Osteoporos Int (2007) 18 (Suppl 1):S29–S175 DOI 10.1007/s00198-007-0333-0

Poster presentations abstracts © International Osteoporosis Foundation and National Osteoporosis Foundation 2007

P100. Calcium and vitamin D administration for postmenopausal osteoporosis treatment in rheumatology. A French national prospective survey R.-L. Dreiser1, Ph. Coste2; 1Bichat Hospital, Paris, France, 2 Expanscience Labs, Courbevoie, France Background: Calcium and vitamin D efficacy for fracture’s prevention has been demonstrated(1, 2, 3) and prevention of calcium and vitamin D déficiencies is recommended prior to osteoporosis treatment outset.(4) Objective: Describe the circumstances of primary administration of calcium/vitamin D association by the French rheumatologists in postmenopausal osteoporosis treatment as well as treatment details (dosage, duration). Method: National prospective epidemiological survey among the French rheumatologists. Eighty-four rheumatologists described 339 postmenopausal patients requiring calcium/ vitamin D association for postmenopausal osteoporosis treatment. Materials: age, size, weight, bone-densitometry, fracture’s history, treatment details (dosage, duration). Statistical analysis: percentages, mean scores, standard deviation. Results: 1. Patients characteristics: 339 patients has been described: mean age 68.2 years. (±10), mean weight 62.1 kg (±11), mean size 159.5 cm (±7.2), mean menopausal age 49.8 years. (21–63). Table 1: Bone-densitometry Achievement Normal result Osteopenia Osteoporosis (T-score ≤2.5 SD)

85% 2% 34% 64%

Table 2: Fracture’s history Occurrence Vertebra Wrist Hip Wrist + vertebra

49.3% 49.7% 47.9% 14.37% 13.17%

2. Calcium/vitamin D association Table 3: Administration’s circumstances Calcium eating deficiency Postmenopausal patients without HRT Association with osteoporosis treatment Biphosphonats 53.1% Raloxifen 10.03% HRT 2.65% Proved osteoporosis (positive bone-densitometry)

77.88% 75.81% 67.85%

52.21%

Table 4: Treatment details Calcium/vitamin D association Dosage per day: calcium 1g+vit D 800 UI Mean treatment duration

96% 72% 5.6 months (±3.4)

Table 5: Dosage’s differences depending on bone-densitometry result

Calcium (mean, SD) Vitamin D (mean, SD) Duration (mean, SD)

None or normal

Osteopenia

Osteoporosis

900 mg (199)

890 mg (208)

962 mg (134)

690 UI (190)

695 UI (182)

738 UI (153)

5.6 months (4.1)

6.1 months (3.4)

5.4 months (3.2)

Conclusions: Bone-densitometry was carried out for 285 patients and revealed osteopenia or osteoporosis in 275 cases. Fracture’s history was reported in 167 cases (wrist 48%, vertebra 50%). The two more common grounds for calcium/vitamin D association’s administration are calcium eating deficiency (78%) and association with an osteoporosis treatment (68%), predominantly biphosphonats. For postmenopausal osteoporosis treatment, French rheumatologists prescribe calcium/vitamin D association in 96% of cases, at 1 g/day calcium dosage and 880 UI/day vitamin D dosage predominantly (71% of cases) with a treatment duration superior to 5 months.

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Depending of bone-densitometry results, calcium dosage is superior when osteoporosis is proved. (1) Cormier C (2004) Osteoporosis prevention. Outcome at dawn on 2005. Rhumatos 1:63–67 (French) (2) Chappuy MC et coll (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. NEJM, 327:1637–1642 (3) Chappuy MC et coll (1994) Effect of calcium and colecalciferol treatment for three years on hip fractures in elderly women. BMJ, 308:1081–1082 (4) AFSSAPS’s recommendations. Medical treatments of postmenopausal osteoporosis. October 2004 update (French) This work was supported by Expanscience Labs (Courbevoie, France).

P101. Adjacent fractures in the thoracic and lumbar spine after Balloon-Kyphoplasty in the treatment of osteoporotic fractures — 2 year prospective follow-up R. Pflugmacher, P. Schleicher, N.P. Haas, I. Melcher; Centrum für Muskuloskeletale Chirurgie, Charité Universitätsmedizin Berlin, Berlin, Germany Objectives: To evaluate the long-term outcomes of 57 patients with 87 osteoporotic vertebral fractures, located in the thoracic and lumbar spine, treated with Balloon Kyphoplasty. Materials and methods: 63 patients (20 males and 43 females) with 96 osteoporotic vertebral fractures were treated with Balloon Kyphoplasty. We were able to have a 2 year follow up in 57 patients with 87 vertebrae treated. Symptomatic levels were identified by correlating the clinical presentation with conventional radiographs, CT and/or MRI. During the 2 year follow-up reduction in pain was determined. The effects on pain symptoms were measured on a self-reported Visual analog Scale (VAS) and the Oswestry score was documented to assess disability. Radiographic scans were performed pre- and postoperatively and after 3, 6, 12 and 24 months. The vertebral height and kyphosis angle were measured to assess the restoration of the sagittal alignment. Results: The median pain scores (VAS) improved significantly from pre- to post-treatment as did the Oswestry Disability Score (p<0.001).This improvement was maintained at 2 year follow up. In nine patients (15.8%) (6 female, 3 male) an adjacent fracture occurred in 12 vertebrae (13.8%) within 2 weeks to 22 months follow-up. In four patients the adjacent fractures were asymptomatic. Five patients with symptomatic adjacent fractures were treated again with Balloon Kyphoplasty. Clinically asymptomatic cement leakage occurred in 12 of 96 vertebral bodies (12.5%). During 2 year follow-up this surgical technique demonstrated restoration and stabilization of the height of the vertebral body. Conclusion: Balloon Kyphoplasty is an effective minimal invasive procedure for the stabilization of osteoporotic vertebral fractures leading to a statistically significant reduction of pain status.

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P102. Two year prospective follow-up after BalloonKyphoplasty in the treatment of spinal metastasis R. Pflugmacher, K.D. Schaser, P. Schleicher, N.P. Haas, I. Melcher; Centrum für Muskuloskeletale Chirurgie, Charité Universitätsmedizin Berlin, Berlin, Germany Objectives: To determine the long-term efficacy of percutaneous Balloon-Kyphoplasty in treating thoracic and lumbar spinal metastases that result in pain or instability. Materials and methods: Forty-six patients (27 men, 19 women; aged 52–85 years) underwent 78 percutaneous Balloon-Kyphoplasty procedures. Preoperatively conventional radiographs in lateral and a.p. view, CT and/or MRI were preformed. Pre- and postoperatively the clinical parameters VAS (Visual Analog Scale) and the Oswestry score were evaluated. Radiographic scans were performed pre- and postoperatively and after 3, 6, 12 and 24 months. The vertebral height and kyphotic deformity were measured. Results: The median pain scores (VAS) (p<0.05) as well as the Oswestry score (p<0.05) improved significantly from pre- to post-treatment. The Balloon-Kyphoplasty was able to have a significantly long lasting reduction of pain and improvement of physical. A slight restoration of vertebral height and reduction of the kyphotic angle could be achieved with the balloon technique. The Balloon-Kyphoplasty was able to stabilize the vertebral height and avoid a further kyphotic deformity in the long term. A radiation therapy and/ or chemotherapy could be performed without loss of time. Conclusion: Balloon-Kyphoplasty of metastases is a minimally invasive procedure that provides immediate and long-term pain relief and contributes to spinal stabilization. P103. Osteoporosis in males: are we referring enough for DXA and how? H.M. Al Attia, B.K. Adams; Departments of Internal and Nuclear Medicine, Mafraq Hospital, Abu Dhabi, United Arab Emirates Objective: To determine the pattern of male referrals to an osteodensitometry unit in a tertiary hospital in United Arab Emirates (UAE). Materials and methods: We reviewed the records of male patients referred for dual X-ray absorptiometry (DXA) over a 9 month since the establishment of the unit. Indications for scanning were listed and categorized into high and medium risk and infrequent causes of osteopenia/osteoporosis. They were ranked according to frequency. The outcome was documented by category with normals being taken as bone mineral density (BMD) of over 0.82 g/cm2, osteopenia of between 0.60 and 0.82 g/cm2 and osteoporosis as a value below 0.60 g/cm2 for hips and lumbar spine. The site with the lowest value was taken as representative of the patient’s BMD status.

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Results: The age of the patients ranged from 16 to 91 years (mean of 55.2 years). Male referral made up 8.8% (71/805) for the total period. The total number of indications was 83 accounting for 1.16 per patient. The most common reasons for referral were patients on corticosteroids therapy (20.5%) followed by bone rarefaction on radiographs (13%) and fragility fractures (12%). Others included back pain, general aches and pains, querying the presence of osteoporosis and miscellaneous causes made up 8.5% each. These were followed by immobilization (6%) and arthropathies (6% each), excess alcohol intake (3.5%), ageing (2.5%) and hepato-renal disorders (2.5%). A positive family history of osteoporosis, treatment for neoplasia, smoking and chronic obstructive airway disease (1% each) were the least common reasons for referral. Thirty five patients (49%) had osteopenia, 16 (22.5%) had osteoporosis and 20 (28%) were normal. Conclusions: The low referral rate of males for DXA and relatively high normal outcome among men suggest that osteoporosis is still viewed as a disease of females. Although there appeared to be some awareness of certain important causes of osteoporosis other significant ones were rarely acknowledged. This aberrant referral pattern when viewing the majority of indications reflects an inability to prioritize the reasons for referral. It is prudent, therefore, to instill an awareness of the increasing importance of osteoporosis in men in the minds of the referring clinicians. Also, we join a still somewhat muted chorus calling for greater attention to be paid to the risk factors in males and for their speedy referral for DXA so as to facilitate timely diagnosis and treatment. P104. Surveying the scope and source of knowledge of osteoporosis in the females: an experience from the United Arab Emirates (UAE) H.M. Al Attia1, A.A. Abu Merhi2; 1Departments of Internal and Nuclear Medicine, Mafraq Hospital, Abu Dhabi, United Arab Emirates, 2Gynecology-/Obstetric Department, Al Noor Hospital, Abu Dhabi, United Arab Emirates Objective: To assess the knowledge of osteoporosis (OP) in relation to levels of education in women attending Obstetric/Gynecology for reasons other than OP and to compare their outcome to that of men attending department of Internal Medicine. Patients and method: Three hundred seventy-eight females and 84 males agreed to participate in this exercise. Their response(s) as to how much they know about OP was matched through a pre-prepared sheet of 11 OP-specific items covering a wide range of information on the disorder including: A B C

disease of aging disease of menopause or post menopause low bone density (BMD)

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D E F G H I J K

related to low calcium and vitamin D intake drugs-induced such as corticosteroids etc./excess alcohol intake etc. induced by immobilization/lack of exercise related to chronic diseases such as rheumatoid arthritis and other conditions related to excessive intake of caffeine/fizzy drinks disease of easily fractured bones may lead to bony deformities any knowledge on treatment such as calcium, vitamin D, biphosphonate etc.

A minimum score of two items or more would then qualify the individual to indicate her(his) source(s) of information. A list of ten possible sources including direct information from the below was prepared for that purpose: 1 2 3 4 5 6 7 8 9 10

relatives/friends doctors/nurses whether the patient was him or herself suffering from OP through personal professional education from the press (magazines/newspapers) reading books on OP watching television (TV) listening to radio programs internet other sources such as seminars, pamphlets etc.

Illiterate and those with primary schooling were doomed as uneducated. Results: Three hundred seventy-eight predominantly, educated Arab women; 186 with high education (49%), 172 (45.5%) with secondary schooling and 20 (5.5%) uneducated, and 84 (62 educated and 22 uneducated) men were invited to this exercise. Males were older with an average age of 43.2 vs females of 28.8 years. The 0–1 score was documented in 31.5% of educated women compared to 55% in the uneducated p= 0.19. The average of correct items expressed by the educated women was 2.12 per patient. Highly educated women had significantly less 0–1 score (37/186, 20%) than that expressed by others with 2 ry schooling (74/172, 44%), p=0.001. The average of correct items was 2.5 in highly educated women compared to 1.69 in others with 2 yr schooling, p=0.002. A maximum of six items was reported in the former subgroup vs five in the latter. “Osteoporosis as a disease of menopause women (B)” had the highest score (85 vs 82.5%, p=NS) among the educated women subgroups, respectively. Items G, H and J identically, were not acknowledged. This parallel way of thinking between these two subgroups has extended to the sources whereby the press (84 and 83%, respectively, p=NS) (5), TV programs (61 and 56%, respectively, p=NS) (7) and friends

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and relatives (38 and 46%, respectively, p=NS) (1) appeared to be the main sources of their information. A noticeable paucity to an absence of information from the internet (9 and 3%, respectively, p=NS) (9), reading books on OP (0% each) (6) and listening to radio programs (0% each) (8). Only 2% in each subgroup were themselves OP patients (3). Uneducated males (22) were excluded from analysis because of their extremely poor performance (17/22, 76% had zero knowledge and only three managed to expressed two items). A limited knowledge was also encountered among the educated ones with a high 0–1 score of 47/62 (76%) and low average of correct responses of 0.8 per patient. These figures were significantly different when compared to those of their female counterparts (p=0.001 and 0.0001, respectively). The remaining 15 (24%) saw OP as “a disease related to low calcium and vitamin D” (D) as their first choice (60%) to be followed by equal expression of 53.5% each on “disease of aging” (A) and “of menopause” (B). Significant discrepancies in other items to those of females were also noted. Males totally, lacked awareness of items G, J and K. Conclusions: The overall status of knowledge was modest in this eye-opening exercise. The female gender and high level of education have significantly influenced the results but males had an obvious inadequate knowledge about the disorder. Osteoporosis remains largely preventable hence; measures are to be seriously considered on how to enhance upon the current understanding of it and on the means of delivering the knowledge. It is perhaps no longer appropriate to turn a blind eye to the presence of the extrapolated realities. P105. The relationship between osteoporosis risk factors and parameters obtained by heel ultrasonometry K. Simic Pasalic1, N. Pilipovic2; 1Railway Health Care Insitute, Belgrade, Serbia, 2Institute of Rheumatology, Belgrade, Serbia Background: Quantitative ultrasound (QUS) is accepted as an effective, low cost method to identify women likely to have osteoporosis (OP), with similar potential in the fracture prediction as central DXA measurements. Objective: To evaluate the impact of osteoporosis risk factors (RF) on parameters obtained by heel ultrasonometry. Materials and methods: Quantitative ultrasonometry of os calcis was performed on Hologic Sahara device at 502 women who took part in screening campaign of bone status. We took the data on age, time since menopause, irregular cycles, personal and family history for osteoporosis or fracture in adulthood, lifestyle, cigarette smoking, consumption of the drugs and presence of diseases relevant for bone metabolism, measured height and weight of each woman.We analysed the effect of each risk factor on quantitative ultrasound index (QUI), estimated BMD (g/cm2), T and Z score (SD) obtained

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by ultrasonometry. The relationship between each clinical RF on parameters obtained was analysed by student’s t test or Pearson’s test, as appropriate. Results: Out of 502 women, 476 (94.8%) were postmenopausal. The mean age was 58.44 (24–83±9.56) years, menopause duration was 11.43 (0.5–47±9.31) years, average BMI was 28.l (18–46±10.2) kg/m2. Fragility fracture after age of 40 had 79 (15.7%). A significant inverse correlation was observed between age, time since menopause as clinical RF and QUI, est. BMD, T score but not Z score. Only among women beyond 65 years, Z score was significantly lower. High impact on Z score was observed in RF as early menopause (before 45 years), low Ca intake, loss of height and chronic glycocorticoid treatment, but not on other parameters obtained. Cigarette smoking, poor vision, chronic sedative use were significantly correlated with QUI, est. BMD and T score, not with Z score. No relevant relationship between irregular cycles, low BMI, fragility fracture in adulthood and any ultrasonometry parameter was observed. Only concomitant diseases relevant for OP and family history for OP or fracture proved to exert an important effect on all four parameters. Conclusion: With various correlations as here observed, no definitive statement can be made. Still QUS is a promising tool for assessment of bone status, and combination of RF and QUI, est. BMD can increase sensitivity of any fracture risk evaluation. P106. Osteoporosis in young Human T-cell Lymphotropic Virus type I (HTLV-I) carriers: a new incapacity disease for a neglected population A. Silva-Santos1, C. Carneiro de Campos1, S. Gadelha2, N. Boa-Sorte12, C. Nunes1, B. Galvão-Castro1,2; 1HTLV Center/Bahiana School of Medicine and Public Health/ Sciences Development Foundation, Bahia, Brazil, 2 Advanced Laboratory of Public Health/Gonçalo Moniz Research Center/Oswaldo Cruz Foundation, Bahia, Brazil Objective: To estimate the incidence of bone disorders in young HTLV-infected asymptomatic patients. Materials and methods: Between April and November 2005, 47 HTLV-I asymptomatic subjects derived from a state surveillance system of HTLV infection set up in Salvador, Bahia, Brazil (HTLV Center) and 108 healthy subjects were enrolled in the study. Inclusion criteria were an age of 20–45 years. Biochemical markers of bone metabolism were measured and bone mineral density (BMD) was determined at the femoral neck and at the lumbar spine (L1–L4). Results: Of the HTLV-infected patients, 31.91% had reduced BMD, compared with 11.11% of the control subjects. In logistic regression analysis among all subjects, HTLV infected patients were significantly more likely to have osteopenia

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(odds ratio 3.75; CI 95% 1.59–8.85) controlling for height, gender masculine and less than 10 years of formal education. Conclusion: This is the first report of reduced bone density among otherwise healthy, ambulatory HTLV-infected carriers. HTLV-infected subjects were 3.75 (1.59–8.85) times more likely to have osteopenia as compared to healthy control subjects. Lower bone density may predispose HTLV-infected subjects to increased morbidity and further bone loss with aging. P107. Calcium and vitamin D administration in general practice R.-L. Dreiser1, Ph. Coste2; 1Bichat Hospital, Paris, France, 2 Expanscience Labs, Courbevoie, France Background: Calcium and vitamin D efficacy for fracture’s prevention has been demonstrated(1–4) and prevention of calcium and vitamin D déficiencies is recommended prior to osteoporosis treatment outset.(5) If general practionners are often confronted with situations where administration of calcium/vitamin D association is required, the conditions of their prescription are unknown precisely. Objective: Describe the circumstances of primary administration of calcium/vitamin D association by the French general practionners as well as treatment details (dosage, duration). Methods: Prospective epidemiological survey among the French general practionners (GP). 1,401 GP described 2,791 patients requiring calcium/ vitamin D association for senior’s calcium or vitamin D deficiency, osteoporosis treatment or high risk situation of calcium or vitamin D deficiency. Materials: age, size, weight, bone-densitometry, fracture’s history, treatment details (dosage, duration). Statistical analysis: percentages, mean scores, standard deviation. Results: 1. Patients characteristics 2,791 patients has been described: mean age 67.6 years (±9.9), women (92%) and post-menopausal (97%) by a majority, mean weight 65.6 kg (±11.1), mean size 162 cm (±7.1).

Table 1: Bone-densitometry Achievement Normal result Osteopenia Osteoporosis (T-score ≤2.5 SD)

61% 5% 40% 55%

Table 2: Fracture’s history Occurrence Wrist Vertebra Hip

43% 50.9% 39.2% 15.9%

2. Calcium/vitamin D association Table 3: Administration’s circumstances Postmenopausal patients without HRT Calcium eating deficiency Lack of exposure to sunlight Association with osteoporosis treatment Biphosphonats 76.2% Raloxifen 19.8% HRT 5.4% Proved osteoporosis (positive bone-densitometry) Osteoporosis fracture

71.2% 65% 52.4% 45.7%

38.2% 34.4%

Table 4: Administration’s circumstances depending on bone-densitometry result

Postmenopausal patients without HRT Calcium eating deficiency Lack of exposure to sunlight Senior’s calcium-vitamin D deficiency Post-menopausal women with HRT contre-indicated 3 months oral corticotherapy

None or normal (%)

Proved osteopenia or osteoporosis (%)

67

77

70 58 32

62 48 25

8

14

13

9

Table 5: Treatment details Calcium/vitamin D association 99% Mean calcium dosage: 982 mg Mean vitamin D dosage: 784 IU Mean treatment duration 7 months (±7.3) 8 months when proved osteopenia or osteoporosis

Conclusion: Bone-densitometry was carried out for 60% of the patients and revealed osteopenia in 40% and osteoporosis in 56%. Fracture’s history was reported for 43% of the patients (wrist 51%, vertebra 39%). The more common grounds for calcium/vitamin D association’s administration are postmenopausal patients without HRT (71%), calcium eating deficiency (65%) and lack of exposure to sunlight (52%). When the calcium-vitamin D was associated with osteoporosis treatment, it was biphosphonats by a majority (76%).

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French general practionners prescribe calcium/vitamin D association in 99% of cases, at 1 g/day calcium mean dosage and 800 IU/day vitamin D mean dosage predominantly with a mean treatment duration of 7 months, 8 months in case of osteopenia or osteoporosis. (1) Cormier C (2004) Osteoporosis prevention. Outcome at dawn on 2005. Rhumatos 1:63–67 (French) (2) Chappuy MC et coll (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. NEJM 327:1637–1642 (3) Chappuy MC et coll (1994) Effect of calcium and colecalciferol treatment for three years on hip fractures in elderly women. BMJ 308:1081–1082 (4) Lips P et coll (1996) Vitamin D supplementation and fracture incidence in elderly persons. Ann Int Med 124:400–406. (5) AFSSAPS’s recommendations. Postmenopausal osteoporosis treatment. January 2006 (French) This work was supported by Expanscience Labs (Courbevoie, France).

P108. Level II antalgic administration for osteoarthritis pain in general practice R.-L. Dreiser1, Ph. Coste2; 1Bichat Hospital, Paris, France, 2 Expanscience Labs, Courbevoie, France Background: A recent publication pointed out that major osteoarthritis pain represent 11% of level II antalgic administration (WHO classification) for rheumatologic pain in medical general practice, and painful intensity was the main motivation of this prescription.(1) But nevertheless, few clinical studies assessed precisely level II antalgic position in the treatment of osteoarthritis pain and the conditions of their prescription are unknown precisely.(2,3) Objective: Describe the circumstances of level II antalgic administration in osteoarthritis pain by the French general practionners, as well as treatment details (dosage, duration) and patients characteristics. Method: Three months prospective epidemiological survey among the French general practionners (GP). 1,440 GP described 1,440 patients requiring level II antalgic administration for the treatment of osteoarthritis pain, radiologycaly proved, and specified their prescription’s details. Materials: age, size, weight, BMI, osteoarthritis details, pain visual evaluation scale’s score, treatment details (dosage, duration). Statistical analysis: percentages, mean scores, standard deviation. Results: 1. Patients characteristics – –

1,440 patients has been described: Mean age 62.38 years (±11.84), women (52.15%), age >60 years: 58.1%.

– – – –

Mean weight 76.44 kg (±13.79), mean BMI 27.3 (men) and 27.05 (women) >25 for 44.48% and >30 for 22.56% of the patients. Mean size 167.63 cm (±8.34). Mean baseline score at the pain visual evaluation scale: 65.93 mm (±12.82). Mean pain attack duration: 53.51 days (<7 days in 42.37% of cases).

69.1% of the patients showed only one osteoarthritis location, 24.65% two locations (knee and rachis 49.3%; hip and rachis 18.87%) and 4.93% three locations (with knee and rachis in 75% of cases). Table 1: Main locations of osteoarthritis Rachis Knee Hip Hand

35.84% 34.89% 14.34% 10.33%

Table 2: Osteoarthritis locations depending on gender

Knee Rachis Hip Hand

Men (%)

Women (%)

52.03 47.97 19.19 5.81

45.01 51.26 20.51 34.62

2. Day survey’s antalgic treatment Table 3: Treatment the day of the survey Treated patients (%) 1 treatment (%) 2 treatments (%) Paracetamol NSAID

74.24 50.9 23.33 59.85% of prescriptions 19.65% of prescriptions

3. Level II antalgic treatment prescribed by GP Table 4: Details of level II antalgic treatment mainly prescribed by GP Tramadol Immediate release form Effervescent tablets form Long acting form Mean dose per day Mean treatment duration

95% 87.89% 65.17% 12.11% 259.81 mg (±142.6) 16.18 days (±11.51)

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of the knee, with an emphasis on trial methodology. Semin Arthritis Rheum 26:755–770

Table 5: Level II antalgic administration’s motives Ineffectiveness of previous treatment Maximale antalgic efficacy Pain intensity

71.33% 47.64% 28.74% (VAS >60 mm: 73.45%) 23.94% 13.11%

NSAID intolerance NSAID contraindication: antivit K treatment Patient’s NSAID refusal

11.58%

This work was supported by Expanscience Labs (Courbevoie, France).

P109. Complex therapy of pain syndrome during osteopeny and osteoporosis A. Ignatyev1, T. Yermolenko2, L. Batsulya1; 1Occupational Diseases Department, State Medical University, Odessa, Ukraine, 2Obstetrics and Gynecology Department, Odessa State Medical University, Odessa, Ukraine

Table 6: Recommendations in using treatment Precautions in using treatment Progressive dosage administration Laxative

59.39% 43.06% 20.69%

Table 7: Complementary prescriptions Associated antalgic treatments Local NSAID NSAID NSAID at antalgic dosage Delayed action anti-osteoarthritis drug

68.13% 22.57% 24.38% (coxibs 4.3%) 9.24% 27.5%

Conclusions: The two main osteoarthritis locations are rachis (35.84%) and knee (34.89%). Mean pain intensity score at visual analogic scale was 65.93 mm. 74% of patients were already treated with antalgic, including paracetamol 60%, or NSAID. Ineffectiveness of previous treatment was the level II antalgic administration’s main motive for 71% of French GP, NSAID intolerance for 24% and patient’s NSAID refusal for 12%. The more often prescribed level II antalgic is tramadol (95%) in immediate release form (88%) including effervescent tablets form for 65%, at 260 mg/day dosage during 16 days. Its administration respect a progressive dosage in 43% of cases and associate laxative treatment in 21%. One third of treated patients received delayed action anti-osteoarthritis drug’s coprescription (27.5%). 68% of GP associate another antalgic treatment: local NSAID in 22.5% of cases and NSAID in 30% in spite of level II antalgic administration. (1) Bailly C, Maheu E (2004) Les douleurs intenses d’origine rhumatologique en médecine générale. L’enquête SAFIR. Lettre Rhumatol 304/305/306 (French) (2) Bannwarth B et al (1997) L’association paracétamol-codéine en rhumatologie. Rev Rhum 64:421–423 (French) (3) Towheed TE et al (1997) A systematic review of randomized controlled trials of pharmacological therapy in osteoarthritis

Introduction: The pathology of bone-muscle apparatus is one of the most considerable medical problems with influence on the economy of society, health and quality of life of individuals and their families. The work is aimed to create efficient complex therapy, directed to weakening of pain syndrome, decreasing and ceasing of bone mass loss, rising of quality of life. Materials and methods: 54 women (age from 53 to 60 years) with postmenopausal syndrome, who refused to have replacing hormonal therapy, have been examined. The average age of patients was 57.2±2.5 years, the average of menopause duration—8.1 ± 2.7 years. The diagnostic program included the evaluation of complaints, anamnesis and clinical status, the determination of nervous system’s functional state. The pain syndrome, the display of athenoneurotic syndrome, general weakness were evaluated by the Bone Mineral Density (BMD) numbers and examined by the method of ultrasound densitometry with densitometer Achilles-express (Lunar, the USA). Clinical symptoms of osteoporosis were evaluated before treatment and in the dynamics of it in one, three, six and twelve months of therapy. The treatment of postmenopausal form of osteoporosis was carried out by “Miacalcic” and “Vitrum Calcium-D3”. With basis therapy the electrophorus of mud-treating extract method was used. For treating the back pains the “Xefocam” was taken. The treatment has been conducted for 12 months. Results: The patients were divided on three groups: the first—20 women, who had the complex therapy; the second—24 women, who had complex therapy and mudtreatment. The comparing group were formed by patients (10), juxtaposed by their age, the menopause duration, the endured diseases, BMD state and pain syndrome. In this group the treatment was accomplished only by the use of “Xefocam.” The improvement was noticed by all patients by the end of the first month. In the first group after the 6 month of treatment Stiff. index grew to +4% (p<0.05), in a year it grew to +6% (p<0.05%). In the second group in 6 month Stiff. index grew to +6.5% (p<0.05), in a year it grew to +10% (p<0.05), the pains disappeared among the majority of patients. In the third group in 6 months Stiff. index lowered to −1.5% (p<0.05), in a year it lowered to

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−4.5% (p<0.05). The patients noted the improvement of their health and reducing of pain only for the time of taking the “Xefocam.” Conclusions: Thus, during postmenopausal osteoporosis complex treatment, that includes “Miacalci” combined with “Vitrum Calcium-D3” and “Xefocam” and mud-treatment makes many-sided effect: it improves “the quality of bone,” reduces pain syndrome, preventing the fractures. The reducing of back pain intensity in bones and the enlargement of movement activeness both lead to increasing of quality and independence of life. P110. Management of osteoporotic fragility fractures and falls assessment R. Al Mahfoud1, N. Giotakis2; 1Department of Surgery, Royal Liverpool University Hospital, Liverpool, United Kingdom, 2Department of Orthopaedics, Royal Liverpool University Hospital, Liverpool, United Kingdom Purpose: – –

To determine the demographics of patients with fragility fractures attending fracture clinic. To ascertain if the NICE guidelines for managing fragility fracture are being followed. Biphosphonates are indicated for the secondary prevention of fragility fracture in:

Women aged 75 years and older without the need for DEXA scanning. Women aged 65–74 years if the presence of osteoporosis is confirmed by DEXA scanning. Post menopausal women younger than 65 years if they have a very low BMD (T-score: −3 SD or below) or confirmed osteoporosis plus 1 or more risk factors. Before biphosphonates or teriparatide are prescribed, adequate levels of Ca and Vitamin D should be established, and dietary supplements should be prescribed or advised if levels are below normal. –

To determine how to improve the practice, policies and care pathways for patients with osteoporotic fragility fractures.

Methods: Prospective study. Only discharged patients were studied as relevant management should have been commenced before discharge. Two weeks of fracture clinic discharges were included 18/03/06–31/03/06. Patients with possible osteoporotic fractures were identified (fractures that result from low level trauma (i.e. mechanical forces that would not ordinarily cause a fracture/WHO definition: A fracture resulting from a force equivalent to a fall from a standing height or less). These were analyzed (site of fracture, previous fragility fractures, risk factors, BMD

measurement, prescription of Ca supplements and biphosphonates when indicated). Results: Total 134 patients were discharged over the 2 weeks period. Ninety-nine fractures out of these, 29 possible osteoporotic. Males=24%, Females=76% Age distribution: <65 years=38%, 65–74 years=38%, >=75 years=24% Out of three women >=75 only one was prescribed a biphosphonate. Only 1/3 the women <75 had a DEXA scan performed. None of the male patients had a DEXA scan or appropriate investigations to rule out secondary osteoporosis. Out of 29 patients only nine had any form of lab investigations. Conclusions: Each year in the United Kingdom over 200,000 fractures occur as a result of osteoporosis. This figure in itself suggests an obvious socio-economic problem burden for patients and the National Health Service. This audit was performed in conjunction with a second department audit for inpatient management of fragility fractures. Both audits concluded poor results regarding treatment prescribing for these patients and DEXA scanning or referring patients on to geriatrics/ clinical chemistry. In addition to failure of identifying falls risk. A proforma was suggested to be used in fracture clinic to assist in identifying these patients and commencing treatment or referrals. Once this is in place a re-audit can be organized. P111. Longitudinal densitometric and radiographic changes of the mandible versus changes in other skeletal sites W. Pluskiewicz1, B. Drozdzowska2, M. Dilling3; 1Metabolic Bone Diseases Unit, Departments and Clinic of Internal Diseases, Diabetology and Nephrology, Silesian School of Medicine, Katowice, Poland, 2Department of Pathology, Silesian School of Medicine, Katowice, Poland, 3Private Public Dental Unit, Bytom, Poland Objective: The aim of the study was to evaluate 2-years longitudinal densitometric and radiographic changes of the mandible. Material: 18 postmenopausal women in mean age of 61.9± 8.0 years. (9 women with caries and 9 women with periodontitis). The main inclusion criterium was complete edentoulism at the mandible. Methods: Densitometry of the hip, lumbar spine and mandible; QUS at hand phalanges (Amplitude-dependent Speed of Sound—Ad-SoS); radiography of mandible, PMI—panoramic mandibular index, MR—mandibular ratio and ML—mandibular loss were performed.

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Results: Generally, a trend to drop was observed, and statistically significant decreases were noted in whole group and in women with caries. Changes in mandible BMD (f′ BMD) with changes in densitometric and QUS value showed and association of mandible f′ BMD with f′ FN BMD in whole group (r=0.48, p=0.042). Mandible BMD correlated with Ad-SoS with Ad-SoS in whole group (r= 0.47, p<0.05) and with spine in women with periodontitis (r=0.74, p<0.05). Radiographic measurements showed a decrease in PMI and an increase in ML; in subgroup with caries a decrease in PMI. Changes in mandible radiography for PMI, MR and ML with dynamic of changes in mandible BMD (f′ BMD) showed following significant correlations: in whole group—f′ BMD—f′ PMI (r=−0.51, p<0.05), in subgroup with periodontitis—f′ BMD—f′ PMI (r=−0.75, p<0.05). Correlation analysis of radiographic parameters (PMI, MR, ML) with densitometric and QUS data showed several significant relationships: whole group positive correlations of MR and negative of ML with mandible, spine, FN and Wards BMD, at third measurement positive correlation of MR and negative with ML and mandible BMD; in women with caries a positive correlation of MR and negative of ML with mandible BMD; in women with periodontitis a positive correlation of MR and negative of ML with Ad-SoS. Conclusion: In the study a decrease in mandible BMD was noted only in women with caries, and a relationship of mandible BMD and femoral neck BMD indicate that these skeletal sites share common nature of bone loss. P112. Efficacy of calcitonin for vertebral fracture pain A. Bazarra-Fernández; Department of Obstetrics-Gynecology, Juan Canalejo University Hospital Trust, La Coruña, Spain Background: Fractures, especially vertebral fractures, are a common complication of osteoporosis, leading to significant pain. Objective: To compare the pain release induced by osteoporotic vertebral fracture, through teriparatide and teriparatide plus calcitonine. Materials and methods: We performed a study to compare the analgesic effect of 20 mcg teriparatide versus 20 mcg teriparatide plus metered dose intranasal spray 200IU/ activation calcitonin in two groups between postmenopausal women undergoing osteoporosis with vertebral fracture. A 10-point visual analog pain scale (1=least to 10=most painful) and a four-point pain grade (grade 1=least to grade 4=most painful) were used to measure the pain perception. Results: The mean pain scores for the teriparatide and teriparatide plus calcitonin were 2.3±1.1 and 8.5±1.1, respectively (P<0.05), while the pain grades for teriparatide and teriparatide plus calcitonin were 1.5±0.3 and 3.5±0.4, respectively (P<0.05). In teriparatide group, analgesics

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were requested, but in teriparatide plus calcitonin group no analgesics were requested (P<0.001). Conclusion: Using teriparatide is more expensive than other osteoporosis treatment. Studies show that taking a bisphosphonate with hormone replacement therapy (HRT), results in increased bone mass when compared to taking either a bisphosphonate or estrogen alone. Besides, calcitonin is better for osteoporotic vertebral fracture pain release than HRT. However, a larger investigation will be needed to achieve more significant case number. P113. Genetic and environmental influences on bone turnover markers O.S. Donescu1, M.C. Battié2, T. Videman3; 1Toronto Rehab Institute, University of Toronto, Toronto, Canada, 2Department of Physical Therapy, University of Alberta, Edmonton, Canada, 3Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada Objectives: Biochemical markers of bone turnover originating from type I procollagen synthesis or type I collagen breakdown were examined in men using a classic twin study design based on monozygotic (MZ) and dizygotic (DZ) twins. The aim was to estimate the influence of heredity (genes and shared family childhood elements) and environmental factors (lifetime physical activities at work and leisure time, smoking, alcohol, calcium intake and other health related factors) in determining procollagen type I amino-terminal propeptide (PINP), type I collagen carboxy-terminal telopeptide (ICTP) and urinary aminoterminal type I collagen telopeptide (NTx) marker levels in a sample of in 98 monozygotic and 108 dizygotic male twin pairs. Materials and methods: An extensive, structured interview was conducted to obtain data on medical history and information on medication use after study subjects came to a central location in Finland (city of Kuopio). Clinical examinations of each subject were conducted, including dual magnetic resonance imaging (MRI) of the lumbar spine and femoral neck, and serum and urine samples (obtained over a one and a half-day period). All subjects slept at a hotel adjacent to the testing site the night before the sample collection. Results: The findings support a dominant role for heredity in the variation of bone resorption marker levels in men, with additive genetic effects explaining two thirds of the variance in the bone resorption markers NTx and ICTP, and similar or lower variance in the bone formation marker PINP, depending on the model used. The genetic loci influencing the marker PINP or NTx and body weight/disc axial area, although related in part, appeared to be largely independent, indicating that genetic effects on bone

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turnover are unlikely to be to a large degree a result of genetic regulation of individual body weight. Conclusion: The genetic variance in bone markers was largely independent from the other anthropometric and behavioural co-variates studied, supporting the hypothesis that heredity plays a dominant role in bone formation and degradation in men, while dietary calcium, smoking, and physical activity after childhood have a lesser influence on these markers. P114. Calcified large arteries, osteoporosis and acute stroke. What is the relationship? H.S. Hamoud1, H.M. Husein2, A.E. Gmal3; 1Rheumatology Department, Al Azhar University, Cairo, Egypt, 2Neurology Department, Al Azhar University, Cairo, Egypt, 3Clinical Pathology Department, Al Azhar University, Cairo, Egypt Background: Atherosclerosis and osteoporosis are currently considered unrelated diseases. As age advances, osteoporosis is more frequently found in women than men; atherosclerosis is an illness predominantly affecting men.(1) A parallel relationship has been noted between spinal osteoporosis and aortic calcification due to atherosclerosis.(2) Osteoporosis and stroke share several risk factors, such as age, smoking, low level of physical activity, and hypertension.(3) Thus Low bone mineral density (BMD) and a high risk of stroke may thus be related, but studies on this relationship are sparse. Both bone and atherosclerotic arteries contain osteopontin, matrix gla protein, bone morphogenetic protein collagen I, osteonectin, osteocalcin, nitric oxide, and matrix vesicles.(4) Atherosclerosis and osteoporosis both involve recruitment and differentiation of monocytic cells that differentiate into macrophage-foam cells in artery and osteoclasts in bone.(5) The artery wall contains cells capable of differentiation into osteoblasts, following the same stages of differentiation as occur in bone-derived osteoblasts, and ultimately producing bone mineral.(6) Objectives: To examined the relationship between calcified large arteries, BMD and acute stroke in hospitalized patients aged >60 years. Materials and methods: Seventy-five stroke patients (40 women and 35 men) in addition to 65 ages matched control group were included in the study. Careful family history, full clinical exam. Radiological examination for both lumbar and pelvic regions. Routine lab, lipid profile investigations were done. The atherogenic index was calculated as the ratio of (total cholesterol-HDL cholesterol) to HDL cholesterol. Body mass index (BMI) was calculated for the entire studied group. BMD was measured by using dual-energy X-ray absorptiometry at both distal forearms to avoid fallacies that done by the calcified aorta. BMD measurements of the stroke patients were performed 1 week after the onset of stroke.

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Results: There was a highly significant difference between the stroke patients and their controls as regards total cholesterol, LDL, HDL and BMD. However in males; no difference was found between the stroke patients and their controls regarding BMD. As regards aortic calcifications, the noncalcified aorta was significantly higher in controls than stroke group. The advanced calcified aorta and moderate one was significantly higher among stoke group than controls, despite the mild aortic calcification show a non significant difference between both groups. Conclusion: High total cholesterol and LDL, but low HDL and BMD in addition to aortic calcification whatever moderate or advanced may early predict stroke both in females and males. This may be an important explanation for the increased incidence of hip fracture in stroke patients. (1) (2) (3) (4) (5) (6)

Fujita T. et al. 1984 Dent CE. et al. 1968 Nguyen TV. et al. 2000 Nguyen TV. et al. 2000 Pinals et al. 1972 Parhami F. et al. 1997

P115. The influence of biomechanical injury on rabbit cartilage chondocytes apoptosis through the accumulation of intracellular calcium Z.A. Adnan; Department of Internal Medicine, Surakarta National University, Surakarta, Indonesia Objective: To determine the role of biomechanical insults on the increasing of IP-3 and cytosolic Ca++ and chondrocyte apoptosis. Materials and methods: A randomized control group posttest design was used in this animal study. A randomized completely design were then applied in dividing the samples into two groups, case and control groups. Four male flame rose rabbit on each group (calculating by Higgins and Klinbaum method), age over 2 months and body weight between 2.0–2.5 kg, feds by water spinach, carrot and sweet potato were enrolled in this study. Medial meniscectomy and anterior cruciate ligament transection on the knees was performed in case group. The rabbit was sacrifices 4 weeks later. The expression of IP-3 and Ca++ and chondrocytes apoptosis determined by histochemical method and Tunnel assay. A comparison between the groups analysed by Kolmogorov Smirnov Z for normality distribution and Hotteling’s trace for multivariate analysis. Results: The means of IP-3 in control group and case group were 0.25±0.10 and 6.85±0.60, respectively. The Ca++ in control and case group were 1.20±0.83 and 8.10±0.90, respectively. The numbers of apoptotic chondrocytes were four times greater in case group that was 14.05±2.61 compare to control group by 3.55±1.04. Z value on IP-3, Ca++ and apoptosis in control group were 0.883, 0.310 and

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0.835, respectively. In case group, the Z value on IP-3, Ca++ and apoptosis were 0.324, 0.879, 0.567, respectively. Both groups with normal distibution. There is positive correlation between IP-3 and Ca++ (r=0.987, p<0.01), Ca++ and numbers of apoptosis (r=0.908, p<0.01), and IP-3 and apoptosis (r=0.913, p<0.01). Analysis on the correlation between IP-3, Ca++ and apoptosis influenced by biomechanical insults giving the Hotelling’s trace value of 860.197 with probability value of 0.000 (p<0.01). Conclusion: Biomechanical insult has a positive correlation with the increasing of IP-3, and Ca++ influx and stimulates chondrocytes apoptosis. P116. Factors related to correct compliance with treatment for osteoporosis R. Sánchez Borrego1, S. Palacios2, J.L. Neyro3, F. Quereda4, F. Vázquez5, M. Pérez6, A. Raber6, M. Pérez7; 1Clínica Diatros, Barcelona, España, 2Instituto Palacios, Madrid, España, 3Hospital de Cruces, Vizcaya, España, 4Hospital Universitario San Juan de Alicante, Alicante, España, 5 Centro Ginecológico CEOGA, Lugo, España, 6Laboratorios Almirall Prodesfarma, Barcelona, España, 7Adelphi Targis, Barcelona, España Objectives: Osteoporosis is a disease characterised by a loss of bone mass together with alterations of the bone tissue’s microarchitecture, resulting in increased bone fragility and risk of fracture. Knowledge of the disease can prevent cessation of therapy and thus reduce osteoporotic fractures. We therefore evaluated the knowledge, attitudes and expectations of patient receiving treatment for postmenopausal osteoporosis in relation to their condition, analysing the factors related to good compliance with treatment. Materials and methods: National, epidemiological, crosssectional study collecting personal medical history, family history, bone densitometry (when was possible), treatment and compliance according to Haynes–Sackett test of patients over 45 years of age who were receiving treatment and provided their informed consent. The patients anonymously completed a questionnaire about their knowledge of osteoporosis and the Morisky Green treatment compliance evaluation test. Results: Three hundred fifteen investigators participated, recruiting 1,179 patients with postmenopausal osteoporosis. The mean age was 59.9 years (SD=7.5), 49.2% were aged from 51 to 60. 11.6% of the women presented obesity (BMI >30 kg/m2). 92.1% of the patients were Caucasian. Each patient completed a knowledge questionnaire with 13 questions. Only 22.6% of the patients showed acceptable knowledge of osteoporosis (the criteria established was correct response to 80% of the questions). Treatment compliance was evaluated using a combination of

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Morisky–Green and Haynes–Sackett criteria. 39.2% of the patients were classified as compliant. 74.6% of the patients were very or quite concerned about their condition. 53.3% described their state of health as excellent or good. However, 63.6% of the patients indicated that they need more information about osteoporosis. The factors related to good compliance were the presence of concomitant diseases (presence of one or no associated condition: OR=1.38, p=0.043) and the type of knowledge about their disease (acceptable knowledge: OR=1.33, p=0.043). Conclusions: Correct knowledge of osteoporosis increases the possibility of appropriate compliance with the prescribed treatment, thus reducing the risk of osteoporotic fractures. P117. Bone mineral density in patients on long-term orlistat treatment E. Giorgadze, M. Tsagareli, K. Asatiani, K. Bochorishvili, N. Tsagareli, L. Bestavashvili, T. Sulikashvili; Department of Endocrine Disorders, N4 Clinical Hospital, Tbilisi, Georgia Objective: To determine whether the long-term orlistat treatment affects bone mass, ionized calcium and phosphorus values in patients with obesity. Materials and methods: We have investigated 49 patients (21—male, 28—female) from age 19 to age 57 with II and III degrees of obesity. We measured body mass index (BMI), oral glucose tolerance test, plasma lipids, leptin, ionized calcium, phosphorus, parathyroid hormone (PTH), osteocalcin (OC) values and bone mineral density (BMD) with ultrasound bone densitometry. Results: Patients were divided into two groups. Patients in group I (n=22) received only low calorie diet for 1 year. Patients from group II (n=27) in addition were prescribed to orlistat 120 mg, three times a day. In group I mean values of Ca++ and phosphorus were within the normal range (1.18±0.02 mmol/l and 4.4±0.01 mg/dl, respectively), mean value of T-score was −0.8±0.1. In group II, T-score equaled to −0.7±0.1. Ca++ and phosphorus values were 1.2±0.01 mmol/l and 4.2±0.02 mg/dl, respectively. Orlistat treatment resulted in significantly graet weight loss in group II. In both groups after the treatment Ca++ level was decreased to 1.15±0.01 and 1.13±0.01 mmol/l, respectively. T-score was not changed significantly. In group II PTH was increased insignificantly to the upper level of the norm (from 41.6±0.01 to 58.2±0.01 pg/ml). No changes were detected in OC values. Conclusions: 1. Long-term orlistat treatment results in significant weight loss in obese patients. 2. Long-term orlistat treatment doesn’t affect BMD and calciumphosphorus metabolism in obese patients.

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P118. Prevention of osteoporosis in patients with type 1 diabetes E. Giorgadze, V. Chachibaia, M. Tsagareli, K. Asatiani, N. Tsagareli, T. Sulikashvili, A. Surmava; Department of Endocrine Disorders, N4 Clinical Hospital, Tbilisi, Georgia Objective: Type 1 diabetes is associated with reduction in Bone Mineral Density (BMD). It is thought, that low BMD in patients with type 1 diabetes is caused by metabolic abnormalities. The aim of our study was to assess the effectiveness of Calcium Carbonate, Vitamin D3 and Calcitonin on the development of osteoporosis in patients with type 1 diabetes. Materials and methods: We studied 54 patients (29— male, 25—female) with type 1 diabetes. The inclusion criteria was duration of diabetes 20–25 years. We measured HbA1c, ionized calcium, phosphorus, parathyroid hormone (PTH), osteocalcin (OC) values and BMD with ultrasound bone densitometry. Results: In patients with type 1 diabetes we revealed osteopenia, the mean value of T-score was −2.0±0.01. The mean value of HbA1c was 5.6%, Ca++ values were at the lower level of the norm (1.08±0.01 mmol/l), PTH was at the upper level of the norm (52.3±0.01 pg/ml) and OC was at the lower level of the norm 9.7±0.02 ng/ml. In patients with early age of onset, longer duration of disease and higher levels of HbA1c lower values of T-score and OC were detected. In order to prevent osteoporosis patients with lower BMD received Calcium Carbonate, VitaminD3 and Calcitonin. In 2 years from the initiating treatment the mean value of T-score was −1.8±0.01, OC values increased significantly (18.2± 0.01 ng/ml). Conclusions: Care of patients with diabetes should include the assessment of BMD. Duration of diabetes and poor metabolic control are the main determinants affecting bone mass. Calcium Carbonate, Vitamin D3 and Calcitonin are effective for prevention of osteoporosis in patients with type 1 diabetes. P119. Paraplegia as a complication of vertebroplasty: a case report C. Ozturk1, I. Tas2, S. Hepguler1, Y. Dusunceli1; 1Department of Physical Medicine and Rehabilitation, Ege University Medical Faculty, Bornova, Izmir, Turquie, 2Department of Physical Medicine and Rehabilitation, Baskent University Faculty of Medicine, Ankara, Turquie Objective: To present an irreversible complete paraplegia case as a complication of vertebroplasty procedure in an osteoporotic compression fracture. Materials and methods: A 74 year old woman applied with the complaints of inability to walk, and bladder and

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bowel incontinence. Her medical history revealed a T12 vertebra fracture associated with pain unresponsive to conservative treatment which was treated afterwards with percutaneous vertebroplasty. Results: Unexpectedly, the acyrlic bone cement has leaked to the spinal cannal which has resulted in complete paraplegia that has turned out to be persistent against urgent surgical decompression. Conclusion: Percutaneous vertebroplasty with polymethyl methacrylate is not such a simple and riskless procedure as suggested. It has to be conducted by experienced surgeons with utmost care and yet some modifications concerning the technique may be necessary. The possible risks and complications of the suggested surgical operation in the treatment of osteoporotic vertebral fractures need to be addressed well and the patients must be informed thoroughly. P120. Impact of age on persistency of French postmenopausal osteoporotic patients treated by bisphosphonates P. Fardellone1, F.E. Cotté2, A. Lafuma3, C. Marchand3, A.F. Gaudin2; 1Service de Rhumatologie, Hôpital Nord, CHU Amiens, Amiens, France, 2GlaxoSmithKline, Marly-le-Roi, France, 3Cemka-Eval, Bourg-la-Reine, France Objective: To compare the persistence of treatment with bisphosphonate (BP) according to their administration regimen and the age of patients. Materials and methods: Patient data were retrospectively analysed from a national computerized database representative of the French GPs prescriptions. Persistence was assessed by the time to discontinuation of BP therapy without a gap in refills for more than 30 days. Two cohorts of patients newly treated by BP for post-menopausal osteoporosis were selected (without prior treatment with BP or SERM the previous year). The first cohort consisted of women whose treatment with daily BP (DBP) was first prescribed in 2000 or 2001 and the second cohort included patients with first weekly BP (WBP) treatment during the period 2002 and 2003. Duration of follow-up was as far as October 2002 for DBP and October 2004 for WBP. Survival analyses were completed in both cohorts using the end of treatment as endpoint. Subsequent analyses were also performed to compare persistence of elderly patients (≥80 years) with all others (<80 years). Results: 1,363 female patients were included in DBP cohort and 3,969 in WDP cohort. Women were 69.7 years old on average in both cohorts (p<0.0001). After 12 months, 50.5% of overall patients with WBP regimen and 43.6% of overall patients with DBP regimen persisted with therapy (p<0.0001). Only 41.1 and 31.5%, respectively were still on therapy after 24 months. The actuarial survival curves below showed that there was no significantly difference of persistence between elderly women treated by WBP (n=626) and ones treated by DBP (n=171) neither at 12 months (45.7 vs 45.5%, p=

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0.7785), nor later at 24 months (36.2 vs 30.4%, p=0.8143). Compared with overall results, curves for patients aged of less than 80 years also indicated a superior gap of persistence between WBP and DBP with, respectively, 51.2 vs 43.1% (p <0.0001) at 12 months of follow-up (39.1 vs 29.5%, p< 0.0001, 24 months). Conclusion: These results indicated that a lower frequency of drug intake improved persistence to osteoporosis treatment of overall patient but showed that women less than 80 years are more sensitive to this parameter than elderly women.

P121. Peculiarities of course of osteoporosis accompanied with the rheumatic diseases L. Kilasonia1, E. Kartvelishvili2, M. Mgaloblishvili3, M. Skhiereli3, N. Kirvalidze5, N. Ganugrava1; 1National Association of Osteoporosis, Medical Centre Uranti, Tbilisi, Georgia, 2Centre of Rheumatology, Tbilisi, Georgia, 3 Medical Centre Uranti, Tbilisi, Georgia Introduction: In the recent years the researchers’ interest to the Osteoporosis (OP), developed against the background of the rheumatic diseases. It is natural, as the significant disorders in immune system in the pathogenesis of rheumatic diseases, accompanied with development and progress of recurrent inflammation provide unique model for determination of the role of immune mediators in the pathogenesis of osteoporosis. Though, according to the classification, osteoporosis belongs to the rheumatic disease, there is not studied its relations with such a widespread disease as osteoarthritis (OA). Do the people suffering with OA have OP? Is arthrosis an alternative to osteoporosis? This issue in not resolved and it is subject to further researches. We should seek osteoporosis not only in the people suffering with osteoarthritis, but according to the most recent data, generalization of osteoporosis, at a time of rheumatoid arthritis (RA) should be regarded, as a prognostic marker of severity of the main disease.

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Objective: In this work we aimed to study the peculiarities of course of osteoporosis at a time of such rheumatic diseases as osteoarthritis and rheumatoid arthritis, with regard to the severity of clinical forms of diseases. Materials and methods: There were studied 90 persons with OA and 62 persons with RA. Into the RA group there were included those patients who did not consume glucocorticosteroids for the last two years; and among the persons with OA there were 65 females of 35–65; and 25 males of age from 41 to 75. In the RA group there were 52 females (of 18–45 age) and 10 males from 29 to 70. In the group of OA patients the fractures were indicated in 12 cases, among which in seven cases—there were vertebral fractures; in five cases—fractures of peripheral bones (2— femoral bone and 3—silver-fork [Colles] fractures). In the group of patients with RA there were seven cases of fractures, in two cases there were compressive fractures of vertebras in the anamnesis and in five cases there were Colles fractures. For diagnostics of osteoporosis there was applied the dual X-ray absorption densitometry (Hologic Q 1000-VSA) and ultrasound densitometry. In all cases there were studied biochemical markers of the bone in the blood. Results: As a result of studies there was determined that the patients with rheumatoid arthritis have reliable increased level of osteocalcin correlating with the activity of RA. Frequency of revealing of osteoporosis, accompanying RA, varies between 58–82%. At the same time according to Tcriterion, the low bone mass was detected with higher frequency in the proximal section of femoral bone, compared with the vertebra of lumber region; in 68% of the studied patient there was found osteopenia and osteoporosis in the distal section of the forearm, among which 40% was the initial stage of the disease. T-criterion correlates with the severity of the disease, activity markers, like “C”-reactive protein (z=−0.57; p<0.001); There is impression that OP and RA are in the equal conditions, but distribution and mechenism of bone mineral density contributing to the bone loss are non-uniform. It is assumable that the frequency of OP at a time of RA should be conditioned be the inflammation process in peripheral bones. Osteoarthritis and osteoporosis are not mutually excluding diseases. Data, obtained through X-ray densitomentry, at a time of OA are non-uniform for different fragments of the skeleton and depend on the clinical form of the disease. High mineral density of the bone is associated with the age, sex, osteochondrosis, accompanied with osteophytosis and functional condition of the frequency. When at a time of peripheral joints arthrosis the low BMD in the proximal section of the femoral bone was detected in 18–20% of the patients. According to our observations, X-ray densitometry for OA creates the precedent of hypo-diagnostics at a time of study of axial skeleton; and among the results of densitometry

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of peripheral bones there is correlation between the results of X-ray and ultrasound densitometries, what allows application of the letter for patients with OA, with the purpose of early diagnostics of OP. P122. Testing of mechanical properties of hip protectors using high tech materials G. Holzer, L.A. Holzer; Department of Orthopaedics, Medical University of Vienna, Vienna, Austria Objective: To test the mechanical properties of hip protectors using high tech materials compared to conventional hip protectors according to a European Standard. Materials and methods: Two hip protectors using new high tech materials and five conventional hip protectors (AHIP, Astrosorb; AHF Hip pant, Hips, KPH, Safehip, Safety Pants) were mechanically tested using an mechanical testing maschine (impact testing with 50 J) according to a European Standard (EN 1621-1). Results are peak (max) expressed in kiloNewton. Results: The results of impact testing of two hip protectors using high tech materials were superior (AHIP 9.10 kN, Astrosorb 12.65 kN) to conventional hip protectors (21.97– 50.62 kN), which differ in performance to mechanical testing. Conclusion: Compliance and adherence of currently available hip protectors are poor. Reasons might be design and wearing comfort. High tech materials with improved mechanical properties allow more appealing design and increased wearing comfort. This can be achieved by using thinner elements with more flexibility and less skin contact to reduce sweating. The results of this study show that new high tech materials with improved mechanical properties are superior to currently available hip protectors from the mechanical point of view. Utilizing these materials allow designing new hip protectors with increased compliance and adherence. AHIP, a hip protector using high tech material, implements modern design, improved wearing comfort and best mechanical properties. P123. Exercise program with the huber system compared with classic exercise program for patients with chronic low back pain M. Bojinca1, V. Bojinca2, D. Bida1, C.M. Mihai1, M. Milicescu1, V. Stoica1; 1Department of Internal Medicine and Rheumatology, Dr I. Cantacuzino Hospital, Bucharest, Romania, 2 Department of Internal Medicine and Rheumatology, Sf. Maria Hospital, Bucharest, Romania Background: Chronic low back pain is one of the most frequent medical problems in the general population. Exercise is generally accepted as treatment for low back pain. Huber® is a new rehabilitation device with complex

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actions on different muscular groups, postural equilibrium and mobility improvement. Objectives: Efficacy assessment of exercise program with the Huber® device compared with classic exercise program in the treatment of chronic low back pain (CBLP). Materials and methods: We studied 50 patients with CLBP. The patients were randomly assigned to one of two groups: exercise program with the Huber® device (test group—25 patients) and classic exercise program (control group—25 patients). The patients were evaluated at the beginning of the study, after eight exercise sessions and after 15 exercise sessions using physical examination, visual analogue scale (VAS) for pain, Schober test and finger-floor distance for spinal mobility, Biering–Sorensen test and Shirado–Ito test for the strength of trunk muscles and Quebec scale for functional status. We used a variant of SPSS11 program for statistical analysis. Results: The mean age was 39.64±10.85 years for the Huber® group and 41.16±9.31 years for the control group (p=NS). After eight exercise sessions and also after 15 sessions both groups had significant improvements (p<0.05) according to pain, Biering–Sorensen test, Shirado–Ito test, and Quebec scale. The Huber® group had a more important improvement for VAS, Shirado–Ito test and Quebec scale compared to control group (p<0.05). Schober test and finger-floor distance did not show significant modifications at the end of the study or between groups. The patients in both groups did not experience significant adverse reactions. Conclusions: Standardised exercise program with the Huber® device is effective, well tolerated, and induces significant improvement for patients with chronic low back pain. Compared with classic exercise program, the program using the Huber® device induces significant more improvement for pain, trunk flexors muscles strength, and functional status. This results open up new prospects for the use of this technique in rehabilitation programs. P124. Spinal stenosis—complication of osteoporotic vertebral fractures M. Bojinca1, V. Bojinca2, D. Bida1, C. M. Mihai1, M. Milicescu1; 1Department of Internal Medicine and Rheumatology, Dr I. Cantacuzino Hospital, Bucharest, Romania, 2Department of Internal Medicine and Rheumatology, St. Maria Hospital, Bucharest, Romania Background: Osteoporosis is the most common metabolic bone disease. Vertebral fractures are the most frequent complication of osteoporosis. Spinal stenosis is a narrowing of normal spinal canal associated with myelopathy or radiculopathy. Spinal stenosis is a potential severe, underestimated, consequence of osteoporotic vertebral fractures.

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Materials and methods: We present five patients (4 women and 1 men) with severe osteoporosis and spinal stenosis due to osteoporotic vertebral fractures, mean age 67.2 years (54– 76 years). The patients were admitted in Internal Medicine and Rheumatology Department of Dr I. Cantacuzino Hospital during 2005–2006 for severe back pain and bilateral sciatica. All women were postmenopausal (mean duration 20.7 years). Three patients (2 women and 1 men) had rheumatoid arthritis and used 10 mg Prednisone daily for more than 3 years. All patients had well-known osteoporosis—mean vertebral T score (DXA) was −3.68. We evaluated the patients using medical history, physical examination (including neurologic examination), dorsolumbar spine X-ray and IRM. Results: The patients accused intense dorsolumbar (4 patients) or lumbar (1 patient) pain with bilateral sciatica (3 patients with bilateral Achilles reflex loss). All patients had paraspinous muscle contraction. All patients had neurogenic claudication and gait disturbances but no incontinence. Spine X-rays showed multiple osteoporotic vertebral fractures. In all cases one vertebral body with osteoporotic fracture (T12—2 cases, L1—2 cases, L4—1 case) had also important retrolisthesis. IRM examination confirmed spinal stenosis at the same site. One case was referred for spine surgery and in four cases spine surgery was delayed due to associated diseases. Conclusions: Spinal stenosis is a potential severe complication of osteoporotic vertebral fractures. Diagnosis is suggested by the combination of osteoporosis vertebral fracture pain and signs and symptoms of myelopathy/ radiculopathy and is confirmed by IRM. Dorsolumbar junction is the most affected region. In severe cases spine decompression is recommended. P125. Screening for osteoporosis with calcanean quantitative ultrasound (QUS) in a group of postmenopausal women less than 50 years V. Bojinca1, M. Bojinca2, A. Balanescu1, D. Opris1, F. Berghea1, D. Predeteanu1, R. Ionescu1; 1Department of Internal Medicine and Rheumatology, Sf. Maria Hospital, Bucharest, Romania, 2Department of Internal Medicine and Rheumatology, Dr I. Cantacuzino Hospital, Bucharest, Romania Background: Osteoporosis is the most common metabolic bone disease. Screening for osteoporosis in early postmenopausal women is important for risk fracture evaluation and initiation of appropriate therapy. Though DXA is the gold standard for osteoporosis diagnosis, calcanean quantitative ultrasound (QUS) is a useful and relative inexpensive method for screening. Objectives: Screening for osteoporosis and osteopenia in a group of postmenopausal women less than 50 years (early

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postmenopause) and assessment of influence of other risk factors for osteoporosis. Materials and methods: We studied a group of 319 postmenopausal women less than 50 years. Screening for osteoporosis was made using QUS (Achilles Sahara device). We assessed the influence of other risk factors (weight, smoking, alcohol intake, exercise, dairy intake) using questionnaire method. We used a variant of SPSS 11 program for statistical analysis. Results: In the studied group mean T score was −1.24± 0.84. Twenty-one patients (6.58%) had T score <−2.5 (osteoporosis). Another 163 patients (51.09%) had T score <−1 (osteopenia). Smoking, alcohol intake and weight <55 kg were associated with significantly lower T score (p<0.01). Dairy intake and exercise did not associate with significant modifications of T score (p—NS). Conclusions: More than half of patients had a T score corresponding to osteopenia and osteoporosis. Smoking, alcohol intake and low weight were the main factors associated with lower T score in early postmenopausal women from our group. P126. Postmenopausal osteoporosis and weight gain A. Bazarra-Fernández; Department of Obstetrics-Gynecology, Juan Canalejo University Hospital Trust, La Coruña, Spain Background: Recent studies have found for weight gained during menopause increase the risk of high blood pressure, the diabetes, heart disease, and has been strongly linked to increased incidence of breast and other hormone-related postmenopause cancers. These healthcare concerns have led to the conception of specific products that target menopausal weight gain. Objective: Looking over weight gain and osteoporosis treatment in climacteric. Materials and methods: Twenty women who were 44– 58 years old have been recruited. BMI was increased for age. Those with an intact uterus have moderate to severe vasomotor symptoms associated with the menopause. Moderate to severe symptoms of vulvar and vaginal atrophy and risk of postmenopausal osteoporosis. They were ascribed to equal two 10 women groups. One group was assigned to 2 mg drospirenone/1 mg 17 beta-estradiol hemihydrate. The other group treated with 40 mg soy bean. Results: In the women on 2 mg drospirenone/1 mg 17 betaestradiol hemihydrate medication decreased, moderate to severe symptoms of vulvar and vaginal atrophy vasomotor symptoms associated with the menopause in regard to the other group treated with 40 mg soy bean. They had weight main loss of 3 kg in 1 year, (P<0.05). Conclusions: Human HRT is in relation to decrease osteoporosis. Nobody noted 17 beta-estradiol is in relation

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to breast cancer. Estradiol is the same oestrogen produced by the ovaries before menopause. Drospirenone has the unique property of reducing water retention often associated with the use of oestrogen and other synthetic progestin hormones. The impact of obesity on hormone replacement therapy is due to many women associate hormones with weight gain. This formula can be beneficial in minimizing uncomfortable symptoms, such as weight gain, hot flashes, night sweats, and mood swings, that are associated with the natural progression of a woman’s life cycle. So, we need to conduct one big try to clarify these points. P127. Kyphoplasty persistently reduces pain in patients with osteoporotic vertebral fractures—3 year outcome of a prospective controlled cohort study C. Kasperk1, K. Da Fonseca2, J. Hillmeier2, P.-J. Meeder2, M. Libicher3, G. Nöldge3, U. Sommer2, U. Hilscher2, P. Nawroth1, I. Grafe1; 1Innere Medizin I (Endokrinologie und Stoffwechsel), UniversitätsKlinikum Heidelberg, Heidelberg, Deutschland, 2Unfall- und Wiederherstellungschirurgie, UniversitätsKlinikum Heidelberg, Heidelberg, Deutschland, 3 Radiologische Klinik, UniversitätsKlinikum Heidelberg, Heidelberg, Deutschland 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. Materials and 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 (1,000 mg calcium, 1,000 IU vitamin D3, oral aminobisphosphonate), pain medication and physiotherapy. Pain (visual analog scale (VAS), range 0–100), mobility (EVOS score 0–100) and radiomorphological parameters and incident fractures were assessed at baseline, after 12 and after 36 months. Results: After kyphoplasty the pain score (VAS) improved from 73.8 to 55.6 during the first year and to 54.0 after 36 months. The pain score of the conservatively treated control group changed from 66.4 to 64.0 during the follow-up period. Mobility scores for the kyphoplasty cohort improved from 43.8 to 54.8 and remained elevated compared to conservative controls (improved from 39.8 to 43.6) for at least 3 years. Remarkably, the fracture incidence of the kyphoplasty cohort was significantly reduced throughout the 3 year study period compared to controls (p<0.05). Clinically asymptomatic cement leakages were observed in 9.7% of the vertebral bodies, which is comparable to previous reports.

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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. Significantly reduced pain and thus improved mobility throughout the follow up period of three years appear to contribute to the reduced fracture incidence after balloon kyphoplasty. P128. Self-referral for osteoporosis assessment with DXA—what is the difference to patients sent by their physician? J. Swanenburg1,2, D. Uebelhart1,2, M. Di Chiara1, G.W. Goerres3; 1Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Zurich, Switzerland, 2 Centre for Prevention and Treatment of Osteoporosis, University Hospital Zurich, Zurich, Switzerland, 3Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland Objectives: The aim of the study is to assess incidence of diagnosis of osteoporosis (OP) in two groups with different motivation. The first group (Group A) were women referring themselves to an OP evaluation as a reaction on an advertisement in a popular Swiss weekly journal, aimed of informing the general public about OP. The second group (Group B+C) are female patients, referred by their general practitioner. Materials and methods: All measurements where performed with dual-energy X-ray absorptiometry (DXA) (Hologic QDR 4500 Elite). The T-scores of three arias were used for comparison; the total hip (T-hip), hip neck (T-neck) and the lumbar spine (T-sp). In a retrospective analysis of 770 consecutive patients undergoing DXA analysed. The analysis was restricted to those patients with an age of ≥40 years and young patients with a variety of medical problems such as anorexia nervosa, cystic fibrosis or Crohn’s disease were excluded from the analysis. Also patients known with OP and patient treated with high dose of steroids (high OP risk) were excluded. The self-referred Group A n=104 aged (mean ± SD) 63.1±8.6 years, group B n=269 aged (mean ± SD) (59.7± 9.4 years) send by their physician based on risk factors without an underlying clinically evident disease and group C n=104 patients, aged (mean ± SD) 68.9±10.3 years send by their physician based on a fracture. Results: The T-scores of the groups are: T-hip (mean ± SD) A=(−0.6±1.1), B=(−0.7±1.0), B2=(−1.7±0.9); T-neck A= (−1.1±1.1), B=(−1.2±1.1), C=(−2.0±0.9); T-sp A=(−1.1± 1.5), B=(−1.2±1.4), C=(−2.2±1.3).

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Group A was not significantly different group B, but it was significantly different to Group C (independent samples T-test; p<0.00). There was a significantly difference of age between A and B (p<0.00) but not between A and C. Conclusion: Wide spread public information, which inform about the risk factors for osteoporosis and promote the use of DXA, recruit similar women as physicians sending female patients with risk factors. However, with advertisements a relatively older population is addressed. Nevertheless the professional assignment of a general practitioner does locate patients at higher osteoporotic risk such as patients with a fracture. P129. Automatic computerized phalangeal joint space width measurement in females X. Bi1, L. Al-Dayeh1, S. Silverman2; 1CompuMed Inc., Los Angeles, California, United States, 2Cedars-Sinai Medical Center, Osteoporosis Medical Center (OMC), Los Angeles, CA, United States Objective: Quantitative assessment of Joint Space Width (JSW) is helpful in the diagnosis and monitoring of both osteoarthritis and inflammatory arthritis. The objective of this study was to perform automatic computerized measurement of phalangeal JSW and compared the results to manual measurements in 100 female subjects. Materials and methods: Fingers’ X-rays of 100 Caucasian and Asian normal female subjects ages 20–79 were taken using direct X-ray technique and scanned using a flatbed scanner at the resolution of 110 μ/pixel. For manual JSW measurement we used standard imaging software [NIH Image and Photoshop®(1)], images were displayed at a magnification of 200% (the equivalent of looking at the X-ray on a light box magnified six times), triplicate measurements of each JSW were performed and the mean was considered the JSW value. JSW of the Distal Inter-Phalangeal (DIP), Proximal Inter-Phalangeal (PIP) and bone length of the middle phalanges (2nd, 3rd and 4th) were measured. Mean and Standard Deviations of JSW were calculated for decade of age as well as the whole population. In automated JSW measurement a special customization for the patented technology of the OsteoGram®(2) (phalangeal bone density assessment) software was introduced (Fig. 1). The customization allowed fully automated and unattended JSW assessment of the DIP and PIP joints from measuring 38 JSW parallel segments in each joint. Fig. 1: The OsteoGram® software was customized to assess JSW of the DIP and PIP joints from measuring 38 JSW parallel segments in each joint. Figure shows a snapshot of OsteoGram® after detecting the axis of the 2nd, 3rd and 4th fingers, the contour of their soft tissues and the contour of their middle phalanges.

Results: JSW followed a normal distribution for all DIP and PIP joints, with a mean DIP JSW of 1.1 mm and a mean PIP JSW of 1.1 mm in the 2nd and 3rd fingers with a slightly narrower width for the 4th finger (0.1 mm less). The mean correlation (r) between manual and automated measurements was 0.71. We also calculated the association of age, height, weight and phalangeal bone length using Pearson’s (r). No significant correlations were found between JSW and age, height, weight or JSW and phalangeal bone length (r=−0.4 to 0.4). Conclusion: We conclude that JSW can be measured in female normals using a fully automated computer software from standard hand X-rays. Further studies in males and patients with arthritis are indicated. (1) Photoshop® is a trademark of Abobe Systems Inc. (2) OsteoGram® is protected by US patent 6,246,745 and a trademark of CompuMed, Inc., Los Angeles, CA

P130. Drug addiction—risk-factor of osteoporosis L. Kilasonial1, Z. Sikharulidze2, M. Skhiereli3, N. Ganugrava1; 1 National Association of Osteoporosis, Medical Centre Uranti, Tbilisi, Georgia, 2Medical Centre Uranti, Tbilisi, Georgia, 3 Medical-Diagnostic Centre Sonokur-Medi, Tbilisi, Georgia Up to the recent times there was accepted that the frequency of osteoporosis (OP) was higher in females. Though, during last few years the numerous research works and the results of our own work indicate that osteoporosis is quite frequent in males. One of three patients with the fracture of femoral bone is a male and mortality among males in higher than among females. High frequency of incidence of the risk-factors among males is confirmed. Though, actually, there are no works about frequency of osteoporosis in the people, who consume the drugs illegally. Taking into consideration the

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high rate of spreading of the drugs all over the world and especially, in our region, we set the goal of studying of the bone metabolism among the drug consumers, regarding the term, narcotization, character of the drugs and their doses. There were examined 111 patients with narcotism, in the abstinence period; among which 60 patients were heroin consumers and 51 buprenorphine consumers; age of the patients from 17 to 25. Average duration of the heroin narcotism—4.5 years and of average period of buprenorphine narcotism—1.5 years. Among the risk-factors of osteoporosis. Among the studied patients there were revealed: hypogonadism (71–80%); low calcium diet (72%); mallabsorption syndrome (64%); low body mass (78%). All patients underwent measurements of bone tissue mineral density, by dual X-ray absorption densitometry; measurements were conducted in the vertebras of lumbar region, proximal section of the femoral bone, in the distal section of the forearm. In all cases there was studied the Ca-P balance, level of osteocalcine in the blood and activity of the alkali-phosphatase; level of general and free testosterone in the blood. The research results showed that the frequency of revealing of osteoporosis (T<−2.5), among the patients with heroin narcotism is 40–48% and frequency of revealing in the trabecular bines is higher. Frequency of low characteristics of the bone tissue, in case of buprenorphine narcotism is lower and varies between 30–35%. There was revealed reliable decrease of calcium and testosterone levels in the blood (p< 0.05) and decrease of the free testosterone level in patients with heroin narcotism. There was revealed correlation between the duration of narcotisation and level of free testosterone in the patients with heroin narcotism (z=−0.58; p<0.001), on one hand and on the other—correlation between the mineral density of the bone tissue and the level of free testosterone (r=0.42; p<0.001). There is considered the issue of possible impact of the drugs on the bone metabolism process. It is recommended, for treatment of patients with narcotism, to include anti-osteoporosis preparations into the complex therapy. P131. ANKH gene is a potentially significant modifying factor for the effectiveness of both, antiresorptive (bisphosphonates) and anabolic (PTH derivatives) types of osteoporosis therapies S. Ermakov1, Y. Vistoropsky1, M. Keter1, I. Malkin1, S. Trofimov1, E. Kobyliansky1, G. Livshits1,2; 1Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 2Yoran Institute for Human Genome Research, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Objectives: Bisphosphonates (BPs) are pyrophosphate analogs that have been successfully used as antiresoptive

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treatment of postmenopausal and glucocorticoid-induced osteoporosis (OP). The inhibition of bone resorption in patients receiving BPs is caused by the inhibition of osteoclast-mediated bone resorption. Anabolic skeletal agents, from which parathyroid hormone (PTH) is the most promising, affect processes primarily associated with bone formation, and have also been successfully applied to treatment of OP. We recently demonstrated that polymorphisms in the human homologue of the mouse progressive ankylosis gene (ANKH)—one of the key genetic factors involved in inorganic pyrophosphate metabolism and bone mineralization—are strongly associated with various bone strength and bone turnover related phenotypes. This suggests that ANKH genetic variation may influence osteoblast and osteoclast physiology, and thus modify the effectiveness of the OP treatment both by antiresorptive and by anabolic agents, and possibly by there combinations. In order to further study the ANKH effects on bone physiology, the objective of the present study was to examine whether polymorphisms in ANKH gene can be associated with PTH levels in apparently healthy human populations. Materials and methods: The study sample comprised 212 nuclear families (743 individuals). Nine ANKH SNPs were studied for association with PTH circulating levels using four different transmission disequilibrium tests. Results: We found a significant association (p<0.05) between PTH and two SNPs: rs39968 and rs875525. However, the association became particularly significant (p-values from 0.0024 to 0.0007) when the association with the haplotypes generated from the above SNPs was tested. This association remained significant even after correction for multiple testing with a false discovery rate of 0.032. Conclusions: Importantly, we also observed strong association between ANKH polymorphisms and circulating osteoprotegerin levels (p=0.0003). The above findings together with previously reported evidence of strong association between ANKH and bone strength phenotypes, demonstrate that ANKH genetic variation affects bone turnover through an elaborate network of pathways. These findings make an important contribution to our understanding of the molecular-genetic mechanisms of BPs effect and make ANKH gene extremely attractive for future pharmacogenetic research of the effectiveness of antiresorptive (BPs) and anabolic (PTH derivatives) types of osteoporosis therapies. P132. Long term hip fracture costs related to institutionalization F. Borgström, O. Ström; European Health Economics, Stockholm, Sweden Objectives: Long-term costs related to hip fracture has often been based on the proportion of patients moving from own

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residence to a long term care facility. This change in living has been assumed to be related to the hip fracture for the remainder of life. However, this is a simplification because with time there is a probability that the patient had been institutionalized regardless of the sustained fracture which has to be accounted for if the long term costs are to accurately assessed. The objective of this study was to estimate how long institutionalization after hip fracture can be said to be related to the fracture event and to estimate the long-term hip fracture costs related to institutionalization in Sweden. Materials and methods: Data on living conditions before and 1 year after a hip fracture were derived from the Stockholm county council. The prevalence and incidence of being institutionalized with increasing age in the Swedish general population was derived from the National Board of Health and Welfare. To obtain the reduced proportion of institutionalizations over time related to a hip fracture the proportion of patients that had moved from private residence to an institution 1 year after fracture was reduced by the annual incidence of being institutionalized in the general population. The annual hip fracture cost was assessed by multiplying the proportion of fracture related institutionalizations with the annual cost of institutionalization (€ 63 035). Results: Women fractured at an age of 65 had on average a fracture cost related to institutionalization that persist for 16 years after fracture; from € 4 711 to € 745. Women fractured at an age of 85 have on average a cost related to institutionalization that persist for 7 years after fracture; from € 13 045 to € 1 182. Conclusions: The hip fracture cost related to institutionalization increases with increasing fracture age of the patient but the period institutionalization can be related to the fracture decreases with increasing age. This might have an important impact on the results of cost-effectiveness analyses of osteoporosis treatments which have to be investigated further. P133. Balloon Kyphoplasty in the management of vertebral compression fractures: an updated systematic review and meta-analysis R. S. Taylor1, P. Fritzell2, R. J. Taylor3; 1Peninsula Medical School, University of Exeter, Exeter, United Kingdom, 2 Department of Orthopaedic Surgery, Center of Clinical Research Dalarna, Falun Hospital, Falun, Sweden, 3Health Economics Facility, University of Birmingham, Birmingham, United Kingdom Objectives: This systematic review updates the understanding the of the evidence base for balloon kyphoplasty (BKP) in the management of vertebral compression fractures. Materials and methods: Detailed searches of a number of electronic databases were performed through to April 2006. Citation searches of included studies were undertaken and

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no language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. Results: Combined with our previous systematic review on balloon kyphoplasty evidence(1), a total of eight comparative studies (3 against conventional medical therapy and 5 against vertebroplasty) and 35 case series were identified. The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with longterm pain that was refractory to medical treatment. In direct comparison to conventional medical management, patients undergoing BKP experienced superior improvements in pain, functionality, vertebral height and kyphotic angle at least up to 3-years post procedure. Reductions in pain with BKP appeared to be greatest in patients with newer fractures. Uncontrolled studies suggest gains in healthrelated quality of life at 6 and 12-months following BKP. Although associated with a finite level of cement leakage, serious adverse events appear to be rare. Osteoporotic vertebral compression fractures appear to be associated with a somewhat higher level of cement leakage following BKP than non-osteoporotic vertebral compression fractures. Conclusion: Increasing body of direct comparative evidence supports the use of BKP as an effective therapy in selected patients with painful vertebral compression fractures, at least in the period up to 3-years following the procedure. Ongoing international multi-centre studies should provide randomised controlled trial level of evidence for BKP within the next 2 to 3-years. (1) Taylor RS, Taylor RJ, Fritzell P. Balloon kyphoplasty and vertebroplasty for vertebral compression fractures: a comparative systematic review of efficacy and safety. Spine 31:2747–2755

P134. Effect of low-level laser therapy on 13-week immobilized articular cartilage in rabbit M. Bayat1, A. Ansari2, H. Hekmat3; 1Anatomy Department and Cell and Molecular Research Center, Medical Faculty Shaheed Beheshti University of Medical Scienses, Tehran, Iran, 2Iranian Islamic Free University, Arak, Iran, 3Anatomy Department, Medical Faculty, Shaheed Beheshti Medical University, Tehran, Iran Objective: The aim of present study was to evaluate the effect of low-level laser therapy (LLLT) on articular cartilage on long term immobilized knee joints of rabbits. Materials and methods: Fiftheen adult male rabbits were divided into normal, control and laser groups. The right hind limbs of control and experimental groups were immobilized in 90° flexion hip. Immololibilized femoral condyles of rabbits of laser group were exposed to LLLT with Helium–Neon laser (13 J/cm2) three times a week. At

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the end of thirteenth week condyles of the right hind limb of rabbits were extracted and were prepared for light microscopy and transmission electron microscopy and scanning electron microscopy studies. Results: Number of chondrocytes and depth of articular cartilage of experimental group were significantly higher than relevant parameters of control group (P<0.001 and P< 0.05, respectively). Surface morphology of control group had rough prominences, fibrillation and lacunae, but surface morphology of experimental group had more similarities to normal group than to control group. There were marked differences between ultrastructure features of normal and experimental groups in comparison with control group. Conclusion: LLLT on 13 weeks immobilized knee joints of rabbits neutrilized adverse effects of immobilization. P135. Unexpected low incidence of vertebral fracture in heart transplant recipients: analysis of bone turnover K. Kerschan-Schindl1, M. Ruzicka2, S. Grampp3, A. Gleiss4, C. Bieglmayer5, V. Fialka-Moser1, R. Pacher6, M. Grimm2, P. Pietschmann7; 1Department of Physical Medicine and Rehabilitation, University of Vienna, Vienna, Austria, 2 Department of Surgery, University of Vienna, Vienna, Austria, 3Department of Radiology/Osteology, University of Vienna, Vienna, Austria, 4Department of Medical Computer Sciences, University of Vienna, Vienna, Austria, 5 Department of Biochemistry, University of Vienna, Vienna, Austria, 6Department of Internal Medicine, Division of Cardiology, University of Vienna, Vienna, Austria, 7Institute of Pathophysiology, University of Vienna, Vienna, Austria Objective: Heart transplantation (HTX) is associated with a reduction of bone mineral density and changes in bone metabolism. Available markers of bone metabolism and the immunosuppressive regimen change in the course of time and, thus, this study was conducted to reinvestigate bone metabolism in HTX recipients. Materials and methods: Twenty-five HTX recipients were compared to 25 HTX candidates in concerns of biochemical parameters of bone metabolism and bone mineral density. Results: Osteopenia or osteoporosis was observed in approximately two thirds of the HTX recipients. Nevertheless, only three patients (12%) of the HTX recipients had a vertebral fracture; no peripheral fractures occurred. Compared to the group of HTX candidates recipients had significantly lower serum calcium levels, higher serum levels of CTX, lower serum levels of osteocalcin, and lower values of serum creatinine and blood urea nitrogen. In males, bioavailable testosterone was significantly lower in HTX recipients than in HTX candidates. In HTX recipients, serum levels of calcium and 25-OH-vitamin D started relatively low but soon increased. Osteocalcin also increased after an initial bottom value

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during the first three months. The bone-specific alkaline phosphatase did not change very much. Serum levels of crosslinked-N-telopeptide of type I collagen and parathyroid hormone remained high throughout the entire year. In male HTX recipients, serum levels of bioavailable testosterone increased especially within the first few months. Serum creatinine and blood urea nitrogen were relatively high at all measurements. Conclusion: Despite the fact that bone turnover increased immediately after transplantation an unexpectedly low rate of vertebral fractures was observed in our patient group. P136. Effects of alendronate and hormone replacement therapy on the bone mineral density of postmenopausal Iranian women F. Sharifi, Y. Jaberi, L. Perse, G.R. Ahmadi; Department of Endocrinology,Vali-e-Asr Hospital, Zanjan University of Medical Sciences and Health Services, Zanjan, Iran Aim: To compare the effect of alendronate and hormone replacement therapy (HRT) on bone mineral density of postmenopausal Iranian women living in Zanjan, one of the north western provinces of Iran. Materials and methods: We treated 115 women (age mean 8/54±9 years). Twenty four women were treated with conjugated equine estrogen (0.625 mg), medroxyprogesterone 5 mg, and elemental calcium 1,000 mg with vitamin D 400 IU daily. Forty four subjects received alendronate 10 mg/day plus calcium and vitamin D in the same dose and 37 women taken placebo with calcium 1,000 mg/day and vitamin D 400 IU/day. Their bone mineral densities (BMD) were measured at the lumbar spine, hip and mid radius every 12 months for 3 years. All cases with secondary osteoporosis were excluded from the study. Results: Significantly higher percentage increases in BMD at the lumbar spine (P<0.008, 2-way analysis of variance) throughout the 36-month treatment period were found in the alendronate group than in the HRT and placebo groups. However, there was no difference in BMD at the femoral neck and mid-radius between alendronate and HRT groups. Treatment with alendronate resulted in a 11% increase at the L-spine BMD (P: 000). A non significant reduction about 4% at the femoral neck BMD was detected in alendronate group at the end of the 3-year study period. Although there was no significant change in the femoral neck, lumbar spine or mid-radius BMD with HRT a significant decline (about 9%) in the BMD of the femoral neck was observed in the placebo group (p: 0.004). There was no difference in upper gastrointestinal or drug-related side effects between groups. Conclusion: Our data suggest that the use of alendronate for 3 years was well tolerated and it significantly increased BMD at the L-spine. It can reduce the rate of BMD reduction

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at the femoral neck seeing in the placebo group in postmenopausal Iranian women. Although HRT can inhibit BMD reduction at the femoral neck and lumbar spine, this regimen can not increase BMD in postmenopausal Iranian women. P137. Osteoporosis and atherosclerosis in postmenopausal women S. Kuzmanova, P. Solakov; Clinic of Rheumatology, University Hospital, Plovdiv, Bulgaria Objective: Both osteoporosis and atherosclerosis increase in frequency with advancing age, both appear worse and more frequent with estrogen deficiency, and both involve calcifications. A number of mechanisms are common to both. It is not clear whether there is significant relationships between two disease processes. We investigated whether the severity of aorta calcification (AC) as a marker of atherosclerosis is an independent predictor of low BMD, accelerated bone loss and risk of incident fractures in postmenopausal women. Materials and methods: From 2004 to 2006, we examined 47 postmenopausal women with: (1) primary osteoporosis (based on BMD T-score criteria), 65 to 74 years old (mean age 72±3.5), with BMI between 19.1 to 27.4; (2) visualized AC on lateral lumbar radiographs. Outcome variables were rate of bone loss from the lumbar spine and proximal femur and amount of calcified deposits in the aorta. DXA studies were analyzed to assess the possible associations between bone mineralization and AC. Primary osteoporosis was defined as a value of BMD T-score 2.5 SD below peak values. Excluded from this study were patients who were received biphosphonates, calcitonine, corticosteroids, or with history of cancer. For evaluation of the calcified plaques in the lumbar aorta Kauppila et al. semi-quantitative standard score was used. The lumbar part of the aorta was divided in four segments adjacent to vertebra L1–L4, an severity of anterior and posterior AC are graded individually for each segment on 0–3 scale. The results are summed in a composite severity score ranging from 0 to 24. The majority of the plaques were visible along the anterior and posterior aortic walls and not between them. The aortic walls are visible only if calcium is present. Results: Overall measures of AC correlated moderate inverse with BMD of the proximal femur (r=−0.50;P< 0.05) and BMD of the spine (r=−0.48;P=0.02). The correlation with vertebral fractures was weak (r=0.29;P> 0.05). Women with heavy severe AC were older, with less physical activity, higher systolic blood pressure and lower bone density. The AC included in multivariate regression analyses were an independent variable of increased risk for primary osteoporosis.

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Conclusion: We found independent moderate inverese correlation between the degree of AC and BMD of the proximal femur and the lumbar spine. Our results show that women with vascular calcifications are predisposed to osteoporosis of the spine and femur. If the localization of the aorta is known on the image, the detection of calcifications becomes easier, but the aorta segmentation is a difficult problem if the non-calcified parts of the aorta are not visible on X-rays. P138. Comorbidity in distant radius osteopenic postmenopausal women A. Popov, N. Izmozherova, M. Fominykh; Department of Internal Medicine N°2, The Urals State Medical Academy, Ekaterinburg, Russia Aim: To assess comorbidity in postmenopausal women with osteoporosis. Materials and methods: Dual energy X-ray absorptiometry of non-dominant arm distant radius was performed in 681 postmenopausal women (average age 54.8±5.81), who filled out the National Osteoporosis Risk Factors Assessment Questionnaire. Results: Distant radius osteoporosis and osteoprenia were found in 112 women. Arterial hyperternsion (AH) was diagnosed in 91 (81.3%) osteopenic women, and 50 (44.6%) of them had severe AH. Coronary heart disease was found in 40 (35.7 %) patients, nine of them had had myocardial infarction, and nine passed through cerebral ischemic events. Besides, 56 women (50%) had chronic heart failure, 41 patients (36.6%) suffered from gastroesophageal reflux and/or peptic ulcer. There were also 34 (30.4%) cholecystectomized persons and 18 cases of type 2 diabetes registered. Thus, each osteopenic person by the date of diagnosis of osteoporosis or osteopenia had been already receiving from 3 to 14 tablets a day (median: 5 tablets a day). The newly emerging necessity to add calcium, vitamin D and antiresorptive agent turned out to be quite annoying both for the patients and their doctors. Conclusion: Alternative routs of administration or intermissive regime of antiresorptive agents should be discussed in cases of comorbidity in osteopenic postmenopausal women. P139. Cross-sectional and longitudinal clinico-radiological correlations in hand OA E. Maheu1, C. Cadet2, G. Baron3, P. Ravaud3, M. Dougados4; 1 Service de Rhumatologie, Hôpital St-Antoine, Paris, France, 2Paris, France, 3Unité d’Epidémiologie et de Biostatistiques, Hôpital Bichat, Paris, France, 4Service de Rhumatologie B, Université René Descartes, Hôpital Cochin, Paris, France

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Introduction: Hand osteoarthritis (H0A) has an unpredictable evolution with respect to both symptoms and structural changes. No clear correlation between symptoms and radiographic severity has been established. We miss studies on this topic. Furthermore, many patients at end radiographic stages of HOA are painless, indicating a high discordance between pain and structural severity of the disease. Objective: To study the cross-sectional and longitudinal prospective relationship between symptom and radiographic severity in HOA. Materials and methods: Two readers scored separately 105 pairs of radiographs (baseline; year 1), selected from patients enrolled in a randomised controlled trial, using Kallman and Kellgren-Lawrence (KL) scoring systems. Patients characteristics were described and baseline and year 1 level of symptoms assessed using a VAS for pain rating and the Functional Index for Hand OA (FIHOA). Statistics: The Pearson correlation coefficient was calculated for cross-sectional correlations, between pain and FIHOA scores and radiographic severity assessed using Kallman and KL radiographic scoring methods. For longitudinal correlations, the Pearson correlation coefficient was also used for comparisons between baseline radiographic severity and the clinical evolution, and between baseline levels of pain and dysfunction and radiographic progression over 1 year. Results: Patients were aged 61±6 years, 93% women, 83% right-handed. The most painful joint at enrollment was the TMC (43%), the PIP (23%) and DIP (31%). Pain rated 56± 16 mm and FIHOA score 12±4.6. Cross-sectional correlations: There was a correlation between the FIHOA and radiographic assessed by both Kallman (R=0.34; p=0.0004) or KL (R=0.35; p=0.0002) scorings. There was also a correlation between pain on a VAS and Kallman scoring (R ranged from 0.19 to 0.21 according to the reader; p=0.05 and 0.03, respectively), but not with KL scores. Baseline values of pain and FIHOA scores were correlated (R=0.3; P=0.0012). Longitudinal correlations: No significant correlations were found between baseline radiographic severity and the subsequent course of symptoms, indicating that pain and function were two independent variables from baseline radiographic severity. Similarly, no correlation was observed between baseline levels of symptoms (either pain or function) and subsequent radiographic progression over one year. Conclusion: In this sample the level of HOA symptoms was cross-sectionally correlated to radiographic severity at baseline. We found no correlation between baseline clinical status and radiographic progression or between baseline radiographic severity and the clinical course of symptoms indicating that radiographic progression and clinical evolution might be independent variables in HOA.

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P140. Sensitivity to change of various radiographic scales in hand OA, including modified Kallman and Verbruggen scores E. Maheu1, C. Cadet2, G. Baron3, P. Ravaud3, M. Dougados4; 1 Service de Rhumatologie, Hôpital St-Antoine, Paris, France, 2Paris, France, 3Unité d’Epidémiologie et de Biostatistiques, Hôpital Bichat, Paris, France, 4Service de Rhumatologie B, Université René Descartes, Hôpital Cochin, Paris, France Introduction: Hand osteoarthritis (0A) could be a relevant model to study OA progression in structure-modification trials. Various methods are proposed to radiologically assess hand OA and its progression. The Kallman and Verbruggen scores have shown good inter- and intra-observer precisions in a previous work. However, these scores could be simplified to be used in structure-modification trials. Objective: To study the sensitivity to change of Kallman, Vergbruggen and modified Kallman and Verbruggen radiological scoring methods proposed to assess hand OA. Materials and methods: Two trained readers scored separately 105 pairs of radiographs (baseline ; year 1), selected from patients enrolled in a randomised controlled trial, for inter-reader reliability and sensitivity to change. They scored twice 60 pairs among the 105 for cross-sectional and longitudinal intra-reader reliability. Radiological hand OA assessment used were Kallman; Verbruggen scoring methods and modified Kallman [each of the six items composing the score were studied and osteophyte (O) and joint space narrowing (JSN) assessments coupled] and Verbruggen scores [without scoring the metacarpo-phanlangeal (MCP) joints]. The sensitivity to change was compared by calculating the standardised response means (SRM). Results: SRMs ranged as indicated in the table below. RSM Kallman

Verbruggen

Total JSN + O JSN O Subchondral sclerosis Subchondral cysts Deformation Erosions Total Without MCP

Reader 1

Reader 2

0.22 0.23 0.17 0.21 0.09 0.14 −0.04 0.23 0.20 0.20

0.26 0.23 0.23 0.12 0.20 0.06 −0.09 0.23 0.23 0.23

Conclusion: All methods compared well with respect to sensitivity to change, which was modest in any case. However, the Verbruggen score doesn’t not loose any sensitivity when scored without the MCPs, and scoring only osteophytes and joint space narrowing does not alter

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the sensitivity of the originally proposed Kallman grading scale. The Kallman and its modification (osteophyte + joint space assessment) were slightly more sentitive to change. Erosions could be separately scored as they assess a particular stage of hand OA progression. P141. Risk factor analysis of post-menopausal fracture—a hospital based study P.-K. Lee 1, C.-C. Chang1, C.-T. Yu1,2; 1Orthopedic Department, Changhua Christian Hospital, Changhua, Taiwan, 2 Department of Mechanical and Automatic Engineering, Da-Yeh University, Changhua, Taiwan Introduction: Osteoporotic fracture poses a substantial clinical, economic, and health-related burden to the individual, family, society and national heath-care system. As we know, the risk of female osteoporosis is related to peak bone mass and early menopause. Low peak bone mass is associated with high probability of fragility fracture. Objective: We investigated the potential associations between the estrogen-related event and osteoporotic fractures. Materials and methods: One hundred and sixty-five postmenopausal women were enrolled in a case-control, hospital-based prospective study from Jan. 2004 to Dec. 2004. Menopausal age, body weight, height and BMD were used as analysis to clarify their relations to osteoporotic fractures. Results: In our study, body weight and height were not related to osteoporotic fractures; however, we found osteoporotic fracture are related to lower BMI (P=0.0169). Early menopausal age (47 vs. 50 P=0.0156) was associated higher fracture rate. After age adjustment, we found age 48 as a suitable cut-off value for osteoporotic fracture (OD= 9.062, 95% C.I. 1.081∼75.942). An appropriate menopausal age cutoff may be an indicator for osteoporotic fracture. P142. Alendronate increases the expressions of osteogenic genes and decreases the expressions of adipogenic genes in human bone marrow mesenchymal stem cells C. Chen, M. Ho, K. Liu, C. Chen, C. Hsu, J. Chang, G. Wang; Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan Objective: Bisphosphonates are well known potent inhibitors of osteoclast activity and widely used clinically. Bisphosphonates act as blockers of in the mevalonate pathway. Statins, HMG-coA reductase inhibitor in mevalonate pathway, are found to increase bone formation. Statins are also indicated to counteract the suppressive effects in osteogenesis and the stimulatory effects in adipogenesis by glucocorticoid in bone human marrow

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mesenchymal stem cells (hBMSCs). Recently, there is increasing evidence that bisphosphonates also interact with osteoblasts. In this study we investigated the effect of alendronate on the expressions of osteogenic and adipogenic genes in hBMSCs. Materials and methods: Human bone marrow was obtained from the iliac crest of a 16-year-old healthy volunteer. After percoll separation, the nucleated stromal cells were isolated for culture. hBMSCs were selected by KNAC medium after 12 days of culture. Drug treatments for culture were dexamethasone (10-7 M), alendronate (10-7 M, 10-6 M, 10-5 M), and combined dexamethasone (10-7 M) with alendronate (10-7 M, 10-6 M, 10-5 M) for 1, 3, 7 and 14 days. The mRNA expressions of bone morphogenetic protein 2, (BMP2) and adipsin were evaluated by RT-PCR. Results: The mRNA expression of BMP2 was significantly decreased by dexamethasone treatment after 3, 7 and 14 days in hBMSCs. In contrast, alendronate (10-7 to 105 M) increased the expression of BMP2 in hBMSCs and partially reversed the suppressive effects of dexamethasone on the expression of BMP2 in hBMSCs. On the other hand, the expression of adipsin was significantly increased by dexamethasone; alendronate significantly decreased the expression of adipsin and partially reverse the stimulatory effect of dexamethasone after 1, 3, 7 and 14 days. Conclusion: Our study demonstrated that alendronate increases BMP2 expression and decrease adipsin expression. Alendronate may be a potent drug to stimulate bone formation other than its potent effect on bone resorption. Furthermore, we also found that alendronate reversed dexamethasone induced adipogenesis and osteogenesis suppression. These results suggest that the effects of dexamethasone on suppressing osteogenesis and enhancing adipogenesis in hBMSCs might act through altering the mevalonate pathway that could be blocked by both statins and alendronate. P143. Complex regional pain syndrome after total knee arthroplasty Ch. Yu1, Ch. Cheng2, P. Lee2; 1Orthopedic Department, Changhua Christian Hospital, Changhua, Taiwan, 2RN Orthopedic Department, Changhua Christian Hospital, Changhua, Taiwan Introduction: Total knee arthroplasty has been approved an effective procedure for pain relief in patients with end-stage knee arthritis. Pain and stiffness following TKA can be extremely disappointing to both patient and surgeon. Among readily identifiable causes for such disability, complex regional pain syndrome represents particularly troublesome and misdiagnosed entity. Case report: A 72-year-old lady underwent cemented TKR due to tricompartmental osteoarthritis. One month after operation, she complained diffuse pain about her knee and

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calf with erythematous swelling and tenderness. Radiographs showed satisfactory position of implants. The findings of Tc99m bone scan were compatible to complex regional pain syndrome appearance. Then, she was transferred to our pain clinic for confirmation and therapy. The patient underwent intravenous regional sympathetic blocks (IRSBs) for block with the formula: reserpine 1 mg plus 1%Xylocaine 10 ml in N/S 40 ml for 30-min duration. Complete resolution was achieved after four injections. Conclusion: Complex regional pain syndrome following total knee replacement is a rare clinic. The mechanism of reflex sympathetic dystrophy remains obscure, and it can be a cause of early poor results following total knee arthroplasty.

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.

P144. Fear of falling in patients newly-diagnosed with osteoporosis C.E. Wetherell1, E.W. Thornton1,2, A.D.M. Davies1,2, L. Poll3, M. Siddiqi3; 1University of Liverpool, Liverpool, England, 2 Mersey Care National Health Service Trust, Liverpool, England, 3Aintree University Hospital National Health Service Trust, Liverpool, England

P145. A comparison of DXA measurement at the lumbar spine and proximal femur for premenopausal women M.R. Salamat1,2, S.R. Farzaneh2,3, A.H. Salari4, H.R. Ziaei5, M. Mir Bagheri6, K. Company2; 1Department of Medical Physics, Isfahan University of Medical Sciences, Isfahan, Iran, 2Isfahan Osteoporosis Diagnosis Center, Isfahan, Iran, 3Rhumatology Private Surgery, Zayandeh Roud Complex, Ferdousi St, Isfahan, Iran, 4Rhumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran, 5Orthopedic Division, Baharestan General Hospital, Isfahan, Iran, 6Orthopedic Division, Sadoughi General Hospital, Bozorgmehr St, Isfahan, Iran

Aims: To measure levels of fear of falling (FOF) in fracture patients newly-diagnosed with osteoporosis and to see if any measured effects were stable over time. Materials and methods: The study design was both crosssectional and longitudinal. Eighty-four post-fracture patients (mean age 63; sd=9.83) were recruited from a hospital bone density clinic and interviewed before their DEXA scan. FOF was measured using the SAFFE(1); the FES(2) and the FHI(3). Personality was measured using the N (neuroticism) scale of the NEO-PI(4). The FOF questionnaires were sent out by post to the patients immediately after diagnosis and again at 6 months post-diagnosis. A total of 54 patients completed all three sets of questionnaires correctly. Analysis showed there were no significant differences between those who did return questionnaires and those who did not. 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=0.008) and the SAFFE Worry subscale (Chi sq =20.31; p=≤0.001) 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 cut-off 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

(1) (2) (3) (4)

Lachman et al., 1998 Tinetti et al., 1990 Markson et al., 1995 Costa and McRae 1992

Objectives: This study compared bone mineral density (BMD) of the lumbar spine (LS) and femur neck (FN) for premenopausal women. Materials and methods: BMD measurements using dual energy X-ray absorptiometry technique (DXA) have been performed at Isfahan Osteoporosis Diagnosis Center, since March 2002. Among the referred subjects 185 premenopausal women who had no known history of diseases 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: Mean BMDs of 0.859±0.136 and 1.012±0.161 for the FN and LS were found, respectively. 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 women, we found a significantly lower (t=−9.02, p<0.0001) BMD mean T-score for the FN. BMD T-scores of −0.551±0.99 SD and −1.09± 1.17 SD for the LS and FN were found, respectively. This

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finding was in consistent with previously reported results.(1) This may be due to physiological and life-style factors. Therefore, further research is required to determine the reason(s). (1) Salamat M.R., Farzaneh S.R., Ziaei H.R., Mir Bagheri M., Company K. A Comparison of dual energy X-ray absorptiometry measurement at the LS and proximal femur for postmenopausal women. Presented at National Osteoporosis Society 11th conference on osteoporosis, 25–28 June 2006, Harrogate United Kingdom.

P146. Efficacy of Ibandronate in preventing bone loss in patients under high dosage of Glucocorticoid therapy—a randomized, 2 parallel groups, open label J. Scali, S. Visentini, E. Morales, Y. Ju, G. Pacheco, S. Veiga, L. Ugarte; Rheumatology and Metabolic Bone Diseases Unit, Durand University Hospital, Buenos Aires, Argentina Objective: Efficacy of Ibandronate in preventing bone loss in a population under high dosage Glucocorticoid (GC) therapy. Design: Open label, randomized in 2 groups. Group 1: on Ibandronate + elemental calcium (1,200 mg/day); group 2: on Vit D (400 U/day + elemental calcium 1,200 mg/day). Materials and methods: Pts on more than 0.5 mg/Kgbw/ day were randomized to receive either G1: Ibandronate 150 mg/month + elemental Ca; or G2: Vit. D 400 U/day + elemental Ca. Baseline demographic data, osteoporosis risk factors, cumulative dosage of GC, serial BMD (Lumbar spine, left hip) at baseline, 3 months and 9 months posttreatment (by DXA Scan) were obtained and compared between 2 groups. Results: Fity-two pts were included (36 women and 16 men) with an average age of 48.8+14 years. Diseases included were: SLE (25 pts), inflammatory myopathies (15 pts) and 12 pts suffering from RA with vasculitis. No patients were GC-naïve. The starting dose of Prednisolone was 0.7+0.2 mg/Kgbw/day and 20 women were menopausal. Osteopenia (T scores) of the spine and hip were present in 57 and 40% of the pts regarding both groups at baseline. Thirty-nine pts had completed the 9 months study, whereas five pts had withdrawn. Data presented at baseline were not significant between both groups. At 9 months a significant gain in spinal BMD was noted on Ibandronate group (+1.0 +2.2%; p=0.02) whereas a drop of BMD of the left Total hip was detected in group on vit D (−0.5+2.9%) p=0.46. A significant drop of BMD of Total Hip (−1.5+3.2, p=0.01) was present in the group 2 but not on group 1. After ajustement of demographic data for baseline, BMI and cumulative prednisolone dosages during 9 months between both groups remained significant (ANCOVA; p=0.022). No new fracture was seen in our pts and the compliance/

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adherence to treatment was good. No patient were withdrawn because of side effects. Conclusion: In this preliminary result at 9 months Ibandronate seems improving spinal and maintain hip BMD, in a population of pts on high dose of GC. Ibandronate was very good tolerated during the study. P147. Osteoporosis and osteopenia in the population of Tirana—Albania D. Ruci1, A. Tafaj1, V. Ruci2, A. Priftanji1, F. Toti3, D. Tole4; 1 Service of Rheumatology, Mother Teresa University Hospital, Tirana, Albania, 2Service of Orthopedics, Mother Teresa University Hospital, Tirana, Albania, 3Service of Endocrinology, Mother Teresa University Hospital, Tirana, Albania, 4INSTAT (Instituti i Statistikës), Tirana, Albania Purpose: The aim of the study was to establish the prevalences of osteoporosis and osteopenia in the population of Tirana, in general and separately for females and males. The study evaluated the prevalence of osteoporosis and osteopenia in women after 50 years old. Materials and methods: Our study was prospective, epidemiologic, cross-sectional. The study included 1,084 subjects, 670 females and 414 males. Were chosen 1 in every 80 habitants from four different Primary Ambulatory Centers. Bone Mineral Density was measured in every subject using a heel ultrasound bone densitometer (Pegasus type). For each subject height and weight were documented. A detailed questionnaire were compiled for every subject. The data gathered were analyzed using STATA program. The criteria of osteoporosis were those of WHO; T-score less then −2.5 SD. Results: The prevalence of osteoporosis in the population of Tirana was 7.28 %. Osteopenia was found in 33.1% of total population over 20 years old. Osteoporosis was more frequent in women, 9.6% compared with only 3.6% in men. Osteoporosis was significantly more common in women after 50 years old 15.2%. Osteoporosis was found more frequent in men after 65 years old, 8.1%. Conclusions: Osteoporosis is a frequent disease in our population. Women are affected more then men with a ratio 2.66:1. Women are affected more after 50 years old and men after the sixties. P148. Alendronate with or without calcium supplementation was significantly more effective than calcium supplementation alone in improvement of bone mineral density and bone turnover markers, with no difference in upper-GI tolerability S. Bonnick1, S. Broy2, F. Kaiser3, C. Teutsch3, E. Rosenberg3, P. DeLucca3, M. Melton3; 1Clinical Research, CRC of North Texas, Denton, Texas, 2Illinois Bone and Joint Institute, Morton Grove, Illinois, USA, 3Merck and Co., West Point, Pennsylvania, USA

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Background: The bisphosphonate alendronate and supplemental calcium are each recommended for treatment of osteoporosis in postmenopausal women. However, no trial has directly compared alendronate to supplemental calcium or examined the effect of calcium supplementation on alendronate treatment. Materials and methods: This 24-month, randomized, double blind, multicenter trial enrolled healthy, communitydwelling, postmenopausal women with low bone mineral density (BMD). Patients who maintained daily dietary intake of at least 800 mg calcium received daily 400 IU vitamin D and (2:2:1) alendronate 10 mg + calcium placebo, alendronate 10 mg + elemental calcium 1,000 mg (in the form of calcium carbonate), or alendronate placebo + calcium 1,000 mg. Endpoints included BMD at lumbar spine, trochanter, and femoral neck; bone turnover markers (BTMs) BSAP and NTX; and adverse experiences. Results: Randomized patients (N=701) were an average of 20.4 years postmenopausal. After 24 months, increases in lumbar spine BMD differed significantly between patients receiving calcium alone (0.8%) and either alendronate alone (5.6%) or alendronate + calcium (6.0%) (p < 0.001). Significant differences were also seen at the trochanter and femoral neck (p<0.001). BTMs were significantly lower with alendronate-containing treatments than calcium alone (p < 0.001). Addition of calcium supplementation to alendronate did not significantly increase BMD compared with alendronate alone (p=0.29 to 0.97) but did result in a statistically significant, though small, additional reduction in urinary NTX. Adverse experiences, including those in the upper gastrointestinal tract, were similar among treatment groups. Conclusions: In postmenopausal women with a daily intake of ≥800 mg calcium and 400 IU vitamin D, 24month treatment with alendronate 10 mg daily with or without calcium 1,000 mg resulted in significantly greater increases in BMD and reduction of bone turnover than treatment with 1,000 mg supplemental calcium alone. Addition of supplemental calcium to alendronate treatment had no effect on BMD and resulted in a small though statistically significant additional reduction in NTX. P149. Denosumab is a selective inhibitor of human receptor activator of NF-Kb ligand (RANKL) that blocks osteoclast formation and function R. Elliott1, P. Kostenuik1, C. Chen1, M. Kelley1, N. Hawkins1, J. Housman1, S. McCabe1, V. Mukku1, JK. Sullivan1, W. Dougall2; 1Amgen Inc., Thousand Oaks, California, USA, 2 Amgen Inc., Seattle, WA, USA Introduction: RANKL, a member of the TNF superfamily, is an essential mediator of osteoclast formation, function, and survival. Increased osteoclast activity is critical in the

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pathogenesis of a broad range of diseases associated with pathologically increased bone resorption. Denosumab is an investigational, fully human monoclonal antibody to RANKL in clinical trials for the prevention and treatment of postmenopausal osteoporosis. Here we report the results of in vitro and in vivo studies characterizing the RANKLbinding properties of denosumab and its effects on osteoclast differentiation and function. Materials and methods: Denosumab binding to human RANKL (huRANKL) was determined by flow cytometry and ELISA, and the binding affinity was measured using BIAcore and a kinetic exclusion assay. The effects of denosumab on osteoclast formation in vitro were assessed using the mouse RAW 264.7 cell line. To evaluate the effect of denosumab on osteoclast function in vivo, mice were administered soluble huRANKL (twice daily at 1.0 mg/kg/day for 5 days), which produced hypercalcemia due to increased bone resorption. Concurrent with the first huRANKL dose, mice were treated with vehicle, another RANKL inhibitor, OPG-Fc (3 mg/kg), or various single doses of denosumab (1, 3, or 10 mg/kg). Results: Binding assays showed that denosumab bound both soluble and membrane-bound forms of huRANKL. Moreover, denosumab binding to either form of huRANKL was inhibited by excess huRANKL, but not by TNF-α, TNF-β, TRAIL, or CD40 Ligand. Using BIAcore methods and a kinetic exclusion assay, the dissociation constants of denosumab were calculated to be 9.5×10−11 and 3× 10−12 M, respectively. Denosumab neutralized the ability of soluble huRANKL to stimulate the differentiation of RAW 264.7 cells into osteoclasts in vitro (IC50 of 1.64 ng/ml vs OPG-Fc IC50 of 1.15 ng/ml). Administration of either denosumab or OPG-Fc delayed the development of hypercalcemia in huRANKL-treated mice, indicating that denosumab neutralized osteoclast activity in vivo. Denosumab caused dose-dependent suppression of hypercalcemia in this model. Conclusion: These data demonstrate that denosumab binds human RANKL selectively and with high affinity, thereby inhibiting osteoclast function in vitro and in vivo. P150. Intravenous injections of Ibandronate for six months increase bone mass in Japanese osteoporotic subjects T. Nakamura1, H. Mizunuma2, A. Itabashi3, H. Wada4, M. Ishibe4, N. Tajima4, H. Yamane4, K. Fukuda4, M. Karube4, T. Hasunuma4, T. Miyazaki4, S.-A. Okamoto4, S-T. Okamoto4, S. Koyanagi4, N. Fujita4, M. Yamamoto4, K. Nakatsuka4; 1University of Occupational and Environmental Health, Kitakyushu, Japan, 2Hirosaki University, Hirosaki, Japan, 3Saitama Medical School, Iruma, Japan, 4The Ibandronate Clinical Study Group, Japan

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Objective: The efficacy and safety of intravenously administered ibandronate, given once every two or three months by rapid injection, have been demonstrated in Caucasian women with postmenopausal osteoporosis. However, responses in Japanese women with osteoporosis were yet to be fully explored. Study design: A multi-centre, double-blind, randomized, placebo-controlled study was performed to examine the dose-response relationship and safety profile of intravenous (i.v.) ibandronate injections in this patient group. In total, 228 osteoporotic women, aged 55–82 years, were randomly assigned to receive and then were fully analyzed by placebo (n=54), 0.5 mg monthly ibandronate (n=50), 1 mg monthly ibandronate (n=55) or 2 mg bimonthly (every 2 months) ibandronate (n=48) by i.v. injection for 6 months. All patients received daily calcium (500 mg) and vitamin D (200 IU). Results: At 6 months, increases in lumbar spine bone mineral density of 0.5, 4.0, 3.7 and 4.1% were observed in the placebo, 0.5 mg monthly, 1 mg monthly and 2 mg bimonthly groups, respectively. Urinary CTX (uCTX) concentrations were reduced by 19.2, 49.4, 64.7 and 63.8%, respectively (p<0.0001 vs placebo for all active treatment groups). At 1 month, dose-related reductions in uCTX were detected in both monthly groups; in the bimonthly group, the 2-month reduction was comparable with the 1-month reduction observed in the 1 mg group. No serious adverse events were reported. Conclusions: These results demonstrate that intravenously administered ibandronate, given monthly or bimonthly by injection, effectively reduces bone turnover and increases lumbar spine bone mineral density in Japanese women with osteoporosis, without serious side effects. For bone marker reduction, the 1 mg monthly and 2 mg bimonthly regimens are nominally more effective than the of 0.5 mg monthly regimen. P151. Peak bone mass determination in the Jordanian female population B. Masri1,2, E. Azar1,2, A. Faqih2,3, E. Sornay-Rendu4,5, F. Duboeuf4,5, P.D. Delmas4,5; 1Jordan Osteoporosis Centre, Jordan Hospital, Amman, Jordan, 2Jordanian Osteoporsis Prevention Society, Amman, Jordan, 3Jordan University, Amman, Jordan, 4Institut national de la santé et de la recherche médicale (Inserm), Research Unit 403, Lyon, France, 5Université Claude Bernard, Lyon, France Objective: In order to establish the normative bone mineral density (BMD) in Jordanian females. Materials and methods: A representative random sample of 1,241 females aged 20–89 years were interviewed in their homes. They were selected using a stratified threestage cluster sample covering urban and rural regions in the

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entire country as drawn by the Jordanian department of statistics. Eight hundred twenty-one women met the study criteria and underwent dual energy X-ray absorptiometry measurement (Hologic Delphi A) as well as other laboratory investigations. Four hundred eighty-three 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). Results: Peak bone mass was achieved in women aged 20– 29 years at the spine (0.995 gm/cm2) and femoral neck (0.794 gm/cm2) and in women aged 40–49 years for total hip (0.936 gm/cm2) and trochanter (0.686 gm/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. Conclusion: We suggest that these measurements could be extrapolated to neighboring countries because of ethnic, social and dietary similarities and thus help determine the magnitude of osteoporosis in the region. P152. Prevalence of postmenopausal osteoporosis in Jordan—the Fijonor study B. Masri1,2, E. Azar1,2, A. Faqih2,3, E. Sornay-Rendu4,5, F. Duboeuf4,5, P.D. Delmas4,5; 1Jordan Osteoporosis Centre, Jordan Hospital, Amman, Jordan, 2Jordanian Osteoporsis Prevention Society, Amman, Jordan, 3Jordan University, Amman, Jordan, 4Institut national de la santé et de la recherche médicale (Inserm), Research Unit 403, Lyon, France, 5Université Claude Bernard, Lyon, France Objective: To determine the prevalence of postmenopausal osteoporosis in Jordanian females. Materials and methods: A representative random sample of 1,241 females aged 20–89 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. Eight hundred twenty-one women met the study criteria and underwent Dual Energy XRay Absorptiometry (DXA) measurement (Hologic Delphi A) as well as other laboratory investigations. Results: Peak Bone Mass (PBM) was calculated at the regions of interest (L1–L4 spine, total hip, and trochanter and femur neck) in the 483 women who were pre-menopausal. Three hundred thirty-three women were post-menopausal (43– 89 years old). Osteoporosis was defined as a T-score <−2.5. Conclusion: Using the Jordanian PBM data, the study revealed a prevalence of osteoporosis of 16.7%. This proportion is lower than what would be obtained using

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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. P153. Is the rabbit an appropriate animal for the study of osteoporosis? S. Castañeda1, E. Calvo2, R. Largo2, C. de la Piedra2, M. Torralbo-García3, G. Herrero-Beaumont2; 1Rheumatology Department, Hospital Universitario de la Princesa, Madrid, Spain, 2Bone and Joint Research Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain, 3Bone Densitometry Unit, Fundación Jiménez Díaz, Madrid, Spain Objective: To characterize an experimental model of osteoporosis (OP) in rabbits induced either by ovariectomy (OVX), corticosteroids or by a combination of OVX and methylprednisolone (MP) hemisuccinate injections, and to determine the bone mass variation in a long period of time. Methods: Thirty-five rabbits were randomly allocated into five groups: bilateral OVX, daily MP injections at a 1.5 mg/ kg/day dose for four consecutive weeks (MP group) or variable dose of MP between 0.5 and 2 mg/kg/day in combination with OVX to experimentally induce osteoporosis (OVX+MP-low, medium and high dose). Twenty-two animals were sacrificed 6 weeks after OVX, whereas 13 animals were sacrificed 4 months later. Dual energy X-ray absorptiometry (DXA) (Hologic QDR-1000/W) was obtained baseline, 6 weeks after OVX and 4 months afterwards. Three different anatomical regions were analyzed: lumbar spine (LS), global knee (gK) and four subregions near joint line as representative of subchondral bone of the knee (sK). Highresolution magnetic resonance imaging (MRI) to rule out collateral effects on subchondral bone due to OVX or corticosteroids was also carried out at baseline and 6 weeks after OVX. Results: BMD decreased significantly at lumbar spine (LS) in MP and OVX+MP-medium dose groups, and at global knee (gK) and subchondral bone of the knee (sK) in MP, OVX+MP-low and medium dosage groups (p< 0.05). Rabbits receiving the highest MP dose died prematurely as consequence of gastrointestinal bleeding. BMD variations in OVX rabbits were not significantly different in any of the three anatomical locations analyzed. BMD variation 16 weeks after OVX was significant at LS and gK in OVX+MP-medium dose, and only at gK in OVX +MP-low dose group (p<0.05). MRI did not show bone or cartilage changes 6 weeks after OVX with respect to baseline conditions.

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Conclusions: OP can be induced experimentally in rabbits through isolated MP or by a combination of OVX and medium dose corticosteroid for four consecutive weeks in cancellous, cortical and subchondral bone. Obtained changes remained stable 16 weeks afterwards. Combination of OVX and MP could avoid highest MP dose and potential deleterious effects of corticosteroids on subchondral bone. OVX alone was not sufficient to induce OP in rabbits. P154. The influence of osteoporosis on the osteoarthritic process in a rabbit experimental model S. Castañeda1, E. Calvo2, R. Largo2, M.A. Álvarez-Soria2, M. Bellido2, G. Herrero-Beaumont 2; 1Rheumatology Department, Hospital Universitario de la Princesa, Madrid, Spain, 2Bone and Joint Research Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain Objective: To evaluate the influence of osteoporosis (OP) on the cartilage damage in an experimental model of osteoarthritis (OA) in rabbits. Materials and methods: Experimental OA was induced in 11 female rabbits by anterior cruciate ligament section and medial meniscectomy (ACL+M) in the left knee. OP was previously induced in six rabbits by ooforectomy (OVX) and methylprednisolone administration (0.75 mg/kg/day for 5 weeks) (OP+OA group). Bone mass was analyzed by DXA at baseline and 6 weeks after OVX in lumbar spine (LS) and subchondral bone of the knee (sK). Contralateral knees were used as healthy in the OA group, and OP knees in the OP+OA group. An experimental magnetic resonance image (MRI, 4.7T) of the knee previous to surgery was obtained to evaluate baseline cartilage status. Animals were sacrificed 20 weeks after ACL+M. A semi-quantitative scale for macroscopic cartilage analysis and the Mankin’s scale for the microscopic analysis were used. Results: Baseline BMD values at LS and sK were: 0.291± 0.018 and 0.440±0.022, respectively in OP+OA group, and 0.310±0.027 and 0.477±0.036 g/cm2, respectively in the OA group. Six weeks after OVX, BMD values at LS and sK were 0.233±0.039 and 0.363±0.086 g/cm2, respectively, in OP+OA group, and 0.303±0.012 and 0.479±0.031 g/cm2, respectively in the OA group (p<0.05). Cartilage thickness measured by MRI previous to ACL+M did not show significant differences between healthy and pathological rabbits. Macroscopic and microscopic findings at sacrifice are shown in table. A statistically significant difference in the histopathological lesions between OP+OA rabbits and the rest of the groups was observed (p<0.01). Furthermore, an inverse correlation between microscopic damage and BMD was found (r=0.75 at LS; r=0.55 at sK).

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Table. Macro and microscopical results

the activation of these proinflammatory events. NFkB activation was only inhibited by GS (60%), DC (75%) and NSAIDs (from 55 to 75%) in chondrocytes, and by GS (45%), DC (69%), CS (65%) and MXC (60%) and DCF (60%) in synoviocytes. GS inhibited MMP-13 activation induced by IL-1 in chondrocytes (75%) and synoviocytes (85%), and also MMP-1 activation in both cell types (65%). Between other nutraceuticals, only CS (60%) diminished MMP-1 activity in chondrocytes. In synoviocytes, CS (75%), DC (75%) and NAC (75%) inhibited MMP-13 release. However, NSAID presence did not modify or even super-induced MMP-1 and -13 synthesis in both cell types. Conclusions: GS inhibited the synthesis of proinflammatory and structural mediators in OA chondrocytes and synoviocytes stimulated by IL-1. The presence of other nutraceticals only partially controlled some of these mediators. NSAIDs were able to significantly inhibit proinflammatory pathways, while structural mediators were unchanged or even activated. Our study supports the role of GS as a symptom and structure-modifying drug.

Group

Control (n=5)

OP (n=6)

OA (n=5)

OP+OA (n=6)

Macroscopic scale Microscopic scale

0.0±0.0 0.2±0.4

0.0±0.0 2.0±1

7.5±2.1* 3.5±0.6

8.0±3.3* 9.0±3.1**

* p<0.01 vs. OP and Control groups; ** p<0.01 vs. OP, OA and Controls

Conclusions: In our model, OP+OA rabbits showed an increase in the cartilage damage in comparison with OA non-osteoporotic rabbits. These results support recent clinical epidemiological findings suggesting that OP could be a risk factor for OA progression. P155. Differential anticatabolic profile of glucosamine sulfate versus other anti-osteoarthritic drugs on human osteoarthritic chondrocytes and synovial fibroblast in culture R. Largo, M.A. Alvarez-Soria, O. Sanchez-Pernaute, E. Calvo, J. Egido, G. Herrero-Beaumont; Bone and Joint Research Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain Objective: To compare the effect of glucosamine sulfate (GS) to that seen for different anti-OA drugs, such as NSAIDs and other nutraceuticals on the activation of several proinflammatory and structural mediators in OA chondrocytes and synoviocytes in culture. Materials and methods: Cells were obtained from OA patients who underwent total knee replacement. In quiescent cells stimulated with 10 U/ml IL-1beta, the effects of GS (1 mg/ml), meloxicam (MXC, 10-6 M), diclofenac (DCF, 10-6 M), indomethacin (IND, 10-6 M), chondroitin sulphate (CS, 1 mg/ml), diacerhein (DC, 10-5 M), and N-acetylcysteine (NAC, 2 mM) on prostaglandin (PG) E2 production, cyclooxigenase-2 (COX-2) expression, nitric oxide (NO) synthesis, metalloproteinase (MMP)-1 and MMP-13 presence and NFkB activation were studied. Results: IL-1 increase the presence of all of these mediators, except NO synthesis in synoviocytes. After stimulation, PGE2 synthesis was significantly inhibited by GS (up to 60%) and NSAIDs (100%) in both cell types, and by NAC (65%) in synoviocytes. COX-2 synthesis was also inhibited in both cell types by incubation with GS (up to 60%) or NSAIDs (up to 40%), while NAC (50%) also diminished COX-2 in synoviocytes. In chondrocytes, only GS (75%), DC (30%) and CS (20%) inhibited NO synthesis evoked by IL-1 and no effect was noted for NSAIDs or NAC. We also studied one of the possible mechanisms involved in

P156. Profile of vitamin D, serum calcium and parathyroid hormone in post menopausal osteoporosis patients at Cipto Mangunkusumo Hospital—Jakarta S. Sumariyono, S. Bambang; Rheumatology Division, Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia Objective: To determine the profile of vitamin D, serum calcium and parathyroid hormone in post-menopausal osteoporosis patients in Jakarta. Materials and methods: A cross sectional study was conducted to determine correlation between age, serum calcium, PTH and 25(OH)D level in post menopausal osteoporotic patients. The exclusion criteria include oral glucocorticoid within last 30 days, renal and liver impairment. Patients who meet criteria were examine for serum creatinin, LFTs, serum albumin, serum calcium, serum phosphate, serum PTH and 25(OH)D. Data collected were analyzed by SPSS. Results: Twenty four patients 51–77 years old and duration of menopause 5–26 years were included in this study. Serum calcium level 8.2–9.5 mg/dl, PTH 13.5–120 pg/dl and 25(OH)D level: 17, 48–65, 38 nmol/l. Correlation between age and serum calcium reveal r = −0.457; p = 0.022; serum calcium and PTH reveal r = −0.498; p = 0.011 and between age and PTH reveal r = 0.471; p = 0.017. Correlation between age and vitamin D reveal r = −0.150; p = 0.484; calcium and vitamin D reveal r = 0.104; p = 0.629, and between PTH and vitamin D reveal r = −0.194; p = 0.326.

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P157. Mikkeli Osteoporosis Index (MOI) identifies osteoporosis and fracture risk in young PMP women P. Waris1, V. Kiviniemi2, J. Sirola3, M. Tuppurainen4, V. Waris5; 1Department of Orthopaedics, Mikkeli Central Hospital, Mikkeli, Finland, 2Department of Statistics, Kuopio University, Kuopio, Finland, 3Clinical Research Center, Bone and Cartilage Research Unit (BCRU), Kuopio University, Kuopio, Finland, 4Department of Gynaecology, Kuopio University Hospital, Kuopio, Finland, 5Department of Orthopaedics, Kuopio University Hospital, Kuopio, Finland Objectives: To identify osteoporosis and fracture risk factors in young postmenopausal women we adjusted Fracture Index (FI) with BMD by increasing the weight thresholds nonlinearly from 57 to 80 kg and decreased the age thresholds by 10 years. Materials and methods: After stepwise multiple regression in the population based Kuopio FPS cohort, 434 women aged 65–72, and in a cohort of 300 low-energy fracture patients, women aged 45–79, MOI includes seven risk factors: age over 54 years (1 point/5 years, max 6 p), weight below 80/71/ 64/58 kg (1/2/3/4 p), earlier adult fracture, maternal hip or spine fracture and smoking (2 p each), shortening by 3/5 cm (1/2 p) and need of arms when rising from chair (2 p), max 20 p. We compared the AUROC for osteoporosis with FI and ORAI in the FPS cohort and in the fracture cohort, extended to 427 patients. We validated MOI further in the population based Kuopio OSTPRE-study cohort, 1,125 women aged 48–59 with 10-year follow-up. The fractures in the OSTPRE population/10 years were recorded by postal questionnaires and validated from X-rays/medical records. Results: The AUROC for osteoporosis of the femoral neck in FPS cohort, in fracture patients, and in OSTPRE cohort at baseline and 10 years later was with MOI 0.67/0.74/0.78/ 0.79, with FI 0.56/0.70/0.72/0.77 and with ORAI 0.62/0.73/ 0.83/0.76. In the Cox survival analysis the fracture-free time was 2.5 times shorter within category MOI 7–11 p than with MOI 0–6 (HR 0.4, p<0.01; Fig. 1). In osteoporotic– osteopenic (T-score <−1) and in non-osteopenic women the risk was identical (HR 0.4). ORAI and FI did not predict fractures in this cohort. Fig.1 Prediction of fractures with MOI. Cox regression model (n=1,125).

1.0

Cumulative survival rate

Conclusion: There were significant correlation between age and serum calcium level and PTH level. No significant correlation between vitamin D and other variable, it might be due to insufficiency of the number of sample. This study is still going on until end of December 2006.

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.9

.8

MOI 4

.7

3 2

.6

1 0

1000

2000

3000

4000

Days from BL to fracture Conclusions: MOI contains all independent risk factors of FI and identifies both osteoporosis and fracture risk in young PMP women. Supported by Academy of Finnland (Grant 113999). P158. Effects of a nutritional rehabilitation program on bone mineral density and bone turnover in women with anorexia nervosa O. Viapiana1, L. Idolazzi1, E. Fracassi 1, D. Gatti 1, M. Rossini1, V. Braga1, R. Dalle Grave2, T. Todesco2, S. Adami1; 1Rheumatologic Rehabilitation, University of Verona, Valeggio s/M (Verona), Italy, 2Nutritional Rehabilitation, Villa Garda, Peschiera (Verona), Italy Objectives: Anorexia Nervosa (AN) is a life-threatening eating disorder characterized by an inability to maintain a normal body weight, and amenorrhoea, often associated with osteoporosis and increased risk of fragility fractures. Materials and methods: Bone metabolism, including markers of bone turnover (serum total alkaline phosphatase, bone alkaline phosphatase [bone AP], osteocalcin [OC], and type I collagen C-telopeptide breakdown products [CTX]) and bone mineral density (BMD) by dual energy X-ray absortiometry (DXA) at the spine and at the hip, were evaluated in 55 consecutive women with AN undergoing a 3 month intensive nutritional rehabilitation program. The control group was constituted of 25 healthy young medical students. Results: In AN patients body weight increased during the 3 month nutritional program from 37.8±5.1 (mean ± SD) to 51.5±4.5 kg. The corresponding BMI rose to values

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>17.5 kg/m2 in all patients. Mean BMD significantly rose by 2.6±3.5% at the hip and by 1.1±3.6% at the spine. The markers of bone formation, serum bone AP and osteocalcin, significantly rose by two folds, while sCTX decreased by 16%. The changes in hip BMD were positively related (p< 0.005) to changes in body weight and in bone AP (p<0.02). The changes in spine BMD were positively related to changes in serum osteocalcin (p<0.05). In the 25 patients who attended the 12 month post-treatment control mean body weight significantly decreased by 3.6±6.0 kg and this was not associated with any significant change in BMD values. In the patients in whom BMI fell again below 17.5 kg/m2 hip BMD values decreased significantly. On the contrary, in the patients who maintained BMI >17.5 kg/m2, BMD values continued to rise up to ! values over the 15 month observation of 4.8±6.2 and 7.1±12.1 at the spine and hip, respectively. Conclusions: In this study we have demonstrated that substantial gains in weight in women with chronic AN are associated with remarkable increases in BMD at both the hip and the spine. If weight is maintained the overall improvement approach 1 SD within one year. The changes in both weight and BMD are correlated with improvements in bone formation markers and diminution in a marker of bone resorption. P159. Bone mineral density (BMD) in patients with rheumatoid arthritis (RA): 1 year follow-up in the best study M. Güler-Yüksel1, F.C. Breedveld1, C.F. Allaart1, B.A.C. Dijkmans2, W.F. Lems2; 1Leids Universitair Medisch Centrum (LUMC), Leiden, The Netherlands, 2Vrije Universiteit Medisch Centrum (VUMC), Amsterdam, The Netherlands Objectives: To evaluate the changes in BMD in the spine and hip in patients with early, active RA after 1 year of treatment in the BeSt study in relation to disease-related and demographic variables. Materials and methods: In the BeSt study 508 early RA patients were randomized into four treatment strategies: sequential monotherapy, step-up combination therapy, combination therapy with high dose prednisone and combination therapy with infliximab and methotrexate. Radiographic damage was assessed using the Sharp-van der Heijde score (SHS). The smallest detectable change (SDC) was 4.2. BMD of the spine L2–4 and the total hip was measured by DEXA at baseline and after one year in 342 patients. Osteoporosis (OP) was defined as T-score ≤−2.5. The BMD change was divided in tertiles with high, low and no BMD loss after 1 year. Relationships between BMD one-year change and treatment strategies, disease related and demographic variables were analysed by regression analyses adjusted for confounders.

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Results: Patients were 243 women and 99 men with at baseline a mean age of 54 years, median symptom duration of 23 weeks and OP present in 10%. After 1 year of treatment, there were no statistically significant differences in BMD changes between the four treatment groups. Patients with high BMD loss were older, included more postmenopausal women, had higher SHS at baseline and after 1 year and more SHS progression, had higher DAS and HAQ and used less bisphosphonates (BP) than patients with low/ no BMD loss. After correction for possible confounders, only SHS at baseline, SHS progression and BP-use were independent predictors for high BMD loss (Table 1). Table 1: Odds Ratios (95% CI) for the annual BMD change (in tertiles) with demographic/disease-related factors at spine/hip Variable

Location High BMD loss

SHS at Hip baseline Progression Spine SHS>SDC during 1st year BP-use Spine

Low BMD loss

No BMD loss

1.07 (1.02–1.12) 2.36 (1.07–5.21)

0.97 (0.94–1.05) 2.35 (1.09–5.07)

1

0.21 (0.07–0.70)

0.37 (0.13–1.05)

1

1

Conclusion: In early RA patients, treated 1 year in the BeSt study, joint damage at baseline and joint damage progression are independent predictors for high BMD loss at hip and spine. Use of BPs reduces BMD loss. P160. Osteoporosis assessment and treatment after hip or forearm fracture: a Belgian experience G. Blondiaux1, W. Esselinckx2, J.P. Devogelaer1, Y. Boutsen 2 ; 1 Department of Rheumatology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium, 2Department of Rheumatology, Cliniques Universitaires de Mont-Godinne, Université Catholique de Louvain, Yvoir, Belgium Medical care for osteoporosis in orthopaedic patients has been evaluated at the St-Luc and Mont-Godinne University Hospitals (Université Catholique de Louvain). Women aged over 50 who had been treated during a 12-month period (01.07.2003–30.06.2004) in either centre for a forearm or hip fracture were assessed for osteoporosis risk factors, bone mineral density screening and treatment for osteoporosis prior and after the fracture. Information was obtained through postal questionnaires. A total of 325 patients was identified (forearm fractures n= 121; hip fractures n=204) and 140 interpretable questionnaires

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were returned (43%). Mean age was 72±9.9 and 79±8.6 years in the forearm and hip fracture groups, respectively. Of the 140 women (forearm fractures n = 66; hip fractures n=74), 43 (30.7%) had previously sustained at least one non traumatic fracture and 58 (41.4 %) had previously undergone a DXA scan. A total of 50 women (35%) were already on a pharmacological treatment at the time of the forearm or hip fracture: calcium supplementation n=50 (35%); bisphosphonates n=35 (25 %); vitamin D n=32 (23%); raloxifene n=5 (3.5%). Of the 58 women who had had a BMD testing previously, 47 (81%) were receiving a treatment against osteoporotic fractures. During the one-year follow-up, 14 women only (10%) had undergone a DXA scan and the total number of patients receiving a pharmacological treatment for osteoporosis remained unchanged: calcium supplementation n = 53 (37.8%); bisphosphonates n=33 (23.6%); vitamin D n=38 (27%); raloxifene n=5 (3.5%). Conclusion: The prevalence of pharmacological treatment for osteoporosis was quite high in our population, with more than 25% of patients on antiresorptive therapy before their forearm or hip fracture. These treatments were mainly prescribed according to previous BMD screening. Very few women with a recent fracture history were assessed for osteoporosis or treated to prevent further fracture. These data once again underline the need for specific management of osteoporosis in orthopaedic departments to offer women over 50 systematic BMD testing after peripheral fractures. P161. Correlation of bone lesion changes with cartilage volume loss in knee osteoarthritis patients as assessed by quantitative MRI over a two-year period J.P. Pelletier1, J.P. Raynauld1, M.J. Berthiaume2, F. Abram3, D. Choquette1, B. Haraoui1, J. Beary4, G. Cline4, J. Meyer4, J. Martel-Pelletier1; 1Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal Hospital Center, Montreal, Quebec, Canada, 2Radiology Department, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada, 3Research and Development, Arthro Vision, Montreal, Quebec, Canada, 4Health Care Research Center, Procter and Gamble Pharmaceuticals, Mason, OH, USA Objectives: To evaluate in knee osteoarthritis (OA) patients the size changes in bone edema and cysts over 24 months, and to contrast these changes with cartilage volume loss using quantitative magnetic resonance imaging (MRI). Materials and methods: A subset of 107 patients from a clinical trial evaluating the impact of a bisphosphonate on knee OA was studied. The mean age was 62.4, 64% were female, with a BMI of 30.6 kg/m2. Patients with K-L grade IV were excluded. MRI of the knees were analyzed at

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baseline and 24 months. Edema, cysts and cartilage volume were quantitatively assessed. Results: At baseline, 86 patients showed the presence of at least one type of bone lesion: 71 had edema, 61 cysts and 51 both. At 24 months, the mean change in the edema size was +2.09 mm, and +1.09 mm in cyst lesion size. No impact of the bisphosphonate regimen was found on the bone lesion changes (edema, p=0.52; cysts, p=0.70). When data were analyzed according to sub-regions, a statistical increase was found for the cysts in the trochlea (+0.67 mm, p=0.02) with a trend in the lateral tibial plateau (+0.15 mm, p=0.09), and for the edema in the medial tibial plateau (+1.73 mm, p=0.05). When the data at 24 months were contrasted to corresponding cartilage volume loss, significant correlations were seen in the medial sub-region between edema size change and the condyle cartilage volume loss (−0.40, p=0.0001) and the tibial plateau (−0.23, p=0.03). Moreover, in the medial condyle, the cyst size changes were also correlated to the cartilage change (−0.29, p=0.01). No statistical correlation was seen for the lateral compartment. A multivariate analysis (age, gender, BMI, meniscal extrusion, meniscal tear) showed that edema size change was strongly and independently associated with cartilage volume loss (−0.31, p=0.0004). Conclusion: These data demonstrate that bone lesions are prevalent in knee OA. The correlation of the edema and cyst size increase over time in the medial compartment with the loss of cartilage volume juxtaposed to the location of the lesions, underlines the importance of the subchondral bone remodeling in the pathophysiology of OA. P162. Bone density in Ethiopian women: the influence of calcium consumption during adolescence D. Dahan1, R. Endevelt3,4, D. Shahar2, R. Peled5; 1Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel, 2Epidemiology Department, The S. Daniel Abraham International Center for Health and Nutrition, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel, 3Macabi Health Services, Tel Aviv, Israel, 4Hifa University, Hifa, Israel, 5Department of Health Systems Management, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel Objectives: The main objective of this study was to describe the prevalence of osteoporosis among Ethiopian adult women who immigrated to Israel during the last decade and to compare them to Israeli born adult women. In addition, to describe the distribution of risk factors for osteoporosis among these women. Materials and methods: Using a cross sectional design, we recruited Ethiopian and Israeli born women. Hip, forearm and spinal bone mass density (BMD) were measured. Risk

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factors information was obtained from Food Frequency and Life Style Questionnaires. BMD and Osteoporosis rate were compared between the two groups by using T- test and Chi square test in addition to non parametric Mann–Whitney Tests. Step wise regression models were constructed for “Osteoporosis” as the dependent variable. Results: One hundred eighty-one Ethiopian women and 98 Israeli born women, living in a Kibbutz participated in the current study. The Ethiopian women demonstrated an extremely higher rates of osteoporosis compare with the Israeli born group, 38.7 and 5.2%, respectively. Dairy and calcium consumption during adolescence, BMI, smoking habits, physical activity and exposure to sun light were lower among the Ethiopian women compare with the Israeli born group. Interestingly dairy products consumption during adolescence was negatively associated with osteoporosis. Conclusion: We showed that Ethiopian women who immigrated to Israel have high prevalence of bone related morbidity. Free access to drug therapy and BMD tests should be considered for this group in edition to ethnic specific multidisciplinary life style interventions. P163. Chronic low back pain in rheumatoid patients with osteoporosis. A randomized clinical trial D. Matei1, R. Traistaru2, L. Marinescu2; 1Rehabilitation Department, Emergency Hospital of Craiova, Craiova, Romania, 2UMF of Craiova, Craiova, Romania Objectives: Chronic low back pain (LBP) is one of the most common symptom in osteoporosis rheumatoid arthritis patients leading to complex disability. The aim of our study is to compare the effects of three therapeutic approaches in these patients in terms of pain, disability (severity of rheumatoid arthritis) and self-control of the complex disorders. Materials and methods: Eighty-seven patients (mean age 41.8 years) with rheumatoid arthritis (mean disease duration 9.8 years) and osteoporosis (mean disease duration 2.8 years) were randomized to the three groups in accordance to the type of treatment: I (23% of patients)— only medication, II (40% of patients)—medication + physiotherapy (TENS, interferential current, ultrasound), III (37% of patients)—medication + aerobic training. The rehabilitation program was represented by 12 physiotherapy sessions and 18 aerobic training sessions (3 sessions/week). Outcome measures were VAS pain, DAS 28, BMD (TScore), HAQ score and Arthritis Self-Efficacy Scale (ASES). All assessments were performed pre-post intervention and at 6 month follow-up. Results: All the groups showed similar decrease in pain on the third assessment and there was no significant difference between the groups. In the first and group the second there was a significant improvement in DAS28 values (p<0.05) as well as HAQ (p<0.05) after treatment.

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The third group also showed significant improvement in DAS28 value as well as ASES and T Score at 6 month follow-up (p<0.01). Conclusions: All of the three therapeutic approaches were found to be effective in diminishing pain and disability in osteoporosis rheumatoid arthritis patients with chronic low back pain, but aerobic training was found to be more effective in improving bone mineral density (T-Score) and psychological status. Our results confirm the literature data: physical activity is an interesting therapy for the prevention and treatment of bone loss and osteoporosis because it has no adverse side effects, it is low cost, and it confers additional benefits such as postural stability and fall prevention. Type and duration of physical training must be individualized to each patient, in accordance with severity of rheumatoid arthritis. P164. The physical exercise benefits in secondary knee osteoarthritis rehabilitation D. Matei1, R. Traistaru2, M. Macovei2; 1Rehabilitation Department, Emergency Hospital of Craiova, Craiova, Romania, 2UMF of Craiova, Craiova, Romania Aim: Although physical effort represents a physiological stress into whole body, it was proven its benefice effects. In our prospective study, we mentioned the results of rehabilitation program, based on the kinetic aspects, in the patients diagnosed with bilateral secondary knee osteoarthritis. Materials and methods: We studied forty-two patients (71.4% women, 28.6% men), aged between 49–83 years. All patients were clinical, functional, imagistic (X-rays and sonography) and oscilometric point of view (lower limbs). It performed a complex rehabilitation program (educational, dietetic, pharmacological, physical-kinetic), 5 days/week, 2 weeks. The aerobic kinetic program was represented by: relaxation training, correct posturing, active joint movements, muscle and soft tissue stretching applied to the knee, spine, hip and ankle, stationary cycling, muscle strengthening exercises for the hip and knee. Each patient was asked to score pain intensity on a 10 point visual analogue scale (VAS), to complete the WOMAC index and to fill the adapted Sickness Impact Profile (SIP) at entry into the study (Time 1), after 4 weeks (Time 2) and after 12 weeks (Time 3). Results: The studied parameters had a good evolution, especially in T2 moment. Patients that presented a previous regular exercise for lower limb (submaximal exercise) showed a statistic significantly improvement for the studied parameters. Conclusions: The results of our study confirm the data into medical literature about the favorable complex effect (clinical, functional and sonographic) of regular and therapeutic submaximal exercise performed in the patients with secondary knee osteoarthritis. At these patients is no

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risk of accelerating knee arthritis. The pain improvement is correlated with sonographic aspects. It is known that pain reduces maximal voluntary contraction and endurance time during submaximal contractions. These aspects have morphological consequences. The regular kinetic program correlated with correct diets determines beneficial changes of the life style in the patients with secondary knee osteoarthritis. Kinetotherapy is the best controller “medication” for musculoskeletal structures.

P166. Medial tibial and femoral cartilage volume and thickness measurements correlate with pain and function in individuals with knee OA K.A. Beattie1, P. Boulos1, D. Inglis1, C. Webber2, F. Eckstein3, J.D. Adachi1; 1McMaster University, Hamilton, Ontario, Canada; 2Department of Nuclear Medicine, Hamilton Health Sciences, Hamilton, Ontario, Canada, 3 Department of Anatomy, Paracelsus Medizinische Privatuniversität, Salzburg, Austria

P165. Risk factors for generalized osteoporosis in rheumatoid arthritis. Observational study D. Matei1, R. Traistaru2, R. Popescu2; 1Rehabilitation Department, Emergency Hospital of Craiova, Craiova, Romania, 2UMF of Craiova, Craiova, Romania

Objectives: Although the source of osteoarthritic pain is unknown, some evidence suggests it may be linked to cartilage damage. The purpose of this study is to investigate the relationship between medial femoral cartilage volume and thickness and WOMAC and SF-36 outcomes in osteoarthritic individuals. Methods: Men and women ≥35 years old clinically diagnosed with knee OA underwent a 3D SPGRE fat-sat sagittal MRI scan (0.31×0.31×1.5 mm3) using a 1T OrthOne™ peripheral machine. Images were analyzed for medial tibial and central femoral cartilage morphometry using a proprietary software program (Chondrometrics GmbH). Participants also completed WOMAC and SF-36 questionnaires. Results: Study participants included 25 females and 12 males, mean (SD) age and BMI of 63.1 (10.7) years and 27.1 (5.1) kg/m2, respectively. Linear regression analyses determined femoral and tibial cartilage thicknesses were significantly related to all WOMAC domains and the physical function, bodily pain and social function domains of the SF-36 (Table). Femoral and tibial cartilage volumes were significantly related to all WOMAC outcomes except pain. A 1 mm decrease in femoral thickness was correlated with 16.0 and 22.2 point decreases in physical function and total WOMAC scores, respectively, compared to 24.1 and 32.0 point decreases with every 1 mm change in tibial thickness. With the exception of social function, femoral thickness was not more significantly related to symptoms than tibial thickness. Generally, medial tibial and medial femoral cartilage thickness was more strongly related to OA symptoms than volume as shown by standardized regression coefficients presented in the Table.

Objectives: Generalized osteoporosis in rheumatoid arthritis is characterized by a complexity of risk factors, including primary osteoporosis risk factors in addition to inflammation, immobilization, and use of corticosteroids. In our observational study we tried to evidence the importance of risk factors for development and evolution of generalized osteoporosis in patients with rheumatoid arthritis. Materials and methods: We studied 87 patients aged between 32–68 years (88% women, 12% men) with established rheumatoid arthritis; 51 patients presented generalized osteoporosis (defined as T score ≤−2.5 SD); the corresponding percentages for osteoporosis were 13.5% at femoral neck and 45% at lumbar spine. 24 patients were treated with antiresorptive drugs, 43 with calcium, vitamin-D or both and ten patients got no treatment. We followed the correlations between osteoporosis and different parameters: DAS28, corticosteroids treatment, immobilization, rehabilitation programe, smoking. Results: In this study we found a significant correlations between generalized osteoporosis and the following parameters: the stage of disease, the functional Steinbroker class and immobilization; no important correlations were found between osteoporosis and smoking or the activity of disease (DAS28); the values of correlation and predictivity were semnificant to a long disease duration parameter to the postmenopausal women and for the patients with corticosteroids therapy (mean duration of treatment: 2.75 years). Conclusions: The bone mineral density loss in rheumatoid arthritis occurs early in the evolution of rheumatoid arthritis, emphasizing that osteoporosis management should be considered early in the disesase. The individual rheumatoid arthritis patient with osteoporosis could be identified by either a case findings strategy based on risk factor assessment for osteoporosis or screening of all patients with rheumatoid arthritis.

β Coeff. (p-value) Fem. Cart. Vol WOMAC −0.257 Pain (ns) WOMAC −0.444 Stiffness (0.009) WOMAC −0.332

β Coeff. (p-value) Tibial. Cart. Vol.

β Coeff. (p-value) Fem. Cart. Thick.

β Coeff. (p-value) Tibial Cart. Thick.

−0.270 (ns) −0.362 (0.026) −0.360

−0.549 (0.005) −0.561 (0.003) −0.624

−0.318 (0.041) −0.513 (0.006) −0.661

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Function WOMAC Total Phys. Function (SF-36) Bodily Pain (SF-36) Social Function (SF-36)

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β Coeff. (p-value) Fem. Cart. Vol

β Coeff. (p-value) Tibial. Cart. Vol.

β Coeff. (p-value) Fem. Cart. Thick.

β Coeff. (p-value) Tibial Cart. Thick.

(0.007) −0.326 (0.026) 0.397 (0.009)

(0.014) −0.354 (0.015) 0.323 (0.001)

(0.001) −0.630 (0.001) 0.678 (0.001)

(0.001) −0.637 (0.001) 0.532 (0.001)

0.439 (0.016)

0.223 (0.207)

0.641 (0.001)

0.446 (0.021)

0.391 (0.028)

0.069 (ns)

0.536 (0.007)

0.084 (ns)

Conclusions: These results suggest medial tibial and central femoral cartilage thicknesses are significantly more strongly related to WOMAC symptoms than volume in the same region. Although β-coefficients correlating femoral thickness with symptoms appear slightly larger than tibial thickness, no statistical differences existed between variables. P167. Body weight is better than body mass index to evaluate post-menopausal osteoporosis risk N. Hammoumraoui, M.El Rakawi, C. Haouichat, D. Acheli, S. Lehtihet, F. Sadouki, H. Djoudi; Rheumatology Department, Douera Hospital, Algiers, Algeria Background: Osteoporosis is a disease characterized by low bone mass, micro-architectural deteriorations of bone tissue, and consequent skeletal fragility with an increase in fracture risk. One of the ways to reduce the burden of this disease is to fight against osteoporosis risk factors and to treat at-risk women defined by the presence of those factors. The main diagnosis tool is bone mineral density measurement but economic issues prevent mass screening, so the pre-screening for BMD testing is essential and needs an evaluation based on risk factors. Among osteoporosis risk factors, low body weight is one of the most important one; however its quantification by the calculation of the body mass index (BMI) or the weight only is not clearly established. Objectives: The aim of our study is to determine which of body mass index or weight is better to evaluate the postmenopausal osteoporosis risk. Materials and methods: The study population consisted of 394 post-menopausal women, referred for bone mineral density measurement. Women with other bone diseases than osteoporosis were excluded. Correlation between weight and bone mass and correlation between BMI and bone mass are calculated. The coefficient of determination

of both weight and BMI are calculated as well to determine which of the two is more accurate to evaluate the risk of low bone mass. Results: There is a good correlation between BMI and body mass (R=+0.42) as well as a good correlation between weight and body mass (r=+0.52). The coefficients of determination are, respectively, 17 and 27%. There is a significant difference between the two correlations (p=0.03). Discussion: The bone mass determination depends essentially on weight (fat mass acts physiologically on bone mineralization). The estimation of the risk by the calculation of the BMI gives a greater importance to the height (BMI = weight / height × height) though there is no influence of height on bone mineralization. Conclusion: This study showed clearly that weight is most accurate to predict osteoporosis risk in post-menopausal women than BMI. P168. High prevalence of undiagnosed morphometric vertebral fractures in patients with a recent clinical fracture P. Geusens1, B. Dumitrescu2, S. van der Linden3, G. Willems3, G. Udrea2, S. van Helden3, A. Nieuwenhuijzen-Kruseman4; 1 Division of Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands—Biomedical Research Center, Hasselt University, Diepenbeek, Belgium, 2Rheumatology Department, Clinical Hospital Dr I. Cantacuzino, Bucharest, Romania, 3Department of Trauma Surgery, University Hospital Maastricht, Maastricht, The Netherlands, 4Endocrinology Department, University Hospital Maastricht, Maastricht, The Netherlands The percentage of patients admitted to the emergency room with a nonspine clinical fracture is over 90%. The prevalence of vertebral fractures in such patients is not well documented. Patients admitted to the hospital with a clinical fracture had fracture and fall risk assessment, BMD in the hip and spine and vertebral morphometry (MXA) using dual X-ray absorptiometry (DXA). Vertebral fractures were defined according to semiquantitative approach by Genant.(1) We included 712 consecutive and consenting women and men that were able to participate with a mean age of 66 years (range 50–91). Prevalent vertebral fractures (any vertebral height (H) ≤0.80) were found in 51% of the patients (95% confidence interval (CI): 47–55%). Mild fractures (any H=0.76–0.80) were found in 40% of patients, moderate (any H=0.61–0.75) in 29% and severe (any H< 0.60) in 6%. One fracture was present in 21% of the patients, two fractures in 14% and ≥3 in 16%. Fractures with any H≤ 0.80 were found in 58% of patients (CI: 50–65%) with

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normal BMD, 48% (CI: 42–57%) of those with osteopenia and 50% (CI: 43–53%) of those with osteoporosis. Similar values were found in men and women and also if only patients with a fall from standing height had been included. We conclude that nearly one out of two patients with a recent nonspine clinical fracture have undiagnosed morphometric vertebral fractures when measured by MXA, even when BMD is normal. MXA significantly increases the number of patients with the diagnosis of osteoporosis, even when more stringent criteria (any H≤ 0.75) are applied. (1) Genant et al. JBMR 1993, 1137

P169. Secondary osteoporosis in patients with a recent clinical fracture and low bone mineral density B. Dumitrescu1, S. van Helden2, A. NieuwenhuijzenKruseman3, C. Wyers4, G. Udrea1, S. van der Linden3, P. Geusens 5 ; 1 Rheumatology Department, Clinical Hospital Dr I. Cantacuzino, Bucharest, Romania, 2 Department of Trauma Surgery, University Hospital Maastricht, Maastricht, The Netherlands, 3Rheumatology Department, Academic Hospital Maastricht, Maastricht, The Netherlands, 4Epidemiology Department, Academic Hospital Maastricht, Maastricht, The Netherlands, 5 Department of Medicine and Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands— Biomedical Research Center, Hasselt University, Diepenbeek, Belgium Osteoporosis is a multifactorial bone disease that results in fragility fractures with significant morbidity, mortality, healthand social costs. Relatively little attention has been paid to the medical evaluation of patients with a clinical fracture. We therefore investigated bone -and fall-related risks for fractures along with causes of secondary osteoporosis in patients admitted to the hospital because of a recent clinical fracture. All patients older than 50 years, who presented at the hospital with a fracture, had fracture and fall risk evaluation according to the Dutch guidelines, including bone densitometry. Patients with a T-score ≤−2.5 in the hip and/or spine were further investigated for secondary osteoporosis. We evaluated 100 consecutive and consenting patients, 73 women and 27 men with a mean age of 68 years (50–90 years). Sixty-six had contributors to secondary osteoporosis. Forty-one patients had previously undiagnosed vitamin D deficiency (≤50 nmol/l), 28 had endocrine diseases (13 known thyroid pathologies, 1 primary, 5 secondary undiagnosed hyperparathyroidism (PTH >5.5 pmol/l), three men had unknown hypogonadism (testosterone <9.4 nmol/l), 14 had known renal insufficiency (creatinine clearance <40 ml/min)), six had inflammatory rheumatic diseases and four men had alcohol abuse. Thirty

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patients reported history of non-vertebral fracture and one history of a clinical vertebral fracture. On morphometry 61 patients had prevalent vertebral fractures. There were 54 patients with clinical fracture risks (73 when morphometry included), 79 had fall risks and 61 had both fall and fracture risks, including morphometric vertebral fractures. We conclude that secondary osteoporosis is frequent in patients entering the hospital with a recent clinical fracture and a T-score ≤−2.5. Nearly two in three had previously undiagnosed morphometric vertebral fractures. P170. Clinical risk evaluation contributes to case finding and diagnosis of osteoporosis in postmenopausal women P. Geusens1,2, B. Dumitrescu3, A. Cloet4, J. Vanhoof1; 1 Academic Hospital Maastricht, Maastricht, The Netherlands, 2 Biomedical Research Center, Hasselt University, Diepenbeek, Belgium, 3Clinical Hospital Dr I. Cantacuzino, Bucharest, Romania, 4MSD, Brussels, Belgium Clinical case finding for those at risk of osteoporosis and fractures is advocated in all guidelines of osteoporosis, but its application in daily practice remains unsatisfactory. We studied the effects of clinical fracture risk evaluation on case finding and diagnosis of osteoporosis in postmenopausal women consulted by their general practitioner (GP). From 42,690 postmenopausal women age, weight and history of fractures after the menopause were recorded by 1,080 GPs. The OST index was calculated from age and weight as integer of (0.2 times [weight—age]).(1) An OST of >1 indicated low risk (LR), −3 to 1 moderate risk (MR) and <−3 high risk (HR). A prior DXA had been performed in 6,637 women (16%) in 7% in the LR, 22% in the MR and 26% in the HR. After clinical evaluation 10,841 (29%) additional women were sent for DXA (p<0.001 vs. number (16%) of those with prior DXA): in 8% of the LR, 47% of the MR and 72% of the HR (p<0.001 for distribution between risk groups compared to patients with prior DXA). New cases of osteoporosis in the spine and/or hip were found in 2,353 (7%) of all clinically evaluated patients and in 23% of those send for DXA (15% of the LR, 27% of the MR and 47% of the HR, p<0.001 between risk groups). A history of fracture after age 50 was present in 6,732 (16%) of all women (in 8% of the LR, 19% of the MR and 42% of the HR) (p<0.001). Altogether 27% of patients with a previous fracture had a prior DXA, compared to 13% of women without fracture history (p<0.001). After clinical evaluation, 66% of patients with a fracture history, but not having had a DXA, were sent for DXA (p<0.001). In these patients, 979 (32%) new cases of osteoporosis were diagnosed (21% in the LR 36% in the MR and 57% in the HR, p<0.001). In patients without a fracture history, 13% had a prior DXA. After OST evaluation, 24%

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additional women were referred to DXA (p<0.001 vs. prior DXA), 50% of the LR, 83% of the MR and 72% of the HR (p < 0.01). New cases of osteoporosis were diagnosed in 1,477 (20%) of those send for DXA (12% in the LR, 23% in the MR and 40% in the HR, p<0.001). We conclude that clinical screening in postmenopausal women using fracture history and the OST-index tripled the proportion of women referred for DXA, with a significant shift towards referring more women at high risk. (1) Geusens et al. Mayo Clin Proc, 2002, 629

P171. Influencing of Glucosamine Sulphate at cartilage morphological changes in osteoarthritis R. Yatsyshyn, Y. Neyko, N. Yatsyshyn; Department of Internal Diseases, Medical University, Ivano-Frankivsk, Ukraine Background: Osteoarthritis is the most prevalent type of arthritis. Glucosamine Sulphate (GS) was shown to be an effective slow acting chondroprotective drug in OA. However the mechanism responsible for the chondroprotective effects of GS has not been documented yet. Objectives: The objective of this study was to use ultrasound and MRI examination to visualize the quantitative structural changes induced by glucosamine sulphate treatment in patients with knee OA. Materials and methods: A cohort of 75 patients suffering from knee OA, average age 56 years was studied. A control group of 30 OA patients of a matched age and clinical stage was included. The patients received 1,500 mg of glucosamine sulphate daily for 12 months after informed consent. The control group continuted their classical treatment without taking GS. The HDI 3000 ATL US machine, equipped with 5–12 MHz linear transducer was used. MRI 0.5 T using axial T1/wt, T2/.wt axial Fat saturated FSE and coronal or sagittal fast STIR sequences were used to measure the thickness of the articular cartilage at baseline, 6 months, 1 year following glucosamine treatment. Results: Pretreatment cartilage defects, diffuse cartilaginous thinning, partial thickness or full thickness irregularities with and without subchondral cyst and/or sclerosis and bone marrow edema, were the most common findings seen in OA knee cartilage of the study population. Following GS treatment, both ultrasound and MRI images showed a significant improvement in the quality of the three layers of knee articular cartilage (superficial, intermediate and deep layers) in 74.2% of patients. The cartilage outlines became well defined in 63.6%. The echotexture showed a significant decrease of echogenic white dots in 82.4%. The diffuse cartilage thinning of both medial and lateral compartments had a substantial increase of thickness compared to pretreatment measurement in 74.9% of patients. The post-

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treatment recorded articular cartilage measurments were statiscally significant compared to the controlled group P<0.5. Conclusion: Following glucosamine sulphate treatment of patients with knee osteoarthritis, both ultrasound and MRI images showed a significant improvement in the quality of the three layers of knee articular cartilage. The cartilage outlines became well defined. The U/S echotexture showed a significant decrease of echogenic white dots. This study provides reliable imaging evidences for the effectivness of glucosamine sulphate treatment in patients suffering from knee osteoarthritis. P172. Comparison of analgesic effects of etidronate, alendronate and risedronate by measurement of fall of skin impedance T. Fujita1, M. Ohue2, Y. Fujii1, A. Miyauchi1, Y. Takagi3; 1 Medicine, Calcium Research Institute, Kishiwada, Japan, 2 Katsuragi Hospital, Osaka, Japan, 3Hyogo Chuo Hospital, Hyogo, Japan Measurement of exercise—induced fall of skin impedance parallelling pain in electroalgometry (EAM) has made it possible to evaluate pain objectively and quantitatively. In 602 patients with back and knee pain due to osteoporosis and/or osteoarthritis, fall of skin impedance in response to standing and squatting (knee load), walking and climbing (combined load), and lying and rising (spine load) was measured along with recording of subjective pain by visual rating scale (VRS). Highly significant correlation (p<0.0001) was found between EAM—measured and VRS— recorded pain. All three bisphosphonates, alendronate (5 mg/ day) (A), etidronate (200 mg/day) (E) and risedronate (2.5 mg/day) (R) administered for 12 months exerted analgesic effects on both EAM and VRS pain. EAM pain expressed as % fall of skin impedance from pre-load level was the least, 2±0.5 after knee load on A, followed by 13±0.5 on E, and 14±0.7 on R (Mean ± SEM, p=0.0004 between A and E and 0.0001 between A and R, Fisher’s PLSD). Combined load gave the least pain, 23±0.9 on E, followed by 25±1.5 on A and 29±1.1 on R (p=0.0265 between E and A and 0.0001 between E and R). Spine load gave the least pain, 25 ±4.1 on E followed by 29±4.4 on A and 32±5.8 on R. Mean and maximum pain alleviation by E was distinctly better than that by R (p<0.0001) but A was not (p=0.0403 and ns). On E, the degree of reduction of EAM pain after/before treatment indicating a pain alleviation was significantly higher than unity after combined load (p=0.0258) and, spine load (p= 0.0006), and in mean (p=0.0079) and maximum response to all exercise load (p=0.0419), but only after knee load (p= 0.0498) on A. VRS pain showed significant reduction on R after knee, combined and spine load, and in mean and maximum response, but only after spine load and in maximum

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response on E. The effect of E appeared to be most rapid in appearance among the three, already evident in the first and second months of treat ment. A appeared to be especially effective on knee load-induced pain and R on VRS pain. P173. Local muscle contraction is not the major driven force of bone adaptation in response to loading Q. Wang1, S. Cheng2, E. Seeman1; 1Austin Health/Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia, 2Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland Based on the evidence that bone strength is highly correlated with muscle strength or size, it is postulated local muscle contraction the major cause of bone adaptation to loading. However, large increase in local muscle strength induced by resistance training is not associated with apparent change in bone structure or strength index in children, adolescents and young adults. Therefore, there is no strong evidence to support that muscle and bone relationship is causal. It is highly possible that the phenotypes of bone and muscle are both genetically and environmentally determined. Two hundred fifty-eight 10–13 year-old Caucasian girls was included at baseline in a 2-year longitudinal study. The muscle area (MA) and tibial bone traits of their left leg were assessed using peripheral quantitative computed tomography (pQCT) at the site 60% of the lower leg length up from the lateral malleolus. The site was chosen because the size of calf muscle is biggest here. MA was correlated with tibial bending strength index (Imax, area moment of inertia) and compressive strength index (CSI, cortical bone area) significantly (r=0.68 and 0.63, respectively). The indices of bending load (BLI, the product of body weight and the lower leg length) and compressive load (CLI, body weight) on tibial shaft was also correlated significantly with tibial BSI and CSI, respectively (r=0.82 and 0.73, respectively). Adjusting for load indices, the relationship between MA and tibial bone strength indices weakened markedly (partial r=0.14 and 0.21 for BSI and CSI, respectively). These results suggested that the local muscle contraction is not the major driven force of bone adaptation in response to loading. The local muscle force is more like a neutralizer of the external force applied to bone than a direct load that bone has to tolerate. P174. An osteoporosis awareness poster: where should it be located? A.G. Juby1, P. Davis1, D. Hanley2, J. Prior3, M. AbuHakima2, Members Canadian Western Region Osteoporosis Board; 1Department of Medicine, University of Alberta, Edmonton, Alberta, Canada, 2University of Calgary, Alberta, Canada, 3University of British Columbia, Vancouver, British Columbia, Canada

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Objectives: Several studies have highlighted the care gap in osteoporosis diagnosis and treatment, even after the occurrence of a fragility fracture. Several methods have been tried to address this gap, but are often very timeconsuming and expensive. No other studies have been published objectively evaluating the impact of location of an osteoporosis awareness poster on requests for further osteoporosis information. Materials and methods: An osteoporosis awareness poster was designed which included a postcard that could be forwarded to the Osteoporosis Society of Canada (OC) if further information was desired. The location of each poster was recorded and the postcards coded by location, to enable tracking of requests. Ethics approval was obtained. Results of requests were collated by the OC and forwarded to the investigators. Results: Posters were placed in 14 different locations, 13 in British Columbia and one in Alberta. Locations included Women’s Health Clinics, an orthopaedic surgeons office, a hospital emergency room, a rheumatologists office, and a bone density (BMD) waiting room. Forty-two reply postcards were received. Thirty-three percent were from a Woman’s Health Centre in BC where posters were located in the waiting room, washroom and pharmacy. Twenty-one percent came from three posters located in an Orthopedic Surgeons office. The next highest, 12% came from the Bone Mineral Densitometry waiting room. The remaining 34% were from six other locations, with 9% from the Emergency Room(ER). Conclusions: Osteoporosis awareness posters are low cost to produce, and have the potential to be placed in many locations. This study would suggest that targeting patients in the ER is less-effective than in a Women’s Health Clinic or an Orthopedic Surgeons office. This study does have limitations: it implies that awareness was only improved by sending a postcard to the OC; it does not account for those who may have accessed further information from their physicians or from the OC website. Nonetheless, it is a cost-effective method to try and address the diagnosis and treatment care gap. P175. Prevalence of low bone mineral density among older men in Sri Lanka S. Lekamwasam1, M. Rodrigo1, L. Wijayarathne2, U. Hewage3; 1Center for Metabolic Bone Diseases, Department of Medicine, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka, 2National Hospital of Sri Lanka, Colombo, Sri Lanka, 3Sri Jayawardenapura University, Kotte, Sri Lanka Objectives: Prevalence of osteoporosis among men in Asian countries is not well known and this study was done to estimate the prevalence of low BMD among older men in Sri Lanka.

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Materials and methods: Phalangeal BMD in 1,174 community dwelling men aged 50 years or more (mean age 57.6, SD 6.6) from seven provinces in Sri Lanka was measured using AccuDXA. These men were free from diseases or had not taken medications which can affect bone metabolism. T scores were calculated using the local reference data. Men were considered to have low BMD when their phalangeal BMD T score was equal or less than −2.50. Results: Mean (SD) phalangeal BMD in age groups 50–59 (n=810), 60–69 (n=250), 70 and above (n=81) were 0.576 (0.068), 0.558 (0.077) and 0.522 (0.079) g/cm2, respectively (p<0.001). Increase of age by one year was associated with a reduction of BMD by 0.002 (se 0.0004, p<0.001) g/cm2 while 1 kg increase in body weight was associated an increase in BMD by 0.002 (se 0.0003, p<0.001) g/cm2. Age and weight together accounted for 20% (r2 =0.20) variation in BMD. Total of 66 men (5.8%) were found to have low bone mass and the prevalence of low bone mass showed a sharp rise with advancing age (3.3% in 50–59, 9.2% in 60– 69 and 18.4% in 70 or more age groups). Conclusions: There was a gradual and significant reduction of BMD with age and 5.8% of older men were found to have abnormally low BMD. Age and weight contributed only for 20% of BMD variation and the rest remains unexplained. P176. Management of the patients with osteoporotic fracture by orthopaedic surgeons A. Akkurt1, O. Gulbahar 2, O.S. Atik1, B. Sancak2; 1 Department of Orthopaedic Surgery, Gazi University, Ankara, Turkey, 2Department of Biochemistry, Gazi University, Ankara, Turkey Objectives: 1. To increase the awareness and the knowledge of the orthopaedic surgeons in the management of osteoporotic fracture. 2. To evaluate the effectiveness of the antiosteoporotic medical treatment. Materials and methods: We (orthopaedic surgeons; AA and OSA) treated 32 patients with osteoporotic fracture in our clinic. The mean age was 71 (range, 53–93). None of them received treatment for osteoporosis before. The fractures were treated either with conservative or surgical methods. Antiosteporotic medical treatment using bisphosphanates, SERM, and calcitonin was started during postoperative period. We measured bone mineral density using DEXA (Hologenic®) at the beginning and at the end of first year, and assessed N-telopeptide type 1 collagen quantities in urine using Osteomark® at 0, 3, 6 and 12 months for the evaluation of the effectiveness of the antiosteoporotic medical treatment. The statistical study was performed using the SPSS 10.0.

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Results: The prescription rate for the antiosteporotic medical treatment in our clinic was raised significantly. By taking the urinal quantity at the beginning as the reference points, the urinal NTx was decreased by 25.2, 39 and 43.9% at 3, 6 and 12 months, respectively. The difference between these values were statistically significant. These results display that the decrease in urinal NTx quantity is more significant in the first three-month period. After a treatment period of 1 year, it is found that an increase of 18.3% in bone mineral density in femoral neck is and 16.3% in L1–L4 vertebrae. The difference between these values were statistically different. Conclusions: 1. NTx is a valuable biochemical marker for assessing the effectiveness of osteoporosis management in such a short time as 3 months. 2. These kind of studies are useful to increase the awareness and the knowledge of the orthopaedic surgeons in the management of osteoporotic fracture. P177. Nutritional survey in Beijing area in 2004— dietary intake of K, NA, CA, P and MG of inhabitants S. Bao, L. Zhao, Z. Li, T. Gong, G. Cheng, H. Zou; Department of Nutrition, PLA General Hospital, Beijing, China Subject: Better understand dietary intake of potassium, sodium, calcium, phosphorous and magnesium of inhabitants in Beijing area. Materials and methods: The multistage stratified random cluster process was used. Twelve communities distributed in six districts, i.e., Shunyi, Changping, Chaoyang, Haidian, Xuanwu and Dongcheng were chosen for the project. 15 families from each community were selected. In practice, a total of 503 subjects from 189 families were involved in this survey. Two methods of weighing dietary record and duplicated sampling with determination in laboratory were used in data collecting and analysis: During the 6-day-survey including two weekends in each community 15 well-trained investigators were allocated to 15 different families, respectively, to weigh and record the food name and amount what the family members ate. Meanwhile, duplicated whole diet of five members from five different families chosen by random in each community were collected respectively and determined for contents of K, Na, Ca, P and Mg in Lab. Results: The median of dietary Ca intake of inhabitants in Beijing area was 497 mg/day. Of 503 subjects, 117 (23%) had intake of Ca below 350 mg/day, 253 of 503 subjects (50%) below 500 mg/day, moreover, 92% (461/503) of subjects had daily dietary Ca intake below 800 mg/day of RNI (Recommended Nutrient Intake) in China. Only 8% (42/503) of subjects had sufficient Ca intake. The median of dietary Mg intake of inhabitants in Beijing area was 301 mg/day, 412 subjects (82%) had dietary Mg intake

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lower than 400 mg of RNI. Median of dietary potassium was 1,740 mg/day, 68% of subjects (340/503) had dietary intake lower than 2,000 mg/day of RNI. In contrast, daily P intake was 976 mg/day, 75% (375/503) of subjects had intake more than 700 mg/day of RNI. The ratio of Ca to P in diet was 0.49. In addition, median of daily dietary Na intake was 3,810 mg/day. Daily dietary intake of Na in 91% of subjects (459/503) was equal or more than 2,200 mg/day of RNI. The ratio of Na to K was 2.19. Results from two different methods showed there is a good correlation between calculated value with food composition table and measured value actually. The coefficient of correlation were K: 0.7159, Na:0.7391, Ca: 0.6118, P:0.6877 and Mg:0.6794, respectively (P<0.01). In general, calculated value was 1.1∼1.3 times of measured value in all of these five elements. Discussion: Dietary intake of K, Ca and Mg of inhabitants in Beijing area is lower than that of RNIs in China. However, inhabitants in Beijing take excessive Na and sufficient P from diet, leading improper ratio of Ca to P and Na to K in diet. P178. A retrospective research in standardization of BMD machines in China Z. Zhang1, J. Shen2, Z. Liu3; 1Department of Orthorpaedic Surgery, Aviation Industry Center Hospital, Beijing, China, 2Department of Orthorpaedic Surgery, Peking Union Medical College Hospital, China Union Medical University, Beijing, China, 3Osteoporosis Committee of China Gerontological Society (OCCGS), Beijing, China Objectives: Because of the different kinds and tapes of Bone Mineral Density detecting machines, the results of BMD in China were differents. In order to change these results into a union conversion formula, here we try to research retrospectively Chinese cultures and try to reflect the real BMD. Materials and methods: To find out all the published Chinese cultures since 1994–2004, we quilt 137,929 casetime’s women BMD results, according to the measuring parts, get some BMD measuring machines’ conversion formula. Results: According to the results of LUNAR-DPX-L which is used most popularly, we get the followed conversion formula. In lumbar post-anterior film, LUNAR-DPX-L=NORLAND-XR× 1.102 + 0.00137, LUNAR-DPX-L=LUNAR-EXPERT × 0.991 + 0.0005, LUNAR-DPX-L=LUNAR-DPX-IQ × 1.025 + 0.0003 LUNAR-DPX-L=HOLOGIC- QDR4500 × 1.184 + 0.0281 LUNAR-DPX-L=HOLOGIC- QDR2000 × 1.156 + 0.00048. In femoral neck, LUNAR-DPX-L=NORLAND-XR × 1.0377 + 0.00026 LUNAR-DPX-L=LUNAREXPERT × 0.965 + 0.00083 LUNAR-DPXL=LUNAR-DPX-IQ

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× 0.986 + 0.00031 LUNAR-DPX-L=HOLOGIC-QRD4500 × 1.142 + 0.00033 LUNAR-DPX-L=HOLOGIC-QDR2000 × 1.126 + 0.00042. In femoral TROCH area LUNAR-DPX-L= NORLAND- XR × 1.137 + 0.0021, LUNAR- DPX-L= LUNAR EXPERT × 0.985 + 0.0124, LUNAR- DPX-L= LUNAR-DPX-IQ × 0.972 + 0.00024, LUNAR-DPX-L= HOLOGIC-QRD4500 × 1.030 + 0.0001, LUNAR-DPX-L= HOLOGIC-QDR2000 × 1.205 + 0.00019. So, the average conversion formula are: LUNAR
DPX
L ¼ NORLAND
XR  1:092 þ 0:0012; LUNAR DPX
L ¼ LUNAR
EXPERT  0:980 þ 0:00706 þ 0:0012; LUNAR
DPX
L ¼ LUNAR
DPX
IQ  0:994 þ 0:00028; LUNAR
DPX
L ¼ HOLOGIC
QDR4500  1:119þ 0:0094; LUNAR
DPL
X ¼ HOLOGIC
QDR2000  1:162þ 0:00036: Conclusion: From this research results, we can compare Chinese BMD results in each other with some coefficients. The retrospective research could reflect the real relationships of these machines with some creditability. This kind of research method maybe a good means to set up a Chinese standard bone mineral density. P179. A retrospective research of osteoporosis diagnostic criteria in China with evidence based medicine Z. Zhang1, J. Shen2, Z. Liu3; 1Department of Orthorpaedic Surgery, Aviation Industry Center Hospital, Beijing, China, 2Department of Orthorpaedic Surgery, Peking Union Medical College Hospital, China Union Medical University, Beijing, China, 3Osteoporosis Committee of China Gerontological Society (OCCGS), Beijing, China Objectives: According to evidence-based medicine, about past 10 years bone mineral density (BMD) results were analyzed retrospectively which came from DEXA, pDEXA, RA, and SPA measuring methods in China mainland. All these efforts tried to get out Chinese osteoporosis diagnostic criteria more objectively and more exactly. Summary of Background Data: In recent years, many researches and reporters disputed if The China Osteoporosis Diagnostic Criteria should be BMD lose 2.5 SD, which were accorded to American Criteria. Though Osteoporosis Committee of China Gerontological Society (OCCGS) had commended this China Criteria in 1999 and 2001, a retrospective study with huge samples has rarely been reported in order to prove this result. Materials and methods: To search The Chinese Medical Database from China Union Medical University Library, 52,166 male case-times and 107,929 female case-times

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BMD lose rate data were quoted and calculated from 49 related published papers. The average values and standard deviations also were calculated by SPSS 11.0 (SPSS Inc., Chicago, IL) and the BMD lose rate curves were drawed from 20 to 90 years old phases. The independent sample Ttest also was calculated between the results of femoral neck and that of other measured sites. Results: From upper data and curves, most curves coincide or are close to each other. All these curves could reflect the real trend of old Chinese people. The results and curves of men and women femoral neck are located in the middle that could show the actual osteoporotic state. There are 18% BMD lose rate when men are 60–70 years old and 22% at 70– 80 years old. For women, it is 25 and 30%, respectively. It is suggested that the Chinese criteria of osteoporosis diagnosis should use 25% in BMD lost rate or 2 SD. In addition, the measure position is suggested in some sequence that femoral neck is better than forearms, lumbar P-A position, phalanges (2nd, 3rd, 4th) detected by RA and femoral Troch region. Because there are obvious differences from the values of femoral neck (p<0.05), the femoral WARD’s region and lumbar lateral measurements are not supported. Conclusions: To use evidence-based medicine can get more accuracy and more reliable results of the China Osteoporosis Diagnostic Criteria. If it reaches 25% the BMD lost rate or 2 SD, Osteoporosis can be verified. It is worthy of developed, deeper research with more samples.

bioavailable T (Bio-T), free androgen index (FAI), free E2 (FE2), bioavailable E2 (Bio-E2), TT/ E2, FT/ FE2 and BioT/ Bio-E2 were calculated. Result: CYP19 AA genotypes increased, whereas GA and GG genotypes decreased obviously in normal group than those in decreased BMD group (70.45, 20.45, 9.09 vs 36.00, 44.00, 20.00%; X2=15.25, P=0.001). In older men, those with CYP19 GA and GG genotypes had lower BMDs at lumbar spine (L2–4), femoral neck, Ward’s triangle and trochanter (1.08±0.22, 1.07±0.24 vs 1.25±0.22; 0.80± 0.14, 0.82±0.10 vs 0.90±0.13; 0.65±0.17, 0.68±0.14 vs 0.76±0.16; 0.76±0.14, 0.79±0.11 vs 0.86±0.14; P<0.01, P<0.05; GA, GG vs AA). There were significant correlation between CYP19 genotype and BMDs at lumbar spine (L2–4), femoral neck, Ward’s triangle and trochanter (P= 0.003, 0.001, 0.013) however no association was found with BMDs at Ward’s triangle. No significant association was seen between CYP19 genotype and serum sex steroids (P>0.05); CYP19 G allele and fracture history were risk factors and BMI was protective factor of osteoporosis in elderly men (P=0.0285) 0.0031, 0.004, respectively. Conclusion: In elderly Chinese men, CYP19 GA and GG genotype can lead to decreased BMDs at lumbar spine, femoral neck, Ward’s triangle and trochanter. The polymorphysims in exon 3 (G→A substitution) of CYP19 is associated with osteoporosis and CYP19 is candidate gene for osteoporosis in elderly Chinese men.

P180. A study of the association of polymorphisms in the P450 C19 with serum sex steroid concentration and osteoporosis in elderly men Y. Zhang, T. Tao, P. Gao; Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China

P181. Association of estrogen receptor gene polymorphisms with bone mineral density in adolescent idiopathic scoliosis J. Wu, Y. Qiu, L. Zhang, Y. Sun, X. Chen; Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China

Objectives: To explore the association of the polymorphisms in CYP19 with serum sex steoid concentration and osteoporosis in elderly men. Materials and methods: One hundred eighty-two elderly men including healthy (n = 88) and decreased BMD (osteopenia and osteoporosis, n=94) group attended this study. Spinal and hip BMD were measured by dual energy X-ray absorptionmetry. The polymorphysims in exon 3 (G→A substitution) of CYP19 and total testosterone (TT), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were determined by RIA in all subjects. Levels of free T (FT),

Objectives: To investigate the relationship between polymorphism of the estrogen receptor (ER) gene and bone mineral density (BMD) in adolescent idiopathic scoliosis. Materials and methods: Ninety-two patients with adolescent idiopathic scoliosis, aged 10–19 years and Cobb angle ranged from 25 to 134° were included in this study. BMD of the lumbar spine (L2–L4) and proximal femur (including the femoral neck, the greater trochanter and Ward’s triangle) was measured by dual energy X-ray absorptiometry. Two polymorphic loci, PvuII and XbaI locus, of estrogen receptor were analyzed by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs).

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Results: The distribution of ER genotypes in adolescent idiopathic scoliosis patients was PP (19.6%), Pp (46.7%), pp (33.7%), XX (22.8%), Xx (33.7%) and xx (43.5%). The frequencies of XX genotype in patients whose height >160 cm and Cobb angle >40° were greater than those whose height <160 cm and Cobb angle <40° (p<0.05). The BMD at lumbar spine and proximal femur (greater trochanter and Ward’s triangle) of genotype XX was lower than that of genotype xx (p<0.05), while there was no significant relationship between the PvuII polymorphism of ER and BMD. The BMD at lumbar spine and and proximal femur (greater trochanter and Ward’s triangle) of genotype PPXX was lower than that of genotype Ppxx and ppxx (p<0.05). Conclusions: There is high correlation between XbaI polymorphism of ER and BMD in patients with adolescent idiopathic scoliosis, and genotype PPXX has lower BMD which may help to find the patients with osteopenia at early time in adolescent idiopathic scoliosis. P182. Association of testosterone and estradiol deficiency with BMD in Chinese aged men L. Xu, H. Gao; Department of Geriatrics, Qi-Lu Hospital, Shandong University, Jinan, PR China Aims: The association of testosterone and estradiol with bone mineral density (BMD) in Chinese aged men is uncertain. The aim of this study is to examine the association of testosterone and estradiol deficiency with osteoporosis in aged men in China. Materials and methods: Two hundred forty-seven aged Chinese men (age 71±6.79 years ) were recruited into the study from May, 2004 to Nov, 2006. Total testosterone and total estradiol were examined by radioimmunoassay. BMD was determined by DEXA. The relatioship between hormone levels and BMN were analysed by Pearson’s correlation test. Results: BMD was negatively correlated with total testosterone and total estradiol (P= 0.03, P= 0.04, respectively). Conclusions: Older men with total testosterone or estradiol deficiency were more likely to have low BMD in Chinese aged men. BMD testing of older men with sex steroid deficiency may be clinically warranted. P183. Bone mineral density and its related factors in old male Chinese patients with type 2 diabetes L. Xu, H. Gao, M. Cheng, X. Liu; Department of Geriatrics, Qi-Lu Hospital, Shandong University, Jinan, People_s Republic of China Introduction: This retrospective study covered 131 aged male patients with type 2 diabetes over 65 years old (age

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73.12±5.54 years, diabetic duration 5.28±3.56 years, HbA1c 7.88% ±1.81%, BMD of L1–L4 0.889±0.064 g/cm2). Aims: To evaluate the prevalence of osteoporosis and osteopenia at lumber level and to investigate the possible factors that influence lumber Bone Mineral Density (BMD). Materials and methods: The subjects were submitted to a bone densitometry scan (DXA) to evaluate the BMD at lumbar spine (L1–L4), meanwhile, the data of lifestyle habits, diet and medical history were derived from the medical records.Fasting blood samples were taken to check hormones and biochemical levels. Demographic data were also measured. Osteopenia and osteoporosis were diagnosed according to the World Health Organization criteria. Results: The prevalence of osteoporosis and osteopenia in this group of patients was 31.3 and 29.0%, respectively. Weight, diabetic duration, and HbA1c and testerone were correlated with BMD by Pearson Correlation test (p<0.05). Weight was the the best predictor of BMD by linear regression test (p=0.023) among diabetic duration, HbA1c and testerone. Conclusion: We found a high prevalence of osteopenia and osteoporosis in this population, with weight being the the best predictor of BMD. P184. Determination of bone mineral density by absorptiometry in normal people in Urumqi B. Li, P. Zhang, X. He, Y. Xia, L. Wei; Imaging Center, First Affiliated Hospital, Xinjiang Medical University, Xinjiang, China Objectives: To determine the normal bone mineral denity (BMD) values of lumber spine, proximal femur and further to investigate the regularities of BMD with gender on this basis according to the BMD measurement. Materials and methods: Duel energy X-ray BMD detector (Model lexxos made by DMS Co., Ltd, France) were submitted to BMD determination in the 1–4 lumber spine, proximal femure (including neck, G.T, Inter Tro and Ward) among the age group more than 20 years in Urmuqi area. Subjects with both acute and chronic diseases and with drug treatment which probably cause bone metabolism affection were strictly excluded in this study. Among all the subjects to these criteria, 865 were males and other 1,403 were females. All the analysis was performed with SPSS 11.0 software. The total 12 male and 12 female groups were determined by age (per 5 years as in one group) and gender, the mean BMD value standard deviation (SD) and accumulated losing ratio were acquired on this substructure at the same time. The subtraction 2.5 fold SD from gender and location matched peak BMD were served as the diagnostic reference for osteoprosis.

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Result: 1. The pek bone mass of lumbar vertebra will emerge in the 35∼39 age-group of males (0.995±0.127 g/cm2) and 40∼44 of females (0.976±0.159 g/cm2), that of proximal femur in the 20∼24 of males (0.815±0.141 g/cm2) and 35∼39 of females (0.745±0.1000 g/cm2). The females BMD showed a sharp decline after 50 years while no such a tendency occurred in males post the peak. 2. The diagnostic reference for lumbar vertebra osteoprosis in urban Urmuqi will be 0.678 g/cm2 in males and 0.579 g/cm2 in females, for proximal femur will be 0.463 g/cm2 in males and 0.495 g/cm2 in females. Conclusions: The skeleton site and gender difference will straightly affect the peak BMD reached age and peak bone mass level. This study may provide useful evidence and data for osteoprosis study in the Han ethnic group of Urmuqi area. P185. Effects of simulated weightlessness on the kinase activity of MEK1 induced by bone morphogenetic protein-2 in rat osteosarcoma cells B. Wang, Z. Yang, Y.-H. Wu, S. Zhang; Key Laboratory of Aerospace Medicine, National Education Ministry, Fourth Military Medical University, Xi’an, China Objectives: The mRNA expression of α1 chain of type I collagen (COL-Iα1) in rat osteosarcoma (ROS17/2.8) cells induced by bone morphogenetic protein-2 (BMP-2) was reduced under simulated microgravity. The protein kinase MEK1 of MAPK signal pathway plays an important role in the expression of COL-Iα1 mRNA. But there was no report on the kinase activity of MEK1 under simulated microgravity. To investigate the effects of simulated weightlessness on the activity of MEK1 induced by BMP-2 in ROS17/2.8 cells. Materials and methods: ROS17/2.8 cells were cultured in 1 G control and rotating clinostat simulated weightlessness for 24, 48 and 72 h. BMP-2 (500 ng/ml) was added into the medium 1 h before the culture ended. Then the total protein of cells was extracted and the kinase activity of MEK1 was detected by means of Western Blotting. The cells were divided into seven groups as follows: group 1 was a control group in which ROS17/2.8 cells were cultured in 1G condition without BMP-2; group 2, cells were cultured in 1 G for 24 h; group 3, in weightlessness for 24 h; group 4, in 1 G for 48 h; group 5, in weightlessness for 48 h; group 6, in 1 G for 72 h; group 7, in weightlessness for 72 h. Cells in group 2 to group 7 were all cultured with BMP-2. The expression of phosphated-ERK1/2 (p-ERK1/2) protein were detected. Results: There were no significant differences in the expression of total ERK1/2 among all groups. The expression of p-ERK1/2 was unconspicuous in the control group without BMP-2 but increased significantly when

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BMP-2 was added (P<0.01). The level of p-ERK1/2 in simulated weightlessness group was much more lower than that in 1 G group in every time point (P<0.01). The expression of p-ERK1/2 gradually decreased along with the time of weightlessness simulation (P<0.01). Conclusion: The kinase activity of MEK1 induced by BMP-2 in rat osteosarcoma cells was reduced under simulated weightlessness. P186. Investigation of correlated factors about falls of old people L. Zhou1, S. Wang1, L. Jiang2; 1Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, China, 2Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China Background and Purpose: To investigate ability of balance and falls, and the other correlated factors of falls so as to offer preventions for the old people, reduce falls and improve life quality. Materials and methods: Descriptive study by giving questionnaires as well as measurement of bone mineral density and testing of balance ability to people in Fangzhuan district, Beijing, who are over 60 years old and can walk around independently. The Questionnaire includes general of health, food and drink, exercise, fall and fracture occurrence. The balance ability includes standing, standing on one foot, walking manners, standing up and walking, walking tandem and horizontal walking and also grasp force. Results: First, the rate of falls was 49 and 79% in men and women, respectively, during last 3 years. There are no significant correlation between the quantity of milk drunk, the time of housework and the frequency of falls, fracture and bone mineral density (P>0.05). But exercise in the past and present is significantly correlated with the frequency of falls, fracture and bone mineral density (P<0.05). Furthermore, the subjects who insist on exercising display good balance ability, agility and balance. But the people engaged in housework had higher rate of falls and fracture than those who insist on exercising. Second, there was no significant correlation between prevalence rate of diseases and the frequency of fall (P>0.05). The frequency of falls had no significant correlation with bone mineral density (P>0.05). That shows the decrease concordance is the first sign of low balance ability and it has no relation with bone strength.Third, the frequency of falls of both women and men is significantly correlated with erecting time with two feet and single foot, respectively, when eyes shut, the carriage of walking, standing up and sitting down, walking tandem and horizontal walking and grasp force of right and left hand (P<0.05). That indicates the old people are more dependent on vision for balance. The decrease of

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vision worsens the adjustment of balance, and also, the degeneration of the vibration sense of skin , the deep sense of joint and strength of muscles are all important causes for the decreasing of balance ability. Conclusion: The rate of falls in old people is comparatively high. The deterioration of the body balance adjustment is mainly caused by the decreasing of the vision and the degeneration of joints and muscles. For improvement, we suggest the old people should reinforce the exercise of concordance. They can wear proper glasses for the adjustment of vision to compensate the physiological deficiency. As women have higher rate of falls, our advice is that they should be more focused exercise. As to whethertaking sea food with calcium, drinking milk,and taking drugs for preventing osteoporosis has certain relation with the improvement of balance ability, reducing falls and fracture should be further studied. P187. Update of biological markers for osteoarthritis D. Zhao; Beijing Ji-Shui-Tan Hospital, Beijing, China Osteoartharitis (OA) is the most common joint disease worldwide. Assays of biological markers serve three purposes in patients with osteoarthritis: To ensure the early diagnosis of osteoarthritis before the development of radiological changes, to predict the potential for structural damage, and to monitor the effects of treatments with potential chondroprotective effects. The diagnosis is made using clinical parameters and radiological analysis (join space narrowing, osteophytes, sclerosis). However, these diagnostic tools lack sensitivity for the early stage of OA. Once these clinical and radiological parameters indicate OA, the disease is likely to be in an advanced stage. A number of markers have been convincingly shown to reflect collagen type 2 and proteoglycan turnover in patients. These markers have been investigated in patients with osteoarthritis, such as PIINP, CPII, Col 2-3/4, HELIXII, GAG, HA, CS, KS et al. The turnover of collagen type 2 is virtually nonexistent in normal adult cartilage, is increased in posttraumatic arthropathy and in early stage OA. The C-terminal fraction of collagen type 2 (CTX-II) is separated from the rest of the collagen molecule by metalloprotease and be assayed in urine and joint fluid. CTX-II is specific of mature fibrillar collagen, and consequently CTX-II levels do not reflect the breakdown of newly synthesized collagen and may be a very early marker for cartilage breakdown and consequently for osteoarthritis. CTX-II is stable during storage of urine samples at room temperature for up to 1 day, and they resisted more than seven freeze-thaw cycles. Assay of markers that reflect breakdown of collagen type 2, most notably CXT-II, holds considerable promise for patients with knee or hip osteoarthritis but are not yet

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performed in everyday practice. The clinical relevance of these markers remains to be determined. P188. Low incidence of osteoporosis treatment after hip fracture V. Rabenda1, R. Mertens2, V. Fabri2, J. Vanoverloop2, F. Sumkay, K. Thorre5, J. Voisey, C. Vannecke3, A. Deswaef 3, G. Verpooten6, J. Devillers4, J.Y. Reginster1; 1WHO Collaborating Center for Public Health Aspects of Osteoarticular Disorders, Department of Epidemiology, Public Health and Health Economics, University of Liege, Liege, Belgium, 2Agence Intermutualiste, Bruxelles, Belgique, 3Institut National d’Assurances Maladie-Invalidité, Bruxelles, Belgique, 4Mutualité Socialiste, Bruxelles, Belgique, 5Mutualité Libre, Bruxelles, Belgique, 6Université de Gand, Gand, Belgique Objectives: To assess the proportion of patients treated with bisphosphonates (BP) or selective estrogen receptor modulators after hip fracture and to evaluate, among them, the 12-month compliance and persistence. Materials and methods: Data from mutual insurance company collected by AIM (Agence Intermutualiste) for the Belgian national social security institute (INAMI). We selected all postmenopausal women naïve to BP, hospitalized for a hip fracture between April 2001 and June 2004. For patients who received alendronate treatment after hip fracture, we categorized them according to their formulation use during the follow-up study (daily group, weekly group, daily followed by weekly (switch) group). Compliance at 12 months was quantified using the Medical Possession Ratio (MPR) (i.e. the number of days of alendronate supplied during the first year of treatment divided by 365). Persistence was calculated as the number of days from the initial prescription to a lapse of more than 5 weeks after completion of the previous refill. The cumulative treatment persistence rate was determined by using Kaplan–Meier survival curves. Results: A total of 23,146 patients incurring a hip fracture were identified. Among them, 6% received treatment during the study period (Alendronate or Risedronate=5.4%; Raloxifène=0.6%). 2.6 and 3.6% of patients were dispensed BP treatment within, respectively, 6 months and 1 year after the occurrence of the hip fracture. Among women who received alendronate daily (n=124) or alendronate weekly (n=182) after hip fracture, and followed during at least one year, the 12-month mean MPR was 67% (daily= 65.9%; weekly=67.7%; NS). For the analysis of persistence, a total of 726 patients were included (daily: n=142; weekly: n=261; switch: n=323). At 12 months, the rate of treatment discontinuation was 41.2%. The median time to discontinuation was 40.3 weeks. Conclusions: The results of this study show that the vast majority of patients who suffered a hip fracture are not taking

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recommended therapy after the fracture. Furthermore, among patients who initiate alendronate treatment after the fracture, the adherence to treatment decreases over the time and remains suboptimal. P189. Relation of serum folate to bone mineral density postmenopausal women Z. Sheng1, L. You1, L. Zhang2, J. Chen1; 1Osteoporotic Department, Affiliated First People’s Hospital, Shanghai Jiaotong University, Shanghai, China, 2Nuclear Medicine Department, Affiliated First People’s Hospital, Shanghai Jiaotong University, Shanghai, China Objectives: To study whether in postmenopansal women levels of serum folate are related to bone mineral density (BMD). Materials and methods: 1. Experimental subjects: 93 voluntee women, who had been postmenopausal for at least 12 months and were recruited from those (487 women) of our first osteoporotic outpatients (age 65.62±11.49) between August 2005 and December 2005, all subjects gave their informed consent to participate into the study. All subjects were no use of multivitamin B and vitamin D supplements, no gastric surgery, no liver and renal abnormal, no use of hormone in 6 months, no diabetes mellitus, hyperthyroidism and hyperparathyroidism or other metabolic bone diseases, no excessive smoking and alcohol. 2. Groups: Osteoporosis (n=29), osteopenia (n=50) and normal (n=13). 3. Serum sample: Blood sample from fasting subjects were collected between 8.00 A.M.–10.00 A.M., and serum was stored at −20°C, within 3 days, samples were measured. 4. Biochemical assays: (1) Serum folate levels were measured using chemiluminescence (DPC corporation), the sensitivity of this assay is 50 pg/mL, normal range 3–17 ng/ml. (2) Serum BGP and serum PTH levels were measured by chemiluminescence (equipment is Roche E170). (3) SerumALP, serum Ca and serum P were measured by automated biochemistry techniques. (4) BMD was measured using dual energy X-ray analysis (GE PRODIGY Inc.) at the lumbar spine (L1–L4) and at the left hip (total hip, trochanter, Ward’s area and femoral neck). 5. Statistical analyses: BMD values, biochemical parameters were expressed as mean ± SD. Multiple regression analysis was used to assess the relationship between BMD values and serum folate levels. Comparisons between two groups were made with t-tests. P-values less than 0.05 were considered significant. All statistical analysis were performed by SPSS11.5 system. Results: 1. Osteoporotic women had lower values of serum folate [osteoporosis group (11.27±6.04 pg/ml), osteopenia

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group (13.18± 6.14 pg/ml) and normal group (11.9 ± 3.73 pg/ml)]. No statistical significance. 2. Low folate levels and low BMD value at each of the hip sites and for total hip are no correlation (total hip r=0.005, P> 0.05, trochanter r=−0.021, P>0.05, shaft of femur r=0.017, P>0.05 and femoral neck r=0.021, P>0.05). 3. Low folate levels and low BMD value at lumbar spine (L1–L4) are no correlation (r=0.078, P>0.05). Conclusions: Serum folate levels are not an important risk factor for osteoporosis. P190. Relationship between polymorphism of Apolipoprotein E gene and descent of bone mineral density in older adults B. Zhou1, X.-H. Wang1, S.-T. Wang1, L.-Y. Guo1, Ch. Xu1, Z.-Y. Kan1, Y. Liya2, A. Prentice2; 1Department of Nutrition and Food Hygiene, Shenyang Medical College, Northeastern University, Shenyang, China, 2Medical Research Council (MRC) Human Nutrition Research (HNR), Nutrition and Bone Health Research, Cambridge, United Kingdom Objectives: Apolipoprotein E (ApoE) gene is one of candidate genes contributing to osteoporosis. The objective of this study was to explore the correlation between polymorphism of the ApoE gene and bone mineral density (BMD). Materials and methods: One hundred one healthy Han volunteers over 60 years old living in Shenyang were selected (age 66.5±4.1). ApoE gene was measured by polymerase chain reaction–restriction fragment length polymorphism (PCR-RELP). BMD at hip was measured respectively using dual-energy X-ray (DPX-L) absorption apparatus (Lunar, USA) in 2000 and 2005. Results: The ApoE gene phenotype in the population was E2/3: 16.8%, E3/3: 67.3%, E4/3: 14.9%, E4/4: 1.0%, while E2/2 and E4/2 was not found. The ApoE all lelomorph frequencies were 8.42% forå2, 83.16% forå3, 8.42% for ɛ4. These people were divided into two categories: The presence ApoE4 group (E4/3 and E4/4 n=16) and the absence ApoE4 group (E2/3 and E3/3 n=85). There were no difference in age, height, but the weight of the presence ApoE4 group was a little heavier than the weight of absence ApoE4 group (P<0.05). After adjustment for height, weight, and age, there was no significant difference of the BMD in the femoral neck, tuverosity and Ward areas in 2000. After a 5 years interval, the BMD of the presence ApoE4 group and absence ApoE4 group are decreased at hip. After adjustment for height, weight and age, the various percentage of the BMD at hip was no significant difference between the presence ApoE4 group and the absence ApoE4 group.

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Conclusion: There is no significant association between ApoE genotype and BMD of hip. P191. The application of imaging in osteoporotic fracture Y.-Z. Cai, J.-X. Li, X.-L. Tian; Radiological Department, Tianjin General Hospital, Tianjin Medical University, Tianjin, China Objectives: The spine, hip, and wrist fractures are the most important complications in elderly population with osteoporosis. It is also established that the presence of the vertebral fracture may play an important factor for subsequent osteoporotic fracture. Although vertebral, hip or wrist fractures are common, they are difficult to identify in clinic without radiographs. Further more, the occurrence of osteoporotic fracture is not only closely related to low bone density but also dependent on decreased bone quality. Owing to fact that the imaging examination can provide a lot of informations about quantitative and qualitative changes of bone, now imaging examination is becoming a widely accepted method with remarkable success. However some unresolved or interesting problems still remain to be deliberate carefully. To discuss the mechanisms of some osteomalacic imaging features in metabolic and endocrinic disorders, and to evaluate their signification in diagnosis and differential diagnosis. Materials and methods: Thirty-six patients who had osteomalacic appearance in radiograms were collected in this study. All of them were performed radiologic analysis of bone structure and density. Six patients with pseudofracture line were examined by thin slice CT scan. Results: All patients showed different degree bending deformity and abnormal density of bone. Thirteen patients had pseudofractures, three had true fractures, two had insufficiency fractures. Conclusion: The ability of evaluation in osteoid tissue by imaging method, as well as mechanism of bone trabecular radiologic appearance in osteomalacia and osteoporosis were further explained. The fracture line in metabolic and endocrine osteomalacia may be pseudofracture, true fracture or insufficiency fracture. The diagnostic criteria of these three kinds of fracture was induced. (1) Imaging examination may provide an important role in predetermination, prevention, and diagnosis of osteoporotic fracture as well as in evaluation of therapeutic effect. (2) The diagnostic creteria for true- and pseudo-fracture proposed by author may be useful in clinical practice. (3) Insufficient fracture means that the osteoporotic fracture is in severe degree and it is also one of the risk factors for subsequent fracture, while the evaluative ability of fatigue- and micro-fractures should be taken a

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comprehensive consideration with BMD determination. (4) In differentiate the benign from malignant fractures, MR examination especially enhance method is superior to plain film or CT scan. During the follow up, a lot of MRI findings such as the changes of vertebral signal intensity both on pre-and postenhancement, changes in shape and signal intensity of pedicle, and intravertebral accumulation of fluid or air resulted from bone necrosis may play important roles in differentiating benign from malignant vertebral fracture. P192. The bone mass and growth of Han, Tibet and Qiang nationalities children in China Q. Zhang1, X. Hu1, B. Zhang1, J. Zhang2, B. Cui1, G.S. Ma1; 1The Institute for Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing, China, 2 West China Center of Medical Sciences, Sichuan University, Chengdu, China Objectives: To investigate the forearm bone mass accrual and bone growth and development of children and adolescents in Chinese Han, Tibet and Qiang nationalities. Materials and methods: Total 1,822 children aged 7 to 18 years from Han, Tibetan, and Qiang nationality (about 25 per gender per age per nationality) were recruited from two counties of Sichuan Province, China. Their bone mineral content (BMC), bone areas (BA) and bone mineral density (BMD) at distal 1/3 and 1/10 forearm were measured by Norland peripheral dual energy X-ray bone densitometer (pDEXA). Their body height, sitting-height, knee-height and forearm length were measured by trained investigators following a standardized procedure. Results: At distal 1/10 forearm, the bone mass indices of Tibetan children and adolescent were higher than those of Qiang and Han nationalities with same age and same gender, especially for BMD and BMC of Tibetan boys aged 9– 12 years. Usually, bone mass indices of boys were higher than those of girls with the same age and same nationality, especially for BMD and BMC of boys less than 11 years or more than 14 years, however BA of girls once were significantly higher than those of boys at 15 years for Tibetan, at 11 and 12 years for Qiang and at 13 years for Han. At distal 1/3 forearm, there were no significant difference in BMC and BMD between nationalities with same age and same gender, except that BA of Tibetan children aged 7– 13 years were significantly higher than those of Han or Qiang nationality. Usually, bone mass indices of boys were higher than those of girls with same age and same nationality, while significantly for Tibetan and Qiang boys aged more than 16 yrs in BMD, more than 15 years in BMC and more than 13 years in BA and 1 year later correspondently for Han.

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In early age, there was a trend of sitting-height, kneeheight and forearm length in Tibetan children higher than those of Qiang and Han nationalities with same age and same gender; however the difference disappeared for adolescents aged more than 16 years except that knee-height of Tibetan girls aged 18 years and forearm length of them aged more than 17 years were significantly higher. During 7–9 years, there was a trend of the sitting-height, knee-height and forearm length of the boys higher than those of girls. From 10 years old, this trend became opposite with indices of girls higher than those of boys, while significantly for sittingheight and forearm length at 11 years, and knee-height at 10 years. However, the indices of boys were significantly higher than those of girls at more than 14 years for sittingheight, more than 13 years for knee-height and more than 12 years for forearm length. Conclusions: The bone mass accrual and bone growth and development were related to their nationality and gender in Chinese Han, Tibet and Qiang nationalities children and adolescents. P193. The effect of fluvastatin on interleukin-6 of rats with osteoporosis during union of fracture M.-W. Yang, Y. Zhu, G.-J. Tu, G. Lu; Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang, China Objectives: To explore the effect of fluvastatin on interleukin6 (IL-6) of rats with osteoporosis during union of fracture. Materials and methods: Models with fracture at intermediate piece of femur were made with 72 Sprague Dawley (SD) rats with osteoporosis after ovariectomy for three months, then these rats were divided into medication administration group and control group (36 rats each group). The previous group was given fluvastatin lavage on the next day of operation for 6 weeks, 10 mg/kg per day and the control group was given placebo. Then the expression of IL6 and IL-6mRNA in bony callus of two groups was measured respectively using immunohistochemistry and hybridization in situ on 3rd, 7th, 14th, 21st, 28th and 42nd day, then image analysis was done with real-color image analysis machine. Results: There were no differences in the cellular localization of IL-6 and IL-6mRNA gene expression between the medication administration group and control group during union of fracture and their expression modes were almost similar. On the 14th day postoperatively, the positive extent of positive cells in the medicatin administration group was higher than that in the control group (P<0.05). Conclusion: Fluvastatin can promote IL-6 level in rats with osteoporosis during union of fracture.

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P194. The effects of insulin and IGF-1 on expression of type I Collagen and bone gla protein of human osteosarcoma cell line MG63 Y.-F. Ma1, W.-G. Li2, S. Chen2; 1Department of Geratology, The Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China, 2Department of Indocrinology, The Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China Objectives: To investigate the effect of Insulin (INSU) and insulin like growth factor-1 (IGF-1) on the expression of type I? I collagen (COL1) and bone gla protein (BGP). 17-ß estradiol (E2) were used as the positive contrast medicine. This experiment focus on the exploration of the pathogenesis of the osteoporosis and the providing of the experimental basis for the treatment of the osteoporosis. Materials and methods: The MG63 cells (105/ml) were seeded into the phenol-free DMEM medium. Then the cultured MG63 were exposed to INSU, IGF-1 and E2. The total RNA of every sample was extracted and then do reverse transcription reactions to get the cDNA chains of genes of COL1 and BGP. Fluorescence real time quantitative PCR assay was carried out to examine the mRNA expression of COL1 and BGP. Result: The mRNA copys of COL1 and BGP were significantly different between the every groups of INSU, IGF-1 and E2 (P<0.05). The effect of every medicine increased dose-dependently. The best medical effect concentrations of INSU, IGF-1 and E2 is the highest medical effect concentrations of every group. The mRNA copys of COL1 and BGP were significantly different between the groups of INSU, IGF-1 and E2 (P<0.05). The increased rate of COL1 mRNA copys of INSU and IGF-1 groups was significantly bigger than that of E2 groups (P< 0.05). The increased rate of BGP mRNA copys of INSU group was significantly bigger than that of IGF-1 and E2 groups (P<0.05). Conclusion: Like E2, INSU and IGF-1 improved the differentiation function of MG63. P195. The influence of simulated weightlessness on the expression of Cbfα1 in MG-63 induced by fluid shear stress S. Zhang, B. Wang, Z. Yang, P. Wang, X.-Q. Sun; Key Laboratory of Aerospace Medicine of National Education Ministry, The Fourth Military Medical University, Xi’an, China Objectives: Exposure to weightlessness during space flight may lead to a state of structural and functional alteration in crewmembers skeleton system, which is manifested most clearly by the loss of bone mass and bone mineral, declines in bone mechanical function and negative calcium balance.

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These alterations were described as osteopenia induced by weightlessness in the field of space life science. Bone cells, particularly osteoblasts and osteocytes, can detect fluid flow as mechanical signal in situ, transduce the physical stimuli into biochemical signals and integrate these signals into appropriate changes in the architecture of bone. This process, termed mechanotransduction, is the essential cellular mechanism for the bone adaptation. The role of mechanical load in the functional regulation of osteoblasts becomes an emphasis in osseous biomechanical researches recently. This study was aim to explore the effect of flow shear stress on the expression of Cbfα1 in human osteosarcoma cells and to survey its functional alteration in simulated weightlessness. Materials and methods: After cultured for 48 h in two different gravitational environments, i.e. 1 G terrestrial gravitational condition and simulated weightlessness condition, human osteosarcoma cells (MG-63) were treated with 0.5 or 1.5 Pa fluid shear stress (FSS) in a flow chamber for 15, 30, 60 min, respectively. The total RNA in cells was isolated. Transcription PCR analysis was made to examine the gene expression of Cbfα1. And the total protein of cells was extracted and the expression of Cbfα1 protein was detected by means of Western Blotting. Results: MG-63 cultured in 1G condition reacted to FSS treatment with an enhanced expression of Cbfα1. Compared with no FSS control group, Cbfα1 mRNA and protein expression increased significantly at 30 and 60 min with the treatment of FSS (P<0.01). And there was remarkable difference on the Cbfα1 mRNA and protein expression between the treatments of 0.5 and 1.5 Pa FSS at 30 or 60 min (P<0.01). As to the osteoblasts cultured in simulated weightlessness by using clinostat, the expression of Cbfα1 was significantly different between 1 G and simulated weightlessness conditions at each test time (P<0.05). Compared with no FSS control group cultured in simulated weightlessness, Cbfα1 mRNA and protein expression increased significantly at 30 and 60 min with the treatment of FSS (P<0.05). The difference on the Cbfα1 mRNA and protein expression between the treatments of 0.5 and 1.5 Pa FSS at 30 or 60 min were not significantly (P>0.05). Conclusion: FSS can significantly increase the gene and protein expression of Cbfα1 in human osteosarcoma cells. And this inducible function of FSS was affected by simulated weightlessness. Supported by NSFC: 30300398. P196. Transplantation of wild type bone marrow stromal cell partially rescues 1α-hydroxylasegene knock-out mice from genetic rachitic Z.-L. Zhang; Radiation Medical and Public School, Soochow University, Suzhou, China

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Objectives: To determine whether the transplantation of bone marrow stromal stem cell can rescue the phenotypes of 1α-hydroxylase gene knock-out [1α(OH)ase−/−] mice, an animal model of I type genetic rachitic. Materials and methods: Bone stromal stem cell from wildtype mice were transplanted into lethal-dose irradiated female 1α(OH)ase−/− mice. Two months after transplantation, survival mice were sacrificed. Serum calcium was determined by an autoanalyzer. Serum 1,25(OH)2D3 was measured by radioimmunoassay. Femurs radiographs were taken using a Faxitron model. Micro-computed tomographic imaging (micro-CT) was conducted in analysis the bone architecture. Results: The results showed that the survival rate of recipients was 70% in 2 months after the transplantation. Serum 1,25(OH)2D3 levels were undetectable in 1α(OH) ase−/− mice and rose to 25% of WT mice in survival transplant recipients. Serum calcium and bone mineralization of survival transplant recipients improved. Micro-CT analysis revealed an increase in trabecular number and connectivity, and decreased trabecular spacing in recipients compared to 1α(OH)ase−/− mice. All of these indices did not reach to the normal level. Conclusion: Transplantation partially rescued phenotype of 1α(OH)ase −/− mice. The experiments confirmed our hypothesis that adult bone marrow harbors pluripotent non-adherent BMSCs. These cells in vivo can migrate into most organ of the body through circulation. Furthermore, under the appropriate microenvironment, they can adhere, proliferate and differentiate into specialized cells of the target tissue, and then function normally in metabolism and in damaged tissue repair. P197. Effect of capacitively coupled electric field on pain release in patients with osteoporotic vertebral fractures L. Idolazzi1, O. Viapiana1, E. Fracassi1, M. Rossini1, D. Gatti1, A. Zambito1, D. Bianchini1, F. de Terlizzi2, S. Adami1; 1Rheumatologic Rehabilitation, University of Verona, Verona, Italy, 2Biophysics Department, IGEA, Carpi, Italy Objectives: The pain in patients with multiple vertebral fractures represents a frequent issue in the elderly population. In the present study we have evaluated the effects of capacitively coupled electric field (Osteospine, IGEA, Italy) on chronic pain in patients with multiple vertebral fractures. Material and methods: Forty-four females older than 60 years, with multiple vertebral fractures and chronic lumbar pain, on treatment with analgesic drugs since at least 6 months have been recruited. The patients were randomised in two groups: Group A (n=21) the patients were treated with capacitively technique with an electric signal already used for fracture healing; it is an electrical signal based on sinusoidal waves of 60 kHz frequency and automatically

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settled amplitude; group B (n=23) the patients were treated with same technique but amplitude of electric signal reduced to 0.5%. All subjects were proposed to follow a treatment of 10 h/day for 60 days; total hours of therapy were memorized in the devices. Patients were followed up to 4 months after conclusion of therapy (total duration of the study: 6 months). Pain was evaluated by VAS and pain specific QUALEFFO questionnaire. Results: Thirty-four patients concluded the study, 15 in group A and 19 in group B. In both groups we observed pain reduction, already at first visit. By the way in group A we observed a significant negative correlation between hours of treatment and pain, evaluated by VAS (r=−0.61 p <0.01), and by specific QUALEFFO (r=−0.75 p<0.01). In group B we didn’t observe any association between hours of treatment and VAS or QUALEFFO (r=−0.09 e r=−0.32 vs VAS and QUALEFFO, respectively, non significant). In group A we observed a significant reduction in the use of analgesic (chi-square test p<0.05) during the third month of follow-up. Conclusions: These data indicates that a particular capacitively coupled electric field (Osteospine) may have positive effects on chronic pain. A significant doseresponse effect has been only in the group whit Osteospine signal and a reduction of use of analgesic drugs in these patients have been observed. The study is still in progress and an increase in the number of patients is foreseen in the next months. P198. Osteoporosis is largely underdiagnosed and undertreated: the 2-year Lausanne survey O. Lamy1, N. Simard1, M.A. Krieg1, O. Borens2, P.F. Leyvraz2; 1Service of Internal Medicine and Osteoporosis Unit, University Hospital Lausanne, Lausanne, Switzerland, 2 Department of Orthopaedics and Traumatology, University Hospital Lausanne, Lausanne, Switzerland Objectives: Osteoporosis is a major health problem. Osteoporosis may be suspected on the basis of several risk factors (age, previous fracture, ...) and may be diagnosed by DEXA (T-score <−2.5 DS). A large proportion of fractures in subjects >50 years are attributable to osteoporosis: hip (80–95%), forearm (70–84%), spine (82–89%). Treatments of osteoporosis are effective and particularly cost-effective in patients at high risk for fracture. The aim of this study was to evaluate the medical management of patient at high risk for osteoporosis before the admission for a fracture. Material and methods: All consecutive urban patients >50 years admitted for a fracture at the emergency room of the University Hospital of Lausanne were interviewed by a study nurse (October 2004–September 2006). Patients with a fracture of the face/skull, or related to traffic accident were excluded. A simple questionnaire included age, sex, previous

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clinical fracture, previous DEXA, previous treatment for osteoporosis, was administered. The patient’s GP was asked about the DEXA performed. Results: A total of 1,314 fractures occurred in 1,155 patients (men 28%; women 72%; mean age: 74.5±12.6). Nine hundred four (78%) patients were hospitalised (length of hospital stay: 12±8 days) and 514/904 (57%) were transferred in a rehabilitation unit. Sixty percent of patients have had a previous fracture in adulthood. Eighty-seven percent of fractures were due to low energy traumatism. Sites of fractures: hip 33%; humerus 16%; forearm 14%; vertebral 11%; ankle 10%; shin/fibula 5%; pelvis 5%; costal 4%. The medical management before this episode of fracture was as follow: DEXA performed 7.8% (men 0.3%; women 10.7%); calcium and/or vitamin D 28.8% (men 5.6%; women 37.7%); bisphophonates 7.0% (men 1.0%; women 9.3%); hormonal therapies 2.6%. Conclusions: The medical cost of fracture is high, particularly when we consider the length of hospital and rehabilitation stay. Very few patients at high risk for fracture (age, previous fracture) have had a clinical investigation and/or medical management for osteoporosis. Implementation of strategies to increase the identification and treatment of patients at high risk is needed. P199. Comparison of risk factors in postmenopausal patients with and without nonvertebral fractures Ü. Akarırmak, M. Sarıdoğan, M.-A. Terzibasoğlu, N. Bozok, Y. Terzi; Physical Medicine and Rehabilitation Department, Istanbul University Cerrahpaşa Medical Faculty, Istanbul, Turkey Objective: To compare risk factors in postmenopausal osteoporotic patients with and without nonvertebral fractures. Materials and methods: A total of 313 patients, 158 patients with nonvertebral fracture (Group1) and 155 patients without fracture (Group2) were screened retrospectively. Family history of osteoporotic fracture, age at menopause, mean age, chronic disease, bone toxic drug use were evaluated. In group1, age at time of fracture and localization were determined. DXA Tscores were measured at the lumbar spine (L1–L4) and proximal femur (neck and total). Independent t-test was used for statistical analysis. Results: Mean age was 63.1±11.9 in group1 and 60.8± 10.5 in group2. Family fracture was positive in 23% group1 and 21% in group2. Mean age at menopause was 46.4±5.7 in group1 and 45.4±5.6 in group2. Chronic disease was present in 36% of group1, 41% of group2. Use of bone toxic agents was negative in 83% of group1, 73% in group2. T-score: L1–L4 −2.4±1.18, neck −2.4±0.9, total hip −1.9±0.8 in group1. T-score: L1–L4 −2.29±1.2, neck −2.2±1.0, total hip −1.6±1.09 in group1. Hip fracture was

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reported in 8%, distal forearm fracture in 41% and other types of fractures in 60% of the patients. Conclusion: There was no significant difference between groups with respect to mean age, age at menopause and family fracture, respectively (p>0.05). T-scores at femoral neck and total hip in group1 were significantly lower (p<0.05). There was no difference between T-scores at L1–L4. Therefore, in nonvertebral fractures it is recommendable to take into account primarily the results of femoral densitometry. There was no correlation between nonvertebral fractures and age. Localization of the fracture was wrist in 41% which occur in younger ages. This may explain lack of correlation between age and nonvertebral fracture. There is need for prospective studies on this subject for determination of risk factors for nonvertebral fractures. P200. Modulation of ibandronate cytotoxicity by calcium F. Journé1, N. Kheddoumi1, C. Chaboteaux1, G. Laurent2, J.J. Body1; 1Laboratory of Endocrinology, Institut Bordet, Brussels, Belgium, 2Laboratory of Histology, University of Mons-Hainaut, Mons, Belgium Bisphosphonates are standard therapy to reduce breast cancerinduced skeletal complications. Although their therapeutic effects mainly result from an inhibition of osteoclastic bone resorption, in vitro data indicate that they may also act directly on breast cancer cells, inhibiting proliferation and inducing apoptosis. In the present study, we examined the effects of an increase in extracellular calcium levels on the cytotoxic activity of ibandronate in MDA-MB-231 (ER-) and MCF-7 (ER+) breast cancer cell lines. Cancer cells were cultured in RPMI 1640 containing 5% FCS and supplemented with CaCl2 to achieve Ca++ concentrations from 0.6 to 2.0 mM. In presence of 0.6 mM Ca++, 30 μM ibandronate had no effect on MDA-MB-231 cells growth, while it slightly inhibited MCF-7 cells growth by 13.6 ± 6.6%. By contrast, in presence of 2.0 mM Ca++, 30 μM ibandronate dramatically inhibited cancer cells survival by 55.5±7.8% and 76.1± 4.6% (p < 0.05) in MDA-MB-231 and MCF-7 cells, respectively. An increase in Ca++ concentrations from 0.6 to 1.6 mM decreased the IC50 values of ibandronate from 100 to 30 μM in MDA-MB-231 cells and from 60 to 10 μM in MCF-7 cells. Ca++ chelation by EGTA at 0.5 mM, a concentration which did not affect cell growth, significantly reduced the growth inhibitory effects induced by 30 μM ibandronate in culture medium containing 1.6 mM Ca++. In addition, increasing Ca++ concentration enhanced ibandronate-induced inhibition of protein prenylation. Indeed, 10 μM ibandronate was sufficient to produce a detectable inhibition of Rap1A prenylation in

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presence of 2.0 mM Ca++, while 100 μM ibandronate was required to achieve a similar effect in the presence of 0.6 mM Ca++. Altogether, our data suggest that extracellular calcium, at physiologically relevant concentrations, markedly increases the intracellular inhibitory activities of bisphosphonates. Thus, Ca++ released during the process of bone destruction could enhance the antitumor effects of bisphosphonates and contribute to their therapeutic activity. Whether this enhancing effect of Ca++ on bisphosphonate activity is also true for osteoclasts in osteoporotic bone needs to be investigated. P201. Agreement between self-reported and diagnosed osteoarthritis R. Lucas1, N. Cordoeiro2, RA. Santos3, I. Ramos2, H. Barros1; 1Department of Hygiene and Epidemiology, Porto Medical School, Porto, Portugal, 2Department of Radiology, São João Hospital, Porto, Portugal, 3Hospital Militar Principal, Lisboa, Portugal Background: Clinical and radiographic evaluations allow for the assessment of the validity of self-reported osteoarthritis in prevalence estimations. Objectives: To describe self-reported and diagnosed prevalence of knee, hip and hand osteoarthritis in the population of Porto, and to assess the agreement between both methods. Materials and methods: During the ongoing follow-up of a cohort of Portuguese adults, 231 participants were evaluated [43.4% women, mean (sd) age was 64.6 (9.5) years]. Evaluation included the collection of sociodemographic and clinical variables. Participants were inquired about history of knee, hand and hip osteoarthritis. Additionally, each participant answered questions about musculoskeletal symptoms and was selected for rheumatologic evaluation if one or more of the following criteria were met: (1) medical appointment with exams or medication prescribed in the previous year; (2) three or more pain episodes in the previous year with a perceived pain intensity equal to or over 60 mm in a visual analogue scale (VAS); (3) one or more pain episodes lasting over 1 week in the previous 6 months; (4) one or more pain episodes in the previous month with a perceived pain intensity equal to or over 60 mm in a VAS. Rheumatological evaluation comprised clinical and radiographic examination. Radiographic changes were considered present if their severity was scored equal to or over two in the Kellgren–Lawrence scale. Results: Prevalence of osteoarthritis and agreement between methods are shown in table. Participants for whom both methods agreed were younger (knee: 63.7 vs. 68.1 years, p= 0.012; hip: 63.9 vs. 70.2, p=0012; hand: 64.0 vs. 67.3; p= 0.043) and more educated (8.1 vs. 6.4 schooling years;

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p=0.035; hip: 8.0 vs. 5.6, p=0.011; hand: 8.1 vs. 6.0, p= 0.019). Agreement in hand osteoarthritis was higher in men (92.9 vs. 81.8%, p=0.015). Positive diagnosis Knee

Hip

Hand

women, no significant associations were found between corrected aLM and the functional scores. Conclusions: Data shows that aLM assessed after hip fracture is significantly associated with the functional outcome in men, but not in women. Sex-specific changes in muscle quality may explain the results in our sample of elderly patients. (1) Am J Phys Med Rehabil (2006) 85: 209–215, 2006

Self-reported osteoarthritis 16 (44.4%) 2 (40.0%) 15 (41.7%) No self-reported osteoarthritis 19 (9.8%) 16 (7.2%) 9 (4.7%) Agreement k=0.35, k=0.14, k=0.43, p<0.001 p=0.004 p<0.001

Conclusion: The asymmetry in agreement between different education classes suggests that in lower socioeconomic strata osteoarthritis is misdiagnosed. P202. Appendicular lean mass and functional outcome in hip-fracture men M. Di Monaco, F. Vallero, R. Tappero, A. Cavanna; Osteoporosis Research Center, Presidio Sanitario San Camillo, Torino, Italy Objectives: We have recently shown that appendicular lean mass (aLM) assessed by dual-energy X-ray absorptiometry (DXA) is not significantly associated with the functional outcome in hip-fracture women(1), but no studies focused on the same issue in hip-fracture men. Our aim was to investigate the association between aLM and functional outcome in a sample of men with hip fracture. Materials and methods: We investigated 27 of 33 hipfracture men admitted consecutively to our rehabilitation hospital. For each patient we studied two control women, matched for age and fracture type. Lean mass (LM) was assessed by DXA, 21.9±7.5 (mean ± SD) days after fracture occurrence in the 27 men (22.8±7.2 days in the 54 control women). We calculated aLM as the sum of LM in arms and legs. Because metal implants (prostheses and nails) affect the regional assessment of body composition, aLM was corrected by substituting LM in unfractured leg for LM in fractured leg: corrected aLM = (LM in unfractured leg ×2) + LM in arms. Functional recovery was assessed by using Barthel index scores. Barthel index efficiency was calculated as the change in the Barthel index score after rehabilitation divided by the length of stay in hospital (days). Results: After adjustment for age, height, fat mass, Barthel index scores at admission, and time between fracture occurrence and DXA assessment, aLM was significantly associated with Barthel index scores after rehabilitation (r=0.480; p=0.013) and Barthel index efficiency (r=0.633; p=0.001) in the 27 men. Conversely, in the 54 control

P203. Systemic exposure to inorganic sulfates after oral administration of glucosamine as hydrochloride alone or in combination with chondroitin sulfate or as crystalline glucosamin sulfate in man S. Persiani, D. Paganini, L. Lavizzari, R. Chistè, L.C. Rovati; Rottapharm, Monza, Italy Objective: Two recent randomised, controlled trials assessed the effects of glucosamine on knee osteoarthritis symptoms: the GUIDE study confirmed the efficacy of prescription glucosamine sulfate 1,500 mg once-a-day, but the NIHsponsored GAIT failed to show any benefit of nutraceutical glucosamine hydrochloride 500 mg t.i.d. These results may depend on glucosamine peak plasma levels that are much lower with the GAIT formulation. However, it has been suggested that sulfates may also contribute to the effects of glucosamine. Actually, the combination of glucosamine hydrochloride and chondroitin sulfate was effective in the subgroup of patients with moderate-to-severe pain. The present study assessed preliminarily, the systemic exposure to sulfates after administration of glucosamine sulfate or glucosamine hydrochloride alone or in combination with chondroitin sulfate, by determining the urinary excretion of inorganic sulfates. Materials and methods: Two males and two females volunteers received for five consecutive days either crystalline glucosamine sulfate 1,500 mg once-a-day (CGS), or the combination of glucosamine hydrochloride 500 mg and chondroitin sulfate 400 mg t.i.d. (GHCL + CS) in a randomised cross-over fashion. In a parallel study arm, two males and two females volunteers received glucosamine hydrochloride 500 mg t.i.d. (GHCL) The urinary excretion of inorganic sulfate was determined over 24 h at baseline and during the last day of administration by ion exchange chromatography, with a LOQ of 0.01 mM. Results: The mean (SD) baseline urinary excretion of sulfate in the cross-over study was 12.9±4.5 mM/24 h. After both CGS and GHCL + CS, urinary sulfate excretion was higher in all subjects averaging 17.9±5.2 mM/24 h and 18.4± 3.8 mM/24 h, respectively. The mean increase was 5.0± 1.8 mM/24 h and 5.6±2.5 mM/24 h, respectively, i.e. similar between groups and corresponding to 40–50% over baseline.

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As expected, GHCL induced no or negligible changes in sulfate excretion, reflecting only physiological fluctuations and averaging 2.0±2.2 mM/24 h, or 13% over baseline. Conclusions: Glucosamine hydrochloride provides no systemic exposure to inorganic sulfate. Conversely, the combination of glucosamine hydrochloride with chondroitin sulfate and the standard glucosamine sulfate formulation produce similar exposure to inorganic sulfates, possibly explaining the contradictory findings within GAIT and in comparison with GUIDE. P204. A prospective study of sex steroids, sex hormone-binding globulin and non-vertebral fractures in women and men: the Tromsø study Å. Bjørnerem1, L.A. Ahmed1, R.M. Joakimsen2, G.K.R. Berntsen1, V. Fønnebø1, L. Jørgensen1, P. Øian2, E. Seeman3, B. Straume1; 1Institutes of Community Medicine and Clinical Medicine, University of Tromsø, Tromsø, Norway, 2 Departments of Medicine and Obstetrics/ Gynecology, University Hospital of North Norway, Tromsø, Norway - Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway, 3Department of Medicine and Endocrinology, Austin Hospital, University of Melbourne, Melbourne, Australia Objectives: As bone fragility is partly the result of sex hormone dependent bone loss, we sought to determine whether measurements of circulating sex steroids or sex hormone-binding globulin (SHBG), a determinant of the free hormonal fraction, predict non-vertebral fractures in women and men. Materials and methods: Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels and SHBG were measured in 1,386 postmenopausal women and 1,364 men aged 50–84 years at baseline in the Tromsø Study 1994–95. Non-vertebral fractures were documented between January 1994 and February 2005. Results: During 8.4 years (range 0.01–10.4) and 23,034 person-years follow-up, 281 (20.3%) women and 105 (7.7%) men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD, higher SHBG, but sex steroids were no lower than participants remaining fracture free. Each standard deviation (SD) increase in SHBG increased non-vertebral fracture risk by about 20% in women (HR 1.17; 95% CI 1.03– 1.33) and men (HR 1.27; 95% CI 1.03–1.55). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95% CI 0.95–1.24, P=0.21) or men (HR 1.22; 95% CI 1.00–1.50, P=0.06). Each SD decrease in BMD increased fracture risk by about 40% in women (HR 1.36; 95% CI 1.19–1.56) and men (HR 1.41; 95% CI 1.15– 1.73). Fracture rates were highest in participants with SHBG

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in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1,000 person-years in women and men, respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone, as the ROC curves were similar. No association between sex steroids and fracture risk was detected. Fig. The incidences of non-vertebral fractures per 1,000 person-years in tertiles of sex hormone-binding globulin (SHBG) and bone mineral density (BMD) in women and men. The Tromsø Study 1994–95. The SHBG tertiles in women: <57, 57–84 and >84 nmol/l, in men: <43, 43–58 and >58 nmol/l. The BMD tertiles in women: <0.362, 0.362–0.423, >0.423 g/cm2, in men: <0.509, 0.509–0.565 and >0.565 g/cm2. Women

Conclusions: Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.

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P205. Total joint replacement after glucosamine sulfate treatment of knee osteoarthritis: results from a 8-year prospective cohort O. Bruyère1, K. Pavelka2, L.C. Rovati3, J. Gatterová2, G. Giacovelli3, M. Olejarová2, R. Deroisy1, J.Y. Reginster1; 1 Bone and Cartilage Metabolism Research Unit, University of Liege, Liege, Belgium, 2Institute of Rheumatology, Prague, Czech Republic, 3Clinical Pharmacology Department, Rotta Research Laboratorium-Rottapharm, Monza, Italy Objectives: To assess the incidence of total joint replacement during the long-term follow-up of patients with knee osteoarthritis formerly receiving treatment with glucosamine sulfate or placebo. Materials and methods: Knee osteoarthritis patients participating in two previous randomised, placebocontrolled, double-blind, 3-year trials of glucosamine sulfate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement. Results: Out of 340 patients with at least 12 months of treatment, 275 (i.e. 81%) could be retrieved and interviewed per the present evaluation: 131 formerly on placebo and 144 on glucosamine sulfate. There were no differences in baseline disease characterstics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation. Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulfate, 9/144 (6.3%) (P=0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% CI: 0.20 to 0.92), i.e. a 57% decrease compared with placebo. The Kaplan Meier/Log Rank test survival analysis confirmed a significantly decreased (P=0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulfate. Radiographic joint-space narrowing of more than 0.5 mm during the 3-year trial was a good predictor of joint replacement during the follow-up. Finally, a subgroup pharmacoeconomic analysis suggested that patients formerly on glucosamine sulfate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up. Conclusions: Treatment of knee osteoarthritis with glucosamine sulfate for at least 12 months and up to 3 years may prevent total joint replacement in an average follow-up of 5 years after drug discontinuation.

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P206. Prevalence of vertebral fracture among postmenopausal women in southern Sri Lanka S. Lekamwasam1, P. Kolombage2, J. Lenora1; 1Center for Metabolic Bone Diseases, Department of Medicine, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka, 2 Department of Radiology, Teaching Hospital, Karapitiya, Galle, Sri Lanka Objectives: Prevalence of vertebral fracture (VF) among postmenopausal women in South Asia is not well known. This study was done to estimate the prevalence of VF among postmenopausal women in southern Sri Lanka. Materials and methods: Radiographs of thoraco-lumbar spine from T4 to L4 in lateral projection were taken in the standard manner in 188 community dwelling healthy postmenopausal women who participated in a community osteoporosis survey conducted in southern Sri Lanka. These women were free of diseases or had not taken drugs which can affect BMD. They had lumber spine (L2–L4) and hip BMD estimated using Noland Eclipse scanner. VF was diagnosed semi-quantitatively using the method described by Genant et al. Results: Eight radiographs had poor clarity and were excluded. Age of the women ranged from 46 to 96 with mean (SD) of 64.5 (8.7) years. Mean (SD) spine, femoral neck and trochanteric BMD were 0.723 (0.168), 0.656 (0.134) and 0.538 (0.111) g/cm2, respectively. Eighteen (10%) women were detected to have either one (n=13) or more (n=5) VF. Mean (SD) spine BMDs of women with and without VF were 0.567 (0.097) and 0.733 (0.167), respectively (P<0.001). The risk of VF for a 1SD reduction of spine BMD was 2.9 (95% CI=1.4 to 5.9, p=0.003) while I SD reduction of femoral neck BMD was associated with a relative risk of 2.5 (95% CI=1.3 to 5.0, p=0.008). Conclusion: Despite low BMD, VFs were less common among the women studied in this study. BMDs both in spine and femoral neck were strong and significant predictors of VFs. P207. Homocystein serum levels in hemodialysis patients with normal PTH status M. Ioannou1, E. Gigas1, P. Ioannou2, N. Pekopoulos1; 1 Department of Orthopaedic Surgery, General Hospital of Chalkis, Euboea, Greece, 2Department of Internal Medicine, SRH-Waldklinikum, Gera, Germany Objectives: Hyperhomocysteinemia may contribute to the development of osteoporosis. The aim of our study was to examine the association of Hcy plasma levels with bone mineral density in a selected group of hemodialysis patients with normal PTH serum levels.

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Materials and methods: From 154 hemodialysis patients we selected 96 (53 males, 43 females, mean age 64.7 years) who had a normal PTH serum level (100–500 pg/dl). Plasma Hcy was measured in these 96 patients and was correlated with bone mineral density findings which were measured in all patients by L1–L4 DEXA. Results: A/From the 53 males: 24 (45.2%) had a normal Hcy serum level (5.9–16.0) and four of them (16%) had a T-score <−2,5 SD. The remaining 29 males (54.8%) had an increased Hcy plasma level (>16) and 13 of them (45%) had a T score <−2.5 SD. B/From the 43 females: 25 females (58%) had a normal Hcy plasma level and nine (36%) had a diagnosis of osteoporosis while the remaining 18 females (42%) had increased Hcy levels and nine (50%) of them a T score <2.5 SD. Conclusion: In this selected group of hemodialysis patients with normal PTH level (suggesting normal bone turnover) high Hcy serum levels seems to associate with low bone mineral density.

effects on both bone resorption and osteoclast apoptosis were almost completely reversed with neutralizing antibody against M-CSF suggesting that M-CSF originating from MM cells might play a critical role in the process of bone destruction during MM. Clinical relevance of these in vitro experiments was established by demonstrating that MM patients exhibited higher serum levels of M-CSF compared to age-matched controls and that serum levels of M-CSF positively correlated with the presence of bone lesions. Finally, we demonstrated that imatinib mesylate, a tyrosine kinase inhibitor known to targets the M-CSF receptor, prevented both the CM effects on osteoclast apoptosis and bone resorption. Conclusion: Based on these findings, we conclude that: M-CSF produced by MM cells, by increasing at local sites osteoclast survival, greatly contributes to MM bone disease. Serum levels of M-CSF may have an interest as a prognostic factor in MM. Therapeutics targeting M-CSF such as imatinib may be of clinical value in treating MM bone disease.

P208. Macrophage colony stimulating factor originating from multiple myeloma cells suppresses mature osteoclasts apoptosis, stimulates bone resorption D.I. El Hajj1, M. Gressier1, V. Salle2, R. Mentaverri1, M. Gallet1, J.P. Ducroix2, M. Brazier1, S. Kamel1; 1Laboratoire de Biologie et Pharmacie Clinique, UPRES-EA 2086 et INSERM ERI-12, Faculté de Pharmacie, Université de Picardie Jules-Verne, Amiens, France, 2Service de Médecine interne, CHU Amiens, Amiens, France

P209. Alendronate decrease the expression of IL1-beta, TNF-alpha and improve the OPG/RANKL in synovitis tissue at rheumatoid arthritis R. Yatsyshyn, Y. Neyko, N. Yatsyshyn; Department of Internal Diseases, Ivano-Frankivsk State Medical University, Ivano-Frankivsk, Ukraine

Objectives: Multiple myeloma (MM) is characterized by devastating bone destruction due in part, to an increased number of active osteoclasts causing increased bone resorption. So far, the mechanisms of enhanced number of osteoclasts in MM are not yet completely understood. In order to clarify the mechanism of development of MM bone disease, we attempted to identify MM-derived factors responsible for enhancement of osteoclasts survival. Materials and methods: In this study, we collected conditioned media (CM) prepared from two MM cell lines (RPMI 8226 and U-266) as well as from primary MM cells purified from heparinized bone marrow drawn from two patients with MM under written informed consent. Effect of MM conditioned media on bone resorption was assessed using rabbit mature osteoclasts. Results: We demonstrated that CM from MM cell lines as well as from primary plasma cells exerted a potent inhibitory effect on mature osteoclast apoptosis that contributed to increase the number of active osteoclasts and bone resorption. Among the cytokines known to increase osteoclast survival, only macrophage colony stimulating factor (M-CSF) was found to be constitutively secreted by MM cells. The CM

Background: The erosion of local bone at rheumatoid arthritis (RA) is driven by pro-inflammatory cytokines and RANKL released from the inflamed synovium, the latter representing the major activator of osteoclast function. The catabolic state of periarticular and articular bone metabolism is reflected by a decreased ratio of OPG/ RANKL expression. Controversy exists, whether in therapy of RA, bisphosphonates (BP) have the properties to ameliorate bone catabolism and synovial inflammation. Objectives: To investigate the effects of an amino-BP (alendronate, AL) on gene expression and protein levels of OPG/RANKL, IL1-beta and TNF-alpha in RA articular synovitis tissue ex vivo. Materials and methods: The in vitro effects of AL were compared in carpal articulosynovitis tissue (CAST) from n=12 patients with mutilating RA. CAST was obtained during partial or complete carpal arthrodesis. RA synovitis and periarticular osteoporosis was confirmed by means of histology and X-ray, respectively. Ex vivo, the protein detection of OPG/RANKL, IL1-beta and TNF-alpha was performed using Western blot. Within the incubated tissue, respectively, the target gene expression and the corresponding protein level was measured by means of real time RT-PCR and ELISA.

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Results: Western blot confirmed the presence of OPG/ RANKL, IL1-beta and TNF-alpha protein in the synovium of all investigated carpal joints. Compared to the synovial expression in vivo, in the untreated controls the relative expression (NR) was increased for OPG (+3.5-fold), IL1beta (+4.6-fold) and TNF-alpha (+0.4-fold) and decreased for RANKL (−0.6-fold). While increased and decreased expression of OPG and RANKL, respectively, is most likely due to the absence of the inflammatory synovial fluid ex vivo, the induction of TNF-alpha and IL1-beta might reflect their pronounced sensitivity for cell alteration due to the tissue preparation and the incubation procedure itself. Furthermore, BP sign. (P<0.05) inhibited the expression of TNF-alpha (9.1%) and IL1-beta (59.6%). ELISA for OPG, TNF-alpha and IL1-beta released from synovitis tissue showed corresponding results, while RANKL was not detectable. Conclusion: In concentrations achievable in serum under a continuous, oral anti-osteoporotic therapy, BP sign. improved OPG/RANKL ratio and exhibited anti-inflammatory properties in vitro. The data seems to contradict the established concept, that rather high concentrations of BP are necessary to exert antiinflammatory effects in synovitis tissue. P210. Age-dependent effects of combined therapy on bone mineral density of elderly women with osteoporosis E. Karzewnik1, E. Sewerynek2; 1Outpatient Clinic of Endocrinology, Piotrkow Trybunalski, Poland, 2Department of Bone Metabolism, Medical University of Lodz, Lodz, Poland—Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland Objectives: Despite the findings that hormone replacement therapy (HRT) is associated with an increased risk of breast cancer, endometrium cancer or cardiovascular disease, there are still women, using this form of treatment. Bisphosphonates alone, as well as HRT alone, are effective treatments for postmenopausal osteoporosis but the effect of multidrug treatment is not well recognised. 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 in three different periods of live. Materials and methods: A total of 112 women with osteoporosis, who had been HRT naive for 1 year were randomised to receive 1 mg of 17b-estradiol plus 0.5 mg of 19-norethisterone acetate daily, per os (n=62), or in combination with ALE in a dose 10 mg/d (HRT+ALE; n=50), for 1 year. Changes in bone mineral density of the lumbar spine were measured, using QCT at baseline and after 1 year of treatment. Each group was divided into three age-dependent subgroups (A=50–60; B=61–70: C=over 70 years old).

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Results: After 1 year of treatment, increasing spinal BMDs were found in all the examined groups. Compared with HRT alone, ALE+HRT produced significantly higher increases in BMD of the lumbar spine only in women between 50 and 60. Addition of ALE to ongoing HRT therapy was well tolerated without any gastrointestinal side effects. Conclusion: The combination of HRT and ALE in elderly women with osteoporosis, did offer an extra gain of BMD vs. HRT therapy alone only during the first 10 years after menopause. P211. Economical aspects of arthroplasty in osteoarthritis treatment D. Orlic, Z. Beck, M. Bergovec, D. Bitunjac, E. Biuk, T. Crncevic, M. Franic, H. Jurdana, F. Klaic, N. Korkut, D. Matek, B. Novosel, D. Tripalo, Z. Zubak; Croatian Orthopaedic Society, Croatian Medical Association, Department of Orthopaedic Surgery, Clinical Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia Objectives: Nowadays, osteoarthritis as the major factor that causes disability of bone and joint system is recognized as an important public health problem. Also, primary and secondary osteoarthritis are the most common indication for hip and knee arthroplasty, especially in the elderly population. The Republic of Croatia has population of 4,437,460 inhabitants, 14.5% being older than 65. It is estimated that in 2030 there will be 24% of older population with osteoarthritis. In Croatia, arthroplasty costs are paid through public health system. Simulation of older population increase showed higher expenses in arthroplasty in Croatia public health system what can be additional burdening for economical situation for a small country. Materials and methods: Fourteen orthopaedic institutions and departments from all over Republic of Croatia are included so far in Croatian Arthroplasty Register. In 2005, there was in total 15,082 operative procedures of bone and joint system; 3,934 of them were arthroplasty procedures (2,945 hip and 989 knee replacement). Osteoarthritis was the most common diagnose for arthroplasty: 2,562 (87%) in hip and 969 (98%) in knee arthroplasty. Results: The amount of 14.8 million euros is the cost of using modern endoprostheses in yearly budgets of all hospitals, 10.5 million euros are for hip, and 4.3 million euros for knee endoprostheses. It is estimated that in the year 2030 the cost will rise to the amount of 22 million euros. Conclusion: Arthroplasty, as a part of modern orthopaedic surgery, is the major factor in life quality improvement in patients with osteoarthritis. Arthroplasty is burdened with several problems, one of them beingfinancial. Improvements in operative techniques and better implants make arthroplasty better surgical procedure and hospital disbursements are

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lower. Still, in spite of that most of orthopedics surgeons might have tended to concentrate on surgical treatment rather than medications for prevention, efforts should be made in improvements in quality of osteoarthritic bones and joints for a longer time with medications and physical activity, delaying arthroplasty as long as possible. P212. Pregnancy-associated bone loss in young women M. Zodelava 1 , A. Kistauri 1 , N. Tskhovrebashvili 2 , T. Mamaladze2, S. Matitashvili3; 1Department of Internal Medicine, Tbilisi State Medical University, Tbilisi, Georgia, 2Department of Osteoporosis and Diabetic Foot, Clinic of Aesthetic, Reconstructive and Plastic Surgery, Caraps Medline Clinic, Tbilisi, Georgia, 3Department of Ultrasonography, Clinic of Aesthetic, Reconstructive and Plastic Surgery, Caraps Medline Clinic, Tbilisi, Georgia Objectives: Influence pregnancy on the bone system in young women is especially important as they are going through the period of accelerant growth and pregnancy at the same time risk developing decrease of BMD which can cause osteopenia and osteoporosis. The goal of present study was to research the BMD in young pregnant women. Materials and methods: The study was carried out on the pregnant women aged from 16 to 20 years (n=92). The pregnant were divided in two groups: I—pregnancy of 20 weeks and II—from 20 to 40 weeks. This groups were compared with age-matched control group (n=24). BMD was measured at three sites (distal radius, midshaft tibia and proximal phalanx) using the ultrasound bone sonometer (Sunlight Omnisense). Results were interpreted in accordance with criteria adopted by the WHO by T-score. Results: In the group of young pregnant women the mean BMD was decreased in 72% of patients (n=67), reflecting different degrees of osteopenia from moderate to severe. In the I group T-score was: distal radius −1.5±0.06, midshaft tibia −1.6±0.06; proximal phalanx −1.7±0.08; in the II group T-score was: −1.8±0.08; −1.9±0.06; −1.9±0.07, respectively. In some cases (n=6) there was found the signs of osteoporosis (mainly in the group from 20 to 40 weeks of pregnancy). In control group decrease of BMD was not so significant and reflected osteopenia in 20% of patients (n=5). T-score was −1.4±0.07; −1.5±0.06; −1.3± 0.06, respectively. Discussion and conclusions: In both groups of young pregnant women we have found decrease of BMD, but in the group with pregnancy from 20 to 40 weeks this decrease was more severe and more strongly marked in comparison with the patients of control group. It is possible to say with certainty that BMD monitoring during the pregnancy will give a possibility to avoid the problem connected with calcium deficiency of both mother and fetus. Young pregnant

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may need to increase the recommended calcium dose to counterbalance the bone loss. Prevention of osteopenic complications during the pregnancy is a fairly effective approach for future post-menopause osteoporosis global prevention. P213. Prevalence of fractures in children with chronic viral hepatitis and liver fibrosis J. Konstantynowicz1, D.M. Lebensztejn2, E. Skiba2, M.E. Sobaniec-Lotowska 3 , J. Piotrowska-Jastrzebska 1 , M. Kaczmarski2; 1Department of Pediatrics and Auxology, Medical University of Bialystok, Bialystok, Poland, 2Third Department of Pediatrics, Medical University of Bialystok, Bialystok, Poland, 3Department of Clinical Pathomorphology, Medical University of Bialystok, Bialystok, Poland Objectives: Chronic liver disease in adults is a risk factor of osteoporosis but little is known about bone mass and risk of fractures in children with chronic non cholestatic liver disease and liver fibrosis. The aim of this cross-sectional study was to investigate associations between the severity of liver fibrosis, bone mineral density and fractures during growth. Materials and methods: History of fractures (all fractures documented by X-ray examination), anthropometry, Tanner stages and bone mass were examined in 39 Caucasian children (26 boys, 13 girls) aged 7.1–18 years (mean 11.9± 3.1) with chronic hepatitis B and liver fibrosis evidenced by liver biopsy. Severity of liver fibrosis was based on histological classification according to the method of Batts and Ludwig (mild: 1–2 scores, advanced: 3 scores) and Ishak (1–3 and 4–5 scores, respectively). Bone mineral density (BMD) and content (BMC) in the total body and lumbar spine, and area of vertebrae L2–L4 were determined using dual energy X-ray absorptiometry (DXA). Results: Eight subjects (4 girls, 4 boys; 20% of the sample) had low BMD in the total body and lumbar spine region (Zscore below minus 2.0 SD). No association was found between BMC, BMD, vertebral area and the severity of liver fibrosis. Of all studied children, 10 boys (38% of boys) and one girl reported 21 fractures (forearm, tibia, wrist, ankle, humerus). Fractures were not associated either with lower BMD/BMC or with the scores of liver fibrosis. No differences in height, weight and BMI were found between boys with and without fractures. Conclusions: Deficits in BMD of children and adolescents with chronic viral hepatitis B are common, however, not associated with the severity of liver fibrosis. This study suggests that boys with liver fibrosis may have an increased fracture risk, independent of their BMDs, although the reason for bone fragility in these subjects is not clear. Whether the risk associated with chronic viral hepatitis is sustained in adulthood remains to be established.

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P214. RANKL inhibition with denosumab increases bone mineral density in patients with rheumatoid arthritis R.K. Dore1, E. Hurd2, W. Palmer3, W. Shergy4, L. Zhou5, R. Newmark5, W. Tsuji5; 1Robin K. Dore, MD, Inc., Anaheim, California, USA, 2Arthritis Centers of Texas, Dallas, Texas, USA, 3Westroads Medical Group, Omaha, Nebraska, USA, 4 Rheumatology Associates of North Alabama, Huntsville, Alabama, USA, 5Amgen Inc., Thousand Oaks, CA, USA

Table. Least squares mean ± SE percent change from baseline in BMD at 6 months.

Rheumatoid arthritis (RA) is characterized by articular and periarticular bone erosions and systemic bone loss. RANKL is a key factor implicated in bone destruction associated with many diseases, including RA. Denosumab, a fully human monoclonal antibody, inhibits RANKL and increases bone mineral density (BMD) in postmenopausal women with low bone mass. As part of a study to determine the effects of denosumab on bone erosion in patients with RA, the effect of denosumab on systemic bone loss was examined. Patients with mild to moderately active RA for at least 6 months with manifest erosions and maintained on methotrexate (MTX) were randomly assigned to treatment with subcutaneous injections of placebo or denosumab (60 or 180 mg) every 6 months. BMD was measured by dualenergy x-ray absorptiometry (DXA) at baseline, 1 month, and 6 months. Adverse events were monitored throughout the study. A total of 227 patients were enrolled in the study (78 placebo, 73 denosumab 60 mg, 76 denosumab 180 mg). Mean ± SD lumbar spine BMD T-score at baseline was −0.45±1.60. Approximately one-fifth of patients used bisphosphonates during the study, and use was balanced between groups (25% placebo, 18% denosumab 60 mg, 18% denosumab 180 mg). An additional 5% of patients in each group had previously used bisphosphonates. At 6 months, denosumab significantly increased BMD at the lumbar spine, total hip, and trochanter compared with placebo (Table). Positive effects on femoral neck BMD at 6 months were also observed in both denosumab dose groups compared with placebo. Adverse events occurred with similar frequency among the treatment groups. Flare of RA was the most common adverse event.

*P<0.01 versus placebo based on an ANCOVA model adjusting for treatment, baseline steroid use, prior use of biologics, and baseline BMD value. **P=0.052 and 0.075 versus placebo for the 60 and 180mg groups, respectively, based on an ANCOVA model adjusting for treatment, baseline steroid use, prior use of biologics, and baseline BMD value.

Skeletal site

Placebo (n=68)

Denosumab 60 mg (n=69)

Denosumab 180 mg (n=68)

Lumbar spine Total hip Femoral neck Trochanter

0.87±0.41 0.04±0.26 −0.18±0.40 0.07±0.39

2.35±0.41* 1.02±0.26* 0.84±0.41** 1.67±0.39*

2.64±0.42* 1.21±0.26* 0.75±0.40** 1.70±0.39*

In summary, denosumab treatment increased BMD in patients with RA and showed similar frequency and severity of adverse events across treatment groups. P215. The risk of new nearby vertebral compression fractures after Balloon Kyphoplasty P. Stavros, A. Richter, M. Krammer; Spine Surgery Department, Asklepios Klinik Lindenlohe, Schwandorf, Germany Objectives: Balloon kyphoplasty (BCP) as a minimally invasive surgical procedure is well established in the treatment of the Vertebral Compression Fractures (VCF) reducing the pain and restoring the sagittal profile of the affected spinal segments. A major concern to many physicians constitutes the possibility of inducing new VCFs in the nearby segments. With our clinical series we try to evaluate the risk of consequent nearby osteoporotic fractures after a BCP. Materials and methods: To evaluate the influence of BCP in the nearby segment VCFs, a retrospective study of consecutive BCP patients treated from a single surgeon and analysis of the epidemiological and biomechanical data of the literature regarding the influence of the cement augmentation on the transfer of the loads through the spine, were performed. 176 VCFs were treated through BCP on 127 osteoporotic patients (mean age, 79 years—24% male and 76% female). Outcome measures: Patient-reported Visual Analogic Scale pain ratings were obtained. Perioperative and intraoperative complications as cement extravasation were recorded. Ante-

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rior and midline and posterior vertebral height were assessed through standing, lateral radiographs preoperatively and postoperatively. Most important, the patients who returned with symptomatic, new VCFs were specially monitored. Mean follow-up was 12 months (range: 8–24 months). Results: Immediate postoperative pain relief was reported by 95.2%. No significant intra- or perioperative complications were recorded. The pain relief after 8 months was reported by 87.4%. Patients with persistent or increased pain were diagnosed with either new VCF or degenerative spinal disease. Overall mean vertebral hight restoration was of 62%. In 12.6% (16/127) of the patients additional BCP procedures were performed to treat 22 symptomatic new fractures. All new fractures occurred in postoperatively asymptomatic patients. Meticulous instruction of the patients reduced the nearby segment fractures rate significantly. Conclusions: BCP constitutes a protective factor against nearby segment fractures through restoration of the sagittal profile of the spine. BCP is a safe and effective, minimally invasive procedure for relief of pain associated with VCF. Meticulous information and instruction of the patient is cardinal to avoid nearby segment fractures. Medical treatment of the osteoporosis is paramount. P216. Pain reduction after treatment with teriparatide in 33 patients affected by severe osteoporosis U. Massafra1, L.S. Martin2, A. Ragno2, A. Migliore1; 1 Operative Unit of Rheumatology, St. Peter Hospital FBF, Rome, Italy; 2Department of Internal Medicine, Regina Apostolorum Hospital, Albano (Roma), Italy Objectives: Teriparatide is the first anabolic drug for the treatment of osteoporosis. Italian National Health System limits use of teriparatide to patients affected by severe osteoporosis, with at list two or more vertebral collapses. This kind of patients usually report a severe pain in dorsal and lumbar spine, that reduce significantly their quality of life. We evaluated clinical improvement in dorsal and lumbar spine pain in patients affected by severe osteoporosis with two or more vertebral collapses after treatment. Materials and methods: We selected 33 patients, female, of mean age 68.6 years (DS 8.2) affected by severe osteoporosis, defined according to WHO criteria, by a Tscore value <−3.0 with DEXA determination at lumbar spine or femoral neck and at list two or more vertebral collapses. The mean T-score value was −3.2 and the mean number of vertebral collapses at baseline was 2.6. They underwent to teriparatide treatment with one subcutaneous injection daily. All patients were supplemented with oral calcium (1,200 mg daily) and Vitamin D (800 UI daily). Visual-Analogical-Scale (VAS) pain score was recorded at baseline and after 6 and 12 months.

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Results: Five patients completed 18 months of treatment, 31 performed 12 months of treatment and 33 performed 6 months of treatment. The mean VAS value outcome is summarised in table. At baseline VAS was 7.73 and decreased after 6 months of treatment to 5.15 (reduction 34%), still maintained after 12 months of treatment (mean value 5.25, reduction 34%). This reduction was statistically significant (p<0.001 and 0.002, respectively after 6 and 12 months). VAS baseline VAS 6 months VAS 12 months

7.73 5.15 5.25

−34% −34%

Conclusion: Our preliminary data show that teriparatide treatment is rapidly effective to improve clinical pain in the dorsal and lumbar spine due to vertebral collapses in patients affected by severe osteoporosis, just in the first six months of treatment. P217. Reduction in NSAIDs consumption after intra-articular injection of hyaluronic products in patients with symptomatic hip osteoarthritis: report from italian national register A. Migliore1, U. Massafra1, S. Tormenta S2, G. D’Avola3, G. Bagnato4, R. De Chiara5, M. Falchi6, A. Favilli7, L.S. Martin8, M. Massarotti9, M. Ranieri10, Terracina D11, M. Granata12; 1U.O.S. of Rheumatology, S.Pietro-FBF Hospital, Rome, Italy, 2Dept of Radiology S.Pietro-FBF Hospital, Rome, Italy, 3Rheumatology Service AUSL 3 of Catania, 4 U.O. of Rheumatology G.Martino-Hospital, Messina, Italy, 5 Fisical Medicine and Reabilitation service, Mater Domini Hospital, Magna Graecia University of Catanzaro, 6Dept of experimental medicine, section of Radiology, University of Genoa, 7Direction of Narni association against cancer, 8 Department of Internal Medicine, Regina Apostolorum Hospital of Albano-Roma, 9Operative Unit of Rheumatology, Clinical Institute Humanitas Rozzano (Milan), 10Rheumatology service Umberto I Hospital Tagliacozzo(AQ), 11 Division of Internal Medicine Velletri Hospital, 12O.U. of Rheumatology San Filippo Neri Hospital, Roma, Italy Objectives: Clinical reports showed that intra-articular treatment with Hyaluronic products is safe and effective for treatment of Knee osteoarthritis (OA). Similar results appeared in some reports about treatment of hip OA, but data are scarce due to the difficulties associated with the injection technique which requires use of X-ray or ultrasound (US) guidance. We report from the Italian national database of ANTIAGE (National Association for Ulrasound Guided Intra-articular Treatment of Hip) about

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reduction of NSAID intake after intra-articular injection with hyaluronic products in patient with hip OA. Materials and methods: Adults, ambulatory patients with hip OA, selected from February 2004 to July 2006, underwent to intrarticular injections, performed with US guidance, according to Migliore-Tormenta technique. Every 6 months patients were injected with several products, Low and High MW, like Hylan GF-20 (2 ml), Hyalgan (4 ml), Hyalubrix, (4 ml) and Jointex (4 ml). Monthly NSAID intake, by measuring the number of days the patient had used NSAID during the previous month, was evaluated at baseline and every three months. Follow-up period was of 12 months. A multivariate analysis with Wilcoxon test was performed. Results: 1,767 patients were injected. We found a statistical reduction of NSAID after the injections (p<0.001), decreasing from 8 days per patient at baseline to 6 and 4.5 after 6 and 12 months post first injection, respectively (see table). NSAID intake baseline NSAID intake 6 months NSAID intake 12 months

8 day/month 6 day/month

−25%

4.5 day/month

−44%

Conclusion: Our data suggest that hip viscosupplementation mat be an effective and cost-saving treatment for both patients and Healthcare system, not only because the spending for NSAID is lowered (direct costs), but also because gastrointestinal and cardiovascular side effects commonly associated with NSAID may be reduced (indirect costs). Duration of benefit is at least up to 12 months. P218. Cost-effectiveness of Balloon Kyphoplasty in Sweden. Results based on interim data O. Ström, F. Borgström; European Health Economics, Stockholm, Sweden Objectives: To assess the cost-effectiveness of Balloon Kyphoplasty (BKP) in an osteoporotic Swedish population with a recent vertebral compression fracture (VCF). Materials and methods: The cost-effectiveness, from a societal perspective, of Balloon Kyphoplasty compared to conventional medical management (CMM) was estimated in a Markov cohort model populated with relevant cost, utility and epidemiological data. In the base case, the costeffectiveness was estimated for a 70 year old population with an average T-score of −3 SD eligible for BKP and with the same proportion of women and men as the FREE-trial (RCT comparing BKP to CMM). Utility (EQ-5D) values were from the 1-month analysis of the FREE-trial and differences between treatment alternatives were conservatively assumed only during 36 months followed by a 36 month linear offset-

time when QoL difference linearly approaches zero. Reduced rate of additional fractures after BKP were assumed to persist 5+5 years. Mortality was estimated by linkage of the cause of death and inpatient registers. 5-year mortality rates after 1st and 2nd fracture were calculated using Poisson and Weibull survival modelling. Post-fracture mortality was assumed to be equal in both groups. Costs 0–18 months after VCF were based on results from the KOFOR study and health care contact costs for BKP patients were partially reduced based on published estimates of reduced health care utilization. Results: The cost (€) per QALY gained of BKP compared to CMM for 70 year old patients was estimated at € 11,600 from a societal perspective and € 17,500 when mortality cost was included. When reduced rate of additional fractures after BKP were assumed to persist 3+3 years, or for lifetime, the ICER was estimated at € 14,300 and € 7,200, respectively. Costeffectiveness improved when high risk populations with lower T-scores were simulated, and vice versa. Although, costeffectiveness was better in younger populations since longer life expectancy increases the accumulated benefit of BKP. Conclusion: BKP can be considered cost-effective compared to CMM under assumptions of equal mortality and near equal post-fracture costs. The ICER is dependant on assumptions regarding the persistence of increased QoL and reduced fracture rates but fell below all commonly used monetary thresholds in all scenarios. P219. Incidence of hip fractures in southern Sri Lanka S. Lekamwasam1, A.S. Dissanayaka2, N.P. Premawardana2, J. Lenora1, M. Rodrigo1; 1Center for Metabolic Bone Diseases, Department of Medicine, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka, 2Department of Radiology, Teaching Hospital, Karapitiya, Galle, Sri Lanka Objectives: Compared to European and Scandinavian countries, hip fractures are less common in Asian countries. The incidence of hip fractures in South Asian countries, however, remains unknown. This study examined the incidence of hip fractures in Galle district in Southern Sri Lanka. Materials and methods: All hip fracture patients admitted for a period of 1 year commencing from March 2002, to the orthopedic department of the Teaching Hospital, Karapitiya, which was the only orthopedic referral center in the Southern province during the study period, were included in the study. Patients admitted to private hospitals during the same period were also included (n=10). Type of injury and demographic data of patients were recorded. Fractures resulting from falls from the standing height or less were recorded as fragility hip fractures (FHF) and the rest as traumatic fractures. Only the patients who were resident in the Galle district at the time of the fracture were included in the analysis. Results: One hundred eighty hip fracture patients were admitted during this period and 146 of them had FHF. Mean

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(SD) age of patients with FHF was 72.9 (9.8) years while 74.6% of them were women. There was an exponential increase in the incidence of FHF with advancing age. The age adjusted annual incidence of total hip fractures and FHF were 90 and 73 per 100,000, respectively. Conclusion: Compared to western countries, the incidence of hip fracture was less in Southern Sri Lanka. Some fracture patients may not have been brought to hospital while another small number may have sought treatment from native physicians contributing to less number of admissions. P220. Osteoporosis predictors in diabetes mellitus (type 1) patients M. Nekrasova, L. Suplotova; Tyumen Medical Academy, Tyumen, Russia Objectives: High invalidisation frequency in diabetes mellitus type 1 (DM1) patients is considered to be an important medical problem because of disease complications, including diabetic osteopenia (DO). The bone metabolism defects in DM1 are explained by the deficiency of insulin as anabolic agent, responsing for the bone formation and mineralization. Aims: To study BMD in DM1 patients and to find the most considerable predictiors of DO development. Materials and methods: One hundred twenty-three DM1 patients at the age of 18–50 years (the average age 33.8 years [31.6; 36.0]), including 61 premenopausal females (49.6%) and 62 males (50.4%). BMD was inspected in ultradistal (UD) and mediodistal (MD) forearm parts by DEXA on DEXA-Scan DX-10 (Direx Medical Co., Israel) according to WHO recommendations (1994). The low traumatic fractures (LTF) in the nearest anamnesis, glicoHb level (HbA1c) as diabetes compensation marker and body mass index (BMI) were studied. All results were processed statistically with STATISTICA Soft (6.0 version). Results: Fractures were registered in 12%. The main fracture predictors were the young age of the DM1 manifestation (16.1 years [10.2; 21.9] against 22.5 years [20.2; 24.7], p=0.034) and the disease duration (17.6 years [12.0; 23.2] against 10.0 years [4.0; 16.0], p=0.014). By DEXA low BMD was established in 62.6% (in females 62.3%, in males 40.3%), including osteoporosis in 11.4% (8.5% and 14.2% correspondingly). The average T-score in UD was found −1.12 SD [−1.32; −0.93], in MD −0.94 SD [−1.10; −0.77]. We fixed right correlation between BMD and BMI, age of DM1 manifestation (table); negative correlation with diabetic complications stage and HbA1c.

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Table 1: DO predictors in different BMD groups Predictor

Age (years) BMI (Kg/m2) Manifestation age (years) Disease duration (years)

BMD (Mean [95% CI]) Normal (N=46)

Osteopenia (N=63)

Osteoporosis (N=14)

35.7 [32.2; 39.1] 24.8 [23.7; 25.9]* 24.0 [20.8; 27.2]* 10.6 [7.8; 13.4]

33.1 [30.0; 36.3] 23.8 [22.9; 24.7] 21.3 [18.2; 24.5] 11.0 [6.0; 18.0]

30.4 [23.1; 37.8] 22.3 [20.0; 24.5]* 14.9 [9.7; 20.1]* 15.4 [9.1; 21.8]

*p<0.017.

Conclusion: The early DO predictors determination allow to prevent osteoporosis development and avoid invalidization because of progressive bone mass loss and low traumatic fractures. P221. Efficacy of different dosing regimes of alendronate and ibandronate V. Iriski; Health Center Indjija, Indjija, Serbia Background: Bisphosphonates are the base of the modern therapy of osteoporosis. Objectives: To evaluate therapeutical effect 24-months ibandronate or alendronate treatment in a group of postmenopausal women with established osteoporosis. Materials and methods: Twenty-nine patients were divided into groups. Group 1: eight subjects have received alendronate 10 mg daily during 12 months and ibandronate 150 mg monthly during next 12 months. Group 2: four subjects have received alendronate 70 mg weekly during 12 months and ibandronate 150 mg monthly during next 12 months. Group 3: nine subjects have received alendronate 10 mg daily during 24 month continuosly. Group 4: eight subjects have received alendronate 10 mg daily during 12 months and 70 mg weekly during next 12 months. Control measuring of bone mineral density had performed using DXA after 12 and 24 months. Statistical analysis: there was used t-test for independent samples. Results: No Age BMI T score Group 1 Group 1 8 46.00 25.77 3.52 / Group 2 4 49.00 26.10 3.92 P=0.03*

Group 2 P=0.03* /

Group 3

P=0.003** P=n.s P=0.02* P=0.05* P=0.0008** / P=0.006**

Group 3 9 52.00 25.50 3.52 P=0.003** P=0.02* P=0.0008** Group 4 8 49.00 22.98 3.50 P=n.s. P=0.05* P=0.006**

* after 12 months; **after 24 months

Group 4

/

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Conclusion: There was statistical significant difference among groups 1 i 2, 2 i 3, 2 i 4 after 12 months; among groups 1 i 3, 2 i 3, 3 i 4 after 24 months. Different antiresorptive potential of different drugs and dosing regimes was proved by this results, clearly. P222. Is the polymorphism of the Sp1 spot collagen type I COL1A1 gene A marker of a risk of low-energy fracture? W. Horst-Sikorska1, M. Marcinkowska1, E. Gowin1, R. Slomski2,3; 1Department of Family Medicine, Poznan University of Medical Sciences, Poznan, Poland, 2Department of Biochemistry and Biotechnology, Agricultural University, Poznan, Poland, 3Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland Introduction: The type I collagen is a main structural protein of bone matrix. It contributes over 90% of its proteins. A triple helix structure of a collagen is stabilized by hydrogen bonds. Gene of collagen type 1 alpha (COL1A1) is one of the strongest candidates to have an influence on the development of osteoporosis. Environmental factors and interactions between genes have a significant modifying influence on phenotypic expression of this disease. Objectives: The aim of study was to analyze correlation between genetic polymorphism COL1A1 gene with bone mineral density and risk of osteoporotic bone fractures within postmenopausal women. Materials and methods: The study was done in a group of 247 postmenopausal women from the region of Greatpoland (Poland) aged 45–85 years (mean 65.5 years). For all patients BMD were measured by dual energy X-ray absorptiometry (DEXA) apparatus (Lunar) in femoral neck and lumbar spine L1–4. There were, according to WHO criteria, 113 patients with osteoporosis, aged 51–85 years (mean 70.3 years), 110 with osteopenia aged 47–81 years (mean 63.5 years). The control group consisted of 24 women, aged 45–77 years (mean 62.1 years). Polymorphisms of Sp1 spot COL1A1 gene were done by PCR and RFLP-restriction fragment length polymorphism method analysis with DNA isolated from peripheral blood lymphocytes. Statistical methods: the χ-square test was used to evaluate the distribution of genotypes. The significance level was set at p<0.05. Results: Distribution of alleles COL1A1 SS/Ss/ss agreed with Hardy–Weinberg equilibrium. Polymorphism SS occurred in 161 subjects, Ss in 77 and ss in nine patients. There were no statistic differences between values of BMD in the subgroups within polymorphic variants. In opposite to it a high tendency to association between allele s COL1A1 gene and low-energy fractures (p=0.012).

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Conclusions: 1. In Polish postmenopausal women a high tendency in association allele s COL1A1 gene to osteoporotic bone fracture has been proved. 2. The analysis of Sp1 spot COL1A1 gene may be useful in diagnosis of vulnerability to osteoporotic fractures within postmenopausal women population. P223. Secondary fracture prevention measures in orthopedic wards in Belgium S. Goemaere1, Y. Boutsen2, L. Declercq3, S. Poriau4, P. Geusens5, J.P. Devogelaer6; 1Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium, 2Department of Rheumatology, Université Catholique de Louvain (UCL), University Hospital of MontGodinne, Yvoir, Belgium, 3Department of Rheumatology, St Augustinus Ziekenhuis, Antwerp, Belgium, 4Department of Rheumatology, St Elisabeth Ziekenhuis, Sijsele, Belgium, 5 BIOMED, Universiteit Hasselt, Hasselt, Belgium— Department of Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands, 6Department of Rheumatology, Université Catholique de Louvain, Louvain, Belgium Objectives: In-hospital diagnosis of osteoporosis in fracture patients in the orthopedic wards is lower than 10% and the prescription rate of treatments is less than 5%. The present report describes the efficiency of a secondary prevention program in Fracture patients in Orthopedic Wards (FORWARD) in a Belgian hospital care setting. Materials and methods: Orthopedic surgeons willing to participate in the program were requested to refer their patients with clinical fractures for bone densitometry and an osteoporosis specialist’s advice. Results: In 36 hospitals data were collected about 4,116 fracture patients. Females represented 73.5% of the population. Fracture prevalence increased until the age of 80–85 years, with mean age of 78 year in women and 74 year in men. Most of the fracture cases were hospitalized (88%) and the main fracture type included in the program was hip fracture (45%). Previous clinical fractures were reported in 21% of the patients. Nine percent had previous DXA examination or concomitant osteoporosis treatments and were therefore excluded for DXA referral. Appointments for DXA examination were made in 66% (n=2,718) of the patients and results were obtained from 53% (n=2,181). The diagnostic classification was as follows: osteoporosis 56%, osteopenia 33% and normal bone density 11%. Nearly all cases were referred for diagnostic confirmation of the problem by an osteoporosis specialist, mainly rheumatologists and physiotherapists. Final clinical diagnosis of osteoporosis was accepted in 39% of the cases. Treatment with calcium and vitamin D was started in 1,303 patients (31%), with bisphosphonates in 888 patients (21%)

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and with SERMs or others drugs in 108 patients (<3%). No data about compliance to these treatments were obtained in the present project. Conclusion: The active referral by orthopedic surgeons of the fracture patients in the orthopedic ward to DXA units and osteoporosis specialists results in the identification of osteoporosis in 39% of the patients. Implementing effective measures and treatments for (secondary) fracture prevention in this high risk population could lead to cost-savings in the short term. Initiatives to promote the patient flow needs to be elaborated and maintained by an active local care organisation. P224. A novel approach to the assessment of bone quality: ultrasonic imaging of bone porosity S.R. Ghorayeb; The Feinstein Institute for Medical Research, North Shore-Long Island Jewish (LIJ), New York, USA—Biomedical Sciences, Hofstra University, Hempstead, New York, 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 (SXA), dual energy x-ray absorptiometry (DXA), broadband ultrasonic attenuation (BUA), and quantitative computer tomography (QCT). 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-of-concept object 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 late-breaking 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 percent bone loss increases with decreased bone mass, decreased density, and increased porosity. This is reflected in the excellent correlation between the two methods. Data extrapolation of DXA

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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). P225. Effects of alfacalcidol on bone markers and bone mineral density in alendronate-treated postmenopausal women with osteopenia or osteoporosis: one year interim analysis of the ALFA study H. Boerst1, O. Bock1, M. Runge2, C. Degner1, M. StephanOelkers1, F. Umrath2, G. Armbrecht1, P. Martus3, E. Schacht4, J. Hashimoto5, D. Felsenberg1; 1Centre for Muscle and Bone Research, Charité—Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany, 2 Centre for Muscle and Bone Research, Aerpah Kliniken Esslingen-Kennenburg, Esslingen, Germany, 3Institute of Biometrics and Clinical Epidemiology, Charité—Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany, 4ZORG—Zurich Osteoporosis Research Group, Zurich, Switzerland, 5Bone Disease Area Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan The purpose of the ALFA study (three-year prospective, randomized, double-blind, placebo-controlled trial) is to evaluate the effect of alfacalcidol 1 μg daily on the number of falls in postmenopausal, alendronate-treated, osteopenic or osteoporotic women. A pre-planned one year interim analysis was performed to examine the effect of alfacalcidol on bone turnover markers ad bone mineral density for safety reasons. A total of 278 postmenopausal women (mean age 73.7 years, SD 4.8) received either alfacalcidol 1 μg or placebo daily, in addition to alendronate 70 mg weekly and calcium 500 mg daily. Lumbar spine and hip BMD were measured by DXA at baseline and after 12 months of treatment. Biochemical markers reflecting calcium metabolism and bone turnover [serum calcium, 25-OH-vitamin D, calcitriol, intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP) and serum N-telopeptide (sNTX)] were measured at the beginning of the study, before treatment and after 3, 6 and 12 months of treatment. Baseline characteristics of patients, including age, body mass index, biochemical markers of bone metabolism, lumbar spine BMD (mean T-Score −2.33 SD vs. −2.40 SD), and hip BMD (mean T-Score −1.40 vs. −1.45) were not significantly different between the two groups. The decrease of bone turnover markers was more pronounced in alendronate-treated patients who additionally received alfacalcidol. It was significant for BAP and missed just shortly the significance level of 0.05 for sNTX.

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Table: Bone markers, percent change (SD) from baseline after 1 year

calcium 25-OH-vitamin D calcitriol iPTH BAP sNTx

alfacalcidol (n=139)

placebo (n=139)

p value (t-test)

+1.6 (±5.0) −13.8 (±28.6) +4.7 (±44.7) −21.9 (±31.9) −34.7 (±22.0) −28.5 (±24.6)

−0.7 (±4.6) −14.8 (±25.7) −4.8 (±38.0) +26.5 (±53.1) −23.4 (±24.9) −22.4 (±24.5)

<0.001 0.778 0.086 <0.001 <0.001 0.060

The increase of lumbar spine BMD after 1 year was significantly greater in alendronate-treated patients with additional alfacalcidol treatment (5.02 vs. 2.99%). It was not significantly different for hip BMD. Our data showed an additional, potentially beneficial, effect of alfacalcidol 1 μg daily in alendronate-treated postmenopausal women on bone turnover markers and lumbar spine BMD measured by DXA. Alfacalcidol in alendronate-treated patients is safe, since only one case of clinically relevant hypercalcaemia was observed. The ALFA Study was supported by an unrestricted research grant from GRY-Pharma GmbH, Teva Pharmaceutical Industries and Chugai Pharmaceutical Co., Ltd. P226. Effect of choline-stabilized orthosilicic acid as an adjunct to calcium/vitamin D3 on bone turnover and BMD in a randomized, placebo-controlled trial of osteopenic females T.D. Spector 1 , M. Calomme 2 , S. Anderson 1 , R. Swaminathan1, R. Jugdaohsingh1, D. Vanden Berghe2, J.J. Powell1,3; 1St Thomas’ Hospital, London, United Kingdom, 2 Faculty of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium, 3MRC Human Nutrition Research, Cambridge, United Kingdom Objective(s): Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA; Si(OH)4) in bone formation. Mechanisms are unclear but collagen synthesis and improved mineralization have been demonstrated in cellular and animal models. Human data are lacking so here we have investigated the effect of oral silicon on markers of bone turnover and BMD in a randomized, placebo-controlled trial. Materials and methods: Over 12 months, 114 women (mean age: 61 years) out of 184 randomized (T score spine <−1) completed the study and received, daily, 1,000 mg Ca and 800 IU cholecalciferol (Vit D3) ± Si as cholinestabilized orthosilicic acid (ch-OSA). Three different Si doses were used (Table) which, in this population, would typically increase dietary Si intakes by 12.5, 25 and 50%.

Results: In all groups, there was wide variation in the changes to bone markers at 6 and 12 months compared to baseline (Table) so covariate analysis was used to adjust baseline values. Overall, there was a trend for Si to confer some additional benefit to Ca and VitD3, especially for markers of bone formation (Table), but only PINP was significant by ANCOVA: LSD post-hoc analysis indicated significance at 12 months for the 6 and 12 mg Si dose (p< 0.05 vs placebo) where there was also a trend for a corresponding increase in the bone resorption marker, collagen type I C-terminal telopeptide (data not shown). Table. Change in markers of bone formation vs baseline (%, mean ± SD) Calcium/vit D3 plus:

Placebo

3 mg Si

6 mg Si

12 mg Si

Serum Marker

Change at (months)

n=30

n=26

n=28

n=30

PINP

6 12 6 12 6 12

−12.9±17.5 −19.9±24.7 −11.6±16.6 −12.0±20 −4.62±31.4 −15.0±23.6

−8.92±26.2 −15.9±26.6 −2.40±20 −5.28±15.5 −3.36±33.6 −6.08±54.5

−11.3±21.8 −0.88±27.6* −5.44±12.8 −7.27±16.6 −7.24±18.6 −12.4±18.2

−9.03±21.7 −7.42±20.7* −3.31±15.5 −5.69±17.3 −3.65±20.4 −7.79±26.4

BAP Osteocalcin

BAP Bone specific alkaline phosphatase, PINP procollagen type I N-terminal propeptide. *p<0.05 vs placebo (ANCOVA). BMD in the spine did not change significantly. Subgroup analysis (femur T score <−1) however was significant for the 6 mg dose at the femoral neck (t-test). Conclusion: This study suggests that combined therapy of ch-OSA plus Ca/vit D3 is a safe, well tolerated treatment that has a potentially beneficial effect on bone turnover, especially bone collagen, and possibly the femoral BMD compared to Ca/vit D3 alone. We acknowledge support of the National Osteoporosis Society and Bio Minerals n.v. P227. Evaluation of validity of IOF’s one-minute osteoporosis risk test for postmenopausal women V.V. Povoroznjuk, N. Dzerovich, T. Karasevskaya; Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine, Kiev, Ukraine This research was aimed at proving validity of IOF’s OneMinute Osteoporosis Risk Test and evaluating the relation between structural-functional state of bone according to the ultrasound densitometry and results of IOF’s OneMinute Osteoporosis Risk Test for postmenopausal women.

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We’ve examined 33 postmenopausal women aged 50– 69 years (mean age 59.0±1.4). Structural-functional state of bone was evaluated by means of an ultrasound bone densitometer (“Achilles+”). We created additional index of sum total (the answer “yes” was awarded 2 points, “no”—1 point). Parameters of ultrasound bone densitometry were as follows: SOS=1,525±5 m/s, BUA=107.5±2.1 dB/MHz, SI=77.8±2.7, T-range=0.39±0.24, Z-range=0.73±0.22. Significant correlation was found between index of sum total and the BUA (r=−0.37, p=0.034) which characterizes the quality of bone, and between positive answer to question 4 [“Have you lost more than 3 cm (just over 1 inch) in height?”] and the following indexes of structuralfunctional state of bone: SOS (r=0.45; p=0.09), BUA (r= 0.36; p=0.038), SI (r=0.42; p=0.014), T-range (r=0.42; p=0.015), Z-range (r=−0.27; p=0.14). In conclusion, application of IOF’s One-Minute Osteoporosis Risk Test gives an opportunity to determine structural-functional changes of bone. Among the test questions, the most reliable and informative as for postmenopausal women proved to be question 4 [“Have you lost more than 3 cm (just over 1 in.) in height?”]. Research is continuing. P228. Structural-functional state of bone loss of the postmenopausal women with verterbral fractures V.V. Povoroznjuk, N.V. Grygoryeva; Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine, Kiev, Ukraine This research was aimed at studying the bone tissue state among women with vertebral fracture with aid of the ultrasound densitometry method. The total of 71 postmenopausal women 50–74 years old having vertebral fracture in their anamnesis (VF) were examined by ultrasound bone densitometer (“Achilles+”) and X-ray absorptiometry (“Osteolog”). The control group included postmenopausal women without any osteoporotic fractures in their anamnesis (CG), being standardized by age, BMI, etc. The speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and a calculated “Stiffness” index (SI, %), T and Z-range were measured. The main risk factors for the osteoporotic vertebral fracture turned out to be a menarche after 15 years, an early and late menopause. All indexes of ultrasound densitometry in postmenopausal women were significant lower compared the data of healthy patients during all postmenopausal period (Table).

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Table. 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, % 83.5±1.7 65.7±5.5 Z-range, SD. 0.4±0.2 −1.2±0.5 Duration of postmenopausal period—11–19 years Stiffness index, % 76.8±1.3 64.8±3.3 Z-range, SD. 0.2±0.1 −0.9±0.3 Duration of postmenopausal period—more than 20 years Stiffness index, % 76.2±2.0 60.3±4.0 Z-range, SD. 0.4±0.2 −1.0±0.4

In summary, ultrasound densitometry is an effective screening method to reveal the women of risk group having future osteoporotic vertebral fracture in postmenopausal period. P229. Experimental and clinical research into effectiveness of calcemin for prophylaxis and treatment of osteoporosis V.V. Povoroznjuk, N.V. Grygoryeva, V.S. Forosenko; Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine, Kiev, Ukraine The aim of this study was to estimate the effectiveness of calcemin drug for prophylaxis and treatment of osteoporosis in otherwise healthy elderly people, and in patients with proximal hip fractures in anamnesis. This research came forth as a result of a previous study of calcemin effectiveness in experimental model of two-sided ovariectomy. During the experimental research 18 adult rats were examined and divided into three groups (I group—intact animals, II group—rats after surgical castration, III group— operated animals treated with calcemin). Twelve somatically healthy postmenopausal women with structural-functional disorders of bone (osteoporosis or osteopenia) and ten patients aged 58–78 years with hip fractures (duration of postmenopausal period up to 6 months) were clinically examined and prescribed 1 tablet of calcemin twice a day. Experimental research showed that application of calcemin for adult rats after two-sided ovariectomy brings about considerable improvement of bone solidity, changes in chemical bone composition. Analysis of calcemin’s effectiveness in treatment of postmenopausal patients revealed that application of the drug leads to the reliable decrease of vertebral pain syndrome over 6 month of treatment (index dynamics by visual analogy scale: −2.4±0.4 sm, p<0.05) compared to lack of reliable index

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dynamics of ultrasound densitometry, testifying effectiveness of the drug for prophylaxis of postmenopausal osteoporosis. Application of calcemin to treat patients with proximal hip fractures led to the reduction of pain syndrome in the damaged extremity (index dynamics according to the data of visual analogy scale: −2.3±0.4 sm, p<0.05), improvement of functional status of the extremity (index dynamics by Neverov’s scale: −0.8±0.3 points, p<0.05). Calcemin is an effective means of prophylaxis and treatment of osteoporosis. It certainly decreases intensity of pain syndrome, brings about increase of indexes of structuralfunctional bone state, and improves functional abilities of patients. P230. Effectiveness different forms of glukosamine and chondroitine in patients with knee osteoarthritis V.V. Povoroznjuk, N.V. Grygoryeva, T.V. Orlyk; Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine, Kiev, Ukraine The aim of our study was to determine effectiveness of different forms of glukosamine and chondroitine in patients with knee osteoarthritis. It was examined 20 women aged of 55–75 years with knee osteoarthritis (II–III stages). Patients were divided into two groups. First group (n = 10) accepted ointment of glukosamine and chondroitine at one knee during 3 weeks, one time at 3 months; second group (n = 10) took ointment on the same circuit and glukosamine and chondroitine per os (250 mg) two times per day. The general course of treatment was 6 months. Both groups were similar as regards age, anthropometric indexes, history of illness. We used X-ray method, questionnaires and studied the evaluation of pronouncement of the pain syndrome (WOMAK scale, functional index Leken, EuroQol questionnaires, determination of life quality and health self-assessment). It was shown the reduction of the intensity of pain syndrome by pain index in treated knee: in first group from 5.2±0.5 at the beginning, to 3.4±0.6 and 3.1±0.5 after 1 and 3 months, respectively; in second group from 4.9±0.3 at the beginning to 4.2±0.3 after 1 month, to 3.2±0.5 and 3.3±0.5 after 3 and 6 months, respectively. In bought groups was significant increase of functional status by Leken index in first group after 3 month of treatment (from 16.2±0.6 to 12.8±1.4), in second group from 15.2±0.9 to 14.4±1.2 and 13.2±0.8 after 3 and 6 months, respectively. It was significant decrease the pain syndrome by WOMAK scale and improves the physical condition of the patients, just after 1 month of treatment in first and second group. Glukosamine and chondroitine is effective in complex treatment patients with knee osteoartritis. It decreases the

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intensity of pain syndrome, improves the physical condition of the patients, and promotes the increasing of the quality of life. Effectiveness of treatment more prominent and state in case of combine application of different forms of glukosamine and chondroitine. P231. Influence of orchectomy on bone mineral density in male rats of reproductive age V. Povoroznjuk1, I. Gopkalova2, E. Kreslov1; 1Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine, Kiev, Ukraine, 2V. Danilevskiy Institute of Endocrine Problems, Kharkov, Ukraine The aim of the present study is to evaluate the influence of orchectomy on bone mineral density and bone mineral content in male rats of reproductive age. There were inspected 16 male rats of reproductive age, “Vistar” line. Bone mineral density (BMD) and bone mineral content (BMC) were measured using dual energy X-ray densitometry (DEXA) and “Experimental animals” software. Examination was made before orchectomy and over 30 days after operation. Comparative dynamics indexes of bone mineral density and bone mineral content in male rats of control group and group after orchectomy is presented in table. Group BMD ref.

Δ BMD

Δ BMD BMD (%) ref.

Δ BMC

Δ BMC (%)

CG

0.019± 0.009 −0.003± 0.003 3.89 0.047

19.33± 9.82 −2.87± 2.43 4.01 0.041

2.44± 0.28 −0.30± 0.31 32.52 <0.00001

25.88± 3.48 −2.41± 2.65 26.7 <0.00001

ORC F p

0.105± 0.002 0.113± 0.002 5.84 0.015

9.65± 0.26 11.62± 0.31 7.12 0.009

Annotation: M ± m, CG—animals of control group, ÎRC— animals with orchectomy, BMD ref.—initial indexes of bone mineral density of the entire body, BMC—initial indexes of bone mineral content of the entire body, F—Fisher index. The orchectomy leads to a substantial decrease of bone mineral density and bone mineral content in male rats of reproductive age, allowing this method to be used for creation of experimental model of osteoporosis. P232. Age-dependent features of bone tissue state in men V.V. Povoroznjuk, Y.A. Kreslov; Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine, Kiev, Ukraine This research was aimed at studying the age-dependent peculiarities of bone mineral density and bone mineral consent

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in men. The total of 210 men 20–89 years old (54.6±1.2) were examined and divided into age-dependent groups. Mineral density and mineral consent of bone were determined using dual X-ray densitometry by means of “Prodigy” apparatus. Mineral density and mineral consent of lumbar spine and hip in dependence on age are presented in table. Age in men has a substantial influence on hip BMD: the lowest indexes were observed in group of 70–79 year-olds. Parameters

N Age BMI BMD spine

20–29 years

20 24.1±0.6 22.9±0.6 1.19± 0.04 BMC spine 74.7±3.3 BMD hip 1.08± 0.05 BMC hip 39.8±2.1

30–39 years

40–49 years

50–59 years

60–69 years

70–79 years

80–89 years

24 34.7±0.4 25.7±0.8 1.16± 0.04 71.7±3.1 1.01± 0.04 38.1±1.4

44 44.6±0.5 27.7±0.7 1.18± 0.03 76.7±2.7 1.04± 0.02 40.0±1.1

38 55.2±0.4 27.8±0.6 1.15± 0.03 74.1±2.7 0.99± 0.03 38.8±1.2

36 65.6±0.5 28.4±0.7 1.21± 0.05 80.9±4.2 1.04± 0.03 41.3±1.1

27 75.1±0.5 27.1±1.0 1.17± 0.05 77.4±4.1 0.95± 0.05 36.6±1.5

21 82.9±0.6 27.0±0.8 1.30± 0.06 83.2±3.9 1.0±0.05 38.7±1.8

The osteoporosis of lumbar spine was observed in 19.2%, hip osteoporosis in 7.6% of patients in this group. P233. Life style determinants of bone mineral density in Turkish women S. Akin1,2, O. Ozyemisci1, F. Atalay1,3, B. Karaoglan1,3, Y. Gokce Kutsal1,4, G. Dincer1,5, A. Hasanoglu1,6, A. Basaran7; 1The Society of Life with Osteoporosis, Ankara, Turkey, 2Medical Center, Middle East Technical University, Ankara, Turkey, 3Department of Physical Medicine and Rehabilitation, University of Gazi, Ankara, Turkey, 4 Department of Physical Medicine and Rehabilitation, University of Hacettepe, Ankara, Turkey, 5Department of Physical Medicine and Rehabilitation, University of Ankara, Ankara, Turkey, 6Department of Pediatrics, University of Gazi, Ankara, Turkey, 7Department of Statistics, University of Hacettepe, Ankara, Turkey Objectives: The aim of this study was to determine the factors which affects statistically bone mineral density (BMD) scores for Turkish females aged between 20 and 96. Materials and methods: The total number of participant was 1,934. The whole data were collected with questionnaires. The questionnaire covers long range of questions from age, weight, educational status, marital status, income and sickness to medicare, smoking and alcohol consumption and to duration of breast feeding, number of births. BMD measurements were carried out using quantitative ultrasound technique. In this cross-sectional study bone status was assessed by Omnisense 7000S (Sunlight Medical Systems, Tel Aviv, Israel). Speed of sound (SOS) (m/sec) measurements were taken at the distal 1/3 radius.

Results: According to World Health Organization criteria 191 (9.9%) women had osteoporosis, 451 (23.3%) women had osteopenia, and 1,292 (66.8%) women were defined as normal. Analysis of variance was conducted for the variables which are categoric such as smoking habit, education, occupation, physical activity and also some continous variables such as age, body mass index scores, duration of breast feeding and number of birhts were categorized to allow us to conduct analysis of variance. Therefore, it is possible to see how the level of categorized variable affects BMD scores. With the results obtained from analysis of variance, it is easily can be seen that BMD scores denotes drastic changes. For the two level categoric variables such as outfit (veiled or unveiled) and exposure of menopause, two sample independent t-test was conducted to determine if these factors were important. The last analysis was the stepwise linear regression which has found that duration of menopause, age that menopause begins, number of months in which bresat feeding has been done, smoking habit and outfit (veiled) were statistically important variables which explain BMD with 0.40 coefficient of determination. Conclusion: The attributes which decrease BMD are the number of births, duration of breast feeding, duration of smoking, outfit (veiled), menopause and age. However some atrributes are believed to increase BMD such as physical activity, overweight and quiting smoking in the early years of this habit. P234. Radiographic osteoarthritis and calcaneus ultrasound parameters in Portuguese adults R. Lucas1, P. Cardoso2, R.A. Santos3, I. Ramos2, H. Barros1; 1 Department of Hygiene and Epidemiology, Porto Medical School, Porto, Portugal, 2Department of Radiology, São João Hospital, Porto, Portugal, 3Hospital Militar Principal, Lisboa, Portugal Background: The inverse association between osteoarthritis and bone mineral density that had been found in early studies has been contradicted by more recent work. The majority of studies were conducted using Dual-energy X-ray Absorptiometry (DXA) to estimate bone density. The measurement of bone quality by ultrasound can clarify the properties that account for the possible association between osteoarthritis and osteoporosis. Objectives: To estimate the association between radiographic osteoarthritis and calcaneus ultrasound parameters in an adult Portuguese population. Materials and methods: During the ongoing follow-up of a cohort of Portuguese adults, we evaluated 218 participants [57.8% women, mean (SD) age 64.9 (9.5) years]. Evaluation included the collection of sociodemographic and clinical variables. Calcaneus ultrasound parameters were obtained: Broadband Ultrasound Attenuation (BUA), Speed of Sound

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(SOS), Quantitative Ultrasound Index (QUI) and Estimated Bone Mineral Density (EBMD). Osteoarthritic changes were considered present if the radiographs of the knees, hips, hands, and lumbar spine were scored equal to or over two in the Kellgren–Lawrence scale. Results: The overall prevalence of radiographic osteoarthritis in one or more anatomical sites was 85.1% (95% confidence interval: 79.7–84.5). The mean (SD) BUA in participants with any radiographic change was 66.7 (18.2) dB/MHz and 62.0 (15.7) dB/MHz in those with no changes (p=0.113), mean values for SOS were 1530.3 (29.4) m/s and 1525.0 (22.8) m/s (p=0.295), mean QUI was 83.8 (18.9) and 79.2 (15.0) (p=0.154) and mean EBMD was 0.453 (0.119) g/cm2 and 0.428 (0.095) g/cm2 (p=0.198), respectively. Table presents ultrasound measurements means according to radiographic changes in the anatomical sites tested. Table. Mean ultrasound parameters according to radiographic changes in the anatomical sites tested. Radiographic n (%) osteoarthritis Knee Absent Present Hip Absent Present Hand Absent Present

BUA

SOS

QUI

EBMD

84 (39.1) 66.0 (16.9) 1,530.7 (25.6) 83.6 (16.7) 0.452 (0.106) 131 (60.9) 66.6 (19.1) 1,529.3 (31.4) 83.3 (20.1) 0.450 (0.127) 215 (100.0) p=0.925 p=0.482 p=0.713 p=0.700 151 (75.9) 63.8 (16.5) 1,526.2 (26.1) 80.8 (16.7) 0.435 (0.105) 48 (24.1) 70.7 (18.4) 1,535.8 (28.5) 87.7 (18.8) 0.478 (0.119) 199 (100.0) p=0.021 p=0.043 p=0.023 p=0.023 117 (52.0) 68.5 (19.2) 1,535.2 (31.5) 94.2 (86.5) 0.471 (0.128) 108 (48.0) 64.5 (17.3) 1,525.4 (26.5) 80.9 (17.2) 0.435 (0.109) 225 (100.0) p=0.231 p=0.033 p=0.081 p=0.068

Lumbar spine Absent 116 (52.2) 67.5 (18.1) 1,531.6 (30.4) 84.6 (19.4) 0.459 (0.122) Present 106 (47.8) 64.3 (17.9) 1,526.9 (27.1) 81.4 (17.7) 0.438 (0.112) 222 (100.0) p=0.361 p=0.402 p=0.378 p=0.367

Conclusion: The means of the two original ultrasound parameters were higher among participants with hip osteoarthritis, revealing higher calcaneus bone quality. No differences were found between these parameters and osteoarthritis in other sites. The present study supports that the association between osteoarthritis and bone mass depends on the anatomical site of the radiographic changes. P235. The identification of patients in need of treatment for osteoporosis is improved by using vertebral fracture assessment at the time of DXA scanning S. Chavrimootoo 2 , B. Whelan 2 , P. Hodnett 3 , M. O’Sullivan 2, E. Falvey 2, M. Daly 2, S. Harney 2, F. Shanahan1, M. Maher3, MG. Molloy2; 1Department of Medicine, University College Cork, Cork, Ireland, 2 Department Of Rheumatology, Cork University Hospital, Cork, Ireland, 3 Department of Radiology, Cork University Hospital, Cork, Ireland

Introduction: Vertebral fractures are the most common type of osteoporotic fracture. They affect about 25% of women over the age of 50. The presence of one osteoporotic vertebral fracture is a major risk for further fractures and up to two-thirds of patients with vertebral fractures are asymptomatic. Vertebral fractures can be diagnosed by obtaining a lateral image of the spine using a DXA scanner. This technique is called Vertebral Fracture Assessment (VFA). Objectives: To determine the effect of age and BMD on the prevalence, severity, type and site of vertebral fractures and to determine the number of patients with osteoporotic vertebral fractures who would not have met treatment criteria based on BMD measurement alone. Materials and methods: Three hundred randomly selected postmenopausal women who had VFA scans performed at the time of DXA scanning using an iDXA® scanner were included in the study. VFA images were assessed by a blinded investigator (PH) and fractures were graded based on the semiquantitative system of Genant and Wu. Results: Of the 300 patients, 106 (35.3%) had at least 1 vertebral fracture. Those who had fractures were significantly older and had significantly lower BMD. Based on NICE (National Institute for Health and Clinical Excellence) guidelines from the U.K, 38 patients aged 65–74 met criteria for bisphosphonate therapy without VFA and 58 met criteria with VFA. Twenty-one patients could potentially be treated with bisphosphonates under 65 years of age but when VFA was included the number suitable for treatment increased to 60. Fifteen patients met criteria for treatment with teriparatide without VFA and 25 met criteria for treatment with teriparatide with VFA. Conclusions: Future fracture risk determination is dependent upon accurate determining of current clinical status. Given that large numbers of vertebral fractures are asymptomatic some form of screening for vertebral fracture should be undertaken. VFA is a simple method of doing this and will significantly improve the appropriate treatment of osteoporosis. P236. Use of bone turnover markers to predict patient response to ibandronate treatment M.C. Hochberg1, S.L. Silverman2, C.E. Barr3, P.D. Miller4; 1 University of Maryland, Baltimore, Maryland, USA, 2 Cedars-Sinai Medical Center/UCLA, Beverly Hills, CA, USA, 3Roche Laboratories, Nutley, New Jersey, USA, 4 Colorado Center for Bone Research, Lakewood, CO, USA Objectives: The relationship between changes after 3 months in the bone turnover marker serum C-telopeptide cross-linked collagen type I (sCTX) and after 12 months in bone mineral density (BMD) in patients receiving oncemonthly ibandronate was explored in this post-hoc analysis.

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Materials and methods: MOBILE study data from postmenopausal women who received 150 mg oncemonthly ibandronate (n = 323) were included. After 12 months of treatment, patients were classified as BMD responders at the lumbar spine (LS), total hip (TH), trochanter (TR), or femoral neck (FN) based on BMD changes from baseline (≥0.0% or ≥3.0%). Correlations between percent decrease from baseline in sCTX at 3 months and BMD responder status were determined. Results: The percentage of patients with no loss in BMD (BMD changes ≥0%) was approximately 90% for all sites except FN (74%). Two-thirds (LS and TR), one-half (TH), and one-third (FN) of patients achieved ≥3% increases in BMD from baseline. In general, for all four skeletal sites, women with larger decreases in sCTX at 3 months were more likely to be classified as BMD responders at 12 months. Changes in sCTX levels at 3 months were significantly associated with BMD responses at 12 months (≥0% change from baseline); across all skeletal sites, a 1% greater reduction in sCTX levels corresponded to an approximately 3% (range 0.9–4.2%) increased odds of a BMD response at 12 months (Table). Pearson correlation coefficients demonstrated an inverse correlation between the percent change in BMD at 12 months and the percent change in sCTX at 3 months which was statistically significant only at the LS (r=−0.19; P=0.0016). Table. Unadjusted logistic regression analysis of association of BMD response (>0%) at 12 months with sCTX % change at 3 months. BMD responder site

Odds ratio (95% CI)

P-value

LS TR TH FN

1.029 1.035 1.033 1.013

<0.0001 <0.0001 <0.0001 <0.0001

(1.023–1.036) (1.028–1.042) (1.026–1.039) (1.009–1.017)

CI Confidence interval, LS Lumbar spine, TR Trochanter, TH Total hip, FN Femoral neck. Conclusion: Changes in sCTX at 3 months are associated with BMD increases at 12 months in women receiving oncemonthly ibandronate. Long-term adherence to treatment may be improved by providing early, positive reinforcement to patients on osteoporosis therapy. P237. Treatment induced osteoporosis in patients with breast cancer—update 2006 H. Resch, M. Gnant; Austrian Breast and Coloncancer Study Group, Medical Department II, KH Barmherzige Schwestern (St. Vincent Hospital), Vienna, Austria — ABCSG, Medical University of Vienna, Vienna, Austria

Bone health is an increasingly important concern in patients surviving malignant diseases. Beside bone loss and consecutive fracture risk induced by most of chemotherapies and adjuvant therapy strategies, it is anticipated that tumor cells per se interact with the bone marrow microenvironment to drive bone destruction and tumor growth in a symbiotic relationship. Women with breast cancer for example are often treated with adjuvant hormonal therapy using antiestrogens (tamoxifen) to compete with endogenous estrogen for binding sites on estrogen receptors and aromatase inhibitors to inhibit conversion of androgens to estrogens. The contrasting safety profiles of anstrozole and tamoxifen are well known. We noted significantly more fractures and significantly fewer thromboses in patients treated with anastrozole than in those who received only tamoxifen. The ATAC trial had already provided evidence that the fracture rate in the group switched to anastrozole was higher than in the group who received continous tamoxifen. However, the fracture rate in the anastrozole group was lower than that seen at a similar point in the anastrozole group of the ATAC trial. This finding could suggest a continued protective effect of tamoxifen on bone in the ABCSG trial 8/ARNO 95 patients; anastrozole-treated patients in the ATAC trial had received no previous treatment with tamoxifen. However, data from another aromatase inhibitor, exemestane, do not support this hypothesis. Results from a bone substudy of that trial showed that after 1 year, exemastane was associated with significantly greater reductions in the lumbar spine and total hip bone-mineral density (BMD) than tamoxifen. Presently there are several pharmakologic therapies (including different galenic preparations of bisphosphonates and raloxifene) available which inhibit accelerated bone loss and decrease the risk of fracture. Furthermore RANK Ligand inhibition has been shown in several preclinical and clinical models to be an effective way to limit bone loss. Those therapies not only reduce fracture risk but also the number of days of bed disability and limited activity due to back pain. P238. Physical activity reduces the risk of hip fractures in elderly women. The HUNT study A. Grønskag1, B. Schei1, P. Romundstad1, S. Forsmo1, A. Langhammer2; 1Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway, 2 HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU), Trondheim, Norway Objectives: Hip fracture is a major threat to the health of the elderly individual, and is also associated with high socio-economic costs. Physical activity has been identified

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as a principal external regulator of bone mass and architecture. The aim of this study was to analyze the association between physical activity, forearm bone mineral density and hip fractures in a population-based sample of elderly women in Norway Materials and methods: During 1995–1997 all inhabitants in the county of Nord-Trøndelag 20 years or older received a comprehensive health questionnaire and an invitation to a general health examination (the HUNT 2 study). This study included 5,924 women >65 years old at baseline who underwent densitometry performed with single-energy Xray absorptiometry at the distal forearm and ultradistal radius, non dominant arm. Physical activity data are self-reported based on structured questions in the health questionnaire. This is a prospective study, in which the participants have been followed for 8–10 years in order to register hip fractures. We present preliminary results using logistic regression. Results: During the follow-up period 548 women (9.5%) had a hip fracture. Women reporting physical activity (PA) for more than 1 h a week (n=2,489) had a mean distal BMD of 359 mg/cm2, while those not physically active had a mean distal BMD of 345 mg/cm2 (n=695), p<0.001. In physically active women, a decreased risk of hip fracture [OR=0.5, 95% CI (0.35–0.59)] compared to those reporting no PA was found. This association did not change when adjusting for age, BMD, BMI and use of estrogens, OR=0.5, 95%CI (0.40–0.73). Conclusion: Elderly women who are physically active have a decreased risk of hip fractures. Further studies are needed in order to explore other factors explaining the increased risk of hip fractures among inactive elderly women. P239. Calcaneal bone mineral density reference data of Turkey Ş. Tüzün1, U. Akarýrmak1, M. Uludağ1, R. Kullenberg2; 1 Department of Physical Medicine and Rehabilitation, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey, 2Department of Radiology, County Hospital, Halmstad, Sweden Osteoporosis and consequent fractures have become an important health problem all over the world. However, there are quite differences for bone mineral density (BMD) values rate among different populations. In this study our aim was to obtain the BMD values at calcaneus using a DXL Calscan bone densitometer in healthy Turkish population. The total number of the subject was 951 consist of 639 women and 312 men and age ranged from 15 to 79. The mean weight was 65.8±12.8 kg in women and 77.1±12.6 in men. Peak bone density (PBD) at the calcaneus was reached in the 30–39 years age group in women whereas it was reached earlier in the 20–29 years age group in men. Mean BMD value for healthy young women (20–39 years old) was 0.411±0.058 g/cm2 and for healthy young men

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0.504±0.068 g/cm2. BMD values tended to be decreased with age in both gender. In this reference population 4% of the women are osteoporotic and 25% osteopenic according to WHO criteria. Who BMD cut off limits for Turkey for DXL Calscan in women, osteopenia was between 0.353 and 0.266 g/cm2 and osteoporosis was below 0.266 g/cm2. P240. Osteopathy in thalassemia. Evaluation by bone mineral densitometry and biochemical indices A. Udani1, D. Patkar2, V. Puri3, S. Shetty3, S. Panjwani4, R. Merchant1; 1Department of Pediatrics, Dr Balabhai Nanavati Hospital, Mumbai, India, 2MRI Department, Dr Balabhai Nanavati Hospital, Mumbai, India, 3P.D.Hinduja National Hospital and MRC, Mumbai, India, 4Thalassemia Center, Dr Balabhai Nanavati Hospital, Mumbai, India Introduction: Osteopathy (Osteoporosis) in beta thalassemia has emerged as a topic of interest since optimized transfusion regimens have increased life expectancy and improved quality of life in children with thalassemia. Thalassemia patients have an increased incidence of bone disease than the general population. The pathogenesis of thalassemic osteopathy is multifactorial and is due to the imbalance between bone resorption and bone formation. Objectives: In this study we intend to evaluate the markers of bone turnover in order to better understand the cause of osteopathy and ultimately propose appropriate treatment. Materials and methods: Over 3 months period we evaluated bone resorption markers and Dual Energy X-ray Absorptiometry (DEXA) in 35 thalassemic children of age group 10–25 years. These children were receiving regular blood transfusions at our thalassemic centre and at that time data was collected. Serum ferritin was taken as a marker of body iron overload. DEXA as an index of bone density. Urine C-terminal crosslinked telopeptide of type 1 collagen (crosslaps) by ELISA as a marker of bone resorption and serum vitamin D, parathyroid and osteocalcin by RIA were evaluated as bone formation markers. Results: Of 35 patients, 21 (60%) had osteoporosis and 6 (17%) had osteopenia by Z-score of DEXA. Urinary crosslaps were high in 18 (52%) indicating increased bone resorption. In terms of bone formation 21 (60%) had normal osteocalcin levels, 23 (66%) had low vitamin D levels and 15 (43%) had high parathyroid levels. Ferritin levels (Mean: 5951 ng/dl) were high in all. Conclusion: This preliminary study reveals that there is increased bone resorption in beta thalassemia patients due to hyperparathyroidism secondary to low Vitamin D levels. Above observations indicate that along with Vitamin D supplementation, early intervention to prevent bone resorption with drugs like Bisphosphonates will help in prevention of osteopathy in thalassemics.

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P241. Utility of DXA body composition for anorexia nervosa patients S. Di Gregorio1, J. Vanmanshoven2, L. Del Rio1, C. Sole1, E. Bonel1; 1CETIR, Centre Mèdic, Barcelona, Spain, 2 Katholieke Universiteit Leuven, Leuven, Belgium Anorexia nervosa is the third most common chronic disease in adolescent girls and can lead to severe bone loss with a low bone turnover state. Anorexia nervosa is a condition of weight loss by self-imposed caloric restriction. With the use of total body DXA measurements it is possible to follow changes in bone mineral and body composition. We evaluated the impact of changes in fat and lean mass on bone mass in anorexic patients followed for 1 year. A total of 36 female patients (18.5±4 years) participated in the study. Twenty-seven subjects suffered from irregular menses or even amenorrhoea. All subjects had a baseline total body DXA measurement. Thirteen subjects also had a follow-up measurement after 11.5±4.3 months of treatment, on average. Total and regional body composition was measured by a GELunar-Prodigy DXA device, which calculates fat mass and %fat in the abdominal (android) and hip (gynoid) regions, and the android/gynoid-%fat ratio. In addition, total body bone mineral content(BMC), lean mass (g), fat mass (g) and total mass (kg) were measured. Baseline measurements showed a positive correlation between BMC and lean mass (r=0.613; p< 0.0001) and between BMC and total mass (r=0.587; p< 0.0001). At follow-up, there were significant correlations between the percent change in BMC and percent weight change (r=0.801; p=0.002) and between percent BMC change and the percent change in fat mass (r=0.876; p< 0.0001). However, no correlation was found between percent BMC change and the percent change in lean mass (r=0.209; p=NS). When we analyzed the changes in regional fat, the percent BMC change showed a significant correlation with android fat mass (r=0.759; p<0.004). We may conclude, from this small sample, that the changes in BMC in these anorexic patients are modified especially by changes in fat mass. The main advantage of DXA is that changes in both fat and lean mass can be monitored. Scale weight indicates the overall weight change, but without specific differentiation of fat and lean mass in various regions of interest. DXA may be a valuable tool to evaluate total and regional changes in fat and lean tissue, as well as BMC, in anorexia nervosa patients. P242. Clinical assessement of painful osteoarthritis of knee joint by fat satured MRI C.F. Tan; Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Taipei, Taiwan

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Objectives: Fat saturated magnetic resonance imaging (FSMRI) is used for assessment of clinical cases in osteoarthritis of knee (OA-knee). Materials and methods: Fat saturated T1 and T2 weighted images were used in fifty seven consecutive patients with atraumatic painful OA-knees in addition to conventional MRI. Patterns of painful OA-knee were classified into: cartilaginous form for the presence of cartilaginous lesion or erosion; osteocartilaginous form for the presence of subchondral osteosclerosis and/or marrow edema; and arthropathic form for the presence of arthritis. Results: The study group enrolled 29 males and 28 females with age ranged from 30 to 78 of years (mean 55.4). Forty two patients (74%) had cartilaginous form of knee pain from osteoarthritis with common internal derangements of degenerated cruciate ligaments and/or menisci. Cartilaginous lesions in OA-knee ranged from blister formation, cartilage plate thinning to subchondral bone denudation. Seven patients (12%) had osteocartilaginous form of painful OA-knee characterized by subchondral sclerosis with or without bone edema resulting from reactive subchondral bone edema or spontaneous osteonecrosis. Eight patients (14%) had joint disease in knee osteoarthrosis with joint effusion, synovitis or hemarthrosis. Conclusions: Conventional MRI provides general information of OA-knee such as osteophyte formations, degeneration and/or tear of ligaments and menisci. However, a correlation of such findings to knee pain in OA-knee is not clear enough. Supporting evidence demonstrated pain in OA-knee maybe originates from cartilage degradation, bone marrow edema and knee arthritis. T1-weighted fat-saturated sequence allows accurate cartilage imaging by a high signal to noise ratio and a less chemical shift artifact of cartilage plates to neighboring joint structures. Marrow edema can be assessed on T2-weighted fat-saturated images. In this study, cartilaginous form in painful OA-knee is more commonly occurred than osteocartilaginous form and arthropathic form although the latter forms may also caused painful OA-knees. Subchondral sclerosis (reactive bone fibrosis and pain source) may be obscured by fat suppression technique that is remediable by comparing findings on conventional MRI. P243. Bialystok osteoporosis study 2: intervention threshold—one for all or age dependent one? A simulate analysis J.E. Badurski, A. Dobrenko, N.A. Nowak, S. Daniluk, E. Jeziernicka; Center of Osteoporosis and Osteoarticular Diseases, Polish Foundation of Osteoporosis, Bialystok, Poland Osteoporosis is characterized by decreased of bone strength being a risk of low trauma fractures. It requires the evaluation of individual absolute risk of the fracture

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(ARF) and of need of therapeutic intervention. Several nationally oriented analyses considered therapeutic intervention threshold (TIT) on different levels oscillating between 10, 14 up to 20 and 25% of absolute 10-years risk of hip fracture (ARhpF-10), but one threshold for all ages. Young person lives longer being burdened by any of risk factor then older one, which is the need to take into the consideration life risk of fracture. We realize, that any one TIT will overestimate or younger or older population. That is way we are considering the possibility to use agedependent threshold (ADTIT) increased with age, namely, at 6th decade TIT would be 10% of ARhpF-10, at 7th—15%, at 8th—20%, and over 80—25%, respectively. To analyze consequences of such strategy we evaluated ARhpF-10 of 906 women from data-base of our center, in the mean age 64.3 years, volunteers, who completed Clinical Report Form Questionnaire with independent fracture risk factors and passed BMD DXA of hip (taking into account Zscores less then 0 only), in last 2 years. All 902 women have been grouped according to decades of age into that in 6th, 7th, 8th and 9 ones. The estimation of ARhpF-10 was based on an algorithm elaborated by Kanis et co.(1) Results: If TIT at 14% of ARhpF-10 is used 0.6% patients in 6th, 18.9% in 7th, 15.5% in 8th and 90% in 9 decade out of 902 women in BOS 2 cohort would be treated. If ADTIT is used 6.5% patients in 6th, 16.5% in 7th, 8.2% in 8th and 50% in 9 decade would be treated. Conclusion must be drown, which segment of age in polish population of women needs more care in regard of number of fractures. According to our BOS(2), highest rate of fractures we noted in 6th and 7th decade of life. (1) Kanis J et co, Osteoporosis Int, 2005, 16 (2) Badurski J et co, Post Osteoartrologii, 2003, 14

P244. The Vienna teriparatide database—clinical experience with 158 patients Ch. Muschitz1, E. Edlmayr1, E. Buchinger1, J. Patsch1,3, T. Pirker1, I. Pollhammer1, G. Nirnberger2, H. Resch1; 1 Medical Department II, KH Barmherzige Schwestern (St. Vincent Hospital), Vienna, Austria, 2Bioconsult Ltd, Perchtoldsdorf, Austria, 3Department of Pathophysiology, Medical University of Vienna, Vienna, Austria Objectives: Patients with progressive osteoporosis and no response to antiresorptive therapeutic regimens benefit from 18 months teriparatide therapy (rhPTH [1–34]). We established a prospective single-center open-label database to obtain a documentation system of all our patients to evaluate parameters of bone metabolism and treatment efficacy. Patients and methods: The database consists of 158 patients (141 females, 17 males). 78.4% were considered as bisphosphonate non-responder and 9.6% as bisphosph-

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onate incompatibility. 1.2% had steroid induced osteoporosis. At 10.8% we performed a bone biopsy due to uncertain diagnostic findings. All patients were subject to standardised diagnostic examinations (BMD, serum parameters, X-ray, side effects). Due to pre-existing spine deformities 44% of vertebral DXA scans were not applicable for evaluation. Results: Mean age was 71.94±9.97 years (females 72.64± 9.44, range 26–89; males 65.40±12.57). 86% presented more than 1 vertebral fracture (mean: 3.6 fractured vertebrae). Serum parameters of calcium, phosphorus, alkaline phosphatase, PTH, P1NP, osteocalcin and vitamin D were within normal range at baseline. Lowest T-score of all 158 patients at hip was −2.86±1.01, lowest T-score at spine was −3.20±1.09 SD. After 9 months we found no statistically significant variations of serum calcium, phosphorus, vitamin D levels and 24 h calcium excretion. Alkaline phosphatase increased from 68.87±87 to 93.77±38.36 U/l (p<0.001), S-OC (ng/ml) changed from 17.21±12.82 at baseline to 71.70± 34.90 (p<0.001), S-CTX (ng/ml) increased from 0.25±0.14 to 0.80±0.49 (p<0.001), P1NP (ng/ml) increased from 39.12±25.76 to 144.87±22.18 (p<0.05) and PTH (pg/ml) decreased from 41.65±14.56 to 28.83±12.87 (p<0.001), respectively. Lowest T-score at hip (44 patients) enhanced from −3.08± 1.10 to −2.55±0.91 (p<0.001), lowest T-score at spine (32 patients) improved from −3.38±1.09 to −3.23±1.18 (n.s.) after 9 months of treatment. Conclusion: The database offers a specific standardized documentation system in daily clinical use for these patients suffering from progressive osteoporosis and prior ineffective treatment. P245. Lack of guideline on osteoporosis in Poland reduces the availaibility of diagnostic procedures J. Przedlacki, K. Księżopolska-Orłowska, A. Grodzki, A. Świrski, J. Musiał, E. Łuczak, E. Loth, P. Teter, A. Łasiewicki, A. Walkiewicz, I. Drozdowska-Rusinowicz; National Center of Osteoporosis, Warsaw, Poland Objective: Intensive work of Polish medical societies interested in osteoporosis is expected to result in introduction of generally accepted guideline on this issue. Without it, we are obliged to perform free diagnostic procedures for every patient, who is referred to specialist center by his general practitioner. Since it is not possible to perform examinations (mainly DXA) for every interested patient as a part of free procedures, there is a crucial need for a uniform guideline. Materials and methods: We examined all 856 patients (110 males and 746 females) aged 63.6±9.9 years, who were referred to our Center between 21.03.2006 and

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20.11.2006 by their general practitioners in order to diagnose osteoporosis under the contract between medical centers and National Fund of Health. Diagnostic procedures (DXA examination, biochemical tests and visit) are free (but limited) in this case. To make a diagnosis we use our own procedures, which are based on available data (WHO, IOF, NOF, ISCD, Canadian, Dachverband Osteologie). The main indication to perform an assessment (mainly DXA) of bone fracture risk is: previous bone osteoporotic fracture, fracture of the hip in parents, chronic use of steroids, age ≥65 years in women and ≥70 years in men. Results: Four hundred sixty six patients (54.4% of all) had at least one criterion for diagnostic procedures based on our method of qualification [59 males (53.6%) aged 69.3± 9.9 years and 407 females (54.6%) aged 69.5±7.5 years]. Ninety seven out of them (10 males and 87 females) had been already diagnosed and treated. There were 390 patients (45.6% of all) (51 males, aged 56.4±10.2 years and 339 females, aged 56.7±6.7 years) without any clinical indication for diagnosis. The main premise for referring these patients was only their awareness of risk of osteoporosis and bone fracture in future. Conclusion: There is a need for generally accepted guideline on osteoporosis in Poland. Without it a vast amount of money is spent on the procedures which are not necessary or useful. At the same time, many patients with the significant indications for diagnosis are not able to be free examined due to the limited access to these examinations. P246. Is the subchondral plate involved in osteoarthritis development? Histological analysis of canine tibiae after anterior cruciate ligament section and calciton in treatment A. Berners 1 , D.H. Manicourt 2 , J.P. Devogelaer 2 , C. Nyssen-Behets1; 1Experimental Morphology Unit, Université Catholique de Louvain, Brussels, Belgium, 2 Rheumatology Department, Université Catholique de Louvain, Brussels, Belgium Objectives: To highlight the role of subchondral bone remodeling in osteoarthritic (OA) cartilage deterioration by studying the effects of calcitonin (CT) on epiphyseal bone changes in the early stages of canine experimental osteoarthritis. Materials and methods: Twelve dogs underwent anterior cruciate ligament transection (ACLT) in the right knee. Thereafter each of them received a daily nasal spray delivering either 400 U of CT (CT group, n=6) or a placebo (placebo group, n=6). The animals were killed 84 days after surgery. Both proximal tibiae of each dog were embedded in methylmethacrylate and cut into unde-

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calcified 80-mm-thick coronal sections which were microradiographed. The microradiographs were observed under ordinary light microscope in order to assess the thickness of the subchondral bone plate and the qualitative aspect of the epiphyseal trabecular bone. The quantitative data were analysed with a two-tailed paired test. A p value <0.05 was considered statistically significant. Results: Macroscopic signs of OA were visible in all operated knees, though less numerous and less developed in the tibiae of the CT group than in the placebo one. Neither ACLT nor CT treatment had a significant effect on the thickness of the subchondral bone plate. However, this latter showed microradiographic signs of increased remodelling in the ACLT knees which were less extensive in the CT-treated dogs than in the placebo group. In the same way, epiphyseal trabecular bone in the operated knees showed eroded and disrupted trabeculae. This bone loss was also less pronounced in the CT-treated animals than in the placebo group. Conclusions: Increased subchondral epiphyseal bone remodelling, leading to bone loss, is suggested to contribute to the osteoarthritic cartilage deterioration. By reducing the bone loss correlated to increased turnover, CT can attenuate the OA lesions in this experimental model. P247. Dietary calcium intake: a French nationwide survey on women’s behaviour in regard to their calcium consumption P. Fardellone1, P. Alpe2, R. Juvin3; 1Service de Rhumatologie, CHU Amiens, Amiens, France, 2Rhumatologie, Digne-lesBains, France, 3Service de Rhumatologie, Hôpital Sud, CHU de Grenoble, France Objectives: It’s widely believed that a poor dietary intake of calcium is a risk factor for osteoporosis. Furthermore, adequate intake of calcium and vitamin D should be maintained during osteoporosis treatment. The purpose of this survey was to evaluate the daily calcium consumption in diet of a sample of the French population, according to their sex and age. Materials and methods: From April to November 2006, a survey was conducted among 1060 people in three French cities (Paris, Digne-les-Bains, Grenoble). A validated computerized questionnaire, has been completed by 907 women and 153 men. It concerned their everyday nutritional habits and beyond that, their daily calcium intake. The survey was implemented in lay public places. Results: The average calcium consumption of the 1,060 women and men was established at 960 mg (SD: 495) per day. Women average calcium consumption reaches 975 mg (SD: 585) intake per day, when men only consume 926 mg

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(SD: 405) of calcium. 37% of the 907 women are below the target with less than 800 mg of daily calcium intake per day. Two third of the 907 women are at target or above (one third above 1,200 mg, mainly over 60 years old). Nutritional habits are not the same according to the generations. Thus, 66% of the women over the age of 60 consume more than 800 mg of calcium per day compared to 60% for women under 60 years. Results have been classified as a function of the daily calcium consumption. It appears that the most represented stratum is an alimentary intake over 1,200 mg/day one (26%); thanks to the older generations. In addition to the age of the sampled women, regional differences also exist. The survey was performed in Paris and in French provincial cities. Conclusion: In France, the majority of women has an adequate alimentary calcium intake. The results of this survey show that calcium intake is not an issue for two third of women in France. The issue today is to know if there is a sufficient vitamin D status to protect those women against osteoporosis. P248. Osteoprotegerin (OPG): a link between bone disease and arterial calcifications in chronic renal failure (CRF)? M. Mesquita1, E. Wittersheim3, N. Damry2, C. Melot5, A. Demulder3, D. Willems3, M. Dratwa1, P. Bergmann2,3,4; 1 Department of Nephrology, CHU Brugmann (ULB), Brussels, Belgium, 2Department of Medical Imaging, CHU Brugmann (ULB), Brussels, Belgium, 3Laboratorie of Clinical Clinical Biology, CHU Brugmann (ULB), Brussels, Belgium, 4Laboratorie of Experimental Medicine, CHU Brugmann (ULB), Brussels, Belgium, 5Intensive Care Department, Erasme Hospital (ULB), Brussels, Belgium Objectives: OPG, a member of the tumor necrosis factor receptor family, has been involved in the premature calcification of the vascular system in renal patients. The aim of this cross sectional study was to examine the relationship between the serum levels of OPG and the degree of coronary and aortic arch calcifications in pre-dialysis (CKD) and hemodialysis patients (HD). Patients and methods: We studied 77 out-patients: 32 CKD patients with estimated filtration rate (GFR)>10 ml/min and 42 HD patients with GFR<10 ml/min, selected according to defined exclusion criteria. In addition to demographic and clinical characteristics, mineral metabolism markers as well as OPG (OPG ELISA, R&D, Abingdon, UK) and soluble RANK-L (Biomedica, Austria) were measured. Vascular calcification (VC) were assessed using a Siemens Multidetector CT (MDCT) and calcium scores were calculated

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according to Agatston method. Multivariate regression was used to study the predictors of the Agatston score. Results: Our results showed that serum OPG levels increased as GFR decreased, but no correlation between serum OPG and dialysis vintage was observed except in HD patients over 50 years old. In CKD, there was a positive correlation between serum OPG levels and age, blood pressure, GFR, phosphate, Ca × P product and hs-CRP. In HD patients, OPG did not correlated with any of the clinical or biological variables measured in our study except for age. OPG correlated positively with Agatston scores (coronary arteries and aortic arch) in both CKD and HD patients. In multivariate analysis OPG was an independent predictor of the Agatston score in both CKD and HD patients, at the level of coronary arteries. There was no correlation between GFR and Agatston scores in these two groups of patients. Conclusion: OPG is an independent predictor of the Agatston score for coronary arteries in renal patients and could be a promising biomarker in the early detection of VC. P249. The effect of hepatic or renal impairment on the pharmacokinetics of PTH (1-84) D.S. Wells; NPS Pharmaceuticals Inc., Salt Lake City, UT, USA—NYCOMED, Roskilde, Danmark Objectives: The purpose of this study was to compare the pharmacokinetics of ALX1-11 (full length recombinant human parathyroid hormone, PTH [1-84]) given as a 100-μg subcutaneous injection in subjects with moderate hepatic or mild-to-moderate renal impairment to gender- and BMImatched subjects with normal function. Materials and methods: This was an open-label, singledose study in 12 hepatically-impaired subjects (6 women and 6 men), 16 renally impaired subjects (8 women and 8 men) and 28 matched normal subjects. Following injection of PTH (1-84), blood samples were collected over 24 h for plasma PTH and serum total calcium determination. In addition, the following safety parameters were collected: 12-lead electrocardiograms, physical examinations, vital signs, clinical laboratory evaluations (hematology, serum chemistry, urinalysis), and adverse events (AEs). Plasma PTH data were corrected for baseline levels of PTH and subjected to non-compartmental analysis. Cmax and AUC values were log-transformed and fit by an analysis of covariance model with impairment group as a factor, and age and BMI as covariates. Results: The mean and individual plasma PTH concentrationtime profiles were comparable between the impaired and normal subjects. Regardless of the type of impairment, the mean ratios of baseline-corrected PTH exposures between

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Effect of age on Hmean parameter (n=153) 0.640 Hmean 0.630

regression before 40 years regression after 40 years Equation before 40 years y = 0.630

0.620

Hmean

the impaired and normal groups were in the range of 1.0–1.4. The 90% confidence intervals for the mean ratios were wide, exceeding 200% in most cases. There were no significant differences in the serum total calcium concentration-time profiles between the impaired and normal groups. The AEs were generally mild in intensity and were consistent with other studies using a similar dosing regimen. Conclusion: Moderate hepatic and renal impairment lead to small mean increases in mean PTH (1-84) exposure of less than 40% and do not warrant dose-adjustment.

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0.610

0.600 Equation of polynomial regression after 40 years y = -0.0000157x² + 0.0012698x + 0.6039495 R² = 0.994

0.590

P250. Effect of age on a fractal bone texture parameter assessed by high resolution digital X Ray: a multicenter pilot study C. Gadois1, B. Zegels2, J.P. Dohuu3, E. Lespessailles1, J.P. Neveu4, P. Fardellone4, C. Roux5, S. Kolta5, J.Y. Reginster2, C.L. Benhamou1; 1Institut de prévention et de recherche sur l’ostéoporose (IPROS), CHR d’Orléans, Orléans, France, 2 Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium, 3D3A Medical Systems, Orléans, France, 4Service de Rhumatologie, CHU Amiens, Amiens, France, 5Service de Rhumatologie, CHU Cochin, Paris, France Objectives: High proportion of osteoporotic fracture occurs in subjects with a BMD T-Score >−2.5SD according to the WHO’s T-Score criteria. We have previously developed and validated a bone texture analysis which may be useful for assessing fracture risk in addition to BMD. Such a risk factor determination necessitates a normal curve in the target population. This study presents the preliminary data concerning the age effect on our fractal bone texture parameter Hmean measured on a new high resolution digital X Ray device (BMA™, D3A Medical Systems). Materials and methods: European multicenter (4) study, 153 healthy women, aged 18–85 years were investigated. Women with disease or treatment known to interfere with bone metabolism were excluded. Women were considered postmenopausal at least 1 year after menstruation cessation. In this study, we measured BMD at the hip and lumbar spine (DXA) and bone texture analysis by BMA™. The images were obtained on calcaneus by direct digitization. The population was stratified for 10 years age groups and regression techniques were used separately before and after menopause. Results: Women enrolled were 57.74±14.85 [18–85] years old. Changes in Hmean parameter occurred after 40 years. The best fitting curve was polynomial second degree. Texture parameter was inversely correlated with age in the global population (r=−0.165; p=0.03). The best fitting curve of the Hmean parameter according to age is illustrated below.

0.580

0.570 20

30

40

50

60

70

80

90

100

Age

Conclusion: These data confirmed the decrease of the texture parameter studied with age in this women population. A larger group of pre and post menopausal women has to be assessed in order to plainly characterize the pattern of the Hmean parameter evolution with age. P251. Osteoporosis related vertebral fractures: its prevalence in the Saudi Arabian society M. Sadat-Ali1, A.H. Gullenpet2, F. AlMulhim2, H.A. AlTurki3, H. Al-Shammary2, A.M. Al-Elq4, A. Al-Othman1; 1 Department of Orthopaedic Surgery, College of Medicine, King Faisal University, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, 2Department of Radiology, College of Medicine, King Faisal University, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia,3 Department of Obstetrics and Gynecology, College of Medicine, King Faisal University, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, 4Department of Internal Medicine, College of Medicine, King Faisal University, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia Background: The prevalence of osteopenia and osteoporosis among the ethnic postemenopausal Saudi Arabian women is reported to be high but the prevalence of osteoporosis related vertebral fractures in Saudi women is not known. Objectives: The aim of this study was to establish the hospital based prevalence of vertebral fractures. Patients and methods: Consecutive Saudi women who had chest radiograph during the emergency room visit at King Fahd Hospital of the University between January 2003 and December 2005 were evaluated for vertebral fractures. Seven-hundred and eighty five radiographs were reviewed for the presence or absence of vertebral fractures

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which were diagnosed as mild, moderate or severe as per the semi-quantitative technique by Genant et al. The medical records of the women who had a fracture were reviewed for the diagnosis and medication which they were taking. Women with malignant disease and on steroids were excluded from the analysis. Results: A total of 159 (18.2%) patients had 198 vertebral fractures. The average age of these patients was 65.74 SD ± 8.52 (range 50–91 years). Tenth, 12th and 9th thoracic vertebra are the most commonly affected in that order. There were 89 (44.9%) mild fractures, 65 (32.8%) moderate and 44 (22.2%) severe fractures. All patients who had more than one fracture were over the age of 70 years. The number and severity of fractures were more common in the older group of patients (p=<0.001). A review of the medical records showed that the 51 (32%) were suffering from cardiovascular diseases, 30 (18.9%) had respiratory illnesses, 32 (20.1%) combined cardiovascular and respiratory diseases and renal failure 7 (4.4% ). Twenty-one patients (13.2%) were on the anti-resorptive therapy. Conclusion: This study raises some deficiencies in our system. Firstly the prevalence of vertebral fractures is 18.2% which is similar to reports from the western countries and still we are complacent in dealing with the problem of osteoporosis. As the Saudi Arabian population is ageing and number of the elderly is bound to increase in future making tremendous impact on the health care budgets. P252. Benefits of PTH or pamidronate treatments in the prevention of the diminished titanium osseointegration associated with long–term protein deprivation R. Dayer, R. Rizzoli, P. Ammann; Division of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospital Geneva, Geneva, Switzerland Isocaloric low protein intake impairs titanium implant osseointegration in rats, with a decreased strength needed to loose the implant and altered bone microarchitecture in its vicinity. Whether drugs, such as stimulator of bone formation or inhibitor of bone resorption could improve titanium osseointegration under chronic protein deprivation is not known. We measured the resistance to pull-out of 1 mm diameter sandblasted and acid etched titanium rods implanted into the proximal tibias of 10 month-old female rats receiving a normal (n=9) or isocaloric low protein diet (n=27). After 8 weeks on either diet, the implants were inserted. The rats fed a low protein diet received PTH (1–34) (40 μg/kg, 5/7 days), pamidronate (APD) (0.1 mgP/kg, 5/28 days) or saline vehicle (control groups) for 8 weeks. The tibias were then removed for microtomographic histomorphometry, followed by a pull-out test. All results are means ± SEM.

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Significance of difference was evaluated with an ANOVA (* vs normal protein and ° vs low protein control—see Table).

Pull-out Strength (N) BV/TV (%) TB.N (1/mm) BIC (%)

Normal protein control

Low protein Low control protein APD

Low protein PTH

35.9±4.2

23.9±2.3*

30.4±3.2°

84.5±6.2* °

28±4 4.85±0.26

18±3* 4.30±0.21*

68±4

55±3*

41±3*° 5.37± 0.17° 84±3*°

47±4*° 5.09± 0.19° 86±3*°

Pull-out strength was significantly lower in rats fed an isocaloric low protein diet. APD prevented the decrease in pull-out strength in animals fed a low protein diet, and PTH markedly increased it. PTH and APD effects on pull-out strength were associated with significant changes of trabecular bone volume (BV/TV), trabecular number (TB.N) in the vicinity of the implant, and in bone-to-implant contact (BIC). Pull-out strength and microarchitecture including BIC were strongly correlated in controls with or without dietary protein insufficiency (r2 =0.66, p<0.0001). In contrast with PTH or APD treatments, the correlation was only (r2 =0.15, p=0.03) suggesting that other factors than microarchitecture could be involved. These could include intrinsic tissue quality and/or ingrowth in the microscopic pits of the textured titanium surface with PTH treatment. In conclusion, treatments with pamidronate or PTH corrected the negative effects of protein undernutrition on implant osseointegration. PTH even led to a 3 fold increase in pull-out strength. These results suggest a risk of uncemented arthroplasty loosening in protein undernourished patients, a risk reversed by treatments with pamidronate or PTH. P253. Sickle cell disease: is it a cause of secondary osteoporosis M. Sadat-Ali1, A.M. Al-Elq2; 1Department of Orthoapedic Surgery, College of Medicine, King Faisal University, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, 2 Department of Internal Medicine, College of Medicine, King Faisal University, King Fahd Hospital of the University, Al-Khobar, Saudi Arabia Objectives: The risk of osteoporosis and osteopenia in patients with sickle cell anemia is not well established. This prospective study is conducted to assess the prevalence of osteoporosis and osteopenia in sickle cell anemia. Design and setting: Cross-sectional study on adult Saudi patients with sickle cell anemia who were treated at the

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department of orthopaedic surgery of King Fahd University Hospital, Al-Khobar, Saudi Arabia. The study was conducted between April and July 2006. Methodology: After a verbal consent to participate in the study, patients age and sex were documented and body mass index (BMI) was calculated. Blood was extracted for hematological and biochemistry which also included hemoglobin electrophoresis. Bone mineral density (BMD) measurement was done using dual energy X-ray absorbtiometry (DEXA) at the lumbar spine and the upper femur. Osteopenia and osteoporosis was diagnosed as per the WHO criteria. Results: The results of 36 patients were analyzed. There were 23 males and 13 females. The average age in males was 34.21±6.35 years, and females was 35.38±5.40 years. Eighty-two percent of males and 76% of the females were either osteopenic or osteoporotic. The prevalence of osteoporosis in males was highest at lumbar spine (P=0.001). Conclusions: This study finds the prevalence of osteopenia and osteoporosis is quite high among Saudi adult SCA patients. Physicians should be aware of the risk of osteoporosis in sickle cell patients and every effort should be made to treat them adequately and prevent osteoporosis related fractures.

and 40 mcg/day) of teriparatide (N=793) versus placebo (N=398) group data from the Fracture Prevention Trial. Results: New adjacent fracture risk in untreated women was approximately 2-fold higher than non-adjacent VFX risk, 4.03 vs. 1.59%, respectively. The incidence of new adjacent VFX was higher than the random fracture rate at four vertebrae (T8, T12, L1, L3) and new adjacent VFX risk increased with the number and severity of prevalent VFX. Teriparatide reduced the risk for any new VFX, new adjacent VFX and new nonadjacent VFX by 72, 75 and 70%, respectively, versus placebo. In the pooled teriparatide groups versus placebo, adjacent VFX risk in women with two or more baseline prevalent VFX was reduced 81 and 68%, adjacent VFX risk was reduced 62% in women with a prevalent mild and moderate VFX, and reduced 86% in women with a severe prevalent VFX. Conclusion: New adjacent VFX are common in mid-thoracic and thoracolumbar regions of the spine and increase with both the number and severity of prevalent VFX. Teriparatide reduced the risk for new adjacent VFX associated with increasing number and severity of osteoporotic fractures in the Fracture Prevention Trial.

P254. Teriparatide reduces the risk for new adjacent vertebral fractures M. Bouxsein1, P. Chen2, E.V. Glass2, D.F. Kallmes3; B.H. Mitlak2; 1Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA, 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA, 3Department of Radiology, Mayo Clinic, Rochester, MN, USA

P255. Cost-benefit analysis of treatment of vertebral fractures in osteoporotic patients in Italy: Balloon Kyphoplasty vs Conventional Medical Treatment G. Lippi1, G.C. Guizzardi2; 1Servizio per l’innovazione degli strumenti per il controllo direzionale, Azienda Sanitaria Di Firenze, Firenze, Italy, 2Neurochirurgia, Azienda Ospedaliera Careggi, Firenze, Italy

Objectives: Vertebral fractures (VFX) are known to increase the risk of new VFX, but no studies have reported the risk of new VFX adjacent to existing VFX. Moreover, although several therapies have been shown to reduce VFX risk among postmenopausal women, little is known about their ability to influence the risk of new adjacent VFX. Materials and methods: In a post-hoc analysis, data from women in the placebo group of the Fracture Prevention Trial (N=398) and two-year data from women in the placebo group of Multiple Outcomes of Raloxifene Evaluation trial (N=828) with prevalent VFX at baseline were examined. Placebo group data were analyzed to determine the distribution of prevalent VFX, and new adjacent and nonadjacent VFX across vertebral levels. New adjacent VFX and new non-adjacent VFX risk was determined and stratified by number and severity of prevalent VFX and compared using logistic regression analysis. The effects of teriparatide on new adjacent VFX and new non-adjacent VFX risk was determined using pooled doses (20 mcg/day

This work was sponsored by Eli Lilly and Company.

Objectives: To assess the net benefit, in terms of reduced temporary disability, of Balloon Kyphoplasty (BKP) compared to Conventional Medical Treatment (CMT) in osteoporotic patients in Italy. As intermediate objective, to assess medical and social costs associated with the treatment of vertebral fractures in osteoporotic patients in a selected geographic area. Materials and methods: The cost-benefit model has a societal perspective. Two therapeutic pathways were designed: one for BKP (Path1) and one for CMT (Path2), both considering inpatient and outpatient-community care. An activity-based costing methodology was used for hospitalization costs(1), with measure and pricing of each resource used. Outpatient-community care services data were obtained from a regional expert panel and valued considering regional fees for relevant services. The outcome was measured in terms of days of avoided temporary disability and was then valued. The value doesn’t consider medical costs and comes from an assessment of local social

Osteoporos Int (2007) 18 (Suppl 1):S29–S175

services fees and market prices. Tuscany hospital data were used for cost analysis and measuring length of stays. Results and conclusions: Cost-benefit ratio of 0.51 and net benefit of 3,146 euros of BKP compared to CMT. The average days of disability were 10.48 for Path1 (BKP) and 91.18 for Path2 (CMT). The analysis was conducted without considering other improved outcomes (long term pain reduction, better quality of life, reduction in incidence of new fractures) that have already been shown in BKP compared to CMM(2) and that, if valorized, would have had a sensible impact in terms of additional BKP’s monetary benefits. Health care specific costs for Path1 and Path2 were, respectively, 6,768 and 3,368 euros. The value of the benefit was 80 euros per day of avoided disability. Taking into account social benefits deriving from a shorter average period of disability, BKP is cost-beneficial compared to CMT. (1) Lippi G (2004) Activity Based Management nelle Aziende Sanitarie. Un modello applicativo sviluppato per l’Azienda Sanitaria di Firenze, Florence (2) Taylor RS, Taylor RJ, Fritzell P (2006) Balloon kyphoplasty and vertebroplasty for vertebral compression fractures: a comparative systematic review of efficacy and safety. Spine 31(23):2747–55

P256. Main risk factors of osteoporosis in Tunisian women A. Laatar1, R. Nasraoui1, S. Kerkeni1, S. Chekili1, S. Zaltni1, R. Ben Aissa2, R. Hajri1, S. Kassab1, B. Zouari3, N. Gueddana2, L. Zakraoui1; 1Rheumatology Department, Mongi Slim Hospital, La Marsa, Tunisia, 2National Office for the Family and Population, Tunisia, 3Epidemiology Department, School of Medecine, Tunis, Tunisia Objectives: The study aimed to identify the main factors associated with osteoporosis in Tunisian women in order to dress up the profile of subjects with high risk. Materials and methods: An epidemiologic survey was conducted in two large regions with demographic characteristics similar to the Tunisian general population. Seventy five districts were drawn out, and from each district 40 households were randomly selected. All women, aged more than 45 years from these districts, were invited to answer a specific questionnaire and to have a BMD measurement by DXA at lumbar spine and hip. BMD results were expressed according to the Tunisian normative data(1) and were correlated to demographic, anthropometric variables, menopausal status, medical history, smoking, some eating habits and others factors.

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Results: Fifty-seven percent out of the 1,123 women who participated to the survey (age: 59.3±10.6 years), were menopausal (age at menopause: 50.1±3.7 years). According to the WHO BMD classification, 24% had osteoporosis, 39.5% osteopenia and 35.6% normal BMD at both sites. When using the univariate analysis, age, weight, body mass index (BMI), number of pregnancies, breast-feeding duration, menopausal status, calcium intake, physical activity, sun exposure and previous history of fracture were significantly correlated to osteoporosis (p<0.001). After multivariate analysis, variables identified as independent risk factors for osteoporosis were (OR-95% CI): age (2.5, [1.8–3.1]), menopause (3.1, [1.8–5.1]), weight (1.9, [1.4–2.7]), BMI (1.6, [1.1–2.2]), sun exposure (1.4, [1.1–1.9]) and personal history of previous fracture (1.6, [1.1–2.1]). Conclusion: The profile of Tunisian female at high risk of osteoporosis can be dressed as a thin menopausal woman aged more than 50 years with a sun exposure lower than 1 h/day. (1) Zakraoui L, Laatar A, Kassab S, Nasraoui R, Kerkeni S et al (2005) Bone mineral density values in a healthy female population from Tunisia. Osteoporosis International 16(3): S91–92

P257. Accurate detection of abdominal aortic calcification on lateral spine DXA (VFA) images J.T. Schousboe1,2, K.E. Wilson3, T.N. Hangartner4; 1Park Nicollet Health Services, Minneapolis, MN, USA, 2Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA, 3Hologic, Inc., Bedford, MA, USA, 4BioMedical Imaging Laboratory, Wright State University and Miami Valley Hospital, Dayton, OH, USA Background: Radiographic abdominal aortic calcification (AAC) is a significant predictor of incident fatal and non-fatal cardiovascular disease (CVD), independent of other clinical CVD risk factors. Post hoc analysis of a previous small pilot study showed that AAC can be accurately assessed with lateral spine DXA images intended for vertebral fracture assessment (VFA), compared to un-digitized lateral spine radiographic films. Objectives: To evaluate the accuracy of AAC assessment on VFA images compared to digital lateral abdominal radiographs. Materials and methods: One reader (JTS) assessed VFA images for AAC in 153 women, mean age 69.2 (SD 7.8) years, first with a previously validated 24 point scale (AAC-24) and subsequently with a simpler 8 point scale (AAC-8), blinded to his AAC-24 readings. One month later, electronic digital lateral abdominal radiographic

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0.00

0.25

Sensitivity 0.50

0.75

1.00

images were assessed for AAC-24 and AAC-8, blinded to the prior VFA readings. Results: Considering radiographic AAC-24 score as the gold standard, ROC curves and areas for radiographic AAC-8, VFA AAC-24, and VFA AAC-8 are shown in figure below.

0.00

0.25

0.50 1-Specificity

vfa24 ROC area: 0.8724 vfa8 ROC area: 0.8547

0.75

1.00

rad8 ROC area: 0.9535 Reference

The bootstrapped non-parametric intra-class correlation between VFA and radiography for AAC-24 was 0.80 (95% C.I. 0.69–0.88) and for AAC-8 was 0.76 (95% C.I. 0.65–0.84). Conclusion: Using a simplified 8-point scale, spine images obtained with bone densitometry to detect vertebral fracture can also be used to accurately detect radiographic AAC, a significant risk factor for incident CVD. P258. The effect of DHEA supplements on bone and body composition: the DAWN study D. von Muhlen, J. Bergstrom, D. Kritz-Silverstein; Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, USA Background: Dehydroepiandrosterone (DHEA) levels decline dramatically with age, concurrent with the onset of chronic diseases associated with aging, including osteoporosis. It has been suggested that replacement of DHEA to youthful levels in older individuals might have beneficial effects on bone and bone metabolism, but clinical trials of DHEA administration to otherwise healthy individuals aiming to prevent bone loss have yielded mixed results. Materials and methods: The DHEA And Well-Ness (DAWN) Study is a double blind, placebo-controlled randomized study designed to determine the effects of a 1-year course of 50 mg daily oral dehydroepiandrosterone replacement in 110 men and 115 women aged 55–85 years who are not currently using any hormone therapy. Body

composition, bone mineral density and markers of bone turnover were assessed at baseline, 3, 6 and 12 months. Drug side effects were also evaluated. Results: Overall mean age was 68.7±7.9 years. DHEA treatment increased serum DHEA and DHEA sulfate to concentrations usually found in younger persons. Mixed model repeated measures analyses showed that C-terminal telopeptide of type-1 collagen (CTx) levels decreased in women in the DHEA treatment group as compared to women on placebo (p=0.03), but bone-specific alkaline phosphatase (BAP) levels were not significantly effected. DHEA treatment had no effects on bone turnover markers in men. After 12 months of treatment there was a positive significant effect of DHEA on lumbar spine BMD in women, but no effect was observed at the femoral neck, total hip or total body BMD, and no significant changes were observed in any site among men. Body composition, whether assessed by BMI, fat mass, lean body mass or lean/ fat index was not affected by DHEA treatment in either sex. Conclusion: Results from the present study indicate that daily administration of 50 mg of DHEA might help prevent bone loss in postmenopausal women not using estrogen therapy. The clinical significance of our findings is still to be determined. P259. Changes in bone mineral density during anti-TNF alpha therapy in rheumatoid arthritis patients C. Ancuta1, R. Chiriac1, E. Ancuta 2, C. Iordache2; 1 Rheumatology Department, Rehabilitation Hospital, Iasi, Romania, 2University of Medicine and Pharmacy, Iasi, Romania Introduction: Secondary osteoporosis related to increased pro-inflammatory cytokines activity (IL-1, TNF alpha), medication (corticosteroids, methotrexate) and impaired exercise, has been well recognized as a common complication of rheumatoid arthritis (RA). Objectives: To assess both generalized (spine and hip) and local (hand) changes in bone mineral density (BMD) and bone metabolism markers in RA patients (pts) receiving anti-TNF alpha therapy. Materials and methods: Fifty-two pts (43 women, 9 men; mean age of 37.9 years, mean disease duration of 4.5 years) with active RA, receiving biological therapy (infliximab— 35 pts, adalimumab—12 pts, etanercept—5 pts), were enrolled in this prospective 1-year study. Assessments included BMD (spine and hip dual X-ray absorptiometry, hands dual X-ray radiogrammetry) at baseline and 1 year; bone metabolism markers (alkaline phosphatase, serum

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calcium, osteocalcin levels) at baseline, 3, 6, 12 months; inflammatory (ESR, CRP levels) and immune (rheumatoid factor) parameters and disease activity score (DAS28) at baseline, month 6 and 12. Patients were not allowed to take any anti-rezorptive therapy (bisphosphonates, selective estrogen receptor modulators, etc). Results: Both spine and hip bone loss is arrested, while no significant impact upon hand BMD is reported during anti-TNF alpha therapy; statistically significant increase in axial BMD was demonstrated after 1 year in all patients with initial decreased BMD (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 was reported. Statistically significant negative correlation between axial BMD and RA activity was reported at baseline and after 1 year of therapy (r=−0.72, p<0.01; r=−0.78, p<0.01). Conclusion: Changes in axial BMD after one year of biological therapy in patients with active RA are related to decrease in pro-inflammatory cytokines levels and RA activity.

between manufacturers. In a reanalysis with QDR Apex, precision of the total hip improved between 13 to up to 37%.

P260. Monitoring BMD with DXA K.E. Wilson, C. Ruth, T. Kelly; Hologic, Inc., Bedford, MA, USA

(1) Journal of clinical densitometry, 9(1): 31–36 2006

At the last Position Development Conference, the International Society for Clinical Densitometry published a position paper with a meta-analysis of 58 recent peer reviewed short-term precision studies. This review(1) founds statistically significant differences in the precision between manufacturers for the AP Spine and Femoral Neck, but not for the total hip. An analysis of these 58 peer reviewed studies shows that in both cases where statistical significance was found, Hologic scanners had the best precision (see table below). Region

All Hologic GE/ Norland p value manufacturers (%) (%) Lunar (%) (%)

AP 1.17 spine Femoral 1.85 neck

1.08

1.22

1.58

0.02

1.50

1.97

2.30

0.03

However, with the introduction of the new QDR Apex software, there have been further improvements in Hologic precision, particularly at the Total Hip where the previous peer reviewed studies found no statistically significant difference

Study (Scan time) #1 #2 #3 #4 #5 #6

(60 (60 (60 (30 (10 (10

s) s) s) s) s) s)

Degrees of Old freedom algorithm (%)

QDR Apex (%)

Improvement in total hip BMD (%)

69 71 17 19 173 65

0.90 0.73 0.66 0.54 0.87 0.95

13 18 33 27 24 37

1.03 0.89 1.00 0.74 1.15 1.50

However, short term precision studies represent a best case scenario. Significant long-term variation can be introduced by different positioning of the subject either due to a different operator or due to the same operator positioning the patient in a slightly different manner. To aid in long term precision and reduce operator dependence, the Apex software displays the baseline scan during both the patient positioning step and during scan acquisition.

P261. A statistical atlas of the proximal femur O.M. Ahmad1, K. Engelke2, K. Ramamurthi 3, K.E. Wilson3, R.H. Taylor1; 1Center for Computer-Integrated Surgical Systems and Technology, The Johns Hopkins University, Baltimore, MD, USA, 2Institute of Medical Physics, University of Erlangen, Erlangen-Nuremberg, Germany, 3Hologic, Inc., Bedford, MA, USA Background: Reconstruction of the three dimensional volume of an anatomic region or organ from a limited number of views has a number of useful applications in medicine. One promising method employs a statistical atlas containing substantially all of the individual variation of the anatomy of interest. If the variation of statistical atlas can be well described by a limited number of parameters, computational complexity, time and resources can be significantly reduced. Objectives: We hypothesized that the 3D anthropometric variation of the proximal femur can be adequately explained by a limited number of normal modes. Materials and methods: Sixty-two Caucasian male femurs were acquired with multi-slice CT (1 mm3 resolution) and segmented to separate bone and soft tissue. To model the data, a tetrahedral mesh (2.5 mm between vertices) with associated density functions for each tetrahedron was derived. Principal

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component analysis (PCA) was then performed on the tetrahedral mesh to obtain a statistical model. The model consists of a “mean-shape” and with associated eigenvectors (modes of variation). The eigenvalue of each eigenvector measures the amount of variation the eigenvector explains. Results: As expected, the eigenvalues declined approximately exponentially, indicating that most of the individual anatomical variation is captured by the 10–20 eigenvectors with the largest eigenvalues.

Eigenvalues 50 45

Magnitude

40 35

underwent the DXA (Lunar DPX pro-GE) scan on at least three bodily regions (L1–L4, dual femur). Results: Sixteen patients had normal densitometry results; 30 patients were diagnosed osteopenia with a T-score varying from −1.0 to −2.5; ten patients were diagnosed with osteoporosis with a T-score higher than −2.5. Patients were divided in two groups. Group A included patients with height lower than 175 cm. Group B included patients with height above 175 cm. In group A, nine patients had normal densitometry results, 18 had osteopenia and eight had osteoporosis. In group B six patients had normal results, 12 had osteopenia and two had osteoporosis. Results of biochemical analysis were evaluated for the study. Discussion: Evaluation of the results showed that small height is an important predetermined factor for osteoporosis in male patients, not depending on the patient’s age.

30 25 20 15 10 5 0 0

10

20

30

40

50

60

th

i Eigenvector

Conclusions: A statistical atlas of the proximal femur was constructed using a tetrahedral mesh to model the geometry and density of the anatomy. The variation was substantially captured with a small number of eigenvectors. Further investigations will focus on the use of the atlas to reconstruct the proximal femur from several two dimensional views of the anatomy and compare this to CT volumetric reconstruction of the same femur. P262. Small height: a predetermining factor for osteopenia and osteoporosis in male patients M. Panajotovik Radevska1, N. Nasteska1, D. Grujoska-Veta2, S. Ranogajec 3; 1Prama Medica, Skopje, Macedonia, 2 University Clinic for Orthopedic Surgery, Skopje, Macedonia, 3Acus Medica , Delcevo, Macedonia Objectives: The aim of this research is to demonstrate the incidence of osteoporosis in men with small height (smaller than 175 cm) as a relevant predetermined factor for osteoporosis. Materials and methods: A group of 56 male patients was observed. Main symptoms were pain in different parts of musculoskeletal system and decreased range of motions. Average age of patients was 56 years (20–84). They all

P263. Risk factors for osteoporosis and fragility fractures in postmenopausal women attended in a primary care center of Spain. The Camargo cohort study J.M. Olmos1, E. Pariente2, J.L. Hernández1, J. Martínez1, C. Valero1, P. García2, D. Nan1, I. Pérez2, J. González Macías1; 1Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain, 2Centro de Salud “José Barros” (Camargo), Universidad de Cantabria, Santander, Spain Objectives: To determine the prevalence of several risk factors for osteoporosis and fragility fractures in a population of postmenopausal women from Cantabria, Spain. Materials and methods: We present preliminary results of the first 394 postmenopausal women included in the Camargo Cohort Study, a community-based study designed to evaluate the prevalence of metabolic bone diseases and disorders of mineral metabolism, as well as the prevalence of fractures and risk factors for osteoporosis and fragility fractures, in postmenopausal women and men older than 50 attended in a primary care center of Spain. Studied women were 63±9 years old, and they were recruited at a primary care center of Camargo (Cantabria), a large semi-urban Spanish city. Demographic, anthropometrics, and clinical variables were collected, and subjects were evaluated with a questionnaire of risk factors for osteoporosis and fragility fractures. This study was supported by a grant from the “Fondo de Investigación Sanitaria,” Ministerio de Sanidad y Consumo, Spain (FIS: PI05 0125). Results: The prevalence of main osteoporosis risk factors was as follows. Familial history of fragility fractures: 18%; fracture after 40 years: 16%; early menopause (<40 years): 15%; low body weight (<57 kg): 11%; tobacco and alcohol consumption: 12 and 10%, respectively. Fifty percent of women have impairment of visual acuity (cataracts in 13%

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of them), 32% were treated with benzodiazepines, 22% reported at least one fall during the previous year, and 13% has hypoacusia. Mean calcium intake in dairy products was 666±322 mg. Six percent of women were receiving thyroid hormone treatment. Five percent and two percent were taking inhaled or systemic glucocorticoids, respectively. Conclusions: Besides age, the most prevalent risk factors for osteoporosis and fragility fractures in our series were a history of fragility fractures, early menopause, as well as the presence of impairment of visual acuity, benzodiazepine use and previous fall. P264. Influence of diabetes duration in the development of the changes in bone mineral density in patients with type 2 diabetes L. Nikoleishvili1, R. Kurashvili1; T. Demetrashvili2, N. Baghishvili2, V. Matishvili2, T. Rukhadze2; 1Georgian Diabetes Center, Tbilisi, Georgia, 2Medical-Diagnostic Center for Bone and Joint Diseases, Tbilisi, Georgia Objectives: The aim of our study was to investigate the changes in bone mineral density (BMD) in persons with type 2 diabetes according to diabetes duration. Materials and methods: Forty men with type 2 diabetes mellitus from the out patients clinic and 20 healthy males were examined. They were divided into three groups: Diabetic males with the age from 50 to 60 years, and diabetes duration less than 10 years (n=20); diabetic males with the age from 50 to 60 years, and disease duration >10 years (n= 20); and 20 non-diabetic males with the age from 50 to 60 years (n=20 years). BMD was measured at the L2–L4 vertebrae and the femoral neck by DXA (Hologic, USA). Results: In the group of diabetic males with disease duration more than 10 years significant decrease of vertebral BMD values were found compared to their respective healthy ones and in the males with diabetes duration less than 10 years (p<0.01). There were no statistically significant difference in the values of BDM in any of the sites measured in the group of non-diabetic persons and diabetic males with diabetes duration less than 10 years. Both presented significantly higher vertebral Z-score values compared to diabetic males, with diabetes duration more than 10 years. There were no statistically significant changes between these three groups regarding to the femoral neck. Conclusion: BMD decreased in diabetic males when diabetes duration exceeds 10 years. This effect is more clear regarding to the trabecular bone. Long standing diabetes seems has influence on trabecular bone mass in males with the age of more than 50 years.

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P265. 25-OH vitamin D levels in patient with rheumatoid arthritis N.G. Villa, A.M. Riopedre, D.O. Mata, S.E. Suarez, G. Redondo, E. Chiuzzi, M.C. De la Vega, OD. Messina; Department of Rheumatology, CIRO Medical Center, Buenos Aires, Argentina Vitamin D is crucial in the skeletal growth and development. Patients with rheumatoid arthritis (RA) exhibit a higher rate of fractures based on a multifactorial mechanisms including impaired mobility, medications such as glucocorticoids, increased levels of inflamatory cytokines from the rheumatoid synovium among others. Vitamin D deficiency in very frequently found even in healthy post menopausal women and in sunny countries. In order to determine the levels of 25-OH vitamin D levels in patients with RA we studied 54 patients (49 women, mean age 58.1 years, mean time of RA 13.5 years) with adult onset RA. Patients receiving vitamin D or having renal or hepatic insufficiency or functional class III– IV were excluded. Determinations were performed during June and July (winter time in Argentina) and determined by RIA. 38/54 patients were received at any time glucocorticoids at doses higher than 2.5 mg of prednisone/day. 7/54 had a history of non traumatic fractures. Levels of 25-OH vitamin D were divided as follows Vit D

N of patients

>30 ng/ml 10–29 ng/ml <10 ng/ml

10 40 4

(18.5%) (74 %) (7.5 %)

Patients with levels higher than 30 ng/ml were younger and showed a shorter mean time duration of disease RA although these differences were not statistically significant. We conclude that 81.5% of patients showed 25-OH vitamin D values lower than 30 ng/ml (normal values for Buenos Aires city latitude). Vitamin D deficiency is not determined routinely in patients with RA. We strongly recommend 25-OH Vitamin D determinations in patients with RA. P266. Hypovitaminosis D in a sunny country: relation to lifestyle, bone markers and bone mineral density F. Allali1,2, S. El Aichaoui1, B. Benyahya1, B. Saoud1, H. Khazani1, R. Abouqal2, N. Hajjaj-Hassouni1,2; 1Department of Rheumatology, El Ayachi University Hospital, Rabat-Sale, Morocco, 2Laboratory of Biostatistic, Clinical Research and Epidemiology, Faculty of Medecine, University Mohamed V, Rabat, Morocco Objectives: The aims of this study were to determine: 1/ The prevalence of hypovitaminosis D (serum 25-OH D <30 ng/ml) and to characterise its relationship with lifestyle

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factors; 2/The association between vitamin D status, parathyroid hormone (PTH) and bone turn over markers; 3/The correlation between 25-OH and bone mineral density (BMD) in post menopausal women. Materials and methods: It was a cross-sectional study. The group studied included 415 women aged 24-77 years. Exclusion criteria were all factors or treatments influencing bone turn over. For all patient, we assessed between July and September, calcium intake and measured serum calcium, phosphorus, albumin, alkaline phosphate, 25-hydroxyvitamin D (S-25(OH)D), PTH, osteocalcine, CTX and BMD in spine and total femur. Results: The mean levels of vitamin D was 18.1±7.9 ng/ml, b 7.9. Hypovitaminosis D affected 90.6% of patients. Hypovitaminosis D was highly prevalent in post menopausal women (p =0.025), in veiled ones (p=0.004) and in patients with low level of education (p=0.03). Hypovitaminosis D was also associated to the duration of being veiled (p=0.001) and to time spent outdoors less than 30 min/day (p=0.007). There was no association between hypovitaminosis D and dietary calcium intake (p=0.14) nor with the number of parity (p= 0.15). In linear regression, the main negative determinants of S-25 OHD were age (p=0.023), wearing veil (p=0.007) and time spent outdoors less than 30 min/day (p=0.035). A significant inverse correlation between 25-OH and osteocalcine (r=−0.18, p<0.001), 25-OH and CTX (r=−0.15, p=0.003) were observed. By LOWESS (Locally Weighted Regression and Scatterplot Smoothing) technique, there was an increase in PTH level when S-25(OH)D was <30 ng/ml. There was a significant positive correlation between, spine BMD, trochanter BMD and 25(OH)D while Total femoral BMD failed to show any significant correlation with S25(OH)D. Conclusion: Our study shows that during the summer season, vitamin D insufficiency is very common in adult healthy Moroccan women. The lack of sun exposure and veiled clothing style are the most important factors that influence hypovitaminosis D. Patients with hypovitaminosis D had a high bone turn over with a decrease in trabecular BMD. More research is needed to evaluate the clinical impact of the above findings. P267. Influence of parity on bone mineral density and peripheral fracture risk in Moroccan post menopausal women F. Allali1,2, H. Maaroufi1, S. El Aichaoui1, B. Saoud1, R. Abouqal2, N. Hajjaj-Hassouni1; 1Department of Rheumatology, El Ayachi University Hospital, Rabat-Sale, Morocco, 2 Laboratory of Biostatistic, Clinical Research and Epidemiology, Faculty of Medecine, University Mohamed V, Rabat, Morocco

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Background: Moroccan women have many pregnancies, and represent an ideal population to investigate the relationship between parity and osteoporosis. Objectives: The aims of the present study were to determine (1) the relationship between parity and BMD; (2) the relationship between parity and osteoporotic peripheral fractures. Materials and methods: The group studied included 730 postmenopausal women. Patients were separated into four groups according to the number of fullterm pregnancies. Group 1: Nulliparae, group 2: one to three pregnancies, group 3: four to five pregnancies, and group 4: more than six pregnancies. Additionally, patients were separated into three groups according to their ages, as <50 years, 50–59 years and ≥60 years. Results: The median parity was 4 [0–20]. The number of children ranged from 0 to 20 with a median parity of four live births. The mean age of women was 59.4 (±7.6) years and was significantly correlated with parity level. Increasing parity was associated with higher years since menopause (p<0.001), higher BMI (p=0.001) and higher percentage of wearing weil (p<0.001). In contrast, increasing parity was not significantly associated with later age of menopause (p=0.08). All the patients with parity greater than six had spine and hip BMD values significantly lower than values in the other groups (p<0.001). After adjustment for age and BMI, decreased lumbar and total hip BMD were still associated to increased parity (ANCOVA, p=0.04 and p=0.023, respectively). The relation between parity and lumbar BMD was highly significant among women aged 40–49 years (age-adjusted p =0.022), while there was no parity-spine BMD association in the other age groups. The relation between parity and hip BMD was seen only in the group 50–59 years (age-adjusted p =0.042) while in the group >60 years, no parity-BMD association was observed. A positive history for peripheral fractures was present in 170 (23%) patients. There was no relationship between parity and peripheral fractures neither in the whole population nor in the sub-groups according to age. Discussion: The present study suggests that the BMD of the spine and femur decreases with an increasing number of pregnancies, and this situation shows variations in different age groups. However, there was no correlation between parity level and peripheral fractures. P268. A low educational level increases the risk of osteoporosis and fractures S. Rostom1, F. Allali1,2, B. Bennani1, L. Mansouri1, R. Abouqal1,2, N. Hajjaj-Hassouni1,2; 1Department of Rheumatology, El Ayachi University Hospital, Rabat-Sale, Morocco, 2Laboratory of Biostatistic, Clinical Research and Epidemiology, Faculty of Medecine, University Mohamed V, Rabat, Morocco

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Aim of the study: To evaluate whether the prevalence of osteoporosis and related risk factors, might be influenced by the educational level, as has been demonstrated for many other chronic diseases. Materials and methods: A total of 487 women with a mean age of 55±9.6 were included in this study. Patients were separated into four groups according to school educational level, group 1 no education (n=106 patients), group 2: elementary (n=66 patients), group 3: high school (n=201 patients), group 4: tertiary (n=114 patients). Results: The mean age of groups were 63±10.2; 57±8.09; 53±7.4 and 50±8.1, respectively. Better educated subjects tended to be younger, to have younger age at menarche, shorter duration of pregnancies, lactation and veil wearing. Higher education was also associated with higher intakes of calcium and tobacco. The prevalence of osteoporosis showed an inverse relationship with educational level (group1: 48%; group 2: 20%; group 3: 19%; group 4: 16%; p<0.0001; p value from linear trend). Using the lowest educational level as reference category, increases in educational status was associated with a significantly reduced risk for osteoporosis (OR: 0.27; IC 95% 0.12–0.61; p=0.002 for group 2; OR: 0.26; IC 95% 0,15–0.47; p<0.0001 for group 3; OR: 0.21; IC 95% 0.10–0.43; p<0.0001 for group 4). Additionally there was a significant inverse relation between educational level and the risk of peripheral fractures (OR: 0.21; IC 95% 0.09–0.27, p=0.002 for group 2; OR: 0.30; IC 95% 0.11–0.24; p=0.004 for group 3; OR: 0.33; IC 95% 0.15–0.30; p=0.004 for group 4, group 1 was the reference category). After logistic regression analysis, those relations persisted after adjustment on the other potential confounding factors of osteoporosis and fractures. Conclusion: A higher educational level was independently associated with higher BMD, lower osteoporosis and fracture risk among Moroccan women. P269. Risk factors of peripheral osteoporotic fractures in post menopausal Morrocan women L. Bennani1, F. Allali1,2, H. Khazzani1, R. Abouqal2, N. Hajjaj-Hassouni1,2; 1Department of Rheumatology, El Ayachi University Hospital, Rabat-Sale, Morocco, 2Laboratory of Biostatistic, Clinical Research and Epidemiology, Faculty of Medecine, University Mohamed V, Rabat, Morocco Objectives: The objective of this study was to assess risk factors for osteoporotic peripheral fractures in post-menopausal Morrocan women. Materials and methods: Three hundred sixty postmenopausal women in obvious good health were recruited for the study. We excluded women who had use a drug or who had chronic diseases affecting bone metabolism. The patients were interviewed via a questionnaire including socio-

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demographic data; physical activity; calcium intake; gynécoobstetric history. Significant risk factors for osteoporotic peripheral fractures were assessed by univariate analysis and multiple logistic regression. Results: The mean age of patients was of 58.7±7.7 years. 30.7% were osteoporotic and 11.9% had a history of peripheral fracture. In univariate analysis, peripheral fracture risk was associated to older age (p=0.001), multiparity (p=0.031), lower BMD (p=0.006), less physical activity (p=0.050), younger menopause age (p=0.001), increased number of falls (p=0.003), longer breastfeeding period (p=0.004) and lower BMD. Familial history of fractures and body mass index were not associated to peripheral fracture risk. Multiple Logistic regression showed that the age of menopause ≤50 years (ORs=2.58, CI95%: 1.24–5.35; p=0.011), the femoral BMD <0.893 g/cm2 (OR=2.98, CI95%: 1.24–7.18; p=0.015), a high number of falls per year >2 (OR=1.26, CI95%: 1.02–1.56; p=0.029) and a breastfeeding period ≥15 months (ORs=3.03, CI95%: 1.34– 6.81; p=0.007), were the independent factors of peripheral fractures. Conclusion: Low femoral DMO, low age of the menopause, increased falls and long breastfeeding period are an independent risk factors of peripheral fracture risk in post menopausal Moroccan women. P270. The comparison of effectiveness of high and moderate doses of vitamin D3 in prevention of postmenopausal osteoporosis A.V. Dreval, L.A. Martchenkova, I.V. Kryukova, R.S. Tishenina; Moscow Regional Research Clinical Institute, Moscow, Russia Introduction: Moscow region is highly deficient in vitamin D due to only 3% of postmenopausal women have 25(OH) D serum level ≥100 nmol/l.(1) But it is not a consensuses what daily doses of vitamin D are adequate for prevention of postmenopausal osteoporosis in Moscow region. Objectives: The aim of study was to assess and compare effects of high doses (800 IU daily) and moderate doses (400 IU daily) of vitamin D3 with calcium supplementation for prevention of osteoporosis in postmenopausal women with spine osteopenia. Materials and methods: Study comprised 30 postmenopausal women aged 45–70 years with lumbar spine BMD (L2–L4) < −1,0 and >−2,5 SD, who were divided in three equal groups. Women in group 1 were administered vitamin D3 400 mg + calcium 1,000 mg daily, women in group 2 received vitamin D3 800 mg + calcium 1,000 mg daily and patient in control group did not take any medication influence bone remodeling. The duration of the study was 12 months. Effectiveness of therapies was evaluated by measurement of BMD and biochemical markers of bone turnover and calcium homeostasis.

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Results: There was an increase vs. baseline in BMD in lumbar spine (+1.9%, p<0.05) and in trochanter (+5.5%, p< 0.01) in group 1 and no any significant change in all skeletal sites in group 2. But BMD significantly decreased vs. baseline in lumbar spine (−11.9%, p<0.05), Ward’s triangle (−2.3%, p<0.05), trohanter (−5.8%, p<0.05) and total proximal femur (−2.4%, p<0.001) in control group. We found a significant lowering in serum PTH from 69.3± 13.0 to 42.3±18.7 pg/ml (p<0.001) in group 1 and from 78.9± 10.3 to 46.0±28.8 pg/ml (p<0.05) in group 2 and a decrease in serum alkaline phosphatase from 88.4±32.9 to 70.3±25.5 U/l (p<0.01) in group 1 and from 88.4±26.7 to 73.9±12.3 U/l (p<0.01) in group 2. There was an increase in serum PTH from 46.9±14.8 to 55.1±12.4 pg/ml (p< 0.01), in serum alkaline phosphatase from 81.0±18.8 to 92.3±24.1 U/l (p<0.01) and in serum osteocalcin from 24.9±12.5 to 29.4±12.5 ng/ml (p<0.01) and a decrease in serum calcium from 2.31±0.09 to 2.25±0.12 mmol/l (p< 0.05) and daily calcium excretion from 4.32±2.46 to 2.96± 1.53 mmol/day (p<0.05) in control group. Conclusion: High and moderate doses of vitamin D3 are both improve calcium homeostasis and lowering bone turnover in postmenopausal women, but vitamin D3 in high doses better increases BMD in spine and femur. (1) Toroptsova NV., Benevolenskaya LI. et al. 2005.

P271. A rare case of ankylosing spondylitis in woman associated with osteoporosis N. Nasteska 1 , M. Panajotovic 1 , D. Grujoska-Veta 2 , M. Kotevska Nikolovska3, S. Ranogajec4; 1Prama Medica, Skopje, Macedonia, 2University Clinic for Orthopaedic Surgery, Skopje, Macedonia, 3 University Clinic for Rheumatology, Skopje, Macedonia, 4Acus Medica, Delcevo, Macedonia Ankylosing spondylitis (AS) is chronic and usually progressive inflammatory disease involving the articulations of the spine and adjucent soft tissues. The prevalence in men is 0.5–4 per 1,000 and in women 0.05–0.5 per 1,000. The disease predominantly affects young men and begins most often in the third decade. The aim of the authors is to present a rare case of a female patient with AS associated with osteoporosis. A female patient, 40 years old, was referred to medical examinations on few occasions for complaints of back pain on prolonged upright position and stiffness in the neck and spine. She was treated with NSAID for longer period of time and rehabilitation therapy, but with no significant improvement. She underwent several investigations: biochemical examination of the blood, plain radiography and Dual Energy X-ray absorptiometry (DXA with Lunar DPX pro-GE). Reasons for making BMD Testing in this nonmenopausal woman were:

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clinical findings and risk factors for osteoporosis (thin small build, lack of exercise, smoking and low calcium intake). The results of the clinical and other examinations were evaluated and confirmed the diagnosis of ankylosing spondylitis associated with osteoporosis. The patient was subjected to treatment with NSAID, bisphosphonate (alendronic acid 10 mg/day) agents and prolonged physical rehabilitation. Results showed improvement after 1 year follow-up. Conclusion: As is predominantly a disease of young men. But in rare cases it affects women too and differentiation from other rheumatic, degenerative diseases or malignancies, which could also be associated with osteoporosis is a diagnostic as well as therapeutic challenge. P272. Orthopaedic surgeons and their role in the secondary prevention of osteoporotic fragility fractures S. Lidder, A. Rumian, S. Kahane, M. Chatoo; Department of Trauma and Orthopaedics, The Lister Hospital, London, United Kingdom Objectives: Fractures related to osteoporosis are very common and a strong indicator for the risk of future fractures. NICE guidelines for the secondary prevention of fragility fractures are available but there is much debate as to whether the general practitioner or orthopaedic surgeon should initiate treatment. Orthopaedic surgeons are currently missing a major opportunity in preventing future fractures. The aim of this study was to audit current practice in a district general hospital and to show a simple, yet effective method of increasing uptake for the secondary prevention of fragility fractures. Materials and methods: All in and outpatient case notes, over a 4 month period were retrospectively reviewed to audit if appropriate secondary prevention had been initiated. Potential strategies for increasing uptake of secondary prevention were evaluated and a prospective study started. Inpatients identified with fragility fractures were investigated for or treated for osteoporosis according to NICE guidelines and their general practitioners informed in patient discharge summaries. Patients identified in fracture clinic had an automated letter sent to their general practitioner informing them of the current NICE guidelines and requesting the initiation of further investigations or the treatment of their suspected fragility fracture. Results: In our retrospective audit between January and April 2006, 62 patients (35 outpatients and 27 inpatients) had a fragility fracture. More than 95% (59/62) of patients were discharged without further investigating or starting secondary prevention. At 1 month post discharge, after commencing a secondary prevention protocol, 76.4% (26/34) of inpatients and 50% (13/26) of outpatients were on the recommended treatment. Long-term follow-up results are currently awaited.

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Conclusions: Osteoporotic fragility fractures are early predictors of future fractures. Distal radial fractures can occur up to 15 years earlier then those of the hip and warn of a high risk of these later fractures. Medical intervention can reduce the risk of further fractures by 50%. We show here a simple and effective multidisciplinary approach involving orthopaedic surgeons, orthogeriatricians and general practitioners in initiating the secondary prevention of fragility fractures according to current NICE guidelines. P273. Effects of cathepsin K inhibitors on bone resorption markers in estrogen-deficient non-human primates B. Pennypacker, S. Adamski, S. Rodan, G. Rodan, G. Wesolowski, L. Wehren, D. Kimmel; Merck Research Laboratories, West Point, PA, USA Cathepsin K (CatK), an enzyme in osteoclasts, degrades Type I collagen, and may play an important role in bone resorption. Detecting the action of CatK inhibitors (CatKi) non-invasively in a large animal species is essential to demonstrating their action. In this study, we use human biomarkers of bone resorption in estrogen deficient monkeys to detect the action of human CatKis that had previously been validated in enzyme inhibition and in vitro bone resorption assays, and a primary in vivo bone screen in rabbits. Ovariectomized (OVX) female rhesus monkeys (15–19 years old, 5.5–9.5 kg) were studied at 4–8 years post-OVX. They were randomized by body weight and untreated level of urinary N-telopeptides (uNTx). After 3 days of pre-treatment with vehicle, monkeys (N=∼11/each) received either vehicle or active drug orally once daily for 6 days (Days 1–6). Twenty-four hours urine specimens were collected from pans in the monkeys’ home cages on Days 0, 2, 4, 5, 6, 8, 11, and 14. uNTx was measured with manufacturers’ kits (Osteomark, Seattle, WA, USA). Compound H at 20 mg/kg/d reduced uNTx by ∼80%; the suppression resolved within one week of cessation of dosing. Compound J at 3 or 15 mg/kg/day reduced uNTx by ∼65–80%; the suppression resolved within one week. A no effect level of Compound J was identified at 0.6 mg/kg/day (uNTx reduced by ∼25–30%). Compound K at 0.6 mg/kg/day reduced uNTx by ∼65%, while smaller reductions were seen with 0.3 mg/kg/day. We conclude that urinary NTx assay in rhesus monkeys is a rapid, valid, and consistent in vivo screen for anti-resorptive activity that can differentiate compounds according to in vitro activities, and provide data similar to that eventually to be collected in humans.

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uNTx (% Difference between treated and vehicle animals) Day Cpd H Cpd J Cpd J (mg/ kg) (20) (15) (3) 0 +23 −1 +22 −81** −73** 2 −87** ** 4 – −76 −65** – −71** 5 −78** 6 −75** −79** −65** ** ** −82 −47** 8 −58 ** −14 11 − −65 14 −28 −12 – vs. Vehicle (P<0.005**; P<0.05*)

Cpd J (0.6) −7 −29* −29 −24 −40* −32* +2 –

Cpd K (0.6) +11 −59** −68** −61** −73** −59** +22 –

Cpd K (0.3) −10 −51** −46* −63** −38* −13 −6 –

P274. Relation between bone mineral density and atherosclerosis in Moroccan postmenopausal women M. Hmamouchi1, F. Allali2, H. Mâaroufi1, M. Cherkaoui3, A. Quessar3, R. Abouqal2, N. Hajjaj-Hassouni1,2; 1Department of Rheumatology, El Ayachi University Hospital, Rabat-Sale, Morocco, 2Laboratory of Biostatistic, Clinical Research and Epidemiology, Faculty of Medecine, University Mohamed V, Rabat, Morocco, 3Department of Radiology, Cheikh Zeid Hospital, Rabat-Sale, Morocco Background: Due to the lack of convincing data about the association between atherosclerosis and osteoporosis, we evaluated the relation between bone mineral density, bone turnover markers and atherosclerosis in a sample of apparently healthy Moroccan postmenopausal women. We also evaluated the relation between bone turnover markers and atherosclerosis. Materials and methods: We performed a case-control study. The cases were osteoporotic women whose disease assessed by bone mineral density measurement. Each patient was matched with nonosteoporotic women for age. All our patients were without secondary causes or medications that might affect bone density. Were performed ultrasonography of the carotid, arterial brachiocephalic trunk and femoral artery. Prevalent plaques were categorized into four groups ranging from low echogenicity to high echogenicity. Results: Twenty-seven postmenopausal osteoporotic and 27 controls were studied. The prevalence of artery plaques for any of the sites examined was not significantly different in patients with osteoporosis and in controls (70.4% vs 59.3%; p = 0.393). No significant association was observed concerning the plaque morphology echographic (p = 0.241). There were no significant differences among the cases and controls in terms of demographic, clinical and biochemical variables, bone turnover markers or in the

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prevalence of risk factors of osteoporosis or atherosclerosis. In the osteoporotic patients, the femoral neck BMD was significantly lower in the patients having an arterial brachiocephalic trunk plaques [0,814 (0.748–0.879) vs 0.739 (0.671–0.787); p=0.041]. When adjusting for age and body mass index, multiple linear regression analysis indicated the persistence of the relationship between low femoral neck BMD and arterial brachiocephalic trunk plaques (p=0.028). In contrast, no association between lumbar spine BMD and atherosclerosis at any site measured were observed. Conclusion: We concluded that there is no evidence relation between osteoporosis and atherosclerosis. However, our study suggested an association between low femoral neck BMD and arterial brachiocephalic trunk plaques in osteoporotic patient. Prospective studies are needed to investigate this issue further. P275. Dietary zinc increases the effects of essential aminoacids-whey protein supplements on serum IGF-I and on bone turnover in frail elderly A. Rodondi, P. Ammann, R. Rizzoli; Division of Bone Diseases (WHO Collaborating Center for Osteoporosis Prevention), Department of Rehabilitation and Geriatrics, University Hospitals of Geneva, Geneva, Switzerland Protein undernutrition is frequent in elderly. It contributes to the development of osteoporosis, possibly through lower IGF-I levels. Dietary zinc influences IGF-I production. We investigated the influence of dietary zinc addition on the IGF-I and bone turnover responses to essential aminoacidswhey protein supplements in frail elderly. Sixty-one elderly aged 66.7 to 105.8, with a mini nutritional assessment score between 17 and 24 were given a daily oral protein supplement of 15 g whey protein and 5 g essential aminoacids, and 550 mg calcium for 4 weeks. On a randomized, double-blind basis, they received or not 30 mg/day of zinc in addition. At baseline, mean age was 83.6±1.3 (x ± SEM) and 86.4±1.3 (NS), serum IGF-I 82.6±9.0 and 73.3±8.3 μg/l (NS), and albumin 31.0±0.8 and 30.4±0.8 (NS) in the zinc-supplemented group and the controls, respectively. During protein supplements, serum IGF-I increased to a maximum of +44% by 2 weeks. Zinc accelerated this increase with changes of +48.3±14.3 and +22.4±4.7% (p< 0.05) by 1 week, in the zinc-supplemented group and the controls, respectively. Zinc significantly decreased the serum bone resorption marker CrossLaps™ (ng/ml) [−10.3±4.9 vs +3.9±4.7% (p<0.05)] already after 1 week. Osteocalcin similarly increased in both groups, irrespective of zinc supplements. Activity of daily living (ADL score) improved by +27.0±3.1 and +18.3±4.7% (NS) in zinc supplemented and controls, respectively. In the subgroup of patients with baseline albumin lower than the group

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mean, zinc supplements significantly improved ADL score (+25.7±8.1 vs +11.9±6.5%, p<0.05). Thus, in elderly, zinc supplement accelerated the serum IGF-I response to essential aminoacids-whey protein administration, decreased a serum biochemical marker of bone resorption and improved functional performance. P276. Osteoporosis in children with back and hip pain D. Grujoska-Veta 1 , N. Nasteska 2 , M. Panajotovic 2 ; 1 University Clinic for Orthopaedic Surgery, Skopje, Macedonia, 2Prama Medica, Skopje, Macedonia Introduction: Adult osteoporosis begins in childhood. But osteoporosis that occurs in children is usually resulting of another illness, disease or its treatment. Objectives: The objective of the study was to evaluate results of randomly selected children with back and hip pain associated with osteoporosis. Materials and methods: One hundred one children who referred to the University Clinic for Orthopaedic Surgery in Skopje with back and hip pain were included in the study. Children with neurological and metabolic diseases were excluded. Fifty-six were boys (55.4%) and 45 were girls (44,6%), with an average age of 6.90 years (2–12 years). All underwent clinical examination, ultrasound of both hips, biochemical analysis of blood and plain radiography. MRI was done in 13 patients, CT in 4, bone scintigraphy in 5 and DXA in one patient. Results: They showed that osteoporosis occurred in 22 patients with back and hip pain. Underlying conditions were: paediatric rheumatic diseases [7 patients (juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis complicated by calcinosis, juvenile idiopathic)], osteoporosis (1 patient), tumor and tumor like conditions (7 patients), and traumatic disorders of leg (7 patients). DXA established osteoporosis was proved in boy with juvenile systemic lupus erythematosus. Conclusion: All the children were treated for prime illness. In order to obtain optimal peak bone mass, they were supplemented with vitamin D, well balanced calcium rich diet and according to disease, physiotherapy and weight bearing exercises. P277. Relation between the physical performance measures and the risk of peripheral fracture H. Khazzani1, F. Allali1,2, L. Ichchou1, L. Bennani1, R. Abouqal2, N. Hajjaj-Hassouni1,2; 1Department of Rheumatology, El Ayachi University Hospital, Rabat-Sale, Morocco, 2Laboratory of Biostatistic, Clinical Research and Epidemiology, Faculty of Medecine, University Mohamed V, Rabat, Morocco

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Objectives: To evaluate the relation between the physical performance measures, bone mineral density and the risk of peripheral fracture at a Moroccan female population. Materials and methods: This transversal study included 484 women in good apparent health (mean age ± standard deviation [SD], 55.1±9.6 years; range, 25–86 years). Exclusion criteria included any pathology or any treatment which can affect bone. All women answered an extensive questionnaire on their health and lifestyle included questions on sociodemographic parameters, health status, osteoporosis risk factors, and activity level. Main outcome measures: Anthropometrics and BMD of the hip (trochanter, femoral neck, Ward’s triangle, total hip) and spine. Three measures to assess physical performance: timed get-up-and-go test “TGUG,” five-times-sit-to-stand test “5 TSTS” and 8-feet speed walk “8 FSW.” Results: In univariate analysis, “TGUG,” “5 TSTS” and “8 FSW” all had a significant correlation with the trochanter, femoral neck, Ward’s triangle, total hip, lumbar spine BMD (r range from −0.20 to −0.13; p range from <0.001 to 0.005). In multiple regression models containing body mass index, hours of total activity, total calcium intake, and age of menarche, “TGUG,” “5 TSTS” and “8 FSW” were all significantly associated with BMD of various skeletal sites (p range from <0.001 to 0.026). In the group of post-menopausal patients (n=360), 11.9% had a history of peripheral osteoporosis fractures. The scores of the tests “TGUG,” and “8 FSW” were significantly higher at fractured patients vs not fractured patients (14.5±8.2 vs 11.4±4.8; p<0.001 and 5.4±2.6 vs 3.9±2.0; p<0.001, respectively). While test “5 TSTS” was close to the significance (14.8±6.4 vs 13.3±5.1; p=0.079). After adjusting for age, BMI and total hip BMD by logistic regression, a score of “5 TSTS” >12.9 s and a score of “FWST” >3.7 s, respectively, increased the risk of peripheral fracture by 2.2 and 2.8 (OR=2.2; 95% confidence interval (CI) = 1.003–5.187; p=0.049 and OR=2.8; 95% CI=1.192–6.759; p=0.018). Conclusions: This study suggested that the decrease of physical performance was associated with a decrease of BMD and an increase of peripheral fracture risk. Physical performance evaluation may help with osteoporosis prevention and treatment programs. P278. Hyaluronic acid in treatments of gonarthrosis—a case report S. Tisma-Mali1, M. Skenderovic-Culibrk2; 1Health Center, Stara Pazova, Serbia, 2Department of Physical Medicine, Medical Center, Subotica, Serbia Introduction: Osteoarthritis of the knee is one of the most common forms of degenerative rheumatism in clinical practice. In recent years treatments with hyaluronic acid

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injections is becoming more and more common. This viscoelastic substance is a normally occurring ingredient of the joint and synovial liquid. It ensures painless movement, neutralises trauma and oils the joint. This is particularly important for joints which carry body weight. Objectives: The aim of the work is to demonstrate treatment of gonarthrosis with intra-articular injections of 1.0% sodium hyaluronate. Materials and methods: The patient, a 56 year old female, was previously treated with physical therapy and NSAID’s. In the last 5 years, the occurrence of pain in her joints has become more frequent and intense and she walks with difficulty. The patient has received three injections of sodium-hyaluronate in each knee over a period of a week. The first signs of improvement appear only after 2 months, and 5 months after the date of therapy, the patient was freed from pain, with full knee join movement preserved. The effects recede after 18 months. Treatment is repeated at this point in the same manner. At the control check after five months, the knee movement is good, pain rare and of low intensity. The patient is not taking NSAID’s. Conclusion: This is a simple yet effective method of treatment for gonarthrosis is particularly suitable in cases where all other treatment options have been explored or have counter indications. P279. How could alendronate impact on postmenopausal women’s lives with osteoporosis? E. Mir, M. Mirsafa, A. Hossein-Nezhad, H. Adibi, B. Larijani; Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran Objectives: The purpose of this study was to evaluate Alendronate efficacy on quality of life, BMD and similar variables related to osteoporotic patients’ health. Materials and methods: Two hundred ninety-six postmenopausal osteoporotic women, 108 in Alendronate group with the mean age of 62.6±6.8 years, randomly selected from the original IMOS (Iranian Multicenter Osteoporosis Study). The control group with 188 participants with the mean age of 62.9±7.7 years from BMD unit of one of the University Hospitals in Tehran enrolled the study and followed from 2002–2006. All participants took similar amounts of calcium and vitamin D supplements and tried to be comparable at baseline in age, habits, socioeconomic status and BMD at the spine and the hip. The people in Alendronate group has been advised for using the agents correctly by educators up to drug protocol and the ones with underlying risk factors for GI disturbances or documented esophagitis or gastric disorders excluded. Results: In Alendronate group 81–100% has been persisted with the agent in the first year of treatment, with lower rates of persistence between 70–92% in the third year of treatment.

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This rate was 80.6% in calcium and Vitamin D group with no significant difference. There was a significant BMD progress in Alendronate group about 80.6 versus 50% in control group. Moreover 19.4% indicated no progress in drug group and 25% has been deteriorated in control group, P value=0.016. A vigorous pain relief was also observed in Bisphosphonate group, 33.3% compared to 3.2% in controls, P value=0.001. The well being sensation has been reported appropriate in 7.6% of Alendronate group and 4.8% in the other group which showed significant difference. However there was no considerable difference in other indicators of Quality of Life between the two groups. Moreover drug Complications such as obstipation and gastritis have not been significantly varied between two compared groups. Conclusions: Alendronate has been demonstrated a vigorous impact on BMD and pain relief in studied group. The GI adverse effects of this drug have been revealed no significant difference between the two groups.This may recommend the necessity of patients’ education and alert initiating with these oral agents. P280. A pilot study to create an international registry of fragility fractures in the young On behalf of the Study Group on International Registry of Fragility Fractures in the Young (M. Bayer, S. Bechtold, D. Chlebna-Sokol, F. Corona, F. Falcini, C. Langman, R. Lorenc, J. Konstantynovicz, O.D. Messina, C. Netelenbos, J.E.H. Pruijs, F. Zulian), M.L. Bianchi1, S. Vai1, A. Bossi2; 1 Bone Metabolism Unit, Istituto Auxologico Italiano IRCCS, Milano, Italy, 2Department of Biometry and Statistics, University of Milano, Milano, Italy Objectives: Fragility fractures are the most relevant manifestation of osteoporosis in adults. In the young, there is no systematic information on fractures due to bone fragility in primary and secondary osteoporosis. Although young people affected by reduced bone mass are less numerous than adults, their number is increasing. Thus, a more precise evaluation of bone fragility fractures in the young is needed. Materials and methods: A 1-year pilot study was conducted to verify the feasibility and validity of a Registry. A simple form was studied to encourage the participation of both specialized centers and general hospitals. The study was conducted in Italy, Poland, The Netherlands, Czech Republic, Germany, United States, Argentina. The Registry is based on two forms for each fracture: Form 1 to be filled immediately after the fracture; and Form 2 to be filled 6 months later. Form 1 records auxological parameters, primary disease and therapy, calcium intake, fracture data, bone density. Form 2 records the consequences of the fracture.

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Results: Two hundred fifty-six patients had one or more fractures during 1-year of observation. The main disease groups were: osteogenesis imperfecta (42), idiopathic juvenile osteoporosis (14), secondary osteoporosis (150), other (rickets, etc.) (50). 362 fractures were reported (71 events were multiple fractures): 36 femur, 24 vertebrae, 72 lower limbs, 143 upper limbs. 36 additional fractures after the first were observed. Vertebral fractures were present in 15% of the patients on long-term glucocorticoid therapy, but only in 1.8% of patients never treated with steroids. Patients with lower bone density (Z-score<−2) had the highest percentage of multiple and recurrent fractures. In the six centers collecting the higher number of fractures, the fracture incidence ranged from 2 to 25% of the young patient population followed during the year of study. Conclusions: This is the first attempt to create an international Registry on fragility fractures in the young. Such a project would provide a sound base to understand the consequences of low bone mass and to estimate the prevalence of fractures in children and adolescents. The pilot study received a scientific grant by IOF (International Osteoporosis Foundation). P281. Bone effects of a cathepsin K inhibitor in the adult estrogen deficient rabbit B. Pennypacker, T. Cusick, P. Masarachia, L. Wehren, D. Kimmel; Merck Research Laboratories, West Point, PA, USA Cathepsin K (Cat K), an enzyme that degrades Type I collagen, is prominent in osteoclasts, and may play an important role in bone resorption. Compound J (J) reversibly inhibits human Cat K with an IC50 of 0.2 nM, with greater than 4,000-fold selectivity for Cat K vs. Cathepsins B, L, and S; its potency on rabbit Cat K is 1.5 nM. The goal is to contrast the effect of J in an estrogen deficient animal model with cancellous and cortical bone remodeling, to that of alendronate (ALN). Adult (7 months old, 3.9 kg) rabbits were OVX’d (N=48) or Sham-OVX’d (N=12) during early June. OVX rabbits were given J (0, 2, or 10 mg/kg, orally once daily [N=12 each]) or ALN (0.125 mg/kg; subcutaneous, 3X/wk [N=12]) for 27 weeks. After in vivo dual calcein labeling, all were necropsied. Lumbar vertebrae (LV) 2–4 and whole femurs were excised and fixed in 70% ethanol. LV3 was DXA-scanned. LV4 was sectioned parasagitally at 6 μm and analyzed for cancellous (c) bone formation surface. 100 μm sections of the mid-femur were analyzed in cross-section for endocortical (e), and periosteal (p) mineralizing surface (MS/BS; double+half-single label), mineral apposition rate, and number of double labeled Haversian systems (HS)/mm2. Significant OVX-induced bone loss occurred in LV3. This loss was partially prevented by 2 mg/kg J and fully prevented

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by 10 mg/kg J and ALN. This bone loss was accompanied by increased formation rate at all surfaces and in Haversian bone. 2 mg/kg J partially blocked (P<0.1), and both 10 mg/kg J and ALN completely blocked OVX-induced bone loss (P<.01) in LV3. While ALN reduced MS/BS at cancellous and endocortical surfaces and reduced Haversian labeling, neither dose of J affected MS/BS at these surfaces. Mineral apposition rate at any surface was unaffected by treatment with J. These results suggest that estrogen deficiency bone loss is prevented to a similar extent by Cat K inhibition and ALN. In contrast to the suppression of bone formation observed with ALN, inhibition of resorption by a Cat K inhibitor does not appear to be accompanied by suppression of bone formation. P282. The risk of osteoporosis to the hemiparesis patients A.M. Bumbea, A. Bighea, R. Popescu, S. Pătru; Department of Rehabilitation, University of Medicine and Pharmacy, Craiova, Romania Objectives: The study tries to assess the risk of osteoporosis (OP) at the patients with hemiparesis according to the date when the stroke occurred. Materials and methods: This clinical study was made on a group of 29 patients with stroke, where 11 of them had the stroke up to a year and 18 had it from 1–7 years. The requirements to enter the study: the patients had to be younger than 65, who can stand without support, the absence of severe cardiovascular complications, without OP before stroke. The study lasted more than a year in Neuropsychiatry Hospital, Department of Neurological Rehabilitation, Craiova: April 2005– November 2006. The patients were clinically assess (physical examination), radiological (modifying of height and form of vertebral bone), the determination of bone mineral density (BMD) for confirming loss of bone or osteoporosis, osteodesitometry at the heel. The evaluations were made at the beginning, at the month 6, month 12 and the end of the study, using the same methods. At the beginning both groups received a program of OP rehabilitation and prevention with bisphophonates treatment at patients with bone loss or OP. Results and Conclusions: At the beginning of the study we observed that the patients, who had hemiparesis for more than 1 year, had a lower T score compared with those with a sooner stroke. After a rehabilitation and medicaments treatment the decrease rate of the T score was slower/stationary at the patients with more then 1 year old hemiparesis while at the patients with a recent stroke we observed a stationary/ increased T score with an average of 0.4.

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P283. Efficacy and tolerability of avocado/soybean unsaponifiables (ASU) in osteoarthritis of the knee treatment A.M. Bumbea, A. Bighea, R. Popescu, S. Pătru; Department of Rehabilitation, University of Medicine and Pharmacy, Craiova, Romania Objectives: This clinical study tries to assess the efficacy and tolerability of ASU in the treatment of patients with knee osteoarthritis. Materials and methods: The study involved 50 outpatients of both genders aged 45 years or more that suffer from femoro-tibial osteoarthritis defined by the clinical and radiological criteria of the ACR. They fulfilled all inclusion criteria and were capable of following the instructions. The study was developed during June–November 2006, each patient received 300 mg daily of ASU for 3 months. NSAID’s were not allowed drugs 5 days before entering the study and during it. After entering the trial acetaminophen intake was allowed if it was necessary. Efficacy and tolerability assessments were made at months 1, 2 and 3 by the same investigator. The efficacy was evaluated using: Lequesne index, WOMAC index and global assessment of knee osteoarthritis on VAS. The tolerability parameters were: the incidence of adverse events and overall tolerability. Results and conclusions: All efficacy parameters were significantly improved between baseline and month 3. The mean of Lequesne index decreased from 8.1 to 4.4 and the mean of global assessment of knee osteoarthritis on VAS decreased from 56 to 14 mm. There were no adverse effects and the overall tolerability was good to excellent for all patients. P284. Bone effects of cathepsin K inhibitors in the growing rabbit B. Pennypacker, S. Rodan, G. Rodan, C. Black, R. Oballa, L. Wehren, D. Kimmel; Merck Research Laboratories, West Point, PA, USA Cathepsin K (Cat K) is prominent in osteoclasts, degrades Type I collagen, and may play an important role in bone resorption. However, it has significant interspecies sequence variation, rodent Cat K being only 88% homologous to human Cat K. While Cat K of higher species (rabbit and non-human primate) is 94–98% homologous to human Cat K, its low homogeneity with rodent Cat K presents challenges for efficient in vivo testing of human Cat K inhibitors in the usual rodent bone test models. Female rabbits (7 weeks old, 1.4–1.5 kg) were used as the tertiary screen for reversible human Cat K inhibitors previously proven efficacious in enzyme inhibition and in vitro bone resorption (pit) assays. Rabbits (N=11/grp) were treated orally for 10 days with multiple doses up to 30 mg/kg/day of the

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Cat K inhibitor, always with comparison to vehicle and 0.1 mg/kg/day alendronate (ALN) subcutaneously. The whole right femur was taken at necropsy. The distal 6 cm of the femur was DXA-scanned (Hologic 4500A). Bone mineral density analysis (BMD; Table) focused on the region located 0–3 cm from the distal end. This “rabbit Schenk” assay, patterned after the growing rat model used for testing anti-resorptive efficacy of bisphosphonates(1), relies on inhibiting normally ongoing resorption in rapidly-growing animals at both the periosteum and the distal aspect of trabeculae in the marrow cavity of the metaphysis of long bones. Histologic examination of specimens from selected experiments showed that both ALN and Cat K inibitors were active at these sites. ALN, the positive control, consistently increased BMD by 11–22%. This assay identified human Cat K inhibitors that increased BMD in a dose-effect fashion, and were generally as efficacious as ALN. On the basis of these results, compounds J and K were tested in estrogen deficient non-human primates, where they reduced bone resorption markers. We conclude that the rabbit Schenk assay is a valid and consistent in vivo screen for anti-resorptive activity. When the rat is inappropriate, the rabbit can serve as a rapid, costeffective, and reliable intermediate model before non-human primate testing. (1) Schenk et al (1986) Calc Tiss Int 38: 342–349

P285. Treatment effects of vitamin D3 8400 IU once weekly on elderly subjects with vitamin D insufficiency N. Binkley1, R. Recker2, A. Holst3, J. Walliser4, P. Lips5, M. Pfeifer6, K. Krohn7, M. Liu8, D. Cohn8, L. Wehren8, D.A. Papanicolaou8; 1University of Wisconsin, Madison, USA, 2 Creighton University, Omaha, USA, 3Clinical Research Hamburg, Hamburg, Germany, 4Hospital Angeles del Pedregal, Mexico, Mexico, 5Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands, 6Klinik Der Fürstenhof, Bad Pyrmont, Germany; 7MCR Rheumatology Associates, Pittsburgh, USA, 8Merck Research Laboratories, Rahway, New Jersey, USA Vitamin D deficiency is common in the elderly. This study examined if treatment with vitamin D3 8400 IU once weekly for 16 weeks would increase serum 25(OH)D to adequate levels in subjects 70 years or older who had vitamin D insufficiency (25(OH)D ≥6 but ≤20 ng/ml). The study was conducted in 226 generally healthy subjects [mean age ± SD: 78.0±6.4] from five countries recruited between October 2005 and February 2006. Subjects were randomly allocated in a 1:1 ratio to receive either vitamin D3 8400 IU once weekly or placebo; 25(OH)

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D serum levels were analyzed at a central laboratory by HPLC. Baseline serum 25(OH)D levels were similar in the 2 treatment groups. [Mean±SD: vitamin D=14.3±3.9; placebo =14.4±4.3]. Following 16 weeks, 25(OH)D levels increased from baseline by 11.9±0.6 ng/ml in the vitamin D group and decreased from baseline by −1.1±0.4 ng/ml in the placebo group (p<0.001). The between-group difference was 13.0 (95% CI, 11.6; 14.4). At 16 weeks 90% of treated subjects reached 25(OH)D levels ≥20 ng/ml vs. 8% of subjects on placebo; none of the treated subjects had 25(OH)D levels <9 ng/ml vs. 14% of subjects on placebo. Treatment with vitamin D3 was safe and well tolerated. No subject reached 25(OH)D levels >60 ng/ml through the study. No treatment differences were observed for serum calcium, phosphate, creatinine, 24-h urine creatinine and creatinine clearance after 16 weeks of treatment relative to placebo. PTH levels decreased by 7.5% in the vitamin D group and increased by 9.2% the placebo group (between-group difference −16.8%, p=0.003). Twenty-four hours urine calcium levels increased by 16.5% in the vitamin D group and decreased by 1.3% in the placebo group. A trend was observed between groups (p=0.080). A similar percentage of subjects had abnormal laboratory at baseline and at week 16. Hypocalcaemia, hypercalciuria, and abnormal creatinine levels did not differ between groups. In conclusion, treatment with vitamin D3 8400 IU was efficacious at increasing 25(OH)D levels and safe in this subject population. P286. Quantitative ultrasound of bone and fracture prevalence in Bulgarian female population A. Shinkov; University Hospital of Endocrinology, Sofia, Bugaria Quantitative ultrasound of bone (QUS) was developed in the 1980s of twentieth century as a cheap and convenient substitute of X-ray bone densitometry. QUS however does not measure bone mineral density (BMD). The parameters measured by QUS depend on BMD, bone elasticity, bone water content, trabecular continuity etc. and are related to fracture risk. The aim of the study was to investigate the known fracture prevalence in a group of presumably healthy women and to seek a correlation between the fracture prevalence and QUS and other factors. One thousand five hundred and seven healthy women aged 40–89 years, mean 54.5±10.3 years, 406 (26.9%) with preserved menstrual cycle and 1,101 (73.1%) postmenopausal were questionnaired and radius speed of sound (SOS) was measured by Sunlight Omnisense unit. Subjects with known

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bone metabolism influencing disorders and therapies and early menopause were excluded. Two hundred and fourteen (14.2%) of the subjects had suffered fractures in the past, 140 (9.3%) single and 76 (4.9%) —multiple. The total number of fractures reported was 338. Ninety-nine being vertebral and 239—non-vertebral fractures. Fracture prevalence increased with age reaching 60% in the eldest group. SOS values were significantly lower in subjects with fractures. The mean number of suffered fractures increased with age and with lower SOS. Mean SOS in subjects with nonvertebral fractures was higher and mean age was lower (p<0.05) than in those with vertebral ones. Multiple stepwise regression analysis revealed significant correlation of vertebral fractures (p<0.001) with SOS, subjects’ age and height and menopausal status. Coles’ fractures were correlated significantly with SOS and age (p<0.05) and all non-vertebral fractures were correlated (p<0.05) with SOS, height, age, menopausal status and smoking. In ROC the AUC for SOS was low (0.122–0.288). Menopausal status and age demonstrated highest AUCs and predictive strength for all types of fractures. In conclusion, low distal radius SOS is related to higher fracture prevalence but the sensitivity and specificity of the method are low and forearm SOS cannot be used as a stand-alone predictor of fracture risk. P287. Clinical significance of the measurement of bone mineral density in femoral neck and total hip S. Suarez, R. Ramenzoni, M.D. Messina, D.M. Andrada, C. Dotzanica, A.M. Riopedre, O.D. Messina; Rheumatology Section, Cosme Argerich Hospital and CIRO Clinical Research Medical Center, Buenos Aires, Argentina During the last 10 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 occurr 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 46 postmenopausal women (aged 50–80 years) (DXA, Hologic Delphi). Patients were classified based on bone mineral density results according to WHO criteria. (T score values, >−1.00 normal, between −1 and 2.5 osteopenia, <2.5 osteoporosis) considering both femoral neck and total hip.

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Results: The categorization coincided in 65% of the patients using either 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. One percent 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 femoral neck in 1/3 of the patients and that considering femoral neck mineral density is still very important. P288. Role of several osteoporosis risk assessment tools when applied to quantitative ultrasound of the heel. Proposal and validation of a new score G. Osella1, M. Ventura1, A. Dovio1, E. Palmas1, D. De Feo2, R. Vitetta1, A. Angeli1; 1Clinica Medica, Dipartimento di Scienze Cliniche e Biologiche, Università degli studi di Torino, Torino, Italy, 2Procter and Gamble, Roma, Italy Objectives: To verify if the anamnestic scores evaluating postmenopausal osteoporosis risk factors are also appropriate for the diagnosis based on quantitative ultrasound (QUS) and to suggest and validate a new score related to QUS. Materials and methods: OST, ORAI, OSIRIS, NOF, ABONE, AMMEB and pBW (patient body weight) were calculated in 352 healthy postmenopausal women evaluated with a QUS of the heel using the Achilles-Express (GE-Lunar) instrument. Combining the three variables better correlated with Stiffness we developed a new risk score (MAW: Menopause duration, Age, Weight), validated on a sample of 4925 women, extracted from the original database of the ESOPO study. The −5 cut-off of the index yielded the better sensitivity and specificity in order to identify the patients with Stiffness in the osteopenic and osteoporotic range. The AUROC (Area Under the ROC curve) of the single scores ranged from 0.57 and 0.71 when calculated for T-score Stiffness <−1 and from 0.56 and 0.65 using the T-score ≤−2.5. AUROC and 95% confidence intervals of the MAW score were 0.71 (0.66–0.76) for the T-score <−1 and 0.64 (0.59–0.69) for the T-score ≤−2.5. The AUROC of MAW score, applied to the validation sample (ESOPO), was 0.67 (0.65–0.68) for the T-score <−1, and 0.69 (0.68–0.70) for the T-score ≤−2.5. The correlation with Stiffness was r=0.36 (p<0.0001). Sensitivity, specificity, positive predictive value and negative predictive value for the −5 cut-off of the MAW

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resulted 71, 64, 82 and 49% to identify the osteopenic + osteoporotic subjects and 78, 44, 26 and 89% to identify the osteoporotic ones. These characteristics remained unchanged applying the score to the validation sample (negative predictive value for osteoporosis 89%). In conclusions, AUROC, sensitivity and specificity of the analyzed scores, used in reference to the QUS, are comparable to those reported in the literature when applied to DXA technique, but our results question the utility of these risk assessment tools. No score has a good diagnostic accuracy (i.e. AUROC >0.90) and only a few (MAW and OSIRIS) achieve the threshold of AUROC 0.70, considered the lower limit to give moderate accuracy. The MAW score, however, is provided of good negative predictive value (about 90%) for excluding the osteoporosis with the QUS of the heel. P289. Bone mineral density reference values for Indonesian men and women G. Tirtarahardja1, B. Setyohadi2, I.A. Rachman3, J.M.F. Adam4, M. Susanti5, K. Suheimi6, Z.N. Heli7, S. Darmasetiawan8, L.S. Weynand9, Q. Zhou10; 1Jakarta Osteoporosis Center, Medistra Hospital, Jakarta, Indonesia, 2Department of Internal Medicine, University of Indonesia, Jakarta, Indonesia, 3Department of Obstetry and Gynecology, Universty of Indonesia, Jakarta, Indonesia, 4Department of Internal Medicine, University of Hasanuddin, Makassar, Indonesia, 5Imuno-Endocrinology Laboratory, University of Indonesia, Jakarta, Indonesia, 6Dr Jamil Hospital, Padang, Indonesia, 7Ulin Hospital, Banjarmasin, Indonesia, 8Gatot Subroto Army Hospital, Jakarta, Indonesia, 9 GE Healthcare, Madison, WI, USA, 10GE Healthcare, Shanghai, China A total of 2223 healthy Indonesian subjects were studied, including 890 men and 1333 women aged 19–88 years. Each individual completed a health status questionnaire; factors known to affect BMD were excluded from the study. BMD values at the L1–L4 spine and proximal femur sites were measured with Lunar DXA densitometers (1 Expert, 4 Prodigy, 2 Bravo, 2 DPX GE Healthcare, Madison, WI, USA) at nine centers in Indonesia. Precision error was assessed on all eight devices by repeat measurements of GE-Lunar spine phantom once weekly during data collection. Young adult (YA) reference values were defined separately as the mean BMD for women and men aged 20–39 years. T-scores were calculated as: (subject’s BMD—YA BMD)/ standard deviation). The best-fit regression model was used to calculate age-related BMD reference curves. Indonesian reference values were compared to USA Caucasian reference data provided by the manufacturer.

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Results: Peak BMD for all skeleton sites in women occurred between the ages of 30–39 years, while peak BMD at all femur regions in men was observed at age 20–29 years. Spine L1–L4 BMD in men remained relatively stable with age. Mean L1–L4 BMD in men aged 20–39 years was 1.1% lower than women’s L1–L4 BMD at the same age. Women’s mean BMD values decreased 17–26% from ages 20–29 to 80–89 years. In comparison, mean BMD in males decreased 10–21% at the femur from ages 20–39 to 70–79 years, while spine L1–L4 BMD remained stable. Osteoporosis prevalence in women, as defined by the WHO at any spine or femur site, increased from 23% at age 50–80 years to 53% of age 70–80 years. Osteoporosis prevalence at any site in women was four times higher than in men. Young Adult (age 20–39 years) BMD of this population was lower than reported for USA Caucasian men and women: 10 and 6% lower at the spine; 8 and 5% lower at the total femur, respectively. Conclusion: In this study, the first Indonesia reference database for men and women was established for spine and hip BMD. The accurate T-scores and Z-scores for the Indonesian population are now available for improving diagnosis. P290. The possible role of vitamin D and falls in relation to lower fracture rates in rural communities K.M. Sanders, A.L. Hayles, M.A. Kotowicz, G.C. Nicholson; Department of Clinical and Biomedical Sciences, Barwon Health, The University of Melbourne, Victoria, Australia We previously reported lower fracture rates in our rural population. BMD did not differ (femoral neck BMD, p=0.56) although rural residents reported lower prevalence of arthritis (p=0.006) and serum vitamin D was 8% higher (p=0.16). Fall frequency and characteristics may be protective but falls ascertainment is often suboptimal, relying on lengthy recall in elderly people. This analysis investigates whether falls risk differs between urban and rural participants using standardised, monthly falls ascertainment. The current analysis is part of an RCT, due for completion in 2008, to investigate whether an annual dose of vitamin D (500,000 IU cholecalciferol) reduces falls and fractures compared with placebo in women aged >70 years. Falls were ascertained from June 2003 to December 2005 providing 1,727 person-years follow-up (median 9 months range: 1–30). The median age of participants in both groups is 76 years (range: 70–93). Baseline serum vitamin D and PTH levels were measured in 30 rural and 81 urban participants. A higher proportion of rural participants have fallen [rural vs urban: n=295/649 (45%) vs n=399/1004 (40%), respectively; p=0.022]. Using Kaplan Meier, time-to-fall did not differ between rural and urban [12.0 months (95%CI: 11.4–12.6)

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vs 12.7 months (95% CI: 12.2–13.3 months), respectively p=0.14]. Sixty-one women sustained a fracture [rural 22/646 (3.4%) vs urban 39/997 (3.9%); p=0.60]. Time-to-fracture was similar (rural: 12.2 months: 95% CI: 11.7–12.6 and urban: 13.0 months: 95% CI: 12.5–13.4; p=0.62). Baseline serum vitamin D was 17% higher and PTH 16% lower in rural participants (rural vs urban: vitamin D: 58.5±20.3 vs 49.8± 13.8 nmol/l; lnPTH 1.34±0.48 and 1.59±0.49; p=0.016). The results support the higher falls rate reported in rural Poland. The baseline vitamin D data suggest it may be protective of falls-related injury. The data are consistent with a proposed role of vitamin D in “fast twitch” muscle fibres helping to “save” oneself during a fall. Since 90% of hip fractures result from a fall, the reliable falls ascertainment and characterisation could facilitate development of effective and economical preventative strategies, including high dose annual vitamin D supplementation. P291. Prevention of bone loss in patients with a spinal cord section with weekly alendronate: a pilot study R. Hizem1, I. Delaunoy1, M. Ventura1, P. Bergmann2; 1 Centre de Traumatologie et de Réadaptation (CTR), Bruxelles, Belgium, 2Department of Nuclear Medicine and Laboratories of Clinical Chemistry and of Experimental Medicine, CHU Brugmann (ULB), Brussels, Belgium Objectives: In patients with a spinal cord section, BMC decreases weekly by 0.7 to 1% in the pelvis and by 0.3 to 0.5% in the legs, and fracture risk is increased. We conducted this preliminary study to examine the effect of weekly oral alendronate on the increased bone resorption and bone loss secondary to disuse. Patients and methods: Thirteen patients (one women and 12 men; median age: 34; range: 23–68) with a recent spinal cord section were included. They were treated with alendronate 70 mg weekly for 6 months. Regional BMC and BMD of the hips were measured by DXA (Hologic). We also followed serum and urinary calcium, iPTH (Sorin) and urinary CTX (Nordic Bioscience). Results: The loss of BMC was 11.5±−6 (2.2)% for the pelvis and 7.3±−4.7 (1.4)% for the lower legs. As compared with an untreated group who had lost 24 and 12%, respectively, at the pelvis and lower limbs, the difference was significant for the pelvis (p<0.01, Mann Whitney). The BMD of the total hip decreased by 6.7±−6.5 (2.2)% and that of the femoral neck by 8.8±−6.9 (2.3)%. Serum calcium did not change during treatment, but iPTH increased significantly (p < 0.01, Kruskall–Wallis). Urinary calcium and CTX decreased significantly during treatment (p<0.01). During treatment, PTH was negatively correlated with serum calcium and urinary CTX (p<0.05), serum calcium was positively

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correlated with urine CTX (p<0.05) and urine calcium and CT were highly correlated (p<0.01). The loss of bone at 6 months was weakly associated with the maximal decrease of CTX during the first month, with a significant correlation for the femoral neck BMD only (p<0.05, n=7). Conclusion: This study on a small number of patients suggests that weekly alendronate can mitigate bone loss in disuse osteoporosis. However, the inhibition of bone loss was not complete, and there was an important inter-individual variability: the classical 70 mg weekly dose could be insufficient in some of the patients. The possible predictive value of a measurement of a resorption marker on the effect on bone loss should be further evaluated in a larger series, since it could allow an early dose adjustment. P292. Long-term normalization of bone remodelling with a single infusion of zoledronic acid in a severe, multifocal, biologically active Paget’s disease of bone, resistant to treatments: a case report B. Uebelhart, P. Casez, R. Rizzoli; Service of Bone Disease, WHO Collaborating Center for Osteoporosis Prevention, Department of Rehabilitation and Geriatrics, Cantonal Hospital, Geneva, Switzerland Bisphosphonates are the first choice in the treatment of Paget’s disease of bone. Their efficacy is well established, but the issue of resistance to bisphosphonate therapy has been repeatidely raised. We report the case of a white Caucasian woman with a 28-year history of Paget’s disease of bone, diagnosed in 1977 on a typical pelvis X-ray examination. Family history was positive with a brother suffering from a Paget disease of bone. In 1987, the disease was found to affect skull, pelvis, sacrum, right proximal femur and 3 lumbar vertebraes. At that time, serum total alkaline phosphatase was 7-fold above upper limit of normal range and urinary hydroxyproline-to-creatinine 5-fold. Since 1987, different treatments, including calcitonin and the bisphosponates etidronate then clodronate, were administered without significant biochemical response. Since 1992, the bisphosponate pamidronate was administered iv at a dose of 180 mg every 6 months, and then 240 mg every 6 months in 1997. Despite that, the decrease in bone remodelling markers was minute, and the effect was rapidly lost. None of the treatments used since 1987 was able to normalize bone remodelling. In October 2002, the patient received a single 4 mg iv zoledronic acid. One month later, deoxy-pyridinoline was normalized and remained so for more than 4 years. Total alkaline phosphatase decreased from 830 IU/l to 73 IU, and followed the same pattern as the bone resorption marker.

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Thus this patient with severe, multifocal and biologically active Paget’s disease of bone, did not show significant responses to various bisphosphonates, but her bone remodelling was fully and steadily normalized by a single injection of zoledronic acid.

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control group (CI=95%, P<0.05). However there was no significant increase at L1–4 and femoral neck BMD among Ga and Gr groups in compared to control group (CI=95%, P>0.05). All BMD values in Ga and Gr groups had significant increase in compared to control group in four regions. No significant difference was found between Ga and Gr groups (CI=95%, P>0.05). Conclusion: Bisphosphonates combined with calcium and vitamin D are effective in the treatment of postmenopausal osteoporosis. There was no significant difference in increasing BMD values between ALD and RIS therapy. P294. Duration of compliant bisphosphonate use and risk of osteoporotic fractures F.J.A. Penning-van Beest1, M. Olson2, R.M.C. Herings1,3; 1 Pharmo Institute, Utrecht, The Netherlands, 2Novartis Pharma, Basel, Switzerland, 3Department of Pharmacotherapy and Pharmacoepidemiology, University of Utrecht, Utrecht, The Netherlands

P293. The effectiveness of bisphosphonates in the treatment of postmenopausal osteoporosis: a prospective controlled study S. Esmaeilzadeh, H. Basat, S. Aký, N. Eskiyurt; Department of Physical Medicine and Rehabilitation, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey Objectives: Several pharmacologic agents can be used in treatment of postmenopausal osteoporosis. Bisphosphonates (BPs) are structurally analogues of pyrophosphate which have potent inhibitory effects on osteoclastic bone resorption. Alendronate (ALN) and risedronate (RIS) are the most widely used BPs. The aim of this study was to research the efficacy of treatment with BPs in increasing bone mineral density (BMD) and to compare the effectiveness of ALN and RID therapy. Materials and methods: Among patients who referred to the Diagnosis and Treatment Unit of Osteoporosis, 237 patients (mean of age: 62.2±9.61) were included in the study and divided into three groups: (Gc: Control group n=77; Ga: Alendronate group n=88; Gr: Risedronate group n=72). The Ga group received Alendronate 70 mg and the Gr group received 35 mg once weekly for 12 months. All patients (Gc, Ga and Gr) received calcium (1,000 mg) and vitamin D (400 IU) daily for 12 months. Patient’s BMD were measured by Dual Energy X-ray Absorptiometry (DXA) in four different regions (L3, L1–4, femoral neck and total femur) before and after 1 year treatment. At the end of the treatment period, BMD differences were calculated and the results were compared between three groups in four different regions by ANOVA method separately. Results: There was significant increase at L3 and total femur BMD among Ga and Gr groups in compared to

Objectives: To investigate the relation between duration of compliant bisphosphonate use and risk of osteoporotic fractures. Materials and methods: The Pharmo database, including drug-dispensing and hospital records of more than two million subjects in The Netherlands, was used to identify new female users of alendronate, risedronate or etidronate, aged ≥45 years or with diagnosed post-menopausal osteoporosis in the period of January 1996–June 2004. Within this cohort a matched casecontrol study was performed. Cases were defined as patients who were hospitalised for an osteoporotic fracture at least 3 months from start of bisphosphonate use and were matched to ten controls without a fracture by duration of follow-up. For cases and controls with at least one bisphosphonate dispensing in the 2-year period before the outcome date (fracture date in cases and random date in controls), the duration of compliant bisphosphonate use (i.e. a Medication Possession Ratio ≥80%) preceding the outcome date was determined. Results: 14,760 new female users of bisphosphonates were identified, of which 387 fracture patients fulfilled the inclusion criteria. Two hundred twenty-one cases had <1 year compliant bisphosphonate use at the time of fracture, and 94, 33 and 39 cases had compliantly used bisphosphonates for 1–2, 3–4 and 5–6 years, respectively. Increasing duration of compliant bisphosphonate use was associated with a decreased risk of fractures (p trend<0.01). Adjusted for age, 1–2 years of compliant bisphosphonate use and 3–4 years of compliant bisphosphonate use decreased fracture risk by 20 and 50%, respectively, compared to <1 year of compliant bisphosphonate use (OR 0.81; 95%CI 0.61–1.07 and OR 0.49; 95%CI 0.32–0.76, respectively). Unexpectedly, 5–6 years of compliant bisphosphonate use was no longer associated with a decreased risk of fractures compared to

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<1 year of compliant bisphosphonate use (OR 1.04, 95% CI 0.62–1.74). Conclusion: These results show a direct link between duration of compliant bisphosphonate use and fracture risk, and confirm the importance of continuing the use of bisphosphonates to maintain optimal bone protection. The advent of bisphosphonates with longer, more convenient dosing regimes is likely to facilitate better long-term compliance. P295. Vitamin D inadequacy in Belgian postmenopausal women A. Neuprez, O. Bruyère, J.-Y. Reginster; Department of Epidemiology, Public Health and Health Economics, University of Liege, Liege, Belgium Objectives: Inadequate 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 postmenopausal Belgian women. Opinions with regard to the definition of vitamin D deficiency and adequate vitamin D status vary widely and there are no clear international agreements on what constitutes a level of vitamin D inadequacy. Materials and methods: Assessment of 25-Hydroxyvitamin D [25(OH)D] was performed in 1195 Belgian postmenopausal women aged over 50 years. Main analysis has been performed in the whole study population and according to the previous use of vitamin D supplements. Four cut-offs of 25(OH)D inadequacy were fixed: <80 nmol/l, <75 nmol/l, <50 nmol/l and <30 nmol/l. Results: Mean (SD) age of the patients was 76.9 (7.5) years, body mass index was 25.7 (4.5) kg/m2. Level of 25 (OH)D was 52.5 (21.4) nmol/l. In the whole study population, the prevalence of 25(OH)D inadequacy was 91.3, 87.5, 43.1 and 15.9% when considering cut-offs of 80, 75, 50 and 30 nmol/l, respectively. Women who used vitamin D supplements, only or combined with calcium supplements, had higher levels of 25(OH)D than non-users. There is a significant negative correlation between age and serum 25(OH)D (r=−0.23; P<0.05). Vitamin D level varied with the season in which it was sampled but did not reach statistical signification (P=0.09). Conclusions: This study points out a high prevalence of vitamin D inadequacy in Belgian postmenopausal women even among subjects receiving vitamin D supplements. We believe that it is important to redefine the amount of vitamin D intake necessary to maintain serum 25(OH)D to an adequate level.

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P296. Long-term beneficial effects of strontium ranelate on the quality of life in patients with vertebral osteoporosis (SOTI study) P. Marquis1, C. Roux2, M. Diaz-Curiel3, C. Cormier4, G. Isaia5, J. Badurski6, J.D. Wark7; 1Mapi Values, Boston, USA, 2 Service de Rhumatologie B, Hôpital Cochin, Paris, France, 3 Jimenez Diaz Foundation, Madrid, Spain, 4Service de Rhumatologie A, Hôpital Cochin, Paris, France, 5Divisione Universitaria di Medicina Generale, Torino, Italy, 6Polish Center of Osteoporosis, Bialystok, Poland, 7 Royal Melbourne Hospital, Parkville Victoria, Australia. Objectives: In osteoporotic postmenopausal women with prevalent vertebral fracture, quality of life (QoL) is severely impaired. After 3 years of treatment, in a prespecified analysis, strontium ranelate was demonstrated to prevent QoL deterioration in women with vertebral osteoporosis.(1) The aim of this study was to assess the long-term effects of strontium ranelate, over 4 years on health-related quality of life (HRQoL). Materials and methods: 1,240 Caucasian postmenopausal osteoporotic women included in the double-blind placebocontrolled SOTI study (618 receiving strontium ranelate 2 g/day and 622 receiving a placebo) were followed for 4 years. HRQoL was assessed every 6 months using both the generic questionnaire SF36 and the specific module QUALIOST® (23 items specific for vertebral osteoporosis, with a Global score and two sub-scores: physical and emotional) in patients with a baseline and at least one post baseline assessment for the SF36 and QUALIOST® questionnaires. The QUALIOST® questionnaire presented an excellent internal reliability and reproducibility and a satisfactory concurrent validity with SF36. Results: Baseline characteristics were similar betweengroups (mean age ± SD: 69.7±7.3 years, QUALIOST® Total score: 39.3±21.4). After 4 years of treatment, QUALIOST® scores were significantly lower at endpoint in the strontium ranelate group than in the placebo group and demonstrated improved QoL compared with a deterioration in the placebo group (p=0.02 for the global score; p=0.01 for the Psychological score and p=0.03 for the Physical score). Analysis of the QUALIOST® item specifically relating to back pain revealed that the number of patients free from back pain was 28% higher in the strontium ranelate group compared with placebo (p=0.005). Conclusion: Strontium ranelate is the first anti-osteoporotic treatment shown by robust methods to be beneficial for the quality of life of patients with vertebral postmenopausal osteoporosis. This beneficial effect on HRQoL was sustained over 4 years of treatment.

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P297. Prevalence of vitamin D inadequacy is high in European postmenopausal women O. Bruyère, O. Malaise, A. Neuprez, J. Collette, J.Y. Reginster; WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders and Department of Epidemiology, Public Health and Health Economics, University of Liege, Liege, Belgium Objective: Inadequate 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 postmenopausal European women. There are no clear international agreements on what constitutes a level of vitamin D inadequacy, but recent publications suggest that the circulating level of vitamin D should be over 80 nmol/l or at least between 50 and 80 nmol/l. Materials and methods: Assessment of 25-Hydroxyvitamin D [25(OH)D] was performed in 8532 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: <80 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/m2. 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 and when considering patients aged less than 65 years, the prevalence reached 86% (cut-off of 80 nmol/l) and 45% (cut-off of 50 nmol/l). Conclusion: This study points out a high prevalence of vitamin D inadequacy in 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. P298. Usefulness of phalangeal quantitative ultrasonometry by DBM sonic (IGEA) in two women populations affected by osteporosis with a sole risk factor: the clothing style for religious reasons A. Ragno1, D. Pierangeli1, E. Russini1, E. Cavallaro1, A. Latini1, B. Salvatori1, A. Pagano1, A. Migliore2, U. Massafra2, L.S. Martin1; 1Department of Internal Medicine, Regina Apostolorum Hospital, Albano Laziale, Rome, 2 Unit of Rheumatology, S. Pietro FBF Hospital, Rome, Italy

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Introduction: Osteoporosis (OP) is a common disorder in the elderly population caused by both genetic and environmental factors, and possible interactions between them. It can be assessed indirectly through a non-invasive measurement of bone mineral density (BMD). Among the methods available to assess bone mass, quantitative ultrasonometry of bone (QUS) is a non radiological, low-cost, and user-friendly technique. Furthermore, this technique not only provides information on bone density, but also on bone elasticity and microarchitecture, which are two of the most important parameters in determining the quality of bone tissue. Several studies showed that vitamin D status of an elderly and healthy population living at home depends mainly on lifestyle. The clothing style is an important lifestyle factor that influences vitamin D production. In women who follow a strict religious dress code, that preclude from ultraviolet sun exposition is increased the risk of osteoporosis. Subjects and methods: Aim of our study was comparing the bone mineral density, measured by quantitative ultrasound technique, of two age-matched women populations differing only in a lifestyle factor regarding the way of dress due to religious reasons. Sixty menopausal women and 40 nuns were screened in our outpatient clinic for the cure and prevention of osteoporosis. The BMD was measured by DBM Sonic (IGEA, Italy), applied to the metaphysis of the proximal phalanges of the last four fingers of the non-dominant hand. According to the most recent international guidelines on osteoporosis, every patient was studied for all the mayor risk factors and the two groups were homogeneous for body anthropometric measures, age, time from menopause. Women with other risk factors for osteoporosis or those assuming drugs influencing mineral metabolism were excluded. Results and conclusion: We found in both groups a significant reduction of quantitative ultrasonometry variables with respect to normal range and in the nuns population is more evident a statistical significant reduction with respect to laic women [Ad-SoS(m/s) = 1902.56±34.95 vs. 1821.75± 60.58 (p=0.002); UBPI (units) = 0.31±0.08 vs. 0.20±0.06 (p=0.003)]. This marked reduction is probably related to the different clothing habit that not allowed a proper and sufficient synthesis of vitamin D at skin level. Besides, the QUS is showed to be useful and safe in order to easily screening osteoporotic patients with different risk factors. Our data reaffirm those of the literature claming that the lifestyle influences the vitamin D status and therefore the risk of developing osteoporosis, besides, underline the usefulness of qualitative ultrasound methods in the evaluation of patient at increased risk of osteoporotic fractures, alternatively to much expensive and less handling techniques.

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P299. Calcium daily food intake is very low in European postmenopausal women O. Bruyère, C. De Cock, A. Neuprez, O. Malaise, J.Y. Reginster; WHO Collaborating Center for Public Health Aspects of Osteoarticular Disorders and Department of Epidemiology, Public Health and Health Economics, University of Liege, Liege, Belgium Objectives: World Health Organization recommendation for calcium daily intake is 1,300 mg for postmenopausal women. The objective of this study is to assess the calcium daily food intake in postmenopausal European women. Materials and methods: Assessment of calcium daily food intake was performed with a validated self-questionnaire in 8,532 osteoporotic European women from nine European countries; Belgium, Denmark, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom. Result: Mean age of the patients was 74.2 (7.1) years with a body mass index of 25.7 (4.1) kg/m2. In the whole study population, only 6% of the women have a daily intake food over 1,300 mg. In European countries, the mean calcium daily food intake was 744 (±332) mg. The lowest calcium food intake was found in Hungary [503 (±247) mg/day] and the highest in United Kingdom [985 (±302) mg/day]. Out of our study population, only 37.2% of the women took calcium supplements. Conclusion: Calcium daily food intake is too low in European postmenopausal women. A greater awareness is needed to resolve this public health problem. P300. Dissociation between bone formation and bone resorption evidenced by changes in biochemical markers of bone turnover in patients treated with strontium ranelate J. Collette1, J.Y. Reginster2, O. Bruyère2, R. Deroisy2, I. Jupsin2, J.P. Devogelaer 3, S. Adami4, C. Marcelli5; 1 Department of Clinical Biology, Bone and Cartilage Markers Laboratory, University of Liege, Liege, Belgium, 2 Unité d’Exploration du Métabolisme Osseux, CHU Brull, Liège, Belgium, 3Louvain Catholic University, Brussels, Belgium, 4University of Verona, Verona, Italy, 5Department of Rheumatology, Caen University Hospital, Caen, France Objectives: To assess the effects on bone turnover of a 2 g/ day treatment with strontium ranelate in postmenopausal osteoporosis Materials and methods: Strontium ranelate is a new oral antiosteoporotic drug to reduce vertebral and hip fracture risks, found in pre-clinical studies to both stimulate bone formation and decrease bone resorption, rebalancing bone turnover toward formation. During phase 3 program, markers

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of bone turnover were assessed in order to clinically assess the dual mode of action of strontium ranelate. From phase 3 SOTI study, it was already demonstrated that serum concentrations of serum bone alkaline phosphatase isoenzyme (bALP) using an immunoradiometric assay (IRMA) was significantly higher and C-terminal telopeptides of type I collagen (CTX ) were significantly lower in strontium ranelate group than in placebo group as measured every 6 months over 3-year treatment period. In TROPOS study (n=4,932 patients, ITT population) both markers were also assessed every 6 months over 3 years. In addition and in both studies, serum procollagen type I carboxy-terminal propeptide (PICP), a marker of bone formation, was measured using a radioimmunoassay (RIA). Results: In TROPOS study, results showed a significant increase in bALP and PICP serum concentrations while serum concentrations of CTX were significantly lower in the strontium ranelate than in placebo group at each time visit from baseline values over 3 years. In SOTI study, PICP serum concentrations showed similar changes as those measured in TROPOS study. Conclusion: Serum bone markers changes obtained in two different studies clinically confirm the dual mode of action of strontium ranelate, already evidenced in non clinical studies, both increasing bone formation and decreasing bone resorption. P301. Prior study: ibandronate is preferred and tolerated in patients intolerant of alendronate or risedronate E.M. Lewiecki1, S.L. Bonnick2, K. Friend3, A. Laster4; 1 New Mexico Clinical Research and Osteoporosis Center, Albuquerque, New Mexico, USA, 2Clinical Research Center of North Texas, Denton, Texas, USA, 3Roche Laboratories, Nutley, New Jersey, USA, 4Arthritis and Osteoporosis Consultants of the Carolinas, Charlotte, NC, USA Objectives: Gastrointestinal (GI) intolerance is a common reason for discontinuing oral bisphosphonate therapy. The PRIOR study evaluated adherence to, and GI tolerability of ibandronate (150 mg monthly oral and 3 mg quarterly i.v.) in women with postmenopausal osteoporosis or osteopenia who had discontinued weekly oral alendronate or risedronate due to perceived or actual GI intolerance. Materials and methods: In PRIOR, an ongoing 1-year, open-label, multicentre study, women who discontinued oral alendronate or risedronate due to physician-assessed GI intolerance can choose either monthly oral, or quarterly i.v. ibandronate. They must be capable of taking either and can switch once to the other formulation if they experience a treatment-related adverse event (AE). Changes from baseline

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in severity or frequency of GI symptoms are assessed quarterly by a self-administered GI Experience Survey. Adherence is being assessed using a compliance threshold of ≥75%, clinical vertebral and non-vertebral fractures are being assessed as AEs and safety laboratory parameters are being continuously monitored. Results: A total of 545 women have been enrolled; 6-month interim data are available for 542 (intent-to-treat [ITT]). Ibandronate i.v. injection was chosen by 73% (396) and monthly oral ibandronate by 27% (146). After 6 months, compliance was ≥75% in 94.9% and 87.7% of patients receiving i.v. and oral ibandronate, respectively. GI tolerance scores improved by ≥10% in 85.6% of i.v. and 77.2% of oral patients. Withdrawals due to any AE after 6 months were 8.1% in the i.v. group and 12.3% in the oral group (ITT populations). A total of 11 (7.5%) patients switched from oral to i.v. ibandronate (all 11 citing GI intolerance), and 15 (3.8%) switched from i.v. to oral (reasons included flu-like symptoms in two patients and injection-site reactions in three). Conclusions: In this 6-month analysis, i.v. ibandronate was chosen by most women who had previously discontinued a weekly oral bisphosphonate due to GI intolerance. In this study, monthly oral therapy was well-tolerated in these patients. GI symptoms were improved in most patients receiving monthly oral or quarterly i.v. ibandronate. Both routes are clinically useful alternatives in patients who are intolerant of a weekly oral regimen. P302. After three years of treatment with strontium ranelate 2 g per day bone strontium content reaches a plateau G. Boivin1,2, P.J. Meunier1; 1Institut national de la santé et de la recherche médicale (INSERM) 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 (SR), has been shown to have a dual mode of action on bone formation and resorption. SR is a new treatment for postmenopausal osteoporosis. In the SOTI and TROPOS phase 3 studies at the posology of 2 g/day per os it has been demonstrated that SR is safe and efficient in reducing the risk of vertebral and hip fractures. Following treatment with SR, strontium which is closely chemically related to calcium is distributed in the bone tissue. During these two studies transiliac bone biopsies were performed in a subset of patients at baseline, 1, 2, 3, 4 or 5 years from the start of a treatment with SR 2 g/day or placebo, to evaluate bone safety and to assess the mechanism of action of SR at the cell or bone tissue level. These bone samples were also measured for the Bone Strontium Content (BSC) by using inductively coupled

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plasma atomic emission spectrometry. BSC, expressed as the ratio of Sr/(Sr+Ca)(mmol/mmol%), was measured in a total of 88 bone biopsies in the SR group: 27 at baseline, 8 at 12 months, 5 at 24 months, 33 at 36 months, 8 at 48 months and 7 at 60 months. Furthermore, some samples have also been analysed by X-ray microanalysis. The findings are expected to complete the current understanding on strontium distribution in the bone tissue. The results show a regular increase of BSC over time until 36 months of treatment: 0.43% at 12 months, 1.06% at 24 months and 1.67% at 36 months. After 3 years of treatment, the BSC reaches a plateau: 1.43% at 48 months and 1.85% at 60 months. Until 36 months of treatment, X-ray microanalysis also demonstrates that strontium is exclusively distributed in recently formed bone during treatment. All these findings indicate that strontium is progressively incorporated in bone with a plateau reached from the end of the third year of treatment and stable until the end of the fifth year. P303. Effect of calcitonin on bone lesion in chronic haemodialysis patients G. Gulsen1, D. Ozen2, B. Görçin2; 1Yeditepe University Hospital, Istanbul, Turkey, 2Turkish Kidney Foundation Hospital, Istanbul, Turkey The aim of the study was to evaluate the effect of salmon calcitonin on renal osteodystrophy and bone mineral density in chronic haemodialysis patients. Forty four patients with renal osteodystrophy, on maintenance haemodialysis were included in to present this study after their informed consent. All the patients were treated in the dialysis centre of the Turkish Kidney Hospital. The patients with bone mineral density Z-Score −2.5 were divided in to two groups: Group I (n: 16) received with vitamin D derivates (1 mg/day/6 months) and group II (n: 28) received with salmon calcitonin (100 U/ day/6 months) and vitamin D derivates (1 mg/day/ 6 months). The observation period was 6 months. The results show that when the group of received salmon calcitonin was compared group I, osteoarticular pain, morning stiffness, received on analgesic medication were significantly decreased (p<0.001). Two patients of group I had sustained wrist factures, three patients of group I had sustained rib fractures, one patient of group II had sustained rib fractures. During 6 months of the study, a substantial reduction in BMD was observed in all examined regions group I, whereas in group II a slight increase of bone mineral was noted (p> 0.05). The inhibition of bone resorption in group II was accompanied by a marked decreased in serum NTX (38 nM BCE/mM, p<0.05). The

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parameters of ALP were decreased in group II (p<0.05). No significant changes in plasma calcium concentrations occured in both groups. The measurement of health related quality of life (Nothingham helth profile index) for group II patients were significant increased during 6 months of the study. We conclude that, synthetic salmon calcitonin is an effective inhibitor of bone reception in patients with chronic renal failure, which must await studies of efficacy in patients given more prolonged treatment. P304. Intermittent intravenous (i.v.) ibandronate injections are more effective than an established daily oral regimen: DIVA 2-year results E. Czerwinski1, J.Y. Reginster2, I. Jonkanski3, C. Neate3, J.A. Eisman4; 1Krakow Medical Centre, Krakow, Poland, 2 University of Liege, Liege, Belgium, 3F. Hoffmann-La Roche Ltd, Basel, Switzerland, 4Garvan Institute of Medical Research, St Vincent’s Campus, University of New South Wales (UNSW), Sydney, Australia Objectives: An effective and well-tolerated i.v. bisphosphonate could provide an attractive treatment option for patients in whom oral bisphosphonates are unsuitable. In women with postmenopausal osteoporosis (PMO) participating in DIVA, i.v. ibandronate injections (2 mg every 2 months [q2 mo] or 3 mg every 3 months [q3 mo]) were more effective at 1 year than daily oral ibandronate (2.5 mg), and were similarly well tolerated(1). Results after 2 years are presented here. Materials and methods: DIVA is a double-blind, doubledummy, phase III, non-inferiority study of i.v. or oral ibandronate in women with PMO. All participants received daily calcium (500 mg) and vitamin D (400 IU). Results: Lumbar spine bone mineral density (BMD) increased in all treatment groups after 2 years (Table). Bone strength, and hence fracture resistance, is considered to be determined by BMD, bone turnover and the structural and material composition of bone. Measuring BMD and markers of bone turnover gives some assessment of bone strength. Both i.v. regimens achieved improvements in spinal BMD that were non-inferior (margin at year 2: 1.3%) and in fact superior (p<0.001) to the oral regimen. BMD increased at all hip sites (Table) with gains always larger in the i.v. arms than the oral arm. Serum CTX levels were markedly reduced in all arms (median reduction: 53–60%). Comparable BMD gains and reductions in serum CTX were reported in the intent-to-treat population. The good tolerability at 1 year was also seen after 2 years for both i.v. regimens; drug-related adverse events were 36.8–46.4% and drug-related adverse events prompting withdrawal were 6.0–7.7%.

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Table. Mean change (%, SD) from baseline in lumbar spine and hip BMD at 2 years (per-protocol population). 2 mg q2 mo i.v. IBN

3 mg q3 mo i.v. IBN

2.5 mg daily oral IBN

n=320 6.4 (4.7)

n=334 6.3 (5.0)

n=334 4.8 (4.9)

n=316 Total hip 3.4 (3.0) Femoral 2.7 (4.2) neck Hip 5.0 (4.5) trochanter

n=333 3.1 (4.5) 2.8 (4.7)

n=330 2.2 (3.7) 2.2 (4.3)

4.9 (7.5)

3.5 (4.7)

Lumbar spine

Conclusions: Intermittent i.v. ibandronate injections are an effective and well-tolerated treatment option for women with PMO. The BMD gains better than the oral regimen may provide additional antifracture benefit. (1) Delmas PD, et al (2006) Arthritis Rheum 54:1838–46

P305. Strontium ranelate decreases vertebral fracture risk whatever the level of pretreatment bone turnover markers J. Collette1, J.Y. Reginster2, O. Bruyère1, C. Roux3, R. Lorenc4, D. Felsenberg5, T.D. Spector6; 1Service de Chimie Médicale, CHU de Liège, Liège, Belgique, 2WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, University of Liege, Liege, Belgium, 3Department of Rheumatology B, Cochin Hospital, Paris, France, 4National Center for Osteoporosis, Warsaw, Poland, 5Centre of Muscle and Bone Research, Charite-Campus Benjamin Franklin, Free and Humboldt University, Berlin, Germany, 6Department of Rheumatology, St Thomas’ Hospital, London, United Kingdom Objectives: Pretreatment bone turnover levels may influence antifracture efficacy of anti-osteoporotic treatments.(1) To choose the best treatment for the patient’s individual profile, vertebral antifracture efficacy of strontium ranelate was studied according to pretreatment bone turnover markers (BTM) levels. Materials and methods: Two double-blind placebocontrolled studies were performed in women with postmenopausal osteoporosis. SOTI(2) (N=1,649) focused on vertebral fracture efficacy and TROPOS(3) (N=5,091) on non-vertebral efficacy, incident vertebral fracture being a prespecified secondary end-point in patients having spine X-rays (N=3,640).

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The risk of new vertebral fracture over 3 years was compared between groups in 5082 women with paired spinal X-rays and baseline bALP, or sCTX values, pooled from SOTI and TROPOS and stratified into quartiles (Q) of baseline BTM. Results: Baseline characteristics were similar between groups (age 74.0±6.2 years; lumbar BMD T-score −3.0± 1.6; femoral neck BMD T-score −3.0±0.7). Over 3 years of treatment, the risk of new vertebral fractures was significantly lower in the strontium ranelate group than in the placebo group regardless of the class of BTM considered. New vertebral fracture risk reduction compared to placebo was 32% (p=0.040) in the lowest quartile of bALP (bALP≤9.3 ng/ml), 39% (p=0.001) in Q2 (9.3≤bALP<11.5 ng/ml), 43% (p<0.001) in Q3 (11.5≤ bALP<14.5 ng/ml) and 40% (p<0.001) in Q4 (≥14.5 ng/ ml). For sCTX, new vertebral fracture risk reduction compared to placebo was 36% (p=0.001) in Q1 (sCTX≤ 2,931 pmol/l), 29% (p=0.018) in Q2 (2,931≤sCTX< 4,003 pmol/l), 46% (p < 0.001) in Q3 (4,003 ≤ sCTX<5,338 pmol/l) and 44% (p < 0.001) in Q4 (≥5,338 pmol/l). Treatment-effects were not different between the quartiles (interaction test: p=0.349 for bALP and p=0.129 for sCTX). Results were reinforced when analysing patients with both a value of bALP and sCTX in the lowest quartile or in the highest quartile with a risk reduction of having a new fracture compared to placebo of 33% (p=0.042) and 42% (p=0.007), respectively. Conclusion: The efficacy of strontium ranelate to significantly reduce incident vertebral fracture is largely independent of pretreatment bone turnover suggesting that strontium ranelate offers clinical benefits to women across a wide range of metabolic states and disease severity. (1) Bauer et al (2006) J Bone Miner Res 21: 292–99 (2) Meunier et al (2004) N Engl J Med 350: 459–68 (3) Reginster et al (2005) J Clin Endocrinol Metab 90: 2816–22

P306. Good persistence and adherence with oral bisphosphonates reduce fracture rate in patients with osteoporotic fractures H. Gothe1, P. Hadji2, A. Höer1, P. Storz1, M. Olson3, B. Häussler1; 1IGES Institute for Health Care and Social Research, Berlin, Germany, 2Department of Endocrinology, Philipps-University of Marburg, Marburg, Germany, 3 Novartis Pharma, Basel, Switzerland Objectives: In clinical trials oral bisphosphonates have been shown to reduce the risk of fractures in patients with osteoporosis. It can be assumed that the effectiveness of oral

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bisphosphonates depends on persistence and/or adherence with therapy. We therefore investigated the influence of persistence and adherence with oral bisphosphonates on fracture risk in a naturalistic setting. Materials and methods: Claims data from a large German sickness fund (about 1.5 million lives insured) were considered. Within the period 2000–2004, patients with a defined index prescription of a bisphosphonate (no prescription of bisphosphonates within 180 days before, observation time at least 360 days before and 180 days after index prescription) were included. Fracture rates within 180, 360, and 720 days after the index prescription were compared between persistent and non-persistent patients. In an extended Cox regression model applying multiple event analysis, the influence of adherence was analysed. Persistence was defined as the duration of continuous therapy, and adherence was measured in terms of the medication possession ratio (MPR; proportion of days supplied with medication). Results: We identified 4.451 patients with an index prescription. In patients with a fracture before the index prescription, fracture rates were reduced by 29% (p=0.025) comparing persistent and non-persistent patients within 180 days after the index prescription and by 45% (p< 0.001) within 360 days. Within 720 days a 9% (p=0.752) reduction was observed. In patients without a fracture before the index prescription, low incident fracture rates made it difficult to see a significant effect. However, within 720 days after the index prescription, a non-significant reduction of 11% (p=0.709) in fracture rates was observed in persistent patients. The extended Cox regression model showed that good adherence (MPR≥0.8) reduced the fracture risk by about 39% (hazard ratio 0.61, 95% CI 0.47–0.78; p<0.01). Conclusion: In patients with osteoporosis-related fractures, good persistence and adherence with oral bisphosphonates reduce fracture risk significantly. The effect can be observed within 180 day after therapy onset. In patients without a known fracture, a longer period of continuous oral bisphosphonate therapy may be needed until a significant fracture reduction can be observed. P307. 3D femur geometry from 2D DXA scans: preliminary study of bone volume estimation L. Del Rio, R. Vila, L. Del Rio (Jr), J. Pascual, S. Di Gregorio, C. Solé, M. Garcia, J. Rosales; Centre Mèdic CETIR, Barcelona, Spain Introduction: Dual energy X-ray absorptiometry is a primary diagnostic tool for assessing skeletal fragility. Bone geometry, spatial distribution and micro-architecture also play important roles in bone strength. We evaluated a

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new method to measure bone volume from femur DXA scans, comparing the calculated virtual measurements to known volumetric measurements in animal femur samples. Materials and methods: A total of 25 proximal pig femurs (mean weight 78 kg and age 5 months) were evaluated. The pig femurs were scanned with a narrow angle fan beam DXA device (GELunar-Prodigy), using standard femur scan mode. Virtual bone volume was derived with special software by summing the individual 0.25 mm slice volumes obtained from each cross sectional area, and assuming a variable elliptical geometry. True bone volume was calculated for two sections, femoral neck (FN) and femoral head (FH), sliced from the pig femur, with the cut axis perpendicular to the FN-axis. The Cavalieri method of fluid displacement was used to calculate the volume of these sections. The DXA scans and the Cavalieri measurements were repeated three times to determine in vitro reproducibility. Measurements were compared by a paired sample T-test and the relationship was studied by linear regression equation and Pearson’s bivariate correlation. Accuracy error was calculated as (1−r2), reported as a percentage. The measurement reproducibility was shown as the coefficient of variation (CV) and results were expressed as a percentage. Results: There was a strong correlation between the virtual DXA3-D and the Cavalieri3-D measurements at the FN (r2 =0.938, p<0.0001) and for the FN+FH (r2 =0.928, p<0.0001). The paired t-test did not show significant differences between the measurements. Using the Cavalieri measurements as reference, the accuracy error for calculated volume was 12% at FN and 13.8% for FN+FH. The CV for FN and FN+FH calculated volume was 5.66 and 4.93%, respectively. The true volume CV for FN and FN+FH was 3.61 and 1.7%. Conclusions: Even assuming a fixed relationship between geometrical shape and animal specimen, our results showed a very good correlation between measured 3-D volume and the 3-D volume calculated from a DXA-scan. This technique may offer a non-invasive and economical method to assess spatial bone distribution in critical areas of the skeleton. P308. Renal safety of once-yearly infusion of zoledronic acid 5 mg in postmenopausal women with osteoporosis: results from HORIZON-PFT P. Miller, D. Sellmeyer, S. Boonen; HORIZON-Pivotal Fracture Trial (PFT) Research Group Objectives: To assess the impact of once-yearly infusions of zoledronic acid (ZOL) 5 mg on renal function in postmenopausal women with osteoporosis.

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Materials and methods: The HORIZON-PFT trial was a multinational, 3-year, randomized, double-blind trial that compared once-yearly ZOL 5 mg, infused over 15 min, to placebo (PBO) in 7.736 postmenopausal osteoporotic women 65–89 years of age. Serum creatinine and calculated creatinine clearance (Cockcroft formula) were assessed at 12, 24, and 36 months. To evaluate short-term safety, renal assessments were conducted 9 to 11 days after infusions in a subset of patients (2521 ZOL, 2514 PBO). Results and conclusions: There were no long-term differences between ZOL 5 mg and PBO in renal function effects as assessed by mean change from baseline in serum creatinine concentration and creatinine clearance calculated with the Cockcroft formula (Table). The rates of renal abnormalities requiring expert adjudication, including renal adverse events, increase in serum creatinine >0.5 mg/dl, creatinine clearance <30 ml/min, and baseline creatinine clearance ≤60 ml/min and decline ≥30%, were also comparable between treatment groups. In the subset of patients assessed for short-term renal changes, transient post-infusion increases in serum creatinine >0.5 mg/dl occurred in more ZOL 5 mg than PBO patients (1.34 vs 0. 43%). In the ZOL 5 mg group, increases in serum creatinine ≥0.5 mg/dl relative to baseline ranged from 0.61% of patients after infusion 1 to 0.96% after infusion 3. All ZOL 5 mg patients (n=31) and eight of ten PBO patients recovered to within <0.5 mg/dl of their predose values within 12 months.

Mean (SD) absolute change from baseline (n) Treatment 1 year Serum ZOL creatinine, 5 mg μmol/l [mg/dl] PBO

Creatinine ZOL clearance, 5 mg ml/min PBO

2.5 (10.30) [0.028 (0.117)] (3,595) 2.5 (10.75) [0.028 (0.122)] (3,624) −3.1 (8.9) (3,574) −3.4 (9.2) (3,615)

2 years

3 years

4.3 (10.84) [0.049 (0.123)] (3,289)

6.7 (12.27) [0.081 (0.139)] (3,022)

4.1 (11.94) [0.046 (0.135)] 3,344)

6.7 (13.17) [0.078 (0.149)] (3,066)

−5.7 (8.9) (3,284)

−8.8 (9.6) (2,989)

−5.7 (9.5) (3,338)

−8.7 (9.6) (3,031)

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These results suggest that in both groups, long-term changes in renal function were related to age and other conditions. Post-infusion increases in serum creatinine occurred at a slightly higher rate in the ZOL 5 mg group, but these changes were mild and transient. P309. Effect of dairy consumption on BMD values A. Gasparik, E. Nagy, S. Mihalcea, D. Dragoi; Association of Osteoporosis Prevention-Romania, Tirgu Mures, Romania Objectives: To evaluate the influence of dietary habits, especially milk consumption on bone mineral density parameters. Materials and methods: We assessed data of 1.656 patients (men and women, mean age 54 year, range 34–80), comparing T- and Z-scores of those who declared to be high dairy consumers to those who don’t have a daily dairy intake. We also compared the influence of dietary factors to other osteoporosis risk factors. Results: There was no difference in Z-scores of the two subgroups. The minor difference in T-scores is related to the lower mean age of those who don’t consume milk. In comparison, other risk factors, such as body mass index, sedentary lifestyle and early menopause had an impact on T- and Z-scores of patients, with statistically significant differences between the yes/no subgroups. Smokers and coffee drinkers also did not show lower density values compared to non-tobacco/coffee consumers. Conclusion: We could not show a real effect of dietary habits, especially milk-consumption on T- and Z-scores, compared to the impact of other osteoporosis risk factors. P310. The incidence of osteoporosis at female patients with hyperthyroidism F.L. Popa, M. Stanciu, M. Rotaru, I.Gh. Totoianu; Faculty of Medicine “Victor Papilian”, University “Lucian Blaga” of Sibiu, Sibiu, Romania Objectives: Hyperthyroidia is one of the causes of secondary osteoporosis. We want to evaluate the frequency of osteoporosis in hyperthyroidia and how the euthyroidia can normalize the bone destruction. Materials and methods: We evaluated in our study 21 female patients with untreated hyperthyroidia with an evolution of at least 6 months, aged between 35–50 years, in active genital period. To all patients we achieved DEXA (dual energy X-ray absorptiometry) before and after 6 months of antithyroid specific treatment (antithyroid drugs, surgery, radioiodotherapy).

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Results: At 7 patients (33.3%) we found osteopenia (T-score< −2), and the rest without osteoporosis. After 6 months of therapy, BMD (bone mineral density) of this patients was normal, T-score was −0.9±0.4. Conclusion: This study confirmed the effect of hyperthyroidia on bone and benefic role of removing the excess of thyroid hormones. P311. Effect of once-yearly infusion of zoledronic acid 5 mg on biochemical markers of bone turnover: data from HORIZON-PFT P.D. Delmas, D. Bauer, D. Black, S. Boonen, F. Cosman, R. Eastell; HORIZON-Pivotal Fracture Trial (PFT) Research Group Objective: To evaluate the effect of once-yearly infusions of zoledronic acid (ZOL) 5 mg on biochemical markers of bone turnover in postmenopausal women with osteoporosis. Materials and methods: The HORIZON-PFT trial was a multinational, 3-year, randomized, double-blind, placebocontrolled trial involving over 7,000 postmenopausal women with osteoporosis. Changes in levels of β-C-terminal telopeptide of type I collagen (β-CTX), a marker of bone resorption, and in bone-specific alkaline phosphatase (ALP) and serum N-terminal propeptide of type I collagen (PINP), markers of bone formation, were measured in subsets of patients from selected centers. Results and Conclusion: Treatment with ZOL 5 mg significantly decreased levels of bone turnover markers (Table). In the ZOL 5 mg group, geometric means for βCTX corresponded with 74, 61, 57, and 52% decreases relative to baseline at 6, 12, 24, and 36 months, respectively. The 61% decrease at 12 months is between the 12-month decreases with alendronate (73.8%) and risedronate (54.7%).(1) In the placebo group (PBO, n = 260) the geometric mean at 36 months for β-CTX corresponded to a 6% increase from baseline. Serum β-CTX levels were significantly reduced in the ZOL group versus PBO at all post-baseline timepoints (P<0.0001), and median levels were within the premenopausal reference range (0.13–0.54 ng/dl) at the end of each annual dosing cycle. During year 3, βCTX was measured at 9–11 days and at 1, 3, 6, and 12 months post-infusion. At 9–11 days, the median level in the ZOL group was 0.04 ng/mL, rising to 0.13 by 6 months. We conclude that once-yearly infusions of ZOL 5 mg resulted in significant reductions in biochemical markers of bone turnover compared to placebo over 3 years. The decrease in β-CTX in the ZOL 5 mg group is comparable to that seen with other bisphosphonates.

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Geometric mean (log e [time point/baseline]) Marker 6 months ZOL 5 mg 0.26

12 months

PBO ZOL 5 mg 0.86 0.39

Serum CTX Bone 0.63 0.94 0.70 ALP PINP NA NA 0.39 P<0.0001 for all comparisons.

24 months

36 months

PBO ZOL 5 mg 0.97 0.43

PBO ZOL 5 mg 1.00 0.48

PBO

1.00 0.69

1.00 0.74

1.04

0.92 0.41

0.98 0.47

0.98

1.06

(1) Rosen et al (2005) J Bone Miner Res 20:1

P312. Aid for the diagnostic of osteoporis based on shape parameters of bones in radiological images A. Formella1, J.R. Caeiro2, S. Dapía3, J.M. Rodríguez1, E. Cernadas4; 1Computer Science Department, University of Vigo, Ourense, Spain, 2Traumatology and Orthopaedic Surgery Department, University Hospital Complex of Santiago de Compostela, Santiago, Spain, 3Novaria IDI S.L., Technological Park of Galicia, Ourense, Spain, 4 Computer Science Department, University of Santiago de Compostela, Santiago, Spain Objectives: The purpose of this work is to design and implement an automatic system which is able to place geometric shapes that describe sufficiently close the form of bones onto radiological images to help in the osteoporotic diagnostic. The shape parameters, e.g., aspect ratios, relation of opposite borders, or curvature of the shape, can be used by the medical doctor to analyze a possible deformation of the bone whenever the shape parameters differ from their normal characteristics. Moreover, the description of the bones through geometric shapes adapted to the radiological images allows for a more objective interpretation of the data and for a comparison of different patients in a quantitative manner. Materials and methods: A set of conventional radiological images of the lateral lumbar spine from ten patients were obtained from the local Hospital and digitalized to a resolution of 570 ppi (3.662×4.971 pixels) using 16 bits/ pixel following the A.C.R. directives. To achieve the adaptation of a geometric shape to the underlying bone the following steps are executed: Noise reduction, adaptive range expansion of the gray levels, detection of regions of interest taking advantage of the knowledge how the radiological image has been taken, detection of regions

close to the borders of the bones with an imprecise edge detection method, hierarchical grouping of regions for posterior segmentation, initial shape adaptation with an optimization method being able to adapt a set of initial geometric shapes to a set of points, final shape adaptation of the individual bone with active contours applied on the original. Once the shapes have been placed on the bones in the radiological image, its shape parameters are used for classification. Results and conclusions: We present the automatic detection of the individual vertebrae and the simple shapes which describe the characteristics of the bones. The results are encouraging and we will proceed to achieve a more precise evaluation of the system applying the method to the large set of images and compare the results with the diagnostic of the medical doctor. It would seem to be a cost-effective and useful method to distinguish in the clinical evaluation of patients at risk of osteoporosis as an adjunct to BMD scans. P313. Prevalence of asymptomatic vertebral fractures in postmenopausal women with osteoporosis in Buenos Aires, Argentina M.S. Larroudé, M.P.D. Yantorno, M.S. Moggia, Z. Man; Centro TIEMPO, Buenos Aires, Argentina Introduction: Underdiagnosis of vertebral fractures (VFx) is a common problem. The semiquantitative evaluation provided by the Genant Method is a very useful tool in the assessment of these fractures, by means of plain lateral thoracic and lumbar radiographs. Objectives: To determine the prevalence of asymptomatic VFx in postmenopausal women (PMW) with osteoporosis diagnosed by the DXA scans performed at our center, located in Buenos Aires, Argentina, who attended for control. Materials and method: After ruling out history of VFx through medical interrogatory, 337 PMW [mean age, 67 years (range, 51–85)] with at least 5 years postmenopausal, had plain lateral thoracic and lumbar X-rays done. A reduction >20% of the vertebral body height was considered for the diagnosis of VFx. Results: We found 146 VFx, of which 1O3 VFx (70%) and 43 VFx (30%) were located in the thoracic and lumbar spine, respectively. 94 PMW with osteoporosis (27.89% of the total sample) had VFx; 31 of these (33%) had more than one VFx. Conclusion: It is well known that the presence of a VFx is a predisposing factor for future fractures. Their diagnosis

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represents a useful tool for establishing risk groups. Plain radiographs of the spine are accessible and inexpensive imaging methods, whose benefits are important in terms of public and the individuals health.

Conclusion: Our results confirm earlier reports that dietary intake of calcium is 650 mg below the recommended amount. Consequently Ca/vit.D supplementation has to be recommended in virtually all patients treated for osteoporosis.

P314. Low dietary calcium intake in patients treated for osteoporosis J.Y. Reginster1, J. Imschoot2; 1Department of Epidemiology, Public Health and Health Economics, University of Liege, Liege, Belgium, 2Medical Department, Christiaens Pharma, Brussels, Belgium

P315. Comparative evaluation of local and international reference databases for forearm densitometry S. Mészáros1, V. Ferencz1, P. Berkõ2, G. Genti3, E. Hosszú4, B. Keszthelyi5, F. Teremi6, E. Csupor7, E. Tóth3, K. Bors8, C. Horváth1; 11st Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary, 2 Semmelweis County Hospital, Miskolc, Hungary, 3Flór Ferenc County Hospital, Kistarcsa, Hungary, 4 2nd Department of Paediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary, 5Spa Hospital, Harkány, Hungary, 6City Hospital, Százhalombatta, Hungary, 7The Health Service of Budavári Local Authorites, Budapest, Hungary, 8The Health Service of Ferencváros Local Authorites, Budapest, Hungary

Objectives: International guidelines recommend a dietary intake of 1,000–1,500 mg of calcium to patients treated for osteoporosis. The objective of this trial was to estimate the habitual dietary intake of calcium in patients with treated osteoporosis. Materials and methods: Patients treated for osteoporosis but not taking calcium/vitamin D supplements (Ca/vit.D) at the moment of the consultation were recruited in daily clinical practice by 533 GP’s. Calcium intake was estimated by questionnaire and a chewable (Steovit D3 500 mg/ 400 IU) or effervescent (Steovit D3 1000 mg/880 IU) Ca/ vit.D supplement was recommended in patients with insufficient dietary intake. Compliance and acceptability of the Ca/vit. D supplement were evaluated after a 3 month period. Results: 4,788 evaluable patients (93% females and 7% males; mean age 68.4 years) participated in this survey. Patients were treated for osteopososis with bisphosphonates in 77.0%, SERM in 13.1% or hormone substitution in 7.8%. Mean calculated daily calcium intake for the whole cohort was 848 mg. Intake was higher in younger patients. Green vegetables provided 15.9% of dietary calcium while supply from milk accounted for 17.1%, yoghurt/diary desserts for 14.3% and cheese for 38.1%. Daily requirements of calcium were not covered in 95.3 % of patients. Supplementation with Ca/vit. D was recommended in 97.6% of patients. This increased the mean total calcium intake for the cohort to 1,547 mg calcium and decreased the proportion of patients in whom dialy requirements were not covered to 28.1%. After a three months period patients said they were taking their Ca/ vit. D supplement daily in 57.8%, 5–6 days/week in 26.2%, 3–4 days/week in 13.2% and 1–2 days/week or less in 2.8%. On a 0 (very bad) to 10 (very good) Likert scale, patients rated the taste of Steovit D3 as 7.2 and the easiness of use as 7.7. 95.8% of patients said they were willing to continue the use of the Ca/vit.D supplement.

Objectives: Reference databases play a key role in the management of osteoporosis. The aim of this study was to compare the diagnostic consequences of using either an international or a local reference database in peripheral densitometry. For this purpose, standard curves for bone mineral density, measured by dual-energy X-ray absorptiometry at the distal and proximal forearm, were generated for healthy Hungarian men and women. Materials and methods: In total, 303 healthy volunteers of both sexes, aged between 20 and 94 years, were recruited from four osteoporosis centres. Subjects with medical conditions or taking medication affecting the bone metabolism were excluded. Bone densitometry was performed with pDEXA (Norland-Stratec) devices in each centre after crosscalibration of the machines. Results: In males, the highest bone mineral density was found in the 30–39-year group for the distal forearm, but one decade later for the proximal site. Subsequently, a 5% decrease in density occurred per 10 years, except in the eighth decade, where a 20% decrease was demonstrated. In females, the peak forearm density was detected in the 30 to 39-year group. The density decreased by 8% per 5 years in early postmenopausal females, and by 10% per 10 years in late postmenopausal females. One thousand four hundred thirtyfour patients with suspected osteoporosis were classified according to the forearm density T-scores using both the new Hungarian reference database and the international database provided by the manufacturer. Comparison of the results

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measured at the distal forearm with the two different databases led to similar outcomes. At the proximal site, however one fifth of the female patients were reclassified from the low-density group to the normal group using the domestic normative database. An opposite difference was observed for the males: use of the Hungarian reference data resulted in 40% more men being categorized in the low density group than when the international normal database was applied. Conclusion: Our results suggest that not only geographic differences, but also the reference database used, can influence the prevalence of the diagnosis of osteoporosis. P316. Variations in morphology in surfaces of human bone—possible collagen collapse T. Hassenkam1, H. L. Jørgensen2, J.E.B. Jensen3, J. B. Lauritzen4; 1Nano-Science Center, University of Copenhagen, Copenhagen, Denmark; 2Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, 3Department of Endokrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark, 4Department of Orthopaedics, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark Understanding the structural relationships between the building blocks of bone is important for understanding the mechanical properties of the bone tissue. Human bone tissue is composite material consisting of small mineral plates extended in a matrix of organic fibres. The size scale of the individual building blocks of bone is in the nanometer range with collagen fibrils being 100 nm in diameter and mineral plates being about 50 nm in diameter. To understand bones ability to resist fracture as a tissue, and thus its quality, one has to elucidate the intricate interplay between these building blocks. We have used the Atomic Force Microscope as tool to elucidate this interplay in structural sense as well as in nanomechanic sense. We show detailed images of the surface from several trabecular struts in several patients. The images reveal big variances in morphology. The morphology reveals that the collagen fibrils degenerate into a lesser order. Struts from young patients reveal less structural degeneracy while struts from elderly patients show greater variances in morphology, suggesting that the collagen fibrils falls apart with age. The nanomechanics of the various morphologies found is also presented. Figure: AFM deflection mode images from a patient suffering from osteoporotic fractures. The black bar marks 1 μm. The image is dominated by large bundles of collagen fibrils. A few fibrils are running across the large bundles thus forming links between bundles. The white arrows indicate some examples of fibrils that are falling apart.

The results seems to contradict a consensus of collagen fibrils generating more internal crosslinks from AGE, thus forming stiffer and more brittle fibrils over time. In addition we have mapped the imprint of bone remodelling, to elucidate the structural relationship between old bone and the osteoid. We have also investigated Arthritis surfaces from knees and hips with the AFM. The images reveal cracks and dislocations in the surface. P317. The burden of osteoporosis in Africa. A preliminary report A.O. Adebajo1, J. Morales-Torres2, J. Romero-Ibarra2, J.A. López-García2; 1Academic Rheumatology Group, University of Sheffield Medical School, Sheffield, United Kingdom, 2 Hospital Aranda de la Parra, León, México Introduction: Osteoporosis causes considerable morbidity, mortality and resource utilization in industrialized nations. Currently, our knowledge of the magnitude of this problem in most countries in Africa remains extremely limited. Objectives: To know the burden of osteoporosis in Africa through a review of literature and publicly available information. Materials and methods: Transversal and descriptive study. Information from 52 countries in Africa was collected from diverse published and electronic sources. Rheumatologists and Bone Specialists were asked for additional information through a questionnaire created by consensus. Results: In year 2005, the population of Africa was 867 millions from diverse ethnic origins. Mean life expectancy is of 51 years (largely associated with a high infant mortality), but is higher than 70 years in the North African countries.

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Population aged 50 years and older composes a mean 5.06% (±0.328) of the general population in Africa, while the population 65 years and older compose 1.63% (±0.176) of total population. A study in Morocco using World Health Organization’s criteria for osteoporosis, and local normal values, reported osteoporosis in vertebrae in 37.9% and in proximal femur in 6.7% of women 50 years and older. A few studies report in small cohorts of some other countries lower bone mass values than those found in Europe using peripheral devices. A community-based study in Morocco reported an incidence rate of hip fractures of 80.7 in women and 58.5 in men, per 100.000 persons 50 years and older. A hospital-based study in Cameroon, reported an incidence rate of hip fracture of 4.1 in women and 2.2 in men per 100.000 persons aged 35 and more. Mortality and direct costs of hip fractures have not been reported. Conclusions: The burden of osteoporosis is difficult to ascertain given the short life expectancy in most of SubSaharian Africa, but still may impact the already limited health resources. A considerable support for research is required, since numerous gaps in knowledge need to be filled to face the anticipated increase of elderly population in the coming decades.

disability caused by others pathologies will be excluded. For all subjects a detailed medical history and the evaluation of dietary calcium intake will be obtained. The patients will perform some clinical analysis in order to choose the appropriate medical therapy and to monitor the effects. All subjects will undergo the following basal, one year and two year instrumental analyses: lumbar and femoral DXA, finger QUS and lumbar QCT. At time 0 and after 6, 18 and 24 months, biochemical and urinary tests will be also performed to evaluate bone metabolism and bone turnover. Conclusions: The results of this study may contribute to define, in the next future, guidelines of management of patients after a surgical treatment of prosthesis of hip caused by the fragility fracture of the femoral neck, through appropriate lifestyle changes and earlier target therapy.

P318. Osteoporotic patient course after a surgical treatment of hip prosthesis C. Cepollaro, R. Imbriaco, R. Monaco, L. Masi, A. Falchetti, G. Leoncini, A.Gozzini, A. Tanini, ML. Brandi; Department of Internal Medicine, University of Florence, Florence, Italy

Objectives: DKK-1 is a potent inhibitor of the Wnt signalling pathway (regulating cell-cell interaction) affecting osteoblast differentiation and bone growth.(1) The protein may be involved in diseases with abnormal bone remodelling, as found in the context of osteoporosis(2) or bone malignancies.(3) The development of state of the art immunoassays requires in depth knowledge of the molecular structure and of the protein’s role in regulatory pathways and the histopathological context. Therefore our aim was to develop an ELISA for human DKK-1 utilising computational biology for candidate protein characterization and antigenic determinant selection for highest assay specificity. Materials and methods: We have utilised given data sources on bone metabolism disorders, and have studied the molecular context of DKK-1 with respect to differential gene expression, transcriptional co-regulation, and protein interaction networks. After elucidation of the role of DKK-1 itself further computational routines have been applied for selection of ideal candidate epitopes tailored for antibody production. Antibodies against selected candidate epitopes were raised in sheep, their avidity was determined and compared against commercially available DKK-1 antibodies. An assay prototype has been developed and the serum DKK-1 levels were determined in samples from patients with low bone mass density. Results: A significant correlation was found between DKK-1 and: LS BMD (T- and Z-score, p=0.003 and 0.001, respectively); TROH BMD (for Z-score: 0.046 and

Objectives: Hip fractures are the most devastating result of osteoporosis; they require the patient to be admitted to hospital and cause serious disability and excess mortality. Only 25% of hip fracture patients make a full recovery and nearly one of four of them die within 12 months after the injury. In this study we will evaluate the introduction of the appropriate medical therapy as a variable in the osteoporotic patient course after a surgical treatment of prosthesis of hip caused by the fragility fracture of the femoral neck in order to compare the outcome of the groups following a traditional and a modified course (with a prescription of a target therapy). Materials and methods: Approximately 100 patients (M/F) with hip prostheses following fragility femoral fractures will be enrolled and random distributed in two groups of 50 subjects: control group, formed by patients which will follow the traditional course and sample group, formed by patients which will follow a modified course (presence of the variable medical therapy). Subjects with indications to surgical intervention of hip prosthesis caused by fragility femoral fractures will be included in the study, whereas subjects affected by metabolic bone diseases, except osteoporosis, dementia and exhibiting an elevate grade of

P319. Immunoassay for DKK-1: a new tool for the assessment of bone remodelling S. Maitzen1, G. Hawa1, A. Lukas2, J. Marc3; 1Biomedica Gruppe, Vienna, Austria, 2Emergentec Biodevelopment, Vienna, Austria, 3University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia

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0.026); TOT BMD (for T-score p=0.040); Serum levels of CTx (p=0.043). Conclusion: The developed assay for DKK-1 seems a valuable tool for bone research but more data are needed to clarify its clinical usefulness. (1) Krishnan V, et al (2006) J Clin Invest 116:1202–9 (2) Ohnaka K, et al (2004) Biochem Biophys Res Commun 318:259–64 (3) Gunn WG, et al (2006) Stem Cells 24:986–91

P320. Prevalence of deficiency, insufficiency and hypovitaminosis D in postmenopausal patients in the city of Buenos Aires M.S. Moggia, M.S. Larroudé, R.D. Díaz, M.G. Torres Cerino, M.P.D. Yantorno, G.A. Macías, J.C. Morgenstern, M. Perez Sainz, Z. Man; Centro TIEMPO, Buenos Aires, Argentina Introduction: The definitions for normal serum Vitamin D (VD) level and deficiency have not been clearly established yet. A classification that included the concepts of “desirable” (>40 ng/ml), “hypovitaminosis D” (20–40 ng/ml), “VD insufficiency” (10–20 ng/ml), and “VD deficiency” (<10 ng/ml) have been proposed. Aim: To assess the prevalence of hypovitaminosis D in a postmenopausal population attending TIEMPO Center for osteoporosis evaluation. Material and method: 405 women (median age 65 years old; range 51–84 years old) from Buenos Aires City and its metropolitan area (Lat: 35° South) who attended Centro TIEMPO between September and December for osteoporosis evaluation were selected. VD serum concentration was determined with a radioimmunoassay kit, Diasorin®. Patients with thyroid, liver, or renal diseases, steroids, antiepileptic and anticoagulants use were excluded. VD values were divided according to the McKenna classification in deficiency (≤10 ng/ml) insufficiency (10–20 ng/ml) hypovitaminosis (20–40 ng/ml) desirable >40 ng/ml. The hypovitaminosis group was classified into two categories: (A) 20–30 ng/ml and (B) 30–40 ng/ml. Results: – – – –

VD deficiency=1.5% (n=6): 61–70 years old 33.3% (2); 71–80 years old 50% (3), >80 years old 16.7% (1) VD insufficiency=34% (n=138): 51–60 years old 27.5% (38); 61–70 years old 42.7% (59); 71–80 years old 26.8% (37); >80 years old 3% (4) Hypovitaminosis A=45.7% (n=185): 51–60 years old 34.1% (63); 61–70 years old 40% (74); 71–80 years old 24.3% (45); >80 years old 1.6% (3) Hypovitaminosis B=15.8% (n=64): 51–60 years old 32.8% (21); 61–70 years old 45.3% (29); 71–80 years old 20.3% (13); >80 years old 1.6% (1)

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Desirable 25-(OH) VD=3% (n=12): 51–60 years old 50% (6); 61–70 years old 41.7% (5); 71–80 years old 8.3% (1).

Conclusions: In the population studied (n=405), only 3% (n=12) had desirable values of 25-(OH) VD; and 81.7% (n=11) of these were younger than 70 years old. P321. Oral ibandronate (150 mg) continues to be effective and well tolerated when administered monthly: the mobile study lone-term extension J.A. Stakkestad1, R. Lorenc2, E. Czerwinski3, F. Sedarati4, C. Neate5, J.Y. Reginster6; 1CECOR, Haugesund, Norway, 2 The Children’s Memorial Institute, Warsaw, Poland, 3 Krakow Medical Centre, Krakow, Poland, 4Hoffmann-La Roche Inc., Nutley, New Jersey, USA, 5F. Hoffmann-La Roche Ltd, Basel, Switzerland, 6University of Liege, Liege, Belgium Objectives: Bone strength is determined by structure and material composition. Measures of bone mineral density (BMD) and bone turnover allow assessment of the strength of bone. In the 2-year MOBILE study(1,2), monthly oral ibandronate provided superior increases in BMD compared with daily oral ibandronate. Pronounced reductions in serum CTX (sCTX) were maintained for the study duration(1,2). The efficacy and safety of monthly ibandronate are being further investigated in a 3-year long term extension (LTE) study. Materials and methods: In this double-blind extension study, eligible patients from MOBILE continued to receive monthly ibandronate (100 or 150 mg), or were re-randomised from 50+50 mg monthly or 2.5 mg daily to 100 or 150 mg monthly ibandronate. Results: Compared with the 2-year endpoint in MOBILE, lumbar spine BMD increased by 1.5% (150 mg) and 1.1% (100 mg) after the first year of MOBILE LTE (all patients). sCTX (measured immediately before next monthly dose) remained within the premenopausal range. A post-hoc, pooled analysis over 3 years, excluding re-randomised patients, showed consistent lumbar spine BMD increases from MOBILE study baseline: 7.6% (150 mg) and 6.4% (100 mg; p< 0.0001 for both). Total hip BMD also significantly increased (4.1 and 3.4%, respectively; p< 0.0001). In the pooled analysis, median peak sCTX (month 30) decreased by 83.3% (150 mg) and 70.1% (100 mg; p< 0.0001 for both), relative to the MOBILE study baseline, and median trough sCTX (month 36) by 64.9% (150 mg, p<0.0001) and 52.0% (100 mg, p=0.0003). There were no clinically meaningful imbalances in the frequency of adverse events (AEs; 56.0 and 53.3%) or treatment-related AEs (8.4 and 7.8%) with 100 and 150 mg, respectively. Of particular importance was the low incidence of clinical

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osteoporotic fractures (3.6 and 2.2%, respectively), and withdrawal due to an AE (1.7 and 1.9%, respectively). Conclusions: In MOBILE LTE, lumbar spine and total hip BMD increased progressively in patients who received 3 years of continuous treatment (100 or 150 mg monthly). Substantial sCTX reductions were maintained over the third year of treatment. The overall AE profiles were consistent with data seen in the 2-year MOBILE study. (1) Miller PD, et al (2005) J Bone Miner Res 20:1315–22 (2) Reginster J-Y, et al (2006) Ann Rheum Dis 65:654–61

P322. Interest of an education program on the knowledge on osteoporosis and on calcium intake: interim analysis E. Lespessailles1, C. Gadois2, N. Villequenault2, B. Blot1, S. Loiseau-Peres1,2, C.L. Benhamou1; 1Service de Rhumatologie, CHR d’Orléans, Orléans, France, 2Institut de prévention et de recherche sur l’’ostéoporose (IPROS), CHR d’Orléans, Orléans, France Objectives: We have previously started an educational program based on three classes which covered the following issue in osteoporosis: preventing falls, exercise, diet. This education program is proposed to all subjects referred to our densitometry unit and to the general population (advertising by general practitioners). We examined in this study whether calcium intake and knowledge on osteoporosis can be improved by this program. Materials and methods: This preliminary analysis comprised 200 subjects who attended a total of three classes once a month for 3 months. We estimated spontaneous calcium intake by a food frequency questionnaire at the beginning of the first class and a second questionnaire was sent one month later. The questionnaires were interpreted under supervision of the dietician of the lab. In addition, a questionnaire covering general knowledge on osteoporosis was also administered before the first class and sent one month after the last class. Results: Among the whole group who attends the three classes 146 subjects (73%) answer to the questionnaire at baseline and then one month after. The mean calcium intake was 962±263 mg at the first questionnaire and 993±254 at the second. In subject aged ≥70 years, there was a 9.2% (NS) increase in calcium intake between the two questionnaires. In a small group of patients aged ≥70 years and having a T-score under −2.5, there was a trend for a more pronounced increase in the mean calcium intake 802 mg versus 1.024 mg. Among the 50% patients who answered to both questionnaires on osteoporosis knowledge, we have found an increased score of knowledge in 63%.

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Conclusion: This education program leads to an increase in knowledge on osteoporosis. It could be more useful in selected subjects based on age and BMD results. This study was supported by an grant of Eli Lilly France.

P323. Results of osteologic assessment in a cohort of patients after low-impact fracture of proximal femur K. Pavelka1, G. Šimková1, S. Skácelová1, M. Scheinost1, H. Hulejová1, M. Braun1, J. Vaculík2, P. Dungl2; 1Institute of Rheumatology, Prague, Czech Republic, 2Department of Orthopedic Surgery, University Hospital, Institute for Postgraduate Medical Education, Prague, Czech Republic Background: Low-impact fractures of proximal femur are associated with high morbidity, mortality and a considerable economic burden. In the early phase of our research project we focused on the demographic characteristics of our cohort consisting of 39 subjects evaluated so far after a low-impact fracture of proximal femur. Materials and methods: Within the first 6 months we have evaluated the total of 39 patients who have undergone proximal femur surgery after sustaining a low-impact fracture, of which 71.8% were females and 28.2% were males. Basic laboratory tests, PTH, calcidiol, calcitriol, THS levels and measurements of bone markers were performed. Patients underwent bone densitometry and X-rays of thoracic and lumbar spine. Results: Mean age of patients was 73.0 years, mean age of male subjects was 69.8 years, mean age of female subjects was 74.2 years. The average time since menopause in females was 26.9 years. Prior to the evaluation, 20.5% of the patients were aware of the diagnosis of osteoporosis, two of these patients were treated with bisphosphonates, one with calcitonin and the rest were receiving only vitamin D and calcium. 43.5% of the patients were diagnosed with vertebral fractures by X-ray, 25.6% had a history of forearm fracture, 20.5% had a previous history of one hip fracture, some of the patients sustained multiple low-impact fractures in the past. Overall, 69% patients had a history of low-impact fracture and only 20.5% of the total of 39 patients had been previously evaluated for possible osteoporosis. Lumbar spine was assessable by densitometry in 33 of the 39 patients with a mean T-score of −2.2 SD (−1.84 SD in males and −2.37 SD females), therefore in the osteopenia range. Proximal femur scan was performed in 31 patients, the rest had total joint replacement of both hips. The mean T-score value of the total hip was −2.08 SD in males and −2.28 SD in females, again in the osteopenia range. On the femoral neck scan the T-score value was −2.31 SD in males and −2.85 SD in females. Thus falling in the osteoporosis

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range for females only and again in the osteopenia range in males. The diagnosis of primary osteoporosis was established in 61.5 % of patients (based on the presence of vertebral fracture or BMD T-score ≤−2.5 SD on total hip, femoral neck or lumbar spine region). Concurrent secondary etiology of osteoporosis was confirmed in 38.5% patients in the cohort (primary hyperparathyroidism 5, chronic renal failure 3, hyperthyroidism 2, glucocorticoid induced osteoporosis 5). Decreased calcidiol level was detected in 50.2% subjects. Conclusion: Current results demonstrate a high incidence of hypovitaminosis D in the cohort. T-score values were, with the exception of the femoral neck values in females, within the osteopenia range, which confirms that the bone mineral density is only one of the risk factors determining bone fragility. Only 20.5% patients had been evaluated for possible osteoporosis prior to the femoral neck fracture. Supported by a research grant from the Ministry of Health of Czech Republic, MZ0 0002384101.

P324. The favorable effects of Gerimax® on bone tissue and its hormonal regulation in stressed mothers’ offspring L.Yu. Sergienko, N. Malova, L. Pivovarevich, O. Kartavceva, G. Cherevko, T. Bondarenko; Department of Histopathology, Institute of Endocrine Pathology Problems, Kharkov, Ukraine Objectives: It is widely accepted that glucocorticoides activate the bone resorption and their increased level lead to osteoporosis. Recently we demonstrated that offspring of mothers stressed within early pregnancy have elevated basal corticosterone (CRT) concentration during postpartum life. We also discovered that short immobilization causes formation of numerous osteoporosis loci in the hips of these offspring in reproductive age. The aim of this study was to investigate is it possible to prevent the active bone resorption in stressed offspring using Gerimax (G®, Nicomed) for adaptation to stress. Materials and methods: Forty-eight female pups were received from Wistar rats which were daily exposed to social stress starting from second to eighth day of pregnancy and randomly divided into 4 groups (S-1,-2,-3, -4). Before to be lost the model of immobilization stress had been reproduced in S-2; S-3 was treated by G® (1.5 mg/kg, daily, 1 month); G-4 was treated by G® and immobilization simultaneously; G-1 received placebo. The offspring of intact mothers of the same age, sex, quantity at similar experimental conditions were used as control animals (C-1,-2,-3,-4). All rats were killed at 12 months old. The hormone concentrations were determined by the RIA methods. The histological examination of the bone was performed by microscope “Olympus” with a computer of microstructure.

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Results: It has been established that immobilization increased CRT by 20% in stressed offspring and by 55% in intact ones (S-2 vs. C-2, P<0.05). Treatment by G® reduced basal CRT by 98% in stressed offspring (S-3 vs. C-3, P<0.05) and by 115% in stressed offspring with immobilization (S-4 vs. C-4, P<0.01). Calcitonin (CT) in S-1 was decreased compared to C-1 by 27% (P<0.05) but parathormone was steady. G® increased CT concentration in S-3 and C-3 by 17 and 10%, corresponding. G® had most eminent action on CT in S-4 (CT increased to 42.72± 4.56 nmol/ml). Pathological examination showed that the destructive impact on bone tissue of immobilization in stressed offspring characterized by numerous and extensive areas of bone resorption in hip cortex. At that time we did not observe the osteoporotic loci in hips of rats from group S-4. Conclusion: Our finding suggest that G® proves the protective effects on bone tissue and can be used in preventive treatment of osteopenia and osteoporosis. P325. Chilean osteoporosis risk assessment R. Arinoviche, M. Arriagada, H. Amaral, A. Milinarsky, S. Oviedo, P.P. Marin, S. Fischer, C. Grant, M. Arinoviche; Fundación Chilena de Osteoporosis, Santiago, Chile Objectives: To evaluate prevalence of osteoporosis and risk factors for osteoporosis in chilean population. Materials and methods: In a cross sectional study we assessed for calcaneal quantitative ultrasound (QUS) a population across 4 of the most inhabitated 12 regions of Chile. We recruited trough radio, TV and newspapers advertisement, 30.797 women and 6.840 men from 20 to 93 years old. Lately a self-completion questionnare covering osteoporosis risk factors was administrated previous to the QUS assessment and nowadays we analyze the results in 2.393 women. For statistical analysis T-test, ANOVA, Pearson correlation (r) and multivariate analysis with stepwise were used. Results: In 30.797 women we found osteoporosis 1.447 (4.7%) and osteopenia 12.442 (40.4%) and in 6.840 men osteoporosis 158 (2.3%) and osteopenia 2.599 (38%). In women and men older than 70 we found 21 and 11% of osteoporosis. Variables associated (yes/no) with BMD (Tscore) included: Loss of height (>3 cm)−1.32/−0.69 p< 0.001, Glucocorticoids use −0.94/−0.74 p=0.02, Rheumatoid arthritis −1.21/−0.73 p<0.001, Previous non vertebral fracture −1.08/−0.7 p<0.001, Parent’s hip fracture −0.93/ −0.73 p<0.001, Menopause −1.09/−0.52 p<0.001, HRT −0.73/−0.98 p<0.001 and Alcohol −0.68/−0.8 p=0.004. With others discrete variables as smoking, thyroid hormones use, hyperthyroism, renal stones we did not find significant differences; renal insufficiency and chronic diarrhea shown important but not significant differences. A multiavariate

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analysis indicate that Age −0.021 (SE 0.001) p<0.0001, Non vertebral previous fracture −0.224 (SE 0.055) p<0.0001 and Height loss>3 cm −0.141 (SE 0.070) p=0.044 were independently associated with BMD, the final model equation was R ¼ 0:2:0896 þ ð
0:021Þ  Age þ ð
0:224Þ Fracture þ ð
0:141Þ  Height Loss. Conclusions: In Chile osteoporosis has a profile of developped countries and the assessment with calcaneal QUS is usseful for screening population. P326. The relationship between the increased body mass index and the bone fracture prevalence in postmenopausal pollen allergic women F. Viktória1, M. Szilvia1, C. Emőke2, T. Edit3, B. Katalin4, F. András5,6, H. Csaba1; 11st Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary, 2Health Service, Budavar Local Authorities, Budapest, Hungary, 3Department of Rheumatology, Ferenc Flor County Hospital, Kerepestarcsa, Hungary, 4 Regional Osteoporosis Centre Ferencvaros, Budapest, Hungary, 5 Molecular Immunology Research Group, Hungarian Academy of Sciences, Budapest, Hungary, 6 Department of Genetics, Cell and Immunbiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Our aim was to investigate whether pollen-allergy can affect fractures in postmenopausal women. A total of 125 postmenopausal pollen-allergic women (mean age 61.26 years) were split into four groups: Treated neither with H1 histamine receptor (H1R) antagonist nor with inhaled corticosteroid (n=43), treated only with H1R antagonist (n=53), treated both with H1R antagonist and inhaled corticosteroid (n=17), treated only with inhaled corticosteroid (n=12) for at least 5 years, seasonally. Onehundred non-allergic postmenopausal subjects matched for age, body mass index (BMI) and age at menopause served as controls. Overweight and obesity (25 kg/m2 ≤ BMI) were common among allergic women (76%). Untreated allergic had almost triple the rate of prevalent low-energy fractures (distal forearm, hip and clinical vertebral fractures: 34.9%) compared to non-allergic women (13%, chi2p= 0.003). Bone fracture occurred more often in H1R-only treated patients (30.19%) than in controls (chi2p=0.01), however, clinical vertebral or hip fractures developed neither in those treated only with H1R antagonist nor in those who received both H1R antagonist and inhaled corticosteroid. Bone fractures were more frequent among patients with inhaled steroid treatment than among patients with a combined treatment of inhaled steroid and antihistamine (50% vs. 29.4%). BMI predicted prevalent fractures

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at 1.278 (95% CI, 1.047 to 1.559, p=0.016) for 1 kg/m2 increase among untreated allergic patients. In conclusion we found a high prevalence of low-energy fractures among pollen-allergic postmenopausal women, which was associated with obesity. It is possible that the H1R antagonists compensate for the negative effect of pollenallergy and the adverse effect of inhaled corticosteroid treatment on bone fracture risk. P327. The effect of treatment with the biological agent infliximab on bone mineral density in patients with rheumatoid arthritis P. Athanassiou1, I. Kostoglou-Athanassiou2, G.N. Karachalios3, D. Papadopoulou1, Ch. Galanaki1, G. Vosvotekas1, S. Spyridonakou 1 , Ch. Antoniadis 1 , Ph. Kaldrymidis 2 ; 1 Department of Rheumatology, Asclepeion Hospital, Voula, Athens, Greece, 2Department of Endocrinology, Metaxa Hospital, Piraeus, Greece, 3Second Department of Internal Medicine, Red Cross Hospital, Athens, Greece Osteoporosis is a well-known characteristic of rheumatoid arthritis (RA). Low bone mineral density has been observed in RA patients, especially those with a flare of the disease. Infliximab is a chimeric monoclonal antibody against TNF-α, which is used in the therapeutic management of RA and is considered to contribute to disease remission. The aim was to study the effect of treatment with infliximab on bone mineral density in patients with RA. A group of 35 patients, nine men and 26 women, aged 32– 67 years, with RA were studied. All the patients fulfilled the American College of Rheumatology criteria for the diagnosis of RA and had resistant RA, not responding to the administration of disease-modifying agents for a period of at least 6 months. All the patients received treatment with infliximab and methotrexate or leflunomide. All the patients received also low dose corticosteroids (5–7.5 mg prednisolone). In all patients bone mineral density in the lumbar spine was measured before treatment with infliximab and 1 year later. An improvement in bone mineral density of 1.23% was observed. No correlation of bone mineral density with the improvement in inflammation indices, erythrocyte sedimentation rate and C-reactive protein and the DAS28 clinical index was observed. The use of infliximab in RA treatment seems to inhibit the progressive decrease in bone mineral density, which is related to the disease. Longer studies with measurements of bone mineral density in more than one skeleton sites and a larger number of patients are needed for the estimation of the effect of the biological agent infliximab on bone metabolism in patients with rheumatoid arthritis.

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P328. Bone mineral density in premenopausal subclinical and clinical hyperthyroid women Z. Zengin, A. Sertkaya Cikim; Department of Internal Medicine, Division of Endocrinology and Metabolism, Inonu University Turgut Ozal Tip Merkezi, Malatya, Turkiye Objectives: The aim of this study is to evaluate the effects of subclinical hyperthyroidism (SH) and clinical hyperthyroidism (H) on bone metabolism, and mineral density (BMD) in premenopausal women. Materials and methods: Sixteen H (31.3±9.5 years), 23 SH (33.7±7.3 years) and 20 healthy (31.7±8.1 years) premenopausal women were enrolled into the study. BMD was assessed by DXA through lumbar vertebrae and femur. Osteocalcin, total alkaline phosphatase (tALP), homocysteine and β-2 microglobulin, hsCRP were assessed in serum samples; and deoxypyridinoline (DPD) and calcium in urinary. The groups were matched for demographic, anthropometrical parameters; and osteoporotic risk factors. Results: None of the parameters were different between control and SH groups. Serum calcium, tALP, osteocalcine, β-2 microglobulin and thyroid receptor antibody (TRAb) as well as thyroid hormones, DPD were significantly different in H group than both SH and control groups. BMD was not different either in SH or even H groups than controls. Thyroid hormones (FT3 and FT4) were correlated with osteocalcin (p=0.0001 for both FT3, FT4), β-2 microglobulin (p=0001; p=0.006, respectively), ALP (p=0.0001 for both); lumbar vertebrae BMD (p=0.026; p=0.027, respectively) and femoral BMD (p=0.03; p=0.02, respectively). Both osteocalcine and tALP were significantly and negatively correlated with vertebrael (p=0.004 and p=0.0001, respectively) and femoral BMD (p=0.004 for both). Additionally β-2 microglobulin; as marker of bone resorption, was slightly but significantly higher in H group. hsCRP was neither different within groups nor correlated with any study parameters. Despite homocysteine was not different within groups; it was significantly correlated with ALP (p=0.0001) and DPD (0.001). Conclusions: There is limited and conflicting data about the effects of subclinical hyperthyroidism on bone turnover in premenopausal period. Despite we could not establish any difference for bone turnover markers between control group and subclinical hyperthyroid patients; with tight correlations between thyroid hormones; we can conclude that SH patients are prone to osteoporosis. The limitation of this study was the lack of longitudinal follow up of these patients in long period of

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time and the awareness of the condition until diagnose. Additionally younger age could possibly the preventive factor on bone mineral density. P329. Efficacy and safety of a novel transdermal low-dose estradiol delivery system (Menostar) for the prevention of postmenopausal bone loss compared with raloxifene (Evista): a 2-year randomized clinical trial L. B. Tankó1, M. Schaefers2, C. Muysers2, C. Christiansen1; 1 Center for Clinical and Basic Research, Ballerup, Denmark, 2 Schering AG, Berlin, Germany Objectives: To investigate the efficacy and safety of a novel transdermal low-dose estradiol delivery system for the prevention of vertebral bone loss with reference to raloxifene 60 mg/day. Materials and methods: The study was a multicenter, randomized, double-blind, double-dummy, active-controlled non-inferiority comparison trial. Participants were 500 osteopenic, postmenopausal women aged 55–80 years. Patients were randomized to receive either a weekly transdermal patch delivering 0.014 mg estradiol daily (Menostar®, Schering AG) together with placebo capsules in lieu of the active oral therapy, or oral treatment with raloxifene 60 mg daily (Evista®, Eli Lilly), together with a weekly placebo patch for 2 years. The primary efficacy endpoint was the percentage change from baseline in BMD at the lumbar spine (L2–L4) after 2 years. Secondary efficacy endpoints reported herein were the proportion of patients with no loss of lumbar spine BMD and the percentage change in bone turnover markers (CTX-I, D-Pyr, OC, BSAP). Safety assessments included careful assessment of endometrial effects (bleedings/endometrial thickness/biopsy), changes of breast density, laboratory parameters, and self-reported adverse events. Results: Number of discontinuation in the estradiol and raloxifene groups were 56 (22.1%) vs. 41 (16.4%). In the full analysis set, the percentage change from baseline at the lumbar spine for the estradiol (n=233) and raloxifene (n=241) groups were 2.3 (95% CI 1.8–2.7) and 2.7 (95% CI 2.2–3.1), respectively. Thus, the difference between estradiol and raloxifene were −0.39% (non-inferiority test p=0.004). The proportion of patients with no bone loss at the lumbar spine at the end of the study was 77.3 and 80.5%, respectively. Changes of the different bone resorption (CTXI and D-Pyr) and formation (osteoclacin and BSAP) markers indicated comparable degree of inhibition by the two treatments. Number of serious adverse events in the estradiol

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and raloxifene groups were 36 (4.9%) and 41 (5.4%). There were no clinically significant signs of endometrial or breast stimulation by either treatment. Conclusions: In the growing are of low-dose estradiol therapies, the herein described transdermal delivery system offers a useful option for the prevention of vertebral bone loss with efficacy and safety comparable with that of Evista. P330. The effect of treatment with the biological agent etanercept on bone mass in patients with rheumatoid arthritis I. Kostoglou-Athanassiou 1 , P. Athanassiou 2 , G.N. Karachalios 3 , D. Papadopoulou 2 , Ch. Galanaki 2 , E. Vritzali2, E. Bastakis2, Ch. Antoniadis2, Ph. Kaldrymidis1; 1 Department of Endocrinology, Metaxa Hospital, Piraeus, Greece, 2Department of Rheumatology, Asclepeion Hospital, Athens, Greece, 3Second Department of Internal Medicine, Red Cross Hospital, Athens, Greece Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology. The disease is characterized by bone erosions and a progressive decrease of bone mineral density. The biological agent etanercept, a human soluble receptor of TNF-α, which binds to the circulating TNF and prevents its binding to the receptor, its interaction with the receptor and the induction of inflammation, is used in the treatment of RA. The aim was to study the effect of treatment with the biological agent etanercept on bone mineral density in patients with RA. A group of 28 patients, eight men and 20 women, aged 27– 68 years, with RA were studied. All the patients fulfilled the American College of Rheumatology criteria for RA diagnosis and had resistant RA, not responding to the administration of disease-modifying agents for a period of at least 6 months. The patients were given etanercept subcutaneously, 25 mg twice weekly. Amongst the group of patients, 24 continued to receive at least one disease modifying agent and four were given only etanercept. Within the group of patients, 12 continued to receive methotrexate (7.5–15 mg weekly) and 12 leflunomide (100 mg daily for 3 days and thereafter 20 mg daily). Low dose corticosteroids were also administered (5– 7.5 mg prednisolone). Bone mineral density was measured at the lumbar spine in all patients, before treatment with etanercept and 1 year later. An improvement of bone mineral density of 1.38% was observed. No correlation of bone mineral density with the improvement in inflammation indices (ESR, C-reactive protein) and the clinical index DAS28 was observed. The use of etanercept in RA treatment appears to improve the clinical picture of the disease and to inhibit bone mineral density decrease. Longer studies with measurements of bone

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mineral density in more than one skeleton sites are needed to assess the effect of treatment with etanercept on bone metabolism in rheumatoid arthritis. P331. The effect of treatment with the biological agent anakinra on bone mass in patients with rheumatoid arthritis P. Athanassiou1, I. Kostoglou-Athanassiou2, G.N. Karachalios3, Ch. Galanaki1, D. Papadopoulou1, Ch. Antoniadis1, Ph. Kaldrymidis2; 1Department of Rheumatology, Asclepeion Hospital, Voula, Athens, Greece, 2 Department of Endocrinology, Metaxa Hospital, Piraeus, Greece, 3Second Department of Internal Medicine, Red Cross Hospital, Athens, Greece Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology. The disease is accompanied by osteoporosis, which is due to the inflammatory nature of the disease as well as drug treatment. The biological agent anakinra is a recombinant, non-glycosylated form of the human antagonist of interleukin-1 receptor (IL-1Ra) and is used in the treatment of RA in subcutaneous administration. The aim was to study the effect of treatment with the biological agent anakinra on bone mineral density in patients with RA. A group of 14 patients, three men and 11 women, aged 29– 65 years, were studied. All the patients fulfilled the American College of Rheumatology criteria for RA diagnosis and had resistant RA, not responding to treatment with diseasemodifying agents for a period of at least 6 months. The patients were administered anakinra subcutaneously 100 mg daily. All the patients continued to receive at least one diseasemodifying agent, 7 of them receiving methotrexate (7.5– 15 mg weekly) and 7 leflunomide (100 mg daily for 3 days and thereafter 20 mg daily). Corticosteroids in low dose were also administered (5–7.5 mg prednisolone). In all patients bone mineral density was measured in the lumbar spine before treatment with anakinra and 1 year later. A small improvement of bone mineral density of 0.6% was observed. No correlation of bone mineral density with the improvement in inflammation indices, ESR and C-reactive protein, and the clinical index DAS28 was observed. The use of anakinra in RA treatment seems to improve the clinical picture of the disease and to inhibit the progressive decrease in bone mineral density. Longer studies with measurements at more than one skeleton sites are needed in order to assess the effect of the biological agent anakinra on bone metabolism in patients with rheumatoid arthritis.

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P332. Methodological issues when measuring compliance and persistence with bisphosphonates for osteoporosis in claims databases J. Cramer1, N.O. Lynch2, H. Middelhoven3; 1Yale University School of Medicine, New Haven, Connecticut, USA, 2 GlaxoSmithKline, London, United Kingdom; 3F. HoffmannLa Roche, Basel, Switzerland

(1) Siris et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US Claims Databases. Mayo Clin Proc 81(8):1013–1022 (2) Peterson AM, Nau DP, Cramer JA, Benner J, Gwadry-Sridhar F, Nichol M. A (2006) Checklist for medication compliance and persistence studies using retrospective databases. Value in health, (in press)

It has been recognized that improved treatment adherence is linked to a better clinical outcome, including in the field of osteoporosis.(1) The approach taken with bisphosphonates has been to lengthen the dosing interval from daily to weekly, and recently to monthly. Most analyses of compliance and persistence with bisphosphonates, as well as other medications, use administrative databases to assess prescriptions refills and medical diagnoses in association with utilisation of healthcare services. This method provides an opportunity for unobtrusive observation of patients in the community, in contrast to clinical trials where patients volunteer to participate in observation. Both compliance and persistence can be evaluated for large numbers of patients. The limitations of these claims databases include the observational nature (non-randomized) and limited information about non-prescription medical treatments. To overcome challenges associated with claims database studies, the International Society for Pharmacoeconomic and Outcomes Research (ISPOR) published a checklist that is of help to researchers in the field.(2) When studying bisphosphonates in the treatment of osteoporosis in US claims databases, several baseline confounding factors are known to influence a persistency outcome, including age, co-morbidities, healthcare costs, and average co-pay. Therefore, careful consideration of the data source and controlling for confounding variables is important. In addition, the refill gap allowed before considering a patient as non-persistent should be both clinically sensible and consistent with approved product labeling. For example, FDA approved labeling allows a 6 day dosing window for weekly bisphosphonates and a 21 day dosing window for monthly bisphosphonates—a 15 day difference. Although compliance, often measured as Medication Possession Ratio (MPR), estimates the maximum drug utilisation it does not factor in time sequence or pattern. Persistence measures time staying on therapy, which is the link to clinical benefit and fracture reduction. Thus, persistence is probably a more valuable approach to treatment outcomes for bisphosphonates. Further, comparisons of compliance and/ or persistence must consider different time frames observed. The above described challenges show that a scientific robust methodology in claims database studies is necessary to quantify changes in persistence with bisphosphonates for the treatment of osteoporosis.

P333. Monthly ibandronate improves persistence vs. weekly bisphosphonates after 9 months of treatment P. Hadji1, M. Cziraky2, C. Harley3, H. Middelhoven4, C.E. Barr5, S. Poston6, C. Cooper7; 1University of Marburg, Marburg, Germany, 2HealthCore, Inc., Wilmington, Delaware, USA, 3i3 Innovus, Eden Prairie, Minnesota, USA, 4F. Hoffmann-La Roche, Basel, Switzerland, 5Roche Laboratories Inc., Nutley, New Jersey, USA, 6GlaxoSmithKline, Collegeville, Pennsylvania, USA, 7MRC Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom Objectives: Bisphosphonates play a key role in the treatment of osteoporosis. However, optimal clinical outcomes need patients to persist with therapy. Less frequent dosing improves persistence as shown in studies of weekly versus daily oral bisphosphonates. The current retrospective analysis compares “real-world” persistence for women receiving monthly oral ibandronate versus weekly oral bisphosphonates. Six-month findings showed approximately 25% better persistence with monthly ibandronate than weekly bisphosphonates.(1) We report here the results of the 9-month analysis. Materials and methods: Two healthcare databases provided patient data from April 2005, excluding patients with Paget’s disease, drug-induced osteoporosis, cancer, or hyperparathyroidism. Persistence with monthly ibandronate and weekly alendronate or risedronate was defined as the proportion of patients staying on therapy without a gap in coverage. These gaps were 30 and 45 days for weekly and monthly dosing, respectively, consistent with FDA-approved labeling to allow for the 15-day difference in dosing windows. Cox regression was used to analyse persistence, controlling for potential confounders. Results: As at 6 months, patients receiving monthly ibandronate were significantly more likely to persist with treatment relative to those in the weekly cohort. In the database from i3 Innovus, the crude (unadjusted), 9-month persistence rates for patients using monthly ibandronate (n=967) or a weekly bisphosphonate (n=8,662) were 47.7 and 35.4%, respectively (p<0.0001). Monthly ibandronate users were 38% more likely to persist with therapy than weekly bisphosphonate users after controlling for age, copay and comorbidities (hazard ratio=0.620, 95% CI 0.563,0.683, p<0.0001). Similar differences between crude

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persistence rates were found for the HealthCore database: 41.3 and 33.4%, respectively (p=0.003), for patients receiving monthly ibandronate (n = 213) or a weekly bisphosphonate (n=4.335). Monthly ibandronate users were 31.0% more likely to persist with therapy than weekly users after adjusting for confounding factors using Cox regression (p<0.0001). Conclusions: Consistent with the 6-month findings, women were significantly more likely to persist for at least 9 months with monthly oral ibandronate compared with weekly bisphosphonates. (1) Silverman S, et al (2006) J Bone Miner Res 21(Suppl. 1): S290 (Abstract SU335).

P334. Alterations in bone metabolism during infective exacerbations in patients with cystic fibrosis E. Shead1, C. Haworth2, H. Barker2, E. Gunn2, D. Bilton2, M. Scott1, G. Wakley3, J. Compston4; 1Department of Haematology, Addenbrookes NHS Trust, Cambridge, United Kingdom, 2Papworth NHS Trust, Cambridge, United Kingdom, 3Department of Anatomy, Bristol University, United Kingdom, 4Department of Medicine, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom Objectives: Osteoporosis is a disease characterised by low bone mass, bone fragility and increased risk of fracture. Approximately 25% of CF adults have low bone mineral density (BMD) and CF disease severity is the most consistent correlate. Infective exacerbations are associated with increased circulating pro-resorptive cytokines and may result in increase bone resorption. The aim of this study was to investigate variation in levels of receptor activator of nuclear factor B ligand (RANKL), osteoprotegerin (OPG) and bone turnover markers (osteocalcin and NTx) before (baseline), during (day 1 and 14) and after (day 42) an infective exacerbation treated with intravenous antibiotics. Materials and methods: Twenty-four patients (14 male, mean [SD] age 24.7 years [6.0], FEV1 48.8% of predicted, BMI 21.3 kg/m2) were recruited. None of the patients had been prescribed oral glucocorticoids for at least 3 months before the baseline visit and all patients were colonised with Pseudomonas aeruginosa. The ELISA kits used were sRANKL (900-K142) from Peprotech Ltd. (Europe), OPG (DY805) from R&D Systems, competitive inhibition human NTx (9021) from Osteomark (Unipath Ltd., United Kingdom) and Osteocalcin (KAP1381) from Biosource (France). Results: Increased levels of serum NTx were observed at day 1 (p=0.008) and day 14 (p=0.014) of exacerbation, which had decreasd by day 42. Osteocalcin levels at baseline were lower than control levels (p<0.05); however levels did not vary during an exacerbation. Serum RANKL

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levels had increased significantly by day 14 (p<0.05) and were decreased by day 42. OPG levels at baseline were lower than control levels (p<0.05) and levels increased by day 14 (p<0.05) before reducing at day 42. Conclusions: These data support the hypothesis that the systemic response to pulmonary infection results in increased bone resorption in patients with cystic fibrosis. These episodes of increased resorption are likely to play an important role in the development of osteoporosis in these patients. P335. Association of sex steroids deficiency with osteoporosis in older men F.L. Popa1, M. Stanciu1, M. Rotaru1, I.Gh. Totoianu1, A. Banciu2; 1Faculty of Medicine “Victor Papilian”, University “Lucian Blaga” of Sibiu, Sibiu, Romania, 2University “Iuliu Hatieganu” of Cluj-Napoca, Cluj-Napoca, Romania Objectives: Low testosterone and estradiol levels are associated with low bone mineral density at elderly men. The objective of this study is to determine the testosterone and estradiol levels and the incidence of osteoporotic fractures at older men. Materials and methods: We studied 68 patients (aged 60 to 85 years; mean age=72.5 years) with osteoporosis or osteopenia. Testosterone and estradiol levels, as well as spine and hip bone mineral density using dual energy X-ray absorptiometry were evaluated. Radiographs of the spine, hip and fracture place were also made. Results: Fifty-seven patients (83,82%) presented osteoporosis and 11 (16,17%) osteopenia. The prevalence of total testosterone deficiency (with normal estradiol level) was 22.05% (15 men), 20% (3 men) of them presented peripherical fractures (distal epiphysis of radius, ankle). The prevalence of total estradiol deficiency (with normal testosterone level) was 23.52% (16 cases), 18.75% (3 cases) of them with hip fracture and 25% (4 cases) with vertebral fractures. Twenty-one patients (30.88%) presented both testosterone and estradiol deficiency and an incidence of vertebral fractures 14.28% (3 men). 16 men (23.52%) had normal levels of sex steroids and no fractures. Conclusion: Although both serum testosterone and estradiol levels decline with age at men, it is estradiol which may serve as a major predictor of their bone loss and may identify men with highest risk of fracture. P336. Assessment of cartilage and bone degradation markers in patients with osteoarthritis B. Bozic1, N. Prodanovic2; 1Faculty of Biology, University of Belgrade, Serbia, 2Military Medical Academy, Belgrade, Serbia Objectives: Inflammation, a common property of osteoarthritis (OA), has an influence on increased cartilage and

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bone degradation. At the other side, osteoporosis (OP) is a skeletal disorder characterized by decreased bone density and increased risk for bone fractures. Assessment of the biochemical metabolites of bone resorption and formation are good parameters which picture bone metabolism in OA patients. The aim of this study was to assess and correlate levels of cartilage oligomeric matrix protein (COMP) as cartilage degradation marker and helical peptides (HP) as bone resorption marker in patients with knee OA without antiresorptive therapy. Materials and methods: This study took place in the Department for Osteoporosis at the Military Medical Academy. Twenty-one patients with OA had their bone mineral density (BMD) and degradation molecules (COMP, HP) measured. The serum COMP and urine HP levels were determined using ELISA. BMD was measured by Lunar DEXA DPX 2000 device, on the lumbar spine. Results: Demographic, clinical characteristics and values of COMP and HP of OA patients included in the study showed in table. In OA patients the COMP and HP values were higher compared to normal values which for COMP and HP are <5 U/l and <50 μg/mmol creatinine, respectively. The COMP values were correlate with HP values r= 0.544, p=0.000. BMD measured on the lumbar spine L1–4 T-score was −2.71±−0.53 SD. Table 1: Demographic, clinical characteristics and values of COMP and HP of OA patients Parameters

Values

Female/male (numbers) Disease duration (years) Age (years) ESR (mm/hg) COMP (U/l) HP (μg/mmol creatinine)

9/12 7.04±8.9 56.24±15.15 33.24±20.24 8.18±2.32 120.81±33.58

Conclusions: Our results confirmed that the degradation markers of cartilage and bone are very important markers of cartilage and bone degradation in OA patients. P337. Epidemiological profile of symptomatic knee osteoarthritis in adults: a population based study in Igbo-Ora, Nigeria B.A. Adekanla1, T.O. Alonge2, A.O. Akinpelu1; 1Department of Physiotherapy, College of Medicine, University of Ibadan, Ibadan, Nigeria, 2Department of Orthopaedic and Trauma, University College Hospital, Ibadan, Nigeria Objectives: Many people with osteoarthritis do not seek medical care and are therefore not included in the hospitalbased prevalence estimates. The true prevalence of symp-

tomatic knee osteoarthritis in the community is therefore unknown. This study was designed to investigate the prevalence and pattern of symptomatic knee osteoarthritis (OA) in a rural Nigerian community. Materials and methods: This cross-sectional survey involved a total of 1.054 residents aged 40 years and above in Igbo-Ora, a rural community. Participants were recruited through a multi stage cluster sampling technique. Symptomatic knee osteoarthritis was diagnosed using standardized joint examination based on the American College of Rheumatology (ACR) clinical criteria. Severity of knee osteoarthritis was assessed in individuals who met the clinical criteria for knee OA positive using the Lequesne severity Index of knee osteoarthritis. Data was analyzed using descriptive statistics. Results: The estimated prevalence of knee OA was 21.8%. The prevalence of knee OA was more in females (58.3%) than males (41.7%). The peak prevalence of OA (33.0%) was in the 50–59 year age group. Prevalence was also high (27.8%) in the 60–69 year age group and lowest (47.0%) in the above 70 years age group. 62.6% have had symptoms of knee OA for more than 3 year, while 37.4% have had symptoms for less than 3 years. The severity of Knee OA was extreme in 23.5%, very severe in 45.7% and moderately severe in 30.9%. Conclusion: The prevalence of knee OA in the community is high with about 1 out of every five adults affected by symptomatic knee osteoarthritis. Prevalence is higher among females than males with large percentage having very severe symptoms. P338. Influence of bisphosphonate therapy on the prevalence of hip and vertebral fractures in postmenopausal Iranian women (primary results) P. Tofighi1, N. Sedighi2, M. Mirsafa1, A. Hossein-Nezhad1, H. Adibi1, B. Larijani1; 1Endocrinology and Metabolism Research Centre, Tehran University, Shariati Hospital, Tehran, Iran, 2Department of Radiology, Shariati Hospital, Tehran, Iran Objectives: Vertebral fractures have a high prevalence in postmenopausal women. Furthermore, one third of the patients with vertebral fracture do not aware of it. There are not many studies on the effect of bisphosphonates on bone density and fractures in the lumbar area of spine. The aim of this study is to evaluate the effect of bisphophonates on prevalence of hip and vertebral fractures in postmenopausal Iranian women. Material and methods: In this study, 155 postmenopausal women who were undergone BMD (bone mineral densitometry) at BMD unit of EMRC (Endocrinology and Metabolism Research Centre of Tehran University) (from 2004 till now) were selected. The x-ray of lumbar (anterior-

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posterior and lateral) were obtained. Among them 34 patients were taking bisphosphonates for more than 1 year (case) and the others were not, but taking calcium supplements (control). The demographic factors were matched. A radiologist reported the fractures in L1–L4 vertebrae and classified them according to Genant et al. The BMD of lumbar and total hip were obtained. Results: The mean age in case group was: 59.38±9.68 years and in control group: 56.32±7.25 years (P=0.1). The vertebral height (L1–L4) in case group was 12.8±0.7 and in control group: 12.9±0.6 (P=0.4). The T-score in lumbar area (L1–L4) was −1.8±1.5 in case group and −1.4±1.5 in control group (P=0.2). The total femur t-score was −1.13± 0.9 in case group and −0.7±1.19 in control group (P=0.1). The percent of vertebral fractures was 47% in control and 57.1% in case group (P=0.2). In case group there were 14% improvement in spine BMD and 45% in hip BMD. Odds ratio in femur of case group in comparison with control group was 1.48. Conclusion: Vertebral fractures are common in postmenopausal women, especially in osteoporotic patients. According to our results, although bisphosphonates had no role in decreasing the prevalence of vertebral fractures, they had effects on reducing hip fractures and improvement of total femur BMD. P339. Evaluation of the technical positioning during DXA measurements E. Özgüçlü, L. Özçakar, A. Çetin, A. Akinci Tan; Department of Physical Medicine and Rehabilitation, University of Hacettepe, Ankara, Turkey Objectives: Osteoporosis is the most prevalent metabolic bone disease. For prompt diagnosis of osteoporosis, properly instructed dual-energy X-ray absorptiometry (DXA) measurements are required. To get correct DXA results, recommended technical positions for specific body regions such as hip and spine are to be achieved. The aim of this study was to assess the accurateness of the technical positions for hip and spine regions. Material and methods: One hundred thirteen patients’ paired hip and spine DXA reports were reviewed retrospectively. In spine, four technical positions were assessed; whether (a) the spine is in the midline of the image and (b) is in a straight line, (c) both iliac crests come into view, (d) half of the bodies of T12 and L5 vertebrae are seen. For the hip region, three technical positions were considered; whether (a) the femoral shaft is in a straight, (b) the trochanter minor is not visualized or is seen slightly, (c) the ischium and the trochanter major are seen. Discordant positions according to these criteria were accepted as “technically invalid position.”

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Results: Out of 113 hip and spine DXA reports, 52 hip and 19 spine DXA reports fulfilled all mentioned criteria. 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 DXA reports, 40.7% of the femoral shaft was deviated to one side. 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. Conclusion: We found the ratio of invalid positions surprisingly very high. This may stem from local technical problems, such misinterpretations would definitely affect clinicians’ decisions in an inappropriate way. We suggest that relevant inconveniences should be kept in mind both by the clinicians and the technical staff for better production and prompt estimation of bone mineral density measurements. P340. Quality of life in postmenopausal osteoporosis P. Borman, O. Tanyolac, C. Atan, H. Bodur; Clinic of Polymyalgia Rheumatica (PMR), Numune Training and Research Hospital, Ankara, Turkey The aim of this study was to determine the impact of osteoporosis on the quality of life in a group of postmenopausal women. Thirty females with osteoporosis, 30 females with osteopenia and 30 healthy control subjects; all age-matched were included to the study. Demographic data, lumbar spine and femoral neck bone mineral density (BMD) were collected. Quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) was used to assess health-related quality of life. The mean age of the subjects was 58.1±8.32 years. There was nine patients with non-traumatic lumbar and/or femoral fracture history. The mean scores of pain and physical activity domains of QUALEFFO were significantly higher in the osteoporotic group than in the osteopenic females and control subjects (pain: 56.8±21.1 vs 42.9±20.2 vs 36.1±21.9 ; physical activity: 47.2±16.7 vs 36.7±12.5 vs 331.7±17.9, respectively). The scores of psychosocial domains were also higher in the osteoporotic females than in other subjects but the difference did not reach to significance. Women who experienced a fracture had significantly higher total QUALEFFO scores, indicating lower quality of life, compared with non-fractured females (48.8 ± 15.2 vs 31.6±11.3, respectively). The BMD levels were similar betweeen the females with and without fractures. In conclusion, osteoporotic females have a reduced quality of life, especially related with fractures. The negative impact of osteoporosis on quality of life, seems to be more

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related to physical subgroups rather than psychosocial domains. P341. The efficacy of nasal calcitonin on the treatment of osteoporosis in male patients with ankylosing spondylitis P. Borman, H. Bodur, N. Bingol; Department of Physical Medicine and Rehabilitation, Numune Education and Research Hospital, Ankara, Turkey Osteoporosis is a prominent feature of ankylosing spondylitis (AS) as suggested by an uncoupling of bone formation and resorption. The aim of this study was to determine the lumbar bone mineral density (BMD) and evaluate the efficacy of nasal calcitonin 200 mg in a group of male AS patients with osteoporosis. Thirty-two consecutive AS patients with a mean age of 35.1±11.4 years and with a mean duration of 14.8 years were included to the study. Demographical, clinical and laboratory characteristics of the patients were recorded. Lateral spine radiographs were taken and lumbar lateral BMD were determined for the assessment of vertebral fractures and osteoporosis, before and after the study. Patients who were defined as osteoporotic according the WHO criteria were received nasal calcitonin 200 mg daily for 1 year. The primary outcome measure was the percentage of change in the lumbar spine BMD. Osteoporosis was determined in 11 (34.3%) of patients and ten patients (31.2%) had osteopenia. Although not statistically significant, at the end of 12 months with calcitonin therapy, the lumbar spine BMD of osteoporotic patients was increased (0.81±0.47 vs 0.85±0.34) (p>0.05) and a trend toward a decrease in the incidence of new vertebral fracture was also observed. Calcitonin was well tolerated and no adverse event was reported. We conclude that nasal calcitonin 200 mg daily may be effective in the treatment of male AS patients with established osteoporosis. Further studies are needed to confirm these preliminary findings. P342. Role of age in investigation and treatment of osteoporosis S. Eltabal1,2, F. Giurani1; 1Department of Medicine, King’s Mill Hospital, Sutton in Ashfield, United Kingdom, 2 Department of Endocrinology, Garyounis University, Benghazi, Libya Osteoporosis is a global health care problem. It has a wide spectrum ranging from asymptomatic to vertebral or hip fracture. Fractures due to osteoporosis are a principal cause of disability and death and economical burden on health

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resources. Less than one third of patients who have had fragility fractures are properly evaluated and treated for osteoporosis even lower among those without a history of fragility fracture. Risk of fracture determines whether medication is warranted. Previous vertebral or hip fracture is the most important predictor of fracture risk. Bone density is the best predictor of fracture risk for those without prior adult fractures. Deciding which patients are appropriate candidates for effective treatment is a clinical challenge. In order to review the current NICE guidelines for treating osteoporosis, and their economic and clinical implication the present study was conducted. We retrospectively studied subjects referred for BMD assessment by DEXA Scan and patients attending the Osteoporosis Clinic in King’s Mill Hospital, United Kingdom. The study involved a total number of 400 patients, 196 of them were females of 75 years old or above, the rest are post-postmenopausal women 55 to 74 years of age. Parameters including age, BMI, smoking, alcohol, age at menarche and menopause, hysterectomy, family history, and medications as risk factors for osteoporosis were studied in all groups of subjects with or without history of fragility fractures. In patients above 75 years who have previously suffered a fragility fracture, one in 15 had a normal T-score, whereas, only 1 in 3 had normal T-score in subjects without history of fragility fracture. These figures are different from the younger age groups. Based on our data we believe that the current NICE guidelines to treat patients 75 years old or above with fragility fractures without the need for DEXA Scan are probably justified on clinical and economic bases, and the 75 years limit should be lowered. This does not preclude BMD testing in subjects at risk without fractures. P343. Bisphosphonates effect on bone mineral density from osteopenic women with breast cancer E. Rodríguez Rodríguez1, L.M. Rodríguez Rodríguez2, E. Martín Ponce1, R. Alemán Valls1, R. Ros Vilamajó1, M.C. Durán Castellón1, M. Rodríguez Gaspar1, A. Gómez3, E. González Reimers1, F. Santolaria1; 1Internal Medicine Service, Canary Islands University Hospital, La Laguna, Tenerife, Spain, 2Medical Oncology Service, Canary Islands University Hospital, La Laguna, Tenerife, Spain, 3 Nuclear Medicine Service, Canary Islands University Hospital, La Laguna, Tenerife, Spain Objectives: Adjuvant therapies for breast cancer can produce bone damage. Chemotherapy induces bone loss mainly by enhancing ovarian failure. Tamoxifen has certain protective effect on bone from postmenopausal women but it seems to have a deleterious effect on bone from

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premenopausal ones. Bone effects of new aromatase inhibitors are under study. Bisphosphonates are nowadays the elective treatment for osteopenia induced by adjuvant treatments for cancer. We studied their effect in a group of breast cancer osteopenic women. Patients and methods: We prospectively measured bone mineral density (BMD) from 100 osteopenic women (57± 11 years old) with breast cancer (6.7±3.5 years from diagnosis) that were treated with bisphosphonates (oral alendronate/risedronate or IV zoledronate indistinctly) plus calcium and vitamin D supplements during at least 12 months (38±18 months) between December 1995– August 2006. Lumbar and hip BMD (g/cm2, Hologic 2000 densitometer) was measured before treatment and every 12–18 months. Results: Forty-five percent of the women had osteoporosis and 55% osteopenia by OMS criteria. Eighty-nine percent of the patients were menopausal. BMD increased or maintained unchanged along the follow-up period (Table).

Before treatment After 12 months After 24 months After 36 months After 48 months

Lumbar spine

Femoral neck

Trochanter

Total hip

0.872±0.1

0.709±0.1

0.627±0.1

0.837±0.1

0.893±0.1*

0.725±0.1*

0.631±0.1*

p=NS

0.884±0.1*

0.720±0.1*

0.639±0.1*

p=NS

0.916±0.1*

0.744±0.1*

0.646±0.1*

p=NS

0.875±0.1

0.739±0.1*

p=NS

p=NS

*p<0.05

Seventy-three percent of the women had received chemotherapy and 80% tamoxifen. Sixteen percent received aromatase inhibitors after tamoxifen treatment. BMD evolution of women treated with tamoxifen did not differ from that of the other women. Eighty-three percent of the women referred good adherence to bisphosphonates treatment. The non adherence group showed progressive BMD decrease at femoral neck (p=0.049). Twenty-eight percent of the patients had some secondary effect with the treatment, but only 6% of them dropped it out. Two women returned to normal BMO values and bisphosphonates were suspended. Only one woman died during follow-up. At the end of the study 94% of the women were free of cancer disease.

Conclusions: Globally, our patients showed a progressive increase of BMD. Many authors preconize today bisphosphonates use during cancer adjuvant treatment, with the aim to prevent bone loss in these patients. P344. Relationship between PVUII and XBAI polumorphisms of estrogen receptor alpha gene and bone mineral density in postmenopausal women with osteoporotic fracture J. Espinoza Pineda1, M.L. Villahermosa3, A. Drozdowskyj4, M. Andrade1, P. Llamas2, M. Diaz Curiel1; 1Internal Medicine Service, Fundación Jiménez Díaz, Bone Metabolic Disease Cathedra, Universidad Autonoma, Madrid, Spain, 2Molecular Biology Section, Hematology Service, Fundación Jiménez Díaz, Universidad Autonoma, Madrid, Spain, 3GENOMICA, Madrid, Spain, 4Bioestatics Department, PIVOTAL, Madrid, Spain Introduction: Genetic factors have been implicated in the regulation of bone mineral density (BMD). Estrogen receptor-alpha gene (ESR a), is a candidate for osteoporosis susceptibility. Objectives: Our objective was to investigate the genotypic frequency of PvuII and XbaI polymorphisms in a group of patients with post-menopausal osteoporosis and fracture and its possible contribution to development of osteoporosis. Patients and methods: Seventy patients (age range, 57– 86 years) with post-menopausal osteoporosis and fractures were enrolled (78% had vertebral fracture; 7% Colles’ fracture; 12% hip fracture, and 3% other). Thirty-six healthy post-menopausal age matched female subjects served as controls. Estrogen receptor-alpha PvuII and XbaI polymorphisms were determined by a DNA-chip methodology (Metabone Clinical Arrays®), where capital P and X, and lower-case p and x represent reflect absence and presence of the restriction site, respectively. Bone mineral density was measured by dual energy X-ray absorptiometry [Hologic® densitometer QDR4500 (Hologic Inc, MA, USA)] in lumbar spine (L2–L4), femoral neck and total hip. Results: All patients had BMD less than−2.5 t-score at lumbar and/or femoral neck. The genotype frequency of estrogen receptor-alpha PvuII (PP, 32.3%; Pp, 39.4%; pp, 25.3%) and XbaI (XX, 16.9%; Xx, 42.2%; xx, 39.4%) of postmenopausal osteoporotic patients with fracture were not statistically different from those of the healthy agematched control group. Conclusions: None of the polymorphisms analyzed in this paper was associated with decreased bone mineral density, in postmenopausal osteoporosis.

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P345. Polymorphisms in the calcitonin receptor gene are not associated with osteoporotic fractures J. Espinoza Pineda1, M.L. Villahermosa3, A. Drozdowskyj4, M. Andrade1, A. García Raso2, M. Diaz Curiel1; 1Internal Medicine Service, Fundación Jiménez Díaz, Bone Metabolic Disease Cathedra, Universidad Autonoma, Madrid, Spain, 2Molecular Biology Section, Hematology Service, Fundación Jiménez Díaz, Universidad Autonoma, Madrid, Spain, 3GENOMICA, Madrid, Spain, 4Bioestatics Department, PIVOTAL, Madrid, Spain Introduction: Osteoporosis is a skeletal disease characterised by low BMD and microarchitectural deterioration, with increased susceptibility to fracture. The AluI calcitonin receptor gene polymorphism has been correlated to bone mineral density and osteoporosis. Objectives: The goal of our analysis was to analyze the genotype frequencies of AluI polymorphism of the calcitonin receptor gene (CTR) in a group of postmenopausal women with osteoporotic fracture and its possible contribution to osteoporosis development. Materials and methods: After DNA extraction, the polymorphism was detected by the restriction enzyme AluI, by a DNA-chip methodology (Metabone Clinical Arrays®), developed by Genomica S.A.U. (MAD, Spain) in 70 postmenopausal patients with osteoporosis, (aged 57–86 years) and 35 healthy age-matched controls (aged 57–87 years). Seventyeight percent had vertebral fracture; 7% Colles’ fracture; 12% hip fracture, 3% other fracture. Bone mineral density of the lumbar spine, total hip and femoral neck were measured using dual-energy X-ray absorptiometry [Hologic® densitometer QDR4500 (Hologic Inc, MA, USA)]. Results: The allelic frequencies for the 70 postmenopausal women with osteoporotic fracture were 12.7% for AA, 36.6% for Aa and 49.3% for aa in AluI restriction fragment polymorphism. Conclusions: AluI calcitonin receptor gene polymorphism was not distributed differently between postmenopausal osteoporotic women and controls. No association was found between the polymorphisms and low bone mineral density values nor osteoporotic fracture at either position. P346. SP1 binding site polymorphism prevalence of the collagen type I alpha1 gene in postmenopausal osteoporotic women with fracture J. Espinoza Pineda1, ML. Villahermosa3, P. Llamas2, A. Drozdowskyj4, M.J. Moro Alvarez1, M. Diaz Curiel1; 1 Internal Medicine Service, Fundación Jiménez Díaz, Bone Metabolic Disease Cathedra, Universidad Autonoma, Madrid, Spain, 2Molecular Biology Section, Hematology Service, Fundación Jiménez Díaz, Universidad Autonoma, Madrid, Spain, 3GENOMICA, Madrid, Spain, 4Bioestatics Department, PIVOTAL, Madrid, Spain

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Introduction: Genetic factors regulate BMD and possibly development of osteoporosis. It is known that polymorphism at the Sp 1 Colagen type I gene, the most common protein, is associated with low BMD in postmenopausal women. Objectives: Determine the prevalence of COL1A1 genotype in an population of postmenopausal women with osteoporotic fractures. Material and methods: In this study, we investigated the possible functional contribution of the SP1 site of the collagen type I regulatory region (COLIA1) polymorphism to the pathogenesis of osteoporosis. We genotyped 70 (57– 86 years) postmenopausal women with osteoporosis: 78% had vertebral fracture; 7% Colles’ fracture; 12% hip fracture, 3% other fracture, and 35 healthy controls. After DNA extraction, the appropriate segment was amplified by PCR and the Sp1 COLIA1 polymorphism was determined by a DNA-chip methodology (Metabone Clinical Arrays®). Bone mineral density (BMD) of the lumbar spine, femoral neck and total hip was measured by dual energy X-ray absorptiometry [Hologic® densitometer QDR4500 (Hologic Inc, MA, USA]). Results: COLIA1 genotype frequencies were 69.0% for SS, 25.3% for Ss, and 11.5% for ss (uppercase letters signifying the absence and lowercase letters the presence of the restriction site). The genotype frequencies for the control group were as follows: SS 56.2%, Ss 30.4% and ss 13.0%. Conclusions: The distribution frequencies of COLIA1genotypes were no difference by compared with 35 nonosteoporotic women. No association was found between COLIA1genotypes and BMD either at the lumbar spine or the proximal femur within group of postmenopausal women. P347. Polymorphisms in the vitamin D receptor gene and osteoporosis J. Espinoza Pineda1, ML. Villahermosa3, P. Llamas2, A. Drozdowskyj4, M.J. Moro Alvarez1, M. Diaz Curiel1; 1 Internal Medicine Service, Fundación Jiménez Díaz, Bone Metabolic Disease Cathedra, Universidad Autonoma, Madrid, Spain, 2Molecular Biology Section, Hematology Service, Fundación Jiménez Díaz, Universidad Autonoma, Madrid, Spain, 3GENOMICA, Madrid, Spain, 4Bioestatics Department, PIVOTAL, Madrid, Spain Introduction: The genetic background of postmenopausal osteoporosis, and VDR gene polymorphisms-related bone loss have been established, particularly those demonstrated by the Bsm I and Fok I restriction enzymes. Objectives: The objectives of this study was to document the frequency of Bsm I and Fok I VDR polymorphisms, as well as their relationship with low bone mineral density and fracture in postmenopausal women.

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Materials and methods: Subjects consisted of 70 Spanish postmenopausal osteoporotic women with a range of age 57–86 years (mean 70 years) and at least one osteoporotic fracture (78% had vertebral fracture; 7% Colles’ fracture; 12% hip fracture, and 3% other), and 35 age-matched normal controls for the disease. Bone mineral density was measured by dual energy X-ray absorptiometry [Hologic® densitometer QDR4500 (Hologic Inc, MA, USA]) in lumbar spine (L2–L4), femoral neck and total hip. We determined the Bsm I and Fok I VDR polymorphisms using a DNA- chip methodology (Metabone Clinical Arrays®), developed by Genomica S.A.U. (MAD, Spain). Results: The allelic frequencies for the 70 postmenopausal women in our study were 43.6% “FF” homozygotes, 36.6% “Ff” heterozygotes, 18.3% “ss” homozygotes, 9.8.% “BB” homozygotes, 52.1% “Bb” heterozygotes, and 36.6% “bb” homozygotes. The percentage of subjects with vertebral fracture and osteoporosis not differed significantly among the two genotypes respect to healthy control group. Conclusion: The absence of difference between subjects with osteoporotic fractures and a age-matched healthy women, suggests a low influence of the Bsm I and Fok I VDR gene polymorphism on this group and do not seem to identify women who are at risk of postmenopausal osteoporosis. P348. Newly diagnosed patients with inflammatory bowel disease are at high risk of osteoporosis H. Abera, P. Shah, R. D’ Souza; Department of Gastroenterology, Chase Farm Hospital, Enfield, United Kingdom Introduction: Bone densimetry scan should be performed in all patients with inflammatory bowel disease. Objectives: Patients with inflammatory bowel disease are at risk of oteoporosis due to many risk factors: steroid use, low BMI, malabsorption, multiple surgical resections. Guidelines suggest that only those patients with risk factors should be assessed for osteoprosis. Our study was designed to elucidate if patients with inflammatory bowel disease per se (without risk factors) are at risk for osteoporosis. Materials and methods: Forty patients (25 females and 15 males) with newly diagnosed inflammatory bowel disease following gastroenterological investigations were recruited. The inclusion criteria for this study included untreated patients aged between 18–40 who had been diagnosed histologically with either crohns disease or ulcerative colitis. They had no previous exposure to steroids, were non- smokers and with no history of surgical resections. Bone densimetry scanning was performed on each patient. Results: Thirteen of the forty patients with inflammatory bowel disease had osteopaenia or osteoprosis (32%). There was a correlation between T-score, BMI and extent of disease. There was a statistically significant difference in T score between patients with disease duration >6 months and

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those less than 6 months (p<0.02). There was no difference between T score and age of patient or between the type of inflammatory bowel disease—Crohns disease or Ulcerative colitis. Conclusions: At present gastroenterologists are only screening those patients with inflammatory bowel disease who have risk factors. Our data suggest that all patients with inflammatory bowel disease should have assessment of osteoporosis via bone densimetry scanning. More research needs to be done to investigate this further. P349. Zoledronic acid influence bone strength V. Luzin, D. Astrakhantsev; Department of Normal Anatomy, State Medical University, Luhansk, Ukraine Introduction: Bone loss of any origin constitutes a major problem for both basic and clinical specialists. Deranged processes in bones eventually lead to fractures extremely resistant to conventional treatment methods. Although the modern maintenance and treatment methods are considered sufficient the novel strategies are continuously being designed. One of the recent invents is zoledronic acid, a cytostatic drug which inhibits bone resorption and thus may prevent bone mineral loss. So we decided to study an influence of zoledronic acid on bone strength. Materials and methods: To test the hypothesis we designed an extended study using laboratory animals separated into three age groups. Sodium zoledronate (Zometa, Novartis Pharm) was administered according to common schemes. The control group consisted of intact animals. For biomechanical tests we used a standard threepoint loading device. Shoulder-bones were loaded at 0.25 mm/min up to complete destruction. From the data acquired we calculated specific bending deflection, breaking point, Young’s modulus and minimum destruction work. Results and discussion: In old intact animals specific bending deflection decreased from 3.96 ± 0.17 NμM (7 days) to 3.91±0.21 NμM (90 days), breaking point decreased from 125.69±4.95 GPa (7 days) to 117.75± 4.91 GPa (90 days), Young’s modulus decreased from 4.53 ±0.33 GPa (7 days) to 4.09±0.15 GPa (90 days) and minimum destruction work decreased from 86.72±4.32 MJ (7 days) to 82.41±3.66 MJ (90 days). These data confirm bone senescence and osteoporosis development. In the animals treated with zoledronic acid we found Young’s modulus and breaking point to exceed the controls by 15.84% and 12,51% (<0.05) at the 30th day and at the 90th day by 10.63% (<0.05) and 18.19%, respectively. Minimum destruction work values were lower than controls at the 15th and the 30th days by 19.93 and 12.42%, respectively. Specific bending deflection values did not change significantly in all observation terms.

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Conclusions: Here we showed that zoledronic acid leads to increased bone fragility yet bone strength still increases. Zoledronic acid did not completely restore the condition of bone yet it showed possibility to save the bone construction which may play a critical role in prevention of osteoporotic fractures. P350. Study on the effects of physical exercise on the quality of life of osteoporotic patients G. Mologhianu, A.S. Nica; The Third Rehabilitation University Clinic, Bucharest, Romania Objectives: This study evaluates the improvement in the quality of life of patients suffering from primary osteoporosis, using a series of clinical, functional and psycho-social factors. Materials and methods: This is a prospective, epidemiological and clinical study, performed on two groups of patients suffering from primary osteoporosis type I and II. 31 Female subjects were used, each carefully selected. They were monitored over a period of six months, from June to November of 2006, before and after performing a controlled physical exercise program. The patients were assigned to one of two groups: G1 with the controlled physical exercise program and no medication; G2 with both the exercise program and the antiresorbtive medication. Quality of life was measured using the standardized QUALEFFO 41 questionnaire, the scale of which indicates a “good” for scores lower than 110, “mediocre” for scores between 110 and 119, “poor” for 120–130 and “very poor” for 131 and above. The questionnaire consisted of five questions regarding vertebral pain appeared in the week before the evaluation, four questions regarding day to day activities, five questions regarding household chores, eight questions about mobility, seven regarding relaxation and social activities, three questions about the self-evaluation of the state of welfare in general and nine about the state of mind of the patients. Results: They have been statistically evaluated, the progress of the patients was monitored and registered before and after the exercise program was performed. Also, a comparison between the two study groups was made. Conclusions: One could state that the specific kinetic program administred in the present study has improved the patients’ state of health both for the patients in the first and the second groups, with a statistical signifiance only for the first lot, the one without the antiresorptive medication. A valuable factor for this result is that according to the “initial values” principal, the patients in lot II had higher scores in the beginning of the program. Also, the patients of the second lot were on antiresorptive medication for two years before entering the program, and also the averidge age of the second lot was lower than that of the first lot.

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P351. Significance of antiosteoporotic therapy in patients with inflammatory disease N. Prodanovic1, B. Bozic2; 1Military Medical Academy, Belgrade, Serbia, 2Faculty of Biology, University of Belgrade, Belgrade, Serbia Objectives: Inflammation, a common property of all systemic inflammatory diseases, has an influence on increased bone resorption. Osteoporosis (OP) is a skeletal disorder characterized by decreased bone density and increased risk for bone fractures. The aim of this study was to assess bone mineral density (BMD) in patients with systemic inflammatory disease with and without antiresorptive therapy. Material and methods: This study took place in the Department for Osteoporosis at the Military Medical Academy. This study included 89 patients with rheumatoid arthritis (RA) and 29 patients with ankylosing spondylitis (AS). Twenty-four RA patients treated with alendronate and eight patients with AS treated with pamidronate. BMD was measured by Lunar DEXA DPX 2000 device, on the lumbar spine and the hip. Results: The group of patients with RA included 58 women and 31 men, average age 65±14, with RA lasting 7 years in average. RA patients treated with alendronate during 4 years had increased BMD at L1–4 for 2.8% and at hip for 1.9%. At RA non-treated patients were detected decreased BMD for 3.9% at L1–4 and at hip for 4.7%. The group of patients with AS included 11 women and 18 men, average age 52±18, with AS lasting 12 years in average. AS patients who treated with pamidronate during 4 years had increased BMD at L1–4 for 1.2% and at hip for 0.9%. At the other side, like RA patients, AS patients who not treated had decresed BMD at L1–4 for 2.0% and at hip for 1.2%. Conclusions: On the based given results we can concluded that the treatment with bisphosponate patients with RA and AS have influence to significant BMD incresemnet compared to BMD patients who did not take antiosteoporotic drugs. P352. Influence of bisphosphonates on the economic burden of osteoporosis in Iran M. Mirsafa, E. Mir, P. Tofighi, A. Hossein-Nezhad, H. Adibi, B. Larijani; Endocrinology and Metabolism Research Centre (EMRC) of Tehran University, Shariati Hospital, Tehran, Iran Objectives: Osteoporosis presents an enormous health burden. Bisphosphonate treatment increases BMD (bone mineral density) and probably decreases risk of fracture. The aim of this study is to evaluate whether Bisphosphonates decrease the burden of osteoporsis or not.

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Material and methods: We studied 142 postmenopausal women came to the outpatient osteoporosis clinic of EMRC (Endocrinology and Metabolism Research Centre of Tehran University) from January of 2002 to October of 2006 who had osteoporosis based on BMD. They consumed bisphosphonates for at least 1 year. We selected a control group of 423 postmenopausal women came to the BMD centre of EMRC who had osteoporosis and did not consume bisphosphonates. We calculated the cost of osteoporosis treatment, including drugs (vitamine D, calcium supplements and bisphosphonates), transportation, doctor’s fee, and the cost of hip fracture operations and hospitalizations. We also evaluated the quality of life based on cultural adapted questionnaire of IOF, in both groups. Results: The mean age of 565 postmenopausal women was 60.5±9.68 years. We followed them for a period of 1 to 4 years. Of case group, 58% had a regular drug consumption that was not significantly different from the control group. Women in case group had a better pain relief after bisphosphonate consumption and expressed the feeling of well being more than the control group. The average cost of osteoporosis treatment in the case group was 66.1$ a year for each person, and 20$ a year in the control group. 18.5$ saved a year for the cost of of hip fracture operations and hospitalizations in the case group. Conclusions: Bisphosphonates have special roles in treatment of osteoporosis. In this study we show that these drugs decrease the cost of hip fracture operations and hospitalizations in osteoporotic women. Also bisphosphonates increase well being and decrease pain in these patients.

population mainly composed of women (Lips, Osteoporos. Int. 1999) and with those of women patients with at least one vertebral fracture in the MORE study (Oleksik, Osteoporos. Int. 2005). Results: Our patients were 89 men aged 61±13 years whose osteoporosis had been diagnosed for an average of 6 years. 82% had osteoporosis with fractures (vertebral fractures 60%, proximal femur fractures 9%, appendicular fractures 31%). Their osteoporosis was primary in 51% of cases, 45% were retired, 14% on sick leave, 1% on extended sick leave, 6% were unemployed and 34% were in employment, while 28% took analgesics for their osteoporosis.

P353. Quality of life in osteoporotic men B. Debray, L. Popa, I. Roitg, S. El Mahou, B. Mazières, M. Laroche; Rheumatology Department, CHU Rangueil, Toulouse, France

P354. Low usage of calcium and vitamin D with bisphosphonate therapy in post-menopausal osteoporotic women in France and in Spain J.M. Quesada1, B. Mann2; 1Unidad de Metabolismo Mineral, Hospital Universitario Reina Sofía, Córdoba, Spain, 2Procter and Gamble Pharmaceuticals, CMK, Schwalbach, Germany

Introduction: Osteoporotic fractures affect 7 to 10% of men. While numerous studies, based on questionnaires devoted to osteoporosis, have highlighted the impaired quality of life due to the disease in women, very few have aimed to evaluate quality of life in men with osteoporosis. With this objective, we studied a cohort followed in our department. Patients and methods: We reviewed the discharge reports of 275 men coded as “osteoporosis” in the PMSI (computerised system for assessment of hospital activity) between 1995 and 2006; 198 patients who corresponded to the inclusion criteria: osteoporotic fracture and/or T-score at one site <−2.5, were selected. Of these men, 89 responded to postal questionnaires on their present occupational status, consumption of analgesics, and the Qualeffo-41 questionnaire translated into French. As statistical analysis was not possible, we compared our data with those of a control

Comparative table of Qualeffo-41 findings (the higher the score, the poorer the quality of life) Items

Osteoporotic men

Osteoporotic Controls women

Pain physical function social function general health mental function Total Qualeffo score

45 (25–65) 23.5 (17–35) 47 (29–64) 58.5 (42–75) 41.5 (28–55) 35.3 (21.5–46)

35.2 17.6 30.1 46.3 31.8 27

15 (0–35) 10.3 (2.9–16.2) 28.4 (12.3–41.2) 41.7 (33.5–58.3) 30.6 (18.8–36.1) 20.3 (12.3–29.5)

Conclusion: In men, osteoporosis appears to cause as much or even more disability than in women. Criteria for bone density screening for osteoporosis in men should be established in order to treat the disease before fractures occur and the therapeutic arsenal should be broadened, as for women.

Objectives: Calcium and Vitamin D (Vit-D) supplementation are recommended as co-medication to antiresorptive therapy by European guidelines for osteoporosis treatment. However, co-prescription of calcium and Vit-D with bisphosphonate across Europe does not seem to be very high in clinical practice. The aim of this study was to determine in patients with osteoporosis taking once a week (OAW) bisphosphonates the actual co-intake of calcium and Vit-D and to evaluate how they use their supplements. Material and methods: A total of 400 women (200 France, 200 Spain) taking OAW bisphosphonate for at least 3 months, were selected for telephone interviews (15 min) by an independent market research organization. Partici-

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pants were asked about the type of medications taken for the treatment of osteoporosis, including information on supplementation. The participants interviewed in Spain had been taking bisphosphonates for an average of 2 years (range >3 months to 5 years or more) and participants in France had been taking bisphosphonates for an average of 1.6 years (range >3 months to 5 years or more). Results: The study shows that a large proportion of patients, 46 and 40% in Spain and in France, respectively, do not take any calcium and/or Vit-D supplementation with their bisphosphonates treatment. Those women that take calcium and Vit-D get it by prescription 91 and 88% in Spain and France, respectively. Few patients buy supplementation themselves. 14% of women in France and 7% in Spain incorrectly take their calcium supplementation with their bisphosphonate (at the same time or within 30 min of their BP intake). Conclusions: Despite clear recommendations for supplementation of calcium and Vit-D for osteoporotic patients taking OAW bisphosphonates, study results show that coprescription and adherence to supplementation are suboptimal. The low level of co-prescription by physicians is not compensated by self intake. There are patients who take their calcium supplements at the same time as their bisphosphonates, potentially reducing the effectiveness of the therapy. There is a clear need to improve the usage and the adherence to calcium and Vit-D supplementation in osteoporotic patients taking OAW bisphosphonate therapy. P355. Prevalence of vertebral deformity in the very elderly using lateral vertebral assessment F. Birrell1,2,3, L. Ottewell4, A. Farley3, D. Rawlings2, R. Francis1,2; 1School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Musculoskeletal Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom, 3Northumbria Healthcare NHS Trust, United Kingdom, 4Sunderland Royal Hospital, Sunderland, United Kingdom Objectives: Vertebral deformity is common in the elderly in clinical practice, but no epidemiological data exist in the 85+ age group. As part of the Northumberland 85+ Musculoskeletal Pilot study, our objectives were to: – –

Estimate the prevalence of vertebral deformity Demonstrate the feasibility and validity of lateral vertebral morphometry in this setting.

Materials and methods: One hundred sixty-seven subjects aged 85 years and older from one General Practice in Northumberland were invited to participate through three mailings at 2 week intervals. Those who agreed to attend the local hospital had comprehensive musculoskeletal assessment including thoracic and lumbar radiographs and

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dual energy X-ray absorptiometry (iDXA, GE Healthcare). DXA assessments included lumbar spine and bilateral femoral bone mineral density, whole body bone mineral content and Lateral Vertebral Assessment (LVA): lateral iDXA images scored using Genant’s method. Descriptive statistics included demographics, prevalence of vertebral deformity and prevalence of osteoporosis by WHO T-score criteria (≤−2.5). Lateral lumbar and thoracic spine radiographs will also be scored and agreement of morphometry using LVA and radiographs calculated using 2×2 tables, with radiographs as the gold standard. Results: Unadjusted response rate: 74%. 83/123 responders (67%) agreed to participate in the study: 48 (56%) agreed to attend the hospital for full assessment. Those who attended had a median age of 87 years (range 85–97); 69% female. Of the 48, 47 completed LVA and 47 lateral radiographs. LVA showed a high prevalence of vertebral deformity (28/ 47; 60%, 95% CI 45–72%), compared to only 30% who satisfied WHO bone density criteria for osteoporosis. Of the 28 with vertebral deformity, 7 (25%, 95% CI 11–45%) had only mild deformity (20–24% height reduction); 19 (68%, 95% CI 49–82%) had moderate deformity (25–39% height reduction), and 2 (7%, 95% CI 1–25%) had severe deformity (≥40% height reduction). Conclusions: The prevalence of osteoporosis is surprisingly low in those 85 years and older, but LVA identified twice as many subjects with vertebral deformity in this community study who may benefit from treatment for osteoporosis. This suggests LVA should be included in bone density assessment of the elderly, as part of more comprehensive fracture risk assessment. P356. Pentadecapeptide BPC-157 and rat temporomandibular join osteoarthritis N. Kokic, P. Sikiric, S. Seiwerth, A. Dundjer, D. Saifert, B. Gracin; Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia Temporomandibular joint osteoarthrosis in the rat was attenuated by a stable gastric pentadecapeptide, BPC 157 (GEPPPGKPADDAGLV, M.W.1419), that healed a nonunion fracture and deep thickness skin burns, and reduced adjuvant arthritis, without special carrier. In procedure ((1) unilateral condylar articular surface damage (i.e., partial removal), (2) horizontal incision of both, the collateral ligament at the lateral border of the disk, and the posterior discal attachment) with consequent articular disc instability, and vascularization disruption. BPC-157 10 μg, 1 μg, 100 ng, 10 ng, 1 ng/kg b.w. or an equivolume of saline (5.0 ml/kg b.w.) (control) were given intraperitoneally immediately after the surgery. Assessment was at 6 months following surgery. In all directly injured temporomandibular joints of controls, a failure or a lack of cartilage healing/

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repair was noted, as all of osteoarthrotic changes, already described, consistently appeared, along with severe functional disability. At the same time, healing/repair cartilage reaction in damaged temporomandibular joint in pentadecapeptide BPC-157 rats was noted since all of osteoarthrotic changes were markedly attenuated. This was especially supported by BPC-157 structural characteristics shown by computational investigation. Along with this is in vitro effect on cartilage cells exposed to 4-hydroxynonenal (HNE) an end product of lipid peroxidation considered as a mediator of oxidative stress. P357. The use of a soluble activin receptor type IIa as a novel anabolic agent for treatment of bone loss R.S. Pearsall1, M. Cornwall-Brady1, M. Mangini1, D. Barbosa1, J. Seehra1, L. Stadmeyer2, V. Glatt4, E. Rosen4, E. Canalis2,3, M.L. Bouxsein4; 1Acceleron Pharma, Cambridge, Massachusetts, USA, 2 St. Francis Hospital and Medical Center, Hartford, Connecticut, USA, 3University of Connecticut School of Medicine, Farmington, CT, USA, 4 Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA Activin, a member of the TGF-Beta superfamily, has been implicated as both a positive and negative regulator of bone metabolism. We tested an activin antagonist, a soluble form of extra cellular domain of the murine activin type II receptor (ActRIIa) fused to a murine IgG-Fc fragment (RAP-011), to determine if Activin inhibition could reverse bone loss in a murine osteopenia model. For osteopenia studies, 4 week old C57BL/6 mice were ovariectomized (OVX) or SHAM operated. Eight weeks later they began twice weekly treatment with RAP-011 (10 mg/kg, ip) or vehicle (VEH) for 12 weeks. In vivo pQCT measurements were taken at baseline, 4, 6, 8 and 12 weeks of treatment. MicroCT and mechanical testing was performed at the conclusion of the study. In vivo pQCT indicated that RAP-011 treatment increases trabecular bone density (TbBD) in the proximal tibia in both OVX and SHAM compared to VEH by as early as 4 weeks of treatment. By 12 weeks, TbBD in RAP-011 treated OVX mice had increased 12% versus baseline, compared to a 15% decrease in VEH- OVX. In SHAM, RAP-011 increased TbBD by 27% vs baseline. Ex vivo uCT of 5th lumbar vertebrae and distal femur revealed that compared to VEH treatment, RAP-011 significantly increased vertebral Tb BV/TV and Tb number, as well as distal femur Tb BV/TV and Tb number. At both sites, Tb separation decreased and connectivity density increased in RAP-011 vs VEH. At the mid-femoral diaphysis, RAP-011 signifi-

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cantly increased total cross-sectional area, cortical bone area and cortical thickness compared to VEH in both OVX and SHAM. Three point bending tests on the femur, and compression testing on the 5th lumbar vertebrae revealed that RAP-011 was able to increase the failure load (N) and energy to failure (N*mm) in both OVX and SHAM mice relative to VEH. In summary, twice-weekly treatment of OVX mice with RAP-011 improved bone quantity (BV/TV and microarchitecture) and bone quality (strength and toughness) to levels equal to, or better than SHAM-operated VEH controls, providing strong evidence that the use of a soluble ActRIIa (RAP-011) may be a novel anabolic therapy for osteoporosis. P358. Co-prescription of calcium and/or vitamin D with once weekly bisphosphonate therapy: findings from a French longitudinal patient database P. Fardellone1, B. Mann2; 1Department of Rheumatology, CHU d’Amiens, Amiens, France, 2Procter and Gamble Pharmaceuticals, CMK, Schwalbach, Germany Objectives: Calcium and Vitamin D (Vit-D) supplementation are recommended as co-medication to antiresorptive therapy. The objectives of this study were to analyze general practitioners (GPs) co-prescription habits of Calcium and/or Vit-D in patients taking once a week bisphosphonate therapy. Materials and methods: The French Thales longitudinal database, comprising patient records from a representative sample of 1,200 GPs was used. These patient data, collected daily, were extrapolated to represent 56,000 GPs. Data collected during 1st June–31st August 2004 from patients taking either weekly alendronate 70 mg or risedronate 35 mg formed the basis of the analysis. Summary statistics of Calcium and/or Vit-D co-medication with once a week bisphosphonate therapy were performed. Results: Of the 369,828 patients included in the analysis, 44% (162,171 patients) received a prescription for either Calcium and/or Vit-D in addition to their once a week bisphosphonate therapy. The majority (87%) of the patients receiving such co-medication took Calcium and Vit-D in addition to their bisphosphonate. Conclusions: Over half of the patients (56%) treated with once a week bisphosphonate therapy did not receive any supplementation with either Calcium or Vit-D. New approaches towards helping osteoporotic patients adhere to recommended guidelines of taking Calcium and Vit-D supplementation in addition to their bisphosphonate are required.

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P359. The utilization profile of non-steroidal anti-inflammatory drugs and its association with the self-report of rheumatic diseases and polypharmacy C. Pinheiro1, M. Severo1, H. Barros1; 1Service of Hygiene and Epidemiology, Porto Medical School, Porto, Portugal Objectives: To estimate the overall prevalence of nonsteroidal anti-inflammatory drugs (NSAIDs) use and to estimate its association with the self-report of rheumatic diseases and polypharmacy. Materials and methods: Out of the 1,430 interviewed participants (62% women and 38% men), 1,120 (78.3%) reported the current use of drugs, while 350 (24.6%) reported to suffer from a rheumatic disease. A questionnaire inquired the participants about their social, demographic, and behavioural features, but also, about whether their physician ever diagnosed them as having any rheumatic disease, and if they were taking any medication. All drugs were registered on a medicine-by-medicine basis and classified according to the Anatomical Therapeutical Chemical (ATC) classification index. To estimate the associations adjusted for all variables logistic and multinomial regression were used. Results: 10.5% (118) of the participants under any drug were taking a NSAID. NSAIDs use was significantly higher in women (10.3 vs 5.0% in men) and increased in both sexes with age, the self-report of rheumatic diseases, and with a worse appreciation of the household income. After running a multinomial regression adjusted for sex, age, education, the number of drugs taken and the household income appreciation, women who self-reported a rheumatic disease are more likely to use a NSAID than men (OR=3.9, 95%CI [1.91–7.95], p<0.001). Moreover, participants that concurrently use five or more drugs (Major Polypharmacy) that reported a rheumatic disease are more likely to use a NSAID than those who did not reported any of such diseases (OR=14.5, 95%CI [5.09–41.43], p<0.001 vs. OR=10.6, 95%CI [2.57–43.85], p=0.001), though the odds diminishes for participants that did reported at least one rheumatic disease but did not use a NSAID (OR=2.9, 95%CI [1.474–5.900], p=0.002); by last, among participants who reported a rheumatic disease, those who estimated their household income as being insufficient were more likely to use a NSAID (OR=3.1, 95%CI [1.48– 6.67], p=0.003). Conclusion: The use of NSAIDs by Portuguese adults affected by rheumatic diseases, especially elderly people, deserves a more serious insight, particularly when associated with other drugs concurrently used.

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P360. Secondary osteoporosis and ankylosing spondylitis in Hungarian male and female patients: clinical, laboratory and densitometry data É. Lányi 1, E. Nagy2, C. Horváth3; 1Department of Rheumatoplogy I, Polyclinic of The Hospitaller Brothers of St. John of God, Budapest, Hungary, 2Laboratory of the Polyclinic of The Hospitaller Brothers of St. John of God, Budapest, Hungary, 3Department of Internal Medicine, Budapest Semmelweis University, Budapest, Hungary Background: Spontan spine fractures in patients with ankylosing spondylitis (AS) may occur without a significant intensification of pains permanently torturing the AS patients and draw attention to the seriousness of AS connected with osteoporosis (OP). Objectives: The goals of our studies were to establish the correlation between the occurrence of AS and OP depending on the duration of the malady and on the mobility of the spine and to compare male and female patient groups. Materials and methods: For 210 patients with AS (60 females, age: 25–84 years, 150 males, age: 24–78 years), the early and present complaints and symptoms, the functional state (BASFI) and activity (BASDAI) of the illness, the spine mobility, the OP risk factors (assessed by a questioner) were studied, OP of other origin was excluded. The OP diagnostic was based on lumbal spine and on femoral neck BMD with additional total body BMD and ultrasound measurements. X-ray pictures were taken on the lumbal spine and on the sacroiliac joints. Laboratory studies were made on the Ca-household (Serum-Ca, P, AP, CN, kreatin, urin-Ca and P, furthermore, CRP, TSH, PTH) and on the bone turnover. Results: Laboratory data evidenced increased bone resorbtion, with the highest rates in the early phase. The BMD values exhibited a progress of AS with increasing age, with slight differences for the lumbal spine and for the femoral neck. BUA and SOS values for the heel also show a decrease with increasing age and with the progress of AS. Trendlines for males had a lower inclination as those for females. No discrepancy between the spine and femoral neck BMD values was found for female patients, like reported earlier and observed also here for male patients. Conclusions: A correlation between the activity of AS, the severity of the secondary OP of AS patients and shrinking BMD, BUA and SOS values was found. The differences between female and male data might be explained by two factors: hormonidal change in women lead to a more rapid decrease of BMD whereas for male patients the more pronounced calcification of the syndesmophites artificially increases the BMD values.

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P361. Effects of pentadecapeptide BPC 157 on transosseous rat mandibular defects healing in vivo N. Kokic, P. Sikiric, S. Seiwerth, A. Dundjer, D. Saifert, N. Warouw; Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia Objectives: The efficacy of local and systemic delivery of pentadecapeptide BPC 157 (currently in clinical phase II for inflammatory bowel disease) to promote bone healing was evaluated in transosseous rat mandibular drill defects. Insufficient or absence of bone healing is a frequent problem within all surgical fields. This often necessitates treatment by various bone grafting procedures, utilization of osteopromotive membrane techniques, local delivery of growth-stimulatory factors, or compression-distraction (Illizarov) procedures. Based on the previously recognized positive osteogenic results of gastric pentadecapeptide BPC 157 on non-union fracture, segmental osteoperiosteal bone defect, its pure peptidergic effect with no carrier interference, together with gastric epithelial cells induced osteogenesis, and a hypothetical gastric hormone opposing bone disturbances development, the aims of the present study were to further develop a possibility of osteopromotion by various routes (Bone 24 195, 1999). Materials and methods: Transosteal defects were performed proximal to the entry of the inferior alveolar artery in the left rat mandibular ramus using extraoral approach. Rats received agents (1) BPC 157 10 μg, 10 ng/kg intraperitoneally immediately after the injury, or (2) BPC 157 2 μg, 2 ng/ml (1 ml bath) locally at the injury site. The effects were assessed at 3 or 10 days post injury using densitometry assessment. Results: Results indicate that gastric pentadecapeptide BPC 157 given either systemically or by local application significantly improves transosseous mandibular defect healing. Conclusion: A novel gastric pentadecapeptide BPC 157 seems to be potentially usefull agent for osteopromotion, especially in view that this peptide needs no carrier addition, and has no recognized toxicity, that put this peptide in highly distinctive category, like no other peptide. P362. Calcitonin protects against experimentally induced osteoarthritis in part through direct actions on chondrocytes B.-C. Sondergaard1, S. Madsen1, E. U. Sumer 1, S. Oestergaard1, P. Qvist1, C. Christiansen2, M. A. Karsdal1; 1 Nordic Bioscience Diagnostics, Herlev, Denmark, 2Center for Clinical and Basic Research (CCBR), Ballerup, Denmark Purpose: To investigate the potential chondroprotective effects of oral calcitonin in an experimental non-traumatic model of osteoarthritis (OA), and secondly, to investigate

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possible direct anabolic effects of calcitonin on human articular chondrocytes using ex vivo explants cultures. Materials and methods: Human OA cartilage obtained from knee arthroplasty operations was dissected and cultured in the presence of salmon calcitonin [1 aM– 10 nM]. Effects of calcitonin was measured by (1) incorporation of radioactive labeled 35SO4 after 6 days of culture (2) measurement of sulphated glycosaminoglycans (sGAG) in N2 pulverized explants extracts by the alcian blue binding assay after 21 days of culture. Direct effects of calcitonin on isolated human chondrocytes were investigated through measurement of both intra-cellular and extracellular cAMP levels. The ovariectomized (OVX) rat was used as a non-traumatic model of accelerated cartilage loss. Fifty rats were randomly allocated into five intervention groups and treated for 9 weeks: (1) Sham, (2) OVX, (3) OVX + s.c. implanted 17-beta-ethynyl-estradiol pellet, (4) OVX + daily oral dose calcitonin [2 mg/kg] + vehicle, 5CNAC [50 mg/kg], and (5) OVX + daily oral dose of vehicle 5-CNAC [50 mg/kg]. Serum samples were taken at baseline, and 2, 4, 6 and 9 weeks. Cartilage degradation was assessed by measurement of serum C-terminal telopeptide fragments from collagen type II degradation (CTX II) by ELISA and histological scoring of articular cartilage erosion in rat knees by histology Results: In vivo, ovariectomy resulted in 150% increased cartilage degradation measured by both erosion scoring (P <0.01) and sCTX-II (P<0.001). Calcitonin abrogated this increased cartilage degradation measured by both CTX-II (P<0.001) and cartilage erosion scoring (P<0.01). Ex vivo, human cartilage formation was concentration-dependently induced by calcitonin treatment (1 aM–10 nM) with a 3fold maximal induction, as measured by radioactive sulphate incorporation. In alignment, calcitonin resulted in significant 30% increased levels of proteoglycan content in the articular explants. Conclusion: In vivo, calcitonin strongly inhibited cartilage degradation. Ex vivo, calcitonin had direct chondroanabolic effects on human articular cartilage. This direct effect on chondrocytes of calcitonin in addition to the well-established anti-resorptive effect on osteoclasts, suggests calcitonin as a potential dual action treatment for osteoarthritis. P363. Does hip arthritis limit the life expectancy in the elderly? A comparative study of operated and non-operated groups of patients suffering from hip osteoarthritis S.M. Karuppiah, P.A. Banaszkiewicz, WM. Ledingham; Department of Orthopaedics, Grampian University Hospitals Trust, Woodend Hospital, Aberdeen, Scotland—United Kingdom

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Introduction: Hip osteoarthritis can be a debilitating disease restricting mobility causing pain resulting in poor quality of life in the elderly. The benefits of hip arthroplasty such as pain relief and better quality of life, may reflect as an increased life expectancy in the elderly population. Objectives: The aim of this study was to compare the life expectancy of two groups of patients ≥85 years of age, referred with severe disabling hip osteoarthritis; one group was managed medically (non-operated group) while the other was operated with total hip arthroplasty (operated group). Patients and methods: Twenty-eight patients were managed medically (non-operated group) and 28 patients underwent joint replacement surgery (operated group). Records of patients were individually analysed and at the time of study, patients were interviewed by phone or in person. Results: The average age of patients, at the time of clinical appointment, of both non-operated and operated groups were 91.4 years (±1.3). At the time of follow-up, 36% of the patients in the non-operated group were restricted in mobility and living in nursing homes while 96% of the patients in operated group, were mobile and living independent. Patients in the operated group had a significant improvement in pain relief (p<0.0001) while patients in non-operated group continued to complain of hip pain and were on regular pain killers. The mean survival period of the non-operated group was 2.5 years and operated group was 3.9 years (Graph 1).

Number of patients

30

Operated group

25

years. Unlike other joint injections, hip injection requires theatre facilities and X-ray imaging, hence more medical staff time with additional radiation exposure to patients. Objectives: The aim of our study was to determine if hip joint injection with corticosteroieds can be used as a therapeutic tool in osteoarthritic hip pain. Materials and methods: Patients treated with hip joint injection between Jan 2000 to Jan 2005 were identified from hospital database. A total of 128 patients had hip joint injection; 125 patients for osteoarthritis and three patients with rheumatoid arthritis. All patients had radiological and clinical symptoms of hip osteoarthritis. Patients were injected in operating theatre as a day case, by a consultant or trainee, under X-ray guidance. The position of the needle was confirmed with X-rays and arthrogram. All patients were followed up in the clinic at 2 months and the duration of pain relief after the injection was noted. Results: Fifty-one patients (40%) had pain relief for more than a month, while 60 patients (47%) had pain relief for less than 3 weeks and 17 patients (13%) with no pain relief at all (Table). There was no observed complication from hip joint injection and the average follow-up time was 3.2 years. Table 1: Duration of pain relief in patients injected with steroids and local anaesthetic Duration

No of patients

Range

Percentage (%)

Years Months Weeks Days No pain relief

6 45 33 27 17

1–2 years 1–11 months 1–3 weeks 1–6 days

4.68 35.16 25.8 21.1 13.9

Non-operated group

20

Conclusion: There is adequate pain relief from hip joint injection (p<.001) however it is only temporary and the duration of pain relief is not reliable.

15 10 5 0 1

13

25

37

49

61

73

85

97

Survival in years

Conclusion: The results of this study showed that there was an improved quality of life and longer survival period of elderly patients, suffering from osteoarthritis of the hip, after total hip arthroplasty surgery. P364. Is hip injection the solution for the treatment of hip-osteoarthritis? S. Vail Karuppiah, P. Gibson; Department of Orthopaedics, Grampian University Hospitals Trust, Woodend Hospital, Aberdeen, Scotland—United Kingdom Background: Injection of corticosteroids into arthritic joints has been used as a treatment for arthritic joint pain for many

P365. A convenient new approach to simplify osteoporosis treatment regimen for risedronate plus calcium and vitamin D P. Fardellone1, A. Varbanov2; 1Department of Rheumatology, CHU d’Amiens, Amiens, France, 2Biometrics and Statistical Sciences Department, Procter and Gamble Pharmaceuticals, Cincinnati, USA Objectives: Calcium and Vitamin D (Vit-D) supplementation are recommended as co-medication to antiresorptive therapy. Convenient combination packaging can facilitate appropriate intake of Bisphosphonates (BP) plus calcium and Vit-D supplementation. The objectives of this study were to evaluate patient understanding of dosing instructions and patient preference for two types of packaging of risedronate 35 mg, calcium and Vit-D supplementation.

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Materials and methods: A combined package was developed containing four weekly boxes with each weekly box containing a blister pack with one 35 mg risedronate tablet, 6 sachets of calcium 1000 mg and Vit-D 880 IU and a patient information leaflet. A quantitative patient research study was conducted on women aged 55 years and older in five cities within France. Participants were BP users with diagnosed osteoporosis and Non-BP users regardless of osteoporosis diagnosis. All participants gave consent to participate in face-to-face interviews, using a standard questionnaire. The participants were presented the combined and separate packages once. The between-packaging comparison of participant understanding of the dosing instructions was analyzed using generalized estimating equation methodology and patient preference was analyzed using a cumulative logit model. Results: The study included 200 women. The combined packaging resulted in a significantly higher proportion of questions being answered correctly (80.3%) compared to the separate pack (70.7%) (p=0.0004). Seventy-two percent of participants preferred the combined pack (p<0.0001). The main reasons for preference were: “practicality of a weekly box” (51.7%), “less likely to forget/to get wrong” (51.7%), “having two products in the same box” (33.6%) and “clarity of the schedule” (30.8%). Conclusion: This patient study provides evidence that the combined pack of risedronate plus Calcium plus Vit-D is preferred over separate packs and improves overall understanding of dosing instructions. Combined packaging offers a convenient combination osteoporosis therapy, potentially improving treatment compliance and providing the maximum efficacy of an osteoporosis therapy.

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tablet, six sachets of calcium 1,000 mg and Vit D 880 UI and a patient information leaflet. A quantitative patient research study was conducted with 200 women, in three cities in France during October 2006. Participants were 55 years or older (mean age 67 years; sd=9) and divided into two groups: Group 1 (N=100) had a diagnosis of osteoporosis (OP) and were BP users either with or without supplementation; Group 2 (N=100) was included in the study regardless of OP diagnosis and were receiving no treatment for OP. All participants gave consent to participate to face-to-face interviews using a standard questionnaire. Results: The study showed that 60% of patients found the product practical to use. 63% and 67% found it easy to use and easy to remember when compared to separate packaging. Patients believed that the combined packaging would help them to take their BP regularly (66%) and correctly (67%) and to take Calcium and Vit D supplementation more regularly and correctly (68%) than the separate packaging. 70% of patients believed that the combination packaging would help them not to forget to take Calcium and Vit D supplementation. When exposed to the combination packaging only, 80% of patients considered the combination packaging to be a complete OP therapy. Conclusion: Patients found the combined packaging more practical and more convenient to use. They believed it would help them taking their prescribed OP therapy correctly and more regularly. This study provides evidence that the new combined packaging of risedronate 35 mg plus Calcium and Vit D provides patients with a tool to better adhere to the recommended OP therapy and to optimize the effectiveness of their treatment.

P366. A new combination packaging for osteoporosis treatment. Patient preference and expected adherence to the therapy P. Fardellone1, B. Mann2; 1Department of Rheumatology, CHU d’Amiens, Amiens, France, 2Procter and Gamble Pharmaceuticals, CMK, Schwalbach, Germany

P367. Bone mineral density in the renal form of primary hyperparathyroidism E. Csupor1, J. Szűcs2, S. Mészáros2, E. Tóth3, C. Horváth2; 1 The Health Service of Budavári Local Authorities, Budapest, Hungary, 2First Department of Medicine, Semmelweis University, Budapest, Hungary, 3Department of Rheumatology, County Hospital Flór Ferenc, Kistarcsa, Hungary

Objectives: Calcium and Vitamin D (Vit D) supplementation are recommended as comedications to antiresorptive therapy. Combination packaging may facilitate the correct administration of bisphosphonates (BP) plus Calcium and Vit D supplementation. The aim of this study was to evaluate patient perception of compliance, convenience and completeness of a new packaging of risedronate 35 mg plus Calcium and Vit D supplementation. Materials and methods: A combined packaging was developed containing four weekly boxes with each weekly box containing a blister pack with one 35 mg risedronate

Object: The most frequent manifestations of primary hyperparathyroidism are renal stones or calcipenic osteopathy. The aim of the authors was to examine how bones are affected (change of bone mineral density and frequency of fractures) in the renal form of primary hyperparathyroidism. Materials and methods: The average age of the 37 patients enrolled (4 males, 33 females) was 57 years (26– 81 years). Bone mineral density was measured by densitometry in the lower third of the radius, the femoral neck and the lumbar spine. In addition, the authors examined the occurrence of fractures in the medical history and the

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biochemical variables proving the hyperparathyroidism (serum parathormone, calcium, phosphorus, alkaline phosphatase, urine calcium/creatinine). Results: Bone mineral density was normal in only 6 patients, osteopenia was seen in ten patients, while decreased densities seen in osteoporosis was found in 21 patients. Fractures had occurred in five patients. There was no difference in bone density and the biochemical parameters between patients with or without previous fractures. Conclusion: Bone mineral density decreases in the renal form of primary hyperparathyroidism even if the clinical picture does not include bone diseases. Thus, bone densitometry is advisable for all patients with hyperparathyroidism. P368. A new quantitative ultrasound device (Sunlight Omnisense): comparison with calcaneus ultrasound and DXA S. Guadalix, M. Gómez-Juaristi, G. Martínez Díaz-Guerra, E. Jódar, F. Hawkins, D. Puente; Endocrinology Department, University Hospital 12 de Octubre, Madrid, España Objectives: There is a growing interest in the use of quantitative ultrasound (QUS) measuring as an alternative to current radiation-based bone densitometry techniques for non-invasive fracture risk assessment. Several studies have shown a correlation between ultrasonografic parameters and bone mineral density (BMD) measured with bone mineral densitometry (DXA). The objective of this study is to compare a new quantitative ultrasound device (Sunlight Omnisense) with other known methods: calcaneus ultrasound (Sahara) and DXA. Materials and methods: Forty-nine patients (26 women, 23 men, average age 58.88 years) were studied. They were consecutively sent to our unity to have a bone densitometry. The following measurements were taken: distal third of the radio and mean tibia speed of sound (SOS) through Sunlight Omnisense sonometer; calcaneus SOS, BUA and QUI through Sahara sonometer (Hologic Inc.); BMD lumbar (L1–L4) and BMD femoral (total, femoral neck, trocanterea and intertrocanterea) through DXA (Hologic QDR 4500). Results: The SOS values obtained in mean tibia had significative correlation with the lumbar BMD (r=0.31, p <0.05) and with femoral neck BMD (r=0.32, p<0.05). The calcaneus SOS showed a positive correlation with lumbar BMD (r=0.52, p<0.01) and femoral neck BMD (r=0.31, p <0.05). No correlation was observed between radio SOS and lumbar or femoral BMD, neither between tibia and radio SOS and calcaneus SOS. The prevalence of densitrometic osteoporosis was 32.7%, with OMS criteria. The prevalence of osteoporosis by ultrasound was 36.7% (Sahara) and 22.4% (Sunlight Omnisense) for a cutpoint

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SOS T-score of −1.8 SD. Instead, the prevalence of osteoporosis for a cutpoint T-score of −1.4 was 44.9% (Sahara) and 42% (Sunlight). Conclusions: The tibia SOS shows correlation with lumbar and femoral BMD. The lack of correlation with calcaneus QUS could be due to the different structural characteristics of the analized bone. More studies will be necessary in order to find our more about the clinical use of this new quantitative ultrasound device. P369. Cost-effectiveness of risedronate vs. Ibandronate: impact of persistence D. Grima1, M. Pasquale2, J. Lange2, M. Thompson1; 1 Cornerstone Research Group Inc., Burlington, Ontario, Canada, 2Procter and Gamble Pharmaceuticals, Mason, OH, USA The effectiveness of a drug in actual medical practice is dependent on drug efficacy, which is established through clinical trials, and on patient characteristics that include persistency of drug use. This study uses a Markov model of postmenopausal osteoporosis (PMO) to compare the therapeutic-and cost-effectiveness of risedronate and ibandronate at a wide range of persistency levels, measured by the percentage of patients on therapy at the end of this threeyear period. The Markov model simulated a cohort of women aged 65+, with previous vertebral fracture and BMD-T-score <−2.5, under a three-year time-horizon. Fracture rates were derived from US epidemiological studies. Vertebral and nonvertebral risk reduction measures are 52 and 0% for ibandronate, respectively (Chesnut-2004), and 41 and 40% for risedronate, respectively (Harris-1999). Annual drug costs were $876.46 for risedronate and $809.04 for ibandronate. For simplicity, the model assumes all patients who discontinue do so early (within the first 3 months), and that patients who discontinue in this time frame incur months of drug costs but without any efficacy benefit. At equal levels of persistence, treatment with risedronate results in fewer total fractures (nonvertebral and vertebral combined), lower fracture costs and lower total costs of treating fractures. The difference in fractures, fracture costs and total costs rises with increasing persistence. Fracture costs are always lower for risedronate, even at 10% risedronate persistence and 100% ibandronate persistence, due to the lack of proven efficacy of ibandronate on nonvertebral fractures (figure a). Cost-effectiveness (CE)ratios (cost of avoiding one-fracture) versus no therapy are also lower for risedronate. Persistence at 20% or above for risedronate results in lower CE ratio than ibandronate at a perfect 100% (figure b). The lower (improved) CE-ratio for

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risedronate is expected given its better efficacy. In this analysis, overall cost-effectiveness is more dependent on efficacy than persistency.

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Objectives: To verify the analgesic effect of alendronate 70 mg weekly on the knee pain in rheumatoid arthritis (RA) patients with secondary OA of the knee. Materials and methods: Is was a pilot, outpatient, randomized, open-label, parallel group study. Forty females diagnosed with moderate RA (DAS28 between 5.1 and 3.2) and OA of the knee were enrolled into the study. Twenty patients received alendronate 70 mg once weekly in addition to standard RA therapy, 20 matching controls did not. Patients remained on stable doses of drugs used for rheumatic conditions. Pain level referred to OA of the knee was assessed at baseline visit and after 3 months. Pain Visual Analogue Scale (PVA) and Verbal Analogue Scale (VRS) were done. Results: Thirty-five patients were statistically evaluated; 19 patients received alendronate 70 mg once weekly and 16 matching controls. The mean VAS score at baseline was 55.4 mm and mean VRS was 3.6 (on a scale from 0 to 5, 0 =none, 5=severe). After 3 months VAS but not VRS were significantly improved in group receiving alentronate compared to control group. Mean VAS score after 3 months was 41.3 and 53.6 mm, respectively (p<0.05). Conclusion: In this pilot study, addition of alendronate 70 mg once weekly to standard RA therapy showed to be superior to standard RA therapy in referring to diminishing OA knee pain. P371. Alendronate on osteoporosis secondary to chronic treatment with anticonvulsivant drugs in epileptic male patients M. Fasani1, D. Fiore1, M. Guicciardi1, M. R. Romagnuolo1, E. Bartelucci2, S. Magari2, M. Celestini1; 1Department of Physical Medicine and Rehabilitation, Azienda Sanitaria Locale (ASL) Roma E, Roma, Italy, 2Opera Don Guanella Maschile, Roma, Italy

P370. Analgesic effect of alendronate on osteoarthritis knee pain in rheumatoid arthritis patients J. Olas; Department of Rheumatology, Malopolskie Centrum Reumatologii, Immunologii i Rehabilitacji, Cracow, Poland Background: For the last years bisphosphonates proved to be a very important part of the treatment of osteoporosis. Due to their anti-resorptive and anti-inflammatory properties new indications for use may come into effect such as treatment of inflammatory diseases: ankylosing spondylitis and rheumatoid arthritis. Observations suggest that they also may turn out to be a valuable part of osteoarthritis (OA) treatment.

Objectives: The first aim was to confirm the decrease of BMD after one year of observation in male patients on chronic treatment with antiepileptic drugs. The second aim was to show the improvement of BMD after one year and two years of treatment with alendronate (Fosamax 70®), calcium and vitamin D. Materials and methods: We studied 40 institutionalized male patients (mental disabled patients) on treatment with anticonvulsivant therapy for more than 25 years. We evaluated them by ultrasound MOC (Hologic-Sahara) and considered estimated BMD at basal time (Tb) and after 1 year without antiresorptive therapy (T0). For the following years we gave patients alendronate (70 mg once a week) plus calcium and vitamin D; then we evaluated BMD after one (T1) and two years (T2) of treatment.

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Results: Tb: medium T-score was −2.3 (medium Z-score −1.7); 30 patients (88.2%) had BMD below normal values and 13 (38.2%) were osteoporotic (T-score <−2.5). T0: medium T-score was −2.7 (medium Z-score −2.0); osteoporotic patients increased from 13 (38.2%) to 21 (61.8%). T1: medium T-score −2.5 (medium Z-score −1.9); osteoporotic patients decreased from 21 (61.8%) to 15 (44.1%). T2: medium T-score was −2.3 (medium Z-score −1.7); osteoporotic patients decreased furtherly from 15 to 13 restoring basal values in spite of persisting risk factors. Conclusions: Alendronate is effective treatment to stop the decrease of BMD in patients on chronic treatment with anticonvulsivant therapy, and it is necessary to monitor BMD and treat these patients by antiresorptive therapy (bisphosphonates), calcium, vit. D and regular physical exercise.

T-SCORE 2006 10%

43%

47%

< -2.5 T-SCORE 2006 TRA -2.5 E -1 >1

T-SCORE E Z-SCORE 0

T-SCORE BEGINNING WITH ALENDRONATE

-0.5

Z-SCORE

-1

-1.5

2003

P372. A role and utility of serum osteoprotegerin, pentosidine, urinary cros-linked N-telopeptide and Gla-type osteocalcine as markers in glucocorticoid-induced osteoporosis I. Tanaka, H. Oshima; Department of Laboratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan Objectives: In GIO, bone fractures are often seen even at high bone mineral density. This suggests bone quality is an important factor in GIO for bone strength, which is usually evaluated with bone markers on the clinical basis. In this study, we tried to clarify the clinical usefullness of various bone makers in predicting the bone quality in GIO. Subjects and methods: Fifty nine patients (47 females and 12 males) with collagen diseases under glucocorticoid treatment were enrolled in this prospective study. An incidence of the vertebral compression fracture in 2 years after the start of glucocorticoid therapy was evaluated in 37 patients among those. The mean of age, daily glucocorticoid dosage (prednisolone equivalent), and total glucocorticoid dosage were 46 years old, 20.3 mg/day, and 6.3 g, respectively. Serum Glu type and Gla type osteocalcin (GluOC and GlaOC), NTX in the urine (uNTX) and Pentosidine (PEN) were measured by the ELISA methods. Vertebral compression fractures were evaluated with X-ray photography. Results:(1) After the start of glucocorticoid therapy, uNTX increased and GluOC decreased, but GlaOC did not changed significantly. (2) Doses of glucocorticoids, were significantly correlated with uNTX positively and with GluOC negatively. (3) GluOC and GlaOC were significantly increased in patients with vertebral deformities. (4) In patients treated with menatetrenone, GlaOC was lower in patients without incident fractures in 2 years than in those with the fractures. (5) uNTX seemed correlated with an incident fracture after corrected with risk factors. (6) PEN was decreased after the start of glucocorticoid therapy. Conclusion: Bone markers might be valuable for selection of anti-osteoporotic agents and prediction of incident fractures in GIO.

2006 2004

2005

-2

2003

2006 2004

-2.5

2005

-3

2003

2004

2005

2006

T-SCORE

-2.3

-2.7

-2.6

-2.3

Z-SCORE

-1.7

-2

-2

-1.7

P373. Indirect costs and QoL related to wrist fractures in patients below the age of 65 O. Ström, F. Borgström; European Health Economics, Stockholm, Sweden Objectives: Compared to the other investigated fracture types, wrist fracture patients are more often working at the time of fracture and the indirect costs of wrist fractures should not be

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neglected. In the ages 50–64, the Swedish female incidence of wrist fractures is 1.5 times higher than that of hip and vertebral fractures combined. The objective was to investigate indirect costs and QoL related to wrist fractures in patients below the age of 65 included in the Swedish KOFOR study. Materials and methods: One hundred thirty-three osteoporotic wrist fracture patients under the age of 65 from Sweden were included in the analysis. Patients were asked about their quality of life (EQ-5D) and fracture related resource use directly after the fracture, at 4 months, 12 months and after 18 months. Recollected QoL before the fracture was also collected. Results: Approximately 66% of the patients were working full or part-time at the time of fracture. Indirect costs associated with an average wrist fracture amounted to €796 during the first 12 months and €423 during the period 13–18 months after fracture. Indirect costs represented 31% and 72% of total wrist fracture costs during the two periods, respectively. In a subanalysis of patients that all were employed at the time of fracture, the total indirect cost during 18 months was estimated at €1,853. Patients working at the time of fracture had a higher pre-fracture QoL and recovered QoL faster compared to the group that was not working at the time of fracture (See figure). Conclusions: Indirect costs constitute a large proportion of the costs associated with wrist fractures in patients below the age of 65. In terms of QoL, all wrist fracture patients recover well from fracture but patients that were unemployed at the time of fracture show a slower recovery.

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P374. In vivo co-registered proton T1ρ and sodium MRI of the human knee S. Niyogi, M. Kasam, R.B. Shashank, A. Borthakur, R. Reddy; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA Objectives: To combine sodium MRI and proton T1r MRI to obtain information about both structural and molecular changes and thereby increase the reliability of diagnostic imaging of incipient changes in osteoarthritic patients. Materials and methods: Knees of three healthy volunteers (mean age: 29) were imaged on a 3T broadband-capable MRI scanner. For higher filling factor, we used a custom-built sodium birdcage radiofrequency (RF) coil suspended inside a vendor-supplied proton head coil. A custom-built apparatus was used to support and extract the sodium coil from the proton coil between acquisitions. Sodium and T1r MRI experiments were performed with same slice position and thickness. Images were used to generate sodium and T1r maps offline. Sodium MRI was performed using a 3D fast gradient-echo pulse sequence (turbo-FLASH) with these parameters: TE/TR =3.3/18 ms, FOV=200 mm, Acquisition Matrix=128×64, Number of Slices=10, Slice Thickness=5 mm, and 195 signal average for imaging time of 30 min. The sodium coil was extracted along the support apparatus without disturbing positioning of the subjects’ knees. 3D proton T1r -weighted images were then collected using the steady-state-freeprecession-based SLIPS sequence with these parameters: TE/ TR=2.7/5.4 ms, FOV=200 mm, Acquisition Matrix=256× 128, Number of Slices=20, Slice Thickness=5 mm, Delay Time=1 s, spin-lock Amp=500 Hz. Five acquisitions with various spin-lock durations (1–40 ms) generated a T1r map. Results and conclusions: Co-registered maps show (Fig.) an inverse correlation between T1r and sodium data. Similar trends were observed in two other subjects. Sodium maps can be used to calculate tissue’s fixed charge density (FCD), which is a map of proteoglycan distribution, while T1r maps provide integrated changes due to proteoglycans and collagen. The T1r data set provides 3D structural images of cartilage for computing changes in cartilage morphology. These results demonstrate feasibility of obtaining high-resolution T1r maps and lower-resolution sodium maps simultaneously. Integrated

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measures provide increasingly reliable sets of metrics for determining degradation of articular cartilage.

P375. Elderly people with hip fractures hospitalizations in Northeast Brazilian communities A.F. Oliveira-Filho1, R.C. Martiniano2, W.E.C. Chagas2, A. B. Nunes2; 1Health Consortium Curimatau, Cuite, Brazil, 2 Department of Internal Medicine, Federal University Paraiba, Joao Pessoa, Brazil Hip fractures are associated to great morbidity and mortality. As a result of improving life expectancy, the number of elderly people susceptible to hip fractures is increasing rapidly in the developing world. In this study, our objective was to describe the incidence of hip fracture in Paraiba, northeast Brazil, a sunny place where direct costs of a hip fracture contrast with the poor income per capita. The data used were obtained from the hospitalizations data from Public Primary Health Care System Health Ministry using hip fractures diagnosis CID10 S72. From September 2005 to September 2006, a total of 828 hospitalizations for hip fracture occurred among persons aged more than 50 years old, and 66.07% of these admissions occurred among women. Hip fractures occurred

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more frequently in >80 year age group (50.25%). In 50– 59 year age group we could observe hip fracture more frequent in males (6.04%) when compared to females (3.75%). In women, the absolute number of fractures and incidence rate continuously increased with age; up to 36.6% in older than 80 years old. With advancing age, the incidence rate of hip fractures in women approached that in men and surpassed it; the female:male ratio rise from 0.62 to 1.2 and 2.5 (1.2–2.8) in the 60–69, 70–79 year age groups, respectively. Despite the continuing increase with age, almost one-half (59.07%) of the hip fractures occurred before the age of 80 years in men. Percent number of deaths were documented was more frequent in women (rate 1.89:1). Persons aged > or =50 years constitute the fastestgrowing segment of the Brazilian population. Without effective intervention strategies, the number of hip fractures will increase as the Brazilian population ages. Effective public health strategies need to be implemented to promote behavioral changes, improve current interventions, and develop new efficient, safe and economically accessible treatments to our population besides prevention strategies to reduce future morbidity and mortality associated with hip fractures among older adults. P376. A low-dose alfacalcidol and calcitonin therapy in prevention of bone loss in pre-dialysis chronic renal failure patients L.P. Martynyuk1, V.V. Povoroznyuk2; 1Department of Nephrology, Ternopol State Medical University, Ternopol, Ukraine, 2Department of Clinical Physiology and Pathology of Locomotor Apparatus, Institute of Gerontology AMS Ukraine (Clinicheskaya, Ternopol), Kiev, Ukraine The aim of this study was to study the safety and efficacy of a combined low-dose therapy of alphacalcidol and calcitonin in the prevention of bone loss in chronic renal disease (CRD) pre-dialysis patients with mild to moderate renal failure and secondary hyperparathyroidism (SPTH). We analyzed data on 29 adults aged 23–61 years (mean 42.6±2.8 years) with advanced CRF, elevated PTH concentration and reduced BMD. All 29 patients were diagnosed II–III stages of CRD (mean GFR 58.6+5.4 ml/ min). Serum concentration of calcium, phosphorus, alkaline phosphatase and iPTH were studied before starting treatment and after 12 months. BMD was measured at two sites —lumbar spine (L1–L4) and femoral neck using dual energy X ray absorptiometry at baseline and after 12 months of treatment. Patients were randomized into two groups: in first group, 18 patients were prescribed low phosphate diet and administered calcium carbonate as phosphate binder at a daily dose that didn’t exceed 1.0 gram of elemental calcium and calcitonin 100 IU×3 times weekly intramus-

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cular. The starting and most common dose of alfacalcidol used was 0.25 μg once daily, the dose was adjusted to maintain PTH levels at target values to avoid the risk of adynamic bone disease. In second group (11 patients) a low phosphate diet and calcium carbonate as phosphate lowering agent at daily dose 1.0 gram of elemental calcium were prescribed. In alfacalcidol group the mean iPTH level declined significantly and achieved target levels according to CRD stage, serum calcium increased and both the phosphorus level and alkaline phosphatase activity declined significantly after 12 months of treatment. In the control group the levels of iPTH and phosphorus increased. In the control group, the mean BMD at lumbar spine decreased in −5.57± 0.56 % from at baseline. In alfacalcidol and calcitonin group it increased in 2.12±0.68 % from baseline (p<0.01). No patients had side effects of the therapy. The study supports the idea for beneficial effect of low dose of alfacalcidol and calcitonin treatment in prevention bone loss in mild to moderate CRF patients with SPTH and reduced BMD. P377. Drug budget planning for ibandronate quarterly I.V. injection (Bonviva® I.V.) for the treatment of post-menopausal osteoporosis (PMO) in the UK National Health Service (NHS) DR. Millar, W. Cowell; Healthcare Management, Roche Products Ltd, Welwyn Garden City, United Kingdom Objectives: IV ibandronate offers an alternative treatment option for patients unsuitable or intolerant to standard 1st line oral bisphosphonate therapy. This work aims to investigate the financial impact of introducing the 1st and only licensed IV bisphosphonate for PMO in the NHS. Materials and methods: Numbers of PMO sufferers likely to receive IV ibandronate were estimated using epidemiology data from published literature, registry data, and market research. Scenarios were investigated, ranging from replacement of the commonly used unlicensed IV bisphosphonate pamidronate, to treating additional patients who previously did not receive bisphosphonate therapy due to being unsuitable for the oral therapy. The forecasted budget impact of replacing pamidronate (marginal acquisition cost between ibandronate and pamidronate) assumed 100% replacement of pamidronate by year 3, and equal usage of the three pamidronate regimens typically used to treat PMO (30 mg/45 mg/60 mg); sensitivity to changes in the assumed proportional usage of the regimens was examined. Results: Approximately ∼157,000 (26%) (1) of the 602,269(2) patients treated for PMO are unsuitable for oral bisphosphonates of which ∼5,000(1) receive pamidronate. Replacing pamidronate with IV ibandronate is estimated to

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save the NHS £92.2k pa in drug costs by year 3. Third year costs/savings of replacing pamidronate ranged from a saving of £658k pa to an additional cost of £473k pa depending on the assumed proportion of pamidronate regimens used. Seventy percent (∼110,000)(1) of treated sufferers that are found to be unsuitable for oral therapy stop treatment or receive only vitamin D/supplements; treating 10% (∼11,000) of these patients with ibandronate would cost an additional £3.52 m pa in drug cost. Conclusions: The cost impact of IV ibandronate replacing unlicensed pamidronate is relatively small and potentially cost saving. However, there are additional patients unsuitable for oral therapy (currently untreated or receive only vitamin D/supplements) that may now benefit from bisphosphonate treatment; possibly due to the shorter administration time (15–30 s) of IV ibandronate, or perhaps due to the availability of a licensed formulation avoiding issues associated with off license product use. (1) Roche/GSK Data on File (DoF) 1. Quantitative Market

Research Survey. (2) DIN-LINK data. Compufile Ltd. MAT. January 2006.

P378. Interrelation of quality indicators for osteoporosis research in panoramic X-rays of Brazilian women P.C. Watanabe, S.A.C. Monteiro, E.S. Arita; Department of Radiology, Faculdade de Odontologia de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil The osteoporosis is a world problem. With the progress of the medium age of the world population, the osteoporosis becomes a problem of public health. Individuals with the disease present pain, movement and function loss and dental loss. The osteoporosis study deserves prominence in the Brazilian population due to the great mixture of races. The authors of the present work evaluated the correlation of the some radiographic panoramic signals for morphologic pattern of inferior cortex of mandible, done in X-rays digital panoramic images, with measures of DEXA, in the column, femur and forearm, of Brazilian women. The results showed significant correlation among the two techniques. P379. The effect of antiresorptive agents on QoL in patients with postmenopausal osteoporosis P. Borman, C. Atan, H. Bodur; Clinic of Polymyalgia Rheumatica (PMR), Numune Training and Research Hospital, Ankara, Turkey The assessment of quality of life (QoL) has become a very important tool to evaluate patients with osteoporosis. Antiresorptive agents have been shown to produce mean

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increases in bone mineral density (BMD), decrease the risk of fractures and promote an increase in QoL in patients suffering from osteoporosis. The aim of this study was to retrospectively evaluate the changes in mean BMD values and QoL scores of osteoporotic patients receiving antiresorptive agents. The demographic variables, QoL scores assessed by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and BMD levels of the postmenopausal patients with a mean age of 62.7 ± 6.36 years, were recoreded from the files. None of the patients had fracture history. Eleven patients were receiving alendronate 70 m/weekly (group 1), ten patients were taking risedronate 35 mg/weekly (group 2) and ten patients were on nasal calcitonin therapy 200 IU/day (group 3). All the patients were receiving calcium and vit D3 supplements daily in addition. The groups were compared with each other according to demographic variables, BMD and QUALEFFO scores which were recorded at baseline and at the end of 1 year. There was no difference between the groups in regard to demographic properties including age, years of menopause, smoking and exercise status. No fracture was observed in one year in the study groups. No significant difference in the incidence of adverse events was recorded beween the groups. There was a significant increase in BMD values of patients in groups 1 and 2 at the end of first year. An improvement in patients’ QoL was observed in all groups (Table). Table 1: The comparison of the patients’demographic variables and the difference between the baseline and the first year levels of BMD and QUALEFFO according to the groups.

Age (years) Duration of menopause (years) T score L1–4 Baseline

group 1 n=11

group 2 n=10

group 3 n=10

60.4±8.3 18±10.3

65.5±0.7 19.3±7

62.6±8.08 20.5±6.3

−2.62± 0.56* −2.41± 0.52* −1.96± 0.66* −1.75± 0.67* 26.6± 4.02* 11.1± 2.28*

−2.92± 1.47 −2.85± 1.44 −2.35± 0.08 −2.32± 0.84 35.7±2.83*

−3.02± 0.69* First year −2.46± 0.45* T score femur Total baseline −2.12± 1.04* First year −2.03± 0.65* QUALEFFO Baseline 27.5± 4.03* First year 11.4± 1.26*

17.2±4.8*

This preliminary study indicates that antiresorptive agents increase QoL in patients with postmenopausal osteoporosis. Although calcitonin seems to have no significant effect on BMD values in 1 year period, it has similiar effects on QoL like biphosphonates. P380. The effect of osteoporosis risk factors on quantitative ultrasound measurements at radius A.G. Kayalar, D. Keskin; Clinic of Physical Medicine and Rehabilitation, Numune Educational and Research Hospital, Ankara, Turkey 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 speed of sound (SoS) at the radius with Sunlight Omnisence 7000S. We studied 87 postmenopausal women between 40–77 years of age with a mean age of 52.7±0.17. All participants were questioned 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, body mass 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 the most of the risk factors for osteoporosis are associated with SoS. It should be pointed out that the SoS value is predictive method in detecting patients with osteoporosis. Prospective studies are needed to support the role of Omnisence in assessing the risk factors of osteoporosis. P381. Vertebral deformities in osteoporosis and quality of life A.G. Kayalar1, N. Yildirim2, B. Sayın2, D. Keskin1, D. Dede 2 ; 1 Clinic of Polymyalgia Rheumatica (PMR), Numune Educational and Research Hospital, Ankara, Turkey, 2Clinic of Radiology, Numune Educational and Research Hospital, Ankara, Turkey Objectives: 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. Materials and methods: Lateral radiographs of the spine were obtained in 46 female patients with spinal osteoporosis with a mean age of 61±10.23. Vertebral deformities were measured semiquantitatively, and vertebral degenerative changes of the thoraco-lumbar spine was measured by

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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 Tscore 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). Results: The height of the vertebra correlated with BMI (p <0.05), Z and T score of the femur neck and femur wards score (p<0.01), menapause 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 menapause age. Besides age negatively correlated with DXA scores and BMI correlates with femur total and neck Z scores (p<0.05). Conclusions: Vertebral deformities have no affect on spinal osteoporosis and quality of life. Additionally there seems to be no consistent relationship between BMD and vertebral deformities in this patient group. P382. Shoulder involvement in rheumatoid arthritis A.G. Kayalar1, D. Sancak2, D. Cýlýz2, E. Alemdaroğlu1; 1 Clinic of Polymyalgia Rheumatica (PMR), Numune Educational and Research Hospital, Ankara, Turkey, 2Clinic of Radiology, Numune Educational and Research Hospital, Ankara, Turkey To determine the role of ultrasound and magnetic resonance imaging (MRI) compared with conventional radiography in the detection of chronic and acute manifestations of rheumatoid arthritis (RA) of the shoulder joint. Fifty-four consecutive patients with known RA prospectively underwent clinical examination, radiography, ultrasound and MRI of the shoulder joints. Each patient was assigned a clinical/laboratory including measurements of the shoulder mobility. Disease activity was assesed with erithrocyte sedimentation rate, C-reactive protein level, RÝTCHÝ articular index, pain (VAS), patients global assesment (VAS) and quality of life (HAQ). Conventional radiography was standardized and performed in two planes. Ultrasound was performed in ten predefined planes using a 7.5-MHz linear transducer. MRI at 0.5 T comprised transverse and oblique coronal T1-and T2 weighted fast spin echogradient echo (GRE), and inversion recovery sequences with a matrix size of up to 512 pixels. Erosions were assessed using all three imaging techniques on a 4 points scale. Soft tissue involvement was evaluated according to the presence of synovitis, tenosnovitis, and bursitis on ultrasound and MRI. The results in the study group were compared with those obtained in a control group of 20 patients with shoulder

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pain. Erosions of the humeroscapular joint were detected by conventional radiography in 12 patients, by ultrasound in 22 patients and by MRI in 23 patients. The differences were statistically significant for the comparisons of conventional radiography with MRI and for ultrasound versus MRI (p< 0.0001). Synovitis was demonstrated in eight patients by ultrasound and 14 patients by MRI; tenosynovitis was observed in eight patients by ultrasound and in eight patients by MRI; bursitis was detected in 13 patients by ultrasound, and in 17 patients by MRI. The differences were not statistically significant for the comparisons of ultrasound and MRI. There were positive correlations between ESR, CRP, pain, RÝTCHÝE and HAQ. There were not correlation between clinical variables and Larsen score, and ultrasound and MRI. Ultrasound and MRI supplement conventional radiography in assessing the shoulder joint. Although conventional radiograhy can be used as the sole method of following up known joint destruction in RA. Ultrasound and preferably MRI are recommended as additional techniques in the initial diagnostic evaluation when radiography yields negative results. P383. The value of calcaneal bone mass measurement using DXL Calscan device in screening risk of osteoporosis A.G. Kayalar1, A. Çevikol2, G. Yavuzer3, Y. Sanisoðlu4, A. Çakci2, T. Arasýl3; 1Clinic of Physical Medicine and Rehabilitation, Numune Educational and Research Hospital, Ankara, Turkey, 2Department of Physical Medicine and Rehabilitation, Dýpkapý Training and Research Hospital, Ankara, Turkey, 3Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Ankara University, Ankara, Turkey, 4Department of Biostatistics, Gülhane Military Medical Academy (GATA), Ankara, Turkey The objective of this study was to evaluate how BMD in calcaneus measured by DXL Calscan device correlates with BMD in spine and hip in Turkish women over 40 years old, and to determine whether calcaneal DXL variables are affected by clinical risk factors to the same extent as axial BMD measurements obtained using DXA. A total of 2,884 Turkish women, aged 40–90 years, living in Ankara were randomly selected. The calcaneal BMD was evaluated using a DXL Calscan device. The subjects, whose DXL T-score was ≤−2.5, did thereafter receive a referral for DXA of spine and hip. Besides DXL measurements, all subjects were questioned on medical history and the most relevant risk factors for osteoporosis. Using a T-score threshold of −2.5 (WHO), DXL heel measurements showed that 13% of the subjects had osteoporosis, and other 56% had osteopenia. Mean DXL T-scores of the smoker, postmenopausal subjects with a

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positive history of fracture, HRT, covered dressing style, lower educational level, no regular exercise habit, and low tea consumption was significantly lower than the other group. There was a significant correlation between DXL Tscore and age, BMI, age at menarche and menopause, number of live birth and breast feeding time. Correlation between DXL T- and Z-, and DXA T- and Z-scores at spine and femoral neck were significantly correlated. We concluded that BMD measurement in calcaneus by DXL Calscan device is valuable in screening Turkish women over 40 year of age for risk of osteoporosis. P384. Relationship of volumetric BMD and structural parameters with ERα polymorphisms in men C. Cepollaro1, F. Lauretani2, A. Gozzini1, L. Masi1, A. Falchetti1, A. Amedei1, S. Carbonell-Sala1, A. Tanini1, A.M. Corsi2, S. Bandinelli3, L. Ferrucci4, M.L. Brandi1; 1 Department of Internal Medicine, University of Florence, Florence, Italy, 2Tuscany Health Regional Agency, Florence, Italy, 3Rehabilitation Unit, Azienda Sanitaria di Firenze, Florence, Italy, 4Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging (NIA), National Institute of Health, USA Objectives: Bone strength is determined by bone mineral density (BMD) and bone quality, which encompasses a number of dynamic processes, such as bone turnover, mineralization, microarchitecture, and geometry; therefore BMD reflects only one component of bone strength and methods for clinical assessment of bone quality are awaited. Peripheral quantitative computed tomography (pQCT) allows for separate assessments of cortical and trabecular bone and provides direct information on bone geometry. Both BMD and bone structure have a strong genetic component. Previous studies examining the relationship between estrogen receptor α (ERα) polymorphisms and BMD have been performed on women. However, there are no comparable published data for men. Moreover, only few studies have investigated the possible role of ERα polymorphisms on bone properties, as assessed by pQCT. The aim of our study was to evaluate the association of XbaI and PvuII polymorphisms of the ERα with pQCT parameters in men. Materials and methods: We studied 449 men, age range: 23–92 years, participating to the InCHIANTI study. In all subjects we performed pQCT (XCT 2000, Stratec, Germany) at the tibia level obtaining the follow parameters: trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/ cm3), cortical bone area (tCSA mm2) and cortical thickness (Ct.Th, mm). The subjects have been genotyped for the PvuII and XbaI polymorphisms, identifying, respectively, X and x, P and p alleles, according to the absence (X, P) or the presence (x, p) of the restriction sites.

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Results: No significant effects on pQCT parameters were seen for XbaI. Regarding PvuII polymorphisms, multivariate regression analysis showed a negative trend in all densitometric and geometric parameters in PP group with respect to Pp and pp group, although the differences did not reach statistical significance. Analyzing PP respect to Pp and pp, Ct.Th showed a significant (p<0.05) higher values in the first group, also after adjustment for multiple confounders. Conclusions: These results indicate a relationship between the presence of P allele and higher values of Ct.Th and suggest that bone geometry could be influenced by PvuII identified genotype in men. P385. Localization of strontium, by X-ray microanalysis cartography, in bone biopsies of postmenopausal osteoporotic women treated for 3 years with strontium ranelate G. Boivin1,2, M.T. Khebbab2, X. Jaurand2, D. Farlay1,2, P.J. Meunier1, P.D. Delmas1; 1Institut national de la santé et de la recherche médicale (INSERM), 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 (Protelos®) is a new effective and well tolerated treatment for postmenopausal osteoporosis (PMOP). It provides early and sustained vertebral and nonvertebral (including hip) antifracture efficacy.(1) In PMOP women, the distribution of strontium (Sr) in bone tissue has only been reported after focal X-ray microanalysis.(2) However, a global cartography on the entire bone biopsies has never been yet performed. Cartography, a time consuming approach (1 month full time per sample), was performed on bone samples to evaluate the global distribution of calcium (Ca), phosphorus (P) and Sr in both cortical and trabecular bone on all the surface of samples (analysis on a thickness of 1 μm), and to measure the percentage of bone volume containing Sr. Cartography was performed on four bone biopsies from PMOP women treated for 36 months with strontium ranelate at 2 g/day (phase III clinical trials). PMOP women received daily calcium and vitamin D supplements according to their needs. Global cartography showed that the volume covered by Sr represented 25 to 50% of the total bone volume, up to 57% of trabecular volume and up to 46% of cortical volume. This was in perfect agreement with the focal distributions of Sr reported in women. In trabecular and cortical bone, Sr was taken up by bone tissue and heterogeneously distributed. On three of the biospsies, bone formed under treatment was identified by the tetracycline labeling carried out at baseline and Sr was exclusively located in bone formed after this

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baseline tetracycline labeling. Furthermore, this bone area was characterized by a low degree of mineralization as expected in bone tissue recently formed. However, the degree of mineralization of bone is preserved at the level of the entire biopsie.(2) To conclude, cartography of strontium in bone tissue after 36 months of treatment with strontium ranelate, demonstrated the presence of strontium only in tissue resulting from a formation activity during the period of treatment. (1) Meunier et al (2004) N Engl J Med 350:459–68; Reginster et al (2005) J Clin Endocrinol Metab 90:2816–22 (2) Boivin et al (2006) Calcif Tissue Int 78 suppl.1:S36–7

P386. Induction of increased cAMP level in articular chondrocytes blocks matrix metalloproteinase but not aggrecanase mediated cartilage degradation M.A. Karsdal1,2, E.U. Sumer1, H. Wulf1, S.H. Madsen1, Cl. Christiansen3, A.J. Fosang4, B.-C. Sondergaard1; 1Nordic Bioscience Diagnostics, Herlev, Denmark, 2Pharmos Bioscience, Herlev, Denmark, 3Center for Clinical and Basic Research (CCBR), Ballerup, Denmark, 4Melbourne University Department of Paediatrics and Murdoch Childrens Research Institute, Arthritis Research Group, Royal Children’s Hospital, Melbourne, Australia Objectives: Calcitonin has been suggested to have chondroprotective effects. One signalling pathway of calcitonin is via the second messenger cAMP. We investigated whether increased cAMP levels in chondrocytes would be chondroprotective. Materials and methods: Cartilage degradation was induced in bovine articular cartilage explants by 10 ng/mL oncostatin M (OSM) and 20 ng/mL TNF. In these cultures levels of cAMP was stimulated by treatment with either forskolin (4– 64 μM) or IBMX (4–64 μM). Cartilage degradation was assessed by (1) quantification of cross-linked C-telopeptide fragments of type II collagen (CTX-II), (2) matrix metalloproteinase (MMP) mediated aggrecan degradation by 342 FFGVG-G2 cleavage-site, (3) aggrecanase mediated degradation by 374ARGS-G2, and (4) release of sulphated glycosaminoglycans (sGAG) into culture medium and (5) immunohistochemistry with the CTX-II-Ab and Toluidineblue staining of proteoglycans. MMP expression and activity was assessed by gelatin zymography. Results: OSM and TNF induced an 8,000% increase in CTX-II compared to control (P<0.001). Both forskolin and IBMX dose-dependently inhibited release of CTX-II (P< 0.001). OSM and TNF induced a 7-fold increase in 342 FFGV-G2, which was dose-dependently inhibited by forskolin and IBMX by more than 80%. OSM and TNF stimulated MMP expression as visualized by zymography, which was dose-dependently inhibited by forskolin and

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IBMX. The highest concentration of IBMX lowered cytokine-induced release of sGAG by 72%. Conclusion: cAMP levels in chondrocytes play a key role in controlling the catabolic activity. Increased cAMP-levels in chondrocytes inhibit MMP expression and activity, and consequently a strong inhibition of cartilage degradation. Specific cAMP-modulators in chondrocytes may be potential treatments for cartilage degenerative diseases. P387. Strontium ranelate effects on bone formation and bone resorption: an in vitro in human osteoblasts T.C. Brennan1, M.S. Rybchyn1, A.D. Conigrave2, R.S. Mason1; 1School of Medical Sciences (Physiology) and Bosch Institute, University of Sydney, New South Wales, Australia, 2School of Molecular and Microbial Biosciences, University of Sydney, New South Wales, Australia Strontium ranelate reduces the risk of vertebral and hip fractures in post-menopausal women. Previous studies have shown that strontium ranelate increases bone formation and decreases bone resorption. In the current study, we investigated in primary human osteoblasts (HOB) the strontium ranelate effects on indirect markers of bone formation [proliferation, alkaline phosphatase (ALP) activity], on the capability of osteoblasts to regulate osteoclastogenesis (OPG mRNA level and RANKL mRNA and protein level) and on osteoblast lifespan. HOB were cultured in Dulbecco’s modified Eagles medium with 10% fetal bovine serum, adapted to serumfree and calcium-free medium for 24 h, and then treated with strontium ranelate in physiological Ca2+ (1 mM). After a 48 h-treatment, strontium ranelate increased HOB proliferation, assessed by thymidine incorporation, in a dose-dependent manner, up to 3.8-fold (2 mM, p<0.01). ALP activity was increased after 72 h with strontium ranelate by almost 2-fold (1 and 2 mM, p<0.01). After only 24 h, strontium ranelate increased OPG mRNA expression, by qRT-PCR, up to 1.9-fold (2 mM, p<0.001). Under the same conditions, low doses of strontium ranelate strongly decreased RANKL mRNA expression: remaining expression was below 25% with strontium ranelate concentrations ≥0.1 mM (p<0.001). These results were confirmed at the protein level by RANKL-specific Western blotting. Finally, strontium ranelate dose-dependently increased HOB survival under oxidative stress conditions induced by peroxide (0.1 mM, p<0.05, 1 and 2 mM, p<0.01), and decreased serum deprivation-induced apoptosis as measured by caspase 3 and caspase 7 activities (0.1 and 1.0 mM, p< 0.05). In conclusion, strontium ranelate, at strontium concentrations close to those observed in patients treated with the therapeutic dose of 2 g/day, increases human osteoblast replication, differentiation and the ability to withstand

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stress, parameters associated with promotion of bone formation. In parallel, strontium ranelate stimulates human osteoblasts to express more OPG and less RANKL, thereby decreasing their capability to stimulate osteoclastogenesis. Overall, these results strongly support the dissociation effect of strontium ranelate on bone formation and bone resorption in human osteoblasts.

To summarize, SR increased osteoblastic differentiation and mineralization in a COX-2 dependent manner in murine MSCs, as well as PGE2 production, IGF-1 and VEGF mRNA expression. In conclusion, the positive effect of SR on bone formation could then involve the PGE2downstream production of growth factors, which could directly stimulate osteoblastic differentiation.

P388. Strontium ranelate effects on osteoblastic differentiation are associated with PGE2-dependent growth factor production S. Choudhary1, P. Halbout2, C. Alander1, L. Raisz1, C. Pilbeam1; 1Musculoskeletal Institute, University of Connecticut Health Center, Farmington, USA, 2Institut de Recherches Internationales Servier, Courbevoie, France

P389. FDPS, GGPS1 and FDFT1 gene polymorphisms may play an important role as pharmacogenetic markers for N-BPs therapy response S. Carbonell Sala, F. Del Monte, V. Martineti, S. Silvestri, F. Marini, I. Tognarini, C. Cepollaro, L. Masi A. Tanini, M. L. Brandi; Metabolic Bone Unit, Department of Internal Medicine, University of Florence, Florence, Italy

Strontium ranelate (SR) is a new treatment for osteoporosis that has both antiresorptive and anabolic effects. SR increases osteoblastic differentiation and prostaglandin (PG) E2 production in murine marrow stromal cells (MSCs). To investigate the hypothesis that strontium ranelate exerts some of its anabolic effects on osteoblasts via PG production and growth factors produced downstream, we examined the ability of SR to stimulate osteoblastic differentiation and mineralization in MSC cultures from cyclooxygenase-2 (COX-2) knockout (KO) and wild type (WT) mice. COX-2 KO MSCs have a marked decrease in PG production relative to MSCs from COX-2 WT mice. MSCs from 7–8 wk old WT and KO mice were cultured up to 21 days with SR (1 and 3 mM). Alkaline phosphatase (ALP), osteocalcin (OCN), IGF-1 and VEGF mRNA expression were determined by real time PCR. Mineralization was assessed by alizarin red staining. After 14 and 21 days of culture, SR significantly and dosedependently increased ALP and OCN mRNA expression, respectively, in WT cultures. These effects were associated with an increase in IGF-1 and VEGF mRNA expression by 1.4–1.5-fold (p<0.01) and 1.4–1.7-fold (p<0.01), respectively, after 7 days in SR treated cultures. There was also, a dose-dependent increase in PGE2 production, which occurred after a treatment with SR for 7 days. In MSCs from COX-2 KO mice, ALP and OCN mRNA levels were decreased 50% (p<0.05) and 60% (p<0.01), respectively, compared to WT MSCs, and there was no increase in ALP and OCN mRNA expression with SR. No increase in IGF-1 and VEGF mRNA expression or in PGE2 production was induced by SR in COX-2 KO mice. Osteoblast mineralization was dose-dependently increased in WT cultures after a treatment with SR for 21 days. Mineralization was decreased in COX-2 KO cultures compared to WT cultures, and mineralization induced by SR was decreased in the COX-2 KO cultures.

Pharmacogenetics represents an interesting tool to predict in individuals the customized treatment to be received, with important consequences for pharmaco-economy of longterm therapies chronic diseases. Our aim is to study how genetic traits influence efficacy and acute response to amino-bisphosphonates (N-BPs) therapy. Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, divided in two classes: those who inhibit protein prenylation (N-BPs) and those who are metabolized to ATP-analogues (not N-BPs). N-BPs can specifically inhibit some mevalonate pathway enzymes required for protein prenylation. The response to NBPs is highly variable among treated patients, maybe due to the individual genetic variability. Genetic polymorphisms can predict drug response, although actually there are only few reports of pharmacogenetics applications in metabolic bone disorders. The aim of this study is to analyze farnesyl pyrophosphate-synthase (FDPS), geranilgeranil pyrophosphate-synthase (GGPS1) and squalene synthase (FDFT1) gene polymorphisms to assess genetic aspects of N-BPs response. We evaluated the genotype distribution for FDPS A/C polymorphism (intron 1) in Italian population. A-allele frequency is 0.82, C-allele frequency is 0.18, with an heterozygosity index of 0.2981 (χ2Test; p=0.29). The polymorphism information content of this marker is informative (PIC=0.29). After the evaluation of the PIC value of GGPS1 and FDFT1 selected polymorphisms, our future goal is to perform a cohort study with patients involved in clinic trials with N-BPs, searching eventual correlation between genotype/haplotype and response to therapy. We are performing a cohort study to analyze the relation between the genotype frequency and bone mineral density; as well as, the association with the response to treatment with different aminobisphosphonates in 200 Caucasian postmenopausal women. Preliminary data shows no statistically significant association between FDPS

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polymorphism and baseline-BMD, with a tendency of lowest response in patients with CC-genotype. Further studies including larger populations are needed. Our final goal is to identify the segregation of clinical response to N-BPs with genetic profile of their targets in chronic metabolic bone syndromes; and to provide models for N-BPs pharmacogenetic functionality studies. Our results may provide clinicians and scientists powerful tools to enhance drug-surveillance strategies and to improve the selection of optimal therapeutic guidelines in patients treated with N-BPs. P390. Incidence of osteoporotic fractures in Hong Kong Chinese men and women E. Lau1, P.C. Leung2; 1Hong Kong Orthopaedic and Osteoporosis Center, Hong Kong, China, 2Jockey Club Center for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong, China Objectives: To study the incidence of osteoporotic fractures in Hong Kong chinese men and women by a cohort method. Materials and methods: Two thousand elderly men and 2,000 elderly women aged 70 years and over were recruited from the community. They were followed up for 2 years. A history of fracture were obtained every 4 months. Fracture was validated by hospital data or by X-rays. The results were compared with data from Caucasians eg from the Dubbo Osteoporosis Study. Results: Nos and incidence of fractures (per 100,000/per year) Hip forearm spine others men 4/103 8/205 3/77 32/ 821 women 9/239 22/585 6/160 67/1,782. Conclusion: The incidence of osteoporotic fractures in Hong Kong Chinese men and women was around 50% of those observed in Caucasians. P391. Functional ability, disease activity and bone mineral density in patients with ankylosing spondylitis S. Grazio1, A. Balenović2, F. Grubišić1, T. Nemčić1, Z. Kusić2; 1Department of Rheumatology, Physical and Rehabilitation Medicine, Sisters of Mercy University Hospital, Zagreb, Croatia, 2Department of Nuclear Medicine and Oncology, Sisters of Mercy University Hospital, Zagreb, Croatia Objectives: Patients with ankylosing spondylitis (AS) tend to have osteoporosis (OP). The aim was to examine the relationship between disease activity, functional ability and bone mineral density in patients with AS. Materials and methods: Eighty patients responding to the modified New York criteria (46 men, 34 women; mean age 52.30 ± 10.38 years; mean disease duration 21.87 ± 10.32 years) were consecutively included from the rheu-

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matology clinics. BMD measurements, expressed as Tscore, of the lumbar spine and left femoral neck were determined by DXA. Functional ability was measured by Bath Ankylosing Spondylitis Functional Index (BASFI). Disease activity was measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (available for 48 patients) and by measuring the acute phase reactants (ESR and CRP). Results: There were significantly more patients classified as osteopenic or osteoporotic in comparison with normal at lumbar spine than at femoral neck (p=0.000). BASFI index was 50.34±24.45 and BASDAI index 54.42±23.20. Regarding BASFI index one way ANOVA showed difference between three WHO categories at femoral neck (p=0.004) but not at lumbar spine (p=0.181). Inversely, regarding BASDAI index the difference was not found at femoral neck (p=0.782) but at lumbar spine (p=0.011). Post hoc analysis showed that significantly more patients with osteopenia at lumbar spine had lower BASDAI index than those with normal BMD (p=0.030), while there was a borderline difference between osteoporosis and osteopenia (p=0.055). Consistent association was found between higher values of ESR or CRP and osteoporosis status at lumbar spine (p=0.002 and p=0.011, respectively) and at femoral neck (p=0.004 and p=0.027, respectively). Conclusions: Osteoporosis is more prominent feature of AS at axial than at peripheral sites. Osteoporosis status at femoral neck seems to be associated with BASFI index. We can assume that osteoporosis in AS is primarily influenced by inflammation. Syndesmophytes and ligament calcification could have influenced our results. P392. Comparison of skeletal effects of a soluble activin receptor type IIa (ACTRIIa), PTH and zoledronate in ovariectomized mice E.Rosen1, R.S. Pearsall2, V. Glatt1, M.L. Bouxsein1; 1 Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA, 2Acceleron Pharma, Cambridge, MA, USA Objectives: Activin, a member of the TGF-β superfamily, has been implicated as both a positive and negative regulator of bone metabolism. We previously showed that treatment with an activin antagonist, a soluble form of extra cellular domain of the murine activin type II receptor fused to a murine IgG-Fc fragment (RAP-011), reverses bone loss in ovariectomized (OVX) mice.(1) The goal of this study was to compare skeletal effects of RAP-011 to known anabolic [PTH(1–34)] and antiresorptive (zoledronate, ZOL) treatments. Materials and methods: Eight weeks old female C57BL/6 mices were OVX (n=38) or SHAM-OVX (n=10) and allowed to lose bone for 8 weeks prior to initiation of treatment. OVX

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mices were randomized (stratified by body weight) to receive RAP-011 (10 mg/kg, I.P. 2x/week), PTH(1–34) (80 μg/kg, s. c., 5x/week), ZOL (single i.p. injection, 20 μg/kg) or vehicle (VEH, i.p., 2x/week), and treated for 6 weeks. Results: In vivo total body BMD measurements by PIXImus were unchanged in VEH (0.0±0.8%) and SHAM (1.2±0.6%), but increased significantly in PTH (10.6± 1.9%), RAP-011 (7.6±0.9%), and ZOL (6.4±1.3%) versus baseline. The increase in the PTH group was greater than in the ZOL group (p=0.03), however the difference between PTH and RAP-011 was not significant. Ex vivo μCT analysis of trabecular bone in the distal femur showed that compared to OVX-VEH, bone volume fraction (BV/TV, %) was increased in RAP-011 (+180%, p<0.001) and ZOL (+60.5%, p<0.005), but not PTH. Trabecular BV/TV in RAP-011 was greater than SHAM (10.3±0.9% vs. 5.5± 0.3%, p<0.001). At the femoral midshaft, cortical thickness was increased significantly compared to VEH in PTH (+14.5%, p<0.001), RAP-011 (+6.4%, p=0.001) and ZOL (+3.8%, p=0.04) treated mice. Cortical thickness was significantly higher in PTH than RAP011 and ZOL groups. Conclusions: These data confirm our previous observation that treatment with an activin antagonist (RAP-011) increases trabecular and cortical bone in adult OVX mice. The pattern of skeletal response to RAP-011 differed from PTH and from ZOL, suggesting that activin inhibition represents a novel mechanism for restoration of bone mass following estrogen deficiency. (1) Pearsall et al. ASBMR 2006.

P393. Radial and calcaneal quantitative ultrasound: a correlation study with Dual-Energy X-ray absorptiometry of the lumbar spine and proximal femur M. Boyanov1, A. Shinkov2, R. Nestorova3; 1Endocrinology Clinic, Alexandrovska Hopsital, Sofia, Bulgaria, 2Thyroid and Bone Metabolic Clinic, Endocrinology Hospital, Sofia, Bulgaria, 325th Policlinic, Sofia, Bulgaria Objectives: The quantitative ultrasound (QUS) has been successfully used in the osteoporotic fracture risk prediction for longer than a decade. The “gold standard” in the diagnosis of osteoporosis is however the Dual-Energy Xray Absorptiometry (DXA). Aim of this study was to perform QUS at the calcaneus and the distal radius, as well as DXA of the lumbar spine and proximal femur in female patients and to compare both QUS techniques with DXA. Materials and methods: Two hundred thirty postmenopausal Bulgarian women aged 42 through 80 years took part in this study. Calcaneal QUS was performed on a Hologic Sahara device and radial QUS—on a Sunlight Omnisense device. At the calcaneus the combined index Quantitative Ultrasound Index (QUI) was used and at the

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radius—the speed of sound (SOS). DXA was performed on a Hologic QDR 4500. A bone densitometer and bone mineral density (BMD) was measured. Results: The best precision was observed at the radial site (precision error 0.59%), followed by the total hip (0.95%). The lowest mean T-scores were found at the lumbar spine (−1.94), followed by the calcaneus (−1.85) und radius (−1.74). The correlation coefficients between calcaneal QUI and BMD of the lumbar spine and proximal femur were 0.285 and 0.442 (p=0.059, resp. 0.001); the respective values for radial SOS were 0.201 und 0.061 (p=0.019, resp. 0.513, n.s.). T-scores of −1.0 for the Sahara device and of −0.5 for the Sunlight device could identify women without spinal osteoporosis with 90% probability. Conclusions: Women with normal bone density of the proximal femur could better be identified with transversal QUS at the calcaneus. When lumbar spine is considered both QUS techniques (transversal and axial) are well suited. P394. Rationale and development of an individual patient–based model to precisely assess the efficacy of osteoporosis management M. Hiligsmann, F. Richy, J.Y. Reginster; Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium Objectives: Health economic evaluations are a very useful tool to evaluate the efficiency of osteoporosis management. Interest and reliability of these evaluations depend on both the methodological aspects of the model by itself and on the quality of the data feeding the model. Most of the existing evaluations are cohort-based Markov models lacking comprehensive memory management and versatility. In the light of these limitations and the need for accurate evaluations, the objective of this research was to develop an individual patient-based model reflecting the complexity and heterogeneity of osteoporosis. We also wish to determine theoretical and empirical evidence, data sources and methodology for this approach. Materials and methods: This research was based on theoretical and empirical literature. An evidence-based approach was applied throughout the conception and validation processes. In particular, we needed to argue and to evaluate the consequences of fracture interactions on the different components of the Markov model, including fracture risk, costs and quality of life. A registered copy of Treeage pro was used to build the model. Results: The major advantage of an individual patientbased model is that the full patient history is recorded by the use of tracker variables. According to the majority of the existing literature, the impact of prior fracture increases with the number of them; therefore, we considered that a second and following fracture had a similar but cumulative

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impact compared to the first one on the future risk and on the quality of life; the cost of fracture depends on the number of fractures, these hypotheses are coherent with the existing literature. Individual patient-based model are moreover able to account for the intra- and interindividual variability to reflect inter and intra-personal heterogeneity and give an estimate of the variance of the results. In addition to these advantages due to the modelling technique, our model is able to discriminate between first year and subsequent year effects of a fracture on future risks, costs and quality of life and it takes into account the characteristics of the selected population and all the specificity of treatments such as compliance, off-set and on-set time of action and adverse effects. Conclusion: This research illustrated the rationale to use a patient-based model to accurately evaluate the strategies against osteoporosis. This approach presents some major advantages over cohort-based model, increasing the reliability of the results and being largely compatible with the existing state of the art, evidence-based literature. P395. Oral ibandronate preserves trabecular microarchitecture: micro–computed tomography findings from the bone study P.D. Delmas1, D. Masanauskaite2, D. Ethgen3, R.R. Recker4; 1Claude Bernard University and INSERM Research Unit 403, Lyon, France, 2F. Hoffmann-La Roche Ltd, Basel, Switzerland, 3GlaxoSmithKline, Collegeville, Philadelphia, USA, 4 Osteoporosis Research Center, Creighton University, Omaha, USA Objectives: In BONE, daily and intermittent oral ibandronate increased lumbar spine and proximal femur BMD, reduced bone turnover (urinary CTX) and reduced vertebral fracture incidence (3-year fracture risk reduction: 62%).(1) However, bone strength also depends on the quality of bone microarchitecture. Micro-computed tomography (microCT) provides a quantitative three-dimensional (3D) method to assess trabecular architecture. Materials and methods: In BONE, postmenopausal women with osteoporosis were randomised to daily oral ibandronate (2.5 mg), intermittent oral ibandronate (20 mg every other day for 12 days every 3 months) or placebo. All participants received daily calcium and vitamin D supplements. Of 110 single transiliac bone biopsies obtained after 22 or 34 months of treatment(2), 84 evaluable samples were analysed using micro-CT (28 from the placebo arm and 56 from the pooled ibandronate arms). Analysis was performed in one laboratory (Creighton University, Omaha, Nebraska) using a Scanco μCT 40 scanner (Scanco Medical, Bassersdorf, Switzerland). Deterioration in trabecular structure due to osteoporosis is characterised by a change from plate to rod elements. The structural model

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index (SMI) using 3D view quantifies the bone structure in terms of rods and plates using differential analysis of the triangulated bone surface. Results: Micro-CT analysis demonstrated that SMI was significantly lower with ibandronate vs placebo (median: 1.001 vs 1.365, respectively; 90% CI: −0.626, −0.033), indicating that trabecular bone in the ibandronate-treated group contained more plate elements. In addition, connectivity density was significantly greater with ibandronate vs placebo (median [/mm3]: 3.904 vs 3.112, respectively; 90% CI: 0.159, 1.517). Micro-CT analysis of structural elements associated with bone strength showed greater preservation of trabecular bone after ibandronate treatment compared with placebo. This is consistent with the quantitative histomorphometric analysis conclusions.(2) Further, it supports the results obtained for BMD, bone turnover(1) and hip structural analysis(3) in the BONE study. Conclusions: The reduction in fracture incidence following ibandronate therapy(1) is accompanied with an overall increase in bone strength. (1) Chesnut CH, et al (2004) J Bone Miner Res 19:1241–9 (2) Recker RR, et al (2004) Osteoporos Int 15:231–7 (3) Fuerst T, et al (2006) J Bone Miner Res 21(Suppl. 1): S287 (Abstract SU323)

P396. Diabetis mellitus (DM) and hyperparathyroidism are other unusual risk factors associated to osteoporosis in Afro-Brazilian patients J.F. Marques-Neto1, S. Appenzeller2, A.M. Samara2; 1State University (Unicamp) and Vera Cruz General Hospital, Campinas, São Paulo, Brazil, 2State University, Campinas, São Paulo, Brazil Objectives: As in afro-descendents osteoporosis can be unexpected condition, the authors analyze the risk factors, clinical and laboratory features in 70 non-caucasoid (AfroBrazilian) osteoporotic patients. Materials and methods: The files of 70 Afro-Brazilian patients, assisted in the Osteoporosis Unit at the Rheumatology Division of the State University of Campinas, and in the IPECC-Osteoporosis Clinic, both in Campinas, Brazil were reviewed. Mean body index mass, age, age at menarche and menopause, drugs, associated diseases, habits as smoking and drinking, and abnormalities in calcium balance were studied. Evaluation of bone mineral density (DMO) were performed at lumbar spine and femoral neck (DXA—Lunar equipment). Results: Mean age of the affected patientes=64.6 years (DP=2.3); body index mass=54.8 kg (DP=1.3); DXA values: at lumbar spine (L1–L4) = −2.9 (DP±0.36) at femoral neck=−2.4 (DP±0.31). Vertebral fractures were present in 30 patients (42.8%). They were related to DM (RR=5), hyperparathyroidism (RR=6), osteoporosis family

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history (RR=2.1) and to co-morbidities such as systemic sclerosis (1 patient), disseminated psoriasis (2 patients), Crohn Disease (1 patient) and hypergamaglobulinopathy E (1 patient). Conclusions: Although osteoporosis could be a rare disorder in non-caucasoid patients, in this sample of Afro-Brazilian population it showed to be related to other risk factors besides hypoestrogenic conditions, inflammatory diseases and glicocorticoid therapy. Diabetis melitus and hyperparathyroidism were also related as important risk factors. P397. Impact of systemic sclerosis spectrum on bone mineral density in 148 Brazilian women J.F. Marques-Neto, P.D.S. Barros, A.M. Samara; Rheumatology Unit, Medicine Department, State University, Campinas, São Paulo, Brazil Objectives: Systemic Sclerosis is a severe inflammatory chronic conective tissue disease, with cutaneous-visceral involvement, impairment of disgestive, pulmonar, cardiac and renal functions. The authors study the impact of the disease on bone mineral density, in order to point the disease as a important risk factor for osteoporosis. Materials and methods: In a prospective study 148 female patients with 18 years and more, affected by Systemic Sclerosis were evaluated through a rigid clinical protocol and submitted to bone mineral density evaluation (DXA Lunar equipment) at lumbar spine and femoral neck. These results were compared to Systemic Sclerosis variables as age, race, body index mass, clinical subtypes (lSSc and dSSc), severity of the disease, age of menopause and previous treatment (cyclophosphamide or d-penicillamine). Results: Values of DMO were normal in 68 patients, osteopenia in 52 and established osteoporosis with vertebral fractures in the other 28 patients. There were no statistical correlation between DMO results and clinical subtypes of the disease and severity of cutaneous involvement. The same to age, race, disease duration, and previous treatment with cyclophosphamide or d-penicillamine. At lumbar spine (L1–L4) reduced T-score showed a positive correlation (p = 0.001) with body index mass, time/age of menopause (mainly over 10 years), physical incapacity and pulmonar hypertension. The same with femoral neck Tscore values (p=0.001). Conclusions: It was expected that a very severe disease as Systemic Sclerosis, with extense cutaneous-visceral involvement shoul be impactant on bone mineral density. It seems no to be that. Even the involvement of digestive tract did not correlate with osteopenia or osteoporosis. Only general and usual risk factors such as body mass index, age of menopause and imparment of pulmonar function were associated with bone loss. The authors wonder if the massive overproduction of collagen in all tissues coul not

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be involved in some kind of unknown protection against bone loss in Systemc Sclerosis. P398. The assessment of a group of patients with hip and knee osteoarthritis from Felix Spa Romania using WOMAC index D. M. Farcas1, M. Cevei1, L. O. Burta1, S. Mihalcea2, A. M. Tiurbe3; 1Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania, 2Rehabilitation Clinic Felix Spa, Baile Felix, Romania, 3University of Medicine and Pharmacy, Cluj-Napoca, Romania Objectives: To assess the responsiveness of the WOMAC Index in patients with osteoarthritis of the hip and knee undergoing rehabilitation treatment in Felix Spa, Romania. Materials and methods: Two hundred sixty-four patients with hip (142 patients) and knee (122 patients) osteoarthritis underwent inpatient rehabilitation treatment for 18 days including: hydrotherapy, hydrokinetotherapy, electrotherapy, kinetotherapy, thermotherapy and massage. The patients fulfilled the ACR criteria for lower limbs osteoarthritis. They were assessed with WOMAC questionnaire at baseline, discharge, at 6, 12, 24 months. Effects were analysed with sensitivity statistics (effect size, ES). Results: In our group of study both pain and physical function improved moderately (WOMAC pain ES=0.52 for hip OA group and ES=0.56 for knee OA group, WOMAC function=0.37 for hip OA group and 0.38 for knee OA group) until discharge. The effect in pain reduction remained moderate at 6 months (ES=0.48 for hip OA and ES=0.50 for knee OA), at 12 months (ES=0.32 for both hip and knee group), at 24 months (ES=0.22 for both groups), but the physical function at 6 months (ES=0.26 for hip group and ES=0.28 for knee group) and deteriorated close to baseline values at 12 months in both groups. Conclusion: Our study showed the benefical effect of the rehabilitation treatment for patients with hip and knee osteoarthritis. It seems that pain improves for a longer period than physical function. However, even a slower deterioration in physical function represents a gain for such desabilitating diseases. P399. The efficacy and safety of oral phenyramidol in spinal painful muscle spasms–an open study H. Koyuncu, M.G. Erdem, S. Eşen; Cerrahpasa Medical Faculty, Physical Medicine and Rehabilitation Department, Istanbul University, Istanbul, Turkey Muscle spasm is seen in spinal disorders. It increases pain and the pain may create severe spasm. Muscle relaxants are often used and effective in mucle spasms with other drugs or alone. Phenyramidol (PP) are non-sedative drug. In this study, 31 patients were evaluated between 24–60 years. Oral

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phenyramidol 800 mg/day for twice a day was given for 30 days. Pain (VISUAL ANALOG SCALA=VAS), muscle spasm (Standard) and function limitation (Standard) in patients were evaluated. The side effects were reported for clinical safety. The evaluation was made at baseline and after the treatment. Pain reduction, spasm and function improvement were significant. Severe advers events were not seen in patients. All patients finished the study. The efficacy was good in all patients. The drug was well tolerated. In conclusion, oral phenyramidol was effective and safe for 30 days. It can be used alone without other drugs. P400. Preferences of patients receiving bisphosphonates—how to influence the therapeutic adherence J. Payer1, P. Celec2, I. Sulkova3, Z. Killinger1; 1Faculty Hospital Bratislava, 5th Internal Department, Comenius University, Bratislava, Slovakia, 2Institute of Pathophysiology, Comenius University, Bratislava, Slovakia, 3GlaxoSmithKline, Bratislava, Slovakia Objectives: Therapeutic adherence is a key factor of treatment success in clinical praxis, although it is often neglected. Several studies have shown that insufficient persistence and compliance cause differences in the efficiency of treatments in clinical studies and clinical praxis. The treatment of osteoporosis using bisphosphonates is considerably influenced by the low adherence of patients due to the complicated drug application. The primary aim of this study was to determine the preference rate of monthly treatment regimen between postmenopausal osteoporosis patients. Materials and methods: This was a questionnaire survey using simple questionnaires with three questions completed by the patient either naive to bisphopshopnates, on treatment or withdrawn from bisphosphonates treatment. Results: The preferences of 1,635 patients with osteoporosis in Slovakia were analyzed. The majority of patients— 76% preferred monthly regimen of bisphosphonate therapy, 22% of patients preferred weekly regimen and only a minority—2% preferred daily application. The preferences of patients were motivated by various different aspects of improved quality of life, which is offered by new bisphosphonate regimen once monthly. Conclusions: These results are in agreement with the results of the BALTO I & II studies and the SWIFT study in Switzerland, but were obtained in considerably higher number of patients. The study suggests that women with osteoporosis would prefer monthly treatment and the reasons for this preference further suggest that monthly regimen could improve patients compliance and persistence on treatment.

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P401. The effects of strontium ranelate on pain, fracture and mineral density in postmenopausal women with osteoporosis H. Koyuncu, M.G. Erdem, Selma Eşen Cerrahpasa Medical Faculty, Physical Medicine and Rehabilitation Department, Istanbul University, Istanbul, Turkey Minerals and trace elements affect bone formation and resorption through direct or indirect effets on bone cells or bone mineral. Strontium has several effects on bone cells and anabolic actvity. The effects of strontium ranelate on pain, bone mineral density and antifracture efficacy were assessed in on open, noncontrolled trial conducted in postmenopausal women. Oral strontium ranelate was given at a daily dose 2 g for six months in 31 patients. All women received calcium and vitamin D supplements. Pain (visual analog scala) score was 6.12±1.05 at baseline and 4.25± 0.92 sixth month. Vertebral and appendicular radiographs were obtained before treatment and at sixth month and fractures were totally mean 1.87±1.54 at baseline and 1.87± 1.54 at sixth month. Measuremants of bone mineral density were performed every six months. Pain decreased at sixth month sıgnıficantly (p<0.05). New fractures no occured during the study. Strontium renalate increased bone mineral density at month 6 at the lumbar spine and at the femoral total. The changes were significant (p<0.05). There were no serious adverse events. The patients didn’t leave the study for side effects. The blood chemistry was normal at baseline and end of trial. Global efficacy was good 64.5% at sixth month. Tolerability was excellent during the study (80.6%). Treatment of postmenopausal osteoporosis with strontium ranelate can decrease the pain, and can prevent new fracture and can increase bone mineral density. The study must be done in more wide population. P402. Efficacy of physical therapy upon pain and disability in knee osteoarthritis M. Mihailov, D. Popa; Faculty of Medicine and Pharmacy, University of Oradea, Medical Rehabilitation Hospital, Felix Spa, Romania Objectives: Osteoarthritis is the most common chronic medical condition, one of the leading causes of disability and pain in elderly population. Physical therapy plays an important part in the complete management of osteoarthritis of the knee (OA); it may diminish symptoms and improve the course of knee OA by increasing local circulation to the affected joints, improving the tone of supportive musculature, enhancing joint flexibility, and relieving pain. Research into the efficacy of physical therapy is growing steadily and it is essential in the present cost conscious health market.

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Materials and methods: This is a randomized controlled observational study to examine the efficacy of three weeks physical therapy on symptoms of knee OA in older patients. In this trial, 70 adults with radiographically confirmed OA of the knee (stadium I–III Kellgren Lawrence) were randomized either to physical treatment group (n=35) which has included: pain medications, physical therapy, massage, thermotherapy or control group (n=35) which has included electrotherapy, both for a session of three weeks. The main endpoints were changes in the Western Ontario and Mc Master Universities Osteoarthritis Index (WOMAC) pain, stiffness and functional scores. Assessments were made at baseline and after 3 weeks. Results: The physical therapy group had significant improvements in mean WOMAC domains, and no significant change was seen in the control group, as we present in the next table. Table. WOMAC Evolution Variables

WOMAC stiffness

WOMAC physical function

WOMAC pain

Groups

Control group Physical therapy group Control group Physical therapy group Control group Physical therapy group

Initial

Final

Statistic signification

Average SD

Average SD

5.23

0.27 5.5

0.26 P<0.7

5.51

0.27 5.04

2.7

38.87

1.85 39.7

1.83 P<0.05

41.09

1.85 35.3

1.83

10.75

0.54 10.77

0.54 P<0.05

12.4

0.54 10.71

0.53

(BP) of 1–5 mmHg have been shown to be associated with 7100–35 700 additional ischaemic heart disease and stroke events in a year-long US study of osteoarthritis (OA) pts (Singh et al. J Rheumatol 2003;30:4). NSAIDs and COX-2 inhibitors have been shown to increase BP, therefore chronic treatment of arthritis pts requires careful drug selection to minimize the impact on BP. In TARGET, lumiracoxib at a chronic dose of 400 mg od (4x the recommended dose in OA) has a superior BP profile to the comparator NSAIDs, ibuprofen 800 mg tid and naproxen 500 mg bid. We conducted a meta-analysis of placebocontrolled trials to investigate whether lumiracoxib increased BP compared to placebo-treated pts. Methods: Office-visit, seated BP measurement data were available from 9719 pts in 12 placebo-controlled trials of up to 3 months’ (m) duration. Change from baseline in diastolic and systolic BP was examined for 6 dose regimens of lumiracoxib (50 mg bid, 100 mg od, 100 mg bid, 200 mg od, 200 mg bid and 400 mg od). Meta-analyses were conducted using individual data from 9611 pts providing BP measurements at baseline and at least one post-baseline evaluation. The effects relative to placebo were evaluated at 1 and 3m and averaged across 3m. Total daily doses of lumiracoxib were used to investigate a dose–response relationship. The effects of baseline variables and prognostic factors on the relative effect of lumiracoxib were also studied. Results: Change from baseline for systolic and diastolic BP of lumiracoxib relative to placebo, derived from a model combining dose regimens (total daily dose) is shown in the table below. m1

Conclusions: This study suggests that physical therapy is efficacious in the treatment of OA of the knee, with beneficial effects persisting for weeks following treatment cessation. It seems to be well tolerated by patients, decreasing pain and improving function in participants who were allowed to maintain their usual treatment. P403. Lumiracoxib has a similar blood pressure profile to placebo in arthritis patients A. Whitehead1, M. Simmonds1, B. Mellein2, T. Friede2, X. Gitton2, P. Sallstig2; 1MPS Research Unit, University of Reading, Reading, UK; 2Novartis Pharma AG, Basel, Switzerland Objective: Hypertension is a leading comorbidity in elderly arthritis patients (pts). Increases in systolic blood pressure

Lumiracoxib dose [mg/day]

m3

Change relative to placebo [mmHg]

95% CI

p

Change 95% relative CI to placebo [mmHg]

Systolic BP 100

0.21

0.66 0.94

200

0.16

400

0.37

-0.75, 1.17 -0.68, 1.10 -0.48, 1.23

0.71 -0.32 0.39 0.16

-0.32, 2.20 -1.42, 0.79 -0.98, 1.31

p

0.14 0.57 0.78

Diastolic BP

None of the lumiracoxib regimens were significantly different from placebo in terms of change from baseline for systolic or diastolic BP after 1 or 3 m. Also, no dose–response was observed. Adjustment for prognostic risk factors (age, baseline systolic BP, history of hypertension or prior use of

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antihypertensive treatments) had no statistically significant effect on the results. Conclusions: This BP meta-analysis of data from 9611 patients with arthritis demonstrated that lumiracoxib (100– 400 mg od) had a BP profile (both systolic and diastolic) comparable to patients receiving placebo.

Conclusions: In this study, adverse renal effects were observed with i.v. zoledronate, with evidence of injection site lesions and tail necrosis dependent on the dose, rate and administration frequency. Single and repeated administration of high dose i.v. ibandronate (1mg/kg) resulted in mild, subclinical renal changes with no adverse physical signs observed.

P404. Evidence for diffrent local and renal tolerability of I.V. bisphosphonates T. Pfister1, E. Atzpodien1, F. Bauss2; 1Preclinical Research and Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 2Roche Diagnostics GmbH, Pharma Research Penzberg, Penzberg, Germany

(1) Pfister T, et al. Toxicology 2003;191:159-67.

Objectives: Intermittent administration of minimally nephrotoxic doses (MND) of intravenous (i.v.) zoledronate, but not i.v. ibandronate, can cause renal damage accumulation in Wistar rats(1). Here, the impact of these doses, dosing frequency and administration rates of i.v. zoledronate and i.v. ibandronate on nephrotoxicity and local tolerance is reported. Materials and methods: Groups of six female rats received intermittent i.v. zoledronate (1mg/kg or 3mg/kg [MND] 3-weekly) by bolus injection or 30-minute infusion, intermittent i.v. ibandronate (1mg/kg [MND] 3-weekly) by bolus injection or 30-minute infusion or placebo for 25 weeks. Concurrent groups of rats remained untreated until week 25, when they received a single i.v. bolus injection (1mg/kg or 3mg/kg zoledronate or 1mg/kg ibandronate). Results: No deaths occurred. I.v. zoledronate and i.v. ibandronate induced renal changes, including proximal tubule degeneration/necrosis. For zoledronate (3mg/kg), however, there was evidence of slight-to-marked (Grade 2–4) degeneration/necrosis of the proximal tubules in all animals, which were generally more severe when zoledronate was administered repeatedly or by i.v. bolus injection than as a single dose or by i.v. infusion, and when given at 1mg/kg. For i.v. ibandronate (1mg/kg) changes were minimal (Grade 1) regardless of the administration frequency or rate. Adverse physical signs were restricted to injection site lesions and were only seen with zoledronate (both infusion doses and 3mg/kg injections). In four animals receiving i.v. zoledronate, these lesions progressively deteriorated, even after cessation of zoledronate administration, resulting in tail degeneration (2 in the 3mg/kg zoledronate infusion group and 1 each in the zoledronate 1mg/kg infusion and 3mg/kg bolus injection groups). The lesions had marked chronic inflammation associated with bone remodelling in the adjacent tail vertebrae. No lesions were observed with repeated 1mg/kg injections or single bolus injection (1mg/kg or 3mg/kg) of zoledronate or with any ibandronate regimen.

P405. Management of osteoarticular conditions: The role of piroxicam revisited F. Richy1, C. Scarpignato2, A. Lanas3, G. Singh4; 1 Public Health, Epidemiology and Health Economics Unit, University of Liege, Faculty of Medicine, Belgium; 2 Pharmacology & Therapeutics, University of Parma, Italy; 3 Faculty of Medicine, University of Zaragoza, Spain; 4 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, California, USA Background: The relative efficacy/safety profiles of various NSAIDs, particularly Piroxicam (PIR), have been repeatedly challenged for decades. Meta-analyses of casecontrol studies show a more deleterious GI and skin profile of certain NSAIDs while no such comparison is available from meta-analyses of –available- randomized controlled trials, evidence that study design impacts the reported effect-sizes. We planned and realized these meta-analyses to bridge the gap in the understanding of the relative efficacy/ safety profile of PIR using level 1 evidence. Methods: We performed comprehensive systematic research of any comparative randomised controlled trial, peer review, data extraction, quality scoring, and outcome-specific metaanalyses of the relevant data. Inclusion criteria were: clinical trial, osteoarticular condition, PIR, active comparator, oral administration, duration over 7 days, publication year 19802006, English language. Conservative analyses were stratified by outcome, indication, duration, and doses. Publication bias and robustness were exhaustively investigated. Results: 75 comparative trials were ultimately included for analyses. The comparators were Naproxen, Tenoxicam, Indomethacin, Etodolac, Diclofenac, Meloxicam, Ibuprofen, Salicylates derivates, Nabumetone, Aceclofenac, Droxicam, Flurbiprofen, Ketoprofen, Nimesulide, and Diflunisal. Regarding global efficacy, PIR was more effective than Naproxen OR=1.37 [1.05; 1.77] and Nabumetone OR=1.72 [1.26; 2.34], while equivalent to other NSAIDS OR=1.06 [0.96; 1.18]. For Pain and articular swelling, PIR was statistically equivalent to all other NSAIDs OR=0.99 [0.80; 1.23] and OR=0.81 [0.48; 1.37], respectively. For mobility, PIR appeared to be more effective than Indomethacin, while

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equivalent to all other comparators OR=1.05 [0.80; 1.38]. Patients’ global assessments of efficacy were better for PIR over Naproxen OR=1.41 [1.02; 1.93], and equivalent to the other NSAIDs OR=1.12 [0.98; 1.28]. Physicians’ global assessments of efficacy were equivalent over any other NSAIDs OR=1.08 [0.88; 1.34]. Regarding global safety, PIR was globally safer than other NSAIDs OR=0.84 [0.73; 0.96], notably Indomethacin OR=0.53 [0.43; 0.64], Naproxen OR=0.75 [0.65; 0.85] and Salicylates OR=0.36 [0.17; 0.75]. For GI safety, it was better tolerated than Indomethacin OR=0.46 [0.36; 0.58], Naproxen OR=0.66 [0.53; 0.83] and Salicylates OR=0.45 [0.27; 0.78] while less tolerated when compared to Meloxicam OR=1.49 [1.05; 2.13]. Particularly, minor GI effects investigation underlined its better profile over Naproxen OR=0.66 [0.43; 0.998] and Indomethacin OR=0.51 [0.39; 0.66]. Major GI effects were comparable among PIR users as in comparator drugs users OR=1.33 [0.96; 1.84], except Meloxicam OR=2.37 [1.13; 4.97]. The skin safety of PIR was statistically comparable to those of comparators OR=1.01 [0.68; 1.51]. When focusing on efficacy/safety ratios, PIR was statistically comparable to any NSAIDs while superior to Naproxen, Salicylates derivates, and Nabumetone. Sensitivity analyses confirmed the robustness of these findings. Conclusion: Intrinsic and extrinsic findings support a similar to more favourable profile of Piroxicam as compared to other NSAIDs.

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P406. Autologous conditioned serum (ACS) compared to hyaluronan and saline-injections for the treatment of knee osteoarthritis: A prospective, randomized, placebo-controlled, double-blind, parallel-design trail. Therapeutic study, level 1 (randomized controlled trial-RCT, ISRCTN: 71311752) C. Moser1, Wehling2, A.W.A. Baltzer2; 1Department of Orthopaedics, Heinrich-Heine University Hospital Duesseldorf, Germany; 2Centre for Molecular Orthopaedics, Duesseldorf, Germany Objectives: A new therapy, based on the intra-articular injection of autologous conditioned serum (ACS), is used in several European countries for osteoarthritis (OA) treatment. ACS is generated by incubating venous blood with medical grade glass beads. Peripheral blood leukocytes produce elevated amounts of endogenous anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1Ra) and growth factors that are recovered in the serum(1). ACS has been shown to improve the clinical lameness in horses significantly to enhance the healing of muscle injuries in animal models, and in human athletes. In the present study, the efficacy and safety of ACS was compared to intra-articular hyaluronan (HA), and saline in patients with confirmed knee OA. Methods: In a prospective, randomized, patient- and observer-blind trial with three parallel groups, 376 patients with knee OA were included in an intention to treat (ITT-) analysis. Efficacy was assessed by patient-administered outcome instruments (WOMAC, VAS, SF-8, GPA) after 7, 13 and 26 weeks. The frequency and severity of adverse events were used as safety parameters. Results: In all treatment groups, intra-articular injections produced a significant reduction in WOMAC-scores and weight-bearing pain (VAS). However, responses to ACS were far stronger. The superiority of ACS and either HA or saline was statistically significant for all outcome measures and all time points. No significant differences between HA treatment and saline injections (p>0,05, at all time points and all outcome measures) were recorded. Frequency of adverse advents (AE) was comparable in the ACS- and the saline-group (p>0,05). Conclusion: The results demonstrate that ACS is effective and well tolerated in the management of chronic, idiopathic OA of the knee.So far, the efficacy of ACS is defined through improvement in clinical signs and symptoms, particularly pain. It remains to be determined whether they are disease-modifying, chondroprotective, or even chondroregenerative, sequelae. (1) Meijer H, Reinecke J, Becker C, Tholen G, Wehling P. The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflamm Res 2003;52(10):404-7.