ROC Estrogen replacement therapy has been shown to reduce postmenopausal osteoporosis. In the present study, we examined the eﬀects of phytoestrogens: coumestrol on neonatal and adult osteoblasts metabolism. The neonatal mice calvaria oseoblasts and the adult mice long bone osteoblasts cell cultures were used in this study. The eﬀects of coumetrol on the cellular activities were analyzed by the MTT (Tetrazolium) assay, the secretion of alkaline phosphatase (ALP) and intracellular calcium content and the expression of bone matrix protein, estrogen receptors and osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL). The results showed that the proliferation of neonatal mice osteoblast cells was enhanced by treatment of coumestrol. In the presence of 10–9 M coumestrol, the osteoblasts counts attained 139.5% of the control and that the coumestrol can increase the intracellular Ca and P contents. Type I collagen gene expression up-regulated 167% at the 1st day’s culture; ALP gene expression upregulated 360% at the 7th day’s culture; while the osteocalcin gene expression upregulated 222% at the 14th day’s culture. When adult mice osteoblasts were cultured in the presence of 10–9 M coumestrol, the osteoblasts population increased significantly earlier and attained its maximal eﬀect at the 21st day’s culture with 207.4% of control group. The content of ER-; and osteoprotegerin secretion by neonatal mice control cells gradually increased during osteoblasts diﬀerentiation, whereas the ER-; and OPGL content decreased in this study. But, the cellular responses to the estradiol and counmestrol were quite diﬀerent in the neonatal or adult mice origin of osteoblasts.

P486MO. ONE YEAR RESULTS: VERTEBROPLASTY AND KYPHOPLASTY IN OSTEOPOROTIC FRACTURES OF VERTEBRAL BODIES Pflugmacher R, Schleicher P, K.-Klostermann C; Universitätsmedizin Berlin, Centrum für Muskuloskeletale Chirurgie, Charité, Germany Objectives: Kyphoplasty and vertebroplasty oﬀer two minimal invasive operative stabilisation procedures for vertebral compression fractures. The purpose of this prospective study was to investigate whether both procedures are able to reduce pain and to preserve postoperative vertebral height during a 1-year follow up.

Study methods: Osteoporotic vertebral fractures were treated in 42 cases, 20 patients (15 female, 5 male) underwent vertebroplasty, 22 patients (14 female, 8 male) underwent kyphoplasty. 32 vertebral fractures were treated with vertebroplasty and 35 vertebral fractures were treated with kyphoplasty. Symptomatic levels were identified by correlating the clinical presentation with conventional radiographs, CT or / and MRI. During the follow up reduction of pain was determined. Radiographic scans were performed pre- and postoperatively and after 3, 6 and 12 months. The vertebral height and endplate angles were measured to assess the restoration of the sagittal alignment. The eﬀects on pain symptoms were measured on a self-reported Visual Analog Scale (VAS) and the Oswestry score was documented. Results: The median pain scores (VAS) decreased for kyphoplasty and vertebroplasty from pre- to post-treatment significantly as well as the Oswestry score (p < 0.05). No significant diﬀerences could be found between both groups for the median pain score (VAS) and the Oswestry score. Kyphoplsty led to a significant restoration of the vertebral height and reduction of kyphosis (p < 0.05). During the 1 year follow-up both operation techniques were able to stabilize the height of the vertebral body. Conclusion: Kyphoplasty and vertebroplasty are eﬀective minimal invasive procedures for the stabilization of osteoporotic vertebral fractures leading to a statistically significant reduction of pain. Kyphoplasty restores significantly vertebral body height in fresh fractures. The restoration of vertebral height and reduction of kyphosis may have an influence on the long term clinical outcome. This has to be evaluated in a long term prospective study.

P487SA. PREVENTION OF OSTEOPOROSIS IN PATIENTS ON LONG TERM LEVOTHYROXINE TREATMENT Giorgadze E, Chachibaia V, Tsagareli M, Mirianashvili K, Asatiani K, Bochorishvili K, Korinteli M; N4 Clinical Hospital, Department of Endocrine Disorders, Tbilisi, Georgia Objective: The aim of our study was to determine the protective eﬀect of calcium carbonate, vitamin D3 and ossein -hydroxyapatite compound on bone mass in patients on Levothyroxine therapy. Materials and methods: We studied 127 patients (83 males, 44 females) with hypothyreosis on hormone replacement with Levothyroxine (mean duration of treatment was 7 years). We measured ionized calcium, phosphorus values, thyrotropin (TSH), free thyroxine (FT4), parathyroid hormone (PTH), osteocalcin (OC), bone mineral density (BMD) with ultrasound bone densitometry. Results: The mean value of BMD was -1.9 0.12, Ca++ values were at the lower level of the norm (1.09 0.01 mmol/l), PTH and OC were within the normal range but at the upper level of the norm (52.4 0.01 pg/ml and 23.7 0.21 ng/ml, respectively). In order to prevent osteoporosis, all patients received calcium carbonate 500–1000 mg and vitamin D3 at 400 IU daily. In patients with lower levels of BMD, ossein-hydroxyapatite compound was also administered. After two years from the initiating treatment, Ca++ value increased to 1.25 0.12 mmol/l. We found a decrease of BMD (-1.4 0.05), but the change was not significant. Significant changes in PTH and OC values were not observed (47.2 0.15 and 21.6 0.02 ng/ml, respectively). Conclusions: (1) Maintaining bone mass in patients on Levothyroxine treatment deserves special attention. (2) Administration of calcium, vitamin D3 and osseinhydroxyapatite compound prevents bone loss in these patients.

P488SU. ADMINISTRATION OF CALCIUM, VITAMIN D3 AND OSSEINHYDROXYAPATITE COMPOUND IN COMBINATION WITH HORMONE REPLACEMENT THERAPY IN POSTMENOPAUSAL PATIENTS Giorgadze E, Chachibaia V, Tsagareli M, Asatiani K, Jikurauli N, Tsagareli N, Svani N, Doliashvili T; N4 Clinical Hospital, Department of Endocrine Disorders, Tbilisi, Georgia

S267 Objective: The aim of our study was to detect the prevalence of osteopenia and osteoporosis in postmenopausal patients on hormone replacement therapy (HRT) and determine the eﬀectiveness of calcium carbonate, vitaminD3 and ossein-hydroxiapatite compound in combination with HRT on the development of osteoporosis. Subjects and Methods: We investigated 110 postmenopausal women on HRT. We measured ionized calcium (Ca) and phosphorus (P) values, detected osteocalcin (OC) and parathyroid hormone (PTH), investigated bone mineral density (BMD) by ultrasound bone densitometry. Results: 78 from the whole number of patients have revealed osteopenia, the mean value of T-score by ultrasound bone densitometry was -2.2 0.01, mean value of ionized Ca was 1.07 0.1 mmol/l. PTH and OC were within the normal range but at the upper level of the norm (54.1 0.1 pg/ml and 24.8 0.01 ng/ml, respectively). In order to prevent osteoporosis all patients received calcium carbonate 500 -1000 mg, vitamin D3 at 400 IU daily and osseinhydroxyapatite compound. After a year from initiating treatment, we detected an insignificant increase of BMD (-1.8 0.01), Ca++ value was increased to 1.26 0.12 mmol/l. Significant changes in PTH and OC values were not observed. Conclusions: (1) Women on hormone replacement therapy need an additional treatment for maintaining bone mass. (2) Calcium carbonate, vitamin D3 and osseinhydroxyapatite compound in combination with HRT are eﬀective for prevention of osteoporosis in postmenopausal women.

P489MO. TWO YEARS EXPERIENCE WITH THE CLINICAL USE OF BALLOON KYPHOPLASTY Schulz JU; Katholische Kliniken Oberberg, St. Josef Krankenhaus, Dept. of Orthopaedics, Engelskirchen, Germany The most frequently occurring vertebral fractures are osteoporotic of origin and mainly occur in older patients. Conventional management of vertebral fractures, consisting of pain medication and immobilization represents a serious socioeconomic burden. Balloon kyphoplasty is a minimally invasive percutaneous technique for the management of vertebral body fractures, allowing stabilization of the vertebral body but also partly correcting the loss of vertebral height and kyphotic angle. Inflation of balloon tamps in the vertebral body will create a void. This allows for use of viscous cement and low pressure deposition of cement, adding to the safety of the technique. It has been documented in the literature that the patient will experience immediate pain relief and the majority of patients can be mobilized the same day of the intervention. Balloon kyphoplasty can be performed under short general anesthesia, which makes it suitable for older patients. In our clinic we selected balloon kyphoplasty for the management of vertebral body fractures and treated since May 2004 over 70 patients. The majority suﬀered osteoporotic fractures between T6 and L5, also younger patients suﬀering traumatic fractures A1 or A3.1 and patients with benign and malignant infiltration were treated. When treating vertebral body fractures in patients younger than 50 years we used the bioresorbable calcium triphosphate cement. We noted a significant pain reduction, measured with a visual analogue scale (VAS), in all patients. The height of the compressed vertebral body was in many cases considerably restored when compared to prefracture height. In the patient group already evaluated at 2 year follow-up, a maintained pain reduction was noted which resulted in a fast return to normal daily activities. X-ray control showed an insignificant loss of vertebral body height correction at follow-up. In no case subsequent vertebral fractures were detected on x-ray. During the presentation we will provide information on the pathophysiology of osteoporotic vertebral fractures, demonstrate

the balloon kyphoplasty procedure and provide suggestions for patient selection. We will provide statistically analyzed outcome data on our patient population regarding pain reduction, mobilization, vertebral reconstruction, intra-operative complications and follow-up results. Selected cases will be used to illustrate the obtained results.

P490SA. EFFECT OF CIMICIFUGA EXTRACT ON OSTEOPOROSIS IN OVARIECTOMIZED RATS Chunmei LI1, Zhifeng LIU1, Min LI1, Guisheng LI2, Yonglin GAO2, Ke LIU1; 1School of Pharmacy, Yantai University, 2Shandong Engineering Research Center for Natural Drugs, Yantai, Shandong Province, China Aims: To study eﬀects of Cimicifuga extract from Cimicifuga foetida L. on biomechanical characteristics of femur in osteoporosis rats. Methods: Osteoporosis was induced by ovariectomy. After three months, the concentrations of estradiol in serum was measured by electric radiation immunologic method. Bone density and mineral content of femur metaphysis of rats was mesured by Dual-energy X-ray Absorbtionmetry (DXA). Biomechanical characteristics of femur were measured by three point bending test. Results: The bone density and mineral content of femur metaphysis of rats increased remarkably. The resistance of bending and compression of rat femur was enhanced. While there is no eﬀect on the level of estradiol and index of uterus. Conclusion: Cimicifuga extract had antiosteoporotic eﬀects on ovariectomized rats. The Cimicifuga extract exerted estrogenic eﬀects on bone, particularly in osteoblasts, but not in the uterus of ovariectomized rats. The extract appears to contain rat organspecific selective estrogen receptor modulators (SERMs), and if these findings can be approved in humans it may be an alternative to hormone replacement therapy (HRT).

P491SU. THE EFFECTS OF ANGELICA SINENSIS OIL ON BONE HISTOMORPHOLOGY IN OVARIECTOMIZED RATS Liu Z1,2, Li C1, Li G1, Gao Y2, Li M2, Liu K1; 1School of Pharmacy, Yantai University, 2Shandong Engineering Research Center for Natural Drugs, Yantai, Shandong Province, China Aims: To observe the eﬀects of Angelica sinensis on bone histomorphology in ovariectomized rats. Methods: 60 SD rats were randomly divided into 6 groups, which included control group, model group, 3 drug treated groups (the drug doses were 80, 40, 20 mg/day/kg body weight of Angelica sinensis oil, respectively), and positive drug control group (Long mu zhuang gu granule, 5 g/kg). After 3 months of ovariectomy, the rats were administered Angelica sinensis oil by ig once daily for 3 months. After the last administration, all the rats were killed. The 1/3 distal femur sections were taken out, and processed with paraﬃn embedding and fluorescein coloration. The bone histomorphology characters were estimated by Leica Qwin figure analysis system (Germen), which included the percent of total bone trabeculae volume (TBV%), percent of total reabsorbed bone trabeculae surface (TRS%), percent of total bone trabeculae formation surface (TFS%), percent of active fluorescein surface (AFS%), etc. Results: After 3 months of ovariectomy, the TBV% decreased markedly, and the TRS%, TFS% , AFS% increased remarkably in model group. It showed that the osteoporosis model had been succeeded. After the drug treatment for 3 months, the TBV% in all drug treated groups heightened compared to model group, and TRS%, TFS%, AFS% decreased remarkably (P<0.05). Conclusion: The Angelica sinensis oil could modify the attenuation of bone formation in ovariectomized rats.

P492MO. EFFECTS OF 2-YEAR TREATMENT WITH RISEDRONATE IN POSTMENOPAUSAL OSTEOPOROSIS Sendur OF, Gurer G, Aydemir AH, Tastaban E; Department of Physical Medicine and Rehabilitation, Adnan Menderes University Medical Faculty, Aydin, Turkey

S268 Introduction: The risk of bone fractures is higher in elderly people, particularly in postmenopausal women, which is associated with the development of osteoporosis. Aminobisphosphonates provide an eﬀective protection against a decrease in bone mineral density (BMD) in the treatment of osteoporosis. Objective: This study was performed to research the eﬀects of risedronate treatment with 2 years duration in postmenopausal osteoporosis. Methods: Eighty women with postmenopausal osteoporosis were enrolled in this study. Risedronate at one dose of 35 mg weekly was gived to all of the patients. BMD in the lumbar spine and left proximal femur was measured by dual-energy X-ray absorptiometry (DXA) three times at before treatment, first and second year. Results: A significant improvement was found both of the lumbar spine (p<0.001) and femur BMD (p<0.05) at the end of treatment. However, increasing of lumbar spine was more significant than the femur measures with this treatment. In the conclusion, risedronate treatment by 2 years produced a increasing in BMD of the trabecular bone and cortical bone in postmenopausal osteoporosis. Reference 1. Hamdy RC, Chesnut CH 3rd, Gass ML, Holick MF, Leib ES, Lewiecki ME, Maricic M, Watts NB. Review of treatment modalities for postmenopausal osteoporosis. South Med J. 2005 Oct;98(10):1000–14; 1015–7, 1048

P493SA. SIGNIFICANCE OF VITAMIN D IN THE PATHOGENESIS AND MANAGEMENT OF OSTEOPOROSIS Morii H; Osaka City University, Osaka, Japan Vitamin D plays an important role as one of calcium regulating hormones in the pathogenesis of osteoporosis. It is also regarded as one of the essential nutrients to maintain bone health and to prevent osteoporosis. Vitamin D analogs have been developed for the prevention and treatment of bone diseases, especially of osteoporosis. In the 1980s it was proposed that 1,25 dihydroxyvitamin D (1,25D) be decreased in postmenopausal osteoporosis. However, the definite results of 1,25D deficiency have not been obtained in postmenopausal osteoporosis in later studies. Instead it was proposed in the 1990s that serum 25 hydroxyvitamin D (25D) level was shown to have a significantly negative correlation with PTH level. Vitamin D insuﬃciency would be a cause of osteoporosis and vitamin D deficiency a cause of osteomalacia. Similar observations have been reported from various countries including Japan. The eﬀect of vitamin D analogs on postmenopausal osteoporosis have been studied in many countries. However, the results were inconsistent. WHO Scientific Group described that C rank (inconsistent results from randomized controlled trials) was assigned to calcitriol and alfacalcidol from evidence for the eﬃcacy of therapies in osteoporosis (WHO Technical Report #921). Studies conducted in Japan have given positive results probably because low calcium intake and diﬀerent genetic background from Caucasian populations. However, regarding combination therapy and the treatment for glucocorticoid-induced osteoporosis vitamin D analogs have been shown to have additive eﬀects to bisphosphonate or raloxifene treatment. Recently a new vitamin D analog ED-71 has been developed in Japan (Matsumoto T et al. J Clin Endocrinol Metab 90:5031– 5036, 2005). This compound has characteristics that it are eﬀective in increasing BMD up to 3.8% compared with placebo group and decreasing bone resorption and formation markers in vitamin D replete subjects who had been in the range of vitamin D insuﬃcient state and supplemented with plain vitamin D3. While vitamin D abnormalities may have an important role in the pathogenesis of osteoporosis, vitamin D analogs may have potent actions in improving deranged metabolism in osteoporosis.

P494SU. ACTIVE ABSORBABLE ALGAE CALCIUM IS MORE EFFICIENT THAN CALCIUM CARBONATE IN MANAGEMENT OF OSTEOMALACIA Kalra S, Kalra B, Kumar S; Bharti Hospital, Karnal, Haryana, India

This 3 month long prospective, randomized, open label, interventional trial was designed to compare two calcium preparations in patients of osteomalacia patients. 72 patients of biochemically proven osteomalacia were randomized into two groups. Group I was administered 3 capsules of active absorbable algae calcium (AAA calcium)(150 mg elemental calcium each) daily, while group II took 3 tablets of calcium carbonate 1.25 g (500 mg elemental calcium each) daily. Both groups took 0.25 mg calcitriol daily. Clinical and biochemical assessment was done at monthly intervals. Health distress score and social activity/role limitations score (measured by validated scales of Stanford Patient Education Centre) reduced significantly in both groups. Serum calcium rose from 8.29 0.31 to 8.93 0.19 at one, 9.31 0.15 at two and 9.47 0.21 mg% at three months in Group I, while alkaline phosphatase fell from 468.3 162.3 to 313.6 101.1 at one, 273.1 69.13 at two and 241.7 48.8 IU/ml at three months. In Group II, serum calcium rose from 7.78 to 0.31 to 8.16 0.29 at one, 8.46 0.25 at two and 8.95 0.20 mg % at three months. Alkaline phosphatase reduced from 454.8 163.4 to 375.2 105.8 at one month, 326.6 77.8 at two months and 260.8 55.1 IU/ml at 3 months in Group II. The improvement in both parameters was significantly higher in the AAA calcium group at 1 and 2 months and insignificantly higher at three months as compared to Group II. The AAA calcium group experienced no dropouts. Two patients complained of belching. No significant weight gain was reported. The calcium carbonate group experienced weight gain (R3 kg)(7/ 36), belching (5/36) epigastric burning (4/36) and constipation (10/36). Two patients dropped out because of side eﬀects. Active absorbable algae calcium is eﬀective, more eﬃcient, and better tolerated then calcium carbonate in the management of osteomalacia. 450 mg elemental calcium given as AAA calcium showed eﬃcacy equivalent to 1500 mg elemental calcium given as calcium carbonate.

P495MO. PROMOTING OSTEOPOROSIS WELLNESS THROUGH EDUCATION, EXERCISE AND RESOURCES: THE POWER PROGRAM Robertson CD1,2, Izukawa T1,2,3, D’Arpino M1,2, Chu J1, Logan S1,2; 1Baycrest Centre, 2North York Seniors Centre, 3University of Toronto, Toronto, Canada POWER is a program committed to providing older adults with a diagnosis of osteoporosis with the strategies that will empower them to self manage their disease, to make healthy lifestyle choices and to optimize their overall quality of life. The program goal is to provide a multi-site, culturally sensitive core curriculum designed to increase clients’ perceived health status by increasing knowledge of the factors aﬀecting bone density, injury and falls prevention to decrease fracture risk and to improve functional abilities. POWER was developed based on three core components: osteoporosis education including injury prevention, osteoporosis specific exercise information as well as an opportunity to participate in an appropriate exercise program, and nutrition topics including adequate calcium and vitamin D intake and how appropriate amounts of many other nutrients are necessary for bone health. Each component is delivered by a health professional from the fields of nursing, fitness and nutrition respectively. Components are designed with specific content areas complementary to one another and are developed over seven sessions from a general to a more specific individualized focus. As participants rotate through the three components each week, they gain the knowledge, skills and confidence needed to become informed consumers and to advocate for their own health. They become aware of reliable community resources and services that will support the new management strategies that they have learned, including the development of a personal injury and fracture prevention program. POWER participants receive pre and post program knowledge, practice and satisfaction tests to gauge program impact in the short term. Group as well as matched pairs feedback on the program have been very favourable. Resources are needed to implement longer term program evaluation. Participant focus groups have assisted with refining the program.

S269 POWER was developed to meet the unique needs of the older adult with a diagnosis of osteoporosis. Current literature and environmental scanning have clearly indicated the additional need for a program for younger adults emphasizing prevention overall and strategies that can be embraced when bone mineral density is still greater than -2.5 SDs (T-score) below the mean value for young adults.

P496SA. BONE DENSITY CHANGES THREE YEARS AFTER TREATMENT OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN IN ZANJAN: A COMPARISON BETWEEN ALENDRONATE, CALCIUM+VIT D AND ESTROGEN Sharifi FSH1,2, Perse LP2, Falakolaphlaki BF1,2, Jamshidi MJ1,2; 1 Zanjan University of Medical Sciences, 2Vali asr Hospital, Zanjan, Iran Aims: Regarding diﬀerent ways of treatment in osteoporosis and fair knowledge about their eﬃcacy, this study was designed to determine the eﬃcacy of diﬀerent regimens of treatment on bone density of postmenopausal women with osteoporosis in Zanjan from 2001 to 2004. Methods: In this historical cohort study 115 patients who were under treatment for osteoporosis were investigated. Their osteoporosis was diagnosed from 2001 with DXA in a unique center and with the same instrument. The patients were divided into three groups based on their treatment modalities: The first group(n=47) were treated with Calcium (1000 mg/d) plus Vit D (400 IU/d), the second group(n=44) with Alendronate (10 mg/d ) + Calcium + Vit D, and the third group(n=24) received HRT with conjugated estrogen(0.625 mg/d) + medroxy progesterone (5–10 mg/d)in a cyclic method plus Calcium + Vit D with the same dosage. After 18–44 months their densitometries were repeated at the same center and the bone density changes in femoral neck, lumbar spine and forearm were evaluated. Data were analyzed with paired t-test and key-square test. Results: Bone density increased significantly in the second group (Alendronate+Calcium+Vit D) only in lumbar spine (P=0.000). There were no significant changes in femoral neck or forearm density with Alendronate plus Calcium and Vit D. No changes were seen in bone density of the three sites with Calcium+Vit D treatment and with HRT. We had some decreases in hip density in patients were treated with Calcium+Vit D alone. There were no diﬀerence between Calcium+Vit D and HRT+Calcium+Vit D for their eﬃcacy on bone density. Conclusion: The most eﬀective treatment for postmenopausal women with osteoporosis is bisphosphonate plus calcium and vitamin D. This treatment can be eﬀective only in femoral neck density.

P497SU. PULSED SIGNAL THERAPY (PST) FOR THE TREATMENT OF OSTEOPOROSIS: A MULTICENTER INVESTIGATION Markoll R, Da Silva Ferreira DM, Martin H; Institute for Innovative Medicine, Infinomed, Munich, Germany Aim: The concept of bone function regulation by bone’s intrinsic electromechanical properties may be traced back to Fukada and Yasuda (1957) who demonstrated that bone has piezoelectric properties. This was subsequently verified by many others and alternatives, including electromagnetic fields, put forth to resolve some bone-related disorders that were incurable by conventional intervention of orthopaedic surgery. It was noted that as a result of bone’s biopotentials, repair and remodeling processes that normally occur in response to mechanical loading, could be elicited by an electrical stimulus – an exogenously applied electrical current, including PEMF. Methods: Pulsed electromagnetic signals, quasi-rectangular in waveform and varying energy parameters are emitted from a medical device consisting of a magnetic field generator, connected to a ring-shaped coil, or other applicator, by means of an electronic interface producing a pulsed ELF DC magnetic field of 0.28W, with field intensity 5–15G and frequency 1–30Hz. The pulse-modulated signals are non-invasive, but transduced through the aﬀected tissue by direct induction. Biophysically, PST passively

induces a pulsating fluid flow and ionic displacement in the targeted area and surrounding connective tissue, generating a type of ‘‘fluid shear stress’’ over cell membranes. This piezoelectric eﬀect (‘‘streaming potential’’) results in interaction of the pulsating signals with cell membranes and activation of various interconnected signaling pathways. PST thus emulates the innate physiological and mechanical stresses evoked and required in bone formation (mechanotransduction). Results: Over 25 clinical and 5 in vitro studies have confirmed the positive eﬀects of PST in the treatment of musculoskeletal conditions, namely osteoarthritis. In a pilot study, increasing trends in vBMD and an associated decrease in pain was observed in postmenopausal women with osteoporosis (OP), resulting in initiation of a multicenter, post-marketing surveillance investigation. Both DXA measurements and bone-specific markers for resorption (beta-crosslaps) and formation (alkaline phosphatase) are employed to assess the positive eﬀects of PST on BMD and decreased fracture risk. Conclusions: Currently, 17 medical centers in central Europe are actively participating in this investigation. A meta-analysis conducted with data from over 50 patients will assess the eﬀects of PST on BMD, in decreasing pain and in reducing fracture risk.

P498MO. TERIPARATIDE TREATMENT INCREASES BONE MINERAL DENSITY IN PATIENT WITH SPINAL CORD INJURY INDUCED OSTEOPOROSIS: A CASE REPORT Uebelhart B, Rizzoli R; Service of Bone Diseases, Department of Rehabilitation and Geriatrics, Geneva, Switzerland Patients with spinal cord injury are known to develop severe osteoporosis with high prevalence of non-traumatic fractures leading to a marked increase of morbidity . In the acute injury phase, bone resorption is increased and the use of bisphosphonate treatment has been shown to be eﬀective in reducing bone loss. In the chronic phase, bone remodelling as assessed by histomorphometry analysis or biochemical markers is rather low. Teriparatide, a potent bone anabolic agent, could be of interest to stimulate bone formation and to decrease bone fragility and hence to reduce fracture risk. We report the case of a 48-year-old-man suﬀering from a tetraplegia with traumatic fracture of the 5th cervical vertebra since the age 23. He presented a right hip fracture at the age of 47 during a transfer from his chair to a car and a spontaneous right diaphysal femoral fracture, 6 months later. At the time of the first fracture, bone mineral density measurements showed a severe osteoporosis at the hip and radius levels. Before treatment, total alkaline phosphatase value was normal (77IU/L, N:30–125) and d-pyridinoline was slightly increased (19.7nmol/mmol-creatinine, N:8–18) reflection of bone resorption. Teriparatide treatment was clinically well tolerated with a slight increased in albumine-corrected calcemia from 2.15 to 2.31mmol/L (N:2.2–2.6) after one month of treatment. After 7 months of teriparatide and despite no significant diﬀerences in markers of bone remodelling, bone mineral density values increased at all sites: This patient with spinal cord injury of long term duration presents a severe osteoporosis with two recent major long bone fractures. Bone response to teriparatide treatment was rapid and of high magnitude. No new fracture occurred during the 7-month follow-up. Table

Lumbar spine Femoral hip Total hip Total radius

Pre-treatment

7 months duration of Tériparatide

BMD g/cm2

T-score SD

BMD g/cm2

T-score SD

Delta

0.871 0.306 0.330 0.523

-1.5 -4.8 -5.0 -3.2

0.906 0.367 0.422 0.557

-1.2 -4.4 -4.4 -2.5

+4 % +20 % +28 % +6.5 %

S270 Thus teriparatide appears to be eﬃcacious in a patient with severe osteoporosis consecutive to spinal cord injury.

P499SA. THE BENEFITS OF PHYTOESTROGEN (COMBINED RED CLOVER AND BLACK COHOST) IN PRE-AND POSTMENOPAUSAL OSTEOPOROSIS Rachman IA, Susanti M, Patria F, Suhartono DS; Division Reproductive Immunoendocrinology, Dept. of Ob/Gyn, Faculty of Medicine, University of Indonesia/Dr/ Cipto Mangunkusumo, Jakarta, Indonesia Several research centers discontinued the use of estrogen and progesterone as HRT, and some others limited the use of HRT administration for 5–7 years with strict observation. The replacement of HRT with combined SERM and bisphosphonate life remained low. Currently, the benefits of phytoestrogen and several isoflavones are being studied. Two of its isoflavones have constituent formulas that are very similar to 17 estradiol. Isoflavones bind receptor estrogen seven times to receptor estrogen but the aﬃnity to receptor estrogen is 5% and the aﬃnity to receptor is 35%, so that is why phytoestrogen can improve clinical menopausal symptoms. Black cohost contains triterpene glycoside, biochanine A, flavonoid cumifugine, in which cumifugine plays a part in the complaint of vasomotor, bone, and vagina. Red clover contains several isoflavones have proved to eliminate vasomotor complaint and improve bones. Combined red clover and black cohosh and calcium and weight bearing exercise were studied in 312 cases of premenopausal osteopenia-osteoporosis and postmenopausal osteoporosis in one year. Of this figure, three cases (0.96%) were found to have dermatitis allergy, and 309 cases (91.04%) could complete the treatment in one year. After a treatment of 3–4 months, 158 cases of premenopausal osteopeniaosteoporosis showed a decrease in clinical complaint of estrogen deficiency of <1% was still observed in some patients, and interaction between participation of weight bearing exercise made the complaints insignificant. HDL and LDL levels became normal after one-year administration of 56.3%-57.8%. A decrease in clinical complaints of estrogen deficiency was observed in 151 cases of postmenopausal osteoporosis after 4–5 months administration of therapy. After one-year administration of therapy, clinical complaint of estrogen deficiency of 2–11% was still observed, but it did not pose problems to patients who could interact positively in the exercise center. HDL and LDL that reached normal levels were 47.6%-48.6%. Additional, with combined therapy of red clover and black cohoct and calcium and weight bearing, a mean bone density of 2.4–4.9% was found in premenopausal osteoporosis, and 2.3–4.6% in postmenopausal osteoporosis.

following: Ba LS 0.7350.127 g/cm2 and 6 Mo LS 0.7880.120 g/cm2 Ba FN 0.6300.129 g/cm2 and 6 Mo 0.6750.126g/cm2; T-score Ba LS (–3.020.87), 6 Mo T-score (–2.200.85) Ba FN (–2.731.05) and 6 Mo (–1.921.08). Conclusion: Comparing data from baseline to 6 months treatment with teriparatide in postmenopausal women with osteoporosis, there was an increase of bone mineral density at the lumbar spine and femoral neck. At both locations T-scores values at 6 Mo evaluation are criteria for osteopenia instead of osteoporosis as in baseline.

P501MO. CT-GUIDED PERCUTANEOUS VERTEBROPLASTY IN THE THERAPY OF VERTEBRAL COMPRESSION FRACTURES Proschek D1,2, Hochmuth K2, Kurth AA2, Mack MG1, Vogl TJ1; 1 Dep. of Interventional and Diagnostic Radiology, University Hospital, 2Dep. of Orthopaedic Surgery, University Hospital Friedricjsheim, Frankfurt, Germany Purpose: To determine the eﬃcacy and safety of CT-guided percutaneous vertebroplasty in the treatment of vertebral compression fractures. Primary objectives were pain reduction and bone cement leakage during a long-time follow-up in patients with osteoporotic vertebral compression fractures. Materials and Methods: CT-guided percutaneous vertebroplasty was carried out in 61 patients (mean age 71.4 years; range 42–83; female ratio: 73.8%) with vertebral compression fractures. Treatment was carried out as an outpatient procedure. Pain, bone cement leakage and complications were monitored and recorded. Mean follow-up time was 19.8 months (range 3–52). Paired comparison procedures were used for analysis of the results. Results: All patients had a significant reduction of pain. Mean visual-analogue scale (VAS) before treatment was 8.8 points (range 6.5–9.8 points). Mean VAS-score after treatment was significantly reduced to 2.6 points (range 1.5–4.1 points; p<0.01). No clinical or neurological complications were documented. Minor and asymptomatic bone cement leakage was observed in 54% of the cases. Conclusion: Percutaneous vertebroplasty is an eﬃcient and safe interventional procedure, which rapidly improves the mobility and quality of life of patients with vertebral compression fractures. CT-guidance is a reasonable upgrade which reduces the amount of bone cement leakage.

P502SA. ONTARIO OSTEOPOROSIS STRATEGY Jiwa F; Ministry of Health and Long-Term Care, Ontario, Canada

P500SU. BONE MINERAL DENSITY VARIATIONS IN POSTMENOPAUSAL WOMEN TREATED WITH TERIPARATIDE Osório F1, Barata S1, Pauleta J1, Santo S1, Neves J1,2, PereiraCoelho A1,2; 1Obstetrics and Gynecological Department, Santa Maria Hospital, 2Medicine Faculty – University of Lisbon, Lisbon, Portugal Introduction: Teriparatide, a recombinant human parathyroid hormone, is a new alternative for osteoporosis treatment in postmenopausal women with a very low BMD and at high risk for bone fracture, in osteoporotic women with prior fracture, in women who do not tolerate or respond to the standard treatment for osteoporosis. Objective: To assess bone mineral density response regarding teriparatide administration during the first 6 months of treatment. Methods: 15 postmenopausal women with diagnosis of osteoporosis as described by WHO criteria were evaluated. BMD was analysed in lumbar spine (LS) and femoral neck (FN), at baseline (Ba) and 6 months (6Mo) after treatment. The following parameters were collected – age, menarche, menopause, BMI, LSBMD, FN-BMD, respectively T-scores and Z-scores. Data are represented in meansd and comparison had been done with Student’s t-test and significance was considered for p value <0.05. Results: We found the following epidemiological data – age 64.26.85 years, menarche 131.37 years, menopause 49.53.74 years and BMI 18.33.51 kg/m2. Results on BMD were the

The Osteoporosis Strategy is an integrated and comprehensive approach aimed at health promotion and disease management. In February 2005, Ontario’s Ministry of Health and Long-Term Care (MOHLTC) announced a million annual investment to implement the ‘‘Osteoporosis Strategy’’. The goal of the Strategy is to reduce fractures, morbidity, mortality and costs from osteoporosis. The Strategy comprises 5 components: (1) Increase senior’s knowledge of osteoporosis and improve bone health of seniors and school children. (2) Improve the appropriate use and accuracy of bone mineral density (BMD) testing in populations at risk of osteoporosis and fractures, to improve early diagnosis of osteoporosis. (3) Enhance the integration of osteoporosis services across the entire spectrum of care to improve osteoporosis treatment and management across post-fracture care, rehabilitation, complex cases, long term care and selfmanagement. (4) Improve medical professionals’ utilization of clinical practice guidelines through interdisciplinary standards of care, decision aids and other osteoporosis resources. (5) Support mechanisms to drive and sustain the Osteoporosis Strategy including: leadership to ensure that planned outcomes are eﬀectively and eﬃciently achieved; and research and evaluation to increase information about osteoporosis and improve knowledge transfer.

S271 These initiatives are in the early stages of implementation. Performance and outcome measures to determine eﬀectiveness will be shared as the projects evolve.

P503SU. COMBINATION OF CALCITONIN AND STATIN IN A THERAPY OF OSTEOPOROSIS Sokolovic S, Buksa M; University Clinical Center, Sarajevo, Bosnia and Herzegovina Introduction: Salmon calcitonin is a hormone for treatment of postmenopausal osteoporosis and statins are hypolipemic drugs used for lowering cholesterol and its fractions. Animal models and some clinical studies proved statins to be eﬀective in osteoporosis. Aims: The purpose of this study was to investigate whether combination of calcitonin and statin (i.e., simvastatin) are more eﬀective than calcitonin or statin alone in a therapy of postmenopausal osteoporosis. Material and Methods: Open randomized clinical prospective study was designed. Total of 99 patients were included in this study, and 3 groups of subjects with postmenopausal osteoporosis were formed. Group A received Calcitonin 100 IU s.c. every second day plus simvastatin 20mg orally; group B received calcitoin only, while group C received simvastatin alone. Diagnosis of osteoporosis was set by DXA method. Duration od treatment was 1 year with analysis of eﬀectiveness and eventual side eﬀects after 6 months. Results: The results obtained in this study showed that combination therapy with calcitonin and statin is more eﬀective than calcitonin or statin alone with significantly 23% more compared to single therapy. Conclusion: Salmon calcitonin and statins are eﬀective in a therapy of postmenopausal osteoporosis, but in combination are highly eﬀective. This approach of therapy should be administered to patients with moderate to severe osteoporosis.

P504MO. HARPAGOPHYTUM PROCUMBENS (DEVIL’S CLAW): A POSSIBLE NATURAL ANTI-INFLAMMATORY AGENT (AN EXPERIMENTAL STUDY) Younos IH, Afifi MI, Ahmad MI; Clinical Pharmacology Department, Faculty of Medicine, Minufiya University, Shebeen Al Koam, Minufiya, Egypt The aim of this work was to investigate the eﬀect of harpagophytum procumbens on both acute and chronic inflammatory processes in rats and pain responses in mice. Also, safety on gastric and duodenal mucosa is evaluated histopathologically. Eighty rats of both sexes weighing 150–200 grams each and 24 mice of both sexes weighing 25–30 grams each, were used in this work. For a pharmacological study, these animals were classified for induction of the diﬀerent experimental models. The acute model of inflammation includes Carrageenan-induced rat backpaw edema test. The chronic model of inflammation includes Complete Freund’s adjuvant-induced arthritis test and cotton pellet-induced granuloma test. The analgesic model includes writhing test in mice. A biochemical study was done on the Complete Freund’s adjuvant-induced arthritis test group. Blood samples were taken for measuring acute phase proteins: C-reactive protein and serum albumin, and serum cortisol. Histopathological assessment of gastric and duodenal mucosa for the eﬀect of harpagophytum procumbens compared to the eﬀect of indomethacin was done in the Complete Freund’s adjuvant-induced arthritis test group. Carrageenan-induced rat back-paw edema test revealed that devil’s claw pretreatment induced a highly significant reduction in right back-paw thickness, the same eﬀects as indomethacin. Complete Freund’s adjuvant-induced arthritis test in rats revealed that devil’s claw and indomethacin administration caused insignificant eﬀects on serum cortisol, serum albumin and C-reactive protein and caused significant reduction of paw thickness. Cotton pelletinduced granuloma test in rats revealed that devil’s claw and indomethacin intra-peritoneal administration caused a highly significant decrease of cotton pellet weight. Writhing test in mice revealed that devil’s claw and acetyl salicylic acid caused a highly significant reduction in the number of writhing reactions. His-

topathological study results revealed the greater safety of this product on GIT mucosa in comparison to the more injurious eﬀect of indomethacin as a NSAID. It can be concluded that harpagophytum procumbens is a new herbal agent having reasonable anti-inflammatory eﬀect compared to indomethacin, as a standard anti-inflammatory agent and reasonable analgesic eﬀect compared to acetyl salicylic acid, as a standard analgesic agent without harmful eﬀect on gastric and duodenal mucosa.

P505SA. SHORT-TERM RESULTS WITH THE INVERSE DELTA-III PROSTHESIS IN OMARTHROSIS AND MULTIPLE FRAGMENT FRACTURES OF THE PROXIMAL HUMERUS Klein M, Hinkenjann B, Scherger B, Ostermann PAW; Department for Trauma, Reconstructive and Orthopaedic Surgery, St.Agnes-Hospital Bocholt, Germany Introduction: How are the clinical and radiological and short-term results after implanting the inverse Delta-III prosthesis in patients with arthritis and multiple fragment fractures of the proximal humerus? Methods: Between July 1, 2002 and October 30, 2004, 46 Delta-III prostheses were implanted in patients with omarthrosis and multiple fragment fractures of the proximal humerus. 44 patients (30 females, 14 males) with 46 implanted prostheses and a mean age at the time of operation of 73 years (range 53–88) could be followed up after a mean of 13 months (range 6–30). Patients at the time of follow-up were examined and an x-ray was done a.p. and axial. The postoperative functional results were measured by the Constant Score. Results: A high Constant Score with 80,82 points was evaluated. Compared with the results of other typs of shoulder protheses this outcome is high. 6 patients had complications. In one patient a loosening of the prosthesis shaft was found. Here an exchange was done. In 3 patients a dislocation happened. In 1 patient the inlay was changed, in another patient the epiphysial component was enlarged to 9 mm and 1 patient only used a reduction without operation. 3 patients had a soft tissue infection (2 early, 1 late infection). Conclusion: Because of the excellent functional results after implanting a Delta-III prosthesis we conclude that the indication for implanting this type of prosthesis can be enlarged.

P506SU. THE EFFICACY OF COMBINED CHONDROPROTECTIVE TREATMENT IN OSTEOARTHRITIS OF THE KNEE Yatsyshyn RI, Neyko YEM, Yatsyshyn NG; Medical University, Ivano-Frankivsk, Ukraine Objectives: The aim of the study was to evaluate combined chondroprotective treatment in patients with osteoarthritis of the knee. Methods: The study included 75 patients with osteoarthritis of the knee (ACR criteria) with the mean age 631.25 years, disease duration 7.10.82 years, radiological stage I-III (KellgrenLawrence). All patients were randomly divided in 3 groups: First group - 25 patients received Synvisc 2.0 ml intra-articular weekly, Nr. 3; Second group - 25 patients received ’’Artron Complex’’, Unifarm, USA - 2 tablets per os daily, 6 weeks; Third group - 25 patients received a combined treatment: Synvisc 2.0 ml intraarticular, weekly, Nr. 3 + Artron Complex - 2 tablets per os daily, 6 weeks. The treatment duration was 1 year, with courses repeated every 3 months. As evaluation criteria, Lequesne, WOMAC indexes and health assessment questionnaire were used. Biochemical and radiological investigation were performed before the beginning of treatment. Results: The clearest results were observed in the 3rd group: the functional index Lequesne decreased 82% (64% in the 1st group, 56% in the 2nd group), WOMAC index (pain) decreased 91% (69% in the 1st group, 63% in the 2nd group). The quality of life improved 90% in the 3rd group, 71% in group 2 and 65% in group 1. None of the patients from the 3rd group presented radiological

S272 progression of the process (compared to 15% in the 1st group and 23% in group 2). Conclusion: The combined chondroprotective treatment of osteoarthritis of knee was eﬀective, well tolerated and represents a promising trend in the management of osteoarthritis.

P507MO. ROLE OF CALCITRIOL IN PREVENTION OF OSTEOPOROTIC FRACTURE Miskic B1, Cosic V2, Bistrovic D1, Miskic DJ3; 1internal Department, 2Ginecological and Opstetric Department, 3Surgical Department, General Hospital ’’Dr.J.Bencevic’’, Slav.Brod, Croatia We estimated changes of BMD in 455 women who take calcitriol (Rocartrol) 0.5 ug and 1000 mg calcium daily in one group and compared with the other group of 400 women who take only 1000 mg calcium. We observed eﬃciency of this therapy on all fractures during two years period. The average age for all participants was 55 years, who were in 5 to 7 years in postmenopause. All of them had osteopenia based on DXA and normal calcemia and calciuria during this period. Women on Rocartrol and calcium had a significant increase in BMD at the spine OR 4.48 (p < 0.05) at the hip OR 2.13 (p < 0.05) and on the forearm with OR 2.34 (p<0.05). We did not havee fracture during this period, and nobody got osteoporosis on control DXA. Therapy with Rocartrol and calcium is good choice in prevention of fracture in osteopenia.

P508SA. POSTMENOPAUSAL OSTEOPOROSIS PREVENTION WITH PHYTOESRTOGEN BISCUITS Molnár V1, Garai J1,2, Hock M3, Répásy I2, Schmidt E4, Világi SZ2, Zámbó K4, Bódis J2; 1Dept. of Pathophysiology, Medical School, University of Pécs, 2Baranya County Hospital ObstetricsGynecology Dept., 3Dept. of Physiotherapy of Healthcare High school, University of Pécs, 4Central Clinical Radioisotope Lab. of Medical School, Pécs, Hungary Aim: Women at menopause often suﬀer from hot flushes; nevertheless, losing bone mass and cardiovascular problems due to estrogen deficiency are more of a threat to their health. To avoid these consequences, menopausal hormone therapy is often prescribed, but an increasing number of women wish to refrain from hormone use. Our aim was to assess the eﬀect of phytoestrogen dietary intervention and of a specific exercise program on the progression of osteoporosis in a menopausal population. According to the exclusion criteria, 72 participants started the study from the 121 volunteers screened. Of the participants, 56 completed the one year long intervention in the groups. The volunteers were distributed into four groups: control (n=21), diet (n=15), exercise (n=6) and complete (diet and exercise) (n=14) groups. Exercise was performed 3 times for 1 h/wk, with one of these occasions under physiotherapist control. Methods: The daily 60–80 mg phytoestrogen and significant lignan intake were ensured by seedbiscuit consumption. To control the biscuits intake, phytoestrogen serum levels (genistein, daidzein, equol, O-DMA and enterolactone) were monitored by TRFIA (DELFIA) kit of Wallac. Bone density was monitored by DXA. Results: Those who consumed seedcakes have attained highly elevated serum levels of the phytoestrogens monitored, confirming both acceptable compliance and eﬀective absorption, although there is considerable interindividual variation. This variation was especially high in connection with equol, whose estrogenicity is stronger than other phytoestrogens. Concerning bone density, one year follow up is insuﬃcient to draw definite conclusion. No significant diﬀerence between the groups has been detected, however, a tendency toward beneficial eﬀect of the combined intervention is perceived concerning femoral neck density. However, we could see distinction in the bone mineral density between the equol producer and nonproducer patients. The BMD of the hip was found to rise in equol producers. Longer follow-up is needed to

determine whether the eﬀect persists. No serious side eﬀect or injury has occurred during this study. Conclusion: Dietary and exercise intervention might be a useful tool against bone loss especially in the equol producer population.

P509SU. APPLIED BIOMECHANICS IN MOTORIC THERAPY FOR OSTEOPOROTIC PATIENTS Wendlova J; University Hospital and Policlinic, Bratislava, Slovakia Aim: To set up a methodology of motoric therapy based on biomechanical laws of strength and elasticity of osteoporotic skeleton. Methods: We have established the methodology of motoric therapy for osteoporotic patients on the basis of biomechanical analysis of the spinal load by compressive and tensile forces and bending moments. It is based upon: 1) mechanical characteristics of the resistance of biomaterial – bone – against its disruption and permanent deformation; 2) action and reaction forces, the stress intensity developed in the bone during the load and local concentrated stress intensity in the area of osteoporotic vertebral microfractures. Results: The principal axiom in the methodology of motoric therapy is that during the exercise, whether lying down, standing or sitting, the position of the spine is stable and retains its physiological curvature. In the set of exercises we exclude strengthening exercises with weights, dynamic strengthening of one UL with rubber resistance band, jumps and vaults (exercises with transferring compressive force to long bones, vertebrae and joints), stretching dynamic and rapid swinging movements, strengthening dynamic rapid exercises, twisting spinal exercises, forward, side, and back bending. In the set of exercises we prefer slow relaxing, stretching and strengthening exercises, strengthening exercises, symmetrical exercises with both UL, isometric exercises to reinforce the muscular corset of the spine, exercises activating coordination movements in simulated balance disruption. Conclusions: The aim of motoric therapy is as follows: (1) to prevent further bone mass loss and in combination with medicamentous therapy to improve bone quality (biomechanical properties: strength and elasticity); (2) by removing the disbalance of torso musculature to alleviate or abolish pain and so to reduce the costs of medicamentous pain therapy, to achieve a proper posture that eliminates the incorrect mechanical load of osteoporotic vertebrae, preventing their deformations; (3) to improve the coordination of movements in balance disruption (preventing falls).

P510MO. EVALUATION OF QUALITY OF LIFE IN SELF-CARE OF STUMPS SKIN IN JANBAZAN: PERSONS WHO SUFFERED AN INJURY IN IMPOSED IRAN-IRAQ WAR LEADING TO LOWER LIMB AMPUTATION Saeidolzakerin MA; Shaheed Beheshti University, Tehran, Iran This study was conducted as a semi-experimental research in order to examine the eﬀects of home visit in self-care techniques(stump’s skin, prosthesis, and musculoskeletal system) in Janbazan. The subjects were persons who suﬀered an injury in imposed Iran-Iraq war leading to lower limb amputation with lower limb amputation done in Bandar Anzali in 1997. A questionnaire and checklist regarding subject population with stump’s skin, knee flexion angle (with goniometer), femur circumference, femur strength (with dynamometer),BMI and back pain intensity (with numberic visual analog scale) were used before and after home visit as means of data collection. The data were gathered in the first home visit and after 6 visits, each took 40 minutes with 10-day intervals (2 months). The subjects consisted of 25 persons with lower limb amputation who have lived with their families in Bandar Anzali. The findings were analyzed by using descriptive paired t-test and 2 method.

S273 It can be concluded that home visits lead to improvement in the self-care techniques [stump’s skin, prosthesis, and musculoskeletal system (P<0.001)] as well as improvement in physical condition [healing of stump’s skin (P=0.05), (P=0.01), (P<0.001) and musculoskeletal system: increase in femur circumference (P<0.001), increase in femur flexion, abduction and adduction strength (P<0.001), increase in femur extension strength (P=0.001), decrease in BMI (P=0.01) and back pain intensity (p=0.001)].

P511SA. PREDICTION OF FEMORAL HEAD COLLAPSE FOR PATIENTS WITH FEMORAL HEAD NECROSIS USING BONE MINERAL DENSITY AND MAGNETIC RESONANCE IMAGING Ma HZ, Zeng BF; Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China Aims: To explore whether the combination of BMD and MRI could improve the prediction of collapse of the femoral head for patients with femoral head necrosis. Methods: forty-two patients (sixty-two hips) with femoral head necrosis were followed up for an average of sixty-three months (range, forty-five to eighty-four months). Bone mineral density (BMD) was measured for femoral head using dual-energy X-ray absorptiometry (DXA) and coronal and sagittal magnetic resonance imaging (MRI) were taken. Index of necrosis (IN) of the femoral head was determined in the coronal and sagittal images. IN could be calculated by the formula: (A/180)[m|]mf(B/ 180)[m|]mf100 (A is the angle of necrotic area in the mid-coronal image and B is the angle of necrotic area in the mid-sagittal image). BMD was classified into three grades: grade A. >0.6 g/cm2; grade B. 0.45 to 0.6 g/cm2; grade C. <0.45 g/cm2. The IN was also classified into three grades: grade 1. %33; grade 2. 34 to 66; grade 3. 67 to 100. Results: Twenty-two (35 percent) of the sixty-two femoral heads had collapsed by thirty-six months. According to BMD , the survival rate of the femoral heads initially classified as grade A, grade B and grade C was 100 percent (20/20), 63 percent (14/22) and 35 percent (7/20), respectively. According to IN, the survival rate of the femoral heads initially classified as grade 1, grade 2 and grade 3 was 100 percent (15/15), 68 percent (17/22) and 40 percent (10/25), respectively. Combination of the data for BMD and IN showed that, by thirty–six months, collapse had occurred in eighteen (86 percent) of the twenty-one femoral heads in which the BMD initially had been less than 0.45 g/cm2 (grade C) and the IN initially head been more than 33 (grade 2 or grade 3). Conclusions: The combination of BMD and index of necrosis could improve the assessment of the risks for collapse of the femoral head.

TBBMC, intakes of calcium, protein,and potassium (i.e. indicator of V&F) height, and weight in the follow up study, comprised early adulthood data. Factorial analysis of covariance was used for data analysis. Results: In both genders, there was a significant increase in TBBMC, height and weight from peri-adolescence to early adulthood. In males, the intake of calcium from peri-adolescence to early adulthood was sustained, whereas in females, there was a significant decrease (15%, p<0.05). We previously showed V&F was low in peri-adolescence, and that this, as well as calcium, was an important risk factor for TBBMC in boys. However, no significant eﬀect of these dietary factors on TBBMC persisted into early adulthood. There was a significant main eﬀect of gender on TBBMC (p<0.01). Significant covariates were height and weight in young adults (p<0.01). Conclusion: We detected no eﬀect of calcium or of vegetables and fruit intake during peri-adolescence on TBBMC of young adult males or females. Current height and weight in young adults were the significant covariates influencing their TBBMC.

P513MO. ANDROID/GYNOID FAT MASS RATIO MEASURED BY DXA AND THE RISK OF CARDIOVASCULAR DISEASE AMONG OVERWEIGHT POSTMENOPAUSAL WOMEN Ragi-Eis S1, Barros SA2, Machado RR1, Moana EJ1, Albergaria BH1, Borges JLC3; 1CEDOES-Centro de Diagnostico e Pesquisa da Osteoporose do Espírito Santo, Vitória, Brazil, 2Laboratorio de Biomecânica da Universidade Federal do Espírito Santo-UFES, Vitória, Brazil, 3Universidade Católica de Brasília, Brasília, Brazil Cardiovascular disease (CVD) is a primary cause of death and morbidity around the world. Body fat distribution has been shown to be an important predictor of risk for CVD. The relationship between intra-abdominal fat and CVD is not fully understood. Several studies have used DXA to provide measures of body fat distribution. Aims: To explore the applicability of fat mass measured by DXA at the total body (%TFM) as well as the ratio between the fat mass measured at the Android and Gynoid standardized regions (%AG Ratio), as predictors of CVD. Methods: 100 postmenopausal women with BMI values between 25 and 29.9 were evaluated and divided into two groups as follows: Group A: 50 women with recent diagnosis of CVD established not more than 90 days before the inclusion date, and Group B: 50 women without such diagnosis. The study was approved by an IRB and all subjects gave written informed consent before their inclusion. All women had a total body DXA scan with a Lunar Prodigy (GE Healthcare, Madison USA) densitometer using Encoret software ver.9.15. Also, a blood sample was taken to perform a biochemical analysis. Table 1: Results and p-values for the measured parameters

P512SU. A 14-YEAR LONGITUDINAL STUDY OF THE RELATIONSHIP OF PERIADOLESCENT CALCIUM INTAKE AND VEGETABLES AND FRUIT CONSUMPTION TO ADULT BONE MINERAL CONTENT Vatanparast HV1, Whiting SW1, Faulkner RAF2, Mirwald RLM2, Bailey DAB2, Baxter-Jones ABJ2; 1University of Saskatchewan, College of Pharmacy & Nutrition, Saskatoon, Canada, 2University of Saskatchewan, College of Kinesiology, Saskatoon, Canada Aim: To investigate the influence of vegetables and fruit (V&F) consumption, and calcium intake in peri-adolescents on bone mineral content (BMC) in the third decade of life. Methods: Longitudinal data from 133 young adults, mean age of 23 y (59 M, 74 F), enrolled in the University of Saskatchewan Pediatric Bone Mineral Accrual Study (BMAS, 1991–1997) and its follow up study (2002–2004) were used. Dietary intake was assessed via serial 24-hour recalls. Anthropometrics were assessed every six months. Total body (TB) BMC was assessed annually using DXA. The mean of variables of interest (calcium intake, vegetables and fruit consumption) around maturity, i.e., two years before the age of peak height velocity (PHV) to two years after the age of PHV, comprised the peri-adolescent data. The mean of

Control – n=50

CHD – n=50

Parameter

Mean

SD

Mean

SD

p-value for diﬀerence

Age (yrs) Height (cm) Weight (Kg) BMI Total Fat% Android Fat% Gynoid Fat% A/G Ratio (x10) T Cholesterol HDL LDL Triglycerides Uric Acid Homocysteine Fibrinogen Fasting Glucose Hip Circumference (cm) Waist Cirmuference (cm) Waist/Hip Ratio (x10)

64.5 155.4 63.9 26.4 43.1 47.8 49.1 9.733 189.3 53.6 105.8 149.2 4.5 5.7 214.3 92.4 99.6 89.7 9.021

5.95 6.32 5.3 0.94 4.05 6.02 4.7 0.85 47.7 11.91 46.2 53.3 1.21 1.23 71.37 12.39 4.44 5.28 0.64

63.7 154.9 64 26.7 41.7 49.7 46.2 10.81 215.4 55.7 119.1 213.2 5.2 6.4 238.9 90.1 96.3 96.3 10.01

5.44 6.29 4.85 1.39 5.94 7.04 6.49 1.033 38.9 11.39 36.9 79.1 1.4 1.45 64.88 10.74 4.57 5.84 0.631

0.478 N/S 0.681 N/S 0.861 N/S 0.262 N/S 0.174 N/S 0.148 N/S 0.012 <0.001 0.005 0.374 N/S 0.12 N/S <0.001 0.011 0.019 0.077 N/S 0.313 N/S 0.001 <0.001 <0.001

S274 Results: Table 1 summarizes demographics and mean results for measured parameters. T-Cholesterol, Triglycerides, Uric Acid and Homocysteine levels were significantly higher in the CVD group. There were no significant diﬀerences for %TFM or Android Fat Mass, although for Gynoid Fat Mass a significant correlation was found. Amongst all variables, the %AG Ratio and the Waist/Hip circumference ratio were the strongest discriminators for CVD. Conclusions: The %AG Ratio is a sensitive risk factor for CVD in overweight postmenopausal women. Including this information in DXA reports may improve health assessment in this population. Further studies are still needed to confirm the utility of regional body composition measurements in larger samples and in diﬀerent populations.

During the educational intervention QC’s met to discuss profiles of the physician’s management of osteoporosis and to participate in an workshop. The results are summarized using counts (percent). Results: Most FPs were aware (wave I %, numerator/ denominator; wave II %, numerator/denominator) of their patients’ key risk factors status for age (100%, 8317/8317; 100%, 6966/6967), hip fracture (98%, 215/8366; 100%, 6939/6962), spine fracture (90%, 7542/8365; 92%, 6427/6954), and wrist fracture (97%, 8129/8367; 99%, 6871/6962). Fewer were aware of their patients’ family history of fracture status (49%, 4130/8368; 74%, 5145/6958). The number of BMD tests preformed in patients with key risk factors is shown in Table 1. Table 1: Number of women at high-risk for fracture (Fx) who had a BMD test during wave I and II

P514SA. BONE DENSITY RELEVANCE AND INTERPRETATION IN CAUCASIAN CHILDREN AGED 9–16 YEARS OF AGE: INSIGHTS FROM A POPULATION BASED FRACTURE STUDY Jones G, Ma D; Menzies Research Institute, Hobart, Australia The interpretation of bone density measurement in children is more diﬃcult than in adults due to a number of factors. This study asked two questions: Is there a preferred bone density measurement site or type using DXA for fracture risk in children; and what is the best way to interpret bone density in children? This population based case control study included 321 upper limb fracture cases and 321 class and sex matched randomly selected controls. Bone density at the hip, spine and total body (including arm) was measured by a Hologic QDR2000 densitometer (DXA) and examined as bone area (BA), bone mineral content (BMC), bone mineral density (BMD), bone mineral apparent density (BMAD) and BMD/lean mass (BMDLM). The only DXA variables that were consistently significantly associated with total fracture risk in both boys and girls were spine BMD (AUC 0.56–0.58) and spine BMAD (AUC all 0.59) for total upper limb fractures and BMAD at the spine (AUC 0.60–0.63) and hip (AUC 0.58–0.60) for wrist and forearm fractures. No significant associations were observed for BA and BMDLM and inconsistent associations for BMC and other BMD sites. In controls only, all DXA variables were associated with age, height and weight but the weakest association was with BMAD. In conclusion, spine BMAD has the strongest and most consistent association with upper limb fracture risk in this sample of children. The associations with age imply that age and sex specific Z-scores will be most appropriate for interpretation of DXA measures in children.

P515SU. FAMILY PHYSICIANS’ AWARENESS OF KEY RISK FACTORS FOR FRACTURE AND THE USE OF BONE MINERAL DENSITY (BMD) TESTING FOLLOWING A MULTIFACETED OSTEOPOROSIS EDUCATIONAL INTERVENTION: CANADIAN QUALITY CIRCLE (CQC) NATIONAL PROJECT Papaioannou A1, Ioannidis G1, Kvern B2, Hodsman A3, Thabane L1, Gafni A1, Johnstone D4, Crowley C4, Plumley N4, Adachi JD1; 1 McMaster University, Hamilton, Canada, 2University of Manitoba, Winnipeg, Canada, 3University of Western Ontario, London, Canada, 4Procter and Gamble Pharmaceuticals, Toronto, Canada Aim: The CQC Project was designed to improve family physicians’ (FPs) adherence with the new Canadian osteoporosis guidelines (2002). Methods: The project contained five phases: wave I data collection, 1st educational intervention, wave II data collection, 2nd educational intervention, and wave III data collection. This interim analysis (wave I & II) examined the changes in FPs awareness of key risk factors including age (>65 yr), a prior fracture (hip, spine, or wrist), and family history of fracture; and appropriate BMD testing. Guidelines suggest that BMD testing should be conducted in patients with key risk factors. A total of 340 (wave I) and 289 (wave II) FPs formed 34 Quality Circles (QC). For each wave, FPs collected data from diﬀerent patients via chart reviews and a standardized collection form. A total of 8376 (wave I) and 6972 (wave II) patient records were selected at random and analyzed. All patients were women 55 years and older.

Wave I n=8376

Wave II n=6972

Risk factors for fracture

Valid n

BMD tested Count (%)

Valid n

BMD tested Count (%)

All key risk factors Age >65 years Prior fragility hip Fx Prior fragility wrist Fx Prior spine Fx Family history of Fx

5644 5333 152 353 486 431

3829 (67.8) 3564 (66.8) 118 (77.6) 285 (80.7) 394 (81.5) 362 (84.0)

4614 4188 173 368 457 619

3579 (77.6) 3207 (76.6) 134 (77.5) 309 (84.0) 370 (81.0) 549 (88.7)

Conclusions: Fractures may be underreported. Most FPs were aware of their patients’ risk factors status and awareness increased with family history of fracture. More patients over the age of 65 years had a BMD test following the educational intervention.

P516MO. MINIMUM SAMPLE SIZE REQUIREMENTS FOR BONE DENSITY PRECISION ASSESSMENT PRODUCE INCONSISTENCIES IN CLINICAL MONITORING Moayyeri A, Leslie WD; For the Manitoba Bone Density Program, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Aims: Detection of change during bone mineral density (BMD) monitoring is aﬀected by test precision. The International Society of Clinical Densitometry (ISCD) recommends that each center determine precision error using repeat measurements in 30 subjects. We hypothesized that this sample size may be too small for a robust precision estimate which could aﬀect the performance of BMD monitoring in clinical practice. Methods: Replicate measurements of spine and total hip (198 spine and 193 hip scan pairs) were obtained (interval 65 days). The sample was randomly divided into six groups of 30 patients each. Root mean square standard deviation (RMS-SD) precision error (g/cm2) and 95% least significant change (LSC) were calculated for each group and the pooled sample. LSC cutoﬀs were applied to 1420 individuals from the Manitoba Bone Density Program who had follow-up measurements on the same instrument (interval 219 months). Results: The pooled spine RMS-SD was 0.017 (95% CI 0.016– 0.019) and pooled hip RMS-SD was 0.009 (0.008–0.010). Sample sizes of 30 gave a range of RMS-SD point estimates from 0.012 to 0.021 for the spine and from 0.008 to 0.012 for the hip. When the respective LSC cutoﬀs were applied to the 1420 follow-up scan pairs, the fraction of patients categorized with significant change in the spine varied from 20.7% to 46.0%; 4 of the 6 LSCs based upon 30 subjects gave fractions significantly diﬀerent from the pooled LSC of 30.7%. Significant change fractions for the hip varied from 31.1% to 51.1%; 2 of the 6 LSCs based upon 30 subjects gave fractions significantly diﬀerent from the pooled LSC of 40.1% (Table). Conclusions: BMD precision studies using a sample size of 30 are insuﬃcient to reliably characterize precision error or change during clinical monitoring. We recommend precision studies with sample sizes higher than those currently proposed by the ISCD.

S275 Frequency of monitored patients (n=1420) classified as significant change. (* Significant change in group compared with the pooled sample) Lumbar Spine Groups of 30

LSC g/cm2

Significant Change (%)

#1 #2 #3 #4 #5 #6 Pooled sample

0.050 0.034 0.055 0.044 0.036 0.059 0.048

410 653 354 479 616 294 436

(28.9) (46.0) (24.9) (33.7) (43.4) (20.7) (30.7)

Total Hip P value*

LSCg/cm2

Significant Change (%)

0.286 <0.000 0.001 0.084 <0.000 <0.000

0.024 0.024 0.033 0.021 0.029 0.026 0.026

617 617 442 726 536 592 570

(43.5) (43.5) (31.1) (51.1) (37.7) (41.7) (40.1)

P value* 0.074 0.074 <0.000 <0.000 0.191 0.401

P517SA. DEDICATED RF COIL DESIGN FOR 1T MAGNETIC RESONANCE IMAGING OF TRABECULAR BONE AT DISTAL RADIUS Zhang XL1, Inglis D1, Noseworthy MD1,2, Konyer NB2, Adachi JD1, Webber CE1; 1McMaster University, Hamilton, Canada, 2St. Joseph’s Healthcare, Hamilton, Canada Aims: Trabecular bone architecture plays an important role in predicting bone fragility in osteoporosis and is independent of bone mineral density (BMD) as measured by DXA. Magnetic resonance imaging (MRI) based structural analysis is a noninvasive method without the use of ionizing radiation. Signal-to-noise ratio (SNR) suﬀers at high resolution MRI leading to incorrect trabecular bone structure evaluation. This study focused on designing a radiofrequency coil optimized for high resolution MRI at the distal radius. Methods: A quadrature 12 leg, low-pass, birdcage transmitreceive coil was designed for a 1T extremity MRI system (OrthOne, ONI Medical Systems, USA) using the ‘‘Birdcage Builder’’ software (Department of Radiology, Pennsylvania State University). The coil dimensions were 6cm long by 10.2cm in diameter to accommodate a human wrist. SNR and magnetic field homogeneity were evaluated through measurements of copper sulfate solution dissolved in 0.9% saline. High resolution images (0.156mm in-plane voxel size, 0.5mm slice thickness) were acquired (SPGR sequence with TE/TR=17.1/56ms, flip angle = 20() on a bone phantom immersed in gadolinium (Gd-DTPA) doped saline solution. Results: The birdcage coil provided a more homogeneous image and high SNR throughout the imaging volume comparing with a

surface coil based on the copper sulfate phantom. From bone phantom studies, an SNR of 6.7 with homogeneous B1 field was achieved with birdcage coil (Figure 1). The voxel size from which acceptable SNR is achievable to allow reproducible evaluation is 1.22[m|]mf10-2mm3. Conclusions: An optimized RF coil for MR imaging at the distal radius improved image quality over a linear surface coil. By designing a customized RF coil fine bone trabecular structure is possible to visualize with, reasonable SNR, even at a lower field strength of 1.0T. By optimizing RF coil designed for a dedicated extremity MRI we aim to have significant improvements in predicting osteoporosis-related fracture risk.

P518SU. TOPOLOGICAL TEXTURE ANALYSIS OF HIGH RESOLUTION MRI OF THE DISTAL RADIUS: ENHANCED IDENTIFICATION OF POSTMENOPAUSAL WOMEN AT RISK OF OSTEOPOROTIC FRACTURES OF THE SPINE Boehm HF1, Raeth CW2, Monetti RA2, Link TM3, Reiser M1; 1 University of Munich, Munich, Germany, 2Max-Planck-Society, Garching, Germany, 3UCSF, San Francisco, USA Purpose: To use novel texture analysis algorithms based on the Minkowski Functionals (MF) in 3D and the standard HoughTransform (SHT) for structural analysis of the distal radius depicted by high-resolution magnetic resonance imaging (HRMRI) for identification of postmenopausal women with osteoporotic fractures of the spine, and to compare the results with bone mineral density (BMD) and histomorphometric measures using receiver operator characteristic (ROC) analysis. Method and Materials: HR-MRI of the distal portion of the radius in 31 age-matched postmenopausal women (age 6515, range 56–78 yrs) were obtained at 1.5 T using a 3D gradient echo sequence with an inplane resolution of 195 x 195 µm and 500 µm in the z-direction. 17 women had vertebral fractures as diagnosed on lateral radiographs. BMD was measured by quantitative CT in the lumbar spine. The image data was analysed using the MF and the SHT, describing topological properties and higher order correlations of the image voxels. In order to assign a single scalar quantity to each image set, an optimised filtering procedure using independently sliding windows of variable width was employed. For each dataset, two standard histomorphometric parameters (apparent bone volume fraction, apparent trabecular separation) were extracted. The predictive potential of BMD, the histomorphometric and quantitative texture measures was expressed using ROC analysis. Results: Mean values of BMD, histomorphometric and topological parameters significantly diﬀered (p<0.05) for the fracture group and controls. The correlation between BMD and the histomorphometric measures ranged from r = 0.36 to 0.52 (p<0.05), while no significant relationship (p=0.34) was observed for the correlation between BMD and the topological measures. When employing the ROC for identification of fracture patients, an area-under-the-curve (AUC) of 0.64 is found for BMD, whereas the quantitative texture measures result in an AUC of up to 0.83. Conclusions: We have demonstrated that novel quantitative texture measures based on the MF in 3D and the SHT are well suited to identify postmenopausal patients with compression deformities of the spine when applied to high resolution image data of the distal radius in vivo. The diagnostic performance of our approach is superior to bone densitometry.

P519MO. BMD CALIBRATION OF QCT SCANS IN MULTI-CENTER TRIALS IN OSTEOPOROSIS Engelke K1,2, Timm W1, Mastmeyer A2, Fuerst T1; 1Synarc Inc, San Francisco, USA, and Hamburg, Germany, 2Institute of Medical Physiscs (IMP), University of Erlangen, Germany

Figure 1. Axial image of bone phantom with customized design coil.

Aims: Increasingly multi-center pharmaceutical trials in osteoporosis have been including quantitative computed tomography (QCT) to assess therapeutic response. Like DXA, QCT requires several calibration and monitoring steps in order to ensure adequate accuracy and precision. We assessed the accuracy of a QCT

S276 calibration approach as well as the longitudinal stability of eight diﬀerent CT scanner models from three diﬀerent manufacturers. Methods: In QCT a simultaneous calibration procedure is used to calibrate the image and convert CT values measured in Hounsfield units (HU) to bone mineral density (BMD). In this study hip and spine scan calibration was performed using the solid calibration phantom from Mindways Software (Austin, TX). After calibration with this phantom, scanner specific field inhomogeneity corrections (FIC) were calculated using the European Spine Phantom (ESP). We further checked the long term stability of the calibration by assessing variability in the relationship between the HUs and BMD of the calibration phantom by monitoring means and CVs of calibration slope and intercept extracted from the Mindways phantom. Results: HU to BMD calibration and field inhomogeneity corrections we evaluated using ESP scans. For each of the three vertebrae of the ESP the table lists minimum and maximum percentage errors in calibrated BMD with and without FIC. Within one year for all eight scanners the %CV for both parameters was below 1.2% with the exception of one intercept for which the CV was 3.5%. Conclusions: Including the FIC in the calibration of hip and spine scans is mandatory if results from diﬀerent scanners should be compared. For forearm scans this is less critical because the distance between calibration phantom and the bone to be measured is much smaller than in the hip and spine. Long term monitoring can reveal scanner malfunction but the simultaneous BMD calibration corrects at least for minor errors. Percentage diﬀerences between nominal and measured BMD with and without field inhomogeneity corrections using the ESP Nominal BMD values ESP Min/Max BMD errors [%] no FIC correction Min/Max BMD errors [%] with FIC correction

Vertebra 1 50 g/cm3

Vertebra 2 100 g/cm3

Vertebra 3 200 g/cm3

2.6 / 18.2

2.1 / 10.3

0.2 / 9.8

1.3 / 3.5

1.0 / 2.8

0.1 / 0.8

P520SA. LONG TERM PRECISION OF VERTEBRAL BODY HEIGHTS USING QUANTITATIVE MORPHOMETRY Fuerst T1, von Ingersleben G1, Wu C1, Chen Y1, Pourfathi S1, Genant HK1,2; 1Synarc, Inc., 2University of California, San Francisco CA, USA Aims: Vertebral quantitative morphometry (QM) is a common method for detecting prevalent and incident vertebral fractures in radiographs in adult women and men. One advantage of QM is the ability to define objective criteria for fracture based on vertebral height changes. However successful QM requires a standardized protocol for point placement and careful training of QM readers. Even with these eﬀorts QM measurements are not immune to the subjective nature of placing the six points used to define vertebral body shape. In this study we investigated the long term precision of QM. Methods: Standardized lateral radiographs of the thoracolumbar spine were acquired at baseline, one year and two years in 4,157 women participating in multi-center clinical trials. The radiographs were digitized (pixel size was 200 microns) and displayed on a proprietary reading workstation where QM was performed by various readers. Each QM reader was trained in vertebral anatomy, radiographic appearance of the spine and the protocol for point placement. After training readers were validated using a test image set and were required to pass certain criteria before being allowed to measure study data. Reader validation was repeated at regular intervals. Subjects without incident vertebral fracture determined by semiquantitative reading performed by a radiologist were then analyzed to assess the precision of vertebral body height measurement. Variability was computed as the root mean square coeﬃcient of variation in paired readings performed on films acquired and read one or two years apart. Subset analyses

were performed for films read by the same or diﬀerent readers at the two timepoints as well as by readers with and without radiology training. Results: The CV of vertebral body height between baseline and one year was 1.0 (4.2%), 0.9 (3.9%), 1.1 (4.1%) mm for the anterior, middle and posterior height, respectively. This increased slightly at two years to 1.1 (4.4%), 1.0 (4.2%), 1.2 (4.4%) mm. There was a trend toward superior precision when both visits were read by the same person. Individuals with or without radiology training performed similarly. Conclusions: Excellent long term precision of vertebral morphometry can be achieved with careful training and monitoring.

P521SU. NUMERICAL ANALYSIS OF COLLES’ FRACTURE Gdela K1, Pietruszczak S1, Webber C2; 1McMaster University, 2 Hamilton Health Sciences, Hamilton, Canada Aim: Validation of a simple methodology for predicting the fracture of the distal radius in the event of a fall onto outstretched hand. Background: The osteopenic fractures of distal radius, i.e. Colles’ fractures, occur long before more devastating fractures of hip and spine. The rational assessment of radius fracture risk requires an adequate mechanical analysis and may identify subjects at risk for future fractures. An elastic finite element (FE) analysis incorporating transversely-isotropic properties of cortical tissue was performed. The admissibility of the resulting stress field was assessed based on a proposed fracture criterion. The obtained predictions of fracture were compared with outcome of mechanical tests on isolated radii. Methods: The radii geometry was extracted from Spiral CT images and incorporated into FE software, where 60% of the length and embedment was modeled with eight-nodded solid element mesh emulating the experimental setup. The analyses were carried out by a user-defined module incorporating the critical plane approach in which the conditions at failure depend on the orientation of material axes in relation to loading direction. The failure load configuration causing distal radius fracture was established. The results were compared with mechanical tests conducted in collaboration with Catholic University of America, Washington, DC (Drs. P.V. Lade and P. Tsopelas). The tests were carried out on 12 dried radius bones and simulated the conditions of a fall onto outstretched hand. Results: Preliminary results of numerical simulations are presented in Fig.1. Left panel shows the distribution of the failure function with the dark regions indicating formation of macrocracks. The right panel shows the actual experimental failure mode for the same specimen.

Comparison of location of fracture; numerical simulation versus experimental result

S277 Conclusion: It is evident that the numerical prediction of the fracture location is quite realistic, which indicates that the proposed simple methodology may be quite eﬀective in assessing the fracture risk.

P522MO. DETECTION OF ABDOMINAL AORTIC CALCIFICATION WITH LATERAL DXA SCANS Schousboe JT1,2, Wilson KE3, Kiel DP4,5; 1Park Nicollet Health Services, Minneapolis, MN, USA, 2Division of Health Services Research and Policy, University of Minnesota, Minneapolis, MN, USA, 3Hologic, Inc., Bedfor, MA, USA, 4Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA, 5Harvard Medical School, Boston, MA, USA Aims: Cardiovascular disease is the leading cause of death among women age 65 and older. Longitudinal studies have demonstrated that lateral lumbar radiographic scoring of abdominal aortic calcification (AAC) is predictive of cardiovascular disease death, which suggests the possibility of using lateral VFA images for a similar purpose. Therefore, we examined how well DXA images obtained for vertebral fracture assessment (VFA) detected AAC compared to radiography in 59 women (mean age 76.5 years, range 66 to 93). Methods: Both sets of images were blindly evaluated for AAC by a single reader using a previously validated 24-point scale. A 24-point radiographic score of R5 was considered to be significant AAC. Results: The VFA and radiograph readings showed moderate agreement (intra-class correlation coeﬃcient 0.81, 95% C.I. 0.66 to 0.90). The sensitivity and specificity of a VFA score R 5 for those with significant AAC were 65% and 90%, respectively. The area under the receiver operating characteristic curve was 0.83 (figure 1) using the VFA 24-point scale for the detection of those with significant AAC.

scanners to acquire a lateral image of the spine at point of care unit. Aims: Determine specificity and sensibility of LVA in diagnosing vertebral fractures and the correlation coeﬃcient between LVA and conventional lateral radiographs. Methods: Fifty ambulatory women aged 50 and over with osteopenia or osteoporosis were submitted to both LVA and X-ray. Vertebral deformities were graded according to semiquantitative method of Genant and quantitative morphometry. LVA was performed through lateral spine imaging of T6-L4 using a Lunar Prodigy. Images of LVA were analyzed by a same examiner, independently of another examiner that evaluated all images of X-ray. The agreement between LVA and X-ray was determined according to statistics. Results: Seven patients (14%) with vertebral fracture were detected by X-ray; LVA was normal in one of them and in other two it was uninterpretable. LVA detected 6 patients (12%) with fractures; X-ray was normal in one of them and it could not be performed in another because she had escoliosis. The 3 individuals that could not have both tests analyzed were excluded. Agreement about the presence of fracture in the 47 remaining patients had a score of 0.80. X-ray identified 13 vertebra fractured, but six of them were not detected by LVA. LVA identified 8 fractures and X-ray failed to notice one of them - agreement about which vertebra were fractured had a score of 0.74. The agreement about fractures’ severity was poor (score: 0.44), because the densitometer don’t classify fracture as grade 1. The sensibility and specificity of LVA in detect patients with vertebral fracture, when X-ray was considered as gold standard, were 80.0% and 97.6% respectively. Conclusion: LVA is a useful test to exclude the presence of vertebral fracture. It had a good agreement with X-ray in detecting patients with vertebra deformities, except about fracture severity grade 1.

P524SU. A NEW HIGH RESOLUTION PERIPHERAL COMPUTED TOMOGRAPHY SCANNER FOR PATIENT MEASUREMENTS: ACCURACY AND PRECISION MacNeil JA, Boyd SK; Department of Mechanical and Manufacturing Engineering, University of Calgary, Canada

ROC Curve for Detection of Significant AAC with VFA Conclusion: VFA imaging intended to detect vertebral deformities is a promising technology for the simultaneous assessment of a risk factor for cardiovascular disease incidence and death.

P523SA. LATERAL VERTEBRAL ASSESSMENT BY DUAL X-RAY ABSORPTIOMETRY TO DETECT VERTEBRAL FRACTURES Melazzi AC1, Fernandes MB1, Rocha FBS1,2, Lacativa PGS1, Russo LAT1,2, Gregorio LH1, Pinheiro RAC1,2; 1Center for Clinical and Basic Research – CCBR Brasil, 2Hospital Pro Matre, Rio de Janeiro, Brazil Vertebral fractures are not frequently suspected. Ascertainment of them is important, since it’s a hallmark of established and severe osteoporosis associated with increased morbidity and mortality risk. Lateral vertebral assessment (LVA) has been developed recently, a technique that uses dual X-ray absorptiometry (DXA)

Introduction: High resolution peripheral quantitative computed tomography (HR-pQCT) has recently been developed for patient measurements of the distal radius and tibia (XtremeCT, Scanco Medical, Bassersdorf, Switzerland). The nominal isotropic resolution is 82 µm which provides suﬃcient resolution to distinguish individual trabecular structures, thus allowing morphological analyses. This was previously only possible using micro-computed tomography to scan human biopsies or for animal research applications. The purpose of this project is to provide an assessment of the system accuracy and precision for 3D bone microarchitecture measurements. Methods: The accuracy of the HR-pQCT system was tested using fresh intact cadaver specimens of the distal radius. A standard patient protocol (82 µm) on the HR-pQCT included cortical thickness, cancellous morphology, and densitometry measures. Additionally, an in vitro protocol was applied to explore the maximum resolution of the HR-pQCT system (41 µm). Bone mineral density was measured using dual-energy x-ray absorptiometry (DXA). The gold-standard comparison was based on subsequent scans (19 µm) on a micro-CT system (vivaCT 40, Scanco Medical). The precision of the HR-pQCT system was based on repeated patient scans (normal, healthy subjects) at the radius and tibia (bilateral) at a one week interval, and a four month follow-up (N=20 patients). Results: All cadaver scanning (HR-pQCT, vivaCT, DXA) is complete, and 13 of 20 patients have been scanned to date. Initial results indicate BV/TV correlates well with the gold-standard, but that connectivity density is sensitive to measurement resolution. A sample image from the HR-pQCT, vivaCT and DXA are shown for comparison (Figure 1). Conclusions: This new technology, after proper validation, will yield detailed bone microstructure information from patients. Longitudinal monitoring of patient bone architecture will be possible, thus providing valuable insight into bone adaptation in

S278

HR-pQCT and micro-CT of 9mm region of distal radius; DXA of the same radius. diseases such as osteoporosis and the eﬃcacy of therapeutic interventions.

P525MO. EFFECT OF ETIDRONATE IN PREVENTING PERIPROSTHETIC BONE LOSS FOLLOWING CEMENTED HIP ARTHROPLASTY: A RANDOMIZED, DOUBLE BLIND, CONTROLLED TRIAL Fokter SK1, Komadina R2, Repše-Fokter A3; 1Department of Orthopaedic Surgery and Sports Trauma, 2Department of Trauma, 3Department of Patomorphology and Cytology, Celje General Hospital, Celje, Slovenia Introduction: Periprosthetic bone loss is identified after inserting a hip prosthesis and is many times a result of stress shielding or altered loading of the proximal femur. Depending on the severity, the bone loss may threaten the prosthesis survival. Materials and Methods: The current study investigated the eﬀect of cyclic etidronate therapy on periprosthetic and contralateral bone mineral density (BMD) in an one-year, prospective, randomized, double-blind study on 46 patients after cemented hip arthroplasty. Etidronate was administered orally in a regimen repeated every 14 weeks and periprosthetic BMD was measured with dual-energy X-ray absorptiometry (DXA) in the total periprosthetic area and in the seven Gruen Zones at 1 week (baseline), 6 weeks, 3 months, 6 months, and 12 months postoperatively. Results: In the etidronate group there were significant temporal BMD decreases measured in Gruen Zones 2, 3, 6, and 7 as well as in the entire proximal femur; the greatest decrease was 11.1% and was measured in Zone 2 at 12 months. Also in the etidronate group, there was a significant 3.4% increase in BMD of the spine at 12 months. In the placebo group there were significant temporal BMD decreases measured in Gruen Zones 1, 2, 3, 4, 6, and 7 as well as in the entire proximal; the greatest decrease was 16.4% and was measured in Zone 7 at 12 months. There were no significant diﬀerences between the mean BMD measurements of the etidronate and placebo groups with the exception of the mean percent change in the spine at 6 months and 12 months, and in Gruen Zone 3 at 6 months; in all three cases the etidronate group had significantly greater mean values. Conclusion: These findings suggest that cyclic etidronate therapy has no significant eﬀect in surpressing the periprosthetic bone loss following cemented hip arthroplasty.

P526SA. INDICATIONS FOR BONE DENSITY TESTING IN CLINICAL PRACTICE IN ITALY Rossini M1,7, Bianchi G2,7, Di Munno O3,7, Giannini S4,7, Minisola S5,7, Sinigaglia L6,7, Adami S1,7; 1University of Verona, 2 Ospedale ’’Le Collette’’ Arenzano, 3University of Pisa, 4University of Padova, 5University ’’La Sapienza’’ of Roma, 6Gaetano Pini Institute of Milano, 7SIOMMMS TOP Study Group, Italy From an Italian multicenter observational study (Osteoporosis Treatment in Clinical Practice, TOP Study, Società Italiana dell’Osteoporosi, delle Malattie del Metabolismo Minerale e delle Malattie dello Scheletro, SIOMMMS), information was gathered regarding why patients were sent for BMD testing in the various regions of Italy and the results of their testing. The analysed group was made up of postmenopausal women referred to a densitometry center by specialists or general practitioners (GPs); general clinical information, reason for referral and DXA results were collected by an online questionnaire. 9585 forms were collected from 75 centers of 15 diﬀerent regions. Sixty-seven percent of the patients were referred by GPs,

and the remaining 33% by various specialists. In 50% of the cases a DXA at the spine was requested; 33% had a DXA at the hip and in 25% an ultrasound method was utilized (either heel or finger). The mean age of the women was 6310 (SD) years in northerncentral areas and 6110 years in southern regions (p<0.05 between the groups). A diagnosis of osteoporosis (T-score < 2.5) was reported in 36% of the cases, osteopenia in 39% and normal bone mineral density in 25%. The principal motivations for the bone testing were: screening (45%), followup (22%) and back or joint pain (16%). The limitation criteria for obtaining a reimbursement for a bone scan are diﬀerent in diﬀerent regions of Italy. The proportion of patients meeting these criteria and in whom the test was reimbursed was varying substantially: >66% in Liguria, Veneto and Marche (all northern Italy); 33–66% in Lombardia, Emilia and Toscana (all northern Italy); <33% in Lazio, Abruzzo, Campania, Puglia and Sicilia (all central-southern Italy). In 60% of the 2377 patients referred for followup testing, the length of followup was <18 months. On average, 52% of the patients did not have significant diﬀerences between the first and the second test, while 31% registered an improvement (38% if on any therapy, 50% if on alendronate). This preliminary data analysis demonstrates a frequent inappropriate and not homogeneous use of densitometry in Italy and indicates the necessity for the diﬀusion of guidelines.

P527SU. ZINC PLASMA CONCENTRATION COULD PREDICT BONE MINERAL DENSITY AND PROTECT OSTEOPOROSIS IN MEN Mir E1, Bahrami A2, Hossein Nezhad A1, Bekheirnia MR1, Shafahi AR1, Larijani B1; 1Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran, 2Tabriz University of Medical Sciences, Tabriz, Iran Aims: To assess the relationship between serum zinc level and BMD in men (age: 20–75) and to highlight beyond impression of an essential trace element on bone. Methods: 600 healthy men through IMOS study, which is a national project running in 5 provinces for prevention and treatment of osteoporosis in Iran, were selected via a cluster random sampling and enrolled the study. They were divided to two age groups: 20–40 (302/600) and 40–75 (288/600). BMD was measured by DXA method for hip and lumbar spine. Osteoporosis was defined as BMDR2.5 SD below the mean for young women (T-score%2.5). Zinc morning serum concentration was determined by atomic absorption spectrometry and normal range of serum zinc was considered 75–120 µg/dl. Results: The mean age was 40.83 15.06yr. Mean BMI was 24.793.94 kg/m2, 27.3% were smoking, 12.5% had regular physical activities three times a week and 12.2% had a history of renal stone. Mean serum zinc concentration was defined 92.15 35.15 µ g/dl. Among them 30.1% had zinc depletion, 56.8% had normal range and 13.1% had serum zinc excess. Findings in over 40 age group: 57.1% with hip osteoporosis were zinc deficient, whereas 22.1% with normal BMD indicated this deficiency (P<0.001). This amount was not significant for spine. Hip BMD in those with normal serum zinc concentration was 0.980.14gr/cm2 vs. 0.920.14gr/cm2 in zinc deficient ones (P<0.001). This amount was not significant for spine either. Individuals with hip osteoporosis had a mean zinc serum concentration about 72.1516.9 µg/dl while in whom with normal BMD this amount was measured as 98.8435.6µg/dl (Pvalue<0.001). Findings in under 40 age group: Serum zinc concentration has revealed no relation to BMD. There was no significant diﬀerence detected in serum vitamin D level among zinc deficient and normal zinc individuals in both groups. After adjusting variables such as age, BMI and serum vitamin D, zinc had an independent eﬀect on determining hip BMD among over 40’s (Pvalue=0.029). Conclusion: Zinc has a positive association with BMD and maintaining bone content in men over 40 and zinc deficiency is more common in osteoporotic individuals.

S279

P528MO. TOMOGRAPHIC (PQCT) ANALYSIS OF VOLUMETRIC BMD DISTRIBUTION IN LONG BONES AFFECTED OR NOT BY GRAVITY IN NORMAL MEN AND PRE- AND POSTMENOPAUSAL WOMEN Cointry GR, Capozza RF, Feldman S, Ferretti SE, Ferretti MV, Marchetti G, Ferretti JL; Center for P-Ca Metabolism Studies, National University of Rosario, Argentina Aims: To analyze the distribution and sex hormone-related variation of long bone cortical vBMD in healthy adults. Methods: pQCT scans of the sites 38% and 66% proximal to the ankle and wrist joints, respectively, in left tibiae and radii were taken in 50 men, 80 pre- and 120 post-MP women aged 25–85 years. Specific ROIs were previously defined with high or low values of diaphyseal vBMD (voxels with attenuation coeﬃcient values >1.0 cm-1, HD, and 0.4–1.0 cm-1, LD, respectively). Results: Data for tibiae and radii were generally coherent. The distribution of %HD and LD voxel areas was similar in men and pre-MP women. The %HD area was lower and the %LD area was higher in post-MP than pre-MP women. The HD area decreased proportionally to the years elapsed since MP (YSMP). A single, negative exponential relationship between the %HD (y) and LD (x) areas of all the studied bones showed characteristic distribution zones, with decaying values of the HD/LD relationship in the following order: men > pre-MP women > post-MP women with up to 7–9 YSMP > post-MP women with more YSMP. The proportion between the %HD and LD areas, similar in males and fertile females, decayed in the women with YSMP (tibiae, r = -0.384, p<0.001) . Qualitatively, the loss of HD area (representing the relative amount of the stiﬀest and strongest cortical tissue) after MP determined also a geometrical discontinuity of the respective ROI in the cross section, which may have severe mechanical consequences. Conclusion: Congruence of results in tibiae and radii suggest little or no influence of gravity on this aspect of skeletal physiology. The interdependence between the %HD and LD areas was reflected by the negative relationships observed between those variables in both forearms and legs when all bones were studied together. These curves provide reference charts suitable for evaluating the relative deterioration of the structure and mechanical properties of cortical bone (shifts toward the lower-right region of the graphs) in men and women in clinical studies, beyond the DXA scope.

P529SA. MEASURES OF DISTAL RADIAL BONE GEOMETRY PREDICT FRACTURE LOAD Abdulkareem JS1, Muller ME2, Inglis D3, Gordon CL4, Bouxsein ML5, Adachi JD6, Webber CE7, MacIntyre NJ1; 1School of Rehabilitation Therapy, Queen’s University, Kingston, Canada, 2 South City Physiotherapy, Guelph, Canada, 3Department of Engineering, McMaster University, Hamilton, Canada, 4Department of Radiology, McMaster University, Hamilton, Canada, 5 Harvard Medical School, Boston, USA, 6Department of Medicine, St.Joseph’s Healthcare, McMaster University, Hamilton, Canada, 7Department of Nuclear Medicine, Hamilton Health Sciences, Hamilton, Canada A history of a low energy wrist fracture substantially increases the risk for subsequent osteoporotic fractures. Thus non-invasive measures of radial bone variables that estimate bone strength may enable early detection of osteoporosis and fracture risk. Analysis of images acquired using peripheral quantitative computed tomography (pQCT) provides non-invasive estimates of bone density, mass and geometry. Specialized segmentation and analysis software (pQCT Pro) provides additional measures of bone geometry and architecture. The purpose of this study was to evaluate which of these surrogate measures of bone strength best predict failure load at the distal radius. Previously, twenty-one cadaveric forearm specimens were imaged at the 4% site using pQCT (Stratec XCT 960A) and the radius was loaded to failure using a configuration to simulate falling on an outstretched hand (Muller ME et al. 2003). The pQCT images acquired with an in-plane pixel size of 0.33mm2 and a slice thickness of 2.5mm were re-analyzed using specialized

software to quantify features of bone geometry of the whole cross-section, the cortex and the medulla as well as apparent architecture of the trabecular network in terms of connectivity and porosity. The best single predictor was the cross-sectional area of the cortical shell weighted by attenuation values, explaining 83% of the variance in failure load. Surrogate measures of bone strength under bending and torsional loads (major and minor principal second moments of cortical area, and polar moment of cortical area each weighted by attenuation values) and average cortical shell thickness also predicted failure load but these relationships were weaker (R2 values varied from 62 to 75.1%). Geometric and architectural measures of the trabecular compartment were not good predictors of failure load (R2 values varied from 0 to 30.3%). Despite the limited resolution, slice thickness, and thin cortex at the 4% site, secondary processing of the images (with pQCT Pro) corrected for partial volume averaging to reveal the expected contribution of the cortical shell to whole bone strength.

P530SU. DEVELOPING SELF-EVALUATION RISK ASSESSMENT TOOL (VERSION 1) FOR OSTEOPENIA USING DATA MINING TECHNIQUES Maeda J1, Kitazawa M1, Fisher AL2, Konishi E3, Takayama S4, Yoshizawa K4, Stanley G1, Nosaka T1, Tanaka T1, Miyama T1; 1 Nagano College of Nursing, Japan, 2McMaster University, Canada, 3Oita University of Nursing and Health Sciences, Japan, 4 Ueda City, Japan As well as other municipalities in Japan, Ueda city (120,000 population) has provided bone densitometry to women from 30 to 75 years old. However it is hard to screen all osteopenia because of its budget. The purpose of this study is to develop a risk assessment tool to detect osteopenia so that local residents can use for self-evaluation. In the bone densitometry at Ueda city, participants fill selfassessment form developed by Fisher et al. (2004). The form consists of demographic status such as age, height, weight, and age of menopause; symptoms and histories such as back pain, ovarian resection, and kidney disease; lifestyle habits such as smoking, exercise, and intake of dairy products; and bone density (BD) measured by DXA scanning. Participants were stratified into two groups based on their BD levels: a normal cohort (BD-YAM) / YASD > -1.000, and a cohort with osteopenia (BD-YAM) / YASD <= -1.000 as defined by WHO. 0.646 g/cm2 for YAM and 0.052 g/cm2 for YASD were used in this study. The data was entered into Clementine 9.0 and we tried to detect rule sets to explain BD levels from above mentioned variables using decision tree algorithms. 1,245 cases collected in 2004 were used for developing an estimation model, and 609 cases collected in 2005 were used for testing of coincidence. Some rule sets were detected. 10 explanatory variables, for example age, menopausal status, the history of thyroid disease and so on were used for the BD estimation model. This model indicated 87.07% of correct rate in cases of 2004. As a result of coincidence test using cases of 2005, it indicated 86.37% of correct rate. Thus, it is cleared that this model can predict BD status to a considerable extent, although accumulating data should be required to make sure of its validity. Table 1: Actual vs Estimation Comparison; Developing Model using 2004 data Actual

Normal* Osteopenia** Total

Normal

Estimation Osteopenia

Total

Correct %

1,084 87.07

421 33 454

128 663 791

549 696 12,45

Wrong % Total

161 12.93 12,45

*Normal: (BD – YAM) / YASD > - 1.000 **Osteopenia (including Osteoporosis): (BD – YAM) / YASD < = - 1.000

S280 Table 2 Actual vs Estimation Comparison; Coincidence 2005 data Actual

Normal* Osteopenia** Total

Normal

Estimation Osteopenia

Total

Correct %

526 86.37

237 13 250

70 289 359

307 302 609

Wrong % Total

83 13.63 609

*Normal: (BD – YAM) / YASD > - 1.000 **Osteopenia (including Osteoporosis): (BD – YAM) / YASD < = - 1.000

P531MO. VALIDITY AND RELIABILITY OF DXA FOR ASSESSING FAT MASS REGIONAL DISTRIBUTION Di Gregorio S1, Del Rio L1, Ibañez L2, Sole C1, Ferrer A1, Bonel E1, Rosales J1; 1CETIR, Centre Mèdic, 2Hospital San Juan de Dios, Barcelona, Spain Dual-energy X-ray absorptiometry (DXA) is mainly used to measure bone mineral density and body composition. Recent improvements in software have made it possible to automatically determine regional fat mass distribution. Hyperandrogenism is associated with an excess of fat mass, especially in the abdominal region. We evaluated the validity and reliability of DXA for the assessment of regional fat mass distribution in teenagers with hyperandrogenism, and the ability to detect changes in follow-up measurements. Patients/Methods: 36 teenagers with hyperandrogenism (mean age: 15 2.5 years) had DXA total body assessments at treatment baseline and at least six months later at time of final treatment. They were classified according to diﬀerent treatments: without (G0); with oral contraceptive and/or metformine, flutamide (G1) and with metformine and/or flutamide only (G2). Anthropometric parameters were measured (weight; height, waist circumference– WC-; hip circumference–HC-). The total and regional body composition was measured on a GE-Lunar Prodigy, using 8.1 software version. This version measures regional fat mass and lean mass in waist and hips regions, to determine the fat distribution in the abdomen (android–AF-) and around the hips (gynoid–GF-), expressed by percentage. In 11 subjects visceral fat was also measured by MRI. Results:The DXA AF showed a significant correlation with visceral fat measured by MRI (r=:0.989; p<0.0001). We also found a correlation between the WC and AF (r=0.667; p<0.0001) and between the HC and GF (r=0.56; p<0.001). The G0 group showed a positive correlation between the length of treatment and both weight change (r=0.650; p=0.03) and total mass (kg) (r=0.882; p=0.02), but there was no correlation between length of treatment and fat and lean mass distribution. In the G1 group we didn’t find any significant correlations. The G2 group showed a positive correlation between treatment period and both total fat% (r=0.554; p=0.04) and GF (r=0.589; p=0.03), but there was no correlation between treatment period and WC or waist/hip ratio. Conclusion: This study shows that the Prodigy DXA is a valid, economical, and rapid method to evaluate the regional fat distribution with better sensitivity than anthropometric parameters to evaluate the changes in the follow up.

P532SA. TOPOLOGICAL ANALYSIS OF DXA-SCAN IMAGES OF THE PROXIMAL FEMUR FOR ENHANCED PREDICTION OF THE FRACTURE RISK IN-VIVO Boehm HF1, Bitterling H1, Vogel T2, Buerklein D2, Baur-Melnyk A1, Eibel R1, Reiser M1; 1Dept. of Radiology, University of Munich, Munich, Germany, 2Dept. of Trauma Surgery, University of Munich, Munich, Germany Objective: We evaluate clinical DXA-scans of the hip using topological properties of the gray-level distribution for enhanced prediction of fracture risk. We compare the results with conventional densitometry by ROC-analysis. Material and Methods: Hip DXA-scans of 24 postmenopausal women (age 675 yrs), including 7 patients with recent fracture of the contralateral hip, are evaluated using a post-processing algor-

ithm based on the Minkowski Functionals (MF) in 2D for topological analysis of the graylevel information (i.e. mineral distribution) within the scan images. An integrative filtering procedure based on a sliding windows algorithm is employed to extract a scalar quantity (MF_SW) from the spectra of MF for correlation with the fracture status. We use ROC-analysis to determine the predictive potenial concerning discrimination between subjects with/without hip fracture and compare our results with the T-score of standard DXA. Results: Mean T-score in the fracture group was -3.3 1.0 (range -5.2 to -1), for the non-fracture group the T-score was 0.71.2 (range -3.0 to 2.5). The topological parameter MF_SW for patients with was 28.5+/-7.2, for the non fracture group -7012.5. ROC-analysis for fracture identification resulted in an area under the curve (AUC)of 0.85 for standard densitometry (T-score), AUC for our method was 0.93. Conclusion: Topological analysis of the mineral distribution of the hip as depicted by DXA allows to diﬀerentiate between patients with and without fracture of the contralateral proximal femur. The discriminative potential with respect to hip fracture is superior to that of clinical densitometry. The new algorithm may allow to enhance the detection of individuals with high risk of hip fracture.

P533SU. EARLY LIFE LEPTIN STATUS AS A PREDICTOR OF BONE AND FAT COMPOSITION IN CHILDREN AT PRE-PUBERTY Wang DW, Sivagurunathan N, Atkinson SA; McMaster University, Hamilton, Canada Aims: (1)

To confirm the association of serum leptin levels with fat and bone mass in early life. (2) To investigate whether leptin status in early life correlates to bone and fat composition at pre-pubertal age. Methods: Follow-up of 38 children (6 preterm small for gestational age, 21 preterm appropriate for gestational age, and 11 term born) was conducted at pre-puberty to measure growth and body composition by dual-energy x-ray densitometry (Hologic QDR 1000W and 4500 A). The results were compared to body composition and serum leptin status (ELISA, DSL, USA) measured in prior studies at 1, 3, 6, 9 and 12 months of age. Results: The demographic and body composition outcomes (mean SD) at pre-puberty are displayed in the table (grouped by birth size). In early life, the logarithm of leptin was significantly associated with % fat (r=0.44, p=0.006, n=38). At pre-puberty, the logarithm of leptin in early life was positively correlated with fat mass index, kg/m[]2 (FMI) (r=0.38, p=0.02, n=36), lumbar spine bone mineral density (BMD) (r=0.43, p=0.01, n=35) and whole body BMD (r=0.46, p=0.004, n=36) but not BMI or total body weight. Conclusions: The well-known relationship between leptin and fat mass is evident in this study. The findings also illustrate that leptin measured in early life is positively correlated to fat and bone mass status at pre-pubertal age. Further investigations are required to verify whether leptin status in early life could be a predictor of excess adiposity or peak bone mass in adolescence.

Variables

Preterm SGA

Preterm AGA

Term

Age, yr Body height Z-score Body weight Z-score BMI, kg/m2 Fat mass index, kg/m2 % fat Whole body BMC Z-score Lumbar spine BMD, g/cm2

7.30.5 0.230.91 -0.041.09 15.11.5 b 3.30.8 21.13.6 b 0.371.02

6.10.7 a -0.570.81 a -0.741.05 a 14.91.8 a 2.80.8 a 19.03.1 a -0.671.10

9.50.5 0.550.89 1.070.96 19.42.6 4.91.2 25.62.9 -0.200.72

0.5310.046

0.5290.074 a

0.6040.071

a

Preterm AGA vs. term, p<0.05;

b

Preterm SGA vs. term, p<0.05.

S281

P534MO. HIGH RESOLUTION PQCT OF THE RADIUS AND TIBIA 1

1

2

2

3

Dalzell N , Kaptoge S , Koller B , Ruegsegger P , Berthier A , Braak L3, Reeve J1; 1Cambridge University, Cambridge, UK, 2 Scanco, Zurich, Switzerland, 3MEDES, Toulouse, France Aims: The new Xtreme pQCT scanner (Scanco) permits calculation of structural data on cortical and trabecular bone. We investigated young adults at standard sites - distal radius and distal tibia. We recruited so far an unselected population-based sample, 29 men and 39 women aged 20–50 from a primary care medical practice. Our aims were to provide normative and descriptive data. Methods: Subjects were approached by letter. Each submitted to pQCT measurements on the radius and tibia (resolution approaching 0.1mm). The pQCT output includes trabecular bone density from which trabecular BV/TV is calculated, the density of compact bone (Dcomp), mean cortical thickness (C.Th) and trabecular Number (Tb.N), Thickness (Tb.Th) and Spacing (Tb.Sp) according to the Parfitt plate model. Results: Scanning proved uncomplicated and satisfactory for operator and subjects. The tibial and radial cross sectional areas in the region scanned were strongly dependent on height R2adj = 0.72, but not weight or sex. In the distal tibia there were no significant eﬀects of age on Dcomp, C.Th, Tb.N, Tb.Th, or Tb.Sp. But only Dcomp was similar between the sexes; TbSp was higher in women while the remaining parameters were all lower (P<0.008). For women mean BV/TV was 13.7% and for men 16.7% (RMS error 2.8%) and for women mean C.Th was 1.18mm and for men 1.46mm (RMS error 0.30mm). In the distal radius there was a contrast with a radius-specific interaction (P=0.035) between sex and height, with men increasing their radius cross sectional area twice as much as women for a 1 cm height increase. Also, unlike the tibia, radius Dcomp was significantly greater in women by 3% and increased by 2.5% per decade of age (P<0.01 for both). Cortical thickness was lower in the radius (means 0.97, 1.09mm in women and men) than tibia. Conclusions: These data provide valuable insights into the eﬀects of skeletal maturation on the radius and tibia as well as demonstrating contrasts in the eﬀects of sex on the upper and lower limb bones. High resolution pQCT will allow non-invasive micro-structural studies on the human skeleton in the investigation of determinants of bone quality.

P535SA. AGE-SPECIFIC CHARACTERISTICS OF AXIAL SKELETON MINERALIZATION IN CHILDREN Scheplyagina LA1, Moisseyeva TY, Kruglova IV; Research Center of Child Health, Russian Academy of Medical Sciences, Moscow, Russia Objective(s): To analyze formation of bone mass in children. Materials and Methods: In a cross-sectional study, 357 healthy children (194 boys and 163 girls) aged from 5 to 17 years were examined. Mineral bone density was evaluated by dual-energy absorptiometry (L2-L4) using osteodensitometry ‘‘DPX-MD+’’, LUNAR, USA. Absolute values of BMC (g) and BMD (g/cm2) were assessed. Results: Significant variability of age-specific values of BMC and BMD is established. It is demonstrated that on average BMC increases from 13.5 g to 46.4 g in boys and from 13.72 g to 46.23 g in girls. It is established that with age BMD increase repeats BMC increase but its rate is slower. So, BMD increased from 0.64 to 1.09 g/cm2 in boys and from 0.65 to 1.09g/cm2 in girls. It is revealed that intensive mineralization at L2-L4 occurs from I to III Tanner’s stage of pubertas. In all, during pubertas (from 10 to 16 years) BMC increases in 90.7% of boys and in 97.6% of girls. BMD increase comes to 34.6% and 39.7%, accordingly. During pubertas bone mineral density in lumbar part of spine increases in 1.5 times more than in neutral age. It is established that mean values of BMC and BMD in girls younger than 14 years in general were higher than in boys. After the age of 15, BMC and BMD levels in boys began to exceed corresponding parameters in girls. It is demonstrated that BMC and BMD independently of gender have close correlation with body height (r=0.8; p=0.000) and body mass (r=0.7; p=0.000).

Conclusions: Age-specific patterns of bone growth in children are characterized by mutual conditionality of body height increase, mineral accumulation and bone mineral density increase which are most vital during pubertas.

P536SU. QUANTITATIVE ULTRASOUND MEASUREMENTS OF THE HAND PROXIMAL PHALANGES DO NOT DETECT A POSITIVE EFFECT OF CALCIUM SUPPLEMENTATION ON BONE MINERAL MASS IN PREPUBERTAL BOYS: A FOLLOW-UP STUDY Zawadynski SV1, Chevalley T2, Hans D1, Ferrari S2, Conicella G1, Perron C1, Slosman D1, Ratib O1, Bonjour JP2, Rizzoli R2; 1 Service of Nuclear Medicine, Dept of Radiology, 2Service of Bone Diseases (WHO Collaborating Center for Osteoporosis Prevention), Dept of Rehabilitation and Geriatrics, University Hospitals Geneva, Switzerland One year calcium supplementation (Calsup, 850 mg/day of Calcium) versus placebo has been shown to increase BMD (bone mineral density) gains of femoral diaphysis and of the mean of 5 appendicular sites in 235 boys aged 7.40.1 yrs (meanSEM, range 6.5–8.5 yrs). To evaluate whether Calsup eﬀects could be detected with quantitative ultrasound (QUS measurement, hand proximal phalanges BTT (Bone Transmission Time), AdSOS (Amplitude Dependent Speed of Sound) and UBPI (Ultrasound Bone Profile Index) were assessed during the same double-blind placebo-controlled trial using a DBM Sonic BPt (IGEA, Carpi, Italy). Measures were performed at baseline, at the end of Calsup (12 months) and 1 year after Calsup discontinuation. At the end of the study, a blind stringent quality control (QC) was performed by the manufacturer on the raw values (trace analysis). Appropriate statistics were then applied on a ‘‘clean’’ database and only results of Intention to treat analysis at one year are shown. The QC led to the deletion of 8%, 30% and 8% of the BTT, ADSOS and UBPI values respectively while no patients were eliminated after initial control of the BMD values group. A total of 21%, 42% and 21% examinations had to be deleted depending on the QUS parameters at 24 months leading to a too small sample size to correctly interprete the follow-up analysis. For all QUS parameters, we did not observe any significant diﬀerences between the Calsup and placebo groups. However, significant increases were detected in both groups after one year with +8% and +9%, +0.3% and +0.4%, +19% and +21% for the BTT, ADSOS and UBPI both in the placebo and Calsup groups, respectively, indicating that QUS may appreciate bone growth in prepubertal boys. However, 1 out of 3 subjects could not be analysed, because of erroneous or unreliable measurements. Thus, we failed to detect a positive eﬀect of calcium supplementation with QUS of the phalanges in prepubertal boys.

P537MO. EVALUATION OF A NEW DENSITOMETER (GE LUNAR IDXA) IN NORMAL AND OBESE SUBJECTS O’Connor M.K., Enright D; Department of Radiology, Mayo Clinic, Rochester, MN, USA Aim: Evaluation of new dual-energy x-ray densitometer (GE Lunar iDXA system) in normal and obese subjects. This fan-beam densitometer utilizes a more powerful x-ray tube and a high resolution CZT detector relative to the GE Lunar Prodigy system. Materials and Methods: The precision and accuracy of the iDXA and Prodigy were compared at the spine and femur regions in 30 normal and 30 obese subjects (BMI > 30). All normal and obese subjects were scanned twice on each system, at the spine and bilateral femur. Results: There was very high correlation between BMD values obtained on the iDXA and Prodigy systems at the L1-L4 spine, femoral neck, trochanter and total femur (r2 > 0.99 in all cases). Regression analysis showed a small bias (normals = 0.028 g/cm2, obese = 0.039 g/cm2) for spine measurements between the iDXA and Prodigy units. At all other regions, bias was less than 0.01 g/cm2. There was a small improvement in precision with the iDXA system at all measured sites in both normal and obese subjects (see

S282 table), possibly attributable to the improved spatial resolution of this unit. For both systems, poorer precision in the hip was observed in the obese subjects. In spine measurements of obese subjects, the precision was unchanged for the iDXA system but was significantly poorer in the Prodigy system.

the FN. A smaller DR in the FN could be a strong risk factor for hip fracture. Further work is necessary to improve the precision.

P539SU. THE CORRELATION OF POSITIVE ANTITISSUE TRANSGLUTAMINASE (TTG) AND ANTIGLIADIN ANTIBODIES (AGA) WITH BONE DENSITOMETRY IN HEALTHY POPULATION IN SHIRAZ, IRAN

Precision (%CV) in Normal and Obese subjects System

Spine

Neck (Lt / Rt)

Trochanter (Lt / Rt)

Tot. Femur (Lt / Rt)

iDXA Normals Prodigy Normals iDXA Obese Prodigy Obese

0.79

1.10/0.64

1.13/1.00

0.59/0.49

0.94

1.21/1.27

1.16/1.19

0.83/0.68

0.79

1.37/1.43

1.27/1.51

0.89/0.93

1.41

1.79/1.70

1.27/1.22

0.90/0.95

Qualitatively, image quality with the iDXA system was significantly improved over that obtained on the Prodigy. Conclusions: We conclude that BMD correlation between iDXA and Prodigy densitometers was excellent at all measurement sites. The iDXA system has a higher table weight limit and wider patient portal and oﬀers improved precision in both normal and obese patients compared to the Prodigy system. With the increasing incidence of obesity, this system will be important for the measurement of bone density in larger patients.

P538SA. BONE MASS DISTRIBUTION IN FEMORAL NECK BY DXA: DIAGNOSTIC PERFORMANCE EVALUATION del Rio L1, Di Gregorio S1, Bagur A2, Rosales J1, Vila R1, Pascual J1, Garcia M1, Sole C1, Bonell E1, Bambalere D1; 1CETIR Centre Medic, Barcelona, Spain, 2Hospital de Clinicas, Buenos Aires, Argentina Bone density is a major risk factor for hip fractures, but the proximal femur strength also depends on structural characteristics such as geometry and bone mass distribution. The twodimensional x-ray attenuation graphs generated by DXA indicate the amount of bone mineral and its distribution. In this study we explored DXA-derived bone mass distribution and its relationship to hip fracture risk. A total of 392 subjects of both sexes (age 50–91 years old) were evaluated. The fracture subjects(n=196) had sustained a nontraumatic hip fracture (63% neck fractures, 37% trochanteric). The control subjects(n=196), without hip fracture, were individually matched with fracture subjects for age, height and weight. Bone mineral density (BMD) was measured at the proximal femur using a GE-Lunar Prodigy with 9.0software. The right hip was scanned unless there was a hip replacement or surgical treatment. Bone mineral content(BMC) and BMD at the femoral neck(FN) and total hip(TH) were measured. The FN region of interest(ROI) was divided in two equal subregions. The distribution ratio (DR) was obtained by dividing the BMC measurements in the upper sub-region by the lower one. The results were divided into quartiles, a Chi square test was used and the odds ratio (OR) was calculated by comparing the three lower quartiles by the top quartile. The diﬀerence between the groups means was analysed by a t-test. The coeﬃcient of variation(CV) of DR and BMD results was determined by three repeated scans with repositioning in 15 volunteers. The hip fracture group had significantly lower BMD and BMC in the FN, upper half FN ROI, TH ROI, and DR[p<0.0001]. There was a strong relationship between decreased DR and fracture risk. The DR was a stronger predictor of hip fracture than either FN BMD or TH BMD (OR 7,3;3,1and5,1 respectively). The DR precision error was nearly three times larger than FN BMD. The bone mass DR with DXA may detect a disturbance in the bone strength balance causing a loss of mechanical properties of

Saberi Firoozi M, Nejabat M, Sarati A, Ardebili M, Bagheri Lankarani K, Amirzade S, Heidari Taghi; Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Nemazee Hospital, Shiraz, Iran Aims: Celiac disease (CD) as an autoimmune disease has been described to have a relation with osteoporosis. Screening of undiagnosed osteoporotic individuals for CD is recommended especially those with associated anemia and younger than 55 years old. Methods: Among 2000 individuals who were randomly sampled from the telephone directory and invited to participate in the study, 1447 ones who were eligible for this study were accessed. Exclusion criteria for this selection were: history of endocrine disorders, gynecological disorders, liver/kidney dysfunction or drug therapy known to interfere with bone metabolism. The bone mineral density (BMD) at the lumbar spine (L2–L4) and neck of femur was determined in each participant by dual-energy X-ray absorptiometry using the fast scan mode. Blood samples for antigliadin antibodies (AGA) and antitissue transglutaminases (tTG) were accessed in all individuals by the enzyme linked immunoabsorbant assay (ELISA) using commercial kits. Results: Of 1447 individuals 53.8% were female and 46.2% were male with mean age of 45.4646 years (range 20–83 years). Based on tTGs, 20 individuals (1.4%) and based on AGA, 29 (2%) individuals had antibodies more than 10 AU/ml which consumed positive. The mean BMD (Z-scores) values for the lumbar spines and femoral neck were -0.721.18 g/cm_ and -0.380.93 g/cm_ respectively. For T-scores these values were -1.191.38 g/cm_ and -0.931.19 g/cm_, respectively. We found no significant diﬀerences among all T-scores and Z-scores mentioned previously among individuals with positive tTGs or AGA and negatives. Results from the stepwise multiple regression analysis showed that only age and body mass index were the main predictors of BMD at the lumbar spines (L1-L4) and neck of femur and not the presence or absence of tTGs or AGA. Conclusion: This study does not support population screening for celiac disease in our area regarding to its cost and low prevalence

P540MO. ASSESSMENT OF ALVEOLAR AND MANDIBULAR BONE MINERAL DENSITY COMPARING BRIGHTNESS OF MICROSQUARES OF X-RAY FILMS IN NEIGHBORING AREAS OF MANDIBULAR FIRST PREMOLAR IN WOMEN Takaishi Y1, Ikeo T2, Morii H2,3, Takeda M4, Arai T4, Nonaka K5; 1Takaishi Dental Clinic, Himeji, Japan, 2Osaka Dental University,Osaka, Japan, 3Osaka City University, Osaka, Japan, 4 Furuno Electric Co, Nishinomiya, Japan, 5Elk Corporation, Tokyo, Japan It was demonstrated that alveolar bone mineral density (BMD) can be measured by estimating the brightness of microsquares with 80x80 microns in each side. The area of assessment was just neighboring side area of alveolar bone of the first premolar in mandibula. In the last study there was an age-related decline in alveolar BMD and significant correlations with lumbar spine BMD assessed by DXA (dual-energy X-ray absorptiometry, Hologic 4500) and with SOS (speed of sound) measured by QUS (quantitative ultrasound, CM 100, Furuno Electric Co) were shown. In the present study 26 normal young women with ages 20–40 years were selected for the reference data. The brightness in the upper half part (A) and the lower part(B) of neighboring area of the first premolar alveolar bone as well as the area just 4 mm beneath the first premolar was estimated. In 19 peri-and postmenopausal women with ages of 50–69 years, the brightness in C

S283 areas was compared with that in A+B areas. Brightness was 130 at B area of a 23-year-old normal woman. In 26 normal young women the brightness in C areas (143.8818.21[SD]) was significantly higher than that in B areas (131.7220.38) and that in A areas (112.0020.66). The brightness in A and B areas was significantly diﬀerent. The higher average value of brightness was shown in C areas (98.5521.27) than that in A+B areas (89.6316.44), but the diﬀerence was not significant. These data indicate that the alveolar BMD showed lower value in peri- and post-menopausal women compared with young normal women. BMD in alveolar areas showed lower values compared with that in mandibular areas which is situated in lower area of the first premolar. In conclusion this method of evaluation of BMD can compare BMD in alveolar with that in mandibular part of jaw.

The area of assessment.

P541SA. COMPARISON OF A SIMPLIFIED 8-POINT SCALE WITH A PREVIOUSLY VALIDATED 24-POINT SCALE TO SCORE ABDOMINAL AORTIC CALCIFICATION WITH DENSITOMETRY OR RADIOGRAPHY Schousboe JT1,2, Wilson KE3, Kiel DP4,5; 1Park Nicollet Health Services, Minneapolis, MN, USA, 2Division of Health Services Research and Policy, University of Minnesota, Minneapolis, MN, USA, 3Hologic, Inc., Bedfor, MA, USA, 4Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA, 5Harvard Medical School , Boston, MA, USA Aims: Radiographic abdominal aortic calcification (AAC), assessed on a validated 24-point scale, is a risk factor for cardiovascular disease death. Our purpose was to devise a simpler, faster 8-point scoring scale where the total linear lengths of the posterior and anterior aortic wall calcification in front of L1-L4 were assigned a grade ranging from 0–4. Methods: Spine radiographs and lateral DXA images obtained for vertebral fracture assessment (VFA) were each blindly evaluated by a single reader for AAC using the 24-point scale, and subsequently using the 8-point scale in 59 women (mean age 76.5 years, range 66 to 93). A 24-point score of R5 was considered to be significant AAC on either radiography or densitometry. Results: On radiographs, the sensitivity and specificity of an 8-point score of R3 for those with significant AAC (R 5 on the 24-point scale) were 69% and 100%, respectively. On lateral DXA images, the sensitivity and specificity of an 8-point score of R3 for those with significant AAC (R5 on the 24-point scale) were 86% and 97%, respectively. Receiver operating characteristic analyses showed areas under the curves of 0.95 using the 8-point scale to detect those with significant AAC on radiographs, and 0.98 using the 8-point scale to detect those with significant AAC on lateral DXA images. Conclusion: This study shows excellent agreement between the 8-point and 24-point AAC scales, and suggests that the 8-point scale can be used with either radiography or lateral DXA to assess

this cardiovascular disease risk factor. Prospective studies are needed to confirm the utility of the 8-point scale. Study supported by Hologic, Inc.

P542SU. PREVALENCE OF OSTEOPOROSIS IN INDIAN MEN AND THE EFFECT OF LIFESTYLE FACTORS ON BONE MINERAL DENSITY Venkat KK1, Singh P2, Arora MM2, Khatkhatay MI1; 1National Institute For Research In Reproductive Health, Icmr, Parel, Mumbai, India, 2Armed Forces Medical College, Pune, India Osteoporotic studies in men report that hip fractures occur 10 years earlier and more frequent in Indian men compared to western population. Yet in India male osteoporosis is neglected due to lack of ethnicity-based diagnostic criteria. Thus, we aimed to establish reference values for bone mineral density (BMD) measurements in Indian men and to examine the eﬀect of lifestyle factors such as physical activity, alcohol and smoking on BMD. 243 soldiers/retired army personals aged 20–70 yrs were recruited and BMD measured using DXA (Lunar DPX-IQ, Madison, USA). The mean BMD of spine was 1.0950.128g/cm2and that of femur was 1.0660.13g/cm2. The peak bone mass reached at 30–35yrs of age and thereafter a gradual decrease in BMD was observed with 6.01% fall in spinal BMD (r=-0.940) and 6.12% (r=-0.916) in femoral BMD per decade. The prevalence of osteoporosis in army recruit was found to be 13.9% of spine and 2.2% of femur using Western normative data. When ethnic-based T-score was applied osteoporosis dropped down to 3.2% and 0%, respectively. Thus, emphasizing the need to establish ethnic based T-score. Furthermore, the subjects were divided into subgroups according to alcohol intake and tobacco consumption. The mean BMD values of each subgroup was compared with the mean BMD of reference group who were non-alcoholic, non-smokers were regular exerciser using ANOVA and student’s paired t-test on Graph Pad Prism 4. Subjects who consumed more than 4 pegs of alcohol per week had significantly higher mean femoral BMD (1.138 0.1031g/cm2 compared to non-consumers (1.0320.122g/cm2. Significant dose related deleterious eﬀect of alcohol on BMD in subjects with BMI %22kg/m2was observed. Smoking had adverse eﬀects on both spine (0.9940.069g/cm2 v/s 1.1050.1214 g/cm2, p%0.005) and femoral (0.9340.078cm22 v/s 1.0630.1342 g/cm2, p%0.001) BMD and had low BMI (p%0.001). The beneficial eﬀect of exercise and alcohol intake was observed on femoral BMD (p%0.019). The data indicate that lifestyle factors mainly aﬀect femoral BMD which is the major cause of mortality in men. Thus the study first of its kind attempts to improve the bone health of Indian men and investigates the eﬀect of modifiable lifestyle factors on bone mass.

P543MO. EVALUATION OF THE EFFECT OF TWO EXERCISE PROGRAMMES INCORPORATED AS AN ACTIVITY IN COMMUNITY CENTRES FOR THE ELDERLY ON BONE MINERAL DENSITY: A RANDOMIZED CONTROLLED TRIAL Woo J1,2, Hong A2, Lau E2; 1Department of Medicine & Therapeutics, 2Department of Community & Family Medicine, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong Background: Both Tai Chi and resistance exercise have been shown to increase bone mineral density. However, such programmes tend to be carried out fairly intensively as research studies in younger subjects. Extrapolation to the elderly in the community, who may not be able to adopt programmes of such intensity and frequency as part of their lifestyle, may not be appropriate. Evaluation of exercise programmes tailored for regular community activity would be desirable before the exercises are widely promoted. Aims: To document the eﬀect on benehealth of Tai Chi (TC) and Resistance Exercise (RE) programme suitable for elderly people attending community centres. Method: 90 men and 90 women aged 65–74 years living in the community, were randomized to three groups containing equal numbers of men and women (TC, RE, Control). BMD was

S284 measured using DXA (Hologic), at baseline, 6 and 12 months. The TC programme consisted of 45 min group sessions, and the RE programme consisted of seven movements against resistance provided by a thera-band of medium load, three times a week. The control programme consisted of social activities. The programme lasted for 12 months. Analysis of covariance (ANVOVA) for repeated measures adjusted for baseline was used to compare changes between the groups. Results: No diﬀerence in BMD between the groups was observed in men. For women BMD (total spine) showed a significant percentage increase (+1.962.59) in the RE compared to the TC group. BMD (total hip) showed a significant increase (0.212.47) in the TC group, while the control group had more bone loss at the hip (-2.292.43) compared with the RE group. Compliance was good at between 70–80%. Conclusion: Although compliance with the exercise programme was good, TC and RE only had modest eﬀects on BMD in women, TC improving total hip BMD while RE improved total spine BMD. This may not translate into significant clinical benefits. The eﬀect on falls may be more beneficial in terms of fracture prevention.

P544SA. PEDIATRIC TOTAL BODY BMD OF CHINESE FEMALES: PRELIMINARY REFERENCE VALUES Xiang J1, Chen Z1, Xu H2, Zhou Q3, Cheng S4, Barden H5, Weynand LS5, Cheng X6; 1Department of Biomedical Signal Assessment, Jiaxing 1st Hospital, China, 2Department of Nuclear Medicine, The First Aﬃliated Hospital, Medical College, Jinan University, Guangzhou, China, 3GE Healthcare, China, 4Universities of Xingjiang Medical Science & Guangzhou Physical Education, China, University of Jyväskylä, Finland, 5GE Healthcare, Madison, WI, USA, 6Radiology Department, Beijing University Beijing Jishuitan Hospital, China Aims: Bone mass accumulated during childhood and adolescence is a primary determinant of fracture risk and osteoporosis in late adulthood. Average bone mineral density (BMD) values of healthy subjects may vary among populations in diﬀerent geographic regions. Establishing country-specific reference values that reflect these diﬀerences facilitates accurate assessment of normal children, as well as children at risk for bone loss due to various disease states. Methods: We measured total body BMD using DXA (GE Healthcare Lunar) in children from Guangzhou (n = 32) and Jiaxing (n = 247). All children were defined as normal based on health history and questionnaire. Results: BMD data were fitted using a sigmoid regression equation. BMD and bone mineral content (BMC) showed rela-

tively steady increases from age 5 to age 14, with the largest year-to-year percent increments occurring between ages 9 and 10 and between 13 and 14 years, approximating the beginning and end of puberty. There was a marked plateau in BMD and BMC reached at approximately age 14 years. Conclusions: These preliminary reference data for Chinese pediatric females were generally similar to USA reference values, but with a slightly lower peak bone BMD.

P545SU. CAMPARISON OF CALCANEAL BONE DENSITY IN OPERATIVE VERSUS NON-OPERATIVE ARMY PERSONNEL Mokhtari I1,2,4,5, Rezae moghaddam F2, Azma K2, Markazi moghaddam N2, Kamalifard M3,4, Reiis-sadat A2, kochakali M2; 1 Sport Medicine Research Center, Azad University, Tehran, Iran, 2 PMR Research Center, Army University of Medical Science, Tehran, Iran, 3Occupational Medicine and Safety Research Center, Tehran, Iran, 4Iranian Young Research Club, Tehran, Iran, 5Special Medical Center, Tehran, Iran Aim: The aim of this study was to assess values of lifestyle factors including physical activity, job, calcium intake, and smoking in 355 army male personnel. Methods: From feb-june 2004, 355 males (age between 35– 55years) in two equal separate groups; operative(active field soldiers) and non-operative (army oﬃce staﬀ) were evaluated with dual X-ray and laser (DXL) calscan for messurement of calcaneus bone minneral densitometry (BMD). Lifestyle factors including smoking, calcium intake and physical activity were evaluated by the investigators through a specifically designed questionaire. Training programs for operative personel include: (1) marching at least 2 times per week (2) walking at least 30 minutes per day (3) army special field operation at least 4 times per year. Operatives were compared with non-operative personnel who did not perform the regular active field training manoeuvres. RESULT: Linear regression revealed that BMD is significantly associated with job (P<0.001), age(P<0.001), smoking(P<0.01), calcium intake (P<0.05), and years of physical activity(P<0.001). In addition, dual-energy X-ray absorptiometry (DXA) of lumbar spine and femur were performed for 35 participant for correlation that the result was same as for DXL (P<0.05). Conclusion: This study suggests that years of regular physical activity and mechanical loading were the strongest predictors of calcaneus BMD.

P546MO. ASSESSMENT OF LOW BONE MASS IN ADOLESCENT IDIOPATHIC SCOLIOSIS: A CORRELATION STUDY OF DXA AND QUANTITATIVE ULTRASOUND Hung VWY1, Yeung HY1, Qin L1, Lee KM2, Ng BKW1, Cheng JCY1; 1Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, 2Lee Hysan Clinical Research Laboratories, The Chinese University of Hong Kong, Hong Kong, China Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity aﬀecting mainly girls at peripubertal period. Our previous studies with DXA have demonstrated that 30% of AIS girls had low bone mass which may be manifested by either insuﬃcient bone matrix density or structural density. Quantitative ultrasound (QUS) has been shown to be useful in the evaluation of structure and the mechanical properties of bone. The aims of this study are to investigate any bone quality changes due to the low bone mass in AIS girls assessed by QUS and to correlate the results with DXA. 32 AIS girls, aged 11–16, with initial Cobb angle R10( and 28 age-matched health girls were recruited. Bone quality of nondominant calcaneus was assessed by QUS. Parameters provided by QUS included broadband ultrasound attenuation (BUA), velocity of sound (VOS) and a derived stiﬀness index (SI). Femoral neck BMD was measured by DXA. Independent t-test was used to compare the QUS parameters with those of the normal controls.

S285 Pearson correlation was performed between BMD and ultrasonic parameters. The age of AIS girls (Mean Cobb: 31(12() and healthy girls was similar (13.01.2 for AIS and 12.71.1 for control). The mean Z-score femoral neck BMD of AIS was -0.62. AIS had lower BUA (118.515.6 and 124.79.3; p=0.062), VOS (1444.042.8 and 1448.136.7; p>0.08) and SI (357.279.4 and 386.457.2; p>0.07) than those of the control. Femoral neck BMD was significantly correlated with BUA, VOS and SI (r=0.347, 0.341 and 0.443, respectively; all p<0.01). The current study demonstrated all the QUS parameters were found lower in AIS than those of controls. Femoral neck BMD showed a weak to moderate correlation with ultrasonic parameters. Data indicated a potentially poor bone quality which may reflect microarchitectural abnormalities in addition to low bone mass in AIS girls. Previous study demonstrated that low bone mass measured by DXA was a risk factor in curve progression in AIS. Using noninvasive QUS assessment, further study on the association between bone quality and progression could be of great clinical prognostic interest and may also help in the understanding of bone structural properties changes in AIS patients.

P547SA. EVALUATION OF TECHNICAL POSITIONING DURING DXA MEASUREMENTS Özgüçlü E, Özçakar L, Çetin A, Akinci A; Hacettepe University Medical School, Physical Medicine and Rehabilitation, Ankara, Turkey Aims: Whether for accurate diagnosis of osteoporosis or for adequate treatment, proper dual-energy X-ray absorptiometry (DXA) measurements required and recommended technical positions for specific body regions should be achieved. The aim of this study was to assess the accurateness of technical positions for hip and spine regions according to recommendations of the International Society for Clinical Densitometry (ISCD). Methods: 113 patients paired hip and spine DXA reports were reviewed and positions were evaluated in accordance with ISCD recommended positions. In spine, four technical positions were assessed; whether the spine is in the midline of the image and is in a straight line, both iliac crests come into view, half of the bodies of T12 and L5 vertebrae are seen. For the hip, three technical positions were considered: whether the femoral shaft is straight, the trochanter minor is not visualized or is seen slightly, the ischium and the trochanter major are seen. Discordant positions according to these criteria were accepted as technically invalid positions. Results: Out of 113 hip and spine DXA reports, 52 hip and 19 spine DXA reports fulfilled all the above mentioned criteria. Ten patients’ DXA reports (<10%) were technically valid for both regions. In 27.4% of the spine DXA reports, the spine was not in the midline. The spine was not straight in 48.7% of the images. 38.9% of the spinal images did not comprise both iliac crests, and 40.7% did not include T12 and L5 vertebrae -at least half of the corpus. In hip, 40.7% of the femoral shaft was deviated. In 24.8% of the hip images, minor trochanter was seen more than the recommended size and 6.2% of the images did not include the ischium and the greater trochanter. Conclusions: We found the ratio of invalid positions surprisingly very high. This may stem from local technical problems, but no matter due to what reason, such misinterpretations would definitely aﬀect clinicians in an inappropriate way. Thus we suggest that relevant inconveniences should be kept in mind both by clinicians and the technical staﬀ for better production and prompt estimation of bone mineral density measurements.

P548SU. ACCURACY OF T-SCORES FOR DIAGNOSING OSTEOPOROSIS Faulkner KG, Weynand LS, Wacker WK, Barden HS; GE Healthcare, Madison, USA In the field of bone densitometry, accuracy error has referred to the diﬀerence between a measured value and the ‘‘true’’ value, while precision error is a measure of the variability of the test. In the statistical field, the diﬀerence between a measured value and truth

is more often called ‘‘bias’’ rather than accuracy error. Accurate T-scores require a BMD measurement that minimizes both bias (oﬀset) errors and precision (variability) errors that influence the T-score. In this study, we determined the influence of precision error on accuracy of T-scores for the diagnosis of osteoporosis. Reported Lunar Prodigy expert precision (g/cm2) in women (mean age 63 years, SD 9) was 0.010 at L1-L4 spine, 0.013 at femoral neck, and 0.008 for total hip (1). Reported Lunar Prodigy precision at clinical centers in subjects (mean age 61 years, SD 10) was 0.014 at L1-L4 spine, 0.025 at femoral neck, and 0.012 at total hip (2). Assuming BMD is normally distributed, the 95% confidence interval (CI) for a single T-score measurement can be estimated using the following equation: 95% CI = T-score 1.96 (Precision/Population SD) Using the population SD from the Lunar Prodigy reference database of 0.12 g/cm2 for these skeletal sites, clinical DXA T-scores have 95% CI of 0.2 for spine and total hip and 0.4 for femoral neck. Therefore, T-scores variations of 0.2 or less for spine or total hip and 0.4 for femoral neck should not be considered significant when diagnosing osteoporosis. Minimizing precision error can increase confidence in T-scores by reducing the confidence interval to less than 0.2 for spine and total femur and to 0.2 for femoral neck. 1. Shepherd WCO 2004 2. Weynand ASBMR 2004

Table 1: 95% CI for T-scores based on Expert and Clinical Precision

Expert Clinical

Spine

Neck

Total Hip

0.16 0.23

0.21 0.41

0.13 0.20

P549MO. REDUCED BONE MASS IN DAUGHTERS OF WOMEN WITH OSTEOPOROSIS Qin YJ, Zhang ZL, Huang QR, He JW, Hu YQ, Li M, Liu YJ; Osteoporosis Research Unit, Center for Preventing and Treating Osteoporosis, Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China Objective: To determine whether premenopausal daughters of women with postmenopausal osteoporosis have lower peak bone mass than other women of the same age, and to analyze the related risk factors aﬀecting bone mass variation. Methods: According the bone mineral density (BMD) values measured by dual-energy x-ray aborptionmetry at lumber spine 1–4 (L1–4) and proximal femur, 126 mothers with postmenopausal osteoporosis, 126 of their premenopausal daughters, 136 normal postmenopausal mothers, and 136 their premenopausal daughters were recruited from 401 nuclear families including one aged 20 w 40 healthy premenopausal women of Han ethnicity and their healthy parents lived in Shanghai. In addition, the daughters of fathers with osteoporosis or osteopenia were excluded. Results: The daughters of mothers with osteoporosis had lower BMD in all measured sites (all P < 0.001). As compared with daughters of normal mothers, the weight of daughters of mothers with osteoporosis was lower (P < 0.05). Multivariate regression analysis showed that weight was most significantly associated with BMD at all measurement sites in premenopausal daughters. Weight contributed to 9.4%, 16.5%, and 16.6% of BMD variation at L1–4, femoral neck (Neck) and trochanter (Troch) sites, respectively. When weight was excluded in the model, lower BMD of mothers tended to be the most important factor aﬀecting BMD variation, it contributed to 5.1%, 5.3%, and 4.2% of BMD variation at the L1–4, Neck and Troch sites, respectively. Conclusion: The daughters of mothers with osteoporosis have reduced peak bone mass. It is likely due to lower weight of daughter and lower bone mass of mother.

S286

P550SA. PERIARTICULAR DEMINERALIZATION IN RHEUMATOID ARTHRITIS DETECTED BY DIGITAL X-RAY RADIOGRAMMERTY AND PERIPHERE MULTISITE QUANTITATIVE ULTRASOUND Pfeil A1, Boettcher J1, Mentzel HJ1, Petrovitch A1, Lehmann G2, Schaefer ML1, Malich A3, Kaiser WA1, Wolf G2, Hein G2; 1 Institute of Diagnostic and Interventional Radiology, FriedrichSchiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: The development of secondary osteoporosis in rheumatoid arthritis (RA) is recently well recognized, showing demineralization at axial and in particular at periarticular peripheral bone sites. The purpose of our study was to evaluate the ability of multisite quantitative ultrasound (QUS) compared to digital x-ray radiogrammetry (DXR) for the quantification of cortical bone loss dependent on the severity of RA. Patients and Methods: 53 patients with verified RA underwent measurements of QUS (Sunlight multisite Omnisense 7000, Sunlight Medical Ltd., Tel Aviv, Israel) with estimation of the speed of sound (QUS-SOS) at the distal radius and at phalanx III. Also bone mineral density (DXR-BMD) and metacarpal index (DXRMCI) were estimated on metacarpals II-IV using DXR-technology (Pronosco X-Posure System Version 2.0, Pronosco/Sectra ASS, Denmark). Additionally, Larsen score and Steinbroker stage were assessed by digital radiographs. Results: Regarding the Larsen score the DXR-BMD showed a significant decline from -25.9% and DXR-MCI also revealed a reduction upto -38.6%. QUS-SOS (radius) decreased from score 1 to score 5 with -2.6% (p=n.s.). Regarding QUS-SOS (phalanx) a reduction of –3.9% (p=n.s.) was observed. For Steinbroker stage DXR-BMD significantly decreased with -27.1% from stage 1 to stage 4. In this context the relative reduction of DXR-MCI was -38.6% (p<0.001). QUS-SOS (radius) showed a decline of -2.7% (p=n.s.), whereas QUS-SOS (phalanx) documented a relative reduction with -4.0% (p=n.s.). Conclusion: Digital x-ray radiogrammetry revealed a significant reduction of DXR-BMD as well as DXR-MCI dependent on the severity of RA. Regarding multisite QUS (radius and phalanx) no significant severity dependent demineralization was verified. Consequently, digital x-ray radiogrammetry is a promising tool for the diagnosis of periarticular bone loss in RA.

P551SU. DEFINING OSTEOPOROSIS IN HIP FRACTURE PATIENTS Crilly RG, Kloseck M, Nassur R; University of Western Ontario, London, Canada Aim: Not all patients with a hip fracture have osteoporosis and osteoporosis treatment is not appropriate for all such subjects. The purpose of this study was to explore ways of defining osteoporosis in these patients. The type of hip fracture, the presence of other osteoporosis fractures, and bone density and their interrelationships were explored to see if a case could be made to classify some as osteoporotic and others not. Methods: 89 hip fracture patients – 28 male and 61 female – passing through a rehabilitation program were studied. All were within three months of the hip fracture. All subjects had spinal x-rays performed and bone mineral density (DXA) performed. History of fragility fractures (spine, wrist, humerus, ribs, pelvis) was obtained. Results: Mean age of patients was 81.6 6.3 years. 90% of fractures were classified as either subcapital (51.8%) or intertrochanteric (38.8%). These did not diﬀer in age (80.44 6.8 vs. 82.0 6.4 years) but the intertrochanteric fractures had more fragility fractures. Relative proportions of those with fragility fractures in subcapital vs. intertrochanteric fractures are as follows: compression fractures 16.2% vs. 43.3% (p=014); wrist fractures 12.8% vs. 25%. (NS); all fragility fractures 41% vs. 64.3% (NS). Similar proportions of each hip fracture type had experienced previous falls (55.5% vs. 51.9%) and were of similar weight (64.5 11.7 vs. 64.7 14.8 kg.). Those with compression fractures did not diﬀer from those with no compression fractures in any BMD measurement. For spine T-score, the values were: sub-capital -1.44 1.65 vs. intertro-

chanteric –1.66 1.5. Highest BMD was found in subcapital patients with no compression fracture. Spine density was just significantly lower in the intertrochanteric fracture patients (p=.05). Conclusions: These data make a case for considering intertrochanteric fractures as reflecting osteoporosis presenting, as they do, with a greater number of other fragility fractures. Bone density measurements fail to provide clear guidance regarding treatment decisions. The type of hip fracture and the presence of other fragility fractures might be more indicative of osteoporosis in hip fracture patients.

P552MO. PEAK BONE MASS DETERMINATION IN THE JORDANIAN FEMALE POPULATION Masri BK1,2, Azar ES1,2, Faqih AM2,3, Sornay-Rendu E4,5, Duboeuf F4,5, Delmas PD4,5; 1 Jordan Osteoporosis Centre, Jordan Hospital, Amman Jordan, 2Jordanian Osteoporsis Prevention Society, Amman, Jordan, 3Jordan University, Amman, Jordan, 4Inserm Research Unit 403, Lyon, France, 5Université Claude Bernard, Lyon 1, France In order to establish the normative bone mineral density (bmd) in jordanian females, a representative random sample of 1241 females aged 20 to 89 years were interviewed in their homes. They were selected using a stratified three-stage cluster sample covering urban and rural regions in the entire country as drawn by the jordanian department of statistics. 821 women met the study criteria and underwent dual-energy x-ray absorptiometry measurement (hologic delphi a) as well as other laboratory investigations. 483 of those women were pre-menopausal. Their dxa measurements were used to define the peak bone mass (pbm) at the regions of interest (l1-l4 spine, total hip, trochanter and femur neck). Peak bone mass was achieved in women aged 20–29 years at the spine (0.995gm/cm2) and femoral neck (0.794gm/cm2) and in women aged 40–49 years for total hip (0.936gm/cm2) and trochanter (0.686gm/cm2). Pbm was found to be slightly lower than the french ofely cohort and the north american data provided by hologic, but close to the lebanese data. Correcting the t-scores at the various sites using the new pbm measurement allowed us to determine the bmd of normal jordanian women and compare the results with us and european reference data. By these criteria, the prevalence of osteoporosis seems to be lower than in the west. We suggest that these measurements could be extrapolated to neighbouring countries because of ethnic, social and dietary similarities and thus help determine the magnitude of osteoporosis in the region.

P553SA. INFLUENCE OF SOFT TISSUE SWELLING ON THE MEASUREMENT OF THE SPEED OF SOUND (SOS) BY A NEW MULTISITE QUANTITATIVE ULTRASOUND (QUS) Pfeil A1, Boettcher J1, Mentzel HJ1, Petrovitch A1, Lehmann G2, Schaefer ML1, Kramer A1, Malich A3, Kaiser WA1, Hein G2, Wolf G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: To evaluate inter- and intraobserver reproducibility of multisite QUS considering the eﬀects of body mass index (BMI) for healthy individuals and quantifying the impact of disease activity in patients suﬀering from rheumatoid arthritis (RA). Methods: For the measurement of the SOS on phalanx III and radius, a multisite QUS device (Sunlight multisite Omnisense 7000, Sunlight Medical Ltd., Tel Aviv, Israel) was used. Inter- and intraobserver reproducibility were measured including three healthy volunteers from each BMI group (BMI<25, mean:21.7) and overweight controls (BMI>25, mean:32.6), and also six RA patients with advanced disease activity (n=3, CRP>25mg/l) as well as low disease activity (n=3, CRP<25mg/l). Interobserver reproducibility of QUS-SOS was evaluated by 3 trained observers with 10 repeated measurements at the distal radius and third phalanx of patients with RA versus healthy controls for each subgroup at the

S287 same day. To verify intraobserver reproducibility a single observer performed 10 repeated QUS-SOS estimates for all 12 individuals. Results: For healthy controls the intraobserver reproducibility for the QUS-SOS ranged between CV=0.90% (normal weight,radius) and CV=2.55% (overweight,phalanx). The overweight group showed higher CV values (phalanx CV=2.55%, radius 1.43%) compared to the normql weight group (phalanx CV=1.05%, radius 0.90%). The intraobserver reproducibility of measurements taken from patients with advanced RA were limited (phalanx CV=1.88%, radius 1.03%). Interobserver reproducibility for healthy individuals showed the highest coeﬃcient of variation for overweight individuals regarding QUS-SOS at the distal radius (CV=1.79%) and QUS-SOS at the phalanx (CV=2.17%). Improved results were observed for the BMI group<25 (radius:CV=1.66%, phalanx: CV=1.40%). Interobserver reproducibility showed minor CV values for the advanced disease activity group (CV=0.94%) compared to patients with low RA activity (CV=0.65%) measured by QUS-SOS (radius). Regarding QUSSOS (phalanx), increased coeﬃcients of variation with CV=1.81% (low disease activity) versus CV=1.89% (advanced disease activity) were observed. Conclusion: QUS-SOS is characterized by a reduced short-term precision, which is significantly more noticeable in healthy individuals with pronounced BMI and patients with advanced RA. It may be concluded that multisite QUS is of limited priority for patients with active inflammation of the soft tissue in RA and with an elevated BMI, using measurements at the phalanx.

P554SU. CROSS CALIBRATION OF GE-LUNAR IDXA AND PRODIGY BONE DENSITOMETERS Cole L, Mossman E, McClung M; Oregon Osteoporosis Center, Portland, Oregon, USA Bone mineral density (BMD) measurement at the lumbar spine and proximal femur with dual-energy X-ray absorptiometry (DXA) is the acknowledged gold standard for diagnosing and monitoring patients with osteoporosis and assessing fracture risk. The recently introduced Lunar iDXA (GE Healthcare, Madison, WI) fan-beam densitometer uses a new CZT detector that provides markedly improved image quality. We evaluated the BMD performance of the iDXA compared to the Lunar Prodigy at the spine and proximal femur. Thirty postmenopausal women (mean age 61.3 years) were measured once at the spine on both devices, and 29 postmenopausal women (mean age 61.8 years) were measured once at the femur on each of the 2 DXA systems.

BMD measurements for Prodigy and iDXA were highly correlated (r_ = 0.99) at the L1-L4 spine, femur neck, trochanter, and total femur. Neither slope nor intercept diﬀered significantly from the identity values of 1 and 0 respectively (alpha=0.05). There was a small bias of +0.004 g/cm_ for total femur by paired t-test. We conclude that BMD agreement between iDXA and Prodigy densitometers was excellent at the spine, femur neck, trochanter, and total femur measurement sites. This study was funded by a grant from GE Healthcare.

P555MO. QUANTITATIVE ULTRASONOMETRIA OF RADIAL AND TIBIAL BONES IN HEALTHY CHILDREN Moisseyeva TY, Scheplyagina LA, Samokhina EO; Research Center of Child Health, Russian Academy of Medical Sciences, Moscow, Russia Objective: To assess values of bone strength in healthy children depending on age and gender. Material and methods: In all, 634 healthy children (298 boys and 336 girls) aged from 3 to 16 years and residing in Moscow were examined. Skeletal bone strength was evaluated by rate of bone speed of ultrasound (SOS, m/s) at the distal part of radius and at the mid-shaft tibia. All measurements were made using device ‘‘Omnisense 7000S’’ (Sunlight Medical Ltd, Israel). Data statistic was processed with integrated software package ‘‘STATISTICA 6 for MS Windows’’. Results: It is established that in examined children SOS values in both sites were noted for variability and, as a rule, they were the higher the older was child independently of gender. Overall, in children at the age from 3 to 16 years SOS values increased from 3588.2 m/s to 3829.08 m/s (+6.7%) in boys and from 3551.4 m/s to 3978.09 m/s (+12%) in girls. During pubertas, SOS values of radius increased in boys and girls by 2.2% and 5.6%, respectively. Relationship between SOS values of radius and age (r=0.4; p=0.000), body height (r=0.3; p=0.000) and body mass (r=0.3; p=0.000) is established. Analysis of data of tibia quantitative ultrasonometria in children at the age from 3 to 16 years revealed that the level of SOS value of mid-shaft tibia increased from 3527.1 m/s to 3812.55 m/s (+8%) in boys and from 3489.83 m/s to 3795.4 m/s (+8.7%) in girls. During pubertas, the SOS value of tibia increases in boys and girls by 6.4% in and 5.3%, respectively. Relationship between SOS value of tibia and age (r=0.4; p=0.000), body height (r=0.3; p=0.000) and body mass (r=0.3; p=0.000) is revealed. Relationship between SOS value of radius and SOS value of tibia (r=0.4; p=0.000) is also established. Conclusions: Age-specific values of quantitative ultrasonometria of radius and tibia in examined children can be applied as age-specific standards in assessment of bone strength in healthy and ill children.

P556SA. DETECTION OF VERTEBRAL FRACTURES: COMPARISON OF GE LUNAR PRODIGY WITH RADIOGRAPHIC IMAGES del Rio L1, Di Gregorio S1, Rosales J1, Guañabens N2, Peris P2, Schaaf N3, Vila R1, Pascual J1, Garcia M1, Sole C1, Bonell E1, Bambalere D1; 1CETIR Centre Medic, Barcelona, Spain, 2Hospital Clinic of Barcelona, Barcelona, Spain, 3Catholic University Leuven, Leuven, Belgium The detection of vertebral fractures is important in the clinical evaluation of osteoporosis. Qualitative evaluation of radiographs has been the conventional method of detecting these deformities. Fracture definition, however, can vary considerably between observers. Quantitative techniques with lateral radiographs assess the shape of a vertebra using posterior, middle and anterior vertebral heights. Typically, the 6 measurement points used to obtain these heights are positioned manually. Deformities are identified by comparing height ratios to reference values. The aim of this study was to compare vertebral fracture assessment (VFA) by dual-energy x-ray absorpiometry (DXA) (Lunar Prodigy, GE Healthcare) and radiographic morphometry (MRX). Vertebral fractures were identified by two nonradiologists using the Genant semi-quantitative technique with

S288 Lunar Prodigy lateral spine images. These results were compared to semi-quantitative evaluations of the spine radiographs performed by a radiologist. We evaluated data of 42 women aged 33–84 years. Compared to spine radiographs, VFA exhibited a sensitivity of 71% for grade 2 & 3 compression fractures, and 100% for grade 2 & 3 wedge and biconcavity fractures. Two fractures that were undetected by VFA: one grade 1 compression fracture and one grade 1 wedge fracture. All patients identified as without fracture by radiographs were correctly classified as without fracture by VFA. In conclusion, the low dose dual-energy Vertebral Fracture Assessment technique on GE Lunar densitometers provides a rapid, convenient and economical method for non-radiologists to identify patients with, and without, vertebral fractures. This capability should enhance care of osteoporotic patients and may oﬀer an eﬃcient screening technique for osteoporosis.

P557SU. ADEQUATE SERUM COPPER CONCENTRATION COULD IMPROVE PEAK BONE MASS AND POSTPONE BONE LOSS IN WOMEN Mir E1, Hossein-nezhad A1, Bahrami A2, Bekheirnia MR1, Shafahi AR1, Larijani B1; 1Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran, 2 Tabriz University of Medical Sciences, Tabriz, Iran Aims: To determine the protective impact of eﬃcient serum copper concentration on BMD in women and to asses its impression on bone. Methods: 600 healthy women through a national project in Iran, IMOS, were selected via a cluster random sampling and enrolled the study. They were divided to premenopaused (404/600, 67.7% of total) and postmenopaused (190/600, 32% of total) groups. BMD was measured by DXA method for hip and lumbar spine. Morning serum copper concentration was determined by atomic absorption spectrometry. Results: Mean age was 40.9214.8yr. Mean serum copper concentration=105.8540.15 µg/dl and mean BMI=27.134.81 kg/m2. Totally 2.4% was smoking, 5% had regular physical activities three times a week and 17.5% were copper deficient. There was no significant diﬀerence in serum copper concentration in pre and post menopaused women. There was no significant variation concerning copper depletion among two groups, 17.3% of premenopaused were copper deficient vs. 16.8% of postmenopaused. Postmenopaused group findings: Prevalence of osteoporosis was 12.9% in copper deficient persons vs. 11.3% in normal serum copper ones. No significant diﬀerence found according to serum copper concentration and BMD after adjustment for BMI, age and serum vitamin D. Bone loss trend over the spine could be postponed to 5 years later in those with suﬃcient serum copper values compared with copper depleted ones, but this relation did not exist for hip. Premenopaused group findings: Women with serum copper level above 105µg/dl revealed a significant diﬀerence in hip BMD compared to those with less copper concentration 1.020.13gr/ cm2 vs. 0.970.13gr/cm2 (Pvalue=0.001). Actually, BMD was about 5% greater in women with more serum copper concentration. These relations were not significant in spine 1.210.13 gr/cm2 vs. 1.90.19gr/cm2. After adjustment for BMI, age and serum vitamin D, copper had an independent eﬀect on determining hip BMD in premenopaused women (Pvalue=0.001). Conclusion: copper has a significant association with hip BMD in premenopaused and also an adjourning factor for spine bone loss in postmenopaused women. So providing suﬃcient amount of this trace element could be useful for attaining peak bone mass and decelerate osteoporosis trend in future.

P558MO. DEPENDENCE OF METACARPAL INDEX AND BONE MINERAL DENSITY ON BODY MASS INDEX EVALUATED BY DIGITAL X-RAY RADIOGRAMMETRY (DXR) Boettcher J1, Pfeil A1, Petrovitch A1, Teufl F3, Lehmann G2, Schaefer ML1, Eidner T2, Malich A4, Mentzel HJ1, Kaiser WA1,

Wolf G2, Hein G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Clinic of Diagnostic Radiology, Stollberg, 4Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: In addition to many established osteodensitometric methods, digital x-ray radiogrammetry is considered to be a reliable and precise method for the measurement of cortical bone mineral density (BMD) on metacarpals. To investigate the association between diﬀerent body constitution characteristics and osteodensitometric parameters measured by DXR in healthy adults. Patients and Methods: In a prospective study 246 healthy individuals without bone tissue-aﬀecting diseases in their clinical history underwent analysis by DXR. Radiographs of the nondominant hand have been used for the measurements of BMD, porosity index (PI) and metacarpal index (MCI) by the Pronosco X-Posure System (Version 2, Sectra, Sweden), which digitized images with a scanner and derived radiogeometrical parameters from the three middle metacarpals. For each person height, weight and body mass index (BMI) were recorded. All individuals were divided into subgroups as follows: Underweight (BMI < 25), normalweight (BMI 20–25) and overweight (BMI > 25). Results: For all individuals and for all BMI subgroups there was a close association between both height (0.55
P559SA. DIFFERENTIAL EFFECTS OF CASEIN-, WHEY- AND SOY-BASED MILK DIETS ON BONE IN NEWBORN PIGS Budek AB1, Bjørnvad CR1, Mølgaard C1, Vestergaard M2, Pulkkinen P3, Michaelsen KF1, Sangild PT1; 1Department of Human Nutrition and Centre for Advanced Food Studies at Royal Veterinary and Agricultural University, Denmark, 2Department of Animal Health, Welfare and Nutrition at Danish Institute of Agricultural Sciences, Foulum, Denmark, 3Department of Medical Technology at University of Oulu, Oulu, Finland Infancy is an important period for skeletal growth and formula feeding is extensively used during this time. Our aim was to investigate the eﬀects of proteins from infant formulas on bone development in newborn pigs. Nineteen term piglets were fed milk diets (15 ml/kg/1Y h) by orogastric tubes. They were randomly assigned to three groups with diﬀerent protein sources (casein (C) n=5; whey (W) n=9; soy (S) n=5) but with equal content of fat (7.6%), total protein (5.5%), lactose (5.3%), calcium (0.19%) and phosphorus (0.14%). After 7 days the pigs were euthanized. Fasting blood was collected and serum analysed for insulin-like growth factor-1 (IGF-1) and insulin. The femora and tibiae were dissected, and volumetric bone mineral content (BMC), bone mineral density (BMD) and geometric parameters of cortical bone were measured by quantitative computed tomography. Bone mechanical strength was measured by a three-point bending test. During the study, the average group weight increased 8.8% for W, decreased 4.6% and 4.8% for W and S, respectively (p=0.03). After 7 days trabecular BMD at femoral neck (FN) was lower in W (LSMEANS 319.6 mg/cm3) compared with C (LSMEANS 351.0 mg/cm3) and S (LSMEANS 363.2 mg/cm3) (p=0.02).

S289 Trabecular BMC at FN was higher in C (LSMEANS 9.0 mg/mm) when compared with S (LSMEANS 6.8 mg/mm) but not with W (LSMEANS 7.9 mg/mm) (p=0.02). At proximal tibia, W had lower trabecular BMD (LSMEANS 269.2 mg/cm3) compared with C (LSMEANS 305.5 mg/cm3) and S (LSMEANS 296.6 mg/cm3) (p=0.01). Endocortical circumference of midshaft tibia tended to be smaller in C (p=0.053). Cortical BMD and BMC were not diﬀerent between the groups at any sites (all p>0.1). There were no significant changes in bone mechanical strength (p=0.4). Endtime IGF-1 was not diﬀerent between the groups (p=0.6). Most of serum insulin samples were under the detection limit (0.025 ng/ml). The pigs fed C had improved bone quality at trabecular sites already after seven days. Similar eﬀects of milk casein may be present in newborn infants. Further studies with longer duration and higher sample size should be done.

in subsets of this group. The total body precision assessment was conducted following ISCD recommendations in 30 adults (17 males/13 females). Their mean (range) age, BMI and total body BMD T-scores were 34.9 (20–69.2) years, 24.4 (18.3–30.8) kg/m2 and 0.4 (-1.7 – 2.8) respectively. As previously reported, BMD at the L1–4 spine, mean total femur and mean femur neck was very highly correlated (r2 R 0.98) between these two instruments. Similar correlations were observed for total body BMD and BMC (r2 = 0.96) and for one-third radius BMD (r2 = 0.98). Additionally, total body BMD precision (%CV) was similar (0.87% iDXA, 0.65% Prodigy) while total body BMC precision was better (p < 0.0001) with iDXA (0.46%) than with Prodigy (1.71%). In conclusion, there is excellent total body and forearm BMD correlation between iDXA and Prodigy densitometers and enhanced total body BMC precision with iDXA.

P560SU. ABDOMINAL THICKNESS AND ITS IMPACT ON THE ACCURACY OF BONE DENSITOMETRY MEASUREMENTS WITH THE LUNAR IDXA SCANNER

P562SA. COMPARISON OF X-RAY DENSITOMETRY AND ULTRASONOMETRY OF THE HEEL: PREDICTION OF SPINE/HIP T SCORES

O’Connor M.K.; Department of Radiology, Mayo Clinic, Rochester, MN, USA

Michalská D, Stepan JJ; 3rd Department of Internal Medicine, Charles University Faculty of Medicine, Prague, Czech Republic

Aim: To determine the eﬀect of increased abdominal thickness on the accuracy of bone mineral density (BMD) measurements on a new dual energy x-ray bone densitometer (GE Lunar iDXA system). Methods: The iDXA system is a conventional fan-beam DXA device which utilizes a more powerful x-ray tube and a higher resolution CZT detector than the Prodigy system. The iDXA unit was evaluated using 2 spine phantoms. The Hologic spine phantom consisted of 5 vertebrae embedded in Lucite and had a BMD of w1 gm/cm2. The RSD phantom consisted of a spine phantom in a water bath. The spine was sliced into 2 sections to provide spines with BMD values of w0.6 gm/cm2 and 1.3 gm/cm2. Increased abdominal thickness was achieved both by increasing water depth and thickness of Lucite sheets on top of the phantoms. Simulated abdominal thicknesses ranged from w10 cm up to w37 cm. Scans of the spine were acquired at 3 diﬀerent x-ray fluxes (corresponding to thin, normal and thick mode for patient studies). For each phantom, 5 scans were acquired in each mode at each depth. Mean and standard deviation of BMD and eﬀective abdominal thickness were recorded. Results: At high and medium BMD values, results for all 3 scan modes were identical for abdominal thicknesses of 25 cm or less. At the low BMD value, thin mode was required for thicknesses below w17 cm to prevent detector saturation. Thin mode yielded precise results up to w25 cm thickness. Normal mode gave consistent results up to w30 cm, while thick mode could accurately measure BMD in w35 cm of tissue. At thickness beyond the limit of each mode, apparent BMD values increased dramatically. Conclusions: The iDXA bone densitometer should be capable of image patients with a supine abdominal thickness of up to 35 cm. Coupled with an imaging table capable of supporting up to 200 kg weight, this should enable accurate measurement of bone mineral density in patients with severe ascites and patients who are morbidly obese.

Bone mineral density (BMD) measured at spine and femur sites with DXA represent the gold standard for identifying osteoporotic subjects. Peripheral devices that measure the calcaneus however are more portable and less expensive and may be cost eﬀective for identifying individuals at risk who otherwise might be missed. We examined the correlation of quantitative ultrasound (QUS) and DXA at the calcaneus taken with two peripheral devices and evaluated their ability to identify subjects with osteoporosis at spine or hip. One hundred ninety three women (mean age 48 yrs; SD 15; range 19–80) were measured at spine and femur with the Lunar DPX-L and at the heel (calcaneus) with the Lunar PIXI (DXA) and Lunar Achilles (QUS) devices (GE Healthcare). Diagnosis of osteoporosis (T-Score % 2.5) and osteopenia (-2.5 < T % -1.0) was based on the WHO guidelines. The lowest T-scores for central regions were compared with peripheral T-scores for heel QUS stiﬀness and DXA BMD. Receiver operator characteristics (ROC) curves were used to evaluate the ability of the peripheral heel measurements (QUS and DXA) to discriminate between women with normal BMD and those with osteoporosis and osteopenia at the spine and hip. The correlation between the heel DXA and QUS T-scores was r = 0.77. The area under the ROC curve (AUC) for discriminating subjects with osteoporosis at the spine and/or hip was 0.795 for Achilles and 0.842 for PIXI. Slightly lower, but nearly identical AUC scores (Achilles=0.788, PIXI=0.830) were determined for discriminating subjects with either osteoporosis or osteopenia at the spine and/or hip (Table 1).

P561MO. AN EVALUATION OF GE HEALTHCARE LUNAR PRODIGY AND IDXA DENSITOMETERS Krueger D, Checovich M, Vallarta-Ast N, Gemar D, Clodfelter R, Binkley N; University of Wisconsin Osteoporosis Clinical Research Center, Madison, WI, USA GE Healthcare has recently introduced the Lunar iDXA, a new fan-beam densitometer. We previously reported excellent spine and femur BMD agreement between an iDXA and Prodigy densitometer. Here we report the comparability of total body and forearm measurements obtained using these same instruments. In 245 subjects, 153 women, 91 men (mean age 52.8 years, range 20–91.5) measurements of the lumbar spine and bilateral proximal femur were obtained in routine clinical manner. Their mean (range) lowest BMD T-score at the L1–4 spine, mean total femur and mean femur neck was –0.9 (3.4 to –4.3). Total body, total body precision and non-dominant forearm measurements were obtained

Table 1: Area Under the Curve (AUC) for Achilles and PIXI. T Score Diagnosis Osteoporosis at spine and/or hip Osteoporosis or osteopenia at spine and/or hip

Achilles (AUC)

PIXI (AUC)

P value

0.795

0.842

Ns

0.788

0.830

Ns

Conclusion: The ROC analysis showed nearly identical AUC values for both devices. The PIXI and Achilles Plus are similar in ability to predict osteoporosis and osteopenia at the spine and hip.

P563SU. OSTEOPOROSIS RISK ASSESSMENT BY ORTHOPAEDIC SURGEONS: HOW GOOD ARE WE? Robinson E1, Brettle P2, Birrell F2, Reed MR1; 1Department of Orthopaedic and Trauma Surgery, 2Department of Rheumatology, Wansbeck General Hospital, Ashington, UK Aim: to determine if orthopaedic surgeons meet recognised standards in risk assessment for osteoporosis

S290 Methods: standards were determined from the local 2004 Northumberland guidelines. Patients with fragility fractures of the distal radius were identified from hospital records and the number referred for DXA was determined during two 3-month periods (April to June and October to December 2004). Patient notes were obtained to confirm the fracture type as fragility. Guidelines were reinforced during the interim period. Results: during the first audit cycle there were forty-three patients (36 women and 7 men) with a mean age of 73 while in the second cycle there were fifty-two patients (46 women and 6 men) with a mean age of 68 years. In the first cohort 3 patients were referred for a DXA scan (7%), while in the second, 16 (31%) were referred. The diﬀerence in referral rates between the two groups is statistically significant (p<0.05). Conclusion: risk assessment for osteoporosis by orthopaedic surgeons improves significantly following reinforcement of guidelines but still remains inadequate overall.

P564MO. DEFINITION OF A POPULATION-SPECIFIC DUAL-ENERGY X-RAY ABSORPTIOMETRY REFERENCE STANDARD IN ISFAHANI WOMEN Bonakdar ZS, Karimzadeh H, Motaghi P; Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Aims: There is increasing evidence that correct interpretation of bone mineral density (BMD) measurement by dual-energy x-ray absorptiometry(DXA) requires a population-specific reference range. Therefore, we collected data on age 20–80 years to obtain reference values of BMD for Esfahanian women. In this study we measure prevalence of osteopenia and osteoporosis in postmenopausal women. Methods: A total of 1118 healthy Isfahani women volunteers, aged 20–80 years, were recruited for this study. BMD measurements were done using the Lunar DPX-IQ. We calculated peak bone mass(PBM), reference curves of BMD, prevalence of osteopenia and osteoporosis according to WHO criteria, at the lumbar spine and femoral neck. Results: Mean and standard deviation of BMD measurements, the prevalence of osteopenia and osteoporosis at each site were calculated. The prevalence of osteopenia at the lumbar spine was 28.9% in the group aged 51–55 years old, 36.5% in the group aged 56–60, 38.4% in the group aged 61–65, 41.1% in the group aged 66–70, 45.5% in the group aged >70. The prevalence of osteoporosis at the lumbar spine was 7.9% in the group aged 51–55 years old, 19.6% in the group aged 56–60, 26% in the group aged 61–65, 32.1% in the group aged 66–70, 31.8% in the group aged >70. The prevalence of osteopenia at the femoral neck was 28.3% in the group aged 51–55 years old, 39.9% in the group aged 56–60, 43.8% in the group aged 61–65, 50% in the group aged 66–70, 68.2% in the group aged >70. The prevalence of osteoporosis at the femoral neck was 2.6% in the group aged 51–55 years old, 2% in the group aged 56–60, 12.3% in the group aged 61–65, 14.3% in the group aged 66–70, 22.7% in the group aged >70. Conclusions: Our data used a population-specific reference range for DXA measurements and estimated the prevalence of osteopenia and osteoporosis.

P565SA. THE IMPACT OF IMAGE CAPTURING PARAMETERS ON CORTICAL BONE MINERAL DENSITY MEASURED BY DIGITAL X-RAY RADIOGRAMMETRY (DXR) Boettcher J1, Pfeil A1, Petrovitch A1, Lehmann G2, Schaefer ML1, Heinrich B1, Linss W3, Malich A4, Kaiser WA1, Hein G2, Wolf G2; 1 Institute of Diagnostic and Interventional Radiology, FriedrichSchiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Institute of Anatomy I, Friedrich-Schiller-University Jena, 4Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: To evaluate the importance of diﬀerent image capturing conditions, which may influence the characteristics of radiographs and consequently may impact calculation of bone mineral density (BMD) using digital x-ray radiogrammetry (DXR). The investi-

gated parameters include film focus distance (FFD), film quality (sensitivity of 200 versus 400), film brand (Kodak T-MAT-Plus, Agfa Curix), exposure level (mAs) and tube voltage (kV). Furthermore, the impact of imaging technology used in terms of conventional radiographs versus digital x-ray images is considered (Siemens Polydoros SX 80, Diagnost Philips Optimus), either in the original digital format or through digitization of printouts. The reproducibility of DXR-BMD and metacarpal index (MCI) are compared across these diﬀerent image modalities. Patients and Methods: Radiographs of the left hands of deceased males were acquired three times using systematically varied parameters: 4–8 mAs, 40–52 kV, FFD: 90–130 cm, film sensitivity: 200/400 and image modality/source (conventional versus original digital radiographs as well as digital printouts). All BMD and MCI measurements were obtained with DXR technology (PronoscoXposure system, Sectra Pronosco A/S, Denmark), which is originally calibrated for analysis of conventional radiographs. Results: BMD calculation was not noticeably aﬀected by changes of FFD (conventional: CV=0.98%), exposure level (conventional: CV=0.49%; digital: CV=0.35%), film sensitivity/film brand (conventional: CV=0.33%/0.49%), but was influenced by tube voltage (conventional: CV=1.32% for Agfa and CV=0.99% for Kodak; digital: CV=0.57% for Philips printouts and CV=0.50% with original digital images versus CV=2.05% for Siemens printouts and 1.35% with original digital images). No significant diﬀerences in sensitivity towards image capturing parameters were observed between BMD and MCI. Conclusion: Digital x-ray radiogrammetry provides measurements of MCI and BMD with high precision. The measurements are unaﬀected by all tested image capturing conditions with the exception of tube voltage. Regarding conventional and digital radiographs, especially digital printouts, our data revealed a significant influence of varied tube voltage on DXR-BMD and MCI measurements. In addition, an influence of the applied image modality is detected between the original digital images and their corresponding printed versions.

P566SU. QUANTITATIVE ULTRASOUND (STIFFNESS INDEX) IN CHINESE PEDIATRIC SUBJECTS: PRELIMINARY REFERENCE VALUES Xiang J1, Zhou Q2, Cheng X3, Wacker W4, Weynand LS4, Cheng S5; 1Department of Biomedical Signal Assessment, Jiaxing 1st Hospital, China, 2GE Healthcare, China, 3Radiology Department, Beijing University Beijing Jishuitan Hospital, China, 4GE Healthcare, Madison, WI, USA, 5Universities of Xingjiang Medical Science & Guangzhou Physical Education, China, & University of Jyväskylä, Finland Aims: There is increasing demand in using a quantitative ultrasound device (Lunar Achilles Insight, GE Healthcare) for assessing bone status in children in China due to its ability to predict osteoporotic fractures in adults. The purpose of this study is to establish Chinese pediatric reference values for clinical use. Methods: The study goal is to have 30 healthy normals for each age group and sex with a total sample of 900 from two centers located in Guangzhou and Jiaxiang, China. Currently we have measured the heels of healthy males (n=167) and females (n =257) aged 5 to 18 years. Stiﬀness Index was reported as the primary outcome. A sigmoid regression curve was generated to represent pediatric Stiﬀness Index data by mean age using 1-year age intervals. Tabular results of the preliminary reference values for Stiﬀness Index are reported below. Results: The precision error (RMS CV) was 2% in this population. Stiﬀness Index increases gradually with age, similar to the change seen in total body bone density in the same age group (reported elsewhere). Significant diﬀerences in Stiﬀness Index were found between males and females during the teenage years (age 15–17 years): males had significantly higher values than females (p=0.036 for age 15, and p<0.001 for age 16 and 17, respectively). Conclusions: Normal reference data for Stiﬀness Index are necessary to evaluate an individual’s bone status by comparison with healthy peers. These preliminary results for Stiﬀness Index in healthy males and females age 5–17 years are an important tool in assessing skeletal status in the Chinese pediatric population.

S291 Chinese Pediatric Stiﬀness Index Females

Males

Age n

Mean Height Weight Stiﬀness Age (cm) (kg) Index SD

5 6 7 8 9 10 11 12 13 14 15 16 17 18

5.5 6.5 7.4 8.7 9.7 10.5 11.5 12.6 13.5 14.4 15.3 16.7 17.5 18.3

33 29 19 13 8 11 12 10 10 12 10 30 38 22

113.0 120.2 127.8 132.0 125.0 143.0 149.8 153.7 158.3 158.4 153.1 157.8 155.8 157.2

21.4 23.8 27.4 27.9 27.8 33.6 36.5 43.5 46.8 46.6 43.7 54.2 51.1 49.7

68.0 66.8 72.3 75.8 80.0 80.6 81.4 85.0 91.2 96.2 88.5 90.7 92.3 98.2

11.2 8.0 8.2 9.4 8.8 12.0 10.5 10.1 11.7 14.6 11.8 16.7 14.4 10.9

n

Mean Height Weight Stiﬀness Age (cm) (kg) Index SD

23 5.4 25 6.3

126.3 123.7

22.8 20.3

69.8 71.9

others (total BMD, vcBMD or buckling ratio). No correlations were found between cortical bone parameters measured at the peripheral skeleton with areal bone density measured at the axial skeleton. Further studies should be performed to see if pQCT evaluation of cortical bone better predicts fracture risk in uremic patients than areal bone density.

17.6 2.9

P568SA. OSTA INDEX AND BONE MASS DENSITY IN MIDDLE AGED WOMEN AT SIRIRAJ MENOPAUSE CLINIC 10 15 12 30 27 25

13.7 14.6 15.4 16.6 17.6 18.2

154.4 161.5 157.5 166.2 167.8 168.5

20.9 14.4 22.2 7.4 4.5 4.8

96.0 87.8 101.4 106.0 107.2 102.0

19.9 17.3 17.7 15.0 15.7 16.0

P567MO. CORRELATIONS OF AREAL BONE DENSITOMETRY WITH CORTICAL BONE PARAMETRS OBTAINED BY PQCT IN PATIENTS ON DIALYSIS Negri AL1, Barone R2, Lombas C1, Bogado CE1, Zanchetta JR1; 1 Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, 2STR Hurlingham SRL We have previously shown cortical osteopenia with marked cortical thinning at the radius in chronic kidney disease stage 5 (CKD-5) patients on dialysis by peripheral quantitative computed tomography (pQCT). Aim: to compare pQCT cortical bone parameters in a group of CKD-5 patients on continuous ambulatory peritoneal dialysis (CAPD) with total bone mineral content (TBMC) and bone density measured at the axial skeleton by areal densitometry. Methods: Radial cortical bone parameters were obtained in 22 CAPD patients (6 males and 16 females) using a Stratec XCT 960 pQCT machine. Patients mean age was 41.4 12.0 years with a mean total time in dialysis of 78.36 52.6 months. TBMC in the whole skeleton and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) were measured using a Lunar DPX-L densitometer. Results: TBMC was 2399 587 g and correlated significantly with radial cortical content (R Sperman=0.74; p<0.001) cortical Area (R Sperman=0.75; p<0.001) and cortical thikness – cThK- (R Sperman= 0.59; p<0.01) but not with total radial BMD, volumetric cortical BMD or buckling ratio(r/cThK). Mean LS BMD was 1.175 0.208 g/cm2. LS Z-scores <-1 were present in 7 patients (31.8%), and <-2 in 3 patients (13.6%). Mean FN BMD was 0.894 0.158 g/cm2. FN Z-scores <-1 were present in 7 patients (31.8%) and <-2 in 2 patients (9%). No correlations were found between radial cortical content, density, area, thickness or buckling ratio and BMD measured at the lumbar spine or femoral neck. Conclusions: TBMC correlated significantly with various radial cortical bone parameters (content, area and thickness) but not with

Indhavivadhana S, Rattanachaiyanont M; Gynecologic Endocrinology Unit, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand Aims: OSTA index is a screening tool firstly developed to identify postmenopausal Asian women at increased risk of osteoporosis determined by femoral neck BMD. The objective of this study was to validate OSTA index in middle aged women other than natural postmenopausal women. Methods: Medical records of 419 patients having BMD measurements from year 1997 to year 2005 were randomly selected from pooled records of patients attending Siriraj Menopause Clinic and were reviewed. The patients were categorized into perimenopausal, natural menopausal, and surgical menopausal groups. OSTA index was calculated using the formula [integer (0.2x body weight in kilogram)] minus [integer (0.2 x age in year)]. Final risk index of each patient was adjusted by adding 1 if the patient was taking estrogen and adding 2 if the patient was Thai. The final risk index of %-1 was considered high risk of osteoporosis. Results: There were 85 perimenopausal, 203 natural menopausal, and 131 surgical menopausal women included in the analysis. The natural menopausal women was statistically significantly older than the perimenopausal and surgical menopausal women (mean SD were 56.7 5.9, 51.7 4.1, and 51.7 6.2 years, respectively). The time since menopause was longer in the natural menopausal women than the surgical menopausal women (mean SD were 12.3 21.5 and 8.2 9.7 years, respectively. The prevalence of osteoporosis diagnosed by BMD from lumbar spine and femoral neck in the perimenopausal, natural menopausal, and surgical menopausal groups were 1% and 0%, 10% and 2%, and 5% and 0% respectively. The NPV and PPV of risk index in the perimenopausal, natural menopausal, and surgical menopausal groups were 99% and 0%, 90% and 25%,96% and 22% for the lumbar spine osteoporosis; and were 100% and 0%, 98% and 0%; and 100% and 0% for the femoral neck osteoporosis, respectively. Conclusion: The OSTA index adjusted for Thai race and estrogen use is a useful screening tool for rule out osteoporosis, especially at femoral neck, with the higher predictive value in the perimenopausal and surgical menopausal groups than in the natural menopausal group.

P569SU. BONE MINERAL DENSITY OF THE SPINE AND FEMUR IN HEALTHY CHINESE MEN Zhang ZL, Qin YJ, Huang QR, Hu YQ, Li M, He JW, Zhang H, Liu YJ, Hu WW; Center for Preventing and Treating Osteoporosis, Osteoporosis Research Unit, The Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China Aim: To establish bone mineral density (BMD) reference database in healthy Chinese males of Han ethnicity. Methods: A total of 1386 healthy Chinese males of Han ethnicity aged 20–90 years old at Shanghai were measured using dual-energy x-ray absorptiometry (DXA) for BMD in the lumbar spine 1–4 (L1–4) and proximal femur including total hip, femoral neck (Neck), trochanter (Troch), and Ward‘s triangle. Subjects were divided into fourteen decades subgroups for cross-sectional analysis according to five years old. The mean BMD and standard deviation at various sites were measured. BMD association with age, height, and weight were analyzed using Pearson correction and multiple linear regression. Results: The 20–24 years age group was utilized for the mean peak BMD at both the lumbar spine and proximal femur. The mean peak BMD in Shanghai males for the average L1–4, total

S292 hip, Neck, Troch, and Ward‘s triangle was 0.960 g/cm2, 0.984 g/cm2, 0.899 g/cm2, 0.745 g/cm2, and 0.812 g/cm2, respectively. The highly significant negative correlation between age and BMD at any sites of proximal femur was found in males, but no significant correlation between age and BMD at lumbar spine was observed. According to peak BMD in age 20–24 years, BMD at –2.5 SD from peak adult value in the Chinese males database for the average L1–4, total hip, Neck, Troch, and Ward‘s triangle was 0.735g/cm2, 0.697 g/cm2, 0.654 g/cm2, 0.488 g/cm2, 0.487 g/cm2, respectively. Using the current Chinese reference data, the prevalence of osteoporosis at the L1–4, total hip, Neck, Troch, and Ward‘s triangle was 7.4%, 8.9%, 22.8%, 6.4%, and 37.1% in 1085 males aged over 50 years old, respectively. However, using the American Caucasian males database, the prevalence of osteoporosis at any site was significantly higher than that of using the current Chinese reference data. Conclusions: This BMD reference database was established in healthy Shanghai males of Han ethnicity, and provided for more accurate diagnosis of osteoporosis in Chinese males.

P570MO. CORRECTION FACTORS FOR DIGITAL X-RAY RADIOGRAMMETRY (DXR) PARAMETERS IN CASE OF VARIED TUBE VOLTAGE DURING IMAGE CAPTURING Boettcher J1, Pfeil A1, Petrovitch A1, Schaefer ML1, Lehmann G2, Eidner T2, Mentzel HJ1, Linss W3, Malich A4, Kaiser WA1, Hein G2, Wolf G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Institute of Anatomy I, Friedrich-Schiller-University Jena, 4Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: In many studies DXR seems to be a precise method for evaluation of cortical bone partition. Unfortunately, a majority of these studies are presumably based on an extensive variety of diﬀerent image capturing conditions which can influence the reliability of the DXR results. In particular varied tube voltage during conventional and digital acquisition of radiographs aﬀects the short term precision of DXR. Aim of this study is to implement correction factors for cortical thickness (DXR-CT), metacarpal index (MCI) and bone mineral density (DXR-BMD) in case of varied tube voltage during image capturing caused by diﬀerent x-ray settings. Patients and Methods: Radiographs of the left hands of two deceased males were acquired three times using systematically varied tube voltage (40–52 kV), both for conventional x-rays (Kodak T-MAT-Plus film and Agfa Curix film with Philips Super 80 CP device) and digital printouts (Siemens Polydoros SX 80 and Diagnost Philips Optimus devices). All CT, MCI and BMD measurements were estimated by the DXR technique (Pronosco X-Posure System; Version 2, Sectra, Sweden), which is originally calibrated for analysis of conventional radiographs. Results: The following average correction factors could be calculated for one step of kV ( 1 kV) based on our part recommended tube voltage of 40 kV: For DXR-BMD: -0.48% (conventional, Kodak), -0.75% (conventional, Agfa), +0.11% (digital printouts, Philips) and -0.92% (digital printouts, Siemens). For MCI: -0.35% (conventional, Kodak), -0.74% (conventional, Agfa), +0.04% (digital printouts, Philips) and –1.28% (digital printouts, Siemens). Finally for DXRCT: -0.57% (conventional, Kodak), -0.94% (conventional, Agfa), +0.47% (digital printouts, Philips) and –1.18% (digital printouts, Siemens). Conclusion: The calculated correction factors could facilitate and also compensate diﬀerences of DXR results caused by varied tube voltage during image capturing. These correction factors support the extended availability of DXR based on a better comparability of diﬀerent DXR data.

P571SA. PRECISION AND ACCURACY COMPARISON OF BONE DESITOMETERS: PRODIGY ADVANCE AND DELPHI A Wu XP, Liao RE, Cao XZ, Tang S, Sheng ZF, Dai R; Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South, Shanghai, China

Aims: We compared short-term precision and accuracy of the GE Lunar Prodigy Advance and Hologic Delphi A bone densitometers. Methods: We performed duplicate measurements on BA (bone area), BMC and BMD at the femur and lumbar spine (L1–L4)of 66 subjects (age: 54.211.7 years), and compared the precision (RMS-CV). We also measured 54 bone blocks of various sizes measured at multiple heights above the table, and subsequently incinerated them to determine ash weight. Results: There were no significant diﬀerences of lumbar spine precision between the two densitometers (RMS-CV of BA, BMC, BMD: Prodigy 2.10.6%, 2.10.7%, 1.30.4%; Delphi 2.00.8%, 2.20.7%, 1.40.3%). However, average femur precision error was significantly lower with Prodigy vs. Delphi (RMSCV: Prodigy 1.70.6%, 2.11.5%, 1.30.6%; Delphi 3.11.6%, 3.82.1%, 1.71.1%). Bone block measurements obtained by each densitometer were highly correlated with true area, ash weight and density of bone blocks (r=0.975–1.000, p=0.000). However, with increased true area, ash weight and density, deviations of all Delphi parameters increased progressively and to a larger degree than Prodigy. Delphi BMC and BA also decreased significantly with increasing height of the bone block above the table, while Prodigy BMC and BA were relatively constant. Conclusions: We conclude that spine precision of BA, BMC and BMD from both densitometers is similar; but femur precision is significantly better with Prodigy. In addition, Prodigy accuracy is significantly better than Delphi.

P572SU. BONE EROSIONS DETECTED BY PERIPHERAL MRI AT THE METACARPOPHALANGEAL (MCP) AND WRIST JOINTS IN SUBJECTS WITH AND WITHOUT RHEUMATOID ARTHRITIS Xie XM1, Webber CE1, Adachi JD2, O’Neill J2; 1McMaster University, 2St. Joseph’s Hospital, Hamilton, Canada Aims: Bone erosion is considered to be significant in the staging of patients with inflammatory joint diseases. Small bore, high field magnetic resonance imaging (MRI) can detect destructive changes in peripheral joints. The purpose of this study was to compare the diﬀerences in the incidence of bone erosion measured by MRI in three diﬀerent groups of people.

S293 Methods: Sixteen patients with rheumatoid arthritis (RA: Group A, disease duration: (0.75–15y), 10 patients with arthralgia but no RA (Group B) and 8 healthy controls (Group C) underwent MR imaging in the dominant 2nd-5th MCP joints and wrists. Images were assessed by the scoring system recommended by OMERACT (Outcome Measures in Rheumatology Clinical Trails). The diﬀerences in the incidence of bone erosions between the three groups were compared by Fisher’s exact test. Results: The characteristics of the three groups are summarized in the Table. MCP bone erosion was observed in 8 subjects in group A (50%), 5 in group B (50%) and 0 in group C (0%). At the wrist, bone erosion was detected in 6 subjects in group A (37.5%), 6 in group B (60%) and 0 in group C (0%). The incidence of bone erosions was significantly greater than controls in both patient groups. Conclusion: Further study with a larger sample size is necessary in order to evaluate the sensitivity and validity of MR imaging for identifying the incidence and grade of bone erosion in patients with rheumatoid arthritis. Characteristics of study subjects (Mean SD). Variables

Group A (n=16)

Group B (n=10)

Group C (n=8)

Gender (F/M) Age (yr) Height (cm) Weight (kg)

13 / 3 54.416.4 163.910.1 68.715.8

9/1 60.815.3 162.27.1 62.111.7

5/3 31.311.0 172.09.4 72.114.8

P573MO. BONE MINERAL DENSITY IN YOUNG MALE PATIENTS WITH ANKYLOSING SPONDYLITIS Mai Tam, Vu Thuy; Bach mai Hospital, Ha noi , Vietnam Objective: To determine bone mineral density (BMD) in young male patients with ankylosing spondylitis (AS). Methods: Twenty five male patients with AS aged 15–29 years (Modified New York criteria 1984) and twenty age matched healthy men as controls were studied. The subjects were measured for BMD at the lumbar spine and femoral neck by dual-energy X-ray absoptiometry (DXA). The activities of the disease were assessed by a visual analog scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ESR. Results: Mean age: 20.6 (4.2). The mean time of disease duration (year): 3.1 (1.8). BMD was lower significantly in patients with AS compared with controls in the lumbar spine (p<0.001) and femoral neck (p<0.001). BMD was reduced in patients at early active stage and longer disease duration. Conclusion: The majority of patients with AS had reduced BMD and it is possible to have a relationship between BMD and disease activitiy.

P574SA. MAGNETIC RESONANCE IMAGING SCORING SYSTEM FOR KNEE DISORDERS IN PATIENTS WITH OSTEOARTHRITIS OR ANTERIOR CRUCIATE LIGAMENT INJURY Wu H, Webber CE, Fuentes CO, Bensen R, Adachi JD; McMaster University, Hamilton, CA Objective: To compare knee joint changes between normal, osteoarthritis (OA) and anterior cruciate ligament (ACL) rupture knees using a peripheral magnetic resonance imaging system (pMRI). Material and methods: MR images of 28 normal knees, 32 OA knees and 26 ACL damaged knees were acquired with a 1.0 T pMRI system. Two radiologists graded the presence and severity of 9 MRI features including cartilage degeneration, osteophytes, subchondral cyst, bone marrow edema, meniscal abnormality, ligaments integrity, loose body, popliteal cysts, and joint eﬀusion with a published scoring system named KABON (Beattie et al, 2005). Results: Ten of 28 normal knees (35.7%), 24 of 26 ACL knees (92.3%) and all of OA knees (100%) showed diﬀerent severity of cartilage defects; 5 normal knees (17.9%), 20 ACL knees (76.9%)

and all OA knees (100%) had osteophytes; 9 normal knees (32.1%), 21 ACL knees (80.7%) and 29 OA knees (90.6%) had meniscal abnormalities. Almost half of the knees in the OA group had subchondral cysts (16 of 32, 50%) and bone marrow edema (15 of 32, 46.7%), but they were not common in the ACL group (7.7%, and 11.5%) and were not observed in normals. The other features were occasionally detected in the three groups. The OA group had the highest severity in 5 main MRI features including cartilage defects, osteophytes, bone marrow edema, subchondral cysts and meniscal abnormalities, while the ACL group showed more severe cartilage defects, osteophytes and meniscal abnormalities than normals. Conclusion: Our results suggest that ACL damage knees have OA like features and the majority of subjects (19 of 26, 73.1%) could be identified as early stage of OA. The main changes of ACL damage knees are cartilage defects, osteophytes and meniscal abnormalities. Beattie KA, Boulos P, Pui M, O’Neill J, Inglis D, Webber CE and Adachi JD. Abnormalities identified in the knees of asymptomatic volunteers using peripheral magnetic resonance imaging, Osteoarthritis and Cartilage, 2005; 13: 181–186.

P575SU. THE RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND VITAMIN D CONCENTRATION IN POSTMENOPAUSAL WOMEN Zivny P, Pavlikova L, Pavlikova L, Spirkova J, Palicka V; Osteocentre, Institute of Clinical Biochemistry and Diagnostics, Medical Faculty and University Hospital, Hradec Kralove, Czech Republic Aims: Vitamin D plays an important role in normal bone mineralization and its deficiency is a risk factor for osteomalacia and osteoporosis. Vitamin D deficiency negatively impairs calcium and phosphate metabolism and triggers parathyroid hormone increase. Low levels of vitamin D, calcium and phosphate have also been linked to an increase in hip fractures in elderly women. The aim of this study was to evaluate the relationship between bone mineral density (BMD) and serum levels of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25OHD) in postmenopausal women. Methods: This retrospective study included 157 postmenopausal Caucasian women, age 38–79. BMD (g/cm2) was measured at the lumbar spine (L1-L4) and proximal femur using the Hologic Delphi, a DXA densitometer. Osteocalcin and parathormone concentrations were determined by monoclonal competitive enzyme immunoassay (EIA, Modular Roche E170), bone-specific alkaline phosphatase by METRA BAP EIA kit. Ionized calcium were determined by ion-selective electrode. Radioimmunoassay was used to measure vitamin 25OHD and 1,25OHD. Statistical analyses were performed using SigmaStat 3.1 (Jandel Scientific Corporation, San Rafael, CA, USA), tests used were linear regression, Pearson correlation. Results: Obtained results showed correlation between vitamin 25OHD and 1,25OHD (r = 0.232, p = 0.008) and between calcium and ionized calcium (r = 0.831, p = 0.001). Correlation analyses showed lack of correlation between lumbar spine BMD and concentration 1,25OHD (r = -0.143, p = 0.119), between proximal femur BMD and 25OHD (r = 0.113, p = 0.224), as well between BMD and osteocalcin and parathormone concentrations. Conclusions: We did not find correlation between BMD measurement, vitamin D and all investigated bone markers that indicate possible impaired balance between bone formation and bone resorption in postmenopausal women. Some authors stated that direct relation between vitamin D concentration and BMD is the result of pathological conditions associated with renal impairment. Supported by grant MZO 001179906.

P576MO. EVALUATION OF PRECISION AND ACCURACY OF THE LUNAR IDXA FAN-BEAM DENSITOMETER Faulkner KG, Wacker WK, Franz JR, Riewe KP, Barden HS; GE Healthcare, Madison, USA

S294 Increased awareness of osteoporosis as a major health problem of the elderly and continuous technological innovation among manufacturers has driven acceptance of DXA as the gold standard for assessing skeletal health and fracture risk. Recently, GE Healthcare introduced the Lunar iDXA, a high-definition imaging densitometer featuring a new direct-to-digital CZT-HDTM detector with a staggered-element array to deliver precise and accurate results with near-radiographic image quality. We compared the precision and accuracy of two Lunar densitometers, the iDXA and the Prodigy. We measured spine, femur, and total body BMD in triplicate on 30 females and 10 males (mean age 56.7 yrs, SD 13.7) with both densitometers. Subjects were repositioned between each scan. BMD measurements for Prodigy and iDXA were highly correlated at the L1-L4 spine (r2>0.98), femur neck, trochanter, and total femur (r2=0.99), and total body (r2>0.96). Linear regression analyses comparing iDXA with Prodigy showed a unity slope at the L1-L4 spine, the trochanter and total femur, and a small, clinically insignificant, bias at the femur neck (-0.003 g/cm2). Precision (CV) was not significantly diﬀerent at the L1-L4 spine (1.1% vs 1.2%), femur neck (1.3% vs 1.4%), trochanter (1.4% vs 1.2%), and total femur (0.8% vs 0.7%) for iDXA and Prodigy, respectively. iDXA total body precision was significantly better than with Prodigy (CV = 0.6% vs 0.9%). In conclusion, precision at the spine and femur was nearly identical between instruments and total body precision was significantly better with Lunar iDXA. BMD measurements of the spine and hip on the Lunar iDXA and Prodigy were equivalent.

Lunar iDXA vs. Prodigy Total Femur BMD

P577SA. HIP FRACTURE IN THE LEBANESE POPULATION: RISK FACTORS Maalouf G, Wehbe J, Nehme A, Maalouf N, Chidiac RM; Balamand University, Faculty of Medicine, Saint George Hospital, Beirut, Lebanon Fracture of the proximal femur (FPF) is a leading cause of morbidity and mortality around the world. We evaluated potential risk factors for hip fracture in postmenopausal Lebanese women aged 51–86 years. Fracture cases (40 women) were defined as having a clinically diagnosed and treated femur fracture. Controls (64 women) were chosen from the same population of postmenopausal women who visited the clinic for routine check-ups. Participants completed a questionnaire and their health records were reviewed. Each subject was scanned using the GE Lunar Prodigy DXA system. Femur geometry and bone mineral density (BMD) were measured, including hip axis length, neck-shaft angle, upper neck BMD, bone mineral content, total femoral area, and neck area. A series of t-tests was performed to compare the fracture cases to controls. The fracture cases are significantly older, with an average age diﬀerence of 5.3 years. There were no significant

diﬀerences in smoking prevalence or body mass index (BMI). Hip axis length was significantly longer (p=0.003) in fracture cases (104mm) vs. controls (100mm). There was no significant diﬀerence in the neck-shaft angle. BMD values were significantly lower in fracture cases compared to controls, including upper neck BMD (p<0.001) and total femur BMD (p<0.001) as well as total femur bone mineral content (p<0.001). This is reflected in the significantly lower average T-score (-2.2) vs. the control group (-1.2), p value < 0.001. The results of this study confirmed some of the hip fracture risk factors established previously, such as age, hip geometry and bone density. Hip axis length was the strongest predictor of hip fracture among the geometry parameters We found that age is a major, but not independent, risk factor, while age at menarche appeared to be an important risk factor in our study. Bone mineral density of the upper neck and total femur regions, as well as bone mineral content of the total femur regions, were significant predictors.

P578SU. THE RELATION BETWEEN OBESITY AND DIABETES IN PATIENTS WITH OSTEOPOROSIS Circo E1, Circo S2, Chirca I2, Shavazo D1; 1Ovidius University, Constanta, Romania, 2Carol Davila University, Bucharest, Romania Aims: To assess the correlation between ovarian failure and bone mineral density in obese women with diabetes mellitus. To establish possible advantages between body mass index (BMI) and body fat distribution. Methods: This study was conducted on 71 women with obesity and premature ovarian failure or surgically induced menopause. They were divided ito 3 groups: group I included 15 women previously diagnosed with DMI (diabetes mellitus type I); group II included 23 women previously diagnosed with DM II (diabetes mellitus type II), and the control group included 33 women without DM. The patients included in this study were diagnosed with DM in the last 5 years and obesity in the last 10 years. We calculated BMI and the waist-to-hip ratio (WHR) and measured BMD at the level of lumbar spine and femoral neck (DXA). The presence of osteoporotic fractures was taken into account as well. Results: Patients with DMI showed to have a higher incidence of osteoporosis (20%), compared to patients with DMII (4.3%) and nondiabetic obese patients (9.1%). In patients with classI obesity the incidence of osteoporosis was found to be higher (53%), compared to patients with class II obesity (7.7%) and (1%) in patients with classIII obesity. 62% of patients with osteoporosis have had peripheral obesity whereas 12% have had abdominal obesity. The incidence of osteoporotic fractures was 28.5% vertebral fractures, 16.3% Colles’ fractures and 4.3% hip fractures. Conclusions: Obese hypogonadic women with associated DMI may lead to a decrease of BMD, whereas those with DMII maintained a normal BMD. Abdominal obesity and class II and class III obesity have proven to be protective factors against osteoporosis probably due to an elevated aromatisation of androgens in estrogens, taking place in the fat tissue. The presence of DMI in women with premature menopause and obesity is associated with a lower BMD compared to patients with DMII or those without DM. The higher the amount of adipose tissue and abdominal obesity have shown to be protective factors against the loss of BMD.

P579MO. DXA BONE MINERAL DENSITY REFERENCE DATABASE FOR THE INDONESIAN POPULATION Tirtarahardja G1, Setyohadi B2, Zhou Q3, Weynand LS4; 1Jakarta Osteoporosis Center, Medistra Hospital, Jakarta, Indonesia, 2Department of Internal Medicine, Indonesian University, Jakarta, Indonesia, 3GE Healthcare, Shanghai, China, 4GE Healthcare, Madison, WI, USA Aims: Osteoporosis is a major public health problem, particularly in women. Local reference data for bone mineral density (BMD) are necessary for the accurate diagnosis of osteoporosis. Methods: To establish reference data for Indonesian women, we recruited 910 healthy women aged 20–90 years from three centers

S295 in Indonesia. Each subject completed a health status questionnaire, and those with known factors aﬀecting BMD were excluded from the study. Spine (L1–L4) and hip BMD were measured with Lunar DXA devices (GE Healthcare, Madison, WI USA). Results: Precision error measured with an aluminum spine phantom on those devices was 0.27–0.56% CV. The relationship between BMD and age was assessed using various regression models, with the best-fit model used to calculate age-related reference curves. The young normal (YN) reference value to determine T-scores was defined as the mean BMD and SD from 20 to 40 years of age (n=288). YN BMD reference values in Indonesian women are similar to Filipino and Chinese values, but slightly lower than American: SDs are similar in all groups. Conclusions: In this study, the first Indonesian reference database for spine and hip BMD was established. With these locally derived reference values, accurate T-scores and Z-scores for the Indonesian population are now available. Table. The young normal (YN) BMD reference value (g/cm2) YN BMD

L1-L4 (SD) (g/cm2)

Neck (SD) (g/cm2)

Trochanter (SD) (g/cm2)

Total Femur (SD) (g/cm2)

Indonesian Filipino Chinese American

1.115 1.110 1.114 1.180

0.917 0.888 0.930 0.980

0.727 0.720 0.759 0.790

0.947 0.913 0.975 1.000

(0.13) (0.12) (0.12) (0.12)

(0.12) (0.12) (0.12) (0.12)

(0.11) (0.11) (0.11) (0.11)

(0.12) (0.12) (0.13) (0.12)

P580SA. CLINICAL SIGNIFICANCE OF MEASUREMENT OF BONE MINERAL DENSITY IN FEMORAL NECK AND TOTAL HIP

Aim: To assess the relationship between hip geometry and fracture risk in males. Methods: Adult males were included into the study randomly. Presence of metabolic bone disorder (eg., Paget, osteomalasia), renal failure, hepatic failure, malignity, extreme coxarthrosis and being confined to bed were the exclusion criteria. Age, weight and height measurements and family history for osteoporosis, dietary calcium intake, alcohol and smoking habits, coﬀee consumption, inactive or sedantery life, walking and exercise conditions of all patients were recorded. Predictors of bone turnover were checked. Measurements of L2-L4 anterior lumbar spine, left hip femoral neck, trochanter, wards, total hip bone mineral density (BMD), Tand Y-scores and measurements of femoral geometry were obtained by Lunar DPX-Nt DXA equipment using the analysis software. Fracture index scores were calculated. Results: 108 subjects with mean age 58 (SD: 12 + 11.32) were recruited. Among all cases, 8.3% were osteoporotic, 53.7% were osteopenic, and 38.0% were normal for the femoral neck section. The highest frequency for age related distribution was found for 51–60 years (44.4%). Total hip femoral neck width (p=0.035) and neck shaft angle (p=0.006) were significantly higher in osteopenia and osteoporosis group than males with normal BMD. Geometric parameters hip axis length and femoral axis length and femoral neck BMD both showed negative corelations with total hip BMD and positive corelations with fracture risk index. The odd ratios of the hip axis lenght and femoral neck width to fracture risk were 2.4 and 7.0, respectively. The neck shaft angle had no significant eﬀect on fracture risk. The cases with a fracture risk (fracture index score >4) had significant (p<0.05) lower T- and Z-scores in all sections. Conclusion: Fracture index is a simple and useful predictor for assesing the fracture risk, and can be used independent from DXA by clinicians.

Suarez S, Ramenzoni R, Messina MD, Andrada DM, Dotzanica C, Riopedre AM, Messina OD; C:IR:O, Clinical Research Medical Center, Buenos Aires, Argentina During the last ten years there was some debate related to the mineral density measurement of the proximal femur area that should be considered for diagnostic and clinical purposes. Neck fractures occur and bone mineral density of this area is particularly important. The international committee for the standardization of densitometry (1997) recommended the evaluation of total hip (including the whole proximal femur ) mineral density and the T-score of this area. However, some discrepancies between the evaluation of femoral neck and total hip were observed. We compared the T-score values of femoral neck and total hip in 486 postmenopausal women (aged 50 to 80 years)(DXA ,Hologic Delphi). Patients were classified based on bone mineral density results according to WHO criteria (T-score values, >-1.0 normal, between -1 and –2.5 osteopenia, <2.5 osteoporosis ) considering both femoral neck and total hip. Results: The categorization resulted in 65% of the patients using femoral neck of total hip T-score values and diﬀered in 35%. 9.4% of the women presented osteoporosis in femoral neck and osteopenia in total hip while 20.7% showed osteopenia in femoral neck with normal values in total hip. 1% of patients showed osteoporosis in femoral neck and normal values in total hip. Only 5% of the patients showed higher BMD values in femoral neck than total hip. 30.1% of the patients showed lower values in femoral neck than in total hip. We conclude that considering only total hip may underestimate the diagnosis of low mineral density in proximal femur and femoral neck in 1/3 of the patients and that considering femoral neck (the area which really fractures) mineral density is still very important.

P581SU. RELATIONSHIP BETWEEN HIP GEOMETRY (FRACTURE INDEX) AND FRACTURE RISK IN MALES Cerrahoglu L1, Gulesan Y1, Gumuser FG2, Duruöz MT1; 1PM&R Department, Manisa, Turkey, 2Nuclear Medicine Department, Celal Bayar University Medical School, Manisa, Turkey

P582MO. BONE STRENGTH OF STUDENTS IN THE UNITED ARAB EMIRATES Bell PJ; University of Sharjah, Sharjah, UAE Aims: Bone strength in this Arab country, as in the rest of the world, is assessed by measuring bone quality with quantitative ultrasound and bone quantity with dual-energy X-ray absorptiometry, and comparing the results to reference ranges. However, in the absence of accepted Arab reference ranges for either technique, Caucasian reference ranges are used. This study aimed to discover the average male and female values for bone strength in young adults in order to determine the suitability of employing the Caucasian reference range for clinical diagnosis of bone strength. Lifestyle factors known to influence bone strength were also investigated. Methods: The study design was a cross-sectional survey of student volunteers, aged 20 to 25. Bone strength was assessed for all volunteers with quantitative ultrasound and, for a subset of students, with dual-energy X-ray absorptiometry. Lifestyle factors including calcium intake and physical exercise were examined. The study took place during the spring semester of 2005 and included healthy 20 to 25 year old Arabs. Results: The number of volunteers was 337, 41 with exclusion criteria were removed, leaving a total of 296; 120 males and 176 females. Although the nationalities of the students varied, almost all of them had lived most of their lives in the United Arab Emirates. Ultrasound stiﬀness index of the left heel showed that Arab males measured the same as Caucasian females. No male Caucasian reference was available. Arab females, however, had a mean stiﬀness index significantly lower than Caucasian females by 6 percent, p = 0.000. Mean hip bone density for 31 males matched Caucasian male reference data, mean 1.037 g/cm2. Bone density of 38 females scanned was 11 percent lower than the female Caucasian reference, p = 0.000. Calcium intakes were the same for both groups but the females performed 80 percent less exercise. Conclusions: This study suggests that since the diﬀerence in bone strength between Arabs and Caucasians is only seen in females it may not be an ethnic diﬀerence as previously assumed but instead may be due to the diﬀerence in lifestyle, specifically minimal physical activity.

S296

P583SA. DISCRIMINATION OF LOW ENERGY FRACTURES BY A NEW HEEL QUANTITATIVE ULTRASOUND IMAGING DEVICE Damilakis JE, Papadokostakis G, Karantanas A, Perisinakis K, Zourari K, Gourtsoyiannis N; University of Crete, Iraklion, Crete, Greece Aims: The aim of the current study was to evaluate the ability of a new quantitative ultrasound (QUS) imaging device (Achilles Insight, GE, USA) to discriminate between postmenopausal women with and without low energy fractures. Methods: The study group consisted of 40 healthy Caucasian postmenopausal women and 40 age-matched patients with low energy fractures. Scans of the heel were taken with an Achilles imaging unit. This device provides images of the heel bone and measures Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS) values in a circular region of interest. A third QUS variable, the stiﬀness index (SI) was also determined. Alcohol was used as a coupling agent. Bone mineral density (BMD) measurements of the lumbar spine (BMDs) and femoral neck (BMDn) were carried out in all subjects using a dual x-ray absorptiometry system (Lunar Prodigy, GE, USA). The areas under the ROC curves were used to examine QUS and BMD variables in terms of diﬀerentiating patients from healthy subjects. Results: Patients with fractures had significantly lower BMD and QUS values compared with healthy subjects. Significant correlations were found between QUS values and BMD data (p<0.001 for all comparisons). The areas under the ROC curve ranged from 0.76 to 0.79 for QUS variables. Among the QUS measurements, the SI showed the best area under curve. Comparison between the areas under the ROC curve did not show any significant diﬀerences among BUA, SOS, SI and BMDs variables in their power to discriminate between controls and fractured subjects. BMDs discriminated patients with fractures better than BUA, SOS and SI, although diﬀerences did not reach statistical significance. In contrast, the diﬀerentiation of the fractures by BMDn was significantly better than that of the three QUS variables (p<0.05). Conclusions: QUS variables measured using the Achilles Insight QUS unit were significant discriminators of low energy fractures. The diﬀerentiation of the fractures by BMDn was significantly better than that of BUA, SOS and SI.

P584SU. A COMPARISON OF THE PRECISION OF CALCANEAL QUANTITATIVE ULTRASOUND PARAMETERS AND BONE MINERAL DENSITY AT DIFFERENT SKELETAL SITES AS MEASURED BY DUAL-ENERGY X-RAY ABSORPTIOMETRY Oral A, Sindel D, Yaliman A; Istanbul University, Istanbul Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is considered the gold standard for the management of osteoporosis. Recently, quantitative ultrasound (QUS), which is easy to use, inexpensive, portable, does not use ionizing radiation, and has also been shown to provide information about bone quality and to predict fracture risk, has gained growing interest in this area. However, to be more widely used in the management of osteoporosis, QUS needs to be accurate, reliable, and sensitive to change. Our aim was to compare the precision of QUS parameters [broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), and estimated heel bone mineral density (eBMD)] as measured by a gel-coupled calcaneal QUS device and BMD at the lumbar spine and proximal femur as measured by DXA, in an attempt to evaluate the clinical usefulness of these measurement methods. The short-term precision of the measurements was examined as the root-mean-square coeﬃcient of variation (RMSCV%) as measured twice in the same female subjects, aged 43 to 78 years, representative of our clinic’s patient population, on the same day with repositioning the patient after each measurement. Calculations were based on 30 subjects with duplicate scans for BMD measurements and 28 subjects with duplicate QUS measurements, because we failed to make QUS evaluation of the two subjects with lower extremity edema. Least significant change

(LSC) was also calculated as 2.77 times CV% for the group at 95% confidence interval. RMSCV% and LSC% for QUS indices for the right / left heel were 3.15 / 3.24% and 8.73 / 8.97% for QUI, 4.19 / 4.91% and 11.61 / 13.60% for BUA, 0.29 / 0.28% and 0.80 / 0.78% for SOS, and 3.77 / 3.80% and 10.44 / 10.53% for eBMD. BMD measurements showed lower precision errors, RMSCV and LSC being 2.11% and 5.84% for the lumbar spine (L1-L4), 2.77% and 7.68% for the femoral neck, and 1.61% and 4.47% for the total hip. In conclusion, the higher short-term precision errors for QUS indices than those of DXA BMD measurements may limit the use of QUS for patient monitoring.

P585MO. RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND TANNER STAGES IN CHILDREN WITH USE OF NEW PAEDIATRIC LEANS MASS ASSESSMENT ON THE LUNAR PRODIGY Cirmanova V1, Hill M1, Zofkova I1, Kasalicky P2, Rosa J2, Bayer M3; 1Institution of Endocrinology, 2Bone Metabolic Unit, DS Mediscan, 31st Medical Faculty of Charles University, Prague, Czech Republic Aims: Measurement of bone mineral density (BMD) in children has become an important tool in evaluation of skeletal status. Although two dimensional measurements are influenced by other parameters like body size and lean body mass (LBM), dual-energy X-ray absorptiometry (DXA) is the method of choice to evaluate BMD in childhood and adolescence. The authors tried to examine relations between BMD, lean mass and pubertal development in the group of healthy girls. Methods: Fifty eight healthy school girls (age range 9–15 yrs) had lumbar spine and total body BMD measured with the GE Lunar Prodigy. Subject’s correlations height for age, bone mineral content (BMC) for bone area (BMC/BA), and bone area for height were obtained with the enCORE software. At the same moment the Lean Mass Assessment tool provided the LBM for height and the BMC for LBM. Eﬀect of all independent factors was calculated using analysis of variance (ANOVA). Pubertal status was determined by self-assessment, using photographs of the Tanner stages, as previously validated. Pubertal status was classified as prepubertal (stage I), early puberty (stages II and III) and late puberty (stages IV and V). Results: Analysis of results revealed significant relations between BMD (total body as well as lumbar spine) and Tanner stages, BMC and LBM. Conclusion: LBM seems to be a good predictor of BMC and pubertal status (estimated using Tanner staging) has an important eﬀect to BMD in healthy school girls. The new GE Lunar pediatric equipment provides comfortable and reliable assessment of skeletal status.

P586SA. THE RELATIONSHIP BETWEEN BONE SPEED OF SOUND BY QUANTITATIVE ULTRASOUND AND BLOOD BIOCHEMICAL MARKERS IN YOUNG INFANTS Liao XP1,2, Gong XH1, Zhang WL2, He JM2, Sun JH3, Huang P3; 1 Wuxi Hospital for Maternal and Children’s Health Care, Wuxi, China, 2Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai, China, 3Shanghai Children’s Medical Center, Shanghai, China Aims: Quantitative ultrasound (QUS) has been applied to evaluate the bone status of children and there are some QUS reports of bone status for Chinese infants. This study aimed to explore the relationship between bone speed of sound (SOS) by QUS and blood biochemical markers in young Chinese infants. Methods: An ultrasound bone sonometer, Sunlight Omnisense [Sunlight Medical Ltd., Israel], was used to measure the SOS of tibia in 167 infants aged 0–3 months (preterm infant: n=53, mean gestational age 32.62.7 weeks, chronological age 26.78.6 days; full-term infants: n=114, mean gestational age 39.21.2 weeks, chronological age 29.627.4 days). Meanwhile, serum levels of calcium, phosphorus and alkaline phosphatase (ALP) were measured by an automatic biochemistry analyzer (BACKMAN,

S297 America), and bone-specific alkaline phosphatase (BALP) was measured by electrophoresis metrod. Results: There were significantly inverse correlations between SOS and ALP (n=167, r=-0.139, P=0.036), and between SOS and BALP (n=53, r=-0.410, P=0.010) in infants. However, no such relationships between SOS and serum calcium and phosphorus were found. ALP was significantly correlated with BALP (n=32, r=0.992, P=0.001) and BALP accounted for 43.7% of total value of ALP (Fig.1). The study group was subdivided into two groups: in preterm infants there were significant correlations between ALP and chronological age (n=53, r=0.286, P=0.019) and also between BALP and chronological age (n=7, r=0.946, P=0.001), but in full-term infants no such relationships were found. Conclusion: SOS was inversely correlated with ALP and BALP in young infants. Measurement of SOS is able to help us to evaluate infant bone status, whereas the levels of ALP and BALP highly fluctuated in infants.

Interradiograph reproducibility of bone mineral density (BMD) and metacarpal index (MCI) were evaluated by acquiring ten repeated radiographs with repositioning under standard settings. To verify intraradiograph reproducibility, a single conventional image and a single printout underwent 10 repeated DXR analyses (42 kV, 6 mAs, FFD 100 cm) with the Pronosco-X posure System (Version 2, Sectra, Sweden). Results: The interradiograph reproducibility of DXR-BMD using conventional images under standardised conditions was calculated to be CV=0.49% for Agfa Curix film and CV=0.33% for Kodak T-MAT-Plus film, whereas reproducibility error using digital images ranged from CV=0.57% (Philips, digital printouts) to CV=1.18% (Siemens, digital printouts). The intraradiograph reproducibility error was observed to be CV=0.13% and CV=0.26% (conventional, Kodak and Agfa film) versus CV=0.27% and CV= 0.05% (digital printouts, Philips and Siemens). No significant diﬀerences in the sensitivity towards image capturing parameters were observed between BMD and MCI. Conclusion: DXR shows a high inter- and intraradiograph reproducibility for conventional as well as digital images and seems to be a reliable osteodensitometric technique for evaluation of the peripheral cortical bone which approve the quantification of minor disease-related alterations of the cortical bone partition.

P588MO. QUANTITATIVE FOREARM ULTRASOUND IN POSTMENOPAUSAL TURKISH WOMEN Akin S1,2, Ozyemisci O1, Atalay F1,3, Karaoglan B1,3, Gokce Kutsal Y1,5, Dincer G1,4, Hasanoglu A1,6; 1The Society of Life with Osteoporosis, 2Middle East Technical University Medical Center, 3Gazi University Faculty of Medicine PM&R Department, 4 Ankara University Faculty of Medicine PM&R Department, 5 Hacettepe University Faculty of Medicine PM&R Department, 6 Gazi University Faculty of Medicine Pediatrics Department, Ankara, Turkey

Fig.1 Scatter diagram of ALP and BALP

P587SU. EVALUATION OF REPRODUCIBILITY REGARDING DIGITAL X-RAY RADIOGRAMMETRY Boettcher J1, Pfeil A1, Lehmann G2, Petrovitch A1, Schaefer ML1, Linss W3, Malich A4, Kaiser WA1, Hein G2, Wolf G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-SchillerUniversity Jena, 2Clinic of Internal Medicine III, FriedrichSchiller-University Jena, 3Institute of Anatomy I, FriedrichSchiller-University Jena, 4Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: The potential of digital x-ray radiogrammetry (DXR) for estimating cortical bone loss seems to be promising, in particular because of the high precision. To evaluate the inter– and intraradiograph reproducibility of digital x-ray radiogrammetry under consideration of both conventional and digital performed radiographs. Patients and Methods: Radiographs of the nondominant hand from two deceased males were performed according to a predefined study protocol. For conventional radiographs (Philips Super 80 CP) our study considered the following standardized parameters: 42 kV, 6 mAs, Kodak T-MAT-Plus 200 or Agfa Curix 200 film, FFD 100 cm. For digital printouts (Diagnost Philips Optimus and Siemens Polydoros SX 80) the constant image capturing conditions were as follows: 42 kV, 4 mAs, FFD 100 cm.

Aim: Osteoporosis is a major health problem among postmenopausal women. A significant proportion of subjects with low bone density are currently undiagnosed. The aim of this study was to assess determinants of bone mass in postmenopausal women. Methods: This study was held on women and men who participated in educational meetings of ‘‘The Society of Life with Osteoporosis’’ in 12 diﬀerent cities of Turkey. Quantitative ultrasound (QUS) has been introduced as a method for assessment of bone status and fracture risk. In this cross-sectional study bone status was assessed by Omnisense 7000 S (Sunlight Medical Systems, Tel Aviv, Israel). All subjects participated in this study were measured by the same device. Speed of sound (SOS) measurements were taken at the distal 1/3 radius. Results: The QUS measurements were performed in 1577 subjects (1388 were women and 189 were men) and a survey on risk factors leading to osteoporosis was conducted among the participants. All participants were questioned on lifestyle habits and on their medical history. 653 subjects were removed from the statistical analysis because of uncompleted questionnaires. 924 women aged over 40 completed the questionnaire. 625 of them were postmenopausal and 299 of them were premenopausal. 67 of them were under treatment for osteoporosis, so final analysis was made in 558 postmenopausal women. Mean age was 56.58.08 (range 40–85). According to World Health Organization criteria 86 (15.4%) women had osteoporosis, 173 (31%) women had osteopenia, and 299 (53.6%) women were defined as normal. Multiple linear stepwise regression analysis was used to consider risk factors for osteoporosis. SOS measurement was taken as dependent variable and age, height, weight, body mass index, duration of menopause, number of birth and total duration of breastfeeding were the independent variables. The strongest independent factors aﬀecting QUS measurements at the forearm were age and duration of menopause (r2=0.140 p=0.000; r2=0.153 P=0.000). Conclusion: QUS provides a convenient alternative to dualenergy X-ray absorbtiometry especially in population based studies.

S298

P589SA. SHORT-TERM PRECISION OF BONE MINERAL CONTENT AND BONE MINERAL DENSITY MEASURED AT DIFFERENT FOREARM REGIONS OF INTEREST USING DUAL-ENERGY X-RAY ABSORPTIOMETRY Sindel D, Yaliman A, Oral A; Istanbul University, Istanbul Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey Forearm bone mineral density (BMD) is recommended to be measured when posteroanterior spine and/or hip cannot be measured or interpreted in very obese patients and in those with hyperparathyroidism. However, due to the limitations for its use, the precision of forearm bone mineral content (BMC) and/or BMD measured at diﬀerent sites within the forearm has not been studied widely. Therefore, it is not clear which region of interest in a radius scan as measured by dual-energy X-ray absorptiometry (DXA) has a better precision. We aimed to compare the precision errors of BMC and BMD measured at the ultradistal, mid-distal, and 33% radius (also called one-third radius) sites and of the total radius. For evaluating the short-term precision, 30 female subjects aged between 43 and 78 years had duplicate nondominant forearm scans on the same day using DXA (Hologic QDR 1000) with repositioning the forearm after the first scan. The precision errors were calculated as the root-mean-square coeﬃcient of variation (RMSCV%). The short-term precision errors expressed as RMSCV% were 2.29% for BMC, 2.42% for BMD at the ultradistal site, 1.49% for BMC and 1.14% for BMD at the mid-distal site, 1.64% for BMC and 1.35% for BMD at the 33% radius, and 1.16% for BMC and 1.13% for BMD of the total radius. We can conclude that the precision errors of BMC are higher than those of BMD at all regions of interest of the radius except for the ultradistal site. It appears that that the precision errors of the BMD at mid-distal site and BMD of the total radius are lower than those at the other sites, with the ultradistal site having the highest precision error. Since measurements with excellent precision do not always have a high sensitivity, the association between these diﬀerent radius sites and fracture prediction remains to be elucidated.

P590SU. CONCORDANCE BETWEEN CENTRAL AND PERIPHERAL SITES BY DUAL X-RAY ABSORPTIOMETRY Rocha FBS1,2, Russo LAT1,2, Silva RO1, Gregorio LH2, Lacativa PGS2, Melazzi AC2, Fernandes MB2, Oliveira FV1, Silva LGP1, Maisonnette MJP1; 1Hospital Pro Matre, 2Center for Clinical and Basic Research – CCBR Brasil, Rio de Janeiro, Brazil Introduction: Over 70% of all fractures in people over 45 years are due to osteoporosis. The medical and social consequences of fractures and the high costs make osteoporosis an important public health problem and a cost-eﬀective approach to prevent the disease is necessary. Studies show that bone mass at peripheral sites correlates well with measurements at more central sites (hip and spine) and the correlation coeﬃcients between peripheral and central sites in general are between 60–70%. The aim of this study is to evaluate the concordance between peripheral and central sites. Methods: 300 postmenopausal women underwent central site measurement (lumbar spine/femur) and peripheral site (forearm). The agreement between central and peripheral sites was determined according to statistics. Results: Average age was 68.3 8.2 years. We observed that the concordance between peripheral and central sites was 65.40% (=0.6540). Conclusion: Although forearm is not used to diagnosis osteoporosis we found a good agreement on both sites. In our country, due to the diﬃculties of our public health system, the forearm can be an alternative, as it is cheaper and easier and can be used as screening.

Radiology, 2Department of Surgery, Trauma and Orthopedic Surgery, University of Munich, Munich, Germany Purpose: Prospective comparison of bone density measured by quantitative ultrasonometry of the calcaneus (QUS) with DXA of the lumbar spine/femoral neck as gold standard. Material and Method: 179 consecutive patients undergoing DXA (Lunar Expertt) were additionally examined by quantitative ultrasonometry of the calcaneus (Lunar Achillest). Sensitivity and specificity were calculated for QUS, Pearson’s correlation analysis was used to compare resulting T-scores. Reduced bone mineral density was defined a T < -1 in both regions measured by DXA. Results: T-scores for QUS and DXA showed moderate positive correlation (r=0.48 with DXA lumbar spine, r=0.47 with DXA femoral neck, p<0.01 in both cases). Correlation between the two DXA locations was moderately positive (r=0.53, p<0.01). Reduced bone mineral density was defined as T < -1. QUS correctly diagnosed reduced bone density in 122/132 patients. 7/47 cases were falsely positive in QUS. This gives a sensitivity of 0.92 with a specificity of 0.85 for QUS of the calcaneus. Conclusion: QUS is a well known, however not fully established method of measuring bone mineral density. Our results indicate that QUS is able to identify patients with a reduced bone mineral density with high sensitivity and specificity. Simple handling, high practicability and lack of radiation exposure may make QUS a useful additional tool for osteoporosis screening.

P592SA. FINITE ELEMENT ANALYSIS OF THE FEMORAL NECK TO PREVENT OSTEOPOROSIS HIP FRACTURES Tovar-López FJ1, Domínguez Hernández VM1, Araujo-Monsalvo VM1, Diez-García MP2; 1Biomechanics Laboratory, 2Osteoarticular Rehabilitation, National Rehabilitation Institute, Mexico City, Mexico Aims: Studies suggests that the relationship between health of bone and mechanical stimulus occurs through bone adaptive remodeling, which is activated by means of shear stress transmitted by interstitial fluid flow. The aims of this work are to analyze the state of shear stresses in four basic movements of the femoral neck in order to compare the distribution and magnitude of the shear stresses in a common zone of fracture and in critical zones of resistance of the femoral head, with the intention of estimating the movement that could induce a faster adaptive bone remodeling. Methods: This work consists of developing a finite element structural analysis of a femur to simulate the basic movements of the hip: flexion, extension, abduction, and adduction. The finite element model was constructed from a free access threedimensional geometry of a left femur, the mechanical properties and the muscular forces were obtained from specialized bibliography. Results: Extension and abduction were the movements simulated that produce a better distribution and it presents the higher magnitude of shear stresses than flexion and aduction. As much in extension as in abduction, the abductor muscle is one of most important. The internal central zone of the femoral neck works under low shear stresses. Conclusions: We conclude that hip abduction and extension are the movements that show a higher mean value and a good shear stress distribution in the femoral neck. These movements must be in the axis of a rehabilitation therapy to increase bone mineral density of the femoral neck by means of adaptive bone remodeling. This is a first step in the development of a therapy for patients with low bone mineral density, helping them to prevent osteoporotic hip fractures. A rehabilitation medical team will manage a therapy based on the results of this analysis. We are looking for the principles of a therapy to increase bone density in weakened zones by osteoporosis with simple hip movements.

P591MO. PROSPECTIVE COMPARISON OF BONE DENSITY MEASURED BY QUANTITATIVE ULTRASONOMETRY (QUS) AND DUAL PHOTON X-RAY ABSORPTIOMETRY (DXA)

P593SU. PRECISION COMPARISON BETWEEN THE HOLOGIC QDR4500 AND THE GE LUNAR PRODIGY

Bitterling H1, Vogel T2, Weber CH1, Bürklein D2, Böhm H1, Pfeifer KJ1, Reiser MF1, Eibel R1; 1Department of Clinical

Albanese CV, Danti M, Passariello R; University of La Sapienza, Rome, Italy

S299 In a clinical osteoporosis practice today, patient management may involve comparison of bone mineral density (BMD) values obtained from diﬀerent bone densitometers. The ability to identify a significant change in patient BMD obtained by two diﬀerent densitometers is aﬀected by two factors: how well do the measurements between the diﬀerent densitometers correlate and how large is the precision error. A lower precision error allows a smaller measured change in BMD to be identified as biological rather than related to instrument variability. Precision error is influenced by type of densitometer, patient population, and by operator experience and training. A total of 31 women had AP spine (L1-L4), total femur, trochanter and femur neck scans on a QDR4500W (Hologic) system and a Lunar Prodigy (GE Healthcare) system. Subjects were measured twice on each system with repositioning between scans. The average subject age was 67 7 years (54–77 yrs). BMD precision error was calculated as the root-mean-square standard deviation and coeﬃcient of variation (CV) for the repeated measurements. To be able to directly compare the precision error between the devices (1), all Hologic values were converted to Lunar-equivalent BMD. QDR4500 precision error at the AP spine, total femur and femur neck region was significantly higher than Prodigy precision error: AP spine (3.84% vs 1.46%, p<0.001) total femur (2.01% vs. 1.03%, p<0.001), femur neck (2.37% vs. 1.68%, p=0.014). For the trochanter region there was no significant diﬀerence between the Lunar and Hologic scanner (1.84% vs. 1.79%, p=0.310). We conclude that the precision error with the Lunar Prodigy densitometer was significantly lower at the AP spine, total femur and femur neck region compared to the Hologic QDR4500. This lower precision error allows earlier detection of clinically relevant changes in patient BMD. 1. Lu et. al (2001) Osteoporosis Int 12:438–444 Table 1

Spine L1-L4 Left Total Femur Trochanter Neck

n

Prodigy CV

QDR4500 CV

p

31 31 31 31

1.46% 1.03% 1.79% 1.68%

3.84% 2.01% 1.84% 2.37%

<0.001 <0.001 Ns =0,014

P594MO. PRECISION COMPARISON OF THE HOLOGIC DELPHI AND THE LUNAR PRODIGY Gross C, Tracewell BA, Harris LG; Foundation for Osteoporosis Research and Education, Oakland, CA USA Dual-energy x-ray absorptiometry (DXA) is widely accepted as the method of choice for assessment of bone mineral density (BMD). The ability to diagnose and monitor a patient’s BMD depends on measurement precision error, which depends on the type of densitometer and operator experience. Lower precision error increases diagnostic confidence and reduces the least significant change, allowing a smaller measured change in BMD to be identified as biological rather than related to instrument variability. We determined precision error with Hologic Delphi and Lunar Prodigy densitometers. Twenty women (average age 59 + 6 years) were scanned three times each at the lumbar spine (L1-L4) and both femurs on both Delphi and Prodigy systems. Subjects were repositioned between each set of spine/femur scans. A single experienced technologist acquired and analyzed all scans according to manufacturers’ recommendations. BMD precision was calculated as the rootmean-square standard deviation (RMS-SD) and coeﬃcient of variation (RMS-%CV) for the repeated measurements. To compare precision between devices, BMD values were converted to an equivalent standard based on this center’s cross-calibration equations. The error variance estimates for the devices were compared using F-tests. Delphi precision error (CV%) was significantly higher than Prodigy at left total femur (1.1% vs. 0.6%; p<0.001), right total

femur (0.9% vs. 0.7%; p<0.05) and left femoral neck (1.7% vs. 1.4%; p<0.05). Using pooled left and right femur results, overall precision error was significantly greater with Delphi compared to Prodigy for total femur (1.0% vs. 0.6%; p<0.001) and femoral neck (1.8% vs. 1.4%; p=0.017). Precision error was higher with Delphi compared to Prodigy at the spine, right femoral neck and trochanter regions, though this diﬀerence was not statistically significant. We conclude that precision error with the Lunar Prodigy densitometer was significantly lower than Hologic Delphi at total femur and femur neck regions in our clinical patient population.

Precision Comparison of Prodigy and Delphi

P595SA. BONE STRENGTH AND BONE MINERAL CONTENT IN RATS WITH EXPERIMENTALLY INDUCED LIVER CIRRHOSIS Ferencz V1, Kari B2, Meszaros S1, Gaal J3, Szalay F1, Mester A2, Horvath C1; 1Semmelweis University, 1st Department of Medicine, 2Semmelweis University, Department of Diagnostic Radiology and Oncotherapy, 3Technical University Budapest, Polymer Engineering and Textile Technology, Budapest, Hungary Our aim was to investigate the relationship between bone strength and bone mineral content at diﬀerent skeletal sites in experimentally induced osteoporosis in rats. Bone mineral content (BMC) was determined by single photon absorptiometry (SPA, Gamma NK-364) at femoral metaphysis and a value well proportioned to BMC was measured by microSEGAMS at trochanter on soft radiographs (Siemens Mammomat) digitalised by Osiris in cirrhotic rats. Maximal loading capacity (Fmax) was determined by biomechanical tests (Zwick020) at femoral metaphysis. The results were compared to healthy controls. In healthy controls strong correaltion was found both between cortical BMC and metaphyseal Fmax (r=0.901, p<0.001), and between cancellous (trochanteric) bone mass and metaphyseal Fmax (r=0.906, p=0.002). Srong correlation was detected between cortical and cancellous bone mass (r=0.809, p=0.015) at femora of healthy rats. However, in cirrhotic animals only cortical BMC showed relationship to metaphyseal Fmax (r=0.769, p=0.003) and no correlation was found between cortical and trochanteric bone mass. Our results showed, that maximal loading capacity at femoral metaphysis could be described by both cortical and cancellous bone mass in healthy controls. In cirrhotic animals, however, cortical and trabecular bone loss are not parallel. Therefore, metaphyseal loading capacity can not be determined by trabecular bone density. Moreover, our results confirm that digitised radiographs could be used to determine a value correlating to bone mineral content.

P596SU. IS BONE MINERAL DENSITY AND LEAN BODY MASS DIFFERENT IN OSTEOARTHRITIS AND OSTEOPOROSIS? Tarantino U1,2, Andreoli A1,3, Celi M1,2, Iundusi R1,2, Lecce D1,2, Cerocchi I1,2; 1University ’’Tor Vergata’’ Faculty of Medicine and Surgery, 2’’Policlinico Tor Vergata’’ Department of Orthopaedics and Traumatology, 3University ’’Tor Vergata’’ Food and Nutrition Unit, Rome, Italy

S300 Osteoporosis is a disease aﬀecting many millions people around the world. Sarcopenia, the decline of muscle mass with age, causes impaired gait, disability and falls. It may therefore increase the fracture risk in osteoporotic subjects. The preferable method for diagnosing osteoporosis is bone density testing. The inverse relationship between the occurrence of osteoarthritis (OA) and osteoporosis is controversial. Aim: of the study was to compare fracturated osteoporotic subjects with subjects aﬀected by hip osteoarthritis and to determine the prevalence of sarcopenia in osteopenic, osteoporotic and osteoarthritic patients. Subjects and Methods: Bone mineral density (BMD), body composition (fat and lean body mass, LBM) of 34 subjects (23 women and 11 men), from 60 to 85 years of age, were measured by dual-energy X-ray Absorptiomety (DXA); furthermore, urinary type-I collagen N-telopeptide (NTx), IGF-1, osteocalcin serum levels and urinary creatinine were measured before a surgical intervention. 18 subjects had surgical intervention for an osteoporotic fracture and 16 had surgical intervention for osteoarthritis. Sarcopenia was defined as a relative skeletal muscle index (RSMI, appendicular skeletal muscle mass divided by height) below 5.45 kg/m(2). Osteopenia was defined by a BMD T-score (g/cm(2)) below -1.0 and osteoporosis by a T-score below -2.5. T-tests were performed to assess diﬀerences and correlations between the two groups. Results: As expected, BMD was significantly diﬀerent between the two groups (p< 0.01). However, OA patients have low BMD according to an osteopenic status. Furthermore, BMD in Ward’s triangle was significantly lower compared to other segments in both groups (p < 0.01). LBM was correlated with total and segmental BMD (r = 0.77) and was inversely correlated with age in both groups. A negative correlation was observed between U-NTx/Cr value and BMD in both groups (P = 0.005 and P = 0.0265). Conclusions: These results showed that lean body mass (LBM) is the strongest predictor of bone in both groups. The amount of muscle mass may play a role in skeletal maintenance. In fact LBM is a modifiable factor, and increasing physical activity and calcium intake could be useful to prevent bone loss and sarcopenia in OA and osteoporosis.

P597MO. STRUCTURAL-FUNCTIONAL STATE OF BONE LOSS OF POSTMENOPAUSAL WOMEN WITH VERTEBRAL FRACTURES Povoroznjuk VV, Grygoryeva NV, Dmytrenko OP; Institute of Gerontology AMS Ukraine, Kiev, Ukraine The aim of this research was studying the bone tissue state among postmenopausal women with vertebral fracture. The total of 71 women 50–74 years old having vertebral fracture in their anamnesis were examined by ultrasound bone densitometry (‘‘Achilles+’’) and X-ray absorptiometry (‘‘Osteolog’’). The control group included 112 postmenopausal women without any osteoporotic fractures in their anamnesis, being standardized by age, body mass index, etc. The speed of sound, broadband ultrasound attenuation, Stiﬀness index, T- and Z-range (ultrasound densitometry) and 1–4 cortical indexes and integral cortical index (X-ray absorptiometry) were measured. Results: The main risk factors for osteoporotic vertebral fracture turned out to be menarche after 15 years, an early and late menopause. All indexes of ultrasound densitometry in postmenopausal women were significantly lower compared the data of healthy patients during all postmenopausal period (Tabl.1). The ultrasound parameters were veritably lower among of all postmenopausal women with vertebral fracture than among control group (SOS: 1525.52.0 and 1498.04.0 m/s, p < 0.05; BUA: 107.30.7 and 99.51.4 dB/MG, p < 0.05; SI: 78.60.9 and 65.91.9%, p < 0,05; all values are the mean standard error). In summary, ultrasound densitometry and X-ray absorptiometry are eﬀective screening methods to reveal women of a risk group having future osteoporotic vertebral fracture in postmenopausal period.

Tab. 1. Structural-functional state of bone mass in postmenopausal women in depend of duration of postmenopausal period and vertebral fractures. Data / Groups

Control group

Women with vertebral fracture

Duration of postmenopausal period - 1–9 years Stiﬀness index, % 83,51,7 65,75,5 * Z-range, SD. 0,40,2 -1,20,5 * Duration of postmenopausal period - 11–19 years Stiﬀness index, % 76,81,3 64,83,3 * Z-range, SD. 0,20,1 -0,90,3 * Duration of postmenopausal period – more than 20 years Stiﬀness index, % 76,22,0 60,34,0 * Z-range, SD. 0,40,2 -1,00,4 *

P598SA. ULTRASONIC IMAGING OF OSTEOPOROSIS: A NOVEL APPROACH TO THE ASSESSMENT OF BONE QUALITY Ghorayeb SR1,2, Wagner C2, Talwar A3, Solounias N4; 1North Shore-LIJ Hospital, The Feinstein Medical Research Institute, Manhasset, NY, 2Hofstra University, Biomedical Sciences, Hempstead, NY, 3Winthrop University Hospital, Bone Mineral Research Center, Mineola, NY, 4New York College of Osteopathic Medicine of NYIT, Old Westbury, NY, USA Currently, there are numerous methods used to detect and determine the level of bone loss in many areas of the body, including the hip, spine, and heel. However, most of these methods require ionizing radiation, which may be harmful to the body. Some of these methods include single-energy x-ray absorptiometry, dualenergy x-ray absorptiometry (DXA), Broadband ultrasonic attenuation, and quantitative computer tomography. The objective of this project is to introduce a less complicated and safer bone diagnostic tool using High Frequency Ultrasound (HiFU) to image and assess bone quality and to determine bone mass in the human ilium. Although the ilium is not the ideal medium for such evaluation, it has been chosen as a proof-ofconcept and for its anatomical shape and flatness. Ten human skeletal ilium samples were used in this study. All of the specimens were assumed to be female while age and race were unknown. For comparison and correlation, final results from the ultrasonic method are compared with bone scans using the DXA modality due to the latter’s prominence in today’s evaluation of human subjects. Several tests were performed on each of the samples in order to obtain a complete quantitative as well as qualitative outcome. Our results show an overall average percent error of 3.5% when compared to DXA. The data correlates extremely well to the family of bone measurements as provided by DXA (correlation coeﬃcient r=0.903). For instance, ultrasonic PBL increases with decreased bone mass, decreased density, and increased porosity. This is reflected in the excellent correlation between the two Comparison of Ultrasonic and DXA Percent Bone Loss vs. Bone Mineral Density Ilium No.

Percent Bone Loss (HiFU PBL)

Percent Bone Loss (DXA PBL)

BMD by DXA (g/cm2)

10 11 12 15 44 48 49 52 54 63

41.5 51.1 46.2 58.9 48.6 55.4 43.6 46.9 54 50.4

41 51 47 57 52 54 44 46 58 46

0.66 0.548 0.596 0.481 0.536 0.515 0.62 0.501 0.469 0.608

S301 methods. Data extrapolation of DXA PBL versus DXA BMD (r=0.870) parallels those obtained with ultrasonic PBL versus physical dry mass density (r=0.674). When the dry mass density is plotted against BMD data obtained with DXA, an excellent positive match is observed as well (r=0.792).

P599SU. BONE MINERAL DENSITY DECREASE CORRELATES WITH N-TELOPEPTIDE OF TYPE 1 COLLAGEN IN SERUM OF HEMODIALYSIS PATIENTS Nakai T1, Masuhara K2; 1Osaka Police Hospital, 2Osaka Kosei Nenkin Hospital, Osaka, Japan Aims: To document which factors contribute to bone mineral density (BMD) in the distal 1/3 of the radius in patients undergoing maintenance hemodialysis (HD). Methods: 47 male and 19 female patients were enrolled in this study. Mean age was 64 years, and duration of HD was 110 months at the time of investigation. BMD was measured by dual-energy x-ray absorptiometry. Serum levels of total calcium (Ca), phosphorus (P), alkaline phosphatase (Alp), intact parathyroid hormone (PTH) and N-telopeptide of Type I Collagen (NTx) were measured. Results: BMI was 21 kg/m2 and duration of HD was 110 months. Serum levels of total Ca, P, Alp, PTH and NTx were 4.5 mEq/l, 6.3 mg/dl, 248 IU/l, 241 pg/ml and 68.9 BCE/l, respectively. BMD was positively correlated with body mass index (r=0.24, p<0.05) and negatively correlated with NTx (r=-0.27, p<0.05) and duration of HD (r=-0.24, p<0.05). Conclusion: Assessing BMD and NTx in HD patients were important. If high serum levels of NTx was demonstrated, then treatment for osteoporosis should be considered.

P600MO. PRECISION OF A NEW DUAL X-RAY AND LASER (DXL) SYSTEM Pfeil A1, Boettcher J1, Petrovitch A1, Kramer A1, Schmidt M1, Lehmann G2, Eidner T2, Schaefer ML1, Malich A3, Kaiser WA1, Wolf G2, Hein G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: Dual-energy x-ray absorptiometry (DXA) is a widely available technique for the assessment of osteoporosis. The usual DXA has an accuracy between 2% and 20%. But a high precision is necessary for diagnosis and monitoring of minor changes in the course of osteoporosis. Dual x-ray and laser (DXL) is a new technique based on DXA technology combined with a laser for measurements of peripheral bone mineral eensity (BMD) at the calcaneus. The purpose of this study is to evaluate reproducibility of DXL dependent on body fat and textile material in the measurement area. Patients and Methods: Reproducibility of DXL was measured on five healthy volunteers. The DXL (Demetech AB, Solna, Sweden) technique uses two x-ray energies in combination with laser measurement of the object thickness in order to determine all three tissue components (bone mineral, lean soft tissues, and fatty tissues). For each subject, measurements of DXL-BMD on the right and left calcaneus were performed. Data of height, weight and body mass index (BMI) were acquired and the study group was subdivided into individuals with underweight (BMI<25), normal weight (BMI 20–25) and overweight (BMI>25). The influence of textile material was evaluated by five measurements with a textile sock (material: 100% cotton, material thickness: 1.3 mm). Results: Reproducibility of the DXL-BMD was CV=1.75% (left) and CV=1.05% (right) for the underweight group. The overweight group showed higher coeﬃcients of variation (left: CV=2.51%, right: 2.23%) compared to the normal weight group (left: CV=3.08%, right: 1.10%). The data showed the highest coeﬃcient of variation for underweight individuals CV=3.30% regarding reproducibility influenced by textile material. Improved results were observed for the normal weight group (CV=2.97%) as well as overweight (CV=3.04%).

Conclusion: The DXL shows a remarkably high reproducibility. However, our data showed an influence by body mass and body fat. Based on these results an accurate and precise measurement of BMD by this new technique is available. In addition, DXL seems to be a promising diagnostic tool in the assessment of osteoporosis at peripheral measurements.

P601SA. THE VALUE OF CALCANEAL QUANTITATIVE ULTRASOUND AND PHALANGEAL PHOTODENSITOMETRY IN DIAGNOSIS OF OSTEOPOROSIS: A COMPARATIVE STUDY Aktas Ilknur; Saygi Hospital, Istanbul, Turkey Aims: The current method for screening osteopenia or osteoporosis involves dual-energy x-ray absorptiometry (DXA). We think there is a strong need for a safe, inexpensive, and quick screening tool which would enable us to identify patients who could benefit from DXA testing. This would reduce the number of patients unnecessarily undergoing DXA tests. We aimed to determine if calcaneal quantative ultrasound (QUS) and phalangeal photodensitometry (PPD) would prove to be useful tools in screening osteoporosis. Methods: We enrolled a total of 69 community-dwelling people aged between 30–81 years. Phalangeal bone density was measured using PPD and calcaneal bone density was measured by QUS. Bone mineral density (BMD) was measured at the lumbar spine and total hip regions using DXA. The screening results conducted by QUS and PPD were compared with the DXA results. Receiver operating characteristic (ROC) curves were constructed by calculating the specificity and sensitivity of QUS, DXA, and PPA at diﬀerent cut-point values in discriminating osteoporosis, as defined by a T-score below -2.5 at the spine or hip using DXA, and the areas under the curves were computed as well. Results: While QUS measurements revealed osteopenia in 21 cases (30.4%) and osteoporosis in 31 cases (44.9%); PPD measurements revealed osteopenia in 21 cases (30.4%) and osteoporosis in 33 cases (47.8%). Whereas according to lumbar vertebra DXA results: 21 cases revealed osteopenia, and 30 cases revealed osteoporosis; according to hip DXA results: 26 cases revealed osteopenia, and 19 cases revealed osteoporosis. The sensitivity, specificity, positive predictive value, and negative predictive value for identifying cases with osteoporosis by QUS were 66.7%, 78.8%, 77.4%, 68.4%, respectively, and by PPD were 75%, 81.8%, 81.8%, 75%, respectively. Conclusions: These data suggest that QUS and PPD may be as eﬀective as targeting DXA testing. Due to highly concordant PPD and lumbar vertebral DXA results, PPD appears to be a useful technique for assessing osteoporosis.

P602SU. ROLE OF DUAL-ENERGY X-RAY ABSORPTIOMETRY IN THE ESTIMATION OF THE RISK FOR FEMORAL NECK FRACTURES IN OSTEOPOROSIS Makarov MA1, Rodionova SS2; 1Institute of Rheumatology RAMS, 2Central Institute of Traumatology and Orthopaedics, Moscow, Russia It is usual to consider the basic criterion for estimating the risk of development of femoral neck fractures in osteoporosis (OP) to be a reduction in BMD assessed by DXA. Aim: To expose the reliability of DXA for estimating the strength of femoral neck in vitro. Methods: The proximal part of femur, taken from 24 dead therapeutic patients, was investigated. All patients were more senior than 60 years and died of somatopathies which did not influence bone metabolism. The proximal part of femur (n=24) was researched by DXA (LUNAR DPX-L) for determining BMD at the femoral neck area, Ward’s triangle and trochanter. Then samples were tested by the test machine ZWICK to purpose the determination of strength. The vertical physical activity was simulated on to the proximal part of femur and its maximal value when femoral neck was fractured, was fixed. The strength was assessed by the fixed maximal load. Results: High significant correlation between the strength and BMD of femoral neck, Ward’s triangle and trochanter was

S302 detected (r=0.86, p<0.01; r=0.75, p<0.01; r=0.87, p<0.01, respectively). Furthermore, there was higher significant correlation between the limit of resilient deformations of femoral neck and its strength (r=0.95, p<0.01). Conclusion: The results of this study demonstrate that DXA is a high-quality method for evaluating bone strength and the risk for development of femoral neck fractures in patients with osteoporosis. At the same time high significant correlation between a limit of resilient deformations of femoral neck and its strength allows assuming that not only quantitative (BMD), but also qualitative characteristics of the proximal femur determine its strength in osteoporosis.

P603MO. AXIAL DXA AND CALCANEUS DXL IN OLDER WOMEN LIVING IN A NURSING HOME Rodionova SS, Kolondaev AF, Morozov AK, VaretskayaChivilikhina NB; Central Institute of Traumatology and Orthopaedics, Moscow, Russia Aim: To estimate the value of calcaneus DXL to detect osteoporosis in institutionalized women. Methods: Thirty-seven postmenopausal women living in a nursing home in Moscow were studied. The average age was 76.320.87 years (57–88 years). Measurements of BMD were taken at the lumbar spine (AP) and upper femur by DXA (Lunar Prodigy), and at the calcaneus by DXL (Calscan). Vertebral lumbar and thoracic deformities were determined by radiography and radiographic morphometry. Results: The mean T-scores were -1.220.14 SD, -1.760.14 SD, -1.240.26 SD, and -2.450.14 SD for total hip, neck, lumbar vertebra, and calcaneus, respectively. The mean Z-scores were 0.310.14 SD, -0.060.14 SD, 0.400.26 SD, and -0.720.13 SD, respectively. Using the cut-oﬀ point of T-score= -2.5 SD, osteoporosis was determined for total hip in four women (10.8%), for neck in eight (21.6%), for lumbar vertebra in nine (24.3%), for calcaneus in eighteen (48.6%), for axial DXA in accordance with ISCD criteria – in fourteen (37.8%), for axial DXA jointly with calcaneus DXL – in twenty-one (56.8%). The sensitivity of calcaneus DXL was 78.6% and specificity was 69.6% in comparison with axial DXA according to ISCD criteria, accuracy 73.0%. Calcaneus BMD correlated with total hip (R=0.57) and neck (R=0.51) but not with lumbar vertebra. Age correlated negatively with calcaneus BMD (R=-0.32), but not with axial BMD. Moreover, positive correlations were detected between age and Z-scores for lumbar vertebra (R=0.42), neck (R=0.33), and not significant for total hip (R=0.29). Vertebral deformities were diagnosed in 75.7% women. The number of vertebral deformities correlated with T-scores for total hip (R=-0.40), calcaneus (R=-0.40) and with Z-scores for total hip (R=-0.36), calcaneus (R=-0.46), but not for lumbar T- and Z-scores. Conclusion: Calcaneus DXL is a promising relatively inexpensive method for screening and detecting osteoporosis in elderly women. Large studies are needed to determine its value in various population groups.

P604SA. EFFECT OF THE LEVEL OF EDUCATION ON TEETH COUNTS AND BONE MINERAL DENSITY IN TURKISH WOMEN Kademoglu O1, Durmus D2, Ceylan G3, Canturk F4, Coskun M5; 1 O.M.U. The Faculty of Dentistry, 2O.M.U. Physical Medicine and Rehabilitation, 3O.M.U. The Faculty of Dentistry, 4O.M.U. Physical Medicine and Rehabilitation, 5O.M.U. The Public of Health, Samsun, Turkey Objectives: There are many factors that aﬀect indirectly bone mineral density (BMD). One of them can be the level of education. The aim of study is to evaluate the eﬀect of the level of education on teeth counts and bone mineral density. Methods: 110 Turkish women who attended our clinic to examine their oral health were included. Their age ranged from 41 to 71 (mean age 51.7 5.20 ). They had dual-energy X-ray

absorbtiometry (DXA) scans. The subjects’ level of education were classified as literate (group 1), primary-secondary education (group 2), college (group 3) and university (group 4). We counted the teeth number in maxilla, mandible and total (excluding wisdom teeth). BMD (g/cm2) of the hip (neck-BMD, Ward’s-BMD and trochanter-BMD) and BMD of the lumbar spine (L2-BMD, L3-BMD, L4-BMD and Ltotal-BMD) were determined by DXA. Statistically we evaluated the diﬀerence between four groups. Results: There were diﬀerences between the groups and mandibular teeth (p<0.01), maxillary teeth (p<0.05), total teeth counts (p<0.001). The diﬀerence is related to group 1 and group 4 (p=0.001, U=32) and group 2 and group 4 (p=0.002, U=372). There were no diﬀerences between BMD values and groups (p>0.05). Conclusions: This study suggests the level of education is an independent predictor of bone density but decreasing the level of education aﬀects maxillary, mandibular and total teeth counts in Turkish women.

P605SU. THE INFLUENCE OF MENOPAUSE YEARS ON TEETH COUNTS AND BONE MINERAL DENSITY Kademoglu O1, Durmus D2, Coskun M3, Canturk F4; 1O.M.U. The Faculty Of Dentistry, 2O.M.U. Physical Medicine and Rehabilitation, 3O.M.U. Public Health, 4O.M.U. Physical Medicine and Rehabilitation, Samsun, Turkey Objectives: The timing of the last menstruation is important because bone mass usually starts to decrease after this period. For women, the year of menopause is mostly the turning of life especially increasing bone loss. The aims of this study were to examine whether the lumbar-hip bone mineral density (BMD) was aﬀected by menopause years and to determine whether a relationship exists between missing teeth count and menopause years. Methods: We counted missing teeth (including wisdom teeth) in maxilla, mandible and total for 110 Turkish women (ages ranged from 41–71, mean 51.75.20 years) who had DXA scans which were taken in the same month. For all subjects the year of menopause was recorded. Subjects were subgrouped as premenopausal women (group A), the year of menopause was between 1–5 years (group B), the year of menopause was between 6–10 years (group C), the year of menopause was between 11–29 years (group D). Bone mineral density (g/cm2) of the hip (neck-BMD, Ward’sBMD and trochanter-BMD) and BMD of the lumbar spine (L2-BMD, L3-BMD, L4-BMD and L-total-BMD) were determined by DXA. Statistically we evaluated the diﬀerence between four groups. Results: There were statistically very significant diﬀerences between all DXA measurements and four groups (p<0.001). There were no diﬀerences between missing teeth counts, the year of menopause and four groups (p>0.05). Conclusions: The rate of BMD loss decreases while the year of menopause increases except for the first five year period. We found no diﬀerence between missing teeth counts and BMD in premenopausal and postmenopausal women. This can be related to dietary habits and deficiency of oral hygiene.

P606MO. EVALUATION OF DXA SPINE, HIP AND DUAL HIP PRECISION USING THE PRODIGY Hadji P, Ziller V, Bauer M, Gottschalk M, Kauka A; Dept. of Endocrinology, Reproductive Medicine and Osteoporosis, University Hospital of Giessen and Marburg, Campus Marburg, Germany BMD measurements are of major importance in the detection and follow-up of patients with osteoporosis. The precision of the measurement device is a key factor in determining whether a measured change in a patient’s DXA result represents a clinically significant change. Although results on the precision of lumbar spine and single hip measurements have been reported, data on dual hip measurements are rarely available. The aim of our study was to evaluate the short-term precision at all relevant sites using the Prodigy.

S303 Methods: 40 pre-and postmenopausal healthy women without a history of osteoporosis or related fracture were included. BMD was measured by DXA (Prodigy, GE Lunar) at the spine and hip. Each woman was measured in accordance to the following protocol: spine, left hip, right hip, dual femur, standing position before repositioning. We found a significant correlation of the absolute values and the T-score between both measurements at the spine(L1-L4) of 2 R =0.99andR2=0.99 representing a CV of 1.00% and a LSC 2.76%. The correlation of the absolute values and the T-score of the repeated measurements at the left total femur was R2=0.97andR2=0.99. The absolute mean values of the repeated measurements at the left total femur, femoral neck, ward triangle and trochanteric region was 0.97, 0.94, 0.75 and 0.79 representing a CV of 0.49, 1.07, 1.14 and 0.72 and a LSC of 1.36, 2.98, 3.16 and 2.0. The correlation of the absolute values of the repeated measurements at the right total femur was R2=0.94 and R2=0.94. The absolute mean values of the right total femur, femoral neck, ward triangle and trochanteric region was 0.97, 0.95, 0.75 and 0.78 representing a CV of 0.52, 1.82, 2.15 and 1.03 and a LSC of 1.43, 5.05, 5.97 and 2.86. The correlation of the absolute values of the repeated measurements at the dual total femur was R2=0.86 and R2=0.90. The absolute mean values of the dual total femur, dual femoral neck, dual ward triangle and dual trochanteric region was 0.97, 0.94, 0.75 and 0.79 representing a CV of 0.31, 0.91, 1.20 and 0.65 and a LSC of 0.87, 2.51, 3.33 and 1.80 respectively. Our results underline the high correlation between repeated measurements at all relevant measurement sites including the dual femur using the Prodigy. This low precision error is of utmost importance in the calculation of the least significant change and in the clinical decision making.

P607SA. WHICH IS THE BEST REGION OF INTEREST TO DETECT AGERELATED BMD CHANGES? Wendlova J; University Hospital and Policlinic, Bartislava, Slovakia Patients and methods: We analysed 498 women (n = 498) in Bratislava (BA) population aged 21–90. We measured bone mineral density (BMD) in the area of proximal femur with a densitometric instrument DXA Osteocore II, France, applying BMD and T-score values in three standard regions of interest: Neck (ROI1), Ward‘s area (ROI2), great trochanter (ROI3). Statistical analysis: 1) Chi-square goodness-of-fit statistics (chi-square test); 2) Analysis of variance (ANOVA). Results: Measured values of T–score in ROI1 and ROI2 have normal distribution and a lognormal distribution of frequency in ROI3. Using chi-square-test, we determined the distribution of frequency of T-score values and the percentage of osteoporosis incidence in Bratislava female population. The osteoporosis incidence in Bratislava female population, according to T-score values measured in ROI1 is 2.40%, in ROI2 16.34% and in ROI3 3.83%. Following the division of women into ten-year intervals, the statistically significant sample averages of T-score values were decreasing in relation to age only for ROI2. According to the analysis of variance, the age category explains 9.6% of the overall variability of T-score values for ROI1, 24.7% for ROI2 and 11.70% for ROI3. Conclusion: As in ROI2 (Ward’s area) greater fraction of the trabecular bone is measured in comparision with ROI1 and ROI3, ROI2 reflects best the age-related BMD changes. In ROI1 and ROI3 the relation was distorted by a greater fraction of cortical bone in comparison with ROI2 and by an accidental selection of a higher number of osteoarthrotic patients in the 61 to 70-year interval for ROI1, and in the 51 to 60-year interval for ROI3. The age of patients is a significant risk factor. Bone mass decreases with age independently of the period of other risk factor activities, and also independently of the fact whether the patient suﬀers from primary or secondary osteoporosis (osteopenia). The development and application of densitometric methods measuring separately the trabecular and cortical bone excludes the distorting factor of osteoarthrosis and should be preferred in densitometric examination methods for a continuous observation of BMD changes.

P608SU. THE DIFFERENCE BETWEEN MANDIBULAR INDEX AND BONE MINERAL DENSITY AT DIFFERENT AGES Kademoglu O1, Durmus D2, Acikgoz A3, Canturk F4, Coskun M5; 1 O.M.U. The Faculty of Dentistry, Samsun, Turkey, 2O.M.U.Physical Medicine and Rehabilitation, Samsun, Turkey, 3Gazi U. The Faculty of Dentistry, Ankara, Turkey, 4O.M.U. Physical Medicine and Rehabilitation, Samsun, Turkey, 5O.M.U. Public Health, Samsun, Turkey Objectives: The aim of study is to determine if a diﬀerence exists between the mandibular index and bone mineral density (BMD) at diﬀerent ages. Methods: 96 female subjects’ panoramic radiographs whose ages ranged from 41 to 60 were evaluated. The radiographs were grouped into 2 groups. The youngest age group was 41–50 years and the oldest was 51–60 years. The mandibular index included the mandibular cortex width (MCW), gonion (GW) and mandiblar inferior cortex (MCI). MCW and GW were calculated on panoramic radiographs, MCI was classified by the same radiology dental expert. The subjects had dual-energy X-ray absorbtiometry (DXA) Bone mineral density (g/cm2) of the hip (neck-BMD, Ward’s-BMD and trochanter-BMD) and BMD of the lumbar spine (L2-BMD, L3-BMD, L4-BMD and L-total-BMD) were determined by DXA. Statistically we evaluated the diﬀerence between two groups. Results: There were significant diﬀerences between BMD (L2 and Ward’s) measurements and two groups (p<0.05). The results of the study showed no statistically significant diﬀerences in other BMD measurements (p>0.05). For MCW, GW and MCI, statistically the diﬀferences were not determined between two groups (p>0.05). Conclusions: In the study BMD measurements and the mandibular index values decreased by increasing age. The conclusion of statistical diﬀerence was amazing, because the other measurements were not statistically diﬀerent except L2 and Ward’s BMD measurements. The diﬀerences both in spongy and trabecular bone resulted from randomly selected subjects. We are planning further studies about this concept.

P609MO. ASSESSMENT OF NORMAL AP-SPINE AND TOTAL HIP BONE MASS DENSITY IN 20–40-YEAR-OLD NORMAL POPULATION FROM TEHRAN USING WITH NORLAND XR-36 IN 2003–2004 Karimi M1, Emam MM2; 1Zanjan University of Medical Sciences, Zanjan, Iran, 2Shahid Beheshti University of Medical Sciences, Tehran, Iran Aims: Osteoporosis is a serious problem in the world. It’s obvious that the bone mineral density (BMD) in Iranian ethnic group is diﬀerent from the current reference of densitometry devices. In this study, we tried to find the BMD in normal population in Tehran. Materials & Methods: In this descriptive study, we randomly selected 129 20–40-year-old people (100women & 29 men) from 5 regions in Tehran. Densitometry was conducted for them in total hip, femoral neck and AP-spine using Norland XR-36. Results: In L2-L4 spine, the average of sBMD in men was 1158156 (reference 1253198). The average of BMD in our subjects compared to reference decreased by 9.5% (PV<0.01). In women the average of sBMD was 1149139 (reference: 1186175) & the average of BMD in our subjects compared to reference decreased by 3.7% (PV<0.05). Femoral neck BMD in men was 0.9920.157 (reference: 1.1680.125) and the average of BMD in our subjects compared to reference decreased by 17.6% (PV<0.001). In women BMD in this region was 0.8700.127 (reference: 0.9870.117) the average of BMD in our subjects compared to reference decreased by 11.7% (PV<0.001). Total hip sBMD in men was 1020 134 (reference: 1147123) and the average of BMD in our subjects compared to reference decreased by 12.7% (PV<0.05). In women the average of sBMD in this region was 907126 (reference 956123) and the average of BMD in our subjects compared to reference decreased by 4.9% (PV<0.05). Conclusion: According to these findings it appears that we should change the Norland reference. Although the number of men in this study was a few, it seems that the current reference

S304 overestimates the diagnosis of low bone mass especially in men and in hip region. L2-L4 sBMD of men should be changed too. L2-L4 sBMD of women approximates Norland’s amount and no change in the reference is needed.

P610SA. HOW BONE DENSITY MEASUREMENTS CORRELATE WITH FRACTURE SITE IN PATIENTS WITH HIP FRACTURES Tuzun ST1, Kirazli YK2, Palamar DP1, Aksoy HA1; 1Istanbul University, Cerrahpasa School of Medicine, PMR Dep., Istanbul, Turkey, 2Ege University, PMR Dep., Izmir, Turkey Hip fractures that are consequences of osteoporosis could occur at diﬀerent sites of the hip. However it is not clear how bone mineral density (BMD) measurements at several regions of hip correlates with the hip fracture localization. We examined if there is any relationship between BMD measurements and the localization of fracture. We enrolled twenty-one patients with osteoporotic hip fractures. DXA was performed with a Lunar DPX-L (GE Medical Systems, Madison, WI) at the proximal femur of the non-fractured hip and at the spine. The mean age of the patients was 75.8010.52 and 3 of them were men and 18 patients were women. Mean height of patients was 1567.2 cm and the mean weight of them was 5912.6 kg. There were 11 inter-trochanteric, 9 femoral neck and 1 subtrochanteric fractures in the study group. One sub-trochanteric fracture was excluded for statistical analysis. There was no relationship between trochanter, total hip, and lumbar (L1-L4) BMD values and the localization of hip fracture. The best correlation was found between femoral neck BMD values and femoral neck fractures. In this preliminary study, we conclude that the most valuable region of interest (ROI) for BMD measurements is femoral neck considering its direct relationship with femoral neck fractures.

Diagnosis Center, 2Isfahan University of Medical Sciences, 3Rheumatology Private Surgery, 4Orthopedic Division, Baharestan Specialist Hospital, 5Orthopedic Division, Sadoughi Hospital, Isfahan, Iran Ojectives: This study compared the eﬀect of menopause on bone mineral density (BMD) of the lumbar spine (LS) and femur neck (FN). Methods: BMD measurements using dual-energy x-ray absorptiometry technique (DXA) were performed at the Isfahan Osteoporosis Diagnosis Center, since March 2002. Among the referred subjects, 174 early postmenopausal women who had no known history of diseases and were not on hormone replacement therapy (HRT) or any medication that aﬀects BMD were selected. The long-term reproducibility (coeﬃcient of variation, CV) of the DXA scanner for BMD measurements during the study period was assessed using the phantom provided by the manufacturer. A Norland XR46 system was used for the investigations. Results: According to the WHO criteria for normal subjects, osteopenic and osteoporotic patients, 74 (42.5%) of the referred subjects had normal T-score, 96 (55.2%) osteopenic and 4 (2.3%) were osteoporotic LS. Fifty two (29.9%) subjects had normal, 97 (55.7%) osteopenic and 25 (14.4%) osteoporotic FN. Long-term BMD CVs of 1.0% and 1.2% for the LS and FN were found, respectively. Conclusions: In spite of the reported lower BMD T-scores for the LS compared with the FN for the early postmenopausal women, we found a significantly lower (t = -3.50, p < 0.001) BMD mean T-score for the FN. BMD T-scores of -1.130.92 SD and -1.461.01 SD for the LS and FN were found, respectively. This finding may be due to physiological and lifestyle factors. Therefore, further research is required to determine the reason(s).

P613SA. QUS: A PREDICTIVE METHOD IN OSTEOPOROSIS

P611SU. LUMBAR SPINE AND HIP BONE MINERAL DENSITY DISCORDANCE ASSESSED BY DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA)

Kayalarak G, Keskin D; Numune Hospital, Pmr Clinic, Ankara, Turkey

Fausto A, Menicagli L, Aliprandi A, Ulgheri N, Sardanelli F; Department of Radiology, Policlinico San Donato, Italy

The aim of the study was to evaluate the relationship between the most relevant risk factors for osteoporosis and speed of sound (SoS) measurements at radius. We report the reference database for SoS at the radius with Sunlight Omnisence 7000S. We studied 87 postmenopausal women between 40–77 years of age with a mean age of 52.70.17. All participiants were questionned on lifestyle habits and on their medical history. After a physical examination SoS was measured by Omnisence distal third of the radius. The SoS at radius was significantly related with T radius (p%0.01) and, bodymass index (p%0.01), and reduced body height (p%0.05) and dairy calcium intake and tea consumption were significantly related with SoS at radius (p%0.05). The age at menopause and the duration of menopause were negatively correlated with SoS (p%0.05). Daily coﬀee intake and smoking, the time spent outdoors exercising had no eﬀect on SoS. In conclusion, most of the risk factors for osteoporosis are associated with SoS. It should be pointed out that the SoS value is a predictive method in patients with osteoporosis. Prospective studies are needed to support the role of Omnisence in assessing the risk factors of osteoporosis.

Aim: To evaluate concordance and discordance between lumbar spine and hip bone mineral density assessed by dual-energy X-ray absorptiometry (DXA). Methods: Three hundred ninety-seven outpatients (age 6210 yrs.) with lumbar spine (L1-L4) and hip evaluation of bone mineral density with DXA (Hologic Delphi) were retrospectively reviewed. We used WHO criteria for the diagnosis of normal, osteopenic, and osteoporotic bone. The information supplied by DXA, T-score and Z-score of both districts, was compared and scored as follows: same results in both districts = concordance; normal/ osteopenia and osteopenia/osteoporosis = grade 1 discordance; normal/osteoporosis = grade 2 discordance. Results: Analysis showed 215 cases of concordance (54%), 159 grade 1 discordance (40%), and 23 grade 2 discordance (6%). Grade 1 discordances were 23 normal lumbar spine/osteopenic hip (14%), 56 osteopenic lumbar spine/normal hip (35%), 12 osteopenic lumbar spine/osteoporotic hip (8%), 68 osteoporotic lumbar spine/osteopenic hip (43%). Grade 2 discordances were all osteoporotic lumbar spine/normal hip. In all groups, no significant diﬀerence for age, menopausal age, weight, and height was observed. Conclusions: About 46% of DXA of lumbar spine and hip were discordant. In our series, grade 2 discordance (all osteoporotic lumbar spine/normal hip) suggests a lumbar spine selective involvement by the disease, confirmed by the prevalence (35%) of osteopenic lumbar spine/normal hip in grade 1 discordance. Bone mineral density loss aﬀects the lumbar spine more often, and probably then spreads to other body regions.

P612MO. A COMPARISON OF DUAL-ENERGY X-RAY ABSORPTIOMETRY MEASUREMENT AT THE LUMBAR SPINE AND PROXIMAL FEMUR FOR POSTMENOPAUSAL WOMEN Salamt MR1,2, Farzaneh SR1,3, Zeyaei HR1,4, Mir Bagheri M1,5, Kompany K1, Mojahedi T1, Bateni N1; 1Isfahan Osteoporosis

P614SU. THE EVALUATION OF VERTEBRAL DEFORMITIES IN PATIENTS WITH OSTEOPOROSIS Kayalar Ak G1, Yildirim N2, Sayin B2, Keskin D1, Dede D2; 1 numune Hospital,Pmr Clinic, 2numune Hospital, Radiology Department, Ankara, Turkey Vertebral deformities are the classical hallmark of osteoporosis and associated with varieties of adverse health outcomes. However precise criteria for the deformities have not been established and detailed information on clinical significance and quality of life are not available. To examine the occurence of vertebral deformities in spinal osteoporotic female patients and the relationship between vertebral deformities and clinical variables and quality of life.

S305 Lateral radiographs of the spine were obtained in 46 female patients with spinal osteoporosis with a mean age of 6110.23. Vertebral deformities were measured semiquantitatively, and vertebral degenerative changes of the thoraco-lumbar spine was measured by Kellgren-Lawrance classification and the presence of osteophytes was assessed as described by Nathan by an experienced radiologist. A clinical examination including demographic variables was performed, and patients with T-score threshold of –2.5 with dual-energy X-ray laser measurement (DXL) at the heel were also examined by dual-energy X-ray absorbtiometry (DXA) of the spine and the hip. Quality of life was measured with specific questionnaire for patients with osteoporosis QUALEFFO. The height of the vertebra correlated with BMI (p%0.05), Zand T-scores of the femur neck and femur wards score (p%0.01). Menopause age correlated with femur neck T-scores (p%0.05). We found that the presence of vertebral deformities were not associated with age, smoking, exercises, and menopouse age. Besides age negatively correlated with DXA scores. Most of the vertebral deformities were identified in the middle thoracic and the thoracolumbar region 22.3% patients had moderate deformities, none of the patients had severe deformities. Vertebral deformities have no eﬀect on spinal osteoporosis and quality of life. Additionally there seems to be no consistent relationship between BMD and vertebral deformities in this patient group.

P615MO. CHANGES IN BONE MINERAL DENSITY AND BODY COMPOSITION DURING LACTATION IN ADOLESCENTS Mansur JL1, Malpeli A2, Etchegoyen G2, De Santiago S3, Kuzminzuk M2, Villalobos R2, González H2; 1Centro de Endocrinología y Osteoporosis La Plata, Argentina, 2Inst de Invest Pediatricas (IDIP, Hospital de Niños Sor María Ludovica La Plata),Argentina, 3Dept de Salud de la Universidad Iberoamericana, Mexico Bone mineral density (BMD) decreases in lumbar spine (LS) during lactation with recovery at six months of weaning. Studies about body composition showed that fat mass (FM) decreases during lactation and lean mass (LM) is preserved. These data are on adults. The objective of the work is to study these changes during lactation in adolescents of 16 years or less. Patients and methods: We studied prospectively 24 adolescents during lactation at 15 days, 3, 6 and 12 months after delivery. Age: 15.2+/-0.7 years. We measured weight, height, BMI, body composition by skinfold and DXA with FM and LM in arms, legs and trunk, and BMD of LS, femoral neck (FN) and total hip (TH), and total body bone mineral content (BMC) with Lunar IQ with pediatric software. Results: Weight: 54.7 kg(+/-5.1), Height: 155 cm (+/-5.1), BMI: 23.0 (+/-2.0), Calcium intake: 662.73 (+/-248) mg/d. Changes (basal-3m-6m-12m): — BMD LS%: 100–98.2–101.5–106.4# — BMD FN%: 100–94.4#-94.7#-97.7 — BMD TH%: 100–95.5#-95.0#-98.1 — BMC TB%: 100–97.3#-96.9#-98.3 — %FM(DXA): 35.4–32.7–29.6#-27.7# — %FM(SKIN): 29.9–28.5–27.1–23.3# — LM (kg): 32.6–32.5–33.3–34.0 — WEIGHT: 54.8–52.7–51.5–51.0( — #: p<0.001 vs basal (: p<0.01 Fat mass diminish (p<0.001) in arms (2.75 kg basal vs 1.60 kg at 12 months), legs (6.18 vs 4.92) and trunk (9.25 vs 6.57) all p<0.001). Conclusions. In adolescents during lactation LS-BMD has no loss and is better at 12 months. In FN, TH and BMC there is bone loss with recovery. Lean mass does not change. FM diminishes in all regions but these change do not aﬀect bone recovery. These data are important because these women have not reached the peak of bone mass and many of them will have new pregancies before this moment.

P616SA. CHANGES IN BONE MINERAL DENSITY UNDER ANTI-TNF ALPHA THERAPY IN RHEUMATOID ARTHRITIS Ancuta C1,2, Chirieac R1,2, Ancuta E1, Iordache C1, Tacu C1,2, Munteanu C1,2, Macovei L1,2, Nita G1,2; 1University of Medicine and Pharmacy ’’Gr.T.Popa’’, 2Rehabilitation Hospital, Rheumatology Department, Iasi, Romania It is well known that secondary osteoporosis (related to increased levels of pro-inflammatory cytokines such as IL-1 and TNF, corticosteroids and methotrexate administration, impaired exercise) represents a common feature of rheumatoid arthritis (RA). Objective: to assess changes in bone mineral density (BMD) and bone markers in patients diagnosed with RA receiving anti-TNF therapy (infliximab, Remicadet). Patients and methods: 30 patients (15 women, 5 men) with a mean age of 42.7 years and mean disease duration of 3.9 years, suﬀering from severe active RA despite adequate DMARDs and, eventually, corticosteroids were enrolled in a prospective 12 months study. All patients received infliximab at a dose of 3 mg/kg/perfusion according to the standard protocol (week 0, 2, 6 and then every 8 weeks). Assessments included: BMD and bone markers (alkaline phosphatase, serum calcium, osteocalcin levels) at baseline and month 12; inflammatory (ESR, CRP) and immune (rheumatoid factor) parameters, disease activity score (DAS28) at baseline, month 6 and 12. Patients were not allowed to take any anti-resorptive therapy including bisphosphonates and selective estrogen receptor modulators. Results: statistically significant increases in both axial and peripheral BMD were demonstrated at month 12 as compared to baseline in all patients (T-score, Z-score p<0.01); statistically significant increase in osteocalcin level (p<0.01), but no change in alkaline phosphatase and serum calcium were registered at the end of the study. Statistically significant negative correlation between both axial and peripheral BMD and RA activity as defined by DAS28 was reported at baseline and at the end of therapy (r=-0.78, p<0.01; r=-0.81, p<0.01). Conclusion: changes in BMD reported in RA patients after one year of infliximab therapy may be related to the decrease in pro-inflammatory cytokines levels and activity.

P617SU. LONGITUDINAL QUANTIFICATION OF PERIARTICULAR DEMINERALIZATION AND JOINT SPACE NARROWING IN RHEUMATOID ARTHRITIS Boettcher J1, Pfeil A1, Petrovitch A1, Kramer A1, Lehmann G2, Malich A3, Kaiser WA1, Wolf G2, Hein G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-SchillerUniversity Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: This study evaluates digital x-ray radiogrammetry (DXR) and Radiogrammetry Kit (RK) as new diagnostic tools for quantification of disease-related periarticular osteoporosis and joint space narrowing dependent on the course of 6 years in patient suﬀering form rheumatoid arthritis (RA). Patients and Methods: 258 patients with verified RA (ACR criteria) underwent computerized calculations of bone mineral density (BMD) and metacarpal index (MCI) by DXR. BMD and MCI were estimated on the three middle metacarpals from radiographs of hand using the Pronosco X-Posure System (Version 2,

S306 Sectra, Sweden). The RK estimated the joint space distance of the metacarpal-phalangeal articulation II–V (JSD-MCP). This RK technique performed a joint space analysis of the metacarpalphalangeal articulation II–V. The distance between the joint edges were given in cm. A digital performed radiograph of the nondominant hand for DXR and RK measurements was annually acquired for each patient. Results: All RK and DXR parameters significantly decreased depending on the course of RA. The relative joint space narrowing ranged from -18.8% (JSD-MCP V) to –31.6% (JSD-MCP II). The JSD-MCP (mean) showed a relative reduction of -23.5%. On average our study verified an annual narrowing of the JSD-MCP (mean) with -2.0%. In the first year of RA manifestation, thus technique showed a narrowing of –11.8% (JSD-MCP mean). After a disease duration of more than one year a more flattened decline of JSD-MCP (mean) was observed (-11.7%). Over a period of six years a relative decrease of DXR-BMD (-32.1%) and DXR-MCI (-33.3%) was observed, which were pronounced in early RA (disease duration: <1 year). Conclusion: In this longitudinal study significantly marked reduction of JSD-MCP as well as DXR-BMD could be verified and accentuated in the early and prolonged course of RA. Therefore, the operator-independent RK and DXR technology could be an important diagnostic tool in RA by which the clinician can detect those patients who require more aggressive management of their RA in order to prevent joint destruction, which will inevitably lead to major disability.

P618MO. FRACTURES, BONE MINERAL DENSITY AND BONE TURNOVER IN A DUTCH SARCOIDOSIS POPULATION Heijckmann AC1,2, Huijberts MSP1, De Vries J3,5, Wolﬀenbuttel BHR4, Geusens P1,5,6, Drent M5; 1University Hospital, Maastricht, The Netherlands, 2Hospital Bernhoven, Veghel/Oss, The Netherlands, 3Medical Psychology, Tilburg, The Netherlands, 4 University Medical Center, Groningen, The Netherlands, 5Sarcoidosis Management Center, Maastricht, The Netherlands, 6Biomedical Research Center, Hasselt, Belgium Background: Sarcoidosis is a chronic T-cell-driven disease in which patients can have disturbed calcium homeostasis and are often treated with glucocorticoids (GC). However, little is known about the risk of osteoporosis. Aims: To evaluate bone mineral density (BMD), bone turnover, and the prevalence of fractures in patients with sarcoidosis and to identify their determinants. Methods: BMD of the hip and morphometry of the vertebrae were evaluated in 138 patients with sarcoidosis using dual-energy x-ray absorptiometry. Markers of bone resorption (serum C-terminal telopeptide of type I collagen, ICTP) and formation (serum procollagen type I N-telopeptide, PINP) were also measured. Determinants of BMD and bone markers were assessed using multivariate analysis. Results: In the total group, Z-scores for BMD at the femoral neck and trochanter were normal. Z-scores were negatively related to 1,25(OH)2D3 and at the trochanter to GC use. Z-scores at the trochanter were significantly increased in GC-naïve patients [0.5 (CI: 0.1, 0.7), p<0.005] and this was paralleled by increased Z-scores for PINP [0.3 (CI: 0.0, 0.6)] (figure). In the total group, Z-scores for ICTP were increased [1.0 (CI: 0.6, 1.3), p<0.05] and related to inflammatory markers (IL2R, ACE) especially in patients using GC (r=0.534 and 0.414, respectively). The prevalence of fractures was low and was associated with longer disease duration and more GC use. Conclusions: Evaluation of this large cohort of 138 patients with sarcoidosis shows that the overall eﬀects of this inflammatory T-cell-driven disease on BMD are limited. BMD appeared to be normal in patients with sarcoidosis and even increased in GCnaïve patients, who also demonstrated increased bone formation. Bone resorption was increased and correlated with inflammation. Fracture risk does not seem to be increased in this population.

Figure: Z-scores in the GC-naïve group (n=52) versus current GC users (n=52)

P619SA. BONE HEALTH STATUS IN CHILDREN AND YOUTH WITH CYSTIC FIBROSIS: ASSOCIATION WITH BODY SIZE, PHYSICAL ACTIVITY AND VITAMIN D AND K STATUS Atkinson SA1, Grey V1, Drury D2, Casey L3, Ferland G4, Gundberg C5, Lands L2; 1McMaster University, Hamilton, Canada, 2Montreal Children’s Hospital, Montreal, Canada, 3University of Alberta, Edmonton, Canada, 4University of Montreal, Montreal, Canada, 5Yale University, Hartford, USA Aim: To assess bone health in pediatric CF in relation to body size, physical activity (PA) and vitamin D and K status. Methods: A cross-sectional observational study at 3 Canadian pediatric centres was conducted in 52 children (29 M/23 F) not taking systemic steroids. Anthropometry and body mass index (BMI) were computed as Z-scores. Whole body bone mineral content (WBBMC) and lumbar spine L1-L4 bone mineral density (LSBMD) were measured by Hologic Discovery or Lunar Prodigy DXA machines and Z-scores computed (www.bcm.tmc.edu/ bodycomlab/). Pulmonary function tests were conducted and fasting blood samples analyzed for 25-OH vitamin D, vitamin K, PIVKA-II, and undercarboxylated (Glu-OC). Intake of calcium and vitamins D and K from food and supplements and PA were assessed by validated questionnaires. Univariate and multivariate correlations were computed. Results: Subjects (mean age=12.7 yr (range 8.1–17.9 yr) were relatively healthy with 80% of subjects having a FEV% >60 and a BMI >10%ile. Z-score for LSBMD was < -1.0 in 50% of subjects, and for WBBMC was < -1.0 in 38% of subjects. Mean plasma 25OHD was 5420 nmol/l with 16% of subjects classified as deficient (< 30 nmol/l) and 68% as insuﬃcient (>30 < 80 nmol/L). Mean plasma vitamin K was 0.611.1 nmol/L but 64% of subjects were abnormal (<0.29 nmol/L). Low vitamin K status indicated by Glu-OC >20% and PIVKA-II >2 ng/mL occurred in 64% of subjects. Mean intake of vitamin D was 1014 (range 45–1898) IU/d, calcium was 2649 (908–5318) mg/d and vitamin K was 336 (44–694)µg/day. LSBMD (r=0.48, p<0.01) and WBBMC (r=0.35, p<0.04) were weakly correlated with PA. In a multivariate analysis that included PA, weight and height z-score and vitamin D and K status, only weight z-score was a significant predictor for z-scores of WBBMC (r= 0.78, p<0.001) and LSBMD (r=0.61, p<0.001). Conclusions: Low bone mass for age occurs in up to 50% of children with CF despite vitamin supplementation and mild lung disease. We speculate that significantly higher intakes of vitamins D and K, and improved body weight and physical activity will benefit bone health status in pediatric CF patients. (Supported by Canadian Cystic Fibrosis Foundation)

P620SU. MICROCT ANALYSIS OF BONE FROM GLUCOCORTICOID-TREATED MALE PATIENTS Chappard D, Josselin N, Legrand E, Baslé MF, Audran M; INSERM, EMI 0335 – LHEA, Faculté de Médecine, Angers, France

S307 Deleterious eﬀects of glucocorticoid (GC) on the skeleton is recognized in up to 50–100% of patients receiving CS for more than 5 years. Trabecular bone of the appendicular skeleton is particularly sensitive to GC because of its high turn-over rate. The eﬀects of CS on cells of the osteoblastic lineage has been reported by several groups from studies based on histomorphometric analysis of bone biopsies. The consequences of GC on bone cells are a net reduction in bone mass associated with marked alterations of the trabecular microarchitecture. 2D histomorphometric technics based on image analysis of bone sections are helpful to characterize the microarchitectural changes in osteoporosis due to GC. We have investigated the 3D microarchitectural changes of trabecular bone by µCT in 25 male patients having received a prolonged CS treatment. All of them had reveived GC for more than 5 years at a dose >7.5mg/D. Bone biopsies were imaged by µCT and 3D measurements were compared to 8 male controls who died from sudden death. The frequency distribution of trabecular thickness (Tb.Th) and separation (Tb.Sp) were taken into account. Trabecular bone volume vas significantly reduced (13.3 5.3 vs 18.7 2.15 %; p=0.0092) and the trabecular number did not diﬀer between groups (0.93 0.08 vs 0.82 .23). The frequency distribution of Tb.Th indicated that the curve of Tb.Th was markedly displaced toward the low values; however, Tb.Sp curves were similar. In GC induced osteoporosis, there is a global tendency for the whole trabecular network to be composed of thinner trabeculae without removal of trabeculae.

mild hyperparathyroidism with an increased iPTH level and serum osteocalcin level are usually observed in these patients at various times (even late) after Tx; 3) persisting secondary hyperparathyroidism is one of the determining factors for the development of osteopenia at the late stage after kidney Tx.

Serum creatinine (mmol/l) Endogene creatinine clearance (ml/min/1,73m2) Serum calcium (mmol/ l) Serum phosphorus (mmol/l) Serum osteocalcin (ng/ ml) iPTH (pmol/l) Bone speed of sound (m/s) T-score (SD) Z-score (SD) #

Pts < 1 year after Tx (n=32)

Pts 1 - 5 years after Tx (n=35)

Pts > 5 years after Tx(n=34)

0.160.07

0.180.05

0.16 0.06

53.612.8

48.910.5

50.812.3

2.710.29

2.380.31#

2.340.32#

0.860.26

1.010.20

1.000.19

44.830.4

31.817.3#

28.615.7#

17.613.3 2045.581.2

11.07.2 2066.679.1

10.75.3# 1994.8107.4*#

-1.121.15 -0.450.89

-0.811.12 -0.451.04

-1.841.53*# -1.461.48*#

p<0.05 vs 1 year group; * p<0.01 vs 1 – 5 year group

P622SA. LONG-TERM EFFECTS OF ALENDRONATE THERAPY ON BONE LOSS AFTER LIVER TRANSPLANTATION Atamaz F1, Hepguler S1, Akyildiz M2, Karasu Z2, Kilic M3; 1 Department of Physical Therapy and Rehabilitation, 2Department of Gastrology and Hepatology, 3Department of Surgery, Ege University Medical School, Turkey

P621MO. PERSISTING SECONDARY HYPERPARATHYROIDISM AND OSTEOPOROSIS IN LONG-TERM KIDNEY GRAFT RECIPIENTS Adamsone I1, Babarykin D2, Folkmane I1, Amerika D1, Rosental R1; 1Riga Stradins University, 2University of Latvia, Riga, Latvia Disorders of calcium-phosphorus (Ca/P) metabolism observed after kidney transplantation (Tx) could be partly caused by CRF related renal osteodystrophy which persists after even successful kidney Tx. The most serious consequence of high bone turnover induced by elevated iPTH is reduction of bone mass. Our study aimed to investigate Ca/P metabolism and bone mass during the various post-Tx periods in order to analyse risk of secondary hyperparathyroidism in development of post-Tx osteopenia. 101 pts (56 females, 45 males) after kidney Tx were investigated. Mean age was 43.921.2 years (range 20–65 years), the average duration of haemodialysis before Tx was 17.312.8 months (range 3–37 months). All pts were divided in three groups according to the time after Tx: pts up to 1 year after Tx (n=32); pts from 1 to 5 years after Tx (n=35); and pts more than 5 years after Tx (n=34). Biochemical parameters and bone mineral density measured by ultrasound densitometry at hand phalangeal bones were shown in table (see below). Negative correlation (r=-0.41, p<0.01) between iPTH and osteopenia level (expressed as T-score and Z-score) was found in all 101 pts. We also noted a negative correlation between patients age and AdSoS and T-score (r=-0.32, p<0.02). The whole pts population showed negative correlation (r=-0.28, p<0.05) between Z-score and time after Tx. The multiple regression analysis showed that only iPTH concentration were associated (p<0.02) with reduced peripheral trabecular bone mass. We conclude that: 1) osteopenia is common complication after kidney Tx, especially in patients with impaired graft function; 2)

Objective: Our objective was to determine whether the eﬀects of alendronate are persistent 1 year later after drug withdrawal in patients with orthotopic liver transplantation (OLT) who received it during the postoperative 2 years. Patients and Methods: A total 26 patients with OLT were enrolled into the study. Each patient received alendronate 70 mg weekly, calcium 1000 mg daily and 0.5 µg calcitriol daily during 2 years after OLT. Sixteen patients continued the treatment after 2nd year, while 10 patients received only calcium and calcitriol during the 3rd year consisting of the control group. The primary outcome measure was the percentage of change in lumbar spine bone mineral density (BMD) at the 3rd year. Secondary measures were proximal femur BMD values. Additionally, serum osteocalcin and urinary deoxypyridinoline (DPD) were determined every 3 months. Spinal radiographs were obtained to assess vertebral fractures. Results: Compared with baseline, although there was a significant increase in the BMD of lumbar spine at the 2nd year (8.4%, p<0.05 vs baseline), this increase was not persistent in the control group at the 3rd year (6.2%). The mean percent increases in the femur neck and total femur were 5.3% and 4.6%, respectively at the 3rd year, in the control group. The patients who continued alendronate showed a significant increase by 9.4%, 7.1% and 6.5% at the lumbar spine, femur neck and total femur, respectively (p<0.05) at the 3rd year. Serum osteocalcin and urinary DPD decreased significantly at 6th month, with no further change during the 2-year period, by -34.1% and -60.0%, on the average, respectively. In the control group, bone biochemical markers of bone turnover were increased again after withdrawal of alendronate by 12.3% and 21.4%, repectively. No patient developed bone fracture during the follow-up. Conclusion: This is the first report indicating that alendronate therapy was well tolerated and produced a significant increase on lumbar spine BMD during the 3 years after OLT.

S308

P623SU. LOW PHYSICAL ACTIVITY, BODY SIZE AND CALIUCM INTAKE AS PREDICTORS OF BONE HEALTH STATUS IN CHILDREN AND YOUTH TREATED WITH ANTI-EPILEPTIC DRUGS Chauhan P, Wang D, Steele S, Roche L, Ronen G, Atkinson SA; McMaster University, Hamilton, Canada Aim: To examine the contribution of body size, physical activity (PA) and calcium intake to bone health status in children with epilepsy treated with anti-epileptic drugs (AED). Methods: Children (n=176, median age = 11.2 yr, range = 4.4 – 17.9 yr) treated with AED for > 3 yr were recruited for a single assessment that included measures of weight and height, and whole body bone mineral content (WBBCM) and lumbar spine bone mineral density (LSBMD) by dual-energy x-ray absorptiometry (Hologic QDR1000W and Discovery A) with z-scores for WBBMC and LSBMD calculated from reference data (www.bcm.tmc.edu/bodycomlab/). Calcium and vitamin D intake from food and supplements and PA scores were obtained by validated questionnaires. Multivariate correlation was conducted to define significant determinants of bone status. Results: Z-scores of < -1 for WBBMC occurred in 28% of males and 22% of females and for LSBMD in 31% of males and 34% of females. By multivariate analysis WBBMC Z-score was significantly associated (r=0.80) with PA (p< 0.02), weight z-score (p<0.0001) and height z-score (p<0.0001). For LSBMD z-score, the only significant predictor was height z-score (r=0.54, p< 0.0001). Median calcium intake (1563 mg/d, range = 351 - 4842 mg) and vitamin D intake (250 IU/d, range = 0–822 IU) were above the Dietary Reference Intake for age. When calcium intakes were partitioned into high and low, the lower calcium intake group had a significantly lower WBBMC z-score for males (-0.991.04 vs. 0.001.42, p=0.03), but not for females (-0.231.47 vs. 0.151.37). Conclusions: Low bone mass was observed in nearly a third of the children on chronic AED therapy. Inactivity and achieved height and weight appear to be the major predictors. Calcium and vitamin D intake may not be influential to bone mass since this population of children and youth treated with AED generally met recommended intakes for these nutrients. Funded by the Bloorview Children’s Hospital Foundation and the Hamilton Health Foundation.

P624MO. DISEASE-RELATED PERIARTICULAR BONE LOSS IN EARLY RHEUMATOID ARTHRITIS MEASURED BY DIGITAL X-RAY RADIOGRAMMETRY (DXR) Boettcher J1, Pfeil A1, Petrovitch A1, Lehmann G2, Schaefer ML1, Malich A3, Eidner T2, Kaiser WA1, Wolf G2, Hein G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-SchillerUniversity Jena, 2Clinic of Internal Medicine III, FriedrichSchiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: Rheumatoid arthritis (RA) is a systemic inflammatory disease, which prematurely aﬀects the small joints of the hand leading to destruction of periarticular tissue, including juxtaarticular bone. Osteoporosis is a major clinical complication in RA and occurs in two forms: periarticular osteoporosis in near proximity to inflamed joints, which is a typical phenomenon in early RA, and generalised osteoporosis aﬀecting the axial and appendicular bones occurring during the course of rheumatoid disease. Recently receptor activator of nuclear B ligand (RANKL) and osteoprotegerin (OPG) have been identified as central regulators of osteoclast recruitment and activation and appear to systemically influence bone resorption in the juxta-articular bone. Our study evaluates the ability of DXR to measure inflammation-related variations of cortical bone partition in patients with early RA compared with dual-energy x-ray absorptiometry (DXA). Patients and Methods: 77 patients with early RA (disease duration:<1 year) underwent a prospective analysis of bone mineral density (BMD) and metacarpal index (MCI) by DXR. BMD and MCI were estimated from plain radiographs of the nondominant hand using the Pronosco X-Posure System (Version 2.0, Sectra, Sweden), which digitized images with a scanner and derived radiogeometrical parameters from the three middle metacarpals.

DXA (Hologic QDR 4500, Waltham, USA) calculated BMD on lumbar spine and proximal femur. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded. The patients were devided into two groups: group 1: CRP>20 and ESR>15 mm/first hour (n=36), group 2: CRP<20 and ESR<15 mm/first hour (n=41). Results: The relative decrease of DXR-BMD between group 1 and 2 was -15.1% (p<0.01). For group 1 versus group 2, DXRMCI showed a significant reduction of -17.5%. The reduction of DXA-BMD revealed only significant results regarding measurements at the lumbar spine with -7.7%. Conclusion: DXR can quantify inflammation-related cortical BMD loss in patients suﬀering from early RA, whereas DXA only documents minor alterations of bone tissue at the axial measurement site.

P625SA. ESTIMATION FROM EARLY CHANGES OF SERUM PROCOLLAGEN TYPE I AMINOTERMINAL PROPEPTIDE OF THE LUMBAR BMD GAIN AFTER 2 YEARS IN CHILDREN SUFFERING FROM SEVERE OSTEOGENESIS IMPERFECTA Devogelaer JP, Depresseux G; Rheumatology Unit, St-Luc University Hospital, Brussels, Belgium Three-day intravenous (IV) pamidronate every 3 months has become a classical therapy of severe osteogenesis imperfecta (OI) in children. However, this therapy is rather heavy, and a rapid determination of its future eﬃcacy should be welcome. We have therefore determined whether the measurement of changes of serum procollagen type I aminoterminal propeptide (PINP), a biological marker of bone formation, between day 0 and day + 3 could help to foresee the BMD response after 2 years. We have treated 11 patients [M, 9; F, 2; aged 10.4 (3.7 SD)] suﬀering from severe OI with IV pamidronate. sPINP was measured on day 0 and + 3, by radioimmunoassay (Orion Corporation Espoo, Finland). The results were expressed as a percentage value of day 0 and day 3. Lumbar-BMD (L1-L4-BMD) was measured by DXA (QDR 4500 Elite, Hologic Inc, Bedford MA) at time 0 and at time + 24 months. On average, after 3 days of therapy, PINP value decreased from 398 (251) to 194 (193) ?g/l (- 52 %, p < 0.001) and L1-L4-BMD increased from 0.454 (0.134) at time 0 to 0.648 (0.155) g/cm2 (+ 43 %, p < 0.001) after 24 months. A significant inverse correlation was observed between PINP changes (0 – 3 days) and L1-L4-BMD (0 - 24 months) [r = - 0.60 (p = 0.05)]. In conclusion, a significant decrease of PINP between day 0 and day 3 during a 3-day IV pamidronate therapy is accompanied by a significant increase of L-BMD after two years. The PINP measurements could constitute a promising biological measurement leading to a better compliance to therapy.

P626SU. HELICAL PEPTIDES IN THE EVALUATION OF BONE LOSS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS Bozic B1, Prodanovic N1, Petrovic R2; 1Military Medical Academy, 2Institute of Rheumatology, Belgrade, Serbia and Montenegro Introduction: Inflammation, a common property of rheumatoid arthritis (RA) and osteoarthritis (OA), has an influence on increased bone degradation. Bone markers are good parameters which picture bone metabolism. Helical peptides are new sensitive markers of bone degradation. Aim: The aim of this study was to compare concentrations of helical peptides in urine and synovial fluid of patients suﬀering from RA and OA. Methods: The study included 35 patients with rheumatoid arthritis (RA) and 21 patients with osteoarthritis (OA). The inclusion criteria for this research were arthritis of the knee joint and absence of factors influencing bone metabolism without application of any antiosteoporotic drugs to estimate bone metabolism evaluated with bone degradation marker, helical peptides (HP). ELISA assay was used to determine HP in urine (U) and synovial fluid (SF).

S309 Results: The group of patients with RA included 23 women and 12 men, average age 55, with RA lasting 7 years in average. The group of patients with OA included 9 women and 12 men, average age 56, with OA lasting 8 years in average. The patients with RA had increased values of HP detected in urine (161.37+/-84.14 µg/mmol) and synovial fluid (110.57+/-63.65 µg/mmol). Also, the group of patients with OA had increased values detected in urine (120.81+/-33.58 µg/mmol) and synovial fluid (79.41+/-10.86 µg/ mmol). HP values in urine correlated with the values in synovial fluid in both groups of patients: RA (r=0.682 p=0.000) and OA (r=0.448 p=0.041). The HP values in patients with RA were statistically significantly higher than the values in patients with OA in urine (p=0.040) and synovial fluid (p=0.031). Conclusion: Our results confirmed that the bone degradation markers, helical peptides, are very important markers of bone loss in patients with RA and OA. The HP point to increased bone degradation in the system and local level in patients with RA and OA. The process of bone degradation is significantly higher in patients with RA compared to patients with OA. The results of this study show the significance of determining HP in urine and synovial fluid as a marker of bone degradation.

P627MO. RELATIONSHIP BETWEEN DELAYED MENARCHE AND BONE MINERALIZATION IN PATIENTS AFFECTED BY JUVENILE IDIOPATHIC ARTHRITIS (JIA) Lurati A, Cimaz R, Teruzzi B, Gerloni V; Gaetano Pini Institute, Milan, Italy Background: Puberty is an essential step in bone mass accrual. Growth failure and impairment of sexual maturation are frequent manifestations of chronic illnesses in pediatric population, and chronic rheumatologic disorders such as juvenile idiopathic arthritis (JIA) are no exception to this. Methods: The aim of our study was to prospectively evaluate bone density in adolescent females with JIA, and to correlate results with clinical variables, in particular with age at menarche. Lumbar spine (L2-L4) bone mineral density (BMD) (assessed by DXA) was monitored every 6–12 months in a group of 38 girls with JIA. The evaluated bone mass accrual during the peripubertal time as well as absolute and relative (Z-score) BMD in relationship with age at menarche, mother’s age at menarche, JIA type, disease activity (as evaluated by ESR and Hgb), body mass index (BMI) and corticosteroid treatment (mean pro kg daily dose, cumulative dose) was assessed. Results: Patients were divided into two groups: — group I included girls with menarche age within normal limits for Italian standards; — group II included girls with delayed menarche. The BMD values and Z-scores in group I were not significantly diﬀerent to normal population. The BMD values and Z-scores in group II were significantly decreased when compared to the normal population (p<0.001). With a multivariate analysis only age at menarche seemed independently related to peripubertal mineralization (p=0.025, r between –0.65 and –0.75). With a binary logistic analysis only disease activity (ESR and Hgb values) seems indipendently related to a menarche delay (OR 1.16 for each mm/h). Conclusion: Our data show a critical role for disease activity in determination of a regular pubertal onset, and a normal age at menarche in determination of optimal bone mineralization.

P628SA. SEVERITY DEPENDENT JOINT SPACE NARROWING IN RHEUMATOID ARTHRITIS DETECTED BY RADIOGRAMMETRY KIT (RK) Boettcher J1, Pfeil A1, Petrovitch A1, Seidl BE1, Lehmann G2, Kramer A1, Schaefer ML1, Malich A3, Kaiser WA1, Wolf G2, Hein G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: Inflammatory-related joint alteration in rheumatoid arthritis (RA) is associated by cartilage destruction and a consecutive joint space narrowing. This cross-sectional study presents the Radiogrammetry Kit (RK) as a new diagnostic tool for quantification of

disease-related joint space narrowing dependent on the severity of RA . Patients and Methods: 258 Caucasian patients were enrolled without preselection regarding the grade of RA based on ACR criteria. For every patient a radiograph of the nondominant hand was performed. The RK (Version 1.3.5; Sectra Pronosco A/S; Denmark) estimated the joint space distance of the metacarpalphalangeal articulation II–V (JSD-MCP). This RK technique performed a joint space analysis of a finger joint by detection of the joint edges within a rectangular region of interest (ROI). The software based on an edge filtering of the ROI automatically determined the distance between the two edges. The distance between the bone edges were given in cm for the metacarpalphalangeal articulation II–V. Severity of RA was assessed using Larsen score, Steinbroker stage and Sharp score. Results: For Steinbroker stage JSD-MCP (mean) showed a significant narrowing of -52.9%. Regarding the various joints a relative decrease between -40.0% (JSD-MCP V) and -63.2% (JSDMCP II) was observed. Regarding the Larsen score the joint space narrowing varied from –25.0% (JSD-MCP IV) to -44.4% (JSDMCP II). A reduction of -35.3% for JSD-MCP (mean) was observed. In both Sharp scores JSD-MCP (mean) showed an narrowing of –41.2% for the joint space narrowing segment of the score, whereas the Sharp Erosion score revealed a lower decline of JSD-MCP (mean) with –29.6%. For the other joints there was a relative reduction between -16.5% (JSD-MCP IV, Sharp Erosion part) and -52.6% (JSD-MCP II, Sharp joint space narrowing part). Conclusion: The Radiogrammetry Kit could be a promising, widely available diagnostic tool to supplement the diﬀerent scoring methods of RA with quantitative data; andallowing an earlier and improved diagnosis of RA and more precision in determining disease progression.

P629SU. JUXTA-ARTICULAR DEMINERALIZATION DEPENDENT ON DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS Pfeil A1, Boettcher J1, Mentzel HJ1, Lehmann G2, Petrovitch A1, Eidner T2, Schaefer ML1, Malich A3, Kaiser WA1, Hein G2, Wolf G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: To diﬀerentiate the influence of inflammation and soft tissue swelling on measurements of peripheral bone status in patients with rheumatoid arthritis (RA) using multisite quantitative ultrasound (QUS) compared to digital x-ray radiogrammetry (DXR). Patients and Methods: 53 patients with verified RA underwent measurements of QUS (Sunlight multisite Omnisense 7000, Sunlight Medical Ltd., Tel Aviv, Israel) with estimation of the speed of sound (QUS-SOS) at the distal radius and at phalanx III. Also, bone mineral density (DXR-BMD) and metacarpal index (DXRMCI) were estimated on metacarpals II-IV using DXR technology (Pronosco X-Posure System Version 2.0, Pronosco/Sectra ASS, Denmark). Disease activity of RA was estimated by erythrocyte sedimentation rate (ESR; in mm/1st hour). Results: For the group with minor disease activity (ESR<20 mm/1st hour) QUS-SOS (phalanx) was significantly associated to DXR-BMD (R=0.67, p<0.01) and DXR-MCI (R=0.54, p<0.05). Lower correlation coeﬃcients were revealed between QUS-SOS (radius) and DXR parameters (DXR-BMD: R=0.39, p<0.05; DXR-MCI: 0.49, p<0.05). In the case of high disease activity (ESR>20 mm/1st hour) QUS-SOS of the radius showed a closed correlation to DXR-BMD (R=0.74; p<0.01) and DXR-MCI (R=0.89; p<0.01), which surpassed the correlation coeﬃcients compared to patients with minor disease activity of RA. For QUS-SOS (phalanx) no significant correlation to DXR parameters could be observed in patients with high disease activity. Conclusion: Multisite QUS and to a significant extent DXR can also distinguish between patients with minor disease activity and patients with active RA which demonstrates accelerated bone loss characterized by decreased values of DXR- and QUS-SOS parameters. In this study the multisite QUS device is surpassed by DXR. In patients with accentuated disease activity no significant association among the QUS parameters themselves and between

S310 QUS-SOS (phalanx) and the DXR parameters exists. These data seem to indicate a significant influence of soft tissue swelling caused by active RA on QUS estimates at the phalanx as measurement site. In patients with increased disease activity QUS-SOS measurements at the radius should be consistently preferred.

P630MO. BONE CHANGES AND GLUCOCORTICOID REPLACEMENT THERAPY DOSES IN PATIENTS WITH PRIMARY ADRENAL INSUFFICIENCY Vanuga P1, Payer J2, Pura M1; 1National Institute of Endocrinology and Diabetology, Lubochna, Slovakia, 2Internal Clinic, Ruzinov Faculty Hospital, Bratislava, Slovakia Aim: Primary aim of the work was to assign the influence of the doses of glucocorticoid replacement therapy on bone density in patients with the primary adrenal insuﬃciency (PAI) (Addison’s disease). Methods: Altogether 46 patients (12 men and 34 women) with PAI (average age 48.2 yr) were included. Basic parameters of calcium phosphate metabolism, bone markers and serum levels of the adrenocortical hormones were evaluated in all patients. Bone mineral density (BMD, g/cm2) was measured by dual-energy X-ray absorptiometry in forearm and lumbar spine localizations. Control group consisted of 44 subject (8 men and 36 women). Results: BMD in PAI patients as measured in two above mentioned localizations did not diﬀer significantly from the control group. Osteopenia (OPE) was confirmed in 27 (58.7%) and osteoporosis (OPO) in 5 (10.9%) PAI patients, normal bone density was found in 14 (30.4%) patients. These findings were similar to the prevalence of OPE and OPO in control subjects – OPE in 25 (56.8%), and OPO in 5 (11.4%), respectively. Remaining 14 (31.8%) control subjects had normal bone density. However, doses of the glucocorticoid replacement therapy over 25 mg hydrocortisone (HCT) daily negatively aﬀected BMD in PAI patients. In comparison with those PAI patients with the daily dose of HCT less then 25 mg patients with the dose of HCT over 25 mg daily had significantly lower BMD in lumbar spine region only (but not in forearm region). Neither dose nor lenght of the glucocorticoid substitution therapy correlated with the BMD. Conclusions: The glucocorticoid replacement therapy by itself does not comprise significant risk factor for genesis of OPO, as it only supplies physiological levels of deficient endogeneous cortisol secretion. However, higher doses of the glucocorticoids (equivalent the dose over 25 mg HCT daily) in the replacement therapy of adrenocortical insuﬃciency should be considered as the potential risk factor for OPO in patients with PAI.

P631SA. DIFFERENTIAL DIAGNOSIS OF MARFAN SYNDROME, EHLERSDANLOS SYNDROME AND OSTEOGENESIS IMPERFECTA Vyskocil VV1, Varvarovska JV2, Pikner RP1; 1Bone Disease Center Department of Medicine II, 2Department of Pediatric, Plzen, Czech Republic 662 pacients with inherited connective tissue diseases and bone dysplasias were examined by means of a diagnostic system based on revised criteria for Marfan and Ehlers-Danlos syndromes as well as for osteogenesis imperfecta, benign joint hyperelasticity and juvenile osteoporosis. In 541 patients all data necessary for diﬀerential diagnostics were obtained: 145 patients met the criteria for Marfan syndrome (MFS), 82 patients for Ehlers Danlos syndrome (EDS) and 62 persons for osteogenesis imperfecta (OI). 159 patients had benign joint hyperelasticity (BJH) and the remaining patients demonstrated other diagnoses. Examined biochemical parameters, e.g., osteocalcin OC was significantly increased in patients with type IV of OI when compared with type I and significantly lower level of PICP in patients with OI when compared to other groups. Crosslinks were significantly higher in patients with OI as well as in patients with Marfan syndrome up to 13 years, but in older children no diﬀerence was found. The highly specific marker for Marfan syndrome was bird chest and thumb test. On the other hand in osteogenesis imperfecta drum chest and larger head circumference were typical. Decreased vital pulmonary capacity was found in all severe chest deformities and in scolioses greater than 25 degrees Cobb angle. Patients with Marfan syn-

drome were tall and had longer extremities to trunk, the highest incidence of hernias and in addition to that, they had also longer anteroposterior bulbus length measured by ultrasonography. Acetabulum protrusion or spondylolisthesis also occur only in MFS patients. Recurrent luxations, varicose veins and chronic pains were observed only in Ehlers-Danlos syndrome. The presented diagnostic system including clinical, biochemical, densitometric, radiologic and ultrasonic parameters seems to be adequate for diﬀerential diagnosis of connective tissue diseases. Molecular genetic examination was indicated only in few unclear cases.

P632SU. VARIATION OF BONE MINERAL DENSITY AND SOME GENETIC MARKERS IN OSTEOARTHRITIS OF KNEE JOINTS Alexeeva LI, Kolesnik TV, Myakotkin BA, Krylov MJu, Demin NV; Institute of Rheumatology RAMS, Moscow, Russia Objective: Osteoarthritis (OA) is a multifactorial disease, so the heritable predisposition plays a key role in the development of this disease. There are some known genetic markers associated with BMD, however their association with OA was detected too. Methods: The study included 179 women residing in Moscow and its region (median age 64.18.4) with OA of knee joints (according ACR criteria). Control group consisted of 60 women in postmenopausal period (median age 68.66.6) without osteoporosis and OA. BMD was determined by dual-energy X-ray absorptiometry (DXA) with apparatus QDR 4500 (Hologic) at lumbar spine and femoral neck. Radiography of knee joints was done in two planes and assessed by classification of Kellgren-Lawrence. Polymorphism of VDR, ESR, COL2A1 and COLIA2 genes were studied by polymerase chain reaction (PCR) and vertical electropheresis in agarose gel. Results: Based on examination of 179 women with OA the reliable increase of BMD during growth of OA stage in spine (I-st – 0.848 g/cm2, IV-st – 0.962 g/cm2; p=0.034) and femoral neck (Ist – 0.716 g/cm2, IVth- 0.798 g/cm2; p=0.025). Reliable diﬀerences in distribution of genotypes Fok1 (FF), Bsm1 (BB) gene VDR, HindIII (Hh) gene COL2A1, Rsal (Cc) gene COLlA2 in OA pts as compared with control (OR-2.33, 2.79, 2.52 and 2.62, respectively). Carriers of double heterozygotes XxPP, HhCc, PPBB, BBCC, BBHh, PPHh, ppcc have increased risk of OA by 6.5, 6.6, 7.8, 21.4, 15.5, 11.7, 7.4, which could be regarded as an important risk factor for OA onset. There was no correlation between BMD and the studied genetic markers, with the exception of gene ESR alpha; (the association close to significant, r = 0.18). BMD (in spine and femoral neck) correlated with osteophytes in the knee joints (r = 0.4, p < 0.05), and size of the osteophytes - with a gene ESR. Conclusion: Obtained data confirm the hypothesis of participation of increased BMD and genes VDR, COL2A1 and COLIA2 in pathogenesis of OA of knee joints.

P633MO. ASSESMENT OF BONE MASS IN PEDIATRIC PATIENTS WITH CELIAC DISEASE Zielinska A1, Kaczmarski M1, Konstantynowicz J2, Nowowiejska B1, Motkowski R2; 1iii Department Of Pediatrics, 2Department of Pediatrics and Developmental Disorders of Children and Adolescents, Bialystok, Poland Poor bone health is a common complication of chronic celiac disease (CD) in adults. Associations reported between CD and skeletal development, bone quality and mass in children are inconsistent. The study was designed to investigate total and regional bone mineral density (BMD) and content (BMC) in young patients with a clinically apparent CD. Bone mass and body composition were determined using dualenergy X-ray absorptiometry (DXA) in 49 Caucasian subjects (25 females, 24 males) aged 4 - 23 years (mean SD: 12.5 4.2) with CD treated using restricted gluten-free diet. Results were compared with 50 (25 females, 25 males) age and sex-matched healthy controls (mean age 12.1 3.1 years). The diagnosis of CD based on intestinal biopsy and a positive results for IgA-antiendomysial antibodies and tissue anti-transglutaminase. Results: Males with CD had greater deficits in total, peripheral (arms, legs) and spine BMD than females. The results remained

S311 significant after adjustment for lean and fat mass, with the diﬀerence being most distinct at the lumbar spine level. Consistent with previous reports, we confirm that patients with a long-term celiac disease have reduced BMD relative to healthy controls. More deficits in BMD occurred in the axial than appendicular skeleton suggesting a site-specific eﬀect of celiac disease on bone during growth. It also remains to be determined why males suﬀering from celiac disease have more deficits in bone mass than females. Table. (Mean SD) Males

Age (yr) Fat percentage (%) Lean mass (kg) Total BMD (g/cm2) Total BMC (g) Arms BMC (g) Legs BMC (g) Spine BMD (g/cm2) Spine BMC (g) Z score for Spine BMD (SDs)

Females

Celiac n = 24

Controls n = 25

P

Celiac n = 25

Controls n = 25

P

11.63.8 12.17.0

11.93.2 18.612.5

0.87 0.02

13.24.5 21.09.2

12.33.0 25.47.2

0.28 0.06

31.413.5 0.8390.1

38.414.1 1.0150.1

0.08 0.008

28.49.5 0.9070.2

30.57.6 0.9910.1

0.42 0.03

1509808 183.9123.3 535333 0.7460.2

2070848 251.8126.1 769369 0.9170.2

0.02 0.05 0.02 0.009

1497730 166.887.6 525281 0.8230.3

1772605 193.072.9 610228 0.9600.2

0.16 0.27 0.27 0.06

24.814.9 -1.41.0

34.216.6 0.290.9

0.03 27.716.1 <0.001 -1.341.24

34.315.0 0.260.9

0.09 <0.001

P634SA. A RANDOMISED CONTROLLED TRIAL OF THE EFFECT OF HYSTERECTOMY OR LEVONORGESTREL-RELEASING INTRAUTERINE SYSTEM ON BONE MINERAL DENSITY IN MENORRHAGIC PATIENTS: A FIVE-YEAR FOLLOW-UP Halmesmäki KH1, Paavonen JA2, Tuppurainen MT3,4, Hurskainen RA2; 1Central Hospital of Päijät-Häme, Lahti, Finland, 2 University of Helsinki, Department of Obstetrics and Gynecology, Helsinki, Finland, 3Univerisity of Kuopio, Department of Obstetrics and Gynecology, Kuopio, Finland, 4Bone and Cartilage Reasearch Unit, Kuopio, Finland Aims: Hysterectomy and levonorgestrel–releasing intrauterine system (LNG-IUS) are the most eﬀective treatment modalities for menorrhagia. However, it is not well known whether these treatment modalities have an eﬀect on bone mineral density (BMD). The aim of the study was to evaluate how these two often used treatment options of menorrhagia have an eﬀect on BMD. Methods: 107 women referred for menorrhagia to the Department of Obstetrics and Gynecology, University Hospital of Helsinki, Finland, were randomly assigned to treatment with LNGIUS (n=53) or hysterectomy (n=54). All women completed a questionnaire at baseline and at 5 years, including information on smoking, daily calcium intake, alcohol use, medication, and physical activity. Bone mineral density was measured at the lumbar spine (L2-L4) and right femoral neck using dual X-ray absoptiometry (DXA). Results: At the femoral neck, BMD decreased significantly in both groups with no diﬀerence between the groups. At the lumbar spine, BMD decreased significantly in the hysterectomy group (p=0,02) but not in the LNG-IUS group (annual decrease 0,24% and 0,07%, respectively). The change in the hysterectomy group was not explained by any factor included in the linear regression model. Conclusion: As menorrhagia is a common problem among fertile age women, the influence of its treatment modalities on BMD is important to know. Hysterectomy may increase agerelated loss in BMD. The change is first detected at the lumbar spine, as cancellous bone is more sensitive to changes in the hormonal milieu than cortical bone of the femoral neck. This phenomenon is probably explained by decreased blood flow to the ovaries after hysterectomy, which in turn impairs ovarian function. As LNG-IUS does not have such an impact on ovarian function, it does not have an eﬀect on BMD. Hysterectomy may accelerate age-related loss in BMD, but larger studies with longer follow-up are needed.

P635SU. BONE MINERAL DENSITY IN PATIENTS WITH DIFFERENT ETIOLOGY OF SUBCLINICAL HYPERTHYROIDISM Belaya ZE1, Rozhinskaya LYa1, Melnichenco GA1, Alekseeva TM2, Dorofeeva OK2; 1National Research Center for Endocrinology, 2Endocrinology Unit, Moscow, Russia Aims: To compare the eﬀect of subclinical hyperthyroidism with diﬀerent causes on bone mineral density (BMD) in postmenopausal women. Methods: 89 postmenopausal women (age 64 (59–68) years (Median: lower-upper quartiles), were divided into four groups: group (1) (n=21; TSH 0.198 (0.026–0.241)) – women with toxic multinodular goiter (TMG) without history of clinical hyperthyroidism; group (2) (n=25; SH 0.060 (0.015–0.192)) – patients with levothyroxine suppressive therapy (125 (125–150) µg/day during 3 (1.5–6) years)after the thyroidectomy due to diﬀerentiated thyroid cancer; group (3) (n=21; TSH 0.083 (0.014–0.287)) – patients with Graves’ disease (GD) with maintenance of serum TSH suppression long after antithyroid treatment (3 (2–7) years), group (4) – a control group (n=22; TSH 1.862 (0.941–2.22)). All patients had free thyroxine (fT4) and tri-iodothyronine (fT3) levels within the reference range. There were no diﬀerences between groups in age (p=0.11), body mass index (BMI) (p=0.69). BMD was measured by dual-energy x-ray absorptiometry (DXA) (Lunar) in the lumbar spine (L1-L4), femoral neck, total hip and radius. TSH-receptor antibodies were detected with the h-TBII assay (TRAK Dynotest BRAMS) in order to diﬀerentiate GD from TMG Results: ANOVA and the multiple comparison test (The Fisher LSD test) were used to compare the diﬀerence in BMD between the four groups. BMD was 10.6% lower (p=0.023) in L1-L4 and 9.5% lower (p=0.017) in femoral neck in group (1); BMD was 11.6% lower (p=0.006) in group (1) and 10.3% lower (p=0.013) in group (3) in total hip; and also BMD was 14.5% lower (p=0,003) in group (1) and 17.3% lower (p=0.0004) in group (3) in total radius as compared to the control group. There were no diﬀerences in BMD between groups (2) and (4). Conclusions: The etiology of subclinical hyperthyroidism exerts influence on BMD in postmenopausal women. Postmenopausal women with endogenous subclinical hyperthyroidism have significantly lower BMD in all regions of the skeleton versus postmenopausal women without thyroid disease. The lowest BMD has been found in the distal and proximal cortical bone. On the other hand, exogenous subclinical thyrotoxicosis has no eﬀect on BMD.

P636MO. SECONDARY OSTEOPOROSIS IN THE COURSE OF ANOREXIA NERVOSA Smiech A1, Rabe- Jablonska J1, Zygmunt A2, Lewinski A2; 1 Department of Psychiatry, 2Department of Endocrinology, Medical University of Lodz, Lodz, Poland Anorexia nervosa (AN)is a psychiatric disorder concerning mainly adolescents and young adult women. Low bone mineral density (BMD) has been recognised as its concomitant medical complication. The objective of this study was assessement of BMD and bone metabolism in patients with AN. The study involved 47 women diagnosed with AN (AN-G)and 26 healthy women in control group (C-G). All women underwent a standarised psychiatric interview, measurement of body height and weight. The calcium-phosphorus balance was assessed by colorimetric measurements of serum concentration and daily urine exertion. Vein blood samples were taken from all persons. After centrifugation the serum concentration of estradiol by chemiluminescent method, cortisol by radioimmunological method, osteocalcin (OC) and C- terminal telopeptide of type I collagen (CTX) by ELISA has been evaluated. The lumbar spine densitometry by DXA were conducted in all participants. Statistical analysis was performed using the program Statistica for Windows. Results are presented as means. The comparison of means was made using the Student t-test for normal or the Mann-Whitney U-test for the remainder. The level of significance was set at p<0.05. In order to evaluate correlations, Pearson’s coeﬃcients were calculated for normal variances and Spearman’s coeﬃcients for the remainder. The mean age was similar in both groups, respectively, 19.1 y in AN-G and 19.6 in C-G(ns). The mean body mass index was

S312 significantly lower in AN-G than C-G (respectively, 16.2 and 21.9 kg/m2, p<0,001). There were no statistically important diﬀerences between groups regarding mean serum concentrations of calcium, phosphorus and CTX. The mean serum concentrations of estradiol and OC were significantly lower in AN-G than C-G (respectively, p<0.001 and p<0.05). The mean serum concentration of cortisol and daily excretion of calcium were significantly higher in AN-G than C-G (respectively, p<0.01 and p<0.05). Both mean BMD and Z-score index were significantly lower in AN-G than C-G (p<0.001). Over 46% of AN patients met radiological criteria of osteoporosis. The results of the study have shown low bone mass commonly appears in young women with AN.

P637SA. POLYMORPHISM VITAMIN D3 RECEPTOR, COLLAGEN-1-ALPHA-1 GENES AND ESTROGEN RECEPTOR IN PULMONARY OSTEOPENIC SYNDROME Kochetkova EA1,2, Geltser BI1, Bubnov OYu1, Albavichus SA1; 1 Vladivostok State Medical University, Vladivostok, Russia, 2 Vladivostok Department of Tomsk Institute Medical Genetic Siberian Branch of Russia Academia of Medical Sciences, Russia Aim of study was to assess the peculiar distribution of diﬀerent alleles and genotypes for vitamin D3 receptor(VDR3), collagen-1alpha-1 COL1A1 (encoding type I collagen) and the estrogen receptor (ER) genes in chronic obstructive pulmonary disease (COPD) patients with osteopenic syndrome. Methods: We examined 52 patients with COPD and osteopenic syndrome. Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA, ‘‘Prodigy’’, Lunar, USA). Polymorphism of length of restrictive locus VDR3, COL1A1 and ER was studied using PCR. We analyzed the normal (B, s, P, X) and functional defective (b, x, p, S) alleles VDR3, COL1A1 and ER. Results: As known, COPD is associated with osteopenic syndrome. Studying of molecular and physiological mechanisms influence VDR3, COL1A1 and ER on mineral bone density is important for determining the development of osteopenic syndrome in COPD. Our results show that COPD patients with osteopenia have genotypes Bb (BsmI-polymorphism) VDR3 gene, Ss (Sp1-polymorphism) COL1A1 gene, XX (Xba1-polymorphism) and Pp (Pvu II-polymorphism) in the ER gene. COPD patients with osteoporosis have genotypes bb VDR3, SS COL1A1, Xx and pp ER genes. Patients with COPD and normal mineral bone density had summarized genotype BBssXXPp. Distribution allele is counted on risk development osteopenic syndrome independent of genotypes for VDR3, COL1A1 and ER genes. Conclusions: Testing of VDR3, COL1A1 and ER genes opens real possibility for early determination of COPD patients having high risk in developing pulmonary osteopenic syndrome.

P638SU. EVALUATION OF BONE MINERAL DENSITY AND MARKERS OF BONE TURNOVER IN PATIENTS AFTER RENAL TRANSPLANTATION Zygmunt A1, Kurnatowska I2, Kacprzyk F2, Bialkowska J3, Jablkowski M3, Nowicki M2, Lewinski A1; 1Department of Endocrinology and Metabolic Diseases, 2Department of Nephrology, Hypertension and Kidney Transplantation, 3Department of Infections Diseases, Medical University, Lodz, Poland It has been shown that attainment of normal metabolic environment after renal transplantation does not always result in resolution of abnormalities of mineral metabolism and the bone loss may persist or even progress in the post-transplant period. Preexisting renal osteodystrophy, hyperparathyroidism, and steroid therapy are all involved in this process. The aim of this study was to evaluate the relation between bone mineral density (BMD) and specific markers of bone turnover in patients after renal transplantation. This cross-sectional study included 62 patients (40 men aged 43.513.2 yrs, and 22 women 43.012.4 yrs with no history of bone fractures. Mean period after renal transplantation was 61.043.7 months in men and 3731.0 months in men (the

diﬀerence non significant). All patients had a stable transplant function and were on a standard triple therapy that included steroids in a dose 5–10 mg prednisone per day. In all transplanted patients serum levels of beta-CrossLaps, intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) were measured. BMD was estimated in the lumbar spine and in the hip using dual-energy x-ray absorptiometry. Low BMD (osteoporosis and osteopenia) was found in 77.4% (48/62) patients. Diagnostic criteria of osteoporosis were fulfilled by 27.4% of subjects, more frequently in men (30.0%) than in women (22.7%). Osteopenia was observed in 50% of patients and was more frequent in women (59.1%) than in men (45.0%). We also observed a positive correlation between serum CrossLaps concentrations and PTH in women (r=0.74; p<0.05). Plasma PTH levels correlated positively with a length of haemodialysis therapy before renal transplantation (in women r=0.50; p<0.05 and in men r=0.58; p<0.05). Conclusions: The frequency of low bone mineral density in patients after renal transplantation is high. Low bone density is equal in women and men. Longer period of haemodialysis treatment before renal transplantation is associated with higher posttransplant levels of PTH.

P639MO. STEROID-DEPENDENT OSTEONECROSIS RABBITS WITH BOTH INEFFECTIVE AND CATABOLIC SHIFT OF MECHANOSTAT Qin Ling, Zhang GE, Sheng Hui, Hung WY, Cheung WH, Leung KS; Department of Orthopedics & Traumatology, Chinese University of Hong Kong, Hong Kong, China Aims: Osteocytes play an important role in the proposed ‘Mechanostat’ for understanding etiopathogenesis of osteoporosis. Osteonecrosis is characterized histopathologically as a large empty lacunae in bone. We accordingly hypothesized that there might be a shift of ‘Mechanostat’ in our recently established steroiddependent osteonecrosis rabbit model. The aim of this study was to employ a high resolution pQCT scanner on diaphysis of weight bearing humerus for examining our hypothesis in the rabbit model. Methods: Fourteen 28-week old male New Zealand white rabbits were intravenously injected with 10 µg/kg body weight of lipopolysaccharide (LPS). 24 hours later, three injections of 20 mg/kg body weight of methylprednisolone (MPS) was given intramuscularly at a time interval of 24 hours. Six rabbits were injected with 0.9% normal saline and served as control group. 6 weeks after the last MPS injection, bilateral humerus was dissected for scanning the mid-diaphysis with a high resolution pQCT. Volumetric bone mineral density of cortical bone (cBMD) as ‘Material Quality’, cross-sectional area of cortical bone (CSA) as ‘Bone Mass’ and cross-sectional moment of inertia (CSMI) as ‘Tissue Distribution’ were calculated by built-in analysis software. Both ‘Distribution (Y) / Mass (X)’ curve and ‘Distribution (Y) / Quality (X)’ curve were used for describing ‘Mechanostat’ by ‘linear curve estimation’. Statistic diﬀerence in ‘Distribution/Mass’ curve or ‘Distribution/Quality’ curve between the treatment group and the control group was analyzed by linear regression. Results: The equation of ‘Distribution/Mass’ curve was CSMI=611.857+31.574CSA for the control group (R2=0.92, P<0.05), and CSMI=-531.506+27.539CSA for the treatment group (R2=0.96, P<0.05). A significantly higher slope of ‘Distribution/Mass’ curve was found in the control group than that in the treatment group (P<0.05). The equation of ‘Distribution/Quality’ curve was CSMI=1024.827–606.606cBMD for the control group (R2=0.46, P<0.05), and CSMI=1386.130–938.992cBMD for the treatment group (R2=0.52, P<0.05). 95% Confidential Interval in respective group showed the treatment data shifted to the lower-left of the control data, which was defined as significant displacement (P<0.05). Conclusion: There is both ineﬀective and catabolic shift of ‘Mechanostat’ in the steroid-dependent osteonecrosis rabbits.

P640SA. QUANTITATIVE ULTRASONOMETRY OF THE CALCANEUS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS Kutilek S1,2, Bayer M2, Dolezalova P2, Nemcova D2; 1Center for Clinical and Basic Research (CCBR), Pardubice, Czech Republic,

S313 2

Department of Pediatrics, 1st Medical Faculty, Charles University, Prague, Czech Republic

Objectives: To evaluate bone quality by means of quantitative ultrasonometry (QUS) in children with juvenile idiopathic arthritis (JIA). Methods: 70 children (37 with oligoarticular JIA, mean age 10.543.42 SD; and 33 with polyarticular JIA, mean age 11.332.88 SD) were enrolled. QUS was measured on both heels with Cuba Clinical portable device. Body height, weight and BMI were recorded together with disease duration and cummulative dose of prednisone. Results: The lowest QUS parameters were observed in children with polyarticular JIA (p< 0.001 and 0.01 when compared to reference data and oligoarticular JIA, respectively). In children with oligoarticular JIA, the QUS values were also significantly lower in comparison with the reference data (p< 0.002). QUS parameters were strongly influenced by body height and to a lesser degree by body weight. In children with polyarticular JIA there were significant inverse correlations between QUS parameters and disease duration (r = - 0.57, p< 0.01 for broadband ultrasound attenuation – BUA; and r = - 0.67, p< 0.01 for velocity of sound -VOS). Similarly, there were inverse correlations between QUS and cummulative dose of prednisone (r = -0.48, p< 0.05 for BUA; and r = -0.50, p< 0.01 for VOS, respectively). Conclusions: Disease duration and cummulative dose of prednisone in children with polyarticular JIA are risk factors of stunted growth and decreased QUS values of bone quality.

P641SU. VERTEBRAL FRACTURES IN SEVERE ASTHMA PATIENTS TREATED WITH ORAL PREDNISOLONE Lesnyak OM1, Lezhnina MB1, Evstigneeva LP1, Piven AI2; 1Ural State Medical Academy, 2Regional Hospital n 1, Yekaterinburg, Russia Objectives: Oral steroids are still common treatment in patients with severe asthma symptoms. We studied frequency and severity of vertebral fractures in asthma patients who have been taking prednisolone for at least 6 months. Methods: The study was performed in a tertiary pulmonary center. 96 consequent asthma patients were recruited according to the inclusion criterion which was treatment with oral steroids for more than 6 months. Patients were stratified into four diﬀerent sex-age groups: 1st group – females younger than 50 (n=27), 2nd group – females 50 and over (n=26), 3rd group – males younger than 50 (n=20) and 4th group – males over 50 (n=23), the youngest person was 23, the oldest was 74 years old. The disease duration and the duration of prednisolone treatment did not diﬀer significantly in these groups. X-ray investigations of thoracic and lumbar spine followed by morphometric analysis was performed. All findings were classified as normal or having diﬀerent grade of deformities (1–4), grades 3 and 4 corresponding to vertebral fractures. Other diseases which might be a cause of vertebral deformities were excluded. Results: Overall osteoporotic vertebral deformities and fractures were found in 61 (63.5%) patients with no statistical diﬀerence between sex-age groups (p=0.308). Grade 2–4 deformities were more frequent in patients of 50 and over (p=0.017). Vertebral fractures were diagnosed in 15 (15.6%) patients: 1 (3.7%) in 1st group, 7 (26.9%) in 2nd group, 2 (10.0%) in 3rd group and 5 (21.7%) in 4th group, p=0.024. Compression fractures also prevailed in men and women of 50 and over (p=0.001). Conclusions: Vertebral deformities were equally frequent findings both in females and males of any age group with asthma treated with oral steroids. Patients of 50 years and older have shown more severe manifestations: they had more prominent grade of deformities including fractures as well as more frequent compression fractures.

P642MO. EFFECTS OF VARIOUS ISOFLAVONES ON BONE MINERAL DENSITY OF OVARIECTOMIZED RATS Wuttke W, Vortherms T, Seidlova-Wuttke D; Dept. of Clin. and Exp. Endocrinology, University of Goettingen, Germany

Plant derived isoflavones are currently advertised to replace classical hormone therapy of postmenopausal women. Genistein and daidzein the 2 major isoflavones in soy products were shown to have a relatively low bone protective function following ovariectomy (ovx) of rats. It is often stated that the reason for this mild osteoprotective eﬀect is because the intestinal flora of not all individuals can convert daidzein to equol which is claimed to be the most active isoflavone in the bone. In addition pueraria lobata derived puerarin is lately also advertised as beeing bone protective. In the present experiments ovx rats were treated with daidzein (5 and 17.5 mg/day/animal), equol (1 and 7 mg/day/animal) or puerarin (12 and 60 mg/day/animal) given with food for a period of 3 months immediately following ovx. At the beginning and at the end of the experiment bone minerals density (BMD) of the metaphysis of the tibia was determined by quantitative computer tomography. In addition the osteoblast derived osteocalcin and the indicator of osteoclast activity i.e. the c-termial breakdown products of collagen-I--1 (the crosslaps) were determined in the serum at the end of the experiment. Control animals received either estrogen-free potato protein supplemented food or food containing 2 diﬀerent doses of estradiol-17 (E2, resulting in serum concentrations of 41 and 180 pg/ml). Control rats lost more than 53% of their BMD in the metaphysis of the tibia and this was largely prevented by E2 treatment. Eﬀects of high doses of equol were < daidzein < puerarin (bone loss 48 vs. 47 vs. 42%). This was statistcally significant only for daidzein and equol at the high dose (p < 0.05). E2 at both doses suppressed serum osteocalcin and crosslap levels and this eﬀect was only marginally seen in the isoflavone treated animals. These data indicate that estradiol can almost totally prevent ovx induced osteoporosis while the isoflavones equol, daidzein and puerarin were only moderately eﬀective to prevent decalcification of the bone. This reflected also in the serum surrogate parameters of bone metabolism.

P643SA. BONE IN BONE IMAGE AFTER TREATMENT WITH INTRAVENOUS INFUSIONS OF DISODIUM PAMIDRONATE IN TWIN CHILDREN SUFFERING FROM OSTEOGENESIS IMPERFECTA Devogelaer JP1, Lecouvet F2, Depresseux G1; 1Rheumatology Unit, 2Radiology Unit, St-Luc University Hospital, Brussels, Belgium Two twin boys aged 12 suﬀering from osteogenesis imperfecta, complicated by several peripheral and thoracic vertebral fractures, were treated by intravenous infusions of disodium pamidronate (1 mg/kg per infusion), 3 consecutive days every 3 months for 2 years. Their BMD measured by DXA increased from 0.416 to 0.600 g/cm2 at the (L1-L4) lumbar spine and from 0.590 to 0.804 g/cm2 at the total hip after 4 years. In the same time, they grew 16 cm. The views of the postero-anterior DXA scan of the lumbar spine obtained 2 years after the last course of therapy demonstrated the presence of ‘‘arrest lines’’ close to the plateaus of the vertebral bodies. X-ray films confirmed that this aspect was attributable to a ‘‘bone in bone image’’ due to bisphosphonate therapy, a wellknown radiological aspect in growing children treated by cyclical intermittent bisphosphonates (1). This DXA aspect corresponding to the radiological image should be recognized because part of the bone gain can be explained by it. 1. Devogelaer J-P. New uses of bisphosphonates: osteogenesis imperfecta. Curr Opin Pharmacol 2002; 2: 748–753.

P644SU. EFFECTS OF INHALED CORTICOSTEROIDS ON BONE MINERAL DENSITY, BONE FORMATION AND RESORPTION MARKERS AND QUALITY OF LIFE IN PATIENTS WITH PREMENOPAUSAL ASTHMA Cerrahoglu L1, Susin A1, Celik P2, Uyanik BS3, Duruöz MT1; 1 Celal Bayar University Medical School, PM&R Department, 2 Pulmonary Diseases Department, 3Biochemistry Department, Manisa, Turkey Aim: To investigate the eﬀects of inhaled corticosteroids (CS) on bone mineral density (BMD), bone formation and resorption markers and quality of life in premenopausal patients with asthma.

S314 Methods: Subjects in premenopausal period who used CS inhalation more than 3 months regularly and diagnosed with asthma and controls without asthma and without CS inhalation were recruited into the study. The exclusion criteria for both groups were having a disease known to aﬀect the bone metabolism or using such a drug, having neurologic or rheumatologic diseases or diseases that may aﬀect the quality of life. Disease duration, duration and daily and cumulative doses of the inhaled CS were estimated and respiratory fonction tests was performed in patient group. BMD, T- and Z-scores of femoral neck, trochanter, ward’s triangle, total hip and L2–4 anterior were evaluated with DXA. Bone formation and resorption markers were assessed. SF-36 was used to evaluate the quality of life. Results: 22 patients (mean age 37.556.79) and 22 controls (mean age 38.957.74) were recruited. Both groups were equal with respect to the factors that aﬀect BMD and no significant diﬀerence was found when BMD, T- and Z-scores, bone formation and resorption markers were compared. There was no significant correlation between BMD, T-, Z-scores and duration of CS inhalation, daily and cumulative doses of CS inhalation and asthma duration. The femoral neck, trochanter, total hip BMD, T- and Z-scores and ward’s triangle BMD and T-scores were found significantly lower in patients who used inhaled CS for more than 24 months when we compare with patients inhaled CS less than 24 months. However, there was no significant diﬀerence in bone formation and resorption markers between these 2 groups. SF-36 pain score was found to be lower in the control group. Conclusion: Although there is no significant correlation between BMD, T-, Z-scores and inhaled CS use in premenopausal asthmatic subjects, 24 months can be accepted as cutoﬀ point for CS inhalation eﬀect on BMD, Z- and T-scores.

P645MO. ALENDRONATE IN PRIMARY HYPERPARATHYROIDISM: EFFICACY IN MEN AND PREMENOPAUSAL WOMEN Khan AA1, Dubois S2,3, Standish TIM1, Syed ZA1; 1Department of Medicine, Divisions of Endocrinology and Geriatrics, McMaster University, Hamilton, Canada, 2Centre for Education and Research on Aging and Health, Lakehead University, Thunder Bay, Canada, 3Research Department, St Joseph’s Care Group, Thunder Bay, Canada. Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). We conducted a doubleblind, randomized, cross-over trial of alendronate (ALN), 10mg daily for one year, in patients with PHPT and reported that ALN significantly increases BMD at 12 and from baseline values. That sample included both women and men (28/9) and pre- and postmenopausal women (4/24). This analysis focused on the skeletal eﬀects of ALN in men and premenopausal women. Paired t-tests on the baseline and 12 month data were completed for the men. Total hip BMD was significantly improved among the men (mean diﬀ. 0.021; SE 0.009, p=0.045) as it was for the whole group.

Lumbar spine BMD was also improved (mean diﬀ. 0.033, SE 0.10, p=0.010). Femoral neck BMD was significantly improved in the whole group but was not significantly diﬀerent in the subgroup of men. Treatment with Alendronate over 12 months in males with PHPT was associated with a significant increase (4.22%) in LS BMD when compared to baseline (t=3.34; p = .01). The placebo group’s (N=6) lumbar spine remained constant (-0.4%; t=-0.34; p = .75) for the first 12 months of the study. Two markers of bone turnover, BSAP and urinary NTX excretion, were significantly decreased among the men (BSAP mean diﬀ.-10.428, SE 3.579, p=.027; NTX mean diﬀ. -58.289, SE 20.99, p=0.032), as the whole group. The analysis of premenopausal women showed similar results to the total group however the analysis was limited to four premenopausal women. ALN has similar eﬃcacy in increasing BMD among men with PHPT as previously demonstrated in postmenopausal women.

P646SA. OSTEOPOROSIS IS A IMPORTANT PROBLEM IN WHICH PERIOD AFTER LIVER TRANSPLANTATION? Hepguler S1, Atamaz F1, Akyildiz M2, Karasu Z2, Kilic M3; 1 Department of Physical Therapy and Rehabilitation, 2Department of Gastrology and Hepatology, 3Department of Surgery, Ege University Medical School, Turkey Objective: To evaluate the prevalance of osteoporosis in patients who undergo orthotopic liver transplantation (OLT) and to determine whether osteoporosis occurs more commonly in which period after OLT. Patients and Methods: Among the patients with OLT who did not receive osteoporosis treatment in the post-transplantation period, 162 patients in the first 6 months (1st period), 31 patients between 6 and 12 months (2nd period), 18 patients between 12 and 24 months (3rd period), 31 patients after 24 months (4th period), a total 242 patients (168 males, 74 females) were enrolled. Measurements of total lumbar spine and proximal femur were performed by dual x-ray absorptiometry. Results: After the operation in the first 6 month, 38 patients (23.5%) had osteoporosis, 51 (32.1%) patients had ostepenia at the total lumbar spine, while 9 patients (5.6%) and 10 patients (6.2%) had osteoporosis for the femur neck and total femur, respectively. In the 2nd and 3rd periods, the most of patients were osteoporotic by 45.1% (14) and 53.2% (10) at the lumbar spine, respectively. However, osteoporosis was found in the less patients for femur neck (3.2% and 11.1%) and total femur BMD (9.7% and 22.2) in these periods. After the 24 months, osteoporosis was seen in less patients for all sites by 22.6%, 3.2% and 3.2% for lumbar spine, femur neck and total femur, respectively. There were moderate correlations between BMD values and time of the evaluation (spearman’s). The BMD values at the lumbar spine were significantly diﬀerent among the groups (p<0.05). Conclusion: This study demonstrates that osteoporosis occurs more commonly between 6 and 24 months in the posttransplantation period. The bone loss was marked in lumbar spine than proximal femur in our study supporting glucocorticoid osteoporosis in these patients. After the 24 months, a significant decrease in occurence of osteoporosis may be explained by withdrawal of glucocorticoids. For this reason, the potent antiresorptive agents may be needed in preventing bone loss in these patients in the early post-transplantation period.

P647SU. BONE MINERAL DENSITY IN PATIENTS WITH KNEE OSTEOARTHRITIS Stankovic A, Stamenkovic B, Nedovic J, Dimic A, Stojanovic S, Zivkovic V; Institute for rheumatology Niska Banja, Serbia and Montenegro

BMD Lumbar Spine: Percent Change in BMD LS at 12 Months from Baseline.

Objectives: 250 women with knee osteoarthritis from Nis, Serbia, were enrolled in the study to examine the hypothesis that osteoarthrosis (OA) and osteoporosis (OP) are inversed related. Some studies suggest that OA and OP may coexist together and one does not inhibit the development of the other.

S315 Methods: Two hundred and fifty female patients, mean ages 62,4 5,7 (range 45–79) with knee osteoarthritis volunteered in the study. All the women had OA radiographs of the knee. OA was classified radiologically used standard PA X rays of the knee. Radiographs were scored ‘‘blind’’ to the clinical or BMD data, according to the method of Kellgren, by a single trained observer. BMD was measured for all the patients at lumbar spine (L1/L4), using dual energy X-ray absorptiometry (DEXA). The control group, without OA, consisted of 100 subjects. Adjustment for age, BMI, smoking, HRT use, age, menopause, alcohol abuse, social class, physical activity, as well as the presence of LSOA didnt essentially change the results. Results: 250 pts with OA of the knee had increased BMD, compared to the control group. The following average values of BMD were found: 1,09g/cm_ for the pts aged 40–59y and 1,043g/ cm_ for the pts aged 60–79y. Compared to the control group with the same age we didnt notice significant diﬀerence. Conclusion: Our results did not completely confirmed the hypothesis that OA has protective eﬀects on BMD loss, concerning OA of the knee. We concluded thet high BMD was not an obligation in the development of OA; OA was also common in patients who had low BMD. OA and low BMD coexist together frequently in aged population.

P648MO. SCREENING FOR PRIMARY HYPERPARATHYROIDISM IN WOMEN WITH LOW BONE MASS Lopez Gavilanez E1, Huamán Garaicoa F2, Segale Bajaña A2, Castillo Delvalle M2, Macías Briones G2; 1Endocrinology Service of National Police Hospital, 2Internal Medicine Service of National Police Hospital, Guayaquil, Ecuador Primary Hyperparathyroidism (PHP) presents frequently in women over sixth decade of life coinciding with the postmenopausal period. Objective: To perform a screening to know PHP prevalence in women with low bone mass or postmenopausal osteoporosis (PMO) with measurement of parathyroid hormone (PTH) and ionic calcium. Materials and Methods: Patients were referred to Endocrinology Service of National Police Hospital to evaluate their bone mineral density (BMD). Serum PTH level, and ionic calcium were measured. In two diﬀerent times values were confirmed. Patients with renal and/or hepatic disorders or other secondary causes of elevated PTH were excluded from screening. BMD was measured at lumbar spine, femoral neck and/or ultradistal radio by a DXA equipment. All patients had BMD at levels < -1 or < -2.5 T-Score in any three areas. Results: 156 patients with osteoporosis or osteopenia were diagnosed between January 2001 to June 2005. Of seventy patients analyzed, fifty four cases showed normal PTH and sixty six cases showed normal ionic calcium. In only one occassion, elevated PTH was showed in eleven patients. Permanent elevated PTH was found in five patients. Four of them showed persistent hypercalcemia and one showed normal ionic calcium level in all consecutive controls. Prevalence (7.1%) of PHP with low bone mass patients were showed. Conclusions: The measurement of PTH and calcium in the diagnostic approach of patients with osteoporosis permits more frequent identification of PHP. It is necessary to exclude PHP in patients with PMO because surgical treatment allows for the recovery of the BMD. The cost/benefit relationship of the screening is favorable, so we recommend carrying it out in all patients with low bone mass and/or postmenopausal osteoporosis. SCREENNING FOR PHP IN OSTEOPOROSIS

Normal High Total

Parathyroid hormone

Ionic calcium

54 16* 70

66 4 70

*=Permanent elevated PTH was found in five patients

P649SA. LOW BONE MINERAL DENSITY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE Kmecova Z1, Payer J2, Killinger Z2, Rovenský J3, Svac J1; 1 Internal Clinic, Faculty Hospital, Banska Bystrica, Slovakia, 2 Internal Clinic, University Hospital, Bratislava, Ruzinov, Slovakia, 3Clinical Rheumatology, National Institute of Rheumatic Diseases, Piestany, Slovakia Background: Low bone mineral density could be a serious complication of inflamatory bowel disease (IBD). Objective: To find the occurence of low bone mineral density in patients with IBD and to assess the eﬀect of antiresorptive therapy on bone mineral density after two years of treatment. Patients and Methods: – 57 (aged 39 +/- 20 years) patients with ulcerative colitis (UC), disease duration: 6 +/- 5 years. – Patients with Crohn‘s disease (CD) 71 (aged 37 +/- 18 years), disease duration: 5 +/- 4 years. – Bone mineral density (BMD) was assessed by dual X-ray absorptimetry DXA (Hologic) at lumbar spine (LS), and at the proximal femur (PF). BMD was expressed as g/cm2 and T- score – Therapy: calcitonin 200 IU, nasal spray daily, calcium 1200 mg/day, vitamin D 400- 800 IU daily. Results: PF- in UC pts. osteopenia was found in 35% patients, osteoporosis in 18% patients and normal findings in 47% patients LS- in UC pts. osteopenia was found in 39%, osteoporosis in 19% patients and normal findings in 42% patients After 2 years of calcitonin therapy bone mineral density significantly increased. p<0.07 (PF) and p<0.002 (LS). PF- in MC pts. osteopenia was found in 45%, osteoporosis in 22% patients and normal findings in 33% patients LS- by MC pts. osteopenia was found in 39%, osteoporosis in 33% patients and normal findings in 28% patients After 2 year therapy with calcitonin has bone density significantly increased. p<0.03 (PF) and p<0.005 (LS) Conclusion: Low bone mineral density is a frequent complication in patients suﬀering from UC and CD. Calcitonin therapy led to significant increase of bone mineral density in both groups of patients.

P650SU. BONE DENSITY IN RHEUMATOID ARTHRITIS: RELATIONSHIP WITH ISOKINETIC ANKLE MUSCLE STRENGTH Eyigor S1, Kirazli Y1, Capaci K1, Oder G2, Tarhan F2, Inal V2; 1 Physical Therapy and Rehabilitation Dept, 2Internal Medicine Dept Rheumatology Division, Ege University Faculty of Medicine, Bornova, Izmir,Turkey Aims: The aim of this study is to examine relationships of bone mineral density (BMD, g/cm2) with ankle isokinetic muscle strength (IMS) in rheumatoid arthritis (RA). Methods: Twenty-one patients (mean age: 53.9012.43 years, mean disease duration: 12.585.92 years, body mass index: 26.693.60 kg/m2) diagnosed as RA according to the 1987 criteria of the American Rheumatism Association were selected consecutively from a rheumatology outpatient clinic. Twenty healthy subjects (mean age: 58.9011.68 years, body mass index: 26.043.90 kg/m2) matched for gender and age, participated in the study as a control group. Isometric and isokinetic muscle strength were measured in ankle plantar- and dorsiflexion by using an isokinetic dynamometer (Cybex II). BMD of the spine, femoral neck and total femur was measured by dual-energy x-ray absorptiometry (DXA). Results: There are no significant diﬀerences for age, weight, height, body mass index, lumbar and femur BMD values, or any of the isokinetic, or isometric strength measures between the groups (p>0.05). Femoral neck and total femur BMD were correlated with ankle isokinetic measurements both in RA and control groups (p<0.05). The correlation between the ankle dorsiflexor muscle strength and BMD values appeared to be stronger compared with ankle plantar flexor muscle strength. In the RA group, disease duration was correlated with BMD values of all regions (p<0.05).

S316 Conclusions: Ankle isokinetic muscle strength was correlated with femoral neck and total femur BMD in RA and healthy controls. This finding indicates that muscle strengthening exercises may prevent bone loss not only in RA but also in healthy subjects.

P651MO. PARADOXAL RESULTS IN FRACTURE RISK RATIO ON DIABETES TYPE I & II (PRELIMINARY REPORT) Scali JJ1, Salomón JJ1, Visentini S1, Martinez A2; 1Rheuma and Metabolic Bone Diseases Unit, 2Nutrition Unit, Durand Hospital, Buenos Aires, Argentina We studied the diabetic population of our hospital, and data was collected separately on patients with Diabetes Type I and DB Type II. No pts were taking any specific bone active or antiresorptive therapy. Very few of the women on insulin were taking hormone therapy (<4%). Group on insulin had mean lumbar spine (LS) BMD T-score of -2.9 (Men) and -3.4 (Women) and mean femoral neck BMD T-score was -2.1 (men) and -2.9 (women). For the group without insulin, LS BMD T-score was -2.0 (men) and -2.7 (women) and mean femoral neck BMD T-score was -1.7 (men) and -2.5 (women). The relative risk of osteoporosis defined by absolute risk was 1.6 (CI 0.012; 2.86) for pts on insulin prolonged therapy. This was significant for men, women and for the group as a whole during follow-up. Bone density was significantly lower on insulin therapy group for men (p<0.02) and for women, (p<0.00001). The diagnosis of osteoporosis by absolute fracture risk reached significance for noninsulin group for women p<0.02 and a trend for men p<0.15. At 5 years of follow-up, the risk factors assessment, fragility fracture prevalence (vertebral and nonvertebral) in diabetic pts over a range of absolute fracture risk ranged from 20–44%. DB Type I demonstrates a low fragility fracture when compared with DB Type II, even thinking that pts‘s BMD are lower in DB Type I than in DB Type II (Paradoxal results). In the insulin group there was a significant increase in the prevalence of osteoporosis for both sexes. BMD was significantly lower on the group of insulin therapy for men (p<0.02) and for women (p<0.00001) compared with no insulin group. The diagnosis of a new fracture, paradoxally and contrary as we expected, reached more significance for noninsulin group for women p<0.02 and a trend for men p<0.13, but it was less significant for insulin group for both sexes. DB Type I demonstrates less fragility fractures than DB Type II remembering that the last one has high BMD scores but a higher rate of fracture risk when comparing both groups.

P652SA. IMPACT OF BODY FAT AND REPOSITION ON PRECISION OF PERIPHERAL DXA MEASUREMENT Pfeil A1, Boettcher J1, Lehmann G2, Kramer A1, Schmidt M1, Petrovitch A1, Schaefer ML1, Malich A3, Kaiser WA1, Hein G2, Wolf G2; 1Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, 2Clinic of Internal Medicine III, Friedrich-Schiller-University Jena, 3Sued-Harz Klinikum, Department of Radiology, Nordhausen, Germany Aim: Dual-energy x-ray absorptiometry (DXA) is used worldwide in the diagnosis and monitoring of osteoporosis. In the following study reproducibility of a new peripheral DXA system EXA-3000 was verified dependent on body mass index (BMI) and reposition. Patients and Methods: DXA reproducibility was measured on healthy volunteers. For each subject a measurement of peripheral DXA-BMD (EXA-3000, OsteoSys Co Ltd, Seoul, Korea) on the left radius and calcaneus was performed. Data of height, weight and BMI were acquired and the study group was subdivided into individuals who were underweight (BMI<25), normal weight (BMI 20–25) and overweight (BMI>25). To verify the impact of reposition on DXA measurements, five measurements under reposition were performed. The influence of textile material was evaluated by five measurements with a textile sock at the left foot (material: 100% cotton, material thickness: 1.3 mm). Results: For healthy controls the reproducibility for the BMD (radius) was CV=1.20% (underweight), CV=2.21 % (normal weight) and CV=2.29% (overweight). Regarding reposition our

data showed CV=1.12% (overweight individuals) and CV=1.29% (under- and normal weight groups). Improved results were observed for the calcaneus: CV=1.60% (underweight group), CV=1.00% (normal weight group) as well as CV=1.58% (overweight group). Reproducibility presented major CV-values for the calcaneus under reposition: CV=1.52% (underweight group), CV=2.89% (normal weight group) and CV=2.06% (overweight group). Regarding textile sock at the foot no increased coeﬃcients of variation with CV=1.93% (underweight group), CV=1.92% (normal weight group) and CV=1.61% (overweight group) were observed. Conclusion: DXA shows a high reproducibility in comparison to a usual DXA system. In this study an impact of body fat, reposition and textile material on BMD measurements by EXA3000 could not be clarified. EXA-3000 seems to be a promising technique for quantification of peripheral bone mineral density.

P653SU. OSTEOPOROSIS AND OSTEOPENIA IN WOMEN WITH BREAST CANCER Tsikhiseli G1, Nijaradze S1, Kistauri A2, Zodelava M2, Tskhovrebashvili N3, Mamaladze T3; 1Clinic Caraps Medline, Department of Oncology, Reconstructive and Plastic Surgery, 2Tbilisi State Medical University, Department of Internal Medicine, 3Clinic Caraps Medline, Department of Osteoporosis and Diabetic Foot, Tbilisi, Georgia Objective: Breast cancer (BC) patients should be particularly alert to the decrease of bone mineral density (BMD), as many BC patients receive treatments that may increase their risk of developing osteoporosis. The aim of the present study was to determine BMD in women with BC, to consider for them adjuvant therapy after successful treatment for BC with BMD monitoring. Material and Methods: We have studied 80 women with new case histories of BC aged 35 - 76 years. All patients were divided in four age-matched groups. BMD was measured at three sites (distal radius, midshaft tibia and proximal phalanx) using the ultrasound bone sonometer (Sunlight, Omnisense). Results were interpreted according to the criteria adopted by the WHO by T-score. Results: The mean data for T-score in the I group of patients with BC (n=14 age before 45 years) was: distal radius -0.20.02; midshaft of the tibia -0.20.05; proximal phalanx -0.80.11; in the II group (n=24, 46–56 years) T-score: -0.80.09; -1.80.15; -1.60.11; in the III group (n=20, 57–65 years) T-score: -1.80.18; -1.70.13; -2.50.04; and in the IV group (n=22, 66 years and up) T-score -2.20.14; -2.40.08; -3.40.11 at the same measurement sites, respectively. Conclusions: In patients with BC there was a high rate of decrease of BMD from osteopenia to osteoporotic changes, especially in the older postmenopausal groups, where BC and osteoporosis are common, and although both are dependent on estrogens, this leads to conflicting implications for the treatment: estrogen reduce the risk of fractures but increase the risk of BC. In this aspect selective estrogen modifiers (SERM) hold great promise, as they decrease both the fracture risk and the BC risk. So, it is important that BMD must be determined in all women with BC, appropriately monitored and, when necessary, be prophylactically protected so that the full benefit of adjuvant therapy with SERM (e.g. Raloxifene) can be enjoyed by BC patients. This study is the first step in this field in Georgia. In future we are planning follow up monitoring of all these patients considering their postoperative therapy.

P654MO. EFFECT OF DEPRESSION ON BONE MINERAL DENSITY IN PREMENOPAUSAL PATIENTS WITH FIBROMYALGIA Tander B, Cengiz K, Ilhanli I, Canturk F; Department of Physical Medicine and Rehabilitation, Samsun, Turkey Aims: Fibromyalgia (FM) is a chronic pain syndrome characterized by diﬀuse pain, fatigue, sleep disturbances, tender points, depression and anxiety. It is associated with depression as well as sedentary life and inadequate exercise tolerance. Therefore, these patients may develop osteoporosis. In this study, it was aimed to evaluate the severity of depression in FM and to determine the relationship between tender points (TP), Fibromyalgia Impact

S317 Questionnaire (FIQ) scores, the level of pain and bone mineral density (BMD). Methods: Fourty-five premenopausal women with ages ranging from 20 to 55 meeting the American College of Rheumatology criteria for fibromyalgia were included in this prospective study. Exclusion criteria were any previous osteoporosis and prior depression. Social demographical characteristics were evaluated. BMD of lumbar spine (LS) and femoral neck (FN) were performed using DXA. The level of pain was measured by Visual Analog Scala and FIQ. Depression rate was assessed by Beck Depression Inventory (BDI) and patients with high scores (BDI>17, depressive group) were compared to patients with low scores (BDI<17, nondepressive group). For statistic analyses, t-test was used with significance level of p<0.05. Results: The mean age of the patients was 38.519.09 years. Osteoporosis was present in only 3 patients (6.66%). There was no significant diﬀerence between the depressive and nondepressive groups according to mean age, body mass index, age of menarche, number of pregnancies, duration of education and TP. In the depressive group, mean FN T-score and LS Z-score were significantly lower (p<0.05). There was a negative correlation between TP vs LS T-score (r=-0.375, p<0.05); the number of TP vs BMD of lumbar spine (r=-0.430, p<0.01), BDI vs LS Z-score (r=-0.344, p<0.05). Conclusions: We concluded that fibromyalgia may be a risk factor for osteoporosis and the association with depression may have important implications. Demographic values of the patients FM patients (n=45)

Age (years) Body Mass Index VAS (cm 0–10) FIQ BDI Tender points

Mean SD 38.519.09 25.574.91 6.951.69 73.9712.84 16.469.26 14.752.55

Min- Max 20- 55 16.22- 39.91 3- 10 37- 99 0- 45 11- 18

ated by erythrocyte sedimentation rate and serum C-reactive protein levels (r = -0.55, respectively -0.48; all p %0.01). Conclusions: These results confirm that mild and advanced AS patients have decreased BMD values at both the lumbar spine and femoral neck. The similar frequency of osteoporosis in mild and advanced AS suggests that immobility is not an important role in pathogenesis. Patients with active disease have lower spine BMD suggesting that inflammation might play a role in the occurence of OP in AS.

P656SU. EFFECT OF CIGARETTE SMOKING ON BONE QUALITY PARAMETERS Meszaros S1, Bors K2, Hosszu E3, Csupor E4, Ferencz V1, Deli M1, Horvath C1; 1Semmelweis University, 1st Department of vinternal Medicine, 2Regional Osteoporosis Center Ferencvaros, 3 2nd Department of Pediatrics, Semmelweis University, 4The Health Service, Budavar Local Authorities, Budapest, Hungary Smoking is a risk factor for osteoporosis. Our previous study showed lower bone density among smokers in a group of postmenopausal women. After this finding we would like to investigate how smoking could influence bone quality. Forty-five (range: 25–72 ys) smoker women were compared with 45 non-smoker women adjusted for age and anthropometric parameters. Quantitative ultrasound (QUS) method was used to determine the speed of ultrasound (SOS) and the ultrasound attenuation (BUA) transmitting the left heel (Achilles In Sight). Dual photon absorptiometry method was applied to investigate the bone mineral density of lumbar spine and left femoral neck (Prodigy, GE Lunar) and single photon absorptiometry was used to determine the bone mineral content of radius at the nondominant side (NK-364, Gamma). No diﬀerence was found between smokers and non-smokers among the premenopausal group, however, postmenopausal smoker women had slightly lower SOS and BUA values than their non-smoker mates. Postmenopausal smoker women suﬀering from bone fracture had significantly lower SOS than postmenopausal non-smoker women (1508.9 vs 1525.3 m/s, respectively), despite their bone density did not diﬀer from each other. Similar diﬀerences was not found in the premenopausal group.

P655SA. BONE MINERAL DENSITY IN PATIENTS WITH MILD AND ADVANCED ANKYLOSING SPONDYLITIS P657MO. HAS THE PREVENTION OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS (GIOP) BEEN ACCOMPLISHED IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA)?

Muntean L1,2, Simon S1,2, Rednic S1,2, Damian L1,2, Marinescu C1, Nicoara I1, Andrei I1, Bolosiu C1,2, Bolosiu H1,2; 1University of Medicine and Pharmacy Cluj Napoca, Department of Rheumatology and Internal Medicine II, 2Romanian Foundation of Osteoarthrology Osart, Romania

Falcao S, Barros R, Pimentao JM, Branco JC; Unidade de Reumatologia, Hospital Egas Moniz, Lisbon, Portugal

Aims: To determine bone mineral density (BMD) and frequency of osteoporosis (OP) in mild and advanced ankylosing spondylitis (AS). Methods: 29 patients (23 males, 6 premenopausal females) were included in the study. BMD was evaluated at the lumbar spine and femoral neck by dual-energy X-ray absorbtiometry (DXA) using a DPX-alpha (Lunar-General Electric). The patients were grouped into mild and advanced categories according to the absence the presence, respectively, of spinal syndesmophytes. Results: In AS patients BMD was reduced at both lumbar spine 1.080.22 g/cm2 (T = -1.171.79) and femoral neck 0.890.14 g/cm2 (T = -1.341.33). According to the WHO definition of osteoporosis, 55.16% of patients had lumbar spine osteopenia and/or osteoporosis, while 62.06% had femoral neck osteopenia and/or osteoporosis. Patients with advanced AS were significantly older (mean age 45.4 vs. 34.7 years, p = 0.002), and had significantly longer disease duration (18.7 vs. 6.4, p = 0.001). The mean BMD at the lumbar spine and hip of patients with mild and advanced AS was similar (all p R 0.05). For patients with mild AS (n=13), 9 (69.22%) had osteopenia or osteoporosis at the lumbar spine, and 10 (76.91%) at the hip. For patients with advanced AS (n=16), 12 (75%) had osteopenia or osteoporosis at the lumbar spine, and 13 (81.25%) at the hip. Osteopenia and osteoporosis frequency of the mild and advanced AS patients was similar (p R 0.05). We found no correlation between BMD and disease duration. Only spine BMD correlated with disease activity, as evalu-

Glucocorticoid therapy is the most common secondary cause of bone loss; the severity of the bone loss in glucocorticoid-treated patients may vary from an approximately 3 to 20 percent decrease in bone density over 1 to 2 years. American College of Rheumatology (ACR) recommends for the prevention and treatment of GIOP that patients initiating glucocorticoid therapy at a dose equivalent to 5 mg or more of prednisone/day for 3 months or more should modify risk factors for osteoporosis, start weight-bearing physical exercise, initiate intake of calcium and vitamin D and bisphosphonate therapy. Objective: To evaluate in a population receiving long-term glucocorticoid therapy which are followed-up according to international recommendations for prevention of GIOP. Method: In a group of 61 consecutive patients with RA, followed-up in our rheumatic unity, we gathered data referring to sex, age, glucocorticoid therapy, intake of calcium and vitamin D, bisphosphonate therapy, bone mineral density (BMD) and the existence of osteoporotic fractures. Results: In our data, 78.6% were medicated with prednisone 5 mg/day for more than 3 months; 81.3 % were taking calcium and vitamin D; 51.2% were medicated with bisphosphonate therapy. Regarding BMD values: 62.9% not normal (T-score below -1); 5.7% normal; for 31.4 % of our cases we did not get any data. Conclusion: Based on the fact that we had a high percentage of cases with BMD abnormalities, we consider exceptionally low the number of patients medicated with bisphosphonate therapy and

S318 therefore the prevention and treatment for GIOP has been compromised.

P658SA. EVALUATION OF BONE MINERAL DENSITY OF THE LUMBAR SPINE IN PATIENTS WITH BETA-THALASSEMIA MAJOR WITH DUAL-ENERGY X-RAY ABSORPTIOMETRY AND QUANTITATIVE COMPUTED TOMOGRAPHY: A COMPARISON STUDY Angelopoulos NG, Goula A, Rombopoulos G, Kaltzidou V, Katounda E, Tolis G; Endocrine Department, Hippocratio Hospital, Athens, Greece Aim: Osteoporosis represents a multifactorial common cause of morbidity in -thalassemia. The present study was performed to compare bone mineral density (BMD) results in the lumbar spine of thalassemic patients measured by both dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), and to determine their correlations with the markers of bone turnover. Patients and methods: BMD was measured in the lumbar spine of 13 regularly transfused patients with -thalassemia major by both DXA and QCT. Blood and urine samples were obtained for the determination of biochemical and hormonal profiles. Results: Both T-scores and Z-scores were higher when measured by QCT (T-score= -0.411.31, Z-score= -0.561.08, meanSD) compared with the values given by DXA (T-score= -2.570.88, Z-score= -2.321.11, P=0.0005). In comparison to DXA, QCT T-scores were more closely correlated with age (r=-0.19 vs. r=0.70, P=0.0068). Strong negative correlation was found between QCT values and age (r=-0.67, P=0.01). In comparison to DXA T-scores, QCT T-scores were more closely correlated with osteocalcin, urine N-telopeptide cross-links of type I collagen and deoxypyridinoline, but without statistical significance. DXA T-scores were better correlated only with urine C-terminal telopeptides of type I collagen, but again without statistical significance. Conclusions: The above results imply that the two methods cannot be used interchangeably in assessing BMD in thalassemic patients. However, which of the two techniques employed more precisely determines the overall strength of vertebrae in -thalassemia remains to be investigated.

P659SU. TOBACCO SMOKING DOES NOT AFFECT OSTEOPROTEGERIN SERUM LEVELS Supervia A1,2, Enjuanes A2, Mellibovsky L1,2, Ruiz-Gaspà S2, Perez-Edo L2, Carreras R2, Nogués X1,2, Diez-Perez A1,2; 1Department of Internal Medicine, Hospital del Mar, Autonomous University of Barcelona, 2URFOA, IMIM, Barcelona, Spain Aim: Osteoprotegerin (OPG) is a cytokine that regulates osteoclastogenesis. Serum levels of OPG increase with age in men and healthy postmenopausal women, and are higher in osteoporotic postmenopausal women. A correlation between serum levels of OPG and terminal crosslinked telopeptides of type I collagen and osteocalcin has been described. Finally, a correlation with cardiovascular risk factors was described too. Furthermore, tobacco smoke is a recognised risk factor of osteoporosis. Several studies have evaluated their influence in the serum levels of OPG, with contradictory results. The aim of this study was to evaluate the influence of smoking on the serum levels of OPG, and to assess the eﬀects of smoking cessation. Methods: All the study participants were healthy volunteers without cardiovascular risk factors. Twenty active smokers (9 men and 11 women) were included. Control group was formed by 49 healthy never smoker volunteers (22 men and 27 women). A subgroup of 15 smokers (7 men and 8 women) followed a period of abstinence of one month. Serum levels of calcium, parathyroid hormone, and OPG were analysed by ELISA. In the abstinent subgroup, blood analysis was repeated one month later. Statistical analysis was performed with SPSS software. Results: Both groups were comparable in sex, serum levels of calcium and parathyroid hormone. Smokers were older than never-smokers were (36.2 (8.6) vs 30.9 (5.6) years old; p = 0.018). No diﬀerences in OPG serum levels were found between both

groups even after adjusting age diﬀerences. OPG serum levels in smokers before and after smoking abstinence were also not diﬀerent. Conclusions: Tobacco smoking does not aﬀect serum levels of OPG in healthy young volunteers. We have found no variations in OPG serum levels after smoking cessation.

P660MO. INCREASED PREVALENCE OF OSTEOPENIA IN PATIENTS OF A PAIN CLINIC TAKING CHRONIC OPIOIDS McKeough LA1, Paul TL1, Morley-Forster P2, Tokmakejian S3, Nicholson L4, Koren G5, VanUum SHM1; 1Division of Endocrinology, Dept. of Medicine, 2Interdisciplinary Pain Program, 3 Dept. of Biochemistry, 4Dept. of Diagnostic Radiology and Nuclear Medicine, 5Dept. of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada Aims: Long-acting opioids are now widely used to treat chronic non-cancer pain. Chronic opioid treatment can result in hypogonadotropic hypogonadism. Given the association between hypogonadism and osteoporosis, we hypothesized that patients on chronic opioid treatment are at increased risk of osteopenia and osteoporosis. Methods: We prospectively included premenopausal women aged 18–50 years and men aged 18–60 years from a pain clinic. Participants had been using opioid medication for chronic pain for at least 1 year. Each patient underwent a detailed history and physical exam. Bone mineral density was measured using DXA scans of lumbar spine and hip. Biochemical testing included gonadal steroids, Ca and 25OH-vitamin D. Results are presented as median and range. Results: Fifteen patients, 6 men and 9 premenopausal women, aged 43 (28–59) years, were included. They had used a mean 750 mg morphine equivalent dose for 4 (1–8) years. One woman was taking an oral contraceptive agent. Ten participants reported active smoking. Calcium intake was 600 (0–2100) mg per day. A tendency to fall was reported by 53% of patients, 7 patients had lost more than 3 cm in height compared to reported height at age 25. Osteopenia (T-scores between -1 and -2.5 for hip and/or lumbar spine) was present in 40% of participants, 3 males and 3 females. The presence of osteopenia was not associated with duration or dose of opioid treatment. Results of biochemical testing were available for 13 participants. Hypogonadism (testosterone or estradiol below normal range) was present in 62%, insuﬃcient 25OH-vitamin D levels (<80 nmol/L) in 77% of participants. Conclusions: The prevalence of osteopenia is higher than expected in patients of a chronic pain clinic taking opioids for more then one year. Further, this patient group is characterized by a tendency to cluster risk factors for increased loss of bone mineral content, including hypogonadism, active smoking, lack of exercise and insuﬃcient vitamin D levels and calcium intake. Together with the increased fall tendency, this may result in an increased future risk of osteoporosis-related fractures. Comparison to patients with chronic pain who are not on long-acting opioids is needed to confirm these findings.

P661SA. BONE MINERAL DENSITY OF LUMBAR SPINE AND RISK FACTORS FOR OSTEOPOROSIS IN FEMALE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS Palic-Obradovic D, Pilipovic N, Stojanovic R, Radunovic G; Institute of Rheumatology, Belgrade, Serbia and Montenegro The aim of study was to investigate the bone mineral density (BMD) of lumbar spine and risk factors for osteoporosis (OP) in female patients with systemic lupus erythematosus (SLE). Method: In the case-control BMD study, lumbar spine (L2-L4) was investigated in 64 female SLE patients who all used corticosteroides (group I) and in the same number of healthy women (group II). BMD was measured by DXA using a Lunar DPX-L device. The questionnaire for risk factors for osteoporosis applied. The groups were comparable to age (mean age 45.6 yrs) and there

S319 was no diﬀerence between BMI (24.5 vs. 26.1) and menarche (meanage 14 yrs). Results are on the table.

We concluded that loss of bone mass is heterochronous, and it is necessary to monitor it and use prevention and treatment of osteoporosis in patients with rheumatoid arthritis.

Results

P663MO. THE RELATIONSHIP BETWEEN TYPE 2 DIABETES MELLITUS AND BONE DENSITY IN POSTMENOPAUSAL WOMEN

BMDSD (min-max) T scoreSD (min-max) Low BMD Menopause Cigarette smoking Coﬃn abuse Low Ca intake Low physical activity Fracture Family history of OP

SLE (Group I) XòSD

Healthy control XòSD

1.0160.17 0.678–1.343 -0.51.3 - 4.35 - +1.19 N of pts (%) 41 (64,1%) 34 (50%) 36 (56,2%) 61 (95,3%) 14 (21,9%) 59 (92.2%) 11 (17,8%) 1 (1,56%)

1.1720.16 0.785–1.567 -0.21.4 –3.40 - +3.05 N of pts (%) 18 (28,1%) 23 (36%) 31 (48,4%) 21 (32,8%) 12 (18,8%) 43 (82.8%) 6 (9,4%) 10 (15,6%)

p p <0,005 p <0,005 p <0,005 p <0,002 n.s. p <0,005 n.s. p <0,001 p <0,005 p <0,001

Conclusion: BMD was significantly lower in SLE patients and there was a positive correlation with height of patients and a negative correlation with consumption of coﬀee. Menopause was a significant factor for low BMD in both groups. Negative correlation of BMD with age and fractures were found in SLE patients and in healthy controls. Our results confirm that a significant reduction of BMD in SLE patients depend not only on glucocorticoid use, but menopause and other risk factors for osteoporosis are very important for bone loss also.

P662SU. BONE LOSS IN WOMEN OF DIFFERENT AGES WITH RHEUMATOID ARTHRITIS Povoroznjuk VV, Karasevskaya TA, Kreslov YA; Institute of Gerontology AMS Ukraine, Kiev, Ukraine Osteoporosis is recognized as a complication of rheumatoid arthritis (RA). Several studies have explored the relation between osteoporosis and disease related variables. Use of corticosteroids has been found to be related to osteoporosis in RA, and several studies have also indicated that the development of bone loss (osteoporosis) is related to disease course, especially at the early stages. 30 female patients with a mean age of 50.23.1 years with RA (duration of disease R6 months) were examined. All patients had clinical examinations and bone mass measurement by dual-energy X-ray absorptiometry (anterior-posterior spine L1-L4, total hip, and femoral neck, distal and ultradistal radius). The following demographic variables were assessed: age, disease duration, body weight and height, co-morbidities, menopause status. The active nature of disease was assessed by the following variables: acute phase reactants by ESR and CRP, the number of deformed joints, and functional health status by the Health Assessment Questionnaire (HAQ). All women never use corticosteroids or take it in dose less than 5 mg/day (equivalent to prednisolon) and less than 3 weeks. Our aim was to estimate the influence of active nature of disease, duration, presence of deformed joints, on bone mineral density and to determine the patterns of bone loss in female patients of diﬀerent ages. We found out that osteoporosis and low bone mass in RA are more consistently associated with age, menopause status, BMI than disease variables. There was no correlation of bone loss and active nature of disease, results of HAQ, presence of deformed joints. Postmenopausal women featured bone loss at femur neck and total body, whereas young women had osteoporosis at the anterior-posterior spine L1-L4 (compared with reference values). A relation between bone loss at distal and ultradistal radius and other parameters was not found.

Sharifi FSH1,2, Ahmadi moghadam NA2, Jaberi YJ1,2, Ahmadi GH2; 1Zanjan University of Medical Sciences, Endocrine Department, 2Vali asr Hospital, Zanjan, Iran Aims: To determine the importance of type 2 diabetes mellitus as a risk factor for osteoporosis in postmenopausal women, this study was designed in endocrine clinic of Zanjan in 2003. Methods: This analytical study was conducted on 40 diabetic and 40 healthy postmenopausal women. These two groups were matched for their age, length of their menopausal period and their body mass index. Serum calcium, phosphorus, alkaline phosphatase and estradiol were measured in all the cases and bone densities in three sites (femoral neck, lumbar spine and forearm) were evaluated with DXA. All cases with abnormal calcium or phosphate level were excluded. All data were analyzed using t-test, analysis of variance, chisquare and Pearson coeﬃcient test. Results: The mean age for diabetic cases was 57 8 y and their mean menopause period was 9.4 6.8 y that were not diﬀerent significantly from control group. The frequency of osteoporosis and osteopenia in diabetic women were not significantly diﬀerent from nondiabetics. The mean bone density in femoral neck was higher in diabetic group (p: 0.002). In both groups there was a significant relationship between bone density and length of menopause (p%0.01). The relationship between BMI and bone density was significant only in femoral neck (p%0.01) in both groups. There was no relation between serum Ca, P ,Alph and estradiol with bone density. In diabetic women the higher HbA1c the lower bone density in lumbar spine. Conclusion: Although the level of HbA1c as a marker of blood glucose control has some relations with lumbar spine density in diabetics, diabetes type 2 is not a risk factor for osteoporosis. So for screening, diagnosis and management of osteoporosis in diabetes type 2, steps should be taken individually and similar to nondiabetic patients.

P664SA. SEARCH OF SECONDARY CAUSES OF BONE LOSS IN WOMEN Villaseca P1, Valenzuela P2, Campusano C1, González G1, Arteaga E1; 1Department of Endocrinology, 2Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Background: Twenty to thirty per cent of osteoporotic postmenopausal women have secondary causes of osteoporosis. Secondary osteoporosis is not frequently suspected; thus, treatment could be suboptimal. Methods: We describe the disorders found among 31 pre- and postmenopausal women (age range: 44 - 78 years old; years from menopause range: -5 to +20 years) in whom secondary causes of bone loss were suspected based on: Z-score %-2.0 SD, osteoporosis and/or osteopenia predominant in hips relative to lumbar spine (delta R1.0 SD), accelerated bone loss in hips (R2% per year) and/or failure of antiresorptive treatment (R2% per year). A cross-sectional chart review study was done in all consecutive female patients with these conditions who presented to our outpatient clinic of Gynecological Endocrinology during 2004. Each medical history was reviewed, all women had normal CBC, and normal hepatic and renal function. Laboratory testing analyzed included serum calcium and phosphorus, 24-h urinary calcium, TSH, PTH, and 25(OH) vitamin D. Hypovitaminosis D was defined as 25(OH)vitamin D %20 ng/ml, vitamin D insuﬃciency as 9–20 ng/ml and vitamin D deficiency as %9 ng/ml. Results: Our findings among 31 Chilean women who met the inclusion criteria were: hypovitaminosis D (n=14), vitamin D insuﬃciency in 12 and vitamin D deficiency in 2; hypercalciuria (n=7); 6 patients had secondary hyperparathyroidism: one due to celiac sprue, two due to hypercalciuria, one due to vitamin D insuﬃciency and the two others unexplained; 1 patient had

S320 exogenous hyperthyroidism. Two patients had dual unrelated disorders (vitamin D insuﬃciency and hypercalciuria). In nine women we found no cause for bone loss. Conclusions: In 71% of the 31 women in whom secondary causes of bone loss were suspected as stated above, we identified previously undiagnosed metabolic or endocrine disorders which can be corrected, and thus optimize osteoporosis treatment. Disorders of calcium metabolism were the most frequent diagnoses.

P665SU. BONE MINERAL DENSITY IN PATIENTS WITH SCHIZOPHRENIA TREATED WITH SECOND GENERATION ANTIPSYCHOTICS Wyszogrodzka-Kucharska A1, Rabe-Jablonska J2; 1Community Mental Health Team, Whitley Bay, UK, 2Department of Psychiatry, Medical University of Lodz, Poland Introduction: Decrease in bone mineral density may lead to osteopenia or osteoporosis. In patients with schizophrenia it may be attributed to medication-related hyperprolactinemia and hypogonadism, low physical activity, smoking, dietary deficiencies, low exposure to sunshine and/or polydipsia. Many of these factors can be eliminated. Early diagnosis and treatment may decrease the prevalence of osteoporosis amongst people with schizophrenia. Objectives: The aim of the study was to evaluate bone mineral density in patients with a diagnosis of schizophrenia treated with second generation antipsychotics in reference to a control group of healthy, unmedicated volunteers. Also to compare bone mineral density between a group of patients treated with risperidone and a group of patients treated with olanzapine. Both risperidone and olanzapine are atypical antipsychotics which act via blockage of D2 receptors in mesolymbic system, striatum and pituitary gland. This may result in inducing hyperprolactinemia and low estrogen levels. Methods: Participants in the study were 60 schizophrenic patients: 26 subjects were treated with risperidone and 34 subjects were treated with olanzapine and 38 healthy, unmedicated volunteers (control group). Subjects were excluded for any medical condition or treatment known to cause osteoporosis. Female patients were all premenopausal. Bone mineral density was determined by dual-energy x-ray absorptiometry (EXA) at the lumbar region (L2-L4). Results: Twenty patients (37.7%) had decreased bone mineral density, fifteen (28.3%) had been diagnosed with osteopenia and five (9.4%) had osteoporosis. Six subjects from control group (15.8%) had lower bone mineral density, five had osteopenia (13.2%) and one had osteoporosis (2.6%). There was no diﬀerence between groups treated with risperidone or olanzapine. Conclusions: Our research has revealed that patients with schizophrenia suﬀer lower mean bone mineral density and this condition is largely under diagnosed. A number of various risk factors might contribute to the development of osteoporosis in schizophrenic patients.

P666MO. TRANSIENT OSTEOPOROSIS OF THE HIP Aktas I; Saygi Hospital, Istanbul, Turkey Aims: Transient osteoporosis of the hip (TOH) is a relatively rare condition with distinct clinical and radiographic features. Diﬀerential diagnosis includes avascular necrosis, stress fracture, septic arthritis, malignancy, soft-tissue injury, osteoarthrosis and radiculopathy. In the present study, a hard-to-diﬀerentiate transient osteoporosis case of the hip is presented. Case: A 45 year old male patient had referred to the Internal Medicine polyclinic due to complaints such as fatigue, weight loss, diﬃculty in walking, pain in legs. He had been transferred to our clinic as a result of a diagnosis of osteoarthrosis in the hip joint. The mobility of the hip joint was limited and painful, especially at the right side, FABER and FADIR tests were bilateral positive. According to laboratory results, erythrocyte sedimentation rate was 46/hr, gamma GT was 100, and SGOT and SGPT values were 45, 40 respectively. While abdominal USG revealed grade II fat deposition, the complete body scintigraphy showed hyperactive fields at both caput femoris regions. Hip Joint CT revealed bilateral sclerotic degenerative changes at the upper part of the

acetabulum. These results were considered to be inadequate for diagnosis of osteoarthritis and the results were once more evaluated and monitored for localized osteopenia in the region corresponding especially to the right caput femoris in the pelvis. X-ray, alcoholism history, presence of scintigraphic bilateral uptake, and bilateral hip magnetic resonance imaging (MRI) for diﬀerential diagnosis between transient hip osteoporosis and osteonecrosis were required. MRI changes which are bilateral and more apparent at the right side in the femoral head and neck characterized by low signal intensity on the T1 weighted images and high signal intensity on the T2 weighted images. These indistinct, limited, patch-like lesions confirmed bone marrow oedema. The case was diagnosed as TOH. The patient was given a conservative program. The follow-up MRI, applied 6 months later, revealed no bone marrow oedema and the previous complaints of the patient were not present. Conclusions: Due to its association with bone marrow oedema, TOH is a pathology in which MRI is extremely important in diﬀerential diagnosis.

P667SA. HIGH SENSITIVITY C-REACTIVE PROTEIN IS AN INDEPENDENT PREDICTOR OF FRACTURE RISK IN ELDERLY WOMEN Pasco JA1, Kotowicz MA1, Henry MJ1, Nicholson GC1, Spilsbury H2, Box J2, Schneider HG2,3; 1The University of Melbourne, Geelong, Australia, 2Alfred Pathology Service, Melbourne, Australia, 3Monash University, Melbourne, Australia Aims: Inflammatory cytokines are known to modulate bone remodeling. Among patients with inflammatory diseases, reduced bone mass and increased risk of fracture are common. We aimed to test the hypothesis that subclinical systemic inflammation is implicated in the pathophysiology of bone fragility. Methods: The association between serum levels of highsensitivity C-reactive protein (hsCRP) and risk of fracture was examined in 444 women aged 65 years and older, randomlyselected from the community and enrolled in the Geelong Osteoporosis Study. Baseline hsCRP levels were measured immunoturbimetrically (median 2.44 mg/L, interquartile range 1.32–4.37). BMD was measured at the spine, proximal femur, whole body and forearm. Fractures were identified prospectively from radiological reports. Subjects were followed longitudinally for 5–8 years, or until sustaining a fracture, death, or migration from the study region. Cox proportional hazards regression was used to determine the association between hsCRP and fracture. Results: During 2208 person-years of follow-up, 96 fracture cases were identified. Multivariate models of relative risk for fracture demonstrated significant contributions from hsCRP, BMD and prevalent fracture; the relative risk was increased by at least 24% for each SD increase in natural log-transformed hsCRP, 32% for each SD decrease in BMD and 52% by prevalent fracture. Further adjustment for lifestyle factors, diet and medication use failed to explain the observed increased risk for fracture. Conclusions: Circulating hsCRP is an independent predictor of fracture risk in elderly women. These results implicate subclinical systemic inflammation and oxidative stress as factors in the pathophysiology of bone fracture.

P668SU. VITAMIN D STATUS IS NOT ASSOCIATED WITH BONE MINERAL DENSITY, BONE TURNOVER, BONE LOSS AND FRACTURE RISK IN POSTMENOPAUSAL WOMEN: THE OFELY STUDY Garnero P1,2, Munoz F2, Sornay-Rendu E2, Delmas PD2; 1Synarc, Molecular Marker, Lyon, France, 2INSERM Unit 403, Lyon, France Vitamin D status is considered as an important determinant of bone health. This belief is mainly derived from crossectional studies. Supplementation trials with vitamin D3 using fracture incidence as an outcome have yielded conflicting results. Aim: To investigate the relationships between serum levels of 25 OHD and intact PTH, bone turnover, BMD and incidence of fracture in postmenopausal women

S321 Methods: In the 671 postmenopausal women (mean age : 62.2 yr; range: 50–89 yr) belonging to the population-based OFELY cohort, we measured at baseline 25 OH D, intact PTH, bone turnover markers (BTM) and BMD by DXA at the total hip and radius. Women were followed for a median (IQ) of 11.2 yr (11–12.3). BMD at the radius was repeated annually and all incident fragility fractures which occurred in 134 women were confirmed by radiographs. Results: At baseline, 25 OH D correlated modestly with intact PTH with no suggestion of a plateau eﬀect (r2= 0.023, p<0.0001), but not with BTM or BMD after adjustment for age. When 25 OHD or PTH levels were considered as continuous variables or in quartiles, there was no significant association between these two hormones and radius BMD loss or fracture risk. For example, the relative risk (95% CI) of fracture for women with levels in the lowest quartile of 25 OHD was 1.11 (0.64–2.03) compared to women with levels in the highest quartile. We also separated women using a cut-oﬀ of 75 nmol/L of serum 25 OH D which has recently been recommended by a panel of experts as the optimal threshold for fracture prevention (Dawson-Hughes et al, Osteoporos Int, 2005). After adjustment for age, there was no significant diﬀerence between the 254 women (38%) with 25OHD below 75 nmol/l and the other women for grip strength, physical activity, % of fallers in the previous year, serum PTH, BTM, BMD, bone loss and the % of women with incident fracture (23% vs 18%, p=0.80). Further adjustment for seasons did not modify these associations. Conclusion: Vitamin D status may not be an important determinant of bone health in a healthy population of postmenopausal women.

P669MO. BONE MICROHARDNESS IN CONTROL AND OSTEOPOROTIC MEN: RELATIONSHIP WITH THE MEAN DEGREE OF MINERALIZATION OF BONE TISSUE Boivin G1, Bala Y1, Simi C1, Ste-Marie LG2, Meunier PJ1; 1 INSERM Unité 403, Faculté de Médecine R. Laennec, Université Claude Bernard Lyon1, Lyon, France, 2Centre de Recherche du CHUM, Hôpital Saint-Luc, Montréal, Canada Primary mineralization measured at calcification front is followed by a slow process of secondary mineralization1. Changes in the degree of secondary mineralization of bone tissue (DMB) have been used to explain the mechanism of action of anti-osteoporotic treatments in women 2–4. Mineralization and microhardness were measured in iliac bone samples from 13 control men (aged 664 years) and idiopathic osteoporotic men [13 from France (5011 years) and 17 from Canada (498 years)]. Quantitative microradiography5 allowed to measure mean DMB and heterogeneity index (HI) reflecting the distribution of the mineralization 1,5,6. Microhardness was measured (indenter Vickers: load of 25 g for 10 sec.) either on surfaced blocks or on the surfaced sections used for microradiography. On each sample, 60 impressions were measured (40 in cortical bone and 20 in cancellous bone) to calculate the mean microhardness. The intra-and inter-observer coeﬃcients of variation for the microhardness testing were 5%. DMB and microhardness values (Table) were significantly decreased (p%0.003) in osteoporotic men compared to controls. HI was not modified leading to a decrease of DMB without modification in the distribution of mineralization. All parameters analyzed were similar in the two populations of osteoporotic men. Measured separately at BSU level, there are significant (p%0.0004) positive correlations between DMB and microhardness in control (r2=0.36) and osteoporotic men (r2=0.52). Thus, the level of secondary mineralization appears to be the major cause of change in the microhardness of bone tissue. (1) Meunier & Boivin 1997, Bone 21:373–7 (2) Boivin et al. 2003, J Clin Endocrinol Metab 88:4199–205 (3) Boivin et al. 2005, Bone 36:562–7 (4) Boivin et al. 2000, Bone 27:687–94 (5) Boivin & Meunier 2002, Calcif Tissue Int 70:503–11 (6) Boivin & Meunier 2003, Osteoporos Int 14 suppl 5:22–8

Table. Mean values (SD) for the mineralization and the microhardness Vickers (HV25) of bone tissue.

Men

DMB (g/cm3)

DMB freq.max. (g/cm3)

HV25 HI (g/cm3) (Kg/mm2)

Controls 1.100.09 1.100.12 0.220.08 Osteoporotic 1.020.05 1.010.09 0.220.05 France Osteoporotic 1.020.06 0.980.08 0.240.07 Quebec

48.921.85 40.901.87 40.231.90

P670SA. THE FEMORAL NECK OPTIMIZES ITS STRENGTH BY ADAPTING ITS SPATIAL DISTRIBUTION AND ARCHITECTURE, RATHER THAN ITS MASS, TO PREVAILING LOADS Zebaze R1, Jones A2, Knackstedt M2, Maalouf G3, Seeman E1; 1 Austin Hospital, University of Melbourne, Melbourne, Australia, 2 Department of Applied Maths, RSPhysSE, Australian National University, 3Orthopaedic Department, Babmand University Hospital, Beirut, Lebanon The structural basis of femoral neck (FN) strength was studied in 692 women and in 26 postmortem specimens. A larger FN was not constructed with more material. FN size and mass were independent so that a bigger FN was relatively lighter - a 1 SD higher FN volume had a 0.67 SD lower volumetric bone mineral density (vBMD). A 1 SD increment in height was achieved by increasing FN volume by 0.32 SD with only 0.15 SD more bone so taller individuals had a larger but relatively lighter FN (vBMD was 0.13 SD lower). The independence in FN size and mass was recapitulated in vitro. At each of 200 micro-sections along the FN, total FN cross sectional area, shape and proportions of cortical and trabecular bone varied, bone area did not. At the FN-shaft junction, where bending forces were greatest, the FN cross section was largest, most elliptical with its long axis in the supero-inferior direction and largely cortical with greatest thickness inferiorly. Loading was more compressive moving proximally, the FN was more circular and the constant bone area was increasingly trabecular and proportionally less cortical. Strength yet lightness in larger and smaller bones is achieved by adapting the size, shape and distribution of similar amounts of material; ellipticity and cortical bone favor resistance bending, circularity and trabecular bone favor resistance to compression. Failed adaptation of the distribution rather than mass of bone to prevailing loads may contribute to bone fragility.

P671SU. POSTMENOPAUSAL BONE FRAGILITY: A DISEASE OF FAILED ADAPTATION Szulc P1, Seeman E2, Dubeouf F1, Sornay-Rendu E1, Munoz F1, Delmas PD1; 1INSERM 403 Research Unit and Université Claude Bernard Lyon 1, Lyon, France, 2Department of Endocrinology, University of Melbourne, Melbourne, Australia Postmenopausal bone loss results in decreased bone strength and increased fracture risk. Morphological basis underlying cortical bone loss was partly studied. We evaluated age-related changes in bone size and mass at one-third distal radius by yearly repeated DXA measurements (Hologic QDR2000) during a long term follow up in 846 women aged 31 to 89. In premenopausal women, the outward shift of constant amount of bone mineral (bone mineral content [BMC]) increased estimated bending strength (cross-sectional moment of inertia [CSMI], section modulus) despite cortical thinning. In perimenopausal women, slight slowdown of periosteal apposition and mild acceleration of endocortical resorption resulted in decreased BMC and cortical thinning but the bending strength remained stable. After menopause, periosteal apposition was slower and endocortical resorption was faster than before (p<0.05). Consequently, BMC, cortical thickness and estimated bending strength declined (p<0.0001). The higher the remodelling rate (elevated serum levels of osteocalcin and betaCTX-I), the greater was the decline in BMC, cortical thickness and

S322 estimated bending strength. The rate of periosteal expansion was independent of the bone turnover rate. In postmenopausal women with slow bone turnover (lowest quartiles of both markers), periosteal apposition oﬀset the loss of strength due to low endocortical resorption and the estimated bending strength remained stable despite the BMC loss. In postmenopausal women treated with hormone replacement therapy (HRT), expansion of the medullary cavity and decline in cortical area were less than in untreated women. In 637 postmenopausal women, estimates of bone strength predicted the risk of all fracture occurrence (e.g., CSMI – O.R. = 2.21 per 1 SD decrease, 95 % C.I.: 1.64 – 2.98). In summary, accelerated endocortical resorption and decreased periosteal apposition after menopause result in the loss of bone mass and bending strength which is partly inhibited by HRT. Increased bone turnover is associated with faster cortical thinning and greater decline in the estimated bone strength. Low estimated bone strength based on morphological parameters is predictive of the increased fracture risk. We conclude that postmenopausal osteoporosis is characterised – in the cortical compartment – by a failure of periosteal apposition to compensate for endocortical resorption.

P672MO. COLONY FORMING UNIT FIBROBLASTS AND THEIR DIFFERENTIATION IN BONE MARROW OBTAINED FROM GLUCOCORTICOID-INDUCED OSTEOPOROSIS IN RATS Sheng H1,2, Qin L1, Zhang G1, Jin WF2, Wang HF2, Leung KS1; 1 Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China, 2Department of Bone Metabolism, The Institute of Radiation Medicine, Fudan University, Shanghai, China Aims: Glucocorticoids are often indicated for treatment of infectious diseases and the side eﬀects may involve osteoporosis. We established a osteoporosis animal model using dexamethasone for analyzing the colony forming units fibroblast(CFU-F) and their diﬀerentiation into osteblasts and adipocytes. This would help to explore the underlying mechanisms of glucocorticoid-induced osteoporosis and develop corresponding strategies for its prevention and treatment. Methods: Twenty-four mature male Sprague Dawley rats were randomly assigned into experimental group and control group. The rats in experimental group received 1.5 mg/kg dexamethasone injection intramuscularly, twice a week, for up to 8 weeks. The other group received corresponding physiological saline as control. Bone marrow was drawn from bilateral femurs, contrifuged with Ficoll for nucleated cells. The CFU-F were then cultured with standard medium: Dulbecco’s Modified Eagle Medium+10% fetal bovine serum plus antibiotics. The bone marrow stromal cells were stained with Giemsa for CFU-F quantification with computer software in one week. After two weeks culture with osteoblastic and adipocytic induction medium, the CFU-F were collected for alkaline phosphatase(ALP) activity and stained with Oil Red O for neutral lipids to analyze osteoblasts and adipocyes diﬀerentiation, respectively. At same time, RT-PCR was used to analyze the expression of key genes of core binding factor 1(Cbfa1)and peroxisome proliferator activated receptor 2(PPAR2) in osteoblast and adipocyte diﬀerentiation. Results: Compared with control, the number of CFU-F from the osteoporosis model group decreases significantly, accounts for only 22.8% of control group. According to ALP activity and Oil Red O staining quantitative results, the ALP activity in the osteoporosis group accounts for only 43.2% of the control group, but the value of Oil Red O is 3.1 times of the control group. Cbf1, the key gene for osteblast diﬀerentiation, mRNA expression decreases by 33.5% in the osteoporosis group, and the gene PPAR2 responsible for adipocytes diﬀerentiation increases by 2.5 times in the osteoporosis model, as compared with the control group. Conclusions: Decrease in the number of CFU-F, and priority diﬀerentiation into adipocyes at the cost of osteblasts diﬀerentiation may be one of the important mechanisms of the glucocorticoids induced osteoporosis.

P673SA. MAINTENANCE OF BONE MASS IN ADOLESCENT WOMEN AFTER REDUCTION OF PHYSICAL ACTIVITY: A SEVEN-YEAR FOLLOW-UP STUDY Rautava E1, Lehtonen-Veromaa M1, Kautiainen H2, Kajander S3, Heinonen OJ1, Viikari J1,3, Möttönen T1,3; 1University of Turku, Turku, Finland, 2MedCare Ltd, änekoski, Finland, 3Turku University Central Hospital, Turku, Finland Aims: To investigate the influence of reduced physical activity on bone mineral content (BMC) at the femoral neck and lumbar spine. Methods: A total of 142 Caucasian healthy peripubertal girls were included. Weight, height, and the type and amount of physical activity were recorded at 6-months’ intervals over 3 years and once at seven years. BMC of the femoral neck and lumbar spine were measured by dual-energy x-ray absorptiometry (DXA, Hologic) at start, 3-year and 7-year visits. Results: The study groups were divided into tertiles according to the amount of physical activity during the whole follow-up time. The increase of unadjusted BMC of the femoral neck was higher in the highest activity tertile compared with the middle and the lowest tertile (24.0%, 20.2%, 15.7%, respectively). The corresponding figures for the increase of unadjusted BMC at the lumbar spine were 49.1%, 46.8% and 40.0%. The study population was divided into three groups according to the diminution of their physical activity during the last four follow-up years. The amount of physical activity of 30 girls decreased by more than 50% during the follow-up (discontinuers) and in 29 girls reduction was 25% - 50% (reduced activity). The rest of the girls (N=81) were assessed to continue their exercise habits as previously (continuers). The 4-year changes from 3 to 7 years in adjusted (for age, increase in weight and height, and change of measured bone area) BMC were 0.202 g (95% CI 0.054 g to 0.351 g, P = 0.004) and 1.65 g (95% CI 0.025 g to 3.054 g, P = 0.015) higher among the continuers than the discontinuers at the femoral neck and at the lumbar spine, respectively. Conclusions: High-impact loading during peripubertal years is beneficial for growing skeleton. Regular exercise is crucial in preserving the acquired bone mass. The negative eﬀect of reduced physical activity is more pronounced at the femoral neck.

P674SU. ENDOTHELIN-1 PROMOTES OSTEOSARCOMA INVASION VIA METALLOPROTEASES INDUCTION Guyot MC1,5, Felx M1, Vujanovic J5, Isler M2, Doyon J2, Turcotte R3, Moreau A1,4, Moldovan F1,4; 1Research Center, Sainte-Justine Hospital, 2Maisonneuve-Rosemont Hospital, 3McGill University Health Centre, 4Faculty of Dentistry, Université de Montréal, 5 Université de Montréal, Montreal, Canada Aims: Osteosarcoma (OS) is the most common type of cancer in children. OS demonstrates aggressive growth with a high risk of early, pulmonary metastasis. Osteosarcoma invasion involves the infiltration of neighbouring tissues surrounding the tumor as a consequence of abnormal cellular proliferation and for the development of metastases. The crucial step in tumor progression involves matrix metalloproteases (MMPs) activity. Previously, we demonstrated in MG63 osteosarcoma cells, that ET-1 is an inducer of the gelatinases (MMP-2, MMP-9), critical factors of tumors invasion and malignancy. Here we investigated expression of malignancy-related factors in OS derived cells and in osteosarcoma cell lines. Methods: For this project, we are using RT-PCR and immunohistochemistry to detect PARP, ET-1, ETA and ETB receptor. Zymography and Northern Blot were use to determine the presence of MMP-2 and MMP-9 and finally, we showed the presence of ET-1(1–31) by Elisa-immunoassay. The invasion of osteosarcoma cells was quantified using the Cell Invasion Assay Kit in presence or absence of selective antagonists of ETA receptor (BQ123), ETB receptor (BQ788), and the specific inhibitor of NF-B activity (PDTC). Results: In OS tissues and cells, we observed ET-1, MMP-2, and ETA receptor overexpression, in contrast to under-expression of MMP-9 and ETB receptor. Additionally, in high malignant OS cells, MMP-2, MMP-3, MMP-13 and PARP were overexpressed and TIMP-1, TIMP-2 and TIMP-4 expressed at low levels. Using

S323 a specific immunoassay for ET-1 (1–31), we showed presence of this alternative form in OS-derived cells. We showed that, in cells exposed to ET-1, the inhibition of NF-B pathway drastically blocked MMP-2 production and activity. Only selective antagonist of ETA receptor alone significantly diminished the cellular invasion (P%0.05). In combination, ETA and ETB antagonists did not demonstrate additional or synergistic eﬀect on osteosarcoma cell invasion. Conclusion: We concluded that expression of malignancyrelated factors could be beneficial for malignancy understanding. Tumor cells invasion and aggressiveness of osteosarcoma cells are the results, in part, of the tumorigenic potential of alternative forms of ET-1 generated by MMPs. Finally, our work provides new evidence for ET-1 receptor antagonists as a potential therapeutic target in the treatment of osteosarcoma.

P675MO. FTIR IMAGING OF ‘‘BONE QUALITY’’ IN A DIETARY INDUCED MODEL OF OSTEOPOROSIS IN THE EWE Boskey AL1, West PA1, MacLeay JM2, Wheeler DJ2; 1Musculoskeletal Integrity Program, Hospital for Special Surgery, NY, USA, 2Colorado State University, CO, USA Introduction: FTIR imaging of bone from iliac crest biopsies of normal vs. osteoporotic patients demonstrates alteration in mineral content, mineral crystal size, and collagen maturity based on chemically validated spectroscopic parameters. Changes in these ’’bone quality’’ parameters post therapy have also been reported, but are limited due to patient heterogeneity. The purpose of this study is to describe a sheep model that can be used to monitor therapeutic eﬀects on bone quality. Methods: Adult female sheep (4–7 yrs) were either placed on a metabolic acidosis diet (MA), ovarietomized (OVX), treated by (OVX+MA), or sham-operated (CONTROL). Ewes were sacrificed after 6 mo treatment, serum BAP and OCN were monitored along with mechanical properties of L3,L5 and L7 vertebrae. L4 was processed for FTIR analyses (n=6/group). Results: The MA diet did not cause histomorphometrically detectable osteomalacia, but did cause mechanical weakening of the bones to a greater extent than OVX. The mineral content determined by FTIRI was significantly decreased relative to CONTROL in MA and MA+OVX, but not in OVX. MA and MA+OVX showed increases in mineral crystallinity and alterations in the distribution of parameters related to collagen maturity (fig), while OVX showed no change in these parameters. Carbonate content was decreased relative to CONTROL in MA and MA+OVX. Conclusions: The changes in the MA group are comparable to those reported in untreated osteoporotic patients. Lack of change in the OVX sheep suggests that the 6 mo time point is too short to observe significant changes, while dietary manipulation (chronic MA) results in significant changes. These data suggest that the ovine MA model will be useful for monitoring ’’bone quality’’ changes following therapy, and also point to the negative eﬀects of high protein, high grain diets (MA). SUPPORTED by NIH AR043125

Pixel distribution for collagen maturity; MA (dark) has a broaer distribution than control (light)

P676SA. CONTRIBUTION OF SERUM INSULIN-LIKE GROWTH FACTOR I (IGF-I) AND THE CYTOSINE-ADENOSINE REPEAT POLYMORPHISM OF THE IGF-I GENE TO BONE HOMEOSTASIS IN ELDERLY MEN Crabbe P, Boie A, Goemaere S, Zmierczak HG, Van Pottelbergh I, Toye K, Kaufman JM; Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Belgium Aim: Insulin-like growth factor I (IGF-I) is known as an important local and systemic factor for growth and skeletal development. In this study we assessed the role of IGF-I and the cytosine-adenosine (CA) repeat polymorphism of the IGF-I gene in bone homeostasis in elderly men. Methods: We performed a cross-sectional evaluation in healthy community-dwelling men aged over 70 years (n=270). We determined levels of sex steroid hormones, IGF-I and IGF-binding protein 3 (IGFBP3), the CA repeat length of the IGF-I gene, body composition, baseline bone mineral density (BMD) at the hip and forearm and biochemical markers of bone turnover. Results: In our population of 270 elderly men, serum IGF-I was negatively correlated with age (r=-0.266, P<0.01) and positively correlated with BMI (r=0.143, P<0.05). After adjustment for age and BMI, serum IGF-I levels were negatively correlated with testosterone (r=-0.125, P<0.05) and positively correlated with IGFBP3 (r=0.690, P<0.01), BMD at the total hip (r=0.186, P<0.01) and biceps strength (r=0.152, P<0.05). There was no significant correlation with any of the biochemical markers of bone turnover. The CA repeat polymorphism of the IGF-I gene was neither a significant determinant of serum IGF-I levels, nor of other hormonal values, body composition, BMD or biochemical markers of bone turnover. To determine the independent eﬀect of IGF-I and the IGF-I genotype on BMD, we applied multiple linear regression analysis with age, BMI, bioavailable testosterone and bioavailable estradiol as covariates in the model. IGF-I remained significantly associated with BMD at the total hip (P<0.01), but not at the forearm. As for the IGF-I genotype, no associations with BMD could be established. Conclusion: The findings indicate that IGF-I plays an only limited role in determining bone homeostasis in elderly men. The positive association between serum IGF-I levels and BMD appears to be site-specific, prevailing at the hip, but not at the forearm. Serum IGF-I levels were not influenced by the CA repeat polymorphism of the IGF-I gene. Furthermore the IGF-I genotype did not aﬀect bone homeostasis in elderly men.

P677SU. VOLUMETRIC BONE MINERAL DENSITY BUT NOT BONE SIZE PREDICTS PREVIOUS FRACTURE IN YOUNG ADULT MEN: THE GOOD STUDY Lorentzon M, Mellström D, Ohlsson C; Center for Bone Research at the Sahlgrenska Academy (CBS), Dept. of Internal Medicine, Gothenburg University, Gothenburg, Sweden It is well known that areal bone mineral density (aBMD) measured with dual-energt X-ray absorptiometry (DXA) is associated with fracture risk in both male and female children as well as in adolescents. However, due to the limitations of the DXA technique, it remains unclear whether it is the volumetric BMD (vBMD) or the bone size of the cortical and trabecular bone compartments that is associated with fracture risk. The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population based study that consists of 1068 young men, age 18.90.6 yrs (meanSD). aBMD of the total body, lumbar spine and femoral neck was measured using DXA. Volumetric BMD and bone size of the trabecular and cortical bone of the radius and tibia were measured using peripheral quantitative computerized tomography (pQCT). Fracture incidence during childhood and adolescence was assessed using questionnaires. 304 out of the 1068 study subjects had sustained any kind of previous fracture. The most commonly reported fracture was upper and lower arm fractures (121 aﬀected subjects). Subjects with any kind of reported previous fracture had significantly lower aBMD of the total body (1.24 vs. 1.25 g/cm2, p=0.03) and lumbar spine (1.22 vs. 1.24 g/cm2, p=0.04), but not of the femoral neck (1.15 vs. 1.17 g/cm2, p=0.10). Using pQCT, we found that subjects with any kind of previous fracture had significantly lower cortical (radius: 1162

S324 vs. 1166 mg/cm3, p=0.02; tibia: 1154 vs. 1156 mg/cm3, p=0.046) and trabecular (radius: 211 vs. 223 mg/cm3, p<0.0001; tibia: 258 vs. 269 mg/cm3, p<0.00001) vBMD of both the radius and tibia. There were no diﬀerences in any parameter of cortical bone size (cortical cross sectional area, cortical thickness, periosteal and endosteal circumference) between subjects with reported fractures and nonfractured subjects. Trabecular vBMD (radius: Odds Ratio/SD 1.35; 95% CI 1.17–1.55, p<0.001) and cortical vBMD (radius: Odds Ratio/SD 1.18; 95% CI 1.03–1.34, p<0.05) of both the radius and tibia predicted previous fracture. In conclusion, our results indicate that it is the vBMD of the trabecular and cortical bone, and not the cortical bone size that is associated with fracture risk in children and adolescents.

P678MO. THE ROLE OF CORTICAL BONE IN FEMORAL NECK STRENGTH IN OSTEOPOROSIS Makarov MA1, Rodionova SS2, Kolondaev AF2, Vardikova GN1, Kolomatsky VV1; 1Institute of Rheumatology RAMS, 2Central Institute of Traumatology and Orthopaedics, Moscow, Russia Inspite that cancellous bone makes up 70% of femoral neck diameter, its role in the strength of this segment is still under discussion. Aim: To investigate the influence of cortical bone on the strength of femoral neck in osteoporosis. Methods: Quantitative CT evaluation was conducted on 24 autopsy specimens at the proximal femur with BMD measures correspondent to osteoporosis. Assessed separately were the mass of cancellous and cortical bone (g/cm3). Bone mass was assessed in 3 zones: subcapital, transcervical, basal. The speciments were subjected to mechanical testing (ZWIK-1464) until fracture occurred. Results: In 3 sections total BMD was identical. Ratio between cancellous and cortical bone is listed in a table. During mechanical testing the fractures occurred mainly in subcapital zone, where there is a maximum content of cancellous bone and minimum content of cortical bone. Conclusion: The mass of cortical bone is more important for femoral neck resistance to fracture than the mass of the cancellous bone. Ratio between cancellous and cortical bone in femoral neck Zone

Cancellous bone (mg/cm3)

Cortical bone (mg/cm3)

Subcapital Transcervical Basal

122,9 84,1 98,9

Upper plate 472,4 517,0 488,6

Lower plate 757,3 974,9 897,6

P679SA. DIETARY CALCIUM AND BONE MINERAL DENSITY IN ADOLESCENTS Mikhaylov EE, Demin NV, Benevolenskaya LI; Institute of Rheumatology of RAMS, Moscow, Russia Calcium intake is an important modifying factor in development of peak bone mass. Aim of study: To examine the eﬀect of dietary calcium intake on the mineralization of bone tissue in adolescents. Materials and methods: 412 adolescents (192 boys and 220 girls), 15–18 yrs age, were enrolled in the study. Mean age was 15.8 and 15.9, respectively. The evaluation of bone mineral content (BMC) and bone mineral density (BMD) in the hip and lumbar spine (L1-L4) was performed on the densitometer Hologic-4500/W with pediatric reference base for L1-L4. Daily calcium intake (Ca) in mg was assessed by 7-day food diaries a week before examination + 350 mg. Pearson correlation coeﬃcients was used to evaluate the correlation between levels of dietary Ca intake and BMC and BMD. The analyses of mean values of BMC and BMD were performed in two groups of adolescents: a group with high Ca intake (I group) and a group with low Ca intake (II group).

Results: The average level of Ca intake (mg/day) was 720.6275.0 in boys and 561.9170.8 in girls (p<0.001); and it satisfied the recommended daily level (1300 mg/day) in only 6.3% boys and in none of the girls. A significant positive correlation was observed between Ca intake and BMC of femoral neck (FN) and trochanter (T) and BMD of L1-L4, trochanter (T) and hip (H) in boys. The similar association in girls was observed only in the group of 15 yrs old. In boys with high Ca intake BMC and BMD were significantly greater compared to those with lower Ca intake: BMC of FN (5.21 vs. 4.88; p<0.02) and BMD L1-L4 (0.945 vs. 0.895; p<0.02), FN (0.935 vs. 0893; p<0.04) and H (1.033 vs. 0.982, p<0.02). In girl’s group such diﬀerences were observed only for hip BMC (p<0.04 – 0.01). In 15 yrs old girls, similar diﬀerences were observed both for BMC L1-L4, FN and H (p<0.02–0.002), and BMD of same sites (p<0.05–0.01). Conclusion: It is evident that dietary calcium intake significantly influences the bone mineralization in adolescents. The revealed substantial Ca-deficiency in most adolescents requires correction by calcium medications.

P680SU. MECHANISMS OF TRABECULAR BONE LOSS IN AN OVINE MODEL OF OSTEOPOROSIS Zarrinkalam M.R1, Nattrass G2, Beard H1, Atkins G.J3, Findlay D.M3,4, Moore R.J1,5; 1The Adelaide Centre for Spinal Research, Institute of Medical and Veterinary Science, Adelaide, Australia, 2 South Australian Research and Development Institute, Roseworthy Campus, Roseworthy, Australia, 3Department of Orthopaedics and Trauma, University of Adelaide, Adelaide, Australia, 4 Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, Australia, 5Department of Pathology, University of Adelaide, Adelaide, Australia Aims: Sheep are being used increasingly for skeletal-related research but compared to rats there is limited information about molecular pathways of bone remodeling in this species. The aim of this project was to investigate the expression of receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) in trabecular bone (TB) of the ovariectomised steroidtreated osteopaenic sheep. Methods: Osteopaenia was induced in ten mature lactating ewes. Histomorphometric analysis was undertaken on TB from the Lumbar Spine (LS) and Proximal Femur (PF) 1 and total RNA was extracted from both sites for complementary DNA (cDNA) synthesis. DNA encoding RANKL and OPG were sequenced and ovine specific primers were designed to amplify the cDNA by real time RT-PCR to generate products corresponding to mRNA encoding RANKL and OPG. The results were normalized to 18S RNA. Results: Erosion surface area increased over 5 fold in the treated animals but the number of active osteoclasts was significantly lower. Real time RT-PCR showed that treated animals had higher expression of OPG mRNA but not RANK-L mRNA. Consequently the ratio RANK-L/OPG mRNA was down regulated in these animals. RANK-L and OPG expression were higher in the LS region (P<0.05) but there was no significant diﬀerence in the ratio RANK-L/OPG between the two anatomical sites. Conclusions: The gene expression data suggest that the TB loss and increased erosion surface area in TB was not due to increased osteoclastic activity. The significant reduction in osteoclast number supports the molecular data. It is proposed that the bone loss is mainly due to lack of osteoblastic activity and function. Higher expression of OPG and RANK-L and greater bone loss in PF compared to LS suggest that the rate of bone turnover is greater in the PF region. Further investigation of the molecular pathways of bone loss in this animal model will increase its usefulness for osteoporosis research. Reference 1. Beard, H., C.G. Schultz, M.R. Zarrinkalam, and R.J. Moore. Further characterisation of an ovine model of steroid-induced osteopaenia. in Spinal Motion Segment: From Basic Science to Clinical Application. 2005. Davos, Switzerland: European Cells and Materials.

S325

P681MO. EFFECTS OF ANTIANDROGEN THERAPY ON BONE MINERAL DENSITY AND PLASMA AMYLIN LEVELS IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME* Üçkaya G1, Bolu SE1, Kutlu M1, Yazici M1, Azal O1, Beyhan Z1, Özgürtas T2, Arslan N3, Emer Ö3, Corakçi A1; 1Dept. of Endocrinology and Metabolism, 2Dept. of Biochemistry and Clinical Biochemistry, 3Dept. of Nuclear Medicine, Gulhane School of Medicine, Ankara, Turkey Aim: Amylin is a member of the calcitonin gene-related peptides produced in pancreatic beta-cells that inhibits bone resorption and stimulates osteoblastic activity. Amylin circulates in high concentrations in insulin resistant conditions, such as obesity. Polycystic ovary syndrome (PCOS) is characterized with hyperandrogenism and insulin resistance. We monitored plasma testosterone, insulin, total amylin concentrations and bone mineral density (BMD) in patients with PCOS, before and sixth month of anti-androgene therapy to determine possible correlations between these parameters. Methods: Seventeen non-obese women with PCOS (mean age; 25.75.9 years and BMI; 24.84.5 kg/m2) and normal insulin sensitivity (mean HOMA-IR 2.390.16) were followed during treatment of 0.035 mg ethinylestradiol/2 mg cyproterone acetate combined pills (DIANE-35t) for six menstrual cycles. Pre- and post-treatment oral glucose tolerance tests (OGTT), plasma testosterone, insulin, total amylin levels and BMD with dual-energy x-ray absorpsiometry in radius were determined. Results: Both total and free testosterone levels reduced significantly after six cycles of treatment (84.927 vs. 63.920 ng/dl, P=0.03 and 5.11.5 vs. 2.561.2 pg/ml, P=0.01, respectively). Mean BMI of subjects did not change significantly (24.84.5 vs. 24.13.3 kg/m2, P=0.55) by the end of treatment. Plasma glucose on 0 and 120 minutes of OGTT improved significantly (95.111.3 vs. 76.99.4 mg/dl, P=0.03 and 102.89 vs. 87.311.9 mg/dl, P=0.01, respectively) after treatment. Plasma insulin levels on 0 minute of OGTT did not change (9.86.4 vs. 9.65 mIU/ml, P=0.78), but significantly reduced on 120 minutes of OGTT (46.728 vs. 37.718.6 mIU/ml, P=0.03). Plasma total amylin levels were reduced but the diﬀerence was insignificant (3.31.2 vs. 2.61.1 pmol/L, P=0.07). BMD of patient remained unchanged. Both plasma glucose and insulin levels were in strong correlation with plasma total amylin levels (r=0.52 and r=0.63, both P=0.001). Conclusions: Anti-androgen medication has resulted in improved glucose metabolism correlated with reduced plasma amylin concentrations in patients with PCOS without change in BMD. Circulating amylin levels simply depends on insulin secretion and changes in insulin sensitivity do not aﬀect BMD in short term. * This study was supported by Gulhane Research Center (Grant Number: AR-GE-2004/36).

P682SA. REDUCED VERTEBRAL VOLUMETRIC BONE MINERAL DENSITY (VBMD): LOWER ACCRUAL, EXCESS LOSS AND MAKING BIGGER BONES WITH RELATIVELY LESS BONE Duan Y1, Garnero P2, Wang X-F1, Szulc P2, Borel O2, Delmas PD2, Seeman E1; 1Department of Medicine, The University of Melbourne, Melbourne, Australia, 2INSERM Unit 403, Hôpital Edouard Herriot, Lyon, France Reduced vBMD is due to reduced accrual of bone during growth, excessive bone loss during ageing, both, or due to construction of a larger bone using relatively less bone. Mother-daughter pairs share half their genes and so provide insights into the growth- or age- related origins of disease. To define the origins of reduced vBMD, we measured remodelling markers, bone volume, and vBMD at the third lumbar vertebral body (VB) in women and their premenopausal daughters. We hypothesized: (i) The deficit in mother’s vBMD is due to low peak vBMD if the daughter has about half the deficit in vBMD. (ii) The deficit in vBMD in mothers with high markers is due to excessive loss if the daughter has normal vBMD and markers. Using DXA lateral scanning, we measured VB volume and vBMD in 150 mother-daughter pairs. Serum osteocalcin and -CTX were measured. We identified 42

mothers (61.4 yrs) with low vBMD (T-score = -2.6 SD) and 44 premenopausal daughters (32.7 yrs). Results are expressed as age-, height- and weight-adjusted standardized deviation (SD, mean sem). The 42 mothers with low vBMD (–0.68 0.10 SD) had 0.26 0.19 SD higher VB volume but normal markers suggesting the larger bone size contributed to the lower vBMD. Their daughters had low vBMD (–0.30 0.15 SD), normal VB volume (0.11 0.16 SD) and markers supporting a growth related origin of low vBMD. In 15 mothers with high markers (1.25 0.28 SD), the vBMD deficit was –0.85 0.18 SD and VB volume was increased (0.52 0.36 SD) while their 15 daughters had normal VB volume (0.22 0.31 SD), vBMD (– 0.18 0.22 SD) and markers suggesting the deficit in vBMD was partly due to excessive bone loss. In 27 mothers with low vBMD (–0.59 0.11 SD) and normal markers had normal VB volume (0.12 0.21 SD); their 29 daughters had normal VB volume (0.03 0.19 SD), reduced vBMD (–0.37 0.19 SD) and normal markers consistent with a growth related deficit. The origin of low vBMD in old age is heterogenous.

P683SU. INSULIN RESISTANCE AND CHRONIC INFLAMATION MIGHT BE RELATED TO THE PATHOGENESIS OF OSTEOPORSIS IN POSTMENOPAUSAL WOMEN Tong NW, Cao L, Liu HL; Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, China Objective: to evaluate the diﬀerence and correlation of parameters of insulin resistance(IR) and chronic inflamation(CI) among postmenopausal subjects with diﬀerent bone mineral density(BMD),bone mineral content(BMC) and correcting BMC[cBMC, surrogate index of bone strength], in order to investigate the possible role of IR and CI in osteoporosis. Materials and methods: women who were 45 to 75 years,menopaused over two years, divided into three groups-control, osteopenia and osteoporosis. We measured serum parameters, eg. osteoclain(BGP), CTx, insulin, adiponectin, hypersensitive C-response protein(CRP) and BMD and BMC at femoral neck(FN) and lumber 2–4 vertebra(L2–4). Correcting BMC(cBMC,for BS) was calculated (BMC/BW). One-way ANOVA was used to observe the diﬀerence of markers in groups and bivariate correlate analysis was used to assess the relation between biochemical measurement(IR and CI) markers and BMD, BS of FN and L2–4. Results: Ninety were included 22 in normal group(NG), 30 in osteopenic (OG),38 in osteoporotic (OPG). BMI was 25.12 2.21, 23.583.03 and 22.272.87 kg/m2 respectively. NG presented higher BMI than OG(P=0.030) and OPG(P=0.000). OG with higher BMI than OPG. In NG, OG and OPG, BGP was 10.083.70, 7.772.63,7.132.31ng/ml; CTx was 0.340.15, 0.300.18,0.340.14 ng/ml, respectively. 1. HOMA-IR index in NG, OG and OPG was 2.891.10,2.501.41 and 2.090.64,not diﬀerent between NG and OG(P=0.436), OG and OPG(P=0.286),but NG was significantly higher than OPG(P=0.001). Adiponectin was 176.58137.96,191.86133.83 and 299.07209.48ng/ml respectively. NG presented lower adiponectin than OPG(P=0.001), OG was lower than OPG(P=0.001). No significance between NG and OG(P=0.675). 2. HOMA-IR index correlated in postive tendency with the BMD of L2–4 (r=0.093), but negative with BMD of FN(r= –0.140), with BS of L2–4(r= –0.069) and FN(r= –0.286, P<0.05). Adiponectin correlated in negative tendency with the BMD of L2–4 (r= –0.039) and positive with BMD of FN(r=0.185), BS of L2–4(r=0.155) and FN(r=0.426,P<0.05). 3. CRP level was 2.002.07 , 3.134.33 and 3.615.76mg/l in NG,OG and OPG respectively. Although no significance was found between NG and OG(P=0.245), NG and OPG(P=0.082), the CRP changed increasely with decreased BMD. The CRP correlated in negative tendency with BMD of L2–4 (r=–0.090) and FN(r= –0.044), also negative tendency with BS of L2–4 (r=–0.312,P<0.05) and FN(r=–0.220). Conclusions: We deduce that IR might paly an unprotective role in the pathogenesis of osteoporosis and osteoporosis might be a chronic inflammatory disease.

S326

P684MO. PREVALENCE AND FACTORS INFLUENCING LOW BONE MINERAL DENSITY IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS Setiyohadi B, Wijaya LK, Kasjmir YI, Isbagio H, Albar Z; Divison of Rheumatology, Dept. of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia Aims: To determine the prevalence rate of low BMD (osteopenia or osteoporosis) in SLE patients, and factors influencing the incidence rate of reduction of BMD i.e., duration of illness > 6 weeks, dosage of prednison R7.5 mg/day, and disease activity (Mex-SLEDAI R2 ) in SLE patients. Methods: An observational cross sectional study of SLE patients diagnosed based on the ACR criteria was performed. Nonprobability sampling with consecutive sampling was applied for collecting sample. Bone mass density was assessed by dualenergy x-ray absorptiometry (DXA); Low BMD was classified at T-score less than -1.0 at lumbar spine or femoral neck. Patients with renal impairment and not willing to sign informed consent were the excluded. Results: 55 patients were enrolled in this study. Patient age ranges from 20 to 51 years old, mean age is 32.3 8.4. There were 53 females and 2 males. The prevalence of lower bone mass was 45.5%. Decreased bone mass profile was as follows: osteopenia and osteoporosis was seen in 41.8% and 3.6%, respectively. Normal bone mass was defined in 54.5%. It was demonstrated that 92.7% had duration of illness more than 6 weeks; 56.4% received prednisone R7.5 mg/day; and 45.5% had Mex-SLEDAI R2. Bivariate analysis showed that duration of illness more than 6 weeks giving OR 2.67 (95% CI 0.22–71.37 p=0.617), patients who took prednisone R7.5 mg/day had an OR of 1.31 (CI 95% 0.39–4.42 p=0.823) and those with Mex-SLEDAI R 2, had an OR of 0.49 (CI 95% 0.14–1.66 p=0.311). Conclusion: The prevalence of low bone mass density in this study was 45.5%. It failed to demonstrate any significance influences between duration of illness > 6 weeks, prednisone R 7.5 mg/day, and disease activity (Mex-SLEDAI R2) as factors of low BMD. We suggest doing early detection of bone mass densitometry and giving prevention for every SLE patient.

P685SA. POTENTIAL PREDICTIVE FACTORS OF OSTEOPOROSIS IN HIVPOSITIVE SUBJECTS Fausto A1, Bongiovanni M2, Cicconi P2, Menicagli L1, Melzi S2, Ligabo’ EV2, Bini T2, Sardanelli F1, Cornalba GP3, d’Arminio Monforte A2; 1Department of Radiology, Policlinico San Donato, 2 Institute of Infectious Diseases and Tropical Medicine, University of Milan, 3Department of Diagnostic and Interventional Radiology, San Paolo Hospital, University of Milan, Italy Aims: To evaluate frequency of osteopenia/osteoporosis in HIVinfected subjects and to invastigate about the mechanism on the basis of this alteration. Methods: One-hundred-sixty-one consecutive HIV-infected outpatients aged 30–50 years, both naive and treated with highly active antiretroviral therapy (HAART) for more than 1 year, were enrolled. An interview questionnaire was performed to establish prior pathological, toxic, epidemiological histories, medications intake, physical activity and eating habits. Blood and urinary tests were performed to exclude concomitant diseases. Markers of bone metabolism and vitamin-D3-metabolites were tested. Each subject underwent to a blinded assessment of lumbar spine and left hipbone mineral density by dual-energy x-ray absorptiometry (DXA), using World Health Organization criteria for diagnosis of osteopenia or osteoporosis. For groups’ homogeneity Chi-square, Fisher’s exact, and Student’s t tests were used. Logistic regression analysis was used to find predictive factors of osteopenia/ osteoporosis. Results: Demographic characteristics of the two groups, 48 naive subjects (29 males) and 113 on HAART (74 males), were comparable. Eighty subjects (49.7%) showed osteopenia/ osteoporosis: 22 (45.8%) naive and 58 (51.3%) on HAART (p=0.46). Independent predictors of osteopenia/osteoporosis were female gender (OR:3.02, 95% CI: 1.26–7.25, p=0.01 vs male), older age (OR:1.10, 95% CI:1.01–1.20, p=0.03, for each year more), low body mass index (OR:0.78, 95% CI:0.68–0.91, p=0.001 for each

unit more) and higher HIV plasma viremia at DXA (OR:1.97, 95% CI:1.16–3.34, p=0.01 for each Log10 more); no association was found with use of HAART (OR:2.61, 95% CI:0.66–10.27, p=0.17 vs naive) and with markers of bone metabolism. Conclusions: HIV-infected subjects have a high risk to develop osteopenia/osteoporosis. Traditional risk factors confirmed to be predictive of osteopenia/osteoporosis also in HIV-subjects; the association with high HIV plasma viremia can be suggestive of a possible role of HIV in the development of bone disease.

P686SU. LOW BONE MASS IN ELITE FEMALE ATHLETES Coris EEC; The University of South Florida College of Medicine, Tampa, FL, USA Aims: Given the psychological and physical demands placed on the competitive female athlete participating in any given Division I NCAA season, many female athletes are thought to be at risk for disordered eating, menstrual disturbances, and bone mass deficiencies. The purpose of this study is to examine the prevalence of the female athlete triad in this collegiate athletic population as well as the prevalence of subclinical variants, components of the triad including mild eating disorders, menstrual abnormalities and low bone mass in a typical collegiate athletics setting comprised of both low and high risk sports programs. Methods: One hundred female student athletes at a Division I intercollegiate athletics program elected to participate in an initial study to assess the prevalence of eating disorders, menstrual dysfunction, and low bone mass in competitive female athletes. Athletes completed a FAST disordered eating inventory, comprehensive menstrual history questionnaire, and Cooper Exercise Inventory. Athletes also underwent calcaneal ultrasonography to assess bone density. Results: Preliminary data analysis reveals an amenorrhea prevalence of 25%, eating disorder prevalence of 14%, and an abnormally low heel ultrasound T-score in 25% of all female athletes assessed. The clinical significance of these remarkably high rates of ‘‘subclinical’’ disease is yet to be determined, but the implications are significant for the future health of these young athletes. Conclusion: Subclinical disordered eating, menstrual abnormalities, and reduced bone density appear to be alarmingly common in elite female athletes. More aggressive screening and education protocols need to be developed to better ensure the health of our athletes now and in the future.

P687MO. EFFECTS OF VANADIUM TREATMENT ON BONE QUALITY IN TYPE I DIABETES AND OSTEOPOROTIC RAT MODELS Chiu A1,2, Battell ML3, Yuen VG3, McNeill JH3, Grynpas MD1,2; 1 University of Toronto, Toronto, Canada, 2Samuel Lunenfeld Research Institute, Toronto, Canada, 3University of British Columbia, Vancouver, Canada Introduction: Vanadium-based pharmaceuticals alleviate hyperglycemia in type I diabetes by enhancing the eﬀects of insulin. Vanadium accumulates in bone as vanadate, replacing phosphate in the apatite lattice of bone mineral. Type I diabetes aﬀects bone, causing an osteopenia-like symptom. Some diabetic, postmenopausal women with osteoporosis might be treated with vanadium. It is thus necessary to examine how diabetes aﬀects osteoporotic bone, and how vanadium treatment aﬀects bone qualities in the combined diabetic and osteoporotic skeleton. Methods: Six-month Wistar rats were ovariectomized to induce bone loss similar to post-menopausal osteoporosis. Streptozotocin – a drug that destroys pancreatic beta cells – was given to half of the rats to induce type I diabetes. Bis(ethylmaltolato)oxovanadium(IV) (BEOV), a vanadium-based anti-diabetic drug, was administered in drinking water for 12 weeks. Non-diabetic rats were treated with 0, 0.25, and 0.75 mg/ml BEOV, whereas diabetic rats were either untreated, or treated with 0.25–0.75 mg/ml BEOV and were then grouped into either controlled glucose or uncontrolled glucose groups, according to their blood glucose levels. Bone quality parameters accessed were: bone mineral density (BMD), mechanical, mineral, and structural bone properties.

S327 Results: Diabetic-osteoporotic rats had lower BMD in both cortical and trabecular bones as compared to osteoporotic. Bone strength, crystal length, trabecular volume, and connectivity were also reduced in diabetic-osteoporotic rats. BEOV treatment to diabetic groups with controlled glucose improved all the above parameters, whereas BEOV treatment to osteoporotic groups did not have any significant impact as compared to non-treated. Conclusion: These results suggested that diabetes further worsen bone qualities in osteoporotic bones. BEOV treatment helps to prevent deterioration in bone qualities in type I diabetes when glucose is controlled. BEOV treatment at the doses given does not have any negative eﬀects on bone qualities.

P688SA. ESTRADIOL AND BONE MINERALIZATION IN ADOLESCENT GIRLS Scheplyagina LA, Moisseyeva TY, Kruglova IV; Research Center of Child Health, Russian Academy of Medical Sciences, Moscow, Russia Objective(s): To analyze the relationship between bone mass and main indicators of pubertas in adolescent girls. Materials and methods: Random sampling was applied to select 95 healthy girls at the age of 13–17 to be examined. In all children physical development (body height, body mass, body mass index), total score of sexual development and Tanner’s puberty stages. Bone mineral density (L2-L4) was determined using osteodensitometer DPX-MD+ Lunar. Osteocalcin (bone formation marker) and estradiol were analyzed in blood serum using immune enzymatic method. Results and Discussion: Mean age of menarche in examined girls was 12.7 years. It is established that as a rule body height and body mass in examined girls did not diﬀer norm and was positioned within the limits of 25 – 75% percentiles. In observed adolescents, stages of pubertas corresponded established norm. According densitometry results, in 22% of girls osteopenia was established. This did not diﬀer substantially from corresponding index in children population of the same age and gender. It is established that values of BMC and BMD, independently of Z-score, correlated with body height (r=0.6, p<0.01), body mass (r=0.7, p<0.05), body mass index (r=0.4, p<0.05), total score of sexual development (r=0.5, p<0.01), Tanner’s puberty’s stages (r=0.6, p<0.01). Relationship between osteocalcin level and body height (r=0.5, p<0.05) and age of menarche (r=-0.5, p<0.05) was established. It is demonstrated that in girls, before age of 14, unidirectional increase of body height, osteocalcin level, BMS, BMD and estradiol takes place. It is noticed that after age of 16 and with establishment of menstrual function blood estradiol increased significantly (up to 49.9 pg/ml). At the same time decreased longitudinal growth rate, osteocalcin level and bone mineralization. Conclusions: Study findings permit to suggest that estradiol impact on bone mineral density in girls during pubertas is caused by relationship of estradiol with longitudinal growth rate and bone mineralization.

P689SU. SELECTIVE EFFECT OF OVARIECTOMY AND PROTEIN UNDERNUTRITION ON RAT MANDIBULAR AND PROXIMAL TIBIA SITES: LOWER SENSITIVITY OF MANDIBULAR BONE TO ESTROGEN DEFICIENCY Mavropoulos A1,2, Rizzoli R1, Ammann P1; 1Division of Bone Diseases, University Hospital, 2Department of Orthodontics, University of Geneva, Geneva, Switzerland Aims: The mandible diﬀers significantly from other peripheral and axial skeletal sites. It is functionally subjected, through the teeth and their periodontal ligament, to extremely heavy, abrupt and intermittent forces during mastication, and it presents particular morphological characteristics. Ovariectomy and isocaloric protein undernutrition are known to cause bone loss and deterioration of bone micro-architecture in man. We compared the mid-term eﬀect of ovariectomy and of protein undernutrition on the microarchitecture and bone mineral density of the mandible and proximal tibia in a Sprague-Dawley rat model.

Methods: Forty-four six-month-old female Sprague-Dawley rats underwent transabdominal ovariectomy (OVX) (n=22) or sham operation (SHAM) (n=22), and were pair-fed isocaloric diets containing either 15% or 2.5% casein (SHAM 15% [n=11], SHAM 2.5% [n=11], OVX 15% [n=11], and OVX 2.5% [n=11]) for 16 weeks. At the end of the experiment bone mineral density (BMD) and bone micro-architecture parameters (e.g. bone volume fraction BV/TV) of the mandible and the proximal tibia were measured, using dual-energy x-ray absorptiometry (DXA) and micro-computed tomography (micro-CT). Results: Both ovariectomy and protein undernutrition had a negative impact on BMD and BV/TV in the proximal tibia (p<0.001), while only protein undernutrition had a negative influence on the mandible (p<0.005). The eﬀects of both ovariectomy and protein undernutrition were significantly less pronounced in the mandible (Figure). In sham-operated animals, low-protein diet led to 17.3% reduction of BV/TV in the mandible and to 84.6% in the proximal tibia. In normal diet fed animals, ovariectomy led to a reduction of BV/TV of only 4.9% in the mandible as compared to 82% in the proximal tibia. Conclusions: Mandibular bone appears to be less susceptible to protein undernutrition and estrogen deficiency in comparison to the proximal tibia. This may be related to functional or morphological diﬀerences.

A. Measurement of mandibular bone micro-architecture parameters. The mandible was scanned dorsoversally (micro-CT 40, Scanco, Switzerland). B. Eﬀect of OVX and low-protein diet on BV/TV of the mandible and the proximal tibia.

P690MO. VITAMIN D STATUS, BIOCHEMICAL PARAMETERS, CALCANEUS BMD, AND VERTEBRAL FRACTURES IN WOMEN LIVING IN A NURSING HOME Rodionova SS, Kolondaev AF, Morozov AK, VaretskayaChivilikhina NB; Central Institute of Traumatology and Orthopaedics, Moscow, Russia Aim: The purpose of this study is to examine the possible relationship between vitamin D deficiency, some biochemical parameters, calcaneus BMD, and vertebral fractures in institutionalized older women. Methods: Fifty-five postmenopausal women living in the nursing home in Moscow were recruited with average age of 78.021.14 years (63–96 years). We studied serum 25(OH)vitamin D, 1,25(OH)2-vitamin D (calcitriol), Ca, Ca ion, P, ALP, osteocalcin, total protein, creatinine, cholesterol, glucose, and urine excretion of deoxypyridinoline. Calcaneus BMD was measured by DXL (Calscan), using the optimal cutoﬀ point of T-score= -2.5 SD. Vertebral lumbar and thoracic fractures were determined by radiography and radiographic morphometry. Results: Definite vitamin D deficiency was determined in 29%, suboptimal 25(OH)-vitamin D levels in 45.6%, and optimal levels (more than 75 nmol/l) only in 25.4%. Low serum calcitriol was revealed in 50.9%. Forty-three women (78.2%) were osteoporotic and 11 (20%) osteopenic. Vertebral fractures were detected in 78.2%, their number varied from one to six per patient. The number of vertebral fractures correlated with serum calcitriol (r= -0.41), Ca (r= 0.31), and total protein (r= -0.49), deoxypyridinoline excretion (r= 0.47), and calcaneus BMD (r= -0.40). Lower calcaneus BMD was determined in elevated deoxypyridinoline excretion as compared with the normal one (T= -3.85 SD vs T= -2.65 SD), in elevated ALP (T= -3.67 SD vs T=

S328 -2.72 SD), in hypercalcemia (T= -3.57 SD vs T= -2.81 SD), and in vitamin D deficiency (T= -3.19 SD vs T= -2.91 SD). Conclusion: The very high rates of osteoporosis and vertebral fractures in older women living in the nursing home are determined. Only a minority of them have optimal levels of vitamin D or normal levels of calcitriol. The calcaneus BMD is lower in elevated deoxypyridinoline excretion, serum Ca, ALP, and in vitamin D deficiency. Vertebral fractures are associated with the low BMD, serum calcitriol, and total protein, high levels of deoxypyridinoline excretion, and hypercalcemia in the studied elderly group.

P691SA. LOW BONE MASS AND HIGH PREVALENCE OF HYPOVITAMINOSIS D COMMON IN FEMALE GARMENT FACTORY WORKERS OF BANGLADESH Islam MZ1, Shamim AA1, Lamberg-llardt C1, Akhtaruzzaman M2, Jehan A3, Khan ASMHU3, Jahan K2; 1Division of Nutrition, University of Helsinki, Finland, 2INFS, University of Dhaka, Bangladesh, 3Centre for Nuclear Medicine & Ultrasound, Mitford Medical College, Dhaka, Bangladesh Background: Garment is the main industry in Bangladesh. More than 70% of the total export revenue comes from this sector. About 1.6 million female workers are employed in this sector who are working 14–16 hours a day, seven days in a week. Little is known about vitamin D and bone mineral status (BMD) in these subjects. Objective: We hypothesized, due to their lifestyles and low income status they could be at risk of vitamin D deficiency and low BMD status. The purpose was to examine the vitamin D status and bone mass in female workers (aged 18–36 years) of a garment factory at Dhaka city. Design: This cross-sectional study randomly assigned 200 female workers; serum 25OHD, parathyroid hormone, calcium, phosphate and alkaline phosphatase activity were measured. Bone indexes of hip, spine and left forearm were measured by dualenergy X-ray absorptiometry. Results: The characteristics of the subjects is presented in Table 1. The distribution of serum 25OHD concentration in these subjects was shifted overall toward the lower limit of the normal range. A very high prevalence of vitamin D insuﬃciency (S25OHD <50 nmol/l) was observed (88.5%) in these subjects. Serum iPTH level was high (>37.5 ng/l; primary hyperparathyroidism) in 11% of the subjects. There was an significant inverse relationship between the change in serum 25OHD and that in iPTH levels (r = 0.25, p = <0.001). Bone mineral density was overall lower at all sites (Table 1) compared with other Asian and European subjects (Sigurdsson et al. 2000; Patel et al. 2001; Chee et al. 2003). Conclusions: The high prevalence of hypovitaminosis D and low BMD status are indicative of higher risk of osteoporosis. Thus the result of this study indicates that more attention should be focused on vitamin D and BMD status in this group of population. Table 1. Characteristics of the subjects (n=200), x (s.d.) Age (years)

22.6 (3.7)

Weight (kg) Height (cm) BMI (kg/m2) S-PTH (pmol/l) S-25OHD (mmol/l) BMDof femoral neck (g/cm2) BMC of femoral neck (g) BMD of lumber spine L2-L4 (g/cm2) BMC of lumber spine L2-L4 (g)

48.6 (6.8) 149.8 (5.0) 21.6 (2.7) 2.43 (1.20) 36.74 (11.25) 0.79 (0.10) 3.37 (0.53) 0.89 (0.11) 32.22(5.07)

P692SU. TESTOSTERONE AND BONE MASS INDICES IN ADOLESCENT BOYS Scheplyagina LA, Moisseyeva TY, Tsygina EN; Research Center of Child Health, Russian Academy of Medical Sciences, Moscow, Russia

Objective(s): To assess the relationship of serum testosterone level with bone mineral density indices in adolescent boys. Materials and Methods: In all, 43 healthy boys at the age from 10 to 16 years and selected using random sampling were examined. All children were measured for body height and body mass, total sexual development score were calculated. Moreover, level of biologic development was established using both X-ray of hand bones or accordance of bone age to passport age. Sex hormones supply was studied according to serum testosterone level. Mineral bone density was evaluated by dual-energy absorbciometry (L2L4) using densitometer ‘‘DPX-MD+’’, Lunar. Results: Mean age of examined children was 12.4 years. Physical development in observed boys mainly was harmonious (81.4%). Obesity of I-II stage was established in 13.9% and lower body mass in 4.7% of children. In boys, total score of sexual development corresponded to age (81.4%) and in 18.6% pubertas retardation was revealed. Results of densitometric study demonstrated that every fourth child had BMC and BMD values lower than norm. This permitted us to identify development of osteopenia. Osteopenia prevalence (25%) did not diﬀer significantly from corresponding values in population of children of same age and gender. In every fourth boy lower values of serum testosterone (less than 10% percentile) were determined. In examined adolescents, testosterone level correlated with age (r=0.6; p<0.000), body height (r=0.8; p<0.000), total score of sexual development (r=0.8; p<0.000), BMC (r=0.7; p<0.000), BMD (r=0.7; p<0.000) and cortical bone thickness (r=0.4; p<0.05). As a rule, lower testosterone values were accompanied by lower values of BMD and BMC. In case of pubertas retardation decrease of serum testosterone were established much more often (90%; p<0.05). Conclusions: Study findings permit to refer adolescent boys with pubertas retardation to risk group of osteopenia development.

P693MO. GONADAL HORMONES LEVEL, SEXUAL HORMONE BINDING GLOBULIN LEVEL AND GONADOTROPIN LEVEL IN VENEZUELAN MEN WITH LOW BONE MINERAL DENSITY Constantino R, Cedeno-Taborda J, Marcano Lm, Ramos J, Riera-Espinoza G; Unilime UC, Hospital Universitario ’’Dr. Angel Larralde’’, Universidad de Carabobo, Valencia, Venezuela In men there is a decrease in testosterone of 1% to 2%/year after 30 years of age, other gonadal hormones increase such as FSH and to a lesser degree LH. Also the sexual hormone binding globulin (SHBG) increases with age. In contrast is little change in estradiol levels; with a direct relationship with decrease of bone mineral density (BMD) at cortical (2% per decade) and trabecular bone (12% per decade). The objective was to determine serum levels of total testosterone (TT,) free testosterone (FT), bioavailable testosterone (BT), sexual hormone globulin level (SHBG), lutein hormone (LH) and estradiol (E) in men over 30 years of age with low bone density by DXA. 64 patients were studied mean age 58.69 12.91, BMD Total Hip (TH) 0.9110.12 g/cm2 T-Score -1.20.99; Femoral Neck (FC) 0.8420.10 g/cm2 T-score -1.70.79; Trocanter (T) 0.854 g/cm2 T-score -1.660.76; L1-L4 1.0570.14 g/cm3 T-score -1.341.25. TT levels 4.811.87 ng/ ml; TL 0.2820.105 nmol/L; BT 7.124.03 nmol/L; SHBG 47.8924.03 nmol/L; LH 6.444.50 mUI/ml; E 30.749.72 pg/ml. Age was co-related with FT (p=0.01), SHBG (p=0.000) and LH (p=0.001). Regarding BMD and gonadal hormone we found significant correlation between BMD TH, T and L1-L4 with TT (P<0.007, <0.05, <0.004, respectively); with FT and L1-L4 p=0.04 and with SHBG TH p=0.002, FN p=0.01, T p=0.006, of these correlations the strongest was between BMD and SHBG; not like with BT, LH and E (p > 0.05). We can conclude that the gonadal axis is modified with the process of ageing, producing a direct decrease of serum level of TT increase of SHBG and LH, with a decrease in cortical and trabecular bone mineral density, SHBG seems to be the main hormonal maker in men with low bone density.

S329

P694SA. EFFECT OF ENDOGENOUS INSULIN SECRETION ON BONE MINERAL HOMEOSTASIS IN POSTMENOPAUSAL WOMEN WITH AND WITHOUT DIABETES Harinarayan CV, Sudhakar D, Himabindu H, Kumar EGTV, Prasad UV; Department of Endocrinology and Metabolism, Sri Venkateswara Institute of Medical Sciences, Tirupati, India Aim: To study the eﬀect of endogenous insulin on bone mineral parameters of postmenopausal women with and without T2DM. Materials and methods: Thirty postmenopausal women recently detected as T2DM (group-A) and 14 postmenopausal women without T2DM (group-B) were evaluated for their biochemical and hormonal parameters [25(OH)D and intact PTH] of bone mineral homeostasis. After a standard two hour oral glucose tolerance test was done. Plasma glucose and insulin levels were estimated. Insulin resistance (IR) and beta cells function(BCF) were calculated. Results: Both groups had comparable age, biochemical and hormonal parameters, and basal insulin levels. Group–B had significantly (p<0.01) high insulin levels at 30’ and 120’ after glucose load compared to group-A. Both groups were subclassified as normal IR(<6.8) and high IR(>6.8). Their parameters(meanSD) are shown below: In group-A insulin levels at 0’ and IR correlated with urinary phosphorous (r0.4; p<0.5), 25(OH)D levels correlated with PTH (r=0.6; p<0.04). In group-B the 25(OH)D levels correlated with IR (r0.5; p<0.05). In group-B 25(OH)D levels positively correlated with basal insulin levels (r0.8; p<0.01) and IR (r0.8; p<0.002). IR correlated with urinary phosphorus (r0.6; p<0.03). Conclusions: 25(OH)D levels have an impact on basal insulin secretion. IR has a phosphaturic eﬀect which could aﬀect the bone homeostasis adversely. Hypovitaminosis D and insulin resistance can adversely aﬀect bone mineral homeostasis of postmenopausal women with T2DM. PMO_INSULIN_TABLE GROUP-A

GROUP-B

Parameter

Group-1 No IR (n=11)

Group-2 High IR (n=15)

Group-3 No IR (n=10)

Group-4 High IR (n=03)

Insulin 0’(µIU/ml) Insulin 30’(µIU/ml) IR BF(mmol/l) 25-OHD(ng/ml) U.Pho(mg/day) S.PTH(pg/ml)

148 6146 42 3431 217.17 308.45146.43 2718

4322.37*** 7342.09 1812 2028 16.539 452157* 23.513

209 170113.27 41.7 146.3196.56 12.446 35393 24.510

75.0716# # # $ 15873.44 $ $ 17.331.29 74.4359.5$ 268.02# # 527.1759.05# # 237

Gr-1VsGr-2: *p<0.05;**p<0.01;***p<0.001 Gr-3VsGr-4: #p<0.05;# # p<0.01; # # # p<0.001 Gr-1VsGr-3: p<0.05; p<0.01; p<0.001 Gr-2VsGr-4: $ p<0.05; $ $p<0.01; $ $ $ p<0.001

other diseases associated with estrogen withdrawal it is concluded that this small and easy to breed primate may be a good model to study development and treatment of postmenopausal osteoporosis in long bones but not in the vertebral bodies.

P696MO. EFFECTS OF DIETARY CALCIUM VS. CALCIUM SUPPLEMENTS ON ESTROGEN METABOLISM AND BONE DENSITY Thompson JN, Napoli N, Civitelli R, Armamento-Villareal RC; Washington University School of Medicine, St. Louis, MO, USA Objective: Higher calcium intake has been associated with both higher bone mineral density (BMD) and higher urinary estrogen metabolites, including the nonestrogenic metabolites 2-hydroxyestrone (2OHE1) and 2-methoxyestrone (2MeOE1), the active metabolite 16-hydroxyestrone (16OHE1), and the weakly estrogenic estriol (E3). Our objective was to investigate the influence of the type of calcium intake, from foods compared to supplements, on BMD and urinary estrogen metabolite levels. Methods: This study included 183 healthy postmenopausal Caucasian women. Outcome measures included average daily calcium intake from food, amount of calcium supplements, urinary estrogen metabolites, and spine and femur BMD. Subjects were analyzed in three groups: no dietary calcium (not eating foods containing calcium) and only taking calcium supplements, dietary calcium (from food) and not taking calcium supplements, and calcium from both food and supplements. Results: BMD (Z-scores) for the spine and femur were significantly higher in subjects receiving calcium only from food compared to those taking only supplements, even though average dietary calcium intake was lower than amount of supplements (Table 1). Total urinary estrogen metabolites (2OHE1+2MeOE1+16OHE1+E3), and individual 2MeOE1 and 16OHE1 levels were significantly higher, with a trend for higher 2OHE1, in subjects receiving calcium from food with or without supplements compared with subjects receiving only supplements. The ratio of 2OHE1/16OHE1 was significantly lower in subjects receiving dietary calcium with or without supplements compared to those with only supplements (0.246 0.02 vs. 0.348 0.05; P = 0.045), consistent with the idea that dietary calcium may preferentially aﬀect estrogen metabolism along the active pathway. Conclusion: Subjects who received calcium from food with or without calcium supplements had higher BMD and urinary estrogen metabolites than those taking supplements alone. Obtaining calcium through diet appears more eﬀective at maintaining BMD. Table 1: BMD (Z-scores) in subjects with only supplements vs. only dietary vs. supplements and dietary sources of calcium. Mean +/- SE. *Analysis of covariance adjusted for BMI.

P695SU. POST-CASTRATIONAL DEVELOPMENT OF OSTEOPOROSIS IN THE COMMON MARMOSET (CALLITHRIX JACCHUS) Seidlova-Wuttke D1, Schlumbohm C2, Wuttke W1; 1Dept. of Clin. and Exp. Endocrinology, University of Goettingen, 2Dept. Primate Husbandry, German Primate Center, Goettingen, Germany The marmoset serves as a primate model for many human diseases. Whether it develops osteoporosis following castration and may thus serve as model for postmenopausal osteoporosis is not yet known. This was tested in adult female and male castrated animals (ovx or orx, respectively). Total surface and mineral density of the cortex and trabecular structures of the metaphysis of the tibia (MT) and the 5th lumbar vertebra (L5) were determined by quantitative computer tomography (qCT) in 3 - 6 months intervals after castration. Surrogate parameters of bone metabolism (osteocalcin = OC, I and c-terminal breakdown products of collagen-I-1 = Crosslaps) were also measured in the serum of blood samples taken at the time of qCT. Male marmosets lost 17% and females 12% of their initial trabecular BMD in the MT within 1 year after castration and this was statistically significant (p < 0.05) 6 months after castration while trabecular surface area remained unchanged. Cortical BMD and surface at the level of the MT remained stable in both sexes after castration. No loss of BMD was observed in L5. Both, OC and the Crosslaps in the serum increased gradually following ovx or orx. As the marmoset is known to develop also

BMD (Z-score)

Calcium supplements (N=31)

Dietary sources (N=81)

Calcium supplements + dietary sources (N=68)

*P value

Spine Total femur Femoral neck Trochanter Intertrochanter Ave. Ca++ intake

0.1380.241 -0.0540.167 -0.2020.101 0.1070.170 0.0030.166 935.59100.38

0.5400.149 0.4150.104 0.2010.101 0.5030.106 0.4340.102 770.1262.81

1.0800.171 0.7470.113 0.4650.110 0.6710.115 0.7460.112 1576.1869.04

0.0042 0.0004 0.0036 0.0249 0.0011 0.0000

P697SA. PROXIMAL FEMUR GEOMETRY AS A RISK FACTOR FOR FEMORAL NECK FRACTURES IN OSTEOPOROSIS Makarov MA1, Rodionova SS2; 1Institute of Rheumatology RAMS, 2Central Institute of Traumatology and Orthopaedics, Moscow, Russia Objective: To investigate the influence of geometric measurement of proximal femur on the risk of femoral neck fracture in osteoporosis. Materials and methods: In this study were included two groups of patients. 64 patients (M:F = 17:47) with femoral neck fracture as a result of minimal trauma (I group). II group consisted of 101 patients (M:F=17:84) comparable by age, with bone mineral

S330 density (BMD) loss, determined by dual-energy X-ray absorbtiometry (LUNAR, DPX-L) with more than 2.5 SD by T-score in proximal part of the femur. BMD measured in the next regions: femoral neck, Ward’s triangle and trochanter major. Also we measured femoral neck axis length, femoral width and neck-shaft angle. Results: BMD was high in patients with femoral neck fracture (I group) in males as well as in females. In females diﬀerences were significant (0.657+0.03 vs 0.769+0.04 in the femoral neck, p<0.01; 0.492+0.03 vs 0.599+0.04 in Ward’s triangle, p<0.01; 0.598+0.03 vs 0.684+0.03 in trochanter, p<0.01, in I and II groups, respectively). Diﬀerence in femoral neck axis length in females with fracture and without fracture was significant (90.5+1.37 mm vs 87.7+1.19 mm, p<0.001). In males significant diﬀerences were found in femoral width. In the group with fractures the femoral width was 33.6+0.75 mm and in the group without fractures –35.9+0.43 mm (p<0.05). Conclusion: The obtained results enable us to suggest that geometric measurement of proximal femur (in particular femoral neck axis length in females and femoral width in males) could influence on the risk of femoral neck fracture in osteoporosis independently from BMD.

P698SU. ASSESSMENT OF BONE TURNOVER IN PATIENTS WITH SUBCLINIC HYPOTHYROIDISM TREATED WITH LEVOTHYROXINE AT PERIMENOPAUSE Circo E1, Chirca I2, Circo S2, Shavazo D1; 1Ovidius University, Constanta, Romania, 2Carol Davila University, Bucharest, Romania Aims: Our aim was to point out the disturbances of bone metabolism in patients with subclinical hypothyroidism (SCHT) found at perimenopause receiving levothyroxine (L-T4). Method: The study was conducted on 53 patients with SCHT, mean age 471.8 years at perimenopause. Based on TSH screening ( N=0.27–4.2 mU/L) by electrochemiluminescence, the patients were divided into 2 groups: Group 1: (n=31) TSH>10 mU/L (16.42.1 mU/L) Group 2: (n=22) TSH<10 mU/L (7.31.6 mU/L) L-T4 was given based on TSH values. Group 1 = 964.5 µg/day Group 2 = 5411 µg/day Initially were estimated: BMD (DXA) using T- and Z-score according to WHO criteria. Osteocalcin: evidence of bone function. Beta cross-lap marker of bone destruction. Marker screening was repeated after 6 and 12 months. After 12 months, BMD (DXA) was measured again. Results: In group 1 after 6 months there was observed increase in serum level of osteocalcin compared to initial values (p%0.001); serum levels of beta cross-lap were not modified significantly. In group 2 after 6 months serum levels of osteocalcin increased but had a poor statistical significance (p0.05); serum levels of beta cross-lap remained unmodified. 12 months after treatment: In group 1 were obtained significantly high levels of osteocalcin and beta cross-lap (p0.001), compared to initial serum levels. DXA results have shown a decreased BMD in lumbar region with 1.2% and 0.6% at the head of femur. In group 2 were obtained significantly high levels of osteocalcin (p0.001) with a poor statistical significance for beta cross-lap (p0.05). DXA results showed decreased BMD values; 0.8% in spinal vertebra and unmodified in femur. Conclusions: Starting treatment with thyroxin in patients with subclinic hypothyroidism in perimenopausal women requires a careful assessment of therapeutical indications. Increased bone turnover during this period can be accelerated by the administration of thyroxine in accordance to the dose and time of administration.

P699MO. MARKERS OF BONE REMODELING CORRELATE NEGATIVELY WITH SERUM TSH IN POSTMENOPAUSAL WOMEN Zofkova I, Zajickova K, Hill M; Institute of Endocrinology, Prague, Czech Republic

Recent in vitro studies have suggested that not only active thyroid hormone, but also thyrotropin (TSH) significantly regulates bone metabolism. The purpose of this cross-sectional study is to evaluate relationships between circulating TSH and parameters of bone metabolism in 60 untreated postmenopausal women. Besides the serum TSH levels and parameters of bone remodeling, a number of osteotropic hormones, such as free thyroxine (FT4), IGF-I, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) levels was determined. Bone mineral density at the spine and at the hip was measured by DXA method. Pearson’s correlations showed negative association between serum TSH and cross-linked telopeptide of type I collagen, urinary deoxypyridinoline/creatinine ratio or serum carboxy-terminal propetide of type I procollagen. No correlations were found between FT4 levels and parameters of bone remodeling. Additionally, 64.7 % variability in TSH levels and 41.1% variability in FT4 values in our cohort shared with the factor of bone remodeling (factor analysis). As to the bone mass, the negative correlations between bone density at the hip and SHBG levels and/or FT4 levels and positive correlation between bone density at the hip and DHEAS levels were found. To conclude, this study suggests negative association between circulating TSH and biochemical markers of bone remodeling in postmenopausal women. In addition, it confirms the strong predictive value of serum SHBG levels for bone density at the hip in these women. The study was supported by grant NB/7391–3 of the Internal Grant Agency of the Czech Ministry of Health.

P700SA. THE INFLUENCE OF CONSUMPTION OF PHYTATES (PHYTIC ACID) ON BONE MASS LEVELS OF THE WORKING CLASS IN THE BALEARIC ISLANDS Lopez Gonzalez A.A1, Mari Solivellas B2, Grases Freixedas F3, Vicente Herreros Mt4, Cabanes Martin T2; 1servicio De Prevencion Gesma, 2servicio De Medicina Del Deporte Fhoemo, 3departamento De Quimica Analitica Uib, 4servicio De Prevencion. Correos, Valencia, Spain Objectives: — Evaluate the influence of consumption of phytates (phytic acid) on the level of bone mass measured by axial densitometry. — Evaluate the influence of consumption of phytates (phytic acid) on the level bone mass measured by peripheral calcaneus densitometry. People and methods: 433 axial densitometries (286 females and 147 males, average age 44.52 and 42, no diﬀerences noted by age group p0.0727) 1473 peripheral calcaneus densitometries. (983 females and 490 males. Average age 42.12 and 43.02, no diﬀerences noted by age group p0.1057) The consumption of phytates (phytic acid) was evaluated through interviews. It is estimated adequate intake if consumed more than two times a week on regular bases. The three food groups considered rich in phytates (phytic acid) are beans, nuts and fiber. The people are grouped by non-consumer, consume one, two or three types of the food groups on regular bases. Result: Spinal column: Non-consumer (T-score average -1.48 dt 1.255), one (-0.876 dt 1.135), two (-0.557 dt 1.349), three (-0.428 dt 1.219). Femoral neck: Non-consumer (-0.774 dt 1.016), one (-0.166 dt 1.109), two (-0.02 dt 1.188), three (0.168 dt 1.132). Calcaneus: Non-consumer (-0.664 dt 1.092), one (-0.1411 dt 1.077), two (0.3221 dt 1.167), three (0.3283 dt 1.242). There are significant statistical diﬀerences between: — Non-consumers and consume one (spinal column p0.0002, femoral neck p0.0002 and calcaneus p0.0008), two (spinal column p0.0002, femoral neck p0.0006, calcaneus p0.00001) and three (spinal column p0.0003, femoral neck p0.0008 and calcaneus p0.00001). — Consume one and two (only calcaneus p0.0001), three (spinal column p0.007, femoral neck p0.0339, calcaneus p0.0005) There are no significant statitical diﬀerences between:

S331 —

Consumption of one and two (spinal column p0.0614, femoral neck p0.3497). — Consumption of two and three (spinal comumn p0.4816, femoral neck p0.2551, calcaneus p0.9415). Conclusion: The consumption of phytates (phytic acid) appears to have a positive influence on bone mass. Better results are appreciated with those who consume once, twice or three times as opposed to the non-consumers. No diﬀerences shown between the consumers of one or two (except calcaneus) and between two and three.

P701SU. STUDY OF ESTROGEN RECEPTORS ER-ALPHA AND ER-BETA IN HUMAN OSTEOBLASTS AND IDENTIFICATION OF XBAI AND PVUII POLYMORPHISMS IN ER GENE IN SCOLIOSIS PATIENTS Letellier K1,3, Lévesque LO3, Azeddine B1,3, Lacroix G1, Wang DS1, Turgeon I1, Leclerc S1, Grimard G1, Labelle H1, Moreau A1,2, Moldovan F1,2; 1Sainte-Justine Hospital Research Center, 2 Faculty of dentistry, Université de Montréal, 3Université de Montréal, Montreal, Canada Objective: Several factors involved in the ethiopathogenesis of idiopathic scoliosis also aﬀect peak bone mass acquisition, which occurs primarily during puberty, a period of progression for scoliosis. Among these, estrogens have a significant impact on bone metabolism. Estrogens receptors (ER et ER) are expressed by osteoblasts from normal and pathological (osteoporosis) cells, but their expression in scoliotic cells and tissues was not demonstrated yet. The objective of this project is to ascertain the expression of the estrogen receptors ER and ER and to analyse polymorphisms of the ER gene in adolescent idiopathic scoliosis patients (AIS). This research aims to clarify the role of estrogens and estrogen receptors in the pathogenesis of AIS. Methodology : Using RT-PCR, we compared ER and ER mRNA expression in osteoblasts from control and AIS patients (n=40). Through use of Western blot, we identified the two known E2 receptors (ER and ER) in osteosblastic cell lines and osteoblasts from scoliotic patients. Polymorphisms of the first intron of the ER gene, which contains the XbaI and PvuII polymorphisms, were investigated by PCR following by digestion with restriction enzyme and using the genomic DNA from lymphocytes isolated from scoliotic patients (n=33). Results: We observed a decrease of ER expression in some osteoblasts from scoliotic patients. The XbaI and PvuII polymorphisms were found in 70% (23/33) and 80% (26/33) of the cases respectively. Of the 33 cases, 21 presented both digestion sites. Western blot analysis allowed us to detect ER and observe the induction of ER by E2 in osteoblasts from scoliotic patients. Conclusion : The expression of ER appears altered in a number of AIS patients. The XbaI and PvuII polymorphisms are represented in the AIS population. The functional impact of these polymorphisms remains to be determined. This research could help in the identification of prognostic tools for the prediction of the development of AIS and assist in the development of new molecular strategies to prevent or reduce spine deformity. The importance of this proposal is in its explicit goal of clearly establishing the specific role of estrogens and their receptors in pathogenic mechanisms involved in AIS.

P702MO. ‘‘ANTHROPOMETRIC’’ PORTRAIT AND BONE TISSUE STRUCTURALFUNCTIONAL STATUS IN MALE SUBJECTS WITH LATE HYPOGONADISM Povoroznjuk VV, Dmitrenko OP; Institute of Gerontology AMS Ukraine, Kiev, Ukraine Testosterone concentration reduction with aging may promote age-dependent bone mass loss in men. Numerous studies involving healthy male subjects revealed correlation between bone density and bioavailable testosterone concentration. Besides, there exist certain male peculiarities influencing bone tissue status: firstly, men have larger skeleton; secondly, bone mass loss in men vs. women begins at later age periods and is proceeding more slowly; and,

thirdly, no bone mass loss occurs in men as it does in women during pregnancy, lactation and menopause with estrogens fall, sex hormone level declines more slowly in men than in women. Early detection of risk groups promotes prevention of osteoporosis and its complications. The study included 43 patients, mean age 58.6 years. Depending on testosterone level the men were divided into two groups: with testosterone level less than 12 nmol/l - 1st group and with testosterone level of 12 nmol/l and over - 2nd group. Bone tissue structural-functional state, like elasticity, density and durability, was examined by an ultrasound densitometer Achilles. Anthropometric examination was performed using the V.V. Bunak’s method in modification of P.F. Shaparenko 1994 and filling in of questionnaire. For males with reduced testosterone level the following anthropometric indices were found to be increased: body weight, circumferences of the chest, belly, behind, shoulder, wide and narrow parts of arms, shoulder diameter, pelvis diameter and hip width; while the ultrasound densitometry index, i.e. the durability index, was decreased. The results obtained suggest that the anthropometric parameters might be taken into account, while identifying risk groups of the development of bone tissue structure and functioning disturbances in male subjects who have low testosterone level, in the formation of their so-called ‘‘anthropometric’’ portrait.

P703SA. CORRELATION BETWEEN RISK OF FALLING DETECTED BY POSTUROGRAPHY AND BALANCE TESTS Saridogan M, Akarirmak U, Terzibasioglu A, Yildiz Aydin F; Istanbul Universty Cerrahpasa Medical School Physical Medicine and Rehabilitation, Istanbul, Turkey Aim: Balance disorders are among the primary risk factors of falls. The Tetrax device is a special posturography device which assesses and measures balance and stability. In this clinical study the correlation between risk of falling detected by Tetrax posturography and balance tests and correlation of clinical balance tests to each other were assessed. Methods: Patients applying to Cerrahpasa PMR Department for diﬀerent muskuloskeletal system problems were included. 100 patients were evaluated (75 females, 25 males). Examination included static and dynamic balance tests (tandem walk), coordinated balance tests with eyes open and closed. Level of falling risk was assessed by posturographic evaluation. According to the results, falling risk was detected to be low, medium, or high. The correlation of the results to each other was assessed by Pearson’s correlation analysis. Results: The mean BMI of the patients was 26.65.7. In the family history, 40% reported presence of kyphosis , while 32% reported osteoporotic fracture. Previous fracture was found in 23% of patients. In 81% of patients, static balance was maintained for over 15 seconds. Dynamic balance tests detected no error in 66% of the patients. Coordinated balance tests were found to be within normal limits in 89% of the patients performed while eyes were open, and in 91% eyes closed. Level of falling risk according to posturography results was low in 48%, medium in 29% and high in 33% of the patients. Conclusion: Clinical balance tests showed a significant correlation to each other. Static and dynamic balance tests, and coordinated balance tests, with open and closed eyes were found to be significantly correlated (p<0.01). Risk of falling detected by posturography showed a significant positive correlation to static (p<0.05) and dynamic balance tests (p<0.01), but not to coordinated balance tests. In conclusion, for assessment of falling risk in osteoporotic patients, dynamic and static balance tests should be a part of the routine physical examination. Physical examination findings can in addition be verified by Tetrax posturography device.

S332

P704SU. SERUM VITAMIN D STATUS AMONG POSTMENOPAUSAL URUGUAYAN WOMEN Mendoza B1, Ronco A1, Mintegui G1, Belzarena MC2; 1University of Republic - School of Medicine, 2Unit of Osteoporosis and Metabolic Diseases, Clinic of Endocrynology and Metabolism, Montevideo, Uruguay Serum vitamin D status is recognized as relevant for prevention and therapy of osteometabolic and other diseases. Female sex and postmenopausal status are strong risk factors for bone demineralization. In order to explore the current levels of serum vitamin D in a population subset with theoretical high risk of osteopenia, during the period 2001–2004 the authors performed a measurement in 137 postmenopausal women, aged 44–86, who consulted the Unit for having a osteometabolic examination. Women proceeded from the capital city of Uruguay, the coastal Montevideo (35( south latitude), belonging to the public hospital medical healthcare. Data collection was performed all along the year. One hundred three (103, 75.2%) were found as having a low level of vitamin D (under 30 ng/ml), while only 34 (24.8%) had a level over 30 ng/ml. Mean levels according to season of measurement were found also under adequate values: summer 26.0, autumn 23.0, winter 18.4 and spring 20.5 ng/ml (p = 0.059). When stratified by median age (<=60 vs. >=61 years ), these findings displayed stronger diﬀerences for values corresponding to summer and winter season, being older women more aﬀected than younger ones. Although geographical location of Montevideo allows to think there would be a suﬃcient sun exposure, results suggest that it would not be so as much as necessary. Results enable us to emphasize preventive measures like sunlight exposure and food fortification among postmenopausal women, which could be considered a high-risk subgroup for bone demineralization. Furthermore, supplementation of vitamin D should be discussed as a possible generalized guideline for the close future.

P705MO. THE DIFFERENCES OF GAINING BONE MASS FROM VARIOUS INTENSITIES FOR EXERCISE IN FEMALE MICE Minematsu AM; KIO University, Nara, Japan Aim: This study was investigated the eﬀects of the various intensity for exercise on gaining bone mass in female mice. Methods: Forty female ICR mice aged 3 months assigned randomly to 4 groups. One group was controlled and remain of 3 groups were run on a treadmill at 8 (A), 16 (B), and 24 m/s (C), 5 days/week for 3 months, respectively. Directly after running, the blood lactic acid level (LA) was measured. Mechanical strength (MS) of the left femur and tibia were measured by the three-point bending test. The bones were burned to ash, and measured ash contents (AC). In statistical analysis, one-way ANOVA and post hoc test (Fisher’s PLSD) were used to find the intensity for exercise and LA to gain bone mass. A significance level of p=0.05 was set. This study was carried out in accordance with the Guide for Animal Experimentation, Hiroshima University and the Committee of Research Facilities of Laboratory Animal Science, Hiroshima University school of Medicine. Results: MS and AC of the femur and tibia in B and C mice were significantly higher than those in control. Compared with control mice, MS of the both bones in all running groups increased from 8.0 to 20.0%. LA in C (7.1mM) group was higher than those in A (3.5mM) and B (4.1mM) groups significantly. Table 1. Results of MS, AC and LA Group

MS of femur (N/kg)

MS of tibia (N/kg)

AC of femur (mg)

AC of tibia (mg)

LA (mM)

Cont A B C

730.4121.3 795.7119.5 838.6131.4* 812.995.1*

516.7113.7 557.8125.7 617.2125.7* 610.6115.8*

38.42.2 39.44.0 42.64.0* 41.72.8*

28.22.0 28.92.5 31.11.9* 30.12.0*

3.50.7# 4.10.5# 7.11.1

MS: mechanical strength, AC: ash content, LA: lactate acid level *: Significantly diﬀerent from Cont group (p<0.05). #: Significantly diﬀerent from Cont group (p<0.05).

Conclusions: Treadmill running increased bone mass and this eﬀect was changed by the intensity for exercise. MS of the both bones in B and C group increased more than 10%, compared with control mice. The eﬀective intensity for exercise was 4.0 l/min of average LA level to gain bone mass.

P706SA. MEDICAL EFFECTS ON OSTEOPOROSIS ASSESSED IN A OVARIECTOMIZED RAT MODEL Chen SH, Chou FF; Chang Gung Memorial Hospital, Kaohsiung, Taiwan Introduction: Statin has been shown to increase bone mass in animal studies. aromasin has a catabolic eﬀect on the skeletalon. This study was designed to determine the eﬀects of aromasin, statin plus aromasin on bone mineral density in a sexually mature, ovariectomized rat model. Materials and Methods: A total 42, 14-week-old SpragueDawley rats were randomized into 3 groups: 1-ovariectomized (control); 2-ovariectomized plus aromasin; 3-ovariectomized plus statin and aromasin. After 4 weeks of surgery and then 12 weeks of treatment, BMD was measured with dual-enery X-ray absorptiometry (DXA). Serum levels of calcium, phasphorus, alkaline phosphatase and urine Ca/P were analysed. Results and Discussion:A significant increase in BMD is seen in statin plus aromasin group. Decreased BMD is seen in the aromasin group. Aromasin which is an irreversible aromatase inactivator is used to treat advanced breast cancer in postmenopausal women. Total suppression of aromatase may have adverse eﬀects including increased osteoporosis. Statins which are widely used for lowering serum cholesterol also enhance new bone formation in vitro and in rodents. In this study, statin plus aromasin group has significantly increased BMD. Thus, in appropriate conditions, statins may have therapeutic applications for the treatment of osteoporosis due to aromasin adverse eﬀect.

P707SU. VALUES OF 25-HYDROXYVITAMIN D (25-OH D3) IN VENEZUELAN MEN WITH LOW BONE MINERAL DENSITY Constantino R, Ramos J, Cedeno-Taborda J, Marcano L, Belzares E, Riera-Espinoza G; Unilime Uc, Hospital Universitario Angel Larralde, Universidad de Carabobo, Valencia, Venezuela Vitamin D (25-OH D) deficiency is associated with increased PTH levels and low bone density, high bone turnover and increased risk of hip fractures. Low levels of vitamin D are present in 34% of white older men. The prevalence is higher in women. Corporal reserves of vitamin D are estimated by serum levels of 25(OH)D3. So called ‘‘reference values of 25(OH)D3’’ are controversial and are aﬀected mainly by sunlight exposure, latitude, seasons and diet. The objective is to determine the values of vitamin D in men older than 30 years with low bone mass determined by DXA. 25-hydroxyvitamin D (25-OH D) levels were measured by enzymeinmmunoassay (OCTEIA 25-Hydroxyvitamin D, IDS, UK). Samples were taken from venous blood in the fasting state, frozen at -70(C and measured in duplicate at the same time. We analyzed 45 male patients with 60.1812.45 years of age, the bone mineral density (BMD) at total hip was 0.9010.123 g/cm2 , T-score -1.350.99; BMD femoral neck 0.8360.106 g/cm3 T-score -1.70.82; BMD L1-L4 1.0440.149 T-score -1.41.24; the serum calcium level was 8.880.39 mg/dl; range 1SD 8.49–9.27 with minimum values and maximum 8.50 and 9.90 mg/dl; vitamin D 52.06215.04 ng/dl. Range 1SD 37.02 – 67.10 with minimal and maximal values 80 and 250 ng/dl. There was no significant correlation between age, BMD and serum calcium levels and 25-OH D. In conclusion, vitamin D levels in Venezuelan men with low bone mineral density were 52.06215.04 ng/dl. Range 1SD 37.02–67.10. These values were similar to the mean levels of Venezuelan premenopausal women (52.8624.28ng/ml. RangeSD 28.58–77.14). However our population was just osteopenic and relatively young, 60 years old on average. There was no significant correlation between age, BMD and serum calcium levels and 25-OH D.

S333

P708MO. THE EFFECT OF STATINS ON BONE MINERAL DENSITY IN DIABETIC PATIENTS Uysal AR, Demir Ö, Delibasi T, Rifat E; Ankara University, School of Medicine, Department of Endocrinology and Metabolic Diseases, Ankara, Turkey Background: It is indicated that statins can have positive eﬀects on bone mineral density by stimulating bone formation. In this study, the eﬀect of statins on bone mineral density in diabetic patients is aimed to be studied. Materials and Methods: Thirty-eight patients with type 2 diabetes mellitus were enrolled into the study. Of these, 21 patients (11 males and 10 females) were on statin treatment and formed the study group while the rest 17 patients (9 males and 8 females) were not taking any antilipidemic drug who were accepted as control subjects. The study and the control groups were matched for age, sex and the duration of diabetes mellitus. Neither of the patients were taking medication which could aﬀect the bone mineral density like bisphosphonates, calcitonin, calcium and vitamine D. Bone mineral density was measured at the femural neck and the lumbar spine with DXA. Results: The median duration of statin use in the study group was two years. In diabetic patients taking statins, mean bone mineral density in lumbar spine and femoral neck were 0.7330.098 g/cm2 and 0.5720.077 g/cm2, respectively. In diabetic patients taking no statins, mean bone mineral density in lumbar spine and femoral neck were 0.718+0.089 g/cm2 vs 0.565+0.075 g/cm2, respectively. The diﬀerence between bone mineral densities, T- and Z-scores of the two groups was not statistically significant (p>0.05). Discussion: In some of the studies, it was reported that statins could have antiresorptive eﬀects and they may decrease osteoporosis risk and pathological fractures in old women. On the other hand in the Women’s Health Initiative study and in some other studies, statins were not found to be eﬀective on the increase of bone mineral density and prevention of the risk of fractures. Wada et al. indicated no positive correlation between statins and bone mineral density in diabetic patients. Conclusion: In this study it was shown that there is no positive correlation between statins and bone mineral density in diabetic patients, at least in this subgroup of patients.

P709SA. REGULATION OF BONE BALANCE: SEQUENTIAL MICRONUTRITION Lugand-Bourgeois Ml, Cornely AC; Bioresearch, Monthey, Switzerland Osteoporosis is becoming a real public health issue. Bioresearch & Partners’ objective is to exploit a new nutritional approach: micronutrition which can be used in prevention as well as to help and strengthen classic therapeutics. Micronutrisequences are a combination of microgram-dosed dietary substances organized in sequence. The micronutritional approach developed is a new mode of utilizing nutrients which targets an action on the global regulation of bone balance, the nutrients have been selected to participate in a nutritional strategy aiming to help the restoration of bone metabolism homeostasis. The aim of the nutritional intervention was the measurement in monotherapy in open study of bone balance regulation by the dosage of biological markers of bone formation (osteocalcin) and resorption (24-hour urine deoxypyridinoline at the creatinine dosage), as well as the increase of bone density observed with bone density test in menopaused women presenting a disturbance of bone balance markers and osteopenia or osteoporosis (BMD). The nutritional intervention lasted two years. Were excluded from the trial patients who were immobilized or taking glucocorticoids, having osteomalacia or unstable diseases: diabetes, thyroid, Crohn’s disease, kidney or active hepatic diseases. Nutrisequence (capsules containing micronutrition granules) was taken three times a day during 3 months. Population studied: 24 women aged 64 in average. All 24 patients are followed on bone markers balance, 10 are complementarily followed in absorptiometry.

Results: Of the 17 cases out of 24 which were presented at the beginning of the trial a bone balance with an excessive increase of dpyr, 94% restabilized their bone balance, 82% totally normalized their balance (in 17.3 months on average). Results on bone density: Of the 10 cases followed in BMD, 7 patients out of 9 had osteopenia or osteoporosis and showed an increase of the trabecular density by 7%. Conclusion: the regulation of bone markers (82%) and the increase of bone density (+7%) oﬀer a satisfactory response to the required therapeutic aims in a population presenting an excessively negative bone balance. Micronutrisequence is eﬃcient and perfectly adapted to a systematic preventive action and can be associated with any other drug therapeutics.

P710SU. SERUM PTH IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS Neves J1,2, Cardoso E1, Barata S1, Osório F1, Pereira-Coelho A1,2; 1 Obstetrics and Gynecological Department , Santa Maria Hospital, 2Medicine Faculty – Lisbon, Lisbon, Portugal Introduction: Parathormone (PTH) is secreted by parathyroids glands and is related with calcium metabolism and react to serum calcium variations; nowadays there is an increase interest in the relationship between serum PTH and bone reabsorption; what is the real impact of PTH enhancement and risk for osteoporosis bone? Objective: To assess serum PTH in postmenopausal women with osteoporosis. Methods: We evaluate the results of serum PTH (pg/ml and normal range 10–65 pg/ml) in postmenopausal women with WHO criteria for osteoporosis. Data are represented meansd, absolute and relative values. Results: We found the following epidemiological data – age 60.37.7 years, menarche 13.51.5 years, menopause 486.03 years and BMI 26.64.17 kg/m2. Serum PTH above the upper levels of normal range was founded in 23 patients – 21%. Conclusion: In this sample of postmenopausal women with osteoporosis, elevated serum PTH was found only in 21% of patients. With those data we can not directly relate serum PTH and risk of postmenopausal osteoporosis.

P711MO. THE RATIO OF OSTEOCLAST ACTIVITY/OSTEOCLAST NUMBER (CTX/TRACP 5B) IS A USEFUL PARAMETER IN EXPERIMENTAL RAT MODELS OF OSTEOPOROSIS Rissanen JP1, Suominen MI1, Oksala R2, Ravanti L2, Kallio PJ2, Halleen JM1; 1Pharmatest Services Ltd, Turku, Finland, 2Orion Pharma, Turku, Finland Rat ovariectomy (OVX) and orchidectomy (ORX) models are the most commonly used experimental animal models of osteoporosis. We studied the use of two bone resorption markers, serum C-terminal cross-linked telopeptides of type I collagen (CTX, a marker of osteoclast activity), and serum tartrate-resistant acid phosphatase isoform 5b (TRACP 5b, a marker of osteoclast number), in rat OVX and ORX models. Two identical 8-week studies were performed with 3-month old male and female Sprague-Dawley rats. The following study groups were included (n=12 in each group): 1) Sham-operated male or female rats receiving vehicle; 2) ORX or OVX rats receiving vehicle; 3) ORX rats receiving testosterone or OVX rats receiving estrogen. Testosterone and estrogen were administered daily by subcutaneous injections. Fasting blood samples were collected before the operation and at days 5, 14, 28 and 56 after the operation. CTX and TRACP 5b were measured using commercial immunoassays. Both ORX and OVX increased CTX values and decreased TRACP 5b values at all timepoints. Testosterone and estrogen increased TRACP 5b values and decreased CTX values to shamlevel at all timepoints. TRACP 5b values changed significantly by both operations already at day 14, while CTX values changed significantly at day 14 in the OVX study and at day 56 in the ORX study. A resorption index was calculated by dividing the CTX values by the TRACP 5b values, demonstrating the mean activity

S334 of a single osteoclast. Both operations increased the resorption index at all timepoints, the diﬀerence being most pronounced at day 5 in the ORX study, and at day 14 in the OVX study. Testosterone and estrogen decreased the resorption index significantly towards the sham-level at all timepoints. These results demonstrate that ORX and OVX increase osteoclast activity and decrease osteoclast number. The decrease in osteoclast number was verified by histomorphometric analysis, and it was probably due to extensive bone loss caused by the operations. These results demonstrate that the resorption index (CTX/TRACP 5b) is a useful tool in rat ORX and OVX models, showing more significant eﬀects than can be observed with either CTX or TRACP 5b alone.

P712SA. THE INFLUNECE OF VITAMIN D ON BONE TURNOVER AND PREGNANCY OUTCOMES Maghbooli Z, Hossein-nezhad A, Shafaee AR, Rahmani M, Madani SF, Mohammad-zadeh N, Larijani B; Endocrinology and Metabolism Research Center of Tehran University of Medical Sciences, Iran Aims: to evaluate serum vitamin D and bone marker concentrations in mothers and their newborns, and influence on pregnancy outcomes. Methods: 449 pregnancies recruited from Tehran University hospitals in winter. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus, parathyroid hormone, and bone markers (ALP, crosslaps and osteocalcin). Daily calcium and vitamin D intake were calculated from a food frequency questionnaire. Newborn anthropometric measurements were performed at birth, by recording of head circumference, height, weight and fontanel diameter. Mother’s weight gain during pregnancy and gestational age at delivery were obtained from the medical record. Results: Mean of serum vitamin D concentration were 31.614.44 nmol/l and 19.365.56 nmol/l, respectively in mothers and newborns. Prevalence of vitamin D deficiency in mothers was 66.8% and in newborns was 92.9%. Only 43.5% of mothers had received adequate vitamin D and calcium during pregnancy. Significant correlation was found between cord blood vitamin D and maternal ALP levels (p=0.001). In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than normal mothers (p=.001). Serum osteocalcin and cross laps had significant correlation in mothers with newborns. There was a significant diﬀerence between serum concentrations of PTH, osteocalcin and cross laps in mothers and newborns. Significant correlation was found between cord blood calcium concentrations and newborn’s head circumference. Fontanel diameter in newborn of mothers with vitamin D deficiency was significantly wider than newborns of normal mothers. Apgar score in infants whose mothers received adequate calcium and vitamin D was higher than others. (p=0.04) The prevalence of low birth weight in girls of mothers who adequately receive calcium and vitamin D was lower than other newborns (p=0.007). After adjustment for height, weight and BMI of mothers, calcium and vitamin D intake had independent influence on Apgar score. Conclusions: Vitamin D deficiency was common in mothers and newborns. Vitamin D and calcium supplementation during pregnancy recommended for improving bone turnover and pregnancy outcomes.

P713SU. DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN WITH DISTAL RADIAL FRACTURE FROM MINIMAL TRAUMA Dasch B1, Endres HG1, Lungenhausen M2, Maier C2, Smektala R3, Trampisch HJ1, Pientka L4; 1Department of Informatics, Biometry and Epidemiology, 2Department of Anesthesiology, Intensive Care and Pain Treatment, BG-Kliniken Bergmannsheil,

3 Department of Accident Surgery, Knappschaftskrankenhaus Bochum Langendreer, 4Department of Medicine and Geriatrics, Marienhospital Herne, University of Bochum, Germany

Aims: Postmenopausal women with forearm fracture resulting from minimal trauma represent a high-risk group for subsequent osteoporotic fractures. The aim of this study was to evaluate the diagnosis and treatment of osteoporosis in postmenopausal women following an acute fracture of the distal part of the radius. Methods: Data from a prospective observational study, evaluating the health care situation of patients with hip or forearm fracture in Germany, were analysed. All hospitalized women aged 55 and older, who sustained an isolated distal radial fracture due to minimal trauma between January 2002 and September 2003, were identified in the database. Information were obtained about potential risk factors for primary osteoporosis, as well as diagnosis and treatment of osteoporosis. A follow-up telephone interview was conducted six to twelve months after hospital discharge. Subsequent skeletal fractures were assessed and related to osteoporosis medication usage at the time of hospital discharge. Results: Among 2031 patients with forearm fractures, we identified 761 postmenopausal women (37.5%) with an isolated distal radial fracture. Of these, 61.5% reported at least one fall during the past three months, 6.6% had a previous history of adult fractures from minimal trauma and 8.8% had a prior diagnosis of low bone mineral density. Only 24 of the 761 subjects (3.2%) underwent a bone density scan. Seventy-two patients (9.5%) were receiving a specific osteoporosis medication (bisphosphonates, estrogen, raloxifene, or calcitonin) during hospitalization and less than 10% (62/761) had been advised to take supplemental calcium or vitamin D. Follow-up data were obtained from 533 participants. Of these, 20 patients experienced a subsequent fracture after hospital discharge. Comparing patients with and without use of specific osteoporosis medication, we could not reveal statistically significant diﬀerence in frequencies of subsequent fractures (2.1% vs. 3.9%, p=0.52). Conclusions: Despite the availability of eﬀective treatments, a substantial proportion of postmenopausal women with distal radial fracture from minimal trauma were not suﬃciently evaluated or treated for their evaluated risk of subsequent osteoporotic fracture during hospitalization.

P714MO. 18F-FLUORIDE POSITRON EMISSION TOMOGRAPHY: A NEW TOOL TO ASSESS MONOSTOTIC PAGET’S DISEASE OF BONE Nzeusseu Toukap A1, Depresseux G1, Installe J2, Lonneux M2, Devogelaer JP1; 1Rheumatology Unit, 2Nuclear Medicine, St-Luc University Hospital, Brussels, Belgium Introduction: The activity of monostotic Paget’s disease of bone (PDB) may be diﬃcult to assess by biochemical parameters. 18F-fluoride positron emission tomography (PET) is able to quantify local skeletal metabolic activity. We assessed this technique in monostotic PDB. Patients and Methods: 9 patients with monostotic PDB underwent a one-hour dynamic 18F-fluoride PET scan before, one month, six months and 12 months after BP therapy. Six patients with the polyostotic form served as controls. Serum total alkaline phosphatase (TAP), bone-specific (B) AP, serum CTX and fasting urinary NTX over creatinine were also measured at the same times. Changes in bone metabolism as measured by PET scans were assessed by a semi-quantitative index such as standardized uptake values (SUVmax), and by plasma clearance of 18F-fluoride to bone mineral (Ki). Wilcoxon signed rank test and simple regression analysis were used for statistics. Results: SUV and Ki correlated significantly with each other both at baseline and during the follow-up (p < 0.0001 at all times) in all patients. In the nine patients with monostotic PDB, the mean 18F-fluoride uptake decreased significantly up to 70.4% and 72.7% of initial values after the first month of BP therapy, as measured by both SUVmax (p < 0.05) and Ki measurements (p <0.01), respectively. Six months later, further reductions of the mean 18F-fluoride uptake were observed up to respectively 56.0% by SUVmax and 60.3% by Ki measurements (p < 0.01 for both values). After 12 months, these values, measured in 8 patients amounted to 56.9%

S335 and 54.5%, respectively. The mean serum TAP simultaneously decreased borderline significantly to 86.4%, 79.3% and 76.2% of initial values after 1, 6 and 12 months, respectively. Conclusions: 18F-fluoride PET is able to demonstrate metabolic bone changes particularly in localized PDB after BP therapy. If more readily available, 18F-fluoride PET could be helpful to monitor the therapeutic response in patients with monostotic PDB.

P715SA. EVALUATION OF 41CALCIUM AS A NEW APPROACH TO ASSESS CHANGES IN BONE METABOLISM: EFFECT OF A THREE MONTH CALCIUM SUPPLEMENTATION IN POSTMENOPAUSAL WOMEN Denk E1, Walczyk T1, Synal HA2, Geppert C3, Wendt K3, Fattinger K4, Harrington M5, Cashman K5, Jacobsen J6, Hennessey C7, Berglund M7, Häuselmann HJ8, Freeman SPHT9, Hurrell RF1; 1Laboratory for Human Nutrition, ETH-Zurich, Zurich, Switzerland, 2Laboratory for Particle Physics, ETH-Zurich, Zurich, Switzerland, 3Institute for Physics, University of Mainz, Mainz, Germany, 4Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Zurich, Switzerland, 5Department of Food and Nutritional Sciences, and Department of Medicine, University College, Cork, Ireland, 6Institute of Food Research and Nutrition, The Danish Veterinary and Food Administration, Søborg, Denmark, 7European Commission Joint Research Centre, Institute for Reference Materials and Measurements (IRMM), Geel, Belgium, 8Center of Rheumatology and Bone Diseases, Klinik im Park, Zurich, Switzerland, 9 Scottish Universities Environmental Research Centre, Glasgow, U.K. Nutritional factors play an important role in maintaining bone health through life. Bone research is limited by available methods to rapidly detect changes in bone metabolism. The aim of the present study was to evaluate the potential of the new Ca-41 technique to assess changes in bone calcium metabolism and to demonstrate its sensitivity using short term Ca supplementation as a rather weak intervention. Ca-41 (100 nCi) was administered orally to 16 healthy postmenopausal women. The urinary excretion pattern of Ca-41 was established by monitoring urinary Ca-41/Ca-40 isotope ratios over time using accelerator mass spectrometry and resonance ionization mass spectrometry. The impact of calcium supplementation (750 mg/d) on Ca-41 tracer excretion was assessed in a 3 month placebo controlled, randomized cross-over trial. Changes in calcium metabolism were identified by population pharmacokinetic modeling techniques (NONMEM) using a sequential three compartment model. Biochemical markers of bone turnover were measured in parallel. Biomarkers responded positively to calcium supplementation but showed well-known limitations in sensitivity. While bonespecific alkaline phosphatase (P=0.04) and deoxypyridinoline (P=0.04) were decreased, other markers (type I collagen crosslinked N-telopeptides, pyridinoline, osteocalcin and parathyroid hormone) remained unchanged. Using the Ca-41 methodology, a positive eﬀect of calcium supplementation on bone was identified as a 56% increase (P<0.001) in the calcium transfer rate from the fast exchanging calcium pool to the slow exchanging body calcium, i.e., bone, with no changes in other Ca transfer rates. We could demonstrate that mean urinary Ca-41/Ca-40 isotope rate after labeling bone with Ca-41 is a highly sensitive method that can be used to monitor nutritional or lifestyle interventions as well as osteoporosis preventions. Financial support: European Union/Swiss Ministry of Science Education (OSTEODIET QLK1–1999–00752)

P716SU. PREDICTION OF BONE LOSS WITH BIOCHEMICAL MARKERS OF BONE TURNOVER Lenora J, Ivaska KK, Gerdhem P, Obrant KJ; Department of Orthopaedics, Malmö University Hospital, Lund University, Malmö, Sweden Aims: The association between baseline levels of eleven bone turnover markers and 5-year change of bone mass, as assessed by

DXA (six skeletal regions) and ultrasound of the calcaneus (stiﬀness, speed of sound (SoS), broadband attenuation (BUA)) were studied in a population based random sample of 882 elderly women selected from the Malmö OPRA cohort. None of the selected women had been treated or were prospectively treated with any bone active medications. Methods: At baseline all were 75-year old. They were investigated by assessing bone turnover with biochemical markers and bone density with DXA and ultrasound technique. Five years later, when all women had reached the age of 80, a follow-up investigation of bone density with DXA and ultrasound was performed. Bone formation was assessed by serum bone specific alkaline phosphatase (S-Bone ALP), four diﬀerent serum osteocalcins (S-OC) (including two diﬀerent assays for S-Total OC, S-OC [1–49] and carboxylated OC (S-cOC)). Bone resorption was assessed by urinary deoxypyridinoline (U-DPD/crea), serum acid phosphatase (S-TRACP5b) and S-CTX (serum Crosslapst). Also three diﬀerent assays for urinary OC (U-OC) were analysed. Results: After 5 years 610 (69%) of the women attended. The mean percentage yearly changes of BMD were in total body-0,32, the legs -0,57, the total hip -1,32, spine +0,38, and for the ultrasound variables; stiﬀness -1,17, SOS -1,5, BUA -1,26. All markers (except S-Bone ALP) were correlated, with forthcoming bone loss, in particular such as assessed by BUA and by DXA of legs. There were no clear patterns which of the markers that could best identify forthcoming bone loss (standardized regression coefficient (R2) always <5), but all four serum S-OCs were correlated with all bone sites (except lumbar spine). High (above median value) bone turnover (in particular when assessed by U-DPD/crea) was predictive for high (above median) bone loss (in particular when assessed by DXA of the legs). Conclusions: Although this study clearly indicates that several of the markers were clearly correlated with forthcoming bone loss, in particular as assessed by ultrasound of the calcaneus, the importance of this finding for clinical decision making, in elderly women, is not very strong.

P717MO. BONE METABOLISM, CALCIUM REGULATING FACTORS, DAILY WALKING AMOUNT, AND GRIP STRENGTH IN OLD WOMEN Yamada T1, Matsuzaki M1, Tanaka A1, Fujimoto M2, Fujimoto S2; 1Department of Health and Nutrition, College of Human and Environmental Studies, Kanto Gakuin University, Yokohama, Japan, 2Akashi Keisen Fukushikai, Akashi, Japan Aims: Although the eﬀects of exercise on osteoporosis are well known, its regulatory mechanism is poorly understood. We investigated the relationship between levels of bone markers, calcium regulating factors including nutritional status of vitamin D and physical activity level and muscle strength. Methods: Ninety-four female volunteers with a mean age of 81 years participated in the investigation. Daily nutritional intake and daily walking amount were recorded for one week. Subsequently, fasting blood and second urine samples were collected early in the morning, and body height, weight, fat percentage and grip strength were measured. In addition, the index of bone mineral density was evaluated by quantitative ultrasound, which determined the speed of sound (SOS) in the right calcaneus. The following blood and urinary markers of bone turnover were measured: serum bonespecific alkaline phosphatase (BAP) and osteocalcin (OC) for bone formation, and urinary crosslinked N-telopeptides of type I collagen (NTx) and deoxypiridinoline (DPD) for bone resorption. Serum intact parathyroid hormone (PTH-intact), calcitonin (CT), 25(OH)D and 1,25(OH)2D were also determined. Results: No significant correlations were observed between age and levels of bone markers, PTH-intact, CT in all subjects; however 25(OH)D and 1,25(OH)2D levels were inversely correlated with age. A significant negative correlation was observed between grip strength and DPD level, while positive correlations were observed between grip strength and both 25(OH)D and 1,25(OH)2D levels. In the high walking amount group (highest 25th percentile), NTx and DPD levels were significantly lower than in the low

S336 walking amount group (lowest 25th percentile). In the high grip strength group (highest 25th percentile), DPD level tended to be lower, and both 25(OH)D and 1,25(OH)2D levels were significantly higher than in the low grip strebgth group (lowest 25th percentile). In contrast, no diﬀerences were observed for levels of SOS, bone formation markers, PTH-intact or CT. Conclusions: These results demonstrate that physical activity and the maintenance of muscle strength may suppress increased bone resorption in elderly women, and be related to the nutritional status of vitamin D.

P718SA. SINGULAR AND COMBINED ROLES OF ENERGY DEFICIENCY AND ESTROGEN DEFICIENCY ON BONE METABOLISM IN PREMENOPAUSAL EXERCISING WOMEN West SL1, Williams NI2, Burke TG1, De Souza MJ1; 1Women’s Exercise and Bone Health Laboratory, Dept of Exercise Sciences, University of Toronto, Toronto, ON, Canada, 2Dept of Kinesiology, Penn State University, University Park, PA, USA Aim: The aim of this study was to investigate the singular and combined roles of energy and estrogen deficiency on bone metabolism in premenopausal exercising women. Methods: In this prospective, observational study, subjects were categorized by their energy status [ratio of actual to predicted resting energy expenditure (REE)] into two groups: 1) energy replete (ER, n=29) and, 2) energy deficient (ED, n=14), where energy deficiency is a REE that is 90%below their Harris-Benedict predicted REE. Metabolic hormones (TT3 and ghrelin), menstrual status (daily urinary ovarian steroids) and markers of bone turnover (P1NP, osteocalcin, and uCTx) were measured for 2–3 menstrual cycles or 30-day monitoring periods if oligo/ amenorrheic. Results: ED and ER subjects were similar (p>0.05) in age (23.80.8 yrs), weight (57.71.4 kg), and BMI (21.10.5 kg/m2). The ED group had a REE expressed as percent predicted that was 831%, below that observed in ER group (971%, p<0.001). The ED group had a lower REE (28.90.9 vs. 31.40.4 kcal/kg FFM/day, p=0.007), TT3 (85.95.5 vs 101.14.1 ng/dL, p=0.035), and higher ghrelin (1842.2194.9 vs 1468.872.0 pmol/L, p=0.033) levels than the ER group. ED subjects had lower serum osteocalcin (4.70.5 vs 6.60.4 ng/mL, p=0.009) and P1NP (94.711.4 vs 145.213.2 µg/L, p=0.019) levels, indicative of suppressed bone formation. Bone resorption (uCTx µg mmol/ Cr/day) was similar (p>0.05) between groups, despite lower (p<0.043) E1G area under the curve (AUC) levels. To further explore the relationship of an energy deficiency in the presence of estrogen deficiency, the ED group was subdivided into those that were amenorrheic (n=8), i.e., hypoestrogenic, and those that were not (n=6). The ED group with severe hypoestrogenism, distinguished themselves from the estrogen replete ED group by significantly elevated levels of uCTx (220.632.3 vs 129.210.3, p=0.044), and more severe energy status disturbances, including lower TT3 (76.34.6 vs 98.69.4 ng/dL, p=0.041), higher ghrelin (2195.2281.1 vs 1371.673.7 pmol/L, p=0.030) levels, and a lower ratio of actual to predicted REE (0.800.01 vs 0.870.01, p=0.005). Conclusion: Energy deficiency, in the presence of mildly suppressed EIG levels, is associated with suppressed bone formation, but when E1G is more severely suppressed, increased osteoclastic activity, i.e., increased bone resorption, is apparent.

P719SU. THE PREDICTIVE ROLE OF BIOCHEMICAL MARKERS IN BONE MINERAL DENSITY CHANGES IN MEN Donescu OS, Battie MC, Videman T; University Alberta, Edmonton, AB, Canada Aims: The use of biochemical markers as indicators of overall bone metabolism has been suggested as a potentially valuable clinical method in osteoporosis screening, diagnosis and monitoring the eﬀects of diﬀerent interventions, as they reflect small changes in bone turnover in a short timeframe. The aims of this study were to determine whether bone formation (PINP and PICP), and bone

resorption (ICTP) markers are predictive of changes in BMD over a 5-year period, and also the ability of bone resorption marker NTx to explain the variance in BMD change over the prior 5 years. Methods: Both prospective and retrospective cohort study designs were used. Subjects were selected from the population-based Finnish Twin Cohort. The sample was composed of 203 monozygotic male twins 35–69 years old (mean 49.7, SD 8.4). PINP, PICP and ICTP markers were determined from serum by radioimmunoassay (Orion Diagnostica, Finland); NTx was measured in urine using an ELISA resorption assay (Osteomarkt; Ostex International) (CV<10.0%). BMD was measured with DXA (Lunar DPX, Madison, WI), at the L1-L4 vertebrae (CV 0.9%) and femoral neck (CV 1.5%). Data analysis. Pearson coeﬃcients assessed the correlation between change in BMD and baseline marker values in the whole group, and in the group of subjects older than 60. The ability of markers to explain change in BMD, with age, fat free weight, height and baseline BMD as possible confounding factors was examined using multiple linear regression. Results: Among the markers analyzed in the whole group, only NTx correlated with change in femoral neck BMD(r= -0.21, p= 0.006) and explained 3.8% of the variance. In the group of subjects older than 60 years (n=14), NTx and PICP significantly correlated with change in spine BMD(r= 0.6 and 0.5, p<0.05). Conclusions: Among markers, only NTx explained a statistically significant, yet quite limited portion of the variance in change BMD in the whole group of men 35 to 69 years old, and only at the femoral neck. The correlations of NTx and PICP with the change in spine BMD were notably higher in the group of subjects older than 60 than in the whole group.

P720MO. THE BENEFICIAL EFFECT OF VITAMIN D SUPPLEMENTATION ON OPG/RANKL/RANK PATHWAY IN POSTMENOPAUSAL WOMEN Krivosikova Z, Spustova V, Stefikova K, Dzurik R; Department of Clinical and Experimental Medicine, Slovak Medical University, Bratislava, Slovak Republic Background: Receptor activator of nuclear factor B ligand (RANKL) is a critical cytokine for osteoclast diﬀerentiation and activation and an essential regulator of osteoblast-osteoclast crosstalks. RANKL activates its receptor RANK, which is located on osteoclastic lineage cells. This interaction is prevented by osteoprotegerin (OPG), which acts as an decoy receptor and blocks the RANKL eﬀects. Thus, RANKL binding to RANK promotes osteoporosis by enhancing of bone resorption and OPG has opposite eﬀect. The process of coordinated resorption and formation of bone may be regulated by systemic hormones, cytokines and growth factors. Aim: To evaluate the influence of mild dose of vitamin D on OPG and RANKL, and possible relationships between them and other biochemical parameters. Methods: 88 postmenopausal women were enrolled in the clinical study. Patients received calcium supplement (500 mg/d) and vitamin D (20 000 IU/week) for six months. Serum OPG, RANKL, iPTH, osteocalcin (OC), -CrossLaps (CTx), alkaline phosphatase (ALP), bone specific ALP (BALP), serum and urinary Ca, Mg and P were measured at the beginning and end of the study. Results: The 67 subjects of 88 were suﬀering from osteopenia/ osteoporosis. The average values of biochemical assays, CTx, OC and OPG were in reference range at the beginning, as well as at the end of the study. At month 0, mean serum 25(OH)D3 was in the range of vitamin D insuﬃciency (27.6 ng/ml) and iPTH was on the upper limit of normal range (64.9 ng/ml). At month 6, 25(OH)D3 was markedly increased (47.9 ng/ml; p<0.001) and iPTH was decreased (56.8 ng/ml; p<0.02). ALP and BALP were significantly higher after six months therapy, although still in normal range. RANKL was significantly decreased (p<0.05). Pearson’s correlation coeﬃcients were significant for deltaRANKL vs. delta25(OH)D3 (0.488, p<0.05) and for deltaALP vs. delta25(OH)D3 (-0.547, p<0.01). Conclusion: Administration of mild dose of vitamin D suppresses osteoclastogenesis by decreasing serum RANKL production, along with osteoblast function stimulation via changes in

S337 BALP and ALP. Thus, vitamin D is significantly involved in the OPG/RANKL/RANK pathway and eﬀectively participates in osteopenia/osteoporosis treatment. This work was supported by STAA under the contract No. APVT–21–033002.

P721SA. BONE RESORPTION IS INCREASED IN PREMENOPAUSAL EXERCISING WOMEN WITH OSTEOPENIA Scheid JL1, Williams NI2, West SL1, Burke TG1, De Souza MJ1; 1 Women’s Exercise and Bone Health Laboratory, Dept of Exercise Sciences, University of Toronto, Toronto, ON, Canada, 2Dept of Kinesiology, Penn State University, University Park, PA, USA Aim: Premenopausal bone loss in amenorrheic exercising women has typically been attributed to a suppressed bone formation. The aim of this study was to assess bone resorption in premenopausal exercising women in whom bone mineral density is normal compared to exercising women with bone mineral density (BMD) consistent with osteopenia. Methods: For this prospective, observational study, subjects were divided according to lumbar spine (L1-L4) Z-scores into one of two groups: (1) osteopenia group (n=10), or (2) normal BMD group (n=32). Menstrual status was assessed by daily urinary ovarian steroid measurements for 2–3 menstrual cycles, or 30-day monitoring periods if oligo/amenorrheic. Serum was analysed for P1NP and osteocalcin, and 24 urine samples for CTX. Results: The Osteopenic group and the normal BMD group were similar (p>0.05) in age (24.11.1 yr), height (164.71.1 cm), weight (57.31.9 kg), and BMI (21.10.7 kg/m2). As expected, Z-scores were significantly diﬀerent in the osteopenic group compared to the normal BMD group at the total body (-0.251.5 vs. 1.080.13, p<0.001), L1-L4 (-1.330.07 vs. 0.630.20, p<0.001), L2-L4 (-1.280.07 vs. 0.680.19, p<0.001), and total hip (-0.342.0 vs. 0.880.14, p<0.001). Women who were amenorrheic or oligomenorrheic exhibited osteopenia more often in comparison to ovulatory and luteal phase deficit/anovulatory women (p=0.046). Specifically, 90% of the osteopenic group (9/10) were found to exhibit some form of an exercise associated menstrual disturbance (EAMD). Eight-two percent of the subjects in the lowest BMD quartile (9/11 women) were found to exhibit the lowest EIG area under the curve (AUC) levels. P1NP (134.217.4 and 120.58.2 µg/L, p>0.05) and osteocalcin (8.71.2 and 8.00.8 ng, p>0.05) were not significantly diﬀerent between the osteopenic group and normal BMD group, while uCTX was higher in the osteopenic group compared to the normal BMD group (271.222.0 vs 203.913.8 µg mmol/Cr, p=0.030), in concert with lower (p<0.042) E1G AUC levels. Conclusions: Bone resorption in exercising women with osteopenia was higher when compared to exercising women with normal BMD. This study demonstrates a link between EAMD characterized by decreased ovarian steroid production and increased bone resorption. The lower BMD observed with compromised menstrual status is potentially associated with increased bone resorption.

P722SU. SUB-OPTIMAL VITAMIN D STATUS IN CHILDREN AND YOUTH WITH DISEASES ASSOCIATED WITH LOW BONE MASS Atkinson SA, Docherty-Skippen S, Wang D, Grey V, Barr R, Ronen G, Odame I; Dept. Pediatrics, McMaster University, Hamilton, Canada Aims: 1) To determine the vitamin D status of children and youth with various clinical disorders living in southern Ontario (latitude w 43(N) in relation to the recent recommendations (Whiting and Calvo 2005) for cut-oﬀ values for plasma 25-hydroxyvitamin D (25OHD) to define deficiency (<30 nmol/L), insuﬃciency (30–80 nmol/L) and suﬃciency (>80 nmol/L) for vitamin D status. 2) To determine if diﬀerences in vitamin D status exist in children and youth (age = 2–18 yr) diagnosed with epilepsy treated with valproate and/or lamotrigine (E n=52) pediatric, cystic fibrosis (CF n=48), acute lymphoblastic leukemia (ALL n=10), brain tumour (BT n=10), or survivors of treatment for malignant lymphoma

(ML n=19) or Wilm’s tumour (WT n=23), compared to healthy children at pre-pubertal age (N n=26). Methods: Serum obtained as part of protocols to study bone and mineral metabolism within each disease group was assayed for 25OHD after acetonitrile extraction by RIA (Diasorin) or Nichols Advantage (for CF only) and PTH by IRMA (Nichols). Results: Mean serum 25OHD was not diﬀerent between winter (Nov-Mar) and summer (Apr-Oct) samples within disease groups but was lower in winter for all groups combined (5745 vs. 7733 nmol/L, p<0.03). The figure presents individual subject and meanSD values within disease groups, with horizontal lines indicating lower cut-oﬀ values for deficiency and insuﬃciency. Insuﬃcient status occurred in 12% of E, 71% of CF, 90% of ALL, 30% of BT, 37% of ML, 48% of WT. 25OHD status was inversely but weakly correlated with serum PTH (R = - 0.2, p = 0.005). Conclusion: Vitamin D deficiency or insuﬃciency occurs frequently in some pediatric diseases and may be a factor in the low bone mass observed in these populations. The determinants of low vitamin D status and associated health risks for those in the insuﬃcient category require further investigation.

25OHD status in pediatric diseases in relation to proposed deficient, insuﬃcient and optimal ranges

P723MO. MILK SUPPLEMENTATION DECREASES BONE TURNOVER IN DANISH PRE-PUBERTAL BOYS Budek AB, Hoppe C, Michaelsen KF, Mølgaard C; Department of Human Nutrition and Centre for Advanced Food Studies at The Royal Veterinary and Agricultural University, Frederiksberg, Denmark The risk of osteoporosis later in life can be reduced by achieving high bone mass during growth. Milk supplementation was reported to increase bone mineral density when compared with habitual diet. It is unclear whether this eﬀect is due to a higher protein intake by milk supplemented groups or due to other active compounds derived from milk (e.g. calcium). Furthermore, increased bone mineral density has been associated with reduced bone turnover. Our aim was to compare the eﬀect of proteinbalanced milk and meat supplementation on bone turnover in pre-pubertal boys. Twelve 8-year-old healthy Danish boys were assigned to consume 1.5 L of skimmed milk and twelve to consume 250 g of low fat meat daily. The 7-day intervention was designed to supplement participants’ habitual diet with 53 g of protein per day. Daily intake of energy, macronutrients and selected micronutrients was calculated from 3-day weighted food record. Fasting serum was collected at baseline and after 7 days. Bone formation was measured by s-osteocalcin (OC) and s-bone-specific alkaline phosphatase (BAP). Bone resorption was measured by s-C-terminal telopeptides of type I collagen (CTX). We applied general linear model including baseline confounders for computation. There was no significant diﬀerence in baseline s-OC (p=0.9), s-BAP (p=0.9) and s-CTX (p=0.3) between the groups. Apart form energy percentage from carbohydrates (p=0.007) and fat (p=0.02), habitual dietary intake did not diﬀer significantly between the groups (all p>0.2). During intervention, protein intake increased in both groups by 56–58% (p=0.4). Only the milk group had increased total energy and selected micronutrients intake compared with baseline (all p<0.005). After the intervention, s-OC was reduced (p=0.001) in milk group compared with meat group (35.27

S338 ng/ml 9.4 SD vs. 54.54 ng/ml 17.1 SD, respectively) and s-CTX was reduced (p=0.037) in milk group compared with meat group (1.78 ng/ml0.4 SD vs. 1.97 ng/ml 0.3 SD, respectively). There was no significant change in s-BAP between the groups (p=0.06). In conclusion, high milk intake in contrast to high meat intake decreases bone turnover in pre-pubertal boys already after seven days. Long term eﬀect of presented treatment on bone turnover should be studied next.

P724SA. EVALUATION OF 41CALCIUM AS A NEW APPROACH TO ASSESS CHANGES IN BONE METABOLISM: EFFECT OF A BISPHOSPHONATE INTERVENTION IN OSTEOPENIC, POSTMENOPAUSAL WOMEN Denk E1, Hillegonds D2, Hurrell RF1, Vogel J2, Fattinger K3, Häuselmann HJ4, Kränzlin M5, Walczyk T1; 1Laboratory for Human Nutrition, ETH-Zurich, Zurich, Switzerland, 2Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA, USA, 3Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Zurich, Switzerland, 4Center of Rheumatology and Bone Diseases, Klinik im Park, Zurich, Switzerland, 5Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, University Hospital Basel, Switzerland Isotopic labeling of bone using Ca-41, a long living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome limitations in precision and sensitivity of currently available techniques. Once isotopic labeling of the skeleton is achieved, changes in urinary Ca-41 excretion reflect changes in bone Ca balance. The aim of this study was to compare findings made by the Ca-41 technique with observed changes in bone mineral density (BMD) and biochemical markers of bone metabolism. Changes in bone Ca balance were induced by giving a bisphosphonate (risedronate). Six postmenopausal women with diagnosed osteopenia received a single oral dose of 100 nCi Ca-41 for skeleton labeling. Urinary Ca-41/Ca-40 isotope ratios were monitored by accelerator mass spectrometry up to 700 days following the labeling process. Subjects then received 35 mg risedronate per week for six months. A positive response to the treatment was observed by BMD measurements which increased for spine by +2.5% (P=0.01) but not in the hip. In parallel, the intervention reduced bone formation markers by -36% for BALP (bone alkaline phosphatase) (P=0.002) and by -58.9% for PINP (Procollagen type I propeptides) (P=0.001). Urinary DPD (deoxypyridinoline) and PYD (pyridinoline) were reduced by -21.1% (P=0.019) and -22.9% (P=0.009) respectively while serum und urinary CTX (carboxy-terminal teleopeptide) were reduced by -59.8% (P=0.001) and -57.0% (P=0.001), respectively. The urinary Ca-41 signal parallelled these findings for conventional techniques. A linear three-compartment model of population pharmacokinetic analysis (NONMEM) of the Ca-41 data indicated that Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment was reduced by 56% (P<0.001) by bisphosphonate treatment. The new technique is ideally suited to evaluate the impact of pharmacological and nutritional interventions or lifestyle on bone. Financial support: European Union/Swiss Ministry of Science Education (OSTEODIET QLK1–1999–00752) and LLNL (LDRD 04-ERI-009).

P725SU. LABELING OF THE HUMAN SKELETON WITH 41CALCIUM ISOTOPE FOR THE ASSESSMENT OF CHANGES IN BONE CALCIUM METABOLISM Denk E1, Hillegonds D2, Vogel J2, Synal HA3, Geppert C4, Wendt K4, Fattinger K5, Hennessy C6, Berglund M6, Hurrell RF1, Walczyk T1; 1Human Nutrition Laboratory, Institute of Food Science and Nutrition, ETH-Zurich, Zurich, Switzerland, 2Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA, USA, 3Laboratory of Particle Physics, Paul Scherrer Institute/ETH-Zurich, Zurich, Switzerland, 4Institute of Physics, Johannes Gutenberg University, Mainz,

Germany, 5Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Zurich, Switzerland, 6 European Commission Joint Research Centre, Institute for Reference Materials and Measurements (IRMM), Geel, Belgium Bone research is limited by available methods to detect changes in bone metabolism. While dual x-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intraindividual variation. Within the presented study, we evaluated isotopic labeling of bone using Ca-41, a long living radiotracer, as an alternative approach to study bone Ca metabolism. After successful labeling of the skeleton, changes in the systematics of urinary Ca-41 excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of Ca-41 (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary Ca-41/Ca-40 isotope ratios up to 700 days post dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Ca-41 data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model for describing urinary Ca-41 tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to fit the Ca-41 data best. By introducing the intervention as an additional variable into the model and identifying relative changes in transfer rates between compartments, inaccuracies in the underlying model cancel out for the labeling and the intervention period. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While bone formation and resorption can be assessed, in principle, by monitoring urinary Ca-41 excretion over the first weeks post dosing, a more reliable assessment of an intervention eﬀect is possible after ca. 150 days post dosing when excreted tracer mainly originates from bone. The Ca-41 bone labeling technique can be considered as a new tool to compare the impact of intervention strategies on bone health within the individual and to better understand their mechanisms of action on bone. Financial support: European Union/Swiss Ministry of Science Education (OSTEODIET QLK1–1999–00752) and LLNL (LDRD 04-ERI-009).

P726MO. FRUIT AND VEGETABLE INTAKE AND BONE TURNOVER IN POSTMENOPAUSAL OSTEOPENIC WOMEN Ebrahimof S1, Haghighian Roudsari A1, Hossein-nezhad A2, Larijani B2, Kimiagar SM1; 1School o f Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences and Health Services, 2Endocrinology and Metabolism Research Center, Shariati Hospital, Tehran, Iran Introduction: Nutritional factors have great impact on bone health and metabolism. Reducing bone turnover through appropriate nutritional strategies can be eﬀective in decreasing bone fracture risk in postmenopausal women. Although individual eﬀects of some nutrients on bone have been studied, combining eﬀects of some nutrients abundant in fruits and vegetables are not well known. Method: The present cross-sectional study was carried out on 51 postmenopausal women aged 50–60 years. Bone mineral density was measured by dual-energy X-ray absorptiometry at lumbar spine and total hip. All women were osteopenic according to WHO citeria. Intake of food groups was assessed by 2 days 24 hour recall; other lifestyle factors were assessed by additional questions. Bone resorption was calculated by measuring carboxy-terminal telopeptide of type I collagen (crosslaps) and bone formation by measuring serum osteocalcin. Results: No significant correlation was found for current intake of food groups and bone mineral density at either lumbar spine or total hip. Fruit and vegetable intake was significantly negatively correlated with osteocalcin level (r = -0.4, p%0.001). Serum osteocalcin level in those who consumed more than 400 g of fruit and vegetable daily was significantly lower than the others (186.5 ng/l compared with 3013.7 ng/l, p%0.05). In a regression analysis with age, body mass index, duration of menopause

S339 and intake of food groups entered into the model, duration of menopause and fruit and vegetable intake accounted for 30% variation in serum osteocalcin level. Conclusion: Increasing fruit and vegetable intake upto WHO recommendations for prevention of many chronic diseases can be also eﬀective in prevention of osteoporosis and reducing fracture risk in postmenopausal osteopenic women. Intake of at least 400 g of fruits and vegetables can complement what is currently recommended for osteoporosis prevention.

P727SA. ROLES OF BETA2-MICROGLOBULIN IN POSTMENOPAUSAL BONE REMODELLING Mesci E1, Hocaoglu S2, Hizmetli S3, Nacitarhan V3, Elden H3; 1 Haseki Education and Research Hospital, Istanbul, Turkey, 2 Sultan I. Izzettin Keykavus Hospital, Sivas, Turkey, 3Cumhuriyet University, Sivas, Turkey Aims: Beta-2microglobulin(2m) is a small polypeptide with demonstrated dual eﬀects on both bone formation and resorption. The objective of this study is to evaluate long-term changes observed in serum 2m levels during treatment parallel to interactions with bone remodeling process in postmenopausal osteoporotic patients administered antiresorptive molecules. Methods: This is a prospectively designed, randomized and controlled study in which 90 postmenopausal patients with osteoporosis and 30 premenopausal normal women were enrolled to compare their serum 2m values. Osteoporotic patients had not received previous treatment with any antiresorptive or calcitropic drugs. Lumbar and femoral bone mineral density (BMD), serum calcium (Ca), phosphate, alkaline phosphatase (ALP), osteocalcin (OC), 2m and urine calcium measurements were obtained from all cases. Postmenopausal osteoporotic patients were randomized into three treatment groups for 6-months of follow-up. 1) group was scheduled to receive 100 IU nasal salmon calcitonin + Ca and Vitamin D (Vit-D); 2) group to receive cyclic treatment with 400 mg etidronate for 14 days and again Ca and Vit-D; and 3) group (control group) to receive only Ca and Vit-D. During treatment course serum 2m, OC, ALP and 24-hour urine calcium levels were measured at Months 3 and 6. Results: Serum 2m levels of osteoporotic women were found to be higher compared to healthy women (p<0.001). Serum 2m levels of patients who received calcitonin and etidronate as treatment significantly increased at Month 3 (p<0.001) but decreased at Month 6 (p<0.001) and returned almost to pretreatment levels. However, in the control group serum 2m levels increased progressively and at the end of 6 months it was considerably higher compared to pretreatment levels (p=0.006). During 6-month therapy, significant decreases in serum osteocalcin, alkaline phosphatase and 24-hour urine calcium levels and significant increases in lumbar and femoral BMD levels were observed in groups treated with calcitonin and etidronate. Conclusions: In the light of these results, it was considered that 2m synthesis was sensitive to changes in bone metabolism and it might have a role in regulation of metabolism due to its opposite eﬀects on bone and its serum levels were limited when metabolism was in balance.

P728SU. CIRCULATING OSTEOPROTEGERIN AND RECEPTOR ACTIVATOR OF NF-KB LIGAND SYSTEM IN EUGONADAL FEMALE PATIENTS WITH BETATHALASSAEMIA MAJOR Angelopoulos NG, Goula A, Rombopoulos G, Kaltzidou V, Katounda E, Livadas S, Tolis G; Endocrine Department, Hippocratio Hospital, Athens, Greece Aim:The etiology of osteoporosis in patients with -thalassaemia major is multifactorial, and culminates in a state of increased bone turnover with excessive bone resorption and remodeling. It has been recently reported that two new cytokines, osteoprotegerin (OPG) and receptor activator of NF-B ligand (RANKL), have been implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to characterize the possible role of the OPG/RANKL system in -thalassaemia-related bone loss.

Serum concentrations of OPG, soluble RANKL (sRANKL), markers of bone turnover and bone mineral density (BMD) were measured in 16 eugonadal young females with -thalassaemia major and 18 age- and sex-matched healthy controls. Results: Bone turnover was significantly increased in thalassaemic patients compared to controls but OPG was significantly higher in healthy subjects. Regarding markers of bone metabolism, there was a negative correlation between age and plasma values of osteocalcin. BMD values negatively correlated with urine NTX (r =-0⋅872; P < 0⋅001) and D-PYR (r =-0⋅608; P < 0⋅05). Concerning the correlations for the OPG/sRANKL system, OPG/log (sRANKL) correlated negatively with plasma values of osteocalcin in thalassaemic patients. Conclusion: Our data suggest that although the circulating OPG/sRANKL system may play a role in bone metabolism of females with -thalassaemia, conventional markers of bone turnover more accurately represent changes in the bone mineral density of these patients.

P729MO. THE ROLE OF CIRCULATING OSTEOPROTEGERIN AND RECEPTOR ACTIVATOR OF NUCLEAR FACTOR LIGAND (SRANKL) IN PRIMARY BONE MINERALIZATION DISORDERS IN CHILDREN Chlebna-Sokol D, Lewinski A, Rusinska A, Michalus I, Zygmunt A; Department of Paediatric Propedeutics and Bone Metabolic Diseases Medical University, Lodz, Poland, Department of Endocrinology and Metabolic Diseases Medical University, Lodz, Poland The aim of the study was to determine osteoprotegerin contribution to the etiopathogenesis of primary bone mineralization disorders in children. Patients and methods: The study comprised of 80 patients, 5–18 years of age. In this group there were 50 children with idiopathic decrease in bone mineral density (18 with osteoporosis and 32 with osteopenia) and 30 with normal bone mass, recognized as healthy controls. Bone mineral density was assessed on the basis of dual-energy X-ray absorptiometry. Osteoporosis was diagnosed when coincidentally with other clinical symptoms of bone disease Z-score index for bone mineral density was below -2.0, and osteopenia for Z-score between -1.0 and -2.0. In all children osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa B ligand (sRANKL) concentrations in serum were assessed by means of enzyme-linked immunosorbent assay (ELISA). Osteoprotegerin/ sRANKL ratio was also determined. The obtained results were compared with values of bone mineral density, concentration of calcitropic hormones and markers of bone turnover. Results: A statistically significant diﬀerence was found between groups in relation to osteoprotegerin/sRANKL ratio; the mean value in children with osteoporosis was 9.4, in patients with osteopenia 21.6, and in controls 14.2 (p<0.05), whereas in relation to OPG and sRANKL concentrations we did not find such diﬀerences between groups. In children with low bone mass we revealed a positive correlation between OPG and OPG/sRANKL ratio, and mineral density (AP Spine Z-score). Moreover, in this group of patients a significant correlation between OPG, sRANKL, calcitropic hormones and markers of bone turnover was observed. Conclusions: Studies we performed point out that osteoprotegerin is a key factor aﬀecting idiopathic mineral disorders of skeleton in children. Acknowledgements: The study was supported by the State Committee for Scientific Research (Grant no. 3P05E 05624).

P730SA. EVALUATION OF WEEKLY RISEDRONATE TREATMENT IN POSTMENOPAUSAL WOMEN WITH OSTEOPROTEGERIN Karadag-Saygi E1, Bizargity P1, Ay P1, Saygi B2, Akyuz G1; 1 Marmara University, 2TCSB Hospital, Istanbul, Turkey Risedronate has been used in the treatment of postmenopausal osteoporosis with success in the recent years. Osteoprotegerin (OPG) is a glycoprotein which inhibits both osteoclast activation

S340 and diﬀerentiation. The aims of our study were twofold: 1) to show whether risedronate treatment eﬀects OPG, C-terminal crosslinking telopeptide of type 1 collagen (CTX), osteocalcin, deoxypyridinoline levels and 2) to establish the correlation of OPG levels with other markers. This was a randomized, prospective study with 80 osteoporotic patients randomized into two groups. In the first group, 37 patients received 35 mg risedronate once a week and 600 mg elementary calcium with 400 IU vitamin D per day; the second group, 34 patients received only 600 mg elementary calcium with 400 IU vitamin D per day. OPG, osteocalcin, CTX and deoxypyridinoline levels were measured at baseline, 1st, 3rd and 6th months. Mean OPG levels at the baseline were 9.93.8 pmol/l for treatment group and 11.66.5 pmol/l for control group. Percentage change of OPG scores showed a significant diﬀerence at 1st, 3rd and 6th months in the treatment group (p<0.01) but not in the control group (p>0.05). Diﬀerence in CTX and osteocalcin levels was observed in the 3rd month in contrast to deoxypyridinoline which appeared at 6th month post-treatment. The baseline OPG levels correlated with age, time of menapause and CTX levels. There was no correlation between OPG levels and any of the other markers. As a result, decrease in the levels of CTX, osteocalcin and deoxypyridinoline in the first month of treatment risedronate once weekly use indicated early onset risedronate eﬃcacy in osteoporosis treatment. As OPG expressed a decrease according to control group during treatment, it can be used as a bone marker in new future.

P731SU. CHANGES IN THE SERUM OSTEOPROTEGERIN LEVEL IN ELDERLY FEMALE PATIENTS AFTER FEMORAL NECK FRACTURES Sebestyen A1, Borsiczky B2, Fodor B3, Boncz I4,5, Jeges S6, Ghodratollah N7, Naumov I3, Nyarady J3, Vermes C8; 1County Baranya Health Insurance Fund, Pécs, Hungary, 2Department of Surgical Research and Techniqus, University of Pecs, Hungary, 3 Department of Traumatology and Hand Surgery, University of Pecs, Hungary, 4Department of Health Policy, National Health Insurance Fund Administration (OEP), Budapest, Hungary, 5Institute of Diagnostics and Management, University of Pecs, Hungary, 6Institute of Bioanalysis, University of Pecs, Hungary, 7 Institute of Public Health and Preventive Medicine, University of Pecs, Hungary, 8Department of Orthopeaedix Surgery, University of Pecs, Hungary Aim: We have systematically searched for mediators reflecting the changes of bone metabolism in female patients undergoing osteosynthesis following femoral neck fracture. The aim of the study was to monitor the serum osteoprotegerin (OPG) level pre- and postoperatively in a prospective manner in order to distinguish the diﬀerent types of fractures and also to determine the activiy of bone remodelling following osteosynthesis. Data and Methods: Serum was collected from 24 patients (mean age: 77.678.21 years) with femoral neck fracture. Following admission, patients received appropriate surgical treatment according to the AO principles. Serum OPG levels were determined at certain time points (preoperatively and postoperatively on the 1st, 4th, 7th days and on the 6th, 12th weeks) by enzyme-linked immunosorbent assay (ELISA) kits. Results: The serum OPG level showed significant negative correlation (Pearson’s corr.=-0.430, P=0.036 (2-tailed)) with the time between the injury and the index operation (4–336 hours). The OPG level significantly (t=2.681; P=0.013) increased on the 1st postoperative day comparing to the preoperative level. This was substantially greater when the operation was performed within 24 hours after the injury. The OPG level started decreasing on the 4th postoperative day and became significantly suppressed at 12 weeks (t=2.438; P=0.025) compared to the preoperative level. Conclusions: The activity of local bone metabolism following femoral neck fracture in females can determine the eﬀectiveness of a surgical method. The more active the remodellation the greater the chance of the successful fracture healing. This is supported by this study where we found significantly higher levels of OPG within the first 24 hours in which time period osteosynthesis can be performed safely. The biochemical support to the regular clinical

and x-ray examination can be a useful tool in the assessment of the fracture healing process following osteosynthesis. In the future, one can envision a diagnostic system where biochemical markers can determine the development of non-unions following various types of osteosyntheses.

P732MO. SERUM LEVELS OF RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KB LIGAND (RANKL) IN HEALTHY WOMEN AND MEN Kerschan-Schindl K1, Wendlova J2, Kudlacek S3, Gleiss A4, Woloszcuk W5, Pietschmann P6,7; 1Department of Physical Medicine and Rehabilitation, Medical University of Vienna, Vienna, Austria, 2Division of Osteological Surgery, Derer’s University Hospital and Polyclinic, Bratislava, Slovakia, 3Department of Internal Medicine, Krankenhaus der Barmherzigen Brüder, Vienna, Austria, 4Section of Clinical Biometrics, Core Unit for Medical Statistics and Informatics, Vienna, Austria, 5Ludwig Boltzmann Institute of Experimental Endocrinology, Vienna, Austria, 6Department of Pathophysiology, Medical University of Vienna, Vienna, Austria, 7Ludwig Boltzmann Institute of Aging Research, Vienna, Austria Background: The receptor activator of nuclear factor kB ligand (RANKL) is an important regulator of bone metabolism. The aim of this investigation was to evaluate potential age- and genderrelated changes in free RANKL and total RANKL and to determine correlations, if any, between these parameters and bone mineral density (BMD). Methods: Two hundred and forty-five volunteers with a median age of 48 years were included in the study. Serum levels of free RANKL and total RANKL were evaluated. BMD of the spine and the right hip were measured. Results: On average, men had a 1.53-fold higher free RANKL level and a 2.17-fold higher free/total RANKL ratio than women after correction for potential age diﬀerences. On the other hand, one subject compared to another who is five years younger had a free RANKL level that is only 0.89 times and a total RANKL level that is only 0.91 times as high on average. In women, there was a minor significant negative correlation between total RANKL and the Z-score of the spinal BMD as well as the Z-score of the hip BMD. The correlation between the free/total RANKL ratio and the Z-score of the spinal BMD was positive. In men, a minor positive correlation existed between total RANKL and the Z-score of the spinal BMD. Conclusion: This study showed that serum levels of free RANKL and total RANKL decrease with age, and also revealed some gender-related diﬀerences.

P733SA. BONE REMODELING CHANGES AND VITAMIN D STATUS IN CHRONIC RENAL FAILURE PATIENTS WITH SECONDARY HYPERPARATHYROIDISM AFTER PARATHYROIDECTOMY Peters BSE1, Sarkis KS1, Moyses RMA2, Martini LA1; 1Sao Paulo University,Health Public School, Nutrition Depatment, Sao Paulo, Brasil, 2Sao Paulo University, Medicine School, Nephrology Division, Sao Paulo, Brasil Chronic renal failure (CRF) is often associated with bone disorders including secondary hyperparathyroidism (SHPT). This study was carried out in order to evaluate changes in bone remodeling after parathyroidectomy (PTX). Twelve adult patients, mean age 43.4 12.7 years old, both gender, were evaluated, before and 6 months after PTX. Biochemical markers of bone metabolism, such as total and ionized calcium, phosphorus, 25(OH)D3, total alkaline phosphatase (TAP), bone specific alkaline phosphatase (BAP), intact parathyroid hormone (iPTH), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase isoform 5b (TRAcP) were performed. No changes were observed in the serum total and ionized calcium, TAP and BAP after PTX. After surgery there was a significant decrease in the serum phosphorus, iPTH, and TRAcP (6.7 1.8 mg/dl to 4.5 1.5 mg/dl, 1221.6 685.1 pg/ml to 153.1 189.2 pg/ml, 9.07 6.17 U/l to 2.7 5.14 U/l, respectively; p<0.001). No significant changes were observed in the 25(OH)D3. However, the prevalence of the hypovitaminosis D (20–40 ng/ml)

S341 and vitamin D insuﬃciency (10–20 ng/ml) decrease from 50% and 30% to 16.7% and 25%, respectively. The patients with suggested ‘‘optimal’’ concentration of 25(OH)D3 (>40 ng/ml) increased from 20% to 58% after PTX. No significant change was observed in OPG, however there was a positive correlation between OPG and 25(OH)D3 before and after surgery (r=0.774, p=0.014; and r=0.706, p=0.01, respectively), also a negative correlation between OPG and TAP was observed after PTX (r=-0.63; p=0,028). The present study indicates that after 6 months after PTX the osteoclastic activity decreasens and the OPG remain elevated, suggesting a high index of bone formation. Furthermore, high iPTH seems to contribute to higher prevalence of the hypovitaminosis D and vitamin D insuﬃciency.

P734SU. CONCURRENT OCCURRENCE OF PAGET’S DISEASE OF BONE AND HYPERPARATHYROIDISM Leens C, Devogelaer JP; Rheumatology Unit, St-Luc University Hospital, Brussels, Belgium Simultaneous occurrence of Paget’s disease (PD) and hyperparathyroidism (HPT) has been observed relatively frequently. An elevation of iPTH has been documented in around 18 % of cases. At least thirty-three cases of Paget’s disease complicated by adenomata and 5 cases with hyperplasia of the PTH glands have been reported. We have looked in our files what was the frequency of both conditions occurring simultaneously in our hospital. 256 cases of PD were reviewed. Measurements of iPTH (at least at once) was retrieved in 26.5 % of cases (n = 68). An elevated iPTH was observed in 37.9 %, and a simultaneous elevation of iPTH and sCa in 10.7 %. In 19 %, 25OHVitamin D was low, out oﬀ whom 56.5 % had concurrent elevated iPTH. In 15 %, 25OHVitamin D was normal (i.e. superior to 20 ng/ml), but still 43.5 % of these patients had elevated iPTH. Elevated iPTH was not seen more frequently in resistant PD than in good responders. There was a trend to have increased iPTH, more elevated the number of courses of therapy with antipagetic drugs. The eﬀect of age and age-related creatinine increase was the main explanation for that, however. What is the nature of the association PD and PHPT ? It could be fortuitously coincidental. However, the prevalence of HPT in PD is significantly increased as compared to the general population. Some cases could be explained by hypovitaminosis D which could lead to secondary HPT. A stress on extracellular fluid calcium of variable duration and degree when lytic lesions become denser might be capable to induce secondary HPT. Repetitive episodes of hypocalcemia provoked by several courses of antiresorptive drugs could also provoke secondary hypersecretion of the parathyroid glands, potentially leading to their hypertrophy.

athyroidism, and hyperparathyroidism patients, as well as patients with renal disease. The resulting regression equations are LIAISON = 0.91(Advantage) + 2.1 pg/mL (r = 0.97), and LIAISON = 1.02 (Immulite 2000) + 8.5 pg/mL (r = 0.97). The results demonstrate good correlation overall between the LIAISONt N-Tact PTH assay and the other intact PTH immunoassays.

P736SA. EFFECT OF CALCIUM, VITAMIN D IN POSTMENOPAUSAL WOMEN ON TREATMENT WITH RALOXIFENE Harinarayan CV1, Prasad UV1, Srinivasa rao PVLN2, Mohan D1, Kumar EGTV1; 1Department of Endocrinology and Metabolism, 2 Department of Biochemistry, Sri Venkateswara Institute of Medial Sciences,Tirupati, India Aim: To study the response of calcium, vitamin D and raloxifene on bone mineral parameters in postmenopausal women. Materials and methods: One hundred and twenty-three postmenopausal women were evaluated for their daily dietary calcium and biochemical parameters [serum calcium, phosphorous, alkaline phosphatase(SAP), 24 urinary calcium, phosphorous and calcium/creatinine ratio (Ca/cr) and phosphate excretion index (PEI)], 25(OH)D, and intact PTH (PTH) before and one year after therapy (per day 1000 mg of elemental calcium, 400 IU of 25(OH)D, and Raloxifene 60 mg). Results: The mean age was 51+7.5 yrs age (11 yrs after of menopause). The dietary calcium intake was 32455 mg/day. Twenty seven percent of patients had 25(OH)D deficiency, 46% had 25(OH)D insuﬃciency. In the 25(OH)D deficiency group, one year after therapy the 25(OH)D levels significantly improved (p<0.001), SAP decreased (p<0.01). PTH correlated positively with SAP before (r0.75; p<0.0001) and after therapy(r0.76; p<0.0001). Post-therapy urinary calcium correlated with urinary phosphorous(r 0.65; p<0.0001). In the 25(OH)D insuﬃciency group 25(OH)D levels and Ca/cr ratio increased, SAP and PEI decreased with therapy. Serum calcium correlated with PEI (r0.35; p<0.01). Conclusions: The dietary calcium intake was far lower than the recommended daily allowance of the country. Three fourths of postmenopausal women had varying degree of 25(OH)D deficiency. With therapy the 25(OH)D levels increased, SAP levels decreased. All post menopausal women should be treated with calcium supplement and vitamin D therapy. PMO_THERAPY_TABLE 25(OH)D-levels

Parameters

P735MO. COMPARISON OF LIAISONT N-TACTY PTH ASSAY WITH OTHER CLIA METHODS Podgorski AL, Vaught DL, Fenske JS, Brandt EM, Olson GT, Schmidt JA; DiaSorin Inc., Stillwater, MN, USA The maintenance of proper calcium concentrations in cells and extracellular fluids is essential for fundamental biological processes. Parathyroid hormone (PTH) is an important regulator of calcium homeostasis. The measurement of PTH is used in conjunction with calcium determinations to assess disorders in calcium metabolism. The accurate diagnosis of primary hyperparathyroidism (PHPT) has been facilitated by recent development of increasingly sensitive and specific assays for PTH. The DiaSorin LIAISONtN-Tact PTH assay oﬀers excellent sensitivity and precision on a fully automated, random access system using chemiluminescence detection. This study compares the performance of the LIAISONt N-Tact PTH assay with other commercial methods, including the Nichols Advantaget Intact PTH assay, the DPC Immulite 2000t Intact PTH assay, and others. In the first study, 226 samples were assayed using the LIAISONt N-Tact PTH assay and the Nichols Advantaget Intact PTH assay. An additional 89 samples were assayed using the LIAISONt N-Tact PTH assay and the DPC Immulite 2000t Intact PTH assay. The samples used in these studies include normal, hypopar-

PTH (pg/ml) 25(OH)D (ng/ml) S.Ca (mg/dl) S.Phos (mg/dl) SAP (IU/l) U.Ca (mg/day) U.Pho (mg/day) Ca/Cre PEI

<10ng/ml(n=33)27% 25(OH)D-deficiency

10.1–20ng/ml(n=57)46% 25(OH)D-insuﬃciency

>20ng/ml(n=33)27% Normal-25(OH)D

Basal

Review

Basal

Review

Basal

30.428

31.0620

26.2415.17

2512

23.4710.41 2410.41

82.03

1710***

15.323

24.111*** 26.446

29.0512.28

100.49

100.39

100.49

100.43

100.46

100.4

3.520.61

40.56

3.550.81

40.77**

3.460.61

3.560.79

8023.01*

7216

9639*

7522.11

92.2255.42 70.0824

196416.57 134.1277 13468.54

166.57108 14889.49

Review

171.48120

416395.44 426.02176 396.06195.52 352214.55 361140.27 366.37191 0.150.13 0.150.08 0.0010.12 0.010.07

0.160.08 0.0040.11*

0.20.12* 0.180.1 -0.030.07 -0.010.07

0.210.13 -0.0020.07

*p<0.05;**p<0.01;***p<0.001

P737SU. HIGH BONE REMODELLING ACCORDING TO VALUES OF C-TELOPEPTIDE IN PATIENTS WITH POSTMENOPAUSAL OSTEOPOROSIS Ramos J, Lopez D, Velasquez G, Riera-Espinoza G; Unilime UC, Hospital Universitario ’’Dr. Angel Larralde’’, Universidad de Carabobo, Valencia, Venezuela Ovarian suppression leads to an increase of markers of bone remodelling, this increase can be variable and stable for many

S342 years, in some cases during the whole life. High rates of bone turnover are associated with greater loss of bone mass and fractures. C-telopeptide is a collagen degradation product that reflects osteoclastic activity and is a specific marker of bone resorption. The objective of this study was to evaluate the values of C-telopeptide in postmenopausal osteoporotic women and compare them to healthy premenopausal women. C-telopeptide ( Cross-Laps) was determined by electrochemiluminescence inmmunoassay ‘‘ECLIA’’ in a Elecsys 1010, Roche Laboratory (intra assay VC 2.6%), in 105 patients who attended for the first time a consultation of osteoporosis at the Clinical Research Centre UNILIME UC, from January 2004 to January 2005. They had not received previous treatment for osteoporosis nor hormonal replacement therapy; in addition there were determined risk factors and bone mineral density at lumbar spine and femoral neck by DXA (Lunar DPX. VC 1.5%). The average age was 58.6910.84 years; mean age of menopause was 48.293.98 years. The most common risk factors for osteoporosis were: breast feeding: 88.6%; low dairy products consumption: 81%; sedentarism: 50.5% and smoking habit: 26.7%. The BMD values were: L1-L4 0.902 g/cm2, T-score -2.31, femoral neck 0.778 g/cm2, T-score -1.74. 16.2% of patients had previous fractures. The average value of C-telopeptide was 0.4210.22 ng/ml, percentile 10–90:0.160–0.792. 70.5% of the patients were over the premenopausal value (0.2810.134) and 45.7% over 1 SD of this premenopausal average. There was significant correlation between CTx and Tartrate Resistant Acid Phosphatase r:0.660 p<0.001. In conclusion, mean value of C-telopeptide ( Cross Laps) in postmenopausal women with low BMD was 0.4210.22 ng/ml. 70.5 % of them were over the premenopausal mean (0.281 ng/ml) obtained in healthy premenopausal Venezuelan women, with normal bone mineral density and 45.7% had values over 1 SD above this mean.

Introduction: One of the most common menopausal symptoms is bone mass loss resulting from sex hormone deficiency. Increased remodeling rate especially bone resorption leads to accelerated bone loss and bone fragility. ‘‘Isoflavones’’ present in plants especially soy have estrogen-like biological activity. These compounds may reduce bone resorption in postmenopausal women because of their structural similarity to estrogens. This study was carried out to assess the eﬀects of soy isoflavones on bone resorption markers in osteopenic postmenopausal women in Iran. Materials and Methods: In this ’’before and after clinical trial’’ on 15 women 45–64 years of age were selected. Subjects were given 35 g soy protein for 12 weeks. Blood and urine sampling, antropometric measurement and 48 h dietary recalls were carried out at the beginning of the study, and at 6 and 12 weeks. Food consumption data were analysed using food processor software. For assessment of bone resorption markers and changes in anthropometric data as well as dietary intake, repeated analyses were employed. Results: Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during diﬀerent stages of the study. Soy isoflavones consumption resulted in a significant reduction in the urinary deoxypyridinoline (the most sensitive and specific marker of bone resorption) (p%0.05), although the alterations in CTX (collagen type I cross-linked c-telopeptide) and ITCP (serum carboxyterminal telopeptide of type I collagen) were not significant. Conclusion: In view of beneficial eﬀect of soy protein (as a rich source of isoflavones) on bone resorption markers, consumption of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis.

P740SU. BONE MARKER VARIATIONS IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS TREATED WITH TERIPARATIDE P738MO. BONE TURNOVER, SIGNIFICANCE OF BIOCHEMICAL MARKERS FOR BONE METABOLISM IN PATIENTS WITH HYPERTHYROIDISM Payer J, Baqi L, Killinger Z; 5st. Internal Clinic of University Hospital, Bratislava, Slovakia Objective: Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity and untreated hyperthyroidism and treatment with high doses of thyroid hormones are associated with osteoporosis. Biochemical markers for bone metabolism have been established as a sensitive and reliable predictor for future changes in bone mass, since good correlations are found between early changes in bone markers and late changes in bone mass. Patients and Methods: We studied 82 patients (40 premenopausal; 42 postmenopausal women) with history of hyperthyroidism, all of them were euthyroid at the time of our examination, and 79 control euthyroid women (40 premenopausal and 39 postmenopausal). Thyroid function was examinated using freeT4 (FT4) and thyroid-stimulating hormone (TSH). Bone resorption was measured by serum N-telopeptide (NTX) and bone formation by serum osteocalcin (OC). Results: In all hyperthyroid groups OC and NTX levels were significantly higher than in age-matched control group (P<0.05). Correlation between thyroid hormones and bone markers was found only between FT4 and OC (r=0.318, P<0.05) in premenopausal women. In postmenopausal women we found correlation between TSH and OC (r=-0.37, P<0.05), and TSH and NTX (r=-0.32, P<0.05). Conclusions: Hyperthyroidism is associated with high bone turnover and patients suﬀering from hyperthyroidism are in high risk of osteoporosis and fractures.

P739SA. SOY ISOFLAVONES AND BONE RESORPTION MARKERS IN POSTMENOPAUSAL WOMEN Haghighian Roudsari A1, Ebrahimof S1, Larijani B2, Kimiagar SM1; 1School o f Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran, 2Endocrinology and Metabolism Research Center, Shariati Hospital, Tehran, Iran

Barata S1, Osório F1, Pauleta J1, Santo S1, Neves J1,2, PereiraCoelho A1,2; 1Obstetrics and Gynecological Department, Santa Maria Hospital, 2Medicine Faculty – Lisbon, Lisbon, Portugal Introduction: Teriparatide a recombinant PTH is used in osteoporosis treatment acting as an anabolic agent stimulating bone formation and so can improve bone microstructure, increasing bone mass above normal values. The teriparatide eﬀect will increase bone structural integrity, bone diameter and bone strength and so can reduce risk of fracture regarding osteoporosis. Objective: To assess bone marker variation in teriparatide treatment. Methods: We evaluate the results of teriparatide eﬀect on markers of bone turnover in 15 postmenopausal women with WHO criteria for osteoporosis. Serum osteocalcin (ng/mL) and urinary desoxipiridoline (nmol Dpd) were measured at baseline and 6 months after treatment. Data are represented meansd. Results: We found the following epidemiological data – age 64.26.85 years, menarche 131.37 years, menopause 49.53.74 years and BMI 18.33.51 kg/m2. Results on serum osteocalcin at baseline 62.94 and 6 months 14.29.86; data from urinary desoxipiridoline at baseline 64.248.75 and 6 months 93.978.67. Conclusion: Teriparatide treatment increases bone metabolism markers; there is a significant increase in both formation and resorption markers of bone turnover. The serum osteocalcin enhancement at 6 months is double than baseline; the urinary deoxypyridinoline both at baseline and 6 months after had a huge variability.

P741MO. THE UTILITY OF BONE TURNOVER MARKERS IN OSTEOPOROTIC PATIENTS Hulejova H1, Braun M1, Adam M1, Skacelova S1, Simkova G1, Pavelka K1, Dungl P2; 1Institute of Rheumatology, 2Orthopaedic Clinic of IPVZ, Prague, Czech Republic Aims: Osteoporosis (OP) belongs to one of the most serious disorders of bone metabolism with very high and increasing incidence, and represents even significant economic consequence

S343 concerning aspects of its treatment. That is why a set of important biochemical markers are studied and new sophisticated and sensitive analytical methods are developed in eﬀort to reduce the development of OP to late stages. The aim of this work was the comparison and evaluation of bone metabolism markers of osteoclastic activity – urinary deoxypyridinoline (UDPD), serum C-terminal telopeptide of type I collagen (CTX) and osteoblastic activity – bone alkaline phosphatase (BAP), osteocalcin (OC), C-terminal propeptide of collagen type I (PICP) in OP patients. From a clinical point of view, the influence of conservative therapy of OP and aspects of lowering the risk of new fractures will be evaluated as well. Methods: UDPD and OC were determined by the IMMULITE Automated Immunoassay Analyser (DPC, Los Angeles, CA, USA), a continuous random access instrument which performs automated chemiluminescent immunoassays. BAP, PICP and CTX were determined by ELISA kit (Metra Biosystems, Inc., USA and Nordic Bioscience Diagnostic A/S, Denmark). Results: From the preliminary results it is clear that markers of osteoclastic activity were increased in comparison with healthy controls (UDPD=10.143.55 vs. 8.122.81 nmol/mmol creat.; CTX=1.100.68 vs. 0.320.25 ng/ml) as well as osteoblastic activity markers (BAP=0.750.36 vs. 0.310.11 ukat/l; OC=8.245.01 vs. 4.792.83 ug/l; PICP=186.77141.26 vs. 125.1050.21 ng/ml). Conclusions: We can summarize that markers like UDPD, CTX, BAP, OC and PICP are valuable indicators of remodelling of bone tissues in OP and in other diseases as well. Obtaining data from wider groups of patients is the object of future study. Supported by Ministry of Health of the Czech Republic (Research Programme No. 0002384101)

P742SA. CLINICAL IMPORTANCE OF VITAMIN D IN OSTEOPOROSIS: ANALYTICAL ASPECTS OF ITS DETERMINATION Braun M1, Hulejova H1, Adam M1, Skacelova S1, Simkova G1, Pavelka K1, Dungl P2; 1Institute of Rheumatology, 2Orthopaedic Clinic of IPVZ, Prague, Czech Republic Aims: Vitamin D is necessary for regulation of calcium and phosphorus serum levels, and crucial for mineralization of bone tissues. The main forms, ergocalciferol and cholecalciferol are hydroxylated in liver to 25-hydroxyvitamin D2 or D3, in kidney to biologically active form (1,25-dihydroxyvitamin D3). Clinically relevant is determination of both 25-hydroxyvitamin D forms to evaluate eﬀect of vitamin D supplementation. In osteoporosis (OP), vitamin D status is one of the most important parameters in diﬀerential diagnostics. In this work we explain both, the clinical importance of vitamin D and analytical aspects of determination of its forms. Advantages and limitations of diﬀerent analytical approaches are discussed. Methods: The first methods for determination of 25hydroxyvitamin D were based on RIA, later immunochemical EIA and ELISA methods appeared. They are fast, but burdened by nonspecific interactions (big interassay variations) and only one analyte can be measured. HPLC represents another modern approach - high eﬃciency, reproducibility, accuracy and economic aspects are its main advantages. In combination with sensitive detectors and shortened sample preparation procedures, HPLC became perspective for simultaneous measurement of diﬀerent forms of calciferols and even other biochemical parameters in one chromatographic run and provides highly reliable results. From all the methods developed for determination of vitamin D, we decided to apply fast HPLC in reversed phase using C18 column and UV detection as the most suitable for our purpose to determine all the clinically important forms of vitamin D. In our OP group we focused on the diﬀerential diagnostics. Patients will be controlled in one-year intervals for five years, both clinically and by means of laboratory diagnostics, including assessment of vitamin D status, bone metabolism markers, calcium and phosphorus levels, and other biochemical parameters which will be mutually correlated. Results and conclusions: In this study we summarized and discussed both the clinical importance of vitamin D and also the analytical approaches and aspects of determination of its diﬀerent

forms in osteoporotic patients. The results and correlations with the clinical aspects will be the subject of our further work. Supported by Ministry of Health of the Czech Republic (Research Programme No.0002384101)

P743SU. FAMILIAL AGGREGATION AND HERITABILITY OF BONE SIZE AND BODY SIZE: EVIDENCE FOR SHARED AND UNIQUE GENETIC EFFECTS Wang XJ1, Kammerer CM1, Wheeler VW2, Patrick AL2, Bunker CH1, Cauley JA1, Zmuda JM1; 1Departments of Epidemiology and Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, 2The Tobago Health Studies Oﬃce, Scarborough, Tobago, West Indies Bone size (e.g., periosteal circumference, PC) is an important determinant of bone strength and is highly correlated with measures of body size (e.g., weight and height), but we know very little about the underlying genetic architecture of these traits. In particular, the role of genetics as a source of covariation between these traits (i.e., as a source of ’’pleiotropy’’) has rarely been considered. Thus, we dissected the genetic architecture of body size and bone size related phenotypes measured by peripheral quantitative computed tomography (pQCT) in 283 women and 188 men aged 18 and older (mean, 43 years) from 8 large, multigenerational Afro-Caribbean families with a mean family size >50 individuals (range from 21 to 112). Residual heritabilities (after accounting for age and gender) were moderate to high for height (0.730.09), leg length (0.510.09), trunk length (0.410.11), periosteal circumference of the tibia (0.710.10), and body weight (0.450.10). The phenotypic correlation between body size and bone sizerelated traits was then partitioned into genetic and environmental components using bivariate variance-components methods. Significant (p<0.01) positive genetic correlations (rG) were found between leg length and trunk length (0.730.12), and between tibia PC and leg length (0.420.12), trunk length (0.660.11), and standing height (0.570.09). RG between body weight and the other traits was low (0.390.13 for tibia PC) or non-significant (rG < 0.200.16 for height, trunk and leg length). Our results confirm that genes are important contributors to the normal variation in body size and bone size. Further, only 15–44% of the shared variation between tibia periosteal circumference and height related traits is due to a common set of genes. The low rG between body weight, periosteal circumference and the height related traits also indicates low pleiotropy between these traits. Our results suggest that although common genes aﬀect variation in bone size and body size related traits (pleiotropy), most of the genetic variation in these traits appears to be due to diﬀerent sets of genes.

P744MO. LINKAGE TO A REGION ON CHROMOSOME 11 IN TWO MALTESE FAMILIES WITH SEVERE OSTEOPOROSIS Vidal C1, Galea R2, Brincat M2, Xuereb-Anastasi A1,3; 1Department of Pathology, University of Malta Medical School, 2Department of Obstetrics and Gynaecology, University of Malta Medical School, 3Institute of Health Care, University of Malta, Malta Osteoporosis is a metabolic bone disease with a strong genetic component. Family based linkage studies were performed by a number of investigators to try to identify loci that might contain genes responsible for an increased susceptibility for osteoporosis. A whole genome linkage scan using 400 microsatellite markers was performed in 27 members from two Maltese families with a highly penetrant form of osteoporosis. The phenotype was defined by lumbar and femoral z-scores calculated after measurement of bone mineral density (BMD) by DXA. Both males and females were among the aﬀected individuals. Multipoint parametric and non-parametric linkage analyses were performed by EasyLinkage v4.0 using GENEHUNTER v2.1, assuming dominant and recessive modes of inheritance with variable penetrance. Evidence of linkage was observed to a marker at 11p13 where a non-parametric LOD score (NPL) of 4.99 was obtained. A maximum heterogeneity LOD (HLOD) score of 2.74 (p=0.0091) for this region was obtained for the dominant mode of inheritance with 90% penetrance and a phenocopy rate of 1%. Suggestive linkage

S344 was observed at a number of other chromosomal loci including 5q34, 6q22, 9q21, 13q33 and 17q21. These results suggest that a major gene responsible for osteoporosis might be present in region 11p13 while other contributing genes might be present on other chromosomes. Identification of these genes is important for the early identification of individuals at risk and for the development of eﬀective treatments.

P745SA. GENETIC VARIATION IN THE GONADAL STEROIDS PATHWAY IS ASSOCIATED WITH FRACTURES IN CHILDHOOD AND ADOLESCENCE Ferrari SL1, Chevalley T1, Manen S1, Brandi ML2, Bonjour JP1, Rizzoli R1; 1Service of Bone Diseases, WHO Collaborating Center for Osteoporosis Prevention, Geneva University Hospital, Switzerland, 2Department of Internal Medicine, University of Florence, Italy Children with fractures have a deficit in bone mineral mass (BMC) accrual and bone size relative to longitudinal growth. Despite evidence that BMC is largely inherited, genetic factors for bone fragility during childhood remain unknown. Estrogens regulate peak bone mass acquisition and adult stature in both genders. We hypothesized that genetic variation in estrogen receptor alpha (ESR1) and aromatase (CYP19) genes could be associated with childhood fractures. ESR1 XbaI polymorphisms (X or x) and CYP19 tetranucleotide repeats ((TTTA)n, S, short if n<8 or L, long if nR8–13) were genotyped in a cohort of 384 children (149 girls and 235 boys). BMC at lumbar spine (LS), hip and radius was evaluated by DXA at baseline and after 2 yrs. Mean (SD) age at baseline was 7.6 (0.5) yrs. Among 352 subjects with at least two years (max. 8.5 yrs) of follow-up, 101 children (59 boys and 42 girls) reported 127 fractures. ESR1 and CYP19 genotypes were obtained in 314 and 276 subjects, respectively. Frequency of ESR1 genotypes diﬀered significantly (Chisquare p=0.03) between subjects with fractures (XX, 18% , Xx 35%, xx 47%) and without fractures (XX, 10% , Xx 50%, xx 40%). In females, but not males, XX was independently associated with increased fracture risk (p=0.007), as evaluated by logistic regression including baseline age and BMI, mean dietary calcium intake, and 2-yrs gain in height and BMC. Distribution of CYP19 genotypes was similar among children with and without fractures in the whole cohort. However, homozygous females for CYP19 long allele repeats tended to be over-represented in the fracture group (LL, 38%, SS/SL 62% vs LL, 21%, SS/SL 79% in controls, chi-square p =0.08). These observations are the first to indicate an association between genetic variation in the gonadal steroids pathway and the risk for fractures in childhood and adolescence.

P746SU. ESR1 CA(N) REPEAT POLYMORPHISM IS ASSOCIATED WITH INCREASED RISK OF OSTEOPOROTIC FRACTURES AND ESTROGEN RECEPTOR ALPHA: MRNA EXPRESSION IN BONE Lai BMH1, Luk KDK2, Kung AWC1; 1Department of Medicine, 2 Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China Introduction: Recent studies have shown that intronic CA dinucleotide repeat polymorphisms may be associated with disease risk by modulating mRNA splicing eﬃciency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of estrogen receptor alpha gene (ESR1). Methods: To evaluate the role of D6S440 in bone mineral density (BMD) determination and osteoporosis outcomes prediction, 281 pairs of premenopausal and 395 pairs of postmenopausal Chinese female case-control subjects were studied. The functional significance of D6S440 in determining estrogen receptor (ER) gene expression was examined in human bone. Results: Post- but not premenopausal women with less CA repeats had lower BMD at both spine and hip. A linear relationship was seen between the number of CA repeats and hip BMD in postmenopausal women (;=0.008; p=0.004). Postmenopausal

women with less than 18 CA repeats had higher risks of osteoporosis at the spine (odds ratio (OR) 2.46, 95% confidence interval (CI) 1.30–4.65; p=0.0006) and hip (OR 3.79(1.64–8.74), p=0.0002), and also increased risk of spine and hip fractures (OR 2.31(1.29–4.14), p=0.005). Perimenopausal women with CA repeat size <18 had significantly greater bone loss at the hip (-1.96%) than those with CA repeat size R18 (-1.61%; p=0.029) during 18 months of observation. Subjects with fewer CA repeats had reduced ER mRNA expression in their bone cells. Conclusions: ESR1 CA repeat polymorphism is associated with multiple osteoporosis outcomes and mRNA expression in bone, and this may be a useful genetic marker for fracture risk assessment.

P747MO. OSTEOPOROSIS PSEUDOGLIOMA: A NOVEL MUTATION IN GENE LRP5 Barros ER, Kunii IS, Hauache OM, Lazaretti-Castro M; Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil Osteoporosis-pseudoglioma syndrome (OPPG) is an autosomal recessive disorder characterized by bone mass decrease and ocular involvement. Research of gene candidate had identified to receiver Low-density-lipoprotein receptor Related. Protein 5 (LRP5) as possible causer of this pathology. The LRP5 is a Wnt co-receptor an important regulator of the bone development and its maintenance. The gene that codifies the LRP5 is located in the cromosome 11q13.4 and is composed of 23 exons and codifies a protein with 1615 amino acids. Gong et al. (2001) had shown that LRP5 aﬀects the bom mass during the period of growth and identified mutations in the gene of LRP5 that causes the OPPG. This mutations reduced bone mass when in comparison with the controls adjusted for sex and age. Studies had demonstrated to crucial importance of the Wnt/LRP5 in the signal of transduction in the bone during the growth and the importance of this signal in the stabilization of the peak of bone mass. To demonstrate the presence or not of the mutation in the gene of LRP5 in two brothers with clinical suspicion of OPPG. Two carring brothers of OPPG, normal genitors and 50 controls had been studied. Genomic DNA was isolated from peripheral leukocytes and all 23 exons of the LRP5 were amplified by PCR. Direct sequence analysis of DNA was performed using automatic sequencer and the result was analysed using as reference GenBank. Direct sequencing of the amplified DNA indicate one novel homozygous missense mutation in two brothers of consanguineous parents not described in the literature. The LRP5 mutation is in the third amino acid of exon 8 resulting in a substitution of asparagines by isoleucine in the position 531 (N531I). The parents have heterozygous mutation and we did not find the mutation in 50 control cromosomes. This mutation is located in LDL-R like ligand binding domain. We demonstrate the presence of a new mutation in two brothers that confirm their diagnostic of OPPG and patients with bone fragility and ocular envolviment will be investigate for mutation at LRP5 gene.

P748SA. IDENTIFICATION OF ADIPONECTIN AND ITS RECEPTORS IN HUMAN OSTEOBLAST-LIKE CELLS AND ASSOCIATION OF T45G POLYMORPHISM IN EXON 2 OF ADIPONECTIN GENE WITH LUMBAR SPINE BONE MINERAL DENSITY IN KOREAN WOMEN Oh KW1, Jung CH1, Rhee EJ1, Lee WY1, Yun EJ2, Baek KH3, Kang MI3, Kim SW1; 1Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea, 2Radiology, Hallym University, Seoul, Korea, 3Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea Aims: The role of adiponectin in bone metabolism has been recently reported on in in vitro and in vivo studies. There has been no report on the association of adiponectin gene polymorphism and the bone mineral density (BMD). Therefore, we investigated whether two single nucleotide polymorphisms (T45G and G276T) in the adiponectin gene were related to the BMD. We also report

S345 on the identification of adiponectin and its receptors 1 and 2 in the human osteoblast-like cell lines. Methods: The MG-63 cells were cultured and osteogenic and adipogenic diﬀerentiations from human mesenchymal stem cells (hMSC) were performed. RNA was then extracted from the cultured cells and RT-PCR was performed using primers for adiponectin and for the adiponectin receptor genes. In 249 healthy Korean women (mean age: 51.4 yrs), measurements were made of their lumbar spine and femoral neck BMDs, their bone turnover markers and their serum FSH levels. The genotyping of the T45G polymorphism in exon 2 and the G276T polymorphisms in intron 2 in the adiponectin gene was performed via an allelic discrimination assay with using a TaqMan probe. Results: We found that the mRNAs for adiponectin and for adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) were expressed in the MG-63 cells. Sequencing of the PCR products revealed that they were compatible to human adiponectin, AdipoR1 and AdipoR2, respectively. mRNAs for adiponectin, AdipoR1 and AdipoR2 were also expressed in the osteoblastic and adipogenic cell lines diﬀerentiated from hMSC. For the polymorphism study, the frequencies of T45G and G276T in the adiponectin gene were in compliance with Hardy-Weinberg equilibrium. Subjects with G alleles at the T45G locus had significantly lower lumbar spine BMD than did those subjects with the TT genotype. Conclusions: We observed the expression of adiponectin, AdipoR1 and AdipoR2 in the MG-63 cell line and the osteoblastic cell line diﬀerentiated from hMSC. T45G polymorphism in exon 2 of adiponectin gene is associated with lumbar spine BMD in Korean women. Additional studies are needed to elucidate the real contribution of adiponectin on the bone mineral metabolism.

P749SU. EVIDENCE FOR AN EARLY LIFE - CALCIUM SENSING RECEPTOR GENE POLYMORPHISM INTERACTION IN DETERMINATION OF ADULT BONE MASS: THE HERTFORDSHIRE COHORT STUDY Lips MA1, Syddall HE1, Day INM2, Gaunt TR2, Rodriguez S2, Cooper C1, Dennison EM1; 1MRC Epidemiology Resource Centre, 2Human Genetics Division, University of Southampton, UK Several studies have looked for evidence of an association between one single nucleotide polymorphism (SNP) in the calcium sensing receptor gene (CaSR) with bone mineral density (BMD), but results have been largely negative to date. We have previously found evidence of interaction between growth in early life and SNPs of the vitamin D receptor and growth hormone genes in the determination of BMD. Here, we looked for evidence of interaction between growth in early life and SNPs of the CaSR gene in the Hertfordshire Cohort Study. Four hundred and ninety eight men and 468 women aged 59–71 years were recruited. Birth-weight and weight at one year of age were available from historical ledgers. A lifestyle questionnaire was administered and BMD at the lumbar spine and femoral neck measured. DNA was obtained from whole blood samples using standard extraction techniques. Five SNPs in the CaSR gene termed CASRV001 (rs1801725, G>T, S986A), CASRV002 (rs7614486, T>G, untranslated), CASRV003 (rs4300957, untranslated), CASRV004 (rs3804592 G>A, intron), and CASRV005 (rs1393189, T>C, intron) were analysed. We found no significant associations between BMD at the lumbar spine or total femur with any of the SNPs studied. However, among women the 11 genotype of the CASRV003 SNP was associated with higher lumbar spine BMD within the lowest birth-weight tertile, while the opposite pattern was observed among individuals in the highest tertile of birth-weight (test for interaction on 1df p=0.005, adjusted for age, BMI, physical activity, dietary calcium intake, cigarette and alcohol consumption, social class, menopausal status and HRT use). Similar relationships were seen at the total femur (p=0.042, fully adjusted). In addition, the 1 allele of the CASRV3 SNP was associated with higher total femoral BMD among women in the lowest weight at one-year tertile, while the opposite pattern was again observed among individuals from the highest tertile of weight at one year (p<0.001 fully adjusted).

We have found evidence of an interaction between one SNP in the CaSR gene and growth in early life in the determination of BMD in a UK female population in late middle age.

P750MO. GENETIC AND ENVIRONMENTAL DETERMINANTS OF DXA AND PQCT MEASURED BMD IN AFRO-CARIBBEAN FAMILIES Wang XJ1, Kammerer CM1, Wheeler VW2, Patrick AL2, Bunker CH1, Cauley JA1, Zmuda JM1; 1Departments of Epidemiology and Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, 2The Tobago Health Studies Oﬃce, Scarborough, Tobago, West Indies Bone mineral density (BMD) is an important determinant of bone strength. Numerous family studies have assessed the heritability of two-dimensional DXA measures of areal BMD but none have assessed three-dimensional QCT measures of volumetric BMD. Thus, we estimated the genetic and environmental contributions to areal BMD measured by DXA (whole body, lumbar spine, femoral neck, and total hip) and volumetric BMD measured by pQCT (tibia and radius: total density, trabecular density and cortical density) in 283 women and 188 men aged 18 and older (mean 43 years old) from 8 large, multigenerational Afro-Caribbean families with a mean family size >50 individuals (range from 21 to 112). Measured covariates accounted for 13–33% (for DXA) and 7–32% (for pQCT) of the total phenotypic variation. Age, gender, height and body weight accounted for most (80–95%) for the variation attributable to covariates. Menopausal status and diabetes were associated with strong, negative eﬀects on almost all of the DXA and pQCT traits and accounted for a substantial proportion (40–60%) of the variation in lumbar spine BMD and cortical BMD due to all measured covariates. The residual heritability (after incorporating all covariate eﬀects) for all BMD phenotypes was moderate to high (h2r ranged from 0.290.09 to 0.720.10, P<0.01). Trabecular BMD was more heritable than cortical BMD at both the radius and tibia (h2r: 0.700.10 versus 0.290.09 and 0.690.10 versus 0.420.10, respectively). Our study indicates that both genetic and environmental factors may aﬀect trabecular and cortical BMD diﬀerently. Additional studies of these skeletal compartments should advance our understanding of the bone strength phenotype.

P751SA. COLLAGEN I ALPHA 2 GENE POLYMORPHISM ASSOCIATED WITH LOWER BONE MINERAL DENSITY IN ADOLESCENT IDIOPATHIC SCOLIOSIS GIRLS: A 517-CASES STUDY Hung VWY1, Tang NL2, Yeung HY1, Lee KM3, Qin L1, Cheng JCY1; 1Department of Orthopaedics and Traumatology, 2Department of Chemical Pathology, 3Lee Hysan Clinical Research Laboratory, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity. It is well accepted that patient with AIS are taller and slender during peri-pubertal period. In addition, bone mineral density (BMD) of patients with AIS was generally lower than their peers. Type I collagen is the major protein of the bone scaﬀold and important in bone mineralization. Study showed that polymorphisms of type I collagen 2 (COL1A2) gene was related to the spine BMD of adolescent female. We hypothesized that COL1A2 gene may be associated with abnormal bone mineralization and growth during adolescent period in AIS patients. This study investigated the association of the PvuII polymorphism of COL1A2 gene with anthropometry and spinal BMD of AIS patients. Girls with AIS at age 12–16 years (n=517) were assessed for spinal and nondominant femoral neck BMD by DXA with anthropometric parameters. As we had shown previously that lumbar spine BMC is more reliable parameter than BMD in AIS patients due to rotation of the spine, BMC is used for analysis. Anthropometric parameters and BMD of AIS patients were standardized as Z-score with respect to age and sex-matched controls. The genotype of PvuII polymorphism of COL1A2 gene is characterized by PCR-RFLP.

S346 The genotype frequency of PP, Pp, and pp were 6.1%, 40.2%, and 53.6%, respectively. The BMC of the lumbar spine in AIS girls with pp was significantly lower and smaller than patients with at least one P allele (PP and Pp) (p=0.008). In addition, the femoral neck BMD of AIS girls with pp was also significantly lower than AIS girls carrying P allele (p=0.048). The BMI of the AIS girls with pp genotypes had significantly lower BMI than others as well (p=0.035). AIS girls with pp genotype had significantly lower BMI, spinal BMC, and nondominant femoral neck BMD. It is suggested that COL1A2 gene might play important roles as modifier gene in bone mineralization and growth of AIS girls.

P752SU. A SNP IN THE CBFA1 PROMOTER 1 REGION AND ITS RELATION WITH BMD AND BMI IN SPANISH POSTMENOPAUSAL WOMEN Bustamante M1, Garcia-Giralt N1, Enjuanes A2, Carbonell J2, Nogues X2, Mellibovsky L2, Diez-Perez A2, Grinberg D1, Balcells S1; 1Departament de Genetica-UB, 2URFOA-Hospital del Mar, Barcelona, Spain Aim: Osteoporosis is a multifactorial disease with a strong genetic component. Several genes were reported to be involved in this pathology but there are controversial results and new candidates should be evaluated. Core binding factor 1 (Cbfa1) is a runt domain transcription factor that is essential for osteoblast diﬀerentiation, bone remodelling and fracture healing. Both knockout and overexpression of the CBFA1 gene in mice, result in an osteoporotic phenotype. Because of this, CBFA1 is a good candidate gene for association studies in osteoporosis. The aim of this work was to search for new polymorphisms in the CBFA1 promoter 1 (which codes for isoform II) and in the adjacent 5’UTR region, and to perform association studies between the polymorphisms and BMD or BMI. Methods: Polymorphisms were searched by a SSCP-sequencing combined strategy. A cohort consisting on 729 postmenopausal Spanish women (54.76 8.4 years old) was analysed for association between the polymorphism and BMD/BMI. EMSA experiments were used to assay for nuclear protein binding to the site bearing the polymorphism. Results: We identified a single nucleotide polymorphism (minor allele frequency: 0.15) within a sequence conserved among diﬀerent species. In the HapMap database, the polymorphism was located in a 10 Kb linkage disequilibrium region and gel retardation assays showed that oligonucleotides containing the polymorphic site specifically bound osteosarcoma (MG63) nuclear proteins. No association was observed between this polymorphism and lumbar spine BMD or femoral neck BMD (p=0.612 and p=0.474, respectively). However, we observed a marginally significant association between this variation and body mass index (BMI) (p=0.065 in a dominant model). Conclusions: A new polymorphism was identified in the CBFA1 promoter region that is not associatiated to BMD but seems to be involved in BMI determination in a cohort of 729 postmenopausal Spanish women.

P753MO. ASSOCIATION ANALYSIS BETWEEN SNPS, HAPLOTYPES AND HAPLOGENOTYPES AT THE COL1A1, ESR1, VDR OR TGFB1 GENES AND BMD IN A COHORT OF SPANISH POSTMENOPAUSAL WOMEN Bustamante M1, Nogues X2, Enjuanes A2, Elosua R2, GarciaGiralt N1, Carreras R2, Balcells S1, Mellibovsky L2, Grinberg D1, Diez-Perez A2; 1Departament de Genetica-UB, 2URFOAHospital del Mar, Barcelona, Spain Aim: Genetic studies of osteoporosis have been mostly performed using single polymorphisms in individual genes with inconclusive results. An alternative approach, which better accounts for the complexity of the disease, needs to include haplotypes, haplogenotypes and gene-gene interactions. We have previously shown that two polymorphisms in the upstream regulatory region of COL1A1 were associated with lumbar spine BMD and that there were subtle but reproducible diﬀerences between the two alleles of each polymorphism regarding transcriptional activity. The aim of this

study was to compare the eﬀect on BMD of these two polymorphisms with the eﬀects of polymorphisms of the VDR, ESR1, and TGFB1 genes at the level of individual SNPs, haplotypes and haplogenotypes. Besides, we aimed at assaying pairwise interactions of these four genes in relation to BMD. Methods: In total, 16 polymorphisms were analysed in a cohort of 731 postmenopausal women. Statistic methods included chisquare tests, analysis of variance and covariance. Haplotype and haplogenotype analyses were performed in the subset of women with unambiguous linkage phase. Results: A significant association with adjusted lumbar spine BMD (LS BMD) was found only for –1997G>T of COL1A1 (p=0.043) and for the Leu10Pro of TGFB1 (p=0.020). Two significant interactions were observed: one between the COL1A1 –1997 G/T and Sp1 polymorphisms (p=0.005 for LS BMD) and the other between the COL1A1 –1663 indelT and the VDR ApaI polymorphisms (p=0.002 for FN BMD). Two COL1A1 haplotypes were associated with LS BMD (p=0.028 and p=0.035), and a third one with FN BMD (p=0.026). Consistently, haplogenotype results were significant for LS BMD (p=0.001) where GDs/TIS individuals had the highest BMD. Weaker associations were found for ESR1: one haplotype (LPX) appeared associated with FN BMD (p=0.023) and a significant diﬀerence was obtained between LPX/HPX and Lpx/Hpx haplogenotypes (p=0.009). Conclusions: COL1A1 haplogenotypes show a stronger association with BMD than those of ESR1, VDR or TGFB1 in a cohort of Spanish postmenopausal women.

P754SA. VARIABLE NUMBER OF TANDEM REPEATS (VNTR) POLYMORPHISM IN THE PTHRP GENE AS DIAGNOSTIC PREDICTOR OF PEAK BONE MASS IN YOUNG FINNISH MALES Gupta A1, Välimäki V-V2, Välimäki MJ2, Löyttyniemi E3, Richardson M1, Goltzman D4, Karaplis AC4; 1Osta Biotechnologies Inc., Pointe Claire, Québec, Canada, 2Helsinki University Central Hospital, Helsinki, Finland, 3University of Turku, Turku, Finland, 4McGill University, Montréal, Canada Parathyroid hormone-related protein (PTHRP) has been identified as a pivotal regulator of osteoblast diﬀerentiation, proliferation, and apoptotic cell death. In mice, targeted disruption of Pthrp in cells of the osteogenic lineage leads to profound decreases in bone formation and premature osteoporosis. Whether similar biological properties can be attributed to PTHRP expressed in human bone remains unclear. In this study, the association between a PTHRP variable number of tandem repeats (VNTR) polymorphism and peak bone mass was examined in 234 young healthy Finnish males, aged 18.3 to 20.6 years. They were participants in a study aimed at elucidating the role of genes, hormones, and lifestyle factors as determinants of peak bone mass, and studying exercise-induced changes in bone mass during military service. VNTR length was determined by PCR amplification of genomic DNA extracted from peripheral blood leucocytes and its association with osteodensitometry of the lumbar spine and hip, and calcaneal quantitative ultrasound measurements was determined. The relationships between BMC, BMD, BUA, and SOS and individual PTHRP VNTR alleles and their combinations were analyzed by multiple regression models. The results show that the presence of at least one 252 base pair (bp) allele is associated with increased skeletal densitometric and ultrasound parameters and the presence of at least one 378 bp allele is associated with decreased trochanter BMC and lumbar spinal BMC & BMD. The correlation with increased bone mass is strengthened by pairing of the 252 bp allele with a 460 bp allele. In contrast, bone mass is reduced by pairing of the 252 bp allele with a 378 bp allele. Consequently, PTHRP VNTR polymorphisms are described which predict either high or low bone mass in young Finnish males. These studies therefore highlight the importance of these PTHRP polymorphisms as diagnostic predictors of risk for low bone mass and osteoporosis in this population.

S347

P755SU. INVESTIGATION OF THE ASSOCIATION OF POLYMORPHISMS IN THE TRANSFORMING GROWTH FACTOR-BETA-INDUCIBLE EARLY GROWTH RESPONSE 2 GENE WITH VARIATION IN BONE MINERAL DENSITY Hegarty KG1,2, Drummond FJ1,2, Daly M1, Shanahan F2,3, Molloy MG1; 1Department of Rheumatology and Sports Medicine, 2Department of Medicine, 3Alimentary Pharmabiotic Center, National University of Ireland, Cork, Ireland Osteoporosis is a complex polygenic disease. Suggestive evidence of linkage between low bone mineral density (BMD) and the 2p25 locus was observed in an Irish cohort. We investigated the possible association between single nucleotide polymorphisms (SNPs) in the transforming growth factor--inducible early growth response 2 (TIEG2) gene, mapped to 2p25, with variation in BMD crosssectionally in premenopausal and postmenopausal Caucasian women and longitudinally with annualized rate of change in BMD. The TIEG2 gene is a SP1-like transcription factor that has been shown to repress transcription and cell proliferation, this gene is also upregulated by TGF--1. Genotypes were identified using CodeRed SNP Genotyping. Statistical analysis was performed using SPSS. TIEG2 genotypes were not significantly associated with variation in BMD in either the premenopausal (n=180; P>0.02) or postmenopausal (n=380; P>0.02) cohorts. However, an allele dose eﬀect as indicated by linear trends was observed between both the TIEG2 T/C (rs6432053) and TIEG2 G/A (rs7632) SNPs and annualized percentage rate of change in lumbar spine (LS) BMD. Mean annualized percentage rate of change in LS BMD across the TIEG2 T/C genotypes was -0.09, 0.22 and 0.83/year for CC, TC and TT individuals, respectively. This approached significance (P=0.07). The mean annualized percentage rate of change in LS BMD across the TIEG2 G/A genotypes was -0.09, 0.22 and 0.77%/year for AA, GA and GG individuals, respectively (P=0.11). The cohort (n=257) was stratified according to HRT usage. Non-HRT users with one or more copies of the TIEG2 C allele had a greater rate of bone loss (-0.56%/year) at the LS than homozygous T women (0.57%/year). This approached significance (P=0.04). A similar trend was observed with the TIEG2 G/A SNP. Women with one or more copies of the TIEG2 A allele had a greater rate of bone loss (-0.56%/year) at the LS compared to homozygous G women (0.62%/year), which approached significance (P=0.03). This trend in bone loss was abolished among HRT users. These two TIEG2 SNPs are in strong linkage disequilibrium (LD) (A-C (49.3%) and G-T (50.7%) D’=1.0, r2=1.0). In conclusion, TIEG2 may be involved with postmenopausal bone loss and this eﬀect may be nullified by HRT.

P756MO. GENE-BY-SEX INTERACTION: EVIDENCE OF EFFECTS ON SERUM OSTEOCALCIN LEVELS IN THE FELS LONGITUDINAL STUDY Czerwinski SA, Lee M, Choh AC, Demerath EW, Chumlea WC, Sun SS, Towne B, Siervogel RM; Lifespan Health Research Center, Wright State University School of Medicine, Dayton, OH, USA Introduction: Epidemiologic studies have demonstrated bone turnover markers to predict fracture risk independent of bone mineral density. Serum osteocalcin (OC) is regarded as an overall marker of bone turnover since measures of OC reflect both bone formation and resorption. Few studies have examined the genetic architecture underlying variation in bone turnover markers. Since sexual dimorphism exists in osteoporosis risk it seems likely that there may be a genetic basis underlying these sex diﬀerences. Aims: The goal of this study is to estimate the heritability of serum OC levels in men and women, and to determine whether a significant gene-by-sex interaction eﬀect exists on OC levels. Methods: The study sample includes 360 adults (174 men and 186 women) ages 18 to 90 years (mean SD: 39.3 14.1 yrs) who belong to 102 nuclear and extended families participating in the Fels Longitudinal Study. Serum levels of OC were determined by ELISA (Quidel Corp. San Diego, CA) from stored samples obtained after an overnight fast. To reduce skewness, values of OC were log-transformed prior to quantitative genetic analyses. Using a maximum likelihood variance components-based method (SO-

LAR), we estimated the heritability of serum OC levels while simulateously acounting for the eﬀects of age, age2, sex, age-bysex, and age2-by-sex. Extensions of these methods were then used to test for gene-by-sex interaction. To test for a gene-by-sex interaction, additional sex-specific variance terms were included in the model, as well as a genetic correlation term between the sexes. Results: Serum OC levels were significantly heritable with h2= 0.345 (p=0.0031) in the total sample. Comparisons of nested models revealed significant evidence (p=0.003) for a gene-by-sex interaction eﬀect on OC levels. Conclusion: In our population, we found serum OC levels to be significantly heritable. We also found significant evidence for a gene-by-sex interaction eﬀect. These results indicate that the gene or suite of genes regulating OC levels is likely the same in both sexes, but that the expression of genes may be diﬀerent between the sexes.

P757SA. MUTATION ANALYSIS OF THE SQSTM1 GENE IN PAGET’S DISEASE OF BONE IN A HUNGARIAN FAMILY Donáth J, Gergely jr P, Blazsek A, Poór G; National Institute of Rheumatology and Physiotherapy, Budapest, Hungary Paget’s disease of bone (PDB) is a common disorder characterized by focal and disorganized increases of bone turnover. Genetic factors play an important role in the pathogenesis of PDB and recent studies have shown that mutations of the SQSTM1 gene are associated with the disease in both the sporadic and familial forms. We analysed the occurance of mutations in the SQSTM1 gene in a Hungarian family with PDB. In three family members PDB was diagnosed on the basis of clinical and radiological criteria, serum alkaline phosphatase (SAP) and bone scintigraphy. The family consisted of 3 generations. DNA was isolated from 3 aﬀected patients and 8 additional family members and mutation analysis of the SQSTM1 gene was performed. All three family members aﬀected with PDB carried the P392L mutation in heterozygous form. Genomic sequence analysis of exon 8 in eight nonaﬀected family members revealed no sequence variations. All three patients had polyostotic PDB and significantly elevated SAP; however, the age at onset and the locations of the pagetic lesions were diﬀerent in each patient. Our data provide further evidence of a causal role of SQSTM1 P392L mutation in familial PDB. SQSTM1 P392L mutation can contribute significantly to disease susceptibility; however, additional factors may probably influence clinical course and outcome in patients with PDB.

P758SU. ASSOCIATION BETWEEN ANDROGEN RECEPTOR GENE POLYMORPHISM AND BONE DENSITY IN OLDER WOMEN USING HORMONE REPLACEMENT THERAPY Retornaz F1,2, Paris F2, Lumbroso S2, Audran F2, Tigoulet F1, Michelon C3, Jeandel C1, Sultan C2, Blain H1; 1University Hospital Antonin Balmes Center, 2University Hospital Lapeyronnie, 3 University Hospital Arnaud de Villeneuve, Montpellier, France Aims: The objective of this study was to investigate the relationship between bone mineral density (BMD) and both CAG repeat polymorphism of the androgen receptor (AR) gene and skewed X chromosome inactivation (SI) in postmenopausal women. Methods: BMD was measured by DXA. Both the number and the X-weighted biallelic mean of the CAG repeats of AR were analysed by PCR, before and after DNA digestion with methylation-sensitive HpaII in 192 healthy Caucasian postmenopausal women. Results: The number of CAG repeats ranged from 10 to 34, with a median value of 22. CAG)%22 and CAG)R23 alleles were designated as short and long alleles, respectively. In women using hormone replacement therapy (HRT)(n=81), lumbar spine BMD was significantly lower, and femoral neck and total body BMD marginally lower in those with long-long alleles when compared with those with other genotypes. SI (R80%) was observed in 24% of the women and was not associated with BMD. In women using

S348 HRT, femoral neck BMD was significantly lower, and lumbar spine and total body BMD marginally lower in those whose X-weighted CAG repeat biallelic was lower than 22.59 (median value) when compared to other genotypes. These results were not found in women not using HRT. Conclusion: Our results suggest that BMD is associated with AR gene polymorphism in postmenopausal women using HRT but not with SI. Further studies are needed to investigate the mechanisms of the interaction between HRT, BMD and AR found in the present study.

P759MO. ASSOCIATION OF DOUBLE POLYMORPHISMS OF THE KLOTHO AND OSTEOPROTEGERIN GENES WITH SERUM OSTEOPROTEGERIN LEVELS AND BONE MINERAL DENSITY IN KOREAN WOMEN Yun EJ1, Oh KW2, Rhee EJ2, Lee WY2, Kim SW2, Baek KH3, Kang MI3, Choi CS1; 1Department of Radiology, Hallym University, 2Department of Internal Medicine, Sungkyunkwan University School of Medicine, 3Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea Aims: KLOTHO gene has been identified as a suppressor of aging phenotypes, and knockout mice for KLOTHO gene show low turnover osteopenia. Osteoprotegerin (OPG) is a decoy receptor for the receptor activator of NF kappa B ligand and an important inhibitor of osteoclastogenesis. Recently, KLOTHO and OPG have been proposed as linkage genes between osteoporosis and arterial calcification, but the precise mechanisms are not clear. We investigated the relationships of double polymorphisms of the KLOTHO and OPG gene with serum OPG levels and bone mineral density in healthy Korean women. Methods: Genotyping were done for polymorphisms of KLOTHO gene, G395A and C1818T, and OPG gene, A163G, G209A, T245G and T950C, in 251 healthy Korean women (mean age, 51.36.9 yr) by allelic discrimination using the 5’ nuclease polymerase chain reaction assay. Serum OPG levels and bone turnover markers were measured, and lumbar spine and femoral neck bone mineral density (BMD) were examined by standardized methods. Results: Allelic frequencies of KLOTHO and OPG polymorphisms were in compliance with Hardy-Weinberg equilibrium and all of the polymorphisms were in linkage disequilibrium. Low serum OPG levels in minor allele carriers of KLOTHO gene showed a tendency for increment by the coexistence of minor allele of OPG gene, although statistically not significant. Analyses in double polymorphisms of the KLOTHO and OPG genes revealed that low BMD vales in minor allele carriers of KLOTHO gene was partly rescued by the coexistence of minor allele of OPG gene. Conclusions: The OPG gene polymorphism is at least partly responsible for the change of BMD in the minor allele carrier of KLOTHO gene. Further studies are needed to clarify this relationship.

P760SA. A COMMON POLYMORPHISM OF GROWTH HORMONE RECEPTOR IS ASSOCIATED WITH BONE MINERAL DENSITY IN GIRLS Qiu XS1,2, Qiu Y1,2, Sun X1,2, Xia CW1,2, Cheng JCY1,3; 1Nanjing University Medical School, Nanjing, China, 2Department of Spine Surgery, Drum Tower Hospital, Nanjing, China, 3Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China Aims: Bone mineral density (BMD) in adolescence is under strong genetic control. The growth hormone receptor (GHR) is involved in the regulation of bone growth. Exon 3 deletion polymorphism of the GHR has recently been associated with increased responsiveness to growth hormone. We investigated whether this polymorphism was related to BMD in girls. Methods: In 80 girls with idiopathic scoliosis (mean age 14.61.2 years, (mean SD)); the fl and d alleles were determined using a simple multiplex PCR. BMD (g/cm2) of the hip and lumbar spine was measured using dual-energy X-ray absorptiometry.

Results: The genotype frequencies were 67.5% (54/80) fl/fl, 28.8% (23/80) fl/d and 3.7% (3/80) d/d. The genotypes were divided into presence (32.5%) or absence of d allele (67.5%). Subjects with the d allele had higher BMD at all sites detected than the subjects lacking the d allele, and the diﬀerence was found significantly in the lumbar spine (0.9090.116 vs 0.8060.123, p=0.001, using independent samples t-test), and marginally significantly in the femoral neck (0.8490.106 vs 0.8050.097, P=0.06), greater trochanter (0.6900.093 vs 0.6540.074, p=0.06) and Ward’s triangle (0.7650.135 vs 0.7120.117, p=0.07). Conclusion: The GHR exon 3 deletion polymorphism is strongly related to BMD in girls with idiopathic scoliosis in this small sample, and large samples are needed to confirm this result. Also further study is encouraged to investigate whether this polymorphism is related to BMD in healthy girls and adult.

P761SU. KNOWLEDGE, HEALTH BELIEFS, AND HEALTH-RELATED BEHAVIORS IN FIRST-DEGREE RELATIVES OF WOMEN SUFFERING OSTEOPOROSIS: A COMPARATIVE STUDY Chang SF; Taipei, Taiwan, ROC No previous study has examined knowledge, health beliefs, and health-related behaviors in first-degree relatives (FDRs) of osteoporosis suﬀerers, especially focusing on Asian women. Aim: This study explored osteoporosis knowledge, beliefs and behaviors of women with a family history of osteoporosis, and drew a comparison with women with no such history. Design: This study recruited women at a large public health center in northern Taiwan. A questionnaire was applied on FDRs and non-FDRs women with a focus on osteoporosis knowledge, health beliefs and behaviors. Descriptive analysis was initially conducted. Diﬀerences between FDRs and non-FDRs were rated via Student’s t-tests for continuous variables and the 2 test for categorical variables. Results: Overall, most of the participants were aware of some osteoporosis-related information but the proportions of correct responses to the questions that tested knowledge between FDRs Diﬀerence between FDRs and non-FDRs in demographic characteristics, knowledge, health beliefs, and health-related behaviors Characteristic Mean age (SD) Average number of children (SD) Average amount of calcium intake (SD) Monthly income (%) Up to US $700 US $701+ Marital status (%) Single Married Widowed Divorced/separated Education (%) Less than high school High school graduate College graduate or more Aware of some osteoporosisrelated information osteoporosis (%) Yes No Knowledge about osteoporosis (SD) Health beliefs about osteoporosis Perceived susceptibility (SD) Perceived seriousness (SD) Perceived benefit (SD) Perceived barrier (SD) Health-related behaviors Screening behavior (%) Yes No Preventive behaviors (SD) P < 0.05

*

FDRs (n=97)

Non- FDRs (n=207)

p

48.5 (2.9) 2.7 (0.2)

48.3 (3.1) 2.9 (0.5)

0.209 0.476

456 (24)

550 (10)

0.577

456 (24) 30.2 69.8

550 (10) 32.0 68.0

0.577 0.334

6.3 81.3 6.2 6.2

2.4 73.2 17.1 7.3

12.4 49.0 38.6

19.1 44.6 36.3

0.434

0.324

0.546 73.4 26.6 6.6 (2.4)

77.4 22.6 6.3 (2.4)

0.545

3.9 3.5 3.3 3.9

1.1 1.7 2.9 2.1

0.013* 0.029* 0.212 0.041*

(0.7) (0.8) (0.4) (0.7)

(0.7) (0.5) (0.6) (0.2)

0.012* 48.4 51.6 2.2 (0.7)

17.3 82.7 1.9 (0.6)

0.432

S349 and non-FDRs were only 44% and 42%, respectively. Meanwhile, participants in the FDRs group not only reported higher concern in developing the disease but also perceived higher barriers compared to the non-FDRs group. As the study demonstrates, for health-related behaviors, the FDRs group did not undertake actual preventive behaviors, and only bone mineral density screening behavior diﬀered significantly from the non-FDRs group. Conclusions: This study highlights the inadequate information on osteoporosis and constraining beliefs of FDRs women. Additionally, since preventive behaviors of osteoporosis are not noticed in FDRs group, community health nurses and researchers should make participants’ concerns and assist women to reduce the diﬃculties of taking practically preventive behaviors not merely by the bone density results. Relevance to clinical practice: This investigation reviews the knowledge, beliefs and behaviors of the FDRs group for Taiwanese women with osteoporosis. The results of this work can be used to provide eﬀective implementation guidelines for preventing osteoporosis especially for women with a family history of the disease.

P762MO. CORRELATION BETWEEN BONE MINERAL DENSITY OF PREMENOPAUSAL WOMEN AND THEIR POSTMENOPAUSAL MOTHERS Messina OD1, de la Vega MC1, Riopedre AM1, Trobo R2; 1C Argerich Hospital – CIRO, 2Somer Hospital, Argentina Aims: To determine if premenopausal women with osteoporotic mothers have got lower BMD than those with mothers without osteoporosis. Secondarily: the relationship between dietary habits, activity, sun exposure, menarchae and fractures with BMD. Premenopausal women were recruited. They were 25 years old or more, without gynecologycal alterations. Those with any metabolic diseases , having any medication that interferes on bone metabolism or with impaired mobility were excluded. Their mothers were postmenopausal, 75 years old or younger, without metabolic diseases and not having medications for osteoporosis. BMD of mothers and daughters were measured by DXA (Hologic Delphi). A questionnaire about feeding and habits were completed. Osteoporosis was considered with a T score of –2.5 or lower in lumbar spine (LS) and/or femoral neck (FN). It was considered without osteoporosis the women with a Tscore of –1.5 or more in both regions. Proportions were compared with chi square test and T test for medias. A lineal multiple regression analysis was used to report the mothers‘ osteoporosis eﬀect, adjusted by others confounding variables. Results: 100 premenopausal women were evaluated. Seventy were included, according to inclusion and exclusion criteria. These women were distributed in two groups, according to their mothers BMD. 29 women had got mothers without osteoporosis and 41 had got mothers with osteoporosis. Demographic characteristics of both groups analyzed were similar. LS BMD of women whose mothers had got osteoporosis were significantly lower than LS BMD of women whose mothers had not osteoporosis Tscore –0.54 vs. Tscore +0.11, p=0.008 (IC 95% 0.17–1.15). This diﬀerence persisted after multivariate analysis, resulting that BMD of mother is an independent risk factor for low BMD in daughters. Other variables that correlated significantly with low LS BMD of daughters were: sitting hours (p:0.025), sunlight exposure (p:0.002) and menarchae (p:0.009). Correlation with age, feeding, exercise, fractures and tobacco were not significant. Diﬀerences between FN Tscore of both groups were not observed. Conclusions: Premenopausal daughters of mothers suﬀering osteoporosis have significantly lower BMD of LS than those daughters whose mothers do not suﬀer osteoporosis. Sunlight exposure, sedentary and menarchae are, significant independent variables related with low LS BMD

P763SA. ASSOCIATION BETWEEN OSTEOCALCIN GENE HIND III POLYMORPHISM AND BONE MINERAL DENSITY IN CHILDREN WITH JUVENILE CHRONIC ARTHRITIS Kostik MM1, Glazkov PB2, Vorontsov IM3, Larionova VI2; 1 Hospital Pediatric Department, 2Laboratory of Molecular Diag-

nostic, 3Department of Pediatry, Pediatric Medical Academy, Saint-Petersburg, Russia Osteopenia (OP), or low bone mineral density (BMD) for age, is a frequent complication in children with juvenile chronic arthritis (JCA). Osteocalcin is a biochemical marker that is often used in the assessment of bone turnover in OP patients. Previous studies have suggested an influence of osteocalcin gene Hind III alleles on bone metabolism. In the present study we investigated whether this polymorphism is related to BMD in JCA patients. Seventy JCA children (51 girls, 19 boys) were included in our study. The mean age of patients was 11.56 4.17 years. Osteocalcin gene Hind III polymorphism was tested in all patients by PCR. Uppercase letters represent absence, and lowercase letters represent presence, of gene restriction site. BMD was detected by dual-energy X-ray absorptiometry (Hologic QDR-4500C) in lumbar spine (L1-L4) with national reference database (L.A. Cheplyagina, 2005). Using the data of BMD we sorted the children into two groups: with OP - 13 children, 9 girls and 4 boys (18.7%) and without OP – 57 children, 15 boys and 42 girls (81.3%). For statistical analysis of the allelic frequency distribution in this polymorphism the two groups were compared using chi-squared test and Fishers exact test. Genotype and allele distributions are in underlying table. In children with hh genotype BMD (Z-score) was higher (p=0.01), when in carriers of HH and Hh. In girls BMD diﬀerences analogical (p=0.05). No diﬀerence in BMD and BA. Conclusion: We consider that Hind III osteocalcin polymorphic alleles and genotypes may be molecular genetic markers of high risk OP realization and they are suitable for OP predisposing and early prevention in JCA children. We also consider that h allele has some protective eﬀect in JCA girls from OP. Osteocalcin Hind III polymorphic genotypes and alleles distribution in JCA children with and without osteopenia. Boys

Girls

All children

Genotypes Total

with OP 4

without OP 15

with OP 9

without OP 42

with OP 13

without OP 57

HH Hh hh p Total H h p

2 (50,0%) 1 (25,0%) 1 (25,0%) 0,1 8 5 (62,5%) 3 (37,5%) 0,00003

1 (6,7%) 4 (26,7%) 10 (66,6%)

2 (22,2%) 3 (33,3%) 4 (44,5%) 0,06 18 7 (38,9%) 11 (61,1%) 0,06

1 (2,4%) 14 (33,3%) 27 (64,3%)

4 (30,8%) 4 (30,8%) 5 (38,4%) 0,005 26 12 (46,2%) 14 (53,8%) 0,04

2 (3,5%) 18 (31,6%) 37 (64,9%)

30 6 (20,0%) 24 (80,0%)

84 16 (19,0%) 68 (81,0%)

114 22 (19,3%) 92 (80,7%)

P764SU. ESTROGEN RECEPTOR GENE HAPLOTYPE IS ASSOCIATED WITH PRIMARY KNEE OSTEOARTHRITIS IN RUSSIAN POSTMENOPAUSAL WOMEN Krylov MYu, Kolesnik TV, Alexeeva LI, Myakotkin VA, Benevolenskaya LI; Institute of Rheumatology RAMS, Moscow, Russia Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis. To investigate the associations between ER gene polymorphisms and primary knee osteoarthritis (PKOA) a case-control study of Russian patients with PKOA (n=103) and healthy women (n=60) were used. Analysis of haplotypes to determine the relationship between two polymorphisms in the ER gene (intron 1 T/C, intron 1 A/G) and PKOA were studied. Genotypes of the ER gene polymorphisms were determined by PvuII PCR-RFLP for T/C and XbaI PCR-RFLP for A/G. There was no significant diﬀerence in the distribution of genotypes between PKOA patients and healthy control women. However, we found that the combined XxPP haplotype frequency was significantly diﬀerent between PKOA patients and control women (odds ratio = 6.5, 95% confidence interval = 1.48 - 59.73; P = 0.005). The significant diﬀerence in haplotype frequency between PKOA women and control women (degrees of freedom = 4, 2 = 15.9; P = 0.003) was evaluated. Although the number of PKOA patients studied is quite small, the present study shows that ER gene haplotypes may be involved in PKOA pathogenesis in Russian population.

S350

P765MO. ASSOCIATION BETWEEN ANTHROPOMETRY, BONE BIOCHEMICAL MARKERS AND OSTEOCALCIN GENE HIND III POLYMORPHISM IN CHILDREN WITH JUVENILE CHRONIC ARTHRITIS Kostik MM1, Glazkov PB2, Vorontsov IM3, Larionova VI2; 1 Hospital Pediatric Department, 2Laboratory of Molecular Diagnostic, 3Pediatric Department, Pediatric Medical Academy, SaintPetersburg, Russia The purpose of present study is to determine association between Hind III osteocalcin gene polymorphism and anthropometry and bone metabolism in chronic arthritis patients. Seventy JCA children (51 girls, 19 boys) were included in our study. The mean age of patients was 11.56 4.17 years. Osteocalcin gene Hind III polymorphism and serum levels of intact osteocalcin, -crossLaps, parathyroid hormone, Ca2+, phosphate, common alkaline phosphatase were tested in all patients. Uppercase letters represent absence, and lowercase letters represent presence, of gene restriction site. Boys, carriers hh genotype, had tendency towards lower body mass index than girls with hh (p=0.08). Children with hh had tendency to a more higher total calcium level than children with HH and Hh genotypes (p=0,065). Also hh boys had more higher levels of osteocalcin (p=0.005), -crossLaps (p=0.003) and total alkaline phosphatases (p=0.05). Conclusion: In our study we have revealed sex diﬀerences in bone metabolic markers dependent on Hind III osteocalcin gene polymorphic alleles and genotype. We consider that these polymorphic genetic markers diﬀerently influence bone metabolism and they are suitable for detecting osteopenia predisposition and early prevention.

P766SA. ASSOCIATION OF TAQI POLYMORPHISM OF THE VITAMIN D RECEPTOR GENE WITH LOW BMD AND FRACTURE OF PATIENTS WITH SEVERE ASTHMA RECEIVING LONG-TERM SYSTEMIC GLUCOCORTICOID THERAPY Moskalenko MV1, Putilin AM1, Baranova IA2, Aseev MV3, Demin NV4, Baranov VS3, Chuchalin AG1,2; 1Pulmonology Research Institute, Moscow, Russian Federation, 2Russian State Medical University, Moscow, Russian Federation, 3Ott’s Institute of Obstetrics & Gynecology RAMS, St-Petersburg, Russian Federation, 4Institute of Rheumatology, Moscow, Russian Federation Aim: To estimate the prognosis of undesirable action of systemic glucocorticoids (SGC) it is possible to carry out genetic testing for predisposition for the development of glucocorticoid-induced osteoporosis. To investigate in cross-sectional study the association between TaqI polymorphism of the vitamin D receptor gene (VDR), bone mineral density (BMD) and incidents of osteoporotic fractures in patients with severe asthma receiving long-term glucocorticoid therapy. Methods: 75 patients (22 men and 53 women aged from 18 to 50 years, premenopausal women) were included in analysis. BMD was measured at lumbar spine and proximal femur using dualenergy X-ray absorbtiometry (Hologic QDR-4500A). The TaqI polymorphism of VDR gene was studied by PCR-RFLP method (TT, Tt and tt genotypes; T and t alleles). Results: Median (lower and upper quartiles) of age was 43 (35; 47) years, daily dose of SGC – 10 (5; 15) mg/day, cumulative dose of SGC – 21.9 (8.2; 49.2) g. Patients with tt genotype had lower BMD (g/cm2, T-score and Z-score), more often fractures as compared to careers of TT (p<0.05 – for lumbar spine (L1-L4); p<0.001 – for femoral neck; p<0.0005 – for fractures, Fisher exact test) and Tt genotypes (p<0.005 – only for femoral neck) independently from age, daily and cumulative doses, duration of SGC use. Conclusion: Testing of TaqI polymorphism of the VDR gene will extend the possibilities of identifying patients at greater risk of glucocorticoid-induced osteoporosis.

P767SU. ASSOCIATION OF G2014A VARIANT IN EXON 8 OF ESTROGEN RECEPTOR-ALPHA GENE WITH OSTEOPOROSIS IN MEXICAN WOMEN Magana JJ1,2, Gomez MR1,2, Cisneros B2, Casas L1, Suastegui G1, Diez MP1, Valdes M1; 1Rehabilitation National Institute, 2 CINVESTAV-IPN, Mexico City, Mexico

Estrogen deficiency plays a major role in postmenopausal women, which is characterized by increased bone resorption and finally a possible development of osteoporosis. Among the mediators of estrogen hormone action, the genes encoding estrogen receptors have been considered as important candidates for the determination of osteoporotic risk. Estrogen receptor-alpha (ESR1) is diﬀerently expressed during osteoblast diﬀerentiation, implying its functional role in bone metabolism. Aims: To evaluate the relationship between ESR1 gene G2014A polymorphism and bone mineral density (BMD) in Mexican women. Methods: We examined the correlation between a G2014A single nucleotide polymorphism (SNP) in exon 8 of the ESR1 gene in 70 osteoporotic women, 70 non-osteoporotic women (control group) and 177 subjects from a Mexican general population, which were genotyped using the 5‘exonuclease assay. Lumbar BMD was measured using DXA only in osteoporotic and non-osteoporotic women. Results: We found that the allele frequency of the G allele was 78% in osteoporotic women, a value that was significantly higher than that of the non-osteoporotic women (64%) (p<0.05). The guanine homozygous (GG genotype) was 60% in osteoporotic women, a value that was significantly higher than that found in non-osteoporotic women (40%) (p<0.05). The risk to present osteoporosis increased successively from heterozygosis to homozygosis of the G allele. Therefore, the G allele and GG genotype were related to the presence of osteoporosis (odds ratio: 2.01 and 2.25, respectively). The loss of BMD and T-scores were compared between individuals who possessed one or two G alleles and those who did possessed the A homozygous. Subjects who possessed two or one G alleles had lower BMD and T-score average values than those who did not present any G allele (lumbar BMD: 79.86% , 84.59%, 87.08% and T-score: -1.88, - 1.26, -1.25, respectively). The importance of analyzing population genetics in a case-control study permitted us to associate adequately this polymorphism. Conclusion: The significant association observed between BMD and genetic variation at ESR1 gene implies that this polymorphism may be a useful marker for the genetic study of osteoporosis.

P768MO. CYP17 GENE POLYMORPHISM IS ASSOCIATED WITH BONE MINERAL DENSITY IN RUSSIAN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS Krylov MJ, Toroptsova NV, Nikitinskaya OA, Maslova KA, Myakotkin VA, Benevolenskaya LI; Institute of Rheumatology Russian Academy of Medical Sciences, Moscow, Russia The cytochrome P450c (CYP17) gene is located on chromosome 10q24.3 and encodes steroid 17-alpha-hydroxylase, which mediates both 17-alpha-hydroxylase and 17,20-lyase activity. It plays a key role in steroid hormone biosynthesis. Polymorphism of this gene in primary postmenopausal osteoporosis has not been investigated. Objective: To study the relationship of T/C polymorphism in the promoter region of CYP17 gene with bone mineral density (BMD) in patients with primary osteoporosis. Material and Methods: The CYP17 gene T/C polymorphisms was determined by PCR-RFLP in 69 postmenopausal osteoporotic women (mean age 68.6 years). BMD at L1-L4 (LS) and femoral neck (FN) were measured by DXA (Hologic QDR4500W). Results: Frequency distributions of CYP17 genotype in osteoporotic patients did not show significant diﬀerence from European populations. We found no significant correlation with LS and FN BMD in overall group of patients. However, after the stratification of patients by CYP17 genotypes the carriers of TC genotype (n=32) showed the association with BMD of LS and FN (r=0.41, p<0.05). In overall group of patients a weak correlation between BMD of LS and age (r=0.2) and negative correlation with BMD of FN (r=-0.32) were revealed. After the stratification by CYP17 genotypes the correlation coeﬃcient between LS BMD and age did not change. On the other hand we observed a significant increase of negative correlation between FN BMD and age for TC and CC genotypes (r=-0.22 and -0.71, respectively, p<0.05). Inside every genotype group a correlation coeﬃcient between BMD of LS and FN was respectively: in TT (r=0.1), in TC (r=0.41), in CC (r=0.15). The average values BMD of LS were significantly lower

S351 in TC genotype carriers than in patients with CC genotype (0.6900.045 vs. 0.7250.061). Conclusion: Our preliminary data indicate the role of CYP17 gene as a candidate gene in primary postmenopausal osteoporosis in Russian population.

P769SA. RELATIONSHIP OF GENE CANDIDATES VITAMIN D3 RECEPTOR AND COLLAGEN1ALPHA1 WITH BONE METABOLISM MARKERS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE Kochetkova EA1,2, Geltser BI1, Grigoreva OY2, Albavichus SA1, Bubnov OY1; 1Vladivostok State Medical University, 2Vladivostok department of Tomsk Institute Medical Genetic Siberian Branch of Russia Academia of Medical Sciences, Vladivostok, Russia Aim of study was to study relation of vitamin D3 receptor (VDR3) and collagen1alpha1 (COL1A1) gene polymorphisms in COPD. Methods: We investigated 62 patients with COPD. Condition of bone metabolism was estimated on blood osteocalcin (OC) and CrossLaps (CL) concentration by immunoassay method. BsmI polymorphism of length of restrictive fraction VDR3 (genotypes BB,Bb, bb) and Sp1 polymorphism COLIA1 (genotypes SS, Ss, ss) were studied using PCR. We analyzed the normal (B and s) and functional defective (b and S) alleles VDR3 and COL1A1. Control group consisted of 50 healthy patients at similar ages and sex. Results: We discovered significant diﬀerence between average indices of OC level in COPD with genotypes BB, Bb and bb (BsmI-polymorphism) (p%0.01). So, the maximal level of OC is marked in BB homozygote as in COPD as in healthy. Besides, more low level of CL consists with that allele. So, the maximal low OC concentration and increase of CL is associated with genotype bb. That phenomenon speaks about depression of bone formation and intensification of bone resorption. The diﬀerence between CL levels is found only for SS and Ss genotypes (p%0.01). Conclusions: A polymorphism VDR3 and COLIA1 gene has intimate relationship with bone metabolism markers in COPD and they are key genes in development of pulmonary osteopenic syndrome.

P770SU. THE INFLUENCE OF VITAMIN D RECEPTOR GENE POLYMORPHISM ON BONE MINERAL DENSITY AND BONE TURNOVER 1

1

1

1

Hossein-nezhad A , Haghpanah V , Maghbooli Z , Arami S , Shirzad S1, Ghaﬀari H2, Shoshtari P1, Larijani B1; 1Endocrinology and Metabolism Research Center, 2Hematology -Oncology and BMT Research Center, Tehran University of Medical Sciences, Tehran, Iran Aims: To determine association of vitamin D receptor (VDR) gene polymorphisms with bone mineral density (BMD) and bone turnover. Methods: We studied allelic frequencies of the FokI,BsmI, ApaI, and TaqI restriction fragment length polymorphisms (RFLPs) in 38 osteoporotic patients in comparison with 40 age-matched healthy pre- and postmenopausal women aged between 30 and 65 years, and correlated their bone mass with the VDR genotypes. Aﬀected criteria were include: T-score <-2.5 , Z-score <-1 and have a positive history of familial osteoporosis (in first degree). Genomic DNA was isolated from peripheral blood leukocytes according to standard methods. After an overnight fast, blood was taken for measurement of serum parathyroid hormone, 25hydroxyvitamin D, alkaline phosphatase, alkaline phosphatase, osteocalcin and cross laps. Bone measurements were performed with the same instrument (DXA, Lunar Corporation) in two regions (lumbar spine, total femur). Questionnaire was filled for all of participants that included information about general characteristics, dietary habits, drug, lifestyle, past medical history, sunlight exposure, menopausal status, age at menarche, age at menopause and other factors aﬀecting bone metabolism. Calcium and vitamin D intake estimated from a detailed food recall interview for the previous month.

Results: The most common VDR genotypes were Aa (52.5%), Bb (37.1%), FF(52.5 %), and Tt (47.4%). When the genotypes for all polymorphisms were combined, the most frequent were AaBbTtFF (21.8%) and aabbTTFF (10.2%). There were statistical diﬀerences in the allelic distribution of FokI and TaqI between osteoporotic patients and controls. After adjustment for age, BMI, calcium and vitamin D intakes, statistical associations were found between TaqI VDR gene polymorphisms and BMD and were weakly correlated with serum concentrations of osteocalcin, alkaline phosphatase. The vitamin D receptor gene alleles in other three genotypic groups were not associated with the serum concentrations of calcium or other biochemical values, calciotropic hormones, or markers of bone turnover. Conclusions: Vitamin D receptor gene alleles predict the bone density and bone turnover. Our results showed that a significant diﬀerence in frequency of the VDR allelic distribution in comparison with the Asian population. This finding is similar to Western populations.

P771MO. FOKI AND BSMI POLYMORPHISMS OF THE VITAMIN D RECEPTOR GENE AND BONE MINERAL DENSITY IN A RANDOM BULGARIAN POPULATION SAMPLE Ivanova JI, Doukova PD, Boyanov MB, Popivanov PP; Alexandrovska Hospital, Sofia, Bulgaria Numerous studies on vitamin D receptor (VDR) gene polymorphisms diﬀer with conflicting data in various populations. We studied the association of FokI and BsmI polymorphisms in the gene encoding the vitamin D receptor with bone mineral density (BMD) in 100 persons of Bulgarian nationality. The calculated relative risk (RR) for low bone mineral density is higher for FokI marker (3.14) compared to BsmI marker (2.44). The etiological factor which shows association between polymorphisms investigated and illness on populational level is defined as EF=0.51 for FokI marker and EF=0.42 for BsmI marker. On account of this we conclude that FokI and BsmI polymorphisms are closely related to low BMD at the forearm and lumbar spine. Both polymorphisms are useful genetic markers in determining BMD and osteoporosis risk. Further studies of larger cohorts and in ethnically diverse subgroups are necessary.

P772SA. STRONTIUM RANELATE STIMULATES MURINE OSTEOBLAST REPLICATION INDEPENDENTLY OF CALCIUM SENSING RECEPTOR-MEDIATED ERK1/2 ACTIVATION Fromigué O1, Barbara A1, Hay¨ E1, Petrel C2, Traiﬀort E2, Ruat M2, Marie PJ1; 1Inserm U606 & University Paris, 7, Hôpital Lariboisière, Paris, FRANCE, 2Cell and Molecular Neurobiology Laboratory, UPR 9040 CNRS, Gif-sur-Yvette, France Recent clinical trials showed that strontium ranelate is an eﬀective treatment for osteoporosis. We previously showed that strontium ranelate stimulates cell replication and type I collagen synthesis in rat or mouse osteoblastic cells. However, the cellular mechanisms by which strontium ranelate may act on osteoblasts are not fully characterized. We hypothesized that strontium ranelate may promote cell proliferation through activation of the membrane calcium sensing receptor (CaSR) expressed in osteoblasts. To test this hypothesis, we determined the eﬀects of strontium ranelate in osteoblastic cells isolated from wild type (CaSR+/+) and CaSR null (CaSR-/-) mice. Primary mouse calvaria pre-osteoblasts were obtained from the first and second collagenase digestions and used for DNA synthesis determination. We found that strontium ranelate and calcium (1–3 mM) increased DNA synthesis at 24–72 h in pre-osteoblasts from both CaSR+/+ and CaSR-/- mice, as evaluated by tritiated thymidine incorporation and BrdU ELISA assay. Activation of MAPKs ERK1/2 is an important signaling pathway acting downstream of CaSR, which is involved in the control of cell replication. We therefore determined whether strontium may activate ERK1/2 and whether this eﬀect is dependent on CaSR expression. In pre-osteoblasts from CaSR+/+ mice, calcium and strontium (0.5–10 mM) rapidly (10 min) and markedly (3-fold) increased phospho-ERK1/2 levels, as shown by

S352 western blot analysis. In contrast, calcium or strontium at the same doses had no eﬀect on phospho-ERK1/2 in pre-osteoblasts from CaSR-null mice, even after prolonged treatment for 30 min. These results show that 1) CaSR expression is not essential for the eﬀect of strontium ranelate on mouse calvaria pre-osteoblast replication, 2) strontium activates ERK1/2 via CaSR in primary preosteoblasts, and 3) the stimulatory eﬀect of strontium ranelate on pre-osteoblast replication is independent of CaSR-mediated ERK1/2 activation. This work shows that strontium ranelate can stimulate ERK1/2 via the CaSR in osteoblasts. However, the results obtained in the CaSR-null mice allow us to conclude that a receptor distinct from CaSR could also be involved together with CaSR in the strontium ranelate eﬀect on the pre-osteoblast replication in mouse primary calvaria cells.

P773SU. ANDROGEN RECEPTOR COORDINATES BOTH OSTEOBLASTIC DIFFERENTIATION AND MINERALIZATION Kang HY1,2, Huang CK1, Chang J1, Huang KE1; 1Center for Menopause and Reproductive Medicine Research, Chang Gung Memorial Hospital, 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan Androgens have important eﬀects on the human skeleton in both males and females. Hypogonadism in men is associated with increased bone turnover and bone loss, which is reversed after treatment with androgens. Clinical studies suggested that combined therapy of estrogens plus androgens might enhance bone mineral density and bone mass to a more significant degree than estrogen therapy alone in postmenopausal women. Our studies demonstrated that cancellous bone volumes are lower in the 8-week-old androgen receptor knockout (ARKO) mice than in both female and male wt littermates. These data indicate that AR is required for bone formation and prevents osteoporosis. To determine whether AR play a role in control of osteoblast diﬀerentiation and mineralization, we compared diﬀerentiation rates of primary calvarial cells isolated from wild-type and AR-null 3.5 days fetus in the presence or absence of DHT treatment by ALP activity assay, calcium deposition and Von Kossa stain. We also generated osteoblastic MC3T3-E1 cells in which over-expression of a stably integrated AR and knockdown expression of a stably AR siRNA to study the role of AR in osteoblastic cell diﬀerentiation. Our data showed that androgens accelerate cell diﬀerentiation of osteoblast cells in a time and dose dependent manner. Western blot analysis showed that the expression level of AR correlates with the duration of androgen treatment and degree of mineralization in osteoblasts. In addition, androgen promotes mineralization of primary calvarial cells isolated from wild-type mice but not from ARKO mice and AR-siRNA prevented DHTinduced osteoblast diﬀerentation. To further study the roles of AR on various diﬀerentiation stages of osteoblastic cells, the mRNA expression of AR, diﬀerent stage bone marker genes and AR targeted genes from long-term wild-type and ARKO osteoblastic cell cultures with or without androgens, were quantified using real time PCR. Our data indicates that the role of AR on mineralization is dependent on the diﬀerentiation stage of the osteoblasts and the duration of androgen treatment. Together, these findings strongly suggest that the AR signaling is required for androgenic eﬀects on bone metabolism, osteoblast diﬀerentiation and mineralization.

P774MO. MELATONIN SIGNALLING NEGATIVELY REGULATES OSTEOCLAST MATURATION AND ACTIVITY THROUGH TRANSCRIPTIONAL INHIBITION OF RANK EXPRESSION Azeddine B1, Forget S1, Wang DS1, Angeloni D2, Fraschini F3, Moreau A1,4; 1Research Centre, Sainte-Justine Hospital, Montreal, Canada, 2Scuola Superiore Sant’Anna and IFC-CNR, Italy, 3 Department of Pharmacology, University of Milan, Italy, 4Department of Stomatology and Biochemistry, Université de Montréal, Montreal, Canada Aims: Hormonal modulation of bone metabolism by melatonin signalling has been classically proposed to proceed through stimu-

lation of osteoblast diﬀerentiation and subsequent upregulation of osteoprotegerin (OPG) expression leading to inhibition of osteoclast activity. The goal of this study was to investigate the role of melatonin in osteoclastogenesis and how melatonin signalling selectively modulates osteoblast and osteoclast functions. Methods: Human osteoblast cell line MG-63 and human osteoclasts derived from the peripheral blood mononuclear cells were used to determine the localization and distribution of melatonin receptor subtypes MT1 and MT2 by immunohistochemistry using specific MT1 and MT2 antibodies. Gi proteins interacting with individual melatonin receptor subtypes were determined by coimmunoprecipitation (co-IP) assays. Melatonin eﬀect on osteoclastic resorption activity was evaluated with the pit resorption assay in presence of melatonin or in combination with MT2 melatonin receptor antagonists (luzindole or 4-PPDOT). RNA isolated from these cells was reverse transcribed and used to analyze the expression of OPG and RANKL in presence of melatonin or MT2 melatonin receptor antagonists. Results: We demonstrated the presence of MT1 and MT2 melatonin receptor subtypes in both osteoblasts and osteoclasts using co-IP. However, MT2 melatonin receptor was found as a predominant receptor subtype. Changes were observed in the preferential coupling and phosphorylation state of Gi proteins interacting with both receptors indicating that melatonin signalling is regulated by distinct mechanisms in osteoblasts and osteoclasts. Functional in vitro analysis showed that melatonin treatment of diﬀerentiating osteoclasts abrogated completely osteoclastogenesis and inhibited the formation of resorption pits by mature osteoclasts through the repression of RANK expression and induction of OPG expression. Similar assays in presence of melatonin antagonists, luzindole and 4-P-PDOT, demonstrated that such inhibitory eﬀect was mainly mediated through MT2 receptor activation. Conclusion: Collectively, these data define a novel and more direct mechanism whereby melatonin regulates osteoclast maturation and activity by inhibiting RANK expression in osteoclasts. Clinically, aging associated melatonin decline could lessen the inhibitory action of melatonin on osteoclasts, thus contributing to the senescence osteoporosis development or to the exacerbating of the pre-existing osteoporotic conditions in postmenopausal women.

P775SA. ALTERED DEVELOPMENTAL PATHWAYS AS NOVEL DRIVERS OF OSTEOPOROSIS IN PRIMARY HUMAN OSTEOBLASTS Butler JS1,2, Hurson C1,2, Murray D1, Sadlier D1, O’Byrne JM2, Doran PP1; 1General Clinical Research Unit, Dublin Molecular Medicine Centre, University College Dublin, Mater Misericordiae University Hospital, 2Dept. of Orthopaedic Surgery, Royal College of Surgeons in Ireland, Cappagh National Orthopaedic Hospital, Dublin, Ireland Introduction: Osteoporosis is a common systemic skeletal disorder characterised by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and propensity to fracture. After aging and sex steroid deficiency, therapeutic use of glucocorticoids is the third most common cause of osteoporosis. Glucocorticoids modify the proliferative and metabolic activity of bone cells. They inhibit osteoblastogenesis and osteoclastogenesis and reduce the lifespan of osteoblasts. They are also potent repressors of osteoblast function and probably stimulators of mature osteoclasts. Together, these changes lead to glucocorticoid-induced osteoporosis, mainly via reduced bone formation. Objectives: To assess gene expression profiles of primary human osteoblasts in the setting of dexamethasone exposure with a view to identifying key genes driving osteoporosis and to determine the eﬀect steroid exposure has on developmental pathways in the primary human osteoblast. Methods: We established primary cultures of human osteoblasts. Cell lines were grown in vitro and exposed to 10 ng/ml dexamethasone. To determine gene expression perturbations comparisons were made between control and 30, 60, 120 and 240 minute time exposures to dexamethasone. RNA isolation, cDNA synthesis, in vitro transcription and microarray analysis were

S353 performed. Validation of micoarray data was achieved by performing quantitative real time RT-PCR on the selected genes. Results: Global changes in gene expression are elicited by dexamethasone stimulation of primary human osteoblasts. Development associated gene pathways are co-ordinately regulated in primary human osteoblasts in response to dexamethasone exposure. The expression profile of key developmental genes of the Wnt Pathway are altered with reduced expression of pro-osteogenic Wnt genes and increased expression of Wnt antagonists. These results were validated by real time RT-PCR, confirming the fold changes in mRNA expression as observed by microarray analysis. Conclusions: Dexamethasone suppresses the Wnt pathway in primary human osteoblasts, resulting in reduced osteoblastic proliferation, reduced bone mineral density and ultimately osteoporosis.

cultured in a ‘near to natural’ 3D structure under a physiological loading pattern. Cylindrical biopsies precisely machined (10mm diameter, 5mm height) from young bovine sternum were fitted in culture chambers. Daily cyclic compressions (4000 µstrain, 1Hz, 5 min./days, jumping waveform) during 3 weeks induced greater Young Modulus associated to thicker trabeculae with a more plate-like shape in loaded compared to unloaded samples. Bone resorption (osteoclast histology, CTX level in the media, cathepsin K mRNA amount) was unaltered but bone formation (bone formation rate, Runx2 and osteocalcin expressions and protein levels) was stimulated in loaded bone cores. The system has thus the potential for reproducing in vitro what we saw in vivo making it an essential laboratory aid able to reduce animal experimentation. The system has potential for studying bone remodeling in normal and osteoporotic animal or human bone, bone biomechanics, and the eﬀects of drugs, hormones or growth factors on cancellous bone.

P776SU. SUPPRESSION OF ADIPONECTIN RECEPTORS BY SIRNA INHIBITS OSTEOBLAST-RELATED GENE EXPRESSION Ikeo T1, Kamada A1, Tamura I1, Goda S1, Takaishi Y1, Morii H2; 1 Department of Biochemistry, Osaka Dental University, 2Osaka City University, Osaka, Japan Aims: Adiponectin, a relatively abundant plasma protein secreted by adipocytes, exhibits various biological functions. Adiponectin receptor AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver, and they are known to mediate adiponectin stimulation. Previously, we reported that adiponectin increased the transcription of macrophage colony-stimulating factor (M-CSF) in osteoblasts, and suggested that the adipokine may be concerned in osteoblastic remodeling. In this study, we demonstrated the expression of adiponectin receptors in cultured osteoblasts, and investigated the influences of adiponectin on the osteoblast diﬀerentiation and mineralization using small interfering RNA against adiponectin receptors (siRNA-AR). Methods: Murine pre-osteoblastic cell line, MC3T3-E1 cells were cultured in a -MEM with 10% FBS. Two days after transfecting siRNA-AR, the culture medium was supplemented with ascorbic acid and -glycerophosphate to induce osteoblast diﬀerentiation. Total RNA was extracted from the cultured cells 2 days after ascorbic acid addition, and the mRNA expression level was measured using real-time quantitative RT-PCR technique. Results: RT-PCR analysis demonstrated the expression of both adiponectin receptors, AdipoR1 and AdipoR2 in osteoblasts. Both siRNA-AR1 and siRNA-AR2 suppressed the mRNA expression for M-CSF compared with non-silencing siRNA controls (p<0.01). Interestingly, both siRNA-AR1 and siRNA-AR2 also suppressed the ascorbic acid-dependent induction of mRNA expression of bone morphogenetic protein-2 (BMP-2) and osteopontin, which are known to stimulate osteoblast diﬀerentiation and bone formation (p<0.01). Conclusions: These results indicate that adiponectin may be involved not only in osteoblastic remodeling but also in osteoblast diﬀerentiation through its receptors on osteoblasts. Supported by Grant-in-Aid for Scientific Research (C)(16591877)

P777MO. IN VITRO LONG-TERM CULTURE OF CANCELLOUS BONE EXPLANTS UNDER PHYSIOLOGICAL STRAIN REGIMEN David VN1, Guignandon A1, Jones DB2, Vico L1; 1INSERM E366 Fac Medicine, St-Etienne University, France, 2Experimental Orthopaedics and Biomechanics, Philipps, Marburg University, Germany The bone adaptation to its mechanical environment is largely described but, mechanotransduction at the bone tissue level remains uncertain. To study coordinated bone cellular responses and the resulting tissue alteration while avoiding systemic regulation, we used a new tissue culture model: the ZetOSTM system. It comprises culture chambers where defined culture media passed through cancellous bone cores without any shear stress and a loading device which can apply physiological levels of strain of various waveforms and amplitudes. The system allows bone to be

P778SA. THE RATIO OF OSTEOCLAST ACTIVITY/OSTEOCLAST NUMBER (CTX/TRACP 5B) IMPROVES THE INTERPRETATION OF THE EFFECTS OF ANTI-RESORPTIVE COMPOUNDS IN HUMAN OSTEOCLAST CULTURES Rissanen JP1, Suutari S1, Ylonen S1, Baugh M2, Long C2, Halleen JM1; 1Pharmatest Services Ltd, Turku, Finland, 2Organon Laboratories, Newhouse, Scotland We studied the use of two bone resorption markers, serum C-terminal cross-linked telopeptides of type I collagen (CTX, a marker of osteoclast activity), and serum tartrate-resistant acid phosphatase isoform 5b (TRACP 5b, a marker of osteoclast number), in human osteoclast cultures. CD34-positive osteoclast precursor-cells were cultured on bovine bone slices for 7 days in the presence of M-CSF and RANKL, allowing their diﬀerentiation into bone-resorbing osteoclasts. At day 7, the culture medium was changed and test compounds were added. A baseline group without added compounds, a control group with the reference inhibitor E64 and groups with 7 diﬀerent concentrations of two potential resorption inhibitors named as resorption inhibitors A and B were included in the study. The formed osteoclasts were cultured for an additional 3 days, allowing them to resorb bone in the presence of the test compounds. TRACP 5b was measured from the culture medium collected at day 7 as an index of osteoclast number. At day 10, CTX was measured from the culture medium as an index of osteoclast activity during days 7–10. CTX and TRACP 5b were measured using commercial immunoassays. The reference inhibitor E64 significantly decreased medium CTX. The second lowest test concentration of compound A as well as the two lowest test concentrations of compound B showed decreased CTX in the medium compared with baseline CTX levels. However, TRACP 5b values at day 7 were lower in these three groups, suggesting that the decreased CTX values at day 10 were due to the presence of lower number of osteoclasts in these groups before the addition of the test compounds. CTX values were divided by TRACP 5b values to obtain a resorption index calculated per osteoclast. The resorption index was dosedependently decreased by both compounds A and B. These results demonstrate that the resorption index (CTX/ TRACP 5b) is a useful endpoint measurement in human osteoclast cultures when studying the eﬀects of test compounds on osteoclast activity, preventing variable results caused by the presence of diﬀerent number of osteoclasts in diﬀerent test groups before adding the test compounds.

P779SU. THE EFFECTS OF GLYCITEIN ON OSTEOCLAST GENERATION Winzer M1, Rauner M1,2, Hofbauer G1,2, Wahl K1, Pietschmann P1; 1Center of Physiology and Pathophysiology, Medical University of Vienna, 2Ludwig Boltzmann Institute of Aging Research, Vienna, Austria Background: The isoflavones glycitein and genistein are plantderived, nonsteroidal molecules showing estrogenlike eﬀects in humans. These eﬀects are mainly explained by the interaction with estrogen-receptors and may prevent postmenopausal bone loss. As

S354 single isoflavones diﬀer with regard to their biological eﬀects, our aim was to study the eﬀects of the very poorly investigated glycitein. Methods: Bone marrow cells from four to eight weeks old female mice were cultured in the presence of 10-8 M of 1,25dihydroxyvitamin D3 for 7 days. The number of osteoclast-like cells was determined by staining for tartrate-resistant acid phosphatase (TRAP), a marker enzyme of osteoclasts. Furthermore, the activity of caspase 3 and caspase 7 was measured by a fluorometric assay. Results: The number of multinucleated TRAP+ cells induced by 1,25-dihydroxyvitamin D3 (10-8 M) was significantly decreased by glycitein (10-8 M) (p%0.05, n=12). The apoptosis assay showed a significant increase of caspase 3/7-activity in the presence of glycitein (10-8 M) (p%0.01, n=4). Conclusions: Data reveal that the stimulating eﬀect of 1,25dihydroxyvitamin D3 on osteoclast diﬀerentiation is significantly inhibited by glycitein. This eﬀect is at least in part caused by inducing apoptosis in osteoclast-like cells and/or stromal cells. This study indicates that glycitein may reduce bone loss due to decreased bone resorption.

P780MO. PROPRANOLOL PROMOTES OSTEOGENIC DIFFERENTIATION OF MICE BONE MARROW STROMAL CELL IN VITRO Zhang ZL; Radiation Medicne and Public Health School of Soochow University, Suzhou, China Beta-blockers are widely used for the management of cardiovascular disease and may have the dual benefit of increasing bone mass density. More and more data suggest that beta-blockers stimulate bone formation and inhibit bone resorption. To explore the mechanism underlay this phenomenon, the eﬀects of propranolol on diﬀerentiation of mouse bone marrow stromal cell was investigated. Bone marrow cells were isolated from four-week old mice and cultured in DMEM medium. Propranolol were applied at diﬀerent concentration 10–10M,10–9M,10–8M,10–7M. At concentrations of 10–10M and greater, propranolol produced a dose-dependent increase in cell number and [3H]thymidine incorporation in cultures of bone marrow stromal cells. Compared with control group, alkaline phosphatase activity of bone marrow stromal cells was increased in all treatment groups, and its value was significantly higher in 10–7M group than other groups. Propranolol treatment upregulated several osteoblast-specific genes, including collagen type I and osteocalcin, enhanced biological mineral deposition. It is concluded that propranolol had the capacity to promoted osteogenic diﬀerentiation of mice bone marrow stromal cell and enhanced capacity of mineralization of bone marrow stromal cells and contribute to the prevention and treatment of osteoporosis.

P781SA. BONISTEINY, A SYNETHIC ISOFLAVONE, SIGNALS VIA THE ESTROGEN RECEPTOR ALPHA PATHWAY IN HUMAN OSTEOBLASTS Heim M, Sochocky N, Fuchs P, Pennimpede T, Riegger C, Weber P, Bendik I; DSM Nutritional Products Ltd, Basel, Switzerland Estrogen deficiency in women after menopause is associated with an increased risk of osteoporosis. Hormone replacement therapy reduces the incidence of osteoporosis in women but increases the risk of breast cancer. The problem may be overcome by selective estrogen receptor modulators (SERMs) that display tissue specific actions. The phytoestrogen genistein, BonisteinTM, has no estrogenic eﬀect on the uterus but prevents bone loss in ovariectomized rats and in early postmenopausal women. Both estrogen and BonisteinTM, stimulate osteoblasts to upregulate the expression of osteoprotegerin (OGL), a cytokine that prevents osteoporosis. In the present study we established cultures of human osteoblastic cells (hOB) in order to determine whether this bone protective eﬀect of estrogen and genistein is mediated by the same or by diﬀerent estrogen receptors (ERs). The hOB cells expressed ER and three ER splice variants, ER5 and at much lower levels ER1 and ER2. Targeted inactivation of ER by short interfering RNA (siRNA) was used to generate hOB cells that expressed

the ER splice variants but not ER. In contrast to untreated cells ER deficient cells failed to upregulate OGL as well as collagen production in response to estrogen and BonisteinTM. We conclude that BonisteinTM, shares with estrogen at least one important mechanism of bone protection.

P782SU. EFFECTS OF LIGUSTILIDE ON ADIPOGENESIS OF MARROW STROMAL CELLS IN VITRO Tian JW, Li GS; School of Pharmacy, Yantai University, China Aim: To investigate the eﬀects of ligustilide on the diﬀerentiation of marrow stroma cells into adipocytes in vitro. Methods: We used the marrow stroma cells isolated from the intact rats and rats treated with either prednisone or other drugs. Three month old SD male rats received 3 mgckg-1cd-1 of prednisone oral gavage, or prednisone plus ligustilide at dose of 50 mgckg-1, or prednisone plus compound recipe calcium carbonate. At the end-point, the marrow stroma cells were isolated by density-gradient centrifugation and cultured. The adipocytes were stained with oil-red-O stain and counted, and mRNA expressions of lipoprotein lipase were examined by RT-PCR. Results: Through density-gradient centrifugation isolation and subculture attachment selection the cultured marrow stroma cells became more purified. Ligustilide prevented adipogenic diﬀerentiation of marrow stroma cells in prednisone-treated rats by decreasing adipocyte number and downregulating lipoprotein lipase mRNA expression. Ligustilide prevented adipogenesis of marrow stroma cells more potently than compound recipe calcium carbonate. Conclusion: Ligustilide provided more predominant opportunities with which to prevent adipogenic diﬀerentiation of marrow stroma cells isolated from the rats treated with prednisone compared with compound recipe calcium carbonate.

P783MO. OSTEOSARCOMA DEVELOPED ON OSTEOMALACIA BACKGROUND: A CASE REPORT Konuralp Nilnur, Sendinc Berrin, Ozguzel Hayri; Okmeydani Education and Research Hospital, Istanbul, Turkey Oncogenic osteomalacia is a clinical syndrome characterized by hypophosphatemia, decreased 1,25(OH)2D and elevated alkalen phosphatase (ALP) levels associated with a tumoral formation. Although relevant tumours are usually benigne and of mesenchymal origin, some cases with malignant tumours have been reported. We are presenting a case that we treated due to osteomalacia and after four years osteosarcoma at femur distal end has been recognised. A white, 14 year old female covering herself with a scarf because of her religious believes came to our clinic with signs of pain in both legs and diﬃculty during walking. Blood research showed high ALP (5380 U/L), low calcium (Ca=7.8 mg/dL) and normal phosphate (PO4=3mg/dL) levels. Skeletal system radiographies showed generalized osteopenia, coarsened trabeculae and Looser lines vertical to cortex on pubic and ischial bones. After diagnosis of osteomalacia patient was treated by 0.5 µg 1,25(OH)2D and 500 mg Ca daily. Laboratory findings got back to normal in six months following this medical treatment. After four years the patient returned with the complaints of edema, pain and limited motion of her left knee. Blood ALP was high (1610 U/L), Ca and PO4 levels were normal. Magnetic resonance research of the knee pointed out osteosarcoma formation at distal end of the femur. Histologic diagnosis was verified as osteogenic osteosarcoma by biopsy. In oncogenic osteomalacia symptomatic period before diagnosis of tumour is above an average of four years and delay up to 12 years was reported. Our case has some sides contradictory to hypophosphatemic oncogenic osteomalacia. We know that hypophosphatemia accompanying osteomalacia develops in a huge manner in the result of secondary hyperparathyroidism. In our case we think that the medical treatment given four years before prevented secondary hyperparathyroidism development and therefore hypophosphatemia was not seen.

S355 Transformation of basal epidermal cells in cutaneous tissue and mononuclear cells in bone tissue to osteoclasts occurs via the peresence of 1,25(OH)2D. We reached an opinion that it is a

subject needed to be investigated whether in the deficiency of 1,25(OH)2D interruption of these cells development process is related to oncogenic osteomalacia or not.

Poster Presentation Abstracts

Recommend Documents