IL001 EPIDEMIOLOGY OF OSTEOPOROSIS ~

MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, UK Osteoporotic fractures are among the most important causes of ill-health among elderly people. In western countries, the remaining lifetime risk of hip, clinically diagnosed vertebral, or wrist fracture among white women at the age of menopause lies at 39%, while the comparable estimate among men is 13%. These estimates are conservative, as they do not include fractures at many other skeletal sites which are also associated with reduced bone density. Epidemiological studies over the previous two decades have characterised the heterogeneous patterns of incidence by age, sex, race, geography, season and time, of these fractures. They have also characterised the distribution and changes of bone mass with advancing age in men and women, and the relationship between bone mass and the future risk of fracture. There are two general strategies which may be adopted to reduce fracture incidence: the high risk strategy and the population approach. Information on the risk factors for bone loss and fracture informs both these approaches. Recent studies of vertebral osteoporosis in Europe confirm the importance of low body mass index, physical inactivity, and oestrogen deficiency in women, as risk factors for vertebral deformity. In addition, cohort studies from the United States suggest that the risk of hip, wrist and other limb fractures is significantly increased among women who have sustained a clinically diagnosed vertebral deformity. Finally, novel risk factors for osteoporosis might enhance our understanding of the pathophysiology of the disorder. Recent investigations suggest that osteoporosis might have environmental origins during early life. Retrospective cohort studies in Britain and Sweden have shown that weight in infancy is a determinant of the bone mass of subjects during adulthood. These associations are independent of adult risk factors for osteoporosis. The mechanism underlying this link is believed to be the programming of a range of metabolic and endocrine systems which control skeletal growth. It is now important to progress beyond these epidemiological associations to characterise the impact of maternal environment on fetal skeletal development.

IL002 NON BONE MASS RELATED RISK FACTORS FOR HIP FRACTURE AND THERAPEUTIC IMPLICATIONS B. Allolio Med. Univ. Klinik WOrzburg, Department of Endocrinology, WOrzburg, Germany While low bone mass is a major determinant of bone fragility, it makes only a limited contribution to the exponential age-related increase in hip fracture incidence. In recent years large prospective studies have identified a number of additional risk factors for hip fracture independent of bone mineral density (BMD). These can be classified as skeletal factors and fallrelated factors. Decreased bone quality as assessed by ultrasound examination or a history of prior fractures is associated with increased hip fracture risk independent of BMD. Long-term exposure to fluoride leads to incorporation of the fluoride ion into bone crystals and can influence bone strength without affecting bone mass. Body height and hip axis length are positively correlated with fracture risk. Neuromuscular impairment with low gait speed, difficulty in doing a tandem walk, lower limb dysfunction or inability to rise from a chair without using one's arms predicts future fracture risk. In addition, decreased visual acuity, medications that diminish alertness, and cognitive impairment increase the risk of falls, and hence fractures. Genetic influences on hip fracture risk are well documented and may affect both skeletal (e.g. bone geometry) and fall-related factors. Similarly complex may be the association of hip fracture risk with changes in body weight. Large prospective studies aiming at the modification of risk factors to prevent hip fractures are still lacking. Moreover, important risk factors (e.g. genetic background) cannot be modified. However, identification of subjects with a high risk of future hip fracture may greatly improve the benefit/cost ratio for therapeutic interventions. Simple measures as external padding have been proved to be effective in reducing hip fractures. Moreover, pharmacological interventions (e.g. bisphosphonates, estrogens, calcium plus vitamin D) have been shown to reduce hip fracture incidence. Risk factor based patient selection will, therefore, improve the cost effectiveness of drug therapy.

IL003 NUTRITIONAL DETERMINANTS OF ACQUISITION AND LOSS OF BONE MINERAL MASS. R. Rizzoli P. Ammann Th. Chevalley S. Ferrari. M.-A. SchOrch D. Siosman. J.-P. Bonjour Division of Bone Diseases, WHO Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, 1211 Geneva 14, Switzerland. Bone mineral density (BMD is the best predictor of fracture risk. It is determined by the amount of bone accumulated at the end of skeletal growth, the so called peak bone mass, which is achieved for most parts of the skeleton by the end of the second decade, and by the amount of bone lost subsequently, as a consequence of menopause or aging. Various studies, including mother-daughter pairs analysis, estimate the contribution of genetics to the variance of peak bone mass as more than 70%. BMD appears to be genetically determined as early as before puberty with bone growth following a track throughout puberty. Nutritional interventions are able to modulate this genetic potential. For instance, calcium supplements in prepubertal girls not only increased the gain in BMD, but also led to an increment of outer bone dimensions. Similarly, through mechanisms likely to involve IGF-I secretion and action, protein intakes in children and adolescents are susceptible to influence BMD accumulation and bone growth. The response to nutritional interventions appears to be genetically influenced, since a higher BMD gain following calcium supplementation was mostly detectable in girls with specific vitamin D receptor gene alleles. Whereas sex hormone deficiency is recognized as playing a major role in bone loss occurring during the sixth decade, evidences are accumulating that undernutrition, particularly low protein intakes, are contributing to higher fracture risk in elderly. Indeed, through mechanisms probably involving low IGF-I secretion and action, protein deficiency contributes to accelerated bone loss and lowered muscle function, both implicated in fracture risk. By stimulating the endogenous production of IGF-I, protein supplements were able to attenuate bone loss following osteoporotic fracture of the proximal femur, to improve patient outcome and to hasten rehabilitation process.

IL004 MEASUREMENT OF BONE BY DXA: IS THERE ROOM FOR IMPROVEMENT? J.A. Kanis Centre for Metabolic Bone Diseases, Sheffield, UK Bone mineral density measurements form the cornerstone for the diagnosis of osteoporosis. In addition, the assessment of bone mineral density provides information on prognosis, namely the likelihood of fractures in the future. The risk of fracture increases approximately 2-fold for each standard deviation decrease in bone mineral density, but the gradient of risk varies according to the site and technique used. The accuracy of bone mineral density measurements to predict fracture is as good as blood pressure to predict stroke, and significantly better than serum cholesterol to predict myocardial infarction. There is no one site or technique that subserves all the possible uses of bone mineral density measurements. At the time of the menopause, assessment at the forearm predicts the risk of any osteoporotic fracture as well as that determined from other sites. In the elderly where hip fracture is of greatest concern, the hip is an advantageous site because of the high risk of hip fractures. The spine is not a suitable site for diagnosis in the elderly because of the high prevalence of arthrosis and arthritis, but is the preferred site for assessing response to treatment. All absorptiometric techniques have inherent accuracy errors which impair their diagnostiC accuracy. These vary from approximately 7% in the case of DXA at the axial skeleton to 2% for single energy absorptiometric techniques atthe appendicular skeleton. In addition, none ofthe techniques assess true volumetric density. The large errors in relation to the population variation (CV approximately 10%) suggest that small improvements in accuracy would have large dividends in diagnostic as well as prognostic use. The use of bone mineral density alone to assess risk has high specificity, but low sensitivity. The low sensitivity (approximately 50%) means that half of all osteoporotic fractures will occur in women said not to have osteoporosis. For this reason the test is most useful in the context of a case finding strategy than for population screening.

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IL005 CLINICAL USE OF BONE MARKERS Robert Lindsay Helen Hayes Hospital, West Haverstraw, New York, USA Bone markers are degradation products of bone resorption, enzymes involved in bone cell function, or proteins synthesized by osteoblasts. All have one feature in common. They can be detected and measured in serum or urine and used to estimate the rate of bone turnover. Over the past several years these tools have been used with considerable success in clinical (and basic) research on bone physiology and pharmacology. Increasingly they are now being used in clinical practice where three specific uses have been suggested. The most advance is the use of markers to determine if there is a response to pharmacological intervention for osteoporosis. In this setting a baseline measurement and a second determination 3-6 months after initiating treatment is the usual protocol. Thus, physicians and patients can have a more rapid determination of the efficacy of the treatment, before this could be measured by densitometry. In addition, such information it is argued may improve patient adherence to therapy. The second clinical utility for these tests is in predicting the response to treatment. It is argued that the higher the level the greater the response will be. This remains to be proven, and since in many countries the only therapeutic agents available are anti resorptive agents this does not seem to have great clinical utility at present. Finally biochemical markers may assist in predicting the risk of fracture. In observational studies markers can be shown to predict risk independently of bone mass. Protocols forthis use are currently in development. Clinical utility, however, will depend on improvements in variability that is both technical and biological in origin.

IL006 GLOBAL ASSESSMENT OF FRACTURE RISK. IMPLICATIONS FOR THERAPEUTIC DECISION. P.D. Delmas INSERM Research Unit 403 and Claude Bernard University of Lyon, France. A low bone mineral density (BMD) as assessed by dual energy X-ray absorptiometry (DXA) is by far the major determinant of fragility fractures, and the cutoffs for osteopenia and osteoporosis based on peak bone mass proposed by the WHO have been validated in women in large prospective epidemiological studies. Major risk factors for fractures that are - at least in part - independent from BMD include age, some major clinical risk factors (such as maternal history of hip fracture, prevalent fragility fractures, a low body weight), ultrasound evaluation of bone and increased bone turnover assessed by bone markers. It is important, therefore, to define how these parameters should be combined to improve the global assessment of fracture risk. We have addressed this issue using data from the EPlDOS study, a prospective study of the determinants of hip fracture performed in more than 7,500 healthy women >75 years of age followed for 3 to 4 years. The combination of clinical risk factors and/or bone markers with DXA improves the prediction of hip fracture obtained with hip DXA alone. In the absence of DXA, a combination of heel ultrasound and bone markers provides similar sensitivity and specificity. Data obtained with younger cohorts will be reviewed, and therapeutic will be discussed.

IL007 WHAT CAN WE LEARN FROM BONE BIOLOGY FOR THE TREATMENT OF OSTEOPOROSIS? G.R. Mundy University of Texas Health Science Center, San Antonio, Texas The current treatments for osteoporosis have mostly been identified by serendipity. None have been developed based on the classical drug discovery process of identifying a key molecular target, and then utilizing this molecular target for screening of small molecules in order to identify an orally available and acceptable agent with appropriate pharmacokinetic qualities. Agents such as bisphosphonates, estrogen and estrogen-related compounds, fluoride and parathyroid hormone all work through mechanisms which have not been clearly identified and which in many cases remain controversial many years after it was shown they have therapeutic efficacy in patients. The search for new and better agents should be based on a rational understanding of their mechanism of action. To this end, current techniques in bone cell biology should be aimed at clarifying potential molecular targets which could be useful to current drug discovery techniques such as high throughput screening of diverse random chemical libraries, utilized in conjunction with combinatorial chemistry. For this reason, studies on the molecular mechanism of action of bisphosphonates, estrogen and estrogen-related compounds, fluoride and parathyroid hormone could prove very fruitful. If such critical molecular targets could be identified, then these could be utilized for new drug discovery. Other approaches which will likely lead to identification of suitable molecular targets for screening include observations on animals in vivo in which specific genes are over or underexpressed. For example, osteoporosis represents the disease of the non-functioning osteoclast, and wherever the molecular mechanism responsible has been identified, then this could be utilized as a drug discovery target. Similarly, some knockout mice (for example, osteocalcin, 5-lipo-oxygenase and bone sialoprotein) are now recognized to show increases in bone formation. The gene products responsible for these in vivo effects are potential targets in the drug discovery process. Thus, bone biology can be very important for identification of better drugs for the treatment of osteoporosis, either by leading to better understanding of how the currently known and effective drugs work, or by identifying new molecular targets critical for either bone resorption or bone formation.

ILOOS NUTRITION IN THE TREATMENT OF OSTEOPOROSIS (CALCIUM, VITAMIN D, VITAMIN K) P.J. Meunier Department of Rheumatology and Bone Diseases- Edouard Herriot Hospital, Lyon, France Like hormonal deficiency and sedentary lifestyle, nutritional deficiencies are important determinants of bone loss and represent correctable risk factors of fragility fractures. This is true at any age but particularly in elderly people where adequate intakes of calcium (1 000-1500mg/day), vitamin D (400-800 IU/day) and vitamin Kare important for the preservation of bone mass. Calcium functions as a threshold nutrient. This means that below some critical value - about 600mg/day - bone mass will be limited by available calcium supplies, whereas above that threshold value, no further benefit will accrue from additional increases in intake. Several recent studies significantly extended the evidence that supplemental calcium reduces bone mineral density loss in adult women or prevent vertebral fractures. Vitamin D insufficiency is increasingly recognised to be a cause of secondary hyperparathyroidism, increased bone turnover and bone loss, not only in elderly people living in institutions but also in free-living old people or normal adults. In contrast to studies having used vitamin D alone, two recent studies having used combined supplementation of calcium and vitamin D have shown a significant reduction in the hip fracture and other non vertebral fracture rates in nursing home residents and free living old people, with parallel decrease in serum parathyroid hormone concentration and normalization of serum 25-0HD. The threshold value of serum 25OHD which activates the parathyroid response is very likely much higher than the classical one of 12ng/ml and could be in the order of 30ng/ml. Vitamin K deficiency has been found in elderly patients with hip fracture and on impaired gamma carboxylation of osteocalcin could be a marker of osteoporosis in elderly people .

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IL009 HORMONE REPLACEMENT THERAPY M. DOREN King's College, Department of Obstetrics & Gynecology, London, UK Bone fragility is an age-related phenomenon and common in women after menopause. Apart from prevention of falls or reduction of their immediate impact, both of which are difficult to achieve, a preventive medication to maintain quantity and quality of bone into old and very old age is very tempting. Estrogen replacement counteracts the acceleration of bone loss to occur after menopause in many women and slightly increases bone mass if administered as a long-term therapy. Daily doses of 2mg estradiol orally or 50~ transdermally or 0.625mg conjugated equine estrogens prevent bone loss in a majority of women. Estrogens are at least as effective as other inhibitors of bone resorption. The co-administration of progestins, necessary for endometrial protection, does not attenuate this effect. Epidemiological data suggest that estrogen replacement given for a minimum of five years in early postmenopause reduces subsequent hip, forearm, and vertebral fractures by at least 50%. However, the optimal duration oftreatment and timing of initiation are not well defined. Additional benefits unique to estrogen replacement compared to anti resorptive and bone forming agents include the treatment of vasomotor and urogenital symptoms, the reduction of cardiovascular risk, and possibly Alzheimer's dementia. Nevertheless, adherence to long-term therapy is difficult to achieve; a major reason of non-compliance is the occurrence of uterine bleedings. Therefore, only in a minority of postmenopausal women prevention of postmenopausal osteoporosis by hormonal replacement therapy is realized. The increased risks of having breast and endometrial cancer diagnosed in conjunction with long-term therapy demand an individual risk-benefit assessment including an evaluation of the applicability of hormonal and non-hormonal treatment alternatives particularly involving the individual woman's choices and perceptions of risks.

IL010 SEX STEROIDS ANALOGS Claus Christiansen Center for Clinical and Basic Research, Ballerup, Denmark The development oftamoxifen for breast cancer therapy has revolutionized the approach to treatment. In addition to breast cancer therapy with antiestrogens a new strategy is being developed to exploit the target site for the beneficial actions of estrogen, i.e. prevention of bone loss and cardiovascular disease. Today, three selective estrogen receptor modulators are evaluated as atreatment for osteoporosis, i.e. raloxifene, levomeloxifene and droloxifene. Raloxifene is the compound which is in the most advanced stage of development. Raloxifene acts as an estrogen receptor antagonist in breast and endometrial tissue, but as an estrogen agonist in the skeletal and cardiovascular systems. Clinical trials have demonstrated that raloxifene is well tolerated and normalizes bone turnover and slows the bone loss in healthy early postmenopausal women without stirnulating uterus and breast tissues. Furthermore, preliminary data suggests that raloxifene may decreaSe the risk of breast cancer. In elderly women with osteoporosis, the same effects were seen as in the younger women, In this study, which was a preliminary fracture study, the effect on fracture incidence was of borderline statistical significance. Raloxifene has been shown significantly to reduce aortic atherosclerosis and related risk factors in cholesterol-fed rabbits. Levomeloxifene, another SERM compound, has previously been shown to inhibit bone loss and arterial cholesterol accumulation in estrogen deplete animal models without stimulation of the endometrial glands and the epithelium. Different doses of levomeloxifene decreases bone turnover parameters and serum cholesterol and LDL -cholesterol in postmenopausal women. Droloxifene, athird SERM compound, has been shown to decrease bone turnover, prevent bone loss and reduce total serum cholesterol in ovariectomized rats without stimulating the endometrium. Generally, the SERM's are well tolerated. The most annoying side affect may be an increased number of hot flushes, which seems to disappear after a few months' treatment.

IL011 CALCITONIN, BONE ACTIVE ISOFLAVONES AND VITAMIN D METABOLITES ~

Institute of Internal Medicine, University of Siena, Italy Alternative options to hormonal replacement treatment of osteoporosis include other anti resorptive agents such as calcitonin, ipriflavone and vitamin D analogs. Calcitonin is a 32 amino acid peptide which acts by means of specific receptors on osteoclasts as a selective physiological anti-resorptive agent. It is given either as a parenteral injection or as nasal spray. The dose for nasal delivery rnust be twice the dose of parenteral injection. A number of clinical trials have demonstrated a favorable effect on bone mass in patients with osteoporosis. Calcitonin seems most effective for women more than 5 years postmenopausal and for patients with particularly high rates of bone turnover. In addition, there is some evidence for a beneficial effect on fracture rate. Calcitonin is also useful in patients with recent osteoporotic vertebral fractures because of its analgeSic properties. This agent has an excellent safety record, but can cause some side effects, such as flushing and nausea. Ipriflavone, 7-isoproproxy-isoflavone, is a derivative of naturally occurring isoflavones, that inhibits osteoclastmediated bone resorption. Despite its structural affinity with some natural phytoestrogens, ipriflavone does not exhibit estrogeniC activity. Clinical trials have demonstrated that ipriflavone may increase bone mass in osteoporotic patients and prevent bone loss in postmenopausal women. Some evidence has been given that ipriflavone may potentiate the effect of exogenous or endogenous oestrogens in bone. A specific study on the prevention of fractures is presently ongoing. Ipriflavone is well tolerated and safe after long-term administration. Adverse reactions are mainly affecting the gastrointestinal system. Active vitamin D-analogs, calcitriol (1,25-D3) and alphacalcidol (1 a-D3), improve both intestinal calcium absorption and bone mineralization, and suppress parathyroid hormone secretion. Several studies have shown that active D-analogs prevent bone loss and reduce fracture rates, even in the absence of positive increases in bone mineral density. The efficacy of active D-analogs therapy seems to be inversely related to the initial rate of calcium absorption. The response may be affected by vitamin D receptor genotypes. The remote possibility of Side-effects, such as hypercalciuria and/or hypercalcemia must be considered.

IL012 BISPHOSPHONATES Graham Russell Department of Human Metabolism and Clinical Biochemistry, Sheffield University Medical School, Sheffield S6 6GH, UK Bisphosphonates are now well established as successful anti-resorptive agents for the prevention and treatment of osteoporosis. In particular, etidronate and alendronate are approved therapies in many countries and both can increase bone mass and approximately half fracture rates at the spine, hip and other sites in post menopausal women. The use of BPs in osteoporOSis is relatively recent compared with the many years of experience in other diseases such as Paget's disease of bone, and bone metastases, for which pamidronate and clodronate have been used extenSively. Newer agents under active development include risedronate, ibandronate, and zoledronate. BPs are selectively concentrated in bone, where they are internalised by osteoclasts. Recent mechanistic studies show that BPs can be classified into at least two groups with different modes of action. Those that most closely resemble pyrophosphate, ego clodronate and probably etidronate, can be incorporated into toxic ATP analogues, whereas more potent nitrogen-containing BPs interfere with the mevalonate pathway, and inhibit protein prenylation, and therefore affect the intracellular trafficking of key regulatory proteins. The clinical pharmacology of BPs is characterised by low intestinal absorption, but highly selective localisation and retention in bone. Significant side effects are minimal, but gastrointestinal problems have been highlighted with alendronate in particular. Current issues with BPs include the choice of therapeutic regimen, eg the use of intermittent dosing rather than continuous, intravenous versus oral therapy, the optimal duration of therapy, the combination with other drugs, and extension of their use to steroid-associated osteoporosis, male osteoporosis, childhood osteopenic disorders etc. The ability of BPs to reduce the activation frequency of bone remodelling units, and possibly to enhance osteon mineralisation may also be related to the reduction in fractures. BPs represent an important class of drugs for the treatment of bone diseases, and their full potential has yet to be realised .

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IL013 WHAT IS THE ROLE OF BONE FORMING AGENTS? Jean-Yves Reginster Bone and Cartilage Metabolism Unit, University of Liege, Belgium Department of Epidemiology and Public Health, Liege, Belgium Georgetown University Medical Center, Washington DC, USA Current therapeutic approaches to postmenopausal bone loss or established osteoporosis have not unequivocally been demonstrated to fully prevent the appearance or the recurrence of axial or peripheral fractures. Inhibitors of bone resorption are mainly used to reduce the risk of new fractures through a stabilisation or a slight increase in bone mass. Therefore, many compounds have been developed with the promise of demonstrating the property of significantly increasing bone mass and restoring bone architecture to provide a radical cure of osteoporosis. Anabolic steroids were suggested to have effects on bone formation. These features were not systematically agreed upon. However, the risk/benefit ratio of these compounds should be considered, at least, problematic. Treatment with parathyroid peptide induces asignificant gain in bone mass, mainly in the axial skeleton. Long-term studies that compare peptide doses and regimens are needed to understand better the exact position of parathyroid peptides as treatment of osteoporosis. Prolonged administration of strontium to postmenopausal osteoporotic women resulted in a decoupling between bone resorption and formation that yielded a significant increase in the lumbar spine bone mineral density of treated subjects. Additional studies are requested to evaluate the potential benefit of growth hormone or insuline-like growth factors in the treatment of osteoporosis.

IL014 COST-EFFECTIVE TREATMENT STRATEGIES FOR OSTEOPOROSIS. L. Joseph Melton III Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Skepticism about the actual value of many treatments has led to the notion that clinical practice should be based on evidence that interventions improve patient's lives at some reasonable cost. However, there are many formidable barriers to implementing this "rational" approach to the management of osteoporOSis: 1) It is difficult to determine the optimal application of various treatments because of insufficient data on fracture risk among different subsets of the population; 2) little reliable information is available on the frequency of adverse outcomes of fractures, or their social or economic impact, which makes it difficult to calculate the social burden of osteoporosis that might be alleviated by treatment; 3) the efficacy of treatment is hard to discern because few randomized controlled trials have evaluated fracture outcomes and these have been of short duration and methodologically incomparable; 4) there is almost a total lack of data on compliance with treatment, on the frequency or significance of drug side effects or on the actual way that therapies are used and monitored in clinical practice so the cost-effectiveness of various treatment options is hard to estimate; and 5) finally, there is great controversy about the economic value that should be placed on preventing the adverse outcomes of osteoporosis and on the perspective (society at large versus the individual patient) that should be taken. Despite these serious limitations, efforts to model the cost-effectiveness of osteoporosis treatments are worthwhile because the data may be sufficient to justify some current practices. More importantly, critical gaps in knowledge are illuminated, particularly with respect to medical practice in the "real world." While such analyses can be abused by those wanting to limit clinician prerogatives, authoritative pronouncements are no longer sufficient to compete effectively for scarce health care resources.

IL015 OSTEOPOROSIS IN MEN Ego Seeman Austin & Repatriation Medical Centre, The University of Melbourne, Melbourne, Australia Osteoporosis in men is a public health problem. One third of hip fractures occur in men; mortality following hip fracture is higher in men than women, higher in blacks than whites, and related to the comorbidities, not fracture. The similar prevalence of vertebral deformities in men and women may reflect trauma in youth in men rather than bone fragility (crush fractures are less common in men). Men have wider (not taller) vertebrae than women so the sam.e volumetric bone mineral density (BMD) should confer a lower fracture risk. However, men and women with the same areal BMD appear to have the same fracture risk (despite the size difference). Vertebral (not femoral neck) size is reduced in men with spine fractures, femoral neck (not vertebral) size is reduced men with hip fractures. Reduced size may result from reduced growth or reduced age-related periosteal apposition. Delayed puberty may reduce long bone periosteal expansion, trunk growth and vertebral expansion. Reduced size accounts for -30% of the lower areal BMD. A deficit of the amount of bone in bone (volumetric BMD) may also be growth- or age-related; excessive endocortical relative to periosteal expansion, or failed pubertal endocortical contraction will reduced cortical thickness, trabeculae may fail to form, be resorbed excessively during development, or fail to thicken at puberty. Age-related reduced volumetric BMD may occur by reduced subperiosteal expansion, increased endocortical resorption, trabecular thinning and perforation, and increased intracortical porosity. Testosterone and growth hormone/lGF-1 deficiency may reduce periosteal expansion producing narrower bones and reduce bone formation during ageing in the basic multicellular unit (BMU). Estrogen deficiency may result in longer bones (delayed epiphyseal closure) and increase remodeling contributing to bone loss. The deficit in bone mass following aromatase inhibition is similar to the deficit produced by orchidectomy. Androgen receptor disorders (high circulating testosterone and estrogen) result in cortical, not trabecular bone deficits. Secondary hyperparathyroidism in old age may increase remodeling, endocortical resorption and intracortical porosity. Treatment options are testosterone if hypogonadism is present (undefined in the context of remodeling rate and BMU balance), calcium reduces endocortical resorption, bisphosphonates increase BMD by reducing the remodeling space, perhaps reducing the negative BMU balance and increasing true BMD. Eventually, inferences regarding efficacy and safety of drugs in men will have to be based on trials in men.

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ORD1 FACTORS ASSOCIATED WITH MORTALITY SUBSEQUENT TO HIP FRACTURES H.E. Meyer', A. Tverdal', J.A Falch', J.I. Pedersen 3 'National Health Screening Service, 'Aker Hospital, and 31nstitute for Nutrition Research, University of Oslo, Oslo, Norway There is a well-known excess mortality subsequent to hip fractures. We studied some factors which could influence on this mortality. 248 hip fracture patients and 248 age and sex matched controls who participated in a case-control study (1) were followed for a minimum of three years (mean 3.5 years) with respect to total mortality. So were also 82 hip fracture patients ineligible for the case-control study (28 patients excluded due to high energy trauma (defined as fall from higher than ground level or atraffic accident), and 54 patients who did not pass the standardised Geriatric Mental Status test (scoring less than 10 out of 15 pOints)). The data were analysed using Cox proportional hazards regression, and results were adjusted for age and sex. The cases had a 70% increased risk of dying compared to the controls during follow-up (RR=1.7, 95% CI1.2-2.4), while there was no increased risk in patients with hip fractures caused by high energy trauma (RR=0.9, 95% CI 0.4-2.3). In contrast, a fourfold increased risk of dying was found in hip fracture patients who did not pass the mental test (RR=4.2, 95% CI 2.8-6.4). Caseswho did pass the mental test, but at a low score (10 to 12 points), also had increased risk of dying (RR=2.4, 95% CI1.6-3.7), whereas cases with the highest score on the mental test did not have increased mortality compared to the controls (RR=1.1, 95% CI 0.7-1.9). Hip fracture patients reporting that they did not walk outdoors before the fracture also had a markedly increased risk of mortality compared to the controls (RR=3.5, 95% CI2.3-5.3), whereas there was no such increased mortality in patients regularly walking outdoors before the fracture (RR=0.86, 95% CI 0.5-1.4). Similarly, low hand grip strength in the cases was associated with increased risk of mortality, whereas high hand grip strength was not. In conclusion, this study confirms an excess mortality in hip fracture patients. However, this excess risk seems to be restricted to subgroups of patients. Hip fracture patients with high score on a mental test, high physical ability or fracture caused by high energy trauma did not have increased mortality compared to the control group. 1. Meyer HE et al. Risk factors for hip fracture in a high incidence area: a case-control study from Oslo, Norway. OsteoporoSiS Int 1995;5:239-46

ORD2 RISK OF MORTALITY FOLLOWING CLINICAL FRACTURES J.A. Cauley D.E. Thompson. K.C. Ensrud, J.S. Scott D. Black for the Fracture Intervention Trial Research Group Universities of Pittsburgh, Minnesota, California, and Merck and Co. It is widely recognized that hip fractures are associated with excess morbidity and mortality. The effect of other fractures on mortality is less well studied. We examined the impact of all clinical fractures on mortality using data from the Fracture Intervention Trial (FIT), a trial of alendronate vs. placebo which randomized 6459 women aged 55 to 81 years with low femoral neck bone mineral density (:>0.68 g/cm'). Follow-up time averaged 3.8 years. Person years at risk for the fracture-free period were computed from women without fracture and from women with afracture in the period prior to the fracture. Person years at risk for the fracture period were computed from women with a fracture. Relative risks were calculated using Time Dependent Proportional Hazards models adjusting for age, treatment group, and prevalent vertebral fracture at baseline. Results: There were 122 deaths and 907 symptomatic fractures among the 6459 women enrolled in the study. Of these 122 deaths, 23 occurred after a symptomatic fracture. The number of person years at risk (PYR) in the free period was 22,866 compared to 1796 in the post-fracture period. The crude rate of mortality in the post fracture period was 12.81 per 1000 PYR compared to 4.33 per 1000 PYR in the fracture free period. The effect of symptomatic fracture on mortality is provided in the table below. Fractu re Class (# of pts with Fx)

Unadjusted RR (95% CI)

Adjusted RR (95% CI)

Any Clinical (907) Non-spine (825) Spine (119) Forearm (216)

2.45 (1.55, 3.87) 1.70 (1.00, 2.89) 12.51 (6.71,23.33) 1.12 (0.35, 3.51)

2.15 (1.36, 6.68 (3.08, 8.64 (4.45, 1.00 (0.32,

3.42) 14.52) 16.74) 3.17)

Conclusion: Fractures are associated with asignificant increase in mortality that is not explained by age. The increased risk differs by site or fracture with the greatest risk observed for hip and spine fractures. There was no increase in mortality following a forearm fracture.

ORD3 INCREASED RISK OF FURTHER FRACTURES AFTER HOSPITALIZATION FOR VERTEBRAL FRACTURES - A POPULATION-BASED PROSPECTIVE STUDY O. Johnell A Oden F. Caulin Dept. of Orthopaedics, Malmo University Hospital, Malmo, Sweden. The major predictor for an osteoporotic fracture is a bone mineral measurement. However, several other risk factors have been discussed, among others a previous fracture. The purpose of this study was to evaluate the risk of having a further fracture after a hospitalized vertebral fracture. Material and Methods: Data on the various fractures were obtained from the Swedish patient register 1987-94 which includes all hospitalized individuals. Death and cause of death of all individuals were also recorded. The first vertebral fracture during 1987-94 was identified and fractures occurring after the first vertebral fractures were registered - pelvic fracture, fracture of the upper end of the humerus, wrist fracture, hip fracture and all fractures. A Poisson model was used to determine the absolute risk of having a hospitalized fracture after the vertebral fracture. The vertebral fractures were divided in low energy and high energy trauma according to the degree of trauma. A total of 28,536 individuals with a first vertebral fracture were found. Among these 17,173 individuals with low energy trauma, mean age 70 years for men and 77 years for women. The incidence after the hospitalized vertebral fracture; a new hip fracture at the age of 60 was for men 21.1/1,000 person years and in the general population 0.95. The corresponding figures for women are 19.1 and 1.46. If only low energy fractures Were included the figures for men were 26.2 and for women 22.7. Thus, more than aten-fold difference compared with what is expected. Similar findings were found for all fractures. The main increase of any fracture occurred during the first year after the vertebral fracture and thereafter a decrease is observed. For hip fractu.res this was less pronounced. Also those with high energy trauma had a higher incidence of fractures after the vertebral fracture compared with the general population. Conclusions: This very high incidence of new fractures after hospitalized vertebral fractures, especially the first years after the fracture, indicates that the hospitalized vertebral fracture itself could be used as an indication for an intervention and this group of patients must be considered in the treatment guidelines.

ORD4 LOCATION OF INCIDENT OSTEOPOROTIC FRACTURES IN RELATION TO PREVALENT FRACTURES ~', W. Gowin', A. Zadeh-Khorassani', A. Boshof', T.W. O'Neil', A.J. Silman', J. Reeve3, D. Felsenbergl and the EVOS-Study Group 'Osteoporosis Research Group, Dept. of Radiology, University Hospital B. Franklin, Free University of Berlin, Germany. 'ARC Epidemiology Research Unit. University of Manchester, UK'lnstitute of Public Health, University Forvie Site, Cambridge, UK The goal of this retrospective study was to analyse relationships of the location of osteoporotic prevalent fractures with the new locations of incident fractures. We examined 100 patients from EVOS with prevalent vertebral fractures which had in addition incident fractures during a period of max. 2 years. Radiographs in standardised technique were taken in a lateral view of the thoracic and lumbar spine. All radiographs were evaluated by two experienced radiologists. The evaluation consisted of a qualitative and a quantitative morphometric assessment. New fractures do not randomly occur. The location of the new incident fractures is closely related to the location of the pre-existing prevalent fractures. New fractures are mostly found at the neighbouring or next to neighbouring levels. We assume that the occurrence of incident fractures is close to the location of prevalent fractures due to biomechanical reasons. The prevalent fractures cause an instability of the spine resulting in changes of the stature. These changes lead to different load applications of the neighbouring vertebrae. The higher load impact may cause the fracturing of the vertebrae closely located to the prevalent fractured vertebrae. Our result has important implications for physiotherapeutic treatments .

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ORD5 RISK FACTORS FOR PERIMENOPAUSAL FRACTURES, A PROSPECTIVE POPULATION BASED STUDY J. Huopio H. Kroger R. Honkanen S. Saarikoski E. Alhava Department of Surgery, Kuopio University Hospital, Kuopio, Finland. Multiple risk factors for osteoporotic fractures have been identified. However, most studies have focused on the risk of hip fracture in elderly. Prospective population based studies of risk factors for fractures in perimenopausal women are few. The purpose of the present study was to find risk factors, beside BMD, in peri menopausal population. The study population (n=3068) was a random, stratified sample of all the women aged 47-56 years (n=14220) residing in Kuopio Province, Eastern Finland, in February 1989. All participants underwent bone densitometry (DXA, Lunar DPX) during 1990-91. Sequential questionnaires were used to collect data on risk factors and subsequent fractures. Fractures were validated by checking radiographs or radiological-reports from patient records. Each variable of interest was first tested in univariate analyses. Finally, all statistically significant variables were simultaneously included in the Cox's regression model to find out independent risk factors for fractures. Results are expressed as relative risk estimates (RR) with 95% CI. The mean follow-up time was 3.6 years (0.0-4.7). Of 3068 women 257 (8.4"10) sustained 295 fractures. Factors which were independently associated with fractures were low BMD (RR for each SD decrease in spinal BMD 1.5 [1.3-1.7] unadjusted and 1.4 [1.3-1.6] adjusted; respectively for femoral neck BMD 1.5 [1.3-1.6] unadjusted and 1.4 [1.2-1.6] adjusted), use of HRT (unadjusted 0.6 [0.5-0.9]. adjusted 0.7 [0.5-0.9]), history of previous fracture (unadjusted 1.9 [1.5-2.6]. adjusted 1.7 [1.3-2.2]) and three or more chronic illnesses (unadjusted 1.4 [1.0-2.0]. adjusted 1.4 [1.0-1.9]). Weight, height, age, menopausal status, use of tobacco, maternal hip fracture and alcohol, coffee or dairy calcium intake were not independently associated with fractures. We conclude that low bone density, previous fracture and three or more chronic illnesses are independent risk factors for peri menopausal fractures where as HRT protects from fractures. Other factors are difficult to find in perimenopausal population.

OR06 BRITISH & OTHER EUROPEAN HIP BONE DENSITY DIFFERS SUBSTANTIALLY FROM US NORMATIVE DATA: IMPLICATIONS FOR CLINICAL DENSITOMETRY G. Holt' , M. Lunt'. A. Bhalla', K-T. Khaw3, A. Woolf', and J. Reeve" 'Institute of Public Health, Cambridge; 'Royal National Hospital for Rheumatic Diseases, Bath; 3Clinical Gerontology, Addenbrooke's Hospital, Cambridge; 'City Hospital, Truro, UK We compared hip BMD measured in several British population samples recruited from population registers to the NHANES III reference data. Four centres (Bath, Cambridgeshire, Harrow, and Truro) recruited subjects aged 50-80+ as part of EPOS and Cambridge recruited additional subjects unstratified. Norfolk recruited subjects aged 65-75. In total, 1997 men and 4917 women partiCipated. All had bone mineral density (BMD) measured at the hip, using a Hologic QDR 1000 densitometer. BMD measurements were converted to T-scores using the NHANES male and female young normal reference data, and to Z-scores using the NHANES age specific mean values, with linear interpolation. The femoral neck (FN) and trochanter (TA) regions were analysed. Multiple regression was used to model Z-scores and T-scores, using age and centre as predictors. Logistic regression was used to estimate the age-adjusted prevalence of osteoporosis and osteopenia, as defined by the WHO guidelines, in each centre, and to test for differences between centres. Results: The BMD of the British subjects was significantly higher at both sites and in both sexes than age-matched NHANES contemporaries, with mean Z-scores in men of 0.17 and 0.24 at the FN and TR respectively, and 0.20 and 0.44 in women. In British women, the Z-score did not change with age, but the Z-score increased by approximately 0.01 per year at both sites in British men. Prevalence of osteoporosis, calculated from the FN data for women in their 7th decade, was 8% in British compared to 15% in US women. Some significant differences between the individual British populations were revealed, which were smaller than the UK-US differences and persisted after cross-calibration with the ESP. Conclusions: These UK-US BMD differences are equivalent to 10-25% differences in fracture risk. These data complemented the previous

demonstration (Lunt et al. Ost Int.1 997;7:175 -189) that different European communities vary considerably in their mean femur BMDs. If the US NHANES III data are to be used as a reference in Europe, Clinical Guidelines for densitometry should recognise that population norms, not only for fracture rates but also for hip BMD, are substantially different between Europeans and Americans. These differences will affect particularly the clinical indications for ordering BMD measurements, but may also influence the interpretation of measurements.

OR07 FOURIERTAANSFORM INFRARED IMAGING ANALYSIS OF HUMAN ILIAC CREST BIOPSY THIN SECTIONS REVEALS SIGNIFICANT DIFFERENCES IN BOTH THE BONE MINERAL AND COLLAGEN COMPONENTS BETWEEN NORMAL AND OSTEOPOROTIC PATIENTS E.P. Paschal is. A. Gericke R. Mendelsohn A L. Boskey Hospital for Special Surgery, New York, NY, USA; University of Halle, Halle, Germany Osteoporosis definitions are based on bone mass considerations. The purpose of the present study was to test the hypotheSiS that consistent and monotonic differences exist between normal and osteoporotic bone, in both the mineral and collagen components, as a function of both anatomical location and tissue age. Fourier transform infrared spectroscopy (FTlR) provides information (both quantitative and qualitative) on all tissue components: mineral, collagen, non-collagenous proteins, proteoglycans, and lipids. Fourier transform infrared imaging (FTlRI) allows the analysis of thin tissue sections (400x400 um'), thus providing information on all the components mentioned previously while retaining spatial resolution (7 j.lfTI). In the present study, FTlRI analysis of 5 j.lfTI thin sections from iliac crest biopsies of both normal (N=3) and osteoporotic (8 high-turnover and 8 low-turnover) patients was utilized to compare mineral and collagen quality, defined as mineral crystallinity/maturity, and amount and type of collagen cross-links, respectively. Areas were selected according to their anatomical location (proximity to: Haversian canals in osteonal bone, periosteal surface in the cortical, and edge in trabecular bone) and tissue age (based on tetraCYCline double-labelling). The spectra were processed in the region of 900-1200 cm· 1 (mineral phosphate) and 1595-1700 cm' (Amide I). IR peaks are composite ones. Each of the underlying bands is representative of a specific environment. The information that may be obtained from the phosphate &Amide I peaks is: (1) Mineral crystallinity/ maturity (from the ratio of the areas of two peaks at 1020 and 1030 wavenumbers). (2) Collagen "quality". Preliminary results indicate that the ratio ofthe areas ofthe peaks B/C (1660/1690) is proportional to amount of non-reducible cross-links (specifically pyridinoline). These two ratios were expressed as a function of anatomical location and tissue age. The results showed that significant differences exist between normal and osteoporotic bone in both the mineral and collagen components. Specifically, osteoporotic bone consistently exhibited higher mineral crystallinity/maturity, and collagen with high Pyridinoline content in the areas of newly formed bone when compared to normal.

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DRDB DIFFERENTIATING PLATE-LIKE AND ROD-LIKE BONE MICRO STRUCTURE IN-VIVO WITH MAGNETIC RESONANCE IMAGING B. Stampa B. KOhn M. Heller C.C GIOer Osteoporosediagnostik Kiel, Klinik f. Radiol. Diagnostik, Christian-Albrechts-Universitiit zu Kiel, Germany High resolution magnetic resonance (HRMR) imaging allows to visualize the internal structure of phalangeal bone in vivo. We tested whether rod and plate like structures can be qualitatively differentiated. Methods. We investigated 27 subjects (age 25 to 78) with a Siemens Magnetom Vision (Siemens Medical Systems, Erlangen, Germany), a clinical whole body MR scanner with 1.ST magnetic field strength. A 4cm surface coil was positioned on the phalanx. We applied a 3-D spin echo sequence with T,=15ms, TR=65ms. With an acquisition time of 17m in this yielded a spatial resolution of 150J.llll x 150J.llll x 280J.llll. For image processing we used a SparcStation 20 (Sun Microsystems, Mountain View, CA, USA) and the image processing software AVS (Advanced Visual Systems, CO, USA). The raw 3-D HRMR images were processed to define a volume of interest (VOl), to segment the data set into bone and marrow in this VOl, and to filter out noise and artifacts. The resulting binary 3-D image contained two objects: the trabecular network inside the cortex and the marrow space. The binary data set was smoothed and rendered. Interactive chariges of the view direction and other viewing parameters enabled us to get an impression whether rod or plate like trabeculae dominate in the bone assessed. Results. Figures 1 and 2 show 3-D images of the trabecular network near the distal joint of the mid phalanges of two different individuals.

Fig.l: Rodlike (age 78 yrs) Fig.2: Platelike (age 27 yrs) Conclusion. HRMR imaging allows for non-invasive visualization of the micro structure in the phalanges in vivo and may be a method for qualitative differentiation between more rod or plate like bone structures.

DRD9 IN SITU DEXA, ASH-WEIGHT, SIZE, APPARENT VOLUMETRIC DENSITY AND FAILURE LOADS OFTHE PROXIMAL FEMUR P. Miller. E -M. LochmUlier. U. Wehr. R. Putz W. Rambeck. E Eckstein I. Universitiitsftauenklinik, Anatomische Anstalt, Institut fOr Physiologie und Tiererniihrung, MOncMn, Germany In a previous study we have analyzed the correlation between dual energy X-ray absoprtiometry (DEXA), performed in situ with intact soft-tissues, and the mechanical failure loads of the proximal femur. (LochmOlier et al. 1998). The objective of the current study was· to relate in situ OEM to femoral ash-weight, to correlate ash-weight with, mechanical failure, and to analyze the relative contributions of bone size and apparent volumetric density to femoral DEXA and failure loads. In 54 femora, which had been previously measured in situ with a DPX-L scanner (Lunar) and mechanically tested in a stance phase configuration (30 male, age 81 ±9 yrs.; 24 female, age 84±11 yrs). The femoral head and shaft were removed and the bone volume determined, using a water displacement method. The bones were then ashed, ash weight measured, and the calcium content determined, using an independent method. Apparent volumetric bone density was calculated, dividing the ash-weight by the femoral volume. Calcium content and ash-weight were highly correlated (r2=97%). There was some deviation (r2=79%) of femoral DEXA derived bone mineral content (BMC neck + trochanter) from ash weight, the standard error of the estimate amounting to 16,2%. The aSh-weight was more highly correlated with mechanical failure (r2=60%) than DEXA derived BMC (r2=48%) Femoral size (volume) made a stronger contribution to trochanteric BMC than apparent volumetric density (r2=37% vs. 16%), but not to cervical BMC (19% vs. 24%). Apparent density was more highly associated with trochanteric and cervical areal bone density (DEXA-BMD) (r2=17%/17%) than bone size (r2=36%/ 33%). However, bone size was more strongly associated with femoral failure

loads (r2=35%) than apparent volumetric density (r2= 10%). We conclude that the inhomogeneous distribution of soft tissue has non-linear effects on in situ DEXA measurements, reducing the predictive capability of femoral failure loads. Moreover, bone size (rather than volumetric bone density) is strongly associated with mechanical failure, and predictions of fracture risk may be improved by taking into account anthropometric variables. LochmOlier et al. (1998) OsteoporoSiS Int.: in press

DR1D A LONGITUDINAL STUDY OF BONE GAIN IN PUBERTAL GIRLS: ANTHROPOMETRIC AND BIOCHEMICAL CORRELATES J. Cadogan A. Blumsohn M,E Barker R. Eastell University of Sheffield, Sheffield, UK The aim of this longitudinal study was to investigate the factors associated with bone mineral acquisition in pubertal girls Subjects were 37 healthy, Caucasian girls aged 12.1 (SO 0.3) years. Measurements were made at 6-monthly intervals over a period of 18 months, and included total body bone mineral content (TBBMC), density (TBBMD), lean mass and fat mass by DXA, anthropometry, lifestyle factors, four biochemical markers, of bone tumover, hormonal status and fractional calcium absorption. In multiple regression analysis, correlates of relative gain in TBBMC were gain in lean mass (p<0.001), and serum estradiol (p=0.008). For TBBMD, correlates were gain in lean (p<0.001) and fat mass (p=0.003), serum estradiol (P
DR11 TYPE I COLLAGEN GENE POLYMORPH ISMS ARE ASSOCIATED WITH SUSCEPTIBILITY FOR FRACTURES IN ELDERLY WOMEN - THE OSTEOLIMB STUDY Vandevyver', P.Stinissen", L Michiels', J.-J. Cassiman', J. Vanhoof', K. Deklerck" .!....B£us'" and p, Geusens',' 'Dr. L Willems-Instituut, 'Limburgs Universitair Centrum, Diepenbeek ' Centrum voor Menselijke Erfelijkheid, K,U. Leuven, Belgium The dimorphisms of ~pe I collagen' gene loci COL-1Al and COL-1A2 and their relationship with bone denSity ,and fracture history were investigated in 347 unrelated postmenopausal Caucasian women of 70 years and older. The overall distribution of the COL-fAl and COL-1A2 alleles in this study was similar to that previously reported in Caucasian study populations, No difference in bone mineral density at the spine, the proximal femur and the proximal radius was seen betweep\he genotypes for any of the studied dimorphisms, However, in nonobese women, bone density in the spine was 10% higher in COL-1Al BIBl genotype compared to B2B2 (p
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OR12 GENETIC RELATION BETWEEN OSTEOPOROSIS AND CARDIOVASCULAR DISEASE: VITAMIN 0 RECEPTOR POLYMORPHISM PREDICTS MYOCARDIAL INFARCTION A.G. Uitterlinden", H. Burger', J.C.M. Witteman', J.P.T.M. van Leeuwen', H.A.P. Pols'·' 'Departments of 'Internal Medicine III and 'Epidemiology & Biostatistics, Erasmus University Rotterdam, the Netherlands Several epidemiological studies have shown low bone mass to be associated with osteoporosis but also with several other common diseases, including stroke and cardiovascular disease (CVD). Yet, the responsible underlying mechanisms are presently unclear. Osteoporosis has a strong genetic component and vitamin 0 receptor (VDR) polymorphisms have been proposed to explain part of this genetic effect. In view of the putative relation between the vitamin 0 endocrine system and myocardial infarction (MI), we investigated the association between VDR polymorphisms and prevalence of MI in a large population based study. The study group comprised 1978 men and women aged 55-80 years from the Rotterdam study - a population-based cohort study of chronic diseases in the elderly. VDR haplotype polymorph isms were typed by PCR and genotypes were related to presence of an ECG-confi rmed MI. We observed VDR haplotype allele 1 (='baT") to be overrepresented in MI cases vs controls corresponding to a Relative Risk of 1.2 (95%CI 0.91.8) for heterozygote carriers and 1.5 (95%CI 1.0-2.3) for homozygote carriers. The allele dose effect was 1.2 (95%CI 1.0-1.5) increase in risk per copy of the VDR haplotype allele 1. There was effect modification by dietary calcium intake, such that the RR was 1.6 (95%CI 1.2-2.2) for individuals with a calcium intake higher than the median of 11076 mg/day in comparison to RR=0.9 (95%CI 0.7-1.3) for those with an intake lower than the median. The relation was not influenced by known risk factors such as age, bmi, serum cholesterol, and serum HDL levels. Also no relation could be observed between VDR haplotypes and left ventricular hypertrophy, aortic calcification and hypertension. We have demonstrated (I) VDR haplotype allele "baT" to be a genetic marker for myocardial infarct and (2) the association to be strongly modified by dietary calcium intake. This observation is in line with the previously demonstrated influence of the vitamin 0 system in cardiovascular function. Our results illustrate the pleiotropic nature of genotype-related differences in the vitamin 0 endocrine system and, thereby provide clues to the underlying biological mechanism of the epidemiological relationship between osteoporosis and CVD.

OR14 BIOCHEMICAL MARKERS OF BONE TURNOVER PREDICT THE RATE OF POSTMENOPAUSAL BONE LOSS: A 4-YR FOLLOW-UP STUDY P. Garnero, F. Duboeut. E. Sornay-Rendu P.O. Delmas INSERM Unit 403, Lyon France We tested the ability of a panel of recently developed bone markers (MK) to predict the rate of forearm bone loss assessed by 4 annual bone mineral density (BMD) measurements using DXA in 305 healthy untreated women, 1-38 yr postmenopause (age: 64±8 yr) who are part of the OFELY cohort. At baseline, blood and urine (first and second morning void and 24 hr collection) samples were collected to measure serum osteocalcin (OC), bone alkaline phosphatase (BAP), N (PINP) and C (PICP) terminal type I collagen propeptides for bone formation, serum (SCTX) and urinary (U CTX) C-telopeptides and urinary (U NTX) N-telopeptides of type I collagen for bone resorption. Baseline levels of all MK, except BAP, negatively correlated with both mid and distal radius bone loss (p
OR13 A DINUCLEOTIDE REPEAT POLYMORPHISM UPSTREAM OF THE ESTROGEN RECEPTOR IS ASSOCIATED WITH OSTEOPOROSIS Bente. L. Langdahl. Elsebet Lokke and Erik F. Eriksen Aarhus Bone and Mineral Research Group, Department of Endocrinology, Aarhus University Hospital, Aarhus Amtssygehus, Denmark Background: Estrogen is important for normal bone turnover and maintenance of bone mass as illustrated by the bone loss associated with postmenopausal estrogen deficiency. Mutations in the estrogen receptor (ER) is accompanied by reduced bone mass in affected humans of both sexes. A dinucleotide repeat polymorphism has been identified upstream of the ER. Since this polymorphism potentially could be involved in regulation of transcription of the ER gene, we wanted to examine this polymorphism in a case-control study of osteoporotic patients and controls. Methods: ER genotypes were determined by PCR analysis of genomic DNA extracted from leukocytes and related to bone mass and the presence of fractures in a study of 182 osteoporotic patients with vertebral fractures and normal controls. Results: The number of repeats ranged between 10 and 25. In the osteoporotic patients and the normal controls the mean number of repeats were: 17.3 and 18.6, respectively, p=0.007. BMD of the lumbar spine (Z score) was correlated to number of repeats (r=0.20, p=0.006). Also BMD of the femoral neck (Z-score) was correlated to number of repeats (r=0.17, p=0.049). Conclusion: We have found that the dinucleotide repeat polymorphism upstream of the ER is associated to BMD of both the lumbar spine and the hip and osteoporotic fractures.

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OC high -2.00* (% of w.) (24%) low -0.52

PICP

PINP

SCTX

UCTX

UNTX

-2.04* (11%) -0.76

-2.44 * (15%) -0.64

-2.56* (22%) -0.44

-2.12* (38%) -0.20

-2.12* (33%) -0.32

* p
OR15 MONITORING OF TREATMENT AND PREDICTION OF EFFECT ON BONE MASS BY BIOCHEMICAL MARKERS IN THE EARLY POSTMENOPAUSAL INTERVENTION COHORT (EPIC) STUDY OF ALENDRONATE P. Ravn* M.E. Bidstrup* N.H. Bjarnason* D. Hosking R.D. Wasnich M.R. McClung and C Christiansen* for the EPIC study Group *Center for Clinical & Basic Research. Ballerup. Denmark To establish whether prospective determinations of biochemical markers of bone turnover can effectively monitor anti-resorptive treatment and predict long-term response in bone mass, we determined at 6-months intervals biochemical markers of bone turnover in the EPIC study. The EPIC study is an ongoing, randomized, double-blind, placebo controlled, 4-center trial of daily oral alendronate (ALN) treatment for prevention of postmenopausal osteoporosis (n=1609). Results from women, who had completed Year 2 of the study and had baseline-, 6-, and 24-months data of the bone markers and spinal BMD available were analyzed (n=1202). U-NTX and U-CTX decreased 50-60% below baseline after 6 months treatment with 5 mg ALN. Serum total osteocalcin (S-OC) and serum N-Mid-fragment osteocalcin (S-N-MID) decreased more gradually to a level 30-40% below baseline. In the vast majority of the participants, the bone markers reached the premenopausal range within 6 months of treatment with 5mg ALN. There was a significant association between 6-months response in all bone markers and 2-year response in spinal BMD (r=-0.30 to r=-0.55, p<0.001). A decrease of 60% or more at 6 months in U-NTX or U-CTXwas associated with a 3.9-4.7% increase in spinal BMD. In contrast, a decrease of 20% or less in U-NTX or U-CTX was associated with a 0.91.2% decrease in spinal BMD. The estimated probability of a positive response in spinal BMD (defined as a 2-year change in spinal BMD above baseline) was 80% (U-NTX) and 89% (U-CTX) if a cut-off level of 40% decrease at 6 months in U-NTX or U-CTX was chosen. This corresponded to a sensitivity of 71 % (U-NTX) and 58% (U-CTX) and to a specificity of 69% (U-NTX) and 86% (U-CTX). For S-OC and S-N-MID a cut-off level of 20% decrease at 6 months gave an estimated probability of a positive response in spinal BMD of 75% (S-OC) and 88% (S-N-MID). This corresponded to a sensitivity of 64%(S-OC) and 54% (S-N-MID), and to a specificity of 63% (S-OC) and 86% (S-N-MID). In concluSion, the bone markers can be used in clinical practice as fast and valid indicators of treatment response.

OR17 DECREASED CALCITONIN RECEPTOR mRNA IN CIRCULATING MONONUCLEAR BLOOD CELLS OF POST MENOPAUSAL OSTEOPOROTIC WOMEN J. Beaudreuil J. Taboulet Ph.Orcel A. Graulet J. Gyeris M A. Denne, A. Julljenne and M C. de Vernejoul INSERM U349, hopital Lariboisiere, Paris, France Calcitonin is a unique physiological hormone that inhibits bone resorption through its receptor on osteoclast. Quantitative changes of hCTR could be associated with the increased bone resorption during menopause and/or osteoporoSiS. We therefore studied hCTR mRNA using a semi quantitative method in circulating mononuclear blood cells (MNBC): MNBC express hCTR and are of easier access than osteoclasts. Seventy one women were included: 24 premenopausal (Pre, age: 35±9) and 47 post-menopausal women with (OP: n=28, age 70±10) or without (Post: n=19, age 67±7) osteoporoSiS. Osteoporosis was defined by a low bone mineral density (lumbar or femoral T-score <-2.5) and/or the existence of at least one non traumatic crushed vertebra on a lateral X ray view or hip fracture in the medical history. OP patients had a higher resorption and lower bone density at the lumbar spine (LS BMD) than Pre and Post women (urine Dpyridinoline (nmollmmol creat): Pre: 4.2±O.2, Post: 5.3±O.3, OP: 8.0±O.8; p
OR16 BROADBAND ULTRASOUND ATIENUATION IN THE HEEL IS SENSITIVE TO ANTI-RESORPTIVE THERAPY D. deTakats E.v. McCloskey K. Pande J.A. Kanis WHO, Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK There are limited data on the responsiveness of various ultrasonic parameters to anti-resorptive therapies in osteoporosis. We wished to compare the effect of a 1-year course of treatment with the bisphosphonate clodronate on broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the heel with its effect at other skeletal sites. A total of 273 women aged 75 years or more completed a 1 year course of treatment with clodronate 800mg daily by mouth (n= 138) or an identical placebo (n=135) in a randomised double-blind placebo-controlled study. BUA and heel SOS were measured at baseline, 6 and 12 months using a McCue CUBAClinical, tibial SOS was measured using a Myriad SoundScan2000, bone mineral density (BMD) at the hip by Hologic QDR2000plus and distal forearm BMD by Osteometer DTX100. Changes from baseline (mean%±sem) were significantly different between clodronate and placebo at the total hip (0.2±O.5% vs -1.4±O.3%, p
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OR18 PROTEIN MALNUTRITION-INDUCED BONE LOSS IS ASSOCIATED WITH ALTERATION OF GROWTH HORMONE-IGF-I AXIS AND WITH ESTROGEN DEFICIENCY IN ADULT RATS. P. Ammann. R. Rizzoli J.-P. Bonjour Div. of Bone Diseases. WHO Collaborating Center for Osteoporosis and Bone Diseases, Opt of Internal Medicine, University Hospital, CH-1211 Geneva 14, Switzerland. Protein malnutrition is known to play an important role in the pathogenesis of osteoporotic fracture of the proximal femur in elderly. However, the mechanisms of bone loss under protein deficiency are still poorly understood. We investigated the effect of various isocaloric diets containing 15,7.5,5 and 2.5% casein on bone mineral density (BMD) and ultimate strength (US) as evaluated at the level of lumbar spine (LS), femoral neck (FN), midshaft femur (MF) and midshaft tibia (MT). Markers of bone remodeling (osteocalcin, Oc; deoxypyridinoline, dPyr), plasma IGF-I and sex hormone status (vaginal smear) were also determined. Values are means±SEM. After 16 weeks of experiment LS BMD (mg/cm') in rats fed 15,7.5,5 and 2.5% casein was 241±7, 240±5, 239±4 and 211±8*, respectively. MT BMD was 258±4, 260±5, 256±4 and 243±2* and plasma IGF-1411±28, 407±20, 380±20 and 271±50* ng/ml in the corresponding groups. Absence of estrus signs in vaginal smear was observed in rats fed 2.5% casein, but not in the other groups. To further investigate the respective roles of estrogen and protein deficiencies, the same determinations were performed in Sham-operated (Sham) and ovariectomized (OVX) rats, pair-fed isocaloric diets containing either 15 or 2.5% casein. Results are summarized as follows; *p<0.05 vs Sham 15%;' vs OVX 15% by ANOVA.

LS BMD LS US (N) MFBMD MF US (N) Dc (ng/I) dPyr/creat IGF-I(ng/ml)

Sham15

OVX15

Sham2.5

OVX2.5

252±5 255±24 248±2 163±4.8 13.4±2.1 18.6±2.2 531±22

233±6* 178±15* 238±2* 151±5.8* 23.3±1.2* 29.6±4.6* 686±28*

220+6* 118+10*' 211 +4*' 1 25+5.8*' 15.7+1.2' 62.7+7.0*' 324+ 17*'

211±6*' 119±14*' 205±*' 1 24±4.2*' 14.7±1.4' 70.9±7.0*' 288±20*'

Similar results were obtained at the level of FN and MT. In contrast to OVX, only protein malnutrition was able to affect cortical bone. Bone biochemical markers suggest that isocaloric malnutrition with 2.5% casein leads to a marked uncoupling between bone resorption and formation. In conclusion isocaloric protein malnutrition decreased bone mass and strength at skeletal sites formed by cortical and by mixed trabecular and cortical bone. This effect might be related to decreased plasma IGF-I and estrogen deficiency with a subsequent imbalance in bone remodeling. This model may mimic osteoporosis observed in elderly women in whom both cortical and trabecular skeletal sites are affected and in whom both sex hormone status and IGF-I are depressed. It represents thus an interesting tool to investigate new nutritional or pharmaceutical treatments of osteoporosis.

OR19 NEW CONCEPT OF VITAMIN 0 EFFICACY IN THE ELDERLY: 25-0H-D3 IMPROVES BODY SWAY AND THUS REDUCES FALLS AND HIP FRACTURES M. Pfeifer, B. Begerow, M. Pospeschill, M. Scholz S. Makosch, T. Schlotthauer, A.D. Lazarescu W. Pollaehne, HW Minne Institute of Clinical Osteology and Clinic DER FUERSTENHOF, Bad Pyrmont, Germany So far we appreciate vitamin 0 supplementation in elderly populations to reduce non vertebral fractures (Chapuy et al, 1992, Dawson-Hughes et al, 1997). This success is probably not only to be attributable to increments in bone density, since non-vertebral fractures are strongly related to falls. We hypothesize body sway to have impact on falls-associated fractures and it may be vitamin 0 to improve balance and to reduce fracture rates. We determined 25-hydroxy-colecalciferol (RIA), bone density femoral neck (QDR 2000, Hologic) as well as history of falls and hip fractures in 237 postmenopausal women with osteoporosis (WHO-definition grade 2 and 3) participating in the Pyrmont-EPOS-study. Body sway according to Lord et al, (1991) was assessed. Mean sway velocity and maximum sway distance have turned out to be most reliable and objective parameters within a separate validation study of 73 healthy men and women with different age groups. SPSS (6.1) was used for statistical analysis and

Pearson coefficients of correlation are presented as follows:

25-0H-Vitamin 0 Falls last 5 years Hip fractu res Rib fractures BMD femoral neck

sway distance

sway velocity

-.1751; p = .008 .2448; p< .001 .3036; p< .001 .1459; p = .025 -.0241; p = .716

-.1756; P =.008 .2465; p< .001 .3026; p< .001 .1465; P = .024 -.0246; P = .711

230 237 237 237 229

Body sway measurements represent a valid method to detect an importaL risk factor for falls, which are to be recognised as a serious event leadin[ to fractures especially in case of low bone mass. Additionally, vitamin 0 is associated with balance. We therefore conclude the efficiency of vitamin 0 - decreasing fracture rates - to work also via body sway, falls, and subsequent fractures. This effect is independent of vitamin 0 action on skeleton metabolism. (This work was supported by the "Rut und Klaus Bahlsen Stiftung" [foundation JGermany.)

OR20 CHANGES IN BONE DENSITY DURING PREGNANCY Cs. More. A. Balogh Obstetrics and Gynaecology of University of Debrecen, Hungary The effects of gestation lactation and weaning on maternal bone metabolism were examined in a longitudinal study. Urinary excretion of calcium and phosphor changes in bone mineral density (BMD), bone markers and calcium homeostasis hormones were monitored The changes in bone mineral density of lumbar spine and of the forearm were measured with LUNAR DPX-L bone densitometer. Measurements were made at 5 observation points prior to conception, between the 22 0d and 241h weeks of gestation (only forearm density), at one week after parturition at 6 months and 12 months after parturition. The sequence of results was analysed for each of 50 volunteers. Blood samples for marker and laboratory examinations were taken during the above periods and on 2 more occasions i.e. between the 141h and 161h weeks and between the 30lh and 34 1h weeks of gestation, respectively. The results suggest that both in the 3fd trimester of gestation and 6 months after parturition bone mineral density measurements of the forearm and of the lumbar spine were significantly lower as compared to those prior to conception and in early gestation. Women with no lactation and those with lactation duration of less than a month had no significant decrease in bone mineral density, however; bone density measurements were lower also in this group during pregnancy. At one week following parturition mean bone loss were -0,069 g/cm', -6,4% (p<0,05) at the lumbar spine both of lactating and non lactating women as compared to those prior to conception. At 6-month (women with lactation duration of 2 months or more) mean BMD decrease were -0,131 g/cm', -11.9% (p<0,05) were detected as compared to those prior to conception. At 12 months after parturition women with lactation duration of 2 month or more showed much lower BMD values as compared to those prior to conception. Marker and laboratory results support an increase in bone metabolism during pregnancy and lactation periods. Both bone resorption and formation markers showed an increase in concentrations which refers to the increase in bone formation and resorption procedures determines the actual bone amount for each period. The study suggests that there is a bone loss in the 3fd trimester of gestation, which increase during lactation Factors influencing bone metabolism during pregnancy and lactation have not been totally elucidated as yet. However, it can be stated that women have to be given appropriate support during gestation, lactation and the postpartum period so that they can save and recover their bone loss.

•

OR21 RALOXIFENE MODULATES BONE CELL HOMEOSTASIS IN VITRO S. Migliaccio A. Taranta A. Teti. D. Agnusdei and J. Termine Histol Medical Embriol Dept, Univ La Sapienza of Rome, Experim Medicine Dept, Univ of L:Aquila, Regional Business Unit, Eli Lilly, Florence, Italy, and Lilly Research Labs, Eli Lilly & Co, Indianapolis, IN, USA Raloxifene (RAL), a non steroidal benzothiopene, has both agonistic and antagonist estrogenic activity and has been named selective estrogen receptor modulator (SERM). RAL prevents bone loss in both ovariectomized animal models and postmenopausal women. Since little is known regarding the direct effect of this compound on bone cells, the aim of this study was to investigate the role of RAL in the modulation of bone cell homeostasis in vitro. To evaluate the effect of RAL on osteoclastogenesis and osteoclast function, bone marrow cultures were established from neonatal mice and treated with 1,25(OH), vitamin 0, (Vit 0" 10'8 M) to induce osteoclast differentiation. Tartrate resistant acid phosphatase (TRAP) activity was used as marker for osteoclasts. Treatment with vit 03 induced osteoclast generation (31±5/field) as compared to untreated control. Addition of increasing concentrations (10'''-10'6 M) of RAL significantly blunted the number of mono- and polynuclealed TRAP-positive cells in aconcentrationdependent manner. Maximal inhibition was obtained at a dose of 10.8M of RAL with a decrease of ~40% of the Vit 03-induced TRAP-positive cells. In addition, to evaluate bone resorption in vitro, differentiated osteoclasts, obtained upon incubation with Vit 03, were trypsinazed and plated on, bone slices. Stimulation of osteoclasts with Vit 0, for further 48 hrs produced a high number of pits. Addition of increasing concentrations of RAL showed an inhibition of osteoclast activity with maximal effect at 10.910.8 M of RAL. Moreover, murine osteoblasts were obtained by sequential collagenase/trypsin digestion of neonatal calvaria to study RAL effects on osteoblastic cells. Osteoblasts were plated at a density of 16000 cells/ well. At 70% confluence cells were incubated in serum-free medium in the presence of increasing concentration of RAL for 24 hrs. At the end of incubation, treatments were removed and cells were further incubated for 4 hrs with 3H-thymidine to evaluate cell proliferation. RAL exposure caused an increase in cell proliferation in comparison to unstimulated cells, with maximal effects at 10 '0 M of RAL used (~2 fold of CTL). In conclusion, these data show for the first time that RAL modulates murine osteoclastic and osteoblastic cells activity in vitro.

OR22 RALOXIFENE MAINTAINS FAVOURABLE EFFECTS ON BONE MINERAL DENSITY, BONE TURNOVER AND SERUM LIPIDS WITHOUT ENDOMETRIAL STIMULATION IN POSTMENOPAUSAL WOMEN. HEAR STUDY RESULTS N.H. Bjarnason PD. Delmas B.H. Mitlak A.S. Shah. w.J. Huster, MW. Draper, C. Christiansen Center for Clinical & Basic Research, Ballerup, OK; INSERM, Lyon, France; Eli Lilly, Indianapolis, IN, USA Raloxifene (30, 60, 150mg/day) decreases bone turnover, increases axial and appendicular BMD, and lowers serum total and LDL-cholesterol compared with placebo without stimulation of the endometrium after 2 years (NEJM 1997; 337:1641). We now report 3-year results. At baseline, 601 women who were 45-60 years of age, within 2-8 years of menopause and had a spinal BMD T-score between -2.5 and 2.0 were included in this double-blind, randomized trial at 11 centres in 8 European countries. BMD at the spine, hip and total body was measured by DEXA (Hologic Inc, MA, US) and endometrial thickness (ET) was determined by transvaginal ultrasound. An intention-to-treat analysiS was applied. 72% of the subjects completed 3 years of the study. There were no differences in the number of subjects discontinuing among therapy groups. Raloxifene was well tolerated. Lumbar Spine BMD (% change±SE)

Compared with placebo, the mean increase in BMD for the 60mg/day group was 2.7% at the spine and femoral neck and 1.9% at the total body.

U-Crosslaps (%) S-osteocalcin (%) S-bone AP (%) S-total Chol (%) S-LDL Chol (%) ET(mm)

y

Months

Femoral Neck BMD (% change±SE

• .---- RLX60

y

Months

-

60mg/day 150mg/day

-12.7 -10.9 -12.9 -2.5 -3.7 0.4

-28.6* -21.8* -14.2* -7.3* -9.1 * 0.4

-33.2* -26.1 * -18.8* -8.1 * -12.5 * 0.3

-32.9* -29.0* -19.9* ·10.2* ·15.1 * 0.2

OR23 RALOXIFENE REDUCES THE RISK OF INCIDENT VERTEBRAL FRACTURES: 24-MONTH INTERIM ANALYSES B. Ettinger D. Black S. Cummings. H. Genant C. GIGer P. Lips R. Knickerbocker, S. Eckert T. Nickelsen B Mitlak for the MORE Study Group Kaiser Foundation Research Institute, Oakland, CA; University of California, San Francisco, CA; University of Kiel, FRG; Vrije University, Amsterdam, The Netherlands; Eli Lilly, Indianapolis, IN. The MORE study is a double-blind, placebo-controlled, clinical trial to evaluate the effect of raloxifene on the risk of vertebral fractures (VFx). Among 180 sites in 25 countries worldwide, 7705 osteoporotic women (hip or spine t-score <-2.5 and/or prevalent VFx) were randomized into 3 equal study arms - placebo, 60mg and 120mg of raloxifene per day. All subjects received supplemental calcium (500 mg/d) and vitamin 0 (400 IU/d). Lateral spine radiographs were assessed for prevalent and incident fractures by semi-quantitative (SO) grading (JBMR 1993;8:1137). If a fracture was detected by SO, both 'binary SO' and quantitative morphometry (with a cutoff of 20% and 4 mm absolute height reduction) were also performed; a fracture was scored if confirmed by either additional technique. The present analyses are based on 6735 women who had paired baseline and endpoint radiographs and compares pooled raloxifene groups with placebo. Approximately 1/3 of women had ~1 prevalent VFx at baseline. One or more incident VFx occurred in 368 (5.5%) of women; relative to women receiving placebo, those receiving raloxifene had a relative risk for fracture (RR) of 0.56 (95% CI 0.46, 0.68; P
t -. - 1

-PLACEBO ......... RLX30

30mg/day

All values are median% change from baseline, except ET, which is median actual change from baseline. *P
,~ ..... :::. A _.-f.'......... .-.: ".:.-r . ""................... .

!..."t::",,·

Placebo

. -RLX150

•

OR24 EFFECT OF ALENORONATE ADDED TO ONGOING HORMONE REPLACEMENT THERAPY IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS R. Lindsay+- F. Cosman! D.J. Caryt C.L. Lisst J. Reagant C.A. Byrnest M.E. Meltont K.J. Pettyt tHelen Hayes Hospital, West Haverstraw, NY and tMerck & Co .. Inc., West Point. PA USA Alendronate (ALN) and hormone replacement therapy (HRT) are effective treatments for postmenopausal osteoporosis when used individually. Data on the efficacy of combined HRT and, bisphosphonate therapy are limited. The purpose ofthis study was to determine ifthe addition of ALN to ongoing HRTwould produce an increase in lumbar spine (LS), hip trochanter (HT), and femoral neck (FN) bone mineral density (BMD) greater than that of HRT alone. The study population consisted of 428 women with the following characteristics: postmenopausal for ~5 years, on HRT continuously for at least 1 year, and a T-score ~-2.0 at the LS or FN and ~-1.5 at the other site. Patients were recruited at 38 sites in the U.S. and they were assigned randomly to treatment (214/group) with either 10 mg ALN daily or placebo (PBO). Their current HRTwas continued for the duration ofthe study (one year). All patients received vitamin D(400 IU daily) and calcium supplements as needed to maintain adaily calcium intake of at least 1000 mg. There was no significant difference in the average age (62 yrs), duration of menopause (15 yrs), or duration of HRT (9.5 yrs) between the treatment groups. The mean percent changes in BMD after 12 months of therapy are summarized below.

SKELETAL SIl:E

ALN + HRT %±SE

PBO + HRT %±SE

P-value ALN vs PBO

Lumbar Spine Hip Trochanter Femoral Neck

3.6*±O.3 2.7*±OA 1.7*±OA

1.0*±O.3 0.5±O.4 0.8*±O.4

< 0.001 < 0.001 0.072

OR26 OPTIFIT 1994 -1997 THREE STANDARDIZED PHYSICAL TRAINING PROGRAMS FOR 3-YEARS REDUCED PAIN AND INCREASED BONE MASS IN ELDERLY OSTEOPOROTIC WOMEN P. Donhauser S. Donhauser P. Watkin M. Baumann et al. Clinic of Physical Medicine, Ludwig-Maximilians-University, Munich, Germany The randomized, prospective, controlled OPTIFIT-Study included 130 osteoporotic women with a mean age of 60 and randomized them to three different training concepts which have been shown as effective in other studies. 26 participants received only estrogen without physical training and were defined as control-group. During 3 years of training BMD of hip and lumbar spine was followed up. Standard Questionnaires about ADL and back pain (Greenough, Fraser) completed the efficacy endpoints. Even half a year of training reduced highly significant the baseline pain score in all three training groups. Overall balance training (BT) with water gymnastics was more effective in pain reduction (VAS scale) than weightbearing exercises (WB) or whole body endurance training (ET), compared to the control group. This normalization of the pain level to about 3 in 10 of the VAS scale has been consistent during the whole trial. ADL also climbed up to normal values of healthy elderly women in all three groups. Only in the ET group a better cardiovascular capacity was seen (lactate level in capillary blood) during bicycle ergometry. The upright position and back posture were improved in all groups, measured by the extent of spine motion with the instrument of a computerized so called "backmouse". In the first year the higher physical activity increased bone mass which has preseryed during year 2 and 3, even without estrogen treatment. BMD at the lumbar spine and total hip raised between 1,8 and 2,8% in the first year (DXA Hologic 1000). In year 2 and 3 the WB group profited in BMD more than ET and BT group: Table:% changes in BMD of lumbar spine, total hip, VAS pain (in tentiles) and daily activity

*p
Training method

LiBMDsp. LiBMD hip LiVAS(0-10) Lifunct.capacity

weight-bearing T. endurance T balance T. control (ERT)

+3,2* +2,8* +1,8* +0,8

+2,3* +2,5* +1,4 -0,3

-2,1 * * -1,2* * -2,3** -0,8

+18%** +23%** +21%** +7%

(*P<0,05, **p<0,01) OR25 STRONTIUM RAN ELATE FOR THE PREVENTION OF BONE LOSS OF EARLY POSTMENOPAUSE. J.Y. Reginster" C. Roux', .L...J.lJ.Jllin', D.M. Provvedini 3, P Birman 3, y. Tsouderos 3 'CHU Liege, Liege, France; 'Hopital Cochin, Paris, France; 31nstitut de Recherches Internationales Servier, Courbevoie, France Strontium Ranelate (S12911 ; SR) is apotential new treatment for osteoporosis. The results of the « STRATOS » study (conducted in postmenopausal osteoporotic women with vertebral fractures) have indicated that the daily dose of 2g/day of SR significantly increases lumbar BMD (approximately, 3% per year) and significantly reduces (44%) the number of patients experiencing a new vertebral fracture during the second year of treatment (as judged by quantitative morphometry). The effects of SR on the prevention of bone loss have been recently investigated during a bi-centre, doubleblind, placebo controlled study. Four groups of 40 early postmenopausal women without vertebral fractures were given either placebo or SR (125mg, 500mg or 1g/day) for two years. All subjects were also given a daily calcium supplement (500mg). The main characteristics of the study population were: age 54±3 years; duration of menopause 3±1.5 years, lumbar BMD (as measured by DXA on Hologic densitometers) 0.932±O.135 g/cm' (mean±SD). The effects of the treatment on lumbar BMD were monitored throughout the study. Due to the absorption of strontium to bone, all measured BMD values were adjusted for bone strontium content, using a model previously established in vivo. At the conclusion of the study, the percent variation of lumbar BMD from baseline was significantly different in the group receiving 1g/day of SR as compared to placebo: +1.41 %±5.33 versus -0.98%±3.14, respectively [p
•

Conclusion: Specific physical training programmes for osteoporotic women are highly effective in pain reduction. Regular training for 3 times a week is capable to preserve from bone loss and even to increase bone-mass to some extent in the first year of an intensive physical training. The women were highly compliant because their activity of life was greater than in the control group. The trained women showed a significantly better quality of life compared to the control group with ERT (estrogen replacement therapy). .

OR27 LARGER INCREASES IN BONE MINERAL DENSITY WITH ALENDRONATE THERAPY ARE ASSOCIATED WITH LOWER RISK OF NEW VERTEBRAL FRACTURES M.C. Hochberg PO Ross. S R. Cummings D. Black. T. Musline[ M.C. Neyitt and 0 Thompson for the Fracture Intervention Trial (FIT) Research Group. Univ. of Maryland, Baltimore, MD, and Merck & Co., Inc., Rahway, NJ, USA In FIT, alendronate treatment increased bone mineral density (BMD), and reduced vertebral fracture incidence by approximately 50%, compared to placebo. Vertebral fracture incidence was significantly related to change in BMD in the alendronate and placebo groups combined. In this analysis we tested the hypothesis that the same relationship existed within the alendronate group alone. A total of 3041 women aged 54-82 years were randomized to receive alendronate at a dose of 5 mg/day for 24 months followed by 10 mg/day for the remaining 12 to 30 months of study. BMD change was defined from baseline to 12 months, and new spine fractures were defined by morphometry as >20% and
N

% with Fracture(s)

Odds Ratio'

~O

622 1323 1029

6.3 3.5 3.2

1.0 0.55" 0.48"

O
• Adjusted for age, BMD, prevalent vertebral fractures at entry. ··p<0.001 Results were similar for spine BMD. Similar findings were also observed for the spine and hip using change in BMD at 24 months. In conclusion, women with the largest increases in BMD during alendronate treatment had the lowest risk of new vertebral fractures.

OR28 SALMON-CALCITONIN NASAL SPRAY PREVENTS VERTEBRAL FRACTURES IN ESTABLISHED OSTEOPOROSIS. FURTHER INTERIM RESULTS OF THE "PROOF" STUDY C. Chesnut D.J. Bavlink D. Doyle H. Genant S. Harris D.P. Kiel M. LeBoff J,L. Stock A, Gimona K. Andriano P. Richardson for the "PROOF" study group Univ of Washington Med Center, Seattle USA; Lorna Linda Univ, Lorna Linda USA; Chingford Osteop, Chingford UK; Univ of California, San Francisco USA; Rhode Is. Hospital, Providence, USA; Brigham and Worn ens Hospital, Boston USA, Mem. Health Care, Worcester USA; Novartis Pharma, Basel CH and East Hanover USA The PROOF (Prevent Recurrence of Osteoporotic Fractures) study is a 5-year, double-blind, randomized, placebo controlled study on prevention of vertebral fractures. 1255 post menopausal women with established OP were randomized to placebo (PL) or 100,200,400 IUlday Salmon Calcitonin Nasal Spray (SCNS). All patients received 19 Ca and 400 IU Vit D. The primary analysis was ITT (n=11 05) on time to first vertebral fracture (Kaplan-Meyer analysis). 783 patients had completed at least 4 years and 378 were ongOing for this interim analysiS of all accrued data to year 5. Results: a 36% reduction in the relative risk of new vertebral fractures compared to PL was observed in the 200 IU group (RR=0.643; 95% CI=0.443-0.934; p-value=0.020). The 400 IU and the 100 IU groups showed a 23% and a 18% reduction in the same analysiS (p=0.165; 0.265 respectively). The mean increment from baseline in L1-L4 BMD for the PL, 100, 200, and 400 IU was 0.7, 1.2, 1.2 and 1.6% respectively. The increases in LS-BMD were statistically significant (SS) over baseline in the active treatment groups at all endpoints, but not in the PL group. The LS BMD changes were SS different compared to PL in all treatment groups for the first 2 years of treatment and for the 400 IU group up to year 3. Urinary NTX was SS decreased over baseline in all treatment groups from year 1 to year 4 and compared to PL at year 1 in the 200 IU group and up to 3 years in the 400 IU group (median -10.7, -19.6, -22.6 ,1-25.1% in the PL, 100, 200, 400 IU group at year 1). Discontinuation rate due to study drug ineffectiveness (by predetermined criteria) was reported less frequently in 200 IU (13 pts.) and in the 400 IU (17 pts.) groups compared to the 100 IU (23 pts.) and PL (25 pts.) groups. Conclusion: In this interim

analysis, salmon calcitonin nasal spray at the dose of 200 IUlday reduces the risk of new vertebral fractures in postmenopausal women with established osteoporosis.

OR29 OFELY: OSTEOPOROSIS AND QUALITY OF LIFE A.R Martin J.M Chandle[ C.J. Girman E Sornay-Rendu PO Delmas Merck Research Laboratories, West Point, PA, USA and INSERM Unit 403, Hopital Edouard Herriot, Lyon, France Long-term outcomes, such as fracture, kyphOSis and pain, are well-known manifestations of osteoporosis (OP). The impact of low bone mineral density (BMD) or the knowledge of one's OP status earlier in the disease process however is less clear. A health-related quality of life (QoL) questionnaire aimed at assessing three QoL domains, Physical Difficulty, Adaptations to one's daily life and Fears about the future was developed and validated as a survey Instrument for population or community based studies to characterize the burden of illness. (Osteoporosis-targeted QoL questionnaire, [OPTQoL)). Objective: To assess the impact of OP on women participating in an ongoing community study of OP in France (OFELY). Methods: Femoral neck bone mineral density (BMD) and the selfadministered OPTQoL were collected from women with varying degrees of OP randomly selected from a large insurance company as part of the OFELY study. Results: BMD and OPTQoL data were obtained on 725 women (mean age:59; range:36-92) of primarily caucasian race. OPTQoL domain scores were worse with increasing OP severity, discriminating between those with normal BMD, osteopenia (OE) and OP, as expected. Additionally, those with prior fractures expressed greater levels of fear compared to those without a history of fracture, after controlling for age Scores on all three domains were significantly worse among women reporting a noticeable change in their posture, regardless of age (p<.001). Conclusion: The negative impact of OP on women with varying disease severity is evident in terms of limited physical functioning, adaptations to daily activities and fear associated with future fractures and pain, regardless of age. Recognition of the impact of OP on various domains of QoL may help the medical community to more fully understand the effects of OP on women and better characterize the burden of illness within a community.

•

OR3D QUALITY OF LIFE IN OSTEOPOROTIC PATIENTS WITH OR WITHOUT VERTEBRAL FRACTURES A. Oleksik. A. Dawson E. Moseley C. Cooper P. Lips for MORE study. Academic Hospital of Vrije Universiteit, Amsterdam, The Netherlands The clinical impact of osteoporosis is determined by fractures and subsequent morbidity. Therefore, quality of life has become an important outcome criterion in the assessment and follow-up of osteoporotic patients. Quality of life was assessed in 751 women with osteoporosis using the questionnaire of the European Foundation for Osteoporosis. The questionnaire, QUALEFFO, contains questions in five domains: pain, physical function, social function, general health perception and mental function. The assessment was part of the baseline measurements of the MORE study, a clinical trial on the effect of raloxifene in postmenopausal women with low bone mineral density (T-score 5-2.5) with or without vertebral fractures. Vertebral fractures were defined as height losses of 20-25% (mild) or 25% (moderate). After reading of spine X-rays in a central facility, patients were divided in substudy 1 and 2. Substudy 2 patients (446) had either at least one moderate or two mild vertebral fractures in presence of low BMD or two moderate fractures regardless of BMD. Substudy 1 patients (305) had low BMD but had no vertebral fractures as defined for substudy 2. The QUALEFFO was scored according to algorithm used in the validation study. Each domain score and the total score (sum of transformed domain scores) were linearly transformed to a 100 scale, with 0 corresponding to good quality of life. In comparison to substudy 2, the substudy 1 patients were 2.5 years younger (95% CI -3.3; -1.6), had lower prevalence of non-vertebral fractures (30% vs. 48%), scored better on neuro-psycho-motoric tests and had lower QUALEFFO scores. The domain scores and the total score discriminated significantly between substudy 1 and 2, also when corrected for age and non-vertebral fractures. OR (95% CI) per 1 point of QUALEFFO total score was 1.0466 (1.035; 1.058)*. In conclusion, this study confirms the decreased quality of life in patients with vertebral fractures. In osteoporotic patients, QUALEFFO discriminates well between those with and those without vertebral fractures. Score

substudy 1

pain 23.8±24.7 physical function 13.9±12.0 social function 23.9±22.1 health perception 37.8±20.2 mental function 28.2±15.0 QUALEFFO total 25.3±14.3

In conclusion, we have shown in a large population of men that crosssectionally bone loss starts early at the hip. A significant bone loss was documented longitudinally at the hip, total body and forearm in men over 50 yrs.

OR32 TRABECULAR BONE ARCHITECTURE IS A DETERMINANT OF VERTEBRAL FRACTURES IN MEN E. Legrand" D. Chappard', C. Pascaretti', S Krebbs" MF. Basle', M. Audran ' Service de Rhumatologie ' et Laboratoire d'Histologie-Embryologie', CHU, Angers, 49033 France Aim: To confirm that altered trabecular bone microarchitecture is a major determinant of vertebral fractures in men. Methods: Spine and hip bone density (BMD), spine radiographs and transilliac bone biopsy were obtained in 107 male patients with osteoporosis (T-score <-2.5 in spine). Histomorphometric analysis was done on a Leica quantimet image processor and the followings measures ere performed: trabecular bone volume (BVfTV) trabecularthickness (Tb Th) and number (Tb N). Interconnectivity Index (ICI). Star Volume of the bone marrow, Characterization of the trabecular network (node and free-end count).

substudy 2 difference 95% CI 39.0±26.8 21.2±17.2 35.1±23.9 49.2±20.5 33.8±17.0 35.7±16.2

-15.2* -8.2* -11.1* -11.5 * -5.6* -10.3*

(-18.9;-11.4) (-10.3;-6.1) (-14.4;-7.8) (-14.4;-8.5) (-8.0;-3.3) (-12.5-8.1) * p
OR3l CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT OF BONE MINERAL DENSITY IN MEN. MINOS STUDY P. Szulc* F. Marchand+ F. Duboeuf* P.O. Delmas* *INSERM 403 Unit, Lyon, France, +SSMB, Montceau les Mines, France In order to evaluate the age-related change of bone mass in men, we performed bone densitometry in a population-based cohort of 1050 men aged 20 to 85 yrs. Bone mineral density (BMD) of, lumbar spine, hip and total body was measured using a HOLOGIC 1500 device, BMD of forearm was measured using an OSTEOMETER 100 machine. In the cross-sectional study, lumbar spine BMD decreased until 54 yrs (r=-0.26, p
•

Results I Age (years) Spine BMD (gr/cm') Hip BMD (gr/cm') BVfTV Tb Th Tb N ICI Star Volume Free-end to Free-end struts (%) Node to Node struts (%)

Fracture

No Fracture

P

n = 60 54 0.70 0.67 11.6 95 1.22 4.31 21.9 28 19.9

n = 47 49 0.74 0.69 13.5 94 1.44 2.24 15.5 16 30.5

ns <0.05 ns <0.05 ns <0.01 <0.01 <0.05 <0.01 <0.01

Results II: The results of the stepwise linear regression analysis suggest that the best model for predicting the fracture number includes hip BMD and Interconnectivity Index: Fracture number =0.52 ICI - 2.4 hip BMD +2.53 In this model (r'=0.59), ICI explains most of the variance in fracture number (partial r'=Oo4O) with a significant hip BMD interaction (partial r'=0.19) These results strongly suggest that trabecular bone architecture is a determinant of vertebral fractures in men.

DR33 LONG-TERM EFFECTS ON BONE MINERAL DENSITY (BMD) BY INHALED STEROIDS (IS) COMPARED WITH NON-STEROID REFERENCE THERAPY A.E. Tattersfield*. M. Aubier**. P Braillon"*. O. Johnell'. R. KarlstrOm'. C. Pjcado *' I. TownA *City Hosp., Nottingham, UK; **HOp. Bichat, Paris France;***HOp E., Herriot, Lyon, France; 'MalmO Gen. Hosp., MalmO, Sweden; ·'Hosp. Clin. y Provin., Barcelona, Spain; ADept. of Med., Christchurch, NewZealand"Astra Draco, Lund, Sweden It is well known that oral steroids have a negative effect on BMD. However, it is still uncertain whether inhaled steroids have an effect on BMD or biochemical markers. A prospective, open, randomized study over 2 years was performed in patients with mild asthma receiving either inhaled steroids or alternative therapy, to document changes in BMDand biochemical markers. 374 patients (205 women, 18 - 66 years with FEV1 86% predicted normal) were randomized to either Pulmico~ Turbuhaler® (BUD) 400 JJi day or Becotide®pMDI (BDP) 500 lllI/day or to non-steroid reference therapy (REF). Treatment was subsequently adjusted to the asthma severity according to pre-defined criteria. Asthma was monitored using diary cards. BMD was assessed by DEXA, and vertebral fractures by morphometry. Biochemical markers were analysed in blood samples. 239 patients'completed the study. The reference group used mainly short- and long-acting 62-agonists, DSCG, and nedocromil. Treatment failures and asthma deteriorations were relatively few; BUD: 0, BDP: 1, REF: 8. The number of short courses of oral steroids was as follows: BUD: 38, BDP: 34; REF: 96, BMD changes: There was no statistically significant difference in BMD between the three groups after 24 months of treatment. The adjusted percentage'rchange of BMD for BUD, BDP and REF was + 0.1, -0.4 and +0.4% in lumpjlr spine, -0.9, -0.9, -0.4% in femoral neck and +0.6, +0.4, +0.9 in total bo(ly. Only four fractures occurred, evenly distributed between the groups. Lung function, asthma symptoms and use of B2-agonists improved in all groups but more so in the inhaled steroid groups than in the reference group. In this study, inhaled steroids over 2 years gave no significant change in BMD but achieved better asthma control compared with reference non-steroid therapy.

DR34 PERSISTENCE OF FAMILIAL RESEMBLANCE IN OLDER SIBS OF OSTEOPOROTIC FAMILIES AT THE FEMORAL NECK C. Baudoin M,E. Cohen-Solal. J, Beaudreuil. M C, de Vernejoul INSERM U 349 and U 21, Paris France To address whether the familial resemblance perSisted in older subjects and by consequence whether sib pairs studies could be used to elucidate the genes of osteoporosis, we collected cross-sectional data of 78 families of osteoporotic patients with 79 children (mean age±SD: 36±10 years) and/or 83 sibs (age 53±13). The osteoporotiC probands were either females (n=47, age: 67±8) or males (n=31 , age 49±12). Bone mineral density (BMD) was measured at the lumbar spine (L2-4) and femoral neck (FN). For each gender (and menopausal status of women), the BMD was adjusted on age, weight and height, using specific control populations, and then standardized (Z-score). We currently report results of FN Z-score. In both genders, the mean Z-score (±SD) was respectively: probands: -1.23±1.1 0, children: -O.64±1.21, and sibs: -0.40±1.26. Z-score were not different whether the proband was a male or a female. Familial resemblance was based on the'lntraclass and interclass correlation, using pairwise estimator. The resemblance among children was r=O.38 (p=O.015) and the one among sibs was r=O,24 (p=O.06). According to the mean age of sibs within each family, we split sibs into two subgroups around 55 years of age (the median value). The Sibs were correlated between them among the oldest (r=0.36, p=O.049) and not the youngest (r=-O.03, p=O.55). Interclass correlation between probands and sibs was r=O.42 (p=0.015) with no difference between age subgroups. In conclUSion, the Z-scor'e at the FN among osteoporotic families 1) confirm the strong familial resemblance of peak bone mass 2) show that in older subjects, there is a familial resemblance which suggest that increased bone loss, which contributes to low bone mass in osteoporosis, would be also under genetiC influence.

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than half the partiCipants requested further information on osteoporosis. In conclusion, this study showed a good level of understanding and knowledge of osteoporosis in this group of seniors. Their major risk for osteoporosis seems to be age. In spite of having good regular medical support, the use of calcium and bisphosphonate therapy is inappropriately low. This study highlights the need to educate patients to be more proactive in requesting osteoporosis treatment from their physicians.

EPIDEMIOLOGY P001 DEVELOPMENT AND EVALUATION OF A PROBLEM BASED LEARNING (PBL) WORKSHOP ON OSTEOPOROSIS (OP) FOR FAMILY PHYSICIANS (FP) P. Dayis N. Donen B. Kvern E. Andrews O. Nixon Universities of Alberta and Manitoba, Canada and Merck Frosst Canada Inc. Osteoporosis is a healthcare issue in which FPs playa major role. Although their knowledge base of OP is high, recent studies suggest that application to the clinical setting is low. We developed a PBL on OP where paired rheumatologists and FPs developed 9 problem solving clinical scenarios. An educational matrix was used to link specific case scenarios with individual teaching objectives based upon a previous needs assessment. FPs participated in the workshop developing best practice responses to the clinical scenarios with a trained facilitator and content expert. To assess the impact of this intervention FPs participated in a pre and post-test utilizing objective structured clinical exams (OSCEs) and standardized patients (SPs). OSCE stations tested knowledge, skills and judgment relating to OP with respect to risk factors, utilization of appropriate investigations including bone mineral densitometry (BMD), treatment strategies for the prevention of OP (both pharmacologic and non-pharmacologic), treatment options for established OP (bisphosphonates and hormone replacement therapy), and management of recent OP fracture. Participants were evaluated using a pre-determined score generated by their responses to OSCEs and SPs, plus an assessment by the SPs Evaluations were undertaken anonymously although participants had access to their own pre and post-test results for personal feedback. The impact of the workshop was assessed by comparing pre and post-test responses by group, by individual and by station. Participants demonstrated a significant improvement in their post workshop scores. Of 39 participants, 25 showed improvement in score (>+10), 13 showed little change (-10 to +10) and one a marked decrease (>-10). The greatest improvements were seen in the management of the male patient, determination of risk factors for OP and the use and interpretation of BMD. FPs reported general satisfaction with the content and format of both the workshop and the evaluation process. We conclude that this type of PBL workshop results in improved knowledge, skills and judgment in the management of OP by FPs.

P002 AN EVALUATION OF THE AWARENESS AND TREATMENT OF OSTEOPOROSIS IN SENIORS A. Juby L. McAuley Department of Medicine, University of Alberta, Edmonton, Canada The purpose of this study was to evaluate the knowledge of osteoporosis in a seniors population, to identify the sources of the information and the prevalence of treatment. A questionnaire was offered to all seniors attending the Seniors Assessment Clinic at the University of Alberta Hospital. The questionnaire was self-administered and consisted of 28 questions covering background knowledge of osteoporosis, family history, reproductive history, and osteoporosis treatment. The results were then pooled and presented as percentages. Data was collected from 60 questionnaires. The ratio of women to men was 4:1 with an average age of 75 years. 87% had heard of osteoporosis and the majority of these were able to accurately define the disease. The most common source of information was television (47%). 71% were aware that men could be affected though 25% were unsure. The majority knew that diet was somehow important in this disease. A positive family history was extremely low (11 %) in this group as was the current smoking status (1 %), although 46% were remote smokers. Steroid intake was very low. With regard to treatment, there was a 14% use of hormone-replacement therapy, 11 % were taking bisphosphonates, 11 % vitamin 0, 28% calcium supplements and 50% a daily multivitamin. 16% had had a bone mineral densitometry. In spite of 92% of patients having a regular family doctor, only 27% of these had discussed osteoporosis with their patients. More

P003 DISCUSSION OF DIAGNOSTIC CRITERIA OF PRIMARY OSTEOPOROSIS FOR CHINESE PEOPLE Tang Hai XianZheng Luo Dept. of Orthopedic surgery, Beijing Friendship Hospital, Capital University of Medical Science, Beijing 100050, P.R.China The diagnostic criteria for primary osteoporosis in women and men, as recommended by the World Health Organisation (WHO) and the western countries, are evaluated. In studying thousands of bone mineral density (BMD) values of hip and lumber 2-4 vertebrae of Chinese men and women, we found that WHO's diagnostic criteria for women, and western countries diagnostic criteria for do not apply to the general Chinese population. We propose the conceptthatthe adult peak BMD in Chinese women be reduced by 2.0 standard deviation (SO). This more accurately reflects the clinical demands in our country but leaves the question of diagnostic criteria of men yet to be answered.

P004 EPIDEMIOLOGICAL STUDY OF PATIENTS ADMITIED TO AN EMERGENCY DEPARTMENT AFTER A FALL. I. Tonolli-Serabian V. Lafay O. Sarrut J.G. Velut H. Roux Service d'Accueil des Urgences, CHU NORD et Service de rhumatologie, Hopital Conception, Marseille, France Most wrist and hip fractures results frorn a fall in osteoporotic patients. In order to define the profile of the "fallers" we carried out a prospective study on the 174 adult patients admitted to the Emergency department after a fall between 10 and 28 of May 1995. The "fallers" were compared with the 1451 other adult patients admitted during the same period; then we compared the "fallers" older than 65 and the "fallers" younger than 65 (chi square test). The "fallers" represented 10.7% of the total of patients. They were characterised by a greater age (48±24 VS 39±18) and a higher proportion of fernales (sex ratio 0.9 VS 1.5). 32% of the "fallers" were over 65. At this age the fall was often the reason for admission (25% VS 8.5%). This sub-group of "old fallers" In comparison with the sub-group of "young fallers" was characterised by: a high proportion of females (sex ratio 0.28 VS 1.47) a previous disability In 25% of the cases, a frequent history of previous fall (44% VS 17%)and a frequent chronic use of medication (60% VS 17%). While the rate of injured patients was the same in both groups (89%), the consequences of the fall were more severe in the sub-group of old "fallers". After 65 the rate of fractures (31% VS 14%) and the rate of hospitalisations (62% VS 29%) were significantly higher.

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PDD5 EPIDEMIOLOGICAL STUDY OF PATIENTS OVER 65 ADMITIED TO AN EMERGENCY DEPARTMENT AFTER A FALL. I. Tonolli-Serabian M. Gulessian V. Lafay A.L. Demoux C. Bel H. Roux. Service d'Accueil des Urgences, CHU Nord et Service de Rhumatologie, H6pital de la Conception, Marseille, France Most wrist and hip fractures results from a fall in osteoporotic patients. In a previous study we showed that one third of the patients admitted to an emergency department after a fall were over 65. In this population the fall results in a fracture in one third of the cases and leads to a hospitalisation in two thirds of the cases. To define the profile of these "old fallers" we compared them to the other patients over 65. We conducted a retrospective study based on the 5230 adult patients admitted to the emergency department from 1 April to 31 May 1997. 774 patients (14.8%) were over 65, the sex ratio being 0.83. Among these patients, a fall was the motive for admission for 223 (28.8%); 18% of the male patients and 42% of the female patients. The sex ratio of fallers was 0.33. Only 8% of heart disease patients, 16% of neural disease patients and 14% of endocrinal disease patients had experienced a fall. The survey revealed previous chronic illness three times more often in non fallers. Falls due to a mechanical cause represented 80% of traumatic admissions. Falls were responsible for 86% of fractures, 75% of luxations, 50% of sprains and 73% of contusions and wounds. Conclusion: Falls in old people are responsible for a large majority of traumatisms. They often happened to previously healthy women.

PDD6 HEIGHT AND FEMORAL BONE MINERAL DENSITY A. Yaliman. A. Oral. D. Sindel. R. Di§Ci Istanbul University, Istanbul Medical School Department of Physical Medicine and Rehabilitation, Department of Biostatistics and Demography Istanbul, Turkey The strength of the femur neck decreases and the risk for hip fracture increases with age. Bone strength of proximal femur is correlated with bone density but not all skeletal influences on hip fracture risk are related to bone mineral density (BMD). Hip axis length and other characteristics of proximal femoral geometry and height may also alter the risk of fracture. Our objective was to evaluate whether there is an association between height and femoral bone density. We studied 688 women aged 26-80 years (mean age 56.9±9.76 years) with no history of medication or disease known to alter skeletal metabolism. BMD values were measured by using dualenergy X-ray absorptiometry (DXA; Hologic QDR 1000) at the hip. Pearson's correlation analysis was used to determine the association between height and femoral BMD values. The mean height olthe participants was 157.7±6.1 cm. BMD values of the total hip, femoral neck, trochanter, intertrochanter and Ward's triangle were significantly correlated with height. Correlation, coefficients ranged from r=0,233 to r=0,306 (p<0.01). There was no significant correlation between height and BMD values of the total hip and its subregions for the premenopausal women but the BMD values at all sites were correlated significantly with height for the 568 postmenopausal women. We grouped the participants according to their body mass index (BMI) there was no correlation between height and BMD values for the group of women with BMI values were lower than 20, but height was significantly correlated with BMD values at all sites for groups of women with BMI values were higher than 20. In conclusion, we found an association between height and femoral bone mineral density.

PDD7 DETERMINANTS OF BONE MINERAL DENSITY AND EFFECTS AT DIFFERENT SKELETAL SITES D. Sindel A. Oral A. Yaliman R. Di§Ci Istanbul University Medical School, Department of Physical Medicine and Rehabilitation, Department of Biostatistics and Demography, Istanbul Turkey In order to identify determinants of bone mineral density (BMD) and effects at different skeletal sites, BMD was measured by dual energy X-ray absorptiometry (DXA) at the anteroposterior spine and hip in 902 women whose ages ranged from 26-84 years. Women were classified as having osteoporosis (OP) if T-score <-2.5 and with low bone loss if -2.5 25 than those BMI <25 at all sites (p<0.01) except the Ward's triangle where BMD was the lowest in both groups. In conclusion aging, the age at menopause, years since menopause, number of pregnancies and body mass were found to be significant determinants of bone mineral density at the anteroposterior spine and the hip.

PODS CORTICOSTEROID-INDUCED OSTEOPOROSIS IN ELDERLY AUSTRALIANS: UNDERDIAGNOSED AND UNDERTREATED? C. Trescoli J. Tulloch T. Masud* St George's Hospital & Inner Eastern Geriatric Service. Kew. Melbourne, Australia, *Health Care of the Elderly, Nottingham City Hospital, Nottingham, UK Introduction: Although often effective in the treatment of inflammatory conditions, long term oral corticosteroid therapy (LTOCST) represents a major iatrogenic cause of osteoporosis and fractures in the elderly. We aimed to study the clinical prevalence and management of corticosteroidinduced osteoporosis in elderly patients on LTOCST. Method: Retrospective study of 50 consecutive elderly patients (mean age: 81 years. 78% women) referred to our unit for geriatric assessment taking LTOCST (mean daily dose Prednisolone: 6.5 mgr) for more than one year (mean period: 9 years). Using a standardised questionnaire approach the patients and their General Practitioners were interviewed and the medical notes were reviewed with regard to osteoporosis related clinical symptoms, investigations and treatment. Results: 37 patients (74%) complained of new or exacerbated backache (60% of them had documented spinal fractures). 37 (74%) had fractures (38% spinal only, 49% non-spinal only and 22% both spinal and nonspinal fractures). Osteoporosis diagnosis was considered in 26 (52%) patients and confirmed in 25 (16 with spinal X-rays, 1 with DXA and 8 with clinical diagnosis). 21 patients were treated with calcitriol and 4 with alendronate. 14 patients with documented fractures (57% of them with spinal fractures) were not taking antiosteoporotic treatment. Incidentally. 15 patients (30% of the total sample) were referred to our unit because of osteoporosis related symptoms. Discussion: 43 patients (86%) had new backache or fractures likely to be due to osteoporosis. However only in 26 of these patients (60%) osteoporosis was considered and confirmed in 25 of them. Elderly patients on LTOCST are most at risk of developing osteoporosis and early diagnosis and treatment should be attempted to prevent fractures in this group .

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POOg RISK FACTORS FOR REDUCED BONE MASS IN CHRONIC

POll PREVALENCE OF OSTEOPOROSIS IN S. MIGUEL ISLAND (AZORES,

HAEMODIALYSIS PATIENTS T. Masud M.w. Taal D. Green M.J.D. Cassidy City Hospital, Nottingham, UK Renal osteodystrophy and osteoporosis result in considerable morbidity in patients with end-stage renal disease. By virtue of their age, post -menopausal status (in women), disorders of vitamin Dand parathyroid hormone (PTH) metabolism, treatment (including previous corticosteroids) and sedentary lifestyle, haemodialysis patients may be expected to be at risk for developing osteoporosis, but little is known about the relative importance of these factors. We aimed to investigate the relationship of a wide range of factors with bone mineral density (BMD) and to determine the prevalence of osteoporosis and osteopenia in a heterogenous group of chronic haemodialysis patients. Dual energy x-ray absorptiometry measured femoral neck and total hip BMD in patients attending the haemodialysis unit. A trained researcher documented demographic, clinical and biochemical data from the casenotes and interviewed the patients for dietary and phYSical activity levels using validated questionnaires. Multiple linear regression analysis was used to identify significant risk factors associated with low bone mass. 88 patients (48 men), aged 18-87 years (mean = 58±17) were studied. The prevalence of osteopenia (T$-1, >-2.5) and osteoporosis (T$-2.5) were 48.9% and 19.3% respectively. BMD had significant negative associations with age, "intact" PTH, current gastric acid suppression therapy, female gender, age at menarche, previous fracture historY,dialysate calcium concentration and serum ferritin levels. Significant positive associations were found with weight, haemoglobin concentration, serum calcium, average serum phosphate, oral calcium supplementation, milk intake in childhood, parathyroidectomy history and (surprisingly) weekly heparin dose. Previous corticosteroid use and activity levels were not significant associations. In conclusion, whilst confirming previous data suggesting the importance of PTH-related bone disease in affecting BMD in such patients, we have found that some other factors which are known to be risk factors of osteoporosis, are also important. In addition, we have reported a negative association between gastriC acid suppression therapy and BMD as anew observation.

POlO PREVALENCE OF OSTEOPOROSIS IN PORTUGAL J.C. Branco V. Tavares A. Briosa R. Costa R. Feliciano A. Rola and Portalegre, Evora, Santarem and Amarante Study Groups of Osteoporosis. SPODOM and APOROS. Portugal Objective: Study of epidemiological characteristics of osteoporosis and densitometric values in the Portuguese population. To date four districts from different regions (north, south, inland, coast) were evaluated. Methods: One thousand two hundred and forty seven individuals were randomly recruited from the files general practitioners and divided in five groups: Group I - 288 post-menopausal women between 51 and 80 years; Group II -222 premenopausal women between 21 and 30 years; Group III -244 premenopausal women between 31 and 40 years; Group IV -244 premenopausal women between 41 and 50 years; Group V-249 men between 51 and 80 years. All individuals were submitted to a clinic and epidemiological questionnaire, a clinical observation, and awrist DEXA measurement (pDEXA -Nordland-Stratec). Results: Mean age was 43.9±15.1 years forthe 998 women and 64.9±8.5 years for the 249 men. Mean age of menopause in group I was 48.1±5.2 years. The following table shows the results of osteoporosis prevalence (percentage) in the four regions (WHO definition)

Amarant Portaleg Evora Santar Total

GI

Gil

Gill

GIV

GV

56.6 73.8 54.9 45.2 59

6.7 5 14.5 10.7 9

6.2 12 11 5.1 9.4

2.7 15.3 20 5.4 13.5

4.1 4.8 4.9 2.8 4.4

PORTUGAL) V. Tavares J C. Branco G. Figueiredo J. Morgado and S. Miguel Study Group of Osteoporosis. APOROS and SPODOM. Portugal Objective: Study of epidemiological characteristics of osteoporosis and densitometric values in the population of S. Miguel Island, Azores. Methods: Two hundred and fifty individuals were randomly recruited from the files of general practitioners and divided in five groups: Group I 73 post-menopausal women between 51 and 80 years; Group II - 41 premenopausal women between 21 and 30 years; Group III - 47 premenopausal women between 31 and 40 years; Group IV - 45 premenopausal women between 41 and 50 years; Group V - 44 men between 51 and 80 years. All individuals were submitted to a clinic and epidemiological questionnaire, a clinical observation, and DEXA measurements of lumbar spine and hip (Nordland XR 36). Results: Mean age was 44.6±15 years for the 206 women and 62.2±8.1 years for the 44 men. Mean age of menopause in group I was 46.2±6.4 years. ConSidering the WHO definition, the prevalence of osteoporosis in premenopausal women was low (Group II: 0%; Group III: 4.3%; Group IV: 2.2%). Prevalence of osteoporosis in post menopausal women was 31.5% while in men aged over 51 years was 36.4%. In men disease prevalence did not correlate with body mass index or reference to alcohol ingestion. Conclusions: In S. Miguel Island 1} prevalence of osteoporosis in premenopausal women was irrelevant; 2} after the menopause prevalence rises significantly; 3} in men over 51 years osteoporosis prevalence was higherthan in post-menopausal women; 4} these differences could not be explained by studied risk factors; 5} sample number must be enlarged in order to elucidate these results.

P012 RISK OF SUBSEQUENT HIP FRACTURE IN ELDERLY ORTHOPAEDIC PATIENTS Klaus Hinds" Jes Bruun Lauritzen Departments of Orthopaedic Surgery, Hvidovre and Bispebjerg Hospital. University of Copenhagen, Denmark Purpose: To evaluate the risk of subsequent hip fractures in older orthopaedic patients. Methods: A cohort of 678 patients, consecutively admitted to an orthopaedic department was established. All patients were 75 years of age or older. At admittance they underwent a structured interview. The patients were followed for at least one year. Risk factors were evaluated through a multivariate Cox regression procedure estimating the Incidence Rate Ratio (IRR) adjusted for the effect of other variables (RRI AD ) Results: The 678 patients were followed for a total of 835 person-years and 30 new hip fractures occurred with an Incidence Rate of 3,6% [95% CI: 2.5-5.1]. The table shows the variables included in the Cox regression analysis with the corresponding IRR (univariate analyses) andlRR ADJ (multivariate analysis):

Osteoporosis was significantly more prevalent in the 4 female groups in the two south and inland districts (Portalegre and Evora) than in the north (Amarante) or the coast (Santarem). Osteoporosis prevalence in men was similar in all districts. Conclusions: The partial results of this ongoing study reveal that: 1} osteoporosis prevalence is greater in inland and south districts than in the north and coast; 2} osteoporosis is more prevalent in women, particularly post-menopausal, than in men.

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Sex (male sex) Age (every 5th year) Dementia Admitted after fall Tobacco (> 10/day) BMI (+ 1 SD) Medical disease Dizziness Nursing home Admitted after hip fracture Impaired Vision

IRR [95% CI]

IRR ADJ [95% CI]

1.3 [0.6 - 3.0] 1.3 [1.0 - 1.9] 2.2 [1.0 - 4.6] 7.2 [1.7 - 30] 2.6 [1.0 - 6.3] 0.7 [0.4 - 1.2] 1.4 [0.6 - 3.2] 1.3 [0.6 - 2.7] 2.5 [0.9 - 7.1] 1.5 [0.7 - 3.0] 2.2 [1.0 - 4.6]

2.1 [0.9 - 5.0] 1.2 [0.8 -1.7] 2.1 [1.0 - 4.5] 5.8 [1.3 - 25] 3.3 [1.3 - 8.7]

Conclusion: In elderly orthopaediC patients the risk of a subsequent hip fracture is increased in males, in patients with advanced age, in demented and in patients admitted after a fall. Smokers had more than threefold increased risk of a subsequent hip fracture.

P013 RISK FACTORS FOR HIP FRACTURES IN ELDERLY ORTHOPAEDIC

P015 BONE DENSITY OF THE LUMBAR SPINE, HIP, AND PERIPHERAL

PATIENTS Klaus Hinds\! Jes Bruun Lauritzen Departments of Orthopaedic Surgery, Hvidovre and Bispebjerg Hospital. University of Copenhagen, Denmark Risk factors for hip fractures in very old persons may differ from risk factors in younger. The purpose in this study was to evaluate risk factors for hip fractures in orthopaedic patients older than 74 years of age. Method: A case-control study including 1,684 patients, aged 74 years or more, consecutively admitted to an orthopaediC department. Hip fractures were sustained in 547 cases whereas 1,137 had other diagnoses. Informations regarding potential risk factors were collected during a structured interview at admittance. In a multivariate logistic regression procedure the potential risk factors were evaluated. Results: The table shows the adjusted Odds Ratios (OR'dj) for variables having independent and statistically significant importance as risk factors for hip fracture. Age and dementia were interacting and stratified analyses were performed. ORadj

FRACTURES T.V. Barkova, L.1. Benevolenskaya E.E. Mikhailov Institute of Rheumatology, RAMS, Moscow, Russia Subjects and methods: Our study was carried out in the frame of EPOS trial. 213 participants from the epidemiological sample of Moscow region passed bone mass measurements of the of the lumber spine (LS) and femoral neck (FN) (Hologic QDR 1000). Retrospective fracture (RF) history after 40 years was collected by questionnaire and interview. Results: Fracture due to fall was found in 21 % (n=27) of women and 15% (n=13) of men. Over 40% of the fractures were of the wrist. There were no significant differences in age, anthropometric properties and duration of menopause between RF group and non-fracture (NF) group. BMD values were significantly lower in the LS in the RF males compared with their NF counterparts, but not in FN. In females there was significant difference in the FN BMD between RF and NF groups, but not in the LS. On the basis of their BMD values, the subjects were assigned to three groups, according to WHO criteria (T score): normative, osteopenia and osteoporoSiS. The prevalence of osteoporosis on the basis of LS BMD measurements of RF vs NF persons was 31 % and 10% respectively in males and 30% and 18% respectively in females; on the basis of FN measurements the prevalence of osteoporosis was 31 % and 19% in males and 37% and 15% in females respectively. Conclusion: our study suggests that patients with peripheral fractures must be rated as persons of high risk, who necessitate BMD measurements.

[95% CIJ

Sex (male sex) Age (5 years increase)

0.8 [0.6 - 1.2J Demented: 1.0 [0.8 - 1.2J non-demented: 1.5 [1.2 - 1.7J Dementia < 80 years: 4.1 [2.1-8.1J 80 - 89 years: 2.1 [1.3 - 3.0J >= 90 years: 0.9 [0.5-1.8J Medical illness 1.8 [1.3 - 2.41 Dizziness [1.4 [1.1 - 1.8J Tobacco (> 10 per day) 1.6 [1.1-2.4J Body mass index (+ 1 SO) 0.65 [0.55 - 0.79J Visual impairment, nursing home or previous hip or forearm fractures, none statistical significance.

P016 OSTEOPOROSIS AND OSTEOPENIA PREVALENCE IN WOMEN

Conclusion: Dementia is important as a risk factor for hip fractures in the elderly subjects up to 90 years of age. Advanced age is only a risk factor for non-demented subjects. The effect of these two variables should be included in future studies regarding risk factors for hip fractures.

P014 RISKS AND CHARACTERISTICS OF FALLS AMONG ELDERLY ORTHOPAEDIC PATIENTS Klaus Hinds\! Jes Bruun Lauritzen Departments of Orthopaedic Surgery, Hvidovre and Bispebjerg Hospital. University of Copenhagen, Denmark Falls and osteoporosis are linked together as important causes of hip fractures. The purpose of this study was to describe falls leading to admittance to an orthopaediC department. Methods: A consecutive series of 1,170 patients, more than 74 years of age, admitted to an orthopaedic department after a fall were interviewed at admittance. Additionally, potential risk factors were recorded. The influence of the risk factors was evaluated in a multivariate logistic regression procedure. Results: Risk of falling was increased in women (OR 1,8) and by advanced age (Odds Ratio 1.5 for every 5th year), dementia (OR 2.1), dizziness (OR 1.7) and self reported tendency for falling (OR 2.5). The risk was lower among patients with a previous hip fracture (OR 0.50). At the interview 966 patients could give some information of the fall. Most falls occurred in the morning or afternoon (38% and 34% respectively) whereas 18% occurred in the evening and 10% during the night. Toilet visiting was related to 70% of the falls during nights and to 12% of the falls at other times. In 47% the patient had stumbled, in 22% the fall was caused by a blackout, in 24% the reason was unknown, and in 7% somebody else caused the fall. There was no difference in time of day, place, activity, or cause between falls creating hip fractures or other injuries. Conclusions: Female sex, advanced age, dementia, dizziness and self reported tendency for falling were independent risk factors for severe falls. Only 10% of the falls occurred during nights and then most often in connection with toilet visiting. Less than half of the falls were caused by environmental factors. Falls causing hip fractures did not differ from falls causing other injuries in respect of time, place, activity, or cause .

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POPULATION OF THE MOSCOW REGION N. Toroptsova V. Kovalev M. Ushakova L. Benevolenskaya Institute of Rheumatology RAMS, Moscow, Russia Objective: to study the prevalence of osteoporoSis in lumbar spine among women 55 and elder. Material and Method: cross-sectional study of 2155 women using standardized questionnaire, bone mineral density with DEXA (Hologic 4500 A and W), x-ray examination of thoracic and lumbar spine of 697 patients with morphometriC analYSis, which was done in Department of Radiology Benjamin Franklin Medical School, Berlin. Results: The mean value of BMD (g/cm') was 0.954+0.032 for lumbar spine. The prevalence of osteoporoSis defining in women as a bone mineral density of 2.5 standard deviations or more below the average value for healthy premenopausal adults (T-score -2.5 or less) was 29.8%. The prevalence of osteoporOSiS increased with age - from 19.6% in 55-60 years to 32.1 % in 75-79 years. The prevalence of osteopenia (T-score <-1.0 to >-2.5) was 43.8%, no differences among age groups were discovered. Spine osteoporotiC fractures were revealed in 107 individuals (15.3%) by the morphometric analysis of x-ray images. The established risk factors for osteoporoSis were age, duration of menopause, thinness, hip fracture in parents. Conclusion: Our data presents the high prevalence of osteoporOSiS and osteopenia in postmenopausal women and indicates that prevention of osteoporosiS we should start in the premenopausal period.

P017 VITAMIN 0 STATUS IS THE MAJOR DETERMINANT OF CALCITRIOL

CIRCULATING LEVELS IN ITALIAN POSTMENOPAUSAL WOMEN P. Bettica M. Bevilacqua T. Vago G. Norbiato Endocrinology Dept., "L. Sacco" H. Milan, Italy The vitamin 0 endocrine system affects bone metabolism mainly via its active metabolite, 1,25 dihydroxyvitamin 0 (1,25(OH)2D). 1,25(OH)2D circulating levels depend both on vitamin 0 status and on hepatic and renal activation. High prevalence of vitamin 0 deficiency was found among free-living postmenopausal women in Northern Italy. On the other hand, contradictory results have been reported on a possible decrease in renal activation in postmenopausal women. In this study we have evaluated which are the major determinants of 1,25(OH)2D serum levels in a large sample of postmenopausal Italian women. Patients and Methods: Blood and 24-hour urine samples were collected by 110 healthy postmenopausal women, mean age 60.3±8.13 years; calcium (sCa), phosphorus (sP), creatinine (sCr), intact parathyroid hormone (PTH), 25-hydroxyvitamin 0 (25(OH)D) and 1,25(OH)2D were measured in serum; calcium (uCa) phosphorus (uP) and creatinine clearance (CrCI) in urine. Simple and stepwise regression were used to determine the major determinants of 1,25(OH)2D circulating levels. 1,25(OH)2D circulating levels were also compared in groups of subjects subdivided based upon their age, creatinine clearance and vitamin 0 status. Results: sCa, sP, sCr, uCa and uP were in the normal range for all patients; creatinine clearance was 74.8±24.5 ml/min (mean±SD). 25(OH)D, 1,25(OH)2D and PTH serum levels were 19.6±9.8 ng/ml, 32.6±11.8 pg/ml and 45.7±17.4 pg/ml, respectively. 1,25(OH)2D correlated only with 25(OH)D (r=0.31, p<0.002). A significant correlation was found also between 25(OH)D and PTH (r=-0.22, P70 ml/min) and low «70) creatinine clearance, while it was reduced in women with low «12 ng/ml) compared to women with normal vitamin 0 status (28.2±13.1 vs 34.5±10.7 pg/ml, p<0.02). Finally when women were subdivided into three age groups, again no difference in 1,25(OH)2D was found. In conclusion our results show that 1,25(OH)2D serum levels are mainly determined by vitamin 0 status and that neither renal function nor age exert any significant influence on 1,25(OH)2D circulating levels in postmenopausal women with normal serum creatinine levels.

PD18 HYPERTENSION. A PROTECTIVE FACTOR AGAINST HIP FRACTURE? D. Mellstrom, J.O. Olsson M. Gunnes J. Skag E. tifjord J. Stakkestad O.Johnell Dept of Geriatric Medicine University of Goteborg, Dept of Ortop University Lund/MalmO, Sweden. Center of Osteoporosis, Haugesund/ Bergen, Norway Earlier studies have indicated that treatment with thiazides might be a protective factor against hip fracture. The aim of this study was to examine if women with hypertension had lower risk for hip fracture. Methods: A postal enquiry regarding risk factors for osteoporosis was collected from 108.000 women aged 50 to 82 years in Bergen, Haugesund and Hamar, Norway. Results: Women with medication against hypertension had a lower risk for hip fracture and radius fracture but a higher risk for ankle fracture. Odds ratio Hipfx Radius fx Ankle fx

0,88 0,89 1,4

CI (0,79-0,98) CI (0,85-0,94) CI (1,26-1,51)

Odds ratio Diabetes Cortisone treatment Smoking Walking 5 km daily Maternal fracture Estrogen treatment Oophorectomi Hysterectomi BMI >25 .

4,0 1,3 0,7 0,7 0,8 0,98 NS 1,3 1,2 2,4

Women with BMI>30 had higher risk for ankle fracture OR 1,52 and lower risk for hip fracture OR 0,56 Conclusion: Women with hypertension had several protective and risk factors for osteoporosis. The risk for hip fracture was lower in women with hypertension.

PD19 EVALUATION OF THE RESULTS OF DUAL-ENERGY X-RAY ABSORPTIOMETRY SCAN IN 1997 IN A REGIONAL HOSPITAL J.K.J. Deegens', W£...Lrun.s.3, P.A.R. Rombout', K. Bakker' 'Department of internal medicine and 2Department of radiology, Spaarne Ziekenhuis Heemstede, 3Department of rheumatology, Free University of Amsterdam, the Netherlands Purpose of the study: To evaluate the indications for DXA examinations and to see if risk factors were reported. To score the outcome of DXA measurements requested by GP's and SP. To assess if appropriate treatment was given in case of osteoporosis. Methods: According to WHO guidelines osteoporosis is defined as a Tscore of -2.5 or less and osteopenia as a T-score between -2.5 and -1, measured at the lumbar spine (LS) or femoral neck (FN). All patients who had their BMD measured for the first time in 1997 were included in the study, patients younger than 35 years were excluded. Only patient charts from specialists were reviewed. Results: A total of 809 patients underwent a DXA scan. 555 (69%) were referred by a GP and 254 (31%) by aSP. 7 patients (2 from GP and 5 from SP) younger than 35 years were excluded. Reasons for requesting a DXA scan were prednisone therapy (29%), endocrinologic disorders (12%), low back pain (9%), early menopause (6%), fractured vertebrae (4%), patients request (4%), family history of osteoporosis (4%) and miscellaneous (32%). Most DXA scans were requested by internists (49%), rheumatologists (22%) and gynaecologists (16%). Mean T-scores of patients referred by GP's were -1.31 (SO 1.57) for the LS and -1.88 (SO 1.30) for the FN. For specialists mean T-scores were -1.41 (SO 1.72) for LS and -2.03 (SO 1.45) for FN. 39% (n=218) of DXA scans requested by GP's and 49% (n= 121) requested by SP showed osteoporosis. Osteopenia was seen in 41% (n=225) of patients referred by GP's and 31% (n=78) of patients referred by SP. 30% (n=36) of patients with osteoporosis from SP were treated with alendronate, 55% (n=66) with etidronate, 2% (n=3) with hormone replacement therapy (HRT), 4% (n=5) miscellaneous, 6% (n=7) was not treated and 3% (n=4) was not known. Few patient charts reported risk factors for osteoporosis: calcium intake was recorded in 7%, menopause in 13% and a family history of osteoporosis in 17% of the patients charts. Summary: 802 patients underwent a DXA scan 42% showed osteoporosis and 38% showed osteopenia. 91 % of patients with osteoporosis were treated according to international guidelines, 3% is not known, 6% were not treated. Risk factors for osteoporosis were reported in less than 17% of the patient charts.

Protective and- risk factors for osteoporosis in women with hypertension .

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PD2D RISK FACTORS OF OSTEOPOROSIS IN 464 PATENTS WITH RHEUMATOID ARTHRITIS Till Uhlig Glenn Haugebera Tore K. Kvien*. Jan A. Falch**. Johan I. Halse * * * *Oslo City Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, * *Dept. of Internal Medicine, Aker Hospital, Oslo, ***Osteoporosis Clinic, N-0172 Oslo, Norway The aim was to identify risk factors for osteoporosis (OPO) in hip and lumbar spine in a cross-sectional, representative sample of patients with rheumatoid arthritis (RA). Patients were recruited from acommunity based register of RA patients comprising 1620 cases. A representative sample of 464 patients 20-70 years of age (mean (SO) age 54 (11.5) years, disease duration 12 (9) years) was examined with a complete joint examination, disease history, self-reported health status measures, body mass index (BMI), laboratory parameters of inflammation and with bone densitometry of the hip and lumbar spine (Lunar Expert). OPO in total hip/lumbar spine L2-L4 as defined by T-score <-2.5 was found in 12.5/14.5%. Multiple logistic regression analyses, adjusting for age, gender, BMI and use of prednisolone revealed a persistent significant, altered risk (odds ratio (OR) with 95% confidence intervals (CI)) of OPO in total hip and lumbar spine for the highest age group 61-70 years against 20-40 years (OR 16.8, CI3.8-75.6 for hip, OR 36.9, CI4.8-284.1 for lumbar spine), for BMI second highest (OR 0.23, CI 0.10-0.54 for hip, OR 0.18, CI 0.07-0.44 for lumbar spine) or highest (OR 0.08 CI 0.02-0.24 for hip, OR 0.18, CI 0.08-0.42 for lumbar spine) quartile and for current use of prednisolone (OR 3.75, CI1 .57-8.92 for hip, OR 3.85, CI1 .80-8.26 for lumbar spine). Measures of disease activity with adjusted risk of OPO were only significant for total hip (number deformed jOints (OR 1.12 CI 1.04-1.21) or swollen joints (OR 1.06 CI 1.01-1.12), "doctor's global assessment" (OR 1.02 CI1.00-1.03)), whereas gender, disease duration, number of tender joints, laboratory markers of inflammation, or modified disease activity score were not independent predictors of OPO at either location. OPO localised in total hip or lumbar spine in RA patients is associated with current use of prednisolone, age, BMI, and some disease activity measures. The effect of disease activity and control of inflammation on the development of OPO in RA needs further exploration in longitudinal studies.

PD21 A CLAIMS DATA ASSESSMENT OF PATIENT COMPLIANCE WITH ALENDRONATE D.L. Faulkner" L.M. Lucy" H. Heath', M.E. Minshall', D.B. Muchmore' 'PCS Health Systems, Inc., Scottsdale, USA, 'Eli Lilly and Company, Indianapolis, USA Controlled trials have defined the optimal beneficial impact of alendronate on bone. However, controlled trials are conducted among patients who are likely to cooperate fully with prescribed regimens. Alendronate compliance outside of the controlled trial setting is likely to be lower, resulting in potentially suboptimal therapeutic effects. The purpose of this study was to use a prescription claims database to estimate alendronate compliance in the general insured population in the USA. A retrospective longitudinal study was conducted among 492 women (ages 45-64 years at baseline) who were new alendronate users. Study subjects were followed for 18 months. For each patient, a series of medication availability ratios (MARs) was constructed, whereby an MAR was defined as the days' supply received during a refill interval divided by the total calendar days in the interval. Time-to-noncompliance was defined as the number of days elapsing before any MAR fell below 0.75 (Method 1),0.50 (Method II), and 0.25 (Method III). Kaplan-Meier survival probabilities were calculated. USing Method I, the percentages of women who were compliant at 6,12, and 18 months were 29.5%, 15.6%, and 11.6%, respectively. Six-, twelve-, and eighteen-month compliance probabilities were 44.1%,28.9%, and 25.8% using Method II, and 55.5%, 47.4%, and 43.5% using Method III. This study suggests that no matter which method is used to define compliance, compliance with alendronate in the general insured population is lower than that reported in controlled trials. The positive impact of alendronate on osteoporosis may be diminished unless patient compliance is improved .

PD22 PREVALENCE OF OSTEOPOROSIS IN OLDER HUNGARIAN FEMALES AND MALES Gy. P06r" ~', E. Lanyi" M. Lunt', J. Reeve' National Institute of Rheumatology, Budapest, Hungary' Institute of Public Health, Cambridge, Great Britain' There are very few valid data on the number of osteoporotic individuals in different populations. The aim of our study was to determine the prevalence of osteoporosis by denSitometry in Hungarian women and men aged 50 years and older. A random sample of 470 individuals (247 women, 223 men) stratified in six 5-year age bands was recruited from a populationbased health register of a district of Budapest. The age bands (50-54, 5559,60-64,65-69,70-74,75 years and over) contained 30-48 persons in either sex. The mean age of females was 63,9 (50-87) years, that of males was 63,6 (50-91) years. Bone mineral density of the lumbar spine (L,-L,) and femoral neck was measured by dual energy X-ray absorptiometry (NORLAND XR-26). The WHO diagnostic criteria for osteoporosis were used in males as well. Reference values and standard deviations for T-score were derived from BMD data gained on the same machinll of 76 young healthy persons (38 females, 38 males) aged 20-34 years, free of established risk factors for osteoporosis. The prevalence of osteoporosis in Hungary was 28,3 (95% CI: 22,734,0) in females and 23,3 (95% CI: 17,8-28,9) in males, respectively in the population aged 50 years and older. The prevalence increased with age in women but not in men. Osteoporosis predominated in males in the age bands 50-59 and in females 60 years and over. Adjusting the results to the population structure of Hungary we can conclude that 597 000 (95% CI: 489 000-705 000) older women and 314 000 (95% CI: 240 000-388 000) older men are affected by osteoporosis out of 10 million inhabitants. The mean Hungarian BMD values measured at the lumbar spine (female: 0,919 g/cm', males: 0,986 g/cm') have been considered very low in both sexes compared to the standardised values of 13 other European countries in the frame of European Prospective Osteoporosis Study.

PD23 SHORT-TIME OUTCOME OF THE REHABILITATION OF SENILE OSTEOPOROTIC HIP-FRACTURE P. Wagener R. Hein G. Meyer-Duncker Geriatisches Rehabilitationszentrum Bruchhausen-Vilsen - Germany Introduction: senile osteoporotic hip-fracture (SOFH) can be a severe life threatening event for old persons. Epidemiological studies show that only 40% of those affected regain their functional status as before the fracture, 25% afterwards need care in a nursing home. Mortality is estimated up to 10%. Objective: Investigation of the outcome of senile osteoporotic hip fractures, rehabilitated in a specialised geriatric centre. Methods: Clinical/functional assessment of 159 pts. (ma age 80 years, 67% females, ma days of rehabilitation: 30 days) in the early phase after SOFH. Results: 1: After a 3 week rehabilitation 80% of patients were mobilised with help of either rollator or stick -20% kept a worse functional status as before the fracture. In a social view, 10% had to move to an old people centre, 12% needed steady care. Mortality was 2%. 10% had to be readmitted to hospital. Conclusion: SOFH in old people is a severe event with a great risk of permanent handicap. Specialised rehabilitation is necessary and can improve prognosis.

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P024 EFFECTS OF LONG-TERM HORMONE REPLACEMENT THERAPY ON BONE METABOLISM AND DENSITY IN WOMEN WITH DIFFERENT SMOKING AND ALCOHOL CONSUMPTION HABITS A. Leino O. Impivaara M. Kaitsaari Research and Development Centre of Social Insurance Institution and Central Laboratory of University Hospital, Turku, Finland This study describes the influence of moderate alcohol consumption ($140 g/week) and smoking ($20 cigarettes/day) on bone mineral density (BMD) and levels of bone resorption and formation markers in postmenopausal women. An age cohort of 418 healthy women aged 45 years followed at five years intervals up to 55 years constituted the basis for this study. At both 50 and 55 years of age, 107 women consistently reported that they were not smoking and abstained from alcohol, whereas 115 women were consistent non-smokers but moderate consumers of alcohol. On the other hand, 57 women were smokers who also consumed alcohol. Only 20 women reported to be consistent smokers who abstained from alcohol. From these, those (126) who had never been on hormone replacement therapy (HRT) and those (n=97) who had had HRT for more than five years (X±Sd=7±2.8 years) formed the present study population. At 55 years of age, significantly higher BMDs at femoral neck and throchanter were observed in women who were non-smoking moderate alcohol consumers with long-term HRT as compared with corresponding women never been on HRT. In these same women the levels of urine resorption markers, type 1 collagen N-telopeptide (NTx) and free deoxypyridinoline (DPD) as well as the serum formation markers, osteocalcin (OC), bone alkaline phosphatase (BAP), amino- and carboxyterminal propeptides of type 1 procollagen (PINP, PICP) were significantly lower in those with HRT as compared with untreated women. Similar effect was also observed in women who were not smoking and abstained from alcohol. However, such effects were not found in women who were smokers using moderately alcohol or were smokers only. These preliminary results suggest that moderate consumption of alcohol apparently does not oppose or prevent the long-term beneficial effects of HRT but may even enhance them, whereas the benefits seem to be nullified by smoking.

P025 NORMAL HUNGARIAN VERTEBRAL HEIGHTS IN A REPRESENTATIVE CROSS-SECTIONAL POPULATION SURVEY Cs. Kiss" M. Szilaayi', D. Felsenberg', TW. O'Neill', A. Silman', G.Y. Poor' National Institute of Rheumatology, Budapest, Hungary' Freie Universitiit, Berlin, Germany' Epidemiology Research Unit, Manchester,Great Britain' The authors' aim was to derive Hungarian normal vertebral heights, height ratios and threshold values. They examined the standardized vertebral morphometric measurements obtained in the European Vertebral Osteoporosis Study. Radiographs were taken according to standardized protocol and morphometric measurements of anterior, central and posterior heights from thoracic 4 to lumbar 4 were made with a semiautomatic technique. The anterior, central, posterior I and posterior II height ratios were calculated for each vertebra. The mean and standard deviation of these ratios for each sex were derived using a statistical procedure to normalize the distribution. From the normally distributed vertebral height ratios the mean and standard deviation give them the threshold values for defining normal vertebraes. Anterior and central vertebral height ratios were smaller in males than females. The authors compared the ratios and threshold values in different European centers using the same method. The data confirm that vertebral height ratios vary between and within populations and the authors suggest that normal values for vertebral height ratios should be derived separately for males and females at each vertebral level. The knowledge of the Hungarian normal vertebral height ratios gives the possibility to carryon multicentre clinical, therapeutic and epidemiologic studies of vertebral deformity in Hungary. Having the normal values the authors suggest the widespread use of morphometry to evaluate vertebral osteoporosis because it can be done in every radiology unit, it is a cheap and easy method for measuring the bone mineral content.

P026 OSTEOPOROSIS AND ITS RISK FACTORS IN THE MESTIZO POPULATION OF COLOMBIA Carlos V Caballero-Uribe Silvia Cuellar Edgar Navarro and Roberto Tamara Centro de Artritis y Osteoporosis, Densomed and Universidad del Norte, Barranquilla, Colombia Osteoporosis is a frequent disease affecting mainly postmenopausal women. Its prevalence is well known in Caucasian and Asian populations. There are few studies assessing the influence of the risks factors for low bone mass in the Latin American populations. PATIENTS AND METHODS: We studied a sample of 352 patients with a social, cfemographic, reproductive and life-style questionnaire of 39 variables, associated with the presence of osteoporosis or low bone mass that patients fill previous to the bone densitometry (DPX alpha LUNAR) in an imagenologic center. Osteoporosis, osteopenia and normal population were defined according OMS (1994) criteria. X2 and ANOVA were included in the statistical analysis. RESULTS: We found 342 women (97.2%) and 10 men (2.8%). In 149 patients had a BMD >-2.5 SO (Osteoporosis 42.3%); 144 patients had a BMD between -1 and -2.5 SO (Osteopenia 40.9%) and in 59 patients BMD <-1 SO (Normals 16.8%). Osteoporotic (62±8 years) were older than osteopenic (56±9 years) and normals (49±6.8) p :0.006; Osteoporotic patients had more fractures (34 (87.3%) vs. 5 (12.8%) p:0.02), history of hysterectomies (47 (34.8%) vs 22 (16.3%) and less use of oral contraceptives (96 (84.2%) vs. 18 (15.2%) p:0.000006) than normal patients. Other risk factors were not statistically associated with osteoporosis. CONCLUSIONS: Although this is a reference center, osteoporosis seems a frequent disease in ourtrietnic population (white, indian and black). Main risk factors for osteoporosis are those associated with age and estrogen balance as in other populations, what suggests that genetic factors could have less influence in its development.

P027 VITAMIN 0 AND DIETARY CALCIUM STATUS IN PATIENTS LIVING IN NURSING HOMES COMPARED TO AMBULATORY PATIENTS J.P. Devogelaer TC. Le Thi D. Dienst G. Depresseux Department of Rheumatology, St-Luc University Hospital, Brussels, Belgium Hypovitaminosis 0 is nowadays considered as a main determinant for hip fracture in elderly people living in nursing homes. The vitamin 0 status of ambulatory patients is comparatively less well known. We have therefore compared the values of serum 250H vitamin 0 and of hip BMD's in 122 females living in nursing homes with those of 102 fully ambulatory females from the outpatient clinic. The result (mean±SEM) are given in the table.

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n= Age (years) 250HD (nmolll) % of values <18 nmol/I S. creat ().lOI/I) Tot. alk. p'se (U/I) Fem. neck BMD (g/cm') Dietary calcium (mg)

Nursing home clinic patients

Outpatients

p

122 83.1±D.6 23.7±1.4

102 74.8±D.6 40.3±2.5

<0.0001 <0.0001

45

16

100.4±3.2

88.2±1.4

0.0010

216.1±6.2

182.8±5.8

0.0001

0.543± 0.009 643.4±31.9

0.011

0.513±D.007 392.9±16.6

<0.0001

There was a positive correlation between 250HD and femoral neck BMDs in ambulatory patients only, with a r amounting to 10.254 (p
P028 REPRODUCTIVE VARIABLES AND FAMILY HISTORY OF OSTEOPOROSIS L. Sinigaglia. M. Varenna L. Binelli. F. Zucchi D. Ghiringhelli. M. Gallazzi* Chair of Rheumatology and * Department of Radiology. "Gaetano Pini" Institute, Milan, Italy The greater risk for osteoporosis (OP) in women with a family history of OP and/or osteoporotic fractures can be considered the clinical result of the genetic determinants which influence bone mineral density (BMD). From a cohort of postmenopausal women we selected 416 subjects who reported a maternal history of postmenopausal hip or wrist fracture and 303 women with one or more sisters diagnosed as having OP after a densitometric assessment (below 2.5 T score). These groups were compared with a sample of 1514 age matched healthy postmenopausal women. BMD was assessed in all subjects by DXA at lumbar level (Hologic QDR 2000). When compared with controls the two groups showed a higher age at menarche (p
P029 PREVALENCE OF OSTEOPOROSIS BY EDUCATIONAL LEVEL IN A COHORT OF POSTMENOPAUSAL WOMEN M. Varenna L. Binelli. F Zucchi D. Ghiringhelli. M. Gallaui*. L. Sinigaglia Chair of Rheumatology and * Department of Radiology "G.Pini" Institute, Milan, Italy Background. To evaluate if the prevalence of Osteoporosis and related risk factors can be influenced by education level as demonstrated for many other chronic diseases. Methods. 6160 postmenopausal women at their first densitometric referral were interviewed about reproductive variables, past and current use of estrogens, prevalence of chronic diseases, lifestyle factors such as calcium intake, physical activity, smoking and overweight. This sample was stratified by years of formal education. Densitometric evaluation was performed by dual-energy X-ray absorptiometry. Results. Age at menarche, past exposure to oral contraceptives, past . or current use of hormone replacement therapy, prevalence of chronic diseases, physical activity, overweight and smoking, showed significant trends according to years of education. Prevalence of Osteoporosis showed an inverse relationship with level of education ranging from 18.3% for the most educated to 27.8% for the least educated women. Multiple logistic regression analysis demonstrated a predictive role towards Osteoporosis by age, age at menarche and menopause, hormone replacement therapy, calcium intake, physical activity and body mass index. Using the lowest education level as reference category, increases in educational status were associated with a significant reduced risk for Osteoporosis (OR 0.76 for 6-8 yrs of schooling; 0.68 for ~g yrs). Conclusions. This study gives evidence of a different Osteoporosis prevalence among educational classes and the protective role played by years of education. If these results will be confirmed in other population studies, public health intervention programs have to consider the socioeconomic and cultural background of population strata at greater risk for Osteoporosis.

P030 THE ASSOCIATION BETWEEN SELECTED RISK FACTORS AND DEMOGRAPHIC VARIABLES ON QUALITY OF LIFE IN ESTABLISHED POSTMENOPAUSAL OSTEOPOROSIS S.L Silvermanl, M E. Minshai!2, ~', KJ:IarJru', ~', ~' 'UCLA, WLA VAMC, OMC, Beverly Hills, USA; and 'Eli Lilly, and Company, Indianapolis, USA Many risk factors for osteoporosis and patient demographics may impact on health-related Quality of life (HRQOL) in patients with osteoporosis. We evaluated selected risk factors and demographic variables on HRQOL in patients with established postmenopausal osteoporosis. We studied osteoporotic patients (n=1417) with vertebra fracture(s) and/or low bone mineral density participating in the MORE (Multiple Outcomes of Raloxifene Evaluation) study, mean age of 68.5±6.8 years, who completed a diseasetargeted, self-administered Quality of life Questionnaire, the Osteoporosis Assessment Questionnaire (OPAQ). We report baseline HRQOL results in four dimensions: physical functioning, emotional functioning, symptoms and social interactions. Age impacted negatively on physical functioning (p
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PD31 THE IMPACT OF A HISTORY OF NON-VERTEBRAL POSTMENOPAUSAL FRACTURES ON QUALITY OF LIFE IN ESTABLISHED POSTMENOPAUSAL OSTEOPOROSIS S.L. Silverman', M.E. Minshall', W. Shen', K. Harper' M.C. Kody', S. Xie' 'UCLA, WLA-VAMC, OMC, Beverly Hills, USA; and' Eli Lilly and Company, Indianapolis, USA Non-vertebral fractures are events that often reveal osteoporosis, yet the impact of non-vertebral fractures on health-related quality of life (HROOL) in patients with established postmenopausal osteoporosis is not known. We specifically evaluated the impact of non-vertebral fractures including ankle, hip (femur), rib, and humerus on HRQOL in patients with established postmenopausal osteoporosis. We studied osteoporotic patients (n= 1417) with vertebral fracture(s) and/or low bone mineral density partiCipating in the MORE (Multiple Outcomes of Raloxifene Evaluation) study, mean age of 68.5±6.8 years, who completed a disease-targeted, self-administered quality of life questionnaire, the Osteoporosis Assessment Questionnaire (OPAQ). We report baseline HRQOL results in four dimensions: physical functioning, emotional functioning, symptoms and social interactions. At baseline, the prevalence of non-vertebral postmenopausal fractures in all patients taking part in the MORE study was 42.8%. The following table summarizes the impact of a history of non vertebral postmenopausal fractures on the four dimensions of HRQOL. OPAQ Domain

No Fractures

;::1 Fractures

p-value

Physical Functioning Emotional Status Symptoms Social Interaction

89.4±12.5 62.3±11.2 67.9±18.6 70.0±14.7

85.8±16.3 59.8±11.6 65.1±19.5 70.5±15.2

< 0.001 < 0.001 0.009 0.488

For patients with a history of ankle (n= 121) or hip fracture (n=55), HROOL was negatively impacted through the physical functioning, emotional status and symptom domains (all p-values ~0.013). For patients with a history of rib fracture, HRQOL was negatively impacted through physical functioning and symptoms (both p-values ~0.016). For patients with a history of humerus fracture (n=76), HROOL was negatively impacted through physical functioning and emotional status (both p-values ~0.002). These data on a history of non-vertebral postmenopausal fractures suggest a significant negative impact on HRQOL for fractures in other parts of the skeleton.

PD32 BASELINE RESULTS FOR THE EQ-5D IN A RALOXIFENE OSTEOPOROSIS TREATMENT STUDY M. Kody', W. Shen" A. Dawson', M. Minshall ' , K...H.a.alli' , P. Dolan' 'Eli Lilly and Company, Indianapolis, USA and 'University of Newcastle, Newcastle, UK The impact of osteoporosis on health-related quality of life (HRQOL) was assessed using the EO-SD (formerly EuroQoL) generiC health instrument. The instrument was administered in the MORE (Multiple Outcomes for Raloxifene Evaluation) study to 964 women with established postmenopausal osteoporosis (mean age: 67.9±6.1 years; mean years postmenopausal: 20.1±7.6 years) in the United Kingdom, Norway, the Netherlands, Belgium, Spain and Sweden. The EO-SD allows for the description and valuation of QOL. We describe baseline self-rated health profiles and valuation of overall health in this osteoporotic population. When asked to describe current health on five dimensions, over 70% of women reported no problems with mobility, usual activities, self-care or anxiety/depression, while only 36% of women reported no problems with pain/discomfort. Women aged 70 years or older more frequently reported problems (some or extreme) with mobility (p<.001) and usual activities (p=0.036). For women reporting problems with usual activities and pain/discomfort, a significant trend was observed with increasing number of vertebral fractures from zero to two or more (p<0.001). A similar association was found between number of vertebral fractures and reported problems with mobility and anxiety/depression (p<0.05). An association was also found between non-vertebral fractures sustained since menopause and reported problems with anxiety/depression (p=0.031). Finally, country differences were found for all five dimensions (p<0.05) .

Women rated overall health on a visual analog scale (VAS) from 0 to 100, representing worst and best imaginable health states, respectively (VAS mean rating: 75.3±18.1). Lower VAS ratings were associated with increasing number of vertebral fractures (p<0.001) as were non-vertebral fractures sustained since menopause (p<0.001). In summary, our findings suggest that the EQ-5D can distinguish between osteoporotic patients with and without vertebral fractures.

PD33 VARIATIONS IN DXA MEASURED HIP STRENGTHS: DO THEY EXPLAIN BETWEEN COMMUNITY VARIATIONS IN HIP FRACTURE RATES IN EUROPE? N.J. Crabtree, H. Kroger, H. Pols S. Grazio, R. Lorenc J. Niis J. Stepan J. Falch, T. Miazgowski, P. Raptou &J. Reeve Institute of Public Health, University of Cambridge, UK & the Lunar equipped EPOS investigational centres The MEDOS study showed large between-community variations in hip fracture rates in Europe. We have investigated the potential contribution of variations in DXA measured hip strength to these differences in fracture rates. Fall Index (FI) is a measure of the resistance to fracture from a force generated during a fall on the trochanter. It is calculated from a Lunar hip BMD measurement as the ratio of yield strength to compressive stress at the weakest point of the femoral neck. We have studied the between-centre variation in hip strength parameters of 1009 community based randomly selected European women aged 5080 from 10 centres participating in the European Prospective Osteoporosis Study (EPOS). All DXA (DPX machines) were cross calibrated using the European Spine Phantom. The scans were all analysed by a single operator using the 'beta' version of Hip Strength Analysis (HSA) software. Rigorous QC procedures excluded a further 54 scans from review, usually due to non ideal positioning of the hip. In a hip fracture study of 60 women, measured 2 weeks after a contralateral hip fracture, the mean FI and femoral neck BMD (FNBMD), adjusted to age 70, were found to be 1.07 (SD 0.36) and 0.661 (0.11 )g/cm' respectively. We then estimated how many subjects in each of the EPOS centres fell below the above values for FI (1.07) and FNBMD (0.661 g/cm'). Chi-squared tests were used to measure the significance of differences between centres. Overall, 22% and 18% of EPOS women were below the FI and FNBMD cut-offs adjusted to age 70. Mean FI for the lowest centre was 81.5% of that of the highest. There was also considerable centre variation in proportions below cut-offs (range for FI 6.3-40%) which was highly statistically significant (x' Tests: FI pdO"; FNBMD pdO· 5). We conclude that community differences in BMD and its geometriC distribution as reflected in HSA are promising candidate mechanisms to explain in part the large community variations in European hip fracture rates.

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P034 PSYCHOSOCIAL IMPACT OF VERTEBRAL DEFORMITY: THE CAMBRIDGE AND HARROW ARMS OF EUROPEAN VERTEBRAL OSTEOPOROSIS STUDY C. Todd J. Reeve C. McClung A. Martin J. Walton E.V. McCloskey Institute of Public Health, University of Cambridge In clinical samples there are small but significant relationships between vertebral deformity and reported disability, pain, and mood. As part of the European Vertebral Osteoporosis Study (EVOS), we sought to clarify the psychosocial impact of vertebral deformity at a population level. EVOS is a multicentre population study of age-sex stratified random sample of 50-80 year aids. Participants underwent a standard interview and spinal x-ray. In addition to standard EVOS protocol, 746 subjects in 2 UK centres, completed a battery of validated psychosocial measures including the Nottingham Health Profile (NHP). Cases of deformity were identified using McCloskey-Kanis method. Analysis uses case-control design. 112 deformities were identified in 79 individuals. Prevalence of deformity increased with age for both sexes; women with deformities were older than controls (p
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PREDICTORS OF EARLIER DEATH FROM BONE MINERAL DENSITY AND BIOCHEMICAL MARKERS OF BONE TURNOVER D. Greenfield" R.A. Hannon', A. Blumsohn', T. Greenfield',~' 'Bone Metabolism Group, Division of Clinical SCiences, University of Sheffield, UK. 'Biostatistics Consultant, Derbyshire, UK The aims of this study were to examine the value of bone mineral density (BMD), biochemical markers, clinical and lifestyle measures in predicting earlier death. 375 women ages 50 to 85 (mean 64.5 years) were selected by age stratified randomisation and recruited from three local general practices and observed over 5years. BMD of the lumbar spine (LS), femoral neck (FN) and total body (TB) and 6 biochemical markers of bone turnover were measured at baseline by DXA. A standardized medical and lifestyle questionnaire was administered by interview at baseline. Risk factors significantly associated with earlier death RISK FACTOR

RELATIVE RISK 95% CONFIDENCE INTERVALS

Prevalent spine fractures Prevalent non-spine fractures Incident non-spine fractures Pyridinoline TRAP LAP Total body BMD Femoral neck BMD

3.16 2.56 4.05 1.51 1.46 1.47 1.86 2.06

1.20,8.34 1.20,5.47 1.50, 10.91 1.21,1.89 1.01,2.12 1.17,1.85 1.25,2.77 1.35,3.14

A univariate model was fitted to identify independent risk factors for prediction earlier death. Factors that provided a significant fit (p
P036 THE INCIDENCE OF OSTEOPOROTIC VERTEBRAL DEFORMITY IN EUROPEAN MEN AND WOMEN: THE EUROPEAN VERTEBRAL OSTEOPOROSIS STUDY (EVOS) D. Felsenberg" G. Armbrecht', T. W. O'Neill', ~" A. J Silman', ~' and the EPOS-Study- Group. 'Osteoporosis Research Group, Dept. of Radiology, Univ. Hospital B. Franklin, Free University Berlin, Germany. 'ARC Epidemiology Research Unit, Univ. of Manchester, UK. 'Institute of Public Health, University Forvie Site, Cambridge, UK The aim of this study was to determine the incidence of vertebral osteoporosis in different regions and populations in Europe. A cross-sectional population-based survey was used. In EVOS the radiographs of 15570 males and females were evaluated and a mean prevalence for vertebral osteoporotic fractures of 11.3% was found. Radiographs of 8630 individuals returned three years later for the follow-up in EPOS (European Prospective Osteoporosis Study). An osteoporotic vertebral deformity was defined by radiological reading and a reduction of 25% of the anterior, medial and/or posterior height. The data was compared with the results in EVOS, a mean prevalence of 8.7% and a mean incidence of 2.4% for vertebral osteoporotic fractures was found. The data present important variations in occurrence in age, sex and geographical regions.

P037 NON-VERTEBRAL FRACTURES IN MEN AND WOMEN: INCIDENCE AND ASSOCIATION WITH BONE MINERAL DENSITY Angeligue E.A.M. Weel'·', Chris E.D.H. de Laet'·', Huibert Burger"', Albert Hofman" Johannes P.T.M. van Leeuwen', Huibert A.P. Pols',' 'institute of Epidemiology & Biostatistics, 'Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, the Netherlands Objective: To provide an estimate of the incidence of non-vertebral fractures and to determine the association between bone mineral density (BMD) and non-vertebral fractures in men and women, Design: Prospective population-based cohort study. Setting: Residents from a district of Rotterdam, the Netherlands. Subjects: 7046 participants (2.778 men) aged 55 and over, were followed over the period 1 January 1991 until 29 February 1996. Measurement: Fractures were reported by general practitioners through an automated diagnosis register and verified by reviewing the medical records of the participants. At baseline in independently living participant's, femoral neck BMD (expressed in g/cm') was measured by dual energy X-ray absorptiometry (Lunar DPX-L densitometer). Main outcome measure: Age- and gender-specific incidence of non vertebral fractures. Subsequently we estimated the age-adjusted relative risk (RR) for a site-specific fracture associated with 1 SO decrease in femoral neck BMD. Results: During a mean follow-up time of 3.8 year the incidence of non vertebral fractures was 6.1 per 1000 person-years (PY) in men and 21.5 per 1000 PY in women. Predominant fracture sites were the femoral neck, distal forearm and proximal humerus in both men and women. These fractures represented 65% of the total number of non-vertebral fractures. Each SO decrease in femoral neck BMD increased the RR (95%CI) of femoral neck, distal forearm and proximal humerus fractures in men with 3.1 (1.7-5.4),2.8 (1.2-6.4) and 2.4 (0.9-6.1), respectively and in women with 2.4 (1.7-3.3), 1.4 (1.1-1.8) and 1.6 (1.0-2.6), respectively. The overall relation of fractures with BMD appears somewhat stronger in men than in women although this was not statistically significant. Conclusion: In both men and women many types of fractures show an increased incidence with low bone mass. Furthermore, the association between BMD and fractures appears to be similar in men and women.

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P038 ASSOCIATION OF BONE MINERAL DENSITY WITH GENETIC POLYMORPHISM IN THE COMMUNITY ELDERLY IN JAPAN T. Suzuki" H. Yoshida" S. Watanabe', K. Tsukamoto', M. Emi', T. Hosoi', T. Nakamura4, H. Orim04 'Tokyo Metrop. Insl. Gerontol., 'Nippon Med. Sch., 3Univ. Tokyo, 4Tokyo Metrop. Gerial. Hosp. Introduction/Purpose: We investigate associations between candidate genes for osteoporosis and bone mineral density (BMD) of the female elderly living in the community in Japan. Subjects and methods: Of the 525 elderly women (age ~6.5), 472(90.0%) women received BMD measurements in the forearm by DXA and the following genotype analysis; Interleukin6 (1L.6), Interleukin6 Receptor (IL6R), Calcium-sensing R. (CASR). Progesteron R. (PGR), Tumor-necrotic factor A(TNFA), c-SRC Matrix Gla protein (MGP), Estrogen R.-Pvu (ER-Pvu), Estrogen R-Xba (ER-Xba), Parathyroid hormone (PTH), Apoprotein E (Apo E), Vitamin-D R. (VDR), Interleukin1 B (IL 1 B). These genotype analysis were carried out by either microsatellite polymorphism (MP) or RFLP method. The genotype detected by MP was classified into several groups according to the number of CA repeats or size of PCR fragment (bp). Result and Conclusion: Genotyping analyzed by either MP or RFLP can detect 81 different alleles among those 13 genes. There are only eight alleles showing significant association of BMD i.e., IL6-124 (P
P039 PREMENOPAUSAL POPULATION SURVEY FOR aONE LOSS R.L. Meckelnbura, N. Watson, C. Geise OsteoReC Mineral Institute, Newark, Delaware, USA Osteoporosis has long been considered a condition of menopausal and post-menopausal concern. We surveyed agroup of mainly pre-menopausal individuals to assess low bone mass prior to the menopause. The survey group was 865 individuals, all full time employees having passed standard pre-employment physical examinations. This random, non selected group of individuals included 723 females and 142 males. Analysis utilized a Norland P-DEXA forearm densitometer. Grouping was by decades of age. Osteopenia and osteoporosis were defined by the World Health Organization. Based upon the distal T-score, 189 out of the 723 females were classified as osteopenic/osteoporotic or 26% and 45 out of 142 males or 31 % were similarly classified. Contributory factors were analyzed. A family history of osteoporOSiS was predominant in only 30% of involved individuals. Based on calcium intake of 1000mg a day, only 50% of the osteopenic/osteoporotics had adequate intakes. 10-25% of individuals with low scores were smokers. This random study demonstrates the significant incidence of low bone mass in the pre-menopausal population.

P040 RELATIONSHIP BETWEEN CHANGE IN BONE MINERAL DENSITY OF THE LUMBAR SPINE OVER THE PERIOD OF SIX VEARS AND LIFESTYLE FACTORS IN MIDDLE-AGED AND AGED FEMALES E. Kajita*, M.lki** H. Nishino*** S. Mitamura****. Y Kusaka***** Depl. of Community nursing, Toyama Med. Pharm. Univ*, Toyama, Japan, Depl. of Public Health Kinki Univ* *, Osaka, Toyama Insl. Health* * *, Fukui Agncultural Cooperative Association* * * *, Fukui Med. School*****, Fukui, Japan ",~,- We investigated the relationship between change in bone mineral density of the lumbar spine from 1990 to 1996 and lifestyle factors in middleaged and aged females for prevention of osteoporosis. The subjects were 209 females over 35 years of age in a farming region of Japan. The bone mineral density (BMD) of the lumbar spine (L,) was measured in the supine position by dual-energy X-ray absorptiometry (QDR-1000/w, Hologic Inc.). The test items were the physical constitution (height, body weight, BMI), grip strength, detailed interviews on habitual exercise, past and present physical load of work, smoking habits, past history and present involvement of illness, and family history of fractures, and nutrient intake assessment according to a food frequency questionnaire. Six years later, we performed the same bone measurement on the same subjects and determined the rate of the change in BMD (%BMD). During the follow-up investigation, 119 females completed the study (follow-up rate, 56.9%). Females who had lumbar deformity and those who underwent bilateral ovariectomy were excluded; as a result, 106 females were evaluated. The subjects were divided into four groups by the quartile values of the %BMD after the adjustment of age. The number of females who did not work or performed sedentary work at menopause was significantly larger in the BMD decrease group than in the BMD non-decrease group. The rate of the family history of fracture was high in the BMD decrease group. However, there were no differences in the past and present habitual exercise between the two groups. Multiple regression analysis of %BMD was performed using ten test items of the period after menopause, age at menopause, and lifestyle factors. It was found that %BMD increased with the age at menopause, family history of fracture, lack of milk-intake habits, and smoking habits.

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P041 DETERMINANTS OF GEOGRAPHICAL DIFFERENCES IN BONE MINERAL DENSITY AND PREVALENCE OF OSTEOPOROSIS IN JAPANESE WOMEN: JPOS STUDY JPOS Study Group M.lki· E. Kajita T. Matsukura S. Kagamimori**. H. Nishino'" Y. Kagawa .... T. Matsuzaki· ..... H. Yoneshima······ E Marumo" ..... 'Kinki Univ School Med, Osaka-Sayama, Japan, "Toyama Med Pharm Univ, "'Toyama Inst Health, ····Kagawa Nut Univ, ·····Inst Comprehens Com Care, ······Kasukabe Shuuwa Hosp, ••••••• Tokyo Med Dent Univ Japanese Population-based OSteoporosis (JPOS) Study has been launched to determine normal values of bone mineral density (BMD) and biochemical markers of bone turnover in Japanese women and to clarify the factors affecting these indices. We found the geographical differences in BMD and the prevalence of osteoporosis and evaluated the determinants of these differences. We randomly selected 50 women in each 5-year age group from 15 to 79 years for each of the 7 municipalities scattered over Japan resulting in 4550 subjects in total. The study comprised of bone mass measurements by DXA at the spine (L,..l, hip and distal forearm, measurements of height and weight, and structural interviews on medical history and on lifestyle factors, i.e., smoking, drinking, exercise and diet habits. From 3985 women (87.6%) who completed the study, 519 were excluded from the analyses because of their history or present involvement of diseases or administration of drugs which may affect bone metabolism. We selected 1115 premenopausal women aged from 25 to 44 years and 1412 postmenopausal women for the assessment ofthe determinants for peak bone mass (PBM) and for postmenopausal bone loss, respectively. Greater physique, milk consumption and grip strength were suggested to be beneficial for both increasing PBM and decreasing postmenopausal bone loss. Further, greater milk intake in childhood, higher sporting activities in junior high school age and current habit of exercise were related to greater PBM and current higher activity of daily living was associated with smaller postmenopausal bone loss. Significant differences in BMD and the prevalence rate of osteoporosis were observed among the seven study areas even after allowing for the difference of age, height and weight. The difference in BMD significantly decreased by additional control for lifestyle factors described above but still remained unexplained. Other factors such as genetic variations seem to produce the geographical differences In BMD and the prevalence of osteoporosis.

P042 CALCIUM SUPPLEMENTS AND FOOD FACTORS IN RELATION TO FRACTRE IN OLD AGE: A COHORT STUDY C.w. McGrother M.M.K. Donaldson D. Clayton M. Clarke O. Machado University of Leicester, Dept Epidemiology & Public Health, Leicester, Leicestershire LE1 6TP, England Nutrition is generally believed to be important in the genesis of osteoporotic fracture but the precise role of dietary factors is unclear, particularly in old age. This analysis investigates the relationship between dietary calcium and related foods and supplements and subsequent minimal trauma fractures. All people aged 70 and over living in Melton Mowbray, England and registered with the local general practice, were invited for interview and assessment as part of a prospective cohort study. Seventy per cent (N=2106) responded. Baseline measures included a validated measure of dietary calcium based on a food frequency questionnaire for foods rich in calcium; use of nutritional supplements, body size, lifestyle and reported health problems including past fracture. The cohort has been followed for fracture· and migration for 5 years. Analysis suggests current dietary calcium is not associated with future fracture in elderly men and women. Bread was associated with a significant increase in fracture risk (OR 1.22.p=0.04) in men but not women. No other calcium rich food showed any clear association with fracture. Calcium supplementation was not associated with any substantial or significant reduction in risk. Vitamin 0 supplementation was associated with a substantial reduction in risk in women (OR 0.66.p=0.16) but not in men. In men vitamin Bsupplementation, mainly on prescription, was associated with a substantial increased risk of fracture (OR 5.27 p=0.11). These results suggest vitamin 0 supplementation may be protective against fracture in elderly women. In men, associations with vitamin Bsupplementation and bread intake may indicate a relationship between fracture and poor diet.

P043 DEVELOPMENT OF A RISK SCORE FOR FRACTURE WITHIN AN ELDERLY POPULATION C.w. McGrother, M.M.K. Donaldson, D. Clavton M. Clarke University ot Leicester, Dept Epideliliology & Public Health, Leicester, Leicestershire LE1 6TP, England The majority of osteoporotic fractures occur among elderly people. Avariety of factors which predict fracture have been identified. This study aims to identify further potential predictors and combine such factors to form a risk score as an aid to management within primary care All people aged 70 and over, living in Melton Mowbray, England, and registered with the local general practice were invited tor interview and assessment as part of a prospective cohort study. Seventy percent (N=21 06) responded. Baseline measures included health, disability, lifestyle and dietary factors, as well as Broadband Ultrasound Attenuation and stature. The cohort has been followed for fracture and migration for 5 years. In a univariate analysis, predictive factors in elderly women include a fall in the last year, previous fracture, body mass index, mobility, physical leisure activities, grip strength and lower body reaction time. In men, predictive factors include falls, body mass index, demispan (young height), foot deformity and peripheral sensory impairment. These and other factors were included in a stepwise logistic regression to develop a fracture risk score. Selecting a threshold to identify 30% of women with the highest risk score provided a sensitivity of 52% a specificity of 74% and a positive predictive value of 26%. A threshold identifying 34% of men with the highest risk score provided a sensitivity of 66%, a specificity of 67% and positive predictive value of 8%. Among the elderly, factors which predict fracture with the following 5 years may be combined into a fracture risk score wherein 50% of women who fracture and 67% of men who fracture are identified in the lowest tertile of risk score. Further development of such a score may help to identify elderly people in need of assessment and advice in a primary care context.

P044 OSTEOPOROSIS IN THE NORWEGIAN MOOSE? R. Bjora H. Staaland L Nordsletten, J.A. Falch Inst. of Biology, University of Oslo, Norway A high frequency of osteoporotic fractures has been reported from Norway. In the last years, hunters have noted an increased frequency of fractures in the wild moose in the southernmost parts of Norway. We have conducted a study on bone mass and mechanical bone strength in moose hunted in Southern Norway (SN) compared to moose in the Eastern parts (EN). The metacarpal bone with soft tissue from 106 SN and 37 EN animals were exised after hunting. The bones were measured at the proximal and 10 cm. distal part using a 14 cm. water bath with Lunar DPX-I (software version 1.33) in the AP-spine mode at medium speed. In 45 specimens the 10 cm distal part was removed and dry weight estimated. Biomechanical testing was carried out in a 3-point bending test in bones from 9 SN and 8 EN animals of the same age. By duplicate testing, the CV of the proximal and distal BMD were 3.3% and 3.9%, respectively. The correlation between distal BMD and dry weight was 0.86. BMD of the proximal part was for SN 2.01 (0.18) g/cm' and for EN 2.45 (0.32) g/cm' (p<0.001) and for the distal part 2.53 (0.18) g/cm' and 2.68 (0.25) g/cm' (p<0.01). In a multiple regression analysis where sex, age, weight and geographical location were included, the BMD of SN was still significantly lower. In the mechanical testing, the correlation between distal BMD and bending strength was 0.94. In the SN animals, bending strength was 9378 (1815) Nand in EN 16708 (3006) N (p
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P045 CONSUMPTION OF ALCOHOL, TOBACCO, TEA, COFFEE AND BONE DENSITY IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN K. Nas R. Qevik A. GOr O.H. GOndOz, O. Senocak Y. Ersoy. S. FOzOn. M. YOcel F. Erdogan A.J. Sarac Introduction: Osteoporosis is recognised as an important cause of morbidity and mortality in postmenopausal women. Epidemiologic evidence suggest that life-style factors such as consumption of alcohol, tobacco, coffee and tea have effects on bone density. Objective: The objective of this study was assess the association between consumption of alcohol, tea, coffee, tobacco and bone mineral density (BMD), bone mineral content (BMC) in postmenopausal osteoporotic women in Turkey. Material and methods: We measured bone density at the lumbar spine and proximal femur in 450 postmenopausal osteoporotic women in four regions of Turkey. The effects of consumption of alcohol, tea, tobacco and coffee on appendicular and axial 3MD and BMC changes were evaluated in these subjects. Results: The mean age of 450 women with post-menopausal osteoporosis was 61, 26±7, 16(36-77). A wide range of variation in BMD and BMC Values was found. Women who were consuming alcohol and tobacco were found to have lower BMD and BMC, While those who were consuming tea and coffee were found to have higher BMD and BMC. These findings indicate that life-style factors such as consumption of alcohol, tobacco are risk factors, and that intake of coffee, tea are not risk factors for low BMD and BMC in PO women in Turkey.

P046 REDUCED BONE MINERAL DENSITY IN POSTMENOPAUSE AND MEDICAL TREATMENT: A SAMPLE FROM TURIN POPULATION M. Gallo G. De Luigi R. D'Amico C. Buzio M. Massobrio Dept. of Obstetrics and Gynecology. "Climateric Clinic". St. Anna O.I.R.M. Hospital. University of Turin Italy Among the postmenopausal women who responded to a questionnaire distributed in the Turin area between January-March 1998, we selected 166 women who had recently undergone a Dual Energy X-ray Absorptiometry (DEXA) on the lumbar spine (L2-L4) prescribed either by a General Practitioner or a private specialist. The mean age (±SD) of the study group was 54.7±5.8 years and the mean body mass index was 24.0±3.1. The mean time since from last menses was 8.26±6.24 years. According to WHO criteria, the prevalence of osteopenia and osteoporosis was 37.3 % and 27.1% respectively, whereas the remaining women had normal bone density. A part of the women were being treated with Hormonal Replacement Therapy and/or Bisphosphonates. Among women with osteopenia (mean age: 54.1±5.3) 27.4% were not on any medical treatment, whereas the corresponding figures for women with osteoporosis (mean age: 57.0±5.6) and women with normal bone density (mean age: 53.5±5.9) were 22.2% and 20.3%, respectively. From these data it is concluded that, at least in this restricted sample of postmenopausal women from the North of Italy, a large proportion was not on therapy despite a pathologic bone mineral density. These results also suggest that a more extensive information about the risks of postmenopausal bone loss should be spread among colleagues and among the general population. This would potentially contribute to a reduction of the social costs deriving from osteoporotic complications later in life.

P047 PREVALENT VERTEBRAL FRACTURES PREDICT HOSPITALIZATION AND MORTALITY IN OLDER WOMEN: THE FRACTURE INTERVENTION TRIAL (FIT) K. Ensrud D. Thompson M. Nevitt M. Hochberg A Santora. D.M. Black for the FIT Research Group. Universities of MN, CA (San Francisco) & Maryland & Merck Research Laboratories Although it is widely recognized that hip fractures are associated with excess morbidity and mortality, it is uncertain whether radiographic vertebral fractures are associated with risk of subsequent hospitalization and death. We addressed this question using data from the Fracture Intervention Trial (FIT), a trial of alendronate vs. placebo which randomized 6459 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) into 1 of 2 study arms based on the presence or absence of existing vertebral fractures. Prevalent vertebral fractures, defined by morphometry as a >3SD decrease in anyone of the ratios of vertebral heights below the mean population norm of that vertebral level, were noted at baseline in 2027 women. Relative risks (RR) of hospitalization and mortality were estimated using proportional hazards models with treatment assignment as a stratum. During an average follow-up of 3.8 years, 1792 women were hospitalized and 122 died. Women with prevalent vertebral fractures were at increased risk of hospitalization (age-adjusted RR 1.31, 95% CI 1.18 to 1.46) and death (age-adjusted RR 2.03, 95% CI 1.33 to 3.11). Further adjustment for other factors including cigarette smoking, health status, history of diabetes, hypertension, and myocardial infarction, body weight and total hip BMD did not substantially alter the association between prevalent vertebral fractures and these outcomes (multivariate RRs 1.27, 95% CI 1.14 to 1.43 and 1.98, 95% C11.27 to 3.06 for hospitalization and mortality, respectively). In addition, the relationship between prevalent vertebral fractures and all-cause hospitalization was not altered by excluding hospitalizations related to fractures (multivariate RR 1.25, 95% C11.11 to 1.40). We conclude that prevalent radiographic vertebral fractures in older women with low bone mass are associated with an increased risk of hospitalization and mortality which is not explained by other known predictors of these outcomes.

P048 VITAMIN-D LEVEL ON POSTMENOPAUSAL WOMEN AND ITS RELATION WITH BONE MINERAL DENSITOMETRY Ora. M. Muelas Ora. N. Sanchez Dr. R. Botin Instituto Ginecologico "Cinca" Madrid - Spain Objective: To see the relation between the level of Vit-D (25-0H) with the existence or not of osteoporosis on lumbar column and left hip. Method: 88 women with a mean age of 54 years, postmenopausal. Without previous diseases, good feeding, no obesity. The studied Vlt-D(25OH) in ng/ml (normal values 12-80) was mean value 34. Double photon densitometry on L.C and left hip. 19 women without H.R.T (Hormonal Replacement Treatment) 69 with H.R.T. Results: Women with H.R.T had a mean value of Vit-D 33,4 ng/ml (separating 3 cases with very high values of Vit-D, was 31). Osteoporosis on lumbar column was 13% but only 2,8% were moderate severe. Only 1 case coexisted with low Vit-D. On left hip mild osteoporosis in 13% and only in 2 cases in relation with low Vit-D. On women with out H.R.T osteoporosis mild-moderate in 26% in L.C and 10% on left hip. Summary: 1° The level of Vit-D on spanish women in this study is below the normal mean value. 2° It doesn't exist relation between the level of Vit-D and bone mineral densitometry neither in L.C nor left hip .

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P049 PREVALENCE OF OSTEOPOROSIS IN 500 PEOPLE REFERRED TO A

P052 CHANGES IN BONE MASS AMONGST PERI AND POST-MENOPAUSAL

BONE DENSITOMETRY CENTER R. Abhari B. Raissi A Akbarian B. Broumand J. Forahanizadeh Sina Bone Densitometry Center.4. Mirza Hasani. Mirzaye Shirazi st, Tehran 15867, Iran Aim: To report the prevalence of osteoporosis among the patients referred to the BM 0 center. Methods: Bone densitometry was done for all patients with DPX-1 on Ap spine and Femur as requested. Results: 31 (6.2%) patients were male 469 (93.8%) of patients were female. The range of age was from 20-85 years. BMD of 218 sites were done for 162 patients from age 20-50 years. In 28 (12.8%) sites osteoporosis were detected. 9 in AP spine & 19 in Femur. In this group 95 persons had some disease (renal, endocrine or rheumatologic ... ) and 59 were postmenopausal but normal BMD. In age more than 50 years (338 patients) in 770 sites BMD was done. In 219 sites osteoporosis were (28.4%) detected. 90 in AP spine & 129 in Femur. (219 patients had other diseases and 312 were postmenopausal). Conclusion: BMD was done in 988 sites in 500 patients. In 247 sites osteoporosis were detected (25%) which is mainly was due to hormone deficiency. In the both group osteoporosis in Femur was

WOMEN: PRELIMINARY FINDINGS H.M. Macdonald SA New M H.N Golden and D.M. Reid OsteoporoSis Research Unit & Department of Medicine & Therapeutics, University of Aberdeen, Scotland. School of Biological Sciences, University of Surrey, GuiJdford. England. United Kingdom In two recent cross-sectional studies, our group has looked extensively at nutritional influences on bone metabolism.'" We are currently investigating the relative strength of nutritional, genetic and physical activity factors on peri- & early post-menopausal bone loss by re-examination of the 1065 women who took part in the original studies. In our second study', forearm bone mineral density (BMD) of79 women was measured. This abstract reports findings of forearm BMD changes in 24 subjects. Peripheral quantitative computed tomography (pOCT) was performed at the ultra-distal radius using the Stratec XCT 960 scanner. The measurement scan occurs at a distance proximal to the ulna styloid process of 4% of total ulnar length. Measurements for Otot and Otrab BMD were obtained. The coefficient of variation for this technique in our centre is 1.24% (Otot) and 1.33% (Otrab). Baseline Otrab g/cm3 Otot g/cm 3

P050 DOES LOCATION IN THE SPINE INFLUENCE THE ASSOCIATION BETWEEN VERTEBRAL DEFORMITY AND ADVERSE HEALTH OUTCOMES W. Cockerill T. O'Neill A. Ismail A. Silman and the European Vertebral Osteoporosis Study ARC Epidemiology Research Unit, Manchester University, Manchester, UK Background: Vertebral deformities are associated with a variety of adverse health outcomes including back pain and disability. The aim of this analysis was to determine whether the spinal location of vertebral deformities ie. lumbar or thoracic, and the proximity of vertebral level in those with multiple deformities, influences health outcomes. Methods: 7386 women, mean age 63.0 yrs (SD=8.0) were recruited from population registers in 30 European centres. Each had an interviewer administered questionnaire and lateral spinal radiographs performed. The questionnaire included questions concerning back pain, general health and a 12 item, back specific, activities of daily living instrument. The radiographs were evaluated morphometrically and vertebral deformity defined according to the McCloskey method. Statistical analysis was performed using logistic regression with adjustments made for age and centre. Results: 596 women had a single vertebral deformity and 145 women had two deformities. Those with a single deformity in the lumbar spine were more likely than those with a single deformity in the thoracic spine to have back pain in the past year (OR= 1.5; 95%CI 1.0,2.3). Restricting analysis to those with two deformities, those with adjacent deformities were more likely than those with non-adjacent deformities to be functionally impaired (OR=1.9; 95%CI 0.8,4.7), have back pain in the past year (OR=1.6; 95%CI 0.7,3.8), and poor general health (OR=2.2; 95% CI=0.9,5.6). Conclusion: In women, location in the spine appears to influence the association between vertebral deformity and adverse health outcomes.

'051 LIFETIME RISK OF HIP FRACTURE IS UNDERESTIMATED A. Oden A. Dawson W. Dere O. Johnell B. Jonsson J.A. Kanis Centre for Metabolic Bone Diseases, Sheffield, UK Estimates of the lifetime risk of hip fracture vary around the world. In Northern Europe and the USA estimates range from 13 to 18 percent. Comparable figures are found for vertebral and forearm fractures. Estimates of lifetime risk of osteoporotic fracture have generally assumed that mortality rates do not change. Since mortality in the elderly is decreasing in all regions of the world we assessed the effect of this on lifetime risks for hip fracture using Sweden as a reference country. Lifetime risks of hip fracture at the age of 50 years were 4.6 and 13.9 percent in men and women respectively assuming all survive to current average life expectancy. Estimates increased to 8.1 and 19.5 percent when based on present mortality and to 11.1 and 22.7 percent respectively based on predicted mortality. We conclude that lifetime risks of hip fracture have been considerably underestimated.

Mean 182.4 387.7

5 Years SO 7.3 10.6

Mean 1 77.5 377.2

SO %change p value 7.7 -2.9 0.02 1 1.3 -2.8 0.001

For Otrab, 25% of subjects lost >6% of BMD and for Otrab, 25% of subjects lost >5% of BMD. Although comparison with BMD measurements using DXA and further investigations of the whole study population are required to establish the full extent of peri & early post menopausal bone loss, these data indicate an average of 0.6% annual decrease in bone mass in the Scottish population. 1. New et al. Am J Clin Nutr 1997; 65:1831-39. 2. New et al Proc Nutr Soc 1996;55: 12A. (Am J Clin Nutr - submitted)

PO 53 USE OF HORMONE REPLACEMENT THERAPY AMONG DANISH NURSES IN 1993 Y. Andersen E.B. Obel Danish Institute for Health & Nursing Research, Copenhagen, Denmark The study is based on data from the Danish Nurse Study on prevention of osteoporoSiS and atherosclerosis. In 1993, a cohort was established, when 23,200 female nurses were mailed a questionnaire of whom 19,953 (86%) returned the questionnaire. The purpose of this study was to ascertain the frequency of women using systemic HRT, to identify their reasons for choosing this, their reason for not choosing HRT, and to estimate the duration of HRT. 6,673 (33%) respondents had ever used HRT. 20% were still using it and 13% had used it in the past. The frequency of current users was highest in the 50-59 age band (2257; 58%). Previous users of oral contraceptives were using HRT more frequently, women with a family history of osteoporosis and with a low BMI were using HRT more frequently than others. Most frequent reasons for choosing HRT was symptom relief and prevention of osteoporosis. Self-reported side effects were the most cited reason for discontinuing HRT (43%). 66% of former users stopped HRT within the first five years. Absence of climacteric symptoms was the most frequent reason for not choosing HRT. Other reasons were that women felt HRT unnatural orthey were afraid of side effects. Using Cox regression analysis it was found that 69% of ever users were still receiving HRT five years after starting, 57% at ten years and 48% at fifteen years. Women with a family history of osteoporoSiS and with a low body mass index were using HRT longer than others.

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PO 54 THE USE OF THE AREA UNDER THE RECEIVER OPERATING CHARACTERISTIC (ROC) CURVE FOR CALCULATING THE SAMPLE SIZE OF A PROSPECTIVE COHORT STUDY IN ELDERLY WOMEN: THE EXAMPLE OF SEMOF STUDY J. Cornuz M.-A. Krieg P. Burckhardt University Hospital, Lausanne, Switzerland and the SEMOF study group. Background: Recent cohort studies have shown that bone ultrasound (BU) of the calcaneus predict the risk of hip fracture (HP) in elderly women. However, comparison of the yield of different types of BU have not been prospectively assessed. One of the major epidemiological issues for such a comparison concerns the sample size calculation. We present the calculation for the SEMOF study (Schweizerische Evaluierung der Messmethoden des Osteoporotischen Frakturrisikos), a prospective cohort study comparing different types of BU among women aged 71-80. Methods: The sample size was calculated by comparing the area under the ROC curve of two types of BU: Lunar Achilles of the calcaneus and the DBM Sonic 1200 of the phalanx. ROC curve is a graphic means for assessing the ability of a screening test to discriminate between healthy (e.g. women HP) and diseased people (e.g. with HP). It is constructed by plotting the true positive rate (sensitivity) against the false positive rate (1 - specificity). Whereas the null hypothesis assumes similar areas under the ROC curve of both BU, the alternative hypothesis should provide a minimal difference of the 2 areas of 2.5% to 10% difference (e.g. 10% =0.825 vs. 0.725). The other parameters included in the calculation were: alpha error (declaring a difference exists when it does not) of 5%, a high statistical power (probability of demonstrating a difference if one exists) of 10%, an stable annual incidence of HP of 1.5% during a 3-year followup and a lost of patients of 10%/year. Results: The table shows the different sample sizes Area under the ROC curve of the first type of BU 0.750 0.775 115000 28000 115000 110000 28000 110000 12500 27000 103000 11800 25000 7000 0.725

Area under the curve of the second type of BU

0.725 0.750 0,775 0.800 0.825

0.800 12500 27000 103000

0.825 7000 11800 25000 96000

96000

Conclusion: The necessary sample size ranges from 7000 to 115000 subjects. The choice of the final sample size depends on the clinically useful difference for preferring one BU from another one.

Conclusions. The results of this first population-based cross sectional study in the Czech Republic document a high prevalence ot osteoporosis and osteopenia which is comparable with that published forthe Netherlands and the United States. The results offer a basis for economical considerations in diagnosis, treatment and consequences of osteoporosis. 160 IlWOMEN Osteopenia

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Osteoporosis

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P056 COMPARISON OF PSYCHOMETRIC PROPERTIES BETWEEN QUALEFFO AND OQLQ IN THE ASSESSMENT OF QUALITY OF LIFE OF WOMEN WITH VERTEBRAL FRACTURE DUE TO OSTEOPOROSIS X. Badia' A.Diez-Perez! C. Alvarez1l J. Gonzalez-Macias*' M. piaz-Curiel±± F. Guillen· B. Diaz-Lopez", M. Roset* and the GRECO aroup. *Institut de Salut Publica de Catalunya, tH del Mar, Barcelona,**H Marques Valdecilla, HF Jimenez Diaz, ··H C Asturias, ·H Getate, ~Rhone-Poulenc Rorer, Spain Purpose. To evaluate and compare the feasibility, validity and reliability of the Osteoporosis Quality of Life Questionnaire (OQLQ) and the QUALEFFO. Methods. We included 280 women (>50 year-Old) with primary osteoporosis confirmed by DEXA (L2-L4) or right femoral neck, (WHO criteria) in the previous 12 months and one or more vertebral fracture (xray) and 300 controls obtained from a population-based random sample. All women randomly received either the OQLQ or QUALEFFO questionnaire Re-test was administered after 7-14 days to 50% of cases. Feasibility (administration time) discriminant validity (mean (95%CI) scores of patients vs. controls) construct validity (correlation of OQLQ and QUALEFFO with SF-36, EuroQol-VAS and clinical variables), internal consistency (a-Cronbach) and test-retest reliability (ICC); were measured.

P055 PREVALENCE OF OSTEOPOROSIS IN WOMEN AND MEN IN THE CZECH REPUBLIC R. Zahora J. Stepan Department of Internal Medicine, City Hospital, Litomerice, and 3rd Department of Internal Medicine, Charles University Faculty of Medicine, Prague, Czech Republic Background. The objective of this study was to evaluate the prevalence of osteoporosis and osteopenia in Czech women and men >50 years old. Methods and Results. Bone mineral density was assessed in an agestratified random sample of 713 women and 429 men from two cities (Prague and Litomerice) in the lumbar spine, proximal femur and total body by dual X-ray absorptiometry and in the distal forearm by single Xray absorptiometry. The proportion of women and men in each age group with bone density below specified levels at any of these skeletal sites was projected to the population structure of the Czech Republic. With advancing age, in women at 55 years and in men at 65 years of age the population with normal bone mineral density becomes smaller and a greater proportion has osteopenia or osteoporosis. Overall, an estimated 428 000 women and 195 000 men over age 50 have osteoporosis and another 680 000 women and 435 000 men have osteopenia.

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Results feasibility mean (SO) time, minutes type of administration discriminant validity patients, mean (95% CI) controls, mean (95% CI) construct validity SF-36 functional status SF-36 well-being EuroQol-VAS Clinical variables

test-retest reliability (ICC) internal consistency

OQLQ (n=138)

QUALEFFO (n= 142)

17.9 (74) interviewer

17.9 (8.6) self

4.0 (3.8,4.2) 5.4 (5.2,5.6)

2.6 (2.4,2.7) 2.0 (1.9,2.1)

0.83 0.66 0.65 fern neck BMD, n fractures, n drugs, n chronic conditions 0.94 (n=57) 0.96

-0.77 -0.73 -0.69 n fractures, n chronic conditions 0.95 (n=53) 0.92

Conclusions. OQLQ has psychometric properties (validity, reliability) and correlation with clinical variables Slightly superior to QUALEFFO but OQLQ has to be administered by interviewer.

POS7 CORRELATION BETWEEN BONE MINERAL DENSITY AND OUALITY OF LIFE IN WOMEN WITH OSTEOPOROTIC VERTEBRAL FRACTURE A. Diez-Perez±. X. Badia*. C. Alvarez1l J. Gonzalez-Macias" M. Diaz Curiel±±. F. Guillen- B. Diaz-Lopez" M. Roset* and the GRECO group. tH del Mar, *Institut de Salut Publica de Catalunya, Barcelona, **H Marques Valdecilla,HF Jimenez Diaz,"H C Asturias, -H Getafe ~Rhone-Poulenc Rorer, Spain Purpose. To analyze the relationship between Bone Mineral Density (BMD) in femoral neck and lumbar spine with quality of life (OoL) scores in women with osteoporotic vertebral fracture. Methods. We included 280 women (~50 year-old) with primary osteoporosis confirmed by DEXA (L2-L4) or right femoral neck, WHO criteria) in the previous 12 months and one or more prevalent vertebral fracture (x-ray). All women randomly received either the OOLO or OUALEFFO questionnaire. To analyze the relationship between BMD and quality of life questionnaires (overall scores and by dimensions) the Pearson's correlation coefficient was used. Results. Lumbar spine BMD correlated with global score of OOLO (r=0.13) and OUALEFFO (r=-0.03). Femoral neck BMD correlated with OOLO (r=21, p
POS9 FACTOR OF RISK FOR HIP FRACTURE IN HEALTHY CHINESE MEN AND WOMEN IN TAIWAN Rong-Sen Yang Tang-Kue Liu, Yj-Shiong Hang, Keh-Sung Tsai* Departments of Orthopaedics and Laboratory Medicine*. National Taiwan University Hospital, Taipei, Taiwan We have investigated the age-related change in estimated factor of risk (<<1» for the proximal femoral load during free fall in 548 healthy females and 240 healthy males aged between 21-79 years. These individuals were divided into younger (age <50 years) and older groups (age ~50 years). An additional fracture group of 18 female patients was included and compared to 165 gender- and age-matched controls. The bone mineral density (BMD) of the proximal femoral neck was measured by a Norland XR-26 dual-energy x-ray absorptiometer (DXA). The estimated fracture load (L) of the femoral neck was calculated from the BMD with the regression equation derived by Courtney et al. and estimated fall force (F) by body weight and height according to the regression equation derived by Nakamura et al. was defined as the quotient of F/L. The results showed an age-related decrease of BMD (p
POS8 INFLUENCE OF TOTAL, FATFREE AND FAT BODY MASS ON ULTRASOUND MEASURES AT THE OS CALC IS IN A POPULATIONBASED SAMPLE OF POSTMENOPAUSAL GERMAN WOMEN A. Kroke H. Boeino K. Weber M. Beromann S. Voss K. Klipstein-G German Institue of Human Nutrition, Potsdam-Rehbruecke, Germany Purpose: To examine the relationship between measures of body composition, e.g. fatfree (FFM) and fat mass (FM), and relative body mass (BMI) with ultrasonically assessed features of the os calcis. Methods: Ultrasound measurement (SOS- speed of sound, m/sec; BUA broad band ultrasound attenuation, db/MHz; at the os calc is (Achilles Plus, Lunar®) was performed in 4548 women, aged 35-65, who participated at the baseline recruitment of a prospective cohort study on diet, cancer, and other chronic diseases (EPIC-European Prospective Investigation into Cancer and Nutrition) in the Potsdam study center. After exclusion of subjects due to missing values (N=119), use of drugs affecting bone metabolism (N=104), and women of pre- or perimenopausal status (N=2606) 1719 postmenopausal women remained for this analysis. Anthropometric measures (height, weight, skinfolds) were obtained by trained personnel, and BMI, FM, and FFM were calculated. Information on lifestyle, medication, and diet were obtained through personal interviews and self-administered questionnaires. HRT status was defined as ever or never users. Tertiles of FM and FFM were cross-tabulated and age-adjusted means of SOS and BUA determined for these 9 strata. Multiple logistic regression was performed to estimate the odds of being in the lowest quintile of BUA for quintiles of FM and FFM, adjusting for each other and age, height, smoking status, physical activity, alcohol and calcium intake. Results: For SOS no clear differences in means were found for tertiles of FM or FFM. Highest values of BUA were observed in women never on HRT with high FFM, not in those with high Fmor BMI. The multivariate adjusted odds of being hi the lowest quintile of BUA was 0.2 (95% CI 0.10.5, p
P060 PROXIMAL FEMORAL DIENSION IN THE CHINESE ELDERLY WOMEN WITH HIP FRACTURES IN TAIWAN Tang-Kue Liu Rong-Sen Yang Department of Orthopaedics, National Taiwan University Hospital, Taipei, Taiwan The purpose of this study is to investigate the impact of proximal femoral geometry on the occurrence of hip fracture and compared the geometry of contralateral hip of 120 elderly women with hip fractures, including 63 femoral neck fractures and 57 intertrochanteric fractures due to minor trauma, to 72 normal elderly women as controls. The mean age for femoral neck fracture was 77.3 years, for intertrochanteric fracture 79.7 years and for controls 72.9 years. The femoral neck length (NL), neck width (NW), diameter of femoral head, femoral shaft width just below lesser trochanter, and neck-shaft angle (e) were measured on anteroposterior plain pelviS xray radiograms. The ratio of NL to NW (NUNW) was calculated. The mean±SD of NL for femoral neck fracture was 50.4±3.3 mm, for intertrochanteric fracture, 50.6±3.1 mm, and for controls, 48.3±3.6 mm Statistical analysis by ANOCOCA showed that NL of women with hip fracture was significantly longer than controls (p
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P061 BONE MASS DENSITY IN NORMAL IRANIAN POPULATION M. Akbarian F. Davatchi A. Salimzadeh F. Shah ram F. Gharibdoust A. Nadji. M. Pajouhi A.R. Jamshidi Osteoporosis Unit, Rheumatology Research Center, Tehran University for Medical Sciences, Tehran, Iran The bone mass density (BMD) may vary in different countries due to different genetic and environmental factors. This study was performed to determine the BMD of the normal population in Iran. Subjects were selected randomly from different social workers classes in Tehran (from the lowest to the highest). For each decade and sexes, 20 normal subjects were selected (140 men and 140 women). BMD was measured with a Hologic 1000 plus machine by Dual Energy X-Ray Absorptiometry (DEXA) method for the lumbar spine (L 1, L2, L3, L4, L14) and the femoral neck (Neck, Trochanter, Intertrochanter, Ward, Total). Data were treated by polynomial approximation (3,d degree). The obtained curves were compared with the standard Hologic curves for Caucasians. In females the Peak Bone Mass (PBM) was 1.019 g/cm' for the lumbar spine and 0.832 forthe femoral neck. In males the Peak Bone Mass (PBM) was 0.987 g/cm' for the lumbar spine and 0.907 forthe femoral neck. The BMD of both lumbar spine and femoral neck were lower than the Hologic standards. Forthe lumbar spine the mean difference was 6.5% (2 to 21 %, CI=1) for women and 13.8% (2to 36%, CI=1.45) for men. In femoral neck the mean difference was 5.4% (2 to 16%, CI=0.96) for women and 4.6% (1 to 14%, CI=0.96) for men. The BMD of the lumbar spine and the femoral neck was lower in Iranian compared to the Hologic standards for Caucasians. This was seen in all age groups and in both sexes. It was less pronounced for the BPM and around it. It is interesting to note that the PBM in spine was lower in men than women. The lower BMD ofthe spine in men was also seen in a cohort of patients with different diseases (inflammatory and non-inflammatory).

P062 ASSOCIATION BETWEEN BODY MORPHOLOGY AND BONE DENSITY IN OVERWEIGHT WOMEN P. Orozco E. Ruiz Gil A. Perez J.M. Nolla ABS Gotic, ABS San Idelfons, Ciutat Universitaria Princeps d'Espafia, Barcelona, Spain To investigate the association between body morphology - waist/hip ratio (WHR) and breast/hip ratio (BHR)- and lumbar and femoral bone mineral density (BMD) in overweight pre- and postmenopausal healthy women. Premenopausal women (n=47, aged 42 y.) had similar body size (BMI=27.1±2.3, WHR=0.80±O.06, BHR=0.96±O.07, BMI increase since age 20=5.0±3.0) than postmenopausal ones (n=51, age = 47-63 y., time since menopause = 1-7 y.). None was taking hormonal drugs. The BMD was measured by DEXA (Hologic QDR 1000®) at lumbar spine (L2-L4) and proximal femur (neck, troch, inter, Ftot and Wards). In premenopausal women, BHR and WHR adjusted by BMI correlated positively with the most femoral sites (troch=0.38, 0,28; inter=0.40, 0,23; Ftot=0.36, 0.30; Wards= 0.41, 0.34), and BHR was better predictor of bone density than BMI at all femoral sites except neck. The increase of BMI since age of 20 did not correlated with any bone density. Lumbar BMD did not correlate with any anthropometric measurement. In postmenopausal women, after adjustment fortime since menopause, BHR and WHR were not correlated with any bone density. Current BMI correlated with femoral bone density (troch =0.29, inter=0.35, Ftot =0.35). The increase in BMI since age of 20 correlated with all femoral BMDs (neck=0.31, troch =0.33, inter=0.39, Ftot =0.44) . Lumbar and wards BMD did not correlated with any anthropometric measurement. As a conclusion in overweight women, the BHR and the WHR has a positive influence on femoral trabecular bone in premenopause, but not prevent bone loss in postmenopause. Weight increased during life have a positive influence on femoral bone in postmenopausal women. Lumbar BMD are not influenced by any anthropometric data in pre- and postmenopausal women.

P063 THE TROMS0 STUDY. REPEATED MEASUREMENTS OF POSTURAL STABILITY. INDIVIDUAL LEARNING EFFECT AS A COMPLICATING FACTOR WHEN ASSESSING BALANCE J.H. Magnus"', V. Fonnebo', G.R. Berntsen', A.J. Sogaard', A. Tollan' 'Dep. Rheumatology and 'Institute of Community Medicine, University of Tromso, 'National Institute of Public Health Oslo, 4Hamar Hospital, Norway Prediction of osteoporotic fractures by measurements of postural instability have been demonstrated in general and patient populations. In connection with the The Tromso Osteoporosis Study body sway was measured according to ~ord et al. (J Gerontol1991; 46: M69-76). The aims of the present study were to evaluate maintenance of a position within a group through time and the predictability of future values by the first measurement. 8000 males and females from the community were screened for osteoporosis. Attendees during one week of the screening were consecutively invited to participate in a validation study of the measurements used. 41 males, mean age 55.4 years (27-70 years) and 35 females mean age 54.0 years (29-73 years) attended. Body sway was measured on a firm and a compliant surface (foam) with open eyes. The measure was repeated two times on each surface by two investigators at first visit (total of eight measures) and repeated one week later (second visit) with the same investigators. 71 persons completed all 16 measurements. The groups were compared according to ranks. Tracking was used to describe the longitudinal development, and a shift of one group in either direction was allowed. With no correlation between the measurements just 17.9% would be expected to stay within the same group or just move to the adjacent level. There were no statistical differences in body sway by age, gender or investigator by Kruskal Wallis test. Pearson correlation coefficients between individual measures were statistical significant (p
P064 VERTEBRAL OSTEOPHYTES AND VERTEBRAL DEFORMITIES IN ELDERLY POPULATION OF ZAGREB S. Cviietic', E. McCloskey', D. Dekanic" S. BolanEa' 'Institute for Medical Research and Occupational Health, Zagreb, Croatia 'Sheffield Metabolic Bone Unit, WHO Collaborating Centre, Sheffield, England The aim of the study was to determine the relationship between osteoarthritis and incidence of vertebral deformities. SUBJECTS: 263 men and 280 women, population sample, Zagreb inhabitants, over the age of 45. The mean age of men was 60,2 + 9,3 years and 61,9 + 10,4 years for women METHODS: lateral radiographs of the thoracic and lumbar spine (Th4L5) were obtained. The degree of osteophyte formation at each vertebral level was scored using a scale of 0 to 4 (0= none, 4= bridging osteophyte) and the total score calculated for the whole spine. Vertebral deformities were detected by comparison of intra- and inter- vertebral height ratios to sex-matched normal ranges. RESULTS: The prevalence of moderate to severe osteophytosis (total score >10) was 25,5% in men and 30,0% in women. In both sex, the prevalence increased with age, from those less than 55 years old (7,8% men; 34,6% women) to those aged 75 years or more (50,0% men; 43,3% women), but the increase was statistically significant only in men (p<0,0001). The prevalence of vertebral deformities was 8,4% in men and 12,5% in women. There was no significant association between vertebral deformities and the presence of osteophytosis (x'= 1,44 men; x'=0,02 women) Moderate to severe osteophytosis was also not associated with the vertebral deformities (x'=0,04 men, x'=0,35 women). In younger age groups, the prevalence of vertebral deformities in those with moderate to severe osteophytosis was bigger in women (4,9% women; / men) while in older age group (75+ years) the prevalence was higher in men (14,3% men; 6,7% women. CONCLUSION: Our data showed that osteophytosis was not associated with an increased prevalence of vertebral deformities. The results suggest the inverse relationship between osteoarthritis and osteoporosis .

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P065 RISK FACTORS FOR POSTMENOPAUSAL OSTEOPOROSIS IN TURKEY F. Erdogan K. Nas A. GOr. R. Qevik C. Yapici V. Kavuncu S. Akku§. C. OztOrk I. Tekeo9lu D. Sindal. G. Dil~en M.B. Atav. Z. Altay R. Ak~it M. Adam A Demirkeser Introduction: Osteoporosis is a large and growing health problem in many countries. The basic factors that determine a woman's susceptibility to low bone are the peak bone mass achieved during adolescence and early adulthood, and the bone loss associated with menopause and increasing age. Many behavioral factors are believed to be determinants of bone mass and bone mineral density. Objective: To assess the risk factors of post menopausal osteoporosis in 13 regions of Turkey. Material and methods: This study was carried out in 13 universities throughout Turkey. A total of 1281 women with postmenopausal osteoporosis were studied as to determine the risk factors. Results: The mean age of 1281 women with postmenopausal osteoporosis was 61,19±7,18. The mean age at menarche was 13,48±1,4 and the menopause was 45, 63±5,71. The mean of weight and height were 68,10±12,08 kg. and 1,57±O,06 m. The mean of fertil duration was 32,92±5,63. Low physical activity, inadequate sun exposure and low calcium intake were the most important risk factors. Population strategies to increase physical activity, calcium intake, adequate sun exposure will be effective in prevention of osteoporosis because of these factors in Turkey.

P066 FEMUR BONE MINERAL DENSITY AND CALCIUM MILK AND DAIRY PRODUCTS CONSUMPTION IN MEN A. Sawicki A. Zakrzewska A. Debinski T. Szvmanska - Debinska J. Jakubas-Przwlocka J. Charzewska Mineral Metabolism and Bone Disease Department and Department of Epidemiology National Food and Nutrition Institute, Warsaw Osteoporosis and Calcium Metabolism Centre "Osteomed", Warsaw, Poland Assessment of bone mineral density of men in different age and its dependence on dietary calcium intake was the aim of this study. Bone mineral density of femur and calcium intake were evaluated in 202 men from Warsaw macro region aged between 20 and 80 years without risk factors of secondary osteoporosis. Bone mineral density (BMD) was measured at the femur by dual-energy X-ray absorptiometry (Lunar DPXL). Current calcium intake from milk and diary products was assessed by food-frequency questionnaire. Association between BMD, age and current calcium intake was evaluated using the linear correlation coefficient. Bone mineral density of femur decreased with age started from the thirties. Calcium intake extended from 1114±412 mgCa/d to 543±253 mgCa/d. Correlation between BMD and age was significant (r=-0.504; p<0.001) as well as between current calcium intake (r=0.254; p<0.001). Also correlation between age and current calcium intake was observed (r=-0.396; p
P067 TO THE EPIDEDIOLOGY OF KNOWLEDCE OF OSTEOPOROSIS IN GERMANY C. Gunther H. KieBling, A Kapner C. Obermanns, O.S. Gunther German Centre of Osteoporosis Prevention, Therapy and Rehabilitation of Johannesbad Clinic, Bad FOssing Germany Effective prevention and treatment of osteoporosis (OPO) are only possible if patients and non-afflicted persons are adequately informed. Therefore we were interested in the state of knowledge about this disease. Using a self-made questionnaire we asked 849 people ("normals") and 132 members of self-supporting groups (SG-members) which we considered as a better informed part of the public (total n=981 mean age 43,4 years±18,6) questions: 1.) Do you know the term "OPO"? 2.) What means "OPO"? 3.) Do you know risk factors? 4.) Is prevention possible? 5.) Is therapy possible? Older persons mostly are better informed and give a total explanation of the term in combination with at least one risk factor. In any case women show better sores than men, but only 34% of all "normals" give a positive "3-combination-answer" (knowing OPO, right explanation, 1 risk factor). Among the risk factors "lack of calcium" dominates (36,3%), followed by "wrong diet" (22,5%) and, "lack of hormones" (15,3%), other risks ranged < 8%. 72,3% of the "normals", think prevention is possible, 63,5% expect. OPO is treatable. We compared the positive "3-combinationanswers" of age-matched "normal women" (n=260) to SG-members (n=121). SG-members show better results (83,5% versus 58,5% chisquare-test p<,0001). Although the term OPO is mostly known only the few (34%) among the "normal germans" could give an explanation of OPO and the risk factors. That means knowledge is not sufficient. Further going efforts should be made to increase the knowledge Reha-centres specialized in osteology are held to work as "health education centres" in the fight against the preventable "people's disease" osteoporosis.

P06S OSTEOPOROSIS IN BRAZIL - PROBLEMS TO BE SOLVED IN THE NEXT MILENIUM J.F. Marques-Neto L.F.O. Barros, F.S. Lira-Neto M.B. Bertolo R. Lederman & A.M. Samara Rheumatology Unit, Department of Clinical Medicine, State University of Campinas - Campinas - SP, Brazil Brazil is the major country of South America, with a surface of 8,5 millions of square kilometers and a population of almost 160.000.000 inhabitants. In order to verify the medical assistance conditions on osteoporosis, a multicentric study was developed, involving 60 experts or opinion leaders in osteoporosis, 3.000 physicians and 3.000 patients. A prospective study with the osteoporosis experts, through the Delphi analysis method, showed the evolution of tendencies from 1995 to 2.000, concerning to epidemiology, risk factors, diagnostic conditions, prevention and treatment. Opinion research with the physicians and patients showed the main problem that Brazil must be able to solve in the next years: 1. Population is getting older in Brazil and the number of a risk patients to osteoporosis can reach 20 millions inhabitants at the year 2.000. 2. Nowadays the diagnosis of osteoporosis risk patients, and 20% have conditions to be treated. 3. The major risk factors in Brazilian population are: age, menopause, diet and ethilism. 4. The main problems in diagnosis and treatment a) education and training physicians involved with osteoporosis; b) education of the patients; c) better diagnostic conditions; d) equipment for early diagnostic; e) better economic conditions for prevention and treatment.

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P069 STRUCTURAL-FUNCTIONAL STATE OF BONE IN THE WOMEN OF DIFFERENT AGE RESIDING IN THE ENDEMIC REGIONS WITH HIGH WATER FLUORIDE CONTENT V.V. Povoroznjuk N.K. Hobzey, L.P. Tkachenko, T.F. Tatarchuk Institute of Gerontology Acad.Med.Sci. of Ukraine, Vyshgorodskaya St.67, 254114, Kiev, Ukraine Effects of an increased water fluoride content on the bone tissue, the rate of its aging, prevalence of osteoporosis were studied in 109 women (gr.l) aged 20-69 years residing in the areas of Lviv Region with a high fluoride content of drinking water. The control subjects (gr.lI) included women of the same age from the areas in which there was a normal water fluoride content, standardized according to the body mass index and peculiarities of nutrition. The bone tissue was examined using an ultrasound densitometer Achilles+ (Lunar Corp.). The speed of the sound (SOS, m/s), broadband ultrasound attenuation (BUA, db/MHz) and an estimated "stiffness" index (SI, %) were measured. The results of studies show the negative influence of the high fluoride content in the drinking water on the structuralfunctional bone tissue state, that leads to the accelerated aging, decrease of the bone density characteristics, development of osteoporosis. The most sensitive turned out to be the female population of age groups 20-29 years (the period of bone peak formation) and 50-59 years (postmenopausal period). In the 1st group women, there was a significant decrease in SOS, BUA and SI (20-29 yrs 1550±5,8 mis, 105,4±2,62 dB/MHz and 85,2±3,3%; 50-59 yrs - 1521±6,8 mis, 98,2±2,65 dB/MHz and 71,2±3,8%) in comparison with control group (20-29 yrs - 1592±6,5 mis, 119,2±3,31 dBI MHz and 92,4±1 ,6%; 50-59 yrs - 1552±5,8 mis, 106,1±2,51 dB/MHz and 83,8±2,3%). The essential difference between indexes characterizing bone tissue state among the age groups 30-39 years and 40-49 years weren't revealed. Structural functional age of bone tissue in the 1st group women exceeded the population standard among the age groups of 20-29 years (by 5,8 years) and 50-59 years (by 6,3 years). Among the group aged 5059 years in the women 1st group osteoporosis was revealed in 26.3%, osteopenia - in 63,2%, while among the women of the II group of the appropriate age osteoporosis was revealed only in 12,5%, osteopenia in 35,4%. In summary, the high fluoride content of drinking water promote the worsening of structural-functional bone tissue state among the women during the period of bone peak formation and the postmenopausal period.

P070 LIFESTYLE CHARACTERISTICS AND RISK FACTORS IN LITHUANIAN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS V. Alekna E. Ceremnych Institute of Experimental and Clinical Medicine, Centre for Gerontology and Rehabilitation, Vilnius, Lithuania The purpose of the study was to assess additional risk factors for osteoporosis in postmenopausal women with established osteoporosis. With the help of special questionnaire lifestyle characteristics and known risk factors were studied retrospectively in 73 postmenopausal osteoporotic women aged 61.9±1.2 years and in 80 controls (random sample) aged 60.7±O.8 year. The study showed that in group with osteoporosis 2.3 greater prevalence of slim women was found. Five main risk factors disclosed on questionnaire were: difference between groups in their nutrition (lower dietary calcium), exercise in adult (p<0.001) and young age (p
P071 PREVALENCE OF OSTEOPOROSIS IN 500 PEOPLEREFERRED TO A BONE DENSITOMETRY CENTER R. Abhari B. Raissi. A. Akbarian B. Broumand J Forghanizadeh Sina Bone Densitometry CenterA. Mirza Hasani, Mirzaye Shirazi st, Tehran 15867, Iran Aim: To report the prevalence of osteoporosis among the patients referred to the BMD center. Methods: Bone densitometry was done for all patients with DPX-I on Ap spine and Femur as requested. Results: 31 (6.2%) patients were male 469 (93.8%) of patients were female. The range of age was from 20 -85 years. BMD of 218 sites were done for'162 patients from age 20-50 years. In 28 (12.8%) sites osteoporosis were detected. 9 in AP spine & 19 in Femur. In this group 95 persons had some disease (renal, endocrine or rheumatologic ... ) and 59 were postmenopausal but normal BMD. In age more than 50 years (338 patients) in 770 sites BMD was done. In 219 sites osteoporosis were (2804%) detected. 90 in AP spine &129 in Femur. (219 patients had other disease and 312 were postmenopausal). Conclusion: BMD was done in 988 sites in 500 patients. In 247 sites osteoporosis were detected (25%) which was mainly due to hormone deficiency. In both groups, osteoporosis in Femur was more common.

P072 DISTRIPUTION OF OSTEOPOROSIS AMONG THE WOMEN IN THE CITY OF TBILISI Nodar Kipshidze and Anna Tskhakaia Institute of Experimental and Clinical Therapy Tbilisi Republic of Georgia The aim of this study was to reveal the osteoporosis among the population of Tbilisi Region. We have esed rendgenological and osteometral methods among the women in postmenopausal period. According to their ages women were divided into three groups: 50-59 1. Group, 60-69 2. Group, 70 and above 3. Group. Compression fracture of the dorsal vertebra was revelled in 38%. Slight and moderate compression fracture was observed among 2/3 of the women with osteoporosis. Osteoporosis in the 3. Group was 1.5 times and 2 times more frequent then in 2. (second) and 1. (first) groups accordingly. We consider that high prevalence of this disorder is a result of neglect of prevention measure of osteoporosis among the population of Georgia.

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P073 RESULTS OF A QUALITY MANAGEMENT CIRCLE FOR DIAGNOSIS AND THERAPY OF POSTMENOPAUSAL OSTEOPORSIS B. Birkner. St. KottmaiL S. Gotte R Gartner Qualitatszirkel Osteoporose der kassenarztlichen Vereinigung Bayerns (KVB), Miinchen, Germany The principles of quality management are important for the evaluation of diagnostic and therapeutic procedures. To evaluate these routine diagnostic and therapeutic procedures in postmenopausal osteoporosis, and compare them with the national guidelines for management of postmenopausal osteoporosis, a questionnaire was elaborated for documentation of the diagnostic and therapeutic procedures performed by practitioners. This questionnaire asked for history, risk factors, clinical signs, diagnostic procedures and therapy of osteoporosis. In addition quality of life was estimated using the SF 12 questionnaire. Seven clinics including endocrinology (2). orthopaedics (1), radiology (1), internal medicine (1), obstetrics (1) and general medicine (1) participated in the study. During three months (May, July and October) in 1997 all patients with supposed osteoporosis should be included in this prospective study. Only three centers documented continuously during all three months, whereas four centers documented only two months. Nevertheless, for 438 patients the questionnaires were completed. In 60% of patients with more than one risk factor the osteodensitometry revealed osteoporosis, whereas in 20% osteoporosis was found without any significant risk factor. The sensitivity of risk factors was 60%, specificity 80%. Three parameters were significantly correlated to the diagnosis of osteoporosis: low body mass index, less than 1h physical activity per week and kyphosis. Quality of life evaluation revealed, that mental Quality of patients with osteoporosis was normal, but physical quality was reduced. Half of all patients received calcium and vitamin D supplementation, only 20% were under hormone replacement therapy and less than 10% were treated with bisphosphonates, fluorides, calcitonin or active vitamin D metabolites. In summary, it could be demonstrated, a) that indicators for quality management can be established, b) that this quality management can be performed under routine conditions, c) a positive risk profile alone is insufficient for the indication to perform osteodensitometry, d) osteodensitometry is necessary for diagnosis of osteoporosis, e) osteoporosis therapy is not sufficient recommended.

P074 PROSPECTIVE STUDY OF VERTEBRAL OSTEOPOROSIS O. Ershova. O. Semenova N. Beloselskv Yaroslavl Medical Ynstitute, Yaroslavl, Russia The goal of this research was to study the development of the osteoporotic process in 193 persons after 3 years of their initial X-ray examination. The examined group includes 11 patients with OP, 55 with signs of osteopenia, estimated as "probable" (non definite) OP, and 127 people without OP. All members of this group were repeatedly examined with X-ray morphometry and QCT methods. The most interesting was the group with "probable" OP as a possible risk-group of the development of OP. The active development of vertebral OP was more frequently in the group with probable" OP (45, 45±6,71%) than in the group without OP (30,71±4,09%); p<0,05. 3 of 4 new non-vertebral fractures in the group of probable" OP were connected with rapid development of OP, bot one patient with femoral fracture had no signs of OP development. From some more 15 persons that had falls but had no fractures. 8 had vertebral OP but 7 persons were without OP. The prevalence of new fractures was 8,66±2,50% in the group with initial absence of vertebral OP. Negative X-ray dynamic was in 5 of 11 persons in this group. Besides that 45,5% of patients had already fractures at the age of 45-61. Interesting, that 8 of 9 women with new fractures had risk factors of OP, connected with gynecologic anamnesis and reproductive status. The next study will be include the facto res, connected with development of OP.

P075 OSTEOPOROSIS AND PROXIMAL FEMUR FRACTURES O. Semionova O. Yershova N. Beloselski Yaroslavl Medical University, Yarosiavl, Russia In order to establish connection of femur fractures and vertebra region with osteoporosis a thorough analyses of image studies of 133 cases was carried out. Among the patients whose age was over 50, suffering from this type of trauma, there were 42 males and 91 females. The analyses consisted of both pelviS joints X rays spondilography of the chest and 38 % of the patients were subjected to Quality computer tomography (QCT) accompanied by evaluation of bone mass in mg/mm3 on the basis of BMD software. When signs of osteoporosis were analysed on X ray images, methods involving evaluation of cancellous as well as cortical bone tissue and phenomena based on Qualitative evaluation of bone mass decrease in the area of femur joints and vertebra were taken into consideration. Roentgenomorphometical sings of osteoporosis changes in the proximal parts of the femur were discovered in 64,78% of all the cases: 72,72% with male and 61.22 female. Osteoporosis of vertebra in the form of deformations or absorptionmetric changes were found in 71 cases, resulting in 52,38 %. Female patients constituted 51,02% and male - 59,09 %. On the whole signs of osteoporosis in the area of femur joints as well as in the vertebrae bodies were encountered in 49 patients (36,84 %) - 26 females and 23 males (28,57 % and 54,54 % respectively). The second group consisted of patients with signs of osteoporosis on femur bones (29,57 %) and signs of systematic changes of vertebra accompanied by the lack of similar phenomena in femur zone discovered in 22 (16,54 %) cases. Thus in the majority of cases (82,95 %) of proximal parts of femur were connected with osteoporosis of various places.

P076 PREDICTORS OF BONE MASS IN POSTMENOPAUSAL WOMEN G.Yavuzer H. GOk P. Yalein G. Dincer Ankara University, Medical Faculty. Department of Physical Medicine and Rehabilitation Ankara, Turkey This prospective, cross-sectional study was deSigned to determine the predictive value of certain behavioral and clinical risk factors on bone mineral density (BMD). Among the patients attending to our "Osteoporosis, Follow-up Clinic", 334 postmenopausal women aged 45 to 69 years were enrolled into the trial. None of them had a history of taking any medication or disease known to affect bone metabolism. A detailed history including relevant lifestyle parameters and risk factors such as dietary calcium and caffeine intake, alcohol and tobacco consumption, age at menarche, parity, time since menopause and level of physical activity was documented by a standardized questionnaire. Measurements of weight, height and body mass index, laboratory studies identifying the urinary markers of bone turnover and BMD in the lumbar spine and femoral neck with dual-energy x-ray absorptiometry were also performed. The mean BMD of the patients was 0.73±O.13 g/cm' in the lumbar spine (L,..l and 0.72±O.14 g/cm' in the femoral neck. Age and body mass index were found to be significantly but weakly correlated with BMD values of lumbar spine (r=-19, r=21 respectively) and femoral neck (r=-13, r=21 respectively). Multiple regression analysis revealed that none of the parameters had predictive value on BMD values. It is concluded that since the risk factors for osteoporosis are of limited value due to their low prediction, measurement of bone mass isan inevitable step for the diagnosis and treatment approach of osteoporosis.

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Conclusion: The menopausal rise in obligatory calcium loss (and fall in calcium absorption) explains the increase in calcium requirement at this time. The marginal rise in serum PTH suggests that the effect of oestrogen deficiency at the bone level is to facilitate the bone response to this increase in calcium demand rather than to generate a spontaneous rise in bone resorption. [1] Morris HA in Metabolic Bone and Stone Disease. Edinburgh: Churchill Livingstone, 1993.

PATHOGENESIS PD77 EFFECTS OF MENOPAUSE ON BONE MINERAL DENSITY, BONE TURNOVER AND CALCIOTROPIC HORMONES IN TYPE I OSTEOPOROTIC PATIENTS C. Dumitrache D. Grigorie E. Neacsu M. Dumitrache M. Grigorie C. Barbu C. I. Parhon Institute of Endocrinology, Bucharest, Romania We studied the effect of menopause on vertebral mineral density (VMD) measured by dual x-ray absorptiometry (DEXA), bone turnover marker levels and serum calciotropic hormones levels in postmenopausal women. VMD decreased significantly with age (r=-0.59, p
PD7B RECONCILING CALCIUM AND OESTROGEN B.E.C. Nordin, A.G. Need H.A. Morris M. Horowitz* Division of Clinical Biochemistry, Institute of Medical and Veterinary SCience, Adelaide, South Australia; *Department of Medicine, Royal Adelaide Hospital Purpose: To investigate whether the rise in urine calcium at the menopause represents a primary increase in calcium requirement or is simply a response to increased bone resorption. Methods: Morning fasting blood and urine samples and 24hr urines were collected from 102 normal pre- and 86 untreated postmenopausal women up to age 60. Calcium, proteins, PTH and electrolytes were measured in serum, and calcium and creatinine in urine. Serum calcium fractions and fasting urine Ca and TmCa per litre of Cer were calculated as previously described [1]. Results: The mean values of the principal variables in the two groups are shown in the table:

PreSE. PostSE P

TCa (

Bic

AnGap Ca++ Comp Ca UFCA 24hCa CaE TmCa PTH mmol/L ) mmol/d (mmollL Cor) (pmol)

2.29 .0082 2.37 .0093 <.001

28.2 .22 29.0 .23 .011

10.5 23 12.8 .33 <.001

1.17 .35 .0031 .0020 118.. 38 0039 0035 .28 <.001

1.52 .0046 156 0056 <.001

340 17 433 .23 007

011 0007 020 0013 <.001

258 024 244 .023 <.001

3.52 16 402 .18 .042

The higher TCa in the Post- was accounted for by their higher bicarbonate and anion gap (and protein - not shown) which accounted for their higher complexed and therefore ultrafiltrable calcium. The higher 24hr Ca in the Post- was entirely accounted for by their higher obligatory calcium loss. 20% of their increased calcium excretion was accounted for by their increased UFCa and the rest represented reduced tubular reabsorption of calcium .

PD79 EFFECTS OF URINARY PHOSPHATE AND SULPHATE ON URINARY CALCIUM EXCRETION Allan G. Need Michael Horowitz* B.E. Christopher Nordin Division of Clinical Biochemistry, Institute of Medical and Veterinary Science; *Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia Urinary calcium excretion, which is significantly linked to postmenopausal bone loss, is dependent on both sodium and protein intake but the mechanism by which protein intake influences calcium excretion is unclear. We have therefore studied fasting urinary phosphate and sulphate excretion and examined their contribution to urinary calcium excretion in 95 postmenopausal women. Urine was collected following a 12 hour fast after emptying the bladder of the overnight urine. Calcium, sodium, phosphate and sulphate were measured by standard methods and divided by urine creatinine to give CalCr, NalCr, P/Cr and S/Cr. CalCr was positively related to NalCr and P/Cr (r=0.47 and 0.37 respectively) but notto S/Cr (r=-0.01). Multiple linear regression gave the following equation:

P CalCr = 0.011 * NalCr +0.056*P/Cr -0.027*S/Cr +0.089 R=0.49, P<0.001

4.0 2.2 -1.1

<0.001 0.03 0.27

We conclude that protein intake may increase fasting urinary calcium excretion by virtue of its phosphate content but that its sulphate content has little effect on urinary calcium loss.

PDBO VITAMIN 0 RECEPTOR GENOTYPE AND EARLY LIFE: EVIDENCE FOR AN INTERACTION? E. Dennison S. Kellinaray N. Ardell R. Keen T. Spector C. Cooper MRC Unit, Southampton S016 6YD Studies of the association between Vitamin 0 Receptor (VDR) genotype and bone mass have given conflicting results in different populations. Secular trends in height observed over the first half of this century suggest that gene-environment interactions may be important in determining adult bone mass. We have previously demonstrated an association between weight at one year of age and i) adult bone mass and ii) VDR genotype, and therefore sought to investigate the possibility of gene-early life interaction in an elderly UK cohort. 173 men and 143 women aged 63-73 at baseline who had been born in Hertfordshire and who still lived there were recruited to a longitudinal study of bone loss. Their birthweight and weight at one year had been recorded. Bone mass was measured at baseline and follow-up four years later. Whole blood samples were obtained and DNA obtained using standard extraction techniques, and polymorphisms identified using the bsm endonuclease. Three hundred and eight individuals from our Hertfordshire cohort were successfully characterised according to VDR genotype. While there was a trend toward greater spine area in individuals of genotype 'BB', this was not significant. Spine bone density was also higher in individuals of genotype 'BB': this relationship was statistically significant in those in the lowestthird of birthweight (p=0.03) but not in the highestthird (p=0.13). No such relationship was demonstrable between VDR genotype and hip area, hip axis length or hip bone density. There was also no trend of bone loss rate at either lumbar spine or femoral neck with VDR genotype. These results suggest that undernutrition in utero may modulate the effect that genotype has on bone mass at the lumbar spine.

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P081 ALLELIC DIFFERENCES IN THE 3' UNTRANSLATED REGION OF THE VITAMIN D RECEPTOR GENE AFFECT mRNA LEVELS IN BONE CELLS M. Beaumont A.J, Bennett D.A. White D.J. Hoskina School of Biomedical Sciences, Nottingham University, The Medical School, Nottingham, UK. Division of Medicine, City Hospital, Nottingham, UK It has been suggested that polymorphisms in the vitamin Dreceptor (VDR) gene might be associated with differences in bone mineral density (BMD). We have cloned the 3' untranslated region (3'UTR) from subjects homozygous for the two most common VDR gene haplotypes defined by RFLPs for three restriction endonucleases, 8sml, Apal and Taql (BAt and baT) and inserted them into the pGL3 vector downstream ofthe luciferase gene. These constructs were tranSiently transfected into human osteoblasts (HOB) and human osteosarcoma celts (HOS) and luciferase was measured 24h and 48h post transfection. Significant differences were seen at 24h in both celt types (1.5-2 fold in HOB, 3-5 fold in HOS) with a3-5 fold difference being maintained in HOB 48h after transfection. In each case the activity in cells transfected with the 3'UTR from the baT haplotype was greater than those transfected with that from the BAt haplotype. Nuclear run on analysis suggested that these differences were due to increased stability of mRNA rather than increased rates of transcription. Thus differences in the 3'UTR of different haplotypes of the VDR gene may contribute to differential effects of VDR polymorph isms on BMD.

P082 BONE MINERAL DENSITY AT THE TIME OF PREMENOPAUSAL HYSTERECTOMY C.E Kearney SA Beardsworth S.A Steel D.w Purdie Centre for Metabolic Bone Disease, Hult Royal Infirmary, Hult, UK The implications of pre-menopausal hysterectomy and ovarian conservation on bone mineral density have been debated over the last 10 years. The assertion by Siddle (1987) that ovarian failure advanced the mean age of menopause by 4.6 years led to concerns about premature bone loss. In 1995 Watson et al compared an age-matched group of women who had under gone premenopausal hysterectomy with conservation of the ovaries with controls retaining the uterus. Bone density in the hysterectomy group was Significantly reduced (p
P083 THE PREMENOPAUSAL ACCUMULATION OF BONE MATERIAL PER UNIT MUSCLE MASS IN WOMEN WOULD BE OF LITTLE MECHANICAL RELEVANCE J.L. Ferretti. J R Zanchetta. R E Caoozza G R Cointrv M Braun P Schnejde[ C. Reiners D Saljca CEMFoC, Natl.Univ.of Rosario; IOIMlFIM, Buenos Aires, Argentina; Universitiit Wiirzburg, Germany Premenopausal women store more bone mineral per unit lean body mass than girls or postmenopausal women or males at any age do (Ferretti et ai, Bone 22(6), in press). This material should be deposited in mechanically little relevant sites, otherwise the bone mechanostat would deal with it. To test this hypothesis, we measured the volumetric BMC and BMD of trabecular bone (vTbBMC, vTbBMD) and the cross-sectional area (CSA) and moment of inertia (CSMI, an indicator of the architectural efficiency of bone modelling related to the periphericity of bone material in the section) of the cortical region in paCT scans [XCT-900, Stratec, Germany) of the distal radius of normal, age-matched German and Argentine men (155, 35) and women (265, 60) aged 20-85 years. The intercepts of the correlations between vTbBMD (y) and vTbBMC were significantly higher for women than for men, and those of the correlations between CSMI (y) and CSA were higher for men. Results indicate (a) that similar trabecular masses are distributed in smaller bone areas (leading to acondensation ofthe trabecular tissue, mechanically little relevant in the region) in women than in men, and (b) that women can store more compact material than men avoiding a significant improvement of the architectural design of the cortex. This can only happen provided that bone material is predominantly accumulated on the endosteal region in women, I.e., where it influences the least the CSMI. These differences are congruent with the hypothesiS that estrogen turns bone remodelling to the «conservative» mode (lOW turnover, even BMU balance) in regions close to marrow [Frost et ai, Bone 22,1,1998). Being of little mechanical relevance, these changes should not significantly distort the regional determination of the radial mechanical quality by the muscle force of the forearm, as already suggested [Frost et ai, CTI 62:1,1998).

P084 CALCIDIOL, PTH AND URINARY OEOXY-PYRIDiNOLINE IN A LARGE COHORT OF POST-MENOPAUSAL WOMEN E. Fradjnger C Bogado J Zanchetta Instituto de Investigaciones Metabolicas. Buenos Aires. Argentina Low levels of calcidiol is common in the elderly population and this was associated with bone loss presumably by inducing secondary hyperparathyroidism (S-HPT). We report herein serum calcidiol (25D) PTH and urinary free-deoxy-piridinoline (DPD) values and the prevalence of SHPT(>65 pg/ml) and vitamin Ddeficiency (<10 ng/ml) from 231 free-living post-menopausal women aged 50-90 years in Buenos Aires (34°S). 109 were recruited in summer and 122 in winter. 25D was measured by competitive binding assay DPD by ELISA and intact PTH by IRMA. Lumbar spine and femur neck bone mineral density (BMD) were obtained by DEXA. We observed seasonal variation of 25D (25.3±6.16 nglml in summer vs. 21.6±6.85 nglml in winter p<0.001). In the whole group prevalence of vitamin D deficiency was 2.16% and S-HPTwas 5.19% both Significantly higher in winter. 39.8% of patients had 25D between 10-20 nglml in winter and 23.2% in summer and both groups had significantly higher PTH in comparison with patients with 25D > 20 nglml. DPD values did not correlate with age but were 30% higher than pre-menopausal values along the range of age studied. The following table shows significant correlations in the study. Total(r) p PTH vs age 25D vs age PTH vs 25D PTHvs DPD fBMD vs PTH

0.236 -0.278 -0.366 0.125 -0.188

<0.001 <0.001 <0.001 ns <0.005

SIr)

p

0.232 -0.275 -0.419 0.98 -0.223

W(r)

0.248 <0.02 <0.005 -0.297 <0.001 -0.353 ns 0.224 <0.02 -0.159

p <0.01 <0.001 <0.001 <0.02 ns

ns= Not Significative, S= summer, W=winter In conclusion prevalence of vitamin D deficiency and S-HPT is lower than other european studies. Higher PTH values found in patients with 25D between 10-20 nglml suggests that the concept of vitamin D deficiency should be revised, specially in the elderly population .

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PUS5 INHIBITORY EFFECTS OF GLUCOCORTICOIDS ON OSTEO BLASTS: CLINICAL AND MOLECULAR STUDIES P.A. Hulley, H. Nortje, F. Gordon and F.S. Hough Department of Endocrinology, University of Stellenbosch, South Africa. Since the major effect of glucocorticoids (GC) on the skeleton appears to involve the suppression of osteoblastic bone formation, clinical (110 atopic asthmatics) and molecular (MBA 15.4 preosteoblast cell line) studies were undertaken to explore this hypothesis. Neither age, gender, menopausal state, conventional risk factors for osteoporosis. Cushingoid Side-effects, duration of therapy nor total cumulative steroid dose (TCSD) could identify GC treated patients with DEXA confirmed osteopenia (46%). When GC treated patients with a normal BMD were however compared with steroid treated patients with a low BMD (matched for age, gender, TCSD and plasma cortisol binding globulin values) the latter had lower basal and 1,25(OH)2 vit D-stimulated serum osteocalcin levels, suggesting that osteoblast sensitivity, and not steroid dose only, may underly the suppression of bone formation by GC. We subsequently showed that GC decreased (25-72%) the proliferation of an early osteoblast cell line, and that this correlated with a40% reduction in the intraceelular activity of TPA stimulated mitogen activated protein kinase (MAPK). This pivotal enzyme in mitogeniC Signalling is activated by upstream kinases and inactivated by phosphatases. Since cell proliferation and MAPK activity could be restored by treatment with specific inhibitors of tyrosine (e.g. vanadate), but not serine/threonine phosphatases (e.g. NaF), we conclude that GC inhibit preosteoblast growth via a novel tyrosine phosphatase pathway.

PUS6 BONE MINERAL DENSITY IN PATIENTS WITH HEMIPARESIS K. Bors A. Bodna[ Z. Radnai E. Boros E. Hosszu C. Horvath Visegrad Rehab. Hospital, Ferenvaros Health Center, Nat. Inst. of Medical Rehabilitation, II. Dept. PediatriCS., I. Dept. Medicine, Semmelweis Univ. Med. School, Budapest. Hungary The aim of this work was to study the role of the neural supply on bone mass. 49 patients with hemipartesis were involved (24 women and 25 men, aged at 61±1.6 ys) with duration of hemiparesis as 86±11 days (mean±SE). All patients participated in an active rehabilitation program ensuring the lack of immobilization. 16 healthy volunteers (7 women and 9 men, aged 52.3±2.2 ys) were also studied. All but one patients and all controls were right-handed. Bone mineral density of the forearm was measured by pDEXA (Norland-Stratec, USA). The measurement was done on both sides and the right-left differences were evaluated.

Right paresis R-L (mg/cm2) R-UR*100 (%) Left pareSis R-L (mg/cm2) R-UR*100 (%)

HEMIPARESIS

CONTROL

n=24

n=16 6.7±5.5 1.9±1.7 n=16 5.7±5.5 1.9±1.7

~17.6±7.0

-7.8±3.8 n=16 11.5±5.8 3.3±1.7

p <0.02 =0.05 NS NS

The hemiparesis decreased bone mineral density in spite of the fact that they were not immobilized. Our observation confirms the importance of neural innervation in the determination of bone mineral mass.

PUS7 PLASMA 25-0HD3 LEVEL IS RESPONSIBLE FOR LOW FOREARM DENSITY AND LOW PHALANX SOS IN WOMEN BUT NOT IN MEN LIVING IN OLD PEOPLE'S HOME S. Meszaros G Novothny E. Hosszu P. Lakatos J Szucs C. Horvath I. Dept. Medicine and II. Dept. Pediatrics, Semmelweis Univ. Med. School, Budapest and Osteoporosis Center, Nagyatad, Hungary The purpose of this study was to assess the role of vitamin D3 deficiency in the osteoporosis of patients living in homes for the aged (40 men and 57 women, age 66.5±O.8 ys). BMD was measured on distal and proximal sites of non-dominant forearm by pDEXA (Norland-Stratec) and SOS was determined on phalanges by DBM Sonic 1200 (IGEA) device. Plasma level of 25-0I-1D 3was also measured. Decreased BMD was observed both on distal and proximal radius, being more expressed in the proximal than distal site and in women than in men. SOS was also definitely more decreased in women. 25-0HD3 levels were found in the lowest quartile in more than 90% of the patients. BMD correlated negatively with age and positively with time from menopause. Positive correlations between BMD or SOS values and 25-0HD3 levels were shown in women: women Distal BMD Prox BMD Phal SOS

R 0.61 0.69 0.51

men p 0.00002 0.003 0.0009

R 0.14 0.45 0.06

P 0.45 0.62 0.75

Our data suggest an important role of plasma 25-0HD3 in the development of osteoporosis in this subpopulation but only in females. However, correlations of previous fractures with BMD, SOS or vitamin D3 were not found.

PUSS DETERMINANTS OF MUSCLE STRENGTH, MASS AND FUNCTION IN RELATION TO BONE DENSITY IN ELDERLY WOMEN P. Geusens1,2, J, vanhoof1, K, Deklerck1, ~1,2 1Dr, L. Willems-Instituut, 1Limburgs Universitair Centrum, Belgium Muscle strength (MS), muscle mass (MM) and muscle function (MF) decrease with aging and are related to fracture risk. However, the interrelations of MS, MM, MF are not well documented in elderly women. We investigated these intercorrelations in muscle parameters and their relation with bone density in 200 women of 70 years and older. Bone density and lean body mass were measured in the total body and regions of interest by DEXA (Hologic aDR 2000), Routine functional tests were performed. Grip and quadriceps strength were measured by standard techniques. Serum IGF1 (n=1 00) and free testosterone (n=200) were measured by RIA. All muscle parameters and bone density in the hip and forearm decreased with age Local bone density was correlated with MS (r=.280*** in the arlns and r=.156* in the legs) and with MM (r=.142* in the arms and r=.306*** in the legs). MSwas correlated with MM (r=.358*** in the arms and r=.214** in the legs), However, simple MF such as raising from a chair orwalking on a line was related to MS (r=.160* to .233***) but notto MM. Physical activity during puberty was correlated with MM (r=.162 in the arms and .217** in the legs) while current physical activity was correlated with MS (r=.128* to .136*). MS and MF, but not MM, were correlated with IGF-1 (r=.153 to .337**). No correlations were found between MM or MS and serum free testosterone. We conclude that in elderly women MM, but not MS or MF, is related to physical activity during growth. MS and MF, but not MM, are related to current phYSical activity and IGF-1. None of the muscle parameters were related with serum free testosterone. ·p<.05, **p<.01, ***p<.001

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POS9 FOK 1 POll MORPHISM OF THE VITAMIN 0 RECEPTOR GENE, BONE MINERAL DENSITY AND OSTEOPOROTIC FRACTURES IN POSTMENOPAUSAL ITALIAN WOMEN ~', L Becherini" R. Mansani" L Masi" S. Gonnelli', C. Cepollaro', and M L Brandi' 'Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Florence and 'Institute of Internal Medicine, University of Siena, Siena, Italy Bone mineral density (BMD), the rnajor determinant of osteoporotic fracture risk, is a quantitative trait, determined by the interaction of genetiC, metabolic, and environmental factors. A novel TIC polymorphism (ATG to ACG) at the translation initiation site of the vitarnin 0 receptor (VDR) gene, defined by Fok 1 restriction endonuclease, has been recently associated with variation in BMD and rates of bone loss. The presence of the restriction site, deSignated as f allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at asecond ATG. In this study we investigated the role of Fok 1 polymorphism in 380 postmenopausal women of Italian descent stratified for BMD in osteoporotic (144), osteopenic (117), and normal (119). Genotypes were detected after PCR amplification of exon 2 of the VDR gene. There were 152 FF homozygotes, 52 ff homozygotes, and 176 Ff heterozygotes. In the whole population we observed a weak association between Fok 1 polymorphism and lumbar BMD (p=0.06, ANCOVA) but not femoral neck BMD (p=0.5, ANCOVA). Interestingly, the effect of Fok 1 genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greatest among women in the first 5 years of menopause (P=0.04, ANCOVA) and progressively declined afterward. In addition, a statistically significant prevalence of FF genotype in osteoporotic than in osteopenic and normal women was observed (p=004, X' test). Finally, FF genotype resulted significantly over-represented in the group of women with a vertebral fracture as compared with controls (p=0.003, x'test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36 - 4.91). We conclude that in this population, Fok 1 polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.

P090 GASTRECTOMY IN THE RAT CAUSES MORE SEVERE OSTEOPENIA THAN OVARIECTOMY OR PREDNISOLONE TREATMENT ~" N Andersson" D. Lehto-Axtelius' and R. Hakanson' 'Department of Pharmacology, University of Lund, Lund, Sweden, 'Departments of Periodontology and Laboratory Animal Resources, Centre for Oral Health Sciences, Malmo, Sweden Osteopenia is a common finding after ovariectomy (Ovx), prednisolone treatment (Pre) and gastrectomy (Gx). While Ovx and Pre are known to induce significant trabecular bone loss after about six weeks as evidenced by histomorphometry, we know from past experience that Gx induces trabecular bone loss already two to three weeks after the operation. The present study was conducted to evaluate and compare the magnitude of osteopenia after Ovx, Pre and Gx. Female Sprague-Dawley rats, weighing 200-225 g were gastrectomised, ovariectomised, treated with prednisolone, or left intact. After 8 weeks they were sacrificed and bones and serum were collected. The body weights were monitored throughout the study. Serum was analysed for calcitonin and gastrin. Calvariae, tibiae, femurs and lumbar vertebral bodies were subjected to bone density measurement, biomechanical testing, transillumination and thickness measurement of the calvaria and histomorphometry. All experimental groups with the exception of the Ovx group had a slower weight gain than the controls, Gx having the, slowest weight gain. Serum calcitonin was normal in all groups. Serum gastrin was low in the Gx group but normal in others. Bone density was reduced in distal femur and vertebral body in the Ovx and Gx groups, more so in the Gx group. Their were no significant changes in femoral neck strength. Transillumination analysis and measurement of thickness of the calvaria revealed bone loss in the Gx group but not in the other experimental groups. Cross-section of the calvariae and tibiae showed a rapidly developing osteopenia in the Gx rats. The bone surface area, expressed as percentage of the total biopsy surface area, decreased dramatically after Gx. No such changes were observed in the other groups. The findings indicate that Gx causes a rapid and dramatic osteopenia than Ovx or Pre. The mechanism behind the Gx-evoked osteopenia remains obscure.

P091 LACK OF BONE HIGH TURNOVER IN PATIENTS WITH RHEUMATIC DISEASES UNDER LONG-TERM LOW-DOSE GLUCOCORTICOID THERAPY (LDLGT) R. Dreher G. Sommer* G. Emrich* Hospital for Rheumatic Diseases, 0 55543 Bad Kreuznach, Germany *Hospital Evaluation Systems, 067655 Kaiserslautern Aim: Bone metabolism was to be investigated in inpatients with different rheumatic diseases (chiefly rheumatoid arthritis) under LDLGT In particular the hypotheSiS of secondary hyperparathyroidism (HPT) induced high bone turnover as pathogenetic principle of glucocorticoid-associated osteoporosis and the presence of seasonal HPT were to be tested. Method: 1. Cross-sectional determination of the parameters of bone metabolism in men as compared to women with and without LDLGT in relation to age (osteocalcin specific bone phosphatase, iPTH DPD, PYD, CA 24hour urine) Women with LDLGT n=402, wornen without LDLGT n=276 2. Cross-sectional determination of the parameters of bone metabolism in men and women aged 55-75 years in relation to the seasons JuneOctoberlNovember-May. 25 OH Vita 03 (n=186/356), iPTH (n=186/394) DPD (n=196/392), PYD (n=186/321) iPTH, DPD, PYD osteocalcin specific bone alkaline phosphatase were determined with ELISA (Metra Biosystems) Results: In men and women with and without LDLGT the parameters of bone metabolism are in the normal range. In women DPD and PYD rise in the postmenopause but remain in the normal range. In the months November - May, 25 OH Vita 03 shows significant lowering, and iPTH a significant increase (both within the normal range). On the other hand DPD and PYD remain unchanged. Conclusion: A secondary HPT which affects bone metabolism cannot be demonstrated neither under long-term low-dose glucocorticoid therapy nor depending on the season.

P092 HYPOVITAMINOSIS 0 IN THE CENTRE OF ITALY. E. Romagnoli P. Caravella* S. Minisola* Ospedale San Giovanni Battista and * II Clinica Medica, Universita "La Sapienza", Rome, Italy. The study was carried out in order to investigate the prevalence and seasonal variation of hypovitaminosis 0 arnong healthy subjects and hospitalized patients living in the Centre of Italy We studied 297 subjects, 131 in February and 166 in July 1997, subdivided into four groups: a) young healthy blood donors (n=88, 70 males and 18 females, mean age 35.0±9.9 years), b) healthy postmenopausal women (n=47, mean age 62.3±Bo4 yrs); c) inpatients with various medical diseases (n=88, 43 males and 45 females, mean age 6504±13.1 yrs) and d) inpatients engaged in long-term rehabilitation programs owing to various neurological disorders (n=62, 26 males and 36 females, mean age 7404±6.9 yrs). Serum levels of 25 hydroxyvitamin 0 [25(OH)D] were measured by RIA, after extraction (Incstar Co., MN, USA); intra and interassay coefficients of variation were 8.1 and 10.2%, respectively. Mean±SD values of serum 25(OH)D (nmol/l) and the prevalence of hypovitaminosis 0 (in brackets, defined as a serum level below 30 nmoll I) are reported in the table.

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GROUP

FEBRUARY

JULY

a b c d

61.2±25.2 (14.6%) 45.9±28.5 (32%) 27.2±17.8 (7104%) 22.5±11.9 (82.3%)

120.3±32.1 (0%) 90.1±49.6 (4.5%) 65.5±45.5 (29.8%) 31.1±21.5 (57.8%)

We found a significant seasonal variation (p<0.0001) of 25(OH)D serum levels, mean values being higher in summer for all groups, except for patients with longer hospitalization time (group d). A significantly higher prevalence of hypovitaminosis 0 was found in winter as compared to summertime (p
P093 AGE-RELATED OSTEOPOROSIS IN CHINESE: AN EVALUATION OF THE RESPONSE OF INTESTINAL CALCIUM ABSORPTION AND CALCITROPHIC HORMONES TO DIETARY CALCIUM DEPRIVATION AWC. Kung K. Luk, L.w. Chu, P. Chiu Departments of Medicine and Orthopaedics, The University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC Low dietary calcium is a recognised risk for osteoporotic fractures. We evaluated the pathogenesis of age-related osteoporosis in a group of Chinese women with a mean calcium intake of 561±183 mg/day. When compared to young healthy controls, the osteoporotic subjects had negative calcium balance, raised urinary calcium excretion (0.63±O.47 vs 0.27±O.16 mol/mol, p
P094 PARATHYROID HORMONE PLASMA CONCENTRATION IN RESPONSE TO LOW 25-0H VITAMIN D CIRCULATING LEVELS INCREASES WITH AGE IN ELDERLY WOMEN R. Deroisy', A-N. Taguet" W. Dewe', A. Albert', J. Collette', C. Gosset', J.Y. Reginster"·3 'Bone and Cartilage Metabolism Unit, University of Liege, Belgium 'Department of Epidemiology and Public Health, University of Liege, Belgium - 3Georgetown University Medical Center, Washington DC, USA We investigated whether or not response of parathyroid secretion to a decrease in Circulating levels of vitamin D is influenced by the age of the subject. We used the values of 25-0H vitamin D and parathyroid hormone Circulating levels obtained from a previously described epidemiological survey in which 1 483 women were tested for these two biochemical parameters. The mean values (SEM) of 25 OH D and parathyroid hormone were respectively 12.2 (0.1) ng/ml and 34.1 (1.0) pg/ml in a population of elderly women. Age was correlated negatively with 25 OH D (r=-0.22; p
P095 INCREASED PARATHYROID HORMONE SECRETIONS AS A RISK FACTOR FOR FEMORAL OSTEOPOROSIS IN ELDERLY WOMEN R. Deroisy', J. Collette" W. Dewe', A. Albert', ~', J.Y. Reginster'·'·3 'Bone and Cartilage Metabolism Unit, University of Liege, Belgium 'Department of Epidemiology and Public Health, University of Liege, Belgium - 3Georgetown University Medical Center, Washington DC USA We investigated the possible role of increased parathyroid hormone circulating levels on the risk of elderly women to develop femoral osteoporosis. 1 483 women aged 70 years and older, agreed to participate in this trial. Their femoral neck bone density was measured by dual X-ray absorptiometry with a specific device installed in a mobile truck. Parathyroid hormone circulating levels were assessed after an overnight fasting. After adjustment for type of housing, a significant relation was found between femoral neck bone mineral density and parathyroid hormone levels (p=0.004). Parathyroid hormone values were significantly higher in women with femoral osteoporosis, both before (p=0.007) and after (p=0.0049) adjustment for age and type of housing. When stratifying our population by quartiles of serum parathyroid hormone values, the odd ratios for femoral neck osteoporosis were significantly increased for the upper two quartiles compared to the lower one both before (p=0.003) and after (p=0.0013) adjustment for age and type of housing. From this study, we conclude that parathyroid hormone circulating levels are important determinants for low femoral density and osteoporosis.

P096 FEMORAL NECK FRAGILITY: THE IMPORTANCE OF REGIONAL CORTICAL BONE STRENGTH K.L. Bell. N. Loveridge, J. Power. H. Kroger*, J. Reeve University of Cambridge Department of Medicine, Cambridge, U.K. *Kuopio University Hospital, Kuopio, Finland Finite element modelling has shown that the supero-posterior (S-P) inferoanterior (I-A) axis of the femoral neck is maximally loaded on impact from a sideways fall (Loll et aI., Osteopor. Int. 5: 252,1995). El'owener, (Calc if. Tissue Int. 53 suppl1 :S68, 1993) has proposed that r "I bone yield strength is only two fold higher than that imposed' .In loading. Therefore, we have measured the circumferenti' ~ .s and cortical bone area, cortical width and porosity in fel"'" ~ Jiopsies from 13 female intracapsular hip fracture cases (f ~ _.1 Y (SEM)) and 10 aged and sex matched cadaveric control~ ~~ • oiopsies were sectioned (101lfTl) and stained with von Kos~' ~~ er's protocols. Bone areas, cortical widths and porosity were· ....\ ' .,ing interactive image analysis systems (Belietal,Bone19: 5' ~~.... J Bone Min, Res. 12: 1231, 1997). In the fracture cases, t~ ~ancellous bone area was similar to that in the controls (p>r .Ioportionalloss of cortical bone was gr~atest in the I-A (31' ~ ~nd S-P (25%, p<0.05) regions compared to the control grr .1 porosity was greatest in the anterior region, being 48% higl. In the control group (p<0.06), principally due to the substantial 10 . case in the proportion of canals of diameter greater than 3851lfTl (p<0.01). From this increase in porosity it would be predicted (Schaffler & Burr, J Biomechan., 21: 13, 1998) that the elastic modulus in this region would be reduced by 30%. The combined effect of the reductions in cortical width and the increase in porosity suggest as 58% reduction in yield strength for a given load due to the increase in stress (force/area) and the decrease in elastic modulus. From this study, it has been demonstrated that in the fracture cases there are marked changes that lead to a substantial weakening in the cortical shell in those very regions which theoretically are maximally loaded on impact of afall leading to a substantial reduction in Biewener's safety factor.

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PD97 LONG-TERM INTRAVENOUS NERIDRONATE THERAPY INCREASES LP(a) PLASMA LEVELS V. Braga D. Gatti G.C. Guidi and S. Adami C.O.C. Valeggio, University of Verona, Italy Lipoprotein(a) [Lp(a)] is a low density lipoprotein-like particle displaying strong athero-thrombotic properties. More than 90% of its concentrations in plasma are thought to be under genetic control. Some other factors, such as diabetes and hormonal disorders can contribute to the regulation of the plasma concentrations of Lp(a). Lp(a) can also be transiently altered by the acute phase response. Intravenous administration of aminobisphosphonates are often associated with the appearance of a unique acute phase response. In this study we evaluated the Lp(a) levels, together with other plasma lipids, in 16 women with postmenopausal osteoporosis given intermittent intravenous Neridronate (50 mg every two months for 12 months). Bone alkaline phosphatase (Alkphase, Metra, CA, USA) decreased by 20% (±20%, S.D., p
PD98 ALENDRONATE TREATMENT REDUCES THE ADVERSE INFLUENCE OF THINNESS ON OSTEOPOROSIS RISK M.E. Bidstrup* N.H. Bjarna.son* M.R. McClung D.J. Hosking R. Wasnich for the EPIC study group. *:CCBR, Ballerup Denmark We have previously shown that thin women have a lower bone mass and a more rapid loss of bone after menopause. During only 2 years of followup of placebo treated women in the EPIC study these associations appeared to become increasingly stronger indicating that thinness is an important risk factor for osteoporosis development. To study the ability of alendronate treatment to control this risk factor we examined the relationship between thinness parameters (Tp):(BMI, and fat % derived from total body scan) and bone status (BMD and bone markers) in the EPIC study, a double-blind, placebo-controlled, randomized trial of long-term alendronate (aln) treatment (2.5 mg and 5 mg) for the prevention of osteoporoSiS (1609 participants at 4 centers). At baseline, in both placebo and aln groups. TP were significantly negatively associated with bone markers (for example r=-0.24; p<0.05 for BMI and urinary CrossLaps). After 2 years this association tended to be stronger in the placebo group, whereas it disappeared in the aln groups suggesting that aln treatment may reverse the deleterious effect of thinness upon bone turnover. In the placebo group there was a strong association between %change in BMD and TP as well as an increasing correlation over time. In contrast in the aln groups the association at 2 years with BMD was unchanged from baseline. Furthermore, the %changes in bone markers at 2 years were uncorrelated with TP and % changes in BMD at 2 years were in general not associated with TP although a borderline effect was seen for BMI (table shows %change (g/cm') from baseline in tertiles of TP) .

BMDhip terti Ie:

2.5 mg alendronate high low mid

fat% BMI

0.77 0.97

1.27 1.03

1.23 1.29

BMDspine 2.5 mg alendronate tertile: fat% BMI

low 2.14 2.08

mid 2.58 3.36

high 2.14 3.45

5 mg alendronate low mid p

high

p

1.56 1.55

2.11 2.19

NS 0.03

high 3.40 3.97

p NS 0.05

NS NS

2.15 2.10

5 mg alendronate p NS NS

low 2.99 2.94

mid 3.53 3.92

We conclude that the deleterious influence of thinness on osteoporoSiS risk is reduced during aln treatment in early postmenopausal women. If a higher aln dose produces even stronger effects remains to be investigated.

PD99 TRABECULAR BONE LOSS IN POSTMENOPAUSAL WOMEN: RELATED TO LIPOPROTEINS? E. Bally-Gerber R. Gass Institute of Social and Preventive Medicine, University of Zurich, Switzerland Background. Bone metabolism may be influenced by lipid metabolism. Serum lipoproteins are valuable predictors for athero sclerotic risk; are they related to postmenopausal bone loss? Methods. In a prospective two-year study 70 healthy postmenopausal women with an intact uterus and without oophorectomy, aged 46 to 55 years, on average two years after natural menopause (not taking hormones, body-mass index <28 kg/m2), were measured by peripheral quantitative computed tomography (paCT, thin- and multislice technique; long-term reproducibility 0.3%), quantifying in mg/cm3 the bone loss in the pure trabecular tissue (without corticalis) at ultradistal radius. Results. The values of LDL -cholesterol or apolipoprotein Bare positively correlated to the trabecular bone mass, also under controlling for bodymass index and annual bone loss rate (p<0.001). Regarding the association between lipid parameters and annual change of bone mass (-19 to 2.6%), the correlations adjusted for body-mass index and trabecular bone mass, show: the higher the trabecular bone loss, the higher is the apolipoprotein B (P3.8 % per year). Conclusions. There is some evidence that during the years of fertility LDL-cholesterol and apolipoprotein B sustain the development of bone mass. After menopause, HDL -cholesterol and apolipoprotein A-1 may have protective effects on bone loss. The atherogenic risk indexes (LDL to HDL, apo-ratio) are strongly associated not only with coronary heart disease, but also with postmenopausal osteoporOSiS.

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P100 PSYCHOPATOLOGICAL ASPECTS OF POST MENOPAUSAL OSTEOPOROSIS L. Monteiro, E. Simoes R. Leitao, C. Raposo, C. Parreira, A. Barbosa Instituto Portugues de Reumatologia, Lisboa, Portugal A study of fifty post-menopausal osteoporotic ambulatory women (densitometric values of T scores< 2.5) sequentially referred to a public rheumatologic center was undertaken to determine the presence of psychopatological parameters of the illness. The control group (n=50) was made up of post-menopausal women who showed no osteoporosis, chosen sequentially in a community health center. The selection criteria for the groups included: age (45-75) and absence of other chronic or psychiatric diseases. 70% of all women were married, 50% were retired and the average age was 62.7 years old. The two groups were assessed by the following psychosocial instruments: SCL-90-R (Derogatis, 1983), NEO-FII (Costa, 1989), HDS (Zigmond, 1963), ISSI (Henderson, 1982), Life events (Paykel, 1980). A psychiatric diagnostic interview was made on higher anxiety and depression scoring of the study population. There were no significant statistical differenCes observed between the two groups when sociodemographic characteristics were compared (age, civil state, social class, level of education) as well as with the five dimensions of personality assessment, the availability and adequacy of social support and the number and the impact degree of life events in the last year. The osteoporotic group showed a statistically significant higher score of depression (t= 2.22; p<.05), somatization (t=4.78; p<.0001), obsessivecompulsive (t= 4.29;<.0001) and phobic anxiety (t= 2.04; p<.05). We concluded for the importance of psychopathological factors in osteoporosis and the need for an early psychological assessment allowing a possible selective psychiatric and/or psychotherapeutic support to some of these patients.

P101 CORRELATION OF MUSCLE STRENGTH WITH BODY MASS INDEX, BALANCE, FUNCTIONAL MOBILITY AND QUANTITATIVE ULTRASOUND MEASUREMENT OF THE CALCANEUS IN ELDERLY PEOPLE H. Bischoff" ,J.,. . B.!!Qr, D. Lindemann" ~1Jj~kP, M. CQnzelmann" H.B. Stahelin ' . R. Theiler' University Hospital Basel, Divisions of Geriatrics ' and Rheumatology'; University Hospital Zurich, Devision of Rheumatology' ,Switzerland Background: Muscle strength can be increased by exercise even in advanced age and plays a substantial role in the risk of falls and fractures through functional status and bone mineral density. Aim: We investigated other clinical (sex, body mass index = BMI, balance, functional mobility) and physical (quantitative ultrasound of bone tissue = QUS as broadband ultrasonic attenuation = BUA) parameters in their relation to muscle strength. Methods: 207 institutionalized elderly men (61) and women (146) were included in a cross-sectional study (mean age: 84.3; range 70-97). Muscle strength was measured as knee flexion in kilopond (isotmetric method). For functional mobility measurements the "timed up and go" test by Podsiadlo was used. Balance was measured as the "functional reach" test by Duncan. BUA was assessed at the calcaneus (Sahara, Hologic). Results: Muscle strength was significantly correlated with sex (r=0.3; p<0.0001), BMI (r=-0.16; p=0.03), balance (r=0.41; p<0.0001), functional mobility (r=0.40; p<0.0001) and BUA of the calcaneus (r=0.30; p<0.0001). Conclusion: In this study muscle strength showed a strong relationship with various clinical parameters (sex, BMI, balance, functional mobility) and QUS of the calcaneus. These findings support the view that through weight bearing exercise and thereby increase of muscle strength in the elderly other clinical risk factors of falls, such as impairment of balance and functional immobility, as well as physical qualities of bone tissue (QUS) might be influenced to reduce fracture risk.

P102 VITAMIN D AND BONE MINERAL ACQUISITION IN FEMALES DURING ADOLESCENCE C. Marcelli" G. SQuquieres ' , J.P. Sabatier', O. Walrant', M. Garabedian' Departments of Rheumatology' and Nuclear Medicine', University Hospital, Caen; CNRS-URA 583', Paris, France To relate the vitamin D status to the bone mineral acquisition during adolescence and early adulthood, the plasma level of 25 hydroxyvitamin D (vitO) was measured in 351 healthy volunteer females aged 11-24 years and was correlated to both the PTH level and the L2-L4 bone mineral content (BMC) measured at entry, and to the relative annual bone mineral acquisition (ABMC) during a 2-year follow-up. BMC was measured by DXA and adjusted for body weight and pubertal development. 133 females were recruited during the October-January period (winter group) and 218 were recruited during the February-May period (spring group). VitO was significantly lower in spring (16.9±9.2 ng/ml; mean±SD) than in winter (24.0±9.9, p<0.0001) whereas PTH was significantly higher in spring (29.7±11.7 pg/ml) than in winter (22.2±B.9, p=0.0001). VitO <12 ng/ml and vitO <5 ng/ml were found in 34.9% and 5.0% of the spring subjects and in 9.0% and 0% of the winter subjects, respectively. 4.8% of the spring subjects and 0% of the winter subjects had PTH >55 pg/ml (upper limit of normal range). When subjects of the spring group were split according to their pubertal stages, vitO weakly correlated with PTH in the subgroup of subjects at stage P4 or less than 2 years after the menarche (r=0.325, p=0.037; n=78). ABMC correlated with vitO only at stage P1 (r=0.58, p=0.035), whereas in females 3 years or more after menarche the BMC at entry was significantly higher in subjects with vitO <12 ng/ml (n=27) than in those with vitO 2 12 ng/ml (n=63). The results of this study show that, though 35% of young healthy females have low vitamin D levels in spring, only a minority (4.8%) have vitamin Dinsufficiency as reflected by elevated PTH levels. Vitamin D status might playa modest role in lumbar bone mineral acquisition during puberty as suggested by a weak correlation between vitamin Dlevel and the increase of BMC in non menstruating females. The higher BMC at entry in the oldest group with low vitamin D levels could suggest a higher consumption of vitamin D stores.

P103 CORRELATION BETWEEN NUTRITIONAL STATUS AND BONE ULTRASOUND IN A POPULATION OF INSTITUTIONALIZED ELDERLY WOMEN V. Gerber M.A. Krieg J. Cornuz P. Burckhardt University Hospital, Lausanne, Switzerland The risk of malnutrition increases with age. It enhances functional dependency, morbidity and mortality. It is supposedly frequent in institutionalized persons, and may increase the risk of osteoporosis, and by that of hip fractures. • 78 women, aged ±B6 yrs living in nursing homes, were assessed by the MNA (Mininutritional Assessment), a validated questionnaire with 18 items for elderlies (score 30-25 = satisfying nutritional status, 24-17 = risk of malnutrition, <17 = malnutrition). In addition, were measured: tricipital skin fold (TSF, Ponflural caliper), grip strength (Jamar dynamometer), and ultrasound evaluation (BUA) of the calcaneus (Achilles LUNAR). Blood Calcium, albumine, and creatinine were measured in 60 women. Results: 73% of the women had a MNA <24, and 21% < 17. MNA was sign-correlated with TSF (r=.531). albumine (r=.408), and by trend with BUA (r=.203, p=.075). There were differences between women with satisfying nutritional status and those at risk of malnutrition (±SD): MNA:

<24 (n=57)

~24

age (years) tricipital skin fold (cm) grip strength (kg) BUA (dB/MHz) S-albumin (g/I) S-creatinine (umol/I)

86±6 1.53±O.62 11.1±5.2 92.1±B.6 41.9±4.9 92.3±17.2

85±7 1.97±O.47 12.2±5.1 94.8±10.8 45.7±4.8 94.1±18.2

(n=21)

p ns .003 ns .207 .012 ns

Conclusion: Malnutrition was Common in institutionalized elderly women, and was associated with low S-albumin, low skin fold and partially with low bone ultrasound .

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P1D4 ASSESSMENT OF THE RISK OF POSTMENOPAUSAL OSTEOPOROTIC FRACTURES USING CLINICAL FACTORS Thanh Thuy Vu Ngoc An Tran Rheumatology Department-Bach Mai hospital-Hanoi-Vietnam Objective: To investigate some factors related to osteoporotic vertebral fractures in postmenopausal women. Design: 270 postmenopausal women were randomly studied, aging from 50 to 82 yrs old, including 67 women with vertebral fractures and 203 women without vertebral fractures. Each woman replied to a standardized questionnaire about clinical risk factors and their height and weight were measured. Thoracic and lumbar spine X-ray were performed. Plasma alkaline phosphastase, estradiol, parathyroid hormone, thyroxine, urinary calcium/creatinine and hydroxyproline/creatinine were measured by standard techniques. Odds ratios were used for assessing clinical risk factors. Results: Six clinical factors can be considered as associated with the development of osteoporotic vertebral fractures. They are: Age: ~70, stature :5145cm, weight :541 kg, early menopause (:542 yrs), duration of menopause ~21 yrs, prior spontaneous bone fracture (or as the result of minimal trauma) at the age of :545. Parity: :53 is a protective factor. Estradiol and parathyroid levels were lower in the vertebral fracture group. Thyroxin; alkaline phosphatase and urine chemical values did not differ in the groups. X-ray characteristics: The fractured vertebrae were mainly from T11 to L2 (57%) and commonly were wedge form. Most women had one or two fractured vertebrae. Conclusions: These findings suggest: These six factors which related to osteoporotic fractures can be used to identify high risk postmenopausal women. Estrogen and Parathyroid hormone levels were lower in the vertebral fracture group. Multiparities (less than 4 times) is a protective factor.

P1D5 VITAMIN 0 NUTRITION AND COGNITION IN THE INSTITUTIONALIZED ELDERLY John D. Wark K. Mead M. Stein C. Nowson S. Scherer M. Facciolo R. Macinnis. l. Flicker University of Melbourne, Royal Freemasons' Homes of Victoria, Melbourne, Australia The prevalence of nutritional vitamin 0 deficiency and cognitive impairment is high in residents of nursing homes and hostels for the elderly. There is also evidence of reduced vitamin 0 nutritional status and elevated parathyroid hormone levels in community-dwelling women with mild dementia (1). We therefore studied associations between vitamin 0 nutrition, cognitive function and other variables in a cohort of institutionalized elderly females. 495 women residing in urban nursing homes and hostels in southeastern Australia entered the study. Vitamin 0 nutrition was assessed by measuring plasma 25-hydroxyvitamin 0 (250) levels (Incstar). Cognitive function was assessed using the Abbreviated Mental Test Score (AMTS). Time outdoors was rated on a 4-point scale. Walking ability was scored on a 7-point scale. 250 levels and AMTS were available in 434 subjects, mean age 83 years. Spearman correlation coefficients (*p<0.01; * *p<0.001) between variables were: .

Age 250 Age AMTS Walking

-.13* -0.19** -0.09

AMTS

Walking

Outside

0.24** -0.19**

0.21 * * -0.09 0.29**

0.27** -0.21 * * 0.34** 0.51 **

0.29**

After adjustment for age, mobility and frequency of going outSide, multiple regression analysis revealed:

250

Age

AMTS

Walking

Outside

-.18

0.95 (.003)*

0.76

3.8 (.005)*

P1D6 FACTORS ASSOCIATED WITH BONE MASS IN MIDLIFE TWINS John 0 Wark C. Cassar, H. Hoang C. Nowson J.L. Hopper L. Flicker B. Kaymakci, R Macinnis J. Alexander A.J. Sherwin R.G. Larkins University of Melbourne, Royal Melbourne hospital, Melbourne, Australia Bone loss with the menopause is an important reason why up to 60% of women may suffer osteoporotic fractures later in life. Yet much is uncertain about the factors influencing the bone mass of women in mid-life. We studied 123 pairs of female twins (mean age 48 years, range 36 60 years) to assess the association of health, lifestyle and body composition factors with bone mineral density (BMD). Regional BMD and total body bone mineral, lean and fat mass were measured by Hologic QDR 1000W densitometry. Dietary, reproductive, medical, exercise, smoking and alcohol intake history were obtained using established questionnaires. Associations between within-pair differences in BMD and within-pair differences in independent variables were sought using univariate and multivariate approaches. By multivariate analysis of all twins, lean mass (all sites, p<0.05 <0.001), fat mass (femoral neCk, p
P1D7 CONTRIBUTION OF BONE COMPOSITION AND ARCHITECTURE TO BONE STRENGTH AND TOUGHNESS OF HUMAN TRABECULAR BONE H. Van Campenhout* H. Druvts* J. Aerssens**. G. Van der Perre* J. Degueker** S. Bognen ** * Division of Biomechanics and Engineering Design, * *Division of Rheumatology, K.U. Leuven, B-3000 Leuven, Belgium Introduction: The effect of bone density on biomechanical characteristics is well known and is highly significant, 64 to 88% (1 ), characteristics, architecture and material properties are considered to play an additional role. Methods: In order to study the effect of architecture and material properties, 64 lumbar spine bone samples, collected in the European Concerted Action BIOMED 1, Assessment of Bone Quality, have been analysed using cylindrical samples for histomorphometric data (BV/TV, trabecular number, thickness and spacing) and biochemical analYSis (calCium, phosphorus, hydroxyproline, total protein, osteocalcin and IGFI) in relation to mechanical testing under compression. Results: In multiple regression analyses, including all histomorphometric and biochemical parameters, the following measures contributed significantly to the breaking force (R'=0.458): trabecular spacing (p
The significant association between cognitive function and 250 suggests that cognitive impairment is a risk factor for vitamin 0 deficiency in the population studied. 1. Kipen E, Helme RD, Wark JD, Flicker l. J Am Geriatr Soc 43:1088 1091,1995.

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PllU PREVALENCE OF OSTEOPOROSIS IN POSTMENOPAUSAL SAUDI

BONE MASS MEASUREMENT

WOMEN USING DUAL X-RAY BONE DENSITOMETRY M. EI-Desouki M. Mohamadiyeh Nuclear Medicine division, Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Objective: To evaluate prevalence of osteoporosis in postmenopausal Saudi women. Patients and Methods: The results of bone densitometry of the lumbar spine (gm/cm') of a group of consequent 482 postmenopausal Saudi women aged between 50 and 60 years (average 55 years) were reviewed retrospectively. Results: The results were related to the mean of bone mineral density (BMD) in young healthy Saudi female subjects (Tscore). Two hundred and twelve (44%) resulted with mild ostepenia (BMD of1.098±O.109, mean T-score of-1 SD), 164 (34%) with moderateosteopenia (BMD of 0.893±O.134, mean T-score of -2 SD), and 106 (22%) had osteoporosis (BMD of 0.795±O.154, mean T-score of -2.7 SD). Conclusion: Osteoporosis is not uncommon among Saudi postmenopausal women and should be made a matter of public concern. Bone densitometry should be used to classify patients and identify those who need therapy. Further studies are needed to investigate the secondary causes of osteoporosis (e.g. vitamin D and its level).

PlUS THE VALUE OF QUANTITATIVE ULTRASOUND IN ASSESSMENT OF OSTEOPOROSIS IN PATIENTS WITH ANKYLOSING SPONDYLITIS M. Yurtkuran M. Yurtkuran Y. Karakog L. Ozbek Uludag University Medical Faculty, Department of Physical Therapy and Rehabilitation, Bursa, Turkey In ankylosing spondylitis (AS), the bone loss is accepted to be important as well as bone formation. We planned a study to asses the prevalence and severity of osteoporosis in AS patients by using quantitative ultrasound (QUS). 38 patients (16F, 22M) with AS was included into the study. Mean age of the patients were 45±11 (21-72) years. Mean disease duration was 7.5 (1-15) years. Broad band ultrasound attenuation (BUA) and speed of ultrasound (SOS) were used as a QUS parameters. BUA and SOS were measured by utilising the DTU-one supplied by osteometer. The system is based on BUA and SOS which scan the heel (os calcanei) immersed in water-bath to detect osteoporosis. Both BUA and SOS measurements were similar and 14 out of 38 patients (36 %) had osteopeni (Tscore <-1). Of the 14 patients with osteoporosis, 3 had osteoporosis (T score <-2.5) (7.8 %). We came to conclusion that heel QUS, non-invasive. easily applicable, portable and relatively inexpensive screening tool, might be used for evaluating the osteoporosis in patients with AS.

Plll BONE DENSITOMETRY AND BONE SCINTIGRAPHY IN CHILDREN WITH OSTEOPETROSIS M. EI-Desouki" M. Mohamadiyeh', A. AI-Herbish', S. AI-Rasheed', N. AI-Jurawan' 'Nuclear Medicine Div., Internal Medicine Dept., 'Pediatric Dept, King Khalid University Hospital. King Saud University, Riyadh, Saudi Arabia Objective: To demonstrate the role of bone mineral density (BMD) and bone scan in the management of patients with osteoporosis. Patients and Methods: Eighteen saudi patients, 10 females and 8 males, of ages between 3 and 16 years (mean 9 years). The patients had undergone BMD measurements and bone scans at the time of diagnosis. The results of BMD measurements were compared to a group of normal saudi patients of the same age and gender. Results: The mean BMD (g/cm') for the lumbar spine and greater trochanter was increased by 181 % and 193% respectively. Bone scintigraphy demonstrated characteristic features of increased tracer uptake in the widened metaphyses of all long bones, particularly in the distal femur and proximal tibia. Conclusion: BMD is a non-invasive and useful method to be recommended for establishing the diagnosis of osteopetrosis in children. The whole body bone scan is valuable in demonstrating the site and extent of the disease.

PlUg ULTRASONOMETRY OF CALCANEUS AND QUANTITATIVE COMPUTED TOMOGRAPHY OF THE FIRST THREE LUMBAR VERTEBRAE (A COMPARATIVE STUDY) J. Wendlova* V. Belan* M. Mikulec!
Pl12 BONE DENSITOMETRY AND BONE SCINTIGRAPHY IN CHILDREN WITH

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OSTEOMALACIA M. EI-Desouki" M. Mohamadiyeh', N. AI-Jurawan' 'Nuclear Medicine Div., Internal Medicine Dept., 'Pediatric dept, King Khalid University Hospital. King Saud University, Riyadh, Saudi Arabia Objective: To demonstrate the role of bone mineral density (BMD) and bone scan in the management of patients with osteomalacia. Patients and Methods: Twenty six Saudi patients, 17 females and 9 males, of ages between 5 and 16 years (mean 13:5 years). The patients had undergone BMD measurements and bone scans at the time of diagnosis and 6 months after therapy with oral vitamin D, calcium, and adequate exposure to sunlight. The results of BMD measurements were compared to a group of normal saudi patients of the same age and sex. Results: The mean BMD (g/cm') for the lumbar spine and femoral neck was 0.53 and 0.55 respectively. After 6 months of therapy, BMD measurements were repeated and showed a significant increase (p<0.001). Bone scan showed increase in tracer uptake throughout the whole skeleton "superscan" and in areas of pseudo-fractures. Bone scan was able to show the changes after therapy. Conclusion: BMD is a non-invasive and useful method to be recommended for assessment of children with osteomalacia before and after therapy. Bone scan is valuable in demonstrating the site and severity of stress fractures .

Pl13 BONE MINERAL DENSITY AND BONE SCINTIGRAPHY IN ADULT PATIENTS WITH OSTEOMALACIA M. EI-Desouki', M. Mohamadiyeh', M. Fouda' 'Nuclear Medicine, 'Endocrine Divisions, Internal Medicine Dept., King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Objectives: This prospective study was conducted to demonstrate role of bone mineral density (BMD) and bone scan in the management of patients with osteomalacia. Patients and Methods: Bone scans using 99mTc-Methylene Diphosphonate (MDP) and BMD of the total body, lumbar spine and fernur using dual Xray Absorptiometry (DXA) were performed at the time of diagnosis, 6 months and one year after therapy with calcium and vitamin D in 80 Saudi female patients, aged between 18 and 73 years (mean 42 yr). Alkaline phosphatase, calcium, and inorganic phosphorous were measured for all the patients before and after treatment. Vitamin D 1,25 levels were also measured at the time of diagnosis. Results: BMD measurements were compared with that of normal Saudi subjects matched for age and sex. Bone scan showed the features of "Superscan" in all patients and demonstrated multiple stress fractures in twenty two. The BMD (mean±SD in gm/cm') before and one year after treatment was for the lumbar spine O. 781±D.256 and 0.882±D.287, for the femoral neck 0:666±D.177 and 0.754±D.222, for the femoral wards 0.562±D.190 and 0.623±D.224, for the femoral trochanter 0.577+0.174 and 0.622+0.182, and for total body 0.903+0.137 and 0.932+0.149. The improvement in BMD values after one year of treatment was the highest in the femoral neck (11.7%) followed by the lumbar spine (11.5%), femoral wards (9.8%), femoral trochanter (7.2%), and total body with the least changes (3.1%). Poor correlation was found between BMD and each of the biochemical markers. Conclusion: Measurements of BMD in patients with osteomalacia are of value and recommended in the initial assessment of the degree of osteopenia and in follow up to monitor response to therapy Bone scintigraphy is valuable in demonstrating the site and extent of stress fractures.

The study highlights the large variability in the individual vertebra T of the lumbar spine. This raises important Questions in clinical practice where one or two vertebra T may be low and the remaining normal. These vertebra may be at higher risk of fracture and pose the dilemma of therapeutic intervention. Further long term studies are needed to confirm the risk of fracture and response to treatment intervention in these subjects.

Pl15 DETERMINATION OF PERIPROS-THETIC BONE DENSITY WITH THE DEXA METHOD AFTER TOTAL HIP ARTHROPLASTY Xianzheng Luo Ai Guo Department of Orthopaedic Surgery, Beijing Friendship Hospital, Capital University of Medical Sciences,Beijing 100050,P.R.China Summary. The purpose of this paper was to study bone remodelling around femoral components after total hip arthroplasty (THA). Our study was divided into 3 stages: THA with cemented, THA with uncemented, loosening THA. We used dual energy X-ray absorptiometry (DEXA) to determined bone mineral density (BMD). Evaluation is carried out by Gruen's method (7 ROls). The results showed that BMD was reduced with increasing time period after surgery in patients after cemented or uncemented THA, the loss ranging from 15% to 29% and 13% to 28% respectively. The bone loss in the proximal end of the femur was much more than that in the distal. The bone loss in patients with prosthetic loosening was much more than that in patients without prosthetic loosening, the loss ranging from 25% to 43%. We consider once anyone of below two circumstances appears, loosening of the stem may have existed: 1. bone loss at any 2 ROls of proximal femur more than 35% 2. suddenly appears significant bone loss around femoral stems after 8 years of operation.

Pl16 OSTEOPOROSIS-RELATED SHIFT OF ULTRASOUND VELOCITY IN Pl14 DIAGNOSIS OF OSTEOPOROSIS AT THE LUMBAR SPINE-VARIABILITY OF THE INDIVIDUAL L1-L4 T SCORE O. Sahota P. San D. Pearson D.J. Hosking Division Mineral Metabolism, City Hospital, Nottingham, England The L1-L4 mean T-Score (T) is used in the diagnosis of osteoporosis at the lumbar spine. It is expected that individual lumbar vertebra (ILV) should have a similar T in the absence of degenerative disease or vertebral collapse. The aim of this study was to examine the variation in ILVT and the change in diagnostic classification using the lowest ILVT compared to L1-L4 mean T. DXA (AP spine) [Hologic aDR 2000] together with radiographs AP/Lat spine were performed on 90 early post-menopausal women. Women with a L1-L4 mean T below -2.5 [WHO criteria] and with diseases/medication known to affect bone metabolism were excluded from the study. Radiographs were assessed for the presence of osteophytes, aortic calcification and vertebral deformity.

CV(%) T-SD

DIFFERENT BONE STRUCTURES A.M. Tatarinov I.S. Adamovich EEMTI, Riga Technical University, Riga. Latvia Changes of ultrasound (US) velocity (USV) were followed in bone structures, that in relation to the wavelength at -0.2 MHz and type of sounding may be considered as: - volume of trabecular tissue: through calcaneus sounding; - volume or thick plate of compact tissue: tibia - diaphysis and ulna distal third, tested by surface sounding; - 3-layer sandwich structure of cortical and spongeous substances: ilium - sounding by the length of crista iliaca. Measurements of USV in the mentioned plots of skeleton were carried out by a pulse US meter UVM-3 with specially arranged probes, developed in the Riga Technical University. About 300 females, conformed to the groups: pre-menopausal age 40-48 of norm and post-menopausal age 55-70 with acute osteoporosis symptoms (severe arthritis, fractures) were investigated. Bone

L1-L4

L1

L2

L3

L4

1.5 0.11

2.8 0.30

2.2 0.28

2.2 0.29

2.4 0.30

The T-SD is CV in Tscore units (ie standard deviation of the normal range) calculated from two repeated measures with repositioning [95% CI of the ILV T was taken as ±D.6]. The mean age (SD) was 52.3 (3.7) yrs [range 47-59], 4.0 (3.3) years past the menopause and 24.5 (3.4) body mass index. 81% of the subjects had a greater than T 0.60 units-difference between their highest and lowest ILV. 48/90 subjects were classified as normal [T>-1.0] and 42/90 osteopenic [T <-1.0] based on the L1-L4 mean T. Using the ILV T re-categorised 17148 (35.4%) normal subjects as osteopenic and 17142 (40.5%) osteopenic subjects as osteoporotic. Further analysis taking a difference 0.60 T units (0.6 representative of a significant difference in T) between the mean L1L4 T and the lowest ILV T made little change in re-categorisation: 11148 osteopenia (normal grp), 12142 osteoporotic (osteopenic grp). 12.2 % were classified with mild grade 1 osteophytes [Orwoll et al (none=OAO, mild=OA1, moderate=OA2, severe=OA3)], 2.2% aortic calcification and no vertebral deformities [Melton et al].

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calcaneus tibia ulna ilium

USV, km/s (+/- S.D.) pre-menopausal

post-menopausal, osteoporosis

2.05 3.80 3.58 2.26

1.74 (0.25) 3.75 (0.47) 3.31 (0.24); 4.12 (0.28) 1.90 (0.21)

(0.19) (0.26) (0.21) (0.23)

Conclusion. Shift of USV in volume of trabecular tissue (calcaneus), as well as in the sandwich structure of the flat bone (ilium), caused by the osteoporosis factor during ageing, has one-way tend - lowering. It is connected with total loss of stiffness of the structure due to thinning of carrying elements -trabeculae and increased porosity. In the case of compact material (tibia, ulna), two directions of changes were observed, the lowering of USV being obviously explained by porosity, but increase of USV - by probable hypermineralization of the external layer of cortex. Thus, the complex multisite US examination of skeleton may be helpful to precise diagnostics.

P117 IN-VITRO DYNAMIC LOADING OF THE PROXIMAL FEMUR: FRACTURE RESISTANCE DEPENDS ON BONE MINERAL DENSITY AND GEOMETRY R.R. van Rijn', R. Niesing', T.F. Lang 3, H.E. Schutte', C.J. Snijders', C. van Kuijk'·3 Depts of Experimental Radiology" Biomedical Physics and Technology', Erasmus University Rotterdam, and Osteoporosis & Arthritis Research Group3, University of California, San Francisco, USA Introduction: To investigate the relation between the strength of the proximal femur, BMD and geometry we performed dynamic loading tests on human cadaver femora. For this study we designed a device which is capable of loading a cadaver femur in a real life fall simulation (1). The aim of this study is to: a) verify if this loading device can produce realistic fractures, as seen in a clinical setting, and b) to compare radiological parameters with measured fracture resistance. Materials: Femora; Thirty-seven embalmed human cadaver femora, median age 82.9 years (54.3-98.7 years), were used. Radiography; The measured geometrical dimensions were: femoral neck axis length (FNAL), head width (HW), neck width (NW), shaft width (SW), neck-shaft angle (NSA), offset, and length of the 'true' femoral neck axis length (TFNAL). In addition the Singh index was scored. After mechanical testing, radiography was repeated to score the femora into four categories: 1) no fracture, 2) incomplete fracture, 3) complete fracture, and 4) comminuted fracture. DXA; All DXA measurements were performed with a Lunar DPX-L scanner. aCT; Measurements were performed on a GE prospeed S-fast. Image analysis was done at the osteoporosis and arthritis research group, UCSF, USA, using custom made software (2). Mechanical testing; For mechanical testing a device was designed simulating a fall to the side. Data analysis; A Tukey HSD test was performed, to test for differences between the four groups. Results: FNAL, Singh index, and all DXA and aCT parameters showed significant differences between groups I and 3 and/or 4 (p
P118 THE CRITICAL AGE FOR THE DIAGNOSIS OF OSTEOPOROSIS AT THE FEMORAL NECK A. Oral* A. Yaliman* D. Sindel* R. Di§Ci** Istanbul University Medical School, *Department of Physical Medicine and Rehabilitation, **Department of Biostatistics and Demography, Istanbul, Turkey The aim of this study was to identify which fraction of aging women is at risk of osteoporosis at the femoral neck. Bone mineral density was measured at the femoral neck by DXA in 688 women aged from 35 to 80 years, who did not have any disease or treatment known to affect bone metabolism Women were classified as being osteoporotic if they had a T score ~ 2.5. By choosing each age as different cut-off pOints, T ~ 2.5 being the gold standard, we determined the number of women with and without osteoporosis above and below each age. From a large set of sensitivity and specificity values obtained for each age, we generated a Receiver Operating Characteristic curve. The ROC curve revealed that the critical age (the cut-off pOint) forthe risk of osteoporosis at femoral neck in women was 61 years of age (sensitivity=0.76 and specificity=0.74). We conclude that women who are aged 61 years and older are at greater risk of femoral neck osteoporosis and this finding might have a potential implication for the diagnosiS of osteoporosis at the femoral neck according to age.

P119 BONE MINERAL DENSITY AND ITS RELATIONSHIP TO AGE AND POSTMENOPAUSAL YEARS A. Oral. * A. Yaliman,* D.Sindel * R.Di§Ci** Istanbul University Medical School, * Department of Physical Medicine and Rehabilitation, Department of Biostatistics and Demography, Istanbul, Turkey In order to characterize the pattern of bone loss with aging at different skeletal sites, bone mineral density (BMD) was measured by DXA at the anteroposterior spine and hip in 688 women whose ages ranged between 35-80 years and results were analyzed according to age and postmenopausal years. The decline in BMD between 35 and 80 years of age was 21 % at the spine, 22 % at the femoral neck, 23% at the trochanter, and 41 % at the Ward's triangle. There was already an 11.6% bone loss at the Ward's triangle for the age range 35-40 years, which continued thereafter and analysis of variance revealed significant bone loss at the spine after 50 years of age and at the femoral neck after the age of 60 years (p<0.05). A significant bone loss was found before the menopause at the Ward's triangle and BMD showed a significant decline within 6-10 years following menopause at all sites and bone loss continued at a slower rate up to 25 postmenopausal years and accelerated thereafter at all skeletal sites. The percentage of women classified as having osteoporosis (OP) showed a significant increase at all sites between 51-55 years of age and duplicated between 56-60 years and increased rapidly at the femoral neck, trochanter, and the Ward's triangle after 66 years (p
P120 SPINAL VERSUS FEMORAL BONE MINERAL DENSITY A. Yaliman A. Oral D. Sindel R. Di§Ci Istanbul University, Istanbul Medical School, Department of Physical Medicine and Rehabilitation, Department of Biostatistics and Demography, Istanbul, Turkey Over the last 10 years, dual X-ray absorptiometry (DXA) has become established as the most widely used technique for assessing patient's skeletal status. Spine and hip are the sites those are affected by osteoporotic fractures. Standard DXA examinations in the posteroanterior projection of the spine include vertebral bodies and posterior elements and degenerative disease of the spine may falsely increase the measured bone density in elderly patients. The aim of this study was to assess the correlation of spinal and femoral bone mineral densities (BMD) as measured by DXA. Nine hundred and two women ages ranging from 26 to 84 years, were evaluated. Their mean age was 56.87±9.64 years. Osteoporosis was defined by the World Health Organization (WHO) criterion. Pearson's correlation analysis was used to examine the relationship between spinal and femoral BMD values. Bone density measured at the spine and the femur correlated significantly (p<0.01) with each other. Correlation coefficients ranged from r=0,619 to r=0,673 for the association between spinal (L,-L,) and femoral BMDs. Correlations were stronger among the femoral subregions (r=0,792 to r=0,850) and between the total hip and its subregions (r=0,818 to r=0,899). There were significant correlations between spinal (L,-L,) and femoral BMDs forthe pre and postmenopausal women. BMD measured at the spine correlated significantly with the femoral BMDs for the women with and with and fractures. Participants were, grouped based on 5 years age increments. Spinal BMD was significantly (p
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P121 THE ASSOCIATION BETWEEN BONE MINERAL DENSITY AND OSTEOPOROTIC FRACTURES D. Sindel A. Oral A. Yaliman R. Di§Ci Istanbul University Medical School, Department of Physical Medicine and Rehabilitation, Department of Biostatistics and Demography, Istanbul, Turkey The aim of this study was to assess the association between bone mineral density (BMD) and osteoporotic fractures. 818 women whose ages ranged from 35 and 84 years were included in this study and BMD was measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L,-L,) and the hip. Comparisons were made between 141 women with fractures (vertebral, distal forearm, hip and the other sites) and 677 women without fractures. Statistical analysis was performed using two-tailed student's ttest. The statistical differences of some of the assessed parameters in the fractured and non fractured groups are reported. BMD was significantly lower in subjects with fractures (Fx) at all skeletal sites.

Lumbar spine Femoral neck Trochanter Ward's

Mean BMD±SD(gr/cm') Fx-group Non-Fx-group

p value

0.88±O.15 0.72±O.12 0.62±O.12 0.56±O.16

<0.001 <0.001 <0.01 <0.01

0.94±O.15 0.76±O.12 0.65±O.10 0.59±O.14

T scores ranged between -1.17 and -2.17 (the lowest score being at the Ward's triangle) in the fractured group and the values were between 0.97 and -1.80 in the non-fractured group, the difference being statistically significant at all sites. A history of fracture in family members did not seem to have a significant effect on fractures. Subjects with a fracture history in a close relative seemed to have lower BMD only at the Ward's triangle. In conclusion, women with fracture were found to have lower BMD at all skeletal sites than those without any fractures.

P123 THE POTENTIAL INTEREST OF MULTIPLE SKELETAL SITES SOS MEASUREMENTS USING A NOVEL QUS TECHNOLOGY C. Sing~. A. DanielL T. Schwartz S. Makovoz R Sason. Y Niv. SLevin" M Weiss', 0 Hans' 'WolfsOA Medical Center, Israel. 'ASAF Harofe Medical Center, Israel. Sunlight Ultrasound Technologies Ltd., Rehovot, Israel. 'CLIOS Lyon France Osteoporosis is a systemic disease, which is manifested in different ways at different skeletal sites. Quantitative Ultrasound serves agrowing interest in non-invasive techniques for risk assessment of osteoporotic fractures. Sunlight Omnisense (Sunlight Ultrasound Technologies, Israel) is the first QUS device capable of measuring the Speed of Sound (SOS) at many sites such as the proximal phalanx of the third digit, distal radius, tibia and others. The device consists of a desktop unit and a family of probes designed to measure various bones. Measurements are performed by scanning a selected site using the appropriate probe. SOS values are recorded at different pOints along the scan, whereas the data is analyzed and the 95 percentile and average SOS of the scan are obtained. The purpose of this study was to perform measurements of several skeletal sites in order to examine the SOS correlation between the sites. 155 female subjects (age 30-97, mean 67±14,) were measured. Each subject was measured at the non-dominant side at the distal third of the Radius, midshaft of the Tibia, Proximal Phalanx of the third digit, and fifth Metatarsal. Coefficient of determination have been calculated by Pearson correlation (R').

P122 A NEW TECHNIQUE FOR EVALUATING 3-DIMENSIONAL TRABECULAR MICROARCHITECTURE IN HUMAN CREST BIOPSIES FROM SYNCHROTRON RADIATION MICROTOMOGRAPHY F. Peyrin*, M.H. Lafage-Proust$ M. Salome* P. CloetensO L. Dupuyo C. Alexandre$ *CREATIS, INSA 502, 69621 Villeurbanne Cedex, °European Synchrotron Radiation Facility, BP 220, 38043 Grenoble Cedex, $ LBTO, Saint Etienne, France Trabecular microarchitecture of bone is an essential determinant of bone mechanical properties. X-ray microtomography is an attractive non destructive technique allowing three-dimensional (3-D) studies. In this paper we present a new technique for evaluating trabecular microarchitecture based on Synchrotron radiation (SR) microtomography. Indeed, SR may be used to produce a high photon flux monochromatic X-ray beam. The high photon flux is essential for increasing spatial resolution while keeping high signal-to-noise ratio, and monochromaticity allows to avoid beam hardening and thus to reconstruct accurate map of linear attenuation coefficient. A SR microtomography device has been developed at the European Radiation Synchrotron Facility (ESRF) in Grenoble (beam line 1019). It uses a large parallel x-ray beam. Human iliac crest bone biopsies, embedded in methylmetacrylate are mounted on a goniometer and are sequentially rotated. For each rotation angle, a 2-D projection is acquired on a 2-D 1024x1 024 detector. The 3-D image of the sample is then reconstructed from this set of 2-D projections. The microtomography imaging system provides 3-D high resolution images of trabecular bone samples with an isotropic voxel size of 6.65 or 10.13 micrometers. Typically (512)' images are reconstructed corresponding to a sample size of about 5mm'. Image processing tools are then applied to quantify trabecular bone architecture from these 3-D images. Morphometric parameters conventionally used in histomorphometry (e.g. bone volume fraction, surface to volume ratio, trabecular thickness, trabecular number) and topological parameters (e.g. number of nodes, number of free ends) are computed on series of consecutive 2-D slices extracted from the 3-D images. Furthermore, since 2-D connectivity parameters give a poor estimation of 3-D connectivity, a 3-D skeletonization technique have been implemented to obtain better information about 3-D connectivity. This technique is both promising forthe quantification of 3-D architecture, and for observing difference of mineralization, particularly in cortical bone .

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95 Percentile

SOSCoefficient of Determination (R')

Radius Tibia 0.44 0.66 PPIII Metatarsal 0.61 All correlation values were found to be statistically significant (p<0.0001)

Metatarsal PPIII 0.38 0.37 0.60 0.62 0.38 0.37 PPIII Metatarsal

0.61 Metatarsal 0.69 PPIII 0.50 Tibia Radius Mean SOS

Correlation (R) between the different sites range from 0.60 to 0.83. These mid-level values suggest that multi-site measurements may have synergistic contributions over the single observation, enabling a better assessment of skeletal status and risk of fracture. Whether some sites could be use for diagnostics only while others may be relevant for the follow-up, still need to be investigated.

P124 COULD SOS MEASUREMENT AT THE PROXIMAL PHALANX REVEAL

P126 DISCRIMINATIVE FORCE OF DIFFERENT METHODS FOR BONE

PROPERTIES OF BONE STRUCTURE? A. Danieli C. Singal .T Schwartz A. Shamaev, S. Makovoz Y. Niv E. Kantorovich, ~', M. We iss', ~' 'Wolfson Medical Center, Israel. 'ASAF Harofe Medical Center, Israel. Sunlight Ultrasound Technologies Ltd. , Rehovot, Israel. ' CLIOS Lyon France Previous in-vitro studies of bone biomechanics using ultrasound have shown that different aspects of bones possess different mechanical properties. A new ultrasound device (Sunlight Omnisense, Sunlight, Rehovot, Israel) enables unrestricted in-vivo studies by measuring the velocity (SOS) at many skeletal sites using a proprietary semi-reflection ultrasound technology. The purpose of the study was to characterize the SOS profile of the proximal phalanx at different circumferential positions and to determine if SOS is related to bone thickness. Eight healthy subjects (age 20-48, 5 females, 3 males) were longitudinally scanned at their non-dominant hand. The SOS profile was determined by 5 separate measurements taken at the medial-I, dorso medial-2, dorsal-3, dorso-lateral-4 and lateral-5 aspects of the bone. SOS values represent the mean of 3 repeated measurement cycles at each position. Results are depicted in the figure below. The phalanges were found to have a similar profile for all subjects measured (2 upper values at pOints 2 and 4 and a lower value at point 3). RMSCV calculated for these measurements was 26 mis, whereas the average difference in SOS between the pOints 4 and 3 was 294 m/s.

According to the Phalanx cross-sectional view the maximal peaks of SOS do not appear in the thickest parts of the bone. This thickness independence of SOS is confirmed by the theory of wave propagation for all cases in which bone thickness is of the order of, or greater than the wavelength passing along the bone. Are these results related to other bone structural properties as suggested by other studies? Such assumptions should be further investigated. Nevertheless, this may point to a new approach of characterizing bone status and fragility.

MINERAL ASSESSMENT: COMPARISON OF HEEL AND PHALANX ULTRASOUND TO DEXA C. Horvath E. Hosszu I. Krasznai J. Szucs S Meszaros I. Dept. Medicine and II. Dept. Pediatrics, Semmelweis Univ. Med. School, Budapest, Hungary We aimed to assess the ability of quantitative ultrasound in separating osteoporotic patients from normals as compared to ability of DEXA in this regard. 65 patients were studied: 57 women and 8 men, aged 21-72 (52.4±11 .3) years. BMD was measured by DPX-L (Lunar) on spine and hip and 6MC was assessed by NK-364 (Gamma, Hungary, an SPA method) on radius. Heel ultrasound by Achilles (Lunar) and Sahara (Hologic) were also done as well as phalanx ultrasound by DBM Sonic 1200 (IGEA). Patients were assorted according to their lumbar T-score as normal (>-1 , n=21) or osteopenia (>-2.5, n=19) or osteoporosis «-2.5, n= 25) . ANOVA was done for different methods among these groups:

Femoral neck BMD Radius midshaft BMC -SOS Achilles -BUA - stiffness Sahara - SOS - BUA -QUI DBM Sonic -SOS

F-ratio

significance

24.58 3.15 10.48 6.49 11 .95 11.21 8.67 11.66 4.27

0.00001 0.05 0.0001 0.003 0.00001 0.0001 0.0005 0.0001 0.02

All measurements except radius BMC were able to discriminate spinal osteoporosis from normals. Osteopenia was surely separated by hip BMD only. After all, quantitative ultrasound proved to be an effective method to diagnose spinal osteoporosis and SOS surpassed BUA in this regard.

P127 HIP FRACTURE DISCRIMINATION BY A QUS PARAMETER THAT,

P125 EFFECT OF TIBOLONE ON BONE MINERAL DENSITY VALUES IN POSTMENOPAUSAL OSTEOPENIA AND OSTEOPOROSIS - 4 YEARS STUDY L. Grzeniewski ' , W. Tlustochowicz" N. Bruyniks', J. Dowgiallo' 'Central Clinic Hospital WAM in Warsaw, ' N.V. Organon, Oss, The Netherlands, ' N.V. Organon Poland Tibolone is a synthetic analogue of the gonadal steroids with estrogenic, progestagenic and androgenic properties, effective in postmenopausal symptoms. In our last study we proved its 2-years efficacy in osteoporosis treatment (7.4% BMD improvement) and its good tolerance with no significant side-effects. Purpose: To investigate the efficacy of Tibolone in 3rd and 4th year of postmenopausal osteoporosis treatment. Methods: 11 women out of 21 that finished the 2-years treatment (age 55.3±4.2; BMI 23.4±2.4 kg/m2, 3-5 years after the menopause received treatment continuously with 2.5 mg of tibolone daily (Livial, N.V. Organon, Oss) for the next 2 years. Bone Mineral Density (BMD) of the L2-L4 region was assessed using the DPX-L densitometer (Lunar) at 24 and 48 months. Results: After the last 2 years of therapy bone mineralization values improved (p=0.251) from 0.984±O.01 glcm' (T-score 1.8±O.94) after the second year of the treatment to 1.001 ±O.01 glcm' after the 4th year (Tscore -1 .66±O.75). The changes were not statistically significant. The overall improvement of BMD value from baseline after the first 2 years of treatment was 7,43% (p 0,001) and after last 2 years 1.4% (p=0.27). The tolerance was good and no significant adverse events were observed. The FSH levels (53.65±5.06 mlUlml) and E2 levels (29.77±5.8 pg/ml) remained stable during the treatment period . Conclusion: Tibolone proved to be effective and safe in the prophylactic and treatment of women with postmenopausal osteopenia and osteoporosis. 1. Kanis J . Osteoporosis, Blackwell; 1994 2. Rymer J. et al. Osteoporosis Int., 1994; 4/6; 314-319

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IN VITRO, IS ASSOCIATED TO BONE ELASTIC MODULUS G.C. Traina L. Massari F. de Terlizzi 1 and R. Cadossi' Dep. of Biomedical Sciences - Section of Orthopaedic Surgery, University of Ferrara. Laboratory of Clinical Biophysics, R&D, Igea. Italy Ultrasound investigation at the phalanxes allows to record both the amplitude dependent speed of sound (AD-SoS) and the characteristics of the graphic trace generated by the US energy at the receiving probe once it has crossed the finger. In vitro we found that AD-SoS is highly correlated to bone density, whilst a specific combination of energy, slope a~d peak amplitude of the graphic trace is mainly associated to the bone elastic modulus, here referred to as "elasticity". Here we calculated the "el~sticity" in 71 women; 16 of these had suffered a recent hip fracture, and '55 were used as controls. All parameters evaluated in the study group were significantly lower in the fractured group (p<0.0001). The table reports the results of the measurements for age matched women.

Subjects Age AD-SoS UBPS "Elasticity"

Control

Hip fracture

p<

16 69±7 1939±55 43±18 297±97

17 69±9 1855±67 25±14 235±25

n.s. 0.01 0.01 0.01

We further compared fractured and non-fractured subjects by stepwise logistic regression and found that AD-SoS is the most significant variable. Nevertheless "elasticity" improved the discrimination between the two groups by increasing the specificity to 75%. These data suggest that the "elasticity" parameter can be used to ameliorate the discrimination between fractured and non fractured subjects.

P128 FUZZY SET THEORY IN THE EVALUATION OF BONE QUALITY, BY ULTRASOUND S. Battista, A. Dorati R. Isani IGEA S.r.l., R&D Dept., Carpi, Italy QUS investigation at the phalanx has been performed in many research centres. Together with the velocity, the pattern of the US signal is available for the analysis. Its features are not sufficient, when considered alone, to classify the signal. Aim of this study is designing a knowledge based expert system for the combination of the US signal parameters. The device used. DBM Sonic 1200, measures the US transmission through the phalanx. The device calculates the ADSoS and displays the graphic trace of the received signal. In orderto train the system, a group of 396 normal subjects have been measured. The group (age range 30 to 75 years, mean 51.1 7.1) was submitted to strict inclusion criteria. A set of parameters were extracted from the signal, according to energetic, dynamic and morphological criteria. A system, based on Fuzzy Logic Set theory, was applied in order to combine all the features extracted from the trace. Each parameter becomes a linguistic variable assuming different linguistic values with degrees going from 0 to 1 (fig. 1): the parameters can be combined considering the whole amount of information that they carry. The output value has been called Ultrasound Bone Profile Score (UBPS) and is not age dependent (fig.2). The range dimension has been selected to optimise the trade-off between resolution and precision. This knowledge based system was tested using the data related to 258 subjects divided in two groups: a) 179 controls, b) 79 subjects with osteoporotic fractures. The results show the absence of relevant age dependency and a highly significant difference (p
Peaks Slope Fuzzy membership functions increasing

',I

steep

··.·1.'1 ..

.• . . . I ·

....

. •. . ··;r,il~:\: . . .: Years

Fig. 1.

Fig.2.

P129 INFLUENCE OF BONE TISSUE DENSITY AND ELASTICITY ON ULTRASOUND PROPAGATION: AN IN VITRO STUDY F. de Terlizzii', S. Battistal', V. Cane', A. Ardizzoni', R. Cadossi' 'IGEA Biophysics Laboratory, Carpi (Mo), Italy; 'Department of Morphological and Medicolegal Sciences, University of Modena, Italy Ultrasounds (US), mechanical vibrations propagating in a medium (such as bone tissue), are used to study material properties. US transmission in a material depends on density, elasticity and microstructure. In this study we evaluated how density and elasticity of trabecular bone tissue influence independently the transmission of 1.25 MHz ultrasound pulses. Twelve cylindrical specimens (0 8 mm, height 5 mm) excised from pig phalanx epiphysis, were singularly decalcified by EDTA 0.5M (pH 8.0) in a closed circuit. For each specimen, during the decalcification, at day 0, 2 and 7, we evaluated: US transmission (velocity and signal pattern analysis), density (weight/volume), elasticity (slope of the stress-strain regression line). Furthermore, to control the decalcification, at day 0, 2, 7, transversal sections of sample specimens, enclosed in methacrylate, were microradiographed and the films digitised. We found a significant correlation between US velocity and bone density (r'=0.70) and between velocity and elasticity r'=0.59. When density and elasticity were considered together, the correlation with US velocity increased to r'=0.84. We observed that after adjusting the correlation by density, US velocity shows a poor correlation with elasticity, whilst the US pattern parameters remain highly correlated with elasticity: ultrasound peak amplitude r'=0.48 and peak slope r'=0.62. Our data show that US velocity is mainly dependent on bone density, while some US signal pattern characteristics are more representative of bone elasticity. These results may have important clinical implications, in particular for the discrimination of fractured and non-fractured subjects with identical bone mineral density.

P13D 2D/3D VISUALISATION OF BONE STRUCTURES IN VIVO AND IN VITRO M.A. Dambacher M. Neff R. Kissling E. Schacht and P. ROegsegger University of Zurich, Switzerland The geometry of bone structures is a cardinal factor in bone strength. With aging and during disease the integrity of bone microarchitecture may be changed such that "osteoporotic" fractures often occur without significant changes of bone density. In patients (in praxi) we visualized the bone microarchitecture with a lateral resolution of 2001JIT1 with a high precision pQCT system and quantified the mineralisation of trabecular and cortical bone separately. Furthermore we analyzed for 3D stereologic parameters of unprocessed bone samples non-destructively down to a spatial resolution of 20x20x201 urn with a microtomography. For the vivo examinations we use a precise, accurate, low-dose, commercially available pQCT system (Densiscan 1000, Scanco Medical, Switzerland), which not only differentiates quantitatively between trabecular and cortical bone density, but which also shows the structures of the bone volumes investigated, with a lateral resolution down to 0.3 or 0.2.mm. For the three dimensional morphometric evaluation of trabecular bone samples we use a commercially available microtomographic system (J.1CT20, Scan co Medical, Switzerland). Our results show, for example, that increases in density occurring under the influence of fluorides and bisphosphonates are closely linked to mechanical bone stress (formation of microcalluses) and that endocrinopathies such as hyperthyroidism or hyperparathyroidism show characteristic structural changes in trabecular and cortical bone, as do osteogenesis imperfecta, plasmocytomas, immobilisation, algodystrophy, aseptic necrosis and fractures. Conclusion: Thin-multi-slice high-precision pQCT of non-weight-bearing and weight-bearing bones allows not only a differentiation between patients with low and high bone turnover or quantification of changes in bone density during treatment after only a few months (dynamic densitometry), but also subtle diagnosis with high resolution of bone architecture. On the other hand microtomography of bone samples is a fast, precise and nondestructive tool to give 3D information of the structures. These data can be used to estimate the internal forces in response to loads .

P13l ASSESSMENT OF THE RISK OF OSTEOPOROSIS USING HIGH RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (pQCT): A COMPARISON IN VALIDITY BETWEEN A STANDARD AND A REDUCED TRABECULAR BONE VOLUME MEASUREMENT PROCEDURE. M.A. Dambacher R. Kissling, M. Neff University Clinic Balgrist and Center for Osteoporosis, Zurich/Switzerland Postmenopausal bone loss affects the trabecular bone first. Therefore methods for early risk-detection of osteoporosis in women should be specific for the trabecular bone. The volumetric trabecular BMD (mg/cm 3) of 111 women between 31 and 80 years of age was measured in the distal radius of the non dominant forearm using high resolution pQCT (Densiscan 1000, Scan co Medical, Zurich/Switzerland). In contrast to the standard program with a stack of 10 measured tomograms (slice thickness 1mm, spacing 1.5mm, evaluated bone volume 3-10cm 3, first tomogram 7mm proximal of the "endplate" of the radius) the screening program measures onlytomograms number 1,4,7 and 10 (total 4 slices), whereas the missing tomograms in between are extrapolated. The results show that the 4 slice screening program is able to detect the true volumetric BMD of the trabecular bone in the distal radius.

•

450

RADIUS

400 350 300

~ '!I

250 200 150 100 50 0 50

100

150

200

250

300

350

400

450

Moreover, skin thickness measurement does not correlate with trabecular bone measurement. Conclusion: The accuracy of the reduced 4 slice screening program specifically measuring trabecular bone volumetrically allows a reliable and early risk assessment in osteoporosis.

P132 LONGITUDINAL ASSESSMENT OF FOREARM BONE LOSS IN WOMEN WITH A NEW SOFTWARE. THE OFELY COHORT F. Duboeuf E. Sornay-Rendu P. Garnero. A. Bouraeaud P.D. Delmas INSERM U 403, E. Herriot Hospital 69437 Lyon Cedex 03 In a large population based prospective study (OFELY study), 684 women were measured once a year during 2 years, with a monoenergy X Rays forearm densitometer (DTX 100, Osteometer Meditech AlS). Measurements were performed on the ultradistal part of the radius (55 % of trabecular bone and 45 % of cortical bone) and on the distal part (25 % of trabecular bone versus 75 % of cortical bone). We also measured a specific trabecular rich region of interest (nROI: two trapezoids regions of interest located proximally to the endplates of radius and ulna, 65% trabecular bone). 215 women were excluded because of medications or diseases known to affect bone metabolism. BMD did not decrease over two years in pre-menopausal (N=138) and peri-menopausal (N=48) women. In 267 postmenopausal women, a significant decrease was observed (-2.14% for the nROI, -2.68% for the Ultradistal part). Within 5 years of menopause, average bone loss was -3.82 % for the nROI and 4.7 % for the ultradistal part and declined thereafter 30 years after menopause (-0.673 for the nROI and -0.715% for the ultradistal part). Forthe Distal region of interest, bone loss decreased from -3.14% at menopause to -1.99% 30 years after menopause. In conclusion, the DTX 100 (Osteometer Meditech AlSR) densitometer device is able to accurately detect bone loss over two years in untreated postmenopausal women and should be useful in the investigation of osteoporosis.

P134 BONE MINERAL DENSITY OF PORTUGUESE POPULATION Ant6nio Vilar Moura Pires Helena Santos J. RibeitilaaSilva Portuguese Institute of Rheumatology- Lisbon - PORTUGAL To determine bone mass in general population a nation-wide survey was conducted in order to evaluate bone mineral density of Portuguese people and to determine specific normative data. . A randomly nation-wide survey was held in 789 male and female through 14 locations representing an appropriate selection of cities. The inclusion criteria were Caucasians between 20 and 80 years old from both sexes without previous fracture of nondominant arm or menopause before 45 years. Height, weight, body mass index, single X-ray absorptiometry of nondominant arm was performed in distal and ultradistal radius with a DTX100 (Osteometer) by the same technician. We analysed results of 701 women divided by decennial age groups from 20 to 80 years. In age groups 40-59 we considered 2 quinquiennal subsets in order to assess menopausal changes. For each age group and region we calculated the Mean and its 95%. Confidence Interval. A short term precision test (GIGer et al.) was conducted in 28 individuals to determine preciSion error (0,007g/cm') and coefficient of variation (0.81%).

P133 BONE ULTRASONOMETRY IN PATIENTS WITH ANOREXIA NERVOSACOMPARISON OF THREE METHODS OF DENSITOMETRY S. Newrkla. P. Weiss. S. Grampp, H. Resch KH Barmherzige Schwestern (St. Vincent), Department of Radiodiagnostics, University Vienna Austria Patients with anorexia nervosa (AN) are to undergo osteologic monitoring for several years which requires short-term as well as simple and cheap investigation methods, if possible radiation free. Methods: Three different techniques of bone mass measurement were evaluated in 30 patients with AN (mean age 22±3 yrs, range 17-30 yrs). The results were compared to an age and sex matched control group consisting of 25 Caucasian females. Bone mass was evaluated by broadband ultrasound attenuation (BUA) and speed of sound (SOS) with bone ultrasonometry (BUS) at the calcaneus (Sonomed systems), peripheral quantitative computed tomography (paCT) at the distal radius (XCT-1400, Stratec) and DXA of the lumbar spine and the hip (Hologic 1000). The CV of the three methods was at least 1.5%. Results: In patients with AN we found significantly reduced values of BUA (35.3±4.1dB/MHz vs. 51.03±4.12 dB/MHz; p<.0001) and of BMD both at femoral neck (0.82±O.18 vs g/cm' vs 1.02±O.07g/cm'; p<.001) and lumbar spine (0.73±O.15 g/cm' vs. 0.97±O.07 g/cm'; p<.003). The differences at the peripheral radius measured by paCT were not statistically different between AN and controls. In addition, SOS did not show any differences. Calculating a Z-score we found the most prominent differences between AN and controls by BUA at the calcaneus (-4.2±O.3) followed by DXA at the lumbar spine (-2.3±O.3) and femoral neck (-2.2±O.3). There were highly significant correlations between BMD-values of femoral neck and lumbar spine (r=0.95;p>.0001) measured by DXA, as well as between BUA at the calcaneus and BMD at the femoral neck (r=0.78,p<.O001) and BUA and lumbar spine (r=0.75,p<.0001). In addition there were statistically significant correlations between BMI and the three different measuring techniques (r=0.7,p<.001). A negative correlation was found between BMD and the duration of amenorrhoea (femoral neck: r=-0.83,p<.05; lumbar spine: r=-0.76,p<.05), as well as between BUA and the duration of ammenorroea (r=-0.45;p<.05). Conclusion: Our data suggest thatthe most prominent differences in bone mass between patients with AN and controls were observed by BUA at the calcaneus.

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Age group 20-29 30-39 40-44 45-49 50-54 55-59 60-69 70-79 Total

N 107 110 72 85 79 60 119 69 701

BMD Distal Radius

BMD Ultradistal Radius

Mean .472 .473 .476 .465 .454 .441 .414 .366 .447

Mean .406 .404 .406 .394 .365 .357 .323 .287 .370

95% IC .464 .480 .464 .481 .464 .487 .453 .476 .443 .464 .426 .456 .404 .425 .353 .380 .442 .451

95% IC .398 .415 .394 .415 .393 .418 .382 .406 .355 .376 .342 .372 .312 .333 .274 .301 .365 .375

Results of BMD in Table show a steady state between 20 and 44 and a progressive decrease of the mean thereafter with age until last decennial; the descending slope beginning at age group 45. The mean annual loss of BMD was 0.002 g/cm' on the lowest side of European studies. Results either from distal or ultradistal radius showed the same pattern. There were no significant differences of the mean BMD between inland and seaside cities. When compared with similar studies these BMD results are in absolute values lower which is attributable to broad inclusion criteria not restricted to healthy population following the same criteria of an NHANES study. Further stratification for health status medication time from menopause and other risk factors already recorded will clarify this first attempt to assess were our BMD stand among European and Mediterranean countries.

P135 INFLUENCE OF LIFE HABITS IN THE MINERAL BONE DENSITY

P137 PHYSICAL ACTIVITY AND BONE MINERAL ACQUISITION IN

MEASURED BY MEANS OF ULTRASOUND A. Rodriguez C. Diaz-Miguel M. Vazquez J. Beltran Servicio de Reumatologia. Hospital Ramon y Cajal. Madrid INTRODUCTION. We have analysed the influence of several factors, related to life habits, on the mineral bone density, using the broadband ultrasound attenuation (BUA) and the speed of sound (VOS) ultrasonic parameters. MATERIAL AND METHODS. We selected 226 healthy women, whose mean age was 48±12.1 year-old, (130 pre-menopausal and 96 postmenopausal ones), who had no risk factors of osteoporosis and we have determined their BUA and VOS rates. For all of them, we measured the weight and height, we recorded the months of lactation, the regular practice of sports and the smoking habit. A survey was done of the alcohol ingestion and of the frequency of global calcium consumption. All these data were analysed by means of the PRESTA statistical package. RESULTS. The mean calcium ingestion was 664±373.3 mg/day; 44% took less than 500 mg/day of calcium; 43.4% took between 500 and 1000 mg/day, whereas only 10.2% took between 1000 and 1500 mg/day and only 2.6% took more than 1500 mg/day. There was no difference in calcium ingestion between pre and post menopausal women. Only 14.6% of them said to regularly practice sport. For 23.4% of the women, a smoking habit was detected. 13.3% of them admitted to regularly consume alcohol. The BUA and VOS rates were lower for post-menopausal women and for the eldest ones «0.00001), notfinding any relation with the rest ofthe factors. CONCLUSIONS. Both BUA and VOS rates decrease with the age. The calcium ingestion in women without risk factors of osteoporosis is under the established recommendations. No relation has been found between life habits (smoking, alcohol, sports and lactancy) and bone mass.

P136 ULTRASOUND MEASUREMENTS ON OS CALCIS AND DUAL ENERGY X- RAY ABSORPTIOMETRY: WHICH TECHNIQUE DISCRIMINATES FRACTURE RISK C. Diaz-Miguel A. Rodriquez M. Vazquez Servicio de Reumatologia. Hospital Ramon y Cajal. Madrid. Spain Introduction: The most commonly used technique for assessing bone mineral density (BMD) is dual- energy x-ray absorptiometry (DXA). Ultrasound measurements are the speed of sound (SOS) and the broadband ultrasound attenuation (BUA) that could be used to identify patients with risk of fractures. Patients and Methods: We have compared the measurements of bone mass on os calcis obtained by ultrasound system with DXA measurements in lumbar spine and femoral neck, in a sample of 198 women aged 37-78 gathered in 3 group: Group A- 15, considered as normal women without history of osteoporosis or medical conditions known to be associated with low bone mass. Group B-1 09 women with several factors of risk for developing osteoporosis, without fractures. Group C- 74 women with osteoporotic fractures. The concordance between techniques were analysed calculating the correlation coefficient. A receiver operating characteristic curves (ROC) were calculated for BUA and DXA. Statistical analysis was carried out by a microcomputer based statistical package PRESTA. Results: BMD values with ultrasound and DXA were significantly lowest in women with osteoporotic fractures. Significant correlation were found between all DXA results and BUA. The best numerical correlation was obtained between lumbar spine DXA values and BUA r=0.393 (p
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PERI PUBERTAL GIRLS M. Lehtonen-Veromaa" T. Miittiinen', E. Svedstriim 3, O. Heinonen''', J. Viikari' 'Paavo Nurmi Centre, Department of Physiology, Turku, 'Department of Medicine, 3Department of Radiology, 'Central Laboratory, Turku University Central Hospital, Turku, Finland Purpose: To investigate the effect of physical activity on bone mineral acquisition in peri pubertal girls. Methods: To the cross-sectional study 191 Caucasian girls aged 9-15 years, were recruited. Sixty-six girls were engaged in gymnastics, 65 in running and 60 nonathletic controls were included. Weight, height and the stage of puberty in the partiCipants were recorded. Leisure-time physical activity of the participants during past six months was expressed as MET hours/week. Bone mineral density (BMD) of the non-dominant femoral neck and lumbar spine was measured by dual energy x-ray absorptiometry. Results: The mean age was 12.8 (SD 1.6) years in gymnasts, 13.0 (SD 1.9) in runners, and 13.1 (SDI .7) in controls. The mean activity scores in gymnasts, runners, and controls were 77.0 (SD 27.8), 45.1 (SD 28.7), and 11.2 (SD 10.1) MET hours/week, respectively. The mean height in gymnasts, runners, and controls were 152.9 (SD 10.6), 157.3 (SD 10.6), and 156.4 (SD 9.7) cm, respectively. There were not differences between the groups at the stages of puberty (p=0.35). When all subjects were classified according to the exercise level, in the lowest exercise group the femoral BMD was 0.81 (SD 0.11) g/cm' while 0.95 (SD 0.16) g/cm' in the highest exercise group (p=O.OOOl) respectively. At the lumbar spine the correspondent figures were 0.77 (SD 0.13) g/cm' and 0.90 (SD 0.17) g/ cm' (p=O.OOOl). In the group of the shortest girls (height <140cm) there were no differences between BMD of any sites. There were significant differences in BMD of the femoral neck between gymnasts and runners (p=0.03) and between gymnasts and controls (p=O.OOOl), when adjusted for height. Whereas the height of the subjects was> 150 cm, the differences in BMD of the lumbar spine were significant between the gymnasts and controls (p=0.0008) and between gymnasts and runners (p=0.045). There were significant differences between runners and controls in BMD of the femoral neck (p=0.0007) and lumbar spine (p=0.0035), when the height was at least 160cm. Conclusion: Physical activity significantly enhances bone mineral acquisition in peripubertal girls and could favourably modify attainment of peak bone mass and bone density. This may provide protection against future development of osteoporosis and osteoporotic fractures.

P14D PREDICTING VERTEBRAL FAILURE LOADS FROM DEXA AND

P138 PRECISION OF BONE DENSITY MEASUREMENT AROUND TOTAL HIP REPLACEMENTS M. Jablonski*. M. Gorzelak*. J. A. Shepherd ' *Orthopaedic Department, Lublin Medical School, Lublin Poland, 'Hologic, Inc., Waltham, MA Bone loss in the proximal femur accompanies total hip replacement and can lead to prosthesis loosening and ultimately revision surgery. To evaluate periprosthetic bone density, metal prosthetic components must be excluded from the analysis. Methods: Peri prosthetic bone density was measured on 9 unilateral hip replacement subjects, 6 cemented and 3 cementless protheses with the Hologic Metal Removal Option on the QDR-4500A. Each subject was scanned 3 times. Between each scan the subject was removed from the scanner and then repositioned. The leg was held in the neutral patella position using a modified hip positioner provided with the option. The proximal femur was divided into seven modified Gruen zone analysis regions where R I was the Greater Trochanter and R7 was the Calcar region. No attempt was made to exclude cement from the analysis. Measurement precision using ANOVA was performed on the individual zones. Results: The scan time was approximately 2 minutes for a 24 cm long scan with a pixel size of approx. 0.56 x 0.56 mm2. The coefficients of variation (CV) are given below.

CALCANEAL ULTRASOUND - IN SITU ANALYSIS E.-M. Lochmiiller F. Eckstein. D. Kaiser. J. Zeller. J. Landgraf. R. Steidinger, R. Putz I. Universtitatsfrauenklinik Miinchen, Anatomische Anstalt Miinchen, Germany The objective of the current study was to experimentally determine the correlation of spinal and femoral DEXA and calcaneal ultrasound, measured in situ with intact soft tissues, with the in vitro failure loads of vertebral bodies. 49 cadavers with intact skin and soft tissues (32 male, 82.1±9.0 yrs.; 17 female, ~3.1±10.1 yrs.) were examined. The bone mineral content (BMC) and density (BMD) of the lumbar spine and proximal femur were determined with a DPX-L scanner, and the ultrasonic properties of the calcaneus with an Achilles instrument. The 4th lumbar vertebrae were then excised with the adjacent intervertebral discs and their mechanical failure loads determined, applying cyclic loads using a material testing machine. Absolute vertebral failure loads were significantly higher in men than in women, but were similar after adjusting for body weight and height. The correlation between the densitometric variables and failure loads are shown in Table 1:

Gruen Zones CV(%)

R1 1.0

R2 3.0

R3 1.8

R4 1.4

R5 12.0

R6 2.1

R7 14

Total 0.8

all (n=49)

men (n=32)

women (n=17)

BMCL2-4 BMD Fem Neck SOS BUA

0.62*** 0.41** 0.48*** 0.27

0.54** 0.26 0.36* 0.16

0.58* 0.41 0.41 -0,22

*p
Conclusions The QDR-4500A measured the bone mineral density around the femoral part of prosthetic hip implants to a precision better than 1% for the total region. This should allow early detection of post operative bone loss, its monitoring and effects of possible preventive pharmacological treatment.

Spinal DEXA was moderately and significantly associated with vertebral failure loads, whereas femoral DEXA and calcaneal ultra-sound showed lower correlation coefficients. Femoral DEXA and ultra-sound, however, added independent predictive information in a step-wise regression model. The speed of sound (SOS) was found to have a higher predictive capacity than ultrasonic attenuation (BUA). We conclude that previous in vitro studies have overestimated the association between spinal DEXA and vertebral failure load, because measurements were not performed in situ, but on excised bones. In situ the inhomogeneous distribution of soft tissue can, however, distort DEXA measurements. Nevertheless, spinal DEXA appears superior to femoral DEXA and calcaneal ultrasound in estimating vertebral failure loads.

P139 BONE MINERAL DENSITY IN THE RATS DRINKING STRONTIUM CHLORIDE WATER M. Jablonski. M. Gorzelak. J. Walawski. M. Patvra Orthopaedic Department, Lublin Medical School, Lublin, Poland The aim of the study was to assess influence of strontium chloride given in drinking water on bone density of different regions of the skeleton of young male adult rat. Materials and methods: Tap water with added strontium chloride was given ad libitum to three groups (n=18) 6 weeks old male Wistar rats (200±20g) fed standard diet (Ca-1, 1%). Three concentrations of strontium in water were used (group Sri - 3,766 mmol/l, group Sr2 7,532 mmol/l, Sr3 -11 ,298 mmol/l). Controls (C, n=20) drank ordinary tap water. After 6 months serum samples were analysed for strontium concentration (S.c. Sr[ppm],GFAASS method) and lumbar vertebrae L1-L4 (LS), right femora (F) and both humeri (H) were harvested for a-p densitometry (area[cm'], BMC[g], BMD[g/cm']) with the use of Small Animal Programme of the QDR 4500A. Statistical analysis (ANOVA) was performed with Statistica 5 PL computer programme. Results were expressed as means and standard deviations (in brackets). P*
Tab. 1

P141 IN VIVO ASSESSMENT OF HIGH RESOLUTION MAGNETIC RESONANCE

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IMAGING OF THE DISTAL RADIUS: A STUDY IN OSTEOPOROSIS B. Cortet N. Bout!}' P. Bourel X. Marchandise A. Cotten University-Hospital of Lille, Lille, France This study aimed to compare magnetic resonance imaging (MRI) parameters in osteoporotic and healthy women. 24 subjects were studied (13 osteoporotic women with at least one vertebral fracture and 11 age-matched control women). MR images were obtained with a 1.5 Tesla MR unit (Siemens®). For each subject both axial and cross-sectional sections were performed in spin-echo and in gradient-echo imaging. 7 axial and 3 crosssectional sections were selected for each subject (both for spin-echo and gradient-echo imaging). The volumetric data set was transferred from the MRI system to a PC computer for image analysis developed in our laboratory. 3 kinds of trabecular texture analysis were performed: statistical analysis (gray level run length method and differential measurements of local variations), fractal analysis ("blanket method") and structural analysis (skeletonization from gray levels and trabecular network characterization). For each subject the mean of the results obtained from cross-sectional and coronal sections was taken into account. Several features were significantly different on coronal sections in controls as compared with osteoporotic women (spin-echo imaging, P<0.05): trabecular separation (0.413±O.02 vs 0.454±O.03), bone marrow partition (0.131±O.03 vs 0.095±O.03), trabecular network skeleton length (1.03±O.04 vs 0.96±O.09), node count (0.53±O.01 vs 0.46±O.02) and node-node strut count (0.5±O.01 vs 0.45±O.02). 2 structural features were significantly different in the 2 groups (i.e. controls and osteoporotic women) on cross-sectional sections in spin-echo imaging (p<0.05) i.e. terminus-terminus strut length and node terminus strut length but also 8/9 statistical features. In conclusion MRI of the distal radius trabecular network seems apromising tool in the assessment of osteoporosis. Further studies are required for confirming these results .

P142 BONE MINERAL DENSITY IN PULMONARY DISORDERS S. TOzOn S. Sipahi H. Talay T. Karayel S. Demirci. F. TOzOn Istanbul University Osteoporosis Research Center, Cerrahpa~a Internal Medicine Pneumology Department, Turkey Corticosteroids are widely used in pulmonary disorders. Bone mineral density (BMD) of the lumbar spine (L 1-L4) and femur (Neck) were measured using dual energy X-ray absorptiometry (DEXA) in 58 patients with pulmonary disorders (26 sarcoidosis, 20 asthma bronchiale, 10 chronic obstructive pulmonary disorder and 2 diffuse fibrosis) and 15 healthy volunteers. The difference of BMD values in all disorder groups when compared with each other was not statistically significant. After postmenopausal cases are excluded the mean BMD value in femur was lower in patients who were treated with oral prednisolone versus inhaler steroids and never users (p=0.02, p=0.03 respectively). There was no significant difference in BMD values between the inhaled corticosteroid group and controls. We did not find any relationship with cumulative dose of prednisolone and BMD. In conclusion this study supports that oral prednisolone treatment is one of the most important reason of low bone mass and inhaler steroids has no effect on BMD.

P143 THE CORRELATION OF ULTRASOUND VELOCITY IN THE TIBIA AND BONE MINERAL DENSITOMETRY OF THE SPINE AND FEMUR E. Kaptanoglu C. Kacar E. Gilgil T. Tuncer A. Akyoku§ B. BOlOn Akdeniz University, Medical School, Department of Physical Medicine and Rehabilitation, Antalya, Turkey Many investigations are being carried out to develop novel instruments that measure the bone mineral density (BMD) accurately. An instrument developed in the last years measures the speed of propagation of ultrasound waves along the cortical layer of the tibia. In this study, we compared the results of measurements which are obtained by quantitative ultrasound (SoundScan 2000) and dual-energy x-ray absorptiometry (DEXA), accepted as a reliable and valid method for assessment of BMD. Twenty-eight peri- or postmenopausal women (mean age =59±9) were included in this study. Ultrasound velocity measurements in the tibia and BMD measurements with DEXA at lumbar spine and femur were performed in all of the patients. Correlation coefficients were calculated for the following parameters: BMD obtained by DEXA at lumbar spine and femur, ultrasound velocity in the tibia and t- and z- scores ofthe former parameters. The mean ultrasound velocity was 3943.5 m/sec with a range of 2171.8 4097.3 m/sec. Calculations were also made by classifying the patients into two groups as obese (9 patients) and non-obese (15 patients) according to the body mass index. No significant correlation was found between the measurements of quantitative ultrasound and DEXA. Ultrasound velocity measurements in the tibia were not found to be a good predictor of the BMD compared to BMD obtained by DEXA at lumbar spine and femur. That the quantitative ultrasound measures ultrasound velocity in the cortical layer of the tibia whereas DEXA takes both trabecular and cortical bone into account as well as the lack of BMD measurements in the tibia with DEXA may explain this partly. However, further studies are needed. .

P144 DIFFERENT PREVENTION OF BONE LOSS AT DIFFERENT SITES: TRANSDERMAL ESTRADIOL VERSUS CALCIUM OVER 5 YEARS C. Bodmer" R. Fridrich', M. Kranzlin 3, M.H. Birkhauser' 'Universitats-Frauenklinik, Kantonsspital Basel, CH. 'Institut fOr Nuklearmedizin, Kantonsspital Basel, CH. 3endokrinolog. Privatpraxis, Basel, CH. 'Universitats-Frauenklinik, Inselspital Bern, CH Introduction: The present prospective study intends to compare the effect of transdermally applied 17-beta Estradiol (HRT) to peroral Calcium intake on bone density and biochemical parameters of bone turnover for up to 5 years. Patients and Methods: 89 healthy postmenopausal women aged from 41 to 55 years (mean 50,4) have been attributed to one of two matched groups and followed up to 5 years. Group A received 1000mg Calcium Sandoz ff p.o./day during the first 2 years and 500-1000mg Ca during the following 3 years. Group B has been substituted by 100ug Estradiol/day (Estraderm TIS 100)-in some cases 50 ug Estradiol/day-from day 1-21, combined with 10mg MPA (Medroxyprogesteronacetat) per os/day from day 12-21; treatment-free interval from day 22-28. BMC was measured at oand then every 6 months mostly; at the lumbar spine and both femoral necks with DPA and at the forearm with SPA. The statistical evaluation within groups was done by Students t-Test and between groups by Wilcoxon Test. Results: At the lumbar spine cyclic transdermal substitution by 100ug Estradiol/day, combined with 1Omg MPAlday protects, in contrast to peroral CalCium, efficiently from loss of BMC. At the forearm BMC is maintained in the Estradiol-group, whereas there is a significant loss of BMC in the Calcium group. At the femoral necks BMC decreases in both groups. The different effect of Estradiol in comparison to Calcium on bone turnover is also documented on the different results in the biochemical analyses, such as alkaline Phosphatase, Osteocalcin and the two-hours fasting urine parameters. Conclusion: The prophylactic effect of HRT on postmenopausal bone loss varies greatly in function of the underlying bone structure. However Calcium seems to provide some benefits too, when compared to nothing, as stated in the literature.

P145 INTEGRATIVE VERSUS SELECTIVE BONE MINERAL MEASUREMENTS IN OSTEOPOROSIS R. Dreher, M. Hesse G. Lingg* Hospital for Rheumatic Diseases, 55543 Bad Kreuznach, Germany *Radiologieal Department Objective: Measurements of bone density with the integrative DXA method (lumbar vertebrae, neck of the femur) are compared with selective cancellous bone measurements of the lumbar vertebrae by quantitative computer tomography (LOCT) Method: For purposes of differential diagnosis, the bone density was measured with the DXA method (LUNAR) on the lumbar spine (LDXA) and on the neck of femur (F DXA) in women inpatients (n=360) with different underlying rheumatic diseases. The cancellous bone density ofthe lumbar vertebrae was determined selectively (L OCT) with quantitative computer tomography (GE 3000). Spearman correlations were calculated FDXAlLDXA (n=688) FDXA/LOCT (n=281), LDXAlLOCT (n=281). The classification of the DYA bone densities into normal bone density osteopenia, osteoporosis and severe osteoporosis was made in accordance with the WHO T score criteria. The OCT values were calculated in comparison to the bone mass of a reference population younger than 50 years Results: There is a moderately positive Significant correlation between the DXA measurements in the lumbar spine and the neck of the femur (r=0.61 p=O.OOO). The LDXA and FDXA values correlate to a moderate extent with the selective cancellous bone values of the lumbar spine (r=0.49 p=O.OOO and r=0.47 p=O.OOO respectively) Out of 360 women investigated 236 (66%) showed osteoporosis in LOCI, whereas only 94 patients (26%) showed osteoporosis in the FDXA. In the LDXA measurements only 88 patients (24%) revealed osteoporosis. In women older than 50 years selective measurement of lumbar vertebrae cancellous bone with LOCT shows osteoporosis in 76% whereas osteoporotic values were determined in less than 30% with the DXA method. Conclusion: Osteoporosis are detected more frequently with selective cancellous bone measurements on the lumbar vertebrae than with the DXA method The risk of fracture may thus already be increased in DXA osteopenia but already existing LOCT osteoporosis .

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P146 CALCANEAL ULTRASOUND MEASUREMENTS IN HEALTHY AND OSTEOPOROTIC SOUTHERN CHINESE WOMEN AWC. Kung GWK. Tang, K.D.K. Luk, L.w. Chu Departments of Medicine, Obstetrics & Gynaecology and Orthopaedics, The University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC Quantitative ultrasound (QUS) bone analysis is emerging as an alternative to photon absorptiometry techniques in the assessment of osteoporosis. The normative data of QUS parameters in healthy southern Chinese women was determined using a waterless calcaneal ultrasound system (Sahara, Hologic, USA). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness (Quantitative Ultrasound Index, QUI) was determined in 1086 healthy women aged 20 to 90 years. BUA was significantly correlated with SOS (r=0.795, p-2.5). Group III, age-matched osteoporotic subjects with vertebral fractures (n=39, age 65±5yr, L2-4 or hip neck T score <-2.5).

BUA (dB/MHz) SOS (m/s) QUI QUI T score

Group I

Group II

Group III

73±18 1574±33 106±22 -0.05±2.2

59±18* 1541±32* 85±19* -2.1±1.9*

46±13*a 1511±23*b 67±14*b 39±1.5*b

vs group I, *p<0.0005, vs group II, a, p
P147 QUANTITATIVE ULTRASOUND AND VERTEBRAL FRACTURE IN POSTMENOPAUSAL SOUTHERN CHINESE WOMEN AWC. Kung GWK. Tang, K.D.K. Luk Departments of Medicine, Obstetrics & Gynaecology and Orthopaedics, The University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC Quantitative Ultrasound (QUS) has recently been demonstrated to be able to evaluate fracture risk in osteoporotic patients. We evaluated the broadband, ultrasound attenuation (BUA), speed of sound (SOS) and stiffness (Quantitative Ultrasound Index, QUI) in 391 osteoporotic women with recent vertebral fractures using a waterless calcaneal ultrasound system (Sahara, Hologic, USA). Bone mineral density (BMD) at the spine and hip was determined by dual X ray absorptiometry (QDR 2000 plus, Hologic). Their results were compared to a group of 256 non-osteoporotic subjects. After adjustment for age, the relative risk (RR) of vertebral fracture for one standard deviation (SO) reduction was 1.9 (95% confidence interval 1.3-2.5) for BUA, 3.4 (1.9-6.0) for SOS and 1.8 (1.3-2.5) for QUI. A similar relation was observed with BMD at the spine (RR 3.6 (2.0-6.8) and at the hip (RR 2.6 (1.6 - 4.3). Adjustment for spine or hip BMD did not significantly alter the relation between BUA and vertebral fracture. e.g. after adjustment for spinal BMD, the RR of vertebral fracture for 1 SO reduction was 1.6 (1.12.4) for BUA, 2.6 (1.4-4.8) for SOS and 1.6 (1.2-2.3) for QUI. In conclusion, the relation between QUS parameters and vertebral fracture is similar to that observed for BMD and vertebral fracture. Our data suggest that QUS is a useful tool in the prediction of vertebral fractures.

P148 STIFFNESS INDEX PREDICTS OSTEOPOROTIC FRACTURE BEDER THAN BROADBAND ULTRASOUND ADENUATION (BUA) OR SPEED OFSOUND(SOS)ALONE P. Hadji Chr. WOster, O. Hars, H.-G. Bohnet University of Marburg, Department of Gynaecology and Obstetrics, Marburg, Germany The aim of this study is to compare a composite measure, the stiffness index, with single parameters of quantitative ultrasound sonometry, speed of sound (SOS) and broadband ultrasound attenuation (BUA), in predicting the risk of osteoporotic fracture in postmenopausal women. A cross$ectional sample of 1217 women (mean (SO) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis had been assessed by detailed questionnaire and women with diseases or taking treatments known to affect bone metabolism had been excluded. Women were allocated to one of four groups: premenopausal women (n=476), healthy post menopausal women (n=583), postmenopausal women with documented osteoporosis (n=101), and postmenopausal women with a history of osteoporotic fracture (n=57). The stiffness index, calculated mathematically from velocity and attenuation measures, was computed as it is considered to minimise artifactual errors caused by variable heel width and water temperature. Analysis of receiver operating curves showed that the stiffness index (young) was significantly better (p~ 0.001) than single measures of velocity or attenuation in discriminating between healthy postmenopausal women and postmenopausal women with a history of osteoporotic fracture; area under the curve (AUC) values for the stiffness index (young), velocity, stiffness index (age-correlated) and attenuation were 0,918%, 0,892%, 0,890% and 0,859% respectively. When healthy postmenopausal women were compared with osteoporotic postmenopausal women with no history of fracture, values were 0,877 %, 0,842%, 0,838%, and 0,815% respectively. In concluSion, quantitative ultrasound sonometry is a precise method of determining the risk of osteoporotic fracture. Of the ultrasound parameters investigated, the stiffness index (young) seems to be the best indicator of osteoporosis.

P149 IS QUANTITATIVE ULTRASOUND SONOGRAPHY ABLE TO IDENTIFY OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN? P...HilltiL. O. Hars, G. Emons, K. -D. Schulz University of Marburg, Department of Obstetrics and Gynaecology, Marburg, Germany The aim of this study was to determine if QUS at the calcaneus is able to identify osteoporosis of postmenopausal women in gynaecological practice. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) ofthe calcaneus were measured in n=764 postmenopausal women, mean age 61 years, using the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). Osteoporotic risk factors were assessed by a detailed questionnaire. Women using any medication known to effect bone metabolism were excluded from the study. Short-term precision in vivo expressed as coefficient of variance (CV) was 1.2 % for BUA and 0.17 % for SOS and 1.3 % for stiffness respectively. A total of 102 women were measured atthe right and left calcaneus with a coefficient of correlation of r=0,92 for SOS, r=0,84 for BUA and r=0.93 for SI (p~O.OOl). There was a significant yearly postmenopausal decrease of 0.06 % for SOS, 0.44 % for BUA and 0.74 % for SI (p~O.OOl). 165 women with a history of osteoporosis (identified by DXA or QCT) due to the WHO criteria, as well as 141 women with an osteoporosis-related fracture of the spine, the hip or the distal forearm showed significantly lower results in all ultrasound parameters (SOS, BUA, SI) (p~O.OOl). In concluSion, quantitative ultrasound sonography of the calcaneus measures properties of bone which show a physiological postmenopausal deCline, a low precision error and a high correlation of right vs. left. Our results indicate that QUS is able to identify postmenopausal women with a history of osteoporosis as well as women with previous osteoporotic fractures .

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P150 AGE-RELATED CHANGES IN QUANTITATIVE ULTRASOUND SONOMETRY (QUS) IN HEALTHY GERMAN WOMEN P. Hadii O. Hars G. Emons K. -D. Schulz University of Marburg, Department of Gynaecology and Obstetrics, Marburg, Germany The aim of this study was to assess the age-related changes in Quantitative Ultrasound Sonometry (QUS) in a large sample of healthy German women within a wide range. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI, expressed as the % in young adults) of the calcaneus were measured in 1333 women (mean age 50,50±11 ,49 years) using the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI, USA). Osteoporosis risk factors were assessed by a detailed questionnaire. Women using any drug treatment known to effect bone metabolism were excluded from the study. We performed separate analyses for pre- and postmenopausal women and within 1O-year bands. There was an overall decline of 14,89 % for BUA, 4,47 % for SOS and 31 ,2 % for SI between women aged 15-89 years leading to a mean yearly decline of 0,20 % for BUA, -0,06 % for SOS and -0,42 % for SI. Analysing premenopausal women (15-49 years), BUA was stable or slightly decreased by atotal of -2.79 %, while postmenopausal women (50-89 years) showed a Significantly higher decline of 12,34%. In contrast, SOS continuously decreased from tfle age of 15, showing a premenopausal (15-49 years) decline of 1,88%. Postmenopausal women (50-89 years) showed a significant larger decline of -2.48%. The SI of premenopausal women (1549 years) decreased by -10,13% and as SOS showed a postmenopausal significantly larger decline of 21,56%. Analysing antrophometric parameters we found a significant reduction in height and a significant rise in weight and BMI in the age-group of 50-59. In conclusion QUS measured properties of bone which decline with age. It provides a radiation-free, low-cost, easy to handle, fast and mobile method.

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WRIST AND METACARPOPHALANGEAL JOINT BONE MINERAL DENSITY IN EARLY RHEUMATOID ARTHRITIS (RA) M. Nitsch T. Pap, and J. Kekow Clinic of Rheumatology, University of Magdeburg, D-39245 Vogelsang, Magdeburg, Germany The determination of an early BMD loss due to arthritis was studied in 25 RA patients using DXA techniques (18 female, 7 male, mean age 59 years, mean duration of disease 18 months) (Hologic QDR 1000). The BMDs were compared with reference values of 18 matched healthy controls. The regions of interest (ROI's) included the wrist and the metacarpophalangeal joints. In addition we measured the BMD of the lumbar spine by DXA in all subjects. In order to identify a disease activity dependent BMD loss, laboratory tests such as ESR, CRP and rheumatoid factors (RF-lgM) were performed. Our data revealed a highly significant loss in the BMD of the hand in the RA group. In addition a significant correlation between hand BMD and disease duration was detectable within the hand BMD and the RF levels in these patients. RA patients with high disease activity (ESR >40 mmlh, CRP <20 mg/l) showed a significantly" lower BMD of the hand than those with low disease activity (ESR 40 mmlh, CRP <20 mg/l). No differences could be detected between RA and controls with respect to the BMD of the lumbar spine. Follow up analysis in 11 of the RA patients revealed an ongoing local bone loss in those patients with poor response to DMARDs. Or results indicate a disease activity dependent, localized early BMD loss in RA which can be easily measured by DXA. Additional studies with pQCT and standard DXA of the forearm revealed no significant bone loss in these patients.

P152 CAN BONE DENSITOMETRY IN PERIPHERAL SITES BE USED TO DIAGNOSE SPINAL OSTEOPOROSIS? J.E. Adams P.L. Selby" I. Hodgkinson E.J. Harrison and M. Davies' Departments of DiagnostiC Radiology and Medicine', University of Manchester, UK Bone Densitometry is important in the diagnosis of osteoporosis. Dual energy X-ray absorptiometry (DXA) is currently the preferred and most widely used technique, but is relatively expensive and not portable. Broadband ultrasound attenuation (BUA) does not use ionising radiation, is portable and relatively inexpensive. Peripheral DXA and single energy X-ray absorptiometry (SXA) use small doses of ionising radiation, but otherwise have the same attributes as BUA. Both SXA and BUA can predict fracture risk and have the potential for use in the diagnosis of osteoporosis in the community. We have compared the bone density results from DXA, SXA and BUA and assessed their ability to identify individuals with osteopaenia, osteoporosis and vertebral fractures. Patients and Methods: 301 (M:F, 36:265); age 61 (mean; 31 81) years. Vertebral fractures define as >25% deformity on lateral spinal radiographs. Measurements made by DXA (L 1-4; femoral neck), SXA - distal forearm and BUA calcaneum. The WHO criteria for osteoporosis (BMD T score less than -2.5) was used. Results: There was significant correlation between results in the same individual by different techniques (r=0.4-0.64; p=0.01). Kappa scores for the probability for consistent classification of osteoporosis by DXA and SXA were 0.24-0.33; p=0.01; for BUA -0.07 to 0.09; p=0.08 to 0.94. All measurements made were lower in the vertebral fracture group than in those without fracture. Odds rations for fracture L1-4 =1.45; femoral neck 1.37; forearm 1.24 and BUA 1.49. Conclusion: Correlations between results were moderate to poor. Results of techniques were not interchangeable and SXA and BUA can not replace DXA in the diagnosis of osteoporosis. Consistent classification of osteoporosis by different techniques was poor but the prediction of fracture risk was similar by each technique.

P153 ULTRASOUND FOR BONE DENSITOMETRY: A COMPARISON OF THREE SCANNERS J.E. Adams E.J. Harrison CW Alsop and P.L. Selby' Departments of Diagnostic Radiology and Medicine" University of Manchester, UK. Broadband ultrasound attenuation (BUA) predicts fracture risk in the elderly'. The technique does not use ionising radiation, is relatively inexpensive and portable and so has the potential for use in the diagnosis of osteoporosis in the community. There are now several different scanners manufactured; most applied to the calcaneum. We have compared the operation of, and results from, three different scanners. Subjects and methods - 92 subjects (M:F 20:76) aged 23-85 years. BUA was measured in both calcanea by one operator using 1) Lunar Achilles with a water bath 2) Hologic Sahara and 3) McCue Cuba Clinical which are "dry" systems (no water bath required). Patients who were included also had DXA lumbar spine (LS = L1-4) and femoral neck (FN). Normal, osteopaenia and osteoporosis were defined by WHO criteria. Results - Precision (CV%) - Achilles =1.5%, Sahara =3.5% and Cuba Clinical =4.1 %. There were correlations between results from different ultrasound scanners r=0.614 - 0.76; p=0.01, but Bland and Altman plots showed results from different scanners were not interchangeable. Kappa values for diagnostiC categorisation for osteoporosis between the scanners (0.471 to 0.541) showed significant agreement; but for BUA and DXA values ranged from 0.129 to 0.54. Conclusions - The "dry" systems were easier to use; precision was acceptable on all scanners, but best with the Achilles. Correlations between methods were reasonable, but results were not interchangeable. There was reasonable agreement in diagnostic classification for osteoporosis by the different ultrasound scanners, but agreement between BUA and DXA was poor. Reference 1. D Hans, P Dargent-Molina, AM Schott et al. Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 348, 511 -4 (1996) .

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P154 PEAK BONE MASS OF ICELANDIC WOMEN AND ASSOCIATED FACTORS

P156 CLINICAL UTILITY OF LUMBAR SPINE BONE MTNERAL DENSITY IN THE DIAGNOSIS OF OSTEOPOROSIS N.F.A. Peel P.R. Bainbridge R. Eastell University of Sheffield, Sheffield, UK Measurements of bone mineral density (BMD) at the lumbar spine (LS) may become unreliable with age due to increasing prevalence of artefacts such as aortic calcification and degenerative arthritis. It has therefore been suggested that in individuals over the age of 65 BMD at the hip is more useful in the diagnosis of osteoporosis and may be used alone. The aim of this study was to determine the diagnostic utility of LS-BMD measurements in clinical practice. We have examined data from 1586 consecutive referrals received between September 1995 and January 1998 for individuals over 40 years (range 40 to 95, median 59.5). BMD was measured at the LS and femoral neck (FN) using the Hologic QDR 4500/A. Osteoporosis was defined as T score <-2.5 (BMD more than 2.5 SD below the manufacturer's sex-matched reference range for young adults). FN-BMD could not be measured in 73 subjects, usually because of bilateral hip prostheses. LS-BMD could not be measured in 15 subjects. In the remaining 1498 subjects a diagnosis of osteoporosis was made in 259 (17.3%) at both FN and LS, in 210 (14.0%) at FN alone, and 124 (8.3%) at LS alone. In 568 subjects (38%) the LS T score was lower than the FN T score. The table shows the proportion of individuals diagnosed as osteoporotic on the basis of each measurement.

brn61fur Valdimarsson Jon brvar Kristinsson. Leifur Franzson Gunnar Sigurdsson. Department of Medicine and Clinical Chemistry, Reykjavik Hospital, University of Iceland Objective: The aim of this study was to evaluate at which age peak bone mass is reached and assess possible anthropometric, nutritional and physical factors associated with peak bone mass. Study Group and Methods: A cross sectional study on a sample of 16, 18,20 and 25 years old women in Reykjavik, altogether 335 women. Bone mineral density (BMD), lean mass and fat mass were measured by DEXA. Physical activity and calcium intake were assessed by a questionnaire. Results: Maximal bone mass was reached for total skeleton, hip and forearm at the age of twenty years, BMD for the lumbar spine was 1% higher at the age of 25 than of 20 years (p>0.05). Physical activity was also a significant factor in a multivariate analysis in the 16-20 years group. Conclusions: Peak bone mass seems to be reached at the age of twenty for most of the skeleton. About 25-30% of BMD variability can be attributed to modifiable factors i.e. lean mass and physical activity.

P155 DIFFERENTIAL EFFECTS ON ULTRASOUND PROPERTIES OF BONE IN PRIMARY HYPERPARATHYROIDISM (PHPT) B.M. Ingle W.E.G. Thomas R. Eastell Division of Clinical Sciences (NGHT and CSUH), University of Sheffield, UK PHPT results in greater cortical than trabecular bone loss. In cortical bone, PHPT results in periosteal rather than endosteal resorption. Thus, ultrasound properties of bone (broadband ultrasound attenuation, BUA, and speed of sound, SOS) could be affected differently in PHPT. The aim of our study was to compare the effect of PHPT on ultrasound parameters with BMD at cortical (hand) and trabecular (lumbar spine) sites. We recruited 30 postmenopausal women diagnosed with primary hyperparathyroidism ages 50 to 76 years (mean 62) and 95 postmenopausal women from a population-based study ages 57 to 80 years (mean 67). Ultrasound (QUS) of the heel was measured using the Lunar Achilles (LA) and McCue CUBA Clinical (CC) and fingers using the IGEA DBM Sonic. Bone mineral density of the hand and spine were measured by DXA using the Hologic 1000/W. We used analysis of covariance to test for significant differences after adjusting for age and weight. The results are shown in the table below.

LA BUA, dB/MHz CC BUA, dB/MHz LA SOS, m/s CC SOS, m/s DBM SOS, m/s LA Stiffness Hand BMD, g/cm' LS BMD, g/cm'

PHPT, mean (SD)

Controls, mean (SD)

103 (10)** 54.7 (17)*** 1523 (34) 1617(36) 1954 (69) 75 (15) 0.31 (0.04)*** 0.85 (0.14)

108 (9) 63.9 (15.8) 1523 (33) 1616 (32) 1958 (78) 79 (14) 0.33 (0.03) 0.90 (0.14)

Age, years

n with osteoporosis

LS and FN %

FN alone %

LS alone %

40-50 50-60 60-70 70-80 >80

32 125 210 187 39

13 27 43 52 60

62 34 36 31 35

25 39 21 17 5

We conclude that the diagnosis of osteoporosis will be missed in a clinically significant proportion of individuals up to the age of 80 if only FN-BMD is used.

P157 DESPITE A DIFFERENT BONE MINERAL STORAGE PER UNIT MUSCLE

* ·P
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MASS; THE DETERMINATION OF RADIAL BONE, QUALITY BY FOREARM MUSCLE STRENGTH FOLLOWS THE SAME RELATIONSHIP IN MEN AND WOMEN AT ANY AGE H. Schiessl G. Tysarczvk-NiemeYer J. Willnecker. J.L. Ferretti CEMFoC, Natl. Univ. of RosariO, Argentina; Stratec Medizintechnik, Pforzheim, Germany Premenopausal women store more whole-body BMC (TBMC) per unit lean body mass (LBM) than girls or postmenopausal women, or males at any age do (Ferretti et al. Bone 22(6), 1998). In the distal radius, that material would be stored in mechanically little relevant places. This shoufd avoid any interference in the determination of bone mechanical quality by the regional muscle force (Frost etal. CTI62;1, 1998). To testthis hypothesis, we measured dynamometrically the maximal forearm-arm flexural moment (FM) and a bone Stress Strain Index (SSI, that accounts for the moment of inertia and volumetric BMD of the cortical section) in ultradistal and diaphyseal radial scans obtained by pQCT (XCT-960, Stratec, Germany) in normal males (42), premenopausal women (8) and postmenopausal women (9) aged 17-75 years. All the slopes and intercepts of the linear correlations between the ultradistal or diaphyseal SSI's (y) and the FM (r=0.94, R2=0.88; r=0.90, R2=0.81, p«0.001; FM range =2.5-12 kgm) were statistically similar, either for males only (y=23.5+6.7x; y=90.2+3.5x), or males plus premenopausal women (y=23.3+6.7x, y=108.4+3.3x), or the whole set of individuals (y=24.7 +6.8x; y=93.1 +3.4x). In addition to confirm that regional muscle force is the chief determinant of bone quality in the region (Frost et al. CTI 62:1,1998), results suggest that the surplus bone stored per unit muscle mass in premenopausal women does not affect the bone muscle interaction, hence keeping the same relationship between radial bone quality and FM in normal men and women. That shows the relative mechanical irrelevance of the "surplus" (supposedly normal) bone per unit muscle mass in women, which may derive from its inadequate location to reinforce the whole bone properties in the studied region, reflecting a differential effect of estrogen on the female skeleton. This would explain why the bone mechanostat does not deal with physiologically until menopause .

P158 MUSCLE CROSS SECTIONAL AREA AND BONE CROSS SECTIONAL AREA IN THE HUMAN LOWER LEG MEASURED WITH PERIPHERAL COMPUTED TOMOGRAPHY H. SchieBI G. Tysarczyk-Niemeyer J. Willnecker Stratec Medizintechnik, Pforzheim, Germany According to Frost's mechanostat theory bone strength is determined by peak muscle forces. Bone strength as determined with peripheral quantitative computed tomography (pQCT) correlates extremely well with maximum muscle Ibending strength in the human forearm ' . Body composition studies showed that lean mass is the best predictor of bone mass.' Correlation coefficients are in the range of 0.94-0.98. pQCT is able to determine the cross sectional area of bone as well as the cross sectional areas of fat and muscle. 60 subject (30 males and 30 females aged 6-78 years) were measured at the lower leg with a XCT 2000. The scan position was chosen at 66% of the tibia length proximal to the ankle joint. Cross sectional area of tibia and fibula were compared with the cross sectional area of the muscles in this section. In men the correlation coefficient between the cross sectional areas of bone and muscle in men is 0.96 irrespective of age. In women the correlation is only 0.5 and also independent of age The reason for the different response of bone to muscle is not yet understood and must be examined in further studies. pQCT is able to measure not only bone parameters but also geometrical distribution of muscle and fat tissue. Literature: [1]SchieBI H, Ferretti JL, Tysarczyk-Niemeyer G, Willnecker J, Noninvasive Bone Strength Index as Analyzed by Peripheral Quantitative Computed Tomography (pQCT). In: Pediatric Osteology. New Developments in Diagnostics and Therapy. E. SchOnau (Ed.) Elsevier, Amsterdam 1996;pp 147-160 [2] Zanchetta, JR, Plotkin H, Alvarez-Figueira ML Bone Mass in Children: Normative Values for the 2-20 Year - Old Population. Bone 1995;16 (Suppl): 393-399.

P159 THE EVALUATION OF DEXA METHOD IN DIAGNOSING ADVANCED OSTEOPOROSIS Witold Tlustochowicz Michal Szklarski Jerzy Przedlacki Malgorzata Konfederat-Kaczmarek. Central Clinical Hospital Military Medical Academy, Warsaw, Poland The aim of the study was to evaluate the DEXA method of measuring the lumbar spine and proximal femur in the diagnosis of advanced osteoporosis. A Lunar DPX-L device was used to examine 97 women with osteoporotic fractures of one or more vertebrae in the thoracic and lumbar regions - the diagnosis was confirmed radiologically. Patients with changes which could have affected the findings of a densitometric examination (except fractures) were excluded from the study. The densitometric criterion of recognition was set at T <-2.5 SD for osteoporosis and at T=-1 to -2.5 SD for osteopenia. Correct recognition of osteoporosis was confirmed in 77.3% of patients in the examinations of the lumbar spine, in 20.6% in the femur neck, in 66% in the Ward triangle and in 19.6% in the greater trochanter. The total interpretation of all measurements increased the sensitivity up to 90.7%. The highest correlation index (r=0.91) was observed between the BMD measurements of the femur neck and the greater trochanter of this bone; and between BMD of the femur neck and the Ward triangle (r=0.74) The correlation indices between BMD of the lumbar spine and the femur neck (r=0.38), the greater trochanter (r=0.35) orthe Ward triangle (r=0.23) were lower. Conclusions: In the diagnosis of advanced osteoporosis of the spine the most useful are the measurements of BMD of the lumbar spine, while measuring the hip can only supplement them. The final recognition of osteoporosis should be based on a full clinical diagnosis .

P160 THE SEXUAL DIFFERENCES OF FEMORAL GEOMETRIC MEASUREMENTS IN TURKISH POPULATION AND ITS RELATIONSHIP WITH HIP FRACTURES S. HepgOler C. OztOrk S. Eyigor M. Avtimur R Ak~it Ege University Hospital, Physical Therapy and Rehabilitation Department, Bornova, Izmir, TOrkiye This study was performed to find out the sexual differences of femoral geometry in 133 women and 53 men. We measured the hip axis length (the distance from blow the lateral aspect of the greater trochanter to the inner pelvic brim), the neck width and the neck/shaft angle on the dual Xray absorptiometry scan print-out. The mean values of hip axis length, neck width, neck length, neck/shaft angle in women were 5.1936 cm, 1.56 cm, 126.57 degrees respectively, and in men were 6.1575 cm, 1.80 cm, 130.54 degrees respectively. The results were analyzed using the independent t-test and showed that the hip axis length, the neck width and the neck/shaft angle were significantly longer in men (p<0.005). The bone mineral density measurements were greater in men compared with women (p
P161 QUANTITATIVE ULTRASOUND BONE MEASUREMENT AND DUAL X-RAY ABSORPTIOMETRY IN THE ASSESSMENT OF BONE DISEASE IN PATIENTS WITH TERMINAL CHRONIC RENAL FAILURE A. PENALOZA A. PERETZ M. MESQUITA M. DRATWA P. BERGMANN. Departments of Internal Medicine and Radioisotopes, CHU Brugmann, ULB, Brussels, Belgium Introduction. Qualitative ultrasounds (QUS) have been shown to predict bone mineral density (BMD) with accuracy and it has been suggested that QUS provide additional informations on bone structure. In chronic renal failure (CRF), bone disease is characterized by highly variable rates of remodeling according to the degree of hyperparathyroidism, and by variable osteoid accumulation. There are few data on QUS in CRF. Aims: To compare the results of dual X-ray absorptiometry (DXA) and QUS in patients with terminal CRF and to explore if the relationship between QUS and DXA differs according to the degree of hyperparathyroidism. Patients and methods: We investigated 54 patients with CRF, 34 on hemodialysis (HD) and 20 on peritoneal dialysis (PD), and 26 controls (C). BMD was measured at the lumbar spine (L) by DXA (Hologic QDR 1000) and QUS of the calcaneum was measured by Achilles (Lunar). Intact iPTH was measured by an immunoradiometric assay (N-Tac PTH, Incstar) (N: 10-55 pg/ml). Results: Sand BUA were significantly lower in HD (p214pg/ml, the slope was 54.0, r=0.54 Conclusion. The present results show that QUS could be useful in assessing bone disease in terminal CRF. The relationship between BMD and stiffness does not change according to the degree secondary hyperparathyroidism suggesting that in CRF, as in osteoporosis, QUS reflect essentially BMD. A limit of this study is that 2 different sites were measured for QUS (peripheral) and DXA (axial).

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P162 PREVALENCE OF OSTEOPOROSIS VARIES DEPENDING ON THE SITE OF BONE EVALUATED ACCORDING TO WHO CRITERION -JPOS STUDY M.lki*. S. Kagamimori**. Y. Kagawa*** T. Matsuzaki****. H. Yoneshima***** T. Akiba****** F. Marumo****** JPOS Study Group: *Kinki Univ School Med, Osaka-Sayama, Japan **Toyama Med Pharm Univ), ***Kagawa Nut Univ, * * * * Inst Comprehens Com Carel, * * * * *Kasukabe Shuuwa Hosp, * * * * * *Tokyo Med Dent Univ. Japanese Population-based OSteoporosis (JPOS) Study has been launched to determine reference values of bone mineral density (BMD) and biochemical markers of bone turnover in Japanese women and to clarify the factors affecting these indices. We established a criterion value of BMD for diagnosis of osteoporosis for Japanese women and clarified the prevalence of this disease. We randomly selected 50 women in each 5-year age group from 15 to 79 years for each of the 7 municipalities scattered over Japan resulting in 4550 subjects in total. The study comprised of bone mass measurements by DXA at the spine (L,..), hip (QDR4500A, Hologic) and distal forearm (pDXA, Norland/Stratec), measurements of biochemical markers of bone turnover, and structural interviews on medical history and lifestyle factors. 3985 women (87.6%) completed the study. Among them 519 were excluded from the analyses because they had past history or present involvement of diseases or administration of drugs which may affect bone metabolism. The rest 3466 women were served as the representative samples of Japanese women free from abnormalities affecting bone mass. We selected from them 1403 premenopausal women aged from 20 to 44 years who were the reference population giving the young adult mean (YAM) of BMD. YAM and SD [g/cm'] were calculated to be 1.031±D.190 for the spine, 0.801 ±D.1 06 for the femoral neck and 0.755±D.064 for distal 1/3 site of the radius, yielding the criterion values for osteoporosis (YAM2.5SD, WHO) to be 0.757, 0.536 and 0.596, respectively. The prevalence rates of osteoporosis in the 1523 women aged 50 years and over selected from our disease-free subjects were 37.6%, 11.5% and 56.6% according to the present cut-offs for the three different sites, respectively. This great discrepancy In the diagnosis is not acceptable. Using BMD of the radius, we may overestimate the prevalence. The diagnostic strategy, YAM-2.5SD as a cut-off, is difficult to apply to all the sites in Japanese women. A higher cut-off for the radius and somewhat lower one for the hip would be more relevant.

P163 ULTRASONIC ASSESSMENT OF TIBIA AND LINEAR GROWTH DURING CHILDHOOD AND ADOLESCENCE M. Kaga" K. Takahashi" H. Suzuki" T .Moriwake', H. Makin03, K. Yamamoto', Y. Seino' '0kayama University, Faculty of Education, 'Okayama University Medical School, Department of Pediatrics, 3Department of Medicine III, Okayama, 'Omron Institute of life science co., Kyoto, Japan [objective] To prevent osteoporosis in adulthood, the process of achieving bone mass is important. In this study, cortical bone acquisition during childhood and adolescence was investigated, and the relationship between linear growth was discussed. [Subjects &Method] One thousand six hundred and seventy nine healthy children and adolescents (862 males and 814 females, 7 to 19 years old) volunteered. Cortical bone of tibia was assessed by ultrasound velocity (SoundScan 2000, Myriad Ltd, Israel). [Results] SOS (speed of sound) of tibia increased dramatically around age 12 and 14 in females and males, respectively. These spurts were observed 1 year afterthe age of peak height velocity (Fig.1), then SOS increased continuously even after the linear growth of tibia completed (Fig.2). [Conclusion] To achieve ideal bone status in tibia, puberty is essentially important, however, careful observation is still required even in young adulthood. 4000 . . -_ _ _ _ _~

_

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1g

3800

3800

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37.5

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P164 BMD TOTAL OF THE WHOLE BODY SCAN - CORRELATIONS TO SUBREGIONAL PARAMETERS AND BMD TOTAL OF THE LUMBAR SPINE AND HIP H. Franck Center of Rheumatology, Oberammergau, Germany Bone loss in men and women seems to differ according to the skeletal regions or particular areas being evaluated. Dual energy X-ray absorptiometry (DXA) is the method of choice for measuring whole body (WB) and regional bone mineral area density (BMD). The aim of the study was to evaluate the importance of DXA measurements of WB in relation to lumbar spine and hip in different scan beam design. Methods: In 300 patients, age range 43 to 80, lumbar spine, hip, WB and regional BMD and soft tissue measurements were performed on all subjects in supine position. Results: All mid term precision areas of BMD total, right and left leg and pelvis, were below 2% with single beam (SB) and fan beam (FB), whereas precision areas of thoracic and lumbar spine varied depending on the scan mode being applied. In contrast, all mid term precision errors of soft tissue measurements were greater (2.6-11 %). All SB values of BMD and soft tissue measurement were significantly higher than FB values, except for BMD values of the head, thoracic spine and pelvis. Furthermore, BMD total of the WB scan correlated significantly (p<0.001) with all subregional parameters with best r-values (0.86-0.92) for the right and left leg in SB and FB design. In addition, there were excellent correlations (r>0.94, p
P165 CORTICOSTEROID OSTEOPOROSIS: QUANTITATIVE ULTRASOUND AND DXA MEASUREMENTS S. DAENS P. BERGMANN M.M. MORIS A. PERETZ Departments of Internal Medicine and Radioisotopes. ULB, Brussels, Belgium Introduction. There are radiological and histomorphometric evidences that bone loss due to corticosteroid (CS) treatment differs from that of postmenopausal osteoporosis with regards to bone structure. CS affect both horizontal and vertical trabeculae while horizontal trabeculae are primarily affected by estrogen deficiency. There are only few data on qualitative ultrasound (QUS) in CS induced osteoporosis Aim of the study. We examined if QUS are useful in the assessment of CS-bone loss and if the relationship between QUS and DXA in· patients with osteoporotic fractures, differed between patients with CS and without Patients and methods. We investigated 80 women with inflammatory rheumatic diseases treated chronically with CS (dose: 7.5-15 mg day, C+), 38 without CS (C-) and 101 controls (C). BMD of the lumbar spine was measured by DXA (Hologic, QDR 1000) and QUS at the calcaneum by an Achilles device (Lunar Corp). Results. Mean SOS, BUA stiffness and BMDL were significantly lower in C+ when compared to C- and C (p<0.001, ANOVA). C+ with fractures (n=43) were significantly different from C with fracture (n=49) for height (p=0.02), SOS (p=0.03) and stiffness (p=0.02). A significant correlation was observed between BML and stiffness in patients with osteoporotic fracture and CS (C+: slope=51, r=0.42, p
3700

3700

_

10

d~

+---r---'--''''''''~-+ : ij age(yr)

=

_

3400

+-_--.-_---._ _+ age (yr)

25

15

Fig.1. SOS and Height Velocity Fig.2. SOS and Length of Tibia in Females

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P166 IN SEARCH OF THE MOST INFORMATIVE SITE FOR HIP FRACTURE DISCRIMINATION: COMPARISON OF QUS MEASUREMENT AT THE PROXIMAL PHALANX, RADIUS AND TIBIA D. Hans"', A. Danieli', ~', T. Schwartz', C.F. Njeh', Y. Niv', ~', ~4, M. Weiss 5, P.J. Meunier' 'OARG, University of California, San Francisco, 'Sunlight Ultrasound Technologies LTD, Rehovot, Israel. 'CLlOS, Lyon France. 4Wolfson medical center, Israel, 5Asaf Harofe Medical center, Israel Lower Speed of Sound (SOS) values have been previously shown to be associated with a higher risk of hip fractures. Previous studies using the prototypes of the Sunlight Omnisense (Sunlight Ultrasound Technologies Ltd., Israel), a novel multi-site sonometer, have demonstrated that multisite measurement may be more informative in assessing hip fracture risk than a single-site measurement in the elderly patient. The purpose of the study is the evaluate the ability of the Omnisense using newer probes with newly defined scanning methodologies to discriminate between fractured and non fractured at the proximal phalanx, the radius and the tibia. Thirty subjects (mean age 77:t£J) with previous hip fractures and 55 controls without fractures (mean age 74:t£J) were included in the study. None of these women had any history of bone disease other than osteoporosis or treatment known to affect bone metabolism. Measurements are performed by scanning the selected skeletal site using a new small probe. The Omnisense records the SOS values obtained throughout the scan and the 95 percentile was used. Inter operator precision was calculated in a subgroup of patient. Discrimination of fractured versus controlled cases and area under the ROC curve (AUC) were assessed using logistic regression analysis (expressed as age- BMI adjusted odds ratios per standard deviation decrease with 95% confidence interval). * ns - non significant. Odds Ratios

P value

AUC

RMS Inter-CV

Phalanx Radius Tibia

0.01 0.03 0.3 ns*

0.85 0.84 0.78

1.0% 0.84% 0.55%

3.3 (1 3-8.7) 2.2 (1.1-4.6) 1.3 (0.8-2.1)

In conclusion: the results confirmed our previous studies in Omnisense ability to discriminate patients with hip fracture versus controls but the tibia site which was not yet investigated until now with this device. In addition, improvements were made in the scanning methodology, electronics and software allowing much better accuracy in the measurement leading to a good inter-operator precision.

Calcaneus Radius 1/3 Patella Spine Phalanx Capitate

OR (95% Confidence Interval) HF Cervical HF

Trochanteric HF

3.8 (2.3-6.1) 2.2 (1.1-4.1) 2.1 (1.2-3.7) 2.3 (1.1-5.0) 1.9 (1.2-2.9) 1.5 (1.0-2.2)

2.7 (1.7-4.2) 3.1 (1.3-7.2) 2.0 (1.2-3.2) 1-9 (1.0-3.6) 2.6 (1.6-4.2) 1.6 (1.0-2.4)

2.5 (1.7-37) 2.3 (1.3-3.7) 1.6 (1.0-2.4) 1.5 (1.0-2.3) 2.1 (1.3-3.2) non significant

In conclusion: the discriminative value of velocity parameter are influenced by the type of hip fracture at a different scale depending of the skeletal site measured. The prototype status of the device at the time measurements were conducted as well as the relatively small sample size should be considered when interpreting these results. Further investigations are still required.

P168 HIP FRACTURE DISCRIMINATION: A COMPARISON OF SEVEN ULTRASOUND DEVICES VERSUS DXA OF THE HIP. D. Hans", LLi'. B. Fan'. C.F. Njeh', Y He', C. Wu'. T. Fuerst', H.K. Genant' 'Osteoporosis and Arthritis Research Group, University of California, San Francisco, 'CLlOS, Lyon France Quantitative ultrasound (QUS) is now being accepted as a useful tool in the management of osteoporosis. In general terms, the commercial QUS devices introduced show a greater technological diversity than bone densitometry equipment. This may reflect astrength of QUS but it also represents a challenge for the validation process. The purpose of this study was to document the capabilities of each commercial bone QUS device with respect to osteoporotic fracture discrimination versus an established method (DXA). 34 women (mean age 73.6±8.7) who had sustained a hip fracture within the past two years and 34 age-matched controls (75.5:t£J.6) were recruited. BMD and Ultrasound measurements were acquired using QDR 4500 (Hologic, USA), Achilles-Plus (Lunar, USA) AOS 100 (Aloka, Japan). CubaClinical (McCue, UK), Sahara and UBA 575+ (Hologic, USA), the Soundscan 2000 (Myriad, Israel) and UBIS 3000 (OMS, France). Discrimination of fractured versus controlled cases were assessed using logistic regression analysis (expressed as age- and BMI-adjusted odds ratios per standard deviation decrease with 95% confidence interval).

P167 THE TYPE OF HIP FRACTURE INFLUENCES THE DISCRIMINATORY ABILITY OF SOS MEASURED AT MULTIPLE SKELETAL SITES D. Hans", ~', C.F. Njeh', C. Singal', B. Fan', P.J. Meunier', H.K. Genant' 'Osteoporosis and Arthritis Research Group, University of California, San Francisco, 'Sunlight Ultrasound Technologies LTD, Rehovot, Israel. 'CLlOS, Lyon France In an earlier age-adjusted multivariate analyses presented in Osaka 1997, we demonstrated that Speed of Sound (SO$) measured at different skeletal sites using a newly introduced Omnisense prototype (Sunlight, Ltd, Israel) discriminated hip fractures. However the influence of the type of fracture (cervical or trochanteric) has never been studied for the velocity at multiple sites. An average of 60 female subjects (mean age 79±8.9) with recent hip fractures (- 25 cervical and 27 trochanteric fractures) and 175 controls without fractures (mean age 70±8.7) were included in the study. SOS measurements at the calcaneus, distal radius, hand phalanges, capitate, patella and the posterior process of the lumbar spine were performed. Discrimination of fractured versus controlled cases were assessed using age and BMI-adjusted logistic regression analysis (Odds ratio: OR) associated with one standard deviation decrease in SOS .

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Site Neck BMD

Age- BMI-adjusted odds ratios (95% CI) 2.6 (1.3 - 5.1) Velocity (m/s) BUA (dB/MHz)

Achilles + AOS 100 Cuba Clinical Sahara Soundscan 2000 UBA 575+ UBIS 3000

2.5 (1.4 - 4.7) 2.5 (1.3 - 4.5) 2.1 (1.1 - 3.9) 2.3 (1.3 - 4.1) 1.6 (0.9 - 2.7) 2.9 (1.5 - 5.5) 2.8 (1.4 - 5.7)

2.7 (1.4 - 5.1) 2.4 (1 .3 - 4.5) 2.5 (1.2 - 5.1) 2.5 (1.4 - 4.5) Non applicable 2.5 (1.4 - 4.6) 3.4 (1.6 -7.1)

All ultrasound devices except the Soundscan 2000 gave similar, statistically significant results independent of the parameter used. The odds ratios for QUS were also similar to that for femoral neck BMD. Ultrasound velocity in the cortical bone of the tibia was not able to discriminate hip fracture in this study group. All heel QUS devices evaluated here showed similar clinical utility independent of the specific measurement technique.

P169 ULTRASOUND VELOCITY MEASURED AT THE PROXIMAL PHALANGES IN NODAL OSTEOARTHRITIS AND EROSIVE OSTEOARTHRITIS OF THE HANDS P. Monteforte G. Rovetta Institute E. Bruzzone, Rheumatological Center - DISEM, University of Genoa - USL 3 GE, Italy Erosive osteoarthritis (OAE) of the hands is a peculiar form of interphalangeal osteoarthritis (OA), characterized by acute inflammatory episodes with erosion and ankylosis especially in interphalangeal joints, although the trapezio-scaphoid area may also be interested. The radiologic changes are characterized by a combination of bone proliferation and erosive changes, apparent particularly in the central aspect of the joint. Despite to absence of periarticular osteoporosis, the bone changes in trabecular and cortical areas suggest the evaluation of a quantitative ultrasound (US) technique for measuring the bone density at the proximal phalanges of the hand in OAE patients compared with OA and non OA of the hand patients. The aims of the study were to evaluate the reproducibility of ultrasound of the hands (inter and intra - operator), the potentiality of ultrasound device to discriminate different groups (ROC analysis) and the comparison in US values of OAE, OA and non OA patients. A total of 60 post-menopause women (aged 63.8±3.2), 20 with OA, 20 with OAE and 20 without OA of the hands, and 8 pre-menopause women (aged 23.5±3.4) were studied. All of our subjects underwent US investigation of the second to fifth proximal phalanxes of the hand. The patients were measured by means of a DBM Sonic 1200 -Igea Italy, that is enable to evaluated US transmission velocity (AD-SoS) and US attenuation pattern (UBPS). The results documented a good intra and inter - operator reproducibility; a good potentiality of ultrasound device to discriminate different groups; a Significant statistical difference between the US values of OAE and OA and non OA patients. Our data indicate that this measurement is reproducible and sensitive to bone mass changes occurring in OAE patients.

P171 SPINE FRACTURE DISCRIMINATION BY IMAGING QUANTITATIVE ULTRASOUND MEASUREMENTS AT THE CALCANEUS H.B. Borgeskov" P.B. Andersen', N.H. Bjarnason', C. Hassager' 'Center for Clinical & Basic Research, Ballerup, Denmark. 'Center for Clinical & Basic Research, Aalborg, Denmark Quantitative ultrasound measurements of the calcaneus has recently been upgraded with imaging facilities. This has made measurements of a specific region of interest possible and improved the reproducibility of the method, but the diagnostic ability of imaging ultrasound has not yet been investigated thoroughly. We. measured Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS) by imaging ultrasound (DTU-one, Osteometer Meditech, Rodovre, Denmark) as well as bone mineral density of the lumbar spine (BMDspine) and total proximal femur (BMDhip) (both DEXA, Hologic 4500, Hologic Inc., MA, US) in 52 women and 22 men with a prevalent vertebral fracture (+ spine fx) and 52 women and 39 men without vertebral fractures (- spine fx), all of similar age, in a cross-sectional stud design. All participants were otherwise healthy and did not receive medication known to affect bone metabolism. The data are given in the table as mean±SEM in the 4 groups and P values are derived from Student's T-test.

P17D BONE MINERAL DENSITY MEASUREMENTS AT THE HAND: EXAMINATION OF A HEALTHY REFERENCE POPULATION F.E. ALENFELD E. DESSEL * M. BREZGER D. FELSENBERG University Hospital Benjamin Franklin, Free University Berlin, Germany *UCSF, San Francisco Bone mineral density (BMD) measurements at the hand are of particular interest in patients with diseases affecting the peripheral bones such as rheumatoid arthritis (RA). However reference values for BMD, measurements at the hand are still missing. Therefore the aim of the study was to compile a reference population for BMD hand scans. Furthermore periarticular subregions (subchondral and metacarpal) were analysed. These are of special interest in disease monitoring in patients with RA. A total population of 119 healthy caucasian women and 91 caucasian men aged 20-91 years was examined. Health status was assessed using a detailed questionnaire. Women and men with diseases known to influence bone metabolism were excluded from the reference population. The body mass index (BMI) was 19-29 kg/m'. In vivo preCision was assessed by repetitive hand scans in 5 healthy volunteers and expressed as standardized coefficient variation (CV) (according to Gluer et aI., Osteoporosis Int 1995,262-270). Short time in vivo precision was 0.9% for BMD measurements of the whole hand and 3% for subregion analyses. In females there was a significant correlation between nominal age and BMD values (whole hand scans and subregions) for patients older than 53 years (r=0.65, p<0.001) reflecting accelerated postmenopausal bone loss. The percentage bone loss was 15% between the age of 53 and 69 yrs in females older 53 yrs. No age dependency of BMD measurements could be shown for women younger than 53 yrs and healthy males. BMD measurements at the hand did not depend on anthropometric factors like body height, weight or BMI in both gender. In conclusion BMD measurements at the hand seem to be a sufficient method to monitor postmenopausal bone loss. At this point it remains unclear why BMD of the hand in men does not show an age dependency. We suspect that degenerative diseases at the hand such as Heberden arthrosis might lead to false high BMD values in the elderly. To prove this hypothesis additional X-rays of the hand are needed. Due to satisfying precision BMD measurements of the hand and its periarticular subregions might serve as a precise tool to monitor patients with bone diseases affecting predominantly the hands.

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BMDspine(g/cm')

BMDhip(g/crn')

43±1 49+ 1 <0.001

1538±2 1545±1 <0.001

0.87±O.02 0.94±O.02 0.05

0.79±O.03 0.85±O.02 0.07

52±2 56±1 0.04

1547±3 1553±2 0.08

1.01±O.06 1.06±O.03 0.4

0.90±O.04 0.99±O.03 0.07

BUA(db/Mhz) SOS(m/s) Women: + spine fx - spine fx P (difference) Men: + spine fx - spine fx P (difference)

The ultrasound parameters (BUA and SOS) separated (+ spine fx) and (spine fx) subjects better than DEXA (BMDspine and BMDhip) did for both adult men and women. We conclude that imaging ultrasound using DTU-one is promising as a fracture risk predictor and should be tested in a longitudinal study.

P172 ASSOCIATIONS BETWEEN BONE STATUS AND AGE IN OSTEOPOROTIC POSTMENOPAUSAL WOMEN FROM 30-80 ' N.H. Bjarnason" ~', S.R. Cummings', C. Christiansen ' for the MORE study group. -'CCBR, Ballerup, DK. 'Prev.ScLGroup, UCSF, US It has previously been shown that in BMDspine does not decrease with age in elderly women, whereas BMDhip seems to be more predictive of bone loss. The reason for this has been proposed to be non-bone degenerative changes in the spine. We therefore investigated BMD at baseline in the MORE (Multiple Outcome of Raloxifene Evaluation) study, since this population were selected to have low BMD and spinal X-rays assessable for digitizing, thus without significant degeneration although a diagnostic evaluation of osteoarthritis was not available. 7704 surgically or naturally postmenopausal, healthy women of different racial origin between 30 and 80 years, who did not receive bone active medication were included. 5063 of these women (substudy I) had a BMD T-score below -2.5, the remaining 2641 women (substudy II) had in addition at least one moderate or two mild vertebral fractures (fx). BMD at all sites were significantly lower in substudy II than in substudy I. Although the women in substudy II (68.53±6.48yr) were older than women in substudy I (65.38±7.11yr), correction for age did not change this. The association between BMD and age were significantly positive in the lumbar spine, whereas these associations were negative for all other sites. In the hip and total body the slope of the regression lines in substudy II were twice the slope in substudy I, indicating a greater decline with age in this population with vertebral fx (significant for BMDneck). Substudy I mean±std

slope

BMDspine BMDarm BMDneck BMDtotal

+0.0017 *** -0.0042 ** * -0.0012 *** -0.0009 * *

0.81±O.13 o55±O.08 0.61±O.07 0.90±O.08

SOS

BMDarm

BMDhip

Fx-group Fall-group P (for difference)

-0.481 +0.161 <0.051

-0.701 -0.061 <0.0011

-0.651 +0.081 <0.051

-0.66 +0.13 <0.001

All parameters were significantly lower in the fx-group compared with the fall-group. None of the parameters in the fall group deviated significantly from expected normal age matched values. Neither BMDarm nor BMDhip separated the fx-group and the fall-group significantly better than ultrasound (RUA or SOS) did. We conclude that imaging ultrasound using DTU-one (BUA or SOS) separates age-matched hip fracture and non-fracture fall-patients as well as BMD measurements do.

P174 INTERNATIONAL REFERENCE DATA RANGES FOR THE SAHARA CLINICAL BONE SONOMETER P. Steiger ' , E. von Stetten" K.E. Wilson" ~', D. Schoenfeld',

Substudy II mean±std slope 0.78±O.15 0.53±O.09 0.59±O.08 0.88I±O.09

BUA

+0.0016 *** -0.0049 *** -0.0026 ** * -0.0019 ***

Mean:g/cm'; Slope:g/cm'/yr; BMDtotal: total body BMD. * *:p<0.01; * **:p<0.001 for a slope different from zero. We found weak but Significant associations between bone markers and BMD at all sites in this cohort of osteoporotic women (For example: UCTXlCr.: r=-0.11- -0.27; S-osteocalcin: r=-0.10- -0.28; p
P173 HIP FRACTURE DISCRIMINATION BY IMAGING QUANTITATIVE ULTRASOUND MEASUREMENTS AT THE CALCANEUS S.H. Prins" J. Lauritzen', H.L. J0rgenSen" L. Rprdam 3, C. Hassager' 'Center for Clinical & Basic Research, Ballerup, Denmark; 'Department of Orthopaedic Surgery, Bispebjerg University Hospital, Copenhagen, Denmark 3Department of Clinical Physiology, Bispebjerg University Hospital, Copenhagen, Denmark Quantitative ultrasound measurement of the os calcis has recently been upgraded with imaging facilities. This has made measurements of a specific region of interest possible and improved the reproducibility of the method, but the diagnostic ability of imaging ultrasound has not yet been investigated thoroughly. We measured Broadband Ultrasound Attenuation (BUA) and Speed Of Sound (SOS) by imaging ultrasound (DTU-one, Osteometer Meditech, Rcdovre, Denmark) as well as forearm bone mineral density (BMDarm) by DEXA in 3 age matched groups of women: 1) 25 women, who were admitted to hospital due to a hip fracture (fx-group); 2) 23 women, who were admitted to hospital due to a fall without any fracture (fall-group); and 3) 26 normal women. Furthermore BMD of the hip (BMDhip) was measured in a subgroup ofthe fx-group and the fall-group. All measurements were performed during the index hospitalisation in order to avoid any influence from bone loss due to immobilization after the fracture. The data are given in the table below as SD's from expected age matched normal values (Z-scores).

•

J.A....Silln1

'Hologic, Inc., Waltham, MA, USA, 'Boston Biostatistics, Inc., Framingham, MA US Reference ranges are critical to the clinical use of any diagnostic instrument, and are particularly important for heel ultrasound systems due to the growing international acceptance of ultrasound and the potential for widespread use in the general clinical community. This multi-center international study was designed to acquire extensive heel ultrasound reference data for female subjects from a number of different countries, and to test the sensitivity of the results to inclusion/exclusion criteria and analysis methods. Heel ultrasound measurements were obtained for caucasian female subjects recruited in 8 countries using the Hologic Sahara Clinical Bone Sonometer. For each country, the study was designed to be large enough for a statistically significant assessment of the effects of inclusion/exclusion criteria and analysis methods, and to minimize the possibility of geographic or recruitment bias. Biographical data and information regarding medications and disease conditions that may affect bone metabolism were obtained from each subject. Data was analyzed with a number of different statistical models, and the effect of inclusion/exclusion criteria was assessed. Sahara ultrasound parameters were found to decline with age, and the age dependence was best described by decade specific mean values. Linear and polynomial fits were found to deviate significantly from the decade means. Population SD values for all parameters varied only minimally with age. While results for subjects with specific conditions or medications deviated from those for the entire population, the net effect of including subjects with all conditions and medications was found to be negligibly small. In conclusion, Sahara reference ranges were generated for caucasian females from 8 countries. Inclusion of subjects with conditions or on therapies which could affect bone metabolisrn had an insignificant effect on results. Final reference ranges were based on all subjects enrolled, and apply to the caucasian female population of each country as a whole.

P175 QUANTITATIVE ULTRASOUND (QUS): SCREENING METHOD FOR DIAGNOSIS OF OSTEOPOROSIS AND RISK OF FRACTURE DEVELOPMENT E.E. Volkov S.S. Rodionova. M.A. Makarov Central Institute of Traumatology and Orthopaedics, Moscow, Russia The purpose of the study was the forming of osteoporosis (OP) development risk groups using screening QUS (Sound Scan 2000, Myriad Ultrasound Systems Ltd). T-scale was used for comparison with norm. Results of the measurements were assessed by age groups. Osteopenia was diagnosed in 40% of women (age group under 30) and 40% of men (age group 41-50 years). In woman from older age- groups the number of patients with osteopenia decreased from 37% at the age of 50 up to 13.3% at the age of 60 and up to 6.2% at 80 years, but the number of patients with osteoporosis increased by 7.5%, 13.3% and 50%, respectively. At the age group of 70 years the increase in number of patients with osteopenia (36.1 %) was accounted for the patients with normal cortical bone density at the young ages. Number of such patients decreased from 40% at 30 years to 37% at the age of 50, up to 21% at 70 years. In men the number of patients with osteopenia decreased from 40% at the age of 70 to 25% at the age group of 80 years. The number of patients with osteoporosis increased in the same age period from 6% to 56.2%. To form osteoporosis risk groups the examination of women from 30 years and men over 50 years is required. The cortical bone loss in men takes place at the older age then in women. This can explain the lower frequency of fractures in men under 70. With age number of women with OP increases at the account mainly for persons who at the younger ages suffered from osteopenia, less from osteoporosis.

P176 EVALUATION OF THE PRECISION OF A NEW SCANNING-DRY ULTRASOUND DEVICE QUS-2 S. Cheng M. Lian L. Wang B. Fan T. Fuerst C. Njeh H. Genant Osteoporosis and Arthritis Research group, University of California, San Francisco, USA The purpose of the study was to establish the short-term and long-term measurement precision of a new scanning-dry ultrasound device - the QUS-2 (Metra Biosystems Inc., USA). The BUA (dB/MHz) results of the right heel were compared with BUA and Stiffness (Achilles+, Lunar Corp., USA). Factors that might affect the QUS-2 results were also evaluated. 118 healthy Caucasian females, aged 20 to 79 years (47.7±16.3), participated in the short-term precision study on both ultrasound devices. 15 healthy male and female volunteers aged 29-54 (38.9±8.2) participated in the long-term precision study (weekly measurements for 10 weeks). Among these 133 subjects, various sub-groups were studied to investigate different measurement set-ups (QUS-2 on the floor and on a 25 cm high suitcase, n=30) and inter operator differences (n=13). The short-term precision was calculated from duplicate measurements at the same day with repositioning. The results were expressed by the percent coefficient of variation (CV,%) and standardized CV (SCV,) where SCV,=CV,(4*SD po / Mean pop )' The long-term precision (CV L) was expressed as a percentage of the coefficient of variation (the root mean squared standard error of the estimate divided by mean). The mean values and precision are given in the following table. Mean

SD

CV,

SCV,

CVL

CVop ,

CVop ,

BUAQ"s.,

84.0 117.7 95.3

15.3 14.8 18.7

1.27 1.83 1.84

1.75 3.65 2.35

2.46

1.54

BUAAcllilles+ STAchilles+

1.59

There were no significant differences between the two measurement setups (r=0.96, p=0.662 paired t-test) and between the two operators (r=0.99, p=0.422 paired t-test). The correlation between QUS-2 and Achilles+ was 0.72. The results indicate that QUS-2 has a good precision compared to the Achilles+. The clinical utility of the QUS-2 for fracture risk assessment and monitoring needs further investigation.

P177 THE DIAGNOSTIC SENSITIVITY OF QUANTITATIVE ULTRASOUND USING AN IMAGING SCANNER B. Fan C.F. Njeh D. Hans Y. He E. Tsuda, J. Li T Fuerst. H.K. Genant Osteoporosis and Arthritis Research Group, University of California, San FranCiSCO, USA Recently, a new imaging quantitative ultrasound (QUS) scanner has been developed that is capable of changing the region of interest. The algorithms used in calculating BUA are different and also phase velocity is calculated instead of group velocity as reported in previous QUS scanners. Retrospectively, we assessed the diagnostic sensitivity of this approach to QUS assessment of bone. Thirty-four women (mean age 73.6±8.7) who had sustained hip fractures within the past two years, and 34 age-matched controls (75.5±5.6) were recruited. Ultrasound measurements (SOS, BUA) and BMD were acquired using UBIS 3000 (DMS, France) and QDR 4500 (Hologic, USA). BUA was standardized (BUA_M) to the range as other water based systems. Short term precision for UBIS was assessed by duplicate measurements on the fracture and control groups. The CV(%), RMSCV(%) and standardized precision error (SCV) were expressed as the mean of standard deviation divided by the mean, root rnean square standard deviation divided by the mean and CV divided by annual change respectively. The associations between measurement values and fracture status was calculated by logistic regression analysis and expressed as odds ratios (OR).

SOS BUA BUA_M BMD-Total BMD-Neck

CV(%)

RMSCV

SCV

OR

0.24 1.73 0.57 0.7-1.2 0.9-1.9

0.30 2.67 0.88 N/A N/A

4.0 1.9 1.6 1.3-2.2 0.9-1.9

3.0(1.5-5.9) 3.9(1.8-8.3) 4.2(1.9-9.4) 2.0(1.2-3.4) 2.6(1.3-5.5)

The SCV of BUA is similar to that reported for BMD of the neck and better than previously reported for other QUS devices. Using a BUA cut-off of 61 dB/MHz resulted in a sensitivity and specificity of 80% and 58% respectively. Similarly a cut-off of 1500 m/s gave a diagnostic sensitivity and specificity of 75% and 54% respectively. It is apparent from the above that the new Imaging QUS devices are highly precise and have a good diagnostic sensitivity similar to BMD of the neck for hip fracture prediction.

P178 COMPARISON OF BMD, STRUCTURAL PROPERTIES AND FRACTURE LOAD IN VERTEBRAL BODIES BASED ON QCT DATA AND HR-CT IMAGES R. Andresen M.A. Haidekker H.J. Werner H-O. Peitgen D. Banzer Purpose: To introduce different non-invasive techniques for the assessment of the individual fracture risk in osteoporosis and to show the correspondence between structural properties of HR-CT images of vertebral bodies, their bone mineral density (BMD) and the fracture load. Materials and Methods: In 21 vertebral bodies with non- and different degree of osteoporosis, BMD was determined separately in spongiosa and corticalis (SE-QCT/85kV). Structural data was acquired with HR-CTapplying the following methods: Fractal dimension in dependency of the binarization threshold (spongiosa), maximum number of clusters with BMD below avariable threshold (corticalis). After performing the CT rneasurements, the vertebrae were excised and compressed until fractured. Single parameters and weighted sums of these parameters were correlated with the fracture load. Results: The fracture load (healthy: 2602-5802, average 3533 N; osteoporotic: 1240-2490, average 1683 N) correlated with single parameters as follows: spongiosa BMD (healthy: 101.8-135.3, average 114.4 mg/ml, osteoporotic: 34.8-57.6, average 46.4 mg/ml; r,=0.81), cortical BMD (healthy: 216.4-361.9, average 289.6 mg/ml; osteoporotic: 142.5-215.2, average 173.5 mg/ml; r,=0.82), spongiosa structure (healthy: 0.32-0.75, average 0.5, osteoporotic: 0.87-1.22, average 1.05; r3=0.72) and cortical structure (healthy: 55-104, average 80; osteoporotic: 102-159, average 135; r4=-0.86). The weighted sum of cortical and spongiosa BMD resulted in r, ,=0.85, of cortical and spongiosa structure in r3,=0.86, aweighted cornbination of all four parameters correlates with the fracture load at r,., 3.4=0.88 and p<0.0001 in all cases. Conclusion: All individual parameters allowed the discrimination between healthy and osteoporotic subjects. The high correlation of the cortical BMD and the structural parameter in the corticalis indicates the important contribution of the cortical shell to the vertebral stability. A weighted sum of multiple parameters results in a higher accordance with the fracture load and is best suited to estimate the individual fracture risk .

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P179 CHANGES IN BONE MINERAL DENSITY AROUND CEMENTLESS HIP PROSTHESIS WITH PROXIMAL HYDROXYAPATITE COATING M. Talalaj P. Kapuscinski W. Ozonek A. Wielopolski. P. Marcinowski E. Marcinowska Department of Internal Medicine and Department of Orthopedic Surgery, Postgraduate Medical Education Centre, Warsaw, Poland Within 7-10 years following the operation the stems of hip prostheses fixed with cement become loose in 20% of patients. The purpose of the study was to determine, by means of DXA, changes in bone mineral density (BMD), around the stems of cementless, hydroxyapatite coated prostheses. Forty four patients (20 women, 24 men) aged 22-71 years, have been examined prospectively for at least 12 months. Thirty two of them (13 women, 19 men) completed 2-year observation period. DXA scans were performed within 3 weeks after the operation and then after 3, 6, 12, 24 months following the procedure. BMD was determined in both standard and Gruen zones. BMD of the lumbar spine and of the opposite proximal femur were measured every 6 months determined to eliminate the influence of BMD changes of the total skeleton as well as biochemical markers of bone turnover. It was found that within the first 3 months following the operation patients after total hip arthroplasty showed the decrease in BMD by 2 15%. During the next months BMD was raising gradually and after two years approached the baseline values with exception of upper medial part of the femur where progressive reduction in BMD was observed. The decrease in BMD was significantly more pronounced in women than in men, in patients with higher bone turnover, and was independent of the changes in BMD in other parts of the skeleton.

P18l COMPARISON OF IN VIVO AND IN VITRO EXAMINATIONS OF PHALANGES OF HUMAN CADAVERS USING ULTRASONOMETRY Chr. Wuster* St. Becker* P. Heilmann* F. de Terlizzi* R. Cadossi* R. Ziegler* Int.Med., Univ Heidelberg, **IGEA, Italy, ***Univ Modena Quantitative Ultrasonometry (QUS) is widely used to determine future osteoporosis fracture risk in postmenopausal women and elderly men as there is equal amount of prospective clinical data for ultrasound as there is for the radiological devices. However the inter observer variance using the system measuring the amplitude dependent speed of sound (adSOS) at the phalanges (DBM Sonic 1200, IGEA, Carpi, Italy) needs to be improved. We therefore conducted a study in 26 human cadavers (14 females, 12 men) with a mean age of 82 years in females and 76 yrs in males. We measured adSOS in vivo at phalanges II-V of both hands and the same again in a water bath after removal of soft tissue. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) (Hologic QDR 1000) was measured of the phalanges, the lumbar vertebra L3 and hips of each cadaver. There was a highly significant positive linear correlation between adSOS and BMD of the phalanges in vitro (r=0.658) and in vivo (r=0.617). There was no significant correlation between adSOS or DXA of the phalanges and BMD of L3 nor the hips. Ultrasound measurements of the phalanges in vitro at different rotational angles showed best results at horizontal direction and 90°, but not at 45° and 135°. Correlation coefficients (r') were 0.64, 0.54, 0.37 and 0.52 respectively. There was no correlation between 0° and 45° except at the middle finger probably due the particular shape of the small phalanges. This study shows that ultrasound measurements at the phalanges are highly independent of soft tissue. The high correlations between QUS and DXA at the phalanges indicate that BMD has a major influence on QUS measurements. However the rotational differences might be explained by the influence of structural properties of the bones on QUS and might be responsible for the lower interobserver precision in vivo. Future studies should investigate the influence of structural components as measured by ~QCT and biomechanical testing on QUS.

P180 ULTRASONOGRAPHY AT THE PHALANXES: ANALYSIS OF A 10677 EUROPEAN WOMAN DATABASE. Chr. Wuster R. Cadossi', S. Battista 3, R. Isani 3 'DCPL of Internal Medicine I, Endocrinology and Metabolism, University of Heidelberg, Germany, ' Dept. of Medical, Radiological and Oncological Sciences, University of Modena, Italy, 3 IGEA, Carpi, Italy The use of ultrasound (US) at the phalanxes of the hand to assess bone quality has been investigated by a number of researchers all over Europe. The results of ultrasonography measurements at the phalanxes performed on 10677 women have been used to create a large database. Subjects' age ranged from 2 months to 100 years: 978 subjects up to 18 years, 3316 in premenopause, 6383 in postmenopause. 495 women had documented osteoporotic fracture. All subjects had been measured by DBM-Sonic 1200 (IGEA, Italy), two parameters had been recorded: Amplitude Dependent Speed of Sound (ADSoS, m/sec) and Ultrasound Bone Profile Score (UBPS, units from 1 to 100). The figure shows the age related changes of AD-SoS, in non fractured subjects.

.

..

.

P182 PREDICTION OF FRACTURE FROM BONE MINERAL DENSITY

I~~----------------------------------

lao

Both ultrasonography parameters, AD-SoS and UBPS, discriminate between age matched fractured (495) and non-fractured (266) subjects: p
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MEASUREMENTS OVERESTIMATES RISK O. Johnell J.A. Kanis A. Oden B. Jonsson A. Dawson Centre for Metabolic Bone Diseases, Sheffield, UK There is a well established relationship between bone mineral density (BMD) and fracture risk. The present study examined the long-term predictive value of BMD assessments. Estimates of the relative risk of fracture from BMD are mainly derived from short-term studies where the correlation between BMD at assessment and BMD in later life range from 0.8 to 0.9. Since individuals lose bone at different rates throughout life the correlation coefficient decreases progressively with time. Thus, low values for BMD overestimate long-term fracture risk. The paper examines and formalises the relationship between current BMD, time and correlation coefficients and long-term risk. The loss of predictive value has important implications for early screening and support the view that assessment and interventions are best targetted in later life.

P183 COMPARATIVE PRECISION OF HIP BMD MEASUREMENTS WITH A MOBILE AND A STATIONARY BONE DENSITOMETER J.P. Devoaelaer TC. Le Thi D. Dienst. G. Depresseux Department of Rheumatology, St-Luc University Hospital, Brussels, Belgium For epidemiological studies, it is more appropriate to use mobile densitometers in order to approach patients who would otherwise not undergo bone mass measurements. A mobile densitometer could, however, be less precise than a stationary one. We have, therefore, compared the precision (CV) of 2 DXA's from Hologic Inc, a mobile QDR-4500 and a stationary QDR 2000+, by measuring the hip BMDs of elderly patients twice after careful repositioning (array mode). 42 females aged 83.5±1.1 (SEM) living in nursing homes were measured on a QDR-4500, and 57 fully ambulatory, outpatients aged 76.5±1.0 on a QDR 2000+. Their total hip BMDs were .586(.015) and .603 (.011) g/cm2, respectively. The CVs (mean±SEM) are given in the table.

QDR 4500 F. neck Troch Intertroch Total hip Ward QDR 2000+ F neck Troch Intertroch Total hip Ward

Predominant hip

Non predominant hip

1.54 1.54 1.44 .90 4.48

(.26) (.22) (.18) (10) (.88)

1.83 1.40 1.54 1.00 3.85

(.23) (.20) (.22) (.20) (.65)

1.60 1.15 1.19 .70 4.60

(.18) (.15) (.12) (.10) (.15)

1.80 1.39 1.51 1.1 6.68

(.23) (.19) (.20) (.20) (.33)

In conclusion, the reproducibility of the DXA measurements of the hip BMDs in elderly people is excellent with both instruments. The mobile DXA possesses a similar precision when compared to the stationary DXA. The use of a mobile bone densitometer can, therefore, be recommended for longitudinal studies of hip bone mass measurements.

P184 DXA PARAMETERS RELATED TO INTERNAL REFERENCE SYSTEM AS PREDICTORS OF IN VIVO VARIABILITY OF BMD MEASUREMENT FROM A STUDY ON 3808 PATIENTS INVOLVING 75 CENTERS D.O. Siosman N. Milsztajn C. Perron P. Meunier* J.-Y. Reginster!i, I. Tupinon° Division of Nuclear Medicine, Geneva University Hospital, CH, *Hopital Edouard Herriot, Lyon, FR, °I.R.l.S., Courbevoie, FR; §CHU, Liege, B, and Georgetown Univ. Medical Centre, Washington DC, USA Introduction: The concept of DXA relies on the calculation of the ratio of the attenuation coefficients for soft tissue at low/high energies (Rs). Hologic Inc introduced an internal reference system (IRS) aiming at reduCing impact of environmental fluctuations, thus improving reproducibility. IRS 'relies' on the calculation of two parameters k and dO. Thus, we evaluate the capability of these parameters to predict the in vivo variability of BMD measurement. Methods: The prospective randomized double-blind study (FIRST) on the effect of the Strontium Ranelate is multicentric and involves 75 centers. To date, it includes 3808 women (age: 74.1+7.0 yr.; femoral neck T-score: -2.5+ 1.2). Pairs of measurement of BMD lumbar spine (LS) and of both BMD femoral neck (FN) were performed with Hologic DXA apparatus (mean interval: 10.1 days). Coefficients of variation (%CV) were calculated and correlated to z-score values of k ordO by polynomial regression. Results: %CVs were 1.37% (95%CI: 1.33-1.41%) for BMD-LS and 1.6% (95%CI: 1.56-1.63%) for BMD-FN; there was no significant difference between type of apparatus (QDR's 1000,2000 and 4500) as well as between center. The parameters k and dO were significantly different between type of apparatus (p
P185 THE BLAND AND ALTMAN METHOD ADAPTED TO QUALITY CONTROL OF DUAL-ENERGY X-RAY ABSORPTIOMETRY D.O. Siosman, I. Alekxandrova J. Billet S. Allaoua J. Lemmon', P. Meunier* J.-Y. Reainster!i, D. Provvedinio Geneva University Hospital, 1211 Geneva 14, Switzerland. Geneva University Hospital, CH; 'Sir Charles Gairdner Hospital, Perth, Australia; *Hopital Edouard Herriot, Lyon, FR; °I.R.I.S., Courbevoie, FR; §CHU, Liege, B, and Georgetown Univ. Medical Centre, Washington DC. USA Introduction: Daily quality control (QC) is needed to warrant good medical practice. Accurate identification of DXA dysfunction remain an issue. We evaluated the efficiency of a novel statistical approach adapted from Bland and Altman method (The Lancet, 8: 307 -310,1986) for daily quality control. Methods: QC of 35 DXA machines (QDR-l 000, QDR-2000, QDR-4500, Hologic, Inc.) was monitored over a period of nine months by measuring daily a dedicated spine phantom (the average number of scans was 200 per instrument). These spine phantom BMD measurements were analysed on a daily basis using 3 QC procedures: Shewhart rules, Cusum charts and adapted Bland and Altman. The adapted Bland and Altman method enables to identify changes between daily BMD and previous measurements. DXA dysfunctions were identified in reference to technical intervention reports. When they were associated to "alarms" - warning of the QC procedures, these events were considered as True Positive, on the contrary, they were considered as False Negative. The efficiency of these procedures was evaluated by comparing sensitivity and specificity of detection of the predefined "alarms". Results: The sensitivity was 0.13 for the Shewhart rules, 0.24 for the Cusum charts and 0.41 for the Bland and Altman approach (with a standard deviation of 2.9). The specificity was 0.86, 0.46 and 0.83, respectively. The Bland and Altman approach has the best specificity when compared to the Cusum charts and the highest sensitivity over both the Shewhart and the Cusum methods. Conclusions: These results suggest that the adapted Bland and Altman approach could be the most effective method for the longitudinal monitoring of DXA instrument stability in private practice as well as in multicenter studies.

P186 GENEVA QUALITY ASSESSMENT PROGRAM (GEQAP): A PROPOSAL FOR A CENTRALIZED QUALITY CONTROL ASSESSMENT OF DXA J. Billet *B. Uebelhart. J. Alexandrova N. Milsztajn *R. Rizzoli, D.O. Siosman Geneva University Hospital, 1211 Geneva 14, Switzerland. Division of Nuclear Medicine and * Division of Bone Diseases, Geneva University Hospital, Switzerland Introduction: BMD measurements with dual energy X-ray absorptiometry (DXA) in clinical setting depend on the quality control of the instrument. The specialized bone disease consultation observed that 87% of the patients referred were due to inappropriate DXA measurements and 45% a misreading of the DXA exam. Because of the multi-factorial aspect of DXA QC, a dedicated data processing tool has been developed to implement the entire QC process. Methods: The GEQAP is based on a concept of global QC involving both apparatus and in vivo measurements. A mUltiple-step process was designed and computed. It uses a database application developed with MSAccess® (for information storage purposes) and automated procedures developed with MSExcel® (to execute the QC protocol). Results: This sequential pathway allows: 1) to store characteristics of DXA apparatus, 2) to store in vitro data of daily QC, 3) to store patient's bibliography, technical parameters and results of in vivo analysis, 4) to attribute qualitative graduations of performance, 5) to control technical adequacy of apparatus, acquisition and analysis as well as patient data coherence with numerical tests, 6) to perform multiple automated methods for daily evaluation of QC in the search for detection of drifts or failures and 7) to normalise (correct) the in vivo data by a cross-calibration procedure. Conclusions: This global quality control concept could become a prerequisite to an adequate use of DXA in clinical private practice as it becomes a rule for medical laboratories. Part of this pathway can be centralized and shared between professional structures.

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P187 CALCANEUS QUS MEASURED BY SAHARA: DETERMINATION OF T SCORE AND REFERENCE VALUES IN A SWISS POPULATION D.O. Siosman° D. Thiebaud', K. Lippuner", S. Allaouao F. LuzuyO, M.A. Krieg', Ph. Jaeger@, R. Rizzoli* Division of Nuclear Medicine and *Division of Bone Diseases, Geneva University Hospital, 'Department of Internal Medicine, CHUV. Lausanne, @Policlinique of Medicine, Inselspital, Bern, Switzerland Introduction: Calcaneus quantitative ultrasonic (QUS) measurement has been shown to predict the risk of fracture. A new system that enables this measurement without the need of a temperature-controlled waterbath has been developed. In addition, several recent reports suggestthat one should not rely on reference value provided by the manufacturer without validation. Therefore, we proposed to determine T-score and reference values as a function of age in a swiss female population. Methods: Thus, 335 healthy normal subjects were recruited in this multicentric study. Non-dominant calcaneus was measured with. Sahara QUS (Hologic Inc.). A subset of 78 women with age ranging between 20 and 35 years was selected in order to constitute the "Peak Bone Mass" group, and, among them, 29 had also a DXA measurement (QDR 4500, Hologic Inc). Results: Cubic regression fitted best the population studied and the calculated SO were 16.7 for QUI, 13.9 for BUA and 28.4 for SOS. T-score could be defined in using the following values (mean±sd): 99.3±16.0 for QUI, 69.9±11.7 for BUA and 1565.0±29.5 for SOS. Finally, the average Tscore for spine and hip BMD were respectively -0.1 ±1.2 and 0.0±1.1, enabling to validate the population used to define QUS T-score. Conclusions: Our multi-centric study provides the reference values needed for proper clinical use and warrant good homogeneity of the results throughout the country.

P189 SHORT-TERM PRECISION OF QUANTITATIVE ULTRASOUNO DEVICES IN A POPULATION OF ELDERLY AMBULATORY WOMEN E. Bovard, M.A. Krieg, J. Cornuz P. Burckhardt University Hospital, Lausanne, Switzerland and the SEMOF study group. Background: Precision is a crucial issue for assessing the response to treatment of osteoporosis. Compared to pQCT and DXA, bone ultrasound (BU) is known to be less precise in middle-age subjects (50-60 yrs). Precision of BU in elderlies has not yet been well studied. Methods: 489 women, aged 76±3 yrs, had BU of their calcaneus (Achilles, Lunar and Sahara, Hologic) and of their phalanges (DBM Sonic 1200, IGEA). To assess short-term precision, women had duplicate measures by the same operator (132 with Achilles, 82 with Sahara, 163 with DBM Sonic). The precision parameters (based on root-mean-square averages) were calculated according to GIOer et al. (Osteoporosis Int 1995;5:262-270) Results: The table shows the standard deviation (SO), precision error (PE), annual change (AC), and standardized precision error (SPE).

P188 COMPARISON OF THE NECK SHAFT ANGLE IN OSTEOPOROTIC PATIENTS WITH AND WITHOUT FEMORAL NECK FRACTURE N. Malavolta M. Veronesi S. Gnudi* Divisione di Medicina Interna, Universita degli Studi di Bologna, Istituti Ortopedici Rizzoli, *Bologna Structural parameters such as femoral neck length (FNL) and neck shaft angle (NSA) are theoretically important for the mechanical resistance to load of this skeleton site. To evaluate if the NSA is different in patients with and without osteoporotic femoral neck fractures, we studied 107 women diagnosed as osteoporotic and classified in two groups according to the presence of vertebral fractures (group 1:43 women) or of femoral neck fractures (group 2:64 women). The two groups were similar for age, period of menopause, weight and height. All enrolled subjects underwent bone mineral density (BMD) measurement by dual Xray absorptiometry of L2L3-L4 and of the safe femoral neck; moreover length, diameter of femoral neck and NSA were taken. Results are shown in table: Group 1:43 pts

Group 2:64 pts

Student T Test

Vert.BMD (mg/cm') Fe. neck BMD (mg/cm') FNL(cm) FND(cm) NSA(degrees)

723.69±125.48

764.38±173.53

N.S.

621.02±106.26

587.12±90.17

N.S.

10.8±O.59 3.34±O.25 122.04±4.85

11.06±O.81 3.35±O.28 126.52±5.66

N.S. N.S. 0.0001

As expected we did not observe any difference between the two groups for bone density. The length and the diameter of femoral neck (FND) were not statistically different in patients of the two groups. NSA was significantly more valgus in the osteoporotic group with fracture of femoral neck than in the group with vertebral fracture. Since the NS on planar projection depends not only on femoral neck rotation but also on femoral antiversion, we cannot exclude that the difference observed between the two groups of patients can be the consequence of a different femoral antiversion. If this is the case the greater antiversion of the patients with femoral neck fracture could have lead to an underestimation of FNL. For these reasons we cannot exclude that also the real length of femoral neck can be different between the two groups. However our study emphasizes that at least one of the structural bone parameters (the NSA) is different between osteoporotic patients with and without femoral neck fracture .

•

SO

PE

Achilles BUA SOS Stiffness Sahara BUA SOS QUI/Sti. AD-SOS DBM UBPS

AC

SPE

1.43 dB/MHz 3.57 m/s 1.43% 2.17 dB/MHz 3.67 m/s 2.17% 37.82 m/s 4.91

% 1.46 0.24 2.09 3.89 0.24 2.87 2.02 12.98

%/yr -0.81 -0.05 -0.98 -1.13 -0.12 -1.35 -0.29 -0.97

yrs 1.8 4.8 2.1 3.4 2.0 2.1 7.0 13.4

Conclusion: These results are in agreement with the data of the literature for BU in middle age women, except for the DBM Sonic whose relatively poor precision might be explained by the morphologic changes (e.g. arthritis, and edema) frequently present in elderly population.

P190 THE IMPORTANCE OF DETERMINING BONE MASS IN THE PREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS-RESULTS FROM A DIAGNOSTIC PROGRAM P. Santos M. Estrela P. Retroz F. Aguas Z. Alves Depart. of Gynaecology - Bissaya-Barreto Maternity, Coimbra, Portugal The purpose of this study was to evaluate the bone mineral densitometry (BMD) of women who attend a gynaecology consultation in the central region of Portugal. BMD was performed with an Osteometer 100 (SXA) densitometer, that evaluated bone mass and BMD of the distal and ultra-distal sites of the radius and cubitus of the non-dominant arm. Before the exam, a questionnaire which evaluated age, residence, profession, scholarity, body mass index, age of menarche, parity, breast feeding, duration of oral contraception, menstrual cycle, age and type of menopause, duration of HRT, life habits (calcium intake, physical exercise, smoking habits, caffein intake, ... ) and previous health record was performed. 448 women were evaluated, whose mean age was 50.8 years. 60% of these women were menopausal, 46% were being treated with HRT. 80% of these women had normal values of BMD (T 2 -1).20% had values below normal and 3% of the population had values suggesting osteoporosis. These had a mean age of 64 years and were menopausal for nearly 19 years, one was premenopausal. 53% didn't take HRT and those who did, only had been treated for a mean time of 11 months. It is important to point out that women with normal BMD, as well as those with osteopenia or osteoporosis, referred adequate intake of milk and other dairy products, practiced exercise regularly, and the percentages were similar to those with smoking habits and caffein intake. 30% of the menopausal women had osteopenia and 5% osteoporosis (32.6% had had a surgical menopause). BMD values from the ultra-distal radius were lower in postmenopausal than in premenopausal women, as expected (mean=0.545 versus -0.354, p<
LUMBAR OPN

SPINE OPR

FEMORAL OPN

NECK OPR

20-44 45-49 50-59 60-69 70-80

13.1 31.9 42.0 50.0 39.4

0.3 4.3 9.1 24.3 40.0

12.6 26.7 39.0 51.4 57.6

0.2 0.0 1.3 5.7 24.2

% (CI 95%)

LUMBAR SPINE FEMORAL NECK LUMBAR SPINE & FEMORAL NECK

8.44 (6.93-14.54) 1.61 (0.93-2.29) 2.68 (1,80-3.56)

The prevalence of osteoporosis at any site -LS and/or FN- in our sample was 12.73% (Approximately 1.974.000 in total female Spanish population). Nevertheless, as previously known osteoporotic fracture was an exclusion criteria in this study, the prevalence of osteoporosis in the total Spanish female population is probably higher.

P192 BONE MINERAL DENSITY ASSESSED BY QUANTITATIVE ULTRASOUND AND DUAL ENERGY X-RAY ABSORPTIOMETRY - NORMATIVE DATA IN SWEDEN Olof Johnell Magnus K. Karlsson. Karl J. Obrant Bo E. Nilsson Department of Orthopaedics, Malmo University Hospital, Malmo, Sweden Introduction: The purpose of the study was to establish Swedish normative data for bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS). We also wanted to correlate the two methods as regard all subjects as well as only in probands with low BMD. Material and Methods: BMD was measured in 128 men and 143 women, age 22 - 90, by the DEXA and QUS methods. Only Caucasians living in Malmo, Sweden, were included. BMD (g/cm') of total body, left hip and lumbar spine (L 2 - L 4) were measured by use of the DEXA technique (Lunar DPX®) and in os calcis by the QUS technique (Lunar Achilles®). Results: We found reduced BMD in relation to age as measured by both the DEXA and QUS techniques. There were correlations between 0.28 - 0.52 in men and between 0.53 - 0.77 in women when comparing the DEXA and QUS measurements. When including individuals in the lower quartile as regard BMD total body, the correlations between the methods were less. Conclusion: The present study indicates a fairly low correlation between QUS, both speed of sound (SOS) and broadband attenuation (BUA), as compared with DEXA, especially in individuals with low BMD. Since both DEXA and QUS predict future fragility fractures, this indicates that the two methods present information about different aspects of bone.

P191 PREVALENCE OF OSTEOPENIA AND OSTEOPOROSIS IN A SPANISH FEMALE POPULATION M. Diaz Curiel" J.J. Garcia', R. Perez Cano', A. Rapado', and C. Alvarez Sanz4 and the Multicentre Research Group on Osteoporosis. 'Fundacion Jimenez Diaz, Madrid; 'Cibest,S.L., Madrid; 'Hospital Clinico Universitario, Sevilla; 4Rhiine-Poulenc Rorer, S.A., Madrid, Spain The aim of this study was to assess the prevalence of osteopenia and osteoporosis in the otherwise healthy Spanish female population previously used to generate standard curves for Bone Mineral Density (BMD) values Osteoporosis Int 7:59-64,1997. In brief, fourteen centers located within nine different geographical areas all overthe country enrolled 1,305 females aged 20-80 years. BMD was measured by Dual-energy X-ray Absorptiometry (DXA) at both Lumbar Spine L2-L4 and Femoral Neck sites using a Hologic QDR-l000TM device. Osteopenia (OPN) and osteoporosis (OPR) diagnosis were made according to WHO criteria. The following rates of prevalence(%) were found according to age groups: AGE (y)

SITE

The following rates of osteoporosis prevalence were found according to site of BMD measurement:

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P193 CAN A FOREARM DENSITOMETER FACILITATE THE MANAGEMENT OF OSTEOPOROSIS IN PRIMARY CARE? T. Wheatley. J.M. Bland. S. Canagon M. Harvey. P. Pearce Princess Royal Hospital, Haywards Heath and St. George's Hospital Medical School, London, UK Common conditions such as osteoporosis will not be managed effectively until many of the initial management decisions are made in primary care. Currently, candidates for preventative treatment are best selected by combining an analysis of clinical risk factors with bone mineral density (BMD) measurements at the spine and hip. However, this test is relatively expensive, may not be readily available and involves travel to the local centre. In this study the DTX 200 forearm densitometer was taken to a general practice and used to scan 202 healthy women, age 50-70 years. They were not taking treatment known to prevent osteoporosis and had never suffered afragility fracture. Each woman also completed a questionnaire to identify risk factors for osteoporosis, current drug treatment and other relevant medical history. They then attended the hospital for measurement of spine and hip BMD using a Lunar DPX plus. This generated 404 sets of results ie. the questionnaire data with hip and spine BMD (A) or questionnaire data with forearm BMD (B). Each set of data was interpreted blind, by a single clinician, who classified the BMD results by WHO criteria. He then evaluated both the questionnaire and BMD data for each set of results and where appropriate recommended specific treatment. The diagnoses and recommendations made using the 2 densitometers were compared, assuming "A" to be the "gold standard". For the diagnosis of osteoporosis the DTX 200 was specific [96% (95% c.i, 92-99)] but less sensitive [60% (95% c.i 42-76)] with a positive predictive value (PPV) of 78% (95% c.i 58-91) and negative predictive value (NPV) 92% (95% c.i. 87-96). In 9.9% of women the clinician felt that to provide clinical advice, a hip/spine DXA was necessary, in addition to the forearm data. For treatment recommendations, the questionnaire + forearm BMD had asensitivity of 75% (95% c.i 64-84) and specificity 96% (95% c.i 91-99). The predictive values were quite good with PPV 83% (c.i 71-91) and NPV 86% (95% c.i 76-91). We conclude that in a primary care setting, appropriate clinical advice for osteoporosis prevention can be given by evaluating a self-administered questionnaire and performing forearm DXA.

P194 PRECISION ERRORS OF THE DTX 200 ARM SCANNER WHEN USED IN THE COMMUNITY BY TRAINED LAY OPERATORS S. Canagon M. Harvey P. Pearce & T. Wheatley Princess Royal Hospital, Haywards Heath, West Sussex, UK Measurement of wrist bone mineral density (BMD) is a predictor of subsequent osteoporotic fracture and for convenience and cost effectiveness, portable machines, often operated by inexperienced personnel, are increasingly used for community screening. However, the assessment of precision error under these conditions has not been reported. In this study a portable dedicated forearm DXA scanner (the Osteometer DTX 200) was taken to a local general practice to screen a random sample of women age 50 - 70 years. Using the methods suggested by Gluer et al (1) short term precision errors were calculated for each of 7operators who had received training to ensure satisfactory technique. Each operator measured BMD 3 times on at least 17 and up to 22 subjects, removing the arm from the machine between each test (study 1). In an additional study, precision errors were assessed when 3 operators each measured BMD once on the same 17 subjects (Study 2). There was no significant difference in height or numbers of women with low bone mass within these various subgroups. In study one, precision errors for all 7 operators were acceptable at 1.16 2.04 (mean 1.89) % for the distal, but less satisfactory at 2.39 - 5.07 (mean 2.93)% for the ultradistal region. Among individual operators there was no relationship between their distal and ultradistal precision suggesting that results for the latter area might be affected either by small differences in technique, or by the physical characteristics of the individuals studied e.g. size and length of arm. In study 2 precision was 1.89 (distal) and 2.93 % (ultradistal) suggesting that there was not a significant difference in periormance amongst operators. These data demonstrate that satisfactory precision errors can be obtained for the distal radius when suitably trained lay volunteers operate the DTX 200 wrist scanner in a community setting. Further studies are in progress to identify variables which could affect the ultradistal precision. We suggest that if meaningful community screening is to be achieved using the DTX 200, further understanding of variables affecting precision and careful training and evaluation of each operator's results are essential. 1. Gluer CC et al. Osteoporosis International 1995: 5:262-270 .

P195 CLINICAL VALUE OF BONE MEASUREMENT OF CALCANEUS IN LATE ELDERLY WOMEN K. Iba T. Satou M. Kinoshita K. Kitatani K. Nakatsuka T. Miki Y. Nishizawa H. Morii Osaka Municipal Kohsaiin Kohsaiin Hospital, Osaka City University Medical School, Osaka, Japan Various instr~ments of bone density measurement have been developed for the diagnosis of osteoporosis. In order to select appropriate methods and sites for the bone loss evaluation, we compared late elderly women with vertebral fractures (age >75yr, 84±5 (SD)yr old, n=24) and the agedmatched women without vertebral fractures (age >75yr, 82±4yr old, n=36). All of them were in the state of independent daily living. The vertebral fractures were diagnosed by lateral X-ray films of spines. Bone loss was evaluated by radiographic absorptiometry in metacarpal bone (M-BMD), by dual X-ray absorptiometry (DXA) in lumbar spines (L-BMD), femoral neck (N-BMD), distal radius (R-BMD) and ultra-distal radius (UD-BMD), by peripheral DXA in calcaneus (C-BMD) and by ultrasound method (US) in calcaneus (stiffness). RESULTS: The values of L-BMD, N-BMD, C-BMD and stiffness in the fracture group were significantly lowerthan those in the non-fracture group (p
P196 ULTRASOUND VELOCITY CHANGES AT THE HAND PHALANXES IN ADULT FEMALE C.V. Albanese M. Kvasnovil S. Pirillo, R. Masciangelo, V. Ruschioni, R. Passariello Institute of Radiology, II Chair, University "La Sapienza", Rome, Italy We evaluate in this cross-sectional study, the bone tissue modifications which occur in a female population with ageing and menopausal status by a quantitative ultrasound (OUS) device which measures US propagation velocity in the distal metaphysis of the first phalanx of the last four fingers of the hand (DBM Sonic 1200, Igea, Carpi, Italy). We studied atotal of 966 female aged (mean±SD) 59±8.1 years (age range: 31-84 years). The subjects were divided into two sub-groups according to climateric condition: 1) 166 premenopausal women; 2) 800 postmenopausal women (years since menopause (YSM): 12.3±8:1, (YSM range: 2-42 years). On the basis of bone mineral density (BMD) measured at lumbar and femoral neck, using a DXA method (Hologic ODR 200plus), we also identified the patients with osteoporosis (T score -<2.5 SD) according to WHO. Spinal radiography was performed in osteoporotic patients to evaluate the presence of vertebral fractures. The values of the amplitude-dependent speed of sound (AD-SoS) was correlated negatively with age (r=O.72, p<0.00001) and YSM (r=0.69, p
•

P197 THE RELATION BETWEEN OBESITY AND BONE MINERAL DENSITY IN EARLY POSTMENOPAUSAL WOMEN Ye§im AkkoC Ye§im Kirazli Ramazan Ak§it. Department of Physical Medicine and Rehabilitation, Medical Faculty of Ege University, IZMIR, TURKEY To study the influence of obesity on bone mineral density of the lumbar spine (L2-L4) and hip (femoral neck, trochanter and ward's triangle), 30 obese and 32 nonobese early postmenopausal women were included in this clinical trial. Patients with body mass index (BMI= weighVheight2) greater than 30 were included in the obese group. Bone mineral density was measured by dual energy X-ray absorptiometry (DEXA). Women with a body mass index above 30 had a significantly higher lumbar vertebral and femoral bone mineral density compared with the nonobese group (p<0.05). In the obese group there was no correlation between bone mineral density and age, time since menopause, serum calcium, phosphorus, alkaline, phosphatase, estradiol, urinary calcium/ creatinine ratio (p>0.05). There was positive correlation between femoral neck and trochanteric bone mineral density and weight and body mass index (p0.05).

P199 COMPUTERIZED RADIOGRAMMETRIC MEASUREMENTS IN DIGITIZED FOREARM RADIOGRAPHS A. Rosholm. M. Grunkin*, L. Hyldstrup** L. Breksgard** *Torsana AlS, Denmark, * *Hvidovre Hospital, Denmark Computerized radiogram metric measurements of the radius and the three middle metacarpals are compared to BMD measurements of the hip and of the radius. The presented study investigates the correlations of the completely automated radiogrammetric measurements with either of the two BMD measurements. The possible advantage of combining all the radiogrammetric measurements into one quantity is evaluated. In addition, we investigate an apparent major difference between the ulnar the radial thicknesses of the radius bone with respect to their correlations to BMD. Conventional radiographic images of the non-dominant distal forearm from 24 women have been digitized. Femoral neck BMD and distal radius BMD have been measured on each woman. In comparison to the BMD quantities, a completely automated (computerized) method has been applied to the images in order to calculate cortical thicknesses of the radius and of the three middle metacarpals. The computerized method analysizes an image of the entire forearm and measures automatically the radiogrammetric quantities of the relevant bones. The obtained correlations between calculated thicknesses and the involved BMD measurements are tabulated below. It may be concluded, that the radial thickness of the radius bone is much more related to the bone status than the ulnar thickness is. It may furthermore be concluded, that a simple sum ofthe radial radius thickness and the mean metacarpal thickness (marked with a *) performs better than the metacarpal thickness alone.

P198 FACTORS INFLUENCING PERI PROSTHETIC BONE MINERAL LOSS AFTER UNCEMENTED TOTAL HIP ARTHROPLASTY A. Bohatyrewicz A. Gusta A. Spoz P. Zietek T. Ogonski E. Dabkowska Department of Ortopaedics and Traumatology, Biochemistry and Chemistry Department, Pomeranian Medical Academy, Szczecin, Poland Dual-energy X-ray absorptiometry (DXA) measurements in seven regions of interests (Gruen zones) were performed prospectively in 18 patients (14 females and 4 males, aged 42-76 years) who had undergone uncemented total hip arthroplasty (THA) due to degenerative hip osteoarthrosis. Peri prosthetic bone mineral density (BMD) was determined postoperatively 2 weeks, 3, 6, 12 and 24 months after operative treatment. The coefficients of variation of BMD measurements ranged from 2,3 to 6,3% in the proximal Gruen zones and from 1,8 to 4,7% in the distal zones. In addition to densitometric evaluation, the calcium, magnesium and fluoride concentrations were measured in cortical and trabecular bone samples taken intraoperatively from resected femoral head and neck. At 12 months after the operation, the regional BMD in all seven zones showed a maximal significant decrease ranging from 7,3 to 38,8% of BMD present at 2 weeks postoperatively. Thereafter the bone density appeared to be stabilized. The most significant postoperative bone loss (12,1-38,8%) was found in the calcar area. The cortical zone below the prosthesis showed lower but still significant decreases (7,3%-18,1 %). The analysis of preoperative femoral neck BMD and fluoride content in trabecular bone proved that osteopenia and lower fluoride concentrations correlated significantly with more bone density reduction after THA. No other factors (age, weight, sex, calcium and magnesium concentrations and fluoride concentration in cortical bone) showed significant associations .

•

BMD Hip Radius

Cortical thicknesses Radius

Meta II-IV

radial* 0.73 0.89

mean* 0.80 0.93

ulnar 0.32 0.36

sum* 0.81 0.95

There was no statistically significant difference in any measured variables between urban and rural adolescents of the same sex. The percentage of body fat was higher in rural adolescents, both girls and boys (approx. 3% and 6%, respectively), but the difference did not reach the level of statistical significance. The eBMD was significantly correlated to percentage of body fat (r=0,28-0,29), except for urban girls (r=0,22), and to the age of menarche for both urban and rural girls (r=-0,27 and r=-0,40, respectively), as well as to the height, but only for rural girls and boys (r=-0,28). In conclusion, there were no statistically significant difference between rural and urban adolescents in the terms of estimated bone mineral density measured by bone ultrasound. The eBMD significantly correlates with the percentage of body fat and the age of menarche.

P200 ULTRASONOGRAPHIC ASSESSMENT OF CALCANEUS IN HEALTHY CROATIAN CHILDREN S. Bolanca S. Cvijetii: D. Dekanii:. Institute for Medical Research and Occupational Health, Zagreb, Croatia Objective of this cross-sectional observation study was to examine the relationship of estimated bone mineral density (eBMD) measured on the as calcis in children by "Sahara Clinical Bone Sonometer" (Hologic Inc., Waltham, MA) to age, puberty, gender and anthropometry. Measured feet were size 411 as recommended by manufacturer. Height, weight and percentage of body fat were also measured and body mass index (BMI) was calculated. This study comprised 431 healthy Caucasian girls (N=217) and boys (N=214) aged 7-10 Y (prepubertal) and 15-17 (pubertal), recruited from local schools. Pubertal girls were at least 2 years postmenarchal, had regular menstrual cycles and Tanner's stage 4 or 5. Pubertal boys had also Tanner's stage 4 or 5. Detailed characteristics of studied children are presented on Table

N Age (years) Height (cm) Weight (kg) BMI (kg/m') % body fat Age of menarche (years) eBMD (g/cm')

PREPUBERTAL

PUBERTAL

Girls 106 9,O±O,8 139,5±7,7 33,7±7,0 17,2±2,5 24,4±5,5

Girls 118 15,9±O,7 166,2±6,3 59,2±7,8 21,5±2,6 27,9±6,0

Boys 111 9,1±O,9 139,9±7,9 35,1±8,7 17,8±3,2 19,0±7,8

P202 ACCURACY OF BROADBAND ULTRASOUND ATIENUATION ON CALCANEUM AS A SCREENING PROCEDURE OF OSTEOPOROSIS M.F. SAFRAOU' M. FAUCHET*' P. ANDRIEUX'" Department of Endocrinology Amiens', Advanced Medical Imaging Center - Technologic University of Compiegne", Department of Rhumatology Amiens' *', France The aim of this study is to test the accuracy of the measurement of the Broadband Ultrasound Attenuation (BUA) on the calcaneum in the screening of osteoporosis. 325 women aged 21-83 years, are examined. Bone status is evaluated by the measurement of bone mineral density (BMD) by Dual Energy X-ray Absorptiometry DEXA (SOPHOS instrument) at lumbar spine and right femoral neck. Women are classified by DEXA as normal or having low BMD. The ultrasound technique used is a portable OSTEOSONIC (OMNISYSTEMS instrument) and mean value of BUA (dB MHz-I) on the calcaneal tuberosity is measured for each subject. Results of this comparative study are shown in the following table:

Boys 96 16,1±O,8 178,5±6,3 70,7±O,8 22,2±3,0 15,3±6,7

12,6±1,2 0,499±O,072 0,511±O,086 0,551±O,113 0,546±O,118

The eBMD values were significantly higher (6,9-1 0,4%) in pubertal children in respect to prepubertal regardless of gender (p<0,01) and it positively correlates with age and anthropometric variables (height, weight, percentage of body fat, and BMI). The difference between genders were not significant neither in prepubertal nor pubertal children. The average annual increase of eBMD in calcaneus, estimated from our results would be 1.01.5%. The longitudinal study should be conducted to certify these results. In conclusion, estimated bone mineral density measured on the as calcis by bone ultrasound was clearly correlated with age and puberty as well as anthropometry but not with gender in children.

URBAN Girls

RURAL Boys

Girls

Boys

N Age (years) Height (cm) Weight (kg) BMI (kg/m') % body fat Age of menarche (years) eBMD (g/cm')

61 16,2±O,4 166,9±5,9 59,0±7,2 21,2±2,6 25,9±4,4

45 16,3±O,6 179,8±7,3 70,4±11,1 21,7±2,5 13,6±5,8

57 16,1±O,7 165,4±6,3 60,9±7,6 22,2±2,4 31,2±5,8

Normal BUA

Low BUA

Total

DEXA Normal BMD Low BMD Total

213 8 221

26 78 104

239 86 325 women

Then, performance criteria of this ultrasound technique are calculated: Sensibility =90,69%; Specificity =89,12%; Positive Predictive Value =75% and Negative Predictive Value =96,38%. These data demonstrate that this ultrasound technique is an accurate method and a good alternative to DEXA in large screening of osteoporosis.

P201 ULTRASOUND BONE MEASUREMENT - COMPARISON BETWEEN URBAN AND RURAL ADOLESCENTS S. Bolanca S. Cviietii: D. Dekanii: V. Juresa', M. Karsh;' Institute for Medical Research and Occupational Health, Zagreb, Croatia, 'School of Public Health "Dr. Andrija Stampar", Zagreb, Croatia, 'Department of Medicine, University Hospital Rebro, Zagreb, Croatia The estimated bone mineral density (eBMD) of the calcaneus was measured by "Sahara Clinical Bone Sonometer" (Hologic Inc., Waltham, MA) in 214 healthy Croatian adolescents, aged 15-18, residents of urban and rural regions. Measured feet were size 4-11 as recommended by manufacturer. In the addition to the ultrasound measurement, height, weight, age of menarche and percentage of body fat were also measured and body mass index (BMI) was calculated. All girls (N=118) were at least two years postmenarchal, with the history of regular menstrual cycles, and Tanner's stage 4 or 5. The boys (N=96) were also Tanner's stage 4 or 5. The main characteristics of studied adolescents are presented on Table.

OSTEOSONIC

P203 TIME RESOLVED LIGHT SCATIERING MEASUREMENTS FOR THE

51 16,3±O,7 178,3±6,3 71,8±9,5 22,6±2,9 16,6±7,2

12,6±1,3 12,6±1,3 0,544±O,115 0,540±0,134 0,547±O,111 0,556±O,117

•

DIAGNOSIS OF OSTEOPOROSIS H.-G. Eberle" J. Beuthan" M. DierolF, D. Felsenberg', W. Gowin', G. MOiler' 'Universitatsklinikum Benjamin Franklin, FU Berlin, Berlin, Germany, 'Laser-und Medizin-Technologie gGmbH, Berlin, Germany Osteoporosis is a systemic bone disease which results in an increased brittleness and fracture risk due to decreasing bone mass, bone quality, and a change in the microarchitecture of bone tissue. Early recognition allows effective therapeutic actions in most cases. Therefore reliable, cost effective, simple and noninvasive diagnostic means (without ionizing radiation as possible) are needed. First attempts for the assessment of bone status by a laser radar technique are described. Significant differences in the angular distribution of 700 nm laser radiation transmitted through healthy or osteoporotic bones are found in cw-scattering measurements. For in situ results the transition to time resolved measurements is needed to suppress the disturbing soft tissue signals. In this way a characterization of the bone part is aimed by selectively recording the scatter signal in a suitable chosen time window. The measurement's principle is based on time correlated single photon counting (TCSPC) using a10 ps laser diode (830 nm) and amicro channel plate- (MCP-) photomultiplier tube. In vitro-results on vertebrae obtained with this equipment show a correlation between the FWHM of the scattered light pulses and the bone mineral densities deter mined by x-ray absorptiometry (DXA). First results on phalanges are compared with DXA- and ultrasound investigations .

P204 BONE RESORPTION MARKERS DURING TREATMENT WITH ALENDRONATE C. Cormier* C. Kindermans# M. Abdenbi# O. Lorin# A. Kahan* J.C. Souberbielle# Service de Rhumatologie A, hOpital Cochin* and laboratoire de Physiologie, hopital Necker-Enfants malades#. AP-HP, Paris, France We report data on 31 consecutive osteoporotic (OP) women treated with Alendronate. They were aged 47-79 yr (mean±SD: 65±8yr) and had been menopausal for 3-30 yr (18±8.9 yr) without HRT. They all had a BMD ~2.5 T-score at the hip and/or at the spine but only 23 (74%) had a previous history of osteoporotic fracture. A cause for secondary osteoporosis was excluded by extensive laboratory testing and careful medical questioning. Total urinary deoxypyridinoline (tDpd) was measured (HPLC) before and after 3.5-6 months (mean±SD: 4.4±O.96 months) of treatment with Alendronate (10 mg daily). Mean pre- and post treatment tDpd was 11.7±3.1 and 1.1 mM/mM creat respectively. However, because or a biological (intra-individual) variability of approximately 20% for urinary tDpd, we considered that only a post-treatment decrease of more than 40% (2CVs) was significant in a given patient. The percentage of patients having decreased significantly their tDpd excretion was greater (Yates corrected Chi-squared test: 7.06; P
P205 ULTRASOUND BONE DENSITOMETRY OF THE OS CALCIS IN NORMAL POPULATION OF UKRAINE V.V. Povoroznjuk Department of Clinical Physiology & Pathology of Locomotor Apparatus, Institute of Gerontology Acad. Med. Sci. of Ukraine, Kiev, Ukraine The bone tissue state in the residents of Ukraine, subjects of both sexes, was studied. Total 1866 persons (1364 women and 502 men) were included. The patients with diseases influencing their bone tissue metabolism were excluded from the study. The heel bone examinations were performed by means of an ultrasound bone densitometer "Achilles+" (Lunar Corp., Madison, WI). The speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and a calculated "Stiffness" index (SI, %) were measured. In ageing men and women, the ultrasound parameters (mean±SD) were changing as follows: Age groups SOS (m/s) (years) men women 20 - 29 30-39 40-49 50-59 60 - 69 70 -79

1575±37,8 1567±35,1 1556±29,6 1562±31,8 1556±32,0 1541±35,4

BUA (dB/MHz) men women

1576±27,9 117±14,5 1565±26,8 115±14,3 1565±29,3 115±11,4 1546±27.6115±11,6 1530±26,4 112±14,4 1509±25,1 110±16,0

112±12,3 112±11,3 114±11,3 106±10,9 102±10,5 96±10,5

SI(%) men

women

99±19,1 95±17,4 92±14,7 94±14,9 91±17,3 85±18,6

96±14,0 93±13,3 94±14,1 84±13,1 77±12,5 67±12,3

P206 DENSITOMETRIC STUDY OF PRIMARY AND SECONDARY OSSIFICATION IN HUMAN FEMUR P. D'Amelio G.C. Isaia M. Di Stefano A. Sciolla G.L. Panattoni* Department of Internal Medicine, *Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin (Italy) In the present study we applied x-ray absorptiometry with "Ultra-HiResolution" software to investigate the ossification pattern of human developing femur. Thirty-one dried femora (belonging to the osteological collection of the Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin), from 11.5 weeks of conceptual age to 1 year of postnatal life, were analyzed by an Hologic QDR 1000 x-ray densitometer with "Ultra-Hi-Resolution" software. The results were expressed as bone mineral content (BMC, g) and bone mineral density (BMD, g/cm'). In order to avoid the possible errors due to the irregular outline of the femur BMC, of diaphysis was calculated on a rectangular area corresponding to the total length and minimum width of shaft; this area was divided into 5 sections along its longitudinal axis to estimate the rate of ossification from a spatio-temporal point of view. BMC and BMD of the proximal end were calculated on the proximal section, including the total outline of the femoral head. To distinguish the ossification area of the lesser trochanter and the one of the greater trochanter; the proximal end was divided into two portions, medial and lateral. Our findings show that the ossification center of the shaft extends more rapidly in proximal direction. A more dense area was recognizable at the level of the lesser trochanter from the 19'h week and atthe level of the greater at term. During development, the trends of BMC and BMD of both trochanteric areas are similar, but the values of the lesser trochanter are significantly higher than the values of the greater (p= 0.006 for BMC. p= 0.009 for BMD). In two samples at term the distal epiphysis ossification center is recognizable as a more dense area; in one-year sample the head ossification center is evident. These findings confirm the data reported in literature on the prevalent proximal progression of the shaft ossification center, on the distal end and femoral head ossification; on the other hand, they disagree with the current literature on the appearance of trochanteric ossification centers, reporting that these centers occur at 8-14 year for the lesser trochanter and at 3-4 yearforthe greater. These findings suggestthatthe erect posture does not play any list in determining the beginning of the mineralization of the trochanteric ossification centers.

Sllower than the fracture threshold was found Age groups (years)

Men (%)

Women (%)

20-29 30-39 40-49 50-59 60-69 70-79 80-89

0,9 4,0 4,1 2,4 9,6 22,6 20,1

1,0 2,3 2,1 1,3,4 24,6 50,0 53,3

Thus, in ageing there decrease significantly the ultrasound parameters characterizing the bone tissue state and there increases the number of the examinees with lower than the fracture threshold indices .

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P2U7 DIFFERENT US TECHNIQUES IN OSTEOPOROSIS M. Di Stefano C. Roggia P. Ardissone G.C. Isaia Department of Internal Medicine-University of Turin Many studies indicate that ultrasound measures something beside bone mineral density and that ultrasound parameters reflect material properties that are unrelated to BMD. The aim of this study was to compare dominant and non-dominant side results at femural, calcaneal and proximal phalanges level, to define the relationship between QUS parameters of the calcaneus and the proximal phalanges and BMD of the femur in a group of osteoporotic patients, and to evaluate whether QUS can detect any difference between osteoporotic women with and without vertebral fractures. We examined 57 Caucasian women affected by primary osteoporosis. Patients were divided into two different groups: Group 1 (30 women, 70-74 age-range, without spine fractures) was selected on the basis of a femoral neck BMD less than 0.600 g/cm'; Group 2 (27 postmenopausal women) was selected on the basis of the presence of one or more vertebral fracture, regardless of femoral neck BMD or age. In all patients we pertormed on the same day bilateral measurement of femoral neck BMD by using DXA technique (Hologic QDR 4500) and of heel and proximal phalanges by using ultrasound technique (Sahara and DBM Sonic 1200, respectively). In vitro shaft term coefficient of precision of our ultrasound units resulted 0.34% for the VOS and 3.25% for BUA (Sahara) and 0.57% for the SOS (DBM Sonic 1200). We did not find any statistically significant difference in all evaluated parameters (BMD, BUA, VOS, Stiffness, SOS and UBPS) between dominant and not-dominant side. In both groups of patients we found significant correlations between some QUS parameters and femoral neck BMD. Group 1 did not statistically differ from Group 2 for femoral neck BMD, BMI and age, despite of the fact that in our study inclusion criteria age range was chosen narrow (70-71 years) in Group 1 and wide (53-81 years) in Group 2. We found significant higher values in Group 1 than in Group 2 for UBPS, but not for other evaluated parameters. We can conclude that the relationships between QUS and DXA are too weak to allow in a single subject, accurate prediction of femoral BMD. UBPS seems to be the better parameter to discriminate fractured and not fractured patients.

P2US ALBINO SUBJECTS HAVE LOWER BONE MINERAL DENSITY THAN CONTROLS IN PUERTO RICO F. Aguila J.A. Montalvo, C. Rodriguez and V. Alicea Endocrine & Metabolic Division, University of PR School of Medicine, San Juan Puerto Rico It is known that dark-skin people are less susceptible to bone fractures & that this relates to a higher BMD than lighter-color individuals. We know the important role that vit 0 synthesized by skin plays in the integrity of BMD. A search of the literature failed to show any BMD data on albinos, the least-pigmented people. Thus we decided to carry out a pilot study measuring AP dual-energy X-ray densitometry (DEXA) of L, to L, spine as well as right hip (neck, trochanteric & intertrochanteric) using a Hologic 1000 QDR and single-photon absorptiometry (SPA) of a non-dominant arm at the distal radius, using a Norland 2780. Adult albinos, (n=18 13 F, 5 M), were age and sex-matched to non-Black controls (White-Hispanics), having similar morphometric features (including BMI (Kg/m'). Results: A highly significant decreased DEXA and SPA among albinos' vs. controls: Female albinos' femoral BD was 0.811 gm/cm' vs. 0.911 among controls (p 0.02) lumbar BMD was 0.952 vs. 1.073 (p
P2U9 CORRELATION BETWEEN PRIMARY LUMBAR VERTEBRAE OSTEOPOROSIS AND OSTEOARTHRITIS Chui Jinfang MD Department of Rheumatism, Guangdong Provincial People's Hospital, Guangzhou, China Objective to investigate the correlation between osteoporosis (OS) and Osteoarthritis (OA), to make physicians pay more attention to OS when OA occurs. Methods, 247 patients (11 male, 236 female age 50 - 84) with primary OS they were divided into 2 groups. One is OS I with 36 patients, another is OS II with 211 patients. Courses lasted for 1/2 year to 20 years. All patients were tested by DEXA made by Norland, USA. Diagnosis of OS was made on the value ;::2DS. X-ray of lumbar vertebrae, blood Ca++, AKP, BGP, PTH, CT and Ca++/Ccr in urine were checked to eliminate secondary OS and OA. Results, 247 patients with lumber vertebrae OS, of which 243 patients with OA meanwhile inferred that OS was significantly correlative with OA (P>0.05). Although causes were not confirmed, they were related to age, gene, nutrition and some cellular factors. Female suffered more and spine was attacked frequently. Conclusion, OS is a commonly encountered disease which morbidity rise with age and menopause. 83.4°/~ patients in the study belong to 60 - 79 years old. 43.8% OS get the value ;::3SD, who tend to fracture. Now 13 million ages in China. Most OA can be found in patients with lumbago by X-ray routine exam, much more than OS. The study showed that 12.1 % patients with OS could be found. When 30 - 50% substains of bone lost, routine X-ray exam can confirm OS. So, X-ray exam can not be the method for early diagnosis of OS. Especially for woman, the lumbago' patients who is over 60 years old should do the DEXA test in order to find OS earlier and to treat earlier and the more important thing is to prevent fracture. Since there are internal relation between OA and OS, we should pay attention to not only OA but also OS.

P21U BONE MINERAL DENSITY ASSESSMENT IN POSTMENOPAUSAL FEMALE RESIDENTS OF MOSCOW CITY SA Makarova A.S. Ametov Medical Academy of Postgraduated Education, Moscow, Russia Although the numbers of Moscow residents above forty and sixty years of age of both sexes are available (2,400,000 and 1,650,000, respectively), the statistical data as to the prevalence of osteoporosis (OP). The aim of the present study was to comparatively evaluate bone mineral density (BMD) in female inhabitants of Moscow City with bilateral postovariectomy (n=75, mean age 48,4, group 1), physiologic menopause (n= 184, mean age 57,1 under 65 years of age, group 2; and 65 + years of age: n=138, mean age 71,7, group 3) and thyroid dysfunction with endogenous or exogenous exposure to T4 (n=98, mean age 54,4 group 4; of which 36 had had autoimmune thyroiditis, and 52 post thyroidectomy); the duration of T4 replacement therapy with the average T4 daily dose of 125 mg/day. Group 4 also entitled the patients with a ten year history of endogenous hyperthyroidism. Prior to the study, none of the women had under gone HRT or anti resorption treatment. The number and the site of bone fractures were both in the cases themselves and in their mothers among the parameters considered. The results obtained were as follows:

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BMD

GROUP 1

GROUP 2

GROUP 3

GROUP 4

normal osteopenia osteoporosis

48% 30,7% 21,3%

51% 34,7% 14,3%

23,9% 36,2% 39,9%

44,8% 30,6% 24,6%

The prevalence of OP among female Moscow inhabitants is high with those above 65 years of age being the most vulnerable. The women with thyroid dysfunction compared to those with physiologic menopause are more likely to develop OP in age-matched groups, thus making high-dose T4 replacement therapy, as well as the long-term history of the hyperthyroidism, the major risk factor of OP. Bilateral ovariectomy tends to be an independent major risk factor of OP, which might account for a higher incidence of the condition in those who had undergone the surgery compared to women with physiologic menopause. The family predisposition for bone fractures with a female trait, found in all groups by means of retrospective analysis does require early prophylactic of OP with an annual long term BDM measurement in that group of patients .

performed on the DPX-IQ (Lunar) densitometer. Significant correlation between peripheral results, proximal femur and lumbar spine was found (r=0.72-0.78). Diagnosis of osteoporosis was also well correlated in peripheral and axial measurements (about 89%). We conclude that measurements of bone mineral density in the forearm is valuable method in diagnosing osteoporosis.

BONE MARKERS P211 STRUCTURAL-FUNCTIONAL STATE OF THE BONE TISSUE IN WOMEN WITH SURGICAL MENOPAUSE VV Povoroznjuk T.F. Tatarchuk, E.N. Boris Department of Clinical Physiology & Pathology of Locomotor Apparatus, Institute of Gerontology Acad. Med. Sci. of Ukraine, Kiev, Ukraine Early surgical menopause is regarded as a main risk factor of the development of systemic osteoporosis and its complications in women. The bone mass loss in such cases is caused by the decrease of estrogen concentration and, thus, the increase of interleukin production (I L-1 and IL-6) that promote considerable acceleration of the osteoclast-originated bone resorption. With an aim of study the structural-functional bone tissue state, prevalence of osteoporosis in women with surgical menopause (SM) 58 women with two-side ovariectomy aged 38-53 years were examined. According to the age of surgical menopause (ASM) the examined were divided into three groups: 1st group (16) - with the SM aged 35-59 years, 2nd group (18) - ASM - 40-44 years, 3rd group (24) ASM - 45-49 years. Control group was made up by women with normal menstrual function, standardized according to age, body mass index, nutrition peculiarities. Patients with endocrine pathology, blood diseases and others influencing metabolism of the bone tissue were excluded from the study. Study of the structural-functional state of the bone tissue, diagnostics of osteoporosis were carried out by means of ultrasound densitometer "Achilles+" (Lunar Corp., Madison, WI). The speed of the sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MH) and estimated "stiffness" index (SI, %). Analysis of the received results gives evidence of the veritable worsening of structural-functional bone tissue state indexes in women from all groups with the SM compared with the CG. Table. Structural-functional state of the bone tissue in women with surgical menopause Groups

2 3 Control

Age of the Age of SM women

Duration of SOS, m/s BUA, SI, % menopause dB/MHz

37,2±O,5 42,7±O,4 47,3±O,4

5,2±1 ,2 4,8±2,0 4,5±1,7 -

43,3±2,5 45,8±3,2 51,3±2,9 46,5±2,1

1542±4,9* 102±2,3* 1553±5,7* 105±2,2* 1565±5,2 * 108±1,8 * 1587±5,4 115±2,0

78±3,0* 85±3,1 * 89±2,9 * 98±2,6

* - veritable difference compared to the control group The received results give evidence that surgical menopause is a factor promoting accelerated aging of the bone tissue and development of the systemic osteoporosis and its complications. Because of this the given quota of patients needs constant medical control, carrying out ofthe densitometric monitoring (once a year) and taking medical-prophylactic measures.

P212 THE VALUE OF BONE MINERAL DENSITY MEASUREMENTS IN THE FOREARM IN DIAGNOSING OSTEOPOROSIS IN WOMEN E. Czerwinski R.T. Kukielka Department of Orthopaedics of Med. Col. of Jagiellonian University, ul. Kopernika 19a, 31-501 Krakow, Poland The DXA method is currently considered the golden standard in diagnosing osteoporosis. Measurements are carried out most frequently in the lumbar spine, proximal femur and forearm regions. Nowadays densitometers allow for precision in each of these regions of at least 0.5%. According to WHO criteria the values of T-scores in any site justifies the diagnosis of osteoporosis. Unfortunately, in everyday practise results of measurements in different sites sometimes indicate various diagnoses. The aim of this study was to estimate the value of measurements of the forearm in diagnosing osteoporosis in comparison to lumbar spine and proximal femur densitometric measurements. We investigated a cohort of 500 women, who applied spontaneously for investigation or were referred by their GP. Forearm measurements were carried out using the DTX-200 (Osteometer) in both "distal" and "ultradistal" regions. Measurements of the lumbar spine and proximal femur were

P213 BONE DENSITY OF THE DISTAL FOREARM IN 30000 INHABITANTS OF KRA~OW

E. Czerwinski R. Kukielka, Z. Oleksik, J. Fredlein A. Dworak Department of Orthopaedics of Med. Col. of Jagiellonian University, ul. Kopernika 19a, 31-501 Krakow, Poland 30.000 inhabitants of the Krakow region were investigated between May 1995 to March 1997 during a population study performed by the Polish Foundation of Osteoporosis Cracow Branch. Patients applied spontaneously for assessment following a massmedia campaign or were referred by their GP's. There were 26.797 women and 3.203 men. Average female age was 56,5 yrs (from 18 to 95 yrs, SD 11) and male 57.0 yrs (from 18 to 89 yrs, SD 13). Patient history including painful symptoms, symptomatic fractures and risk factors of osteoporosis were recorded using a special questionnaire. Bone mineral density was measured in the non-dominant forearm using the DTX-200 (Osteometer). BMD was analysed in the "ultradistal" and "distal" region. Correlation of BMD values and age were estimated in both males and females. BMD was higher in men in comparison to women by 23.28% in "ultradistal" and 19.12% in the "distal" area. Bone mineral density level decreased with age in both groups, but dynamics of decline was quicker in women. Prevalence of normal values, osteopenic and osteoporotic was assessed according to WHO criteria.

P214 THE PREDICTIVE VALUE OF BIOCHEMICAL MARKERS OF BONE TURNOVER FOR BONE LOSS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE C. Schulte S.Ortmans A. Dignass H. Goebell K. Mann Division of Endocrinology and Gastroenterology, Department of Internal Medicine, University of Essen, Germany Purpose: In spite of a well known association of inflammatory bowel disease (IBD) with an increased incidence of osteoporosis, little is known about long term course of bone mineral density (BMD) and the role of bone metabolism as a predictor of enhanced bone loss. Methods: Spine BMD (DEXA, Lunar) was determined at baseline and 18 months later in 63 patients with IBD (age 38±13 years, 35 males and 28 females, 50 patients with Crohn's disease and 13 patients with ulcerative colitis). Markers of bone metabolism were determined at baseline using bone alkaline phosphatase (BAP) as a marker of bone formation andN-terminal telopeptide I of type-I-collagen (NTX) as a marker of bone resorption. Results: 31 patients (49%) showed a normal spinal BMD (within 1 SD of the normal range), 20 (32%) osteopenia (-1 to -2.5 SD of the normal range) and 12 (19%) osteoporoSiS «-2.5 SD of the normal range) at baseline. 18 months later BMD was basically stable in the majority of patients. Gain of BMD averaged 1.22±4.22%, only 14 patients (22%) showed bone loss greater than 2%. Bone metabolism at baseline was characterized by a significant increase of bone resorption (T NTX=1.99±3.64) accompanied by an inadequately low increase of bone formation (T BAP=0.7±2) resulting in an imbalance of bone metabolism (T-coupling score =T NTX - T BAP =-1.S4±3.8). Changes in BMD were not correlated with spine BMD at baseline, age, length and duration of chronic inflammatory bowel disease, body mass index or steroid use, but were correlated with bone marker results at baseline: r=0.008 (T NTX), r=0.08 (T BAP), r=0.02 (T coupling score). Conclusion: Outpatient IBD patients show almost no change in BMD over a period of 18 months. There was a correlation between the amount of bone loss and the degree of imbalance of bone metabolism at the beginning of the study. Only a subset of patients with IBD suffer from a significantly enhanced short term bone loss. Our data suggest that bone markers can be used not only to characterize bone metabolism at an individual time point, but also to predict an increased risk of enhanced bone loss in the future .

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P215 A HOMOGENEOUS TIME RESOLVED FLUOROIMMUNOASSAY FOR

P217 COMPARISON OF ALL URINARY BONE RESORPTION MARKERS WITH THE NEW VITROS ECiTM NTX METHOD AND THE LONG-TERM VARIATION IN INDIVIDUAL WOMEN M.I. Gerrits and J.H.H. Thijssen Dept. of Clinical Chemistry; University Hospital, 3508 GA Utrecht, The Netherlands The amino-terminal telopeptide of type I collagen (NTX) is a very promising marker to detect bone resorption. There are two available methods to measure the marker in urine: the ELISA and the VITROS ECi enhanced chemiluminescent (ECi) method. The ECi method was evaluated as a development assay. The manufacturer (Ortho-Clinical Diagnostics, Amersham, UK) claims target precision of <10% CV across the measurement range (0-3000 nmol BCE/L). The automated method is compared with different bone resorption markers: Hydroxyproline (OH-P); Pyridinoline (Pyr) free and total by HPLC; Deoxypyridinoline (Dpyr) total by HPLC and free by HPLC and 3 immunoassays; Amino-terminal telopeptide (NTX) by ELISA and Carboxy-terminal telopeptide of type I collagen (CTX). In this study we also evaluated the long-term variation in excretion in individual women. The variation is measured in 34 postmenopausal women who collected morning urine at times zero and one and 7 years later, excretion is corrected for creatinine. The correlations with NTX-ECi are:

OSTEOCALCIN USING TRACE® TECHNOLOGY: KRYPTOR-OSTEO F. Rey', A. Dedieu ' , I. Dany', A.H. Davin ' , MY. Rigault', O. Dedesteyre', B. Darbouret ' 'CIS bio international, Division In vitro Technologies, Bagnols/Ceze, France. 'CIS bio international, Gif sur Yvette, France Osteocalcin or Bone GLA protein (BGP) synthetized by osteoblasts, is specific to bone tissue and serum osteocalcin provides a specific indicator of bone formation. Its presence is more marked in cases of hyperremodelling (renal osteodystrophy, early hyperparathyroidism, hyperthyroidism, Paget's disease) and reduced in cases of hyporemodelling (hypoparathyroidism, hypercalcemia, resulting from bone metastasis and long term cortisone therapy). We developed a homogeneous sandwich fluoroimmunoassay using TRACE®technology. This assay has been designed for KRYPTOR, a fully automated multiparametric randomaccess analyser. The results are obtained after 14 minutes of incubation at 3rC of 81ll of sample with the two conjugates and without any washing step. Afactory master curve is recalibrated every two weeks with one calibrator. The assay working range is 0-300 ng/ml. Higher values up to 3000 ng/ml are detected in the first few seconds of incubation and are automatically diluted without any delay. The detection limit calculated using the imprecision profile has been assessed as being 0.3 ng/ml with a probability of 95%. Within-run CVs were 3% at 15 ng/ml and less than 2% at 200 ngl ml, between run CVs were less than 5% at 15 ng/ml and lower than 4% at 200 ng/ml. Acomparative study was carried out with the CIS bio international assay ELSA-OSTEO on 96 samples. The correlation was TRACE =0.98 ELSA -0.59 with an r'=0.98. We conclude that this assay allows a rapid, fully automated, accurate and precise determination of osteocalcin.

CTX

Pyr total

Dpyr total

Dpyr free HPLC

0.9448

0.9185

0.7500

0.7949

0.6390

The other correlations varies from 0.5989 for OH-P to 0.8023 for Dpyr ACS:180. All the correlations are highly significant, p<0.001. The correlation with CTX is excellent, both CTX and NTX are breakdown products of the same collagen molecule and therefore provide almost identical information. The median and range of the calculated individual coefficients of variation is 15.1 (3.3 - 37.9). Forthe ELISA-method the median and range are 19.1 (3.2.-37.3). The correlation with all the other bone resorption markers is very good, and also the long-term variation in individual women is the same in both methods.

P216 VALIDATION OF A NEW IMMUNORADIOMETRIC ASSAY FOR INTACT HUMAN OSTEOCALCIN S. Minisola M.T. Pacitti E. Romagnoli V. Carnevale P. Caravella A. Scillitani R. Rosso F. Dicembrino II Clinica Medica-Universita "La Sapienza", Ospedale S. Giovanni Battista, Roma, "Casa Sollievo della Sofferenza", S. Giovanni Rotondo, Italy We investigated clinical validity of a new IRMA for intact human BGP (Ntact Osteo SP, Incstar Co., Stillwater, MN., U.S.A.). 100 norrnal subjects were studied to obtain normal ranges (4.9±1.7 ng/mL). The mean values found in 28 patients with PHPT (17.5±22.8 ng/mL, p
NTX-ELISA

P218 COMPARISON OF URINARY BONE RESORPTION MARKERS IN PRE-

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AND POSTMENOPAUSAL WOMEN M.I. Gerrits ' , A. Oldenhave', C.M. Vecht-Hart3, and J.H.H. Thijssen' 'Dept. of Clinical Chemistry; 'Dept. of Obstetrics and Gynaecology, University Hospital, 3508 GA Utrecht; 3Dept. of Epidemiology, Utrecht University, The Netherlands To obtain information about the comparability of bone resorption markers we have determined all available markers in urines of women around and after menopause. The following markers were compared: Hydroxyproline (OH-P); Pyridinoline (Pyr) free and total by HPLC; Deoxypyridinoline (Dpyr) total by HPLC and free by HPLC and 3 immunoassays; Amino terminal telopeptide (NTX) and Carboxy-terminal telopeptide of type I collagen (CTX). Two groups of women were used: 24 peri menopausal and 34 postmenopausal women. Correlations between the different crosslink markers varied between 0.63 and 0.92, depending on the kind of the crosslink and on the method of determination. It is possible that the measured free or total pyridinium crosslinks are partly derived from other collagen molecules as well. The automated Dpyr determinations (Immulite and ACS:180) give almost identical values as the ELISA. Crosslinks and telopeptides show similar good correlations, they vary from 0.532 to 0.770. The telopeptides CTX and NTX have an excellent correlation of 0.946. All the correlations are highly significant, p<0,001. We have chosen for the determination of one of the crosslinks and one telopeptide as markers of bone resorption in postmenopausal women .

P219 SHORT-TERM AND LONG-TERM VARIATION OF BONE RESORPTION MARKERS IN INDIVIDUAL SUBJECTS M.I. Gerrits', C.M. Vecht-Hart', A. Oldenhave' and J.H.H. Thijssen' 'Dept. of Clinical Chemistry; 'Dept. of Obstetrics and Gynaecology, University Hospital, 3508 GA Utrecht; 'Dept. of Epidemiology, Utrecht University, The Netherlands Little is known about the long-term variation in the excretion of bone resorption markers in individual women. In this study we evaluated available urine markers: Hydroxyproline (OH-P); Pyridinoline (Pyr) free and total by HPLC; Deoxypyridinoline (Dpyr) total by HPLC and free by HPLC and 3 immunoassays; Amino-terminal telopeptide (NTX) and Carboxy-terminal telopeptide of type I collagen (CTX). Short-term variation was evaluated in 24 perimenopausal women who collected morning samples for 5 days in 2 weeks. The long-term variation was measured in 34 postmenopausal women who collected three morning samples at times zero and one and seven years later. The excretions are corrected for creatinine. The median value (in %) of the day-to-day variation: Pyr free HPLC 11.8; Dpyr free HPLC 22.5; Pyr total HPLC 13.5; Dpyr total HPLC 18.8; NTX 18.1; CTX 20.0. The median value of the long-term variation: OH-P 16.6; Pyr free HPLC 16.2; Dpyr free HPLC 20.7; Pyr total HPLC 17.2; Dpyr total HPLC 18.9; I Pyr ELISA 16.7; Dpyr ELISA 12.0; Dpyr immulite 10.0; Dpyr ACS 16.6; NTX 19.1; CTX 17.1. The seven year period has more variation than the two-week period. Big differences exist in individual long-term variation, some women have very stable excretions whereas others show large fluctuations. In postmenopausal woman the excretion of the crosslinks is high 1 to 5 years after menopause, they decrease in the period of 6 to 15 years and show an increase after 15 years. The telopeptides also show a decrease at 5 to 10 years, butthey start to rise already after 10 postmenopausal years. We suggest that measuring one crosslink and one telopeptide is suitable to obtain reliable information on bone resorption.

P220 DIFFERENT BEHAVIOUR OF URINARY a AND B C-TELOPEPTIDES OF COLLAGEN I IN THE EVALUATION OF BONE REMODELING IN ANOREXIA NERVOSA C de la Piedra JA Calero ML Traba MD Asensio M Espejo* J Araente* MT Munoz* Fundacion Jimenez Diaz, Biochemistry Laboratory and *Hospital Nino Jesus, Division of Endocrinology, Madrid, Spain Fragments derived from degradation of type I collagen C-telopeptide (CTX), can be nonisomerized (a) or B-isomerized (B) depending on the age of bone; i.e., mainly a form in new bone and B form in old bone. We have studied 41 female patients with anorexia nervosa (AN) aged 18.5±2.2 years range (16-24), and an evolution time from 1.5 to 11 years, and 31 healthy control females (C), aged 19±2.3 years, range (16-24). AN patients presented osteoporosis: z-score of bone mineral density (BMD): -3.2±D.8, range (-0.9)(-4.6). The aim of this work was to determine the levels of bone alkaline phosphatase (BAP, Tandem Ostase Hybritech) (bone formation); and urinary a and B CTX (CrossLaps, Osteometer) (bone resorption), and alB CTX ratio (alB), in order to relate them with the degree of osteopenia and the status of bone remodeling, Statistics: Mann-Whitney test. The degree of osteopenia correlated with BAP (p=0.0027), but not with the other parameters. Patients with AN were divided in 3 groups according to their levels of BAP: high (H), normal (N) or low (L) remodeling. We found that BMD was significantly lower in groups Hand N than in group L. Patients of group Hand N presented significant elevation in BCTX with respect to group L. BAP correlates significantly with aCTX (p=0.0012) and alB (0.0095) in Cgroup, but not with bCTX, while in AN group BAP correlates with BCTX (p=O.OOOO) and with aCTX (p=0.022), but not with alB. Conclusions: 1) Patients with AN can be classified as having high, normal or low bone turnover. Patients with the highest turnover presented the highest degree of osteopenia. 2) aCTX is more adequate than BCTX to measure bone resorption in control girls; 3) However, BCTX is more adequate than aCTX in AN. The above results suggest that urinary CTX fragments found in control healthy adolescents come mainly from new bone, while CTX found in AN comes from old bone.

P221 EFFECTS OF ALENDRONATE ON BIOCHEMICAL MARKERS OF BONE TURNOVER IN OSTEOPOROTIC WOMEN RECEIVING OR NOT HORMONE THERAPY B. Siwek, J.J. Body Lab. of Endocrinology, Univ. Libre de Bruxelles, Brussels, Belgium The combined effects of bisphosphonates and hormone therapy (HT) have been little studied in postmenopausal osteoporotic women. In the framework of a study testing the tolerance and the efficacy of 30 mg of alendronate/day taken on two consecutive days each week for 6 months, we measured biochemical markers of bone turnover and of calcium metabolism in 52 postmenopausal women with osteoporosis (T score < 2.5). Median age was 63 years (range, 43-83). Thirty patients only received alendronate and 22 were already receiving HT since at least 2 years (15 were on ERT and 7 on adjuvant tamoxifen for a history of breast cancer). All patients also received 500 mg Ca supplements and 400 IU vit D daily. We determined urinary crosslinks excretion by the commercially available HPLC method of Bio-Rad Laboratories (intra- and interassay CVs <8%), hydroxyproline by HPLC, and serum osteocalcin (BGP, Incstar assay), Ca and intact PTH levels. Baseline pyridinoline (Pyd) and deoxypyridinoline (Dpd) (median value, 95% CI) were significantly (P<0.05) lower in the HT group; for Pyd, 50 nmol/mmol Creat (42.6-67.6), for Dpd, 9.9 nmol/mmol Creat (8.9-13.4) vs in untreated patients 63.4 nmol/mmol Creat (59.5-72) for Pyd and 15.3 nmol/mmol Creat (13.5-19.4) for Dpd. BGP levels were also significantly lower, 10.7 (9.5-12.3) vs 14.7 (13.9-17.8) ng/ml (P<0.001) but the difference in hydroxyproline levels was not significantly different. All parameters fell significantly (at least P<0.05) after alendronate. However, Pyd, Dpd and BGP remained lower (P
P222 AN INVESTIGATION OF THE RELATIONSHIPS BETWEEN URINARY POTASSIUM, SODIUM, CALCIUM AND DEOXYPYRIDINOLINE EXCRETION IN HEALTHY YOUNG ADULTS L. . Gintl", K. Cashman' &A. Flynn' 'Nestle Research Centre, Lausanne, Switzerland. 'Department of Nutrition, University College, Cork, Ireland Increased dietary K has been suggested to promote a positive .calcium balance via its effect on renal calcium conservation. Therefore, the objective ofthis observational study was to investigate the relationship between urinary K and both urinary Ca and the bone resorption marker, deoxypyridinoline (Dpyr) in healthy young adults consuming their usual diets. The relationship between urinary Na and K, Ca and Dpyr was also investigated as increased Na intake has been proposed to reduce renal re-absorption of both K and Ca, and thus promote their urinary losses. Thirty-five healthy subjects with a mean age of 24 years were recruited (24 females and 11 males). First morning void urine samples were collected over five consecutive days and analysed for K, Na, Ca and Dpyr (all variables expressed relative to creatinine (Cr)). Correlation coefficients were assessed by single linear regression analysis. For urinary K, a significant correlation was not found with either urinary CaiCr or Dpyr/Cr. However, in the case of urinary Na, significant positive correlations were observed with respect to urinary K/Cr (p<0.001), CaiCr (p<0.01) and Dpyr/Cr (p<0.001). A significant relationship was also found between urinary CaiCr and Dpyr/Cr (p<0.05). In conclusion, it is possible that the proposed benefits of dietary K in terms of its effect on urinary Ca conservation may be over-ridden by both the urinary Ca and K losses induced by a high Na diet. Additionally, the significant relationship observed between urinary Na, Ca and Dpyr may have negative implications for optimum bone health in this age group.

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P223 BONE MASS UNDER LOW-DOSED ORAL CONTRACEPTIVES IN YOUNG WOMEN M. Hartard P. Bartenstein Technical University of Munich, Departments of Nuclear Medicine and Prevent.-Sports Med. The present study has been designed to examine bone metabolism in young women taking 30J.l(J ethinylestradiol + 75J.1(J gestoden (OC) over 2 years. 70 women between 21 and 35 years were recruited and divided into two groups. Internal and gynecological findings were normal for age. After at least 4 months without contraceptive treatment 35 women received OC's, 35 women served as control. All subjects underwent a bone mass density (BMD) evaluation (spinal level L 2-4 ap/lat and both necks) by DEXA (SOPHOS-LXRA) and measurements of osteocalcine and deoxipyridinoline at baseline, after 6 and 24 months. After 2 years both groups (54 women finished) did not show any significant BMD changes. Just as little changes were found in the deoxipyridinoline levels. Significant lower osteocalcin levels (p<0,05) could be observed already after 6 months under OC (26 women). Our data suggested that long term treatment with an low-dosed oral contraceptive did not modify BMD in this age group but more detailed analysis indicated that the formulation did influence in particular bone metabolism of the younger one's.

P224 SERUM CARBOXYTERMINAL PROPEPTIDE OF TYPE I PROCOLLAGEN AND PHYSICAL GROWTH IN NEWBORNS W. Furmaga-Jablonska B. Kulik-Rechberaer, M. Jabtonski', M. Kozlowska Department of Paediatrics, 'Department of Orthopaedics, Medical University, Lublin, Poland Serum carboxyterminal pro peptide of type I procollagen (PICP) reflects processes of bone formation. As it is widely assumed that the physical growth in newborns depends mainly on skeletal system activity, we tried to establish correlation between serum concentration of prolagen C, selected bone metabolism minerals (Ca, Mg, P), non-specific alkaline phosphatase and different anthropometric traits in newborns. Materials and methods: 70 appropriate for gestational age (AGA) newborns with gestational age range between 27 and 41 Hbd were investigated. Serum PIPC was measured with ELISA method (Metra Biosystem, USA). 14 anthropological parameters were measured in each newborn. Sets of data were statistically analysed with nonparametric methods (tau Kendall and Spearman correlation tests). P<0,05 was considered significant. Results: Concentration of PICP in newborns serum ranged from 1100,25 ng/ml to 1878,00 ng/ml (mean: 1100 ng/ml, SD= 261,4 ng/ml). There were no statistically significant correlations between the serum levels of PICP and investigated electrolytes or alkaline phosphatase in newborns. Serum PICP concentration correlated positively with weight (r=0,26, p<0,04), hip width (ic-ic, r=0,29, p<0,018), width of distal femoral epiphysis (int-fem, r=0,28, p<0,023) and transverse chest dimension (thl-thl, r=0,26, p<0,04). Conclusion. High level of serum carboxyterminal propeptide of type I procollagen in newborns reflects their intensive bone metabolism but poorly correlates with anthropometric traits and physical growth .

P225 SERUM OSTEOCALCIN LEVELS IN RELATION TO SELECTED BONE MARKERS AND PHYSICAL GROWTH IN NEWBORNS W. Furmaga-Jablonska. B. Kulik-Rechberger M. Jabtonski', M. Kozlowska Department of Paediatrics, 'Department of Orthopaedics, Medical University, Lublin, Poland The aim of our study was to assess possible correlations between anthropometrical traits, serum osteocalcin, alkaline phosphatase and electrolyte levels (Ca, Mg, P) in newborns. Materials and methods: 70 appropriate for gestational age (AGA) newborns with gestational age ranging from 27 to 41 Hbd were investigated. Serum osteocalcin was measured with ELISA-method (Metra Biosystem, USA). With anthropological standard methods 14 physical traits were recorded in each child. Sets of data were analysed statistically using nonparametriC tests (tau Kendall correlation test). P<0,05 was considered as significant. Results. Mean serum level of osteocalcin in newborns was 30,06ngl ml, SD= 14,41 ng/ml, ranging from 4,96 ng/ml to 100,00 ng/ml. No significant correlations between serum osteocalcin level and anthropometric parameters in AGA newborns were recorded. Significant negative correlation was found between gestational age and osteocalcin level (r=-0,25, p<0,003). Significant positive correlation was also observed for osteocalcin concentration and level of alkaline phosphatase (r=0,23, p<0,011) and for serum concentration of Ca (r=0,21, p<0,016) and Mg (r=0,18, p<0,042). Conclusion. Serum concentration of osteocalcin in newborns is negatively related to their gestational age. The serum level of osteocalcin in newborns correlates with serum alkaline phosphatase, Ca and Mg. Skeletal growth in AGA newborns do not correlate with serum osteocalcin level.

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P226 THE ROLE OF BONE MARKERS IN OSTEOPOROSIS PREVENTION THERAPY AFTER CARDIAC TRANSPLANTATION C. Werner U. Wehr* C.E. Angermann P. Uberfuhr. W.A. Rambeck* K. Theisen R. Gartner H.U. Stempfle Depts. of Medicine, Cardiac Surgery and Veterinary Medicine*, University of Munich, Germany Immunosuppressive therapy induced osteoporosis is a well known complication after cardiac transplantation (HTx). The aim of this study was to assess the role of bone markers in osteoporosis prevention therapy after HTx. 102 patients (88 m., 14 f., mean age: 51±10 yrs.; 33±30 months post HTx) received a basic therapy (calcium 1000 mg daily and hormone substitution in hypogonadism) and placebo-controlled 0.25 iJ9 Calcitriol (1 a25(OH),D,). Bone mineral density (T-score, %) was measured at the lumbar spine by dual energy x-ray absorptiometry (Hologic-1000). Biochemical markers of bone formation (bone specific alkaline phosphatase, bAPH; osteocalcin, Oc; carboxylerminal propeptide of type I procollagen,; PICP) and bone resorption (pyridinum crosslinks pyridinoline, PYD; desoxypyridinoline, DPD; cross-linked aminoterminal telopeptide, NTX) were assessed at baseline, 3 and 12 months after therapy. Parameter [normals]

Calcitrol Placebo Base, 3 Base- 3 12 line months months line months

12 months

bAPH [10-80 U/I] Oc [4-12 ng/dl] PICP [80-200 ng/ml] PYD [18-24 nmollmmol Cr] DPD [4,5-6 nmollmmol Cr] NTX [25-70 nmollmmol Cr] BMD[%]

40.8 ±28.0 22.1 ±32.1 260.2 ±230.2 34.9 ±30.1 8.6 ±6.5 96.9 ±52.6 85±14

26.2 ±13.7 12.9 ±B.3 190.0 ±100.0 41.6 ±26.8 10.2 ±6.2 63.6 ±39.3 90±12

14.9 ±16.4 10.0 ±B.1 150.9 ±135.6 20.0 ±10.7 4.5 ±2.2 60.8 ±35.9

23.5 ±12.0 9.4 ±B.5 284.7 ±165.2 21.9 ±16.7 5.0 ±4.7 46.4 ±49.7 87±14

36.0 ±14.1 20.5 ±20.3 331.3 ±296.2 21.0 ±11.8 5.8 ±3.1 63.3 ±47.1 88±11

15.4 ±9.1 6.9 ±4.9 124.4 ±78.8 26.1 ±19.1 7.0 ±4.9 67.2 ±48.1

Conclusions: Higher bone turnover in seventy year old women seems to be associated with lower bone mass and this explains at least 10% of total variability in bone mass at this age. This is, however, not related to 25-0H-D levels and sequential secondary hyperparathyroidism.

P228 THE EFFECT OF INTERMITIENT TRANSDERMAL OESTROGEN THERAPY ON MARKERS OF BONE TURNOVER IN HYSTERECTOMIZED POSTMENOPAUSAL WOMEN C.A. Pereda R.A. Hannon. R. Eastell Bone Metabolism Group, Division of Clinical Sciences, University of Sheffield, UK Previous studies in postmenopausal women suggested that transdermal oestradiol patches may stimulate markers of bone formation especially during the first month of treatment and therefore may be anabolic to bone. The aim of the study was to give two courses of oestradiol treatment separated by a rest period and see whether there was a similar increase in markers of bone formation during the second course compared to the first one. We recruited 28 hysterectomized postmenopausal women who were randomly assigned to a treatment or control group. The first group received 50 ugldaytransdermal oestradiol (Estraderm MX patches) for 28 days followed by a rest period of 56 days without treatment. This pattern of treatment was repeated once. The control group did not receive any treatment. We measured serum osteocalcin (Oc) by IRMA and procollagen type I Nterminal propeptide (PINP) by RIA. The results shown in table are mean changes and 95% CI. The statistical analysis was made using area under the curve (AUC) to compare data pOints.

All bone markers showed a high intra-/intervariability with slightly increased bone formation and resorption at baseline indicating a high-turnover status after HTx. During follow-up with prevention therapy, formation markers decreased signif. in all patients. Furthermore, increased resorption markers normalized in the medication group. In conclusion, bone markers may useful to monitor the beneficial effect of osteoporosis prevention therapy (seen as no further decrease of BMD) after HTx.

P227 RELATIONSHIP BETWEEN BONE TURNOVER MARKERS AND BONE MASS IN SEVENTY YEAR OLD ICELANDIC WOMEN Gunnar Sigurdsson and Leifur Franzson Department of Medicine and Clinical Chemistry, Reykjavik Hospital, University of Iceland Objective: To evaluate the interrelationship between markers of bone turnovers (N-telopeptide and osteocalcin), 25-0H vitamin D, PTH levels and bone mass in seventy years old women. Study Group and Methods: A cross sectional study on all seventy-yearold women in Reykjavik (analysis performed after the first 200 participants). Bone mineral density (BMD) was measured by DEXA. N-telopeptide was measured in second morning void urine (Osteomark NTx). Intact PTH and osteocalcin were measured by immunoradiometric assays (Nichols Institute Diagnostics), but 25-0H-D by equilibrium RIA method (INCSTAR Corporation). Results: Urinary excretion of N-telopeptide was inversely related to total skeletal BMD (r=-0.319, p<0.01), positively related to osteocalcin (r=0.638, p<0.01), and PTH (r=0.386, p<0.01), but not related to 25-0H-D levels (p=0.20). Osteocalcin correlated positively with total skeletal BMD (r=0.221, p<0.01), and with PTH (r=0.245, p
•

(week 4)

(week 16)

HRT

PINP Oc PINP Oc

NO HRT

First course Mean % change

Second course Mean % change

13.8% (+1-13.2) * 10.6% (+1- 4.9) * * 4.0% (+1-23.6) -1.0% (+/-14.3)

5.3%(+1-13-4) 7.0%(+1-11) -0.6 % (+1- 20) 0.7 % (+1- 14.3)

*P<0.05 compared to No HRT. * * P<0.01 compared to No HRT. We conclude that there was a significant increase in markers of bone formation during the first course of treatment. The increase during the second course was not significant compared to controls and represented about a quarter of the first course for PINP and half for Oc. The duration of treatment or rest period may be altered to optimise formation stimulating effect of transdermal HRT.

P229 REDUCTION IN CIRCULATING ENDOTHELlN-1 FOLLOWS DECREASING PARATHYROID HORMONE LEVELS AFTER PARATHYROID ADENOMA SURGERY P. Lakatos I. Takacs Z. Nagy A. Tatrai G. Speer Z. Mathe F. Perner J. Zsadanyi 1st Department of Medicine and Department of Transplantation and Surgery, Semmelweis University Medical School, Budapest, Hungary Endothelin-1 (ET) has marked effects on bone metabolism, as well as on PTH secretion. Previously, we have shown that in vitro, PTH stimulates ET production in a dose-dependent manner. We have also demonstrated that in vivo, high PTH states (primary and secondary hyperparathyroidism) are accompanied with elevated plasma ET levels. In the present study, we investigated the changes in circulating PTH and ET ,during and after parathyroid surgery. We selected 11 patients with primary hyperparathyroidism due to adenoma. Blood was drawn at the beginning of the surgery (0), and 20, 60,240 minutes and 24 h after for PTH and ET determinations. The originally high PTH levels became normal 4 h after the removal of the adenomas. ET levels were higher than normal in our patients and they were reduced to the normal range 24 h after surgery. A correlation was found between PTH and ET levels during and after surgery (r=0.9; p<0.05). Decrease of serum PTH preceded that of ET. We conclude that PTH is a phYSiological stimulator of ET production'in vivo, as well.

P231 EFFICACY OF BONE RESORPTION INHIBITORS PREDICTED BY DEOXYPYRIDINOLINE IN POSTMENOPAUSAL WOMEN T. Miki K. Nakatsuka K. Kitatani H Kawakami H. Naka, Y Nishjzawa, H.Morii Osaka City University Medical School, Osaka, Japan Biochemical markers for bone metabolism are potential tools to assess the efficacy of inhibitors of bone resorption and predict long term effects on bone mineral density (SMD). We measured deoxypyridinoline (D-pyr) in postmenopausal women on various anti-resorptive therapies approved in Japan. Allocated were 175 postmenopausal women to the following treatment groups, calcium (Ca; asparaCa 600 mg/day, n=26), low-dose intermittent salmon calcitonin (SCT; 20 IU/week, n=11), ipriflavon (IF; 600 mg/day, n=41), intermittent cyclic etidronate (ICE; 200-400 mg/day, n=50), hormone replacement therapy (HRT; conjugated estrogen 0.625 mg/day, n=47). The SMDs of lumbar spine were measured at an interval of 6 months. Fasting urine samples were obtained at baseline and following therapies to measure HPLC-based D-pyr. The mean % changes of D-pyr in each treatment group is shown as follows;

12 24

350 300

"

--I

200

:I:

150


'0

7

IW

100

~

50

60 _--1, 240 1--_20_ _ min

Ca

SCT

IF

ICE

HRT

-3.93 -0.80

-2.3 -9.8 - 10.9 -15.9

-22.9 -31.9 -36.9

-4.9 -5.6

-5.9

The decline in D-pyr in subjects on HRT at 48 Week are found greatest, followed by that in ICE. ROC analYSis was employed to assess sensitivity and specificity of % changes of D-pyr to discriminate between patients with and without significant increases in SMDs 6 months following ICE and HRT. Areas under the ROC curves showed that the % changes in Dpyr at 4 Week (ICE, AUC: 0.7427 and 12 Week (HRT, AUC: 0.905) from baseline values have superior abilities to discriminate between responders and non-responders. In conclUSion, monitoring of D-pyr are useful in assessing effects of anti-resorptive therapies. Repeated measurement of D-pyr at intervals of 4 weeks and 12 weeks should be recommended to predict efficacy of ICE and HRT, respectively.

250

~ .9:

Week

2 4

24 I hours

P23D ENZYMUN-TEST® B-CROSSLAPS STANDARDIZATION AND PERFORMANCE CHARACTERISTICS B. Draeger, E. Huber, D. Renauer, Ch Ebert, A. Dessauer, W. Naser Boehringer Mannheim GmbH, Tutzing, Germany The CrosslapsTM marker is aspecific and sensitive index of bone resorption. An assay in MTP format for urinary C-terminal telopeptides (CrossLapsTM ELISA, Osteometer Biotech NS) was described by Bonde et al. 1). An automated version of the CrosslapsTM assay (Enzymun-Test® B-Crosslaps, Boehringer Mannheim GmbH) was recently developed. As a main difference to the CrossLapsTM ELISA the Enzymun-Test® B-Crosslaps is standardized with an octapeptide of the C terminal region of the a1 chain of Collagen Type I. This synthetic peptide has a high degree of purity and is characterized via HPLC, mass spectrometry and CHN-analysis: The high purity and the good stability of the standard material allows a reliable lot to lot reproducibility. The automated Enzymun-Test® B-Crosslaps show~ very good precision (inter-assay:CV 2-5%, intra-assay:CV 3-5%). The comparison of Enzymun-Test® B-Crosslaps to CrosslapsTM ELISA demonstrates a dose correlation of both methods (r>0.9). Conclusion: Due to the good analytical performance and lot-to-Iot comparability the automated Enzymun-Test® B-CrossLaps is an effective tool for the management of bone disorders, especially for monitoring long term anti resorptive therapy. References: 1) M. Bonde, P. Qvist, C. Fledelius, BJ. Riis, C. Christiansen Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin.Chem.40 (11 ):2022-2025, 1994.

•

deoxypyridinoline (DPD) by HPLC and crosslinked aminoterminal telopeptid (NTx) by ELISA were measured at baseline and at 3 and 12 month after 1a,25 (OH),D3 intervention. Serum BSP levels were assessed by a newly developed polyclonal RIA for human BSP. Results:

P232 THE ELECTROCHEMILUMINESCENT IMMUNOASSAY OF SERUM CTELOPEPTIDE AS A MARKER OF BONE TURNOVER N. R. Hoyle Boehringer Mannheim Research Centre, Penzberg, Germany Background and Objective: To date there are relatively few fully automated assays for the measurement of C-telopeptide (CTx, a C- terminal marker associated with Type I collagen degradation). We present here I technical and short clinical performance data associated with this new assay and detection technology. Method : The assay method employed uses a recently established technology of ruthenium chelate electrochemiluminescence as a marker, within a conventional immunoassay concept. Results: Short assay performance characteristics are shown below (Table 1). In particular the C telopeptide assay shows a clear correlation with pre-post treatment serum samples taken from patients receiving anti resorptive therapy, against other serum CTx and NTx assays (Fig. 1) and an unexpectedly good correlation between urine sample-based determinations from other CTx assays. Conclusion: Our data indicate that the Elecsys serum CrossLaps assay is very sensitive, highly reproducible and is capable of showing clear bone disease and treatment effects in various patient groups.

A B

0 12

o. 12

28,9±14,7 13,4±6,2* 31 ,1±17,9 27,2±16,5

PYD

DPD nmol 1 mmol Crea

NTx

34,8±26,7 24,5±20,1 25,9±12,7 43,2±30,7

8,9±7,7 5,9±6,2* 6,7±3,6 9,8±7,1

92,5±50,1 44,3±28,2 80,3±60,5 57,2±34,1

mean±SD; differences between month *p<.05, **p<.01 ; for differences between groups at 12 month all p<.05. Conclusions: Our data show that in patients following heat transplantation treatment with 1a,25 (OH),D3 is effective in lowering serum levels of BSP and biochemical marker of bone resorption (PYD, DPD and NTx).

P234 SERUM BONE SIALOPROTEIN LEVELS ARE LOWERED IN WOMEN ON

Assay characteristics Dynamic Range Detection Limit Functional Sens. Sample Volume Intra Assay CV Inter Assay CV Ref. Method Correlation/n Intercept Slope

month BSP ng 1ml

0-10000pg/ml 10pg/ml 100pg/ml 50!JI <1 OOpg/ml 20% <200pg/mI15% Serum CTx EIA

0.955160 10pg/ml 1.4

Table 1 CrossLaps performance

HORMONE REPLACEMENT THERAPY S. Stork, C.K Stiirk* P. AngereL W. Kothny. P. Schmitt WA Rambeck* C. von Schacky Department of Internal Medicine, *Institute for Animal Physiology, Munich, Germany Bone sialoprotein (BSP), a potential marker of bone metabolism, is a phosphorylated skeletal glycoprotein that accounts for approximately 10 % of noncollagenous bone matrix proteins. Findings in humans are scarce and have revealed controversial results. The aim of our study was a) to examine the influence of hormone replacement therapy (HRT) on circulating BSP in postmenopausal women and b) to determine whether serum BSP reflects bone formation, bone resorption , or both. Subjects and methods: 96 healthy postmenopausal women; group A: n=51, aged 62±3 y (mean±SD), on low-dose combined HRT for at least one year; group B: n=45, aged 61 ±3 y, without HRT for at least one year. Serum BSP levels were measured with a newly developed polyclonal RIA for human BSP (1). Bone resorption was assessed by total urinary deoxypyridinoline (DPD) by HPLC, and urinary N-terminal telopeptide (NTx) by ELISA (first morning void; values corrected for urinary creatinine). Bone formation was assessed by serum osteocalcin (Oc) by ELISA, and serum bone specific alkaline phosphatase (bALP) by wheat germ precipitation (immediate processing of blood samples and storage at -80°C). Results: Tab 1: Markers of bone turnover in women with and withQUt HRT. group ~/I

Figure 1. Example of reduction of CrossLaps (Elec 2010) seen in serum from Pagets patient after treatment.

A (n=51) B (n=45)

'233 BONE SIALOPROTEIN AS A MARKER OF BONE TURNOVER IN PATIENTS FOLLOWING HEART TRANSPLANTATION U. Wehr, H.U. Stempfle * C. Werner* M. Schlachter# W.A. Rambeck Institute for Animal Physiology, *Department of Medicine, Cardiac Surgery, Munich, Germany, F. Hoffmann-La Roche Ltd., Dept. of Vitamins and Fine Chemicals, Basle, Switzerland Accelerated bone loss has been recently recognized as a complication following heart transplantation (HTx). This phenomenon is attributed to the use of immunosuppressive therapy, including high doses of steroids and cyclosporine. The aim of our study was to asses a) the suitability of bone sialoprotein (BSP) as a sensitive, noninvasive method to evaluate bone turnover in patients following HTx, and b) to determine the effect of 1a,25 (OH),D3 intervention on bio chemical markers of bone turnover in HTx patients. Subjects and methods: 31 HTx patients were randomly assigned to treatment with either calcium (1000 mg/d) and 1a,25 (OH),D3 (Rocaltrol®; 0,25 ~/d) (Group A) or calcium and placebo (Group B). Patients with hypogonadism were hormone substituted. As markers for bone resorption, the urinary excretion of collagen crosslinks pyridinoline (PYD),

•

BSP DPD nmoll NTx nmoll mmol Crea mmol Crea ng/ml

Oc U/I

bALP

4.8 ±1.6 9.0 ±4.7

10.8 ±4.7 16.8 ±10.6

21.0 ±8.7 36.4 ±16.3

19.5 ±8.9 36.7 ±18.0

25.3 ±12.9 61.3 ±46.3

mean±SD; independent t-test; all p<.001 for differences between groups Tab 2: Correlation between BSP and markers of bone turnover. group A (n=51) B (n=45)

BSP BSP

DPD

NTx

Oc

bALP

~30*

.419** .780***

~65***

.215 .561 ***

~02 ** *

~73 ***

Pearson's correlation coefficient; * * * p<.001; * *p<.01 ; *p<.05 Conclusions: Our data clearly indicate that postmenopausal women on HRT show considerably lower BSP levels (-46 %) than women without HRT. In women without HRT, BSP levels are strongly correlated with markers of both bone formation and bone resorption. In women on HRT, these correlations appear to be weaker. (1) Karmatschek M. et a11997. Clin Chem 43(11 ):2076-82

P235 BIOLOGICAL VARIABILITY OF SIX BONE RESORPTION MARKERS IN PREMENOPAUSAL WOMEN J.P. Hoffmann A. Hoffmann L Weber Division de chimie biologique, Laboratoire National de Sante, Luxembourg We compared the day-to-day variability of one home-made and five commercially available bone resorption assays: Total deoxypyridinoline (t-Dpd), free deoxypyridinoline (f-Dpd), crosslinked N-telopeptides of type I collagen (NTx), crosslinked C-telopeptides of type I collagen, non isomerized (CTx), a isomerized (a CTx) and 8 isomerized (8 CTx). t-Dpd was measured by HPLC, f-Dpd with Pyrilinks®-D (Metra), NTx with Osteomark® (Ostex). CTx were measured with CrossLaps®ELlSA, a CTx with aCrossLAPS®RIA and 8 CTx with 8-CrossLaps®ELlSA (all three Osteometer Biotech). All assays were run according to manufacturers instructions. The results of the resorption markers were corrected for urinary creatinine concentration. For the biological variability experiments 4 premenopausal women collected second morning void urine once a week, each one 10 times over a 3-month period. Day-to-day variation of bone resorption markers Marker Mean concentration Mean CV%

CV range%

t-Dpd f-Dpd NTx CTx a-CTx 8-CTx

8.2-12.6 5.9-12.5 15.2-26.3 8.9-18.0 12.2-19.4 13.4-22.4

15.6 6.2 42.9 193.6 300 6.3

9.5 9.1 19.8 14.5 16.9 17.7

Deoxypyridinoline, free or total, had the lowest day-to-day variation, whereas this variation was higher for the crosslinked telopeptides of type I collagen, N-terminal and C-terminal. Our findings did show no significant differences in the variation between the different isomerized forms of CTx. Beside the analytical variability, the biological variability should be taken into account when interpreting the results of bone marker measurements.

P237 SERUM CROSSLAPSTM ONE STEP ELISA: AN EFFICIENT TOOL FOR MONITORING ESTROGEN AND TIBOLONE, TREATMENT S. Christgau. N.H. Biarnason* P. Alexandersen* C. Rosenquist E.G. Henriksen Osteometer Biotech AlS, Herlev, Denmark. *) Center for Clinical and Basic Research, Ballerup, Denmark The Serum CrossLapsTM One Step ELISA is an immunoassay specific for a 8-aspartate form of the epitope EKAHDGGR, derived from the C-terminal telopeptide region of type I collagen. We have assessed the clinical value of the serum CrossLapsTM assay for monitoring anti-resorptive therapy in osteoporosis treatment. Postmenopausal women treated with different doses of cyclophasic or continuous hormone replacement therapy (HRT), orwith tibolone (a synthetic steroid with estrogenic, progestogenic and androgenic properties) were measured in the Serum CrossLapsTM One Step ELISA at baseline and at 3 or 6 months intervals during therapy as well as monitored for spine BMD. The serum CrossLapsTM measurements showed a significant decrease among the groups of women treated with either one of the two anti-resorptive agents. Furthermore, the annual percentage change in spine BMD correlated with the changes in CrossLapsTM concentration and the serum CrossLapsTM assay showed high specificity and sensitivity for assessing spine BMD changes (83 - 90% and 77 - 83% respectively, calculated by ROC analysis). 8

A

~~", •

!.

1

t.

H

In conclusion, the study demonstrates an important clinical value of the serum CrossLapsTM One Step ELISA for follow up of anti-resorptive treatment in osteoporosis.

P238 DETERMINANTS OF OSTEOCALCIN (N-TERMINAL MID-FRAGMENT) AND BONE ALKALINE PHOSPHATASE LEVELS IN AN UNSELECTED MALE POPULATION. TROMS0 OSTEOPOROSIS STUDY M. Midtby. J.H. Magnus. V. Fonnebo A.J. Sogaard A. Tollan Dept. of Rheumatology and Institute of Community Medicine, University of Tromso, Norway In order to explore the possible predictive value of bone markers as risk factors for osteoporosis and osteoporotic fractures it is important to identify factors that contribute to their variation. The aim ofthis study is to evaluate markers of bone formation in a male population as it appears in a screening situation. Tromso Osteoporosis Study (TROST) is part of the fourth Troms!! Heart Study in Norway. Everybody above the age of 25 was invited to the primary screening. All men aged 55-74 and a five % random sample from the other age groups were invited to participate in TROST. Nearly 85% (n=3597) attended the study. For bone marker measurements 490 men were randomly selected among those attending the screening between 8 a.m. and 12 a.m. during the 12 months of data collection. Blood samples were stored in -70°C until assayed for osteocalcin (ELSA-Osteo, Cis Bio International, France) and bone alkaline phosphatase (Tandem R-Ostase, Hybritech Inc). Bone alkaline phosphatase (S-BALP) had in our population a mean value of 13,31J{J/I (SD 4,5 median 12,6IJ{J/I). Mean value of Osteocalcin (S-OS) was 18,1 nglml (SD 5,2 median 17,3 ng/ml). The Pearson correlation coefficient between markers was 0,35 (p<0,001). Seasonal variation was shown in both markers with an increase in the wintertime; S-BALP 11,8% (p<0,001) and S-OS 5,4% (p=0,07). Age affected both markers with high levels in young males, a linear decrease until the age of 50 and no subsequent change. Individuals with body mass index over 27,0 had significant higher S-BALP level. When assessing bone formation markers in males seasonal variation and anthropometric data must come into consideration in addition to other clinical factors.

P239 THE CORRELATION OF BONE MINERAL DENSITY AND THE URINARY N-TELOPEPTIDES LEVELS IN POSTMENOPAUSAL WOMEN Merih Eryavuz* Hafize Uzan** UlkO Akarirmak* Berna Celik* Seval Aydin** $ansin TOzOn*. Safiye Dondurmaci** * istanbul University Cerrahpasa Medical Faculty Physical Medicine & Rehabilitation Departmant, Istanbul, Turkey * * istanbul University Cerrahpasa Medical Faculty Biochemistry Dept. Urinary N-telopeptides (NTx) is a marker of bone resorption. This study was designed to compare the correlation of bone mineral density (BMD) and the levels of urinary NTx in postmenopausal women. Seventy-three postmenopausal women aged 44 to 83 years were enrolled in the study. BMD at two regions of the hip and lumbar spine was defined by dualenergy X-ray absorptiometry. Serum Ca, P, alkaline phosphatase and bone specific alkaline phosphatase were measured. Urinary NTx levels were within normal values and weakly correlated with age and menopause duration (p=0.0001 and p=0.001 respectively) and were not correlated with BMD. In our study urinary NTx level is not a predictive value of osteoporosis but consecutive measurement of Ntx can be of value in monitoring the response to anti resorptive agents.

....

,..

Monlh

A): Response of serum CrossLapsTM One Step ELISA to HRTand tibolone treatment. B) correlation between changes in the serum, CrossLapsTM assay and a-BMD in the two study populations.

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P24D ONE-YEAR, DOUBLE-BLIND, RANDOMIZED TRIAL OF CONTINUOUS TRANS DERMAL ESTRADIOL AND NORETHINDRONE ACETATE VS. ESTRADIOL TRANS DERMAL HRT ON BONE MARKERS D Archer*, B Carr**, K Furst***, DTipping****, MP Dain**** *Norfolk, VA; * * Dallas, TX; ***Rhone-Poulenc Rorer, Collegeville, PA; * * * * RhOne-Poulenc Rorer, Antony, France A total of 625 postmenopausal women were enrolled in this 52-week, randomized, double-blind, multicenter study of continuous combined transdermal estradiol-norethindrone acetate (E2/NETA) and transdermal estradiol only (E2) on bone markers. Women were assigned to one of four treatments: transdermal E2 501l!l/day or transdermal E2/NETA (Estalis™I Combipatch™) delivering estradiol 50ll!l and NETA 140, 250, or 400ll!ll day. Markers of bone formation (serum bone specific alkaline phosphatase, total osteocalcin) and bone resorption (urinary n telopeptide and ctelopeptide) were obtained at baseline and weeks 24 and 52. Data from 364 women were available. There were clinically significant decreases in the percent change from baseline to one year for all markers. There were no statistically significant differences in the magnitude of decrease in the E2/NETA 50/250 and 50/400 groups compared with the E2 group; while the decrease in the E2/NETA 50/140 group was significantly (p<0.001) less than with the E2 group. At baseline, bone turnover was higher than normal premenopausal range; under E2/NETA and E2, the markers returned to normal premenopausal range. An E2/NETA continuous combined patch demonstrated comparable effectiveness to E2 alone for effects on bone markers.

P241 EFFECTS OF COMBINED SEQUENTIAL TRANS DERMAL ESTRADIOL AND NORETHINDRONE ACETATE HRT ON BONE MARKERS IN POSTMENOPAUSAL WOMEN E Lufkin*, K Furst**, D Tipping***, MP Dain*** *Rochester, MN, US; **Rhone-Poulenc Rorer, Collegeville, US; * * * Rhone Poulenc Rorer, Antony, France The effects of a combined sequential estradiol-norethindrone acetate (E21 NETA) transdermal patch on biochemical markers of bone turnover were evaluated versus an estradiol only (E2) patch in a 52-week, double-blind trial of healthy postmenopausal women. Patients received either a patch releasing E2 501l!l/day alone or a combined sequential therapy consisting of an E2 patch for days 1 to 14 of each cycle and acombined patch releasing E2 501l!l/day plus NETA 140, 250, or 4001l!l/day (Estalis™ Sequi™I Combipatch™) for days 15 to 28 of each cycle. Serum bone specific alkaline phosphatase (BAP), osteocalcin, n-telopeptide and c-telopeptide assays were obtained at baseline, week 24, and week 52. Of 646 randomized women, at least 418 were included in analysis of bone markers at week 52. The C-telopeptide/creatinine and N telopeptide/creatinine ratios were reduced from baseline to week 52 in all treatment groups, but only the E21 NETA 50/400 group was significantly (p
P242 N-MIDTM OSTEOCALCIN: A RAPID, SENSITIVE IMMUNOASSAY FOR ASSESSMENT OF BONE METABOLISM USING FULLYAUTOMATIC ELECTROCHEMILUMINESCENCE A. Kyrjatsoulis, S. Pfister, A. Christ, W. Kraus, G. Rippegather, W. Naser, M. Rottmann Roche Diagnostics, Research Center Penzberg, Germany Background and Objectives: Bonemarkers, like Osteocalcin as bone formation marker, are receiving increased attention as the elderly population continues to rise with concomitant health care costs. Osteocalcin or bone Gla protein (BGP), the major non-collagenous protein of bone is a vitamin K-dependent calcium binding protein containing y-carboxylated glutamic acid. It has a molecular weight of 5800 Da. and consists of 49 amino acids. Osteocalcin is synthesised by osteoblasts. Intact molecules are rapidly cleaved at amino acid position 43-44. Intact osteocalcin (aa 1-49) as well as the large N-mid-fragment (aa 1-43) each account for about 1/3 of the total immuno reactivity of osteocalcin found in the bloodstream. The serum osteocalcin level is directly related to the rate of bone turnover in various clinical pictures (osteoporosis, primary and secondary hyperparathyroidism, Paget's disease and tumor related hypercalcemia etc). We present here technical performance data generated on Elecsys® analyzers Method: By using a two-side sandwich technique, (one mab reacting with a mid molecule and the other with aN-terminal epitope) intact as well as N-MID osteocalcin can be detected. Our assay is independent of the labile C-terminal part (aa 43 49) of the molecule. The method is based on a recently established technology using ruthenium chelate electrochemiluminescence (ECL). Results: Short assay performance characteristics are shown in Table 1. The use of ECL -technology, along with critical antibody selection and processing, yields assays demonstrating a high dynamic range, excellent low detection limit and low inter/intra-assay coefficients of variation. Table 1. Osteocalcin performance

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Assay characteristics Dynamic Range Detection Limit Function. Sens. Sample Volume Sample TAT, Turn A.T. Incubation 3loC Hook Effect Intra-Assay CV Intra-Assay CV Inter-Assay CV Inter-Assay CV Ref. Method N1Correlation Intercept 1Slope

0-400ng/ml 0.2ng/ml 1ng/ml 40J.1l Serum/plasma 20 min. 2 x 9 min. >1000 ng/ml >10ng/mI3% >40ng/mI2% >6ng/mI4% >40ng/mli3% Enzymuni-Tes 262/0.9f 4.5ng/m1 11.3, no standardisat

Conclusion: Our data indicate that the Elecsys N-MID-Osteocalcin assay is asensitive, accurate and precise test with short incubation times, increased measurement range, which requires low sample volumes. In addition, a two point assay calibration contributes to high overall user convenience .

P243 ELECSYS® PTH, PARATHYROID HORMONE: A RAPID AND SENSITIVE IMMUNO ASSAY USING FULLY AUTOMATIC ELECTROCHEMILUMINESCENCE FOR BONE METABOLISM ASSESSMENT A. Kyriatsoulis N. Waechter, S. Feldmann W. Kraus S. Schroeder G. Rippegather, W. Naser M. Rottmann Roche Diagnostics, Research Center Penzberg, Germany Background and Objectives: Intact PTH (parathyroid hormone) is a single chain polypeptide of 84 amino acids (9S00 Da.) secreted by the parathyroid glands. Along with calcitriol and calcitonin PTH regulates the concentration of calcium ions in the blood. The measurement of PTH in serum is complicated due to the PTH fragments in the bloodstream. The clinical relevance of PTH determination is related to the assessment of calcium metabolic disorders. For over 20 years PTH has been measured by various immuno assays, however the so-called intact PTH, for only around 10 years. The ideal PTH assay should show high analytical and functional sensitivity and a great specificity. The PTH assay should cover a large measuring range to support use in the very low concentration range (hypercalcemia of malignancy) as well as in the very high concentration range (prim. and second. hyperparathyroidism or chronic renal failure). We present here technical performance data generated on Elecsys@ analyzers. Method: By'using a two-side sandwich technique, (one mab reacting with a mid molecule and the other with aN-terminal epitope) the sum of these two molecules can be detected. The method is based on a recently established technology using ruthenium chelate electrocherniluminescence. Results: Short assay performance characteristics are shown in Table 1. The use of ECL technology, along with critical antibody selection and processing, yields excellent assay characteristics. Demonstrating a very high dynamic range, excellent low detection limit and very low inter-I intraassay coefficients of variation. Table 1. Interact PTH performance

P244 SERUM CROSSLAPS IN THE ASSESSMENT OF THE EFFECTS OF ALENDRONATE ON BONE RESORPTION IN POSTMENOPAUSAL WOMEN - TWO YEARS COMPARISON OF BIOCHEMICAL MARKERS J. Stepan J. Vokrouhlicka M. Michalsky 3rd Dept. of Internal Medicine, Charles University Faculty of Medicine, Prague, Czech Republic Background and objectives. The aim of the study was to assess clinical value of the degradation product of C-terminal telopeptides of Type-I collagen (CTx) in serum, measured by the CrossLaps ELISA. Methods. Postmenopausal women with lumbar spine BMD less than 2 SD below the mean for healthy premenopausal women were randomly assigned to receive oral alendronate 10 mg or placebo once daily for 1 year. All patients received alendronate on the second year. All patients received SOD mg of elemental calcium daily. Markers of bone resorption were measured in serum (CTx) and urine (N-telopeptide, NTx; hydroxyproline and galactosylhydroxylysine, corrected for creatinine). Results. There was a significant difference between the two treatment groups with respect to the mean percent change in CTx concentrations from baseline at each timepoint (Fig.). A significant negative correlation (p<0,001) was found between the % change from baseline in the lumbar spine BMD after one year and the % change in biochemical markers of bone resorption from baseline after 6 month of treatment (CTx, r=0.64; NTx, r=O.SO). After one year of treatment, a significant negative correlation was found between the % change from baseline in the lumbar spine BMD and the concentration of the marker (CTx, r=0.S3; NTx, r=O.4S, TRACP, r=0.44). Using stepwise regression analysis, CTx was the best marker to assess rates of BMD changes (F-to-Enter=18,46, p<0,001) compared with NTx (F-to-Enter=8,87, p=0,006) and to discriminate between alendronate and placebo treated patient (F-to-Enter=7 4,19, p
Assay characteristics Dynamic Range Detection Limit Function. Sens. Sample Volume Sample TAT, Turn A.T. Incubation 37°C Hook Effect Intra-Assay CV Intra-Assay CV Inter-Assay CV Inter-Assay CV Ref. Method N 1Correlation Intercept 1Slope

0-4000pg/m I O.Spg/ml 1pg/ml SOiJl Serum/plasma 20 min. 2 x 9 min. >SOOO ng/ml >3pg/mI4% >11pg/mI3% >3pg/mIS% >11pg/mI3% RIA 162/0.973 0.6pg/mI/1.01

<1> Cl

c

'"

.<= 0

#c

'" :::!E <1>

-20 -40 -60 -80 -100 12

18

24

30

Month

Conclusion: Our data indicate that the Elecsys intact PTH assay is a very sensitive, accurate and precise test with short incubation times, increased measurement range, requiring low sample volumes. In addition, atwo point assay calibration contributes to high overall user convenience.

P245 THE ACTION OF ALENDRONATE ON THE MARKERS OF BONE TURNOVER N. Eskiyurt. S. Aki, G. GOlbaba, G. AkyOz. B. Aksa~, A. Oncel Department of Physical Medicine and Rehabilitation, Istanbul and Marmara Medical Faculty, istanbul, Turkey. RIA laboratory Istanbul, Turkey The aim of this study is to evaluate the action of this drug on the bone turnover markers. The therapy group were given p.o. 10 mgs alendronate plus 1000 mgs calcium daily for six months. The control group received only 1000 mgs calcium daily for the same period. Before and at the end of the therapy period markers of bone formation (Osteocalcin, bone specific alkaline phosphatase, procollagen I) and markers of bone resorption (Urine pyridinoline, deoxypyridinoline) were measured as evaluation criterias. At the end of the therapy period prominent differences were seen only in the levels of bone specific alkaline phosphatase, pyridinoline and deoxypyridinoline. The rates of reductions in the levels of these markers in the therapy and control groups were as followed (Bone specific alkaline fosfataz; 2.9%, 1%, pyridinoline; 4.2%, 1.7%, deoxypyridinoline; 5.4%, 0.7%). Since the comparison ofthe results obtained in both groups showed a statistically significant difference in favor of the treatment group (p
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P246 CHANGES OF BONE MARKERS IN WOMEN ACROSS MENOPAUSE -

P248 PREANALYTICAL PROCESSING OF URINE SAMPLES FOR ENZYMUN-

A 3-YEARS FOLLOW-UP K.S. Tsai. S.H.J. Hsu Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan We evaluated the long-term intra-individual differences of three bone turnover markers in 117 healthy peri menopausal Chinese women over a 3-year period. These markers are serum bone alkaline phosphatase (BAP), urinary deoxypyridinoline (Dpd/cr) and urinary N-terminal cross-linked region of skeletal type 1 collagen (NTxlcr). The 53 women who were menstruating throughout the 3 years showed significant increases (36% and 30% of the baseline mean values, p=0.001 and 0.0001 respectively, paired t-test) of NTxlcr and Dpd/cr, but not BAP, in the 3 years. The 3 markers of the 24 women who developed menopause during these 3 years increased most remarkably (21 % - 42%, p<0.001 for all, paired t-test). The 35 women who already had menopause at baseline showed a significant decrease in NTxlcr, a small increase in Dpd/cr, and no changes in BAP. The level of each bone marker before and after the 3 years correlated significantly with each other in those who did not change their menstrual status (n=88, r=0.49 - 0.87, SX,y=20% - 54% of the mean baseline values, p<0.001 for each of the 3 markers) and correlated poorly in those who developed menopause during the 3 years. The standard deviation of the changes in bone marker values over the 3 years were 35% - 42% (BAP), 59% - 66% (NTxlcr), and 30% - 57% (Dpd/cr) of the baseline mean values for subjects with various menstrual status. Categorizing the subjects as high or low turnover (higher or lower than the mean), according to their bone marker levels and menstruating status, showed that overall 66% (BAP), 65% (NTxlcr), and 64% (Dpd/cr) of the categories did not change after the 3 year period. We conclude that the long-term intra-individual variation of these bone markers were large and even slightly larger than their reported day-to-day variations.

TEST® B-CROSSLAPS W. Herrmann G. Pape S. Quast Universitiitskliniken des Saarlandes, Klinisch-Chemisches Zentrallabor, 0-66424 Homburg The determination of collagen-type I fragments in urine is used for the observation and quantitative description of bone resorption processes. A spectrum of collagen fragments with different molecular sizes are determined with the presently available tests. There fore exact preanalytical conditions have to be defined in order to control absorption by urinary sediment. The goal of this study was to define an exact centrifugation procedure which rules out the influence of absorption effects. The experiments were done with Enzymun-Test® B-CrossLaps (Boehringer Mannheim GmbH) and the centrifuges Hettich Rotaxa/AP and Hettich EBA 12. A total of 12 native urine samples was investigated, 7 from healthy individuals and 5 from patients with urinary tract infections. In the tested centrifugation intensity range (206g to 10280g), 11 urines showed no significant influence of the centrifugation intensity on the test result. One urine showed a decrease in the results up to 1851g. However, at centrifugation intensities of and above 3200g, no effect was observed. It is concluded that the normal centrifugation procedure in the urine laboratory (3200g/5min) is sufficient to get reproducible results with Enzymun-Test® B-CrossLaps.

P249 THE ROLE OF BONE ALKALINE PHOSPHATASE (BAP)

P247 VALIDITY OF BIOCHEMICAL PARAMETERS IN PREDICTING BONE LOSS Z. Crncevic Orlic University of Rijeka - Internal Clinic - Endocrinology Division, Clinical Hospital Center 51 000 Rijeka, Croatia In a retrospective study of patients with senile osteoporosis we analyzed the usefulness of biochemical parameters in different disease phases. We analyzed 30 patients with senile osteoporosis before bisfosfonate (alendronate) treatment and one year later. In every patient we have measured BMD (bone mineral density) by DPX, calcium, phosphorus, magnesium in serum and urine, bone alkaline phosphatase, osteocalcin in serum and piridinoline and deoxy piridinoline in urine. There were no significant differences in values of serum and urine calcium, phosphorus and magnesium before and after treatment. Ratio Ca, P, Mg/creatinine was significantly higher before treatment (p<0,05) and showed negative correlation with BMD (p<0,05) and positive correlation with piridinolin. Multivariate analysis showed that the combination of four (Ca, P, Mg/creatinine ratio, piridinolin, deoxy piridinolin and BMD) differentiated bone content before and after alendronate therapy. Various biochemical parameters used together and with other clinical features can help to indicate bone loss.

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AS A DIAGNOSTIC MARKER OF FRACTURE REPAIR W. Herrmann S. Quast O. Haaenbouraer* I. Marzi* Zentrallabor und *Institut fUr Unfallchirurgie, Universitiitskliniken des Saarlandes, 066421 Homburg, Germany Osteoblasts playa key role in fracture-repair. Therefore we determined the BAP after trauma with or without bone injury. Patients were recruited from the department of trauma surgery and were subdivided into five groups: 1) Arthroscopy without bone participation (n=11), 2) Proximal femur fracture, treated with osteosynthesis (n= 11),3) Femur neck fracture, treated with endoprothesis (n=6), 4) Diaphysal fracture of tibia or femur (n=18), and 5) Polytrauma (n=20). Venous blood was taken as early as possible after injury and BAP was investigated in serum. Afollow up was carried out daily from the beginning over the period of hospitalization and continued during the observation period up to 12 weeks. BAP was determined as difference between total alkaline phosphatase and supernatant phosphatase activity after lectine precipitation of BAP (according to Rosalki and Foo). Alkaline phosphatase activity was measured by an automated test system on a Hitachi 717 Analyzer (all reagents supplied by Boehringer Mannheim). The comparison of BAP values one day before and at the first day after operation showed no significant difference in any group. Within the first week there was a significant decrease of BAP in all groups. After that period an increase of BAP to a maximum occurred, whereas group 1) just reached the preoperative level. All other groups expressed significantly higher values than those immediately after operation or trauma. The peak values of groups 2) to 5) were also higher than the maximum of group 1), reaching significance in groups 2), 4), and 5). In average, the earliest peak of BAP activity was seen in group 5) about three weeks after trauma, group 4) peaked last six weeks after trauma. The posttraumatic decrease of BAP can be considered as consequence of catabolic reactions within the first days after trauma. Afterwards, the increasing activity of BAP restores the status before the injury. In the bone injured groups a continuing activation of BAP producing osteoblasts is responsible for the fracture repair or the incorporation of the prothesis. The delay in BAP activation in patients with long bone fractures may be a result of prolonged fracture repair in diaphysallocalizations .

P25D FREE AND PEPTIDE BOUND PYRIDINIUM CROSSLINK SERUM AND URINARY LEVELS IN OSTEOPOROTIC POSTMENOPAUSAL WOMEN MaL. Gonzalez" MaV.Garces 2, MaT Del Camp03, ~'. MaE. Martinez3 Biochemical Division, Hospital Militar Gomez Ulla', Madrid, Spain, CIMBUC', Carabobo University, Valencia, Venezuela. BiochemicaP and Reumalology4 Divisions, Hospital La Paz, Madrid, Spain Immunoassay of urinary pyridinolines and telopeptides of type 1 collagen provide a marker of bone resorption. A serum marker of bone resorption would be desirable since it would eliminate the need to correct for urinary creatinine and might be more reproducible. We evaluated a new serum Elisa method (EIA) to detect C-telopeptide of type 1 collagen (CTXs) and we compared with urinary excretion of free deoxypyridinoline (dpd) quantified both by EIA and chemiluminescence (CLEIA) and C-telopeptide of type 1 collagen urinary (CTXu) by EIA in 249 women distributed into four groups: a) 37 healthy young women (HYW) (aged 26.2±2.5), b) 26 healthy premenopausal women (HPW) (aged 39.1±4.5), c) 53 control postmenopausal women (CPW) (aged 55.9±4.5) and d) 133 untreated osteoporotic postmenopausal women (OPW) (aged 55.1±4). Means value and (SD) for markers data are shown below:

Group

CTXs· PM/ml

CTXu IJ(J/mmolCr

dpd (EIA) dpd(CLEIA) Nmol/mmolCr nmol/mmolC

a b c d

3300(816) 1989(674)*' 2191 (782) *' 2620(1230) *'23

212(104.1) 125(52) 273.4(185.5)*2 348(205.5) *123

7.2(2.4) 4.2(1.7) 6-.6(2) 7.9(2.04) 6.5(1.8) 10.2(4.2) *'23 8.3(3.2) *'3

We conclude that TRAP and tAP can be useful screening markers, available to the most clinical laboratories, to evaluate progression of hormone replacement therapy upon bone turnover in postmenopausal women.

P252 T-SCORE AND Z-SCORE AS EXPRESSION OF BIOCHEMICAL BONE TURNOVER MARKERS MaL. Gonzalez', Ma~', MaT Del Camp03, ~'. ~', MaE. Martinez3 Biochemistry HM Gomez Ulla', La Paz3, Reumatology', La Paz Hospital, Madrid, Spain, CIMBUC2, Carabobo University, Venezuela Levels of biochemical markers of bone turnover present analytical and individual variations, such as age and menopause which may difficult their clinical interpretation. To minimize those variations, last tendencies propose to express results in terms of standard deviation units from premenopausal mean (T-score). The aim of this study was to evaluate the ability of new bone resorption markers to discriminate osteoporotic postmenopausal women when results are expressed as T or Z-score. We studied levels of C-telopeptides of type 1 collagen in serum (CTxs) and in urine (CTxu) by enzyme immunoassay and urinary excretion of free deoxvpyridinoline (f-dpd) by ELISA in 249 women distributed into two cohorts of premenopausal healthy women differentiated by age criteria: 37 women aged 26.2±2.5 (Prel) and 26 women aged 39.1±4.5 (Pre2); and two cohorts of postmenopausal women: 53 control women aged 55.9±4.5 (Post C) and 133 untreated osteoporotic women aged 55.1±4 (Post 0) diagnosed by densitometric WHO criteria. Mean values (SE) for markers and T and Z-scores derived data are shown below:

., p
P251 TARTRATE RESISTANT ACID PHOSPHATASE AS SCREENING METHOD TO EVALUATE HORMONE TREATMENT IN VENEZUELAN POSTMENOPAUSAL WOMEN Mav. Garces G. Nicita N.Brito C Callegari R.Rodrfguez M. Vassallo CIMBUC, Carabobo University, Valencia, Venezuela The aim of this study was to obtain information about the rates of bone turnover in postmenopausal women with and without hormone replacement therapy (HRT) by simple and unexpensive methods. Tartrate resistant acid phosphatase (TRAP) was determined by enzymatic method that uses paranitrophenolphosphate as substrate, in fasting blood samples within four hours after they were obtained. Total serum alkaline phosphatase (tAP), serum and urinary calcium (Ca) and phosphorus (P) were also quantified by standard techniques. Bone mineral density (BMD) was measured by DXA in the lumbar spine and proximal femur. We evaluated 699 women distributed into three groups: a) 132 healthy premenopausal women (35.7±1.8 years old). b) 187 postmenopausal women (56.1±.3.6 years old) who were following HRT during at least six months, and c) 380 untreated postmenopausal women (56.7±2.1) years old). The average time since menopause were 10.9±7.4 and 11.1±6.7 years for groups band c, respectively. Serum and urinary Ca and P did not show differences statistical significants associated to menopause or HRT. Untreated postmenopausal women showed the highest TRAP and tAP mean values (9.3±2.3U/L; 171.5±53.2 U/L, respectively) as compared to postmenopausal women who were receiving HRT (TRAP: 6.1±1 7 u/L; tAP: 153.1±48.5 U/L) (p
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Group

CTxs PM/ml

CTx, IJ(J/mmol Cr

f-dpd nmol/mmol Cr

Pre 1 Pre 2 Post C Post 0

3300 (204) 1989 (134) 2191 (117) 2621 (129)

212,02 (13,9) 125,02 (11,1) 273,73 (20,6) 347,98 (18,2)

7,3 (0,37) 6,6 (0,40) 7,9 (0,28) 10,2 (0,37)

·2,84 4,26 0,5

0,63 1,76 1,12

T-score Post C 0,3 T-score Post 0 0,93 Z-score 0,55

It is important to choose the adequate reference premenopausal women (Pre 2) to calculate T-score, because of the higher levels of markers at third decade (Prel), reflecting bone growth during this age. Levels of biochemical markers in premenopausal women (T-score) can be used as reference paints for changes in bone turnover after menopause. Nevertheless, the great influence of age and menopause on biochemical markers shows Z-score as alternative to express changes due to osteoporosis. CTxu, and f-dpd exhibited the best T-scores, but attending to Z-scores, CTxu T-score reflects changes due to age and menopause more than osteoporosis.

P253 STUDIES OF BONE TURNOVER AND MASS IN ADRENAL "INCIDENTALOMA" PATIENTS WITHOUT BIOCHEMICAL SIGNS OF HYPERCORTISOLISM M. Torlontano I. Chiodinl M. Pilerf G. Guglielmi. G. Giannatempo. S. Modoni. V. Carnevale V Trischitta and A. Scillitani Opts. of Endocrinology, Clinical Laboratory, Radiology, Nuclear Medicine, Internal Medicine; Casa Sollievo della Sofferenza IRCCS, 71013 S. Giovanni Rotondo, (FG) Italy Patients with Cushing syndrome have reduced osteoblastic activity and enhanced bone resorption. A recent study suggested a similar bone involvement, although to at a lesser extent, in patients with incidentally discovered adrenal mass (incidentaloma, I). However, since in the above mentioned study patients with biochemical hypercortisolism were included among those affected by I, it is not known whether or not altered bone turnover characterises patients with I independently from hypercortisolism. Methods: to answer this question, 20female (7 pre and 13 post-menopausal, age 53.9±13.5, BMI 28.4±4.2 kg/m2) patients with I without biochemical hypercortisolisrn (normal urinary free cortisol, rhythm of cortisol, serum cortisol response after 1mg overnight dex-suppression test) and 39 healthy women matched for age, BMI and menstrual status were studied. We measured: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked C-telopeptide (ICTP); urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr), calcium (CalCr) and hydroxyproline (Hp) corrected for creatinine; BMD by OCT at lumbar spine and by dual-X-ray absorptiometry both at lumbar spine (DXA) and at three femoral sites: Ward triangle (WT), great trochanter (TR) and femoral neck (FN). Results: AP, Hp and CalCr, (data not shown) and the other markers of bone turnover and BMD (see table) were not statistically different between patients and controls. Markers

Patients

Controls

BMD

BGP (ng/ml) PICP (J.lQ/L) ICTP (J.lQ/L) Pyr (pmol/ pmol) D-Pyr (pmol/ pmol)

5.4±2.5

7.0±3.6

aCT (mg/cm3) 165.5±48.3 151.8±48.7

Patients

Controls

119.3±35.6 118.4±46.7 DXA (g/cm')

0.94±O.16 O.99±O.15

3.4±1.2

WT (g/cm')

O.69±O.19 O.77±O.18

92.3±30.5 79.5±20.9 TR (g/cm')

O.72±D.16 0.71±O.12

18.9±6.0

O.77±O.15 O.81±O.16

3.6±O.9

17.7±6.4

FN (g/cm')

Conclusions: bone turnover and mass are normal in female patients with I and no biochemical hypercortisolism. I per sedoes not affect, therefore, the skeleton.

P254 CHANGES IN SELECTED BIOCHEMICAL MARKERS OF BONE TURNOVER AFTER SIX-WEEKS-LONG SODIUM FLUORIDE EXPOSURE FOLLOWED BY OVARIECTOMY A. Bohatvrewicz Department of Orthopaedics and Traumatology, Pomeranian Medical Academy, Szczecin, Poland The aim of the study was to investigate the effects six-weeks long sodium fluoride treatment on selected biochemical markers of bone remodelling in young growing rats followed by ovariectomy performed on 12-weeks-old animals. Seventy 6-weeks-old female Wistar rats were randomized into seven equal groups. The first baseline control group was sacrificed before the beginning of the experiment. Two groups served as controls receiving distilled water and the other groups received fluoridated water at different doses (two received 8 and two received 60 mgF/I). 30 rats were sacrificed after 6 weeks. Serum was then collected for measurement of fluoride concentration, serum total alkaline phosphatase activity (ALP) and concentration of telopeptide of rat type I collagen (ICTP). Lastthree groups were ovariectomized and received to drink only distilled water. After following six weeks all rats were sacrificed. After six weeks of experiment the group receiving 8 mg F/I showed the lowest ICTP values and the smallest decrease of serum ALP activity compared to the baseline control group. The rats with higher plasma fluoride concentrations six weeks after ovariectomy and sodium fluoride withdrawal demonstrated significantly lower ICTP concentrations and higher ALP activity than animals with lower fluoride concentrations.

P255 MULTICENTRE STUDY FOR THE EVALUATION OF ENZYMUN-TEST® N-MIDTM OSTEOCALCIN AND ENZYMUN-TEST® B-CROSSLAPSTM. INTERMEDIATE REPORT FOR THE TECHNICAL TRIAL C. Christiansen (CCBR, Ballerup), for the study group: P. Burckhardt (Lausanne), P. Delmas (Lyon), R. Fitzner (Berlin), W. Fraser (Liverpool), J. Hoffmann (Luxemburg), M. Kranzlin (Basel), A. Larsson (Uppsala), S. Papapoulos (Leiden), A. Sturk (Leiden), M. Panteghini (Brescia), H. Reinauer (Dusseldorf), P. Rizzotti (Padova). Presently a multicentre study is being performed at 12 European sites in order to evaluate the technical performance and the clinical utility of two new bone marker methods: Enzymun-Test® N-MIDTM Osteocalcin in serum and Enzymun-Test® B-CrossLapsTM in urine (Boehringer Mannheim GmbH). The technical trial has been finalised with good results. The comparability of the tested methods in all participating laboratories has been proven in a ring trial: • Intra-assay precision ranges from 1.0% CV to 2.5% CV for EnzymunTest® N-MID osteocalcin and from 3.0% CV to 5.0% CV for EnzymunTest® B-Crosslaps. • Inter-assay precision ranges from 3.3% CV to 10.0% CV for EnzymunTest® N-MID osteocalcin and from 2.3% CV to 8.4% CV for EnzymunTest® B-Crosslaps. • Linearity is given for both methods in the dynamic range (upto 150 ngl ml for Enzymun-Test® N-MIDTM Osteocalcin and up to 182 nmol/l for Enzymun-Test® B-CrosslapsTM • The lower detection limit ranges at 3.5 - 6.2 ng/ml for Enzymun-Test® N-MIDTM Osteocalcin and 2.0 - 3.3 nmol/l for Enzymun-Test® BCrosslapsTM. • Enzymun-Test® N-MIDTM Osteocalcin correlates to ELSA-OSTEO (CIS bio international), r=0.86. • Enzymun-Test® B-CrosslapsTM compares well to ELISA CrosslapsTM (Osteometer BioteCh), r=0.91. Conclusion: On the basis of these results it was decided to start the clinical part of the trial which is presently ongoing .

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P256 EFFECTS OF RENAL REPLACEMENT THERAPY ON CROSS LAPS AND OSTEOCALCIN SERUM CONCENTRATIONS H.J. Deuber. S Markau. S Niither. B. Osten Martin-Luther-University. Halle-Wittenberg. Dept. of Nephrology. Halle/Saale. Germany In patients on renal replacement therapy markers of bone catabolism cannot be determined in urine. Therefore measurement of crosslaps in serum might be a more appropriate tool for controlling bone metabolism. in these patients. In 10 patients on chronic intermittent haemodialysis before and after a dialysis session serum samples were drawn for determination of crosslaps and osteocalcin concentrations by means of ELISA (commercial kit, IBL. Hamburg. Germany). In dialysis patients crosslaps concentrations are elevated up to threefold upper normal range. Depending on kind of dialyzer minor amounts of crosslaps are removed. Osteocalcin concentrations are within normal range in these patients. In dialysis patients bone catabolism is more pronounced than bone anabolism. Both osteocalcin and crosslaps concentrations are influenced marginally by dialysis.

OTHER DIAGNOSTIC TESTS P257 SPINSHAPE: A PC-BASED WORKSTATION FOR VERTEBRAL MORPHOMETRY AND FRACTURE ANALYSIS K. Engelke'. W. Kalender'. L....Bi!!ID:' •.s...zt!rulo'. D. Felsenberg2 'Inst. of Medical Physics. Univ. of Erlangen. Germany. 2Klinikum Benjamin Franklin. Freie Univ. Berlin. Germany Purpose: To develop an easy-to-use and flexible tool for spinal fracture assessment in longitudinal and cross-sectional studies using digitized thoracic and lumbar x-rays. Methods: Spinshape runs under Windows 95 on standard Pentium based PCs. Up to four digitized AP and/or lateral x ray films can be visualized simultaneously. although analysis is performed on the lateral films. only. Spinshape provides two analysis modes: 1. 6-point morphometry can be performed. and 2. semi-quantitative grading can be applied to each vertebra. Also. labels denoting vertebral levels can be assigned. Generated results can be imported into Microsoft EXCEL for further analysis or transferred to relational databases. Results: Reading images into Spinshape is fast: 15s for 4 2Mbyte images (700*1700 pixel. 16 bit) on a 133MHz Pentium. All analysis tasks can be performed on magnified images. Special image processing routines allow reducing the effect of overexposed areas on the x-ray films. Analysis results are stored with the x-ray films and can be redisplayed on the films. Contrary to digitizing tablets. potential operator errors during 6-point morphometry can therefore be more easily traced and corrected. The sequence of analysis steps is flexible. e.g. labeling can be performed before or after 6-point morphometry. Conclusions: Digital spinal fracture assessment offers advantages as analysis results can be stored and red is played on the x-rays and because image processing may facilitate fracture morphometry and grading. A PCbased solution is cost effective and can be used without special hardware.

P258 ULTRASOUND PARAMETERS IN THE FOLLOW UP OF OSTEOPOROTIC WOMEN TREATED WITH ESTROGEN S. Gonnelli C. Cepollaro. C. Pondrelli. A. Montagnani. D. Bruni. R. Monaco. C. Gennari Institute of Internal Medicine. University of Siena. Italy Speed of sound and broadband ultrasound attenuation of ultrasound in bone have been proposed as alternatives to radiation-based methods for the quantitative assessment of osteoporosis. We have previously shown that speed of sound (SOS). broadband ultrasound attenuation (BUA) and Stiffness (S. which is an index derived from the combination of SOS and BUA values). are able to monitor osteoporotic patients treated with salmon calcitonin. The aim of the present study was to evaluate the ability of US parameters for monitoring osteoporotic patients treated with estrogen. We studied 80 osteoporotic women (age range 49 60 years): 40 of them were treated for 2 years with estrogen and calcium (Group 1); 40 patients were given only calcium (Group 2). At baseline and after 1 and 2 years we measured BMD at lumbar spine by DXA (Hologic QDR 1000) and SOS. BUA and Stiffness at the os calcis. by Achilles (Lunar Corp.). In Group 1 BMD increased by 3.21 %. SOS by 0.26%. BUA by 1.14% and Stiffness by 2.86%. Instead in Group 2 all parameters decreased (BMD -1.71%. SOS 0.44%. BUA -2.64% and Stiffness -4.80%). The differences between groups were significant (p<0.01) for all parameters. At the end of the study period percent changes in BMD and in US parameters significantly correlated (p
P259 AGREEMENT BETWEEN DIAGNOSIS OF OSTEOPOROSIS USING DUAL X-RAY ABSORPTIOMETRY (DXA) AND QUANTITATIVE ULTRASOUND (QUS) WITH THE DTU-ONE Eo Piessel T Fuerst C. Njeh S. Cheng H. Genan!. Osteoporosis & Arthritis Research Group. University of California. San Francisco. USA The agreement for the diagnosis of osteoporosis was investigated for DXA in the femur and QUS measurements of Broadband Ultrasound Attenuation (BUA) in the heel using the DTU-one (Osteometer MediTech. Denmark). 130 women (59 yrs±14 yrs. 30 to 84 yrs) were scanned. Osteoporosis was defined as low BMD based on T-score <-2.5 using NHANES reference data at the four regions of the femur (neck. Total. trochanter. Ward·s). as well as low BUA (T-score <-2.5 SD. DTU-one reference data). The diagnostic agreement between QUS and DXA as well as between DXA regions within the femur was determined by calculating percentage agreement and Kappa scores. Linear regression was performed to determine correlation between the different measurements. The prevalence of women with aT-score <-2.5 in BUA was 23%. Correlation. percentage agreement and Kappa scores (k) between BUA and BMD for T-scores <-2.5 are given in the table. as well as the prevalence of osteoporotic women with low BMD at different sites within the femur

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Femur regions

neck

total

trochanter

Ward's

Prevalence Correlation Agreement K score

16% 0.68 84% 0.49

12% 0.69 81% 0.34

6% 0.60 8-% 0.24

32% 0.66 81% 0.52

There was a moderate to good agreement (although widely varying prevalence) at different regions within the femur (75% to 95%. k=O.4 to 0.7). The agreement between BUA and DXA was moderate for the neck and the Ward's region (k=0.5). and poor for the Total and the trochanteric region (k=0.2 to 0.3). QUS results by the DTU-one differed significantly from DXA. some disagreement was also found among the regions of the femur. However. both techniques have generally proven ability to predict fracture. Further investigation ofthe DTU-one is required to clarify its role in clinical application .

P26D IS THE DIFFERENCE BETWEEN ARMSPAN AND HEIGHT USEFUL IN DETECTING VERTEBRAL DEFORMITIES? R.G.J.A. Versluis', H. Petri', C.M. van de Ven', A.B.J. Scholtes 3, E.R. Broerse M.P. Springer', S E. Papapoulos' 'Dept. of General Practice, 'Endocrinology, Leiden University Medical Centre, 'Merck Sharp & Dohme, The Netherlands, 3General Practice 'Wantveld', Noordwijk, The Netherlands Vertebral deformities are an independent risk factor for new fractures, but only 1/3 of these are symptomatic. We investigated whether vertebral deformities can be detected in practice using a simple method measuring the difference between armspan and height. Acohort of 494 postmenopausal women was randomly selected from a large general practice. Height and armspan were measured and vertebral morphometry of lateral spine radiographs was performed using the method of Eastell. Both height and armspan decreased significantly with age. The correlation between armspan and height was 0.83. Vertebral deformities were present in 32.7% of the women; 22.4% had grade I and 10.3% grade II vertebral deformities. Only the prevalence of grade II vertebral deformities increased with age. A large interindividual variation of measured differences between armspan and height was found. The ranges for the groups with or without grade II vertebral deformities had substantial overlap. However, the difference in means was small between those groups (1.6-cm) and could not differentiate between women with and without vertebral deformities. In conclusion, vertebral deformities cannot be detected by measuring the difference between armspan and height in postmenopausal women.

P261 THE UTILITY OF THE SCORE OSTEOPOROSIS PRE-SCREENING INSTRUMENT H. Kaessmann J. Holzmannhofer G. Galvan Institute of Nuclear Medicine and Endocrinology, General Hospital Salzburg, Austria. Because the assessment of bone mineral density is still limited due to various factors (availability, cost etc.) there is a need for tools to aid identification of postmenopausal women with low bone mineral density levels. For this reason Abbott et al. undertook the development and validation of a questionnaire called SCORE (simple calculated osteoporosis risc estimation). They reported a sensitivity of 0.89/0.91 (developmenV validation cohort) and a specificity of 0.50/0.42 in identifying postmenopausal women with low bone mineral density at the femoral neck. Aim of our study was to look for the utility of this simple and cheap approach to optimize the use of bone densitometry in our osteoporosis unit. We included 316 periand postmenopausal women (age 45-89, mean 58.6) who were referred to our institution for bone mineral measurement (Hologic QDR1000W 130 pat. and Lunar DPXalpha -.186 pat.). Additional to our standard questionnaire we asked women to fill in the SCORE sheet. We excluded women with conditions prohibiting measurement of bone mineral density by, dual x-ray absorptiometry and women with drugs effecting bone mineral density others than estrogens to get conditions close to I the development cohort. We also included measurements at the lumbar spine (L 1-L4). Results:

femoral neck

lumbar spine

Low BMD (T <2SD) Sensitivity Specificity

125 pat. (39%) 0.88 0.29

155 pat. (49%) 0.90 0.35

P262 RELATIONSHIP BETWEEN MUSCLE VOLUME AND CORTICAL BONE AREA USING MAGNETIC RESONANCE IMAGING (MRI) C. Jung G. Wilhelm, J. Rittweger S. Majumdar* D. Felsenberg Osteoporosis Research Group, Dept. of Radiology, University Hospital Benjamin Franklin, Free University, Berlin, Germany, *Dept. of Radiology, University of California San Francisco, USA Maximal evoked loads lead to a modulation of the bone. We performed this study, to examine the effect of the muscle volume on the geometric evolvement of the bone. Therefore, we determined the relationship between muscle volume ofthe lower leg, muscle cross section area, bone cross section area an,d periostal and endostal circumference of the tibia using MRI. A total of 39 subjects (19 male, 20 female) ages ranging from 22 to 68 were studied. MR images of both lower legs were obtained using a 1.5 Tesla MR scanner (axial sections 1 cm thick from ankle joint to knee at the resolution of 0.125 cm, 3 0 gradient echo sequence, TR of 26.0 msec, TE of 6.0 msec and flip angle of 40 degrees). The images were processed using a semiautomated contour tracking and threshold based segmentation algorithm to define the cortical shell, muscles, and tendon. The total muscle volume of the lower leg was calculated. At 4% of the tibia length, starting at the ankle jOint, the cross section area of the achilles tendon and cross section area of the tibia were measured. At 14%, 33% and 66% of the tibial length the cross section area of the muscle, the cortical area and the periostal and endostal circumference of the tibia were measured, too. The correlation of the muscle volume and muscle cross section area measured at 14% of the tibia length is r=0.6, at 33% r=0.71 and at 66% r=0.95 (p
As the above results indicate there is a very high sensitivity in identifying women with true low bone density comparable to that of the development and validation cohort but a much lower specificity in classifying women who do not have low bone density. The reason for the clear difference in specificity might be a larger proportion of peri menopausal women in our group (mean age 58.6 vs. 62.5). Despite the low specificity (in our study) we think SCORE is a useful method and can be used as a prescreening tool to identify postmenopausal women likely to have low bone mass and to reduce the number of unnecessary bone density tests .

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P263 RADIOACTIVE FRACTAL ANALYSIS OF TRABECULAR BONE TEXTURE: DIAGNOSTIC VALUE IN OSTEOPOROSIS I. Pothuaud E. Lespessailles R. Harba R. Jennane C.L. Benhamou CHR ORLEANS, LESI UNIVERSITE D'ORLEANS - FRANCE Characterization of bone architecture remains a difficult issue. We have validated a fractal analysis of trabecular bone texture on calcaneus radiographs. The result is expressed by Hmean (Hmean =2 - fractal dimension). In this study 39 women with osteoporotic (OP) vertebral crush fractures (68.0±10.8 years) were compared to an age-matched control group of 39 women (68.0±1 0.7 years). Discriminant value of fractal analysis and bone mineral density measurement at the femoral neck (FNBMD) and trochanteric region (TRBMD) was assessed using Receiver Operating Characteristic (ROC) curves. Hmean value was 0.691±O.050 in OP cases versus 0.739±O.024 in control cases while FNBMD value was 0.598±O.113 g/cm' versus 0.645±O.109 g/cm' and TRBMD value 0.512±O.10B g/cm' versus 0.594±O.106 g/cm'. The statistical significance of Hmean test (p
P264 COMPLEXITY OF BONE ARCHITECTURE: A NEW METHOD TO ASSESS STRUCTURE W. Gowin', P. Saparin', J. Kurths', D. Felsenberg' 'Osteoporosis Research Group, Dept. of Radiology, Univ. Hospital B. Franklin, Free University Berlin, 'Institute of Theoretical Physics, University of Potsdam, Germany The assessment of the complexity of the structure of composite materials evaluates its architecture ina holistic fashion. The composition as well as the interactions of the composite are quantified rattier than its parts singularly. This study demonstrates the value of complexity assessment of the architecture of human vertebrae and offers a new tool for the determination of bone integrity. We examined 100 human lumbar vertebrae (L3 and L4) and introduced five indices to describe the complexity of the trabecular bone architecture. Continuous 1 mm thick axial slices were obtained in high-resolution mode on aCT-scanner (Somatom Plus S, Siemens AG). QCT-assessment followed to determine the BMD on the scanner. The images were transformed into symbol encoded images, following the rules of symbolic dynamics. Measures of complexity were employed. The Index of Global Ensemble (IGE) evaluates the dynamics of the structure, the Structure Complexity Index (SCI) is an expression of the homogeneity of the architectural elements, the Trabecular Net Index (TNI) informs about the richness of trabecular connections, the Structure Disorder'lndex (SDI) determines the order/disorder of the architecture, and the Maximal L-Block Size is a measure of soft tissue participation. All measures of complexity relate exponentially to BMD. The sensitivity to change is more the 10 times increased compared to BMD, indicating the importance of the architecture of the bone for its integrity. This new method is the first non-invasive holistic radiological assessment of the bone's architecture. Preliminary evaluations of patients demonstrate its value.

P265 AUTOMATIC ASSESSMENT OF VERTEBRAL WIDTH ON DIGITIZED IMAGES USING THE SIX POINTS OF MORPHOMETRIC INDICES A. Zadeh Khorassani G. Armbrecht A Boshof W. Gowin D. Felsenberg OsteoporOSiS Research Group, Dept. of Radiology, Univ. Hospital B. Franklin, Free University of Berlin, Germany Quantitative radiological assessment of vertebral bodies evaluates the vertebral heights and several indices. This morphometric procedure disregards qualitative information, such as differential diagnostic considerations. The inclusion of the vertebral width expands the use of vertebral indices and allows for further differentiation of vertebral deformation. We developed a new software, that calculates the vertebral width in digitized lateral images of the lumbar and thoracic spine automatically. Using the locatien of six pOints for morphometriC measurement of the vertebral heights two lines for the upper and lower end plates of each vertebral body are calculated. The bisector of both lines is found and set at the middle of the posterior height (P1). The point of intersection between the bisector and the anterior height is found next. From this point and along the bisector the algorithm searches for a vertical anterior edge in the image. We define the distance between P1 and the anterior edge of the vertebral body as the vertebral width. Using this method we measured the vertebral widths of 124 females with degenerative deformities from the EVOS study and compared the results with the manually measured values. The comparison shows a good agreement (kappa-score approx. O.B) of both methods.

P266 LEUKOCYTE REDOX AND HYDROLITICAL ENZYMES ACTIVITY IN POSTMENOPAUSAL OSTEOPOROSIS O.P. Kuznetsova', L.A. Marchenkova', A.V. Dreval" IA Komissarova', Ya.A. Nartsissov' 1-Moscow Regional Research Clinical Institute, 129110, Moscow, Russia. 2-Medical Scientific & Production Complex "Biotics", 113452, Moscow, Russia The aim of study was an investigation in peripheral blood leukocytes metabolism in postmenopausal women who had not previously received estrogen and to assess effect of hormone replacement therapy (HRT) on bone turnover and leukocyte activity. Methods. We examined 53 postmenopausal women (1-15 yr. after menopause): 43 women with postmenopausal osteopenia or osteoporosis (osteoporosis group) and 10 ones with normal bone mineral density (BMD) - control group. BMD was measured in lumbar spine and proximal femur by dual energy X-ray absorptiometry. We studied activities (index Keplow) of succinate dehydrogenase (SDH) and succinate cytochrome C oxidoreductase (SCCOR) in peripheral blood lymphocytes, activities of alkaline phosphatase (AP) ,and mielo peroxidase (MP) in peripheral blood neutrophils measured: cytochemically in vitro. Results. There were no significant differences in MP and SCCOR activities between osteoporosis and control groups. The AP activity in control group (17,20±4,47) was significantly lower then in osteoporOSiS group (47,57±6,75) and significantly lower in women of 1-B yr. after menopause (30,50±6,45) then in women of 9-15 yr. after menopause (60,69±9,91). The SDH activity in control group (17,20±0, 77) was significantly lower then in osteoporosis group (22, 17±1 ,05). The AP activity revealed a negative correlation with spinal BMD, and T-score (P<0,05). The SDH activity revealed a negative correlation with femoral neck BMD (P<0,05). There was no revealed any correlation AP and SDH activities with neither age nor postmenopausal age. 25 women from osteoporOSiS group received HRT (CLIMEN or GYNODIAN DEPOT (SCHERING AG)) for 6 month. BMD gain in lumbar spine (1,17±O,7B%) and in femoral neck (1 ,32±O.64%) statistically insignificantly. Changes at the MP activity showed positive correlation with changes at spinal BMD (P<0,05). BMD in control group declined of -4,64±O,B% (P<0,05). Conclusions. The AP activity in neutrophils and SDH activity in lymphocytes increased in postmenopausal osteoporosis. We speculated that activities of these enzymes may serve as contributing factors for the acceleration of bone loss in postmenopausal osteoporosis .

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P267 ALTERATIONS OF QUANTITATIVE AND QUALITATIVE PARAMETERS OF BONES FOLLOWING INFLAMMATION MEDIATED OSTEOPENIA IN RATS A.F. Michailidis H. Sdrenias K. Kavadias. G. Papavasiliou. I. Dontas G.V. loannidis. G.P. Lyritis Laboratory for the Research of Musculoskeletal System, KAT Hospital and MRI Laboratory of "Dimokritos" National Center of Physics Research, Greece Introduction: The purpose of the study was to identify the bone loss with two quantitative and two qualitative methods. Material and methods: Sixty male Wistar rats, aged 15 weeks, were included in a placebo-controlled study. The animals were divided in two groups. In the first group, a non-specific irritant (magnesium silicate), was injected i.m daily for a period of three weeks, while in the second group, nothing was administered and served as control. Two weeks later the animals were sacrificed and the femurs were isolated. Bone properties in both groups were estimated using: 1) Single Photon Absorptiometry (SPA) method, using a SP2 machine with radioactive source of 1'25, 2) Histomorphometry, measuring the total bone volume (%) on nondecalcified sections, 3) Three-point bending, using a 20KN power machine in order to provide strength-strain graphs and 4) Nuclear Magnetic Resonance (NMR), using a Home Built NMR spectometer 0,5 Tesla (32Mhz) applicating the spin-echo technique. Results: Concerning SPA measurements for BMD, significant differences between the two groups were found (p
P268 QUANTITATIVE ULTRASOUND OF THE FINGER PHALANGES OF CHILDREN WITH DISORDERS OF GROWTH AND PUBERTY A. Angelow, R. Barkmann C.-J. Partsch* w.G. Sippell* C.C. GIOer Osteoporosediagnostik Kiel, Klinik fOr Radiologische Diagnostik, *Klinik fOr Allgemeine Padiatrie, Christian-Albrechts-Universitat zu Kiel, Germany Growth disorders may affect the density and quality of bone. We wanted to investigate the impact of pathological skeletal status on Quantitative Ultrasound (QUS) measurements at the proximal finger phalanges and test if velocity results are affected if bone age differs from chronological age. Methods. AD-SoS was measured at the phalanges of 65 children (42; female, 23 male, age 5 to 17 affected by different disorders of growth and puberty using the IGEA DBMSonic 1200. Bone age was determined within 1 year before or after the QUS measurement date. Results were compared with German normative data from Rohrschneider et al. (1997). Based on examination of 14 healthy children (8 female, 6 male, age 6 to 11) an offset of our device of appro 1 population standard deviation was observed and corrected for. We calculated the differences between patient data and normative data relative to chronological as well as bone age and expressed them as Z-score values. Results. Distinct differences in velocity data between different growth disorders were observed. Deviations from normative data were smaller if Z-scores were based on bone age rather than chronological age. Table: Velocity deviations of different illnesses expressed as Z-scores

Tall stature Short stature Neurosecretory dysfunction Precocious puberty Turner syndrome

Number Z-score for chronological age bone age

Z-score

16 21 17 6 5

0,0 0,0 -0,2 -0,7 -1,8

0,0 -0,5 -1,1 0,2 -2,2

Conclusion. The small sample size and the preliminary correction factor for our device have to be considered when interpreting these data. If confirmed in larger groups, QUS measurements at finger phalanges may become a useful radiation free tool for the assessment of bone density and quality in patients with growth disorders.

P269 IMPROVED QUS MEASUREMENTS OF THE FINGER PHALANGES IN RHEUMATOID ARTHRITIS P. Riipen R. Barkmann C.C. GIOer Osteoporosediagnostik Kiel, Klinik fOr Radiologische Diagnostik, Christian-Albrechts Universitat zu Kiel, Germany Preliminary results have indicated that Quantitative Ultrasound (QUS) measurements at the finger phalanges are useful not only for the assessment of osteoporosis but moreover might be sensitive to rheumatoid arthritis. In standard mode the DBMSonic 1200 measures QUS parameters at the metaphysis of the phalanx. Rheumatoid arthritis affects the joint earlier than the metaphysis of the finger. We investigated whether ultrasound transmission directly at the PIP jOint is useful for the assessment of rheumatoid arthritis. Methods. 17 patients with RA were measured in comparison to an agematched control group of 21 vasculitis patients. Because patients in both groups were treated with steroids, the impact of rheumatoid arthritis on the bone structure of the joint could be in part separated from the impact of steroid treatment. In addition to AD-SoS, new QUS parameters extracted from the signal received were investigated. Analogous to calcaneal measurements we introduced a "Broadband Ultrasound Attenuation" (BUA). In the signal received two types of waves could be discriminated by their arrival time. We calculated the area under the "fast wave" and the width of the "fast wave". In addition to the velocity parameter AD SoS we calculated the phase velocity and the velocity of the very first part of the wave. Results. All parameters discriminated between the two groups at a level of significance of p<0.02. Best were AD-SoS (p<0.002) and BUA (p
e..,

P270 COMPARATIVE ASSESSMENT OF PRECISION OF QUANTITATIVE

P271 CROSS-CALIBRATION OF THE DBM SONIC 1200: QUALITY

ULTRASOUND IMAGING VERSUS NON-IMAGING DEVICES R. Barkmann C.C. GlOer Osteoporosediagnostik Kiel, Klinik Hir Radiol. Diagnostik, Christian-Albrechts-Universitiit zu Kiel, Germany Quantitative Ultrasound (QUS) instruments measuring the calcaneus are useful for the assessment of osteoporosis. But systems using fixed transducers do not exactly measure the same anatomical region for every calcaneus. This may affect the diagnostic sensitivity and precision of this method. QUS imaging devices have been introduced to overcome these limitations. One has to consider, however, that differences in the construction of the devices, e.g. focused transducers and moving parts of the scanning system, might induce new errors. We compared both methods with regard to precision and intercorrelation. Methods. 80 subjects (age 24 to 83, 64 female, 16 male) underwent QUS measurements on both the DMS UBIS 3000 (imaging system) and the lunar Achilles+ (fixed transducers) on the same day. A subgroup of 32 subjects was measured twice on both devices. The sequence of measurements was randomly changed from subject to subject. We calculated the correlation of BUA and SOS between both devices and the precision errors. In a subgroup of 60 women, age 45 to 83, we calculated the age dependant slope of the parameters of both devices. To compare the longitudinal sensitivity of measurements adjusted precision errors were obtained by multiplication of the precision error with the response ratio, i.e. the ratio of the slope of BUA of the Achilles+ and the slope of the technique investigated. A new method of soft tissue correction was tested for its ability to improve the preciSion of the UBIS (UBIS i). Results. Correlation coefficients were R'=0.76 for BUA and R'=0.87 for SOS. Results for precision errors, age related slopes and precision errors adjusted to levels of BUA of Achilles+ are listed in the table: BUA Achilles

UBIS

UBIS i

SOS Achilles UBIS

Prec. error / % Slope / %/yr. adj.Prec.err.l%

1.59 0.45 1.6

1.29 0.33 1.8

0.98 0.33 1.3

0.17 0.08 1.0

ASSURANCE PROCEDURES FOR QUANTITATIVE ULTRASOUND MEASUREMENTS R. Barkmann C.C. GIGer Osteoporosediagnostik Kiel, Klinik Hir Radiologische Diagnostik, Christian-Albrechts-Universitiit zu Kiel, Germany Accurate diagnosis of bone status requires validated device-specific reference data and appropriate methods for cross-calibration of measurement devices. For the cross-calibration phantoms that yield results similar to patients need to be developed. For Quantitative Ultrasound (QUS) there is only limited experience with QUS phantoms to date. We investigated the performance a newly developed cross calibration phantom for QUS measurements of the finger phalanges. Methods. The phantom was developed by IGEA (Carpi, Italy) for use with the IGEA DBMSonic 1200 device. Measurements were carried out on 2 devices of this type. The phalanges II to V of a group of 25 children and young adults (age 7 to 23) were measured once on each instrument, while the phantom was measured 20 times on each instrument. Results. Mean difference between the two instruments, %CV and %standard error of the mean WaSEM) were very similar at levels of 1.2%, 0.7%, and 0.1% (p
UBIS i 0.46 0.08 2.6

0.28 0.08 1.6

Conclusions. Both devices show similar performance for BUA and are highly correlated for BUA and SOS. Best precision was obtained for SOS of the Achilles+. Further research on long term preciSion and diagnostic sensitivity of imaging and non-imaging devices is needed.

P272 COllAGEN SPl POLYMORPHISM IN WOMEN WITH COllES FRACTURE M. Weichetova J. Stepan M. Michalsky 3rd Department of Internal MediCine, Charles University Faculty of MediCine, Prague, Czech Republic Background: Osteoporosis is a disease with a strong genetiC component, but genes responsible for a control of bone metabolism are not exactly defined. However, recent studies have shown that the polymorphic Spl binding site in the first intron of the collagen type I gene can determine bone mineral density and vertebral fracture risk. The aim of the study was to test the hypotheSiS that the COllA 1 Spl polymorphism is a determinant of the Colles fractu re risk. Methods: 33 postmenopausal and 59 of the same age (control group). COLIAl Spl genotype was investigated by PCR analysis of genomic DNA extracted from peripheral blood samples from 33 postmenopausal Czech women aged 55 to 70 years who suffered the Co lies fracture up to 2 years ago. The control group consisted of 59 age-matched non-fracture postmenopausal women. Spine and femoral neck BMD was measured using DEXA (QDR 4500, Hologic). Colles fractures were confirmed by X-ray. Results. The following COLIAl Spl genotype distribution was observed in the studied population: Colles fracture group:

SS 54.55%,

Ss 45.45%,

ss 0.00%

Control group:

SS 69.49%,

Ss 30.51 %,

ss 0.00%

The Ss genotype was over-represented in Colles fracture group, although the inter-group difference was not statistically significant. No significant difference between the groups was found in spine BMD T score (Colles fracture: -1,9206, controls: -2,2553), but the femoral neck T score was significantly lower (-2.63) in the fracture group compared with the controls (-1.88) (p<0,05). Conclusion. The Ss genotype is over-represented in the group of postmenopausal women with Colles fracture. A larger population is needed to assess statistical significance of this observation .

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P273 CONCEPT AND GUIDELINES FOR ASSESSING SKELETAL CHANGES C.C. GIUer Osteoporosediagnostik Kiel, Klinik fOr Radiologische Diagnostik, Christian-Albrechts-Universitat zu Kiel, Germany There is still substantial confusion about the interpretation of measured skeletal changes: Statistical fluctuations are mistaken as real changes (problem 1), follow-up measurements are scheduled too early (problem 2), and a confusing number of insufficient methods for standardising precision error (inc!. %CV) have been used (problem 3). We propose a comprehensive concept to describe a technique's ability to monitor skeletal changes applicable for practical use by clinicians. Methods. The concept: Given a technique with a long-term precision error (PE) and a median longitudinal response rate (LR). The following solutions are proposed for the 3 problems. Problem 1: Changes need to exceed the "Clinically Relevant Change" (CRC), given by 20PE. Problem 2: Patients should be called in after the "Monitoring Time Interval" (MTI), given by 2 0 PE I LR . Problem 3: A technique A is superior to a reference technique Rif it has a significantly smaller Adjusted Precision Error(adjPE), given by PE 0 LR(R)/LR(A). An adjustment of technique A specifically to BMD of PA-DXA of the spine (DXAsp) is termed "Standardised Precision Error" (sPE) which can then be used universally to compare the performance of any two techniques. Results (hypothetical examples, adjPE exemplarily adjusted for SOS): Method

PE

LR

CRC

MTI

adjPE(A\SOS)

sPE

DXAsp DXAfn BUA SOS

1.5% 2.0% 3.0% 0.5%

3.0% 2.0% 2.5% 0.3%

3.0% 4.0% 6.0% 1.0%

1.0 yrs 2.0 yrs 2.4 yrs 3.3 yrs

0.15% 0.30% 0.36% 0.50%

1.5% 3.0% 3.6% 5.0%

Discussion: All three parameters have intuitive meaning: for clinical decision making changes exceeding CRC are required; in the majority of patients this will not happen prior to MTI; when comparing techniques sPE can be easily interpreted since it yields results adjusted to the level of precision errors of DXAsp: an sPE of 1-1.5% or less is fairly good, because it equals the precision of DXAsp. Compared to previous concepts sPE is less affected by subject selection bias. Conclusion: A comprehensive assessment of the longitudinal sensitivity of a technique based on CRC, MTI and sPE yields a good characterisation of a technique's ability to monitor skeletal changes.

P274 EVALUATION OF STELLATE GANGLION BLOCKAGE AND SALMON CALCITONIN TREATMENT IN REFLEX SYMPATHETIC DYSTROPHY SYNDROME (RSDS): ASSESSMENT WITH CLINICAL FINDINGS AND FOUR PHASE BONE SCINTIGRAPHY N. Ta~ G. Ozonel T. Atasever A. Babacan F. AzizoQlu B.S. Yurtlu Gazi University Medical School Physical Medicine and Rehabilitation, Nuclear Medicine, Anesthesiology and Reanimation Departments Ankara - Turkey Objective: This study aimed to evaluate and compare RSDS patients treated with salmon calcitonin (sC) and stellate ganglion blockage (SGB) using quantitative Tc-99m MDP bone scintigraphy and clinical findings. Methods: A total of 25 patients of having RSDS of the hands and/ or feet were evaluated. All of the patients had stage 1 or stage 2 disease. 15 patients were treated with 100 IU of sC and 1000 mg calcium (Group 1), other 10 patients treated with anterior SGB I (Group 2) twice a week for four weeks. Clinical symptoms including pain swelling temperature difference and impairment of joint motion were graded and evaluated three times with two weeks interval (0., 2., 4. weeks). Four phase (dynamic, early and late blood pool and bone phase) bone scintigraphy were obtained before and after therapy (0., 4. weeks). Bone scans were quantitatively evaluated by defining regions of interest from the affected bones and contralateral regions. Mean counts of ROls were measured and Lesion/Nonlesion (UN) ratios calculated. Pre and post-therapy UN ratios were compared. Results: Both sC and SGB treatment groups showed clinical improvement. Pre and post-therapy scintigraphies also showed improvement (decreased activity) in each group. In five patients we found better scintigraphic results in further scintigraphies obtained three months after the first evaluation. Conclusion: These findings suggested that both sC and SGB are effective in the treatment of RSDS. Although Tc-99m MDP scintigraphies obtained

1 month after the beginning of the therapy showed improvement, the results of the limited number of patients that we performed a third scintigraphy at three months after the therapy gave more objective and favorable results.

P275 ON THE APPLICABILITY OF X-RAY MICROANALYSIS IN OSTEOLOGY C. GUnther P.M. Wilde, H. Sprenger A. Kapner H. KieBlina German Centre of Osteoporosis Prevention, Therapy and Rehabililation of Johannesbad Clinic, Bad FUssing, Germany. Institut of cristal growth, Berlin-Adlershof, Germany An exact distinction between bone and osteoid is an important histological problem in osteology. Hence, conventional staining methods involve difficulties also in quantitative proof of bone-foreign substances which could playa role in the pathogenesis of any osteopathy e.g. aluminium in renal osteopathy. Using x-ray microanalysis on 20 micro thick undecalcified iliac crest biopsies in patients with renal osteopathy we tried to distinguish clearly between bone and osteoid and to estimate quantitatively the included aluminium. In addition to backscattered electron micrographs, point analysiS and line scans we used an area scan controlled multi-step-scan to make visible the distribution of small element amouts. Our results show that these methods are suitable for a clear distinction between bone and osteoid. Further, the distribution, location and semiquantitative estimation of all elements with ordinal numbers from 6.C to 92 U (e.g. Ca, P, Mg etc.) could be demonstrated. Thus a more improved equipment and higher sensitivity of detection makes this method useful in environmental, forensic and industrial toxicology of human bone.

P276 INFLUENCE OF AGE AND SEX ON VERTEBRAL SHAPE INDICES ASSESSED BY RADIOGRAPHIC MORPHOMETRY F. Grados P. Fardellone M. Benammar C. Muller, !.L. Sebert. Department of Rheumatology, CHU Amiens, FRANCE Vertebral shape indices (VSI) assessed by radiographic morphometry are currently used to define vertebral deformities in clinical trials and epidemiological studies on vertebral osteoporosis. The aim of this study was to assess the influence of sex and age on VSI in order to better define reference values forthe clinical and epidemiological evaluation of vertebral osteoporotiC deformities. Measurements were performed on thoracic and lumbar spine radiographs in 50 men and 50 women (age range: 25 to 75 years) without evidence of osteoporotic, degenerative or other disease-related vertebral deformity. Two different statistical analysis were used to evaluate the effect of ageing on VSI: correlation using linear regression analysis and comparison olthe mean ofVSI in the 25-50 years and 50-75 years age groups assessed by Student's t-test. The effect of sex on VSI was studied by compariSon of the mean ofVSI, assessed by Student's t-test in the 25 men and 25 women under fifty years of age. Wedging and concavity especially at the mid and lower thoracic spine increased significantly with age in both sexes. The influence of age on VSI demonstrated in our cross-sectional study can be related to age per se or can be explained by a cohort effect due to different physical activities or different diet in new generations. It cannot be explained by the trend toward greater adult peak height over the past several decades since VSI are independent of body height. We also demonstrated that VSI especially at the mid and lower thoracic spine were significantly dependent on gender with greater values of wedging and concavity in men than in women. Consequently, reference values used for the definition of vertebral osteoporotiC deformities assessed by radiographic morphometry should take into account both sex and age effects.

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P277 COMPARISON OF VERTEBRAL HEIGHTS IN EUROPEAN AND AMERICAN STUDY POPULATIONS. y. Lu" C. Roux', J. Fechtentaum', S. Zhao" ~" .c.Jllli3, A. Rouillon 3, C. van Kuiik" Uuerst, H.K. Genant' 1Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, CA, USA, 2. Centre d'Evaluation des Maladies Osseuses, Cochin Hospital, Rene Descartes University, Paris, France, 3. Sanofi Research, Malvern, PA. USA The purpose of the study was to investigate whether there are differences in vertebral heights and their ratios between European and American patients. Baseline data of 448 European (age=62±6.S8 years) and 399 American (age=63±6.81 years) post-menopausal Caucasian women were selected from a clinical drug trial. All the women had T-scores below -2 for AP spine BMD and showed no prevalent fractures per adjudicated semiquantitative evaluation ofthe spinal radiographs. Quantitative morphometry (QM) of vertebrae (T,-L,) was performed by operators from two quality assurance (QA) centers. Anterior, middle and posterior heights (Ha, Hm, Hp) and their corresponding ratios (Hap, Hmp, Hpu, Hpl) were calculated for all patients. Ageneral linear model was employed to compare the heights and ratios between two groups after adjustment for body height. The average inter-observer precision of QM (root mean square of coefficient of variation) were 3.S% for US center and 3.6% for European center. Mean and standard deviation of body height (Ht) and vertebral heights and ratios are shown in the Table. Average percentage differences of the mean between the two groups were 1.S% for vertebral heights and 1.1 % for vertebral height ratios before the subject's height adjustment (Diff%), and 1.8% for vertebral heights and 0.9% for vertebral height ratios after height adjustment (Ht adj%).

Conclusion: It is possible to screen asymptomatiC postmenopausal women with a simple clinical test that identifies those that are prone to osteoporosis with a high sensitivity.

.!.JJ"

Ht(SD) Ha(SD) Hm(SD) Hp(SD) Hap(SD) Hmp(SD) Hpu(SD) Hpl(SD) cm cm cm cm Euro USA Diff% Ht Adj%

1S8.7 (6.3) 160.1 (S.9) 1.4

2.76 (0.56) 2.79 (0.58) 1.1 0.3

2.77 (0.47) 2.70 (0.49) 2.S 3.0

2.93 (0.46) 2.90 (0.49) 1.0 2.0

0.94 (0.07) 0.96 (0.07) 2.0 2.0

0.94 (0.04) 0.93 (0.04) 1.0 1.0

1.03 (0.05) 1.04 (O.OS) 1.0 0.3

0.97 (O.OS) 0.97 (O.OS) 0.3 0.3

We conclude that the percentage differences of vertebral heights and ratios between the two patient groups are within the precision errors of measurement. Therefore, for quantitative assessment of prevalent fractures based on comparing vertebral height ratios with normative data, it may not be necessary to establish separate normative data for American and European patients.

TREATMENT: ESTROGENS, PROGESTINS, ANALOGS

P279 EXPERIENCE WITH KLiOGEST® IN SLOVAKIA J. Wendlova Osteological Surgery, Derer's Hospital and Policlinic, Bratislava, Slovak Republic We have monitored postmenopausal patients (with natural menopause) (n=32) with amenorrhoea lasting for 1 to 2.2 years, with discovered/ ascertained lower bone mineral density (BMD) (osteopenyto osteoporOSiS) and with marks of heightened bone turnover in their laboratory picture (so-called "fast-losers"). Before administering the preparation Kliogest® in tablets, Novo Nordisk, Denmark, in a dose of 1 tablet daily and after 12 months of taking it, the following parameters were evaluated: 1) Laboratory parameters of the bone turnover: - osteocalcin in the serum (OC) - amino-terminal N-telopeptide of type 1. collagen in 24-hour diuresis (NT,) 2) Bone Mineral Density in lumbar vertebrae L measured by DEXA " (dual-energy-Xrayabsorptiometry) 3) Questionnaire form evaluated the menopause symptoms (Menopause Symptoms Score) For statistical analysis of the measured values we have used non-pair Wilcoxon - Wilcox test. Results: After the treatment, the levels of OC were statistically significantly lower (a=O.OS, p
P278 A CLINICAL TEST TO IDENTIFY PATIENTS WITH OSTEOPOROSIS G. Albrand E. Sornay-Rendu, F. Duboeuf. P. Garnero, P. Delmas INSERM U 403, E. Herriot Hospital, Lyon, France Presently there is no universally accepted policy for screening to identify patients with osteoporosis. We have developed asimple clinical test to identify asymptomatic postmenopausal women who are at risk of osteoporosis. Method: The OFELY cohort comprised 667 postmenopausal women. All are healthy ambulatory Caucasian volunteers that were randomly selected from affiliates of a large healthy insurance company from Lyon and its surroundings in France. PartiCipants completed an extensive questionnaire on fracture and medical history, dietary and exercise habits. Dual-energy X-ray absorptiometry was used to measure BMD of the proximal femur and its subregions. We dichotomized the variables based on what appeared to be athreshold effectfrom observation of the scatterplot and the frequency distribution. T-score::; -2.S at femoral neck was used to define osteoporosis. Results: Seven variables were formed to be independ predictors of hip BMD: age, years since menopause, weight, history of fragility fractures after 4S yr., estrogen and corticosteroid therapy, disorders associated with osteoporosis. The score of this clinical test range from 1 to 19. The clinical test is positive when the score 2 :20 4 which provides a sensitivity of 93 %, specificity of 61 %. In the OFELY cohort, when the clinical test is positive the probability to find osteoporoSiS by hip BMD measurement is 21.S % as compared to prevalence of osteoporOSiS of 10.3 % in this population. The strongest relation was observed between the clinical test and the Tscore at the femoral neck (r'=0.31; p
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differences were highly significant at the lumbar spine throughout the study (p<0.0004). Seven subjects receiving tibolone withdrew from the study, four because of unable adverse events. Two subjects withdrew from the control group. However there was no significant difference (p>0.05) between the groups in the number of subjects suffering mild, moderate or severe adverse experiences. Vaginal bleeding occurred in 10 subjects, all from the tibolone treated group, but this resulted in only one early termination. Tibolone is thus an effective and well-tolerated alternative to oestrogen in the prevention of osteoporosis with its beneficial effects being most apparent at the lumbar spine.

P280 CHRONIC UNRESTRICTED OESTRAOIOL IMPLANTATION IS ANABOLIC AT LUMBAR SPINE AND FEMORAL NECK S.A. Beardsworth C.E. Kearney C.M. Langton D.w. Purdie Centre for Metabolic Bone Disease, Hull Royal Infirmary, England Disagreement exists as to whether oestrogen simply arrests further bone loss, or whether it causes a sustained gain in bone density. Twelve women who had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) for a benign indication and subsequently received at least 15 years of unrestricted oestradiol implantation on demand were compared with a control group comprised of 12 women who had similarly undergone TAHBSO at least 15 years previously but had received no hormone replacement therapy. All underwent DEXA of lumbar spine, femoral neck, forearm, calcaneus and total body. In addition, velocity of sound (VOS) and broadband ultrasound attenuation (BUA) at the calcaneus was measure. None of the women had any medical condition or had received medication other than oestrogen that might affect bone mineral density (BMD). There were no significant differences in age, age at menarche, age at hysterectomy, or body mass index between the two groups. In the control group, BMD values at all sites were not significantly different from that of age matched controls. In the study group, BMD was, on average, 31% greater than that of controls at lumbar spine (p=0.0008), 28% greater at femoral neck (p=0.001), 25% greater at the forearm (p=0.015) and 20% greater at the calcaneus (p=0.033). Total body BMD forthe study group was 19% greater than that of controls (p=0.0001). In contrast, heel BUA and VOS were not significantly different between the two groups (p=0.05 to 0.29). Lumbar spine and femoral neck BMD in the study group were positively correlated to the maximum plasma oestradiol level recorded in each subject (r=0.60.7, p<0.02). Both spine and more particularly, femoral neck BMD in the study group were also correlated to years since the menopause and to the total oestradiol dose received. Heel and forearm BMD was correlated only with age (r=0.71-0 .. 82, p
P282 HORMONE REPLACEMENT THERAPY WITH AND WITHOUT FLUORIDE

P281 PREVENTION OF POSTMENOPAUSAL BONE LOSS AT LUMBAR SPINE AND UPPER FEMUR WITH TIBOLONE: A TWO YEAR RANDOMIZED, PLACEBO CONTROLLED STUDY S.A. Beardsworth C.E. Kearney D.w. Purdie Centre for metabolic Bone Disease, Hull Royal Infirmary, England The effect of tibolone on bone mineral density (BMD) at lumbar spine, femoral neck, trochanter and Ward's Triangle and its concurrent safety and subject acceptability, was examined in forty seven women aged 50-57 who attended the Humberside Screening Programme. All had been found to have a BMD at lumbar spine greater then the 25 th centile of the young adult population, as measured by dual energy x-ray absorptiometry using a Lunar DPX-L, and were recruited into a two year, randomised, placebo controlled trial. All subjects were followed up for a period of 96 weeks with bone density assessments every 24 weeks. There was clinical contact every 12 weeks to ensure subject continuation and to record concomitant medications and adverse events. All were at least one year postmenopausal and none had any medical condition known to effect BMD. Twenty six were randomised to the tibolone group and 21 to the control group. The demographics of the two groups were comparable. Over the 96 weeks of the study, the BMD of the tibolone treated subjects tended to increase and those of the control subjects tended to fall. The higher densities in the tibolone treated group were statistically significant for the lumbar spine from week 24 (p=0.002) and for the trochanter from week 72 (p=0.014). The lower bone densities in the control group were statistically significant for Ward's Triangle at week 96 (p=0.0001), lumbar spine at weeks 24,48 and 72 (p=0.03 to 0.005) and femoral neck at week 96 (p=0.0005). Between-treatment analysis indicated that the bone densities in the libolone treated group were significantly different from those in the control group. By the end of the study all sites were affected, but the BMD

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FOR POSTMENOPAUSAL OSTEOPOROSIS A.L. Negri M. Sarli A. Insua J.R. Zanchetta Instituto de Invest. Metab6licas. Buenos Aires, Argentina It remains controversial if hormone replacement therapy (HRT) with fluoride (F) gives better or equal results to HRT or fluoride alone in the treatment of postmenopausal osteoporosis. We reviewed the medical records of 42 patients who had been treated for osteoporOSiS at the lumbar spine (T score <-2.5) with HRT (half oral and half transdermal) and calcium carbonate and were followed for at least two years. Half of these patients also received F (14-21 mg) as sodium monofluorphosphate (MFP). The age was 55±5 in the HRT Fgroup and 56±5 years in the HRT F+ group. The interval since menopause was similar in both groups (7.4±4.4 in HRT and 9.7±6 years HRT F+). Baseline values of bone mineral density (Norland XR26) at the lumbar spine (BMDLS) and at the femoral neck (BMDFN) were not significantly different HRT F-: BMDLS 684±46, BMDFN 645±89; HRT F+: BMDLS 673±53, BMDFN 636±58 mg/cm'). The rate of change in BMDLS was 41 mg/cm' (5.9 %) in the HRT F- and 58 mg/cm' (9.2 %) in the HRT F+ (p=0.04) during the first year, and 34 mg/cm' (4.9 %) and 65 mg/cm' (8.9 %) respectively during the second year (p
P283 THE USE OF ADD-BACK TIBOLONE IN WOMEN TREATED WITH GOSERELIN FOR PREMENSTRUAL SYNDROME N. Panay F. Zakaria C. Domoney J.w.w. Studd Chelsea & Westminster Hospital London Studies have demonstrated the benefits of menstrual cycle ablation using the gonadotrophin (GnRH) analogues in the treatment of women with severe premenstrual syndrome (PMS). However, this treatment often produces menopausal side effects such as hot flushes, headaches and depression which reduces efficacy and compliance with treatment. There is also a risk of loss of bone density, even with six mont~ 'sage, which may be unrecoverable. It was hypotheSised that use r' , together with a GnRH analogue, goserelin, should prevent fTl' Jlde effects and protect the skeleton, thus improving the ac' ...\~ .Jf treatment. 14 women with severe PMS were treated wit' ~, J.6mg monthly for 6 months; tibolone 2.5mg daily was used as? ~~ "apy. PMS symptoms and bleeding patterns were rated by prospp' ,')..<\) ,iTI diary analysis .. Baseline tests included hormone profiles anr ~...... ' .d densitometry. Tests were repeated at 6 months. The data we r ' ~" LO 2 historical groups of women (same demographic data) whr ' \ A(her goserelin and placebo tablets (n= 16) or placebo injection~ "i?-\.) J tablets (n= 12) for treatment of PMS. Results analysis re" ~ 11/14 (79%) women had a significant improvement of th'p' ' \ oIptoms with no menopausal side effects. There was no dW <:QCo .leatment efficacy compared to the goserelin/ placebo grow ~ ~roup had vasomotor symptoms. Treatment of PMS in bot' yroups was significantly better than placebo/placebo. 2 women w, ., early due to lack of treatment efficacy. Amenorrhoea was induced by (he 2nd month of treatment in the 8/11 (72%) patients that continued therapy. Oestradiol levels fell from a baseline of 178 to 67pmol/ 1. There was no significant loss of median bone density in the goserelin/ tibolone patients at 6 months (as in the placebo/placebo group); 2 patients did have a significant individual drop in age matched spine density. Median density declined significantly in the goserelin/placebo group (Spine L2L4: -5.0%; Femoral neck: -3.0%). In conclUSion, tibolone prevents vasomotor side effects and appears to maintain bone density in most women using GnRH analogues for treatment of PMS. However, serial bone densitometry should be performed, even with add-back HRT, in view of bone density loss in some individuals. Efficacy of treatment of PMS symptoms is significantly better than placebo and at least as good as with GnRH analogues used alone.

groups in uterine bleeding, thrombophlebitis, breast abnormalities, or endometrial thickness. In conclusion, raloxifene preserves bone mass, reduces serum lipids, and does not stimulate uterine or breast tissue in postmenopausal women with osteoporosis. Raloxifene treatment also had no adverse effects on secondary safety assessments of cognition and mood.

P285 EFFECT OF DIFFERENT ORAL AND TRANSDERMAL ESTRADIOL HORMONE REPLACEMENT THERAPIES ON URINARY EXCRETION OF TOTAL DEOXYPYRIDINOLINE IN POSTMENOPAUSAL WOMEN H. Schmidt-Gayk R. Kaiser R. Rausch'. L. Traber Th. Kniirzer Laboratory Group, Heidelberg and *Gynecology Practice, Osterode, Germany Limited information is available on the anti-resorptive capacity of different drugs widely used for hormone replacementtherapy (HRT) in postmenopausal (pmp) women. Therefore, we measured total urinary deoxypyridinoline (DPD) with HPLC after acid hydrolysis according to the method of Black, Duncan and Robins (Anal. Biochem. 1988;169:197-203), however in an automated procedure. Standards were kindly donated by S. Robins, Aberdeen, UK. Spontaneous urine samples collected at noon were used and DPD was related to creatinine (DPD/cr, ~/g). Results are shown in the table:

P284 RALOXIFENE EFFECTS ON BONE MINERAL DENSITY AND SAFETY ASSESSMENTS IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS E.G. Lufkin M.D. Whitaker, T. Nickelsen R Argueta, R.H. Caplan R.K. Knickerbocker D.A. Cox T.H. Crook and B.L. Riggs Mayo Clinic, Rochester, MN and Scottsdale, AZ; Lilly Research Laboratories, Indianapolis, IN; Gundersen Clinic, La Crosse, WI; Psychologix, Inc., Scottsdale, AZ. Raloxifene (RLX) is a selective estrogen receptor (ER) modulator which acts as an ER antagonist in breast and uterine endometrium but as an ER agonist on bone and lipid metabolism. The purpose of this ~tudy was to determine the effects of raloxifene compared with placebo on bone mineral density (BMD) and serum lipid levels, and to assess the safety of raloxifene with regard to the uterus, cognition and mood, and side effects, in postmenopausal women (mean age 68 years) with osteoporosis. In this 12 month, doubleblind study, 48 women received RLX HCI 60 mg/day, 47 received RLX HCI 120 mg/day, and 48 received placebo. BMD; including lumbar spine (LS), total proximal femur (PF), ultradistal radius (UDR), and total body (TB) were measured at all visits. Serum lipids, including low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (LDL-C) were also assessed at every visit. Cognitive function was monitored with the Memory Assessment Clinic (MAC) Battery and the Walter Reed Performance Assessment Battery (PAB), and mood was assessed by the Geriatric Depression Scale (GDS). Compared with placebo, raloxifene HCI 60 mg significantly improved, BMD at the proximal femur and ultradistal radius. Raloxifene significantly decreased serum total and LDL cholesterol, but did not significantly affect HDL cholesterol or triglycerides. Raloxifene did not impair performance on either the MAC Battery or Walter Reed PAB, and had no effect on mood as measured by the GDS. The incidence of hot flashes, an event that may have secondary effects on mood, was not significantly different between treatment groups. There were also no differences between treatment

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Pat. group

n

median

5 - 95 percentile range

controls pmp no HRT 1 mg E, 2 mg E, 50~ E,TO 25 ~ E, TO 1 - 2 mg E, V Equine 0.3 mg Equine 0.6 mg

36 68 9 16 20 6 6 9 12

41.6 69.8 40.3 46.0 41.5 49.5 40.2 56.1 38.1

27 - 56 27 - 103 31 - 55 27 - 83 27 - 59 39 - 59 29 - 58 34 - 88 22 - 81

19 - 63 20 - 143 27 - 59 20 - 92 16 - 64 36 - 59 27 - 60 32 - 98 20 - 110

E, = estradiol, TO = transdermal, E, V = E,-valerate, equine = Presomen (conjugated E,) Conclusion: 1 and 2 mg E" E, V and equine 0.6 mg normalized urinary DPD in more than 90% ofpmp women. Remarkably, the 50 119 E,TO produced results similarto those found in premenopausal women with normal ovulatory cycles. The 25119 E,TO produced results in the upper half of the normal range.

P286 HORMONE REPLACEMENT THERAPY PREVENTS FALLS IN EARLY

P288 THE BONE FORMING WAVE OF HORMONE REPLACE TREATMENT (HRT) DURING THE FIRST POSTMENOPAUSAL YEARS A.E. Georgiadis E. Georgiou and G. Latsos Osteoporosis Center, LHTO Maternity Hospital and Dpt of Medical Physics, Athens Univ. Med School, Athens, Greece The role of HRT as bone antiresorptive regiment is well established. However little is known about its bone stimulating effect. In order to determine this action we measured the Bone Mineral Density (BMD) of 48 normal Early Postmenopausal Women BMD was measured by DEXA (Hologic 1000 QDR) at Lumbar Spine (LS) and Left Hip (Neck), just after the beginning of Menopause and every year thereafter, for 5 consecutive years. We have randomly allocated 24 women in HRT and 24 in 1 gr Calcium/day. Both treatments had begun 1 year after the beginning of Menopause and lasted for 4 years. For statistical analysis we have used the Software of the Bone Densitometer. Our data suggests that the great bone loss during the first year of menopause has been replaced during the 1st and 2nd year after the initiation of HRT and then the bone mass begins to decrease slowly but progressively (see figures) Percent changes in BMD of LS (Lft) and HIP (Rt) in 6 years

POSTMENOPAUSAL WOMEN R. Honkanen. M. Komulainen K. Honkanen M. Tuppurainen H. Kroger E. Alhava S. Saarikoski University of Kuopio, Kuopio University Hospital, Finland Bone strength and falling tendency are the main determinants of fractures. Hormone replacement therapy (HRT) prevents early postmenopausal bone loss. Some studies suggest that HRT I might also have a beneficial effect on balance maintenance. The purpose of this study was to examine, if HRT prevents falls. The study population consisted of 436 early postmenopausal women from the Kuopio Osteoporosis Study recruited for the 5 year clinical trial in 1990 (baseline age range 48-59). They were randomly divided into four groups of equal size: I) HRT (sequential combination of 2 mg estradiol valerate and 1 mg syproterone acetate), 2) HRT+DVit (cholecalciferol, 300 IUlday), 3) Dvit and 4) Placebo (93 mg calcium lactate/day). Falls during the 12 months prior to the 1st of June 1994 were ascertained with postal enquiry. Falling risk for women in the HRT groups I and 2 was compared to thalter women in the non-HRT groups 3 and 4 by using logistic regression. 135 women reported a fall , 70 due to slipping (mostly on ice or snow) and 65 due to other mechanisms. In univariate analysis, the risk (odds ratio (OR with 95%CI)) of falling related to HRTwas 0.75 (0.48-1.15) for all falls, 1.00 (0.591.71) for falls due to slipping and 0.52 (0.28-0.96) for other falls. After adjusting for age, weight, height, number of chronic health disorders, dairy calcium intake, bone density and grip strength, the corresponding risks were: 0.68 (0.42-1.10), 0.97 (0.54-1.74) and 0.42 (0.20-0.85), respectively. The results suggest that HRT has a beneficial effect on balance maintenance preventing certain types of fall.

P287 THE USE OF DEOXYPYRIDINOUNE (DPD) URINE EXCRETION TO MONITOR THE SKELETAL RESPONSE TO TIBOLONE (UVIAL) THERAPY A. E. Georgiadis. E. Siganos G. Papadimitriou N. KollioDoulos X. Vogialzi E. Megapanos Osteoporosis Center, LHTO Maternity Hospital, Athens, Greece It is well known that Free Urinary DPD is a very good marker of bone resorption during postmenopausal period and can be used for evaluation of the efficacy of Hormone Replace Treatment (HRT). Tibolone is a synthetic steroid which exhibits combined weak estrogenic, progestogenic and androgenic activity. We designed this study in order to examine the possible action of Tibolone on DPD 3 months after the initiation of therapy. 60 Healthy Early Postmenopausal women (MA=48±4 ys) were randomly allocated 30 to Tibolone (Group A) and 30 to Calcium 1gr/day (Group B). The urinary free DPD was measured to all women with ELISA (PyrilinksD, Metra Biosystems, Palo Alto, Cal.) before and 3 ms after the initiation of therapy. For statistical analysis we used the student T-test. Our results demonstrated that: 1) In Group A the levels of DPD were significantly decreased 3 months after Tibolone therapy (From 8,04±3,9 to 4,2±2,1 nm/mm Creatinin(Cr) and p<0,05) and 2) In Group B the levels of DPD were approximately the same before and after treatment with Calcium (From 7,9±3,5 to 8,4±3,1 nm/mm Cr and p=NS). These data suggests that Tibolone exhibits a strong anti resorptive action on bone mass even at the first 3 months of treatment.

P289 EFFECT OF HEAR TREATMENT WITH IPRIFLAVONE ON BONE MASS

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IN WOMEN WITH SEVERE OSTEOPOROSIS L. Bufalino G. Abate M. Pedrazzoni M. Passeri Clinical Research Department, Chiesi Farmaceutici, Parma; Geriatrics Department, University of Chieti; Internal Medicine Institute, University of Parma, Italy Ipriflavone (IP) is a synthetic derivative of natural occurring isoflavones, a class of compounds potentially effective on different chronic diseases, including osteoporosis (op). Forty-nine women affected with severe op, defined as distal radius Bone Mineral Density (rBMD) 2 SD below the mean value of age-matched healthy women and at least 1 non-traumatic vertebral fracture, received for 24 months either three tablets/day of 200mg IP or placebo (PL), according to a randomised, double-blind design. All patients received also 19/day oral calcium. The average percent change of rBMD after 24 mo.s was 5.1±2.0 (p
P290 COMBINED SEQUENTIAL TRANSDERMAL VS. TRANSDERMAL

P292 EFFECTS OF TIBOLONE IN BREAST TUMOR MODELS AND NORMAL

ESTRADIOL AND ORAL NORETHINDRONE ACETATE IN POSTMENOPAUSAL WOMEN H.S. The*. G.Z. Den Helder* K Hesla** M Benhayoun*** R. Bejuit*** M.P. Dain*** *The Netherlands; * * Drammen, Norway; * * *Rhone-Poulenc Rorer, Antony, France This was an open-label, randomized, 24-week study of the efficacy and tolerability of combined sequential transdermal estradiol-norethindrone acetate (E2INETA) in postmenopausal women. Healthy women with> 3 hot flushes/day were randomized to sequential transdermal estradiol 50 Illl for days 1-14 and estradiol 50 Illl combined with norethindrone acetate 250 or 400 Illl/day (Estalis Sequi™/CombipatchTM) for days 15 28, or a transdermal E2 50llll patch for 28 days plus oral progestin 10 mg/day for days 15-28 (reference group). Efficacy was assessed from the change from baseline in number and intensity of hot flushes and sweating. Of 434 women randomized to treatment, 67 discontinued including 42 for adverse events. The mean number and intensity of daily hot flushes decreased from baseline in all treatment groups with no differences between the E2I NETA groups and the reference group. All treatments improved quality of life indices from baseline. No significant differences were reported between groups in the incicfllnce of adverse events. The most common adverse events were breast pain and minor application site reactions. Combined sequential transdermal E2INETA was comparable to a regimen of transdermal E2 and oral progestin for reducing vasomotor symptoms and improving quality of life in postmenopausal women.

BREAST TISSUE H.J. Kloosterboe[ N.V. Organon Department of Pharmacology, Scientific Development Group, 5340 BH Oss, The Netherlands Tibolone (Livial®) is effective for the treatment of climacteric complaints and prevention of bone loss without stimulatory effects on the endometrium in post-menopausal women. In hormone replacement therapy an increased relative risk of breast cancer has been shown. Tibolone is a compound with weak estrogenic, progestagenic and androgenic properties. This combination of activities may mark Tibolone off from other HRT treatments. Various preclinical studies were therefore per10rmed in order to assess the effect of Tibolone on breast tumor risk. In vitro studies using MCF-7 and T47D cell linel> showed that Tibolone induces weak estrogenic responses. In normal human breast epithelial cells, Tibolone showed adecreased cell proliferation rate and the compound promoted apoptosis, In the hormone dependent cancercjllls Tibolone blocks the "sulphatase" pathway, viz. sulfatase and 1(B-hydroxysteroid dehydrogenase activities, in a dose dependent manner leading locally to a diminished production of estradiol and. thus preventioo of stimulation of breast cells. In vivo Tibolone has an inhibitory effect on the formation and development of DMBA induced tumors in rats using different protocols. These preclinical data suggest that Tibolone mostJikely does not aggravate normal tumor risk and may potentially even decrease this risk. That Tibolone has indeed a less stimulating effect on breast tissue in women using Tibolone can be derived from mammagraphs showing a lower density than those of users of other HRT products. From these preclinical and clinical data it can be concluded that Tibolone has no adverse effect on breast tissue.

P291 CONTINUOUS TRANSDERMAL VS. ORAL ESTRADIOL AND NORETHINDRONE ACETATE IN POSTMENOPAUSAL WOMEN N. Kolthof!* J.M. Burggraff* * M. Benhayoun* * * R.Bejuit** * M.P. Dain*** *Hillerod, Denmark; **Emmen, The Netherlands; ***Rhone Poulenc Rorer, Antony, France The efficacy and tolerability of a continuous estradiol norethindrone acetate (E2INETA) transdermal patch and oral E2INETA were evaluated in a doubleblind, double dummy multicenter trial. Healthy postmenopausal women with> 3 hot flushes/day during screening were randomly assigned to continuous transdermal E2INETA patches delivering 50 Illl of estradiol and 140 or 250 Illl/day of norethindrone acetate (Estalis/Combipatch™), or 211 mg/day of oral E2/NETA daily (Kliogest®) for 24 weeks. The endpoints were change from baseline in number and intensity of hot flushes and sweating. Of 410 women randomized, 96 women discontinued. The mean number of hot flushes per day decreased from baseline to week 24 in each treatment group with no significant differences between Kliogest and either E2/NETA group. All treatments improved quality of life indices from baseline. Total- and LDL-cholesterol decreased with both E2INETA drugs with agreater decrease with oral E2INETA, triglycerides decreased with transdermal therapy. The incidence of treatment-related adverse events was 68% for Kliogest, 56% for E2INETA 50/140, and 69% with E2INETA 50/250. Overall, combined continuous transdermal E2/NETA was equivalent to continuous oral E2/NETA in reducing vasomotor symptoms in po"stmenopausal women.

P293 TIBOLONE EXERTS AN ESTROGENIC EFFECT ON BONE LEADING TO

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PREVENTION OF BONE LOSS AND REDUCTION IN BONE RESORPTION IN OVARIECTOMISED RATS A.G.H. Ederveen and H.J. Kloosterboer Department of Pharmacology, Scientific Development Group, N.V. Organon, 5340 BH Oss, The Netherlands Tibolone (Org OD 14) is a tissue specific steroid exerting, depending on the tissue, an estrogenic, progestagenic and/or androgenic effect. In postmenopausal women tibolone has been shown to prevent bone loss without stimulating endometrium proliferation. We have shown that tibolone treatment prevents ovariectomy (OVX)-induced bone loss in rats. The aim of the present study was to elucidate the mechanism of action of tibolone on bone by using the Ov.x rat model. The effect on bone mass and bone turnover was assessed for treatment with tibolone alone and in combination with the anti-estrogen ICI164.384, the anti androgen flutamide or the anti-progestagen Org 31710. Three month old rats were divided into groups of six rats. The shamoperated group and the control OVX group were treated with vehicle, while the other OVX groups received either E2 or tibolone (2x125 or 2x500 Illl/ rat/day, oral) alone or in combination with IC1164.384 (2x500 Illl/rat/day, subc.), flutamide (2x2 mg/rat/day, oral) or Org 31710 (2x2 mg/rat/day, oral). After a 4 week treatment, trabecular bone mineral density (T-BMD) of the distal femur (pQCT; Stratec 960A), plasma osteocalcin and urinary deoxypyridinoline (DPD/Cr ratiO) were determined. Treatment with tibolone or E2 prevented OVX-induced loss of T-BMD, inhibited bone resorption and decreased bone turnover as shown by the reduction in DPD/Cr ratio and osteocalcin, respectively. The protective effects of tibolone and E2 on T-BMD, DPD/Cr and osteocalcin were blocked by the anti-estrogen IC1164.384 indicating an estrogen receptor mediated action of tibolone on bone metabolism. The anti-androgen or anti progestagen could not block the protective effects of tibolone. It is concluded that tibolone prevents Ov.x-induced bone loss through an inhibition of bone resorption and bone turnover similar to estradiol. The fact that the anti-estrogen blocks the effects of tibolone suggests an action through the estrogen receptor.

P294 TIBOLONE, A TISSUE SPECIFIC STEROID, COMPLETELY PREVENTS BONE LOSS AND REDUCES BONE RESORPTION IN MATURE OVARIECTOMISED RATS AND MONKEYS A.G.H. Ederveen and H.J. Kloosterboer Department of Pharmacology, Scientific Development Group, N.V. Organon, 5340 BH Oss, The Netherlands Tibolone (Org 00 14) is a tissue specific steroid exerting, depending on the tissue, an estrogenic, progestagenic or androgenic effect. In postmenopausal women tibolone has been shown to prevent bone loss without stimulating endometrium proliferation. The effects of a 4-week treatment with different doses of tibolone on ovariectomy (OVX)-induced bone loss was studied in mature 3-month old rats. Trabecular Bone Mineral Density (T-BMD) was assessed in the distal femur by pOCT. Biochemical markers of bone formation (osteocalcin) and bone resorption (urinary deoxypyridinoline/creatinine ratio; DPD/Cr) were also determined. In another study, the efficacy of tibolone to suppress bone turnover was assessed in OVX cynomolgus monkeys by measuring biochemical markers of bone resorption and formation after eight weeks of treatment. In the rat, ovariectomy caused a significant decrease in T-BMD, whereas no change in cortical BMD was found. The decrease in T-BMD was dosedependently prevented bytibolone treatment. Tibolone significantly reduced DPD/Cr and osteocalcin levels, which were significantly increased upon OVX, indicating a reduction in bone turnover. Similar results were found with ethinylestradiol on T-BMD and biochemical markers. Cynomolgus monkeys, which were at least 3 months OVX, were treated orally with tibolone for eight weeks. Tibolone gave, in a dose related manner (10 - 1000 J.l!l/kg,day), a more than 60% reduction in markers of bone resorption (DPD/Cr) and bone formation (bone specific alkaline phosphatase; osteocalcine) . In conclusion, tibolone treatment completely prevents OVX induced loss of T-BMD in mature rats. Both in rats and monkeys, a remodelling species, tibolone suppresses markers of bone resorption as well as of bone formation thereby reducing the OVX-enhanced bone turnover indicating an mechanism of action similar to estrogens.

P295 TIBOLONE TREATMENT PREVENTS LOSS OF TRABECULAR BONE MASS IN THE AXIAL AND PERIPHERAL SKELETON AND OF CORTICAL BONE STRENGTH IN OVARIECTOMISED RATS WITH ESTABLISHED OSTEOPENIA A.G.H. Ederveen and H.J. Kloosterboer Department of Pharmacology, N.V. Organon, 5340 BH Oss, The Netherlands Tibolone (Org 00 14) is a tissue specific steroid exerting, depending on the tissue, an estrogenic, progestagenic and/or androgenic effect. In postmenopausal women, tibolone has been shown to prevent bone loss without stimulating endometrium proliferation. Tibolone has been shown to prevent ovariectomy (OVX)-induced bone loss in the axial and peripheral skeleton of young mature and aged ovariectomised rats. The present study was designed to examine the effect of a six-month treatment with tibolone in mature rats with an established bone loss. Three month old rats were ovariectomised and treatment was started not eafive months after surgery to obtain severe osteopenic rats. After six months of treatment with tibolone, effects on trabecular bone volume (BV/TV) in the axial and peripheral skeleton, on bone turnover, and on biomechanical properties of femoral cortical bone in a three point bending test were evaluated. Five months of estrogen depletion, due to ovariectomy, resulted in rats with osteopenia as indicated by significant decreases in bone density of the distal femur and BTITV in the proximal tibia and lumbar vertebrae. A six-month treatment with tibolone prevented further loss oftrabecular bone in the proximal tibia and in the lumbar vertebrae L1-L2. With the highest dose even a 13% increase in BTITV was found as compared to start of treatment but this did not reach statistical significance. In these osteopenic rats, tibolone prevented the significant decrease in maximum bending stress as compared to the placebo treated ovariectomised control. The effects of tibolone may be mediated by a reduction in bone turnover as indicated by the decrease in bone resorption marker (deoxypyridinoline/ creatinine) and formation (osteocalcin). We conclude that in ovariectomised rats with an established severe bone loss, tibolone prevents deterioration of the axial and peripheral skeleton by normalising bone turnover resulting in maintaining cortical bone quality as has been shown for estradiol.

P296 META-ANALYSIS OF THE EFFECTS OF LlVIAL ON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN F. Helmond E. van der Meulen NV Organon, Oss, the Netherlands Livial (2.5 mg tibolone/day) prevents bone loss by inhibiting bone turnover in a comparable way to that of estrogens. The results of a formal metaanalysis on the bone mineral density (BMD) data of six long-term (at least 24 months) clinical trials are presented. Two trials were performed in early postmenopausal women and had an open, non randomized design including a non-treated control group. Four trials were performed in late postmenopausal women using a randomized, placebo controlled design. The BMD has been measured by means of DEXA in all but one study in which DPA has been used. The total number of enrolled subjects was 253 in the Livial treated groups and 217 in the control groups. The total number of com pieters was 191 and 172, respectively. The difference of the mean relative change from baseline of BMD lumbar spine (LS) and femoral neck (FN) values at 24 months of treatment between Livial and the control groups has been analyzed. Combining all studies a treatment effect of 5.7% (95% CI of 4.8-6.5) for LS and 4.3% (95% CI of 3.1-5.4) for FN was shown. The effect of Livial is similar in early and postmenopausal women: 5.5% versus 5.8% for LS and 4.6% versus 3.9% for FN, respectively. The BMD measurements for dropouts fallowed a similar pattern as for completers. In conclusion: in comparison to controls 24 months of treatment with Livial increases BMD of LS and FN consistently and convincingly.

P297 TAMOXIFEN PROTECTION OF BONE MASS IN POSTMENOPAUSAL WOMEN WITH BREAST CANCER J.P. Devogelaer G. Depresseux P. Scalliet C. Kirkove Department of Rheumatology, St-Luc University Hospital, Brussels, Belgium Tamoxifen (T), an anti-estrogen, is able to protect bone mass in small groups of postmenopausal women suffering from breast cancer (BC). The aim of the study is to confirm this effect in larger groups of patients. In a cross-sectional study, we measured the lumbar (L-) and hip-BMD's using DXA (ODR-1000 W Hologic, Inc.) in 257 post-menopausal women with BC. 111 pts had never received T [control (C) group], 69 pts were on T (20-40 mg/d) for 4.6 (3.4)(SD) y (T group); and 77 pts were seen after withdrawal from T for 4.1 (2.7) Y (W group). The ages at menopause, weights, heights and BMI were not statistically different in the 3 groups. Pertinent data are summarized in the table

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Age (y) [M (SO)]

YSM

L-BMD Z-score

T-score

Hip-BMD Z-score T-score

C 63.1 (7.6) 13.4 (8.0) 0.2 (1.5) -1.4 (1.5) 0.0 (1.0) -1.2 (1.0) T 65.2 (7.6) 15.4 (7.9) 0.6 (1.3)* -1.1 (1.2) 0.1 (0.9)*-1.3 (0,9) W 64.3 (8.4) 14.9 (7.4) 0.1 (1.5)* -1.6 (1.4) -0.2 (1.0)*-1.5 (1.0) * p<0.05; YSM = years since menopause Fasting urinary Ca/creat and total alk. p'ase were significantly lower in the T group as compared with C and W groups. In the longitudinal study, maintenance was observed both at L BMD and hip-BMD, whereas an accelerated bone loss occurred atthe hip during the first year after withdrawal from T. In conclusion, pts with BC do not have on average a low BMD, T demonstrates an anti resorbing action as evidenced by alk. p'ase activity and fasting urinary Ca. After T, bone loss resumes at the hip, faster during the 1st y, mimicking what is observed after estrogen deprivation.

P298 COMPLIANCE WITH TEN-YEARS ORAL 17B-ESTRADIOU NORETHISTERONE ACETATE HORMONE REPLACEMENT THERAPY P. Eiken N. Kolthoff University Hospital Gentofte, Medical Department F, DK-2900 Hellerup, Denmark and Department of Clinical Physiology, Hillerod Hospital, Denmark Hormone replacement therapy (HRT) is increasingly used for the treatment of menopausal complaints and for the prevention of longer term effects of hormone depletion. Long term compliance is still a problem. The aim was to study ten years compliance with HRT. Methods: One-hundred-fifty-one early postmenopausal women were initially randomly allocated to three groups in a double-blind, placebo controlled trial for prevention of osteoporosis. Fifty women received continuous combined therapy (17B-estradiol/ norethisterone acetate (NETA), Kliogest®), another fifty were placed on sequential therapy (17B-estradioIINETA, Trisequens®), while the last fiftyone women where given placebo for two years and after that no therapy. After two years in the trial, the women were followed in an open investigation for a total of ten years. Results: One-hundred-twenty-six women (83%) came to a ten year interview, 4% were deceased and the remaining did not want to participate. None of the women in the continuous combined group had changed to other therapies (42% were still in treatment). 28% were still in treatments with sequential therapy and 20% from the originally sequential group had changed to other HRT's (mainly continuous combined therapy because the women disliked the monthly bleeding induced). 18% from the placebo group had started HRT. 53% from the originally placebo group did still not receive any therapy. 87% of the women who had taken combined therapy for eight years were still in therapy at the tenth years' visit. Conclusion: Women may comply much longer with continuous combined HRTthan with sequential therapy because continuous combined HRT does not induce the monthly bleed that postmenopausal women wish to avoid.

P300 COADJUVANT USE OF OSSEIN-HYDROXYAPATITE COMPOUND IN

P299 PREVENTION OF BONE LOSS IN EARLY POSTMENOPAUSAL WOMEN WITH TRANSDERMAL ESTRADIOL - RELATIONSHIP BETWEEN LUMBAR SPINE BONE MINERAL DENSITY AND ESTRADIOL CONCENTRATIONS M.P. Dain P. Chevalier P. Hardy C. Pilate* P.Delmas** *Rhone-Poulenc Rorer, Antony, France, * *Hopital Edouard Herriot, Lyon, France A total of 277 women, 1-6 years post-menopause, were randomized into a 2-year placebo-controlled trial with transdermal17B-estradiol (Menorest, Rhone-Poulenc Rorer) at 25, 50, or 75 j.IQ/day twice weekly for 28 days. Dydrogesterone was given for the last 11 days of each cycle Mean age was 53 3±3 4 years (SO) and average time beyond menopause was 3.4±1.6 years: mean baseline lumbar spine, BMD T-score was -1.44±O.88 L1-L4 lumbar spine (LS) and proximal femur bone mineral density (BMD) were performed at, initial assessment and at 6, 12, 18, and 21 months. Serum estradiol concentrations (E2) were determined by RIA on the third day of patch application at baseline, 3, 6, 12, 18, and 24 months. At 2 years, there were clinically relevant and statistically significant increases in LS BMD percent change (mean±SE) in the 25, 50 and 75 j.IQ/day (2.9±O.5%, 5.5±O.6% and 6.9±O.6%) compared to a decrease by 1.8±O.4% in the placebo group (p
P301 A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE

SUBJECTS ON HORMONE REPLACEMENT THERAPY FOR PREVENTION OF POSTMENOPAUSAL BONE LOSS C. Castelo-Branco* M.J. Martinez de Osabal', F. Pons', E. Casals3, J.V. Vanrell* *Department of Gynecology & Obstetrics. 'Hormones Laboratory. 'Biochemistry Laboratory. 3Nuclear Medicine Department. Hospital Clinic i Provincial. School of Medicine. University of Barcelona, Spain Aim: To evaluate whether the addition of ossein hydroxyapatite (OHC) may improve the effect of hormone replacement therapy (HRT) in postmenopausal bone loss. Subjects &Methods: Ninety-six recent surgical postmenopausal women who were allocated at random to one of 4 groups, completed a one year follow-up. The first group (n=23) received 50 mg/day of transdermal17B-estradiol continuously. The second group (n=26) received 50 mg/day of transdermal 17-B-estradiol continuously plus 3-32 g/day of OHC every day; the third (n=23) received only the OHC daily; and finally, the fourth group (n=24) constituted a treatment-free control group. Bone mass assessed by dual X-ray absorptiometry was measured prior to and at the end of treatment interval. Samples including serum calcium, phosphate, and osteocalcin level were collected before therapy and during the 6th and 12th treatment months. Results: All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous estrogen plus OHC treatment plus OHC treatment group (4.7% p<0.01). Concomitant biochemical effects at 6 and 12 months were compatible with the observed effects on bone mineral. Conclusion: The combined regimen of OHC and HRT increased vertebral bone mass in postmenopausal women to a greater extent that OHC alone or HRT alone, suggesting that this drug association may be useful in the management of postmenopausal bone loss.

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EFFECTS OF TIBOLONE ON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN C.O.M. Wender F.N. Freitas, J.A.S. Castro, S. Mattielo C. Estery, A. Finkelstein P.M. Spritzer Hospital de Clinicas de Porto Alegre, Brazil The aim of the study was to investigate the efficacy and tolerability of tibolone (Livial) treatment in the prevention of osteoporosis in postmenopausal women. Subjects were 40 healthy non-osteoporotic postmenopausal women: 20 were randomized to tibolone (2.5 mg/d) and 20 to placebo. Bone mineral density (BMD) of lumbar spine and femoral neck was measured using dual x-ray absorptiometry before randomization and after 1 year of treatment. From the 40 randomized subjects, 33 completed the treatments (tibolone: N=17; placebo N=16). There were no between group differences in baseline characteristics (age, weight, height, body mass index, menopausal age, lumbar spine BMD or femoral neck BMD). The median BMD of the tibolone group increased at the lumbar spine from 1.006±O.118 to 1.039±O.101 g/cm' (p<0.0001) and at the femoral neck from 0.819±O.088 to 0.862±O.093 g/cm' (p
P3U2 TWO YEARS PREVENTION OF POSTMENOPAUSAL BONE LOSS WITH TIBOLONE C.O.M. Wender EM. Freitas J.A.S. Castro S. Mattielo C. Estery A. Finkelstein PM. Spritzer Hospital de Clinicas de Porto Alegre. Brazil The aim of the study was to evaluate the effect of two years of treatment with tibolone (Livial) on bone mineral density (BMD) of postmenopausal women. Seventeen healthy postmenopausal women were included in this prospective study. The women used tibolone (2.5 mg/d) during 2 years. Bone mineral density (BMD) of lumbar spine and femoral neck was measured using dual x-ray absorptiometry before treatment and after 2 years of treatment. The initial characteristics (average±SD) of the group was 54.7±3,6 years (age), 66.4±12.4 kg (weight), 26.7±4.6 kg/m' (body mass index), 6.53±5.19 years (menopausal age), 0.952±O.109 g/cm' (lumbar spine BMD) and 0.809±O.071 g/cm' (femoral neck BMD). After 2 years of treatment with tibolone, the BMD of the lumbar spine increased to 1.012±O.097 g/cm' (p<0,0001) or + 6.6% and increased in the femoral neck to 0.825±O.065 g/cm' (p
P3U3 IDOXIFENE REDUCES BONE TURNOVER IN OSTEOPENIC POSTMENOPAUSAL WOMEN ~1, !:i..M.u1.rJlll', Uastel]3, M. Greenwald', B. MacDonald 5 1Hopital E. Herriot, Lyon, France; 'Medisch Onderzoekcentrum GCP, Rotterdam, Netherlands; 3University of Sheffield, Sheffield, UK; 'Osteoporosis Research Medical Center, Palm Springs; USA; 5SmithKline Beecham, Philadelphia, USA. . Idoxifene is a novel selective estrogen receptor modulator (SERM) that has estrogen agonist effects in bone, as demonstrated by molecular and in vivo preclinical studies. Clinical evidence of a similar effect was sought in a three month double blind placebo-controlled study that enrolled 331 osteopenic postmenopausal women (BMD T score between -1 and -2.5). Three doses of idoxifene were compared with placebo by evaluating change in biochemical markers of bone turnover. The results are presented as the difference between placebo and idoxifene (% change from baseline).

Biochemical Marker

Urine Crosslaps Serum Crosslaps Serum Osteocalcin

Idoxifene Dose (mg/day) 2.5 5 10 (n=78) (n=82) (n=87)

P-value #

-10

-16'

-25"

0.0004

-13'

-17"

-22"

0.0001

-8

-10'

-18"

-.0001

, p
P3U4 TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH RALOXIFENE. P.J Meunier' E Vignot' p. Garnero" E Confavreux·. E. Paris" S. Sarkar'" S. Liy Leage'''' M. Wong'" M. Draper'" 'Dept. of Rheumatology, Ed. Herriot Hospital, Lyon, France ;"CLlOS, Lyon; "'Lilly Res. Lab.; ····Lilly France. The purpose of the study was to examine the effects of raloxifene, aselective estrogen receptor modulator (SERM), on bone mineral density (BMD), bone turnover and serum lipids in postmenopausal osteoporotic women. Raloxifene was assessed for efficacy and safety in 129 women in Phase II, multi-center,,1 2-month, randomized, double-b' I study. Postmenopausal women (mean age±SD: 60.2±6.7 years), witn osteoporosis (baseline lumbar spine BMD T score <-2.8, with one or fewer previous fractures) were assigned to one ofthree groups: placebo, 60 or 150 mg/day raloxifeneHCI, and concomitantly received 1000 mgJday calcium and 300 Ulday vitamin D3. BMD, biochemical markers of bone metabolism and serum lipids were determined. BMD in the lumbar spine (+3%), femoral neck (+1.7%) and trochanter (+2.5%) were significantly (p
P3U5 SIX YEAR FOLLOW UP OF BONE DENSITY IN A COHORT OF FIFTY POSTMENOPAUSAL WOMEN ON TIBOLONE G.M Prelevic K. Brooke-WaveIP, D.S. Little. H. Randeva C. Bartram' and J. Ginsburg Academic Department of Medicine, Royal Free Hospital, 1University of Westminster, School of Biological Sciences and 'Department of Radiology, The Princess Grace Hospital, London, UK. In an investigation of factors that might influence the effect of tibolone on bone mineral density (BMD) in postmenopausal women, we assessed BMD in 50 women in relation to their previous therapy. All received tibolone 2.5 mg nocte, oral calcium supplementation of 1g daily and had yearly dual energy X-ray absorptiometry (DEXA) for six years. 12 women had taken menopausal therapy (for six months to two years) before starting tibolone; 38 had had no previous menopausal therapy. There was a significant rise in spine BMD in all women, which ,was particularly marked during the first two years of therapy. This increase was, however, Significantly greater in those who had not previously received menopausal treatment. Hip BMD rgse significantly during the first two years, but only in women with no previous therapy. Although BMD continued to increase after two years the level reached after six years was not significantly greater than that reached after two years therapy. Tibolone continues to be effective in postmenopausal women, maintaining the increase effected by the drug over six years of therapy, irrespective of their previous therapy.

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P3U6 EFFICACY OF HORMONAL REPLACEMENT THERAPY (HRT) IN WOMEN WITH DIFFERENT DURATION OF MENOPAUSE Z. Crncevic Orlic" D. Dekanic', S. Bolanca', ~' 'University of Rijeka - Internal Clinic - Endocrinology Division, Clinical Hospital Center, Rijeka, 'Institution for Medical Research and Occupation Health, Zagreb, Croatia. The protective influence of estrogens on bone mass is a well-known fact. Hormonal replacement therapy (HRT) takes a great part in prevention of postmenopausal osteoporosis. The aim of our research is to examine the bone mineral density (BMD) during one year of HRT in different menopausal stages. The study included 62 women (41-77years old) divided in to three groups according to duration of menopause. BMD of lumbar spine was measured by DPX before treatment and one year later. Our results show significantly higher BMD values after treatment in all groups (p<0,001). Women whose menopause lasted longer (more than 5 years) have relatively greater BMD increase (5%) to HRT than those women whose menopause lasted shorter than five years (4%). We conclude that efficacy of HRT is always beneficial whenever we started with it. Benefit is even greater in older age of life when BMD is lower.

P3U7 TREATMENT OF OSTEOPOROSIS WITH ESTRADIOL VALERATE AND LEVONORGESTREL IN PERI MENOPAUSAL WOMEN AFTER SURGICAL CASTRATION J. Zivny, J. JeniCek, J. KOCian', H. Vinglerova 2nd Department of Obstetrics and Gynecology, Charles University and General Faculty Hospital '1st Department of Medicine ILF, KrC, Prague, Czech Repu blic. Osteoporosis is the most frequent metabolic bone disease. In Czech republik 7-8% of the population are suffering from this disease, mainly women in postmenopause and in senium. The bone density (Lunar Achilles), some biochemical markers of bone turnover (serum calcium, phosphorus, total alkaline phosphatase, osteocalcine, excretion of calCium, phosphorus, hydroxyproline in urine) and serum concentration of estradiol and estron were determined in 4 groups of women. Group A - non ovarectomized premenopausal women, Group B - women 3 - 5 years after ovarectomy in the same age as women in the group A, Group C - women of the group B treated with estradiol valerate and levonorgestrel (Klimonorm) for one year and Group D - women of the Group B treated with estradiol valerate and levonorgestrel for two years. Bone density in women of the group B was significantly lower compared to those in the group A. In women of the group Cthe bone density and some biochemical markers of bone turnover were significantly improved compared to women of the group B. In women of Group 0 bone density improved compared to women of the Group C, but no significantly. HRT (Klimonorm) had no impact on BM!. Klimonorm is a suitable HRT for the treatment of climacteric postcastration osteoporosis.

P3U8 HORMONAL REPLACEMENT TREATMENT WITH TIBOLONEAND BONE LOSS: A PROSPECTIVE STUDY DURING THREE YEARS J Vicente C. Casteol-Branco A. Sanjuan F. Figueras F. Pons * J.A Vanrell Departments of Gynaecology and Obstetrics, and *Nuclear Medicine. Hospital Clinic. Barcelona Introduction: Several studies have described a positive effect of hormonal replacement treatment (HRT) on the bone loss in postmenopausal women. However, the persistence of this effect with tibolone, a synthetic steroid, is not far studied. Objectives: to study changes on bone mass in postmenopausal women treated with tibolone compared with untreated women. Methods: 26 spontaneous menopausal patients were treated with tibolone. Bone mineral density (BMD) was assessed before inclusion and then yearly during three years. BMD measurements were compared with a control group of 53 patients free of treatment. Results: at the first year control group lost a 2.4% whereas tibolone group rose a 4% of BMD. At the second year control group lost 3.5% and the treatment group rose a4% of BMD. Althe third year control group lost a 2.1 % and the treatment group rose a 3.5% Conclusion: our study suggest that tibolone maintains a protective effect on bone mass during three years at least.

P3U9 HORMONAL REPLACEMENT TREATMENT AND BONE LOSSERS: A PROSPECTIVE STUDY A. Sanjuan C. Castelo-Branco J. Vicente F. Figueras F. F. *Pons, J.A. Vanrell Departments of Gynecology and ObstetriCS, and *Nuclear Medicine. Hospital Clinic, Barcelona Introduction: it is well known the positive effect of hormonal replacement treatment (HRT) against bone loss in menopausal women. However there are a group of menopausal patients who continue losing bone mass in spite of HRT. Objectives: to quantify the percentage of women who loss bone mass with HRT during five years follow-up. Methods: 136 menopausal women were treated with several HRT regimens that include: tibolone, conjugated equin estrogens, or 17 -betaestradiol (with or without medroxyprogesterone). Bone mineral density was assessed before the treatment and then yearly during five years follow-up. Results: after HRT, we found a 40-45% of subjects who lost bone mass in spite of HRT. This percentage was observed every year with independence of HRT regimen or drug. Conclusion: our study suggest that there are agroup of postmenopausal women in which HRT is unable to stop the bone loss related to steroid ovarian production cessation. These data may suggest that forthese women might be useful to introduce other treatments .

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TREATMENT: CALCIUM, VllAMIN D, NUTRITION

P312 BELGIAN CALCIUM INTAKE EVALUATION BY A NEW SELF-ADMINISTERED QUESTIONNAIRE B. PORNEL, B MATHIEU and *C. DUBOIS Brussels Menopause Center, *European BioStatistics Center, Bruss~ls, Belgium Objective: To evaluate by a new self-administered short food frequency questionnaire (QBMC) the dietary calcium intake in a heterogeneous belgian women population. Setting: Urban and rural belgian medical practices in Brussels, Namur and Charleroi areas and in schools from Brussels and Liege areas. Subjects: Aged 15-75 years, 107 subjects from schools, 90 from the Brussels Menopause Center, 80 from urban medical practices at Namur and 153 from rural medical practices in Namur and Charleroi areas. Of 430 subjects initially recruited, 76 failed to complete the questionnaire. Main measures: Estimates of calcium intake from the QBMC were descriptively summarized and compared in young, middle aged and old women (between 15-75 years), coming from the rural and urban sites and practising regularly physical exercises or not. Results: Overall, the mean dietary calcium intake was equal to 1319.8 mg/day. The distribution of subjects among the dietary calcium intake categories was as follows: 4% had a calcium intake $500 mg/day, 31 % between 501 and 1000 mg/day, 36% between 1001 and 1500 mg/day, 14% between 1501 and 2000 mg/day and 15% more than 2001 mg/day. For women aged 15-45 years the dietary calcium intake was estimated at 1433.7 mg/day while for women aged 46 years and more, it was equal to 1209.6 mg/day. The mean dietary calcium intake was respectively 1286.6 mg/day and 1353.6 mg/day for subjects from rural and urban sites. For women practising physical exercises, the mean calcium intake was estimated at 1402.5 mg/day while it was equal to 1264.9 mg/day for women without physical exercise practices. Conclusions: No significant differences in dietary calcium intake are observed between young and old women and subjects coming from urban or rural sites. Eighty two percent of the women from Brussels and south of Belgium have an acceptable level of calcium intake, larger than 800 mg/day.

P310 A NEW DOSAGE FORM OF A CALCIUM CONTAINING DRUG J. Wendl" J. Stepan 3, P. Masarvk', J. Vokrouhlicka 3, A. Letkovska' 'Slovakofarma, J-S.Co.,Hlohovec, 'Research Institute of Rheumatic Diseases, Piesfany, the Slovak Republic, 30steocentrum of General Faculty Hospital, Praha, the Czech Republic. We tested VITACALCIN PULVIS, a calcium containing drug in the original dosage form aimed especially for long-term supplementation. It contains modified calcium carbonate (1250 mg, i.e. 500 mg of Ca" per dose), adjusted in an instant powder of 10 flavour variations. After adding a teaspoon of water or milk it turns into a tasty "pudding-like substance". RESULTS: 1. The Study of Bioavailability: After one shot of 2 bags of the studied drug or 2 effervescent tablets (eff. tab.) of the reference calcium drug there was a significant (p<0.05) elevation of fS Ca and decline in plasma iPTH in the samples collected 1,2,4 and 5 hours after the drug's intake. The differences between the studied and reference drug were not significant. Hypercalcaemia was found in 2 woman after reference drug intake, but in no women after the studied drug administration. 2. The Study of Tolerance: After 2 months of daily intake of 1-2 bags of studied drug: 99% of the patients tolerated the drug excellently, 68% considered it to be better than previous drugs, 83% of the patient wished to continue the intake. CONCLUSIONS: 1. The desired biological effect of calcium absorbed from studied drug is the same as from the eff. tab. 2. The calcium absorption from the studied drug is more continuous and safer than from eff. tab. 3. VITACALCIN PULVIS is well-tolerated and accepted by most of the given patients.

P311 COMPARISON AND VALIDATION OF A NEW SELF-ADMINISTERED AND PRECISE QUESTIONNAIRE WITH TWO REFERENCE'S QUESTIONNAIRES B. PORNEL, L, ERNES and *C. DUBOIS Brussels Menopause Center, *European BioStatistics Center, Brussels, Belgium Objective: To assess the ability of a new self-administered short food frequency questionnaire (QBMC) to measure dietary calcium intake in postmenopausal women. Design: Estimates of calcium intake from the QBMC were compared with those from two well established questionnaires: a self-administered food frequency developed by Fardellone & Sebert, France and a food frequency based on a set of photographs developed at Institut Paul Lambin (IPL), Belgium; in 117 postmenopausal women aged 42-65 years from Brussels Menopause Center, Belgium. Subjects: Subjects were recruited prospectively from a women population coming for annual check-up at the Brussels Menopause Center. Of 122 subjects initially recruited, 5 failed to complete at least one questionnaire. All three questionnaires were administered on the same day in a random order, two of them were self-administered. Results: Mean dietary calcium intakes were respectively 1196.8 mgl day from the IPL questionnaire, 627.5 mg/day from the Fardellone &Sebert questionnaire and 1239.2 mg/day from the QBMC. The mean difference in calcium intake between the QBMC and IPL questionnaires did not differ significantly from zero (67.5 mg, 95% C.1. [-15.8,150.9], p-value=0.111). While the mean difference in calcium intake between the QBMC and Fardellone & Seben questionnaires did differ significantly from zero (617.9 mg, 95% C.1. [522.1,713.7], p-value$0.001). These results were confirmed by an analysis on the log-transformed data. Conclusions: The QBMC, new self-administered short food frequency questionnaire can be used to assess dietary calcium intake in postmenopausal women. It provides a estimation of calcium intake in 15-20 minutes similar to that obtained with a questionnaire with visual support that takes 45 minutes and the need of a dietician.

P313 IMPACT OF DIETARY CALCIUM ON THE EFFECT OF OVARIECTOMY ON

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BONE DENSITY IN MINI PIGS K.E. Scholz-Ahrens" C.A. Barth' P. Kann'. J. LOttges x, H. Roberts·, J. Schrezenmeir" "Inst. of Physiology and Biochemistry, FDRC, Kiel, Ger, 'DlfE, Rehbriicke, Ger, 'Internal Medicine and Endocrinology, University Mainz, Ger, "Institute of Pathology, University Kiel, Ger, 'Dept. of Radiology, University Mainz, Ger We reported that ovariectomy (ovx) induced estrogen deficiency resulted in reduced Ca content, bone density in computed tomography (QCT), and ultrasound transmission velocity (UTV) of vertebrae in minipigs (1), showing that the ovx Giittingen minipig is an animal model for postmenopausal osteoporosis. Here we report the impact of dietary Ca on the effect of ovx on bone density or quality assessed by different methods. Twenty intact and 20 ovariectomized primiparous two year old Giittingen miniature sows were fed a semisynthetic diet containing either 0.1 % Ca or 0.4% Ca and allocated t04groups: 1) 0.1% Ca-ovx, 2) 0.1 % Ca-intact, 3) 0.4% Ca-ovxand 4) 0.4% Ca-intact. After 12 months defined bone specimens were analyzed from femoral neck (FN) and lumbar (LV) or thoracic (TV) vertebra. Ca content of FN was (x±SEM) 123±6.2, 137±6.0, 164±6.2, and 165+5.9 mg/g in groups 1-4 showing that ovx mediated decrease of BMD required a diet containing 0.1 % Ca since no effect was seen when Ca was 0.4%. Numbers of osteoblasts and osteoclasts, assessed by histology, and activity of plasma BAP were highest in group 1). In LV BMD was 116±2.8, 123±2.7, 128±2.9 and 136±2.6. Under both dietary regimen ovx reduced BMD although the effect was significant only ifthe diet contained 0.4% Ca. Values for QCT ofTV were 645±73, 687±46, 834±73, and 972±51 mg/cm 3 , and for UTV 2176±59, 2305±37, 2482±59, and 2585±41 m/s. QCT and UTV confirmed results of chemical analyses, showing that the dietary regimen is of less importance for the expression of ovx-induced osteopenia in the axial skeleton than in the appendicular where both, Ca and estrogen deficiency, are required to induce osteopenia. Conclusion: The amount of dietary Ca and the choice of skeletal site are important factors that have to be taken into consideration if ovx minipigs are used as animal models. (1) Scholz-Ahrens et aI., (1998) Exp Clin Endocrinol Diabetes 106, Suppl1:9

P314 VITAMIN K2 (MENATETRENONE) AND VITAMIN D FOR THE PREVENTION OF BONE LOSS INDUCED BY LEUPROLID Yoshjaki Somekawa. Akira Wakabayashi. Masae Sakamoto Misako Harada Tomoko Terauti Department of Obstetrics and Gynecology, Toride Kyodo General Hospital, Hongo 2-1-1 Toride City, Ibaraki, Japan Objective: The purpose of this study is to evaluate the efficacy of vitamin K2 and vitamin D in preventing bone loss induced by estrogen deficiency during GnRH analogue leuprolide therapy. Subjects and methods: 58 women (mean age 46.3±O.53 yrs.) receiving leuprolide therapy for estrogen-dependent disease such as endometriosis and uterine leiomyomas were randomly allocated into 3 groups (A group, leuprolide only; B group leuprolide with vitamin K; C group, leuprolide with vitamin K and vitamin D). Bone mineral density (BMD) of the lumbar spine was measured by dual energy x-ray absorptiometry before and after treatment for 6 months. Serum intact osteocalcin (iOC) and urine pyridinoline (Py) were measured before and after treatment for 6 rnonths. Variables in the backgrounds of the patients in each group such as age, weight, body mass index (BMI), age of menarche, and estradiol were compared. Results: There were no significant differences in the background parameters among the three groups. BMD was reduced in all three groups, with reduction rates of 5.21 % (A group), -4.03 % (B group) and -3.8 % (C group). Urine Py was increased in all three groups, at rates of 35.2% (A group), 46.1 % (B group) and 30.7 % (C group). Plasma iOC was increased in all three groups, at rates of 46.7% (A group), 108.4 % (B group) and 100.9 % (C group). Conclusion: Vitamin K has a certain efficacy to prevent bone loss due to estrogen deficiency, and this efficacy is further enhanced when it is combined with vitamin D. And this efficacy is mainly through the activation of bone formation, it is not sufficient for the prevention of GnRH- therapyinduced bone loss.

P315 DIFFERENCES IN CATCH-UP OF MANDIBLE BIOMECHEMICAL VARIABLES AFTER SEVERE PROTEIN RESTRICTION IN WEANING RATS. A TOMOGRAPHIC STUDY A.M. Alippi" M.D. Meta" J.L. Ferretti', P. Schneider', C E. Bozzini' Department of Physiology, Faculty of Odontology, University of Buenos Aires, Argentine1. IDIM-FIM, Buenos Aires, Argentine3. Nuclear Medicine Department, University of Wuerzburg, Germany3 We have previously reported that an early protein restriction in rats reduces mandibular growth and induces deformation of the bone. Catch up growth occurs during rehabilitation which determines attainment of normal bone size after 30 days. The present study was designed to estimate variations in bone mass and mechanical properties of mandibles in 35 SpragueDawley rats fed a diet containing 20% casein, which allows normal skeletal growth, during 60 days after receiving an isocaloric, protein-free diet during the first 10 days after weaning. The same number of age-matched controls were simultaneously studied. Five rats from both groups were sacrificed by ether overdose every 20 days. The excised mandibles were scanned by peripheral quantitative computed tomography (paCT XCT 960A, Stratec, Germany). Protein restriction stopped mandibular growth as well as the natural improvement in bone mechanical quality (as derived from volumetric cortical BMD), mass (cross sectional area) and architectural (moment of inertia) of cortical bone. Mandibular growth parameters recovered after feeding the 20% casein diet. Cortical area, bone mineral content, and moment of inertia remained below control levels despite the catch up observed for volumetric cortical BMD. Results indicate that the mechanical competence of the mandible as a result of an inadequate architectural distribution does not reach normal values during the studied time. Supported by research grants from University of Buenos Aires (OD-033) and CONICET

P316 CALCITRIOL IN THE TREATMENT OF OSTEOPOROSIS G. Dilsen G GOibaba D. Sjndel Istanbul Medical Faculty, Istanbul, Turkey. Wolfson Institute of Preventive Medicine, London, England Calcitriol (Rocaltrol®) (C) is the most biologically active metabolite of vitamin D. The primary role of C is in regulating calcium and phosphate homeostasis and mineralisation of the skeleton. The aim ofthis study is to evaluate the efficacy and safety of C in the prevention and treatment of osteoporosis (OP) 129 patients whose OP was diagnosed by measuring their bone mineral density (BMO) using OEXA (Hologic®) randomly assigned treatment with C (0.2511ll b.d.) for two years. Dietary calcium intake was approximately 900 mg per day. Initial screening consisted of baseline history, physical examination, a lateral radiography of T. to L5, bone mineral measurement and laboratory investigation such as liver function test, serum calcium and phosphate, full blood count, serum urea and creatinine, alkaline phosphatase, osteocalcin, procollagen I and III peptid, parathyroid hormone, 25 hydroxy vitamin 03, 1,25 dihydroxy vitamin 0 urine calcium, creatinine, pyridinolin dexoxypyridinolin and hydroxyprolin. All these measurements were done at baseline, 6, 12, 18 and 24 months later. After Ctreatment, biochemical markers of bone revealed a 3.25% increase in bone formation and a 10.6% decrease in bone resorption in 24 months. Blood Cwas increased to 25.8±1.6 nglml from a baseline value of 14.3±Q.B ng/ml. Totally, BMO was increased from 0.820 gr/cm 2 to 0.891 gr/cm 2in 24 months. T values were also increased from 77.2B±6.90 to 81 .53±6.20 aftertreatment. Osteoporotic patients showed a significant increase in BMD values (p<0.001). No side effects and fractures were occurred. In conclusion, C is a biochemically and clinically effective, as well as inexpensive treatment for osteoporotic patients.

P317 OSTEOBLASTIC BEHAVIOUR IN THE PRESENCE OF BIPHOSPHONATES: AN IN-VITRO STUDY !iJ!jaginP, M.G. Gandolfj2, A. pugnaloni', M. Mattjoli Belmonte" A. De Beneditlis1, ~1, G..""MajnP, A. Caudarella3 1CIBAD- Centre for Innovative Biomaterials, University of Ancona; 21nstitute of Histology and 3Medical Department, University of Bologna Italy The aim of the present study was to obtain new information about the initial steps of osteoblastic growth and extracellular matrix depOSition in an in-vitro osteoblastic model in the presence of biphosphonates, wellknown blockers of bone resorption whose role in osteoblastic and osteoclastic feed-back is still poorly understood. Recent studies of biphosphonates seem to indicate that in the presence of these molecules osteoblast activation may be involved in modulating osteoclast resorbing behaviour. A positive balance in bone remodelling is an important goal of bone metabolism both in the presence of the osteoporotic processes characteristic of ageing and especially of prosthetic implants, in agreement with the aims of any investigation. Our data show a good compatibility between biphosphonates even though alendronate seems to be more suitable for efficient osteoblastic activity. The differentiating features of osteoblasts parallel the presence in the cytoplasm of alkaline phosphatase and osteocalcin. Therefore the detection of these markers in our cultures associated with an ultrastructural picture of correct organellar morphology, supports the hypotheSiS of a metabolically positive action of these molecules on osteoblasts. We intend to continue these studies by applying the same methodologies to osteoblasts from osteoporotic subjects, which are known to display some metabolic differences compared with those or non-osteoporotic ones. This appears a suitable means to study such molecules in vitro without ever losing sight of the fact that human biology must be studied as the biology of a single sick individual ratherthan as a disorder in its "statistical" behaviour degenerative features.

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P32D COMPARISON OF THE ABSORPTION OF CALCIUM CARBONATE VS.

P318 PREVENTION OF POSTMENOPAUSAL-RELATED BONE LOSS WITH OSSEIN HYDROXYAPATITE COMPOUND IN HEALTHY SUBJECTS WHO DID NOT WISH TO USE HORMONE REPLACEMENT THERAPY: RESULTS OF A TWO YEAR PROSPECTIVE TRIAL C Castelo-Branco* F. Pons', J.V. Vanrell* *Menopause Clinic, Department of Gynecology & Obstetrics. 'Nuclear Medicine Department. Hospital Clinic i Provincial. School of Medicine. University of Barcelona, Spain Aim: To evaluate in postmenopausal women who did not wish to use hormone replacement therapy (HRT) whether the continuous administration of ossein hydroxyapatite compound (OHC) may reduce bone loss and prevent osteoporosis. Subjects & Methods: Sixty postmenopausal women were included in this open study and were allocated in three groups. The first group (n=19) received atreatment consisting of 3.32 gr/day of OHC every day; the second group (n=21) received 2.5 mg of calcium carbonate per day; and finally the third group (n=20) constituted a treatment-free control group. Bone mineral density (BMD) assessed by dual X-ray absorptiometry was measured prior to and at 12 and 24 months of treatment. Results: Subjects on OHC therapy group did not show significant changes related to baseline maintaining bone mineral density across the study, whereas a significant decrease was detected in calcium carbonate during the second year -3.7% p<0.05) and control group at the first and second BMO measurement (-3.5%; p<0.05 and -5.6% p
CALCIUM DERIVING FROM MINERAL BONE-MEAL COMPOUNDS L. Rubio J.R. Talbot V. Lotersztein P. Bordelois V. Montagnani A. Marino and J.R. Zancetta Metabolic Research Institute and School of Medicine, Del Salvador University, Buenos Aires, Argentina The objective of this study was to compare the bioavailability of calcium carbonate (CC) and calcium deriving from mineral bone meal compounds (MBC), determined by urinary calcium excretion tests, in healthy women with a mean age of 68±5 years (ranging from 60 to 80 years old). All participants were instructed by trained dietitians to follow throughout the whole study a non-dairy, low sodium diet. Four 24-hour urine samples were collected, two without supplemental calcium intake, one after the intake of 750 mg of elemental calcium as CC and another after 750 mg of elemental calcium in the form of MBC. Thirty three percent of the women showed decreased CC absorption and twenty five percent showed decreased calcium absorption from MBC. Ten percent of the participants with decreased CC absorption corrected such abnormality after MBC administration. The delta of calcium absorption (Figure 1) was significantly higher with MBC compared with CC: 89vs. 58mg/day respectively (p>O.OOl ). 100 , - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - , p<

80 Ci .§. ~

o'"

60 40

20

P319 EFFICACY AND SAFETY OF OSSEIN-HYDROXYAPATITE COMPLEX (OHC) 800 MG TABLETS AND 3200 MG SACHETS VERSUS CALCIUM CARBONATE IN OSTEOPOROTIC POST MENOPAUSAL WOMEN R.S. Lorenc. K. Hoszowski. W. Tlustochowicz The Children's Memorial Health Institute - Warsaw / POLAND Objective: The main objective of this ongoing, open, 3 parallel group trial is to compare the efficacy on Bone Mineral Density (BMD) of the lumbar spine (L2-L4) as well as the tolerability of a 2-year treatment with OHC 800 mg tablets (8 tablets per day), with OHC 3200 mg sachets (2 sachets per day) or with calcium carbonate 500 mg tablets (3 tablets per day) in postmenopausal women. Methods: 125 women older than 55 years were included between January and July 1996, postmenopausal (with amenorrhea >5 years) or ovariectomized (with FSH ~50 IU/ml and estradiol ~:;20 pg/ml). At the inclusion the BMD was s;-2 standard deviations from the normal mean. The main criterion is BMD changes of L2-L4. The secondary criteria are BMD changes of the radius and calcaneus; biomarkers of bone formation and bone resorption (urinary hydroxyproline and deoxypyridinoline) are used. These criteria are assessed every 6 months and clinical examination is done every 3 months. 9 visits are planned. Results: An interim analysis was performed at 6 months on a single marker. Those preliminary results for deoxypyridinoline between baseline and 6 months in each group (A, B, C) show a significant intragroupdifference forthis marker (respectively p=O.Ol, p=0.03, p=0.0002). As the study is still on going, no intergroup-difference has been tested. Conclusion: There is an indication that the three regimens induce a significant reduction in bone resorption over a period as short as 6 months .

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o~~------------cc

mbc

The preliminary results of this study suggest the possibility that 1) decreased CC absorption can be corrected by MBC and 2) calcium deriving from MBC could be better absorbed than CC.

P321 EGG SHELL POWDER AS A CALCIUM SOURCE IN POSTMENOPAUSAL WOMEN WITH EXCESSIVE DEMINERALIZATION A. Schaafsma', I. Pakan " I. Riedstra3, !::!....SNrrn.3, E. Van der Veer 'Friesland Coberco, Leeuwarden, The Netherlands, 'MCL, Leeuwarden, The Netherlands, 3KCL, Leeuwarden, The Netherlands, 4AZG, Groningen, The Netherlands In an open study we compared the effects of an egg shell powder and magnesium-enriched dairy product with a reference product (Ca gluconate) on bone mineral density (BMD) of the lumbar spine and hip in postmenopausal women with excessive demineraHzation. All partiCipants received vitamin D3 Forty-Six women (mean age 62 years, 13.3 years postmenopausal, T-score lumbar spine anteroposterior -2.3) were at random allocated to the reference or test product. The daily intakes of calcium from the reference and test product were 1,000 and 1,200 mg respectively. BMD (DEXA, Hologic QDR 2000) of the lumbar spine, femoral neck and total proximal femur were measured at the start and after 6 and 12 months of intervention. Serum and urine were sampled after 0, 3, 6, and 12 months. Serum was analyzed for bone alkaline phosphatase, active osteocalcin, and pro- and telopeptides of collagen metabolism. Urine was analyzed for pyridinoline and deoxypyridinoline. After 12 months of intervention, an improvement in BMD of the lumbar spine in AP pOSition was seen in the reference group (1.59%, p=0.04; t-test) and test group (1.43%, p=0.06). The effect was particularly established during the last 6 months of the study. The test group also showed an improvement (1.36%, p=0.055) in BMD of the femoral neck. The increases in BMD were substantiated by parameters of ,bone turnover in serum and urine. Despite the small number of participants, this study indicates that the egg shell powder tested is an effective source of calcium that might be able to increase BMD or to prevent bone loss from the lumbar spine as well as from the hip in postmenopausal women with excessive bone loss. Delta BMD 0-12 months, mean (glcm2) +/- 2 SE

.03 .02 .01 0.00 -.01

Test Reference n = 23 n=23

II

lumbar spine AP

.03 .02 .01 0.00 -.01 -.02

II

femoral neck

P322 VITAMIN D DEFICIENCY AMONG HIP FRACTURE PATIENTS: SEVERE MYOPATHY PRECEDES BONE INVOLVEMENT H. Glerup M. GArden J. Jensen E.F. Eriksen Bone and Mineral Research Group, Department of Endocrinology and Metabolism. Aarhus Amtssygehus, University Hospital of Aarhus, Denmark Vitamin Ddeficiency in osteomalacia is known to affect muscle power. We studied Quadriceps muscle power and vitamin D status in 10 hip fracture patients and 10 age, sex, height and weight matched patients, who underwent surgery for localised cancer in the large intestine. Muscle power was measured 5 - 7 days postoperatively. An isometric dynamometer was used for both maximal voluntary contractions (MVC) and electrical twitch measurements. Blood tests were drawn for analysis of vitamin D, PTH, Alkaline phosphatase, CH and P04. The hip fracture patients displayed a low mean level of 25 hydroxyvitamin D: 25,2±4,3 nmolll (mean±SEM) versus 4B,3±7,9 nmolll among the

abdominal surgery patients. All other calcium metabolic parameters were not significant different among the groups. MVC in the quadriceps muscle was: Hip fracture patients Abdominal surgery patients Paired t-test

170,9+26,1 N (Newton) 277,3±25,4 N p<0.01

Furthermore, electrical twitch measurements revealed that the maximal relaxation rate was significantly lower in hip fracture patients. Conclusions: Our results indicate that the vitamin D deficiency seen among hip fracture patients results in significant decreased muscle power and decreased muscle kinetics (contraction and relaxation speed). The severe myopathy was present without any biochemical sign of bone involvement, and may partly explain the higher incidence of falls among hip fracture patients.

P323 THERAPEUTIC EFFECT OF CALCIUM MAGNESIUM IN PRIMARY SENILE OSTEOPOROSIS COMPARED WITH HYPERCALCEMIC DIET INTRODUCTION PiSey Koyilika Military Medical Academy, Belgrade, Yugoslavia Osteoporosis is a bone mass reduction with evident mechanical defect (one fracture at least) There are primary (postmenopausal- type I and senile - type II) and secondary osteoporOSis. Primary, postmenopausal (type 1) osteoporosis occur in the age of 5575 years prevalently in females B:1 ratio and senile osteoporosis (type II) occur in the age of 75 years and over also prevalently in females (2:1) ratio) Osteoporosis (type I) mostly affects trabecular and not cortical structure of the bones, but the type II equally affects both of them. Spinal vertebra are more frequently fractured in the type I while the femur and other long bones are fractured in osteoporosis type II. DIAGNOSIS of osteoporOSiS is established by the X-ray examination (magnetic resonance scan) osteodensitometry as non-invasive method ofthe ionized calcium absorption measurement laboratory findings - osteocalcine, ionized calcium (CaH) and all alkalyne phosphatase in the plasma, urinary calcium, phosphocreatinin and hydroxiproline and finally, by the bone biopsy. The plasma calcium is distributed as the ultrafiltrable calcium (53%) consisting ofthe Ca" (47%) and the calcium complex (47%) with phosphates (1.5%) citrates (1.5%) and bicarbonates (3%) as well as of calcium bound to proteins (47%) that is to albumins 37% and to globulins 10% resulting in the total plasma calcium (100%) with normal levels of 2.12-2.BO mmoill. AIM OF THE STUDY is to present significance of the CaHin the diagnosis of osteoporosis and importance of the CaMg for the courses of the disease . PATIENTS AND METHODS: Randomly selected were two groups each of ten patients over sixty years of age and of both sexes without endocrine, hepatic and renal diseases and malnutrition. All patients were treated with calcitonin and vitamin D(alpha D-3 in the dosis of O.7B micrograms) The first group included patients receiving calcium magnesium ("strorig bones") the dosis of BOO milligrams a day in the following regime: 100 micrograms of calcitonin was snuffed alternately into both nostrils five days a week followed by a two-day break, then two and a half month treatment period followed by the break of the month, then again two and half-month treatment period together with alpha D-3 vitamin 0 75 micrograms a day and BOO milligrams of the calcium The other group received all the same, but instead of calcium magnesium hypercalcemic diet was given. Biochemical parameters Ca" measured by the method without a tourniquet, total plasma calCium, urinary calcium and phosphorus were determined during one month and a half period and the levels were presented as the first ones at the beginning and as the last ones at the end of the treatment. Osteodensitometry was performed at the beginning and after six months and these findings were compared RESULTS are presented in tables and histograms and they, have shown significant affect in the treatment of osteoporoSiS by both methods, but much more significant effect was obtained in the first group treated with calcium magnesium. P
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P324 ALFACALCIDOL IN THE TREATMENT OF OSTEOPOROSIS A. Krasauskiene. L. Lashas. D. Lashiene Institute of Endocrinology, Kaunas Medical Academy To evaluate the efficacy and safety of alfacalcidol, we conducted a two years study in 32 women who had clinical and rentgenological signs of the osteoporosis. All randomly assigned women received treatment with One Alpha (alfacalcidol) 0,251JQ twice a day (LEO Pharmaceutical Products AlS, Denmark). The daily calcium intake was about 1000 mg in diet mainly, except 8 women who got tablets. The patients enrolled in the study were fully ambulatory: 10 women had postmenopausal and 22 senile osteoporosis, 59-77 years old. Clinical investigation, rentgenograms of the thoracic and lumbar spine, serum calcium, creatinine alkaline phosphatase, phospate, LH, FSH, E2, prolactin, TSH, FT4, PTH, and urinary calcium/phospate were obtained before treatment. Calcium, phospate in blood and urine, creatinine and alkaline phosphatase concentrations of were also measured after every 3 months of treating in the two years period. Results. There were no significant changes in biochemical measurements except 3 cases of hypercalcemia (3,3 mmol/l Cal which disappeared after short stop of the treating. The clinical improvement was obtained in 30 patients, in the group of the senile osteoporosis mainly. There were not any new rentgenolocical fractures in this group. Conclusions. The treatment of osteoporosis with ONE ALPHA is safe and reduces clinical sings especially in the group of the senile osteoporosis.

P325 PARATHYROID HORMONE DYNAMICS AFTER DAIRY PRODUCTS INTAKE IN PATIENT WITH MILD PRIMARY HYPERPARTHYROIDISM J.R. Talbot V. Lotersztein A. Marino E. Fradinger J.R. Zanchetta Metabolic Research Institute and Del Salvador University School of Medicine, Buenos Aires, Argentina The objective of this study was to evaluate calcium bioavailability and PTH dynamics after different dairy products intake in a 40 years old female patient with mild primary hyperparathyroidism After a 12 hours fast, two blood samples were drawn at baseline and 1, 2, 3 and 4 h after oral intake of SOD mg of calcium as liquid milk (LM), yogurt (YO) and calcium-citrate enriched powdered milk (PM), or after placebo intake as soybean imitationmilk (SM). Comparing with baseline, calcium-citrate enriched powdered milk induced a significant increase in serum ionized calcium (p<0.001) and significant decrease in serum intact PTH concentration (p<0.001). Yogurt induced a similar, but less Significant effect increasing serum ionized calcium (p
E:::r ~'" ~~

0.04

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.~~ 0_ ~~

cC 0.01

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P326 COMPARISON OF THE EFFECTS ON BONE TURNOVER MARKERS OF ALENDRONATE AND PLACEBO IN EARLY POSTMENOPAUSAL WOMEN Tzay-shing Yang Dept. of Ob/Gyn, Veterans General Hospital -Taipei; National Yang-Ming Univ., SchQol of Medicine, Taipei, Taiwan, R.O.C. Background. Alendronate sodium (Fosamax) is an aminobisphosphonate, it is rapidly distributed to the bone following administration and inhibits osteoclast-mediated bone resorption activities, resulting in reduction of bone turnover rate and leading to progressive gains in bone mass. Methods. A randomized, double blind, placebo controlled study comparing the effects on bone turnover markers of daily treatment with alendronate sodium 10 mg to that of placebo was conducted in the department of Ob/Gyn of Veterans General Hospital-Taipei. Forty early postmenopausal women completed three months, treatment period. Patients received either placebo or Fosamax 10 mg every day continuously throughout the total study period; all the study subjects also received SOD mg calcium carbonate daily. The bone turnover rate was determined by measuring the biochemical markers at baseline, week 6 and at the end of three-month treatment period. The incidence of all the adverse events was recorded during each of the follow-up visits. Results. The patients who received active treatment had significant decreases in urinary excretion of bone resorption marker-deoxypyridinoline (Dpd) as well as one of the bone formation markers-bone specific alkaline phosphatase (Alkphase-B), whereas those who received placebo showed increasing trend of urinary excretion of bone resorption marker and formation markers instead. Atthe end of three months, the mean percentage change of Dpd, Alkphase-B from baseline in the group receiving 10 mg of alendronate was 30.49% and 29.4S% reduction respectively. On the contrary, those receiving placebo were 2.39% and 1.S2% increase respectively. Overall, the mean differences (95% confidence interval) of three biochemical markers (Dpd Alkphase-B and Osteocalcin) between treatment group and control group after 3 months of treatment differed significantly [Dpd:0.752 (0.S83,0.970; p=0.0038), Alkphase-B: 0.727(0.S63, 0.939 ;p=0.0013) and Osteocalcin: 0.S71 (0.3S0,0.932 p=O.OOS). The drug was well tolerated, no significant increase in incidence of adverse effects such as GI discomfort and esophageal irritation was found in the active drug group compared to that of placebo group. Conclusion. Our results demonstrated a similar trend as that shown in published literature. Bone turnover rate decreased quickly following drug administration, the incidence of adverse effects did not differ significantly between active drug group and placebo group. Alendronate may be recommended as an effective non-hormonal treatment for postmenopausal osteoporosis.

E~

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TREATMENT: CALCITONIN, BISPHOSPHONMES, VITAMIN 0 METABOLITES

LM

... u ~

-60

0

2

3

Time (h)

In conclusion, although this pilot study needs to include more patients, our preliminary results suggests the possibility that in patients with mild primary hyperparathyroidism: 1) calcium-citrate salt may induced the better calcium bioavailability and higher iPI Hsuppression observed after calciumcitrate powdered milk intake, and 2) calcium citrate powered milk and yogurt may be better sources of calcium than liquid milk when suppression of serum iPI H its concern.

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P327 THE EFFECT OF ALENDRONATE ON HUMAN OSTEOCLAST FORMATION AND ACTIVITY IN VITRO V. Breuil F. Cosman L. Stein W. Horbert J. Nieves V. Shen. R. Lindsay. DW Dempster Regional Bone Center and Clinical Research Center, Helen Hayes Hospital, West Haverstraw, New York, USA Alendronate (ALN) is now approved for treatment and prevention of postmenopausal osteoporosis. However, its mechanism of action remains unclear. Almost all in vitro studies of ALN's effects on osteoclasts (~C) have been performed in animal models. We describe for the first time studies of the effects of ALN on human DC formation and activity. Peripheral blood mononuclear cells from 14 postmenopausal women were cocultured with ST2 stromal cells on bone slices in the presence of 10·7M 1,2S(OH),D3, 10·8M dexamethasone, and 2S ng/ml human macrophage colony stimulating factor. After 21 days, the cultures contained numerous ~C, which were characterized by multinuclearity, the presence of tartrate-resistant acid phosphatase, vitronectin receptors, calcitonin receptors and the ability to resorb substantial amounts of bone. The percentage area of bone resorbed per slice was highly correlated (r=0.89, p
P329 LONG-TERM INTERMITIENT CYCLICAL ETIDRONATE THERAPY IN STEROID-INDUCED OSTEOPOROSIS: EFFECTS ON BONE HISTOMORPHOMETRY B.F. Boyce R. Daraie* I.T. Boyle* A.J. Freemont** and R. Balena' Univ of Texas Health Sci. Center San Antonio, Texas 78284 USA, Univ of Glasgow*, Univ of Manchester* *, Proctor & Gamble Pharmaceuticals', Staines, England Long-term corticosteroid therapy causes bone loss which is thought to occur due to the combined effects of increased bone resorption and reduced bone formation. We evaluated the effects of intermittent cyclical etidronate (ICT) on bone turnover and mineralisation from a safety perspective in bone biopsies taken from 11 women on long-term glucocorticoid treatment for asthma (4), chronic obstructive airway disease (COAD) (1), asthma and COAD (1), sarcoidosis (1), polymyalgia rheumatica (1), pulmonary eosinophilia (1) seronegative rheumatoid arthritis (1) and dermatomyositis (1). Mean age at the start of ICT was S3 years (range 23 - 66), and the average duration of previous treatment with corticosteroids was 80.6 months (range 26 -1S2). The average duration of treatment with ICT between the baseline and post-treatment biopsy was 26 months (range 8 - 40). Undecalcified bone sections stained with toluidine blue were used for histomorphometric analysis of bone turnover and mineralisation because double tetracycline labelling was performed prior to each pair of biopsies in only three patients. No significant differences were observed between pre- and post-therapy specimens (mean values +SD) for any of the histomorphometric indices of bone turnover: osteoblast surface, ObS/ BS (%) 2.6±1 .8 vs 2.7±2.S; osteoclast surface (OcS/BS%) O.S±O.S vs 0.3±O.4; or of bone mineralisation: osteoid surface OS/BS (%) 11.8±6.S vs 16.7±1 0.7; mean osteoid width OWi (llfTl) 7.S±1.S vs 7.2±1.7; maximum number of osteoid lamellae MNL (n) 2.S±1 vs 3.2±O.9 and extent of mineralisation fronts along osteoid seams (MS/OS%) 9S±3 vs 79±19. No patient developed focal or generalised osteomalacia. It is concluded that intermittent cyclical etidronate therapy given for over 3 years to patients on long-term corticosteroid therapy does not impair bone turnover or have a significant adverse affect on bone mineralisation.

P328 RECURRENCE OF VERTEBRAL FRACTURES UNDER CYCLIC ETIDRONATE THERAPY IN OSTEOPOROSIS: HISTOMORPHOMETRY AND X-RAY MICROANALYSIS EVALUATION T. Thomas O. Barou L. Vi co C. Alexandre M.H. Lafage-Proust LBTO - Faculte de Medecine, St Etienne University, 42023 SAINTETIENNE Cedex 2, France In an open prospective study we evaluated differences between patients with (F group) and without (NF group) recurrence of vertebral fracture (VF) under cyclical etidronate therapy of osteoporosis. Thirty-two patients, 64±1.8 yr. old (mean±SE), characterized by at least one spontaneous crush vertebral fracture received oral doses of 400 mg/d etidronate for 2 weeks, followed by I g/d elemental calcium for 11 weeks, repeated over one year. At baseline in the Fgroup, body mass index (BMI) was significantly lower (23.3±O.6 vs 26.9±1.0 kg/m', P
P330 ETIDRONATE PREVENTS CORTICOSTEROID-INDUCED OSTEOPOROSIS: POOLED RESULTS FROM TWO TRIALS C. Roux" J.D. Adachi A.A. Chines S. Horlait G.F. Stephenson and S. Pack for the Canadian ClOP and European CIBLOS Research Groups 'Centre d'Evaluation des Maladies Osseuses, Hopital Cochin, Paris France (sponsored by P&G Pharmaceuticals) Bone loss is a frequent complication of corticosteroid (CS) therapy, especially within the first few months of treatment. We report pooled results from two similarly designed, randomised, double-blind, placebo controlled trials examining the effectiveness of intermittent cyclical therapy (lCT) with etidronate in patients recently starting CS therapy. One hundred and forty-one subjects (S4 men and 87 women) and 117 subjects (42 men and 7S women) were enrolled into the Canadian (ClOP) and European (CIBLOS) studies, respectively. For both studies, patients starting high dose CS therapy within 90 to 100 days were randomised to receive either ICT-etidronate (400 mg/day) or placebo for 14 days followed by 76 days of calcium supplements (SOO mg/day). This cycle was repeated 3 times over the I year study. The primary outcome measure for both studies was difference in percent change from baseline in lumbar spine bone mineral density (LS BMD), measured by dual x-ray absorptiometry. Of secondary interest was percent change from baseline in BMD of the proximal hip. In both studies, ICT-etidronate and placebo groups were comparable in age, sex, menopausal status, underlying diseases and CS dose. After 1 year, a significant difference between treatment groups (±SE) in LS BMD was observed in both the ClOP (3.7±O.9%) and CIBLOS (3.0±O.8%) study patients (P
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P331 BONE TURNOVER INFLUENCES THE RESPONSE TO ALENDRONATE IN POSTMENOPAUSAL OSTEOPOROSIS C. Cepollaro. S. Gonnelli, B. Rossi, S. Martini, S. Pacini, R. Palmieri, C. Gennari Institute of Internal Medicine, University of Siena, Italy. We have previously shown that in osteoporotic patients the efficacy of calcitonin and estrogen treatment depends on bone turnover. The present study was aimed to investigate the efficacy of Alendronate in women with postmenopausal osteoporosis (PMO). 100 women with PMO were randomized to receive: alendronate (10 mg/day) plus calcium (1000 mg/ day) (N=50) or calcium alone (N=50). Vertebral bone density (BMD-LS, by DXA, Hologic QDR 1000), radial bone density (BMD-R, by DXA, Osteoscan, NIM, Italy) and markers of bone turnover were assessed at baseline and after 1 and 2 years. 94 patients (48 and, 46 respectively) completed the 2-year study period. Alendronate treatment determined an increase of 5.0% and 2.3% respectively at BMD-LS and BMD-R; whereas, in the group treated only with calcium, BMD-LS and BMD-R decreased by 1.9% and 1.3% respectively. The difference between the two groups was significant (p<0.001). Alendronate treated patients were divided on the basis of bone turnover, as assessed by 24-hour whole body retention (WBR%) of 99Tc-methylene-diphosphonate.According to WBR values, 19 patients had a high bone turnover (HT) and 29 had low bone turnover (LT). The response to Alendronate treatment was greater in HT patients compared to LT patients. In fact BMD-LS increased by 7.9% in HT patients and by 3.1 % in LT patients; the difference between the two groups was significant (p<0.001). No significant difference between the two groups was found for BMD-R. The present results suggest that the response to Alendronate, namely at axial level, is influenced by bone turnover. Therefore the evaluation of bone turnover may be useful to identity those postmenopausal osteoporotic women who may especially benefit from treatment with Alendronate.

P332 A SIMPLIFIED THERAPEUTIC SCHEME OF ALENDRONATE FOR POSTMENOPAUSAL OSTEOPOROSIS J.J. Body M.A. Lumen S. DiRomana Bone Diseases Clinic, Inst. J. Bordet, Brussels, Belgium Alendronate (Alen.) at the daily dose of 10 mg has a remarkable efficacy for the treatment of postmenopausal osteoporosis (OPosis). However, the strict and tedious dose instructions can lead to loss of compliance. On the other hand, it is unknown if Alen. has the same efficacy in patients (pts) taking hormonal therapy (HT). We evaluated the tolerance of 30 mg of alendronate/day taken on two consecutive days each week for 6 months. We assessed 59 women with OPosis (T score < - 2.5). 30 were without any other treatment and 29 were on HRT (n=18) or on tamoxifen for a history of breast cancer (n=11) since at least 2 years (range 5, 2-21). Mean age was 63 years (43 - 83). All pts also received 500 mg Ca supplements and 400 IU vitamin 0 daily. Baseline BMD were similar in both groups. Pts filled specific questionnaires weekly on all side effects, especially epigastralgias, pyrosis, nausea, vomiting, diarrhoea and constipation, graded on a scale from 0 to 3+. Six pts stopped prematurely the treatment, two because of adverse events (1 for recurrent erosive gastritis that had healed before starting Alen. and 1 for mild skin rash); 29 pts never noted any side effect. Epigastralgias were noted by 17 pts; they were mild (+) in 14 of them and continuous in only 3 cases. A mild pyrosis was reported by 11 pts, occurring only rarely in most of them. Rare nausea was reported by 13 pts. The type and intenSity of side effects were similar in both groups. Lumbar spine BMD increased significantly (p<0.05) by 2.6±0.7% (mean±SEM) in pts without HT and by 2.3±O.8% in pts under HT. Corresponding figures at the femoral neck level were 1.9±O.7% and 0.8±O.3% (P<0.05), respectively. The response of the two groups was not significantly different. In summary, this convenient therapeutic scheme appears to be well tolerated and its efficacy deserves further evaluation. These preliminary data suggest that the effects of Alen. on bone mass are not less in patients already receiving hormonal treatment.

P333 UPPER GASTROINTESTINAL SAFETY PROFILE OF ALENDRONATE: THE FRACTURE INTERVENTION TRIAL (FIT) D.C. Bauer. D. Black K. Ensrud D. Thompson .M. Hochberg M. Nevitt, T. Musliner and D. Freedholm for the Fracture Intervention Trial Research Group: Universities of California (San Francisco), Minnesota, Maryland, and Merck Research Labs, Rahway, N.J. Background: We have previously reported the upper gastrointestinal (UGI) safety results among the 2027 FIT subjects with baseline vertebral fractures. We now report the UGI safety results among all FIT participants. Subjects: 6459 women age 54 -81 with low BMD were randomized to placebo (PBO) or 5 mg of alendronate (ALN). ALN was increased to 10 mg/d after 2 yrs. with preservation ofthe double blind. Women with major UGI disease (recent or recurrent ulcers, UGI bleeding, or daily use of medication for dyspepsia) were excluded. NSAID users and those with reflux esophagitis were not excluded. Measurements. Self-reported adverse experiences were collected every 3 months over amean follow-up of 3.7 yrs. Serious UGI events were confirmed by hospital or endoscopy records, if available. UGI events were assessed using life-table methods and proportional hazard models. Gastric/duodenal and esophageal events were analyzed separately and perforations, ulcers, and bleeds (PUBs) were combined to assess these more serious events. Results: The incidence of any UGI event was similar in the ALN and PBO groups (47.5% vs. 46.2%, respectively, RR=1.02, 95% CI: 0.95, 1.10). The incidence of gastric/duodenal PUBs was 1.6% in the ALN group and 1.9% in the PBO group (RR=0.86, CI; 0.59, 1.24). Abdominal pain, dyspepsia, nausea, and vomiting occurred with equal frequency in both groups. Esophageal events occurred in 9.9% vs. 9.4% of women in the ALN and PBO groups (RR=1.06, CI; 0.91,1.24). Esophagitis not reported as reflux was more common in the ALN group (0.7% vs. 0.4%), but this was not statistically significant (RR=1.71, CI; 0.90, 3.39). ALN use was not associated with an increase in UGI events even among women at high risk (those ~75, with previous UGI disease, or using NSAIDs). Conclusions: UGI complaints were very common in this study but ALN treatment was not associated with an increased incidence of UGI events, even in high-risk subgroups such as those taking NSAIDs.

P334 SHOULD "NONRESPONDERS" CONTINUE ALENDRONATE? S.R. Cummings W.S. Browner L. Palermo, B. Marcus P. Ross D. Black for the FIT Group University of California, SJ.: Merck Research Labs, Rahway, N.J. USA If a patient loses BMD during the first year of treatment with an agent, such as Alendronate, physicians often believe she has "not responded" and change treatment. To determine whether loss of BMD during the first year of alendronate treatment predicts loss of BMD if alendronate is continued, we analyzed data from two years treatment of 3,017 women with low BMD or vertebral fractures who received alendronate in the Fracture Intervention Trial (FIT) and had annual measurements for 3 years. We compared rates of change during the first year of treatment with 5 mg / day with the probability of gaining or losing bone during the second year of treatment with the same dose. Patients and staff were blinded to treatment and BMD results. Experienced operators used Hologic QDR 2000s to measure total hip BMD with centralized quality control and about 2% preciSion. Data was analyzed by intention to treat. Elimination of noncompliers or analysis of spine BMD produced similar results. Most women who lost BMD during the first year gained during the second. The greater the apparent first year loss, the greater the probability and magnitude of gain in the second year (P<.01; Table). % BMD change during Year 1

Number

% that gained during Year 2

Mean % gain during Year 2

>+4 (gain) +2 to +4 oto +2 -2 to 0 -2 to -4 <-4 (loss)

652 841 894 417 149 64

55 64 68 76 68 81

1.9 2.0 2.1 2.5 3.1 4.7

These results illustrate the principle of "regression to the mean," suggest that alendronate should be continued regardless of change in BMD during the first year, and question the value of monitoring therapy with BMD .

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P335 THE IMPACT OF ALENDRONATE ON HEIGHT LOSS IN WOMEN WITH AND WITHOUT EXISTING VERTEBRAL FRACTURES: THE FRACTURE INTERVENTION TRIAL D.M. Black J. Cauley M. Nevitt D. Thompson. S.R. Cummings for the FIT Research Group Universities of California. San Francisco and Pittsburgh and Merck Research Labs. Rahway, NJ. USA Osteoporosis accounts for 40 to 70% of the height loss associated with aging. The impact of osteoporosis treatment on height loss in women with and without vertebral fractures has been little studied. We analyzed the effect of alendronate (ALN) on height loss using data from the Fracture Intervention Trial (FIT), a randomized trial that enrolled 2027 women with and 4432 women without vertebral fractures (VFx) at baseline. Women were between 55 to 81 years and had BMD (FN hip) <0.68 g/cm. Women initially received 5 mg. of ALN (or placebo, PBO) which was changed to 10 mg. at 2 years without lose of the double blind. Women with VFx were followed for 2.9 years and women without VFx for 4.2 years. Height was measured annually using a Harpenden stadiometer. Prevalent VFx at baseline were assessed by morphometric criteria. New VFx during the trial were defined by morphometry as a reduction of 2':20% (min 4mm) from baseline in the height of any vertebral body (T4 to L4). Among woman assigned to placebo (PBO), those with baseline VFx had 4 times the number of new VFx and 50% greater height loss (9.2 mm) than those without baseline VFx (6.6 mm, p<.001). Overall, those taking ALN lost less height than those on PBO. The difference between the treatment groups was more pronounced in those with baseline VFx (ALN-PBO difference 3.2 mm) compared to those without baseline VFx (1.1 mm, p<.001). Since x-rays were not obtained annually, we could not directly assess the year-by-year effects of ALN on vertebral fractures. However, we examined height loss in each of the first 3 years in all women and in the 4th year in women without baseline VFx. We found that in each year of the study, women taking PBO lost more height than women taking ALN. The difference persisted into the 3,d and 4th years suggesting that ALN continues to reduce VFx incidence after 3 to 4 years of therapy. Conclusion: Women with existing VFx lose height more rapidly than those without VFx. Alendronate is effective in reducing the rate of loss in both groups for at least 3 to 4 years. The potential use of height loss as a surrogate for vertebral fractures in assessing the effects of osteoporosis therapies deserves further study.

Type of Fracture

Prevalent VFx

No Prevalent VFx & FN BMD < - 2.5

Vertebral Any Clinical

RR (95% CI) 0.53 (0.41-0.68) 0.72 (0.58-0.90)

P <0.001 0.007

RR (95% CI) 0.51 (0.31-0.82) 0.64 (0.50-0.82)

P <0.001 <0.001

Hip

0.49 (0.23-0.99)

0.047

0.44 (0.18-0.97)

0.044

The percentage risk reductions with ALN were similar for these 3 types of fractures in the two risk groups The absolute risk differences were also similar for clinical and hip fractures For new vertebral fractures, the risk difference was larger in those with prevalent VFx due to their higher risk of recurrent vertebral fractures. Conclusion: Women with either existing vertebral fractures or with femoral neck BMD T-score s-2.5 experience similar fracture risk reduction on alendronate treatment.

P337 RISK OF NEW VERTEBRAL FRACTURE INCREASES WITH THE NUMBER OF PREVALENT VERTEBRAL FRACTURES, AND DOES NOT VARY BY LOCATION OF PREVALENT FRACTURES M.C. Nevitt P.D. Ross L. Palermo l Musliner D. Thompson, for the Fracture Intervention Trial Research Group Univ. California, San Francisco, USA and Merck Research Laboratories, Rahway, NJ, USA Pre-existing (prevalent) vertebral fractures are a strong risk factor for future vertebral fractures. However, the magnitude of increased risk associated with multiple vertebral fractures has not been thoroughly explored. Furthermore, it is not known whether risk varies with the location of prevalent fractures. To examine these issues, we analyzed data from the 6083 women who participated in the Fracture Intervention Trial (FIT) with baseline and follow-up radiographs. The age range was 54-82 years and patient follow-up ranged from 2 to 4 years. New vertebral fractures, defined as a decrease of at least 20% (and 4 mm) in vertebral height, occurred among 344 women. By design, 32% of FIT women had prevalent vertebral fractures (PFrx) at baseline. The risk of new vertebral fracture increased with the number of PFrx. In the placebo group, new fractures occurred among 54% of the women with 5 or more PFrx, compared to only 4% of women without PFrx. The incidence was much lower in the corresponding alendronate groups.

P336 ANTI FRACTURE EFFICACY OF ALENDRONATE IN WOMEN AT HIGH RISK OF FRACTURE: RESULTS FROM THE FRACTURE INTERVENTION TRIAL D.M. Black D.E Thompson D. Bauer M. Hochberg K. Ensrud lA. Musliner, A.J .Yates, S.R. Cummings for the FIT Research group Universities of California, San Francisco, Maryland and Minnesota and Merck Research Laboratories, Rahway, N.J., USA The Fracture Intervention Trial (FIT) investigated the effect of alendronate (ALN) on fracture incidence in women with one or more prevalent vertebral fractures (VFx) at baseline (n=2027) and those without such fractures (n=4432). The risk of new vertebral fracture, assessed by x-ray, was decreased by 47% and 44% in these groups, respectively, and the risk of any clinical fracture was reduced by 28% and 14%, respectively. Among women with prevalent VFx we found a larger risk decrease in clinical fracture as baseline BMD of the femoral neck decreased. Over 33% of women without a prevalent vertebral fracture had femoral neck T scores 2.5 (WHO threshold for osteoporosis). We compared the efficacy of ALN between two high-risk groups: women with prevalent VFx and women without prevalent VFx but with femoral neck BMD T score s-2.5. In women with prevalent VFx, the annual incidence rates of new clinical fracture were 6.9% (PBO) and 5.1% (ALN), whereas the corresponding rates in women without prevalent VFx and BMD <-2.5 were 5.1% and 3.3%. The corresponding annual incidence rates of hip fractures in the two groups were 0.8% (PBO) and 0.4% (ALN) and 0.5% (PBO) and 0.2% (ALN) respectively. Relative risks (ALN vs. PBO) and 95% Cl's for the two high risk groups are shown below:

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#PFrx 0 2 3-4 5+

Proportion with new frx Placebo Alendronate

Placebo + alendronate combined Odds ratio' Adjusted ORAA

3.8% 8.9% 19.4% 30.8% 54.2%

1.0 2.5* 6.5* 10* 21*

2.1% 5.2% 12.8% 16.3% 18.4%

1.0 2.0* 4.5* 5.7* 10.7*

*p
P338 PREVENTION OF CORTICOSTEROID-INDUCED OSTEOPOROSIS WITH ETIDRONATE: ONE YEAR FOLLOW-UP WITH CALCIUM ONLY R. Josse* J.D. Adachi A.A. Chines S. Pack GJ. Stephenson for the Canadian CIO Research Group *SI. Michael's Hospital, University of Toronto, Toronto, Canada (sponsored by P&G Pharmaceuticals) Patients previously enrolled in a one-year randomised controlled trial on the prevention of corticosteroid (CS) induced osteoporosis with etidronate were followed for an additional year to determine the efficacy of etidronate after 1 year of discontinuation. In the first year of the study, one hundred and forty-one subjects (54 men; 17 pre and 70 postmenopausal women) recently starting high dose CS therapy were randomised to receive either intermittent cyclical therapy (ICT) with etidronate (400 mg/day) or placebo for 14 days followed by 76 days of calcium supplements (500 mg/day). This cycle was repeated 3 times for atotal duration of 52 weeks. Patients in both treatment groups were followed for an additional year on 500 mg elemental calcium per day only. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and trochanter (TROCH). One hundred and fourteen patients (61 and 53 in the placebo and etidronate groups, respectively) completed the first year and entered the follow-up period of this study. Atotal of 101 (89%) of the patients completed the follow-up period. At the end of the second year, the mean percent change from baseline (mean±SEM) in LS BMD was 3.73±O.82% and +0.08±O.58% for patients previously treated with placebo and etidronate, respectively. For comparison, year 1 results were -3.23±0.60% and +0.61 ±0.54%, respectively. The mean percent change from baseline (mean±SEM) was -3.36±O.87% and -0.31±0.63% for the FN and 4.16±O.94% and +0.19±O.68% for the TROCH at the end of the second year for previous placebo and etidronate groups, respectively. For comparison, year 1 results were -1.67±O.67% and +0.19±O.68% for the FN; -2.7 4±O.66% and +1.46±O.67 for the TROCH, respectively. In general patients in the previous etidronate group maintained BMD over the second year. More importantly, there was no accelerated bone loss observed after discontinuation of etidronate. These results suggest that the protective effect of ICT-etidronate therapy in preventing bone loss in patients on chronic CS treatment persists over 1 year after discontinuation of therapy.

P339 EFFECT OF CALCITRIOL IN THE PREVENTION OF TRABECULAR BONE LOSS AFTER CARDIAC TRANSPLANTATION C. Werner S. Florian P. Uberfuhr C.E. Angermann. W.A. Rambeck. K. Theisen R. Gartner H.U. Stempfle Depts. of Medicine, Cardiac Surgery and Veterinary Medicine, University of Munich, Germany. Accelerated bone loss is a well recognized complication after cardiac transplantation (HTx) due to glucocorticoid and cyclosporine therapy. The purpose of this prospective randomized placebo-controlled double blind study was to investigate the effect of Calcitriol (1 a25(OH),D 3} in the prevention of bone loss after cardiac transplantation. Basic therapy included calcium 1000 mg daily and hormone substitution in hypogonadal patients. Patients (88 male, 14 female, mean age: 51±10 yrs.; 33±30 months post HTx) were randomized to 0.25 fl(J Calcitriol or Placebo. Bone mineral density (BMD, g/cm'; T-score, %) was measured at the lumbar spine by dual energy x-ray absorptiometry (DEXA, Hologic-1 ODD); vertebral bone density (VBD) by single energy CT. X-rays of thoracic and lumbal spine for the assessment of vertebral fractures were performed at baseline and after 12 months. Biochemical markers including gonadal hormones, gonadotropins, urinary and serum parameters of calcium metabolism, intact PTH, 25 OHD and renal function were measured.

Results: Baseline BMD [g/cm',] T-Score [%] Fractures VBD [mg/ml] VBD nqrmals

Calcitrol 12 months 0.934 ±O.16 85±14 14 85.7±29.8 125.4±29.4 p<0.0001

Placebo 0.965 ±O.16 87±14 1

Baseline

12 months

0.969 ±O.14 88±11 24 87.9±31.2 122.6±21.5 p<0.0001

1.002 ±O.15 90±12 0

Biochemical analysis showed slightly increased iPTH and an impaired renal function in most patients. There was no significant difference in biochemical markers between the study groups. Conclusion: Patients after HTx showed a significant reduced vertebral bone density using DEXA and CT. Osteoporosis therapy including calcium and hormone substitution in patients with hypogonadism improves bone mass after cardiac transplantation. Additional replacement doses of calcitriol demonstrated no significant extra benefit regarding bone mineral density and fracture rate after one year.

P340 EFFECT OF TREATMENT WITH PAMIDRONATE AND TILUDRONATE IN PAGET'S DISEASE DOCUMENTED WITH QUANTITATIVE BONE SCINTIGRAPHY J. Donath', B. Fornel', Gy. Poor' National Institute of Rheumatology, Budapest, Hungary' Sz1. Imre Hospital, Budapest, Hungary' Objective: To asses the use of quantitative bone scintigraphy (QBS) in the monitoring of bisphosponate treated patients and to evaluate the relationship between biochemical marker of bone turnover and bone scan indices of disease activity. Methods: We investigated one year efficacy of three different dosages of pamidronate and one dosage of tiludronate. 20 patients received a total dose of 180 mg (n:11), 90 mg (n:2) and 60 mg (n:7) pamidronate iv.over 6,3 or 1 days. 3 patients received oral tiludronate 400 mg/day for 3 months. Serum samples were obtained from 23 patients with Paget's disease to determine the levels of total serum alkaline phosphatase (total AP). QBS was performed in every patient and the results were expressed as a ratio, obtained by comparing isotope uptake at an effected and an unaffected control site. Reduction in bone pain was assessed using a pain scale. Efficacy and side effect were monitored for a follow up period of up to one year. Results: Total AP levels fell to minimum of 53±7,8% (180 mg pamidronate) and 42,9±7,2% (60 mg pamidronate) of pretreatment values, respectively. The total AP levels significantly correlated with bone scan score. (Coefficient of correlation=0,634, p=0,0027). The pain scale score decreased significantly (P=0,00009). Side effects, including bone pain, transient fever and stomach-ache have occurred in 3 cases. Conclusion: The treatment with iv. pamidronate and oral tiludronate results in a decrease of the total AP levels and QBS ratio.

•

P341 STEROID INDUCED OSTEOPOROSIS: THE EFFECT OF CALCITRIOL

P343 CALCITONIN TREATMENT IN LATE POSTMENOPAUSAL

VERSUS HORMONAL REPLACEMENT THERAPY IN AMENORRHOEIC PATIENTS AW.C. Kung T.M. Chan, C.S. Lau, R.W.S. Wong Departments of Medicine, The University of Hong Kong, Queen Mary Hospital Hong Kong, PRC. The efficacy of calcitriol and hormonal replacement therapy (HRT) in the treatment of steroid induced osteoporosis in amenorrhoeic women is controversial. We studied 28 patients (aged 37±6yrs) with systemic lupus erythematosus. They were treated with prednisone> 10 mg/d for> 6 months. They were amenorrhoeic for more than 2 years as a result of the disease or treatment with cyclophosphamide. All had osteopenia with T score at L2 - 4 <-1. They were randomised to receive HRT (conjugated oestrogen 0.625mg daily from day 1 to 21 plus medroxyprogesterone acetate 5 mg daily day 10 to 21) or calcitriol 0.5 ~ QD. All received calcium carbonate 1 gm QD. There was no difference in the BMD in both groups at baseline. At 2 yrs, bone mass was maintained in those receiving HRT. Furthermore a 2 % increase in BMD was observed at the spine (p<0.05). Spine BMD did not change in those receiving calcitriol but a significant bone loss at the forearm (2.2%, p<0.02) was observed. Femoral neck BMD did not change in both groups. Comparing both treatment groups, there was a significant difference in the BMD of spine (p
~342

CLODRONATE TREATMENT IN LATE POSTMENOPAUSAL OSTEOPOROSIS R. Tanakol M. Adas S. Yarman H. Bollepe F. Alagol Istanbul Faculty of Medicine, Endocrinology and Metabolism, Istanbul, Turkey Bisphosphonates act in osteoporosis by decreasing turnover and possibly changing the balance at the level of the individual bone multicellular unit. Various bisphosphanates not only prevent the decrease in bone mass in postmenopausal osteoporosis, but actually induce a small increase in bone mineral content. To test the efficacy of continuous oral clodronate treatment in postmenopausal osteoporosis, 14 women with BMD <-2.5 SO T score with vertebral fractures (mean age:57±6 yr; yrs from menopause 12.2±9) received clodronate (800 mg/d) and calcium (500 mg/d) in a 2-yr open treatment trial. Ten randomly chosen postmenopausal osteoporotic patients with T-scores below -2.5 SO (mean age:63±6 yrs; duration of menopause: 14.4±8 yrs) were treated with calcium (500 mg) and vitamin 0 (500 IU/d) for 2 yrs. At the onset of the study, BMD, years from menopause, BMI, age, other risk factors and bone turnover markers did not differ between the two groups (p>0.05 for all). BMD was measured by dual energy x-ray absorptiometry. Markers of bone turnover were also measured. After 2 years (mean:26 months) of clodronate treatment, the BMD increased in the lumbar spine L2-L4 by 12.8% (p=0.0001, compared to baseline), in the femoral trochanter by 7% (p=0.06), in Ward's triangle by 12% (p=0.06), and in the femoral neck by 9.2% (p=0.03). The average percent decrease of BMD in the patients treated with calcium and vitamin 0 was 4.2% in the femoral neCk, 8.3% in the femoral trochanter, 7.4% in Ward's triangle, and 4.8% in the lumbar spine (p>0.05 compared with baseline for all). There was no difference in serum Ca,P, alkaline phosphatase, paratyroid hormone, osteocalcin, urinary hydroxyprolinel creatinine, and urinary calcium/24 h between the groups at the end of the study. There was no significant difference in the overall number of adverse events related to clodronate treatment. In conclusion, clodronate is a safe and effective treatment for severe postmenopausal osteoporosis.

OSTEOPOROSIS R. Tanakol S. Yarman H. Bollene F. Alag61. H. Azizlerli Istanbul Faculty of Medicine, Endocrinology and MetabOlism, Istanbul, Turkey. It is well known that salmon calcitonin has beneficial anti resorptive effect in early postmenopausal osteoporosis. Recent studies demonstrate that significant bone turnover also takes place in the late postmenopausal period. The main purpose of this trial was to determine the effects of salmon calcitonin treatment on BMD and bone metabolism in patients with an average and minimum number of years after menopause of 16 and 5 years, respectively. Twenty-eight randomly chosen patients (mean age:59±9 yr; mean duration of menopause:15±9 yr) with T-score below -2.5 SO were assigned to receive parenteral calcitonin (100 IU/d) and calcium (500 mgl d) for 2 years. Nine patients (Group K1) with a T-score between -1 and -2.5 SO and 6 patients (Group K2) with a BMD< -2.5 SO T-score received calcium (500 mg/d) and vitamin 0 (500 IU/d) for 2 yrs. BMD in gr/cm' was measured by dual energy x-ray absorptiometry. Biochemical markers of bone turnover were also measured. After 2 yrs of calcitonin treatment, BMD at femoral neck and lumbar spine increased by 7.8% and 0.8%, respectively (p<0.05 for both). In K1 and K2 groups, there was no significant change in BMD at any site whether the groups were evaluated separately or together. In calcitonin-treated patients, serum calcium decreased from 9.8±O.3 mg/dl to 9.7 mg/dl (p=0.03), and alkaline phosphatase increased from 82.1±44 lUlL to 86±43 lUlL (p>0.05), and PTH increased from 25.4±16 pg/ml to 35±28 (p=0.05) at the end of the first year of treatment. Urinary hydroxyproline level decreased from 26.6±26 mmol/mol Cr to 13.1 ±4.2 at the end of the second year (p=0.01). One patient had to stop calcitonin treatment due to urticaria. In conclUSion, salmon calcitonin treatment in late postmenopausal osteoporosis seems to be as efficient an anti resorptive treatment as in early postmenopausal osteoporosis. The need for calcium intake may be increased during calcitonin treatment in late postmenopausal osteoporosis.

P344 A 9 MONTH FOLLOW UP OF CYCLICAL I.V. CLODRONATE THERAPY

•

T. Pap W. Flach and J. Kekow Clinic of Rheumatology, University of Magdeburg, 0-39245 Vogelsang, Magdeburg, Germany To evaluate the efficacy of cyclical i.v. clodronate we studied bone mineral density (BMD) and markers of bone turnover in patients with osteoporosis receiving 1500 mg of clodronate split in 300 mg infusions on 5 consecutive days. Infusions were repeated in 3 month intervals (initial mean T-score3.7; 12 postmenopausal women, 10 patients with secondary osteoporosis). Prior to each infusion series the lumbar spine BMD (L 1-L4) was measured by DXA technique. We further analyzed relevant parameters of bone metabolism (osteocalcine rOC]' deoxypyridinolin crosslinks [DPD], Ntelopeptides [NTX)) at entry and all consecutive visits. At the beginning of the study, osteoporosis was accompanied by elevated levels of bone resorption parameters (DPD 10.7 nmol/mmol creatinine; NTX 108.9 nmoll mmol creatinine). Additionally, we found elevated levels of OC (15.8 ~/I). Already 3 month after the first infusion series a significant increase in BMD (+ 5.2%, p<0.01) could be observed. This was associated with a significant decrease in DPD (8.2 nmol/mmol creatinine, p
P345 DUAL X-RAY ABSORPTIOMETRY (DXA) AND QUANTITATIVE ULTRASOUND (QUS) FOR MONITORING ALENDRONATE TREATMENT FOR OSTEOPOROSIS. A.B.C. Machado. B.M. Ingle and R. Eastell Bone Metabolism Group, Clinical Sciences Centre, University of Sheffield, Sheffield, England. Non-response or non-compliance to anti resorptive therapy may be identified by treatment monitoring. The aim of our study was to compare DXA and QUS for monitoring alendronate treatment. We studied 26 women with postmenopausal osteoporosis (BMD T score less than -2.5), ages 50 to 79 years (mean (SD), 65.3 (8.3)) for one year. The patients were randomised in a 2:1 ratio to reCeive alendronate (10 mg/day) and calcium carbonate (500 mglday of elemental calcium) or calcium alone. We measured bone mineral density of lumbar spine and proximal femur by DXA using Hologic Acclaim, heel QUS using 2 different machines, Lunar Achilles and Hologic Sahara, and finger QUS using DBM Sonic 1200. The measurements were done at baseline, 6 and 12 months. We identified responders as those who increased BMD or QUS by more than 2.77 times the short-term CV (the least significant change at P=0.05). The changes in DXA and QUS measurements at one year are shown in the table as mean difference (standard error of the difference) and the number of patients defined as responders (out of the 15 women that completed one year of alendronate and calcium therapy.

Lumbar spine Femoral neck Trochanter Hologic QUI Lunar Stiffness DBM AD-SOS

Mean difference (SE), %

Responders

4.82 (2.03) * 3.11 (2.02) 8.16 (2.36)** -2.87 (3.11) 1.74 (1.67) 1.22 (1.67)

7/15 1/15 6/15 1115 0/15 1/15

*p
P346 SHORT OR LONG-LASTING EXPOSURE TO CLODRONATE IN POSTMENOPAUSAL OSTEOPENIC WOMEN: EFFECTS ON BONE MASS P. Filipponi S. Cristallini G. Policani C. Casciari, L Fedeli* Bone & Mineral Research Unit; *Nuclear Medicine, University of Perugia - Italy There is some uncertainty concerning the offset of bisphosphonates in osteoporosis. Most newer bisphosphonates have been given continuously and it was reported that their effects reverse briefly after discontinuing treatment. Some studies, on the other hand, indicate alonger-lasting effect. AIM &STUDY DESIGN. The present study examined the effects on bone mass of a short- or along-lasting exposure to clodronate in 83 postmenopausal osteopenic women. The women were treated with clodronate (CD) for 18 months: BMD of lumbar spine and proximal femur was measured at the beginning of the study and every 6 months. The patients were given atotal dose of 5400 mg of clodronate using differenttreatment patterns. A) ashort-Iastinq exposure treatment pattern (1800 mg every 6 months in asingle iV infusion, i-day, or 300 mg/day iV infusion over6 consecutive days, 6-days). B) a long-Iastinq exposure treatment pattern (100 mg every 10 days by iM injection or 400 mg/day orally, administered, Os). RESULTS. NO clinical side effect were observed during the iV administration nor alterations in biochemical routine tests, particularly in the renal function. During the 18-month follow-up there was a decrease of BMD in the Pbo group of more than 2% at the lumbar spine; the decrement approached 1% at the various sites of proximal femur. Both treatment patterns involving a long-lasting exposure of the skeleton (iM and Os) caused similar increases in BMD. The increase was in the range of 2% at lumbar spine and of 1% at proximal femur. Shortterm exposure to CD, either with 1 day or 6-days schedules, determined a small increase in BMD or a stabilisation of bone mass. WE CONCLUDE that both short- and long lasting skeleton exposure to clodronate are effective in preventing bone loss in postmenopausal osteopenic women. Short-lasting treatment patterns could be indicated in the prevention of osteoporosis in women without a marked reduction in bone mass. The mechanism by which very short-lasting exposure affects bone turnover, in a manner similar to that observed in Paget's disease of bone, is worthy of further study.

P347 THREE YEAR CONTINUOUS INTRAMUSCULAR CLODRONATE THERAPY OF POSTMENOPAUSAL OSTEOPOROSIS M. Rossini N. Zamberlan D. Gerardi O. Viapiana and S. Adami C.O.C. Valeggio, Verona, University of Verona, Italy Long-term daily administration of oral bisphosphonates has been effectively used for the treatment of postmenopausal osteoporosis, but the duration mode and cost of the therapy may sometimes affect patients' compliance. Clodronate is available in Italy also for the intramuscular (I.M.) route of administration: this study was performed to test its efficacy in postmenopausal osteoporosis. 90 osteoporotic postmenopausal women were enrolled in a randomizlld controlled three year study. The diet of all patients was adjusted to provide 1200-1300 mg calcium daily, eventually by administration of supplements. Patients were randomly assigned to no therapy (30 patients) or to receive Clodronate 100 mg LM. either every two weeks (30 patients) or one week (30 patients). The I.M. injection caused substantial local in site pain which led to treatment withdrawal in almost 50% of the patients receiving weekly dosing. In control patients a progressive slow decline in spine and femoral bone mineral density (BMD), which became statistically significant at the end of the second year of observation, was observed. In the patients given weekly I.M. Clodronate the spine BMD rose by 3,8% (±7,3 S.D.) within six months. A slight not significant increase was observed thereafter, such that at the completion of the 3 years of observation the mean gain was 4,5% (±6,3). In the patients treated with fortnightly injections of 100 mg Clodronate the increase in BMD was somewhat lower and slower, becoming significant only at the 24th month (2,9+4,6%). In none of the two active groups the femoral neck BMD changed significantly during the 3 years of the study. A significant increase in trochanter and Ward's triangle BMD was observed at month 12 only in the patients on the highest dose of Clodronate. In both treated groups all hip BMD changes were significantly different than those observed in control patients. The biochemical markers of bone turnover were suppressed in both Clodronate groups. These results indicate that intermittent I.M. Clodronate administration can provide clinically relevant benefits on skeletal bone density in osteoporotic postmenopausal women, but its extensive use may be limited by the in site pain.

P348 TIMING CYCLICAL DIDRONEL. IS 2 HOURS ENOUGH? P.J. Ryan G. Worcester OsteoporOSiS Unit, Dept. Nuclear Medicine, Medway Hospital Gillingham, Kent, ME7 5NY, UK It is widely recognised that bisphosphonates are poorly absorbed via the gastro intestinal tract. When prescribed orally it is advised that they be taken fasting, and for cyclical didronel at least 2 hours either side of meals or drinks apart from water. There is little data to assess the effect of this advice in clinical practice. In this study we investigated the importance of timing of the didronel component of didronel PMO on change of lumbar spine BMD. Seventy patients who had been taking didronel PMO for at least a year and who had at least 2 DXA scans were sent a questionnaire enquiring as the time of day they usually take didronel and when in relationship to food and drink. Patients all had yearly scans after baseline measurement of spine and hip BMD using the Lunar DPX alpha. Replies were received from 52 patients. They were of average age 67.5 years (SD 6.01) and had been on treatment for an average of 2.7 years. Timing of didronel was divided into 1) fasting on waking, 2) during the day, 3) before'retiring to bed.

•

Timing of Didronel

Nos

Age

Mean (SD) 1 Year BMD Change

Morning Day Night

13 19 20

68 67 68

+3.1 (3.1) -0.14 (5.6) + 5.4 (7.4)

There was a significantly greater rise in spinal BMD for patients taking didronel in the morning or late evening than during the day. We conclude that the 2 hour rule may be insufficient during the day and the didronel component PMO is best taken early morning or late evening.

P349 RISEDRONATE INCREASES BONE MINERAL DENSITY ATTHE HIP, SPINE AND RADIUS IN POSTMENOPAUSAL WOMEN WITH LOW BONE MASS M. McClung', W. Bensen', M Bolognese 3, S. Bonnick4, M. Ettinger5, S. Harris', T. Knecht', R Lang', P. Miller', E. Pavlov 1O , S. Silverman", G. Woodson", K. Faulkner'. D. Ethgen 13 , 0, Axelrod'3 'Portland, OR, USA; 'Hamilton, ON, Canada; 3Gaithersburg, MD, USA; 4Denton, TX, USA; 5Stuart, FL, USA; 'San Francisco, CA, USA; 'Salt Lake City, UT, USA; 'New Haven, CT, USA; 'Lakewood, CO, USA; 100 wings Mills, MD, USA; "Beverly Hills, CA, USA; "Decatur, GA, USA; "Cincinnati, OH, USA. A multicenter, randomized, double-blind, placebo-controlled, dose ranging study was conducted in postmenopausal women (PM) with low lumbar spine bone mineral density (BMD) (t-score below -2) to assess the efficacy and safety of oral risedronate (ris). Patients received placebo, ris 2.5mg or 5mg daily for up to 18 months. All patients received 1g supplemental calcium daily. Patients with active GI disease or on chronic NSAIDs were not specifically excluded from study participation. The % change from baseline (bl) in lumbar spine BMD was the primary parameter of interest. BMD of the femoral neck and trochanter, the midshaft and distal radius was also measured by DXA. Patients enrolled: placebo: 220, 2.5mg ris: 212, 5mg ris: 216 patients. 78% and 62% (of patients completed 12 and 18 months respectively. +*

+ •

_Plac

B

2.5mgris

50 mg ris

the final formulation which will be marketed. Rtreatment did not result in clinically significant changes to laboratory parameters, other than those related to bone metabolism. Paired tetracycline libelled iliac crest biopsies were performed on 14 patients who received 10, 20, or 30 mg of Rfor 28 days. Data from the three groups were combined because of the small sample size. From the histomorphometry performed for pagetic bone (9 patients) and normal bone (5 patients), there is no evidence of osteomalacia; normal lamellar bone is formed in the presence of R. In conclusion, risedronate is a well tolerated treatment for Paget's disease with a favorable safety profile.

P351 INTEGRATED ANALYSIS OF EFFECTIVENESS OF RISEDRONATE FOR PAGET'S DISEASE OF BONE P. Miller" F. Singer', J. Brown 3, E. Siris" D. Hosking', ~', ~', D. Axelrod' 'Colorado Center for Bone Research, Lakewood, CO, USA; 'John Wayne Cancer Inst., Santa Monica, CA, USA; Centre de I'{)steoporose de Quebec, Sainte-Foy, Canada; 4Columbia Univ. Conege af P&S, New York, NY, USA; 5City Hospital, Nottingham, UK; 'Procter & Gamble, CinCinnati, OH, USA Five studies were conducted using 30 mg oral risedronate (R) in the treatment of Paget's disease. All studies were open-label except study RPD, which was double-blind. Efficacy data from these studies are summarised below.

+: signif. incr. from bl *p
-1

Spine

F. Neck

F. Troch

Dis radius

Dose period

Mid radius

The number of dropouts due to adverse events were comparable among the treatment groups (8% per risedronate group, 11 % placebo). In addition, the incidence of mild to moderate upper GI adverse events, and nonvertebral fractures were low and comparable among the groups. In conclusion, risedronate is a well-tolerated and effective therapy in PM women with low BMD. Dose-dependent effects were observed at spine and hip sites. There was also evidence that risedronate had positive effect at the wrist.

P350 A SAFETY REVIEW OF THE USE OF RISEDRONATE IN THE TREATMENT OF PAGET'S DISEASE OF BONE E...fulliNr'. J. Brown', E. Siris3, D. Hoskings4, P. Miller5, D. Ethgen', D. Axelrod' 'John Wayne Cancer Institute, Santa Monica, CA, USA; 'Centre de I'Osteoporose de Quebec, Canada, 3Dept of Medicine, Columbia Univ., New York, NY, USA, 4City Hospital, Nottingham, UK; 5Colorado Center for Bone Research, CO, USA, 'Procter & Gamble Pharmaceuticals, Cincinnati, OH, USA Risedronate (R) monosodium salt is a pyridinyl bisphosphonate which has been recently extensively investigated in the treatment of Paget's disease. Safety data have been collected from 6 completed studies. Five of the studies were open-labelled and performed with either R hard gelatin capsules, delayed-release beads, or enteric-coated tablets. One study (RPD) was conducted as a randomized, double-blind, active control using Didronel 400mg/day for 180 days as the active control group versus R 30mg/day for 2 months. In the latter study, the dosage form of R used is the final formulation to be marketed. Among the 453 patients enrolled in these studies, 392 patients were randomized to receive Rat doses ranging from 10 to 30mg for 28 to 84 days and 61 remaining patients received Didronel. In the combined studies, the overall incidence of AE's was lower in the R treated patients compared to Didronel patients. Between groups, the incidence of withdrawals and serious AE's was similar. Upper GI events were of particular interest during this clinical program. In the combined studies patients in the Rand Didronel groups reported a similar incidence of upper GI AE's. In the RPD study the incidence of individual upper GI AE's was similar between treatment groups. It should be noted that no cases of esophagitis were reported in study RPD in which patients took

•

N AP' criteria AP at Baseline 4 %/in Ap5 % with 2': 50%AP % pts normalized' pAin relief'

88040 28 days

90009 56 days (2x')

RPD 60 days

91007 84 days (2x)

91020 84 days (2x)

21 3x ULN3 8x ULN 72% at 3mo 76%

13 9x ULN 17x ULN 80% (91%) 77% (775) 0% (8%) nm

60 2x ULN 3x ULN 88%

160 3x ULN 7x ULN 75% (78%) 88% (93%) 33% (54%) p<0:001

20 3x ULN 6x ULN 80% (86%) 95% (95%) 40% (65%) p=0.003

14% mnm

93% 77% SF-36, p=.01

'pts could receive 2 courses; 2nd course date in brackets; 'Total serum alkaline phosphatase; 3upper limit of ref. range; 4based on mean AP value; 5% decrease in baseline excess AP at 6 months, except where indicated (bl. Excess = diff. between bl. and midpoint of the ref. range), 'reached AP ref. range; nm = no measured. Observations: (1) a substantial body of data exists: 274 patients treated for 1 to 6 months; (2) most patients had severe Paget's disease; (3) the decreases in AP were consistent and striking, dosing beyond 2 months does not add significant benefit; (4) most patients had 150% decrease from bl. in AP; (5) the % of patients whose AP normalized varied based on bl. disease severity and treatment period, at the 6 month observation 77% of patients in study RPD normalized with the 60-day regimen; (6) retreating less responsive pts is beneficial; (7) pain relief was observed in all three studies in which this was measured. In conclusion, 30 mg oral risedronate was found to be highly effective in the treatment of Paget's disease.

P352 ESTIMATION OF 100 AND 200 IU/DAY OF CALCITONIN INTRANASAL AND CALCIUM AND VITAMIN D PER OS IN THERAPEUTIC TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN FEMALES WITH DIABETES MELLITUS TYPE II (NIDDM) M. Andrianou A. Pappas L. Papagrigoriou E. Theodorou. O. Alexopoulou S. Stathopoulou I. Giannakopoulou M. Zachariou and Ph. Kaldrymidis Endocrinology Department, "Metaxa" Cancer Hospital, Piraeus-Greece Aim: This study was carried out in order to evaluate the effect of intranasal salmon Calcitonin (sCT) in therapeutic treatment of postmenopausal osteoporosis in females with NIDDM. Methods: We studied 22 women with NIDDM who fulfilled the following criteria 1. Time from the last menstruation >3 years, 2. duration of NIDDM >5 years and 3. absence of any other systematic disease or endocrinopathy. Osteoporosis was diagnosed through physical, x-ray examination and Dual energy-x-ray absorptiometry (DEXA) forthe measurement of bone mineral density (BMD) of lumbar spine (L2-L4) and femoral neck. All patients had not been undergoing any other treatment for osteoporosis for at least 6 months before entering the study. The participants were divided randomly into two groups of 11. The patients of group A (aged 56.46±5.37, weight 75.3±13.8, BMI: 29.2±3.7) were treated with 100 IU/d sCT intranasal for a 24-month period whereas the patients of group B (aged 55.95±4.97, weight 74.9±14.1, BMI: 29.1±3.5) were treated with 200 IU/d for the same period. Women of both groups (during the same period) received an additional amount of 1000 mg calcium/d and 0.25 ,ug Vit Did per os. For the assessment of clinical efficacy and safety of the treatment we measured BMD of L2-L4 and femoral neck before, 12 and 24 months after the beginning of treatment. The serum levels of BGP, ALP, Ca, P and the 24 hour urinary concentration of Ca, Pand OH-proline/gr creatinine were also measured before and every 3 months during the treatment. In the beginning of the study we had the following results: group A: BMD L2-L4 0.796±O.08, BMD femoral neck: 0.674±O.06 gr/cm', Group B: BMD L2-L4: 0.792+0.07 gr/cm', BMD femoral neck: 0.674±O.06 gr/cm'. Results: The patients of group A showed an increase of 1.8% in BMD of lumbar spine (L2-L4) and a decrease of 0.9% in BMD of femoral neck. The patients of group B showed an increase of 3.7% in BMD of lumbar spine (L2-L4) and an increase of 0.1 % in BMD offemoral neck. No statistically significant changes of the biochemical markers were observed. No side effects were registered and all patients had a good compliance to therapy. Conclusion: The dose of 200 IU/d sCT intranasal seems to be more effective than the dose of 100 IU/d in therapeutic treatment of postmenopausal osteoporosis in females with NIDDM.

P353 ESTIMATION OF 100 AND 200 IU/DAY OF CALCITONIN INTRANASAL AND CALCIUM AND VITAMIN D PER OS IN THERAPEUTIC TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN FEMALES WITH DIABETES MELLITUS TYPE II (IODM) M. Andrianou L. Papagrigoriou A. Pappas V. Patsiali J. Goudios R. Dallou E. Theodorou Endocrinology Department, "Metaxa" Cancer Hospital, Piraeus-Greece Aim: This study was carried out in order to evaluate the effect of intranasal salmon Calcitonin (sCT) in therapeutic treatment of postmenopausal osteoporosis in females with IDDM. Methods: We studied 22 women with IDDM who fulfilled the following criteria 1. Time from the last menstruation> 3 years, 2. duration of IDDM > 5 years (21±8) and 3. absence of any other systematic disease or endocrinopathy. Osteoporosis was diagnosed through physical, x-ray examination and Dual energy-x-ray absorptiometry (DEXA) for the measurement of bone mineral density (BMD) of lumbar spine (L2-L4) and femoral neck. All patients had not been undergoing any other treatment for osteoporosis for at least 6 months before entering the study. The participants were divided randomly into two groups of 7. The patients of group A (aged 51.21±3.16, weight 67.6±9.3, kg, BMI: 26.2±3.2) were treated with 100 IU/d sCT intranasal for a 24-month period whereas the patients of group B (aged 50.75±2.98 weight 66.9±9.7, BMI: 26.1±3.4 were treated with 200 IU/d for the same period. Women of both groups (during the same period) received an additional amount of 1000 mg calcium/d per os. For the assessment of clinical efficacy and safety of the treatment we measured BMD of L2-L4 and femoral neck before, 12 and 24 months after the beginning of treatment. The serum levels of BGP, ALP, Ca, P and the 24 hour urinary concentration of Ca, P and OH-proline/gr

creatinine were also measured before and every 3 months during the treatment. In the beginning of the study we had the following results: group A:BMD L2-L4 0.753±O.09, BMD femoral neck: 0.631±O.07 gr/cm', Group B: BMD L2-L4: 0.748+0.08 gr/cm', BMD femoral neck: 0.629±O.09 gr/cm'. Results: The patients of group A showed an increase of 2.1% in BMD of lumbar spine (L, -L,) and a decrease of 1.2% in BMD of femoral neck. The patients of group Bshowed a decrease of 4.2% in BMD of lumbar spine (L2L4) and an increase of 0.7% in BMD of femoral neck. No statistically significant changes of the biochemical markers were observed. No side effects were registered and all patients had a good compliance to therapy. Conclusion: The dose of 200 IU/d sCT intranasal seems to be more effective than tile dose of 100 IU/d in therapeutic treatment of postmenopausal osteoporosis in females with IDDM.

P354 THE EFFECT OF 200lU CALCITONIN ADMINISTERED DAILY ON BIOCHEMICAL BONE MARKERS AND BONE DENSITY IN PATIENTS WITH ACUTE HIP FRACTURE I. Kaloudis Th. Karachalios N.T. Roidis K. Baraiotas, G.V. loannidis AA Galanos G.P. Lvritis Laboratory for the Research of Musculoskeletal System, KAT Hospital, Greece Introduction: It is well known that immobilization leads to bone loss and our effort is to prevent and reverse this phenomenon. Materials and methods :In this trial 34 women were studied with acute hip fracture in order to find out if calcitonin prevents bone resorption and bone loss. The study included healthy patients over 70 years old without any cause of secondary osteoporosis. All patients were operated on the third to fourth post-traumatic day. On the first post-traumatic day, blood and two-hour urine samples were taken in order to begin the calcitonin therapy. The patients were divided in two groups: the first group (A) was given intranasal spray of 200lU calcitonin daily for three months, whereas the other group (B) was given placebo. The biochemical bone markers were measured on the 1st , 7th , 15'h, 45'h 90'h day and the bone density in spine and healthy hip, measured the 3,d and the 90'h post-operative day. Results: Alkaline phosphatase was increased in the first week and remained higher than in the beginning during the three months especially in the calcitonin group. The 15'h day the greatest rise was observed (p<0.005). The same phenomenon was found with osteocalcin (p=0.05). Hydroxyproline and cross-laps excretion in two urine samples was seen to be lower in calcitonin group, especially on the 15'h day for both bone markers (p=0.015 and p=0.045 respectively) and on the 45'h day only crosslaps were reduced (p=0.002). Analysing the measurements from the hip and the spine densitometry, it was found that group A (calcitonin group) gained bone mass, statistical significantly, in spine (p=0.005) and neck (p=0.0005). Even though both groups lost bone mass in throchanter and Wards triangle, group B lost much more bone mass than group A. Conclusions: These results show that calcitonin prevents bone mass loss in patients with acute hip fracture. Concerning the biochemical bone markers during treatment with calcitonin, the markers of bone formation were increased and of bone resorption were decreased.

•

P355 ANALGESIC EFFECT OF SALMON CALCITONIN SUPPOSITORIES IN PATIENTS WITH ACUTE PAIN DUE TO RECENT OSTEOPOROTIC VERTEBRAL CRUSH FRACTURES: A DOUBLE BLIND, PLACEBOCONTROLLED CLINICAL STUDY G.V. loannidis A.A. Galanos N. Papaioannou N.T. Roidis I. Kaloudis, A. Theodorou Th. Karachalios G.P. Lyritis Laboratory for the Research of Musculoskeletal System, KAT Hospital, Greece Introduction: The aim of the study was to ascertain the analgesic efficacy of calcitonin suppositories (200IU) in comparison to bed-rest and paracetamol tablets, as a rescue analgesic, in patients with acute pain due to recent osteoporotic vertebral crush fracture. Patients and methods: Forty patients of both sexes, aged 63 - 91 years, suffering from a non-traumatic vertebral fracture on the last five days., were included in a prospective double blind, randomized, placebo controlled, clinical trial. All the patients were hospitalized, divided randomly in two groups and received either one calcitonin suppository, or placebo suppository once a day each evening respectively. All the patients were allowed to take paracetamol500 mg, up to six tablets daily. Their spinal pain was assessed in two ways: 1) Using Huskinsson's visual analogue scale (VAS), 2) By direct pressure on the fractured vertebra, using a painmeter device. At the baseline, pain was assessed in a bedridden pOSition, afterwards (if patient was able to found it possible) in a sitting position and finally in a standing and walking position. The same observers performed a daily clinical estimation of pain for a period of 28 days. Biochemical urine and plasma measurements were carried out at the baseline and on day 14, 28. Results: At baseline no significant differences between the two groups were found, neither in the clinical data (pain estimation), nor in the biochemical measurements. Pain was reduced dramatically in patients receiving calcitonin suppositories (p~0.0005) in all positions. Early mobilization of these patients and the gradual restoration of the locomotive functions, such as sitting, standing and walking accompanied this analgesic effect. On the other hand, patients receiving the placebo suppositories remained in bed for almost the whole of the observation period. The consumption of high doses of paracetamol did not help these patients to get out of bed during their four weeks of hospitalization. Calcitonin-treated patients had low fasting hydroxyproline/creatinine and calcium/creatinine ratios excretion (p~0.0005 at 28 days), while, in the placebo group, these biochemical indexes showed a gradual increase during the study (p~0.0005 at 14, 28 days). Conclusion: Salmon calcitonin suppositories in a daily dose of 200lU have been proved to have adequate analgesic effect to promote the early mobility of patients.

P356 ALTERATIONS OF BONE MINERAL DENSITY IN PATIENTS WITH PRIMARY OSTEOPOROSIS TREATED WITH SYNTHETIC HUMAN CALCITONIN P. Kapuscinski M. Talalai E. Marcinowska Department of Internal Medicine, Postgraduate Medical Education Centre, Warsaw, Poland. The purpose of the study was to evaluate the alterations of bone mineral density in patients with primary osteoporosis treated with synthetic human calcitonin. Twenty patients with diagnosis of primary osteoporosis proved by lateral X-rays of the dorsa-lumbar spine (Th3-L5) and DXA were studied. The patients have been treated with synthetiC human calcitonin (SHC) for 18 months. SHC was injected intramuscularly every day in a dose of 0.5 mg through the period of 28 days, followed by 10 injections given every third day, and then every three months the injections were given for 10 consecutive days. Additionally the patients received 1a OH vitamin D3 in a dose of 0,25 iJ!l daily and calcium carbonate 0.5 - 2.0 g daily according to the results of biochemical tests. Statistical analysis was performed by means of Chi' test for correlated groups. Fourteen patients were analysed because 2 of them resigned from therapy due to adverse events and 4 because of other reasons. After 6 and 12 months of therapy a non significant increase in bone mineral density was observed as compared with baseline values. After 18 months of combined SHC, 1a-OH vitamin D3 and calcium supplement therapy statistically significant increase in bone mineral density (p
P357 TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH ESTROGEN, CALCITONIN, BISPHOSPHONATE, VITAMIN D, CALCIUM AND FLUORIDE A. Slabik-Led6chowska M. Talalai. P. Kapuscinski E. Marcinowska Department of Gynecology and Department of Internal Medicine, Postgraduate Medical Education Centre, Warsaw, Poland The aim of the study was to quantify and compare the effects of estrogen, salmon calcitonin /CT/, bisphosphonate, vitamin D metabolite, calcium, and fluoride on bone mineral density /BMD/ and vertebral fracture rate in women with postmenopausal osteoporosis. 180 women suffering from postmenopausal osteoporosis (T-score below -2.5), aged 55 - 85 years, on an average 11 years after the menopause were enrolled in a 2-year prospective study. The patients were divided into 8 comparable groups regarding age, BMD and years after the menopause, and treated as follows: I n=25) CT 100 IU daily for 10 consecutive days every month and 2g CaC0 3daily; 2 (n=30) estradiol 2 mg daily and CaC0 32 g/day 3 (n=20) CaC0 32 g daily; 4 (n=20) 1a-OH vitamin D3 (1a-OHD 31 0.5 iJ!l daily; 5 (n=20) 1a-OHD3 0.5 IIg/day and Cat;03 2 g/day; 6 (n=25) clodronate 400 mg, 1aOHD 30.25 iJ!l and CaC0 32 g daily: 7 (n=20) NaF 45 mg/day, 1a-OHD3 0.5 iJ!l/day and CaCO, 2 g/daily, 8 (n=20) control group /untreated/. Biochemical parameters of Ca-P homeostasis, bone turnover markers, BMD of the lumbar spine and proximal femur were determined every 6 months and X-rays ofthe thoracic and lumbar spine were performed every 12 months. It was found that 2-year treatment with estradiol, CT, clodronate and 1a-OH vitamin D3 with calcium supplement resulted in a significant increase of BMD in both lumbar spine and proximal femur and decrease in a number of new spine fractures (P<0.02). The therapy with fluoride increased BMD in the spine (P
P358 EFFECT OF CLODRONATE ON CALCIUM-PHOSPHATE MAGNESIUM HOMEOSTASIS, BONE MASS AND VERTEBRAL DEFORMITIES IN POSTMENOPAUSAL WOMEN J. Borowicz M. Talalai E. Marcinowska, P. Kapuscinski Department of Internal Medicine, Postgraduate Medical Education Centre, Warsaw, Poland Estrogen deficiency due to menopause leads to progressive loss of bone mass, vertebral deformities and fractures. Clodronate is an inhibitor of bone resorption, developed as an agent to fight hypercalcemia and bone lysis. The aim of the study was to evaluate the effect of the treatment with clodronate on Ca-P-Mg homeostasis, bone mass and vertebral deformities in postmenopausal women. Thirty nine postmenopausal outpatient women suffering from osteoporosis, with at least one vertebral crush fracture on standard X ray examination or bone mineral density (BMD) more than 2 SD below age matched normal values were included into the study The patients were divided in two groups: 1 - treated with clodronate in a dose of 0.8 g daily, calcium carbonate' 2 - g daily and 1a-vitamin D3 in a dose of 0,25 iJ!l daily; II /controll- treated with calcium carbonate and lOa-vitamin D3 at the same doses as the patients of group 1. In each patient biochemical parameters of Ca-P-Mg homeostasis, bone turnover markers and BMD with the method of DXA were determined and life standard questionnaire was acquired. It was found that combined therapy with clodronate, 1a-vitamin D3, and calcium carbonate decreased bone pain within 14 days and increased BMD by 5.1 % in the lumbar spine (p
o

P359 EFFECTS OF CALCITRIOL OR CALCIUM ON BONE MINERAL DENSITY AND FRACTURES IN MEN WITH IDIOPATHIC OSTEOPOROSIS P.R. Ebeling " , J.D. Wark' ·' S. Yeung" C. Poon ' , N. Salehi', G.C. Nicholson 4 , M.A. Koto'wicz4 Depts Diabetes & Endocrinology' and Nuclear Medicine', Depts. Medicine, University of Melbourne, The Royal Melbourne' and Geelong Hospitals 4, Australia In women with postmenopausal osteoporosis, calcitriol treatment reduces vertebral fracture rates compared with calcium, despite only small increases in spinal bone density (LS-BMD). It is uncertain whether calcitriol has similar effects in men. We therefore studied 41 men with idiopathic osteoporosis and at least one baseline vertebral fragility fracture in a randomised, double-masked, double-placebo controlled trial of calcitriol 0.25 ~ b:i.d. or calcium 500 mg b.i.d. over 2 years. All except 5 men (88%) completed the study. Twenty men aged (mean±SEM) 58±2.5 yrs were assigned to group Aand 19 men aged 60±2.8 yrs (P=NS) to group B. All men had no underlying pathological cause for osteoporosis, and normal baseline 25(OH) vitamin D and testosterone concentrations. At baseline LS-BMD femoral neck (FN)-BMD, and total body bone mineral content (TBBMC) and the median number of vertebral fractures (n=3) were similar in both groups. There were no differences between groups in TBBMC over time. In group B, LS-BMD increased by 4.6±2.3% at 6 mths (p=0.02), however, the increase at 24 mths (7.8±5.5%) was not significant. FN-BMD also increased by 2.7±1.2% (p=0.01) in group B, but was again similar to baseline at 24 mths (2.0±1.4%). BMDs were 5.0% higher at 6 mths at LS (p=0.07) and 2.5% higher at 12 mths at the FN (p=O. 10) in group B vs. group A. A total of 22 incident fragility fractures occurred (16 vertebral and 6 non-vertebral). Only 1 incident vertebral fracture occurred in group B. At 2 years both the mean number of incident vertebral fractures (O.53±O.32 vs. 0.06±O.06. p=0.03) and the number of patients with incident vertebral fractures (9 vs 1, p
P360 EARLY ASSESSMENT OF ALENDRONATE EFFICACY IN POSTMENOPAUSAL WOMEN WITH ADVANCED OSTEOPOROSIS WITH USE OF DENSITOMETRY AND MORPHOMETRY J. Deszczvnski D. Owczarek Department of Orthopedics & Trauma, Hospital Czerniakowski , Warsaw, Poland In recent years biphosphonates play growing role in treating patients with osteoporosis. The aim of our study was densitometric and morphometric evaluate of Alendronate treatment efficacy in postmenopausal woman with advanced osteoporosis. Methods: 54 females aged 49-76 years with initial bone mineral density (BMD) <-2,5 T-score with contraindications for HRT were enrolled into the study. Densitometry with high resolution apparatus Expert-XL was initially performed in all patients with measurements obtained at lumbar spine and proximal femur. Same group of patients underwent morphometric examination in thoracic and lumbar spine. The patients were administered Alendronate 10 mg Iday, Calcium carbonate 1 glday, 1-& hydroxycholecalciferol 0,25 uglday for 9 months with densitometric and morphometric reassessment after this period. Results: In all patients after Alendronate therapy the BMD decrease in all measured areas was insignificant. In 32 patients morphometric examinations didn't reveal any significant structural vertebral abnormalities before and after the treatment. In 22 patients with initial vertebral deformations (vertebrae biconcave, vertebrae V -shaped) slight structural worsening was observed. Conclusions :Spine morphometry in an useful method of assessment of osteoporotic patients and of monitoring theirtreatment. The insignificant drop in BMD and slight progression of vertebral deformations were observed in postmenopausal woman treated with Alendronate for 9 months. Morphometry allows early diagnosing vertebral deformations in patients with osteoporosis.

P361 EFFECTS OF ALENDRONATE TREATMENT ON BONE REMODELING IN CORTICOSTEROID-INDUCED OSTEOPOROSIS P. Chavassieux ' , M...Arf.Q1" J.P. Roux ' , N Portero ' , A. Daifotis', P.J. Meunier' 'INSERM Unite 403, Faculte R.T.H. Laennec, Lyon, France; 'Merck Res. Labs, Rahway, NJ, USA Effects of alendronate (ALN) on bone quality and turnover were assessed in 88 patients (52 women and 36 men aged 22 - 75 yrs) with prior long term steroid exposure. Patients were randomized to receive oral placebo or ALN 2.5, 5 or 10 mglday for 1year and stratified according to the duration of their prio~ steroid treatment. Transiliac bone biopsies were obtained for qualitative and quantitative analysis after tetracycline double labeling at the end of the year of the treatment. ALN treatment was not associated with any qualitative abnormalities. Comparisons between the 4 groups were performed after adjustment for age, sex and steroid exposure. ALN did not impair mineralization at any dose as assessed by mineralization rate. Osteoid thickness (O.Th) and volume (OVlBV) were significantly lower in ALN-treated patients, whatever the dose (p=0.0003 and 0.01 respectively for O.Th and OV/BV). Significant decreases of; mineralizing surfaces (-76%; p=0.002), activation frequency (-72%; p=O.008) and bone formation rate (-71%; p=0.01) were also noted. However, trabecular bone volume, parameters of microarchitecture and resorption did not change. In conclusion, ALN treatment markedly decrease the rate of bone turnover but without complete suppression of bone remodeling and maintained a normal mineralization at any dose in corticosteroid-induced osteoporotic patients 'treated for one year.

P362 INTRAVENOUS PAMIDRONATE AS TREATMENT OF OSTEOPOROSIS AFTER HEART TRANSPLANTATION M.A. Krieg D. Gillard-Berauer J. Cornuz P. Burckhardt JJ. Goy D. Thiebaud University Hospital, Lausanne, Switzerland Immunosuppressive treatment after heart transplantation (HT), principally corticosteroids, leads to a dramatic bone loss (lumbar spine - 6%, femoral neck -9.9% 16 months (D. Gillard-Berguer et al. Transplant. Proc.1994; 2:2649-51). We tested i.v. Pamidronate in post-transplantation osteoporosis (OP), since it avoids GI side effects of oral amino-bisphosphonates. Methods: 8 men, ±48 years old, received cyclosporine A (CA, ±306 mgl d), Calcium Igld, and vitamin D 1000 U/d. BMD was measured at HT, at the onset of treatment (TI) (month 0) and every 6 months. i.v. Pamidronate (60 mg every 3 months) was started ±8 months (5-14) after HT, because of osteoporosis (T score <-2.5 at lumbar spine). Results: % changes of BMD (+SEM) are as follows (Kruskal - Wallis test:* p<0.001):

•

months

prednisone mean mgld

cyclosporine mean mgld

lumb.BMD % change

11.8 4.2 4.2 6.7 5.0 0 0

311 311 333 321 321 321 304

0 -6.4±1.9 +4.D±1.0 +4.1±2.2 +9.9±2.9 +13.4±3.1 +13.1±2.8 +15.2±3.8*

-8

ostart of TI 6 12 18 24 30 36

FN BMD % change 0 -6.0±2.1 -6.1±1.4 -6.1±4.2 -3.3±2.6 -3.8±3.5 -2.9±3.0 -1.8±4.2

Conclusion: a 3-year treatment of iv-Pamidonate of osteoporosis (OP) after HT increased bone mass at lumbar spine and prevented OP at the proximal femur.

P363 TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH SODIUM ALENDRONATE P. Retroz. H. Nascimento I Oliveira M. Estrela F. Ventura Gynecology Department of the Maternidade Bissaya-Barreto, Coimbra, Portugal A prospective study was performed in which the purpose was to evaluate the treatment of postmenopausal osteoporosis with sodium alendronate. 28 patients between the ages of 40 and 69 years were included in this study. All of these women had experienced either surgical (mean age of 48,2 years) or spontaneous menopause (mean age of 45,3 years) for over one year. Diagnostic criteria were established by performing a bone densitometry at spine and / or hip bone sites, where all women had a T score of at least - 1 SD. They were reevaluated one year later, after treatment with sodium alendronate, in which results are here presented and proven positive in terms of bone mass recovery (spine and hip bone sites) in all of these women. No previous or present fractures were verified.

P365 POSTMENOPAUSAL OSTEOPOROTIC CHINESE WOMEN TREATED WITH ALENDRONATE This was a multiple-center open-label clinical trial where 81 postmenopausal Chinese women aged: 64.5±5.8 years (51 - 83) with a postmenopausal period of 15.1±5.8 (3 - 31) years and a BMD of <980 mg/cm', were recruited and treated with alendronate (Fosamax, Merck) 10 mg and elemental calcium 500 mg daily. Their BMD had been measured before treatment by DXA (Lunar Co.), and new measurements were made 3,6, and 12 months after treatment. BMD changes during the Fosamax treatment (mg/cm'X±S)

PINP g/mg protein

CONTROL CT10' nM CT 1 nM CT 10 nM

112.1±D.4 12.1 ±3.2, p>0.01 12.8±1.3, p>0.1 30.1±8.1, p,.01

707±137 443±99, p>0.01 802±229, p>0.1 1493±670, p
Values are mean±SD, n=6; Statistics: Mann-Whitney test Conclusions: These results suggest that pharmacological levels of ICT (10' nM) produce, in confluent human osteoblasts, an increase in the production of AP (mineralization) and collagen tipo I synthesis (PINP), a finding that could be relevant in the evaluation of the effects olthe treatment of bone disorders with CT (supported by Rhone Poulenc Rorer).

L,-L, Increase (%)

Neck Increase (%)

Wards Increase (%)

Troch Increase (%)

omonth

832±95

689±80

545±92

598±72

23(2.8)***

12(1.9**

12(1.9) * *

15(2.6) * * *

33(4.1)***

9(1.4)**

9(1.4)**

16(2.9)* **

45(6.3) * * *## 8(1.6) * *

8(1.6)**

13(22.6) * * *

81 3 months 76 6 months 76 12 months 70

P364 PHARMACOLOG'lCAL LEVELS OF CALCITONIN INCREASE PROCOLLAGEN I AND ALKALINE PHOSPHATASE PRODUCTION IN PRIMARY HUMAN OSTEOBLAST CULTURES R. Guerrero C. Mendez-Davila, M.L. Traba C. Vicario*. C. Alvarez Sanz* *, C. de la Piedra Fundaci6n Jimenez Diaz, Biochemistry Laboratory. * Hospital Clinico "San Carlos", Orthopedic Surgery; **Rhone-Poulenc Rorer, Madrid (Spain) Fragments of trabecular bone were obtained from female patients undergoing replacement hip surgery. Explants were placed on a nylon mesh and incubated with DMEM with penicillin/streptomycin (200 IU/ml and 2001Jll/ml, respectively), 1% non essential aminoacids, 2 mM glutamine and 20% FBS at 37°C, 5% CO,. Cells migrated from explants to mesh. After 45 days, they were treated with 0.25% trypsin and subcultured in 75 cm' masks. After 15 days (confluence) subcultures were made. Osteoblasts were seeded in P24 plates and, at confluence, salmon calacitonin (CT, Rhone-Poulenc Rorer) 10" nM, 1nM or 10' nM was added After 24 h of incubation, culture medium was removed for the further determination of aminoterminal propeptide of procollagen I (PINP) (RIA, Orion Diagostica, Finland). Osteoblasts were removed from the plate and resuspended in 2001ll of Triton X-100 at 0.1%. Total protein content (Bradford method) and alkaline phosphatase (AP) were measured in osteoblast extracts.

AP IU/mg protein

Treatment duration cases

*p<0.05, **p
P366 THE RELATIONSHIP BETWEEN DIABETES MELLITUS TYPE-II AND POSTMENOPAUSAL OSTEOPOROSIS AND THE EFFICIENCY OF CALCITRIOL TREATMENT M. Bicer O. Peker S. Oncel O. Senocak E. Akalin S. Alper, S. Gulbahar Dokuz Eyliil University Medical Faculty PhYSical Medicine and Rehabilitation Department, Turkey This study was planned to investigate the relationship between postmenopausal osteoporosis and Diabetes Mellitus Type-II. The efficiency of calcitriol was also evaluated in diabetic and nondiabetic postmenopausal osteoporotic patients. Bone mineral density (BMO) measurements of 80 patients with postmenopausal osteoporosis (35 diabetic and 45 nondiabetic) were calculated before treatment. Lumbar vertebrae BMD measurements were significantly lower in nondiabetic group. Hip region BMD measurements did not show significant difference between two groups. Calcitriol and calcium were given to all patients. At the end of one year treatment the increase of BMD was found statistically significant in trochanteric region of the diabetic group and in lumbar vertebrae of the nondiabetic group. Based on this results we can conclude that Diabetes Mellitus Tip II has no additive effect on postmenopausal osteoporosis and calcitriol is effective in both treatment groups .

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P367 CALCITRIOL AND VITAMIN D3 TREATMENT RESULTS IN POSTMENOPAUSAL OSTEOPOROSIS O. Senocak O. Peker. E. Akalin S. Oncel 0 Bahgeci S. Alper A. Ozbay Dokuz EylOI University Medical Faculty Physical Medicine and Rehabilitation, Biochemistry Departments, Turkey This study was performed to investigate the efficiency of calcitriol and vitamin D3 in patients with postmenopausal osteoporosis. 45 of 65 patients were given 0.5 mcg/day calcitriol with calcium support. The other 20 patients were given 300.000 IUlmonth vitamin D with calcium support. At the sixth month of treatment blood osteocalcin level increased significantly in both of the groups, but there was no significant change in blood calcium, phosphorus and urinary hydroxyproline levels. At the end of one year treatment there was statistically significant improvement of lumbar density in calcitriol group. On the other hand no increase or bone mineral density in vitamin D3 group was observed. So as to conclude calcitriol treatment appears to be more effective than vitamin D3 in postmenopausal osteoporosis.

P368 CALCITRIOL THERAPY IN POST MENOPAUSAL OSTEOPOROSIS R. GOnaydin A. GOrgan, R. Terzioglu, A. Memi, H. GOnes, A. Uslu, A.Oztin Ataturk Training Hospital Physical Medicine and Rehabilitation Clinic Izmir TURKEY The purpose of this study is to determine the effectiveness and reliability of calcitriol (Rocaltrol) therapy in post menopausal osteoporosis. Fifty cases (mean age 52.16) with an established clinical, laboratory and radiological diagnosis of osteoporosis were administered 0.5 mcg of calcitriol per day. Dietary intake of Ca was approximately 1000 mg. The patients were followed up for 12 months. The pre- and post-therapy results of alcahalen phosphates, blood Ca , 24 hours urine hydroksiproline/creatinine, Ca/creatinine ratiOS, thoracolumbal vertebra radiograms, lumbal vertebral and proximal femoral bone mineral density measurements were compared. Bone mineral density measurements were performed with DEXA (Hologic). The results were evaluated statistically using t test for paired samples of the before and after therapy values. At the end of one year therapy marked elevation of bone mineral density of both lumbal vertebra and proximal femur were determined (p<0.05). No statistically significant change of bone turnover indicators were detected (p>0.05). As a result we believe calcitriol is an effective and reliable agent for the treatment of postmenopausal osteoporosis.

P369 ORAL CLODRONATE REDUCES LOSS OF BONE MINERAL DENSITY IN PRIMARY BREAST CANCER E.V. McCloskey lJ. Powles A.H.G. Paterson. S. Ashley A. Tidy, J.A. Kanis WHO Collaborating Centre for Metabolic Bone Diseases, The University of Sheffield, UK Systemic treatment of primary breast cancer may cause loss of bone mineral density (BMD). We have therefore undertaken a double blind randomised trial to evaluate BMD in women with primary breast cancer given clodronate 1600 mg/day po (n=156) or placebo (n=155) for 2 years. In addition to study treatment, all patients received appropriate primary surgical and"medical treatment (chemotherapy and tamoxifen) and were followed up for at least 2 years without metastatic relapse. The median age, height, weight, menopausal status and type of primary surgical, adjuvant or neoadjuvant medical treatment were well matched for both treatment groups. BMD in the lumbar spine and hip were measured using dual energy xray absorptiometry (Hologic QDR1 000) at the start of clodronate/placebo and after one and two years of treatment and calculated as % change of the initial treatment reading. The placebo group had a mean loss in spinal BMD of .2% whereas the clodronate group had a small mean gain of 0.18%. (Treatment effect +2.38%, CI 1.36 p<0.001). Similarly the placebo group had loss in hip BMD of 0.34% compared to a mean gain of 0.40% in the clodronate group (Treatment effect +0.74%, CI-0.13, 1.6 p=NS). After 2 years the treatment effect for clodronate in spinal BMD was +1.74% (CI 0.12, 3.34 p
P370 PRELIMINARY SAFETY DATA FOR A 3 DAY INTRAVENOUS CLODRONATE REGIMEN USED IN RENAL IMPAIRMENT D. de Takats EV McCloskey K. Pande V. Edwards and J.A. Kanis The WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK We wished to investigate aspects of hepatic and renal safety for a 3 day regimen of i/v clodronate, 300 mg, 600 mg x 2, because caution is generally advised when using i/v bisphosphonates in renally impaired subjects and liver enzymes aspartate amino transferase (AST) and alanine amino transferase (ALT) are known to rise with oral clodronate. This regimen has not been previously evaluated in this respect. 24 hour urine collections were done on all consenting patients prior to intravenous treatment, during the 24 hour period including the last dose and 3 months later. Serum samples for creatinine, (AST) and (All), were taken on completion of the collections. Creatinine clearances were adjusted to 1.73 m' where possible (80% of cases). Patients with a pre-treatment (adjusted) creatinine clearance of <70mls/ min were selected (range 17 - 66, median 45, n=34). The results were analysed by Wilcoxon matched-pairs signed ranks tests and paired t-tests. Both analyses gave similar findings. Comparison of pre-treatment with end-of-treatment results showed no significant change in clearances, ALT or ASl However, comparison of pre-treatment with 3 month post treatment results showed significant rises in creatinine clearance from a mean (±SEM) of 44 (±2.0) to 53 (±3.4) mis/min (p<0.001, both tests); ALT showed a significant tendency to rise, from 14 (±1.2) to 17 (±1.9) U/I (Ref. range 7 - 33) (p<0.013, both tests); AST showed a significant tendency to rise (p<0.007, Wilcoxon) from 17.6 (±1.0) to 21.2 (±2.4) Ull (Ref. range 1034) (p=0.068, paired t-test). In this early study we have not identified any negative consequences of this i/v clodronate regimen on renal excretory function in mild to moderate renal impairment; indeed it may be of benefit. However ALT and AST do rise by 3 months after treatment, though they remain within the reference range, and there were no clinical correlates with this observation .

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P371 CLINICAL EFFECT AND SURVIVAL IN OSTEOPOROTIC PATIENTS TREATED WITH OR WITHOUT ETIORONATE J. Ingerslev Medical Center, Bispebjerg Hospital, Copenhagen, Denmark AIM: To evaluate the effect of treatment with or without etidronate given to osteoporotic patients with acute fractures in the spine. The quality of life, the general well-being, pain, and costs of drugs, plus survival over a period of six years were studied. METHOD: Prospective follow-up study. In the period 01.10.90 to 31.03.91 87 patients were admitted to hospital with acute osteoporotic fractures in the spine. Patients with secondary fractures or in preterminal stage of diseases were excluded. All the enrolled patients daily received 500 mg of calcium, vitamin 0400 I.U., analgeSiCS, and physiotherapy. Out of 68 patients half received cyclical treatment with the bisphosphonate etidronate (Oidronate) 400 mg daily for two weeks followed by a 13-week period without the drug. The sequence was repeated three times. Before, during, and after the observation-period of 32 weeks the quality of life, general well-being, pain, and use of analgesics were registered during six years. Mortality and causes of death were continually monitored. RESULTS: Sixty-eight patients, 16 men and 52 women, aged 54 to 88 years, on average 74 years, fulfilled the protocol, and were enrolled. During the observation-period the patients treated with etidronate had a significantly better quality of life, and well-being, less pain, and reduced drug expenditure. During the six years 35 of the patients had died, 10 from the etidronate-treated group and 25 from the non-treated group. The mortality was significantly higher in the non-treated group. The causes of death were identical. CONCLUSION: Treatment with etidronate was valuable concerning quality of life, general well-being, less pain, and reduced drug expenditure, and longer survival. More studies on prevention and treatment are recom mended.

P372 USE OF ALFACALCIOOL (ALPHA 03-TEVA) FOR TREATMENT OF OSTEOPOROSIS SA Makarova A.S. Ametov Medical Academy of Postgraduated Education, Moscow, Russia Decreased active vitamin 03 metabolite serum levels are known to affect the phosphorus (P) and calcium (ca) metabolism, in turn, leads to inhibition of in bone remodelling and mineralisation. To asses the efficiency of active vitamin 03 metabolite-Alfacalcidol (Alpha-03 TEVA) intake in women both with primary and secondary osteoporosis (OP), bone mineral density (BMO) and blood Ca. P, PTH and osteocalcin levels prior to and following six months of the treatment were evaluated. Sixty women of postmenopausal age entered the study. In terms of their conditions these were divided into three groups (post-ovariectomy; n=17, group 1; physiologic menopause: n=20, group 2; thyroid dysfunction with endogenous or exogenous exposure to T4: n=23, group 3). Prior to Alpha-D3 TEVA administration 0,5-0,75 mg/day all the patients presented with bone pain, hypo- or eucalcemia and reduced BMO (above 2,5S0). The therapy specified resulted in stabilisation of serum Ca levels, decrease in PTH figures with concordant increase in osteocal'cin blood levels; in the course of the treatment the patients reported loss or relief of bone pain, which correlated with significant amelioration of BMO findings (increase by 0-1 SO); no new cases of bone fracture were registered. The tolerence of the drug was satisfactory. Alfacalcidol may thus be recommended for a long-term therapy of OP.

P373 THREE YEARS RESULTS OF ALFACALCIOOL USE IN PATIENTS WITH OSTEOPOROSIS S. S. Rodionova A. F. Kolondaev, L.I. Munina Central Institute of TraumatOlogy and OrthopaediCS, Moscow Russia The purpose of the study was to evaluate the influence of alfacalcidol on BMO in various skeleton segments at its long term application. Alfacalcidol in dose of 0.5-0.7 mkg and calcium drugs in dose up to 1.5 g daily were given to 50 women with menopausal and senile osteoporosis for the period from 1 to 3 years. BMO was assessed (LUNAR OPXI) in the lumbar spine vertebral bodies and in proximal segments of the femur (neck, Warda's triangle trochanter). One year after the start of the treatment and of the background of clinical improvement, BMO in Ward's triangle and in the region of the trochanter increased by 5.(07%6.31 %. in the femoral neck 2.6% and in the lumbar spine - 3. 54,. Three years after the start of treatment, BMO increased by 6.25% and by 6.92% for Ward's triangle and trochanter region, respectively. In the femoral neck the increase made up 3.32%, in the lumbar spine - 6.44%. So, maximum increase in BMO on the background of alfacalcidol treatment took place in the proximal segments of the femur during the first year while in the lumbar spine vertebral bodies the increase of BMO continued even 3 years after the start of treatment. This allows to suggest that at long term applications alfacalcidol mainly affects the spongy bone.

P374 INTERMITIENT CYCLIC ETIDRONATE TREATMENT OF PATIENTS WITH LOW BONE MASS N. Vujasinovic-Stupar P. Vukojevic, N, Pilipovic Institute of Rheumatology, Belgrade, Yugoslavia Aim of the study: to asses effectiveness of cyclical intermittent etidronate therapy on bone mineral density (BMO) and its safety in patients with low bone mass. 82 patients with low bone mass -55 osteoporotic and 27 osteopenic (78 woman and 4 men), age 30 to 82 (mean 58,4 ±10, 1) were prospectively followed-up. In first group - group I (N=64) OEXA of LS spine was done at the beginning and after 6 months treatment with etidronate, while in second group - group II (N=21) assessment was done at the beginning and after 12 months of treatment. Etidronate di-Na was given in doses of 300mg/day for 15 days every three months, followed by 75 days of 500mg calcium tablets/day. Control group was consisting of 10 not-treated patients with low BMO, DEXA measurement was done at the beginning and after 6 months period. Results: In the group I average BMO L2-L4 before treatment was 0,830±O, 12 g/cm', and after 6 months of treatment was significantly increased to 0,860±O,12 g/cm' (t=-5,6; p<0,001). T-score was also significantly improved from -3,08±O,98 SO before to -2,8±O,97 SO after therapy (t=-5,6 p<0,001). In group II after 12 months treatment with etidronate significant increase of BMO was also notified: from 0.870±O, 12 g/cm' before to 0,91 O±O, 12 g/cm' after (t=-3,7; p<0,001). In this group of patients T-score was -2,7±1,03 SO and 2,42±1,03 SO, at the beginning and the end of 12 months treatment respectfully, what is also significantly different (t=-3,7; p<0,001). In controls tendency of further bone loss was notified: BMO was decreased from 0,950±O,70 g/cm' at the beginning to 0,940±O,5 g/cm' after 6 months, the difference was statistically significant (1=2,25, p<0,048). T-score in controls was also decreased from -2,1 ±O,56 SO to -2,2±O,58 SO, but difference was not significant (t=2,18, p<0,056). Overall tolerence of etidronate was good. Other adverse effects of therapy was not reported as well. Conclusion: Cyclic etidronate therapy of patients with low bone mass after 6 months period lead to significant increase in BMO of LS spine, with tendency of further increase after 12 months of treatment. No adverse effects of therapy was reported .

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P375 SALMON CALCITONIN THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS ANO OSTEOPOROSIS P. Vukojevic N. Pilipovic B. Kecman-Prunic. G. Stevanovic D. Gacic D. Novicic-Sasic D. Palic N. Vujasinovic-Stupar Institute of Rheumatology, Belgrade, Yugoslavia The aim of the study: to evaluate salmon calcitonin therapy in pts with rheumatoid arthritis (RA) and osteoporosis: its analgesic effect and possible influence on inflammation and bone mass. Methods: 12 female, postmenopausal pts (average age 67.0±6.5 yrs, and disease duration 18.3±12.8 yrs) with RA and osteoporosis (T-score < -2.5 SO) started the study. They were treated with s.c. injections of salmon calcitonin: 5 days 100 i.u./day; then 10 days 50 i.u./day and next 10 weeks 50 i.u'/2nd day. Two patients withdrew from the study: one, after 2 weeks, due to gastrointestinal intolerance ofthe drug and the other from personal reasons. ESR, Ritchie index, overall pain (assessed by analog scale) and bone density by DEXA (on LS spine orfemur) were followed. Data were analyzed by t-test for dependent variables and Wilcoxon matched pairs test (* marks statistically significant difference, from start, at p<0.05 and * * at p
P377 COMPARISON OF CALCIUM, ETIDRONATE AND CALCITRIOL THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS P. Yalgin G. Yavuzer H. Giik G. GOrer G. Dinger Ankara University, Medical Faculty. Department of Physical Medicine and Rehabilitation Ankara, Turkey In order to compare the efficacy of calCium, calcitriol and intermittent cyclic (IC) etidronate therapy, 240 patients with postmenopausal osteoporosis aged 47 to 69 years were evaluated by means of changes in lumbar spine and femoral neck bone mineral densities (BMD by Dual Energy X-ray Absorptiometry) and bone turnover markers (serum calcium, phosphorus, parathyroid pormone, alkaline phosphatase, urinary calcium and hydroxyproline levels). Evaluations were made at baseline, after 1 year and at the end of the second year. The patients were randomly assigned to receive treatment for 2 years with supplemental calcium alone (1 000 mg/day), or calcitriol (0.5 grl day), or IC etidronate therapy (400 mg/day) for 14 days which was followed by supplemental calcium (1000 mg Iday) for 76 days At the end of the first year a significant increase in lumbar spinal BMD was observed in patients receiving calcium, but it did not continue to increase during the second year. The BMD values of patients receiving IC etidronate therapy were increased at both sides for the first year but at the second year no further significant improvement was observed in the femoral neck BMD values. Significant improvement of lumbar spine BMD values of patients, receiving calcitriol therapy was observed only at the second year whereas the change in femoral neck BMD values was significant during the two years period. No significant change was determined at bone turnover markers. As a conclusion IC etidronate and calcitriol therapies of two years duration are found to be more effective than calcium in postmenopausal osteoporosiS. Calcitriol therapy was considered as superior to IC etidronate therapy for femural neck osteoporosis.

P376 COMBINED TREATMENT WITH ALENDRONATE AND CALCITRIOL IN POSTMENOPAUSAL OSTEOPOROSIS: TWO YEARS OF TREATMENT B. Frediani. A. Allegri PJalsetti L. Storri. S. Bisogno R. Marcolongo Institute of Rheumatology, University of Siena, Italy 120 women with postmenopausal Osteoporosis were enrolled into an open, controlled study of 24-month duration, with the aim of evaluating the metabolic action and the effect on the bone mineral density (BMD) of alendronate 10 mg per day (n=30) or Calcitriol 0,511 g per day (n=30) vs. combined treatment of alendronate 10 mg per day plus calcitriol 0.500 mg per day (n=30). We also studied 30 patients treated with calcium 500 mg per day. BMD was measured by total body dual-energy X-ray absorptiometry (DPX-Lunar) as total body BMD and at different sites of interest, including spine, trunk, arms and legs. In all patient the BMD expressed as T-score was <-2,5. One sample t-test for within group analysis and an overall test performed using an analysis of variance for between-group comparisons analysis were performed on the percent change from baseline. Patients who were on alendronate showed significant increases in bone mass at all sites examined after 6 months of therapy. The greatest increase was observed at spine level (6.% after 24 months). However, if the increase was expressed as change in the T score, the greatest increase was found at trunk, total body and spine, respectively. In the second year of treatment BMD increased more slowly, and BMD increase was significant only at spine and trunk level (p<0.05). BMD appeared to be significantly higher in the group of patients receiving combined therapy than in the group treated with alendronate or calcitriol alone. At the end of the second year, mean percent changes for the former and the latter group were 2.1 % and 3.0% at arms, 3.1% and 4.2% at legs, 4.2% and 5.7% at trunk, 6.3% and 7.4% at spine, 2.5% and 4.2% as far as total body was concerned, respectively. In the placebo BMD decreased significantly (by 3,8% at total body at the end of the second year as compared to baseline values). Depending on the skeletal regions on which BMD was measured (total body or selected areas) 15-23% patients treated with calcitriol, 37-48% patients treated with alendronate and 69-78% patients treated with alendronate plus calcitriol, respectively, had aBMD increase greater than the lowest significant difference (LSD). In patients treated with alendronate, 24 hour urinary calcium and hydroxyproline fell significantly after 3 months, and alkaline phosphatase fell after 6 months; these parameters remained unchanged in all patients on combined treatment. We conclude that combined treatment with calcitriol plus alendronate is more effective than therapy with alendronate or calcitriol alone, particularly in the second year of treatment. A possible explanation could be that calcitriol is able to counteract the inhibitory effect that alendronate exerts on osteoblast activity.

P378 COMPARISON OF CALCIUM, ETIDRONATE AND CALCITONIN THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS G. Dinger G. Yavuzer H. Giik A. Kermalli P. Yalgin Ankara University, Medical, Faculty. Department of Physical Medicine and Rehabilitation Ankara, Turkey In order to compare the efficacy of calcium, intranasal calcitonin and intermittent cyclic (IC) etidronate therapy, 230 patients with postmenopausal osteoporosis aged 45 to 69 years were evaluated by the means of changes in lumbar spine and femur neck bone mineral densities (BMD by Dual Energy X-ray Absorptiometry) and bone turnover markers (serum calCium, phosphorus, parathyrOid hormone, alkaline phosphatase, urinary calcium and hydroxyproline levels). Evaluations were made at baseline, after 1 year and at the end of the second year. The patients were randomly assigned to three groups receiving treatment for 2 years with supplemental calcium alone (1000 mg/day), or intranasal calcitonin (200 IU day) with supplemental calcium (1000 mg/daY),or IC etidronatetherapy (400 mg/day) for 14 days which was followed by calcium (1000 mg/day) for 76 days. At the end ofthe first year, a significant increase in lumbar spinal BMD was observed in patients receiving calcium, but it this increase trend did not continue during the second year. The BMD values of patients receiving IC etidronate therapy were increased at both sites forthe first year but atthe second year further significant improvement was only observed in the lumbar spine BMD values. The change in BMD values of patients, receiving intranasal calcitonin therapy was not significant during entire trial period. No significant change was determined at bone turnover markers in all treatment groups. As a conclusion IC etidronate therapy of two years duration is found to be more effective than calcium and intranasal calcitonin therapy in postmenopausal osteoporosis.

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Discomfort included warmth, too tight fitting and feeling the shells being too hard. Practical problems were related to incontinence, simultaneous use of a girdle or to problems with handling. At three months of follow up 75% were still using their hip protector, 45% were using hip protectors nearly every day. Conclusion: Although the majority seemed satisfied approximately one third of the patients stopped because of discomfort or practical problems. Improvements in design of hip protectors could possibly improve compliance in this group.

OTHER TREATMENTS

P379 EFFECT OF HIP PROTECTORS ON FEAR OF FALLING Klaus Hindsp Jes Bruun Lauritzen Oepartments of Orthopaedic Surgery, Hvidovre and Bispebjerg Hospital. University of Copenhagen, Denmark Purpose: To evaluate the effect of hip protectors on the fear of falling. Method: A consecutive series of 1,684 patients admitted to an orthopaedic department were interviewed about fear of falling and its consequences. All patients were more than 74 years of age. Three pairs of energy dispersing hip protectors (Safehip®) were offered to 1,006 patients, and users received a questionnaire three months later concerning hip protectors influence on the fear of falling. Results: The 1,684 had a median age of 83 year, 81 % were women, 8% were nursing home residents and 69% were admitted after a fall. 572 of the 1,006 patients accepted hip protectors. At interview 1,497 answered the questions related to fear of falling. The remaining 187 were characterised by advanced age, dementia and medical diseases. Fear of falling was reporte/J by 45% [95% CI: 43 - 48%]. For patients admitted after a fall this rate was 48% [45 - 51%]. Among patients with fear of falling 51% [47 - 55%] reported that they some times stayed indoors because of fear of falling. Three months later 255 users received a questionnaire and 227 returned this. More confidence when walking inand outdoors were indicated by 30% [24 - 36%] and 33% [27 - 39%] respectively; and 15% [10 - 19%] had spent more times being outdoors because of the use of hip protectors. Conclusions: Fear of falling is prevalent in old people, and hip protectors may to some extent reduce this fear of falling and influence the activity of daily living in a positive way. It might be relevant to offer hip protectors to these old people with high risk of hip fracture, when falling tendency is also present.

P381 INTERVENTION STUDY WITH HIP PROTECTORS

'380 'BEHAVIOURAL ATTITUDE TOWARDS HIP PROTECTORS IN ELDERLY ORTHOPAEDIC PATIENTS. Klaus Hindsp. Jes Bruun Lauritzen Departments of Orthopaedic Surgery, Hvidovre and Bispebjerg Hospital, University of Copenhagen, Denmark. Purpose: Compliance of hip protectors is an important issue for the hip protectors to be effective. We studied the behavioural attitude towards hip protectors. Method: When admitted to an orthopaedic department 1,006 consecutive patients aged 74 years or more were offered three pairs of energy dispersing hip protectors (Safehip 10). The hip protectors consisted of two stiff shells sewn into pockets of special made undergarments. The use, satisfaction and reasons for non-compliance were evaluated through questionnaires administrated every third month. Results: 572 patients accepted the hip protectors and were followed for a period of at least 12 months. Total follow up time constituted 656 person-years. During follow up a total of 264 persons stopped using hip protectors. The reasons are presented in the diagram. Chanl!O In mobility 18'1'.

no cause

33%

hIp protectors dissapeared 14'1'. prnctiCBI problems

8%

dIscomfort

27%

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Klaus Hinds!! Jes Bruun Lauritzen Departments of Orthopaedic Surgery, Hvidovre and Bispebjerg Hospital, University of Copenhagen, Denmark Purpose: To evaluate the effect of hip protectors on risk of hip fractures in a population of elderly orthopaedic patients. Method: A consecutive series of 1,684 patients, at least 75 years of age, were admitted to two orthopaedic departments. In the intervention hospital patients were offered three pairs of energy dispersing hip protectors (Safehip®). All patients were followed for 12 to 18 months, and the number of subsequent hip fractures was recorded. The effect of the hip protectors was evaluated in a multivariate Cox proportional hazard regression procedure. Results: Most patients were home dwellers and only 8% came from nursing homes. In the intervention group 572 patients accepted hip protectors. During follow up (a total of 1,898 person-years) 78 new hip fractures were recorded giving an annual incidence rate of 4.1% [95% CI: 3.3 - 5.1 %]. Comparing the intervention group with controls the Incidence Rate Ratio (IRR) was 1.1 [95% CI: 0.70 -1.8]. After adjustment for use of the hip protectors (ranging from seldom to everyday use) the overalllRR was 0.88 [0.50 - 1.5]. In subgroup analyses the IRR was 0.33 [0.04 - 2.7] for males, 0.42 [0.21 - 1,4] for demented, 0.71 [0.37 - 1.4] for patients admitted after a fall, 0.67 [0.19 - 2.4] for patients admitted with a hip fracture, and 0.25 [0,085 - 0.85] for patients with impaired vision. During follow up users reported 143 falls with impact on the hip protector. Only 2 hip fractures were sustained while the patients used their hip protectors. In these cases no impact on the hip was reported. Conclusion: Hip protectors offer an effective protection against hip fractures - but only when used. Overall, no statistical significant effect of hip protectors could be observed in this population of elderly orthopaedic patients, predominantly coming from their own home. There seemed to be effect in several high-risk groups, but this study had not the power to give statistically valid estimates in these subgroup analyses.

P382 NO PAIN INCREASE DUE TO NEW VERTEBRAL FRACTURES: PROSPECTIVE ASSESSMENT OF IMPACT OF REHABILITATION M.G. Scholz. D. lazarescu T. Schlotthauer S. Makosch. B. Beaerow M. Pfeifer W. Pollahne H.w. Minne Institut fOr klinische Osteologie. Bad Pyrmont, Germany Associations between pain and other Quality of Life (Ql)-parameters and fracture(lx)rate in patients with osteoporosis are only modest. Still, it is common to consider somatic lesions as acause for loss of QL. But Ql perception varies in patients with same degree of osteoporosis. Methods: We investigated the association of Ql with old and new fxs in a longitudinal study of 87 women with postmenopausal osteoporosis. The EPOS-PYRMONT-Study is based on bio-psycho-somatic assessments including several * technical examinations, Ql-questionnaires (e.g. pain scales) and psychological aspects, e.g. Antonovsky's Sense of Coherence (SOC) which describes a person's capacity to perceive life as meaningful, comprehensible and manageable. At baseline (t,) patients participated in a 4 week rehabilitation program of specific medication, functional and psychological training, and lectures. Follow-up examinations (t" t3) without a rehabilitation program took place one and two years later. Results: Baseline values and changes in pain for 4 groups with different vertebral fx status (assessed by an experienced radiologist) are listed in the table below: Statistics: means±sd: *sig. of pairweise t-test

Group

n

No fx 39 Only 28 baseline Ix + newfx 11 in yr. 1 + new fx 10 in yr. 2

Baseline t, Change in yr. 1:t,-t,

Change in yr. 2:t3 -t,

3.03±74 3.39±79

+.03±99 (p<.90) -.43±1.03 (p<.04*)

±D±92 +.32±9

(p=1.00) (p<.09)

3.36±92

-.36±67

(p<.10)

-.36±92

(p<.22)

(p<.02*)

-.20±79

(p<.44)

3.40±1.07 -.60±70

Subjects with old fxs at t, showed a trend towards higher pain compared to subjects without fxs (p<.07). No changes in pain were observed for the groups without new fxs. During yr.1 pain levels decreased in all groups with fxs. In yr.2 pain levels remained either unchanged or increased slightly for subjects without new fxs. For subjects with new fxs moderate to high correlations of SOC and pain were found (r=-.49, n.s. to r=-.82,: p<.01): if these patients have a high SOC they experience less pain. Conclusion: Subjects with vertebral fxs have somewhat elevated pain levels which can be reduced by rehabilitation measures. Improvements due to rehabilitation are reduced if new fxs occur and the rehabilitation impact levels off in the second year if not repead. The data emphasises the need for holistic therapeutic concepts to enable patients to cope with the disease and prevent them from loss of QL due to physical lesions.

P383 EFFECTS OF AEROBIC EXERCISE ON BONE MINERAL DENSITY, HIP AND KNEE MUSCLE STRENGTH AND EXERCISE TOLERANCE V. Sepici. N. B610kba~i, J. Tan, F. G6g0~ Gazi Medical School, Department of Physical Medicine and Rehabilitation, Ankara, Turkey Object: To see if aerobic training program of 12 weeks makes a positive effect on bone mineral density and metabolism, hip and knee muscle strength and exercise tolerance. Material & Method: A group of 12 people, 6 men (mean age of 52.8±2.7 SE), 6 women (mean age of 41.5±4.5SE) were included in the study. An aerobic exercise program of 12 weeks on treadmill lasting for 30 minutes, three times a week has been applied. Before and after the training program bone mineral densities were measured by DEXA; serum ALP, Ca, P, PTH, osteocalcine, calcitonin, cortisol, cholesterol, HDL -cholesterol levels were assessed; knee extensor, flexor, hip extensor, flexor, adductor and abductor peak torques were measured by Cybex 350 isokinetic dynomometer and exercise tolerance test was performed. Results: No statistical difference was found between t and z-scores, spinal and hip BMC, BMD values and biochemical markers of bone mineral metabolism. In male subjects there was a significant increase in the peak torques of knee extension (p
and double product (p<0.001), increase in duration of exercise test (p
P384 EFFECT"OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR-I I INSULIN-LIKE GROWTH FACTOR I BINDING PROTEIN-3 ON BONE LOSS IN HIP FRACTURE PATIENTS: PRELIMINARY RESULTS FROM A DOUBLE BLIND PLACEBO-CONTROLLED PHASE II STUDY S. Boonen R. Bouillon P. Broos D. Rosen. S. Adams. J. Raus, P. Geusens Katholieke Universiteit Leuven, Dr. L.Willems-lnstituut & Limburgs Universitair Centrum, Belgium, and Celtrix Pharmaceuticals, USA In spite of dramatic effects of recombinant human insulin-like growth factorI (rhIGF-I) on bone turnover in older subjects, a corresponding increase in bone mass has not been documented. The administration of IGF-I complexed with its binding protein IGFBP-3 (rhIGF-I/IGFBP-3) allows the safe administration of higher doses of IGF-I than can be accomplished with rhlGF-1. The aim of this study was to evaluate the ability of rhlGF-1/ IGFBP-3 (Somatokine™) to prevent bone loss after hip fracture in 22 elderly women. Within 72 hours after hip fracture, patients received continuous subcutaneous administration of rhIGF-I/IGFBP-3 (0.5 mg/kg/day, n=8 or 1 mg/kg/day, n=8) or placebo (n=6) for a period of 8 weeks. Efficacy evaluations included a contralateral hip scan by dual emission x-ray absorptiometry and markers of bone turnover (including serum type I procollagen carboxyl-terminal propeptide and urine deoxypyridinoline). During the administration of rhIGF-I/IGFBP-3, serum IGF-I increased significantly from 83±6 ng/ml (mean+SEM) up to 289±18 (0.5 mg/kg/day) and 393±28 ng/ml (1.0 mg/kg/day). Both doses were well tolerated and no therapy-induced hypoglycemia was observed. One month after the 2-month infusion, a femoral bone loss of -7% was observed in placebo-treated patients, compared to a loss from baseline of less than 2% in the I mg/kgl day group. Bone formation and resorption increased in all three groups. From these preliminary data, we conClude that a 2-month infusion of rhIGF-I/IGFBP-3 in elderly women with recent hip fracture is feasible and well-tolerated. In addition, this study is the first to suggest a therapeutic effect of growth factor therapy on bone mass in an elderly target population,

P385 EFFECT OF ELECTROMAGNETIC FIELD STIMULATION ON THE HEALING OF OSTEOPOROTIC HIP FRACTURES. A PROSPECTIVE RANDOMISED DOUBLE-BLIND STUDY E. Betti S. Marchetti. R. Cadossi*, A. Faldini Department of Orthopaedics and Traumatology, University of Pisa. Italy. *R & D Igea, Carpi (MO), Italy Fractures of the femoral neck represent a frequent occurrence in elderly following a trauma of small entity. Their treatment foresees either the use of an internal synthesis device or hip arthroplasty. Low frequency pulsing electromagnetic fields (PEMFs) have been used for many years to favour bone healing: we have investigated whether: the use of PEMF could positively interfere with fracture healing. Seventy-seven patients with fracture were enrolled: 14 males and 63 females, average age 69±6. Patients underwent surgery within 7 days from the trauma. All fractures were fixed by screws. PEMF stimulation (Biostim, Igea, Italy) was initiated within 15 days from trauma: either with active or dummy devices. Patients were instructed to use the stimulator for 90 days 8 hours per day, their compliance was monitored by means of a clock. Patients were controlled, clinically and radiographically at day 30, 60 and 90 after surgery, followup controls were performed at 6 and 18 months. 13 patients have been excluded. At day 90, the % of healed fractures, was respectively 70 and 78.5 for placebo patients and active compliant patients. At the 18 months follow-up non-healed fractures were 7% in the experimental group and 17.6% in the control one. At follow-up necrosis of the femoral head was present in 28.5% of subjects using active stimulators and in 47% of those using placebo stimulators. In the experimental group we observed a diminished pain score that day 30, 60 and 90 (p
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P386 ACUTE PHYSIOLOGICAL EFFECTS OF TRAINING WITH GAll LEO 2000: FIRST RESULTS Jarn Rittweger* Gisela Wilhelm', Gabi Armbrecht', Xenia Bolze', Wolfgang Gowin" Dieter Felsenberg' *Institute of Physiology of the Free University Berlin, 'Osteoporosis Research Group, University Clinic Benjamin Franklin The Galileo 2000 training device has been developed to prevent bone mineral loss. The training evokes rhythmic, mainly reflectory contractions of the lower extremity. In the present study, acute physiological effects on heart rate (ECG), arterial blood pressure (Riva Rocci), on ventilation and gas exchange (Metamax), on muscle electric activity (EMG) and force (isometric force, jump height), on cutaneous blood flow (Laser Dopplerfluxmetry) and skin temperature, on perceived exertion (Borg-scale), and on blood lacatate were monitored. In order to assess the reproducibility of the changes, each subject performed two training sessions. Heart rate, arterial blood pressure, ventilation and gas exchange were measured also during bicycle ergometry in a third session and compared to the Galileo sessions. The results indicate, that training on Galileo 2000 mainly exhausts the lower extremity, without large general effects on the cardiovascular system. From the frequency composition of the EMG it can be followed, that fatigue of the musculature mainly seems to affect type II fibres and is recovered from after 15 min. Considering the comparatively mild cardiovascular and respiratory effects and the marked muscular fatigue, we conclude, that training with Galileo 2000 may be a promising issue in the therapy of bone mineral loss in the elderly.

P387 EVALUATION OF THE LONG TERM EFFECTS OF GALILEO 2000 IN A RANDOMIZED CONTROLLED STUDY G. Wilhelm J. Rittweger G. Armbrecht X. Bolze, W. Gowin D. Felsenbera Osteoporosis Research Group, Dept. of Radiology, University Hospital Benjamin Franklin, Free University, Berlin, Germany Galileo 2000 is a brand new device for dynamic muscle training. By that, it evokes bone modulation strain, which consequently leads to an increase of bone mineral mass and bone stiffness. This study examines the training effects of Galileo 2000 on the lower extremity muscles in 20-30 year old healthy women and men during a training period of 5 months. Thirty 20-30 year old, untrained healthy women and men were examined. After informed consent was given, the probands were randomized into three groups. Group 1 performed a 5 minutes lasting training on Galileo 2000 for 8 weeks with an additional weight of 10% and another 8 weeks with an additional weight of 20% of the maximal isometric load applied to the lower extremity muscles. Galileo 2000 is used to perform a reactive muscle training of the lower extremity and the back muscles. Group 2 performed a progressive dynamic maximum force training on auxotonic training devices for adaptation of the muscles and tendons. Following that, 8 weeks of training with 10-12 repeats within 90 seconds and 8 weeks with 5-6 repeats within 50 seconds were performed. Both groups performed exercises two times a week. The third group was examined as a control and did not perform any training. In the follow-up oiler a period of 5 months we examined the changes of the maximal isometric force, the jump height, the geometry of the muscles and bones of the lower leg, changes occurring in spiroergometric measurements and the muscle electric activity (electromyography). The effects on creatinine kinase (CK) and blood lactate were investigated. The maximal isometric force as well as the cross section area of the muscles at the lower leg are significantly increased in both training groups. The jump height is significantly higher in the group trained on the Galileo 2000 device compared to the control group. Training with Galileo 2000 can be recommended for a maximal force training and stimulation of the type II muscle fibers.

P388 HIP FRACTURE PREVENTION TRIAL USING HIP PROTECTOR IN JAPANESE ELDERLY A. Harada H.Okuizumi National Chubu Hospital Obu, Japan A method to protect the hip bone in a fall could effectively reduce the hip fracture incidence. We report here the results of the first hip protector trial in Japan, performed from July 1996 to Feb. 1998. Thirty-five female nursing home residents were randomly selected to wear a protector (Safehip, Denmark) and 24 controls did not. All falls and injuries were recorded. Ultrasonic evaluation of calcaneal bone and anthropometric measurement were done. Five residents dropped out early. During the 19 months in which the remaining 30 residents continued to wear the protector, they fell a total of 64 times, while 24 controls sustained falls 32 times. Among those wearing the protector, there were two non-hip fractures, so the hip fracture rate was 0%, against 4 hip fractures among the 24 controls, or 10.5% per year. The frequency of hip fractures was significantly lower among residents wearing the protector than in controls (Fisher's exact p
P389 ISOMETRIC RESISTIVE EXERCISE FOR OSTEOPOROSIS R. Swezey A. Swezey J. Adams Swezey Institute, Santa Monica, CA Site specific resistive exercises (EX) have been demonstrated to have an effect on bone mineralization greater than weight bearing activities. The effect of 5 min of site specific isometric back protected home EX on muscle strength (MS) to 10 major muscle groups (5/10 EX performed every other day) for 2 months was assessed. A specially designed ball with attached handles provided resistance. MS was measured in selected muscle groups by a handheld dynamometer. Two cohorts were healthy female Caucasian patients (pts) at least 5 years post-menopause on no osteoporOSiS medication, or on stable hormone replacement therapy or bisphosphonates for at least 6 months.

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PILOT FINAL DESIGN Cohort I (20 pts) (Ages 56-69)

Cohort II (21 pts) (Age 52-69)

Muscles

Strength

Strength

Trunk Ext Neck Ext Left Quad Right Quad

not exer'd p
p
Bone Formation Markers (alk phos) not measu red

p
CONCLUSION: Brief isometric EX on an alternate daily regimen for 2 months increases MS for the neck/back/lower extremities, associated with an increase in bone formation as measured by bone alkaline phosphatase B.

P390 TRUNC MUSCLE STRENGTH CONTRIBUTES TO BONE DENSITY, VERTEBRAL FRACTURES AND LIMITATIONS IN EVERYDAY LIFE B. Begerow M. Pfeifer M. Pospeschill T. Schlotthauer S. Makosch M. Scholz A.D.I Lazarescu W. Pollaehne, HW Minne Institute of Clinical Osteology and Clinic DER FUERSTENHOF, Bad Pyrmont, Germany During the last decade the term "sarcopenia" is shaped to express the process of myopathy from disuse. In particular, it follows the sedentary lifestyle that most individuals get used to. We hypothesize inadequate muscle stimulus transferring to bone tissue and being partly responsible for osteoporotic fractures and subsequent limitations in everyday life. We determined back extensor strength and abdominal flexor strength by isokinetic dynamometry (SinfoMed, Germany), bone density of the femoral neck and whole body (Hologic QDR 2000), and limitations in everyday life (Leidig-Bruckner et aI., 1997) in 235 postmenopausal women with osteoporosis (WHO definition grade 2 and 3) participating in the Pyrmont-EPOS Study. In addition Spine Deformity Index (SDI) was measured and vertebral fractures were defined by an experienced radiologist. SPSS (6.1) was used for statistical analyses and Pearson coefficients of correlation are presented as follows:

Vertebral fractures (SDI) BMD femoral neck BMD whole body Limitations everyday life

Abd. Flexor

Back Extensor

n

-.2452; p<.001 .1965; p=.003 .2570; p<.001 -.2744; p<.001

-.2061; p=.002 .2416; p<.001 .2583; p<.001 -.3425; p<.001

231 227 233 235

Our findings confirm the observation of Sinaki et al. (1996) that muscle strength is associated with vertebral fractures. Muscle strength, however, also determines the extent of limitations in everyday life, at least in part. It gets obvious that atrophy of muscle tissue is an additional risk factor for osteoporosis. For one thing muscle weakness aggravates any type of movement and therefore provokes lack of security; secondly it operates against bone density. Sarcopenia, especially in combination with low bone mass, deprives people of their independence. These data emphasize the importance of educating muscle strengthening exercises during rehabilitative programmes.

P392 EDUCATION OF PATIENTS WITH OSTEOPOROSIS B. Bergman M. Hamne G. Johansson, I. Larsson B-M. Nyhii,II-Wahlin K. Petersen W. Pettersson Department of Rheumatology, Central Hospital, Falun, Sweden Background: Osteoporosis is a major health problem. In recent years improvements have been made to diagnose and treat osteoporosis. As in many chronic diseases patient education should be a part of the treatment. The patients' ability to cope with the disease depends mainly on their knowledge. The aim of this project was to evaluate the benefit of an educational program for postmenopausal osteoporotic women. Methods: 40 postmenopausal women with osteoporosis were invited to attend in the education. 26 women accepted. The women were divided into four groups. The programme comprised 15 hours (three hours four times during two weeks and another three hours after one year). Topics covered included osteoporosis causes, prevention, diagnosis and treatment, dietary advises, exercises, pain, coping and practical aids. Different members of a multidisciplinary team including a doctor, two nurses, a physiotherapist, an occupational therapist, a dietician and a social worker led the discussions. For evaluating the programme four tools were used: 1. Knowledge questions (maximum score 9). 2. Questions about lifestyle factors associated with osteoporosis. 3. Questions about calcium intake. 4. Quality of life questionnaire (SF-36). Measurements of muscle function, muscle strength and balance were also performed. The questions and the tests were fulfilled at the first meeting I and repeated after one year. Results: 25 patients completed the programme. The mean score for the knowledge questions increased from 4,27 to 5,75 (p<0,006). The participants did not change their lifestyle with respect to the questions given before and afterthe education programme. The mean calcium intake was sufficient at the first meeting (1340 mg) and increased still more after one year (1597 mg), but not significantly. The quality of life questionnaire showed a slightly increase in all domains. The tests could be repeated in 19 women. No differences were seen in the muscle tests, but an improvement could be seen in the balance tests. Conclusion: The participants expressed their satisfaction with the education, both initially and after one year. We could show an increase in knowledge of osteoporosis, but no changes regarding to lifestyle factors. The partiCipants had a high calcium intake. Quality of life questionnaire indicated improvement, as did the balance tests. This implies that education of patients can be a part in the treatment of osteoporosis.

P391 BONE MINERAL DENSITY AND BIOCHEMICAL MARKERS OF BONE METABOLISM IN PATIENTS ON LONG-TERM LITHIUM THERAPY. P. Popivanov M. Boyanov P. Doukova-Peneva M. Vretenarska V. Stoyanova Medical University, Sofia, Bulgaria The effect of lithium on bone mineral density and biochemical markers of bone metabolism were studied in patients with affective disorders on a long-term (more than 10 years) lithium therapy. Twenty six persons - 11 men (34-73 years old) and 15 women (36-71 years old) were recruited for the study. Bone mineral density (BMD) was measured on densitometer DTX-100. Serum concentrations on osteocalcin, C-terminal propeptide of procollagen I (PICP) and urine concentrations of deoxypyridinoline were determined by ELISA methods (Metra Biosystems). All patients had normal creatinine clearance. Serum Li concentrations were in therapeutic ranges (0,340 - 0,820 mmol/l). Z-score of the distal radius ranged 102 - 134% and the one of the ultradistal radius 103 - 148% in 50 per cent of the males and 53 per cent ofthe females (exclusively those at postmenopausal age). Serum osteocalcin concentrations were above the reference range in 54 per cent of the males and in 20 per cent of the females. Urine deoxypyridinoline was elevated in 36 per cent of the males and in 73 per cent of the females examined. Our data suggest the positive bone formation effect of lithium with a concurrent activation of bone turnover, estimated through the elevation of bone biochemical markers.

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P393 EFFECT OF GROWTH HORMONE REPLACEMENT THERAPY ON BONE METABOLISM AND BONE MINERAL MASS IN HYPOPITUITARY ADULTS C.M. Francucci F. Massi. E. Tortato. P. Pantanetti. G.G.M. Garrapa. M.D. Petrelli. F. Mantero Division of Endocrinology, Dpt. of Internal Medicine, University of Ancona, Italy The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established, but much less is known about its action on the adult skeleton. Studies on the effect of GH replacement on bone mass in adults with GH deficiency (GHD) have produced conflicting results. Therefore we have investigated the effect of 6 months replacement therapy with biosynthetic human GH on biochemical indices of bone turnover and bone mineral mass in a group of 6 (3 men, 3 women) GHD adults, aged 40.6±15.8 yr. with multiple pituitary hormone deficiencies Following baseline assessments GH was given in a dally dose of 0.020±O.008 IU/kg body weight subcutaneously at bedtime, No patients had received treatment with GH before entry into the study. Each patient received hormone replacement for additional pituitary hormone deficiencies where indicated. All drug regimens had been stable for at least 6 months before entry into the study and remained stable throughout the study period. Urine and blood samples were obtained at baseline, 1st, 3sd and 6th month following treattnent with GH to measure IGF-I, calcium, phoshate, total alkaline phosphatase (ALP), bone-specific ALP (B-ALP), osteocalcin (OC) and HPLC pyridinium crosslinks (Pyr, nPyr). The BMD of lumbar spine (L2-L4), femoral neck and trochanteric region of non dominant hip has been performed with DEXA (mean at baseline Tscore: -1.160 SD, Z score: -1,015 SD). Serum IGF-I increase significantly at 6th month (87.6±68.1 vs 305.8±187 p
P394 L-GLUTAMINE MONOFLUOROPHOSPHATE IN OSTEOPOROSIS THERAPY - TWO MONTHS TOLERANCE STUDY P. Masaryk A. Letkovska M. Stancikova Research Institute of Rheumatic Diseases, Piestany, Slovakia Background of the problem: Fluorids constitute an important part of osteoporosis therapy, especially when decreased osteoformation is to be encouraged. One of the problems of this therapy is, however, decreased gastrointestinal tolerance. New preparations with fluorine in form of monofluorophosphate have better characteristics in this respect, but with uncertain effectivity. Objective: Findings the tolerance of L-glutamine monofluorophosphate and its influence to the bone turnover. Patients and methods: 24 patients (12 males and 12 females) based on densitometrically proven osteoporosis (T-score less than -2.5) were included into an open tolerance study during 2 months. Patients were administered a chewing tablet of Tridin preparation three times a day. It represents 15 mg of elementary fluorine and 450 mg elementary calcium as an addition to their usual diet. Results: 20 patients (83%) finished the study. Both physicians and patients evaluated tolerability of the preparation in a correspondent way: 89,5% as excellent and gOOd. 63,2% of patients were very satisfied with the preparation, 26,3% were satisfied and only 2 patients expressed their dissatisfaction with the preparation. After two months administration, the level of pain measured by VAS significantly decreased and the level of osteocalcin increased (from 10.3 to 11.9, p=0.016). Bone isoenzyme ALP and NTx changed non- significantly (bALP: from 23,3 to 23,0, p=0.275, NTx: from 80,0 to 96,6, p=0.088). Conclusion: L-glutamine monofluorophosphate during two months administration showed very good tolerability and induced detectable changes in the bone turnover.

P39S THE IMPACT OF A SPORT OSTEOPOROSIS REHABILITATION TRAINING ON PAIN COPING STRATEGIES IN PATIENTS WITH OSTEOPOROSIS H. Franck. W. Hohmann Center of Rheumatology, Oberammergau, Germany, Physiotherapy Center, DOsseldorf, Germany Introduction: Pain is acomplex, multidimensional perception with affective cognitive as well as sensory features. Especially patients with osteoporosis experience pain to various degrees and qualities. The aim of the study was to investigate pain coping strategies in patients with osteoporosis before and after a four weeks sport osteoporosis rehabilitation training (SPORT). Are there differences in coping strategies between patients with osteoporosis and osteoarthritis? Methods: Patients with osteoporosis (N=21 0) received coping strategies questionnaires, an inventory of pain related self statements, a questionnaire to pain locus of control to investigate emotional, cognitive and behavioural aspects of coping strategies before and after a four-weeks exercise training for osteoporosiS. Results: After four weeks of SPORT patients with osteoporosis showed a significant improvement of emotional pain coping strategies (emotional distress, anger: 0.92 -> 0.57, p
P39S IMPROVEMENT OF PATIENTS' COMPREHENSION OF THE DISEASE OF OSTEOPOROSIS H Franck, W. Bader U. Loffler Center of Rheumatology, Oberammergau, Germany, Clinic Mayenbad, Bad Waldsee, Germany Introduction: The compliance of patients (pts) with osteoporosis (OPO) and the ability to cope with the disease depends mainly on pts' knowledge. The aim of the study was to evaluate pts' knowledge of OPO before and after a training course. Methods: We examined pts' knowledge of OPO in 273 pts with OPO by standardized questionnaires about OPO before and after a four-weeks training of physical exercise including a 4 hours information course. Results: At the beginning 50% of the pts reported to receive their information about OPO mainly by their physician and 40% claimed, that they haven't been informed at all about OPO. However, they believe (87%), that an efficient therapy of OPO depends on their cooperation with the doctor. Their knowledge about the pathoetiology of OPO is incomplete, especially concerning alcohol, nicotin and hereditary influences. Butthese factors, as well as their knowledge about secondary OPO (eg. cortison, disturbances of kidney and liver) (50%) improved significantly (p
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P397 PEDICLE SCREW FIXATION IN POSTMENOPAUSAL WOMEN SA Papadakis" D.P. Stathakopoulos" N. Roidis ' , G.V. loannidis', G. Sapkas ' 1. Orthopaedic Department, Medical School, Athens University, Athens, Greece. 2. Laboratory for the Research of Musculoskeletal System « Th. Garofalidis », Athens, Greece Purpose of the study: The evaluation of pedicle screw fixation in postmenopausal women. Material and Methods: 27 postmenopausal women underwent spinal stabilization with the use of pedicle screws for various reasons, between 1990 and 1997, aged 64,7 years (range, 55-72 years). Pre-operative control included anteroposterior and lateral plain and dynamic radiographs, CT scan, and in some of them also myelography and MRI scan. DEXA measurements ofthe lumbar vertebrae BMD was evaluated in all subjects. In most cases pedicle screws were fixed without the special guide instrument due to poor bone quality and to the bad holding in of the screws. In this study we do not discuss the total results of the surgical treatment, such as reduction of pain or correction of spinal deformity. Results: Intraoperative and early post-operative complications of pedicle screw fixation were 5,8% pedicle fracture, dura tear in 3 cases, and 2, 9% screw loosening. These complications is relatively easy to happen in postmenopausal patients, due to the poor quality of pedicle cortex, due to osteopenia. Conclusions: The complication rate in pedicle screw fixation in patients with poor bone quality is nearly the double of the patients with normal bone, but it is still low. Pedicle screw fixation is safe in postmenopausal osteopenic women.

P398 PREVENTION OF OSTEOPOROSIS WITH SODIUM FLUORIDE, 25-HYDROXY VITAMIN 03 AND CALCIUM IN KIDNEY ALLOGRAFT RECIPIENTS M. Talalaj L. Gradowska P. Kapusciliski M. Durlik E. Marcinowska Department of Internal Medicine, Postgraduate Medical Education Centre and Institute of Transplantology, Warsaw Medical School, Poland Treatment with glucocorticoids and cyclosporine A results in bone mass loss and decreased mechanical competence of the skeleton. The attempt was made to prevent the osteoporosis in kidney allograft recipients by administration of calcium, vitamin 0 metabolite and fluoride. 111 kidney transplant patients were evaluated for 2 years.lmmunosuppressive therapy consisted of prednisone, cyclosporine A and azathioprine. 41 of the patients additionally received 25-hydroxy vitamin 03 (250HD 3) in a dose of 40 ~ daily and calcium carbonate 2 g daily. 34 of the patients were treated with the same drugs and sodium fluoride - 30 mg daily. It was found that within two years following kidney transplantation patients without preventive treatment showed a decrease in bone mineral density (BMD), as determined by dual energy X-ray absorptiometry by 9% in the lumbar spine (4 times bigger in the first than in the second year), by 7-9% in the three regions of the proximal femur, and by 4% in the total skeleton. The number of vertebral deformities, as determined by X-ray vertebral index, was closely correlated with changes in BMD of the lumbar spine. Treatment with 250HD 3 and calcium carbonate was able to reduce a decrease in BMD in all evaluated regions to less than 0.3% and blocked the development of secondary hyperparathyroidism. The efficiency of the therapy was directly correlated with serum 250HD concentration. Sodium fluoride increased BMD by 5% in the lumbar spine, by 4-5% in the proximal femur, and by 4% in the total skeleton. It prevented the inhibition of bone turnover caused by glucocorticoids. Both treatment regimens with equal efficacy prevented new vertebral crush fractures. Fractures of appendicular skeleton were not observed. Kidney graft function was not influenced by the treatment used .

P399 EFFECT AND OFFSET OF EFFECT OF TREATMENTS FOR OSTEOPOROSIS ON HIP FRACTURE HEALTH OUTCOMES B. Jonsson J. Kanis A. Dawson. A. Oden O. Johnell Centre for Metabolic Bone Diseases, Sheffield, UK We investigated the cost effectiveness of treatments that reduce the risk of hip fracture using acomputer simulation model. The base case simulations assumed a 5-year intervention that reduced the risk of hip fracture by 50% during the intervention period, and an effect which reversed during the next 5 years. Sensitivity analyses included the effects of age, different fracture risks, and different treatment costs and duration of therapeutic effect .once treatment was stopped. Cost effectiveness was critically dependent upon absolute risk determined by the age of intervention and the relative risk for age. Reasonable cost effectiveness was shown even with relatively high intervention costs for women with a risk about twice the average at the age of 70 or more years. Cost effectiveness was critically dependent upon the assumptions made concerning offset of effect of intervention after the end of treatment. Where no residual effect was assumed, it was difficult to show cost effectiveness from any intervention except for the most effective and least expensive. Conversely, cost effectiveness improved considerably where effectiveness persisted for a longer time. These studies support the view that intervention in the elderly may be preferred to intervention at the time of the menopause, and that offset time, hitherto poorly characterised, is a critical component of cost effectiveness particularly in younger women.

P4DD THE ROLE OF PHYSICAL ACTIVITY ON THE PREVENTION OF OSTEOPOROSIS I. Yeldan G. Dilsen Dept. PM&R, University of Istanbul, Turkey Despite some contradictory results most of the studies revealed the effective role of physical activity (PA) on bone mineral density (BMD) in osteoporosis (OP). Therefore we conducted a study to investigate the effects of two different types of exercises: 1. loading type walking, 2. strengthening type back exercises. 12 postmenopausal women received 30 minute walk as loading type exercise and 13 postmenopausal women performed strengthening exercise for back extensors and postural exercise twice a day. Duration of treatment was 6 months. In both group, the present age, age of menopause, duration of menopause, weight, height, BMI, daily calcium intake, PA questionnaire, pre and post treatment BMD were recorded or performed. Mean daily calcium intake was found to be 1076.91±336.7 mgr in walking group, 1049.53±474 mgr in the strengthening exercise group. Mean PA was 33.28±1.54 kcal/kg/day in walking group and 33.58±1.93 kcal/kg/day in strengthening exercise group. There were no statistically significant differences in the height, weight, BMI, daily calcium in take and the mean values of PA in both groups. Considering the post-treatmentTvalues BMD was found to be increased in 50% of women of the walking group and 53.8% in the exercise group, but this was not statistically significant (p>0.05). Although BMD values showed similar changes in both groups, it was found to be significantly decreased in the exercise group (p<0.05). In conclusion, this study reveals that walking and strengthening exercise of back extensors if applied as light activities (1-3 MET) have minimal effect in the prevention and treatment of OP.

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P4D1 THE EFFECT OF VITAMIN K SUPPLEMENTATION ON BIOCHEMICAL MARKERS AND URINARY CALCIUM EXCRETION Ye~im Kjrazli Aynur Tez Arzu On Arzu Keskjn. Mesut Aytjmur Berrin Durmaz Department of Physical Medicine and Rehabilitation, Medical Faculty of Ege University, Izmir, Turkey Although it is known that serum concentrations of vitamin K are reduced in older individuals and persons with osteoporotic fracture, the precise role of vitamin Kin osteoporosis needs to be determined. Circulating levels of osteocalcin may be a sensitive marker of vitamin K inadequacy and have been reported to be increased in both postmenopausal women and individuals who have fractures. Vitamin Kcan also affect the bone indirectly by controlling renal calcium excretion. 40 females with a mean age of 63.1 years who had osteoporosis were included in this study which was designed to study the effect of vitamin K supplements on bone metabolism indices. Osteoporosis w~s confirmed by bone mass measurements of the spine and the hip which was performed by dual energy X- ray absorptiometry. Vitamin K supplement was given over a 2-week period. Bone-specific alkaline phosphatase (an osteoblast enzyme), osteocalcin (a bone matrix protein), deoxypyridinoline and urinary calcium excretion was measured before and after the treatment. The treatment induced increased serum osteocalcin concentration, a decrease in urinary calcium excretion and a decrease in deoypyridinoline levels in the fast losers of calcium. It is suggested that vitamin K plays a role in the loss of bone mass in postmenopausal osteoporosis.

P4D2 EFFECT OF 5 YEARS GROWTH HORMONE REPLACEMENT IN GROWTH HORMONE DEFICIENT ADULTS ON BONE METABOLISM AND BONE MINERAL DENSITY P, Kann B. Pjepkorn, B. Schehler, J. Andreas', J. Lotz' W, Prellwjtz'

P4D3 THE ROLE OF PULSED MAGNETIC FIELD IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS Milica Lazovjc, I Stankoyic M. Kocie Clinic of Physical Medicine and Rehabilitation-Clinical Center of Nish Yugoslavia The task in the healing process of osteoporoSiS is not only the stopping of bone cosing, but the gradual increasing of bone density over the fracture level. The aim of this study was to prove the effect of pulsed magnetic field (PMF) and dosed physical activity in the women with postmenopausal osteoporOSiS. The first group consisted of 27 postmenopausal women, aged 50-60 years. The criteria for starting the examination was the value of bone mineral density (BMD). BMD was for 1 standard deviation less than normal «88%). BMD was measured on the lumbal vertebrae L1-L4, using the DEXA densitometer LUNAR DPX. The PMF was applied on lumbar region in this manner: 5 therapies with the intenSity of magnetic field of 4-6mT, frequency 50Hz, and duration 15 min., 10 therapies 8-10mT, 50Hz, 25 min. every day and than 3 times weekly for 8 weeks. After the 3 months break one series of therapy was repeated. The dosed physical activity was exercised 5 days weekly, 60 min. in duration. The second group consisted of 20 postmenopausal women, who exercised only dosed physical activity. The control group consisted of 22 female patients with no therapy. All the patients had the similar values of BMD before the examination and they were the same age. Results: after 8±1, 7 months the control BMD was measured in all the patients. In the first group with PMF and dosed phYSical activity the increased BMD of 2,7±1 ,32% was found. In the group with closed physical activity BMD was increased for 2,39±1,7%, and in control group was increased 2,19±2,71%. The difference is statistically significant (p<0,01). Conclusion: our results show that the PMF is one of the very important methods in the treatment of postmenopausal women with osteoporOSiS.

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Internal Medicine/Endocrinology, 'Nuclear Medicine, 'Clinical Chemistry, Johannes Gutenberg University Hospital, Mainz, Germany Growth hormone (GH) deficiency is associated with low bone mineral density (BMD) and increased fracture risk. The aim of this study was to investigate the effects of long-term GH replacement therapy on bone metabolism and BMD. In a clinical trial, a subgroup of 110 adult onset GH deficient patients (6 male, 4 female; 46±10 years; stable sexual hormone replacement where necessary) received GH replacement (0.251U1kgIWeek) continuously throughout a period of 5 years. BMD was compared to 10 age- and sex-matched healthy adults. Rates of bone resorption and formation were assessed by measuring serum levels of ICTP and PICP, respectively. BMD was measured at the lumbar spine by DPA and at the non-dominant forearm by SPA. ICTP increased significantly during the first 6 months and remained elevated. PICP also rose, but was significantly higher than baseline only after 24 months of treatment. BMD was subnormal at baseline and decreased during the first six months oftreatment, and increased progressively for the rest of the study. Mean DPA (lumbar spine) values expressed as percentages of age- and sex-related normal values were 12.6% above baseline after 5 years (p<0.01j, a significant difference to healthy controls was already detected after 4 years of treatment. Our results support previous findings that GH replacement stimulates bone turnover and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 5 years.

P4D4 EFFECT OF BIOMIN H® AND VITAMIN D2 ON THE URINARY MARKERS OF BONE TURNOVER IN OVARIECTOMIZED RATS M. StanCikovA K. Svik R. Istok P. Masarvk Z Veselkova Research Institute of Rheumatic Diseases, Piesfany, Slovakia Urinary biochemical markers were monitored in ovariectomized rats during preventive administration of Biomin H® (original Slovak calcium drug, prepared from egg shells) and vitamin O2, Adultfemale rats ofthe SpragueDawley strain with living weight 270±1 0 g were bilaterally ovariectomized (OVX), or a simulative operation was carried out (SHAM) and then divided into 5 groups with 8 rats in each of the groups: SHAM control, OVX control, OVX rats treated with Biomin H®, with vitamin D2 and with the combination of Biomin H® and vitamin D2. The rats were on a standard nutrition diet containing 7.59 Calkg, 6.59 P/kg and 1000 I.U. of vitamin D/kg a day for 15 weeks. A double dose of Ca and vitamin D (in the form of Biomin H® and vitamin D2) was applicated in treated groups. Concentrations of pyridinoline, deoxypyridinoline, calcium, magnesium and phosphorus were analysed and expressed relative to the urinary creatinine concentration. In addition, pyridinoline and deoxypyridinoline ratio was evaluated. Osteoresorption in the ovariectomized female rats was markedly effected compared to SHAM controls. It was evidenced by significantly increased concentrations of pyridinoline and deoxypyridinoline. Ca administration (in the form of Biomin H®) significantly decreased these markers values compared to non treated OVX controls. Pyridinoline/deoxypyridinoline ratio was significantly higher in SHAM controls compared to OVX groups. In the first six weeks of the study, ovariectomized animals excreted Significantly more urinary calcium and magnesium in comparison with SHAM controls. The amount of calcium and magnesium in urine inversely correlated with the amount of phosphorus in OVX groups. The results of our study showed Significant decrease of osteoresorption markers in ovariectomized rats treated with Biomin H®.

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P405 EFFECTS AND REPRODUCIBILITY OF RECOMBINANT HUMAN GROWTH HORMONE (GH) ADMINISTRATION ON BONE METABOLISM IN PATIENTS RECEIVING CHRONIC GLUCOCORTICOID TREATMENT F. Manelli. S. Bossoni* C. Bodini. R. Carointeri M.G. Sozzi G. Bugari** F. Barbieri*** A. Giustina Endocrinologia, * I Medicina, * * III Laboratorio, Spedali Civili, Brescia, Ely Lilly, Sesto Fiorentino; Italy Glucocorticoids are potent osteopenic agents and are well known to inhibit GH secretion in humans. Current evidence suggests that their predominant action is through inhibitory influences via somatostatin. Human GH is apotent anabolic agent known to stimulate, directly or by its peripheral mediator IGF1, protein synthesis, cell growth, and osteoblast activity. The aim of our study was to evaluate the effects of short-term administration of human recombinant GH on bone metabolism in 9 non obese adult patients (seven female and two males; age range 41-68 yrs; body mass index 26±1.3 kg/m2) receiving chronic glucocorticoid treatment for non endocrine diseases and with suppressed response of GH to GH-RH (peak <1 OIlQ/L). After a3-day stabilization period in the hospital, at 18.00 of the fifth day of hospitalization the patients began treatment with a daily s.c. injection of 0.1 IU/kg (0.037 mg/kg) recombinant human GH (Humatrope, Eli Lilly, Italy) for 7 days. Under basal conditions, carboxy-terminal propeptide of type I procollagen (PICP; RIA, Techno GenetiCS, Milano, Italy; normal range: 80-200 IlQ/L) and osteocalcin (RIA; normal range: 7-50 IlQ/L), indexes of bone synthesis, were in the low normal range of our assays (mean daily levels 119.6±2.8 and 17.1±1.3, respectively), while carboxyterminal telopeptide of type I collagen (ICTP; normal range: 1.5-4.5 IlQ/L), index of bone resorption, was in the high normal range in all glucocorticoidtreated patients (mean daily level 3.7±D,4). After GH treatment, a significant (p<0.05) increase in mean daily level of PICP (130.2±2,4 IlQ/L), osteocalcin (18.9±1.5 IlQ/L) and ICTP (4.7±D.5 IlQ/L) was observed with respect to the basal levels. The reproducibility of the effect of this treatment were evaluated in an adult patient (58 yrs age, body mass index 23.5 kg/m') undergoing longterm glucocorticoid therapy for rheumatoid arthritis (duration of disease 26 months). After 7 days of therapy we showed with respect to the baseline values a significant increase in osteocalcin single assay (from 26 to 32 IlQ/L) and an increase in bone isozyme alkaline phosphatase (from 72 to 106 IlQ/L, normal range: 10-50) with no evident changes in urinary desoxipyridinoline (from 10.3 to 10.7 ~ol/mol creatinine, normal range: 2.3-6.7). These data were confirmed in a second cycle of GH therapy after 3 months from the first evaluation. In fact, in this cycle osteocalcin increased from 28 to 41 IlQ/L and bone isoenzyme alkaline phosphatase from 55 to 66 IlQ/L, without modification in urinary desoxipyridinoline (from 11,4 to 11.5 ~ol/mol creatinine. Our findings suggest that acute GH administration cause an effective and reproducible increase in serum levels of bone formation markers without significant changes in bone resorption. Therefore, recombinant GH may be considered and tested as a potential tool in the treatment of glucocorticoid induced osteoporosis.

P406 EFFECT OF EXERCISES ON BONE MASS IN PATIENTS WITH LOW BONE MINERAL DENSITY N. Pilipovic S. Brankovic P. Vukojevic. Institute of Rheumatology, Belgrade, Yugoslavia Effect of exercises on bone mass were investigated in 37 postmenopausal women with low bone mineral density (BMD). BMD were obtained on LS spine using Lunar DXA system. Patients exercised in Institute during the 4 weeks, 3 times a week and after that continued with exercises at home. There were two groups of patients. Group I: 11 pts that only exercised without taking drugs, mean aged 56,54 (45-72) yrs and mean BMD 0,920 (0,73-1,08) gr/ cm' with average T-score -2,34 (-1 ,Oto -3,9). Group II: 26 pts who were using therapy for low bone mass (HST, vitamin D, calcitonin and bisphosphonates) and exercising. Mean age of them was 60,11 (47-76) yrs. and mean BMD 0,870 (0,71-1,03) gr/cm' with T-score -2,67 (-1,41 to -4,09). Groups were comparable in respect of age and BMD. The control DXA was done after average period of 8,4 months in group I and 9,7 months in group II. In group I, BMD was increased to mean 0,930 (0,76-1,07) gr/cm' and T score to -2,21 (-1,04 to -3,62) which was increase in bone mass for 1,2% (non-significant: NS). In group II, bone mass was also increased for 1,48% (NS). The mean value of BMD was 0,880 (0,65-1,0) gr/cm', and T score -2,70 (-1,65 to -3,90). Conclusion: Our results suggestthat exercise have positive effect on BMD apart from medicament therapy. It is necessary to continue investigation in order to assess effect of long term exercise (as single therapy and in combination with medication) on BMD and appearance of osteoporotic fractures .

P407 EARLY X-RAY MORPHOMETRIC SIGNS OF SPINE OSTEOPOROSIS N. Beloselsky O. Erchova O. Semionova Medical University, Department of Radiology, Yaroslavl, Russia Morphometric symptoms of osteoporosis vertebral bones fractures with decreasing of the indexes on 3SD and more is considered to be well known now. Diagnostic importance of less marked deformations has been investigated not fully. For the purpose of the determination early morphometric signs of spine osteoporosis there were investigated values of morphometric examination on EVOS method of 60 patients with minimum X-ray screening indications - the typical deformations of vertebral bones, the decreasing of density bone's shadows and the kyphosis of thoracic spine (40 women, middle age 60,5, 20 men, middle age 65,4). The results of the examinations were compared with morphometric characteristic of our population in common. As a result of our investigations we revealed the following morphometric special features. 1. Disparity between the sizes of vertebral bones to the age of the patients. 2. Decreasing of the height of anterior and medium sizes of T5-T1 0 bones with the most pronounced changes in T8,T9. The formation of wedge deformation of bones. 3 . Decreasing of distinction between the anterior bone's sides with the tendency to be equal in size. 4. Paradoxical sizes of vertebral bones with rotation of bones with the different degree of deformation.

P408 CRITICAL EVALUATION OF THE FAILURE REASONS OF THE DESIRED TREATMENT EFFECT IN RANDOMISED GROUP OF 2000 OSTEOPOROTIC PATIENTS. A TWO-YEAR CLINICAL TRIAL A. Yiatzides, Natasa Apostolopoulou B. Magiasis, V. Fragoulopoulos MEDLAB MEDICAL INSTITUTE, ATHENS, GREECE The aim of this clinical research was to determine the reasons for which a percentage of clinically and laboratory examined osteoporotic patients, while being treated by clinicians, presented remarkable reduction of bone density. Material -Method: The study group comprised of 2000 osteoporotic patients (men and women) who were sent for laboratory screening and were randomly selected. Subjects were followed up for two years. Each patient's database included: i) a detailed medical history, ii) the BMD measurements per skeletal site, iii) the annual rate of bone loss. Treatment agents were not evaluated. Results: Results indicated that 57% (group A) presented stability or improvement of the BMD value while 43% (group B) showed a significant reduction beyond the normal expected for the two years period. A further analysis was conducted on group B in order to investigate the reasons of BMD reduction: A) 22% of the patients had not properly understood doctor's instruction. B) 12% of the patients had an undiagnosed secondary osteoporosis. C) 14% of the subjects continued to take substandard daily doses of calcium despite doctor's recommendations. They also ignored to increase the daily physical activity. D) 17% of the subjects showed remarkably increased rates of bone loss which had not been taken into consideration. E) 28% of the patients reduced treatment due to necessary social insurance financial cuts. F) 7% of the subjects showed no evident reason for bone loss. Conclusion: The caring and careful manner of handling patients, in combination with a detailed medical history, the evaluation of laboratory test results, as well as the analytical medical instruction on the time and way of therapy, along with the parameters that determine the progress of the disease, are considered for the worthwhile effect of the applied treatment. Furthermore, measures will have to be taken by the state health authorities. The insufficient treatment of metabolic diseases due to financial cuts will have disproportionately high socioeconomic consequences.

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SECONDARY OSTEOPOROSIS

P409 BONE MINERAL DENSITY IN CHILDREN WITH CANCER DURING THE FIRST SIX MONTHS OF CHEMOTHERAPY P. Arikoski J. Komulainen P. Riikonen R. Voutilainen H. Kroger' Departments of Pediatrics and Surgery" Kuopio University Hospital, Kuopio, Finland We have previously demonstrated osteopenia in long-term survivors of childhood acute lymphoblastic leukemia, and in children with cancer at completion of chemotherapy. The purpose of this study was to investigate changes in bone mineral density (BMD) in children with cancer during the first six months of chemotherapy. Lumbar spine (L2-L4) and femoral neck BMD (g/cm') was measured by dual energy x-ray absorptiometry at diagnosis and after six months of chemotherapy in 42 children with cancer (age 2.9 -16.0, mean 9.1 years; 20 males, 22 females): 9 acute lymphoblastic leukemias, 4 acute myeloblastic leukemias, 12 lymphomas, 17 solid tumors. Apparent volumetric density (BMDvol, g/cm3) was calculated to minimize the effect of bone size on BMD. A one-sample t-test was used to compare BMD values (z-scores) at diagnosis with those of 121 age- and sex-matched healthy controls. A paired-samples t-test was used to compare the absolute BMD values at diagnosis with BMD values at six months of therapy. BMD values did not differ from those of controls at diagnosis. During the first six months of chemotherapy, femoral areal (g/cm') and volumetric (g/cm3) BMD decreased significantly as compared to baseline BMD (table). N

DIAGNOSIS

6 MONTHS

% CHANGE

Lumbar BMD Lu mbar BM Dvol Femoral BMD Femoral BMDvol

39**

0.737 (0.195) 0.287 (0.047) 0.810 (0.155) 0.364 (0.054)

-0.9 (8.8) -1.1 (8.8) -9.6 (7.5)* -8.6(8.3) * * *

0.759 (0.221) 0.293 (0.050) 21*** 0.886 (0.136) 0.395 (0.043)

* p<0.001; ** lumbar BMD was measured for 39 patients, *** femoral BMD was measured only for children above 7 years of age: values as mean (SO). BMD was found normal in children with cancer at the time of diagnosis. A significant decrease in femoral BMD occurred during the first six months of chemotherapy. The detected decline in volumetric BMD indicated a real deficit in femoral bone density. No significant change was observed in lumbar BMD. A further follow-up of lumbar and femoral BMD is required to identify those who may be left with impaired development of bone density after completion of therapy. Studies determining the mechanisms of the observed reduction in femoral but not in lumbar BMD in children with cancer during the first six months of chemotherapy are currently underway.

P410 SECONDARY OSTEOPOROSIS J. Kocian 1st in!. clinic. Postgrad. Med. Institute, Prague, Czech Republic In accordance with known causes of osteoporosis we may divide our group of 3500 patients into 7 subgroups: 1) nutritional (lactose intolerance, vegans, macrobiotics) 2) malabsorption and maldigestion (sprue, gastrectomy B I., B II., pancreatitis) 3) hypercalciuria (idiopathic, secondary) 4) endocrine diseases (ovarectomy, strumectomy, hyperthyroidism, diabetes mellitus, M. Cushing) 5) immobilization 6) iatrogenic (corticoids, non-thiazide diuretics, surgical interventions on gastrointestinal tract) 7) miscellaneous (smoking, alcoholism, black coffee (drugs) Conclusion: the advantage of finding out all causes of bone demineralization is in efficient, quicker and cost-effective treatment when we are able to remove all its causes with proper measures.

P411 ASSESSMENT OF BONE RESORPTION IN ARTHRITIS WITH A NEW ASSAY FOR SERUM TYPE I COLLAGEN C-TELOPEPTIDES P. Garnero P. Jouvenne. P. Delmas P. Miossec INSERM Unit 403, H6pital E. Herriot, Lyon, France Rheumatoid arthritis is characterized by synovial inflammation and by the degradation of adjacent tissues e.g. articular cartilage and bone. The degree of inflammation activity can adequately be assessed by clinical and laboratory indexes. In contrast, the destruction of the different tissues is more difficult to investigate because of the lack of specific and sensitive markers (MK). The aim of that study was to investigate alterations of bone metabolism in patients (p.) with chronic polyarthritis with or without joint destruction using specific biochemical MK of bone turnover. Three hundred and eighteen p. with chronic arthritis including 173 p. with rheumatoid arthritis and 90 p. with primary Sjogren's syndrome (disease duration >2 yr; mean: 9 yr) were divided in those with severe chronic arthritis with joint destruction, i.e. with Larsen wrist X-ray index ~2 (n=173) and those with benign arthritis without joint destruction, i.e. with Larsen wrist X-ray index <2 (n=145). Bone formation was assessed by serum osteocalcin (OC) and bone resorption by a new assay for serum type I collagen C-telopeptide breakdown products (serum CTX, Crosslaps, Osteometer Biotech). The table reports mean values in chronic arthritis compared to a large group of sex and age-matched controls taken from population-based cohorts. Polyarthritic patients controls Destructive (n:173) Non-destructive (n:145) (n=319) OC (ng/ml) 20.1±B.7* CTX (pM) 4013±2632*

18.9±8.1 * 2861±1973

24.2±10.2 2963±1397

*p<0.001 vs controls. OC was reduced in both destructive (-17%) and non-destructive arthritis (-22%). In destructive arthritis, OC was lower (p=0.02) in those patients taking low dose corticosteroid (n=72) compared to non-users (p=0.02). In contrast, serum CTX was increased (+35%) only in patients with joint destruction. Serum CTX, but not OC, was positively correlated with indices of disease activity and joint destruction (r=0.20-0.35, p:0.002-0.0001). Bone metabolism is uncoupled in patients with chronic polyarthritis. Bone formation appears to be reduced both in patients with and without joint destruction whereas resorption is increased only in patients with joint destruction. Serum CTX reflect disease activity and may be useful for monitoring the progression of joint damage in rheumatoid arthritis.

P412 BONE ULTRASOUND MEASUREMENTS IN RENAL, OSTEODYSTROPHY A. Montagnani. S. Gonnelli, C. Cepollaro, S. Martini, M. Mangeri, C. Gennari Institute of Internal Medicine, University of Siena, Italy Renal osteodystrophy (ROD) can be characterized by both high and low bone turnover states. Although bone biopsy remains the gold standard to diagnose ROD, non invasive tools for the diagnosis and follow up of such bone disease are desirable. Ultrasound (US) techniques have been shown to be correlated not only with bone density but also with bone quality. We have investigated 98 patients on chronic haemodialysis and 98 healthy controls. In both groups US parameters at phalanxes and at calcaneus have been performed. In all subjects intact parathyroid hormone (PTH), total alkaline phosphatase (T-ALP), bone isoemzyme (B-ALP), and carboxy terminal telopeptide of type I collagen (ICTP), have been also assessed. US parameters were significantly lower in the haemodialyses group than in control subjects. Moreover, US parameters at the phalanxes showed a significant correlation with PTH, T ALP and B-ALP. Dialytic age showed a modest, but significant correlation only with US parameters at the phalanxes. On the basis of bone biochemical markers, we considered a group with high (HT) and another with normal-low (LT) bone turnover. US parameters of the phalanxes, but not of the heel, were significantly (P<0.01) lower in HT than in LT group. Furthermore, in HT group US phalanxes parameters strongly correlated with B-ALP. Our results seem to demonstrate that US parameters are a useful tool in the assessment of skeletal status in renal osteodystrophy.

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P413 BIOCHEMICAL MARKERS AND BONE DENSITY IN EATING DISORDERS H. Resch St. Newrkla B. Eibl S. Zapf. P. Weiss S. Grampp K.H. Barmherzige Schwestern (St. Vincent), 1060 Vienna The metabolic changes in eating disorders are known risk factors of osteoporosis. The exact pathophysiological mechanisms responsible for the increased fracture risk remain to be elucidated. Methods: We therefore conducted a comprehensive evaluation of 85 patients (average age 22 years, 17-30 years) with anorexia nervosa (AN), bulimia (BUL), and anorexia/bulimia (AB) comparing bone mineral density (BMD) of four different measuring sites (spine, hip, distal radius and calcaneus) to physical parameters and biochemical indices. Bone specific alkaline phosphatase (ALP), osteocalcin (OC), parathyroid hormone (PTH), procollagen Type 1 propeptides (P-I-CP) were analyzed to estimate bone turnover. Bone density measurements were performed by means of peripheral quantitative CT densitometry (paCT, XCT-1400, Stratec) at the distal radius, ultrasound attenuation (UBA) at the calcaneus (Sonomed Systems) and by DXA (Hologic 1000) at the hip and lumbar spine. The control group consisted of 30 healthy, age and sex-matched caucasian females. Results: Among biochemical parameters, in AN significantly higher serum cortisol concentrations, lower FT3 and significantly decreased (p<.001) levels of ALP and OC were found, when compared to BUL, AB and controls. So far, ALP was the best biochemical marker to assess the risk of osteopenia in AN. BMDs at all measuring sites were significantly lower (p<.001) in the whole group of patients with eating disorders when compared to controls (n=30). In addition, significant correlations between BMD at any measuring site, BMI (r=.7, p<.0001) and the duration of amenorrhoea (r=.6, p<.001) were observed. BMDs were significantly lower in patients with AN (n=45) than in those with BUL (n=25) and AB (n=15). The most prominent differences (p<.0001) were observed in BUA at the calcaneus with a T-score of -4.2±O.3 in AN. In the subgroups with BUL and AB there were no differences in BMD or biochemical markers when compared to controls. Conclusions: Whereas overt osteopenia was uncommon in AB and BUL, in AN BMD was significantly decreased at all measuring sites. The biochemical changes may indicate that the decreased bone mass in AN is caused by a reduced bone turnover.

P414 INTERMITTENT CYCLIC THERAPY WITH ETIDRONATE PREVENTS CORTICOSTEROID-INDUCED BONE LOSS: THREE YEARS OF FOLLOW-UP R.J. Sebaldt J.D. Adachi M. Boratto M. Gordon A. Petrie, GJ. Stephenson C.H. Goldsmith CANDOO Project, St. Joseph's Hospital & McMaster University, Hamilton, Canada We determined the effectiveness of 3 years of intermittent cyclic therapy with etidronate (lCT-E) in preventing bone loss in patients receiving corticosteroid (CS) therapy. We analyzed the clinical records of patients seen at our tertiary care Osteoporosis Centre and whose data are routinely collected prospectively into a standardized database. Patients treated with CS for at least 3 years were selected for the study group if they were concomitantly treated with ICT-E (2 weeks of etidronate 400 mg/day followed by 11 weeks when calcium intake was supplemented if required to at least 1000 mg/day, repeated in 3-month cycles). A comparison (Comp) group was selected of CS-treated patients who were treated with no bone-active therapy other than calcium and vitamin D. Patients were excluded if they had known causes of secondary osteoporosis, were treated with any other bone active therapy within the preceding 2 years or did not have a bone mineral density (BMD) determination at baseline and after approximately 1, 2 and 3 years of follow-up. There were 24 and 37 patients in the ICT-E and Comp groups. The groups were comparable in baseline age, 60;16 vs 55;14 yrs (mean;SD), and mean CS dose during the study period (prednisone 13 vs 10 mg/day). The groups differed in prior duration of CS therapy, respectively 11 ;11 vs 3;4 yrs, lumbar spine (LS) BMD, 0.894;0.143 vs 1.098;0.191 (g/cm'), and proportion of patients with prior vertebral fractures (13% vs 5%). In the ICT-E group, LS-BMD increased significantly relative to baseline at each yearly follow-up time point, by +3.8;5.8%, p=0.006 (1 yr), +5.0;8.0%, p=0.006 (2 yr) and +5.2;9.8%, p=0.01 (3 yr). In the Comp group, LS-BMD changed by -3.6;6.4% (p=0.0005), -3.2;7.8% (p=0.007) and -1.3;9.1 % (p=0.3), respectively. The differences in these percent changes between the two groups were significant at each time point, p=0.00003 (1 yr), p=0.0002 (2 yr) and p=0.01 (3 yr).

These data suggest that ICT-E is an effective treatment for CS induced osteoporosis over a period of 3 years of continuing CS therapy. These findings extend the conclusions of controlled trials conducted over shorter periods of CS therapy.

P415 IMPACT OF DISEASE ACTIVITY ON BONE MINERAL DENSITY AND MARKERS OF BONE METABOLISM IN JUVENILE ARTHRITIS G. Lien M. Haugen B. Flat0 0. F0rre Center for Bheumatic Diseases The National Hospital, Oslo, Norway The purpose of the study was to identify variables that are related to bone mineral density (BMD) in patients with juvenile arthritis (JA). In 337 (males/females 108/229) patients JA (mean age 22,7 years, range 13-31; disease duration 14,9 years, range 7,4-25; pauci/poly/systemic 210/ 96/32), BMD were measured with DXA scanner (Lunar Expert). Disease activity was evaluated by both clinical and laboratory measurements. Markers of bone formation and resorption were analysed. Physical activity, smoking habits and measurements of nutritional status were registered. Multiple regression analysis was used to evaluate the impact of age, sex, doctors global, ESR, months of cortical steroid treatment (5-10mg/day), lean body mass, smoking and phYSical activity on BMD of total hip, femoral neck and lumbar spine. BMD at all three sites were significantly higher in male than in female patients (p<0,001) and correlated positively to lean body mass (p<0,001). BMD was positively correlated to age in lumbar spine (p=0,01) and femoral neck (p<0,001). High disease activity as evaluated by doctors global had negative impact on BMD in femoral neck (p=0,01) and total hip (p<0,01). Use of corticosteroids had negative impact on BMD of the total hip (p<0,05). Physical activity and smoking were not found to affect BMD. BMD was not different in female patients >20 years who never had used corticosteroids from those who had used corticosteroids earlier. However, BMD of total hip was significantly lower in males who had used corticosteroids (p<0,05) compared with those who never had used corticosteroids. In female patients >20 years who never used corticosteroids markers of bone resorption were significantly increased in those with high disease activity as compared to those with low disease activity: (p<0,05 for serum ICTP and urine NTX and p=0,05 for urine Deoxypyridinum, Mann-Whitney test). The same trend was found in the male patients but not found significant. Disease activity had negative impact on BMD in femoral neck, and total hip but not in lumbar spine in patient with JA. Earlier use of corticosteroids treatment seems to affect BMD minimally. In patients who never had used corticosteroids markers of bone resorption were increased in those who had moderate to very high disease activity.

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P416 NUTRITIONAL FACTORS AND TOTAL BODY BONE MINERAL DENSITY IN FEMALE PATIENTS WITH JUVENILE ARTHRITIS M. Haugen. G. Lien. B. Flate 0. Ferre Center for Rheumatic Diseases, The National Hospital, Oslo, Norway The purpose of the study was to evaluate the impact of nutritional status (NS) on bone mineral density (BMD) in female patients with juvenile arthritis (JA). NS was assessed by food frequency questionnaire, anthropometric measurements and measurements of concentration of haemoglobin, albumin, total protein, Ca, ionised Ca, Mg, P;, 1,25-dihydroxyvitamin- 0, 25-hydroxyvitamin 0 and PTH in serum. BMD and lean body mass was measured with a DXA scanner (Lunar Expert) in 129 women with JA, mean age 25±2,7 years (range 20-31), disease duration 15,5±2,3 years (range 1225), diagnosis pauci/poly/systemic 83140/6 systemic. Mean BMI was 23,3±4,4. Twenty patients had previously used corticosteroids for a median time of 8 mo, (range 1-78). 109 patients had never used corticosteroids. There was no difference in total body BMD in the two groups. Disease activity was graded as low in 108 patients, moderate in 14 patients and high in 7 patients. Mean Z-score for total body BMD was 0,34±1,1. Forward multiple regression analysis was used to evaluate the impact of nutritional status on total body BMD. We found no effect of food or nutrient intake on total body BMD, thol'lgh there was a positive trend with intake of fruit and vegetables and a negative trend with intake of bread and cereals. Intake of milk in childhood and in the teens did not affect BMD. Of the laboratory variables serum albumin concentration had impact on BMD (p<0,01). Lean body mass was highly correlated with total body BMD (p<0,001). Lean body mass and serum albumin concentration correlated with disease activity (r=-0,25 p<0,001 and r=-0,29 p<0,001, Spearman's rJ Reduced lean body mass and low albumin concentration were associated with low total body.

P418 BONE MINERAL DENSITY AND BONE METABOLISM IN YOUNG MALES WITH ANKYLOSING SPONDYLITIS D. Felsenberg ' , J. Braun*" E. Gromnica-Ihle*' 1) Free University Berlin, University Hospital Benjamin Franklin, Osteoporosis Research Group, 2) Clinic for Rheumatic Diseases BerlinBuch, Berlin, Germany Our own results of bone mineral density (BMD) measurements in 240 patients with ankylosing spondylitis (AS) showed osteoporosis in vertebral and/or appendicular bone in 75%. A generalised osteoporosis was found in 35% - even in early AS. Frequency and severity of osteoporosis depended on clinical activity of AS. The aim of the following study was to examine bone turnover by various parameters of calcium and phosphate metabolism. We investigated 114 men with AS, aged 20-55 years. BMD was measured with quantitative computed tomography in the lumbar spine and in the ultradistal radius. Serum calcium, phosphate, alkaline phosphatase (AP) and its isoenzymes, osteocalcin (OC), 25-0H-vitamin 0, parathyroid hormone and urinary calCium, phosphate were examined. BMD measurements reflected the results mentioned above. Serum OC was significantly decreased in patients with AS (0.96 ng/ml I 0.38) compared with acontrol group (1.65 ng/ml I 0.82). Serum AP was increased in patients with AS (3.5 ~ol/sl I 1.3 vs 2.8 ~ol/sl 10.9). Other parameters did not show any significant differences between men with AS and healthy men. Bone metabolism in AS is characterised by low bone turnover. This results in a high percentage of local or generalised osteoporosis in patients with AS - even in early AS. ~"

P419 EVALUATION OF BONE USING THE CONTACT ULTRASOUND BONE

P417 PREVALENCE OF OSTEOPOROSIS AND OSTEOPENIA IN FEMALES WITH RHEUMATOID ARTHRITIS G. Haugebera T.K. Kvien T.Uhlig* J.A. Falch** J.I. Halse *Oslo City Dept. of Rheumatology, Diakonhjemmet Hospital, N-0319 Oslo, **Dept. of Internal Medicine, Aker Hospital, N-0514 Oslo, and * * *Osteoporosis Clinic, N-0172 Oslo, Norway The aim: To examine the point prevalences of osteoporosis (OPO) and osteopenia (OPE) in a representative, non-selected sample of female patients with rheumatoid arthritis (RA) between 20 and 70 years of age. Material and method: The patients were recruited from a community based register of RA patients (completeness 85%), comprising 1620 patients. Out of the 913 female register patients between 20 and 70 years, 407 patients (44.6%, mean age 54.7 years, median age 56.3 years, disease duration 12.9 years, rheumatoid factor positive 48.2%, prednisolon use: 153 never, 91 previous and 163 current users) were examined with hip and spine bone denSitometry (Lunar Expert-XL, German female reference values provided by the manufacturer) and a complete clinical and joint examination. 398 underwent hip and 406 out of the 407 patients underwent spine measurement. The conventional WHO definitions for OPO (T-score <-2.5 SO) and OPE (T-score <-I SO and >-2.5 SO) were used. Results: The Table shows the mean (SO) BMD and percentages having OPE and OPO according to the T-score definition and percentages having Z-scores below -1, -2 and -3 SO at various sites of measurement. Hip: Wards, neck, total. Spine L1-L2, L2-L4. BMD Wards Neck Total L1-L2 L2-L4

T-score

T-score

Z-score Z-score Z-score

(g/cm') 0.66 (0.18) 0.88 (0.25) 0.87 (0.17) 1.00 (0.22) 1.10 (0.22)

<-2.5 37.7 13.8 11.6 21.9 17.5

<-1 73.9 54.0 48.7 55.9 44.6

<-3 0.5 0 0.8 1.7 1.5

<-2 9.5 3.5 5.3 8.9 5.2

<-1 42.0 25.9 29.6 28.8 21.2

Conclusion: Depending on the measurement site, the prevalence of OPO ranged from 11.6 to 37.7% in this population based sample of female RA patients age 20-70 years. Age-matched Z-scores below -1 SO expected to be seen in 16% were observed in 21.2-42.0%, and Z-scores below -2SD in 3.5-9.5% in contrast to the expected 2.5%.

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ANALYSER S. Tuzun O. Kasapcopur O. Akarirmak i. Karacan, N. Ansoy F. Tuzun Istanbul University Osteoporosis Research Center, Cerrahpa~a Department of Paediatrics, Turkey In the management of Osteoporosis primary prevention is crucial rather than treatment of the disease itself. For that reason especially in childhood the risk factors for osteoporosis should be well determined. In this study broadband ultrasound attenuation (BUA) was measured at the calcaneum in 207 healthy Turkish schoolchildren (108 girls and 99 boys) aged 6-14 years. Calcaneal BUA was assessed using a prototype paediatric contact bone analyser (CUBA, McCue ultrasonics ltd.) and also a detailed questionnaire from related to eating habits and physical activities of the children was filled out by students and their parent. The mean calcaneal BUA value was 60.02 dB/MHz and it was significantly higher in boys (p=0.003). BUA did not show correlation with age, weight and height. In conclusion calcaneal BUA might be used as a screening method in children because it is free of radiation and its needs less time than three minutes for scanning. However further studies on larger series should be performed in order to obtain normative data and to make sure it is reliable method for bone status in children.

P420 BONE MASS DENSITY IN PATIENTS WITH PAGET DISEASE OF BONE: RESULTS FROM A RETROSPECTIVE STUDY H. Santos A. Faustino P. Araujo E. Simoes M. Parente A. Vilar Portuguese Institute of Rheumatology, Lisbon, Portugal Objective: We planned to study the bone mass density (BMD) in a group of patients with Paget disease of bone (PD), randomly selected, trying to find any particular aspects in values of BMD in this pathology. At same time, we looked for any possible correlation between BMD and metabolic activity of disease, tested by bone biochemical markers (BM). Patients and Methods: We selected a group of 20 patients with PD (age averaged 67,7 years), previously excluding all patients presenting either any risk factors for idiopathic Osteoporosis (OP) or another pathology potentially implicated on a secondary OP. We analysed a result of a dual xray absorption (DEXA) (Hologic QDR 1500) evaluating BMD at lumbar spine (LS) and femural neck (FN). We excluded all values of BMD from places affected by PD; if left FN was affected, we evaluated BMD from right FN. We obtained for every patient a concurrent value of' bone BM (serum alkaline phosphatase, and urinary hydroxyproline). Results: The averaged values assessed by DEXA in the FN and LS revealed a non significant difference when compared to individuals of the same race, sex and age: Z score =0,07±1,1 [-1,88;1,92J in the LS and Z score =0,08±1 ,23 [-1,66;3, 77J in the FN. When we compared BMD values and BM, we did not find any significant correlation between bone density values and metabolic activity of disease. We selected a special sub-group of patients with PD of one of the FN; when we performed the analysiS of opposite FN (not affected by radiological or scintigraphic criteria), we found a significant higher value of BMD Z score averaged =0,68±O,93 [-0,7;3, 77J in the LS and Z score averaged =0,66±1 ,57 [-0,93;3,77J in the FN. In this subset there was no correlation with BMD at LS. Conclusions: The global BMD values in PD patients are similar to standard population, independent of particular OP risk factors and are not correlated with the metabolic activity of disease. We found a particular; trend to a higher BMD in the FN oppOSite to an affected FN.

P422 DETERMINANTS OF OSTEOPOROSIS IN ADULTS WITH CYSTIC FIBROSIS P L. Selby" C.S. Haworth M.E. Dodd E.B. Mawer" J.E. Adams', A.K. Webb University of Manchester Departments of Medicine ' and Diagnostic Radiology' and Adult Cystic Fibrosis Unit, Wythenshawe Hospital, Manchester, UK We have previously demonstrated that bone density is reduced in adults with cystic fibrosis and that this might underlie the increased risk of fracture in such patients. In orderto determine optimal bone sparing treatment for such patients it is necessary to understand the mechanisms which lead to bone loss. We have therefore investigated the relationship between bone mass, bone turnover and disease activity in a large group of adults with cystic fibrosis. 134 (72 male) adults with cystic fibrosis had bone mass measured at the lumbar spine and total hip using DXA, lumbar spine using QCT and distal forearm using SXA. In addition samples were obtained for estimation of serum concentrations of vitamin D metabolites, PTH, osteocalcin (OC) and bone specific alkaline phosphatase (BSAP) and urinary excretion of deoxypyridinoline cross links (DPD). As previously reported bone mass was reduced at all sites measured. There was evidence of increased bone turnover with BSAP elevated in 25% of subjects, OC elevated in 47.9% and DPD elevated in 35%. There was evidence of hYPOVitaminosis D with 250HD less than 5ng/ml in 9% and 1,25(OH), less than 20pg/ml in 16%. PTH, BSAP and DPD were negatively correlated with 250HD concentrations (r=0.27, -0.30 and -0.26 respectively, p<0.01). There was no clear relationship between the measures of bone turnover and bone density. However bone density was related to body mass index (r=0.23 - 0.45) and, at axial sites, forced expiratory volume (r=0.17 - 0.41). We conclude that cystic fibrosis is associated with hypovitaminosis D and increased bone turnover. The relationship between this and bone density is unclear. Whilst disease severity and nutrition may be more important determinants of bone density the presence of increased bone turnover suggests that anti resorptive therapy may be beneficial in these patients.

P421 FK506 (TACROLIMUS) BASED IMMUNOSUPPRESSION LEADS TO BONE LOSS AFTER CARDIAC TRANSPLANTATION C. Werner J. Sytsch, B. Meiser. C.E. Anaermann K. Theisen, R. Gartner H.U. Stempfle Depts. of Medicine, University of Munich, Germany FK506 is a potent immunosuppressive drug which acts in a similar fashion to cyclosporine A with reputedly less severe side effects. Recent experimental studies however, demonstrated deleterious effects of FK506 administration on bone mineral metabolism. We studied therefore 20 patients (18m,2f, mean age: 49±13 yrs.) before and 4±2 months after heart transplantation (HTx) to evaluate the immediate effects of an FK506 based immunosuppression on bone density, fracture rate and disturbances in biochemical markers. Time interval between both examinations was 11±8 months. Immunosuppressive regimen included besides FK506, azathioprine-mycophenolate mofetil and steroids. Bone mineral density (BMD, T-value %) was measured at the lumbar spine and femoral neck with DEXA (Lunar Expert). Fractures were assessed by X-rays of chest thoracic and lumbar spine. Biochemical markers included gonadal hormones, gonadotropins, urinary and serum parameters of calcium metabolism, intact PTH, 250HD and renal function. Data were compare between consecutive measurements. Results: All patients showed already significant impaired bone mineral density before transplantation (lumbar spine: 88±9%; femoral neck 97±3%) compared to normals. After HTx a further decline in BMD (lumbar spine: 85±9%, femoral neck: 92±8%) was seen within an average of 4 months. No fracture occurred after HTx (2 documented vertebral fracture before HTx). There was no significant difference in biochemical parameters before and after HTx. Conclusion: Despite preexisting reduced bone density, these preliminary data demonstrated a rapid further reduction on bone mineral density due to an FK506 based immunosuppressive regimen which may lead to future fractures. In patients under FK506 immunosuppression, bone mineral metabolism should be therefore monitored carefully and therapy should be administered to prevent bone loss.

P423 BONE MINERAL DENSITY IN PATIENTS WITH RHEUMATIC DISEASES UNDER LONG-TERM LOW-DOSE GLUCOCORTICOID THERAPY (LTLGT) R. Dreher, Ch. Kuhn, M. Hesse G. Rippin* Hospital for Rheumatic Diseases, 55543 Bad Kreuznach, Germany. *Ins!. f. Medical Statistics and Documentation, University Mainz Objective: Calculation of the correlation between patient parameters and DXA bone densities in lumbar vertebrae and the neck of the femur and the selective LQCT cancellous bone density in lumbar vertebrae in inpatients. Method: In a multivariate regression analysis, the correlation of bone density values with parameters of the Bad Kreuznach Osteoporosis Questionnaire was calculated. Results: A significant positive correlation to the bone densities (LDXA) is calculated for the menopause (p=0.01), total fractures (p=0.001), osteocalcin values (p=0.03). Significant negative correlations are calculated for diabetes mellitus (p=0.04) and calcium therapy (p=0.025). Duration of LTLGT is not significantly correlated. Significant positive correlations with the bone density values in the neck of the femur (SDXA) are calculated for fractures (p=0.04), NSAR therapy (p=0.03). Significant negative correlations are calculated for male/female sex (p=0.04), age (p=0.0007), function (p=0.008), duration of LTLGT (p=0.01), administration of hormones (p=0.05 and diabetes mellitus (p=0.006). Significant positive correlations of the selective cancellous bone density (LQCT) are calculated for menopause (p=0.0001), fractures (p=0.005), ESR (p=0.02), serum calcium (p=0.05), L-thyroxine therapy (p=0.02). Significant negative correlations are calculated for function (p=0.05), duration of LTLGT (p=0.009), administration of hormones (p=0.0005), sodium fluoride therapy (p=0.009), and DPD (p=0.0003). Conclusion: The duration of LTLGT in rheumatism patients is correlated with lowered SDXA and LQCT values, but not with lowered values LDXA measurements in lumbar spine. Bone density of the lumbar vertebrae is not reliable in diagnostics and progress monitoring of osteoporosis especially in elderly patients.

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P424 BONE MINERAL DENSITY AND BONE TURNOVER IN TYPE I DIABETIC PATIENTS P. Ponfuch J. Payer Z. Killinger E. Toserova P. Feitscherova M. Takacsova 1st Department of Internal Medicine, Teaching Hospital, Bratislava, Slovakia The aim of the study was to investigate bone mineral density (BMD) and parameters of bone turnover in type I diabetic patients without diabetic nephropathy (DN) and with nonazotaemic incipient or overt DN. 25 nonazotaemic patients either with low-range albuminuria or with high range microalbuminuria and proteinuria were selected: Group A (UAE (Urinary albumin excretion) 10 ug/min, n=18, 10M/8F), Group B (UAE 100-1000 ug/min, s.creatinine 150 umolll, n=7, 3M/4F). BMD was measured by DXA (Norland XR36). BMD of femoral neck expressed as T-score was found decreased in group Bas compared to group A (p 0.05). No difference in L-spine BMD (T-score) between both groups was observed. There was decreased L-spine and femoral neck BMD in both groups as compared to normal values (p 0.05). In group B elevated ALP-B (p 0.05) was found. There was no significant difference between the two groups in osteocalcin, ACP-TR and PTH levels although, all parameters were slightly higher in group B. We conclude that in type I diabetic patients with non-azotaemic DN BMD of fem6ral neck is decreased and bone turnover is increased as compared to type I diabetic patients without DN. BMD values in both regions were below normal range in both groups of type I diabetic patients.

P426 PREVALENCE OF OSTEOPOROSIS AND OSTEOPENIA IN MALES WITH RHEUMATOID ARTHRITIS G. Haugeberg* T.K. Kvien* T. Uhlig* J.A.Falch** J.I.Halse*** *Oslo City Dept. of Rheumatology, Diakonhjemmet Hospital, N-0319 Oslo, **Dept. of Internal Medicine, Aker Hospital, N-0514 Oslo, and ***Osteoporosis Clinic, N-0172 Oslo, Norway The aim: To examine the point prevalences of osteoporosis (OPO) and osteopenia (OPE) in a representative, non-selected sample of male patients with rheumatoid arthritis (RA) between 20 and 70 years of age. Material and method: The patients were recruited from a community based register of RA patients (completeness 85%), comprising 1620 patients. Out of the 185 male register patients between 20 and 70 years, 93 patients (50.3%, mean age 57.7 years, median age 61.0 years, disease duration 11.8 years, rheumatoid factor positive 51.6%, prednisolon use: 31 never, 17 previous and 45 current users) were examined with hip and spine bone denSitometry (Lunar Expert-XL, German male reference values provided by the manufacturer) and a complete clinical and joint examination. All patients underwent spine and 89 out of the 93 patients underwent hip measurement. In our study of male RA patients the conventional WHO female definitions for OPO (T-score <-2.5 SD) and OPE (T-score <- 1 SD and >2.5 SD) were used. Results: The Table shows the mean (SD) BMD and percentages having OPE and OPO according to the T-score definition and percentages having Z-scores below -1, -2 and -3 SD at various sites of measurement. Hip: Wards, neck and total. Spine: L1-L2 and L2-L4.

P425 SKELETAL DEMINERALIZATION IN PATIENTS PRIOR TO TRANSPLANTATION OF THE KIDNEY, LIVER, AND HEART I. Sotornik M. Kouba P. Bubenicek Institute for Clinical and Experimental Medicine, Central Military Hospital, Prague, Czech Republic The risk factors of secondary osteoporosis include chronic nephropathy, hepatopathy and, possibly, also circulatory insufficiency. We focused our attention on possible differences in the severity of skeletal damage in the above identified population of patients. A total of 105 patients were examined: 48 pts prior to kidney transplantation (KTX) (31 M + 17F), 37 pts'prior to liver transplantation (LTX) (17M + 20F), 20 pts prior to heart transplantation (HTX) (males only) with a mean age of 49.2 yrs, with n.s. differences in groups. The patients were examined using a DXA Hologic 2000 system (mean BMD g/cm' of 4 sites of the femoral neck (FN) and the lumbar spine (LS) related to SD ranges: up to -1.0, -2.5, -3.5, and over 3.5). The interval between DXA examinations and time of transplantation was up to 3 months. Results: FN demineralization of up to -2.5SD of BMD affected about 30% of pts with n.s. differences in groups; there were 48.6% of pts prior to LTX, 14.6% of pts prior to KTX (p
•

BMD (g/cm')

T-score <-2.5

T-score Z-score Z-score <-1 <-3 <-2

Z-score <-1

Wards Neck Total LH2 L2-L4

0.70 (0.15) 0.91 (0.18) 0.95 (0.16) 1.08 (0.18) 1.19 (0.20)

37.1 12.3 13.5 14.0 10.8

7.9 4.5 7.9 21.5 12.9

84.3 66.3 56.2 48.4 34.4

1.1 1.1 1.1 4.3 3.2

47.2 33.7 37.1 45.2 33.3

Conclusion: Depending on the measurement site, the prevalence of OPO ranged from 10.8 to 37.1% in this population based sample of male RA patients age 20-70 years. Age-matched Z-scores below -1SD expected to be seen in 16% were observed in 33.3-47.2%, and Z-scores below -2SD in 4.5-21.5% in contrast to the expected 2.5%.

P427 EVALUATION OF RISK FACTORS FOR CORTICOSTEROID INDUCED OSTEOPOROSIS ANO PREVENTION OF FRAGILITY FRACTURES IN CHILDREN WITH RHEUMATIC DISEASES F. Fantini M. Gattinara. V. Gerloni. C Arnoldi A. Bellistri L. Aprile Chair of Rheumatology of the University of Milan, Centre for Rheumatic Children, Gaetano Pini Institute, Milan (ITALY) Since 1987 lumbar spine bone mineral density (BMD) is periodically checked by dual-photon absorptiometry (DPA, during the years '87-'90) or DEXA (since 1990) in all children affected by chronic rheumatic diseases on long-term corticosteroid treatment attending our Centre. Until now 220 patients (50 males and 170 females) have entered the study: 47 Systemic Onset JRA, 53 Polyarticular Onset JRA, 41 Pauciarticular Onset JRA, 50 SLE and 29 other Connective Tissue Diseases. In total 674 lumbar BMD determinations have been performed: 150 by DPA and 524 by DEXA. In 1994 on the basis of the results of longitudinal studies, a scoring system of risk factors for osteoporosis in children (RFOSC) was devised in order to plan the intervals between BMD checks. This score considers six factors: disease activity, average steroid dosage, reduced physical activity, Tanner stage or amenorrhea, bad Calcium or Vitamin Dnutritional conditions, other osteopenia-inducing drugs. In cases of increasing osteopenia, treatments with anti-osteoporotic agents are instituted to prevent fragility fractures. Since the RFOSC has been applied, no patient in all series has presented new vertebral collapses, notwithstanding reduction in the number of performed lumbar BMD checks (from an annual average of 1.3 determinations per patient to an average value of 0.4). Almost all rheumatic children on steroids are routinely treated with 250HD3 (0.5-1 mcg/Kg/day). Out of 37 children with impending risk of vertebral collapse (Z-score <-2.5 SD of the sex and age matched reference mean), calcitonin (10 patients), r-hu Growth Hormone (15 patients) and cyclic etidronate (20 patients) were administered sequentially or in combination with successful results all cases but one. In conclusion, thanks to lumbar BMD monitoring and effective antiosteoporotic measures, the prevention of symptomatic corticosteroid induced osteoporosis in children with chronic rheumatic diseases is now feasible.

P428 THE SPEED OF SOUND WAVES PROPAGATING ALONG THE TIBIAL BONE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS N. Mivatake', ~" K. Takahashi', J. Wada" M. Kunitomi" K. Yamamoto', and H. Makino' 1) Department of Medicine III, Okayama University, Medical School, Okayama, Japan. 2) Faculty of Education, Okayama University, Japan. 3) Omron Institute of Life Science co., Kyoto, Japan Background. In patients with non-insulin-dependent diabetes mellitus (NIDDM), there are conflicting data regarding the average bone mineral density. The purpose of the present study was to explore the potential use of ultrasound measurement, a method reflecting both quantitative and qualitative properties, in assessing bone status in patients with NIDDM. Methods. We studied 87 patients (age 36 - 91 years). The speed of sound waves (SOS; m/ s) propagating along the cortical bone was determined at the tibial shaft. SOS was expressed as Z-score, units of standard deviations from age and sex-matched normal mean values, and correlated with relevant clinical parameters. Results. Cortical bone in patients with NIDDM was lower under age of seventy (SOS Z-score: male (age) 30~ <50, -0.40±O.27; 50~ <70, -0.54±O.87: female 30~ <50, -1.1 O±O.21 , 50~ <70, -0.73±O.48) and females with lowered grasping power (SOS Z-score: -1.53±O.68).ln both elder males and females over seventy, SOS Z-scores were almost comparable with normal subjects (male (age) 70~,0.26±O.55 and female, -0.04±O.50), respectively. Females with low bone turnover, revealed by low osteocalcin levels, showed normal level of SOS Z-score (0.05±O.65), which indicating that low remodelling rate may retard the postmenopausal bone loss. Conclusion. Reduced turnover of the bone seems to be the characteristic of the diabetic bone disease, which resulted in the lowered SOS Z-scores under seventy. In turn, low bone remodelling may retard the age related bone loss over seventy and postmenopausal osteoporosis. SOS is quite useful method to assess the bone status of individuals with NIDDM .

P429 CHANGES ON BONE MINERAL DENSITY IN PATIENTS WITH TREATEDADDISON DISEASE E. JOdar, L. Garcia, M B. LOpez G. Martinez, P Collado P. Ruiz-Valdepeiias A. Jara' & F. Hawkins Services of Endocrinology. University Hospitals 12 de Octubre and 'Gregorio Maranon, Madrid E-28041 SPAIN The induction of bone loss in patients with Addison disease on long term treatment with standard replacement doses of glucocorticoids has been suggested. Our aim was to valorate the changes on the bone mineral density in treated patients with Addison disease over a 6 years period. Patients and Methods: Twenty-seven patients with treated-Addison disease (aged 53±9 years; 21 females, 6 males) were studied by dual X-ray absorptiometry in 1991 and six years later in 1997 with the same analyzer (Hologic aDR,OOOw; long-term CV<2%). Bone mineral density (BMD) was measured at lumbar spine (LS; L1-L4) in 1991 and at LS, femoral neck (FN), Ward triangle (WT), distal third and ultradistal radius (DTR and UDR respectively) in 1997. Data were expressed as g!cm' and as z-score (adjusted by age and sex in comparison with national reference population n=2442). Results: At the present time, patients with Addison disease show reduced BMD at LS ((mean±SD) -0.63±1.44; (95% confidence interval) (-1.20; 0.06)) and DTR (-1.03±1.36; (-1.57; -0.49)) and normal BMD values at FN (-0.52±1.38; (-0.52; 0.02)), WT (-0.49±1.26, (-0.99; 0.01) and UDR (-0.28±1.39, (-0.83; 0.28) in comparison with national standards. In the prospective study, the annual rate of bone loss at the lumbar spine from 1991 to 1997 was -0.16±1.08%/year, no significantly different from 0 (95% confidence interval (-0.59; 0.27). Conclusions: Patients with Addison disease treated with standard glucocorticoid replacement therapy show almost-normal bone mass with marginal reductions in lumbar spine and distal third radius BMD, without significant changes in the lumbar bone mass over a 6 years period of follow-up.

P430 DETERMINANTS OF BONE MASS IN PATIENTS WITH CYSTIC FIBROSIS M,L. Bianchi. M,L. Melzio E. Galbiati L. Enfjssio R. Cherubini B.M, Assaelo, A. Giuntao Istituto Auxologico Italiano IRCCS; °Centro Fibrosi Cistica, Clinica Pediatrica, Universita di Milano; Milano, Italy Many factors may influence bone mass changes in cystic fibrosis over an age range from childhood to early adult age. We studied 62 patients (30 F; 32 M; mean age 17±8.6 years), evaluating spine (S-BMD) and total body (TB-BMD) bone mineral density with DXA (Hologic aDR 2000). Calculation of Z-score with respect to our reference age matched population revealed a reduction in BMD in about two thirds of our patients: we found osteopenia (Z-score between -1 and -2) in 32% of cases, and osteoporosis (Z score < -2) in 33%. Only 35% of our patients h'l!l normal BMD (Z score between 0 and -1). . Direct correlation was found between BMD and:

•

• FEV1 (as an index of respiratory impairment), p<0.003; • platelet count (as an index of portal hypertension), p
P431 BONE MINERAL DENSITY AND BODY COMPOSITION IN NON WASTED HIV-INFECTED MALE PATIENTS M. Lazanas I. Lambrinoudaki, G. Tsekes, G. Douskas, A. Georgiadis, E. Georgiou Controversy exists on whether HIV-infection per se is associated with metabolic alterations, including bone metabolism, in the non-wasted patients, which may ultimately lead to the phenomenon of wasting. The aim of this study was to assess possible body composition differences between clinically stable HIV-infected patients with normal body weight and normal age- and sex-matched controls. 93 clinically stable HIV-infected male patients with normal body weight and reciprocal normal age matched controls served as the study group. According to the 1993 revised CDC criteria, 47 patients were at stage A, 31 were at stage Band 15 were at stage C. For each subject the following body composition parameters were recorded by means of an Hologic 4500W whole body scanner: Bone Mineral Density (BMD,lumbar and whole body), Bone Mineral Content (BMC). Body Fat (Fat). %Fat of body weight, Body Lean Mass (Lean) and %Lean of body weight. Mean body weight, body mass index (BMI), both lumbar as well as whole body BMD and BMC in all patient groups did not differ from controls. On the contrary. mean %Fat was higher (stage A: 23,5±7.1%, stage B: 21,4±6,7%"stage C: 22.1±7,1%, controls: 17±5,6). while mean %Lean was lower in all patient groups compared to controls (stage A: 72,9±6.8%, stage B 75±6,4%, stage C: 74.3±6,9%, controls: 79,2±5,3). It is concluded that HIV-infection in patients who are clinically stable and have normal body weight spares bone metabolism but is associated with reduced lean body mass and increased fat body mass. These data suggestthat subtle body composition changes in HIV-patients can be early detected by means of body composition analysis by DEXA.

P432 THE EFFICACY OF SYSTEMIC AND INHALER STEROIDS ON BONE METABOLISM AND BONE MINERAL DENSITY IN ASTHMATIC PATIENTS M. Eryavuz T. Yilmaz M Birtane N. Celik V. Akin O. Tunc M. Akman Physical Medicine and Rehabilitation Department, Cerrahpasa Medical Faculty, Istanbul; Chest Medicine Department PTI Hospital, Istanbul: Biochemistry Department PTI Hospital Istanbul, TURKEY. Inhaler and systemic steroids are frequently prescribed for patients with chronic obstructive pulmonary diseases. Bone mineral density (BMD) decrease is a well known effect of long term systemic steroid administration. However, data on the effect of inhaler steroids on bone metabolism and BMD is controversial. The aim of this study was to assess and compare the BMD and bone metabolism of 29 asthmatic patients who used steroids (Group 1) with 16 asthmatic patients who never used this agent (Group 2). Also we compared bone metabolism determinants and BMD between the systemic (15 patients) and inhaler steroid users (14 patients) in Group 2. No statistically significant L2-4 and femur BMD difference measured by dual photon X-ray absorptiometry was found between Group 1 and Group 2 (p>0.05). Average serum levels of osteocalcin, cortisol, calcium, phosphorus, alkaline phosphatase, creatinine and average urine levels of hydroxiproline, calcium, phosphorus, creatinine were not significantly different between the groups (p>0.05).

P433 THE SIGNIFICANCE OF THE ASSAY FOR URINE PYRIDINOLINE YING SUN Arthritis Clinic and Research Center, People's Hospital of Beijing Medical University, Beijing, P.R. CHINA This study was designed to observe the relationship between urine pyridinoline (PYD) level of rheumatoid arthritis and the activity of the disease by using competitive enzyme immunoassay (Pyrilinks kits from Metra Biosystems Inc.) 61 cases of rheumatoid arthritis including 8 males and 53 females had 3 months to 27 years of disease courses. According to X-ray examinations there were 15 in stage I, 17 in stage II, 18 in stage III, and 4 in stage IV. 45 cases (78.9%) had ESR accelerated, 32 (56.1%) were positive in RF, 29 (51 .8%) had CRP elevated, and 31 (54.4%),22 (38.6%) and 6 (10.5%) had elevated IgG, IgA, IgM. In the active stage of the disease, 14 cases (25.5%) showed that all ESR, RF, CRP, IgG and PYD elevated. In 17 cases had less 2 years of courses, 6 (50%) showed PYD elevation. All figures from the test show a significant correlation between ESR, CRP and PYD (r=0.4832, p
P434 ALENDRONATE IN POSTMENOPAUSAL AND GLUCOCORTICOIDINDUCED OSTEOPOROSIS ~', E. Seeman 2, S. LiunghalP, G. Thamsborg4, M-P. Malice 5 W. Carofan05, and A. Dajfotis 5 for The Alendronate Glucocorticojd . Study Group Hopital E. Herriot, Lyon, France', Austin & Repatriation Medical Center, Heidelberg , Australia 2, Academic Hospital, Uppsala, Sweden' , Kommunehospitalet, Copenhagen, Denmark4, Merck Research Labs, Rahway, NJ 07065 5 Chronic glucocorticoid (GC) use and postmenopausal (PM) estrogen deficiency result in bone loss due to remodelling imbalance. Changes in bone mineral density (BMD) and biochemical markers at 1 year and fracture incidence, were compared in the alendronate GC (n= 477) and PM osteoporosis treatment studies (Phase III, n=997 and FIT Vertebral Fracture Arm (VFA) n=2027). Resorption markers were elevated at baseline in patients on GC, but to a lesser degree than in PM studies. At 1 year, turnover normalized with alendronate treatment (5 or 10 mg) in all study groups with significant increases in spine and hip BMD relative to placebo (figure). Spine

Femoral Neck

= _

Phase FIT III

GlOP

Phase FIT

'"

5"'11 '0"'11

GlOP

The relative risk of new vertebral fractures was significantly reduced in the Phase III and FIT VFA studies at three years (RR=0.52 and 0.53). At one year in the GC studies a nonsignificant reduction in fractures rates of 40% was observed (RR:0.60; 95% C.I.=O.08, 4.42). These data suggest that alendronate may be a useful agent in reducing fracture risk in patients receiving GC .

•

P435 INFLUENCE OF GENDER, MENOPAUSE AND ESTROGEN USE ON ALENDRONATE RESPONSE IN GLUCOCORTICOID USERS U.A. Liberman 5, K. Saag', S.E. Papapoulos 3, S. Epstein', C-J. Menkes 5, J. Rodriguez-Portales6, M-P. Malice', M. Czachur', D. Espinosa', and A. Daifotis' for the Alendronate Glucocorticoid Study Group Rabin Medical Center, Petach-Tikva, Israel', University of Iowa College of Medicine, Iowa City, lA', Academisch Ziekenhuis Leiden, Netherlands 3, Allegheny University of Health Sciences, Philadelphia, PA', Hopital Cochin, Paris, France 5, Universidad Catolica De Chile, Santiago, Chile 6, Merck Research Labs, Rahway, NY. We examined the influence of gender, menopause, and estrogen use on the effect of alendronate (ALN) on BMD and biochemical markers in 477 glucocorticoid users (mean 13.2 mg/day prednisone during study), randomized to receive ALN 5 or 10 mg/day or placebo. Baseline spine BMD was similar in men and women (T-score approximately -1 S.D.). Baseline urine N-telopeptide/ creatinine (NTx) and bone-specific alkaline phosphatase (BAP) levels were similar in men, premenopausal and postmenopausal women on estrogen, and somewhat higher in postmenopausal women not on estrogen. ALN 5 or 10 mg reduced NTx and BAP into the mid-to-Iow normal range for all subgroups. Both ALN doses similarly increased spine BMD in men, premenopausal and postmenopausal women on estrogen, whereas in postmenopausal women not on estrogen ALN 10 mg induced agreater increase (figure). Both ALN doses increased hip BMD, and no difference in treatment effect was seen in gender, menopause or estrogen use subgroups. _

_

.,

~.o

A lfol 1 . 1

f/l"'" , ......

~----------------------

In conclusion, alendronate effectively prevents and treats glucocorticoidinduced bone loss in both men and women.

P436 BONE MINERAL DENSITY AFTER RENAL TRANSPLANTATION. A ROLE FOR IMMUNOSUPPRESSION? J.P. Devogelaer E. Goffin* A. Lalaloui*. J.P. Squifflet* Departments of Rheumatology, Nephrology, and Transplantation, St-Luc University Hospital, Brussels, Belgium BMD's of the lumbar spine (L), of the hip [femoral neck (FN), trochanter (T), intertrochanteric (IT), total hip (TH)] and the total body (TB)-BMC were measured at TO and one yr after renal transplantation (RTP) in 26 patients by DXA. Immunosuppression comprised ATG, prednisone, azathioprine + cyclosporine (CyA n=19) or FK506 (n=7). Prior to RTP, the BMD's were low as compared to age- and sex-matched controls. After RTP, a trend to loose bone was observed at each site, only in the CyA subgroup. The length of pre-RTP dialysis and cumulative doses of glucocorticoids were not statistically different in both groups. Their respective changes in BMD/BMC are summarized in the table

P437 HEPATIC OSTEODYSTROPHY IN POSTHEPATITIC LIVER CIRRHOSIS A. Karan G. Dilsen D. Sindel C. Tascloglu N. Erten K. Guier Istanbul Medical Faculty, Dept. Internal MediCine, Dept Phy Med & Rehab. It has long been recognized that there are significant changes in bone metabolism in liver diseases. Osteodystrophy in liver cirrhosis consists of osteomalacia, osteoporosis or both of them. The aims of this study were to investigate the rate and severity of hepatiC osteodystrophy (HO) in patients with posthepatitic liver cirrhosis (PLC) and to determine the role of the hepatocellular injury in bone loss. 24 patients and 22 healthy controls were selected for study. Initial screening cQnsisted of history, physical examination, questionnaire of daily calcium intake and risk factors for osteoporosis (according to MEDOS), Lateral radiography of T4 to L5, bone mineral measurement and laboratory investigation such as serum calcium and phosphate, alkaline phosphatase, liver function tests, parathormone, calcitonin, osteocalcin, 25 hydroxy vitamin 03, testosteron, lutinizing and fOllicle stimulating hormones, urine calCium, phosphate, hydroxy proline. We found the mean BMD at the lumbar region were significantly lower in the patient withPLC (0.928±0.153 g/cm') than control group (1.058±O.14). In the patients group serum alkaline phosphatase were higher than the controls. Hydroxyproline excretion and urine calcium/creatinine ratio were not statistically different in both groups. Osteocalcine levels were lower in the patients but the difference was not statistically significant. Serum PTH, calcitonin, free testosterone and estradiol levels were not different in both groups, there was not any correlation with BMD values. In our patients there was not any correlation between serum calcium, phosphate, PTH, 25 OH 0 3, osteocalcin levels and BMD values. These results are compatible with studies indicating that the osteopenia of chronic liver disease is chiefly caused by OP rather than osteomalacia. Considering to epidemiological data, we used logistical regression analysis to evaluate and found that the differences between the patient and control group for the osteopenia were due to chronic liver disease (p=0.05, predictive value=75.6%).

P438 THE MORPHOLOGICAL FEATURES OF THE ULTRASOUND BONE SIGNAL SHAPE IN PSORIATIC ARTHRITIS (PsA) F. Sensi A. Siliscavalli A. Sadaro. F. De Terlizzi*, E. Taccari Institute of Rheumatology - University of Rome "La Sapienza" and * Igea, R&D Department, Carpi - Italy We evaluated, by a dedicated software, the ultrasound signal shape (DBM Sonic 1200, IGEA, Italy) of the proximal phalanx of II, III, IV and V fingers of the non dominant hand in 37 male PsA patients [age (M±SD)=48.5±11.9, range =17 - 70 years; disease duration (M±SD)=5.6±5, range =0.7 -'20 years] and in 25 male healthy controls [age (M±SD)=49.2±15.3, range 20 - 71 years]. The mean values of slope (p
n L FN T IT TH TB ONE-YEAR AFTER RENAL TRANSPLANTATION (% OF INITIAL VALUE) CyA 19 P vs TO FK5067 P vs TO

96.2* <0.05 103.8 <0.05

93.0** <0.01 106.0 NS

92.3*** <0.05 104.0 NS

97.6* <0.01 107.9 <0.05

96.1* <0.01 107.5 NS

98.6 NS 103.9 <0.01

P439 ABSTRACT WITHDRAWN

CyAvs FK506; *p
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P44D BONE DENSITY, MASS, AND GEOMETRY IN UREMIC PATIENTS ON MAINTENANCE HEMODIALYSIS C.R. Russo* G. Taccetti* P. Caneva* A. Mannarino** P. Maranghi*** and M. Ricca * 2nd Internal Medicine Department (*), Nephrology) (**) and Radiology (***) Service, Nuovo Ospedale S. Giovanni di Dio, Azienda Sanitaria 10, Florence, Italy The aim of the study was to establish the existence of cortical and/or trabecular osteopenia, and to assess the integrity of bone geometry in the uremic patients undergoing maintenance hemodialysis by means of peripheral Quantitative Computerized Tomography (pQCT). Methods. The study subjects were 39 uremic patients (19 males, age 56.2±17.3, and 20 females- age 5B.2±13.2) on maintenance hemodialysis and 72 age- matched healthy controls (26 males, 46 females). Volumetric bone density was assessed by pQCT (XCT 900, Stratec, Germany) at the distal radial metaphysis (trabecular density) and at the distal third of the radius (conical density). Cortical Area (mm') as an expression of bone mass, Cross-sectional Area (mm') and Cortical Thickness (mm) as expression of cross-sectional geometry have also been non-invasively assessed by pQCT. Results. Cortical density was reduced in both female (p=<0.0001) and male patients (p"
Controls Dialysis Pvalue

C.S.

Area

Cortical

Area

Cort.

Thickness

M 173 ±33 154 ±41 0.02

100 ±18 102 ±19 n.s.

M 97 ±13 97 ±34 n.s.

F 65 ±10 56 ±13 0.02

M 2.6 ±O.6 2.7 ±O.B n.s.

F 2.3 ±O.5 1.9 ±O.5 O.OOB

Conclusions: A selective cortical osteopenia and a gender-specific pattern of geometry impairment, potentially leading to bone fragility, have been detected in dialysis patients. The cortical bone mass reduction observed in the female patients may result from the interaction of prolonged PTH excess and estrogen deficiency. In the males, the reduced Cross-sectional Area in the face of the cortical osteopenia suggests a deficiency in the bone denSity-geometry adaptation.

:>441 BONE STRENGTH IN HEMODIALYSIS PATIENTS: A NON INVASIVE EVALUATION C.R. Russo* G. TacceUi* P. Caneva*. A. Mannarino** P. Maranghi*** and M. Ricca * 2nd Internal Medicine Department (*) Nephrology (**) and Radiology (***) Service, Nuovo Ospedale S.Giovanni di Dio. Azienda Sanitaria 10, Florence, Italy The aim of the study was to non-invasively evaluate by means of peripheral Quantitative Computerized Tomography (pQCT), a recently validated index of bone strength, the Stress-strain index (SSI), in uremic patients on maintenance hemodialysis. Methods. The study subjects were 39 uremic patients (19 males, age 56.2±17.3 20 females age 5B.2±13.2), and 72 age-matched healthy controls (26 males. 46 females). Volumetric cortical bone density was assessed by pQCT (XCT 900 Stratec, Germany, at the distal third of the radius. The SSI was calculated multiplying the cortical density by the section modulus; the latter was obtained dividing the cross-sectional moment of inertia by the maximum distance of each voxel from the centre of gravity (eccentricity). The polar SSI is an index of resistance to compressive and torsional loads, while the X-axis, and Y-axis SSls indicate the resistance to torsional loads along the respective axes.

Results. A consistent reduction in the polar X-axis and Y-axis SSI has been found in the uremic patients of either sex in comparison with the agematched control subjects. The table below shows the comparison of SSls between the dialysis patients and the control subjects (mean values±SD): Polar SSI Control Dialysis p values

X-axis SSIY-axis SSI M 7.5±O.9

6.B±1.3 0.03

F 6.0±O.9 5.1±1.6 0.02

M 6.3±O.7 5.6±1.0 0.02

F 4.9±O.7 4.4±1.2 0.04

M 6.7±O.9 5.3±O.9 5.7±1.4 4.5±1.6 0.01 0.02

Conclusion. Both the index of resistance to compressive and torsional loads (polar SSI) and the indexes of resistance to bending loads (X-axis and Y-axis SSls) were reduced in the patients of either sex. Since fractures in long bones are caused by acombination of torsion and bending stresses, the results of this study suggest an increased risk for Co lies' fracture in the uremic patients on maintenance hemodialysis treatment.

P442 BIOMECHANICAL ADAPTATION OF BONE IN HEMODIALYSIS PATIENTS: A NON INVASIVE EVALUATION C.R. Russo*, G. Taccetti*, P. Caneva*, A. Mannarino**, P. Maranghi***, and M. Ricca * 2nd Internal Medicine Department (*) Nephrology (**) and Radiology (* * *) Service, Nuovo Ospedale S.Giovanni di Dio, Azienda Sanitaria 10, Florence, Italy Cortical osteopenia is known to occur in hemodialysis patients. The aim of this study was to assess the integrity of the adaptive mechanisms which tend to maintain bone strength in the face of osteopenia. Methods. We have attempted to correlate both volumetric cortical density and geometry parameters (cortical area, cortical thickness, and crosssectional area) with age in a group of 39 hemodialysis patients (19 males, age 56.2±17.3, and 20 females, age 5B.2±13.2), and 72 age-matched control subjects (26 males, 46 females). Both cortical density and geometry parameters were obtained by pQCT (XCT 900, Stratec, Germany) at the distal third olthe radius. In orderto further investigate the denSity-geometry relationship we have also attempted to correlate cortical density with crosssectional area. Results. The conical bone density and the parameters indicating, bone mass (cortical area) and geometry (cortical thickness) showed an age dependent decrease in the control subjects of both sexes. In the female uremic patients this inverse correlation was lost. The bone cross sectional area increased significantly with age only in the male control subjects (r=0.42, p=0.03) and was inversely correlated to cortical density in both sexes (r=-0.44 and p=0.005). Conversely, in the male uremic patients there was no increase in cross-sectional area in response to age and there was no increase in cross-sectional area in response to the decrease in cortical density in the patients of both sexes. Conclusion. A defective biomechanical adaptation appears to be present in uremic patients on maintenance hemodialysis of both sexes. In the female patients the loss of the age dependency of cortical bone density and mass suggests that a powerful pathogenic factor contributes to the cortical osteopenia (Le. the prolonged PTH excess). In the male patients on the other hand, a reduced adaptation of cross-sectional geometry to the cortical osteopenia is more evident. The gender difference in the adaptive mechanisms, observed in the control subjects, and in their alterations, observed in the patients, probably reflects the known sexual, dysmorphism in the physiology of biomechanical adaptation of bone.

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P443 BONE MINERAL DENSITY IN ASTHMATIC CHILDREN Krystyna Nowacka Roman S. Lorenc Dept. of Immunology, Dept. of Biochemistry & Experimental Medicine, The Children's Memorial Health Institute Warsaw, Poland Aim: To determine the bone mineral density in children with chronic bronchial asthma with respect to the dose and duration of the treatment with inhaled budesonide. Patients & Methods: 64 children with asthma were studied: I Group of 40 children, aged 7 to 18 years (mean±SD: 13±2.7 years), treated with inhaled budesonide 400 to 800 flQ/day, (mean 535±189 flQ), for 0.5-5 years mean (2±1.8 years), and" Group (control) of 24 children, aged 7 to 15 years (mean 11±2.4 years) with asthma nottreated with glucocorticoids. Dual energy X-ray absorptiometry (DEXA) was used to measure bone mineral density, BMD (gm/cm') in total body and lumbar vertebrae (L2L4). The results were expressed in relation to mean reference data as standard deviation scores: Z-score. Results: The data has shown that bone mineral density of the lumbar spine but not total was reduced in children taking inhaled corticosteroids when in nonsteroid group of 11, age- and sex- matched children BMD values remain in normal range. Conclusion: The data suggest that inhaled budesonide in children with asthma can influence metabolic bone status affecting more trabecular than cortical bone.

P444 IDIOPATHIC CALCIUM STONE DISEASE: BONE MASS EVALUATION BY ULTRASOUNDS R. Caudarella E. Rizzoli A. Buffa *F. de Terlizzi *R. Cadossi Dipartimento Medicina Clinica e Biotecnologia Applicata "D Campanacci"- Bologna University. *Laboratorio di BiofisicaIGEA Carpi Idiopathic calcium stone formers show a reduced bone mass more evident in those with renal or fasting hypercalciuria. The aim ofthis work was to evaluate with the quantitative ultrasound method (QUS) an modifications in bone mass as well as any differences with respect to the results obtained with single Xray absorptiometry in idiopathic calcium stone formers. The relationship between hypercalciuria and bone mass was also evaluated in these patients. 83 male stone formers (mean age: 46.2±12) and 75 females mean age 48.7±14.1} were enrolled for this study. Bone Mineral Density (BMD was evaluated at radius level with a single X-ray absorptiometry. QUS measurements at finger level (DBM-SONIC) were performed only in 9 patients. Male stone formers showed lower values of amplitude dependent speed of sound (AdSoS) than controls (p=0.0354). Both normal and stone forming females showed a decrease of AdSoS after menopause (p=0.001); moreover, stone former females showed lower values of AdSoS both before (p=0.038) and after menopause. The BMD showed a similar behaviour at distal (0.001) and ultradistal radio level (p=0.01) both in normal subjects and stone forming females; moreover stone forming females always showed lower values than healthy female (p=0.03). The osteopenia and osteoporosis incidence was respectively 47.3% and 9.9 % when evaluated according to BMD T-score values whereas with ultrasound method, T-score values gave an incidence of 26.9% and 10.8% respectively. A negative relationship was obtained between AdSoS and age both in females (r=-0.614: p=0.001) and males (r=-0.50; p=0.001). When BMD was correlated with age a negative relation was observed only in females (r=-0.48; p=0.001). Hypercalciuria (urinary calcium excretion> 4 mg/Kg/24h) does not appear to influence the BMC, BMD and AdSoS in our patients. In conclusion, osteopenia is acommon in calcium stone formers. QUS method seems to be a useful tool for the evaluation and follow up of bone mass decrease in these patients .

P445 COMPARISON OF VARIOUS TYPES OF PROTECTIVE THERAPY IN PATIENTS WITH GLUCOCORTICOID INDUCED OSTEOPOROSIS V. VyskoCi!* J. VyskoCilova **. M. PeSek", O. TopolCan *. Department of Medicine" - Department of Bone Disease Department of Tuberculosis and Respiratory Disease Charles University Hospital PLZEN CZECH REPUBLIC The authors assessed 60 patients treated with orally applied corticosteroids for chronic pulmonary or rheumatic diseases. Dose of corticosteroids was higher than 7,5 mg Prednison/kg/day in all examined patients. 25 patients were treated with Miacalcic/200 MRC daily and 1000 mg Calcium/day or fluoride medicaments. Patients were examined first before the beginning of treatment and then after 6-12 months of therapy by means of DXA densitometry - Hologic 2000 / lumbar spine and hip/. At the same time, parameters of bone metabolism were followed. Decline of bone density around 5-20% per year stated according to measured areas in patients supplied with calcium and fluorides. In Miacalcic group, the decline of bone density was 2-5 %. On the contrary the group of patients treated with Fosamax showed increase bone density of both measured areas. Fosamax was beneficial also to bone metabolism markers.

P446 INFLUENCE OF VITAMIN D AND ALFACALCIDOL ON SELECTED PARAMETERS OF BONE METABOLISM IN CHILDREN WITH NEPHROTIC SYNDROME DURING PREDNISONE TREATMENT J. Wojnar, M. Pariczyk-Tomaszewska M. Sieniawska University Children's Hospital. Dept of Paediatrics and Nephrology, Warsaw, Poland The aim of the study was to compare serum levels of PICP, ICTP, iPTH, AP and calciuria during prednisone treatment with vitamin D or alfacalcidol in children with nephrotiC syndrome. Patients (aged 4-15 yrs) were divided into two groups: A - 10 pts treated with prednisone and vitamin D (800 I.U./day); B - 20 pts treated with prednisone and alfacalcidol (0.05 flQ/kg/ week). Blood and urine samples were taken during relapse: TO - before starting prednisone treatment; T1- after 2 weeks of therapy with prednisone 2mg/kg/24h; T2 - after 2 weeks of treatment with prednisone 2mg/kg/ 48h. Mean values (±SD) of studied parameters in both groups are demonstrated in table.

•

T1 A

TO Group

A

T2 A

PICP).l9I1

311±151.2

283.9±153.0 106.1±41.1

96.8±42.3

398.6±1 06.7 297.5±153.1

ICTPf!(j/I

14.9±5.8

15.8±6.6

9.9±4.5

12.5±3.2

12.5±3.5

AP(UA)

223.8±57,4 222.2±60.8

155.8±46.9

149.2±41.8

PTHpg/ml

31.3±23.5

36.1±26.5

30.1±12,4

33,4±24.3

25.6±15.0

23.3±15,4

CU mg/kg/d 1.04±1.09

1.15±1.24

4.04±2.04

3.98±2.14

2.89±1.48

3.28±1.76

8.5±3.1

155.6±46.9 156,4±42.9

There were significant differences between TO and T1 in all parameters, except for PTH. There were no differences between groups. Conclusions: 1. Short-term treatment with high daily doses of prednisone in children with nephrotic syndrome is associated with increased calciuria and with suppression of serum markers of type I collagen's turnover. 2. There are no differences in effects of vitamin D and alfacalcidol on bone parameters in children with nephrotic syndrome during prednisone treatment.

P447 EVOLUTION OF BONE MINERAL DENSITY IN ANKYLOSING SPONDYLITIS M.C.F. Mello A.MV. Coimbra P.D. Sampaio-Barros J.F. Marques Neto A M. Samara Rheumatology Unit. Department of Clinical Medicine, State University of Campinas - Campinas - SP, Brazil Bone mineral density (BMD) of lumbar spine and femoral neck was measured in 42 male patients with Ankylosing Spondylitis (AS) by dualenergy X-ray absorptiometry (DEXA). Patient's mean age was 36 years, mean age at onset was 23,4 years and mean disease duration was 12,6 years. HLA-B27 was positive in 76,2% of patients. All patients underwent clinical and radiological investigation in purpose to determine; lumbar mobility by Schober test, functional index, pattern of articular involvement, grades of sacroiliitis and radiographic changes in spine, as well as presence of radiological hip disease. The influence of these variables on BMD was evaluated. Lumbar osteopenia occurred in 40,S% of pati,ents and osteoporosis in 26,2%. At femoral neck, the values obtained was 4S% ant 22,S%, respectively. HLA-B27 positivity was related to a reduced BMD in lumbar spine, whereas the presence of radiological hip involvement related to an augmented lumbar BMD. Age at outset and presence of peripheral articular involvement exerced no influence on BMD. Sacroiliitis progression was accompanied by a significant increase in lumbar BMD, but by a BMD reduction in femoral neck. Clinical and radiological markers of disease chronicity (longer disease duration, worse functional index and lumbar mobility, advanced sacroiliitis and radiographic changes in spine) correlated to a significant and progressive bone loss in femoral neck. In conclusion, AS can be considered an independent risk factor for bone loss and femoral neck seems to be the most suitable site for serial BMD assessment by DEXA in AS, since it is sensitive to clinical and radiological changes of disease course and avoids interpretation errors caused by new bone formation, as occurs at axial skeleton.

P448 SERUM VITAMIN D LEVELS, BONE MINERAL DENSITY AND ANTICONVULSANT THERAPY S. Filardi J.F Marques Neto L.A. Magna Rheumatology and Genetic Unit, Department of Clinical and Genetic MediCine, State University of Campinas - Campinas SP, Brazil The object of this study was to assess the bone mineral density and the alterations of calcium and vitamin Dmetabolism in outpatients with epilepsy on chronic anticonvulsant therapy. Retrospectively, 69 epileptic males were studied, with a mean age of 37,6 years. They were compared with 30 healthy males with a mean age of 34,6 years. We have measured the serum levels of calcium, ionized calcium, alkaline phosphatase, albumin, PTH, 2S-hydroxy-vitamin D and 1,25-dihydroxy vitamin D. Being determined were the bone mineral density of lumbar spine and femoral neck measured by dual energy x-ray absorptiometry. No differences in bone mineral density, ionized calcium, 25-hydroxy-vitamin D, 1,25-dihydroxy-vitamin D and intact-PTH were-observed between patients and controls, however the mean serum calcium concentration was lower (p<0,05) and the mean serum alkaline phosphatase concentration was higher (p
P449 BONE MINERAL DENSITY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ITS RELATION WITH ESTROGEN LEVELS LB. Coimbra L.T.L. Costallat M.B. Bertolo A.M. Samara Rheumatology Unit; Department of Clinical Medicine; State University of Campinas - Campinas - SP - Brazil The effects of systemic lupus erythematosus (SLE) on bone mineral density (BMD) remain controversial. Preliminary evidence suggests that women with SLE are at risk for low BMD. There is minimal information on the relation with estrogen levels in those patients. To assess BMD in patients with SLE; To assess age, time of disease, body mass index, disease activity by SLEDAI, cumulative prednisone dose and estrogen as predictors for BMD. Sixty SLE women patient were studied. The effect of age, time of disease, body mass index (BMI), disease activity by SLEDAI, cumulative prednisone dose (CPD), as well as the cumulative dose of prednisone in the last year and estrogen levels on BMD at L2, L3, L4, femur, trochanter and Ward's triangle were determined. Low BMD was observed in 29 patients at L2, in 26 at L3, in 32 at L4, in 17 at femur, in 18 at trochanter and in 21 at Ward's triangle. Univariate analysis did not show significant association between BMD and any parameter studied. Multiple logistic regression was performed. The association between, BMD at L2 and interaction age and BMI was significant (p<0,002). Low estrogen level was not probability of low BMD at L2, although the interaction with age, BMI and low estrogen level was not statistically significant No association was found between low BMD and CPD. The SLE women which start earlier the disease and have low BMI, are on higher risk for low BMD at L2.

P450 DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM IN OSTEOPOROTIC ELDERLY WOMEN C. Cormier S. Lee. J. Kaddi P. Ledevic C. Kindersmans* J.C. Souberbielle* A. Kahan Service de Rhumatologie A, Hopital Cochin and Service d'Explorations Fonctionnelles *, Hopital Necker-Enfants malades, Paris, France. This study examined the possibility to diagnose asymptomatic primary hyperparathyroidism (PHP) in elderly osteoporotic women. Hundred and twenty women aged 81 years (SD; 3.2 yr) had a bone mineral density (BMD) measurement study showing a BMD T-Score <2 during an epidemiological. Five years later, they had a new BMD measurement and a biological exploration before osteoporotic treatment. Basal fasting blood (calcium, albumin, creatinine) and urine (second morning void for calcium, creatinine samples) were obtained. Serum total calcium corrected for albumen was calculated (tCac). Serum iPTH was measured. In 7 women, the biological exploration was compatible with primary hyperparathyroidism (6%). Five patients (4%) had high tCac associated with high or normal high PTH and 2 had normal high tCac with unadapted normal high PTH. In the S typical biological hyperparathyroidism, BMD was <3.S T-Score and bone loss at the femoral neck was significant (240 mg/cm'). In 2 patients, ultrasono-graphies and MIBI scintigraphies confirmed the diagnosis. According to published data, PHP is found in 0.1 % to 0.2% of the general population and is most frequent in the sixth decade of life. The frequency of PHP in these elderly women is higher with a particularly low BMD. In practice, before starting calciumNit D or other osteoporotic therapy, a biological exploration with both tCa and Alb is useful. With high tCac or normal high tCac, PTH should be measured because only the "couple" tCac-PTH can diagnose this PHP.

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P451 BONE MINERAL DENSITY AND SPINE FRACTURES DUE TO OSTEOPOROSIS IN ANKYLOSING SPONDYLITIS H. Przepiera-Bedzak. I. Fiedorowicz-Fabrycy. M. Brzosko L. Cyrlowski* Clinical Department of Rheumatology, * Department of Radiology Pomeranian Medical Academy, Szczecin, Poland Objective: To examine the relationship between bone mineral density at different sites of skeleton and vertebral fractures due to osteoporosis in patients with AS. Materials and methods: We studied 46 males with AS (mean age was 49 yrs., mean disease duration was 20,8 yrs.). We measured bone mineral density (BMD) at lumbar spine (LS), femoral neck (FN) and radius (R) by DEXA method and at radius by paCT method. All patients had radiographs of lumbar, thoracic and cervical spine and a radiograph of pelvis. The anterior, posterior and central heights of each vertebral body were measured. The ratio of each height to that of the two adjacent vertebrae, the ratio of the anterior height to the posterior height and of the central height to the posterior height on lateral radiographs were calculated. The subjects were considered to have mild fracture if any of these ratios was 0,8-0,749; moderate fracture if any of these ratios was 0,75-0,59 and severe fracture if any of these ratios was 0,6 or less. We assessed activity of the disease in each subject according to the following Indexes: BASFI, BASDAI, BASG, BASMI. Results: 16 (34,8%) patients had spine fractures. There were 22 mild fractures and 12 moderate fractures. There was only one severe fracture of thoracic spine. 25% out of the total number of patients with spinal fractures had osteopenia measured by DEXA method at LS, 50% at FN and 25% of them at R. 56,3% of these patients had osteopenia at R measured by paCT. We found the strongest negative correlation was between BMD at FN and spinal fractures. Fractures of lumbar spine correlated with decreased BMD at FN; fractures of thoracic spine correlated with decreased BMD at LS whereas fractures of cervical spine correlated with decreased BMD at Rmeasured by paCT. Patients with spinal fractures had lower BMD at FN and R and also higher BMD at LS compared to those without fractures. Conclusion: Measurement of BMD could be a good predictor for detection of spine fractures in patients with AS.

P452 OSTEOPENIA IN THALASSEMIA MAJOR M. Di Stefano *. F. Garofalo * *. P. Chiabotto ** *. R. Lala * * *. M. Mussetta* P. Ardissone* C. Roggia* G.C.lsaia* *Department of Internal Medicine-University of Turin; **Centro Microcitemia University of Turin; ***Division of Pediatric Endocrinology - Regina :Margherita Children's Hospital-Turin. In this study we evaluated in 27 thalassemic patients (15 males and 12 females, aged 8.1-14.9 years) and in 27 normal subjects BMD, BMC at lumbar (L) and femoral (F) level by using DXA technique (Hologic ODR 1000) and bone turnover markers (BAP, PICP, ICTP, Cross-links). All parameters were evaluated both at the beginning of the study, when all 27 thalassemic patients were prepubertal, and after I year follow-up, when 13 of the children showed evidence of beginning puberty. Results: we observed Land F BMD values significantly (p
Conclusions: on the basis of above results, we 'can affirm that osteopenia represents a frequent complication of Thalassemia Major, probably due, in our 8-14 years old patients, to delayed or absent puberty and not to direct effect of the hemopathy.

P453 PHENYLKETONURIA AND BONE MINERAL STATUS ~'. M Bayer' , J. Stepan' 1 Department of Pediatrics and 'ilird Department of Internal Medicine, 1st Faculty ,of Medicine, Charles University, Prague, Czech Republic Dual energy X-ray absorptiometry was performed in a group of 42 children, adolescents and young adults with hyperphenylalaninemia type I aged from 6 to 26 years. The low phenylalanine diet was supplemented with combination of amino-acids mixture and protein hydrolysate in 31 patients, 9 adults patients were supplemented only with protein hydrolysate and two youngest children received as supplementation only amino-acids mixture. Normal bone mineral density (BMD) was found in 24 (57%) patients with phenylketonuria. Spinal BMD was decreased in 18 patients and total BMD in 14 patients, respectively.. Osteopenia was found in 10 patients (24%) and 4 patients (9.5%) had osteoporosis. The significant negative correlation was observed between both of total and lumbal BMD and the amount of protein hydrolysate supplementation per kg of body weight (p<0.02). Conclusion: Long-lasting dietary restriction is necessary in the prevention of the brain damage in patients with phenylketonuria, but it may probably be the cause of increased risk of late complications as are osteopenia as well as spure elements deficiency. The decrease of BMD in children with phenylketonuria despite of adequate diet based on current recommendations seems to be influenced not only by tolerance to phenylalanine but also by type of phenylalanine-restricted formula. Thus, separate types of dietetics used for treatment of patients with phenylketonuria may differ in their influence on patient's BMD.

P454 BONE MINERAL DENSITY AND OSTEOARTHRITIS OF THE HIP M. Laroche L. Costa A. Constantin. A. Cantagrel B Mazieres service de Rhumatologie, CHU Rangueil, Toulouse, France We used DEXA to study osteoarthritic hips in order to discover whether the classic densification of subchondral bone was accompanied by increased mineralization of epiphyseal and metaphyseal areas. Some authors have shown that patients with arthrosis of the digits or knees had above average overall bone mineralization. We compared the BMD of the spine and healthy femoral neck of patients with osteoarthritis of the hip (OAH) with that of control subjects. Patients Sixteen patients with longstanding unilateral OAH admitted to the orthopaedic department for total hip replacement, were included. There were seven men and nine women of mean age 61.8±9 years. Their BMD was compared with that of 16 age and sex-matched controls of mean age 59±1 0.6 years. Methods: Patients and controls underwent DEXA (DPX L Lunar). BMD was measured at both femoral heads (total head, Ward's triangle, trochanter) and at the lumbar spine (L2-L4). In the patients, BMD was measured on a rectangle within the femoral head. A rectangle of the same area was placed symmetrically on the opposite healthy femoral head. Parameters were compared using Wilcoxon's test. Results: BMD was high in OAH hips compared with uninvolved hips: +6% at the head, +3% at the neck and +7% at Ward's triangle, except at the trochanter where it was - 6% lower. Patients with OAH had non significant higher mineral density: + 4.9% (p=0.15) in the lumbar spine, +2% (p=0.3) in the healthy femoral head.

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P455 ULTRASOUND VELOCITY IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH LOW-DOSE CORTICOSTEROIDS V. Mazourov E. Zotkin V. Kharitonov Medical Academy of Postgraduated Education, City Rheumatological Center, St.Petersburg, Russia The objective of this Russian study was to determine whether a low-dose of corticosteroids (CS) decreases of bone mass in patients with rheumatoid arthritis (RA). 452 Caucasian women with RA, aged 37-48 years (non postmenopausal), entered the study. The duration ofthe disease was more then 5 years. Group A: 132 patients were treated for fore years with CS in dosage 2,5-10 mg per day. Group B: 320 patients were on second line treatment including methotrexate, cyclophosphamide or hydroxychloroquine. We have assessed the method for measuring ultrasound velocity (speed of sound, m/sec) in the cortical bone of tibia (SoundScan 2000, Myriad Ultrasound Systems Ltd.). Reduced velocity was detected in group A in 50% of patients and in group B - in 46%. The difference between the two groups was not statistically significant. There is evidence that administration of low-dose CS to patients with RA have not increased the risk of osteopenic syndrome.

P456 ALPHACALCIDOL INHIBITS BONE RESORPTION IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH CORTICOSTEROIDS E. Zotkin V. Mazourov G. Zakharova Medical Academy of Postgraduated Education, City Rheumatological Center, St.Petersburg, Russia The aim of this study was to investigate the possible inhibitory effect of alphacalcidol on bone resorption in patients with rheumatoid arthritis (RA) treated with low-dose corticosteroids (CS) for more then 1 year. 46 Caucasian non postmenopausal women, aged 37-43 years, with ultrasound velocity values lower than 1 SD of age-matched controls, were took part in pilot investigation. Alphacalcidol was given in dosage 0,5-0,75 mcg per day. The measurement of urinary deoxypyridinoline- Dpd (Metra Biosystems Ltd.) was made prior to starting treatment and 3 months later. The urinary excretion of Dpd showed a significant variation. Dpd significantly increased in RA patients (p<0,02) and more in those receiving CS (p<0,01). The urinary excretion of Dpd decreased in RA patients treated with alphacalcidol (p<0,05) during 3 months. There is evidence that alphacalcidol inhibits bone resorption in patients with RA treated with low-dose CS.

and normal sides. For more reliable and sensitive results, further studies with larger numbers of patients are needed. Ultrasound should be considered as a practical procedure to measure bone mineral density.

P458 EFFECTS OF TREATMENT WITH GLUCOCORTICOID ON THE GH RESPONSE TO GH-RELEASING HORMONE (GHRH) AND ON BONE METABOLISM MARKERS IN MEN S. Bossoni F. Manelli R. Carointeri G.L. Beretta D. Godi G. Bugari*. V. Grassi A. Giustina Departiment of Internal Medicine and *Chemistry, University of Brescia, Italy The pathogenesis of the glucocorticoid-induced bone loss is incompletely understood, appearing to be mediated at different sites. Glucocorticoids cause a reduction in both osteoblast recruitment and osteoblast activity, and are well known to inhibit GH secretion through an increase in hypothalamic somatostatin tone. The aim of our study was to evaluate in subjects on chronic therapy (>6 months) with glucocorticoids for non endocrine disease: 1) the correlation between the status of the GHlIGF-1 axis and of bone metabolism; 2) the time course of the GH response to GHRH and of the change in bone metabolism during glucocorticoid therapy. In 5 male subjects (mean age: 45±9 yrs, BMI: 23±2.2 kg/m', blood pressure: 139/80±8/6 mmHg, mean duration of disease: 13.5±8.9 months, mean 1.6 mg/day of prednisolone), we evaluated the markers of bone formation (bone alkaline phosphatase, AP, Alkphase-B, Metra Biosystem - USA, normal range: 10-50 UI/L; serum osteocalcin, RIA, Elsa-Osteo, CIS Bio International, Paris, France, n.r.: 7-50 ug/L) and resorption (urinary desoxipyridinoline, U-Dpd, Pyrilinks-D, Metra Biosystem - USA, n.r.: 2.3-6.7 umollmol creatinine; urinary hydroxyprolin, U-Ipd, Spectrophotometrical assay, Beckman, n.r.: <40 mg/24-h). Each patient was also submitted to a bolus i.v. test (100 ug) with human GHRH-(1-29)NH,. Samples for GH (RIA, Nichols Institute, USA) were taken at -15, 0, 15, 30, 45, 60, 90 and 120 minutes. At baseline was also determined serum IGF-1 (RIA, Nichols Institute, USA). Results showed a positive correlation between GH response to GHRH (DGH, peakbaseline) and osteocalcin (1 D±4.3 ug/L and 18.3±7.3 ug/L; r=0.854, p=0.065). Moreover, we also found a positive correlation between U-Ipd, DGH (1 D±4.3 ug/L and 30.4±13.3 mg/24-h; r=0.924, p=0.025) or IGF-1 (270±82 ug/L and 30.4±13.3 mg/24-h; r=0.924, p=0.002). In two of the patients studied (mean age: 28±2 yrs) were also evaluated the time-course of the GH response to GHRH at 3 and 6 months from the diagnosis of sarcoidosis. After 3 months of therapy with high dose of prednisolone (mean dose/day: 30 mg), we found a reduction of DGH (peak-baseline) with respect to the baseline value (1 0±5 ug/ L vs 32.8±6.1 ug/L). Concomitantly, a relevant decrease in serum osteocalcin and AP was observed. In conclusion, our results suggestthat in glucocorticoidinduced osteoporosis the reduction in GH/IGF-1 axis is probably an important pathogenetic mechanism.

P457 THE EVALUATION OF BONE MINERAL DENSITY OF LOWER EXTREMITIES IN HEMIPLEGIC PATIENTS Dr. Fatma ATALAY Dr. Ova GULEC Dr. Gulcin K. KARATAS Dr. Jale M. TAN Gazi University Medical Hospital, Physical Medicine and Rehabilitation Department, Ankara, TURKEY Immobilization is an important risk factor that enables osteoporosis to occur. Osteoporosis might be seen in the neurologic diseases resulting from immobilization and the studies leading to prevent immobilization which is one of the targets of rehabilitation programs also play an important role in the prevention of osteoporosis. In our study, we aimed to measure bone mineral density of both lower extremities of the hemiplegic patients who had been rehabilitated and investigate if there was any difference between both sides. Thirty-three patients were examined. Bilateral tibial bone mineral densities were measured by ultrasound (ultrasound parameters; speed of sound (SOS), t and z values). The participants were questioned for demographic properties, duration of illness, motor capacity, risk factors for osteoporosis, medications dealing with bone metabolism, daily habits for calcium intake and menopause duration in women. The mean age of the participants was determined as 58.1±9.2, mean duration of illness was 24.1±18.5 months. Speed of sound (SOS), t and z values were not statistically significant in both groups. When men and women were evaluated separately, there were not any significant difference between ultrasound parameters. No significant correlation was found between age, duration of illness and SOS, t and z values of both lower extremities in men. In women there was not any correlation between age, menopause duration and ultrasound parameters, but there was a moderate correlation between illness duration and ultrasound parameters in both hemiplegic

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P459 OSTEOPENIA SYNDROME IN ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS N.S. Shevchenko Ukrainian Research Institute of Children and Adolescents Health Care, Kharkov, Ukraine In adolescents 10-18 aged there were studied bone mineral density (BMD) of radial distal epiphysis and radial diaphysis by single photon absorptiometry and metabolism of mineral and connective tissue components (the level of serum calcium and phosphorus, acid and alkaline phosphatases and creatinkinase activity, the content of chondroitinsulphates, glycosaminoglycansulphates and creatinine in blood serum; the level of excreted oxyproline, calcium and phosphorus in daily urine). There was established reduction of BMD at the epiphysis in 38,1% of patients, at the diaphysis - in 42,9%. At the same time reduction of BMD only althe epiphysis was in 14,3%, only althe diaphysis - in 19,05%: at both levels - in 23,8%. General number of adolescents with osteopenia was 57,14%. The extent of osteopenia syndromes manifestation was determined by disease duration (in a year - in 16,8% of patients, in a three years - in 63,6%; in a five years - in 83,3%) and the pubescence period (prepuberty - in 80,0% of patients, puberty - in 39,9%). In some part (42,0%) of adolescents with favourable course of lupus erythematosus and clinical and laboratory remission there was observed normalization of bone mass. Changes of minerals and connective tissue components metabolism were depended on lupus activities degree and were not depended on osteopenia. At the same time reduction of serum calcium, increase of glycosaminoglycansulphates in blood, increase of excreted oxyproline were more significant. For the purpose of prophylaxis and treatment of osteopenia in adolescents with lupus erytematosus there are recommended inclusion in treatment complex of such patients medicamental means (ipriflavonum, ergosterol metabolits, calcium); physiotherapevtic methods, physical drill.

P460 OSTEOPENIA SYNDROME IN PATIENTS WITH HYPOCORTICISM: WAYS OF ITS CORRECTION G.M. Terekhova V.V. Povoroznjuk V.A. Oliynyk V.P. Komisarenko Department of Clinical Physiology & Pathology of Locomotor Apparatus, Institute of Gerontology AMS of Ukraine, Kiev, Institute of Endocrinology and Metabolism AMS of Ukraine, Kiev, Ukraine 15 patients with hypocorticism have been examined. In all patients it has been revealed a decrease of total and ionized calcium contents in blood serum as compared to a control group. Level of urinary excretion of calcium, hydroxyproline for 24 h, as well as after high fasting, was increased. According to the data of ultrasound densitometry "Achilles+" (Lunar Corp., Madison, WI) and X-ray morphometry (vertebrae deformation index was studied), osteopenia syndrome has been established. Compensation of hypocorticism did not lead to an improvement of the indices of structuralfunctional state of osseous tissue. Combined therapy of hypocorticism using drugs "Kosmol" and alpha calcidol led to an improvement of the indices of structural functional state of osseous tissue. The data obtained point out the necessity of carrying out treatment with drugs having an anti resorptive effect in patients with hypocorticism.

P461 BONE LOSS IN WOMEN WITH RHEUMATOID ARTHRITIS V.v. Povoroznjuk I.Yu. Golovach Z.N. Mytnik Department of Clinical Physiology & Pathology of Locomotor Apparatus, Institute of Gerontology AMS of Ukraine, Kiev, Ivano-Frankovsk State Medical Academy, Ukraine Rheumatoid arthritis is a wide-spread disease causing the development of a severe functional joint deficiency and leading to a stable loss of work ability and invalidization. Secondary osteoporosis and consequent fracture playa major part in determining the long-term morbidity and mortality of rheumatoid arthritis (RA) patients. With an aim of siudy of structuralfunctional bone tissue state in women with the RA 22 patients aging 2044 years we're examined as well as 24 patients aging 45-59 years and 21 patients aging 60-74 years. 35 women were taking steroids (RA + S) among them 10 in group of 20-44 years old; 12 in group of 45-59 years old; 10 in group of 60-74 years old. 36 healthy age-, height and weightmatched women served as controls (CG). The bone tissue was examined using an ultrasound densitometer "Achilles+" (Lunar Corp., Madison, WI). The speed of the sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and an estimated stiffness index (SI, %) were measured. In the age group of 20-44 years women taking corticosteroids had the worst results and ultrasounds parameters: CG (SOS - 1568±7,3; BUA 115±3,9; SI- 94±4,1); RA (SOS -1558±11 ,5; BUA -109±5,0; SI- 89±6, 1); RA+S (SOS -1534±10,0; BUA - 99±2,2; SI-75±4,0).ln the age groups of 45-59 years - CG (SOS -1553±9,7; BUA -109±2,6; SI- 87±3,3); RA (SOS - 1528±9,5; BUA - 102±4,6; SI - 76±5,3); RA+S (SOS - 1530±8,7; BUA101±3,7; SI - 75±4,7) and of 60-74 years - CG (SOS - 1525±7,3; BUA101±2,5; SI-74±3,6); RA (SOS -1505±6,1; BUA - 92±3,7; SI - 63±3,2); RA+S (SOS -1504±6,2; BUA - 89±3,3; SI- 62±4,0) indexes olthe structuralfunctional state were veritably lower among the patients with the RA as well as with the RA+S. In summary, according to the ultrasound densitometry data the structural-functional state of the bone tissue in women of medium (45-59 years) and old (60-74 years) age with the RA veritably worsens disregarding the corticosteroids, meanwhile in the group of young women with the RA the veritable decrease of ultrasound parameters was revealed only in women taking corticosteroids.

P462 STATE OF OSSEOUS TISSUE IN ADOLESCENTS WHO HAVE BEEN OPERATED FOR A THYROID CANCER VV Povoroznjuk. G.M. Terekhova V.A. Oliynyk OV Epshtein, V.P. Komisarenko Department of Clinical Physiology & Pathology of Locomotor Apparatus, Institute of Gerontology AMS of Ukraine, Kiev, Institute of Endocrinology and Metabolism AMS of Ukraine, Kiev, Ukraine During the last ten years, it has been noted a significant increase in thyroid cancer incidence in adolescents of Ukraine. Combined treatment of disease includes suppressive therapy with levothyroxine. Use of such atherapeutic protocol may be complicated by appearance of disturbances of phosphoriccalcium metabolism. 50 adolescents have been examined, who have been receiving suppressive therapy with levothyroxine after thyroidectomy for a papillary thyroid cancer. All the patients had hypercalciuria, increased level of urinary excretion of hydroxyproline. Ultrasound densitometer "Achilles+" (Lunar Corp., Madison, WI) showed a decrease of indices of bone density and velocity of ultrasound passage through osseous tissue, what corresponded to osteopenia syndrome. The changes revealed have to be taken into account in the combined therapy in adolescents who have been operated for a thyroid cancer.

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MALE OSTEOPOROSIS P463 VARIANT OF CANCELLOUS BONE STRUCTURE IN MALE IDIOPATHIC OSTEOPOROSIS H.-P. Kruse I. Frieling Medical University Hospital, Department of Nephrology and Osteology, Hamburg Germany. The roentgenological appearance of a marked vertically aligned cancellous bone structure in the vertebral bodies has already described by Udinger in 1958 as a typical radiological Sign of osteoporosis. This has been called hypertrophic atrophy. From our study of male osteoporosis (Frieling and Kruse, 1996) we tried to elucidate this phenomenon in a subgroup of these patients. Investigated were 305 male patients with osteoporosis, designed by a z-score <-2,0 in the bone mineral density with and without osteoporotic vertebral fractures. The selection of the patients with pronounced verticular cancellous bone structure of the vertebral bodies was made by subjective visual assessment in the absence of objective criteria. From the 305 male patients with osteoporosis 224 had primary osteoporosis, 101, of the latter with different risk factors This sub group includes 18 patients with the characteristic bone pattern. They were compared with 123 patients with primary osteoporosis without risk factors. The mean age was significantly lower than in primary osteoporosis (43.6 versus 53.5 years). Despite analogous low bone mineral density only 16% (n=3) of these 18 men had at least one vertebral fracture, whereas 43% had in the group of primary osteoporosis. The biochemical parameters of bone turnover did not differ significantly. Described by Uelinger (1958) as so called "hypertrophic atrophy this radiological finding has been regarded as a sign of advanced osteoporosis It was considered as the result of resorption of the horizontal trabeculae and an augmentation of the vertical structure elements. The findings of this study favour our opinion that the described bone pattern is not a sign of advanced osteoporosis but is avariant of bone structure that is, despite an analogous low bone mineral density of common idiopathic osteoporosis, more resistant to osteoporotic fractures This interpretation is supported by the younger age of this special group and reports from the literature that the mean trabecular diameters remain constant in progressive bone loss. The common relationship between bone mineral density and fracture risk is not suitable for patients with this variant of trabecular bone architecture. Literature: Frieling I., H. -Po Kruse: Osteologie 5 (1996), 204-209

P464 VELOCITY OF ULTRASOUND AT THE MID-TIBIA IN ELDERLY MALES S. Goemaere, K, Tove, M. Daems R, De Muvnck, H Mvnv J. Van den Saffele. J.M Kaufman Unit for Osteoporosis and Metabolic Bone Disease, Univ. Hospital Ghent, Belgium Relative hypoandrogenism is not uncommon in elderly men. Androgens may playa specific role in the metabolism of cortical bone. In the present cross-sectional study we assessed velocity of ultrasound at the mid-tibia by soundscan 2000 (Myriad Ultrasound Systems Ltd) in 286 community dwelling elderly men (70-85y) and in 137 controls (22-58y). Fasting blood and second void urine were obtained; BMD was assessed by DXA (Hologic QDR1000+). Subjects with diseases interfering with bone metabolism were excluded.

Mean

age n +SD

tUV (y)

Hip m/s

Rad1/3 g/cm 2

FreeT g/cm

CrssLb ng%

Elderly

286

Controls

137

3943 ±109 4020 ±87 ±9.0 -0.70

0.907 ±45 1.047 ±.125 -0.72 -0.96

0.701 ±.080 0.759 ±.0.55 -2.68 -0.72

8.2 ±2.2 14.1 ±3.5 -0.29 -2.68

2.45 ±O.24 2.52 ±O.16

Diff' in SO

75.9 ±4.2 34.6 ±9.0

In the control group tUV is correlated only with hip BMD (r=0.21 *). In elderly males tUVis correlated with age (r=-0.23***), height (r=0.20***), weight (r=0.19**), hip BMD (r=0.33***), radius BMD (r=O.47***), free testosterone (r=0.15 * *), estradiol (r=0.16* *), creatinine-normalized excretion of CrosslapsR (r=-O,24 * * *) and desoxypridinoline r=-0.15 *), and serum osteocalcin (r=-0,28**), but not with serum bone specific alkaline phosphatase, PTH or 25-0Hvit D. Significant determinators in a stepwise multiple regression were radius BMD, age and log Crosslaps (adj R2 0.24). Simple regression shows a decrease of 5.9 m/s/year and 105 m/secl log(CrosslapsR) and an increase of 0.61 m/s/gr/cm 2 (BMD Rad). In this study tUV is decreased in elderly men and negatively related to markers of bone turnover; sex-steroid levels are not independent determinators. The findings for tUV in elderly men are similar to those for BMD at cortical sites. Remark: * p:>.05; * * p:>.001; * ** p:>.0001

P465 INDICES OF BONE TURNOVER IN ELDERLY MEN S. Goemaere, K, Tove, M. Daems R, Demuvnck. H Mvnv, B Vanneuville J.M. Kaufman Osteoporosis and of Metabolic Bone Disease Unit, Hospital Ghent, Belgium Data on biochemical markers of bone turnover in elderly men are scarce. In the present cross-sectional study we assessed markers of bone turnover in community dwelling elderly men (70-85y; n=286) and younger controls (22-58y; n= 137). Subjects with diseases or medications known to interfere with the bone metabolism were excluded. A fasting blood sample and fasting second void urine was obtained before 10 a.m. Bone formation was assessed by serum osteocalcin (~C) and bone-specific alkaline phosphatase (BsAP); bone resorption was evaluated by urinary calcium (Ca), desoxypyridinoline (DPC) and ELISA CrosslapsR normalized for urinary creatinine. Log transformation of the data was performed. Bone mineral density (BMD) was assessed by DXA (Hologic QDR1000+). In younger controls, age was negatively correlated with BsAP, DC and CrssL (r=-0.32,-0.54,-0.28** *, respectively). In the elderly, correlation amongst and between serum markers and urinary markers was highly significant (r=-0.32 to 0.61 ***), except for only weak correlations with Ca o' Ca o was related with serum creatinine (r=-0.41 ***) and PTH (r=-0.18* *). BsAP was correlated with serum creatinine (r=-0.12*) and PTH (r=0.12*). OC was correlated with age (r=-025***) and free testosterone (r=-0.13*). CrssL was correlated with age (r=-0.17***), El=-0.15**) and serum creatinine (r=-0.28***). DPD was correlated with Vit 0 (r=0.17***), creatinine (r=-0.31 * * *) and IGF-BP3 (r=0.19* * *). In multiple regression models only weak predictions of the bone turnover markers could be achieved (adj R2 values ranging from 0.07 to 0.16). In contrast to younger males, in whom BMD was not correlated with indices of turnover, a significant negative correlation between markers of bone turnover and BMD was observed for elderly men (r=0.15 ** -0.30* * *). In conclusion, in men markers of bone turnover are correlated with serum creatinine and it might be useful to adjust data for this parameter. Markers of bone turnover are negatively correlated to BMD in the elderly but not in younger men. Bru!J.ark: *p:>0.05; **p:>0.001; ***p:>0.0001.

-0.29

'difference between elderly men and controls blog transformation for urinary Crossla~sR (llQ/mmol creatinine)

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P466 THE EFFECT OF ETIDRONATE ON LUMBAR SPINE BONE MINERAL DENSITY IN MEN R.J. Sebaldt J.D. Adachi A. Tenenhouse J. Caminis M. Boratto M. Gordon A. Petrie GJ. Stephenson C.H. Goldsmith CANDOO Project, St. Joseph's Hospital & McMaster University, Hamilton, Montreal General Hospital &McGill University, Montreal, Canada We determined the effectiveness of intermittent cyclic therapy with etidronate (lCT-E) in men treated for osteoporosis by analyzing our clinical practice data. We analyzed the clinical records of patients seen at our two university tertiary care Osteoporosis Centres and whose data are routinely collected prospectively into a standardized database. Male patients were selected for the study group if they were treated with ICT-E (2 weeks of etidronate 400 mg/day followed by 11 weeks when calcium intake was supplemented if required to at least 1000 mg/day, repeated in 3-month cycles). A comparison (Comp) group was selected of males who were treated with no bone-active therapy other than calcium and vitamin D. Patients were excluded if they were treated with any other boneactive therapy within the preceding 2 years or if they did not have at least a baseline and one follow-up bone mineral 'density (BMD) determination. There were 114 and 110 men in the ICT-E and Comp groups. The groups were comparable in baseline dietary calcium and caffeine intake, reported alcohol consumption and serum TSH and 25 hydroxyvitamin 0 measurements. The groups differed in baseline age, respectively 60; 13 vs 51 ;15 yrs (mean;SD, p<0.0001), lumbar spine (LS) BMD, -2.4;1.5 vs 1.6;1.6 (t-score, p<0.005), and proportion of patients with prior vertebral fractures (33% vs 18%, p2=0.0142). In the ICT-E group, LS-BMD increased significantly relative to baseline at each follow-up time point, with percent change reaching a plateau at 30 months (+6.0;1.1 %, n=37, p=0.00001) and 36 months (+5.9;2.5%, n=15, p=0.04). In the Comp group, LS-BMD did not change significantly from baseline at any time point over the 3-year study period. Unadjusted mean percent change in LS-BMD from respective baseline differed significantly between ICT-E and Comp groups at 12, 24 and 30 months (each p<0.05). The number of new vertebral fractures during the first year of treatment was 4 (n=108) and I (n=98) in the respective groups. These data suggest that LS-BMD is increased significantly in men treated for osteoporosis with ICTE. These conclusions await confirmation by randomised controlled trials.

P467 BONE MASS IN MIDDLE-AGED OSTEOPOROTIC MEN AND THEIR RELATIVES: FAMI LlAL EFFECT M.E. Cohen-Solal C. Baudoin*. M. OmourL D. Kuntz and M.C. de Vernejoul INSERM, U349, Hopital Lariboisiere, Paris and *INSERMU21, Villejuif, France Severe idiopathic osteoporosis in middle aged men is a rare disease and still poorly understood. We therefore assessed the contribution of familial factors in osteoporotic men. We studied 38 men (mean age: 50±11 yrs) with primary osteoporosis (vertebral or peripheral bone fractures), 73 of their relatives: 19 brothers, 22 sisters, 13 sons and 19 daughters, and were compared to 199 age-matched controls. In all subjects, we measured the bone mineral density (BMD) and calculated the Z score atthe lumbar spine (LS) and femoral neck (FN) according to the fitted value of BMD of the controls. Comparing BMD and Z-score of each of the 4 subgroups of relatives to their aged matched controls showed that LS BMD was decreased compared to their controls. Mean Z-score of all the 73 relatives was decreased compared to their agematched controls at -1.28±1.48 atthe LS and -1.03±1.19 at the FN and was not different according to their sex or whether they were siblings or children. Mean Z-score of controls was not different from zero. The prevalence of low bone mineral density at the LS (Z-score <-1) among the relatives of the osteoporotic patients was 54.8%, whereas it was 17.4% in the control subjects (risk-ratio: 3.2). Among the 38 osteoporotic patients, 7 were heavy smokers, 8 both heavy chronic alcohol drinkers and smokers and 23 had none of these risk factors. There were no difference in BMD, Z score and anthropometric data of the patients according to the presence or absence of these risk factors. LS and FN Z-score was decreased in the relatives independently ofthe presence ofthese risk factors in the osteoporotic patients and was not different according to the presence of risk factors in the osteoporotic patients. In conclusion, low bone mineral density is observed in relatives of osteoporotic men whether or not risk factors are present, indicating the contribution of familial factors in the determination of primary middle-aged male osteoporosis.

P468 FEMORAL BONE DENSITY IN MALE OSTEOPENIA E. Legrand" 0 Chap par' C Rondeau" ~', ME Basle', M. Audran' Service de Rhumatologie' et Laboratoire d'Histologie Embryologie'. CHU, Angers, 49033 France Although bone mineral density predicts fractures in men, current references ranges and optimal site measurement are not validated in clinical practice. Aim: To study the relationships between femoral bone mineral density and vertebral fractures in men with osteopenia. Methods: In 193 male patients with lumbar osteopenia (t-score <-2 in spine) we measured femoral bone density (Hologic QDR 2000) at 4 different sites (nefk, trochanter, ward and total). Spinal X-ray films were analyzed independently by two trained investigators, unaware of the patient status. Vertebral fracture was defined as a reduction of at least 20 percent in the anterior, middle or posterior vertebral height. Results I

Age (years) BMI (kg/m') Spine Ward Neck Trochanter Total Hip

(gr/cm') t-score (gr/cm') t-score (gr/cm') t-score (gr/cm') t-score (gr/cm') t-score

Fracture

No Fracture n=117

p n=78

57.5 24.1 0.72 -3.0 0.411 -3.4 0.65 -2.9 0.55 -2.2 0.73 -2.5

50.4 24.1 0.77 -3.0 0.50 -2.7 0.70 -2.5 0.61 -1.7 0.82 -1.9

<0.01 ns <0.001 <0.001 <0.001 <0.001 <0.001

Results II: Fracture's number was correlated with age. BMI and BMD at all sites but stepwise linear regression analysis showed that the best model for predicting the fracture number includes age and Trochanter BMD (and not spine BMD). In this model (r'=0.23). Trochanter BMD explained most of the variance in fracture number (partial r'=0.18). These results suggest that (1) femoral BMD and particularly Trochanter BMD is an excellent site for predicting vertebral fractures (2) avalue of femoral BMD 2.5 SO or more below the young adult mean (t-score <-2.5) could be a rational threshold for therapy in men.

P469 IS OLiGOASTHENOTERATOZOOSPERMY - (OAT) SYNDROME A RISK FACTOR OF OSTEOPOROSIS IN YOUNG INFERTILE MEN? P. Hadii M. SchOler O. Hars K. Bock G. Emons K.-D. Schulz University of Marburg, Department of Gynaecology and Obstetrics, Marburg, Germany The aim of this study was to examine the effect of Oligoasthenoteratozoospermy - (OAT) syndrome on measurement results of Quantitative Ultrasound Sonometry (QUS) at the Os calcaneus. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) were measured in 131 men, mean age 33,9 + 6,0 years, using the Achilles bone densitometer (Lunar Corp., Madison, WI, USA). Semen analysis were performed and classified due to the WHO definition in all patients. Out of 131,95 patients had normal results while 36 patients had an OAT-syndrome. Additionally, serum levels of FSH, LH and testosterone were determined. Osteoporosis risk factors were assessed by a detailed questionnaire. All patients with drug treatments or diseases known to effect bone metabolism were excluded from the study. The Achilles short-term precision in vivo, expressed in confidence of variance, was 1.2 % for BUA, 1.8 % for SOS and 1 .5 % for SI. Analysing anthropometric characteristics of both groups, no significant difference was found in age, weight, height and BMI. Patients with an OAT-syndrome showed significant lower serum testosterone levels (p~0,001) which were in the low but normal range. No significant group differences were found in FSH and LH serum levels. In ultrasound parameters SOS and SI were significantly higher in OAT-men (p ~ 0,001 and p~ 0,05) while BUA was not significant different in both groups. In conclusion patients with an OAT-syndrome showed significant higher ultrasound measurement results. Therefore, OAT-syndrome is no risk factor of osteoporosis in young infertile men .

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P470 SKELETAL EFFECTS OF TESTOSTERONE AND ESTRADIOL TREATMENT IN A RAT MODEL OF MALE OSTEOPOROSIS U. Kollenkirchen R. Knauthe U.E Habenicht. A. Kirchmann & D. Sonnenberg Schering AG Research Labs., Berlin, Germany. This study was performed to investigate in detail the mode of bone loss in male rats after orchidectomy (ORX) and the effects of treatment with testosterone (tst) and estradiol (E,) We have used the ORX rat model in a set of 3 experiments (i, ii and iii) to characterize the short and long-term effects tst and E, on ORX-related bone loss. Adult male rats were either sham operated (SHAM) or ORX and bone loss monitored at 2, 4 and 6 weeks after surgery (i) or the ORX rats were s.c. implanted with pellets releasing either tst, E, or vehicle (ii and iii). These animals were sacrificed (ii) 0, 4 and 8 weeks after surgery or (iii) in a longitudinal experiment 0, 6 and 15 after surgery. Bone mineral density (BMD) was determined at identical sites in the secondary spongiosa of the proximal tibia using peripheral quantitative computer tomography. Androgen depletion caused a significant loss in cancellous bone at all time points after ORX. Tibia BMD was decreased by (i) 14, 22 and 26 % 2, 4, and 6 weeks, (ii) 24 and 30% 4 and 8 weeks or (iii) 27 and 29 % 6 and 15 weeks after ORX. In both treatment experiments (ii) and (iii) E, fully prevented the cancellous bone loss in the ORX rats. Bone loss was markedly attenuated in tst substituted ORX rats. Tst treatment resulted in (ii) I and 13 % lower BMD 4 and 8 weeks and (iii) 3 and 10% lower BMD 6 and 15 weeks after ORX compared to SHAM. The slight degree of bone loss in the tst treated groups might have been caused by a variable tst release of the s.c. implants resulting in inconsistent serum androgen levels esp. at the end of the experiment. The results are consistent with the current literature and support the hypothesis that androgens and estrogens are important in the regulation of bone metabolism. This might be of significant importance for osteoporosis therapy in hypogonadal and aging men.

P471 CHARACTERISTICS OF MALE PATIENTS REFERRED FOR LOW BONE MASS IN 2 TERTIARY CARE OSTEOPOROSIS CENTRES J Caminis. R.J. Sebaldt. J D. Adachi. A Tenenhouse. A. Petrie Candoo Project, Montreal General Hospital & McGill University, Montreal, and St. Joseph's Hospital & McMaster University, Hamilton, Canada We wished to determine the characteristics of the male patients referred to our two osteoporosis centres (M site and H site) for treatment of their low bone mineral density by analyzing our clinical practice data. Both sites are tertiary care university centres. The M site is an Endocrinology centre and the H site is a Rheumatology centre. Patient data have routinely been collected prospectively into a standardized electronic database at the Hsite, while at the M site, the data for this study were added into the same database by retrospective chart review. All male patients referred for low bone mass were selected for this study. Their ages were 52;17 (mean ;SD) at the M site and 58;14 at the H site. Baseline and treatment characteristics are as follows (all data in %).

Males, percent of patients Percent with OP' at baseline Patients with baseline fractures Percent of above with OP' Patients who are or were smokers Percent of above with OP' Percent with any identified secondary cause Percent using corticosteroids Treated with only calcium/vitamin D Treated with bisphosphonate Treated with calcitonin

M site (n=490)

site (n=420)

10 68 33 71 40 67

9 64 64 69 66 70

22 18 67 31 7

43 36 45 52 2

'OP defined as BMD t-score below -2.0 at lumbar spine or femoral neck

At both sites, OP was present in approximately 2/3 of males, both in all referred males and in the subgroups who smoked or had afracture history. Glucocorticosteroid use for asthma or connective tissue disease (CTD) was the commonest identified cause of secondary OP. At the H site, the greater proportion of patients with CTD relative to those with asthma is associated with a greater chance of receiving bisphosphonate therapy. Males with osteoporosis are an important subgroup of patients with secondary osteoporosis. Standardized multicentre prospective follow-up of these patients will help to define optimized treatment strategies.

P472 OSTEOPOROSIS IN MEN: REVIEW OF 30 CASES E. SimOes. M. Micaelo, H Madeira. M.M Silva V. Lase J. Ribeiro da Silva Portuguese Institute of Rheumatology, Lisbon, Portugal Objective: The aim of the study is to analyse the clinical profile and identify the principal causes of osteoporosis in men. Patients and Methods A retrospective analysis of 30 patients from an out-patient Metabolic Bone department, with the diagnosis of osteoporosis. Results: The mean age of the patients was 52±14,9, and the Principal reason for referral vas back pain (12 patients), osteoporosis based on skeletal densitometry (9 patients), radiographic osteopenia (4 patients), peripheral fractures (3 patients) and vertebral fractures in 2 patients. The major symptom was chronic back pain presented in 19 of the 30 patients (64%). And 10 (33%) patients had appendicular fractures and 7 (23%) had vertebral fractures. The most important demonstrable risk factors were: alcoholism (14 patients), smoking (12 patients), hypercalciuria (9 patients), corticosteroid therapy (6 patients) and hypogonadism (5 patients). Multiple risk factors were observed in 20 (66%) patients. Other secondary causes was: osteogenesis imperfecta in 3 patients and adultonset idiopathic phosphate diabetes in 2 males. Only 5 (16%) patients had no medical condition or known risk factors associated with bone disease. Conclusion: In this study, few men have primary or idiopathic osteoporosis, indicate that a careful evaluation for identifiable causes of osteoporosis is warranted because men frequently have an underlying secondary cause.

P473 RISK FACTORS IN MALE OSTEOPOROSIS J.C. Semler M. Hellmich K. Kociok I. Herrnleben Immanuel Hospital, Dept. Metabolic Diseases and Osteology: Berlin, Germany In the last years the incidence of osteoporosis in male has gained a significant increase. In the period of 1993 - 97 we examined a total of 223 men with osteoporosis, identified by bone density measurements (T-score <-2,5) and histological diagnostiC procedure. The majority (208) of the candidates age group is between 30 - 70 years. The methods used included first physical examination, a detailed risk factor questionnaire and bone density measurements by DXA at the lumbar spine and the femoral neck. In addition X-rays of the thoracic and lumbar spine were taken. The laboratory investigation included the determination of hormonal status and bone marker. Moreover bone biopsy was performed (Delling, Hamburg). From our studies we can extrapolate the following. The probability of developing osteoporosis relates to these risk factors: Nicotin (40,5%), testosteron deficiency (19,8%), long term corticosteroid therapy (13,5%), alcohol intake (11 ,2%), inflammatory joint disease (.6,3%), hyperthyroidism (2,5%). In nearly 20 % of the patients there were no risk factors identified. 41,4% of all the 223 male investigated had one or multiple vertebral fractures. The histological differentiation demarcates low turnover in 55,2% and high turnover in 20,2%. In the remaining percentage it could not be subcategorised. We may conclude that there is a significant correlation between smoking an low turnover osteoporosis. Long term use of corticosteroids and hypogonadism shows a higher incidence of vertebral fractures. In our opinion the risk fracture questionnaire is a helpful instrument defining bone turnover and the consequential beneficial effect of therapy.

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P474 BONE HISTOMORPHOMETRY IN YOUNG MEN WITH OSTEOPOROSIS A. Sawicki A. Debiriiski Z. Polowiec T. Szymariska-Debiriska Mineral Metabolism and Bone Disease Department National Food and Nutrition Institute, Warsaw Osteoporosis and Calcium Metabolism Centre, Warsaw, Poland Osteoporosis is a significant health problem for women but one seventh of all vertebral fractures occurs in men. The aim of the study was assessment of bone histomorphometric in men with osteoporosis. Fifteen men aged between 23 to 50 years without known risk factors of osteoporosis underwent transiliac biopsy following tetracycline-labelling and basic biochemical studies. All of them had spinal bone mineral density below 2SD measured by dual-energy X-ray absorptiometry (Lunar DPXL) none of them had hyperparathyroidism, hypogonadism, malabsorption or renal disease (creatinine level more then 1061lJT101/1). Histomorphometric assessment of their bone including trabecular bone volume, osteoid volume, osteoblasts and osteoclasts surface and dynamic parameters: bone formation rate, mineral apposition rate, (single and double tetracyclinelabelling surface) according to American Society for Bone and Mineral Research were done. Normal values of static histomorphometric parameters were obtained from 26 men aged 20 to 50 years without osteopathy who had died suddenly in traffic accidents. Dynamic parameters were compared with data published by Vedi et al. Mean bone volume was Significantly decreased (17.88 vs. 22.26; p<0.001), the mean osteoclasts surface was significantly increased (2.16 vs. 1.37; p
P475 SEX STEROIDS AND BONE MASS IN HEALTHY MEN: ESTRADIOL BUT NOT TESTOSTERONE CORRELATES WITH LUMBAR SPINE BMD R. Lehmann M. Wapniarz W. Arlt B. Allolio Medizinische Klinik der Universitat Wurzburg, Schwerpunkt Endokrinologie, Wurzburg, Germany Conflicting data have been published on the relationship between endogenous sex hormone levels and bone mineral content. In a population based study we analysed the influence of serum estradiol, testosterone and dehydroepiandrosterone sulphate (DHEAS) and sex hormone-binding globuline (SHBG) on bone mineral density (BMD) in normal men with regard to age-related changes. BMD at the lumbar spine was measured in 138 healthy men aged 20 to 80 years using DXA technique. Testosterone levels and DHEAS decreased with age (y=25.25 + 0.12x - 7.48*1 nx, R=0.46, p<0.OOO1 for testosterone), while estradiol levels were not age dependent (r=-0.07, p=0.04), SHBG was positively associated with age (r=0.37, p
P476 BENEFICIAL EFFECT ON BONE DENSITY IN MALE OSTEOPOROSIS OF TREATMENTS OF POST-MENOPAUSAL OSTEOPOROSIS M. Laroche V Andrieu A Constantin B Mazieres Service de Rhumatologie, CHU Rangueil, Toulouse, France We aimed to evaluate in osteoporotic men the effect on bone mineral density (BMD) of three treatments used in postmenopausal osteoporosis: Fluoride, Etidronate and Calcitriol Patients - Method: Thirty-three osteoporotic men aged 54±10 years were included in the study. They were treated either with disodium monofluorophosphate (200 mg/day) and calcium carbonate (1 g/day) (n=11), c;alcitriol (0.51lQ/day) (n=10) or etidronate (400 mg/day for 14 days, then calcium 1g/day) (n=12). After one year of treatment, dual-energy x-ray absorptiometry (DEXA) (Lunar DPXL) was used to determine lumbar spine (L2-L4) and femoral neck BMD. Results: In patients receiving fluoride, spine BMD increased significantly before treatment +7% (p:0.004), whereas variations at the femoral neck were not significant: -1.5% (p:0.19). Changes in BMD in patients receiving etidronate were not significant: spine: +2,6% (p: 009), femoral neck: 0.4% (p:0.86) Calcitriol treatment resulted in increased spine BMD: +3.5% (p:0.03), but no significant increase at the femoral neck: +1.3% (p: 0.56).

P477 LOCAL BONE DENSITY CHANGES IN MALE REGIONAL MIGRATORY OSTEOPOROSIS S. Ortolani C. Trevisan R. Cherubini F. Cavagnini Osp. San Luca, Istituto Auxologico Italiano IRCCS, Milan, and Clinica Ortopedica Osp. San Gerardo, Monza, Italy Regional migratory osteoporosis (RMO) is a migrating arthralgia of the lower limb associated to severe focal osteoporosis. Few data exist on quantitative assessment of systemic and regional bone mineral densities, in RMO and of their changes during the course of the disease. In this study, we report three cases of adult men with RMO in which spine, hip and whole body serial assessments of bone mass have been performed by DXA (Hologic aDR 2000) during six episodes of RMO. Systemic osteoporosis, with prevalent involvement of mainly trabecular skeletal sites, was present in all the patients, with T-scores below -2.5 at both the lumbar spine and the femoral neck. Bone loss in acute episodes ranged from -75.5% to -14.7% and was significantly correlated to the clinical severity of the episode (r=0.96, p<.02, Spearman Test). In one acute episode bone loss affected not only the symptomatic joint, but the whole limb from hemipelvis to foot: bone loss ranged from -33.6% to -3.5% at sites with mainly trabecular bone and from -19.1% to -1.1% at prevalently cortical sites. Bone recovery was complete in one episode out of six. In five cases, mean residual bone loss was 26% (range 13.9% - 32.7%). Our observations support the hypothesis that in RMO exaggerated regional acceleratory phenomena in bone turnover of unknown origin lead to greatly expanded remodelling space, in presence of systemic osteoporosis.

P477 ABSTRACT WITHDRAWN

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P478 OSTEOPOROSIS IN MEN D. Palie-Obradovi¢. N. Pilipovie G. Radunovie Institute of Rheumatology, Belgrade, Yugoslavia At the Institute of Rheumatology in Belgrade, during 1997, the study of osteoporosis in men was initiated, with particular emphasis on some risk factors. Preliminary examination included 60 mille patients. Each patient underwent osteodensitometric imaging (>Lunar< device, PA region of L2L4) accompanied by simultaneous fulfilment of a questionnaire which, besides the general data, enrolled items relevant for risk factors. >k test for unpaired samples was used for statistical analysis. The mean age of male patients examined was 49,23 yrs (20-72), mean body weight 80,38 kg (54-108) and the mean height 176,25 cm (163193). The mean value of bone mineral density (BMD) was 1,195 g/cm' (0.845-1.764). 23 (35%) patients had decreased BMD, four of them had osteopeny and 19 had osteoporosis. The significance of some risk factors in the development of BMD was analyzed. Existence of the risk factors was as follows: smoking-46, 67%, alcohol and coffee consumption - 51,76 and 81,67%, respectively. 53,33% of patients had decreased physical activity, and 28,33% of them reported low dietary calcium intake. Analysis ot the results obtained showed that consumption of alcohol and coffee, low dietary calcium intake and smoking did not correlate with decreased BMD, but that the patients engaged in sport activities had significantly greater BMD. For the purpose of meeting the definite conclusions, the examination should be continued, including larger population of male patients. The validity of standards applied for osteodensitometric imaging should be considered as well, bearing in mind that those adequate for Italian population were used for the study.

P479 RISK FACTORS AND OUTCOME OF MALE HIP FRACTURES; A PROSPECTIVE ONE YEAR FOLLOWUP . Ira Pande C Pritchard, D.L Scott A.D, Woolf Royal Cornwall Hospital, Truro, Kings' College, London, UK Hip fractures in elderly men is a neglected clinical problem with very little data on causes and consequences. We found low bone mineral density and significantly low testosterone (p
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