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Osteoporos Int (2000) Suppl 2:S57209 2000 International Osteoporosis Foundation and National Osteoporosis Foundation


Plenary Session 2: Mechanisms of Bone Loss (Thursday, June 15, 09000930)
1. GENE THERAPY WITH IL1Ra OR TNF-asR REDUCES OVARIECTOMY INDUCED BONE LOSS A. W. A. Baltzer, J. D. Whalen, P. Wooley1, C. Lattermann, R. Krauspe, P. D. Robbins, C. H. Evans, 1University of Dusseldorf, Germany; 2Wayne State University, MI, USA; 3University of Pitsburgh, PA, USA Objectives: We tested the hypothesis that gene transfer is an appropriate method to administer cytokine-inhibitors to reducing the rapid bone loss after ovariectomy (ovx). Methods: All experiments were conducted in six week old female white balb/C mice. The effect of i.v. injection and intrafemoral vector application was tested. Adenoviral vectors encoding IL1Ra (1x1010 particles) were injected retroorbitally or intrafemorally, systemic levels were measured by ELISA. The ability of the adenoviral vectors to transduce bone were evaluated by injecting Ad-b-galactosidase (Ad-LacZ) and X-gal staining. The body-distribution and the duration of transgene expression, were evaluated after application of the marker gene luciferase (Ad-luc). The dry bone weight was determined twelve days after ovarectomy and Ad-IL1Ra injection. The effect of soluble tumor necrosis factor-alpha receptor (Ad-TNF-a sR) and Ad-IL 1Ra on bone resorption was evaluated by histomorphometry ve weeks after transduction. Controls were completed with sham operated and sham-injected animals. Analysis was done using Student's unpaired t-test. Results: A highly efcient transduction mainly of lining osteoblasts is demonstrated. Systemic IL1Ra levels were higher, transgene expression was longer after intrafemoral injection. Injection of Ad-luc demonstrates local transduction. Low levels of a transient marker gene expression were found only in the liver for two days and in the draining lymph nodes for two weeks. Ovx decreased dry bone weight of humeri, tibiae, and bulae, and the bone matrix content in humeri and femora. Bone loss was signicantly reduced by both, intrafemoral application of Ad-IL1Ra (p<0.01) and Ad-sTNF-aR (p<0.01). Discussion: We demonstrate that gene therapeutic neutralization of IL1 and TNF-a does prevent ovarectomy induced loss of trabecular and cortical bone. Adenoviral gene transfer to bone induces prolonged systemic expression of transgenes in vivo, and proves to be more efcient than intravenous administration of adenoviral vectors encoding marker genes. Using adenoviralmediated in vivo delivery of cytokine-inhibitors is a new concept that has potential to become a treatment option in systemic or local bone resorption. lium lines the esophagus, providing a protective barrier that is continually replaced, in part through cell growth in the stratum basale. To model effects of nitrogen-bisphosphonates on epithelial growth, we examined the effects of alendronate (ALN) and risedronate (RIS) on normal human epithelial keratinocytes (NHEKs). While neither induced apoptosis, both inhibited NHEK growth. Consistent with this, the cell growth regulator, retinoblastoma (pRb), was hypophosphorylated, and p53 expression declined, which accounts for inhibition of growth in the absence of apoptosis. Expression of cdks 2 and 4, which phosphorylate pRb, declined 50%80%. Co-precipitation analyses showed that cdks 2 and 4 were more tightly associated with their inhibitors, p21wat1 and p27kip1. Consistent with their effects on the mevalonate to cholesterol pathway and on geranylgeranylation, responses to ALN and RIS were best mimicked with inhibitors of squalene synthase, HMG-CoA reductase, or type I geranylgeranyl transferase. Furthermore, specic growth inhibitory effects of ALN were blocked through addition of LDL or geranylgeraniol. Together these data suggest that nitrogen-bisphosphonate effects on esophageal stratied squamous epithelium may be mechanism-based. As with the osteoclast, geranylgeranylation may be rate-limiting. However, unlike in the osteoclast, inhibition of cholesterol biosynthesis may also play a critical role in these effects.

3. WHO LOSES MOST BONE AFTER HIP FRACTURE? L. E. Wehren, S. I. Zimmerman, J. Yu-Yahiro, W. Hawkes, J. R. Hebel, K. Fox, D. Orwig, J. Magaziner, University of Maryland, Baltimore, MD, USA Average bone loss after hip fracture is 25% in the rst year, but some groups are likely to lose more bone than others. Are there identiable characteristics that predict who will lose more (or less) bone mineral density (BMD) after fracture? We examined data from 205 women aged 65 and older in the Baltimore Hip Studies to identify characteristics associated with differing rates of bone loss during the year following fracture. Patients or proxies were interviewed and had BMD measured at the contralateral hip at baseline and 2, 6, and 12 months after fracture. Mean age of the women was 81.0 7.8 yr; 52.5% had intracapsular fractures. Comorbidity included cancer (18%), stroke (9.8%), DM (14.1%), and CVD (27.3%). Pre-fracture ADL impairments were common: 25.6% in walking 10 feet; 79% in climbing 5 steps. BMD was lost at every site in the hip in the rst year, from 2.1% intertrochanteric BMD (.675 gm/cm2 at baseline to .659 gm/cm2) to 4.6% of femoral neck BMD (.547 gm/cm2 to .521 gm/cm2), with rate of loss greatest during the rst 2 months. Low levels of pre-fracture activity, later post-surgical ambulation, serious postoperative complications, lower pre-fracture comorbidity (modied Charlson index), and higher intensity physical therapy were associated with greater BMD loss. Women with the lowest baseline BMD consistently demonstrated the greatest losses, even after adjustment for other factors. This suggests that use of bone-strengthening medication in osteoporotic women may have benets both before fracture, in decreasing fracture incidence, and after fracture, in improving recovery and functional outcome.

2. ALENDRONATE AND RISEDRONATE ARREST KERATINOCYTE CELL GROWTH IN A MODEL FOR ESOPHAGEAL IRRITATION VIA EFFECTS ON CYCLINDEPENDENT KINASES A. A. Reszka, J. M. Halasy, G. A. Rodan, Dept. of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA, USA Clinical and animal studies show that bisphosphonates have the potential to irritate the esophagus. Stratied squamous epithe-

4. REVISION OF T-SCORE BMD DIAGNOSTIC THRESHOLDS D. M. Black, for the Joint NOF/ISCD/ASBR Committee on Simplication of the BMS Reporting In 1992, the WHO proposed that a BMD score 2.5 SD below young adult peak be the threshold of osteoporosis. This denition was intended to compare prevalence of osteoporosis across populations, when BMD was assessed using the same technique. However, the prevalence of osteoporosis (% with T-score 52.5) and hip fracture risk among women with BMD T-scores 52.5 varies greatly across sites and techniques. Thus, T-score based diagnoses across techniques are not comparable. To address this problem, a NOF/ISCD/ASBMR committee evaluated several methods to increase technique comparability. The following system will create site-specic threshold values based on hip fracture risk-the most important clinical outcome: 1. Dene a hip fracture risk index level: 5 year, age-specic hip fx risk among women with femoral neck BMD T-score 52.5. 2. Create analogous (``risk-equivalent'') thresholds for nonfemoral neck techniques: Those below the device-specic threshold have a hip fx risk equal to the index risk. This process can produce a threshold BMD value for any technique for which there is data relating the method to hip fx risk. For those above the threshold, the probability of FN BMD T 52.5 should be reported, to determine referral for hip BMD. This risk-based procedure is exible and can incorporate other risk factors (e.g., previous fx or biochemical bone markers). While a number of important issues remain to be resolved, we believe this method provides a powerful, yet exible framework for a unied diagnostic strategy in osteoporosis.

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In conclusion, measurements of DXR-BMD using the Pronosco X-posure SystemTM can predict risk of osteoporotic fracture as well as conventional BMD measurements by DXA.

6. AN INTERLEUKIN 6 PROMOTER POLYMORPHISM IS ASSOCIATED WITH HIP BONE LOSS IN OLDER WOMEN J. Zmuda1, J. Cauley1, K. Stone2, M. Nevitt2, K. Ensrud3, E. Harris4, M. Hochberg5, P. Morin6, R. Saiz6, G. Joslyn6, S. Cummings2, for the SOF Research Group, 1Univ. Pittsburgh; 2San Francisco, CA; 3Minnesota; 4Maryland; 5Kaiser Permanente, OR; 6 Axys Pharmaceuticals, CA, USA Interleukin 6 (IL6) promotes osteoclast formation and bone resorption. A single nucleotide substitution (G?C) at 174 bp in the IL6 promoter region affects IL6 gene transcription. We determined if this polymorphism is associated with bone density (BMD) and bone loss by genotyping 3,529 women (565 yrs) in the Study of Osteoporotic Fractures. Total hip BMD was measured an average of 3.5 yrs apart. Despite similar initial BMD, women with the more active 174G allele experienced greater bone loss compared to women with the less active 174C allele (Table). This association remained signicant after adjusting for age, body mass index, weight change, walks for exercise, smoking, health status, use of oral estrogen, glucocorticoids, and calcium supplements, and study center (p=0.01). These results suggest that elderly women with the 174G allele at the IL6 gene locus experience more rapid hip bone loss with advancing age.
Genotype (%) (g/cm2) C/C (18.6) G/C (48.1) G/G (33.2) P (ANOVA)

BMD{ (%/yr) -.22(1.31) -.41(1.46) -.47(1.42) .004

Bone Loss (mg/cm2/yr) 1.6(9.7) 2.9(10.3) 3.4(10.3) .006

Plenary Session 3: Bone Fragility Thursday, June 15, 11001230)

5. IDENTIFICATION OF WOMEN AT RISK OF OSTEOPOROSIS: COMPARISON OF DIGITAL X-RAY RADIOGRAMMETRY WITH DXA MEASUREMENTS AT THE SPINE AND HIP L. Hyldstrup, T. K. Srensen, L. Baeksgaard, D. Arnbjerg, J. T. Jrgensen, Dept. of Endocrinology, Hvidovre Hospital, University of Copenhagen, and Pronosco A/S, Vedbaek, Denmark BMD of the spine and hip are the best predictors of later osteoporotic fracture. BMD can also be measured by digital X-ray radiogrammetry (DXR-BMD), a new technology that can be widely applied without major capital investments. In the present study DXA-BMD were compared to DXR-BMD, using the Pronosco Xposure SystemTM with respect to identifying women with low bone mass. 420 women were studied. 80 of these were osteoporotic according to WHO criterias, giving a `prevalence' of osteoporosis in this sample of 20%. BMD was measured at the spine and hip by DXA and by DXR using a standard x-ray of the distal forearm and hand. Using The WHO denition of 5T-score 52.5 SD in either hip or spine as reference for osteoporosis, specicity, sensitivity and predictive values of DXR-BMD in the classication of these women were calculated. T-scores of these 3 sites were all tightly intercorrelated. Results for different cutoff levels of DXR-BMD are shown in table.

.76(.13) .76(.13) .76(.13) .765

Values are mean (SD).

7. AGE AND BONE MINERAL DENSITY HAVE SIMILAR EFFECTS ON THE RISK OF INCIDENT VERTEBRAL DEFORMITY IN MEN AND WOMEN : RESULTS FROM THE EUROPEAN PROSPECTIVE OSTEOPOROSIS STUDY (EPOS) M. Lunt, T. W. O'Neill, D. Felsenberg, A. Silman, J. Reeve, the EPOS Study Group, ARC Epidemiology Unit, Manchester University, UK Background: There are few data concerning the inuence of bone mineral density (BMD) in explaining gender differences in the occurrence of osteoporotic fractures. The aim of this study was to assess the inuence of BMD in explaining differences in the incidence of vertebral deformity between men and women. Methods: The subjects who took part in this analysis were recruited from population registers for participation in a prospective study of osteoporosis the European Prospective Osteoporosis Study (EPOS). At baseline subjects had an interviewer administered questionnaire, lateral spine x-rays and a subsample had BMD assessment. Repeat spinal x-rays were performed a mean of 3.8 years later. Radiographs were assessed morphometrically. An incident vertebral deformity was dened as a vertebra that both a) showed a decrease in at least one vertebral height of more than 20% since baseline, and b) was classed as a new prevalent deformity (using the McCloskey method). The association between vertebral deformity incidence, age and BMD was determined using poisson regression. Results: Paired spinal radiographs were available in 3000 men and 3500 women. 70 men and 141 women developed one or more incident deformities. After adjustment to age 65 years, the incidence of vertebral deformity, per 100 person years, was in

cutoff for DXR-BMD (T-score) 51.0 52.0 52.5 53.0

Sensitivity Specicity PV pos .98 .92 .89 .86 .72 .88 .93 .96 .42 .60 .74 .83

Pv neg 1 .98 .98 .97

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women, 1.02 (95% Condence Interval [CI] 0.86, 1.21) and in men, 0.56 (95%CI; 0.44, 0.72). Incidence increased with age, RR=2.1 (95%CI; 1.8,2.5) per decade of age. Incidence increased with decreasing BMD, RR=1.5 (95%CI; 1.3, 1.8) per 0.1g/cm2 decrease in BMD at the spine, and RR=1.7 per 0.1g/cm2 decrease in BMD at the femoral neck and trochanter. None of these effects differed signicantly between men and women. After adjusting for BMD (at any site) the difference in age-adjusted incidence in men and women was no longer statistically signicant. Conclusions. At a given age (>50 years), the difference in incidence of vertebral deformity between men and women may be accounted for by differences in BMD.

infrared micro-spectroscopy (FTIRM) allows analysis of mineral content, mineral crystal size/perfection, and collagen maturity at ~10mm spatial resolution. Previous studies comparing 4mm iliac crest biopsy sections from post-menopausal osteoporosis, vs. normal bone, showed signicant differences in the aforementioned parameters. The present study compares the spatial and temporal variation in mineral and matrix quality and quantity in high-(HOP) and low- (LOP) turnover osteoporosis. Under an IRB approved protocol, biopsies from 8 women with HOP (ages 56 65) and 5 women and 3 men with LOP (ages 3378) were analyzed by FTIRM. HOP was dened as increased resorptive surface, higher than normal numbers of osteoclasts (OC), and normal osteoblast (OB) activity. LOP was dened as lower than normal resorptive surface, decreased OC number, and normal OB activity. The rst 60mm from the mineralizing front of forming bone (based on H&E and tetracycline labeling) were analyzed in 10 mm steps. Percent differences from values at 60mm calculated for both mineral crystallinity and collagen maturity in HOP had negative values, while in LOP, differences were positive. Because small crystals are resorbed rst, the presence of larger/more perfect crystals and a more mature matrix in HOP indicates impaired OB activity. In LOP evidence of new mineral and matrix deposition exists, providing a possible explanation for the lower fracture incidence in LOP patients.

8. HOW WELL DOES BONE MASS PREDICT LONG-TERM RISK OF HIP FRACTURE? D. M. Black, L. Palermo, D. Bauer, for the Study Of Osteoporotic Fractures Research Group, Univ. of California, San Francisco, CA, USA Most previous estimates of the relationship of bone mass measurements and fracture risk have been based on only short periods (12 years) of follow-up. In order to assess the ability of bone mass to predict longer term fracture risk, we compared the relationship of several measurements of bone mass to hip fracture risk using data from the Study of Osteoporotic Fractures (SOF). 9704 women (mean age 71 years at baseline) were enrolled in SOF in 198587 and have been prospectively followed for hip fractures (conrmed by x-ray reports) since that time. Measurements of BMD in the proximal radius and calcaneus (Osteon, Osteometer) was measured at baseline (19857), BMD at the spine and hip (Hologic QDR 1000) 2 years later and calcaneal ultrasound (BUA, Walker-Sonix) 4 years after baseline. We truncated follow-up at 3, 5 and 8 years following each bone mass measurement in order to examine and compare the ability of each measurement to predict hip fracture risk over increasing follow-up time. Approximately 250 hip fractures occurred in the rst 5 years of follow-up. Relative hazards per SD and 95% CI's (age adjusted) are shown below: These data suggest that bone mass measurements continue to predict hip fracture risk for as long as 8 years although the strength of prediction varies greatly among measurement sites. The results also show the long-term advantage of hip BMD for predicting hip fracture.
Bone mass measurement site Follow-up Years FN hip 3 5 8 2.8 (2.2,3.5) 2.7 (2.3,3.2) 2.3 (2.0,2.6) Calcaneus (BMD) 1.8 (1.5,2.2) 1.8 (1.5,2.1) 1.7 (1.5,1.9) Calcaneus (BUA) 1.5 (1.3,1.7) 1.5 (1.3,1.8) (Insufcient follow-up)

10 (2). TIBOLONE MODULATES SULPHATASE IN BREAST BUT NOT IN BONE H. J. Kloosterboer, M. E. de Gooyer, N. V. Organon, Oss, The Netherlands Tibolone exerts tissue specicity by selective metabolism of the compound. Estrogenic metabolites of tibolone are formed in the liver and intestine and are responsible for the effects on bone whereas formation of the delta4 isomer, a progestagenic metabolite, in the endometrium opposes the estrogenic action. The main part of the estrogenic metabolites is in the inactive sulphated form. Previous studies have shown that tibolone diminishes tumor growth in the DMBA model. This effect may be due to a lowering of estrogenic compounds by modulation of sulphatase activity. In bone, a full estrogenic response is observed consistent with high biological effects suggesting that sulphated metabolites become active in this tissue. Apparently sulphatase in bone and breast are differntly modulated. In order to test this hypothesis the effect of tibolone and its metabolites on sulphatase activity in breast cells (T47D) and osteoblast-like cells (MG63; HOS TE 85) were tested. Cells were incubated with estrone sulphate and the amount of intracellular estrone plus estradiol was assessed using HPLC. In these studies EMATE was used as a positive control. A number of sulphated metabolites were also studied. Tibolone and its metabolites do not inhibit sulphatase activity in the two bone cells, but in breast cells a strong inhibition was observed. EMATE has a stronger inhibitory effect in breast cells than in bone cells. The sulphated metabolites of tibolone show a similar discriminatory effect in the two cell types. From these results we conclude that tibolone and its metabolites show tissue selectivity with respect to sulphatase inhibition. This biological effect may serve to avoid estrogenic stimulation of the breast while the estrogenic effect on bone remains.

Spine 1.6 (1.3,1.9) 1.5 (1.3,1.7) 1.4 (1.3,1.6)

P. Radius 1.5 (1.1,1.7) 1.4 (1.2,1.6) 1.4 (1.2,1.5)

Basic Cell Biology

9 (1). MINERAL AND MATRIX QUALITY AND QUANTITY IN ILIAC CREST BIOPSIES FROM HIGH- AND LOW-TURNOVER OSTEOPOROSIS: AN FTIR MICROSPECTROSCOPIC STUDY A. L. Boskey, E. P. Paschalis, 1Hospital for Special Surgery, New York, NY, USA The quality and architecture of the mineral and matrix in bone determines the tissues' mechanical integrity. Fourier-transform

11 (3). RALOXIFENE DIRECTLY MODULATES OSTEOBLASTS ACTIVITY IN VITRO S. Migliaccio, A. Taranta, A. Teti, D. Agnusdei, G. Spera, J. D. Termine, 1Histol & Embr, Medic Phys Depts, Univ ``La Sapienza'' Rome; 2Exper Medic Dept, Univ L'Aquila; 3Eli Lilly, Florence, Italy; 4 Lilly Res Lab, Indianapolis, IN, USA Raloxifene (RAL), a selective estrogen receptor modulator (SERM), prevents bone loss in postmenopausal women and

Numbers in brackets after Publication Number refers to Board Number

ovariectomized animals. We showed that RAL decreases osteoclastogenesis and bone resorption in vitro. Aim of the present study was to evaluate if RAL modulates bone forming cells functions. Osteoblasts, obtained from neonate mouse calvaria, were exposed to increasing concentrations of RAL (1014107M) for 24 hr. Medium was then changed and cells incubated with 3H-thymidine for 4 hr. RAL induced a dosedependent increase in the proliferation rate of the cells (max effect 1011108M). Moreover, osteoblasts were exposed for 24 hr to RAL or 17-b-estradiol (E2, 1010 107M) to evaluate effects on osteoblast function markers. At the end of incubation, RNA was extracted and semiquantitative RT-PCR analysis performed. RAL increased in a dose-dependent manner expression of OSF2 (~10-fold), alkaline phosphatase (~2-fold), matrix proteins collagene-I (~3-fold) and osteopontin (~4.5-fold). E2 increased expression only of OSF2 and osteopontin, suggesting that RAL and E2 modulate osteoblast homeostasis with different patterns. In conclusion, our data show for the rst time that RAL modulates osteoblast activity in vitro, suggesting that this SERM protects bone mass not only inhibiting bone resorption, but also stimulating osteoblast function.

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metabolism. Subconuent Sa-Os2 cells were treated with various concentrations of bFGF and PDGF-BB, respectively, under serum-free conditions, for 24 h. To evaluate cell proliferation, the radiolabeled thymidine incorporation assay was used. BFGF at 1010109 ng/ml increased [3H]thymidine incorporation in Sa-Os2 cells in a dose-dependent fashion (p<0.01). In contrast, no signicant effect of PDGF-BB or T3 at 107 M on DNA synthesis in our cell culture system has been noticed. Preexposure of cultured cells to T3 for 24 h was followed by an enhanced proliferative response to bFGF. Moreover, at 1012 1011 ng/ml, bFGF induced a signicant increase in DNA synthesis only in combination with T3 (p<0.01). Similarly, PDGFBB at 10111010 ng/ml increased cell proliferation in the presence of T3 (p<0.01). These ndings indicate an interaction between T3 and bFGF/ PDGF-BB, thus suggesting an additional mechanism of action of thyroid hormone on bone cells besides direct effects.

14 (6). THE EFFECT OF ESTROGEN ON FRACTURE HEALING IN OVARIECTOMIZED RATS P. J. Sherman, E. P. Paschalis, C. Rimnac, A. L. Boskey, Hospital for Special Surgery, New York, NY, USA Estrogen therapy has been shown to prevent bone mineral loss and increase mineral content in postmenopausal women. Impaired fracture healing following ovariectomy and estrogen deciency has also been demonstrated. In the present study the effect of estrogen replacement on fracture healing in the estrogen decient rat model was evaluated radiographically, biomechanically, and spectroscopically (Fourier transform infrared imagingFTIRI: a technique that provides information on mineral crystallinity and collagen cross-links at the 10 um spatial resolution level). 168 ovariectomized female rats were divided into subcutaneous 17B-estradiol slow release tablets within three days after ovariectomy (1); subcutaneous estrogen pellets at the time of fracture (2); and placebo (3). Fracture of the mid-shaft right femur was produced six weeks following ovariectomy. Animals were sacriced at 4, 6, 8, and 12 weeks. The outcomes measured were delayed union rate, maximum load to failure fracture, mineral crystallinity, and collagen cross-links (DHLNL & Pyr). At four weeks, group (1) had a 25% delayed union rate, while (2) and (3) had rates of 50 and 55% respectively. This rate fell to less than 20% in all groups at 6 and 8 weeks. By 12 weeks there were no delayed unions radiographically. In groups (1) and (2), a statistically signicant linear progression of maximum load to failure was observed from 4 to 12 weeks. The average maximum load values of (3) increased until week 8 and plateaued, whereas (1) and (2) increased to a maximum at 12 weeks. FTIRI analysis suggested that (1) was initially under osteoclastic suppression (4 weeks) followed by osteoblastic upregulation in later time points (8 weeks).

12 (4). EVIDENCE FOR IMPAIRED COLLAGEN FORMATION IN OSTEOPOROSIS: AN FTIR IMAGING STUDY E. P. Paschalis, R. Mendelsohn, A. L. Boskey, Hospital for Special Surgery, New York, NY, USA Fourier transform infrared imaging (FTIRI) is a novel technique allowing visualization of variations in molecular properties of mineral and collagen in thin histologic sections (in 400x400 mm2 areas, at the 10 mm spatial resolution level). Since there is no requirement for tissue homogenization, areas to be analyzed may be selected based on histology and histomorphometry. Examination of model compounds identied spectral regions describing collagen maturity and cross-link patterns. To test the hypothesis that there are alterations in the collagen content and composition of osteoporotic tissues, 4mm sections from iliac crest biopsies obtained under an IRB approved protocol from 5 normal and 19 patients diagnosed with osteoporosis were analyzed by FTIRI. The areas of analyses were selected based on Hematoxylin & Eosin and tetracycline labeling to include only actively forming areas. In the normal bone, the parameter describing collagen cross-links varied from 0.8 to 2.0, indicating a reproducible complementary spatial and temporal variation in between pyridinoline and DHLNL, whereas in osteoporotic bone it fell within this range, but the spatial and temporal distribution was shifted towards the highest values (1.52.0). Furthermore, these differences were statistically signicant within the rst 30mm from the mineralization front, after which the values were the same. These data support our hypothesis that in addition to the abnormal resorption proles in osteoporosis, there may be an irregularity in the bone formation process. Such data may prove useful to the design and choice of therapeutic protocols.

Biochemical Markers

15 (7). BONE DENSITY AND BIOCHEMICAL MARKERS IN RHEUMATOID ARTHRITIS S. Akin1, O. Gulec2, M. Beyazova2, F. Korkusuz1, 1METU Medical Center, Ankara, Turkey; 2Department of Physical Medicine and Rehabilitation, University of Gazi, Ankara, Turkey The purpose of this study was to assess; 1) bone mineral density (BMD) of the hand in women with rheumatoid arthritis(RA) 2) associations of BMD and serum osteocalcin, urine NTelopeptides, pyridinoline(Pyr)and deoksypyridinoline(Dpyr). BMD of the hand was measured by dual energy x-ray absorptiometry (Lunar DPX-IQ). 41 RA patients and 50 healthy controls were included into the study. BMD results of the premenopausal RA group were signicantly (p = 0.002) lower

C. E. Pepene2, R. Ziegler1, L. Gozariu2, C. H. Kasperk1, Department of Medicine, University of Heidelberg, Heidelberg, Germany; 2Department of Endocrinology, University of ClujNapoca, Romania

A large body of evidence suggests that thyroid hormone effects on target tissues may involve growth factors. The present study was undertaken to determine bFGF and PDGF effects on Sa-Os2 cells proliferation, as well as to test for possible interactions between T3 and these skeletal growth factors on bone cell

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than the premenopausal control group. Premenopausal RA patients had higher BMD results than the postmenopausal RA patients, however the difference was not signicant (p = 0.133). Dpyr was signicantly higher in RA patients in both groups. Independent predictors of bone mass of the RA patients were found to be the Larsen Index, erythrocyte sedimentation rate and Dpyr. Among the biochemical markers, Dpyr reects bone resorption in RA patients and this seems to be the most signicant marker presenting bone loss. In conclusion, bone loss begins at the early stages of RA and hand BMD is a useful indicator to assess bone loss even at the premenopausal stage. Furthermore, its correlation to Dpyr is signicant (r2=0.299).

(19) osteoporosis (dened by a BMD T-score of <2.5, or the presence of a vertebral fracture). They were started on antiresorptive therapy with bisphosphonates (28), HRT (16) and calcium and vitamin D (5). Bone turnover markers were measured twice at baseline and at 4, 7 and 10 months. A response was dened as a decrease in a marker by more than the least signicant change (P<0.05, one-tailed). The percent of responders and the agreement with response by spine BMD (more than 4.5%, the least signicant change) at 10 months (kappa) are shown in the table. We found that 59% of subjects had a response as assessed by spine BMD. Marker % Responders 22 41 34 63 Agreement with BMD 0.12 0.01 0.17 0.28

16 (8). BIOCHEMICAL MARKERS OF BONE TURNOVER IN THE ASSESSMENT OF RESPONSE TO TILUDRONATE IN PAGET'S DISEASE L. Alvarez, N. Guan abens, P. Peris, S. Vidal, I. Ros, A. Monegal, J. mez, A. M. Ballesta, L. Bedini, R. Deulofeu, F. Pons, J. Mun oz-Go Hospital Clinic, Barcelona, Spain Aims: To investigate the usefulness of biochemical markers of bone turnover for monitoring tiludronate efcacy in the treatment of Paget's disease. Methods: 43 patients with Paget's disease were prospectively studied. All received 400 mg tiludronate daily for 3 months. Total (TAP) and bone (BAP) alkaline phosphatases, propeptide Nterminal of type 1 procollagen (PINP), serum C-terminal telopeptide of type 1 collagen (s-CTX), hydroxyproline (HYP) and C- and N-terminal telopeptides of collagen type 1 (CTX and NTX, respectively) were measured at baseline (G0) and after 1 (G1) and 6 (G2) months after treatment. Quantitative bone scintigraphy (SAI) was performed at G0 and G2. Response (R%), normalization (N%) and variation (V%) were analyzed for all markers. Results:
G0& TAP U/L BAP ng/mL PINP ng/mL HYP nM/mg CTX mg/mM s-CTX pM/L NTX nM/mM SAI 651108 8617 23142 22519 61486 6370602 26940 92011671 N% 13 6.5 6.5 9.7 32 14 13 G1& V% R% G2& 81 96 96 90 15 32 85 23117# 193# 607# 1037# 2510# 4447327# 818# 5044908* V% R% N% 49 68 63 48 44 24 58 44 71 96 92 46 11 40 78 61 79 68 61 89 44 57

bAP OC Dpd NTx

We conclude: 1) Bone turnover markers are useful for early identication of treatment response; 2) The response rate of some markers is similar to that of spinal BMD; 3) The agreement of responder as assessed by markers if poor to fair; 4) Of the four markers under test, urinary NTx had the best utility for monitoring osteoporosis treatment.

18 (10). FOLLOW-UP WITH BONE TURNOVER MARKERS CAN BE MISLEADING: ROLE OF REGRESSION TO THE MEAN R. D. Chapurlat, T. Blackwell, D. C. Bauer, S. R. Cummings, University of California, San Francisco, CA, USA Follow-up of osteoporosis treatments with bone turnover markers (MK) may sometimes be misleading because of regression to the mean (RTM). To determine how initial change in MK may be inuenced by RTM, we have studied patterns of variations of urinary type I collagen breakdown products (UCTX), serum bone specic alkaline phosphatase (BSAP) and serum osteocalcin (OC) in the Multiple Outcomes on Raloxifene Evaluation (MORE) trial, among the 1585 women treated with raloxifene who had MK measurements and were at least 70% adherent (there were 1127 control group patients with MK). We applied a formula (JAMA 1991;266:167885) yielding an adjusted change: A = (s2d'*D) + (s2D*d')/s2D+s2d', D=true change; d'=post-intervention observation minus the pre-intervention predicted true value; sd'2 and sD2 = variances of d' and D. Patients whose initial change in MK are much larger from the mean decrease (which was of 24% at 6 months for UCTX) often change in the opposite direction in the subsequent months, e.g. among women whose UCTX decreased at least 60% in the rst 6 months, 78% had an increase in the next 6 months. Among women whose UCTX increased in the rst 6 months, 80% had a decrease in the next 6 months. This pattern was also observed with BSAP and OC. The formula allowed us to adjust for RTM. For example, for a 60% decrease in UCTX in the rst 6 months, after accounting for RTM we estimate the true decrease to be of 36% (80% condence interval: 590%). We conclude that measurement of MK in raloxifene treated women is inuenced by RTM, and the formula allows to attenuate this effect.

23723# 54 2223# 68 7015# 70 11911# 46 31755# 47 4669489* 26 9219# 66

(&=meanSEM) *p<0.05 versus G0 # p<0.001 versus G0

Conclusions: Serum BAP and PINP and urinary NTX are the most sensitive markers for monitoring treatment ecacy with tiludronate in Paget's disease. Data of biological variation is useful for assessing true changes induced by treatment.

17 (9). OSTEOPOROSIS TREATMENT MONITORING: UTILITY OF BONE TURNOVER MARKERS P. R. Bainbridge, T. S. Yap, R. A. Hannon, A. Price, I Catch, N. F. Peel, R. Eastell, Northern General Hospital, Shefeld, UK We have introduced bone turnover markers into our nurse monitoring clinic and report here our rst two years' experience. Treatment monitoring may be used to identify non-responders and enhance compliance with therapy. Bone turnover markers may have some advantages over bone mineral density for monitoring treatment in that their response is larger and response may be identied as early as 3 months. We measured bone formation using the bone isoform of alkaline phosphatase (bAP) and osteocalcin (OC) in the serum. We measured bone resorption using free deoxypyridinoline (ifDpd) and N-telopeptide of type I collagen (NTx) in a timed morning urine sample. We studied 49 patients (35 women and 14 men) with primary (30) and secondary

19 (11). PREDICTORS OF TREATMENT VALIDITY Z. Crncevic Orlic, Endocrinology Division, University of RijekaInternal Clinic, Clinical Hospital Center, Rijeka, Croatia We analyzed usefulness of biochemical parameters in different phases in patients with senile osteoporosis and early postmenopause.

In retroactive study, we analyzed 20 patients taking biphosphonates and 20 early postmenopausal patients taking HRT. In every patient we have measured BMD (bone mineral density) by DPX, calcium, phosphorus, magnesium in serum and urine, bone alkaline phosphatase, osteocalcinin serum and piridinoline and deoxy piridinoline in urine before treatment and one year later. There were no signicant differences in values of serum andurine calcium, phosphorus and magnesium before and after treatment. Multivariate analysis showed that the combination of four (Ca, P, Mg/creatinine ratio, piridinolin, deoxy piridinolin in comarison with BMD) differentiated bone content before and after bisphosphonates and HRT treatment. Biochemical parameters used together and with other clinical features can help to indicate bone loss and validity of treatment.

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RESULTS: Mean bone turnover in all groups from both studies decreased from baseline to week 52. At baseline, bone turnover exceeded the premenopausal range; however, under E2/NETA and E2, the markers approached the normal premenopausal range. CONCLUSION: A continuous combined or continuous sequential E2/NETA transdermal HRT* regimen is as effective as transdermal E2 alone for exerting positive benecial effects on biochemical markers of bone resorption and formation. *trademarks: ESTALIS1 (continuous combined) ESTALIS1 SEQUI (sequential)

22 (14). RELATIONSHIP BETWEEN BIOCHEMICAL AND HISTOMORPHOMETRIC PARAMETERS OF BONE TURNOVER 20 (12). EFFECT OF CONTINUOUS SEQUENTIAL TRANSDERMAL ESTRADIOL/ NORETHISTERONE ACETATE VS. ESTRADIOL HRT ON BONE MARKERS IN POSTMENOPAUSAL WOMEN P. Delmas, D. F. Archer, Service de Rhumatologie, Hopital Edouard Herriot, Lyon, France; 2Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA OBJECTIVES: To compare the effects of a combination estradiol/ norethisterone acetate (E2/NETA) transdermal patch given in a sequential regimen on biochemical markers of bone turnover versus an E2-only patch in healthy postmenopausal women. METHODS: A 52-week multicenter, parallel-group, randomized, double-blind study enrolled 646 postmenopausal women with vasomotor symptoms. Subjects received either transdermal E2 50 mg/day twice weekly for weeks 14, or a combination of E2 50 mg/ day twice weekly for weeks 12 and a patch releasing E2 50 mg/ day plus NETA 140, 250 or 400 mg/day for weeks 34 of each cycle. Serum bone formation markers (alkaline phosphatase and osteocalcin) and urinary bone resorption markers (N- and Ctelopeptide) were measured at baseline, week 24 and week 52. RESULTS: The C-telopeptide/creatinine and N-telopeptide/ creatinine ratios were reduced from baseline to week 52 with the majority of the reductions occurring within 24 weeks. Mean bone formation levels decreased in all groups by week 24 and further decreased by week 52. CONCLUSIONS: A sequential E2/NETA transdermal HRT* regimen was as effective as transdermal E2 alone for exerting positive benecial effects on biochemical markers of bone resorption and formation. *trademark: ESTALIS1 SEQUI. T. Eidner, G. Lehmann, P. Oelzner, A. Muller, G. Stein, G. Hein, Department of Internal Medicine IV, Section Rheumatology & Osteology, Friedrich-Schiller-University of Jena, Germany Parameters of bone turnover provide additional information for differential diagnosis and therapy of metabolic osteopathies. Bone turnover can be assessed by biochemical markers or invasively by histomorphometry. Therefore we investigated the relationship between biochemical and histomorphometric parameters of bone turnover. In 186 patients (126 women, age 58.910.6 yr, 60 men 49.913.4 yr), who had undergone an iliac crest biopsy, we determined the excretion of desoxy-pyridinolin in urine (DPyd, HPLC, nmol/mmol Krea) as marker of bone resorption and serum osteocalcin (OC, n=126) as marker of bone formation. Included histomorphometric parameters were: osteoid surface (OS), osteoblast covered surface (ObS), tetracyclin labeled surface (TCO), mineral apposition rate (MAR), resorption surface (ES), osteoclast covered surface (OcS) and number of osteoclasts (NOc). We found a weak, but signicant correlation of OC with OS, ObS (r = 0.22, p = 0.02) und TCO (r = 0.35), but not with resorption markers or MAR. Similar correlation was found for DPyd with OcS (r = 0.20) und NOc (r = 0.20), but not with ES. DPyd also correlated with parameters of osteoblast function (OS: r = 0.27, ObS: r = 0.22). In conclusion, biochemical markers (OC, DPyd) and histomorphometric parameters of bone turnover showed only weak correlations. It has to be supposed, that either biochemical markers are only poor markers of histomorphometrically measured bone turnover or histomorphometry of iliac crest only poorly reects bone turnover of the whole skeleton.

21 (13). OVERVIEW OF THE EFFECT OF TRANSDERMAL ESTRADIOL AND NORETHISTERONE ACETATE VS. ESTRADIOL TRANSDERMAL HRT ON BONE MARKERS IN POSTMENOPAUSAL WOMEN P. Delmas1, D. F. Archer2, E. G. Luftkin3, 1Hopital Eduard Herriot, Service De Rhumatologie, Lyon, France; 2Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA; 3Department of Endocrinology, Mayo Clinic, Rochester, MN, USA OBJECTIVES: Two studies compared the effect of combination transdermal estradiol (E2) 50 mg/day, with 1 of 3 doses of norethisterone acetate (NETA) 140, 250 or 400 mg/day compared with E2 50 mg/day alone on markers of bone metabolism in postmenopausal women. METHODS: In one study, estradiol was administered continuously with NETA whereas in the other study, estradiol was administered throughout the cycle, and NETA was administered in weeks 3 and 4 of each cycle. For each study, markers of bone formation (serum bone specic alkaline phosphatase, total osteocalcin) and bone resorption (N-and C-telopeptide) were measured at baseline and weeks 24 and 52.

23 (15). THE EVALUATION OF THE EFFECTS OF CALCIUM, MAGNESIUM AND VIT D DERIVATES ON BONE DENSITY AND BIOCHEMICAL MARKERS OF BONE TURNOVER IN CASES OF POSTMENAPAUSAL OSTEOPOROSIS N. Eskiyurt, S. Akt, A. Aydogan, B. Aksac, N. Sen, G. Akyu z, A. Oncel, 1Ist. Med. Fac. Dept. of Physic. Med. and Rehabil; 2 Marmara Med. Fac. Dept. of Physic. Med. and Rehabil, Istanbul, Turkey The aim of this study is to evaluate the effectiveness of combined therapies for 12 months consisting of Magnesium (magnesium citrate 300 mgs/day); Calcium (1000 mgs/day) plus Magnesium (300 mgs/day) and Calcium plus Magnesium plus Vit. D derivate (0.50 mgs/day) on the marker of bone turnover and bone density. 45 patients of postmenapausal osteoporosis with a mean age of 56, 75,43 years and the duration of menapause 12.42.32 were randomly chosen and randomly distributed into three different therapy groups. All these patients were evaluated by blood levels, markers of bone formation (osteocalcin, bone alcalyne phosphatase) and resorbtion (deoxypridinolin, pridinolin) and bone density measurements at the beginning and the end of the treatment period.

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The result obtained at the end of 12 months showed a statistically signicant increase (p<0.001) in blood magnesium levels and a signicant inhibition (p<0.01 and p<0.05) of the markers for both bone formation and resorbtion in all groups comparing with the initial levels. Bone density measurement in lumbar spine and proximal femur at the end of 12 months revealed that the increases seen in the third group (Ca + Mg + Vit. D derivate) were signicantly higher than the remaining groups. In conclusion it can be said that the 12 months treatment program consisting of Magnesium, Calcium and Vit. D derivates is more effective in inhibiting the markers of bone turnover and the results of the bone density measurements conrm this fact.

end of puberty, the peak bone mass is nearly achieved and is considered as a major determinant of the future risk of osteoporosis. We therefore decided to study the bone formation as a function of VDR gene polymorphism in young male adolescents. Ninety-four caucasian young males (age: 1417y; Tanner's stage 25) were explored. Their serum specic bone alkaline phosphatase (B-ALP) level was measured and their VDR BsmI restriction genotype was determined. Since B-ALP levels vary according to sexual maturation and plateaus between Tanner's stages 3 and 4, adolescents at these stages of sexual maturity were preferently chosen. Furthermore, we checked that the sexual stages were equally divided among the three genotypes. The bb group (n = 33) had the highest B-ALP level (90.334.1 mg/L) and the BB group (n = 14) the lowest one (65.920.3 mg/L); the difference between the two groups was signicant (p <0.01). The Bb group (n = 48) was intermediate (BALP: 80.326.8 mg/L) and the difference between the Bb and the BB group was signicant (p <0.05). A very signicant (p <0.0001) relationship between the B-ALP serum concentrations and the BsmI genotype was observed. The present results suggest that, during the pubertal burst of growth, BB homozygotes boys have a less active bone turn-over than both bb homozygotes and Bb heterozygotes. It remains to check whether these differences in skeletal metabolism are associated with differences in peak bone mass gain.

24 (16). SHORT-TERM EFFECTS OF A NEW SYNTHETIC CONJUGATED ESTROGENS (CENESTIN) ON BIOCHEMICAL MARKERS OF BONE TURNOVER IN EARLY POSTMENOPAUSAL WOMEN P. Garnero1, R. E. Stevens2, S. A. Ayres2, K. V. Phelps2, 1SYNARC, Lyon, France; 2Duramed Pharmaceuticals, Inc, Cincinnati, OH, USA In a double-blind, placebo-controlled, single-center, clinical study, the effects of a new synthetic conjugated estrogens, A (Cenestin), were evaluated at baseline (3 measurements at day 2, day 1 and day 0), and days 30, 60 and 90 on the following biochemical markers: serum osteocalcin(OC)measured by automated immunouorescent assay(Kryptor,Cis), serum bone alkaline phosphatase by ELISA (BAP,Metra), serum N-terminal propeptide of type I collagen(PINP)by RIA (Orion), urinary Ntelopeptide of type I collagen (U-NTX) by automated ELISA (Vitros Eci, Ortho-Clinical Diagnostics)and serum C-telopeptide of type I collagen (S-CTX) by automated electrochemiluminescence immunoassay(Elecsys,Roche). Fifty healthy, menopausal women, 13 years after cessation of menses, 4065 years of age, were randomly assigned to receive either 0.625 mg/day Cenestin (n=35) or placebo (n=15). The women concomitantly received 500 mg calcium supplement and one multi-vitamin daily (200 mg calcium, 400 IU Vit D). As shown in the table, Cenestin produced a signicant decrease of bone resorption markers (UNTX and S-CTX) from days 30, 60 and 90 (S-CTX only). As expected the decrease of bone formation markers, BAP and PINP was delayed and signicant from day 60. Cenestin reduced the progression in serum OC levels observed in the placebo group by Day 30 (+16.7 vs +0.4 in placebo and Cenestin, respectively p<0.02) to Day 90 (+45% vs +7.4% p<0.0001). In conclusion, this study indicates that this new synthetic conjugated oral estrogen decreases bone turnover in early menopausal women, suggesting that this treatment may be useful for the prevention of menopausal osteoporosis.
% Change from Baseline (*p<0.05, **p<0.01 vs placebo) OC 30 days 60 days 90 days 0.4* 6.5* 7.4* BAP 6.9 12.5** 20.2* PINP 0.2 15.4** 24.5* U-NTX 31.4* 58.0* 34.1 S-CTX 34.2* 17.6** 16.9**

26 (18). LOW-FAT DIETARY INTERVENTION DECREASES ESTRADIOL BUT DOES NOT INCREASE MARKERS OF BONE TURNOVER IN POSTMENOPAUSAL WOMEN R. D. Jackson, D. Zaqqa, The Ohio State University, Columbus, OH, USA Estradiol is an important determinant of bone mineral density (BMD) and subsequent risk for fracture in postmenopausal women. Previous data suggest that both total calories and percent calories from dietary fat are predictors of estradiol (E2) and cholesterol intake may be a predictor of total hip BMD. The purpose of this study is to determine the impact of a reduction in dietary fat on E2, sex hormone binding globulin(SHBG) and markers of bone turnover in postmenopausal women. Sixteen women [57.7+5.6 yrs of age, 6.7+5.1 yrs post-menopause, body mass index(BMI) 28.7+7.7] participated in a nine month prospective study. All subjects followed their usual diet for 3 mo and were then placed on a low-fat diet using a group intervention model for 6 mo. Testing for BMI, plasma E2, SHBG, osteocalcin(OC), bone specic alkaline phosphatase(BSAP) and urinary N-telopeptide(N-Tx) was performed at baseline and 3 month intervals. Baseline dual energy xray absorptiometry (Lunar DPX, Madison, WI) was performed to determine spine and hip BMD, lean body mass and % body fat for use as covariates in analyses. Food frequency questionnaires were obtained at baseline and after 3 and 6 months of dietary intervention. The results through the rst 3 months of diet intervention are presented. The intervention was successful in decreasing the dietary fat intake of the subjects from a baseline of 42.3+7.8% to 26.7+3.8% after 3 mo of the low-fat diet. Although the diet was designed to be isocaloric, during the intervention, subjects had a signicant loss of weight (3.1+3.7kg; p<0.0007) and decrease in BMI (p<0.0005). E2 levels were 10.46 pg/ml at baseline and decreased by 24.2%. There was no signicant change in SHBG. Despite the decrease in plasma E2, the urinary N-Tx, OC and BSAP did not change signicantly with the low-fat diet. In summary, a low-fat diet can decrease plasma E2 but the magnitude of change in E2 noted in this study had no signicant adverse effect on markers of bone resorption or bone formation. Future studies are needed to determine if there is a critical level for low-fat intake or a threshold for decreasing E2 that might impact changes in bone turnover.

25 (17). BONE ALKALINE PHOSPHATASE AND VITAMIN D RECEPTOR GENE RESTRICTION POLYMORPHISM IN MALE ADOLESCENTS J. Guillemant, H. T. Le, A. Allemandou, S. Cabrol, G. Pieres, A. Raisonnier, S. Guillemant, 1Faculte de Medecine Pitie-Salpetriere, Hopital Trousseau, Paris, AFASEC, Chantilly, France The association between BMD and VDR gene polymorphisms has been studied extensively and has generated controversies. At the

27 (19). THE EFFECT OF INTRANASAL SALMON CALCITONIN THERAPY ON TARTRATE RESISTANT ACID PHOSPHATASE IN POSTMENOPAUSAL WOMEN O. Kuru1, Y. Kutlu1, A. Bedir2, A. Bilgici1, M. Tasdemir1, 1Dept. of PM&R, Ondokuz Mayis University, Medical Faculty; 2Dept. of Biochemistry, Ondokuz Mayis University, Medical Faculty, Samsun, Turkey Background and objective: Acid phosphatase is a lysosomal enzyme which is present primarily in bone, prostate, platelets, erythrocytes, and spleen. The bone acid phosphatase is resistant to L(+)-tartrate, whereas the prostatic isoenzyme is inhibited. In plasma, tartrate-resistant acid phosphatase (TRAP) originates partly from osteoclasts and is increased after oopherectomy and in a variety of bone disorders with increased turnover. Salmon calcitonin is a well known inhibitor of bone resorption. The aim of this study was to determine the value of monitoring TRAP in serum during intranasal salmon calcitonin therapy. Methods: Forty postmenopausal women aged 51.40.8 yr and had been menopausal for 4.60.2 yr without antiresorptive therapy were included in the study. They all had a BMD <1 Tscore at the spine (DEXA). All patients received intranasal salmon calcitonin 100 IU/d and calcium 1000 mg/d for six months. TRAP was measured at baseline and at the end of the study period by kinetic spectrophotometric method that uses a-naphtyl phosphate as substrate (Boehringer-Mannheim/Hitachi 747). Total serum alkaline phosphatase (tALP), serum calcium (Ca) and phosphorus (P) were also quantied by standart techniques. Results: There was a statistically signicant decrease in values of serum TRAP before and after treatment (2.490.1 and 2.080.08, respectively)(P<0.001). We couldn't nd any signicant differences in values of serum tALP, Ca and P before and after treatment (p>0.05). Conclusion: We can say that TRAP can be effectively used to assess the decrease in bone resorption in response to calcitonin.

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29 (21). COMPARISON OF FOUR BIOCHEMICAL MARKERS FOR THE ASSESSMENT OF THE EFFECT OF MENOPAUSE AND/OR THYROXINE (T4) TREATMENT ON BONE TURNOVER K. Mavroudis, F. Papandroulaki, P. D. Papapetrou, 2nd Division of Endocrinology, Alexandra Hospital, Athens, Greece Menopause and T4 are known to accelerate bone turnover. We measured serum osteocalcin (OC) and urinary free deoxypyridinoline (DPYR), the C-terminal (CTx, CrossLaps1) and the N-terminal (NTx, Osteomark1) telopeptides of collagen in double-voided morning fasting urine from 53 premenopausal (PRM) and 61 postmenopausal (POM) control women and from 70 treated with TSH suppressive doses of T4 for simple goiter (37 PRMT4 and 33 POMT4). All the patients had normal serum Ca, P, and PTH. T Test, X2 and Receiver Operating Characteristic (ROC) were used to compare the ability of the markers to discriminate among the groups. Results and conclusions. Menopause caused a signicant rise of all four markers, although more pronounced for CTx. The effect of T4 on the markers was compared before and after the menopause: Mean Z-score values for each marker were similar between T4-treated PRM and POM women; however, in the PREMT4 group Z-score of CTx was signicantly higher than NTx or DPYR. ROC analysis showed that the performance of the three bone resorption markers was generally similar with slight superiority of CTx. A highly signicant positive linear correlation was found between NTx and CTx (p<0.0001) in all four groups. 30 (22). SERUM BONE-RELATED DEGRADATION PRODUCTS FROM C-TERMINAL TELOPEPTIDES OF TYPE I COLLAGEN (bCTX) IN MEN S. Minisola1, M. T. Pacitti1, P. Caravella1, S. Barberi1, S. Dionisi1, D. Diacinti1, S. Mazzaferro1, V. Carnevale3, A. Scillitani3, E. Romagnoli2, G. F. Mazzuoli1, 1Dipartimento Di Scienze Cliniche, Universita -La Sapienza-; 2Ospedale S.G. Battista, Rome; 3 Ospedale -Casa Sollievo della Sofferenza-, S.G. Rotondo, Italy This study was carried out in order to evaluate serum levels of bCTx in normal male subjects and patients with various metabolic bone disease. We enrolled 93 normal subjects (NS), 10 patients with primary hyperparathyroidism (PHPT), 12 with established osteoporosis (OP), 6 with established osteoporosis while on alendronate therapy (OPT), 3 with humoral hypercalcemia of malignancy (HHM) and 20 with chronic renal failure (CRF, GFR values <70 ml/min). Each patient had a serum sample to measure serum bCTx (CrossLapsTM One Step ELISA, Osteometer Biotech A/S) and TRAP (by spectrophotometric assay). We found that, in NS, serum values of bCTx with age were best expressed by an exponential equation (y=6558.7e0.0184x p<0.001). There was an inverse correlation between bCTx and GFR values in the range considered (y=32329e0.0219x p<0.001). The table shows mean values 1SD of the two markers. In patients with PHPT and OP, Zscore values of bCTx (PHPT=6.86.4;OP=5.72.5) were signicantly higher than those of TRAP (PHPT=1.31.7, p<0.02; OP=1.852.8, p<0.003). Our results suggest that an increase of bone resorption might not be the main mechanism leading to bone loss with aging in males; the measurement of bCTx should not be used in patients with GFR values below 20 ml/min. In men the measurement of bCTx seems to be superior to that of TRAP in detecting subtle changes of bone turnover, especially those occurring in osteoporotic patients.
AGE NS OP OPT PHPT CRF HHM 4613 73.18.9 65.55.8 6318 48.113.4 462.6 bCTx (pmol/l) 31521581 71211968* 28841174** 96097425* 2123414192* 180824651* TRAP (U/l) 9.82.7 14.87.6* 11.11.3 13.44.6* 15.73.5* 17.96.7*

28 (20). THE RELATIONSHIP BETWEEN MARKERS OF BONE METABOLISM AND BONE ACQUISITION IN PERIPUBERTAL GIRLS: A ONE-YEAR PROSPECTIVE STUDY M. Lehtonen-Veromaa, T. Mo tto nen, K. Irjala, I. Nuotio, A. Leino, J. Viikari, 1Turku University Central Hospital; 2University of Turku, Finland The purpose of this one-year prospective study was to evaluate the association between biochemical markers of bone formation and resorption with bone mineral acquisition in healthy 155 peripubertal Caucasian girls aged 915 years. Height, weight, stage of puberty, and the amount of leisure-time physical activity were recorded. The bone mineral density (BMD) of the femoral neck, the greater trochanter, and the lumbar spine were measured by dual energy x-ray absorptiometry (DXA). Biochemical markers of bone formation in serum [osteocalcin (OC), bonespecic alkaline phosphatase (BAP), aminoterminal propeptide of type I procollagen (PINP)] and bone resorption [C-terminal telopeptide of type I collagen (CTX)] were measured. The correlation of the baseline markers of bone metabolism and one-year increase of BMD were moderate at the lumbar spine (r = 0.440.63, p<0.001), at the femoral neck (r = 0.350.47, p<0.001), and at the greater trochanter (r = 0.280.42, p<0.001). When the one-year increase of BMD (DBMD) of the femoral neck and lumbar spine were divided into tertiles, the baseline concentration of serum OC, BAP, PINP, and CTX were signicantly higher in the highest DBMD tertile than in the lowest. We conclude, that the high rate of bone turnover reected as signicantly elevated bone markers is associated with a high one-year bone gain in peripubertal girls.

* p<0.0001 vs NS; ** p<0.0001 vs OP

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31 (23). THE ACUTE BIOCHEMICAL RESPONSE OF POSTMENOPAUSAL ``BONE LOSERS'' AND ``BONE GAINERS'' TO A BOUT OF EXERCISE N. M. Murphy, R. Donnelly, K. Cashman, Waterford Institute of Technology, Waterford, Ireland; 2University College Cork, Cork, Ireland The purpose of the study was to investigate the acute effect of exercise on biochemical markers of bone turnover in postmenopausal women whose prior rate of bone loss/gain was known. Following broadband ultrasound attenuation (BUA) measurements taken at the calcaneus over an 18 month period in 60 women, 8 postmenopausal women were identied for whom BUA decreased signicantly (``bone losers'', 5.4% to 13%), and BUA increased signicantly in 7 postmenopausal women (``bone gainers'', +8.2% to +21.9%).Twenty four hour urine samples taken the day before, the day of, and the day after exercise were analysed for pyridinoline (Pyr) and deoxypyridinoline (Dpyr) crosslinks, markers of bone resorption. At these same time periods, fasting blood samples were taken for analysis of osteocalcin (bone formation).The hour-long exercise bout consisted of jumping, skipping, stepping, resistance and aerobic work. In the ``bone losers'' urinary Pyr was signicantly lower 2 days post-exercise (mean (SEM), 121(7) to 102(10) nmol/d, p = 0.004), with no change in the ``bone gainers''. Osteocalcin levels did not change in either group. Thus, exercise appears to slow bone resorption in postmenopausal women with a disposition towards rapid bone loss.
Treatment N Percent Change of CTX from Baseline 78.7 73.0 8.6

95% CI for % Change

Alendronate 40 mg/day Risedronate 30 mg/day Placebo

83 87 34

(81.0, 76.2) (75.8, 69.9) (8.9, 29.4)

33 (25). CHANGES IN BONE TURNOVER FOLLOWING OSTEOPOROTIC HIP FRACTURE IN ELDERLY MEN: THE CORNWALL HIP FRACTURE STUDY Ira Pande1, D. L. Scott2, C. Moniz2, T. W. O'Neill3, M. J. Davis1, A. D. Woolf1, 1Royal Cornwall Hospital, Truro; 2King's College, London; 3ARCUnit, Manchester, UK Aims: 1) investigate the change in bone markers following hip fracture in elderly men and 2) compare it with the normal physiological process in a control group. Methods: 100 consecutive male admissions with a low trauma hip fracture aged 50 and over were recruited as cases. Simultaneously, 100 matched controls were randomly selected from a GP register. Fasting blood and urine samples were collected for measuring bone markers [osteocalcin (OC), urinary deoxypyridinoline (U Dpd)] initially and at 6 months. In cases baseline samples were within 48 hours of the fracture. BMD was measured by DXA densitometer (Hologic QDR1000) at both the lumbar spine and femur; in cases this was within one week of fracture. Results: Fracture cases were older, had lower weight, BMI & BMD compared to controls (p<0.01). OC and U Dpd had a modest correlation with each other (rs=0.36, p<0.01). In controls, OC and U Dpd were within the normal range of the laboratory at baseline [mean(SD) OC: 8.3(6.2)ng/ml; U Dpd: 5.5(3.5)nM/nM] and 6 months. In cases U Dpd was signicantly elevated within 48 hours of the fracture [(mean(SD) 11.2(6.1)nM/nM] and exhibited a further rise at 6 months (Wilcoxon signed ranks test, p<0.01). Serum OC was within the normal range both around the fracture [mean(SD) 5.6(2.7)ng/ml] and at 6 months [mean(SD) 8.2(5.3)ng/ ml], but a signicant rise was seen between the two time points (Wilcoxon signed ranks test, p<0.01). Using multiple logistic regression there was a 40% increase in the risk of hip fracture per unit increase in U Dpd (Odds Ratio 1.41, 95%CI 1.2, 1.6). Similarly, there was a reduction in risk of fracture by 18% per ng/ml increase in OC (OR 0.82, 95%CI 0.73, 0.92). This risk/protection conferred was unchanged after controlling for age & BMD. Conclusion: Men living in community exhibit normal bone remodelling. Immediately after hip fracture changes in bone resorption marker preceede formation supporting bone remodelling & callus formation associated with healing. Continued bone loss at 6 months may argue the need to initiate anti-resorptive therapy in these individuals to reduce risk of further fractures. Raised osteocalcin is protective and elevated urinary deoxypyridinoline a risk factor for low trauma hip fracture. The risk/ protection conferred is independent of age and bone density.

32 (24). A HEAD-TO-HEAD COMPARISON OF THE EFFECTS OF FOUR WEEKS OF TREATMENT WITH ALENDRONATE OR RISEDRONATE AT THEIR PAGET'S DISEASE DOSES ON A BIOCHEMICAL MARKER OF BONE TURNOVER T. A. Musliner1, F. L. Lanza2, H. Schwartz3, B. Sahba4, D. Y. Graham5, R. Reyes1, H. Quan1, 1Merck Research Labs, Rahway, NJ; 2Houston Institute for Clinical Research, Houston, TX; 3Miami Research Associates, Miami, FL; 4California Research Foundation, San Diego, CA; 5Baylor College of Medicine, Houston, TX The nitrogen-containing bisphosphonates alendronate (ALN) and risedronate (RIS) have been approved for the treatment of Paget's disease of bone at doses of 40 and 30 mg/day, respectively. ALN has also been approved for the treatment and prevention of osteoporosis (at doses of 10 and 5 mg/day, respectively), and RIS has been studied for the same indications at a maximum dose of 5 mg/day. While no head-to-head comparisons of ALN and RIS for effects on bone mineral density (BMD) or bone turnover have been reported, observed BMD changes over a range of doses in numerous clinical trials suggest that ALN is at least as potent as RIS on a mg-for-mg basis, and also suggest that ALN 10 mg has greater efcacy than RIS 5 mg. In the present study, serum C-telopeptide of type 1 collagen (CTX; CrossLapsTM) was measured on fasting, morning serum samples obtained at baseline and day 29 in a double-blind, placebo-controlled study in which postmenopausal women (63%) or men (37%), ages 45 to 80, were randomized to 28 days of treatment with ALN 40 mg/d (n=90), RIS 30 mg/d (n=89), or placebo (PBO; n=34). The results for all subjects with both baseline and follow-up CTX values were as follows: The reductions in CTX with both ALN and RSN relative to placebo were highly statistically signicant at p<0.001. The ALN vs RIS between-treatment difference of 5.7% (95% CI 1.9, 9.5) was also highly signicant at p = 0.003. We conclude that at the recommended Paget's treatment doses administered over a 4week period, ALN is a signicantly more effective inhibitor of bone resorption than RIS.

34 (26). BONE MINERAL DENSITY IN ASTHMATIC CHILDREN TREATED WITH INHALED BUDESONIDE OR NEDOCROMIL. A 1-YEAR PROSPECTIVE, DOUBLE-BLIND, RANDOMIZED STUDY S. Pedersen, L Agertoft, Department of Pediatrics, Kolding Hospital, Kolding, Denmark The aim of our study was to compare the effect of long-term treatment with inhaled budesonide via Turbuhaler* (BUD) and nedocromil sodium (NED) pMDI on bone mineral density (BMD). Design: Randomized, double-blind, parallel group study. 91

asthmatic children (34 F, 7 11 years, Tanner stage 52) were randomized to BUD 400 mg/day for 3 months, followed by 9 months at 200 mg/day, or NED 8 mg/day for 12 months. BMD was measured with DEXA (total body) at baseline, after 7 months and one year. Utrasound (US) of the calcaneous and bone markers were measured on the same occasions. Results: No statistically signicant differences in BMD or biochemical markers were found between the two groups: Conclusion: One year of treatment with inhaled budesonide at daily doses of 2400 mg and nedocromil sodium 8mg/day had similar effects on BMD and markers of bone turnover in asthmatic children.
Estimated dierence between groups for changes (BUD-NED): BMD: Ultrasound: Total body(%) SOS (m/sec) BUA (dB/MHz) Stiness (%) Bioch. Markers: Osteocalcin (%) P1CP (%) 1CTP (%) 51.6 (95% CI: 52; +148; (p = 0.293)) 2.9 (95% CI: 17.8; +11.9; (p = 696)) 6.5 (95% CI: 16.3; +3.2; (p = 0.187)) 0.34 (95% CI:1.21; +0.52; (p = 0.433)) 6.8 (95% CI: 21.1; +7.5; (p = 0.467)) +5.7 (95% CI: 0.3; +11.7; (p = 0.06)) +2.4 (95% CI: 3.0; +7.8; (p = 0.378))

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METHODS: We have studied consecutively all patients submitted with the suspicion of osteoporosis (OP) to our unit in a three months period. We have done in all patients bone mineral density measurements using DEXA (Norland) to establish the diagnosis of osteoporosis according to HMO criteria and we have measured Ca/Cr and D-Pyr/Cr levels in a sample of 2 hours urine, after 12 hours fasting. To analyze the results between both urinary markers we have used the correlation coefcient of Pearson (r). P values <0.05 were considered signicant. RESULTS: 60 patients were studied (58 female), with a mean age of 59.910.0 (3976) CONCLUSION: We have found a positive correlation between Ca/Cr and D-pyr/Cr levels for the whole group and for patients with OP. Ca/Cr levels are a valid method for the evaluation of bone turnover in patients with OP in Primary Care.

Groups (n) Total patients (60) Osteoporosis (35) Osteopenia (12) Risk factors (13)

r (p) 0.42 0.43 0.18 0.50 (p = 0.001) (p = 0.02) (p = 0.18) (p = 0.08)

Ca/Cr 0.16+0.07 0.16+0.06 0.18+0.1 0.15+0.07

D-pyr/Cr 7.7+4.5 7.9+5.3 7.3+3.9 7.3+2.8

35 (27). THE DIURNAL RHYTHM OF 1,25-DIHYDROXYVITAMIN D L. Rejnmark, P. Vestergaard, L. Heickendorff, F. Andreasen, L. Mosekilde, Aarhus Bone and Mineral Research Group and Centre of Clinical Pharmacology, Aarhus University Hospital, Denmark Previous studies have not demonstrated a diurnal variation in serum levels of 1,25-dihydroxyvitamin D (S1,25(OH)2D). Materials and methods: 12 healthy postmenopausal women. Blood and urine were sampled with intervals for 24hs for determination of S 1,25(OH)2D and serum levels of PTH (S-PTH), calcium (S-Ca), and phosphate (S-Ph), and renal excretions of calcium (U-Ca) and phosphate (U-Ph). Results: S1,25(OH)2D exhibited a circadian rhythm (p<0.001): a decrease at night-time to a nadir in the early morning (at 4 a.m.: 9912 pmol/1), followed by a rapid increase to a plateau at daytime (peak at 4 p.m.: 11313 pmol/1) 14% above nadir level (peak vs. nadir: p = 0.004). The diurnal rhythm of S-Ph (p<0.001) varied inversely with S1,25(OH)2D (R = 0.23, p = 0.03), whereas the rhythm of U-Ph (p<0.001) correlated positively with S1,25(OH)2D (R=0.25, p = 0.002). The rhythm of S-PTH (p = 0.005) and S-Ca (p = 0.009) varied inversely (R=0.24, p = 0.02). Conclusion: By the disclosure of a circadian rhythm of S1,25(OH)2D, all major hormones and minerals related to the calcium homeostasis now have been demonstrated to shown signicant diurnal variations. Furthermore, our study shows the interrelationship between these parameters. 37 (29). DIAGNOSTIC EFFICACY OF SERUM NTX MEASUREMENTS FOR IDENTIFYING ELDERLY WOMEN WITH LOW TOTAL BODY BONE MINERAL DENSITY J. K. Scariano, R. H. Glew, P. J. Garry, R. N. Baumgartner, University of New Mexico School of Medicine, Albuquerque, NM Our previous investigations in healthy elderly women detected statistically signicant inverse correlations between serum levels of cross-linked N-telopeptides of bone collagen (NTx) and bone mineral density assessments (BMD) of the total body, lumbar spine and femoral neck regions made utilizing dual X-ray absorptiometry (DXA). In the present study we determined the diagnostic sensitivity, specicity and efciency of the serum NTx measurement for identifying women with decreased total body BMD. Serum NTx levels and DXA were performed on 196 healthy elderly women (6090 yrs). Twelve women were classied as having low BMD on the basis of a total body BMD that was 1.5 standard deviations or more below an age-adjusted mean (1.012 g/cm2) and were compared with the other 194 women with normal total body BMD. The results of a receiver operating characteristic analysis revealed that a cut-off level of more than 15.0 nMol BCE/ L for serum NTx was associated with a 100% sensitivity and 70% specicity rate for identifying women with low total body BMD. The positive likelihood ratio of an elderly woman with a serum NTx level > 15.0 nmol BCE/L who had a total body BMD 51.5 SD from their age-specic mean was 3.3. These results indicate that serum NTx measurements are a clinically sensitive tool for screening elderly women who are at risk for developing osteoporosis.

36 (28). RELATION BETWEEN BONE TURNOVER MARKERS: URINARY CALCIUM/CREATININE AND DEOXYPYRIDINOLINE/ CREATININE J. A. Ro man, C. Ferna ndez, J. Ruiz, C. Catala n, C. Vivas, L. Abad, J. Milla n, A. Fuertes, 1Hospital Universitario Dr. Peset, Valencia, Spain PURPOSE: The use of new markers of bone resorption more specic and sensitive is, in our setting, restricted to the hospital laboratories and is not available in Primary Care centers. For this reason we have analyzed the relation between the bone turnover markers available in Primary Care (urinary calcium/creatinine, Ca/ Cr) with those restricted to the hospital (Deoxypyridinoline/ Creatinine, D-pyr/Cr). 38 (30). ACUTE EFFECTS OF CALCIUM CARBONATE ON BONE RESORPTION IN HEALTHY WOMEN J. J. Stepan, V. Zikan, Department of Internal Medicine 3, Charles University Faculty of Medicine, Prague, Czech Republic The purpose of this investigation was to examine whether the load of calcium affects the calcium-parathyroid axis and to determine whether these effects are able to depress bone resorption as assessed by serum type 1 collagen cross-linked C-telopetide (Elecsys CrossLaps, Roche). Six young healthy

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COEFFICIENT OF VARIATION (% CV) S-OC Baseline 30 days 60 days 90 days 37 38 41 35 S-BAP 29 33 36 28 S-PINP 31 36 36 38 U-NTX 49 48 54 54


S-CTX 38 52 53 47

women (2327 years of age) received after overnight fasting 1000 mg of elemental calcium (as an effervescent tablet of calcium carbonate) in 250 ml of water. During the fasting period, the subjects were given only plain water. Six healthy elderly women (6369 years of age) with normal bone mineral density (BMD) received after overnight fasting either 1000 mg or/or 200 mg of elemental calcium (as an effervescent tablet of calcium carbonate) in 250 ml of water. Blood samples were collected before and during the 5 hours following the ingestion of calcium or water alone and serum ionized and total calcium, plasma intact parathormone (iPTH) and serum CrossLaps were analyzed. The load of calcium caused a signicant increase of the serum calcium and a signicant decrease of plasma iPTH and serum CrossLaps compared to baseline values. During the rst 3 hrs, the load with both 1000 mg and 200 mg calcium induced a similar decrease in serum CrossLaps. After 5 hrs, however, serum CrossLaps remained signicantly decreased only in subjects loaded with 1000 mg calcium. In conclusion, the results show that a single oral morning dose of calcium suppresses bone resorption as assessed by serum CrossLaps.

40 (32). BIOCHEMICAL MARKERS OF BONE METABOLISM AS INDICATORS OF INFLAMMATORY ACTIVITY AND BONE LOSS IN RHEUMATOID ARTHRITIS Zolta n Szekanecz, Ildiko Kova cs, Andrea Kulcsa r, Gabriella Lakos, Sa ndor Sipka, Gyula Szegedi, Third Department of Medicine, University of Debrecen Medical Center, Debrecen, Hungary Introduction and aims: High turnover collagen metabolism by osteoblasts and osteoclasts is crucial for the pathogenesis of osteoporosis and joint erosions associated with rheumatoid arthritis (RA). Here biochemical markers of bone metabolism and serum cytokine (TNFa, IL1) levels were studied and correlated with the clinical, laboratory activity scores of RA, and RA-associated bone loss. Methods: 140 RA patients were recruited for the study. Bone mineral density was determined by DEXA over one year period. Osteoblast activity was indicated by serum osteocalcin, while osteoclast function was indicated by urinary crosslink and serum CrossLaps. RA activity scores and markers included HAQ, VAS, ESR and CRP. Results, conclusions: Urinary crosslink showed the best correlation with one-year bone loss. Urinary crosslink also showed signicant correlation with ESR and CRP (RA activity markers), plus urinary calcium excretion. Serum CrossLaps was correlated with rheumatoid factor titers, thus it may be prognostic factor in RA. Determination of biochemical markers of bone metabolism may have predictive value for the outcome of RA and RA-associated bone loss.

39 (31). BIOCHEMICAL MARKERS OF BONE TURNOVER: CLINICAL STUDY DESIGN INTERSUBJECT VARIABILITY CONSIDERATION DURING 90 DAY TREATMENT OF A NEW SYNTHETIC CONJUGATED ESTROGENS (CENESTIN) R. E. Stevens, S. A. Ayres, K. V. Phelps, Duramed Pharmaceuticals, Inc., Cincinnati, OH, USA In a double-blind, placebo-controlled, single-center, clinical study, the effects of a new synthetic conjugated estrogens, A (Cenestin), were evaluated at baseline (3 measurements at day 2, day 1 and day 0), and days 30, 60 and 90 on the following biochemical markers: S-OC, S-BAP, S-PINP, U-NTX and S-CTX. Fifty healthy, menopausal women, 13 years after cessation of menses, 4065 years of age, were randomly assigned to receive either 0.625 mg/day Cenestin (n=35) or placebo (n=15). The women concomitantly received 500 mg calcium supplement and one multi-vitamin daily (200 mg calcium, 400 IU Vit D). A unique feature of this study was to house the women 48 hrs prior to baseline collection of a second AM urine void and 10 hours prior to urine collection at Days 30, 60 and 90. This was done in an attempt to reduce large intersubject variability, (approximately 50% CV or greater) associated with AM urine collections observed in published literature. Cenestin reduced the progression in S-OC levels by Day 30 (p<0.02) to Day 90 (p<0.0001). The decrease in S-BAP and S-PINP was delayed and signicant from day 60. Cenestin produced a signicant decrease in U-NTX and S-CTX from days 30, 60 and 90 (S-CTX only). As shown in the table below, the housing prior to AM urine collections did not appear to reduce the inherent intersubject variability associated with measurement of bone markers. Cenestin was effective in reducing bone turnover in menopausal women.

41 (33). DISASSOCIATION OF BONE/MUSCLE RATIO IN LATE POSTMENOPAUSAL WOMEN IMPLICATIONS OF BIOCHEMICAL BONE MARKERS G. Trovas, G. R. Skarantavos, P. Raptou, A. Galanos, G. P. Lyritis, Laboratory for the Research of Musculoskeletal System, Athens Univ. KAT Hospital, Kissia, Greece INTRODUCTION: Bone mass decreases with aging and a considerable body of data implicates the secondary hyperparathyroidism and increased indices of bone turnover at least in part, the cause of the slow, age-related bone loss. Bone strength depends not only on the bone mass but also on the material quality and spatial distribution of this material (geometry). Although there is a lot of data about bone mineral density measured using dual-energy x-ray absorptiometry (DXA) method, there are no clinical data on the consequences of this age-related secondary hyperparathyroidism on the geometrical parameters of long bone and musculo-skeletal balance. In this study the muscle and bone cross-sectional area, along with different geometrical properties of the lower leg have been evaluated non-invasively by means of a new pQCT machine, in a group of postmenopausal women.

MATERIALS AND METHODS: 34 women, osteoporotic by DXA, were measured at the lower leg with a XTC 2000 (Stratec Medizintechnik Pforzheim, Germany). These women were divided in two groups according to their postmenopausal status: early postmenopausal women within 10 years of menopause (mean age SD = 53.84.2) and late postmenopausal women 10 years since menopause and over (mean age SD = 62.57.5 years). The distal end of the tibia and bula and other bone parameters, have been measured at 14%, 38% and 66% of the tibia length, proximal to this point. At the 66% site the maximum muscle cross section is measured to obtain an estimate for muscle force. RESULTS: In comparison with the early group, the late postmenopausal women have had increased levels of PTH and other biochemical indices of bone turnover. The cross-sectional area of muscle was higher in late than early postmenopausal women but the cross sectional area of cortical bone and the ratio of cortical bone to muscle cross sectional area was signicantly lower in the late postmenopusal women indicating that they had fewer bone per unit muscle area than early postmenopausal. By visual inspection of the graphical plot of the data, all women as a group presented a downward, as well as leftward displacement and in the regression analysis by group, there was a mild but signicant relationship, between muscle and bone cross sectional area in early postmenopausal women but not in late, indicating an impairment in the relationship between muscle and bone crosssection. In the early postmenopausal women a highly signicant relationship was found between muscle cross-sectional area at the 66% site and cortical bone area at 14%, 38% and 66%. In contrast no signicant relationship was revealed in the late postmenopausal women. At the 66% site cortical and subcortical bone content and area, as well as cortical thickness were signicantly reduced in the late compared with the early postmenopausal women. This pattern was the same and at the other measurment sites although not always reaching statistical signicance.

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43 (35). BONE TURNOVER MARKERS: DO THEY EXPLAIN RISK ASSOCIATED WITH PREVIOUS FRACTURE? THE EPOS STUDY P Vergnaud, M Lunt, C Scheidt-Nave, G Poor, G Parisi, K Hoszowski, A Lopes Vaz, D M Reid, L Benevolenskaya, S Grazio, K Weber, T Miazgowski, J Stepan, P Masaryk, A Martin, J Walton, F Galan, J Bruges, R Lorenc, S Havelka, R Perez, M Seibel, G Armbrecht, D Felsenberg, A Silman, J Reeve, P D Delmas,] 1IPH, Cambridge, UK Background. In EPIDOS markers predicted hip fractures signicantly after adjusting for low bone density (BMD). Previous fragility fractures (fr) are associated with elevated risk of new fractures independently of BMD. In the European Prospective Osteoporosis Study (EPOS) a prevalent spine fracture increased risk of a subsequent spine fracture 3.612 fold according to its classication (wedge, crush) in men and women aged 5080, after adjusting for BMD. We have now examined the possibility that after fracture, marker levels track with this BMD-independent, unexplained element of elevated fracture risk. Methods 189 incident cases of spine or non-spine fracture were each matched by age, sex and study centre with 2 randomly assigned controls who had never fractured and 1 case of fracture pre-recruitment who had no subsequent fracture in a mean 3.7 years of follow up. Analyses were performed blind, in one centre, in end-of-study samples of: serum osteocalcin, bone-specic alk phos, CTS, total alk phos, serum creatinine, calcium, phosphate and albumin; urine CTX. Most subjects had hip DXA. Results BMD was reduced in spine but not peripheral fr cases. Case-control analyses showed no statistically signicant effect (P>.18) of recent fracture on any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (P<0.05; bone sp alk phos trend similar but NS). This effect was not BMD-related. The study had an a postiori power of at least 95% to detect a difference of 0.2 population SDs between cases and controls for all markers. Conclusions Spine & peripheral fracture risk factors differed. Peripheral fractures in the last 3.7 years were associated with reduced bone formation markers. For spine, high risk of future fracture is partly related to low BMD and partly to other factors, perhaps biomechanical, which relate more closely to previous radiological fracture than to BMD or to persistent, generally altered bone remodelling.

42 (34). MECHANICAL LOADING AND CALCITONIN: IS THERE ANY EARLY BIOCHEMICAL RESPONSE VIA NITRIC OXIDE AND CYTOKINES IN POSTMENOPAUSAL WOMEN? S. Tu zu n, M. Aslanhan, G. Gu lbaba, A Dirican, F. Tu zu n, 1 University of Istanbul, Cerrahpasa, Istanbul, Turkey; 2University of Istanbul, Cerrahpasa, Istanbul, Turkey; 3RIA Lab Sisli, Istanbul, Turkey; 4University of Istanbul, Cerrahpasa, Istanbul, Turkey; 5 University of Istanbu, Cerrahpasa, Istanbul, Turkey An accelerated bone loss results from estrogen deciency in the rst 5 or 10 years after menopause and this appears to be the main pathogenetic factor in postmenopausal osteoporosis. A large number of immune and hemopoietic factors have been shown to be responsible for this stage. The aim of this study was to assess the early response of biochemichal determinants whose effects on bone mineral metabolism are getting apparent such as nitric oxide (NO), interferon-gama(IFN-g), interleukin 1beta (IL 1- b), tumour necrosis factor-alpha (TNF-a) and tartrate resistant acid phosphatase (TRAP). 45 postmenopausal healthy women aged between 38 and 55 were randomly divided into three groups. First group were applied aerobic exercise (treadmill in 5 kms/h velocity) and 500 mg elementary calcium, second group were given 200 IU intranasal calcitonin and calcium and third group were given calcium only, for ve days. Serum levels of NO, IFN-g, TNF-a, IL 1- b and TRAP were measured at baseline, at the 2nd and 5th day. We found NO, IFN-g and TNF-a as increased whereas IL1-b decreased at the 2nd and 5th day in all groups. TRAP remained in its initial value in all measurements. Increased NO and IFN-g levels accompanied by decreased IL1-b suggest that bone formation could be stimulated in the early stage of exercise, calcitonin and also calcium treatment.

44 (36). GUIDELINES ON PREANALYTICAL CRITERIA FOR THE MEASUREMENT OF PYRIDINOLINE AND DEOXYPYRIDINOLINE AS BONE RESORPTION MARKERS IN URINE H. W. Vesper1, L. M. Demers2, R. Eastell3, P. Garnero4, M. Kleerekoper5, S. P. Robins6, A. K. Srivastava7, J. L. Pettis7, G. R. Warnick8, N. B. Watts9, G. Myers10, 1Centers for Disease Control and Prevention, Atlanta, GA, USA; 2Milton S. Hershey Medical Center, Hershey, PA, USA; 3Northern General Hospital Shefeld, U.K.; 4INSERM Unite 403, Lyon, France; 5Wayne State University, Detroit, MI, USA; 6The Rowett Research Institute, Aberdeen, UK; 7 VAMC, Loma Linda, CA, USA; 8Pacic BioMetrics Research Foundation, Seattle, WA, USA; 9Emory University, Atlanta, GA, USA; 10Centers for Disease Control and Prevention Atlanta, GA, USA Variability in pyridinium crosslinks measurement due to preanalytical factors highly affects the reproducibility, comparability and interpretation of results. Preanalytical factors comprise diet, exercise, bed-rest, pregnancy, menstruation cycle, certain diseases and medications, age, gender and race as well as sample collection, storage and treatment and creatinine measurement. Based on a thorough literature review from a working group established by CDC, guidelines will be presented that cover the topics mentioned above to standardize patient status prior to sample collection, and to standardize sample collection

Thursday, June 15, 2000

procedures. Interfering diseases and medications are described. Also, information to establish reference values is provided.

lter mimicking human characteristics. The aim of this study was to evaluate the effectiveness of the EP for monitoring the stability of an ultrasound device and to verify its association to conditions in vivo. Malfunctions (e.g., loss of signal amplitude of different degree of severity at the reception stage) of UBIS5000 (DMS, France) were simulated. Series of measurements on the EP and on ve volunteers were performed at each grade of malfunction. The results were than compared to the baseline (0 dB, equivalent to a stable device) in order to quantify: (a) the sensibility of the EP in detecting device related problems; (b) the impact of those simulations in vivo. The EP was found as sensitive as volunteers to small variations of gain but with different amplitude (see graph). A ratio between measurements in vivo and in vitro of 1:6 was found. Conclusion: The loss of signal amplitude reects the type of malfunction likely seen on the transducer. The fact that the electronic phantom is as sensitive to the simulations as measurements in vivo allows us to propose this type of phantom as a good potential alternative to commonly used external phantoms.

45 (37). BIOCHEMICAL BONE MARKERS AS INDICATORS OF DIFFERENT BONE CELLS FUNCTIONS IN OSTEOPOROSIS I. P. Yermakova, I. A. Pronchenko, V. P. Buzulina, I. E. Borodulin, Research Institute of Transplantology and Articial Organs, Moscow, Russia The goal of the study estimation of bone cells functions in osteoporosis of different genesis by several biochemical bone markers. Markers of osteoblast [bone alkaline phosphatase (bALP), osteocalcin (OC)], carboxiterminal propeptid of type 1 procollagen (C-pr)] as well as osteoclast function [tartratresistant acid phosphatase (bACP)] and resorption rate [urine deoxypyridinolin (UDPYD/UCr)], were estimated in 18 postmenopausal (OP) and 23 women following kidney transplantation (KT), showing osteoporosis. T-score analyses data presented in table 1 (M SE). Data suggest osteoclast activation, increase of resorption rate and decrease of osteoblast collagen production in both groups as well as differences in other osteoblast functions. There were discrimination power between different osteoblast functions in both kind of osteoporosis as well as between resorption rate and all osteoblast functions in OP.


H. Andersen1, J. T. Jrgensen1, A. B. Helboe1, N. H. Bjarnason2, Pronosco A/S, Vedbaek, Denmark; 2CCBR, Ballerup, Denmark

bALP U/L OP KT 0.90.5@ 3.10.5*

OC ng/ml +1.50.26@ 0.50.2

C-pr ng/ml 1.30.2& 0.80.3

UDPYD/Ucr 3.40.75# 4.10.36

bACP V/I 0.70.2 2.40.8

@ P<0.01 vs KT; # P50.05 vs bALP, OK, C-pr; & P<0.01 vs bALP, OC; * P <0.01 vs OC, C-pr.

Bone Mass Density

46 (38). QUALITY CONTROL IN ULTRASOUND: ELECTRONIC PHANTOM VERSUS MEASUREMENTS IN VIVO I. Alekxandrova, D. Hans, D. O. Slosman, Nuclear Medicine Division, Geneva University Hospital, Switzerland Quality control is crucial to check the long-term stability of ultrasound devices. Strict acquisition protocol is required to assure the reliability of the data when using external phantoms. As an alternative to those phantoms, an internal electronic phantom (EP) has been proposed. It represents an electronic

The purpose of this cross-sectional study was to investigate the ability of the X-posure System to discriminate between postmenopausal women with and without vertebral fractures. Based on a plain radiograph of the hand and forearm the X-posure System estimates BMD using the Digital X-ray Radiogrammetry (DXR) technology. A total of 619 women with a mean age of 73 years, range 5580, where included in the study. Lateral radiographs of the thoracolumbar spine were acquired in all women and assessed for vertebral fractures using quantitative morphometry. The fractures were grated from 0 (normal) to 3 (severe) by an experienced radiologist. Spine DXA BMD was measured in the lumbar spine (L1-L4). Using logistic regression to model the relation between the binary response variable (normal or deform lumbar vertebrae) and age as well as DXR BMD or DXA BMD spine results in the following odds ratios (OR):
Cut off score 51 Group DXR BMD Spine BMD N 619 616 OR [95% C.I.] 1.5 [1.1 1.9] 1.2 [0.9 1.5] P value 0.006 0.22 Cut off score 54 N 546 546 OR [95% C.I.] 2.9 [1.46.1] 2.6 [1.54.7] P value 0.004 0.001

Our data show that DXR BMD has a discriminatory ability, which is at least equivalent with spine BXA BMD. This conrms the properties of DXR BMD as a reliable estimate of bone mass. Because DXR BMD uses another measurement site it does not have the constraints known for spine DXA in the elderly, such as osteophytes and lumbar fractures. In conclusion, the data indicate that DXR BMD may be advantageous in elderly, which has a particularly high risk of osteoporosis.

48 (40). ULTRASOUND BONE PARAMETERS IN CHILDREN WITH ASTHMA RECEIVING INHALED FLUTICASONE PROPIONATE M. Bayer1, J. Novak2, V. Derner3, 1Dept. of Paediatrics, Ist Medical Faculty Prague; 2Children's Dept. of Litomysl Hosp.; 3Inst. of Clin. love , Czech Republic Immunol. and Allergology, Hradec Kra Aim of study To nd relation of the bone ultrasound parameters to both cumulative dose and lenght of inhaled steroids therapy.

Methods Anthropometric parameters and laboratory investigations were performed three times in nine months intervals in the group of 55 asthmatic children and adolescents (age range 417 years) treated continuously with inhaled uticasone propionate (FP). Calcaneal ultrasound bone parameters were measured simultaneously using ultrasound bone analyser CUBA McCue. Obtained values of broadband ultrasound attenuation (BUA) and velocity of sound (VOS) were expressed as Z-score using reference group of 818 measurements in healthy Czech pediatric population aged 418 years. Results Growth rate as well as biochemical markers in serum (calcium, phosphorus, alkaline phosphatase, cortisol) and urine (minerals and cortisol in 24 hours urine collection) were within normal limits. Signicant decrease of BUA and VOS Z-score is related to cumulative dose of 100150mg/year and 50100mg/ year of FP, respectively /p<0.04; p<0.006/. These values correspond to average daily dose of 200mg. The signicance subsequently increases with dosing. As for the effect of lenght of therapy, the mean borderline lies in the interval of 2325 months for BUA and 1517 months for VOS, respectively /p<0.001; p<0.043/. Both parameters further decreased to following mean levels: BUA= 1.941; VOS= 1.569 /p<0.001/ after 3050 months of therapy. Conclusions Despite of the fact that laboratory markers are unaffected, inhaled FP at average dose about 200ug/day have measurable adverse effects on bone in asthmatic children and adolescents already after 15 months of treatment. VOS seems to be an early ultrasound sign of negative bone response to FP treatment. Thus, new higher potency inhaled steroids as FP seem to have also increased systemic side effects. We consider ultrasonometry to be a useful tool for bone status monitoring in asthmatic children treated with inhaled corticosteroids.

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50 (42). FOREARM BONE MINERAL DENSITY (BMD) BY AGE AND SEX IN A GENERAL POPULATION G. K. R. Berntsen1, V. Fnneb2, A. Tollan3, A. J. Sgaard4, J. H. Magnus5, 1Univ of Troms, Norway; 2Univ of Troms, Norway; 3 Central Hospital, Hamar, Norway; 4Univ of Oslo, Norway; 5Univ of Troms, Norway Population based studies of the adult life-curve of forearm BMD are few, and standardised reference values are lacking. We invited all men aged 5574, women aged 5074 and 510% samples of other age groups aged 25 or more years, living in Troms (response rate 80.3%). Subjects had BMD measured by SXA at distal and ultradistal forearm sites. BMD was standardised to the European Forearm Phantom, so our values are comparable to similarly standardised results. Distal mean BMD:

Women Age 2529 3039 4049 5059 6069 7074 75+ N 86 220 182 1869 1461 594 68 Mean,g/cm2(SD) 0.476 0.483 0.472 0.446 0.383 0.354 0.327 (0.042) (0.045) (0.050) (0.057) (0.068) (0.066) (0.074)

Men N 52 122 115 836 1311 509 59 Mean,g/cm2(SD) 0.587 0.592 0.579 0.566 0.542 0.513 0.485 (0.050) (0.047) (0.053) (0.059) (0.068) (0.076) (0.095)

There was a slight BMD decline before 50 years in both sexes. From age 50 the annual BMD-decline was 0.6% in men and 1.3% in women. Male BMD-decline was stable throughout senescence, but in women the decline decreased to 0.7% around 65 years of age. The eect of menopause on BMD-levels seemed to wane o in the late post-menopause. Exclusion of 2441 subjects with bone related disease and/ or medication did not aect the overall BMD-life curve.

49 (41). COMPUTING STANDARDISED BONE MINERAL DENSITY WITH THE LUNAR EXPERT M. N. C. Beneton, J. Robinson, A. Dey, K. Kayan, J. A. Kanis, E. V. McCloskey, University of Shefeld, UK We wished to determine whether published algorithms for deriving standardised BMD (sBMD) applied to the Lunar Expert densitometer. In a multicentre osteoporosis study, the European Spine Phantom (ESP) was sent to each of 5 centres operating a total of 6 densitometers (Hologic QDR2000, n=3; QDR1000, n=1; Lunar DPX-L, n=1; Lunar Expert, n=1). At each, the ESP was measured 10 times as a patient without repositioning. The measured vertebral areas were larger using the Lunar Expert (LE) than the other equipment. All data was subjected to nonlinear regression using the published asymptotic model (1). Unlike the other equipment, the LE measurements failed to achieve convergence using this model. Using curve estimation, the best t for the LE data was provided by a cubic model: sBMD = 0.6568BMDLE+0.5124 (BMDLE)20.2218 (BMDLE)3; r2 = 1.000. Measured values for the ESP before and after adjustment were: 51 (43). BONE MINERAL DENSITY OF ELDERLY WOMEN WITH SCOLIOSIS AND/OR SPONDYLOLISTHESIS is, Y. Yapici, O. Cimen Bo lgen, G. Sahin, A. Bic er, H. Gu ler, S. Bag C. Erdogan, Department of PMR, Mersin University, Faculty of Medicine, Mersin, Turkey The aim of this study was to assess the possible effect of scoliosis and spondylolisthesis on bone mineral density (BMD) of elderly women. Thirty seven female patients (mean age 63.275.64) with scoliosis and/or spondylolisthesis (17 scoliosis, 20 spondylolisthesis) were included in the study. Thirty seven female patients (mean age 60.625.64) without scoliosis or spondylolisthesis formed the control group. BMD of lomber spine and femur (neck) was evaluated by DEXA. Scoliosis and spondylolisthesis was evaluated by direct radiographic techniques. There was no signicant difference between groups regarding age, years since menopause, body mass index, number of childbirth and lomber spine BMD. Femoral (neck) BMD of patients with scoliosis and/or spondylolisthesis was signicantly lower, compared to the controls (p<0.001). As a result, we can say that, scoliosis and spondylolisthesis may increase lomber spine BMD of elderly women. However, the numbers of patients were low, existing data is preliminary and longterm studies with double blind controlled are needed.

Low BMD BMD sBMD 0.5690.008 0.4990.008

Medium BMD 1.0540.013 1.0020.013

High BMD 1.6820.031 1.4990.016

We conclude that published algorithms for sBMD do not apply to the Lunar Expert but cubic non-linear regression allows derivation of sBMD. (1) Pearson et al, Osteoporosis Int 1995;5:17484.

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52 (44). EFFECT OF LOWER EXTREMITY AXIS DEVIATION ON BONE MINERAL DENSITY OF PROXIMAL TIBIAE E. Czerwinski, R. T. Kukielka, K. Nowak, Department of Orthopedics of Collegium Medicum of, Jagiellonian University, Krakow, Poland Bone densitometry is currently widely used method for estimation of bone mineral density in many various bone metabolic diseases, particularly in osteoporosis. Nowadays a whole body devices are disposable to evaluate measurements of bone mineral density in any point of the skeleton. That allows to make analysis of different local bone disorders for example diagnosis and monitoring of Sudeck atrophy as well as evaluation of total hip arthroplasty in estimation of bone mineral density in proximal tibia in lower extremity axis deviations. Group of 30 women and men in age 1572 (average 46) were admitted to Orthopaedic Department because osteoarthritis due to lower extremity axis deviations on the knee level with both valgus and varus deformity. All patients were qualied for high tibial osteotomy. For preoparative planning bone density was measured in lumbar spine, femoral neck and proximal tibia on ROI (region of interest). We analysed 3 ROI lateral, middle and the medial side. Results were expressed in g/cm2. Anthropometric measurements of low extremity axis deviation were performed by using Metrecom (Faro). Before operation long standing X-ray (goniometry) was also measured. Results were compared to the control group of 20 patients with normal limb axis. Increased bone mineral density was found on the side of overweighted compartment in comparison to the opposite side in all patients. These differences were not observed in control group. The coefcient (ratio of bmd in overweighted compartment to bmd in opposite side) ranged from 1.2 to 24.5 (SD 5.7), while in control group the ratio was from 0.95 to 1.4 (SD 0.15). It seems that increased pressure for the compartment is bound with increased bone mineral density of the side of proximal tibia. We found strong correlation between differences of bone mineral density in compartments and angle of lower extremity axis deviation. The possibility of application bone mineral density method in prognosis of course osteoarthritis as well as outcome of high tibial osteotomy were discussed.


54 (46). THE EFFECT OF BONE LOADING EXERCISE ON BROADBAND ULTRASOUND ATTENTUATION (BUA) IN PREAND POSTMENOPAUSAL WOMEN R. Donnelly, N. M. Murphy, Waterford Institute of Technology, Waterford, Ireland The purpose of the study was to monitor changes in BUA with exercise (9 months) & following a further 9 months of detraining. 63 menopausal women were chosen from 200. Exercise (ex.) & control (ctrl.) groups were matched on a ratio of 2:1. BUA measurements were taken at 0,9 &18 months (CubaClinical machine). The exercise regime involved high impact bone loading. No signicant differences existed between ex. & ctrl. groups for age, years since menopause, initial BUA, body mass, height or %body fat (p>0.05). Following the 9 month intervention, muscular strength improved for 6 of the 7 exercises performed in the ex. group with no change in ctrls. (p<0.05). The subjects in the ex. group with the lowest initial BUA had the most positive BUA change with exercise (p = 0.011). In the ex. group there was a signicant increase in %BUAchange between 0&9 months mean (SD) (8.8 (11.4)%), a signicant decrease between 9 & 18 months (3.8 (7.6)%) amounting to an overall % increase in BUA of 4.5 (13.2). Percentage BUAchange between 0&9 months & 9&18 months was also signicant in the ctrl. group (p<0.05), but BUAchange between 0&18 months was not signicant. No signicant differences existed between ex. & ctrl. groups for BUA measured at 0, 9&18 months (p>0.05). Menopausal status, HRT use or calcium intake had no signicant effect on BUAchange. The variability of BUA is so large relative to the expected changes due to exercise that it is difcult to observe between group differences. If ultrasound is to be of use in future exercise intervention studies, the precision of the instruments must be improved, or large subject numbers recruited.

53 (45). 3-DIMENSIONAL EVALUATION OF BONE STRUCTURES OF THE HUMAN FOREARM IN VIVO M. A. Dambacher, M. Neff, R. Kissling, P. Ru egsegger, 1University Clinic Balgrist and Center for Osteoporosis, Zurich, Switzerland; 2 Federal Inst. of Technology Zurich, Switzerland So far only bone mass was available quantitatively. Bone structure was analyzed qualitatively with the help of high resolution 2D CT images (hpQCT Densiscan 1000, Scanco Ltd. Zurich). Recently real 3D examinations became available in vivo and it is now possible to characterize quantitatively patients with such microarchitectural features as trabecular number, trabecular thickness, trabecular spacing and relative bone volume. We expect that such a characterization will give new insights in pathogenesis and treatment of osteoporosis and might improve predictions of individual fracture risk in normal subjects as well as in osteoporotics, in osteomalacia, b-thalassaemia, primary and secondary hyperparathyreoidism, in osteogenesis imperfecta and in anorexia nervosa. As an example we present here normal 3D structures in the radius. ``Exploted'' view of trabecular and cortical bone.

55 (47). CROSS CALIBRATION OF FAN BEAM AND PENCIL BEAM DUAL ENERGY X-RAY ABSORPTIOMETERS W. D. Evans, J. C. Martin, K. T. Rajan, 1University Hospital of Wales, Cardiff; 2Dewi Sant Hospital, Pontypridd, Wales, UK The purpose of this study was to investigate the effect on bone Area, Bone Mineral Content (BMC) and Bone Mineral Density (BMD) of upgrading from a QDR1000 pencil beam densitometer to a QDR4500 fan beam device (Hologic Inc., Waltham, MA). Lumbar spine (LS) and total hip scans were performed on 128 patients (10 male) on both machines. Patient age and body mass index (BMI) ranged from 24.9 to 82.7 years and 17.4 to 50.2 kg/m2 respectively. For the LS, mean values of all three variables were

smaller for the QDR4500; this was also true for hip Area and BMC but hip BMD was greater compared with the QDR1000. Linear regression analysis of fan beam data against pencil beam data gave intercepts that were not signicantly different from zero, with the exception of LS Area. Forcing the regression lines through the origin gave slopes in the range 0.94 to 1.03 and r2 values in the range 0.73 to 0.94. These slopes can be used as cross calibration factors. Bland-Altman analysis revealed that differences between corresponding variables measured on the two machines were not signicantly associated with the mean values. The differences in all three LS variables were negatively correlated with BMI while the difference in hip BMD was positively correlated. The other hip variables showed no signicant dependence on BMI. The study conrms that cross calibration factors vary between measured variables and anatomical sites, and that differences are dependent on body size.

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total of the hip was not signicantly different (0.920.15 g/cm2) but men had higher values (0.950.15 g/cm2) than women (0.870.14 g/cm2). The correlation between total hip in lumbar spine was r = 0.364 (p<0.01). Patients with AS and radiological changes of the lumbar spine (n = 135) had lower BMD total values of the hip (0.9190.15), or ward triangle (0.563 g/cm2 p<0.01) than patients without disease specic changes of the lumbar spine (hip 0.9410.15 g/cm2 ward 0.667 g/cm2 respectively). The same applies for patients with radiological changes of the thoracic and cervical (n = 99) spine. These data show that patients with AS present with BMD total of the hip which correlates signicantly with radiological changes of the lumbar spine.

58 (50). COMPARISON OF 3 PERIPHERAL BONE DENSITY MACHINES TO CENTRAL DEXA M. Gass, M. Ferna ndez, E. Silberstein, L. Levin, University of Cincinnati, Cincinnati, OH, USA 245 Caucasian women referred for bone density testing were scanned with the Lunar PIXI, the Lunar Achilles, the Schick nger DEXA, and the Lunar DPX-L. Mean age was 578 yrs, range 41 to 81 yrs. Using the lowest density lumbar vertebra and Ward's triangle as reference sites, sensitivity (Ss) and specicity (Sp) were assessed for each densitometer using a T score of 1 SD as the cutoff on the peripheral scan to identify women with a T score cutoff of 2 SD at the spine and hip.

56 (48). BONE DENSITY MEASUREMENTS IN PRIMARY CARE: COMPARISON BETWEEN PIXI AND BUA IN OS CALCIS C. Ferna ndez, L. Abad, A. Fuertes, J. Milla n, J. A. Roman, Hospital Universitario Dr. Peset, Valencia, Spain PURPOSE: Previous studies have demonstrated that PIXI heel scan can be used for screening for osteoporosis. We have conducted this study to compare the results of bone mineral density (BMD) measurements using PIXI bone densitometer and Bone Ultrasound Attenuation (BUA), both in os calcis. METHODS: 50 postmenopausal women (mean age: 61 years, range: 4080) attending a Primary Care (PC) clinic for different causes were selected for bone density studies. BMD measurements were performed using a PIXI bone densitometer (Lunar) and BUA, both in os calcis. RESULTS: BMD results using PIXI were: normal in 16 (32%), osteopenia in 19 (38%) and osteoporosis in 15 (30%) and with BUA: normal in 12 (24%), osteopenia 27 (54%) and osteoporosis 11 (22%). The Pearson's correlation coefcient between both techniques was r = 0.777 (p = 0.000).

Densitometer Finger DEXA Heel DEXA Heel Ultrasound

Lumbar: Ss 57% 52% 78%

Sp 87% 85% 62%

Wards: Ss 59% 57% 83%

Sp 87% 84% 60%

To approximate 90% sensitivity with the peripheral scan the specicity dropped to an average of 41%, range 3152%:

PIXI Normal BUA Normal BUA Osteopenia BUA OP Total 9 7 0 16 3 12 4 19

PIXI Osteopenia 0 8 7 15

PIXI OP 12 27 11


Densitometer Finger DEXA Heel DEXA Heel Ultrasound

Lumbar: Ss 90% 90% 90%

Sp 37% 39% 40%

Wards: Ss 90% 90% 90%

Sp 37% 38% 48%

Chi-square: 19.35; P=0.000. OP: osteoporosis.

DISCUSION: We have found a relation between both BMD measurements in os calcis. BUA could be useful in the screening of postmenopausal osteoporosis in Primary Care.

Given the low sensitivity that results when a T score of 1 SD is used as the cutoff for peripheral densitometers and given the low specicity when 90% sensitivity is achieved, it is recommended that guidelines be developed for cost effective use of the peripheral densitometers.

57 (49). THE RADIOLOGICAL CHANGES IN PATIENTS WITH ANKYLOSING SPONDYLITIS INFLUENCES BONE DENSITOMETRY H. Franck, Th. Meurer, Center of Rheumatology, Oberammergau, Germany Bone densitometry in patients with ankylosing spondylitis (AS) is controversly discussed in respect to different densitometry techniques. In addition, specic radiological changes in AS as syndesmophytes, impair the interpretations of bone densitometry (BMD). The purpose of our study was to examine BMD in patients with AS depending on radiological staging of the lumbar, thoracic and cervical vertebra. We measured 165 patients with AS, 116 men (mean age 50.511.4 years) und 49 women (mean age 50.211.8 years) with DEXA (QDR 4500 A). BMD of the lumbar spine did not differ in comparison to age matched controls. BMD

59 (51). EFFECT OF SOCIO-ECONOMIC STATUS ON TIBIAL SPEED OF SOUND (tSOS): A MULTICENTER, CASE-CONTROL STUDY IN URBAN AREAS IN TURKEY ncel2, M. Eryavuz3, O. Peker2, S. Y. Go kce-Kutsal1, F. Inanici1, S. O k3, 1Hacettepe University, Ankara; 29 Eylul University, Izmir; O 3 Istanbul University, Istanbul, Turkey The purpose of this study was (1) to evaluate the possible risk factors of low tSOS, which determines cortical bone status, among residents of urban regions in Turkey, and (2) to compare groups of different socio-economic status (SES). A total of 1026 subjects (649 women, 377 men) between 4070 years old from 3 large cities were included in the study. The subjects were all volunteers from two different SES regions of the cities, which were selected randomly according to zip codes. Risk factors of osteoporosis were determined using European

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Vertebral Osteoporosis Study Questionnaire, and the bone status was screened by tSOS. Multivariate logistic regression analysis was used for risk assessment. Age, menopause, physical inactivity, SES and multiparity were the major determinants of low tSOS in females. Major risk factors in male were age and low SES. Tibial SOS was found lower in females than males and in low SES group than high SES group (p<0.001). Besides the well-known risk factors such as age, gender and menopause, low SES was found to be among the major risk factors of low tSOS in our population (Odds Ratio 0.39, %95 condence interval 0.260.58). We concluded that SES was an important determinant of cortical bone status. Additionally, our results conrmed the correlation between tSOS and the clinical determinants of bone mass. Therefore, we propose tSOS as a useful method for screening bone status especially for research trials involving normal control groups.

The study used a balanced design with each participant having 3 radiographs taken with repositioning of the hand and forearm in between each capture. Two groups of females where studied, one consisting of 20 pre-menopausal women, ages 3040 years, and one of 20 post-menopausal women age 565 years. The short-term precision errors were calculated as root-mean-square averages of standard deviations of repeated measurements and expressed as the coefcient of variation (CV) with the corresponding 90% condence intervals. The mean age of the premenopausal women was 35.2 years, and the mean DXR BMD was 0.578 g/cm2 (SD=0.0039 g/cm2). The mean age of the postmenopausal women was 68.2 years, and the mean DXR BMD was 0.489 g/cm2 (SD=0.0030 g/cm2). The CV in the pre-menopausal group was 0.68% with a 90% condence interval of 0.57% 0.83%. The CV in the post-menopausal group was 0.61% with a 90% condence interval of 0.52%0.75%. In conclusion, the present study shows that the short-term in vivo precision error of the DXR technology is very low in both pre- and postmenopausal women. When the results of the study are compared to data reported in the literature, the performance of the DXR technology seems to be at least equivalent with DXA.

60 (52). OSTEOPOROSIS IN LIVER-TRANSPLANTATION: DIAGNOSIS, PREVENTION AND THERAPY M Hommann1, K Abendroth2, U Schotte1, R Voigt1, A Kornberg1, J Scheele1, 1Department of Surgery; 2Department of Medicine, FSU, Jena, Introduction: In liver transplantation osteoporosis becomes a rising problem. Since graft survival is getting prolonged over the last years the problems of immunosuppression and its side effects are growing, e.g. the corticoid induced osteoporosis. The effect is potentiated because of the already existing osteopenia due to hepatic disease. Patients and methods: Our diagnostic schedule of osteoporosis includes X-Ray and measurement of the bone mineral density (DXA/lumbar spine and proximal femur, pQCT/ultradistal radius). We established a protocol for diagnosis, prevention and therapy of osteoporosis in Transplant-patients. Before and 3, 6 and 12 months after transplantation we examine the bone mineral density by DXA and pQCT. In prevention and therapy of the osteoporosis we randomize our patients into two groups. Group 1 receives basic therapy with calcium (1g) and vitamin D (1000 E), group 2 calcium (1g), vitamin D (1000 E) and bisphosphonates (2 mg Ibandronat i.v. every 3 months). Our results and experiences in 32 patients/24 months will be discussed. Results and conclusions: The results in the area of the lumbar spine are different because of the preexisting ascites. Measurement of the proximal femur shows a clear decrease of BMD in the rst three months, results in the ultradistal radius (pQCT) within 6 months after transplantation. Examinations in the area of the proximal femur (DXA) and the ultradistal radius (pQCT) are most expressive. Because of the enormously decreased BMD of about 5% a therapy should start on the day of transplantation. Here Ibandronat seems to be most successful. The measurement of the BMD gives precise information about the actual bone mass and its quality and is therefore the best parameter to determine the risk of bone fracture due to osteoporosis after transplantation. We are able to evaluate the prognosis and monitor the therapy of osteoporosis.

62 (54). DUAL-ENERGY X-RAY ABSORPTIOMETRY MEASUREMENT OF BONE MINERAL DENSITY AROUND CEMENTED AND CEMENTLESS FEMORAL PROSTHESIS S. Kabak, M. Halici, S. Karaoglu, A. Baktir, M. Kula, Department of Orthopaedics and Traumatology and Nuclear Medicine, University of Eeciyes Faculty of Medicine, Kayseri, Turkey The measurement of bone mineral density (BMD) in dened areas around metal implants has improved with the development of dual -energy X-ray absorptiometry (DEXA). The purpose of this prospective study to investigate the course of the periprosthetic bone mass changes after implantation of an uncemented and cemented femoral implants over a 4-year period. A cosecutive homogeneous group of 60 female patients with an average age of 58 years was operated on for unilateral hip osteoarthritis. The types of prosthetic components used were the cemented Protec MS30 and uncemented femoral stem. Periprosthetic bone mineral density was measured in 7 different zones (Zones I to VII) in femoral components. BMD of the femoral components was measured preoperatively and one week, 1 year and 4 years postoperatively. The stem of the Protec prosthesis induced bone mass reduction in the medial femoral calcar and the lesser trochanter area (Zone VI-VII). The cementless femoral stem produced signicant bone resorption in the area of the minor and greater trochanter (Zone I-VII) 4 years after. Cemented and uncemented femoral stems induced bone mass increase in the greater trochanter area (Zone I), and distal lateral femoral cortex (Zone III -IV). No correlation was faund between the age of the patients and bone mineral density values. This evaluations may be of much better prognostic value for aseptic loosening of total hip arthroplasty long before any radiographic or clinical signs of this complication are evident.

61 (53). HIGH SHORT-TERM PRECISION WITH DIGITAL X-RAY RADIOGRAMMETRY J. T. Jrgensen1, P. B. Andersen2, A. Rosholm1, N. H. Bjarnason3, Pronosco A/S, Vedbaek, Denmark; 2CCBR, Aalborg, Denmark; 3 CCBR, Ballerup, Denmark

63 (55). THE EVALUATION OF ACTIVITIES OF DAILY LIVING IN PATIENTS WITH VERTEBRAL COMPRESSION FRACTURES A. Karan, D. Diracoglu, O. Ekmekci, C. Aksoy, Deparment of Physical Medicine and Rehabilitation, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey The most important clinical problem of osteoporosis is vertebral compression fractures which may lead to severe impairment in activities of daily living (ADL). The purpose of this study was to evaluate the impact of vertebral compression fractures on ADL. 36 patients with osteoporosis who had at least one vertebral fracture were included in this study. An ADL questionnaire which included eleven activities were evaluated on a ve point scale

In the present study a new bone densitometer using the Digital Xray Radiogrammetry (DXR) technology (Pronosco X-posure System) was investigated with respect to its short-term precision. The BMD estimate generated by the system is referred to as DXR BMD.

according to the level of difculty when performing these activities, was applied to all the patients was found to be ``carrying heavy bags'' and ``transvers with public transportation vehicles''. Bathing and dressing on the other hand were the easiest activities for these patients to perform. The results of this study suggets that ``carrying heavy objects'' and ``public transportation'' might be harmful to osteoporotic patients with vertebral fractures. Although ``bathing'' seems to be easiest activity to perform. Turkish bath habit are different from the habit of most other countries. The patients should be careful not to fall while ``bathing'' in order to prevent more fractures.

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differences in BMD between Gr. A and Gr. B was noted only in forearm total BMD (p = 0.047), forearm total Z score (p = 0.024), forearm ultradistal T (p = 0.028) and Z (p = 0.009). Inverse correlation between SiPTH and total BMD (r = 1.0) was noted. All pts were treated with VitD and calcium and reevaluated which showed signicant subjective improvement. Repeat BMD was done in seven patients, which showed signicant improvement. Conclusion: VDD is still persisting and is important cause of signicantly low BMD.

Results: BMD of different area shown in Table

64 (56). THE EVALUATION OF BONE MINERAL DENSITY IN POST-MENOPAUSAL WOMEN WITH TYPE 2 DIABETES MELLITUS A. Karan, A. Aydogan, D. Diracoglu, S. Salman, F. Salman, N. Dincag, E. Berker, Istanbul University, Istanbul Medical Faculty, Turkey Bone formation is stimulated in type 2 Diabetes Mellitus (DM) through peripheral insulin resistance which is more pronounced in obese patients. The aim of this study is to evaluate Bone Mineral Density (BMD) in type 2 DM patients and to investigate the correlation between other clinical parameters. 28 post-menopausal women with type 2 DM between ages 43 73 were recruited for the study. All cases had a Body Mass Index (BMI) of over 29.403.30 and were regarded as obese. BMD was measured in gr/cm2 with Dual Energy X-ray Dansitometry (DEXA) in lomber vertebraes (L1-L4), femoral neck, trochanter and wards triangle and Hb A1c was also recorded. Disease duration, number of births and the duration of menopause was also recorded for each case. Student-t test and Pearson correlation coefcient was used for statistical analysis. The BMD values for L1-L4 femoral neck, trochanter and wards triangle were 0.950.17; 0.780.14; 0.630.16 gr/cm2 respectively. BMD in L1-L4 was shown to be signicantly higher than the above mentioned areas (p<0.0001). The average Hb A1c levels of 8.122.35 recorded in these patients pointed to a dysfunction in glucose regulation. The investigation of the correlation between BMD and BMI, disease duration, menopause duration, number of births and Hb A1c showed a weak negative correlation with only L1-L4 BMD and menopause duration (p<0.05; r = 0.43) As a result we may conclude that type 2 DM stimulates bone formation of trabecular bone due to high scores of BMD in L1-L4 in relation to femur BMD. Although the patient group was obese with dysfunction of glucose regulation, the sole correlation was between BMD and menopause duration which points to possibility of a variety of other factors affecting BMD other than those investigated. Long term randomized controlled studies are needed to verify this fact.

Area Forearm total T score Forearm total Z score Spine AP T score Spine AP Z score Hip total T score Hip total Z score Ward's T score Ward's Z score


Group A

Group B

1.56 0.78 2.33 1.53 2.03 1.44 2.76 1.22

2.99 2.26 2.80 2.01 2.85 2.27 3.44 1.86

1.02 0.04 2.41 1.51 1.74 1.06 2.59 0.89

66 (58). BONE MINERAL DENSITY OF THE BOTH FOREARMS IN PATIENTS WITH DISTAL RADIUS FRACTURE P. Leszczyn ski, J. K. Lacki, E. Nowak, S. H. Mackiewicz, Department of Rheumatology, University School of Medicine, Poznan, Poland Objective: The aim of our study was to compare the effect of Colles fracture on bone mineral density (BMD) and bone mineral content (BMC) of the forearms in postmenopausal women. Materials and methods: A sample of 65 postmenopausal women who experienced the left distal radius fracture, average age 63.08.8 yrs (range 50 to 80 yrs), were involved in the study. BMD and BMC of the distal both forearms (left and right) was measured by dual X-ray absorptiometry using DTX200 appendicular bone densitometer (Osteometer Medi-Tech A/S Denmark). The average time since Colles fracture was 7.77.3 yrs (range 1 to 40 yrs). Results: Average BMD and BMC values of the left (fractured) forearm were: 0.3900.073g/cm2 and 2.7680.570g. Average BMD and BMC values of the right (not fractured) forearm were: 0.3900.065g/cm2 and 2.7620.534g. There was no signicant differences between BMD and BMC of the left and right forearm. We have also found no signicant correlation between BMD and BMC of the fractured left forearm and time since previous fracture (r = 0.075, r = 0.166; respectively). Conclusion: Our study conrm no signicant densitometry differences of the forearms in patients with long-term previous Colles fracture.

65 (57). BONE MINERAL DENSITY IN VITAMIN D DEFICIENCY R Khadgawat, S Gupta, A Mithal, Sanjay Gandhi Postgraduate Institute, Lucknow, India Vitamin D deciency (VDD) is not very common in developed countries but is still important in developing countries. Material & Methods: We retrospectively evaluated records of all those patients (pts) who were referred to us between July 1996 to June 1997 (n=107), 23/107 (21.59%, 22 females, 1 male) has S. 25 (OH) vitamin D (VitD) levels <10 ngm/ml (by RIA, Incstar Corp., USA). These pts were divided into severe VDD (VitD levels <5 ngm/ ml, group A12 patients) and mild to moderate deciency (VitD level between 510 ngm/ml, Group B11 patients). S intact PTH (SiPTH, by IRMA, Incstar Corp.) and Bone mineral density (BMD) was measured by DEXA (Hologic QDR 4500). The signicant

67 (59). COMPARISON OF DUAL X-RAY ABSORPTIOMETRY (DXA), HISTOMORPHOMETRY, ASH-WEIGHT AND BONE MORPHOMETRIC INDEX IN AN ANIMAL MODEL OF MALE OSTEOPOROSIS (THE ORCHIDECTOMIZED RAT) H. Libouban, M. F. Moreau, E. Legrand, M. F. Basle , M. Audran, D. Chappard, University and CHU of Angers, France Bone mass was obtained in the orchidectomized (ORX) model of male osteoporosis by different methods: DXA, histomorphometry, ash weight and the bone weight per bone length index (WL index). We have examined results from 144 male Wistar rats: 48 shamoperated control rats, 48 ORX control rat, 48 ORX treated with a bisphosphonate (risedronate 2 or 10 mg/kg/day, 5 days per week). Rats were sacriced at 2, 4, 8 or 16 w. post-orx. DXA was

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The feasibility of measuring the BMC non-invasively and longitudinally in transgenic mice opens new possibilities for determining the function of specic genes and gene products at various stages of bone development. Supraphysiologic levels of GH are shown to exert a sex-specic effect, with a stronger anabolic response in females.

69 (61). CALCANEAL ULTRASOUND IN MALES AND FEMALES: NORMATIVE DATA AND RELATIONSHIP TO DXA S. L. Low, J. C.H. Goh, S. DasDe, 1Dept of Orthopaedic Surgery, National University of Singapore, The aim of this study was to establish the normative data of the calcaneus using ultrasound in the local male and female Chinese population and to correlate the results to DXA of the spine, hip and calcaneus. 237 females and 122 males had broadband ultrasound attenuation (BUA) and velocity of sound (VOS) of the left calcaneus measured using a Paris ultrasound system. 174 females and 104 males also had BMD of the spine, hip and left calcaneus measured using a Norland XR36 bone densitometer. The coefcient of variation (CV) was 0.90% for VOS and 3.93% for BUA. Males were found to have signicantly higher (p<0.001) VOS and BUA values compared to females. There was an overall decline of 11.7% for BUA in females between the ages of 50 to 80 years, which was double the rate of loss in males (6.4%). However, VOS only decreased by 1.8% in females and 0.9% in males. Females above the age of 50 years were divided into `normal' and `osteoporotic' based on their femoral neck T scores dened by WHO. The `osteoporotic' females had signicantly lower (p<0.05) BMD, BUA and VOS values. There was a moderate correlation of calcaneal BMD to BUA (r = 0.581, p50.01) while lumbar spine BMD had the lowest correlation to VOS (r = 0.402, p50.01). In conclusion, calcaneal BUA and VOS decreases with age in both sexes and is lower in osteoporotic subjects than normal individuals. More studies are needed to dene threshold values in VOS and BUA in order to identify truly osteoporotic patients.

performed on an Hologic QDR 2000 (small animal softwares) on the whole body, whole tibia and tibial metaphysis. Total (C.BV/ C.TV) and trabecular bone volume (BV/TV) were measured by histomorphometry on the proximal metaphysis (including both primary and secondary spongiosa). Signicant correlation was obtained between weight measured by DXA and scale weight (r = .993). However, DXA underestimated weight by 0.3%. This discrepancy was dependent of the rat's weight. The WL index was linearly correlated with BMD (r = .86), BMC (r = .96) and ash weigh (r = .97). A signicant correlation was found between BMC of the metaphyseal region and the bone volumes measured by histomorphometry but this was found to explain only 27% of the variance; correlations with BMD were poorer (r = .40). BMC and ash weight were highly correlated (r = .992). However, DXA overestimated BMC by a factor of 11% and the overestimation was found to be dramatically dependent of the net mineral content.

68 (60). BONE MASS IN GROWTH-HORMONE TRANSGENIC MICE VALIDATION AND LONGITUDINAL STUDY WITH HRDXA E-M. Lochmu ller, U. Wehr, A. Weusten, W. Rambeck, E. Wolf, F. Eckstein, 1Universitatsfrauenklinik, LMU Munchen, Germany The purpose of this study was a) to determine the accuracy and precision of non-invasive measurements of body composition and bone mineral content (BMC) in mice, using high resolution DXA, and b) to study the absolute and relative BMC (% body weight) longitudinally in male and female growth hormone (GH) trangenic animals. First we examined 28 transgenic (tg) and control (con) mice aged 3 months in vitro. Four measurements were obtained at different occasions with a high resolution DXA system (pDEXA, Sabre, Norland/Stratec: resolution 0.5 x 1.0 mm). These were compared with a chemical analysis of the bone and fat tissue content. Next, 32 animals (16 tg, 16 con, 8 of each group male and 8 female were examined in vivo from birth over 9 months. The precision of the measurements (RMS CV% and SD) was 4.4% (65 mg) for the BMC, and 13% (1.4 g) for the fat content.The correlation with the ash weight was r = 0.95 (%SEE = 9%) and that with the chemical fat analysis r = 0.94 (%SEE = 13%). At the age of 3 weeks, the BMC was around 150 mg, with no signicant differences between groups. At 9 months the females displayed values of 1800 (tg) vs. 1100 mg (con), and the males of 1680 (tg) vs. 1560 mg (con), showing a signicantly increased absolute and relative BMC in transgenic females, but not in males.

70 (62). ETHNIC DIFFERENCES IN BONE DENSITY AND HIP AXIS LENGTH IN SINGAPORE S. L. Low, J. C.H. Goh, S. DasDe, Dept of Orthopaedic Surgery, National University of Singapore, Singapore In Singapore, the incidence of hip fractures in the Chinese population is more prevalent than in the Malays or Indians. Studies have shown that apart from bone mineral density (BMD), hip axis length is an important predictor of hip fracture risk. A longer hip axis length was associated with an increased risk of hip fracture. The aim of this study is to determine whether there are any differences in bone density and hip axis length among the 3 major races in Singapore. A total of 408 females and 150 male subjects were recruited. All subjects had BMD of the lumbar spine and left hip measured by DXA using a LUNAR DPX-L bone densitometer. The hip axis length, dened as the length from the lateral bone edge below the greater trochanter through the femoral neck to the medial bone edge of the inner pelvic brim, was measured using the software ruler in the hip analysis programme. In males, there was no signicant differences in height, weight, lumbar spine and femoral neck BMD among the 3 races. Chinese males were found to have a longer hip axis length compared to Indian males (P=0.029). In females, the Chinese had signicantly higher lumbar spine BMD compared to the Indians or Malays. Chinese females also had the lowest hip BMD and signicantly longer hip axis length (p<0.05). Therefore the higher incidence of hip fractures among the elderly Chinese population could be partially due to a low hip BMD and a longer hip axis length.

71 (63). BONE MASS CHANGES IN WEIGHT LOADED AND UNLOADED SKELETAL REGIONS FOLLOWING A FRACTURE OF THE HIP H. Magnusson, K. J. Obrant, O. Johnell, K. M. Karlsson, Department of Orthopaedics, Malmo University Hospital, Malmo, Sweden The aim of this study was to investigate the bone mass changes in unloaded skeletal regions in patients just sustained a hip fracture. BMD has been demonstrated to decrease in weightloaded skeletal regions following a hip fracture. If BMD changes in unloaded regions following a fracture is not known. BMD (g/cm2) was measured longitudinally using DXA in 44 hip fracture patients (mean age 76 years, range 5390). The measurements were done in mean 11 days, 5 months and 13 months after the fracture. BMD was assessed of the upper part of the skull representing an unloaded skeletal region and femoral neck a weight-loaded region. Data is presented as mean SEM. BMD increased in the upper part of the skull by 1.9%0.8% (p50.05) the rst 5 months and 3.7%0.9% (p50.001) the rst 13 months after the fracture. BMD decreased in the non fractured femoral neck by 4.7%1.8% (p50.01) the rst 5 months and 4.5%1.7% (p50.01) the rst 13 months after the fracture. In summary, BMD increased in an unloaded skeletal region and decreased in a weight loaded region following the reduced activity after a hip fracture. We conclude that changes in bone mass occurs differently between weight loaded and unloaded skeletal regions related to present activity level a bone mass shift?

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73 (65). RISK FACTORS OF OSTEOPOROSIS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS P. Masaryk, A. Letkovska, J. Lukac, J. Rovensky, Research Institute of Rheumatic Diseases, Piestany, Slovakia Systemic lupus erythematosus (SLE) is a serious chronic inammatory autoimmune disease. Improvement of diagnostics and therapy results into lower mortality rate but on the other hand into increased rate of late complications including osteoporosis. Data on incidence of osteoporosis in SLE vary owing to huge amount of risk factors with different importance. Aim of this study is to determine incidence of osteoporosis in patients with SLE and search for mam risk factors. Methods: 55 in-patient (52 women a 3 men) with SLE were recruited. Diagnosis of SLE was based on ACR criteria, diagnosis of osteoporosis on WHO densitometry criteria. Bone mineral density (BMD) of lumbar spine L2-L4 and femoral neck was measured by means of NORLAND XR26 equipment. Mean age of patients was 44,0 (13,2) yrs, 31 women were postmenopausal. The control group consist of 367 proband of EVOS study. Mean Zscore for SLE group was calculated and relative rate of osteoporosis were determined. By means of multiple regression analysis the importance of 35 possible theumatology risk factors on BMD of spine and neck were performed. Results: Mean Z-score was 0,65 (95% CI: 0.92, 0.39) for lumbar spine and 0.75 (1.05, 0.42) for neck, both signicantly different from Z = 0 of control group. In postmenopausal women osteoporosis of lumbar spine and neck was found in 12/31 (41.9%) and 4/31 (12.9%), respectively. According to multiple regression analysis the only signicant variable were (regr. coeff, signicance): age of onset (L2-L4: 0.003, p = 0.089, neck: 0.003, p = 0.025), duration of SLE (L2-L4: 0.009, p = 0.045, neck: 0.007, p = 0.019), menopause (L2-L4: 0.002, p = 0.024, neck: 0.004, p = 0.020), S- creatinin (L2-L4: 0.001, p = 0.004, neck: 0.002, p = 0.002). Neither any immunology parameters, nor any type of therapy (including corticotherapy) were signicant. Conclusion: Patients with SLE have signicant lower bone mineral density in lumbar spine and femural neck and the main risk factors are menopause, age of onset and duration of SLE and serum level of creatinin.

72 (64). L-THYROXINE TREATMENT AND BONE DENSITY: LONGITUDINAL STUDIES C. Marcocci, F. Golia, E. Vignali, A. Picone, F. Cetani, L. Cianferotti, A. Pinchera, Dipartimento di Endocrinologia, Universita di Pisa, Pisa, Italy Conicting results have been reported o the effect of L-thyroxine (L-T4) on bone density (BD). We evaluated prospectively BD in 3 groups of premenopausal women given suppressive doses of LT4: Group 1: 17 patients with nontoxic goiter in whom BD was measured yearly for 5 yr after institution of therapy; Group 2: 22 women treated with total thyroidectomy for differentiated thyroid cancer (DTC) for more than 5 yr (mean 11 yr), in whom BD density was measured twice after a mean interval of 4 yr; Group 3: included 29 women with DTC in whom BD was measured before surgery and after 4 yr of L-T4 therapy. The daily dose of L-T4 was individually adjusted in order to use the minimal amount of L-T4 able to suppress L-T4 (1.80.2 mg/kg body weight in Group 1, 2.40.4 in Group 2, and 2.30.3 in Group 3). BD (g/cm2) was measured at the lumbar spine (L2-L4) and femur (neck, Ward's triangle and trochanter) by DEXA. The results are presented in the Table. In conclusion, carefully monitored L-T4 suppressive therapy in premenopausal women is not associated with bone loss during the rst 5 yr of treatment nor when given chronically.
Group 1 Basal L2-L4 Neck Ward Troch FT4 pg/ml FT3 pg/ml TSH mU/ml 1.200.1 0.930.1 0.860.1 0.750.1 9.21.9 3.20.7 1.22.8 Group 2 1st 1.240.1 0.97+0.1 0.930.1 0.76.1 15.34.6 3.60.2 <0.07 Group 3 Basal 1.140.2 0.920.1 0.840.1 0.750.1 10.42.1 3.30.6 1.40.8

74 (66). IMPROVEMENTS IN PROXIMAL FEMUR BY DEXA R. Mazess2, R. Nord2, C. D. Fogarty1, K. Nodine1, C. M. Fogarty1, 1 Bone Densitometry Center, Spartanburg, SC, USA; 2LUNAR Corporation, Madison, WI, USA Bone mineral (BMD) at the proximal femur using DEXA may be compromised on thin patients when high ux modes are used. Sufcient soft tissue medial to the greater trochanter is necessary to maintain detector linearity and for accurate determination of the soft tissue baseline. This problem can be eliminated by placing a tissue-equivalent bolus adjacent to the proximal femur. New software (enCORETM), recently introduced for the PRODIGY and DPX-NT densitometers (LUNAR Corp.), eliminates the need for a tissue bolus. The SmartScanTM feature dynamically updates scan acquisition for each subject, which should eliminate the need for the tissue bolus. This study documents the performance of enCORE software on the PRODIGY (fan-beam) and the DPX-NT (pencil-beam) bone densitometers with and without the use of bolus material during acquisition of proximal femur BMD for both subjects and phantoms. Both left and right proximal femur BMDs were acquired on 15 normal subjects (mean age=698 years); two scans were acquired at both the right and left femurs, one with and one without the bolus. Subjects were selected for small body size (BMI 20.22.3) to highlight any difference between bolus/no bolus. Additionally, a quasi-anthropomorphic femur phantom was constructed to simulate a thin individual (BMI = 17), and was used to test the need for the bolus. There was no signicant difference in femur neck BMD or total femur BMD related to non-use of the

5yr 1.180.1 0.940.1 0.850.1 0.740.1 15.22.0* 4.30.5 <0.07*

2nd 1.220.1 0.980.1 0.93+0.1 0.78+0.1 15.63.9 3.70.8 <0.07

4 yr 1.150.1 0.920.1 0.840.1 0.740.1 15.12.3 4.20.5 <0.07

*p50.01 vs basal value

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bolus. The pooled precision in vivo for neck BMD and total femur BMD was 1.3% and 0.6%, respectively. There was no signicant difference, with or without the bolus, on phantoms for either PRODIGY or DPXNT. The use of enCORE software with SmartScan eliminated the need for bolus material at the proximal femur for both the PRODIGY and DPX-NT. This benets clinical practice by reducing patient preparation time.

seconds, with the patient in a decubitus position. Lateral spine BMD acquired on the PRODIGY was compared to that using the QDR4500 (Hologic, Inc., Bedford, MA) and the DPX-IQ (LUNAR Corp.) densitometers. Lateral spine BMD for 12 normal subjects on the PRODIGY was highly correlated (r = 0.95, SEE=0.07g/cm2) to DPX-IQ values. Using a different set of subjects (n=12) there was a modest correlation (r = 0.55, SEE=0.15g/cm2) between the PRODIGY and the QDR4500 results. Precision of lateral spine BMD using the PRODIGY was determined for two subject groups: (a) young, normal volunteers (n=13, mean age 397 years) and (b) older female clinical subjects (n=9, mean age 488 years). Precision was determined from pooled calculations of 34 repeat measurements made on each subject. The coefcients of variation for groups (a) and (b) were 1.7% and 3.4%, respectively. Lateral spine measurements on the PRODIGY were relatively fast and easy to perform. The precision of lateral spine BMD is often 23X worse than AP spine BMD. Comparability between PRODIGY and DPX-IQ lateral BMD was good. Lack of agreement between PRODIGY/DPX-IQ and QDR4500 results may prevent cross-calibration between these two instruments.

75 (67). INTERUNIT VARIATION OF FAN-BEAM AND PENCILBEAM DENSITOMETERS R. B. Mazess, H. S. Barden, J. A. Hanson, Lunar Corporation, Madison, WI, USA Studies have shown that there is good correspondence between fan-beam and pencil-beam DEXA densitometers from the same manufacturer. The results obtained with any densitometer are generalizable because of the high degree of interunit conformity in a single model, typically 0.5% at the factory and 1% in the eld. We have previously shown that there was only a small variation among 2700 DPX densitometers. We recently evaluated a large series of later models (DPX-IQ), as well as a series of the recently introduced PRODIGY fan-beam densitometer. Typically during quality testing at the factory at least 3 to 5 measurements are made of: (a) an aluminum spine phantom in 15 cm of water; (b) an actual lumbar spine embedded in 10 cm of lucite with an additional 5 cm of water, (c) an excised low-density skeleton, (d) a body composition phantom fabricated from acrylic and vinyl. The results are given below:

77 (69). NO SYSTEMATIC DIFFERENCES BETWEEN A FANBEAM (PRODIGY) AND PENCIL-BEAM (DPX-IQ) DENSITOMETER R. Mazess, H. Barden, R. Nord, J. Hanson, LUNAR Corporation, Madison, WI, USA Several previous studies have compared fan-beam and pencilbeam densitometers of the QDR (Hologic) series. Generally there is only a small systematic offset, if any, for BMD, and slightly larger offsets for body composition. However, there are documented differences between fan-beam and pencil-beam results that depend on the magnitude of the variable measured, e.g., relatively large difference at low or high BMD even though there is no difference at the average BMD (see Ellis and Shypailo, 1998, J Bone Miner Res 13:16131618). We performed a BlandAltman analysis comparing results with the PRODIGY and DPX-IQ densitometers on phantoms and on spine/femur scans (n=122) and total body scans (n=46). There were no signicant correlations (R2<5%) between densitometer differences and the measured variable. The regression slope was negligible in each case over the entire biological range.
Table 1. Bland-Altman Comparison of the PRODIGY vs DPX-IQ Dierence Mean Total Body BMD Total Body BMC(g) Total Body Lean(kg) Total Body Fat(kg) Total Body % Fat Femur Neck BMD Lumbar Spine BMD 0.003 14.6 0.44 0.16 0.03 0.006 0.002 Relationship for dierences Slope Intercept R2 0.019 0.034 0.004 0.016 0.011 0.039 0.019 0.02 102 0.28 0.26 0.07 0.03 0.02 0.010 0.015 0.001 0.031 0.007 0.046 0.012

DPX (n=2716) Mean SD Al. spine BMD Actual spine BMD Total body BMD Body comp. %Fat 1.260 1.032 0.745 .011 .005 .008

DPX-IQ (n=2920) Mean 1.262 1.032 0.750 42.1

SD .011 .005 .018 .90

PRODIGY (n=418) Mean SD 1.250 1.028 0.749 43.0 .010 .006 .013 1.44

.011 .003 .002 0.9

As was the case for the DPX and DPX-IQ, the interunit variation for BMD, and % fat with PRODIGY, was small (1%). Results for spine and total body BMD with the PRODIGY were close to DPX results (D); BMD of the aluminum spine diered more. This dierence was due to measurement in water; when the same phantom was measured in 40% fat-equivalent, there was no dierence between the two densitometers. PRODIGY gave a % fat slightly higher than the DPX, but this was not observed for subjects in vivo.

SD 0.019 138 1.08 1.03 1.5 0.03 0.03

76 (68). LATERAL SPINE BMD USING THE LUNAR PRODIGY R. Mazess2, C. D. Fogarty1, K. Nodine1, C. M. Fogarty1, D. Gorsuch2, 1Bone Densitometry Center, Spartanburg, SC, USA; 2 LUNAR Corporation, Madison, WI, USA Bone mineral density (BMD) measurements at the lumbar spine (AP or PA) and the proximal femur are clinically useful for assessing fracture risk and monitoring treatment of osteoporosis. Lateral spine BMD measurements have limited clinical utility; less than 1% of DEXA assessments use lateral lumbar spine. However, there are clinical applications for lateral spine measurements of the elderly (>70 years of age) when AP spine measurements may be compromised due to the presence of artifacts. The PRODIGY densitometer (LUNAR Corp.) uses a narrowangle fan-beam to acquire lateral spine images in less than 90

78 (70). MOST UNTREATED WOMEN LOSE BONE DENSITY AFTER MENOPAUSE M. McClung, P. D. Ross, R. D. Wasnich, C. Christiansen, D. Hosking, D. Thompson, M. Daley, J. Yates, for the EPIC Research Group, 1Oregon Osteoporosis Center, Portland, OR, USA; 2Hawaii Osteoporosis Center, Honolulu, HI, USA; 3Center for Clinical and Basic Research, Ballerup, DK; 4City Hospital, Nottingham, UK; 5 Merck & Co., Inc., Rahway, NJ, USA It is well established that bone mineral density (BMD) decreases after menopause. However, the distribution of rates of loss

among individual women and the exact proportion of women who actually lose bone mass is not well understood. Furthermore, the changes in BMD and variability in changes may vary by skeletal site. We explored these issues using data from 373 women ages 4559 (>6 months postmenopause) in the placebo group of the Early Postmenopausal Interventional Cohort (EPIC) Study, a randomized, controlled trial of alendronate. The women were given general recommendations about calcium intake and exercise for bone loss prevention, but calcium supplements were not provided. During 4 years of followup, the mean (SD) change in BMD was 2.9 (4.1)%, 1.9 (3.4)%, 2.8 (2.8)%, 4.6 (4.2)%, and 6.3 (5.4)% at the spine, hip, total body, total forearm, and ultradistal wrist, respectively. Decreases in BMD (any decrease more than 0.001 g/cm2) were observed at the end of 4 years for 76%, 70%, 86%, 90%, and 90% of women, respectively. There is a large range of changes in BMD, and a substantial proportion of women (1152%) lost >6% over 4 years. At the spine, 24% had decreases >6% more than twice the average loss. We conclude that postmenopausal women lose an average of ~26% over 4 years at skeletal sites measured in this study, with greater losses at the forearm and wrist. Thus, clinicians should anticipate that most postmenopausal women will lose BMD progressively if not treated with more than calcium and exercise recommendations. The effects of pharmacologic treatment should be evaluated against the expected changes in BMD at each site rather than just the baseline value.

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Purpose of the study: To study the possible relation between BMD and the number of igth hours own by crew members. Population and Methods: 147 crew members (74 female, 73 male). Mean age 44.410.4 years (2265). Inclusion criteria: pilots or ight assistants on active duty with more than 1500 hours own. Exclusion criteria: post-menopausal women, chronic diseases bone metabolism modifying drugs. Monophotonic densitometry of the distal and ultra distal radius was performed as well as heel ultra-sound measurement. A questionnaire about osteoporosis common risk factors was performed. Statistics: correlations coefcient with partial correction for risk factors and signicance levels were obtained. Results: Mean ight hours 114655185. Pearson correlation index between igth hours and densitometric values was signicative for distal radius (r = 0.21 p = 0.012) T score Ultra distal radius (r = 0.22 p = 0.007) and close to signicance for the heel SOS (r = 0.16 p = 0.054). When corrected for age and mass index the correlation is signicative for BMD distal radius (r = 0.24 p = 0.004) BMD Ultra distal radius (r = 0.2 p = 0.017). The isolated analysis of the other risk factors did not change the way of the obtained correlations. Conclusion: From the data we can observe that the statistic correlations were negative pointing to a possible inverse relationship between ight hours and densitometric values. This observation can reveal the possible role of ight conditions on bone metabolism. Further studies in this area should be developed. This preliminary study will be completed with a ongoing case-control study.

79 (71). BMD AND OCCUPATIONAL PHYSICAL ACTIVITY vam2, M. E. Simoes1, 1Instituto L. C. Miranda1, M. T. Cristo Portugues de Reumatologia; 2C.S. Portalegre, Lisbon, Portugal Purpose of the study: In the relation between exercise and BMD the available data rarely consider the role of occupational physical activity on bone metabolism. To compare the BMD of two male populations of the same airline company one with high level of occupational physical activity and the other with low level. Population and Methods: Inclusion criteria: Male, over 35 years, caucasian, same occupation at least for 5 years. Exclusion criteria: chronic diseases, regular exercise, bone metabolism modifying drugs. Active group: 67 airplane luggage and small cargo handling staff; Inactive group: 87 Ofce staff. Ultrasound densitometry and a questionaire on osteoporosis risk factors were performed. Results: The active group moved on average 2115 kg per day. The inactive group worked on average 73.2% sitting and only 10% carry cargo (56kg). For the risk factors no statistic difference was found between the two groups as well as for densitometric values (QUI, T score, SOS, BUA) which were always higher on the active group, however, the results are close to that signicance (QUI p = 0.06; Tscore p = 0.069; SOS p = 0.062). When we classied the workers, we also nd that the inactive group has more osteopenic (34.5%), (25.4% in the active) and osteoporotic (6.7%), (3% in the active) but there was not a statistic difference. Discussion: The role of occupational physical activity in BMD is not fully understood. This work points out the possibility of a protective action of work related exercise on BMD.

81 (73). TIME COURSE CHANGES OF BONE MINERAL DENSITY IN HEMODIALYSIS PATIENTS USING DUAL-ENERGY X-RAY ABSORPTIOMETRY T. Nakai1, K. Masuhara2, N. Kanbara3, 1Department of Orthopaedic Surgery, Ikeda City Hospital, Ikeda City, Japan; 2 Department of Orthopaedic Surgery, Osaka Koseinenkin Hospital, Osaka City, Japan; 3Department of Internal Medicine, Kanbara Hospital, Japan We have studied the change of bone mineral density (BMD) at the 1/3 distal radius in 35 male and 20 female patients with maintenance hemodialysis. BMD was measured by dual energy X-ray absorptiometry at an interval of four years (DCS 600 EX; ALOKA) (Osaka, Japan). Mean age was 54.811.0 (meanSD) years for male (range, 3276 years) and 59.612.1 years for female patients (range, 4279 years). Mean duration of hemodialysis was 88.577.9 months for male (range, 4292 months) and 96.379.6 months for female patients (range, 5296 months) at the beginning of the investigation, respectively. BMD value was 0.6560.124g/cm2 for male and 0.4810.123g/cm2 for female patients at the beginning of the investigation. At the end of the investigation, it was 0.6220.129g/cm2 for males and 0.4440.126 g/cm2 for females. BMD values were signicantly lower in female than in male patients at each time point (p<0.01). Signicant decreases were found in both male and female patients (p<0.01). The present study showed an annual change of BMD at the 1/3 distal radius of 1.28% in male and 1.92% in female, respectively. In conclusion, we have shown that prolonged hemodialysis could cause signicant bone loss.

80 (72). BONE MINERAL DENSITY IN THE FLIGHT CREWS L. C. Miranda, M. J. Mediavilla, P. Araujo, M. Parente, E. Simoes, A. Faustino, J. Ramos, A. Vilar, Instituto Portugues de Reumatologia, Lisbon, Portugal Introduction: It is known that the absence of gravity rapidly decreases BMD in space ights. Fligth crew members are not in the same conditions however, there are some working conditions like atmospheric pressure, cosmic radiation, magnetic elds, aceleration and desaceleration whose effect on BMD are still unknown.

82 (74). EVALUATION OF CALCANEAL BONE MINERAL DENSITY WITH FAN BEAM DEXA Y. Nishimura, K. Kushida, K. Yamazaki, T. Fujiwara, Y. Yamato, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan Heelscan (Kyoto Daiichi Kagaku, Kyoto, Japan) is a fan beam type dual energy bone absorptiometry (DEXA) for calcaneus. Heelscan uses a stable X-ray generator, k-edge lter to archive the two energy levels, and CdTe detector elements. The procedure takes

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only 7 seconds for measurement and analysis. The purpose of this study is to evaluate the basic attributes of this densitometer and age related changes in normal Japanese women. Subjects and Methods: 144 women with vertebral fracture, 84 women with hip fracture, and 2557 volunteers were enrolled in this study. T-test, ANOVA, regression analysis, and logistic regression analysis were used for statistic analysis. Results: 1. Precision error in vivo was 0.75% for calcaneus scans. 2. Calcaneal BMD in vivo (n=120) using DXA was closely correlated to prior SXA osteoanalyzer (r = 0.983). There was almost correspondence of DXA and SXA values. 3. The crosssectional study showed that BMD decreased by 34.4% between 20 and 80 years of age, and BMD peaked at 20 to 30 years of age. 4. BMD in women with vertebral fracture was signicantly lower than normal women. The relative risk of vertebral fracture was 2.1 for a decline of 1SD in the bone density at the calcaneus (95% condence interval, 1.9 to 2.5). 5. BMD in women hip fracture was signicantly lower than normal women. The relative risk of vertebral fracture was 4.6 for a decline of 1SD in the bone density at the calcaneus (95% condence interval, 3.5 to 6.2). Conclusion: The results of this study indicate that this rapid technique can accurately predict women with risk of spine and hip fracture, and may be of value as an initial procedure for screening of osteoporosis.

medication affecting bone metabolism. Broadband ultrasound attenuation (BUA), speed of sound (SOS), and QUS index (QUI) of the right heel were measured using a Clinical Bone Sonometer with the ``dry'' technology. The means of all QUS variables were the highest in the youngest age group and the lowest in the oldest one and they showed a signicant inverse correlation with age (r = 0.480 for BUA, r = 0.428 for SOS, and r = 0.478 for QUI). BUA and QUI showed a signicant decline after the age of 50 years, whereas SOS showed a different pattern of decline. BUA, SOS, and QUI decreased by 31%, 3%, and 30% respectively between 20&80 years. When compared to the Caucasian data given by other authors, BUA values seemed to be higher in the younger age groups, while SOS and QUI values seemed to be lower. The pattern of decline in QUS indices seemed similar. In conclusion, this investigation presents preliminary normative data in normal Turkish women.

Age groups

BUA (dB/MHz) mean (SD) 81.14 79.89 76.20 67.67 62.34 55.89 (12.7) (16.3) (15.1) (14.8) (14.5) (14.0)

mean (SD)

SOS (m/s)


mean (SD)

83 (75). NORMATIVE DATA OF A WATER-COUPLED QUANTITATIVE ULTRASOUND DEVICE C. F. Njeh, B. Fan, M. Grigorian, M. Chen, J. A. Shepherd, I. Saaed, T. Fuerst, D. Hans, H. K. Genant, Osteoporosis and Arthritis Research Group, University of California, San Francisco, CA Normative data are essential for the clinical utility of quantitative ultrasound (QUS). As part of a multicenter study we collected normative data for a water-coupled imaging QUS device (UBIS 5000, DMS, France). Short-term precision was also evaluated. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were acquired on 215 healthy Caucasian pre- (n = 126) and post-menopausal (n = 89) females aged 2089 years. In a subset of 30 subjects triplicate measurements were carried out after repositioning to establish short-term precision (CV). The precision was standardized to the biological range (SCV). The CVs were 0.60% and 0.14% for BUA and SOS, respectively. However the SCVs were 1.70% for BUA and 3.82% for SOS. The population mean BUA was 63.24.8 dB/MHz and 151228.9 m/s for SOS. Both BUA and SOS were signicantly dependent on age (r = 0.33; BUA, r = 0.48; SOS) but displayed a large scatter around the regression line. BUA was best tted by a second order polynomial (r = 0.38), with values peaking around the mid thirties (64.7 dB/ MHz), while SOS showed a continuous decrease from the early twenties. The annual change estimated from the linear regression line was 0.089 dB/MHz/yr and 0.78 m/s/yr for BUA and SOS, respectively. However, there was an increase in annual change after age 45, namely: 0.187 dB/MHz/yr for BUA and 1.15 m/s/yr for SOS. The BUA and SOS were not signicantly associated with years since menopause. UBIS is a highly reproducible QUS device, which may be because of its temperature-controlled water coupling. The age decline in the QUS variables is similar to age-related decline observed at the calcaneus using DXA.

2029 (n.66) 3039 (n.41) 4049 (n.95) 5059 (n.131) 6069 (n.112) >70 (n.70)

1554.96 1543.98 1542.03 1531.70 1524.50 1507.45

(24.6) (30.7) (30.8) (28.3) (26.4) (29.7)

99.76 94.81 92.69 84.57 79.65 70.15

(14.3) (18.3) (17.4) (15.4) (14.4) (16.2)

85 (77). BONE MINERAL DENSITY IN PATIENTS ON LONGSTANDING TREATMENT WITH SUPPRESSIVE DOSES OF THYROXIN a ehor ivny ka, P. R kova , P. Z a tko, J. C p, Second , T. Vas V. Palic Medical Clinic and Institute of Clinical Biochemistry and love , Czech Republic Diagnostics, University Hospital, Hradec Kra The purpose of the study was to investigate the effect of longstanding subclinical hyperthyroidism on bone mineral density (BMD). BMD was measured in lumbar spine and proximal femur using HOLOGIC QDR4500A in 76 patients (16 men and 60 women) in the age of 2180 years (median 53 years). These patients have been treated with doses of thyroxin sufcient to suppress TSH levels since thyroid ablation for differentiated thyroid cancer for more than two years (median 7 years). The results were compared with the group of 40 persons matched for age, sex and duration of treatment with replacement thyroxin doses for hypothyroidism. Unpaired T-test has been used for statistical evaluation of differences. No signicant decrease of BMD was found in patients on longstanding thyroxin suppression (Z score: total femur 0.2051.07, neck 0.2021.19, lumbar spine 0.2391.27). The values were lower than in patients treated with replacement doses of thyroxin, the differences were statistically signicant, however, only in postmenopausal women in the femur region (using T-test and Z score: total femur p = 0.026, Ward' triangle p = 0.06, trochanter p = 0.05, intertrochanteric region p = 0.09). No differences were found in the neck (p = 0.24) and lumbar spine (p = 0.40). In the carcinoma group there were 14 patients in whom hypoparathyroidism was present as a complication of thyroid surgery and who were treated with vitamin D and calcium for the whole duration of thyroxin suppression. These patients were found to have signicantly higher BMD than those without hypoparathyroidism. In conclusion the decrease of BMD was small in our group of patients with iatrogenic subclinical hyperthyroidism and was statistically signicant in postmenopausal women only. The BMD was higher in patients with hypoparathyroidism treated with vitamin D and calcium.

84 (76). THE ASSESSMENT OF BONE WITH CALCANEAL ULTRASOUND IN A TURKISH POPULATION A. Oral, D. Sindel, A. Yaliman, D. Tarakci, Istanbul University Medical School, Istanbul, Turkey The aim of this study was to provide preliminary normative data of quantitative ultrasound (QUS) values in a total of 515 Turkish women aged between 20&80 years, who had no disease or

86 (78). THE COURSE OF BONE MINERAL DENSITY CHANGES IN YOUNG LABORATORY RATS a ivny ehor ka, P. Z kova , A. Kasal, V. Novacek, J. C p, , P. R V. Palic Institute of Clinical Biochemistry and Diagnostics, University love , Czech Republic Hospital, Charles University, Hradec Kra The purpose of this study was to assess the rate of bone mineral density (BMD) changes in young laboratory rats and indicate the role of castration and sexual steroid supplementation in this process. After institutional approval 27 male and 37 female Wistar rats with initial body weight (bw) 18020 g were divided into 7 groups. Male: Group M1(n=7): sham operation, given with placebo (emulgel base), M2 (n=10): castration, placebo, M3 (n=10): castration, transdermally daily 2.5 mg of testosterone/kg of bw. Female: F4 (n=7): sham operation, placebo, F5 (n=10): ovarectomy, placebo, F6 (n=10): ovarectomy, transdermally daily estradiol + progesterone (0.05 + 0.025 mg/kg of bw) and F7: (n=10) ovarectomy, transdermally daily 17b-dihydroequiline + progesterone (0.05 + 0.025 mg/kg of bw). Transdermal application was started from day 20 of experiment (operation = day 0 of experiment). BMD measurements using DEXA (Hologic QDR 4500) were performed at days 3, 17, 45 and 82 of experiment in light aether anaesthesia. The constant part of lumbar spine was selected for BMD evaluation. The experiments were nished as soon as we reached signicant differences in BMD between groups. Results are expressed as mean SD. Results: BMD (g/cm2) at day 3 vs. 82 was in M1: 0.1460.01 vs. 0.2070.040, M2: 0.1460.01 vs 0.2030.01. M3: 0.1490.01 vs. 0.2120.01, F4: 1800.02 vs. 0.2080.01, F5: 0.1780.01 vs. 0.2030.01, F6: 0.1760.01 vs. 0.2190.01*, F7: 0.1840.01 vs. 0.2260.01*. Stat. signicance* p<0.05, F6 resp. F7 vs. F4 and F5. We can conclude that castration resp. ovarectomy in the young rats did not lead to decrease in BMD in comparison with sham operated animals. The increase in BMD in placebo given groups should be caused by sexual steroid independent mechanisms. High transdermal doses of sexual steroids leads to signicant increase in BMD, but necessary time to reach signicant differences in BMD was about 80 days.

Thursday, June 15, 2000

88 (80). PERIMENOPAUSAL BONE DENSITY IS PREDICTIVE OF FUTURE BREAST CANCER D. M. Reid1, J. P. Harvie1, D. J. Torgerson2, 1Departments of Medicine & Therapeutics, University of Aberdeen; 2Health Economics, University of York, UK The critical task in the prevention of osteoporosis is to identify those women to whom treatment should be targeted. To determine cost-effective targeting we have examined the role of perimenopausal screening of bone mineral density (BMD) and subsequent changes in bone mass from a unique randomly selected cohort of 5,119 women aged 4554 at their initial assessment carried out between 1990 & 1994. 5 to 7 years later all women were invited for re-examination and 3,645 (75% of those available) attended. Spine and hip BMD was measured in all subjects. A total of 91 breast cancers (prevalence rate 2.5%) were reported of which 26 were incident cases and 36 cases were present at baseline. 28 women (31%) did not give a date of diagnosis. Incident breast cancers were twice as common in those with baseline BMD in the highest two quartiles (F=13.23, P=0.003). BMD at the menopause is predictive of new breast cancers, a fact that can be used to improve the cost effectiveness estimates for the assessment of bone mass in the perimenopausal years.

89 (81). BONE MINERAL DENSITY IN TWO CHILDREN WITH MORQUIO SYNDROME D. Rigante1, P. Ranieri2, G. Segni1, P. Caradonna2, 1Department of Pediatrics; 2Department of Internal Medicine and Geriatrics, Universita Cattolica Sacro Cuore, Rome, Italy Morquio syndrome or Mucopolysaccharidosis type IV (MPS IV) is an autosomal recessive disorder of the connective tissue, resulting from decient keratan sulphate (KS) catabolism and showing a unique pattern among lysosomal enzymopathies for its predominant skeletal involvement, characterized by spondyloepiphyseal dysplasia, odontoid hypoplasia deriving from partial ossication of dens, short trunk dwarsm, kyphosis, growth retardation, joint laxity and normal intelligence. KS accumulation in the skeleton may interfere with the acquisition of bone mass and this might place patients with MPS IV at fracture risk. We have measured bone mineral density (BMD) in 2 children with MPS IV through dual energy X-ray absorptiometry (DEXA, Hologic QDR 2000): BMD is expressed in grams/cm2 both from lumbar vertebra L2-L4 and femoral neck; Z-scores are calculated according to the Hologic database for each respective age of normal children. 1) P.R. (age: 11 years; height: 98 cm; weight: 16.5 kg): lumbar BMD 0.416, Z-score 1.46, 66 % vs normal; femoral BMD 0.356, Z-score 2.58, 51% vs normal. 2) C.V. (age: 9 years; height: 102 cm; weight: 19 kg): lumbar BMD 0.521, Z-score 0.64, 97% vs normal; femoral BMD 0.323, Z-score 2.07, 55 % vs normal. MPS IV involves electively the skeleton and inltration with KS is associated with a number of potential problems, including osteoporosis and possibility of fractures. Osteopenia or osteoporosis may be explained with multiple other contributing factors: a limited deambulation because of hypotonia of the inferior limbs, subsequent to cervical spinal cord compression, or a sedentary life on wheel-chair. Through DEXA remarks we have documented an osteopenia at the lumbar site in patient 1 and a severe osteoporosis at the femoral site in both patients. We believe that the capacity of deambulation must be stimulated in such patients in order to maintain a good mineralization rate of the skeleton and that DEXA represents a useful means to monitor BMD in children with MPS IV.

87 (79). CORRELATION OF OSTEOPOROTIC FRACTURE RISK EVALUATED BY QUANTITATIVE ULTRASOUND BONE DENSITOMETRY (QUS) WITH BODY MASS INDEX (BMI) IN 500 POSTMENOPAUSAL WOMEN C. Poiana1, I. Virtej, C. Dumitrache, Institute of Endocrinology, ``C.I. Parhon'', Bucharest, Romania Measuring bone mineral density (BMD) forms the basis for diagnosing osteoporosis, allowing the diagnosis in an early, asymptomatic phase and optimizing therapeutic strategies. Quantitative ultrasound (QUS) bone densitometry measures bone mineral density (BMD) and evaluates the quality of bone. The parameters measured with QUS are; BUA (broadband ultrasound attenuation), SOS (speed of sound) and the clinical index Stiffness. QUS correlates with osteoporotic fracture risk. We evaluated the inuence of 2 independent risk factors for osteoporosis-body mass index (BMI) and number of years postmenopause-on. BMC and osteoporotic fracture risk in 500 healthy postmenopausal women aged 4374 years. QUS was performed at the os calcis with an Achilles Lunar Plus device. All women were measured for BMI. Conclusions: Our study shows an increased risk for osteoporotic fractures with increased number of years postmenopause; the ultrasound parameter with best statistic signicance was SOS with signicant decreased values (p<0.05) in women more than 10 years postmenopause. The risk for osteoporotic fractures is increased in women with low BMI, independent of number of years postmenopause.

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90 (82). BONE MINERAL DENSITY (BMD) IN CUSHING'S SYNDROME(CS) AND EXOGENOUS HYPERCORTISOLISM L. Rozhinskaya, E. Marova, T. Chernova, N. Sazonova, L. Dzeranova, National Research Center for Endocrinology, Moscow, Russia Chronic exposure to excessive concentrations of endogenous cortisol or to exogenous glucocorticoids (GC) causes osteopenia, osteoporosis and bone fractures. The object of our study was to determine frequency of osteopenia and osteoporosis in patients with CS and in patients taking GC, and to estimate inuence of age, BMI, duration of amenorrea, activity of hypercortisolism in CS or duration of GC therapy on BMD and bone loss. We have studied 187 patients with CS, 58 patients taking GG and 300 healthy subjects (HS) divided according to age and sex. BMD was measured using ``Expert XL'' Lunar densitometer in lumbar spine and femoral neck. Data are presented as mean m in the table. Vertebral and femoral BMD were signicantly lower and frequency of OSP and OP was higher in patients in active phase of CS than in remission CS. BMD reduce did not depend on age, sex and BMI.. GC patients had a signicantly lower BMD and higher frequency of OSP and OP, than in age and sex matched controls. Analysis of our data showed: BMD reduce in CS depends on hypercortisolism activity. Bone loss restores after treatment CS; Bone loss in GC patients closely relates with GC doses and duration of GC therapy.

During one year we follow with bone densitometry scans (zerotime and 12 months) 16 patients, aged from 4 to 61 (median=232.5) years with GD receiving Cerezyme R (Imiglucerase for injection, median doses for adults was 27.6 UI/kg, and for children was 38.5 UI/kg) and both received also 500 mg (twice a day) of calcium carbonate. The median results of BMD in lumbar spine was 0.7420.23 g/cm2 before the treatment and 0.8160.22 after (p<0.0001), with an increase of 7.95.7% in this region of the skeleton. T-score in this region was 1.71.1 before and 1.31.0 after treatment (p = 0.0093). The median results of BMD in femur was 0.9790.23 g/cm2 before and 0.9920.23 g/cm2 after (not statistically signicant) with na increase of 1.11.6%. T-score median was 0.52.2 before and 0.62.1 after treatment (not signicant). In total body median BMD was 0.8380.14 g/cm2 before and 0.8350.15 g/cm2 with na increase of 2.14.2% in this region. Tscore median was 1.31.2 before and 1.51.2 after treatment (not signicant). Our results showed clearly that enzyme treatment plus calcium was important for bone involvement in Gaucher disease, meanly for spine, and bone densitometry is an important tool for following-up this GD patients.

92 (84). PERFORMANCE OF AN AUTOMATIC ANALYSIS ALGORITHM FOR A DXA BONE DENSITOMETER C. Ruth, T. Richardson, E. von Stetten, H. Weiss, K. Wilson, T. Kelly, G. Rappolt, E. Yapchian, M. Barrick, Hologic, Inc., Bedford, MA, USA Inter-operator variability in BMD results has been recognized as an important factor in clinical performance of DXA systems. An algorithm (auto-analysis) was developed to automatically locate the regions of interest used in the analysis of AP spine and hip images. Auto-analysis facilitates ease of use and decreases interoperator variability in results. We evaluated the performance of auto-analysis relative to manual analysis performed by expert operators. AP spine and hip scans (Hologic QDR 4500) of 96 periand post-menopausal women (mean age = 565 yrs) were analyzed separately by two expert operators and by automatic analysis. Auto-analysis was considered successful if no adjustments to the regions were deemed necessary by an expert operator. The mean and standard deviation of the differences in BMD results between two expert operators, and between each operator and auto-analysis were computed and averaged over all scans successfully analyzed for all regions. Auto-analysis successfully analyzed 87% of spine and 87% of hip scans. Expert operator and auto-analysis BMD results were highly correlated (R>0.95). Absolute differences between an expert operator and automatic analysis were not signicantly different than the differences between two expert operators. When all scans are included in the analysis, the mean differences and correlation coefcients are similar and the SD of the differences increases slightly. In conclusion, this auto-analysis algorithm successfully analyzed the vast majority of hip and spine scans obtained in a peri- and post-menopausal population. Agreement between auto-analysis and an expert operator was as close as the agreement between two expert operators. This algorithm simplies analysis, minimizes operator intervention, and may reduce inter-operator variability.



BMD L2-L4 T-score 3.20.26 1.360.31 2.10.15 2.20.24 0.50.16 0,30,12 2,20,32 1.660.22 0.420.18 0.050.12 1.080.1

BMD NECK T-score 2.20.23 0.840.32 1.30.19 1.40.21 0.320.19 0,280,13 1,90,35 1.570.14 0.390.21 +0.130.12 0.750.08

OSP % L2-L4 22 40 66 45 24 24 40 45 28 16 32

OP % L2-L4 78 13 25 42 9 0 40 28 2 0 8

CS, male, a/f CS, male, rem CS, fem., a/f CS, fem., a/f CS, fem., rem CS, fem., rem GC, male GC, female HS, male HS, female HS, female

2050 2050 2039 4065 2039 4065 2050 2055 2050 2039 4065

18 15 32 22 45 55 15 43 42 88 170

a/f- active phase of CS; rem remission; OSP- osteopenia; OP- osteoporosis

91 (83). BONE INVOLVEMENT IN GAUCHER DISEASE PATIENTS L. Russo, L. Gregorio, M. De Paula, C. Petriz, R. Vivaldi Gaucher disease, also called glucosylceramide lipidosis is the most common of the sphingolipidoses, a group of diseases that are inherited in an autosomal recessive manner. Its characterized by the accumulation of glucocerebroside in tissue macrophages, that causes hepatomegaly, splenomegaly and pancitopenia. All patients with GD have some degree of bone involvement and skeletal deterioration like: generalized osteopenia, Erlenmeyer ask deformity of the distal femur, lytic lesions, osteosclerosis, pathologic fractures, and soap bubble appearance of bones. Although the cause of osteopenia is not dened clearly, it is thought that the osteoclast-in GD is overly active leading to osteoporosis and weakening of the bones in affected patients. GD has become the rst intracellular enzyme deciency to be treated with a recombinantly produced enzyme. For monitoring the focal skeletal complications we reviewed of plain X-ray lms and Dual energy X-ray absorptiometry (DEXA, Lunar DPX-L WI) exams, far more sensitive method for detecting subtle changes in bone mineral density and promises to be and excellent mean of monitoring clinical progress in GD patients.

Mean differences (SD) in g/cm2 expert operators (OP1, OP2), and autoanalysis (AUT) Region Neck Hip Total Spine Total OP1 OP2 0.001 (.012) 0.006 (.014) 0.007 (.018) OP1 AUT 0.004 (.014) 0.0 (.016) 0.003 (.015) OP2 AUT 0.005 (.014) 0.006 (.019) 0.010 (.012)

93 (85). VARIABLE INTERPRETATIONS OF BONE MINERAL DENSITY RESULTS IN A GROUP OF FILIPINOS USING CAUCASIAN AND ASIAN REFERENCE VALUES S. T. Saavedra1, T. P. Torralba1, S. H. Dy1, S. V. Navarra1, 1Section of Rheumatology, Immunology and Osteoporosis, Santo Tomas University Hospital, Manila, Philippines OBJECTIVE: To determine variability in the interpretation of bone mineral density (BMD) using Caucasian and Asian reference values. DESIGN: Cross sectional, descriptive study. SETTING: Joing and Bone Center (JBC) of Santo Tomas University Hospital (STUH), tertiary private hospital in Manila. PARTICIPANTS: All patients referred to JBC for bone densitometry from January to December 1999. INTERVENTION: BMD measurements were made by dual energy x-ray absorptiometry (DXA) using Lunar DPX-IQ. The BMD results were interpreted by World Health Organization (WHO) criteria using reference values derived from two populations: Caucasians (American) and Asians (Chinese). Variability in interpretations using either reference population was measured by paired t-test. RESULTS: A total of 1070 Filipinos (944 females, 126 males) were enrolled in the study. The mean age was 51.9 years with body mass index (BMI) ranging from 13.1 to 45.3 (mean 23.97). Using the Caucasian reference values for spine BMD, 354 (33.08%) were categorized as normal, 390 (36.45%) with osteopenia, and 182 (17.01%) were osteoporotic; for femoral BMD, 544 (50.84%) were normal, 446 (41.68%) osteopenic and 80 (7.48%) osteoporotic. Lumbar spine and femoral neck BMD interpretation by T-score signicantly differed using either Caucasian or Asian reference populations, p50.0001. Femoral neck BMD z-scores also showed signicant variability in interpretation using Caucasian vs. Asian reference populations with p value of 50.0001; no difference was noted using lumbar spine z-scores. CONCLUSION: Interpretation of BMD values relies signicantly on the reference population used. This will have signicant implications in therapeutic recommendations.

Thursday, June 15, 2000


S. Sakata1, R. Barkmann1, E. M. Lochmu ller2, C. C. Glu er1, Diagnostische Radiologie, CAU Kiel, Germany; 2Universitatsfrauenklinik der LMU Muenchen, Germany

The cortical shell of long bones gets thinner and more porous due to aging and disease. In this study we tested if ultrasound velocity in the metaphysis of nger phalanges correlated with porosity as well as geometry and cortical density of each other. We used 44 proximal phalanges, age 52 to 98 (15m, 29f) with removed soft tissue, xed in formalin. Cross-sectional area of the metaphysis of nger phalanges were measured using Quantitative Ultrasound (DBM Sonic 1200, IGEA), High Resolution Quantitative Computed tomography (HRQCT, Somatom Plus, Siemens) and High Resolution Magnetic Resonance Image (HRMRI, Siemens Medizintechnik, Erlangen). We used Speed of Sound (SOS) as a ultrasound velocity parameter and Area 2 Peaks (A2P) as a amplitude parameter. From HRQCT we calculated cortical bone mineral density (cBMD), from HRMRI we calculated the site matched relative cross-sectional cortical area (RCA) as the retio of cross-sectional areas of the cortex and the whole bone and cortical porosity (CP) as the ratio crosssectional porosity areas in cortex and cortex areas. SOS was signicantly correlated with RCA (R2=0.39, p50.0001), cBMD (R2=0.47, p50.0001) and CP (R2=0.30, p50.0001), while A2P was correlated with RCA (R2=0.20, p50.01), but not with cBMD and CP. The combination of RCA and cBMD using ANOVA model improved the correlation coefcient to R2= 0.58. RCA and BMD contributed signicantly at p50.05 (RCA) and p50.01 (cBMD). SOS decreased with decreasing cBMD as well as decreasing RCA and with increasing CP. We conclude that these results could prove the impact of phalanx geometry, cortical bone density and cortical porosity on ultrasound velocity and only geometrical factor on amplitude.

94 (86). BONE MINERAL DENSITY AND KNEE OSTEOARTHRITIS IN ELDERLY WOMEN is, Y. Yapici, G. Sahin, O. Cimen Bo lgen, A. Bic er, H. Gu ler, S. Bag C. Erdogan, Department of PMR, Mersin University, Faculty of Medicine, Mersin, Turkey To examine the possible inverse relationship between osteoporosis (OP) and osteoarthritis (OA) we evaluated the association between bone mineral density (BMD) and knee OA. Ninety-two patients were enrolled to the study. Bone mineral density of the proximal femur (neck) was measured by densitometry. Knee OA was assesed from a weight-bearing anterior-posterior radiograph and graded on a scale of 0 (no OA) to (severe OA) according to Kellgren-Lawrence. The subjects included 92 women with an age range of 4075 years (mean 61,58707,4068 years). Of these 21 had no OA, 39 had grade 1 OA, 22 had grade 2 OA, 8 had grade 3 OA and 2 had grade 4 OA. Mean femoral BMD (neck) was 0.75180.1132. There was signicant correlation between knee OA and BMD of femur (neck) statistically (r = 0.235), (P<0.05). For BMD, there was no signicant difference in the distribution of knee OA grades between groups (p = 0.305). There was also no statistically signicant correlation between groups having knee OA (grade 1,2,3,4) and no knee OA (grade 0) for BMD (p = 0.691). So we conclude that relationship between OA and OP may be inuenced by other factors apart from osteophytosis and joint space narrowing. However, the numbers of patients were low, existing data is preliminary and longterm studies with double blind controlled are needed.

96 (88). DOSE RELATED ASSOCIATION OF BONE MINERAL DENSITY (BMD) AND HIGH IMPACT ACTIVITY IN PREPUBERTAL GIRLS T. A. Scerpella, C. M. Morganti, M. Davenport, L. M. Johnson, J. A. Kanaley, 1SUNY Upstate Medical University; 2Syracuse University, Syracuse, NY, USA The purpose of this study was to determine whether there is a dose-dependent association between high impact activity and BMD in prepubertal girls. Methods: Forty-nine 711 year old Caucasian female gymnasts, practicing at 3 different frequency levels [low, 25 hrs/wk (n=11); mid, 510 hrs/wk (n=20); and high, >10 hrs/wk (n=18)] were compared to 23 sedentary controls, matched for height, weight, age, and Tanner stage. Hip, spine, arm, total body BMD and fat free mass (FFM) were determined by dual energy X-ray absorptiometry (DXA) (Hologic QDR4500). Anthropometrics, strength, calcium intake, gymnastics and total physical activity were measured during the 6 months prior to DXA scanning. Results: No difference in BMD between controls and low group was observed at any site. Mid and high groups had greater total and regional BMD than controls and greater arm and hip BMD than low group (p<0.05). Analysis of covariance revealed greater BMD in mid and high groups than in controls when BMD was adjusted for strength or FFM (p<0.05). Conclusions: Total and regional BMD in prepubertal girls are increased with ve or more hours per week of high impact activity.

Thursday, June 15, 2000

97 (89). STANDARD X-RAY WITH INTENSIFYING SCREENS FOR RADIOGRAPHIC ABSORPTIOMETRY: A PILOT STUDY D. Silver1, L. Al-Dayeh2, X. Bi2, K. Hudson3, S. Silverman4, 1Cedars Sinai Medical Center, OMC, UCLA, Los Angeles, CA, USA; 2 CompuMed, Los Angeles, CA, USA; 3OMC; 4Cedars Sinai Medical Center, VAGLAHS, OMC, UCLA, Los Angeles, CA, USA Radiographic Absorptiometry (RA) is a reliable and inexpensive method for assessing BMD. Phalangeal BMD based on hand radiography using RA predicts future fracture risk of the hip and spine. RA has required a two view hand x-ray without intensifying screens. We evaluated the use of RA using a standard radiographic technique and intensifying screens. 101 Caucasian and Asian females between the ages of 20 to 79 had two consecutively acquired x-rays of the non-dominant hand. Phalangeal BMD was performed using an automated PC based system (automated OsteoGram1, CompuMed, Inc., Los Angeles, CA). BMD results obtained with and without intensifying screens were strongly correlated (r = 0.994, p<0.001). The study suggests that standard radiographic techniques with minimal radiation exposure can be used for RA. We conclude that automated OsteoGram1 can provide an inexpensive method to determine phalangeal BMD with readily available conventional xray equipment and technique.

static therapy for 2.40.9 years. The analysis of obtained data showed the correlation between Osteocalcin level and bone mineral density (p<0.05). The data of the research show the variability of Osteocalcin level in patients with Graves disease. The increase of Osteocalcin level in the majority of patients with Graves disease shows the presence of increased bone formation. The decreased bone mineral density in young (age<23 years) and postmenopausal women with Graves disease associates with the increase of Osteocalcin level. BMD in lumbar spine in women of reproductive age with hyperthyroidism was signicantly lower in group of patients with overweight (BMI 25.029.0) in comparison with the group of patients with normal weight (BMI 18.524.9). BMD in femoral neck in premenopausal patients was slightly lower in group with normal weight (BMI 18.524.9) than in group of overweight patients, but this decrease was less signicant, than in the the previous case (p<0,75). Postmenopausal women had no correlation between BMD and BMI.

I Age BMI TSH(mIU/ml) FT4 Osteocalcin BMD (g/cm2) Neck Wards Trochanter L2-L4 20.54.2 24.32.5 0.10.3 18.710.3 50.17.9 0.9280.115 0.7580.120 0.7620.109 1.0240.076

II 35.98.1 23.03.8 0.30.5 12.65.4 13.48.2 1.0180.383 0.8270.289 0.8250.125 1.3470.129

III 58.26.4 22.85.2 0.20.7 20.68.2 57.75.6 0.7960.10 2 0.5950.09 0.6380.11 0 0.8960.09


D. Sindel1, A. Yaliman1, A. Oral1, E. Klyan2, D. Tarakci1, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey; 2Pulmonary Department, Istanbul University Medical School, Istanbul, Turkey The aim of the present study was to investigate trabecular and cortical bone density in asthma patients taking long term inhaled steroids (range: 18120 months, meanSD: 40.0622.06 months) and compare with results from normal controls. The mean disease duration was 9.406.45 years (range 2 to 20 years). We evaluated bone status by dual energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound (QUS) in 30 patients (16 females, 14 males) aged 40 to 71 years (meanSD: 57.168.29 years) having bronchial asthma, treated with inhaled steroids and compared them with healthy subjects individually matched for age and sex. The mean avarage dose was 906.66331.07 mg (range 400 to 1200mg). Paired samples T test and Pearson correlation analysis were used for statistical analysis. The bone mineral density (BMD) of the lumbar spine and of the hip were all signicantly lower than those of the matched control subjects (p<0.001). The calcaneal QUS measurements were also lower in the patient group. Broadband ultrasound attenuation (BUA) showed a signicant inverse correlation with disease duration (r = 0.421), whereas BMD did not. In conclusion, this study demonstrate that long-term use of inhalational steroids for the treatment of asthma is associated with decreased BMD and QUS variables.

100 (92). SRI JAYAWARDENEPURA COMMUNITY SURVEY OF OSTEOPOROSIS REFERENCE DATA FOR BROADBAND ULTRASOUND ATTENUATION (BUA) & STIFFNESS INDEX S. H. Siribaddana, U. Hewage, D. J.S. Fernando, Department of Medicine, Sri Jayawardenepura University, Nugegoda, Sri Lanka Hypothesis; Measurement of the Stiffness Index from a randomized representative sample of sub-urban women will provide a ``young adult'' reference, and an age regression curve for the calculation of T-scores and Z-scores. Methods: Ambulatory women age 21 to 80 years were randomly selected from electoral list in a suburban area. The computation of broad band ultrasound attenuation and speed of sound measured Stiffness Index by heel ultrasound (Lunar Achilles). Results: BUA & Stiffness Index results were obtained from 700 women. The stiffness Index demonstrated age regression described by: Age Regression of Stiffness Index =70.179+ AGE * (0.319). BUA & Stiffness Index begins to decline dramatically after 50 years. The reference value can be taken from women aged between 2050 years (n=446). The mean value for BUA was 116.55 with standard deviation (SD) of 12.12. The mean value for stiffness index was 80.77 with a SD of 14.67. These values are used in calculating the T score. Conclusion: The study provides representative, reference data for assessment of osteoporotic fracture risk in Sri Lankan suburban women.

99 (91). BONE MINERAL DENSITY IN PATIENTS WITH GRAVES DISEASE L. Sipina, N. Kouznetsov, G. Kolesnikova, N. Goncharov, T. Chernova, National Endocrinology Research Center, Moscow, Russia The objective of the research was to assess the correlation between Osteocalcin level and bone mineral density in women with Graves disease. There have been examined 36 patients, aged 2270 years with hyperthyroidism. The BMD of lumbar spine femoral neck was assessed using dual-energy X-Ray absorptiometry (DEXA) LUNAR EXPERT XL. All patients received thyro-

Age Number Stiffness SD BUA SD

2130 143 80.90 15.35 115.61 14.86

3140 144 79.84 15.42 115.77 13.23

4150 159 81.59 16.73 117.94 12.96

5160 160 71.87 18.78 110.33 20.55

6170 70 63.17 15.53 100.59 15.30

7180 24 56.39 13.40 95.04 12.66

101 (93). BONE MINERAL STATUS OF FEMALE ADOLESCENTS 14 MONTHS AFTER THE CESSATION OF A CALCIUM AND EXERCISE INTERVENTION S. J. Stear, A. Prentice, S. C. Jones, T. J. Cole, MRC Human Nutrition Research, Cambridge, UK Our recent 15-month Ca supplementation (1 g/d) and exercise intervention enhanced bone mineral status in 1618 year old female adolescents. A follow-up study 14 months after withdrawal of Ca supplements and exercise sessions was conducted in 84 (64%) girls to investigate the intervention's lasting effect. Whole body and regional measurements of bone mineral content (BMC) and bone area (BA) were made by DXA (Hologic QDR 1000/ W). Table gives mean percent difference (SE) between Ca supplemented and placebo groups, for those with high compliance (>75% tablets taken) in change in BMC since baseline, corrected for BA, body weight, height and baseline BMC. A signicant difference of 2.6% remained at the femoral neck, but differences at other sites were no longer signicant. If the effect of Ca supplement persists it could be of considerable clinical signicance, as it represents nearly quarter a SD in this population, and which, if maintained into old age, might reduce the relative risk of hip fractures by a quarter.

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103 (95). VALIDATION OF BIOELECTRICAL IMPEDANCE ANALYSIS (BIA) IN ASSESSING BODY COMPOSITION: COMPARISON WITH TOTAL BODY DXA AND SERUM LEPTIN B. Sutter, O. Legrand, F. Bianchi, F. Bougon, E. Meys, Institut CALOT, Berck/Mer, France OBJECTIVES: BIA is a fast low-cost radiation free tool for body composition measurement. We evaluate a leg-to-leg BIA system (Bodymaster, Calor) and total body fan beam DXA as the reference method (Hologic QDR4500A) in 109 subjects (women 64 men 45, BMI 28.17.3 kg/m2 48.317.7 yr.). Additionally, leptin was obtained in 60 subjects (Quantikine, R&D). RESULTS: BIA reproducibility is 1.0 0.8%. Correlations between BIA and DXA total fat, real and DXA measured total weight are summarized in table. There is a signicative difference between devices: BIA underestimates fat mass, while DXA underestimates real weight. These errors are related to weight. Leptin correlated in same extent with both methods (r2= 0.541 with DXA fat and 0.532 with BIA). CONCLUSIONS: The leg-to-leg BIA . provides simple rapid and reproducible measurements of body composition . is a good predictor of DXA-derived body fat superior to BMI (r2= 0.908) and leptin A discrepancy is observed between the two methods: BIA underestimates DXA measured fat, while DXA underestimates total weight. These biases worsen with body weight.

(a=P40.05; b=P40.001)

Intervention Ca=21, P=23 +0.9 +2.3 +2.8 +2.7 +5.3 (0.4)a (0.6)b (0.7)b (0.7)b (0.9)b

Follow-up Ca=21, P=23 +0.4 +1.0 +1.5 +2.6 +1.7 (0.5) (0.9) (1.1) (1.1)a (1.6)

Whole-body Spine L14 Hip total Hip neck Hip trochanter

Total fat BIA vs DXA r2 difference 0.939 2.15.2 kg

Total weight DXA vs weighing 0.997 1.92.4 kg

102 (94). IMPACT OF A CALCIUM AND EXERCISE INTERVENTION ON BONE MINERAL STATUS OF FEMALE ADOLESCENTS S. J. Stear, A. Prentice, S. C. Jones, T. J. Cole, MRC Human Nutrition Research, Cambridge, UK To test the hypothesis that increasing Ca intake and taking part in regular exercise are important for the optimisation of peak bone mass, 131 female sixth-form students, 17.30.3 y, took part in a 15-month intervention study. Girls were randomly assigned, double-blind, to Ca (1000mg/d) or placebo and then stratied by supplement type, were randomly allocated to an exercise (3 x 45min/wk) or control group. Whole body and regional measurements of bone mineral content (BMC) and bone area (BA) were made by DXA (Hologic QDR 1000/W). Table gives mean percent difference (SE) between intervention and control groups, for those with high compliance (Supplement >75%, exercise attendance >50%) in BMC at outcome, corrected for BA, body weight, height and baseline BMC. Ca supplementation and exercise enhanced bone mineral status in these female adolescents. If it proves to be a lasting benet, leading to the optimisation of peak bone mass, the risk of fragility fractures should be reduced.

104 (96). COMPARISON OF DISTAL RADIUS SPA, SPINAL AND FEMORAL DEXA AND TIBIAL ULTRASOUND METHODS FOR DETERMINING OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN C Tezel, C Erdogan, A Karabulut Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Diagnosis and prevention of osteoporosis are important because of the cost effects, fracture risk and mortality (1221 % in hip fractures). We investigated the role of osteodensitometry which is a non invasive method, in the diagnosis of osteoporosis in postmenopausal women. Fifty-three women with back or low back pain and/or with general bone pain were included in the study. The means of age, weight, height, period of time since menopause have been determined. Serum calcium, phosphorus, alkaline phosphatase and urinary calcium (24 hours) were measured. Dorso-lumbar antero-posterior and lateral radiographs were taken. Compression fracture was investigated by the method of Yamada et al. Bone mineral density was measured at lumbar spine and femoral neck by dual photon X-ray absorptiometry (DEXA), at distal radius by single photon absorptiometry (SPA) and at mid-tibia by ultrasound (ultraScan). In the rst stage, means and standart deviations of age, weight, height, time since menopause, BMD values, T and Z scores, ultrasound SOS (speed of sound) and T score were calculated. These calculations were made both for the total sample and sub samples of those with or without compression fractures. The relevant correlations were found. In the second stage, the differences of the values of the variables among the sub samples were tested by Student's t test. In the third stage ANOVA was done to see the signicance of the differences of various measurements.

(a=P40.05; b=P40.001)

Calcium Ca=32, P=30 0.8 1.9 2.7 2.2 4.8 1.3 (0.3)a (0.5)b (0.6)b (0.7)b (0.9)b (0.6)a

Exercise E=20, N=56 0.4 0.6 1.4 1.1 2.6 0.1 (0.4) (0.7) (0.7)a (0.9) (1.2)a (0.8)

Whole-body Spine L14 Hip total Hip neck Hip trochanter Radius-ultradistal

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The three methods yield measurements which are weakly correlated.
BMD (gm/cm2) by Site Location Hip Spine Whole Body Mean .563 .502 .719 Low .409 .382 .609


High .736 .685 .850

105 (97). QUANTITATIVE COMPUTED TOMOGRAPHY IN THE EVALUATION OF VERTEBRAL BONE MINERAL DENSITY: COMPARISON BETWEEN 2-DIMENSIONAL AND 3DIMENSIONAL IMAGING APPROACHES D. J. Theodorou, S. J. Theodorou, D. Kubota, M. Andre, J. Weigert, D. J. Sartoris, Department of Radiology, Veterans Affairs Medical Center, and University of California, School of Medicine, San Diego, CA, USA Purpose: Quantitative computed tomography (QCT) has long been used for the evaluation of bone mass and density. Our purpose was to correlate the diagnostic precision of 2dimensional (2D) QCT with that of 3-dimensional (3D) QCT in the assessment of bone mineral density (BMD) in the lumbar spine. Patients and Methods: 21 women (age range, 4282 years) referred for BMD evaluation were selected to participate in the present study. In all patients, a single-energy QCT scan at the L1-L2 vertebral levels was performed, and 10mm thickness transverse midvertebral slices were also obtained. Similarly, 3D QCT studies were performed at the same vertebral levels selected for the 2D studies. Utilizing the scanner special analysis software, measurements of BMD were performed in predened regions of interest (ROIs) of trabecular vertebral bone. Each data acquisition was analyzed twice, yielding 2 pairs of BMD values per patient, and statistical analysis of resultant data was conducted. To validate precision of our measurements, however, variability in values obtained by both imaging techniques was estimated. Results: No signicant difference in variability was observed in the 2D and 3D QCT acquired measurements. 3D QCT BMD measurements were 8% larger than 2D QCT BMD measurements, likely owing to the incorporation of higher bone mass within the ROI measured. Conclusion: Our results indicate a non signicant difference between the BMD values derived from the 2D and 3D QCT imaging approaches, and suggest an important role for 3D QCT in the evaluation of BMD in the lumbar spine.

107 (99). PREVALENCE OF LOW BONE MASS AMONG YOUNG FILIPINO FEMALE NURSES AT SANTO TOMAS UNIVERSITY HOSPITAL T. P. Torralba1, S. V. Navarra1, S. T. Saavedra1, C. C. Bermudez1, M. T. Ong1, S. H. Dy1, L. B. Mercado-Asis1, 1Section of Rheumatology, Immunology and Osteoporosis; Section of Endocrinology and Metabolism, University of Santo Tomas Hospital, Manila, Philippines OBJECTIVE: To determine the prevalence of low bone mass among young Filipino nurses at STUH. STUDY DESIGN: Cross sectional, descriptive study. SETTING: Joint and Bone Center of Santo Tomas University Hospital, tertiary private hospital. PARTICIPANTS: All actively menstruating Filipino female nurses at STUH ages 2040 years old who underwent bone mineral density at Joint and Bone Center, STUH. INTERVENTION: Lumbar spine (L1 to L4), femoral neck and forearm bone mineral density were made by dual energy x-ray absorptiometry (DXA) using Lunar DPX-IQ. The prevalence of osteoporosis was determined using the Asian (Chinese) reference population dened according to the WHO criteria. RESULTS: A total of 100 women were enrolled in the study with a mean age of 27.7. On lumbar spine examinations, 86 (86%) patients had normal results and 14 (14%) had osteopenia. On the femur, 79 (79%) patients had normal results and 21 (21%) had osteopenia. Seventy-seven (77%) had normal results, 22 (22%) had osteopenia and 1 (1%) had osteoporosis at the forearm. CONCLUSION: The prevalence of low bone mass was 14 to 22% in the group of Filipino nurses studied, especially at the forearm. It is important to review the factors underlying osteopenia in this nurses, and perform repeat DXA in the future, to evaluate improvement reecting peak bone mass achievement.

106 (98). DISTRIBUTION OF BONE DENSITY IN CHILDREN 46 YEARS OF AGE J. Torner, S. Levy, T. Burns, M. Willing, J. Warren, K. Janz, University of Iowa, Iowa City, IA, USA The purpose of this study is to describe and characterize factors of bone development. A cohort of 305 children (160 girls and 145 boys) was evaluated for bone density using an Hologic 2000 as part of their annual exam. The children ranged in age from 4.3 to 6.5 years with a mean of 5.2 years. Even within this restricted age range bone mineral density (BMD) had a wide distribution. Correlations of bone mineral content (BMC) between sites were higher (r = .77-.83) than correlations with BMD (r = .42-.58). Weight showed the strongest individual correlation for BMD of the hip and spine and age had the largest for the whole body. A linear model with age, body mass index, height and gender accounted for 27% of the variation for hip BMD, 28% for spine BMD and 11% for whole body BMD. Body size (body mass index and height) and gender was more signicant than age at all sites for BMD. In contrast, regression models for BMC accounted for 55% of the variation for hip, 53% for spine and 74% for whole body with body mass index and height as the strongest variables.

108 (100). PREVALENCE OF OSTEOPOROSIS AMONG PERIMENOPAUSAL AND POSTMENOPAUSAL FILIPINO WOMEN STUDIED AT SANTO TOMAS UNIVERSITY HOSPITAL T. P. Torralba1, S. T. Saavedra1, C. C. Bermudez1, M. T. Ong1, H. mez1, S. V. Navarra1, S. H. Dy1, L. B. Mercado-Asis1, S. Go 1 Section of Rheumatology, Immunology and Osteoporosis; Section of Endocrinology and Metabolism, Santo Tomas University Hospital, Manila, Philippines OBJECTIVE: To determine the prevalence of osteoporosis in a group of perimenopausal and postmenopausal Filipino women. STUDY DESIGN: Cross-sectional, descriptive study. SETTING: Joint and Bone Center (JBC), Santo Tomas University Hospital (STUH), tertiary private hopsital. PARTICIPANTS: All perimenopausal and postmenopausal Filipino women with ages 40 to 49 (n=32), 50 to 50 (n=30), and 60 to 69 (n=43) who were referred for bone mineral density study at the Joint and Bone Center, STUH. INTERVENTION: Lumbar spine (L1 to L4), femur (neck) and forearm (total) bone mineral density (BMD) measurements were made by dual energy x-ray absorptiometry using Lunar DPX-IQ. The prevalence of osteoporosis (T-score SD) was determined

using the Asian (Chinese) reference population based on the WCO criteria. RESULTS: A total of 105 women were enrolled in the study.
AGE LUMBAR SPINE Normal (25) 78% (13) 43% (23) 19% FEMUR Normal (27) 84% (18) 60% (11) 26% FOREARM Normal (21) 66% (8) 27% (10) 23% Osteopenia (7) 22% (13) 43% (23) 53%
(5) 16%

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the cynomolgus monkey, using double X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) before and after ovariectomy (OVX). Aged female cynomolgus monkeys (9 years or older) were used. The animals were used for the measurement of BMD before, and 6 months after OVX or sham-operation. Each animal was held in the supine position under ketamine hydrochloride anesthesia. The BMD of the femoral neck was measured by XCT3000 (Norland Stratec). The BMD of the 3rd to 5th lumber vertebrae was measured by (DPX-a, Lunar). Compared with the sham-operated group, a statistically signicant decrease in BMD in the lumber (assessed with DXA) was noted. BMD in the femoral neck (assessed with pQCT) in the OVX group tended to be lower than that in the shamoperated group, but no apparent differences were noted between trabecular and cortical bone densities.

4049 5059 6069 AGE 4049 5059 6069 AGE 4049 5059 6069

Osteoporosis 0 (4) 13% (12) 28% Osteoporosis 0 (1) 8% (4) 9% Osteoporosis 0 (4) 13% (19) 44%


(4) 37% (28) 65% Osteopenia (11) 34% (18) 60% (14) 33%

111 (103). EVALUATION OF BONE MINERAL DENSITY IN A TURKISH POPULATION F. Tuzun, S. Tuzun, I. Karacan, N. Selim, 1University of Istanbul, Cerrahpasa, Istanbul, Turkey; 2University of Istanbul, Cerrahpasa, Istanbul, Turkey; 3University of Istanbul, Cerrahpasa, Istanbul, Turkey; 4Bestas Group, Lunar, Turkey The aim of this study was to determine the range of bone mineral density (BMD) in normal Turkish adults using a Lunar DPX densitometer. Four sites (total body, AP spine, femur and forearm) were investigated in 370 healthy subjects of both sexes (91 male and 246 female) aged between 20 and 82 years from 29 different centres. There was a positive correlation between BMD, body weight and height in both sexes, especially in postmenopausal women. The timing of peak bone density at AP spine and distal radius was 4th decade in both genders whereas it was 3rd decade in men and 4th in women at femur neck. Total body BMD was signicantly higher in men in all decades. BMD values at distal radius and femur neck were found to be higher in men in the 3rd decade. The major fall in the BMD was observed in women related to the menopause after 50 years. There was no relationship between BMD and both age at menarche and parity whereas there was an inverse relationship between BMD and the duration of menopause.

CONCLUSION: Osteoporosis involving the lumbar, femoral and forearm areas is highest among the postmenopausal Filipino women aged 60 to 69 years.

109 (101). BONE MASS, BODY COMPOSITION AND BONE ULTRASOUND MEASUREMENTS IN ANKYLOSING SPONDYLITIS E. Toussirot, F. Michel, B. Auge , D. Wendling, Rheumatology, Besancon, France Objectives: 1- to examine bone mass using dual energy X-ray absorptiometry (DEXA) and quantitative ultrasound in AS patients. 2- to determine the changes in body composition. Methods: 57 AS patients (modied NY criteria)(41 M, 16 F, mean age 38.02) were compared to 60 healthy controls (HC)(43 M, 17 F, mean age 36.4)(no post-menopausal women). Lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) were evalutated using a DPX-IQ scan (Lunar). Broadband ultrasound attenuation (BUA) and speed of the sound (SOS) were measured at the calcaneus (Achilles, Lunar). Body mass parameters (DPXIQ) included total BMD, total bone mineral content (BMC), lean mass (LM), fat mass (FM). Results:
LS BMD g/cm2 AS HC P 1.075 1.185 .0002 FN BMD gcm2 0.977 1.047 0.01 BUA dB /MHz 122.2 124.1 NS SOS m/s 1555. 1566. NS Total BMD g/cm2 1.202 1.251 0.02 Total BMC g 2896. 3196. 0.006 LM g 47906 50806 NS FM g 16967 17851 NS

112 (104). MULTIPLE SCLEROSIS; THE ROLE OF CORTICOSTEROIDS AND IMMOBILITY ON BONE MINERAL METABOLISM S. Tuzun, A. Altintas, I. Karacan, S. Tangurek, A. Siva, University of Istanbul, Cerrahpasa, Istanbul, Turkey Bone mineral metabolism can be affected in MS due to several factors such as corticosteroid treatment, decreased mobility and potential vitamin D deciency. 83 clinically denite MS patients (60 female.23 male) with a mean age of 39.14+9.37 and 62 agematched controls were enrolled to the study. Besides detailed clinical examination, EDSS, Barthel Index, Functional independence measure(FIM), cumulative corticosteroid (CCS) dosages as total peroral (PO), total parenteral (PE) and cumulative PE dose in a year before enrollment were recorded. BMD was measured using a Holojic QDR 4500 Plus. Serum Ca,P, Mg, bone alkalin phosphatase, PTH, 25OHD3, 1,25(OH)2D3, osteocalcine, urine deoxypridinoline and 24 hour urinary Ca/creatinine exretion were studied. Patients were categorized in ve groups according to the administration and cumulative dosages of CS as follows: Group la, <1500mg, PO, group Ib; >1500mg, PO, group IIa; <10000mg, PE, group IIb; 1000030000mg PE, group IIc; >3000mg, PE, BMD values at lumbar spine and femur (neck, trochanter, ward's area) were signicantly decreased in MS patients (p = 0.000). EDSS, Barthel and FIM scores were correlated with BMD values in all evaluated regions. Signicance was prominent for trochanter and neck regions but not for lumbar spine. There was no correlation

Conclusions: the reduced BMD and BMC in AS patients reect a bone impairment. In contrast, no changes were evidenced by ultrasound measurements and no modications in body composition (lean/fat mass) were observed. As opposed to DEXA, quantitative ultrasound does not appear to be a suitable method for screening AS patients with osteoporosis.

110 (102). CHARACTERISTICS OF CHANGES IN BONE MINERAL DENSITY BEFORE AND 6 MONTHS AFTER OVARIECTOMY IN AGED CYNOMOLGUS MONKEYS Hideshi Tsusaki, Shuichi Kamata, Koichiro Fukuzaki, Hiroaki Miyajima, Ryoichi Nagata, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan The purpose of this study is to clarify characteristics of changes in bone mineral density (BMD) of the lumber and femoral neck of

Thursday, June 15, 2000

between BMD scores and the CCS dosages in any treatment group. Serum vitamin D levels were within normal limits in MS patients and evaluated biochemical markers did not show any correlation with both CCS dosage and disability scores. Signicantly decreased BMD values was found in MS group that was correlated with disability scores but was independent of the CCS dosage received. Disability scores that were consistent with preserved ambulation in our study group and the lack of signicance between osteoporosis at lumbar spine and disability, further that disability is not the only factor responsible for osteoporosis in MS. Immune factors like cytokines those have a role both in MS pathogenesis and bone metabolism could be an alternative explanation of our results.

respectively. Within the Caucasian population, following menopause (age group 5461), SOS declined sharply at an annual rate of 16, 35, 37 and 13 m/sec for the RAD, PLX, MTR and TIB respectively. Largest annual decline was 16 m/sec/y for the RAD, 35 m/sec/y for the PLX, 37 m/sec/y for the MTR and 13 m/sec/y for the TIB. This rate is close to the short-term CV, and could be used to compute the Monitoring Time Interval (=2.8*Rate/ Precision SD) or the Trend Assessment Interval (=1.8*Rate/ Precision SD). We conclude that the time interval between SOS measurements in normal women in this age range who do not have a bone-affecting disease and are not treated with bone affecting drugs should be at least two year apart. Only then, a meaningful change of at least two SD units could be expected. Prospective studies to investigate the monitoring capability of the Omnisnese are currently being performed.

113 (105). MODEL-FITTING AND PREDICTION OF BONE MINERAL DENSITY IN THE LUMBAR SPINE, FEMORAL NECK, AND RADIUS OF HEALTHY WOMEN AFTER NATURAL MENOPAUSE IN A LONGITUDINAL STUDY BY USING AN EXPONENTIAL-TYPE NONLINEAR MIXED-EFFECT MODEL H. Watanabe1,3, M. Fukunaga2, Y. Ohashi1, 1University of Tokyo, Tokyo, Japan; 2Kawasaki Medical School, Okayama, Japan; 3 Teijin Ltd, Tokyo, Japan The subjects of this study were 89 healthy women after natural menopause. An exponential-type nonlinear mixed-effect model was used to estimate and predict bone mineral density (BMD) of three sites: the lumbar spine, femoral neck, and distal 1/3 of the radius. The year since menopause (YSM) and age at menopause (AAM) were used as explanatory variables. The exponential-type nonlinear mixed-effect model was analyzed as (BMD)ij = a + ai + (b ) + eij, ai ~ iidN (0,s 2a), bi ~ iidN + bi)exp(g . (YSM)ij) + d((AAM)i s (0,s 2b), eij ~ iidN (0,s 2e) (i:subject, j:time point, a, b, g, and d as the means of the population, and ai and bi as random effects among subjects). The results were as follows: lumbar spine: (BMD)ij = (0.792 + ai + (0.179 + bi) exp(0.185 x (YSM)ij) 0.00250((AAM)i 50.6), s 2a = (0.106)2 s 2b = (0.0450)2 s 2e = (0.0185)2 femoral neck: (BMD)ij = 0.595 + ai + (0.156 + bi) x exp(0.105 x (YSM)ij) 0.00511((AAM)i 50.6), s 2a = (0.0880)2 s 2b = (0.0659)2 s 2e = (0.0181)2 and radius: (BMD)ij = 0.476 + ai + (0.122 + bi) exp(0.106 2a = (0.0680)2 s 2b = (0.0513)2 x (YSM)ij) 0.00196((AAM)i 50.6), s s 2e = (0.0138)2. These formulae were also used to derive a prediction formula for each individual by using Bayesian approach.

115 (107). QUANTITATIVE ULTRASOUND OF THE CALCANEUS IN HEALTHY TURKISH MEN A. Yaliman, A. Oral, D. Sindel, Department of Physical Medicine and Rehabilitation, Istanbul University Medical School, Turkey The aim of this study was to determine the ultrasound parameters of the calcaneus in a healthy men population and to assess the effect of age, body mass index on the measurements and the relationship between measurements. We measured broadband ultrasound attenuation (BUA), speed of sound (SOS) and quantitative ultrasound index (QUI) of the calcaneus of left feet in 416 healthy men aged 18 to 87 years (mean 45.5417.43 years). Pearson correlation and lineer regression analyses were used for statistical analysis. BUA ranged from 33.50136.60 dB/MHz (mean 76.6717.25); BUA signicantly correlated with SOS r = 0.836), QUI (r = 0.921). SOS ranged from 1472.91658.7m/s (mean 1544.5433.16), SOS signicantly correlated with QUI (r = 0.977). QUI ranged from 49.9165.1 (mean 93.5819.71). Body weight, height, body mass index were not correlated with ultrasound parameters in the study group; measurements correlated with age negatively but nonsignicantly.

116 (108). SEPARATED MEASUREMENT OF TRABECULAR AND CORTICAL BONE IN QUANTITATIVE COMPUTED TOMOGRAPHY (QCT) OF LUMBAR SPINE Akio Yokoi, Tetsuya Katou, National Tokyo Medical Center, Tokyo, Japan Purpose: QCT is thought to be one of the useful methods for measuring the bone mineral density (BMD) in osteoporosis, because of its ability to measure BMD limited to trabecular bone. Placing the region of interest (ROI) at the lumbar spine, we set the three different ROIs; vertebral body spongiosa (SPG), vertebral body cortex (CTX), and vertebral posterior part (PST). We have evaluated the differences of BMD between the area limited to spongiosa and the area including the surrounding cortical bone like as DEXA method. Methods: QCT value was measured in 189 women (3194yearold, mean 65.9) by GE9800 CT-scanner. BMD was determined with a phantom B-MAS (Chugai Pharma. Co.) calculating into the weight of CaCO3. Three ROIs were traced by author after CT scan. The ROI of SPG was placed by the traced line along the inner margin of body cortex without nutritional sinus at the base of body. The ROI of CTX was from the outer margin of body cortex to the front of transverse process without SPG. The ROI of PST was along the base of transverse process, vertebral lamina, facet joint, and spinal process excluding the spinal canal space. Results: Average QCT-value by conventional method was 84.6 mgCaCO3/cm 3. Patients were compared by dividing into two groups: mid-age (<66yo.) vs old-age (66<=), and low-QCT (SPG<=

114 (106). THE IMPORTANCE OF PRECISION-NEW HOPES FOR MONITORING OSTEOPOROSIS TREATMENT BY QUS M. Weiss1, E. Segal2, S. Ish-Shalom2, 1Endocrine Institute and Department of Medicine C, ``Assaf Harofeh'' Medical Center, Zerin; 2Rambam Medical Center and Bruce Rappoport Faculty of Medicine, Technion, Haifa The use of quantitative ultrasound (QUS) measurement in the diagnosis of osteoporosis is growing. The role of QUS still requires the denition of diagnostic criteria and not less important a proof for treatment monitoring capability. A short-term precision of SOS measurements of the Sunlight Omnisense [Omnisense], an ultrasound device that measures speed of sound (SOS) at multiple sites, was determined by three operators, each performing repeated measurement after repositioning in 15 women age 2070. The data obtained indicates intraoperator measurement CV of 0.40% at the Distal 1/3 Radius (RAD), 0.45% at the Mid-Shaft Tibia (TIB), 0.66% at the Metatarsal V (MTR) and 0.81% at the Proximal Phalanx III (PLX). Computed in T-score units, the intra-operator precision is 0.16, 0.18, 0.12 and 0.20 for the RAD, TIB, MTR and PLX respectively. The Interoperator CV was 0.8% at the RAD, 1.3% for the TIB, and 1.4% at the MTR and the PLX, RAD, TIB, MTR and PLX range-normalized standardize precision sCV was 3.3%, 3.3%, 3.0% and 4.5%

96) vs high-QCT (96<SPG). All QCT-values of SPG, CTX, and PST in each groups were multiplied by their areas respectively, which implies each BMC (mgCaCO3). Then, BMD in SPG+CTX+PST which resembles AP-method in DEXA, and BMD in SPG+CTX which resembles lateral method in DEXA were calculated.

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and nodal OA (53,6%) in comparison with OP females (p50.05) (53.3%, 13.3% and 38.9% correspondently). Conclusion: the patients with normal BMD signicantly frequently had knee and nodal OA in comparison with OP patients. These data support the hypothesis that higher BMD is assosiated with OA.

BMD mid-age old-age low-QCT high-QCT

SPG 120 84 66 140

AP-method 283 218 207 294

Lat-method 179 141 122 199

119 (111). STUDY OF HIP FRACTURES INCIDENCE IN MOSCOW REGION (ELECTROSTAL) S. G. Anikin, L. I. Benevolenskaya, Institute of Rheumatology RAMS, Moscow, Russia The goal of this study was to determine the incidence of hip fractures in Electrostal, Moscow region. Materials and Methods. We evaluated the cases of hip fractures among population at age of 50 years and over from Electrostal (population 150 000) in period from January 1st 1992 to December 31st 1997. We used data of Electrostal hospital and town statistic board for analyses. Incidence rates were calculated according to ISD 9, code 820. Results: hip fractures incidence was 54.6/100 000 person/years (p/y) in males, 77.4 p/y in females (in total). The incidence of hip fractures in minimal trauma was 46.9 p/y (from 34.7 in 1994 to 64.8 in 1996 p>0.05) in males and 72.1 p/y (from 35.5 in 1993 to 92.0 in 1997 p<0.05) in females (86% and 97% from total trauma accordingly). The incidence increased with age: from 15.4 p/y (age 50) to 54.7 (age 65) among males (p<0.02) and from 8.6 (age 50) to 60.9 (age 65) among females. It was the highest at age 80 years and over: 165.5 p/y (p>0.05) among males and 361.0 p/y (p<0.002) among females. Ratio female/male was 1.5 (p = 0.01). Conclusion: the incidence of hip fractures was higher among males and increased with age in Electrostal, the typical town of European part of Rassia.

Summary: BMD in AP-method was 2.1~3.1 times of BMD in SPG, and in Lat-method 1.4~1.9 times, suggesting that BMD in DEXA is possibly evaluated so high as at least 1.4 times than BMD in trabecular bone of vertebral body.

Osteoporosis Epidemiology
117 (109). NUTRITIONAL RISK FACTORS IN LITHUANIAN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS Vidmantas Alekna, Elena Cheremnych, Marija Tamulaitiene, Institute of Experimental and Clinical Medicine, Vilnius, Lithuania Introduction. Many behavioral factors are believed to be determinants of bone mass and bone mineral density. One of them is calcium intake from milk and diary products. Patients and methods. A total of 73 women with postmenopausal osteoporosis and 80 controls (random sample) were studied retrospectively as to determine the risk factors. The dietary calcium intake was assessed by the special lifestyle questionnaire. Results. The mean age of women with osteoporosis was 61.91.2 years, controls aged 60.70.8 years. The difference between groups in their nutrition was disclosed by the questionaire. In osteoporotic group 52.2% women were not consuming enough milk and diary products. In control group only in 28.4% cases adequate intakes of calcium-rich milk products were low. Conclusion. These results suggest that low milk and diary products consumption may be important in the genesis of osteoporosis.

120 (112). REPRODUCTIVE FACTORS, BMD, AND FRACTURE HISTORY: THE NORA STUDY E. Barrett-Connor, L. Wehren, D. Furman, T. Abbott, E. Siris, P. Miller, K. Faulkner, M. Berger, A. Santora, L. Sherwood, University of California, San Diego, La Jolla, CA, USA Since estrogen is an important determinant of bone mineral density (BMD) among postmenopausal women, exposure during reproductive years has been hypothesized to affect postmenopausal BMD and fracture risk. NORA, a large observational study of osteoporosis in postmenopausal, ambulatory women, provides an excellent opportunity to examine the associations of elements of reproductive history with peripheral BMD (T-scores) and fracture history after age 45. Baseline data on risk factors and reproductive history were collected from 47,050 women who had not had hysterectomies. The key variable of interest was the duration of endogenous estrogen exposure (difference between the ages of menarche and menopause). Other variables examined included parity, lactation, oral contraceptive (OC) use, age of mother at birth of rst- and last-born children, and postmenopausal (PM) estrogen supplementation. We estimated the separate and collective effects of these variables on BMD and fracture risk using bivariate analyses and (linear and logistic) regression models adjusted for age, ethnicity, and level of education. Using women with less than 30 years of endogenous estrogen exposure for comparison, T-scores increased .12, .25, .41, and .53 and the odds ratios for fracture were .92, .87, .76, and .76 among women with 3034, 3539, 4044, and 45+ years of endogenous estrogen, respectively. OC usage, parity, and PM estrogen usage also had signicant positive effects on BMD. The study provides evidence that the duration of endogenous estrogen exposure has a benecial effect on BMD and lowers fracture risk (even after adjusting for BMD)!

118 (110). INCIDENCE OF OSTEOARTHRITIS (OA) IN PATIENTS WITH DIFFERENT MEAN VALUES OF BONE MINERAL DENSITY (BMD) OF THE LUMBAR SPINE AND FEMORAL NECK FROM EPIDEMIOLOGICAL SAMPLE OF MOSCOW L. Alexeeva, L. Benevolenskaya, E. Mikhailov, A. Smirnov, Institute of Rheumatology of RAMS, Moscow, Russia Aim: to determine the incidence of knee-, hipand nodal OA in patients with different mean values of bone mineral density (BMD) of the lumbar spine and femoral neck from epidemiological sample of Moscow. Materials and methods: 103 females from epidemiological sample of one of the Moscow regions had bone mass measurements of the lumbar spine (L1 L4) and femoral neck (Hologic QDR1000) and X-ray of knee and hip joints. Presence of knee and hip OA was dened by Kellgren-Lawrence grade 52 Nodal OA was diagnosed clinically according ACR criteria. Their age ranged from 50 to 79 yr. Results: patients with normal BMD had more frequently tibiofemoral OA of knee (78.6%), patello- femoral OA of knee (53.6%)

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121 (113). BONE MASS AND FRACTURE RISK IN THE PROXIMAL FEMUR AMONG OLDER WORLD-CLASS MALE TRIATHLETES G. Bibb, S. Farooki, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, 1University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate the bone mineral content (BMC) and density (BMD) in the proximal femur among elite, high performance male triathletes over 45 years of age. METHODS: 95 males were randomly recruited from the 1000 participants competing in the 1999 Ironman World Championship Triathlon at Kona, Hawaii. Subject age ranged from 4576 (mean 54) years. Detailed information regarding diet, exercise regimen, medical problems, lifestyle habits, and personal/family fracture history were obtained from all study participants. BMC and BMD of the proximal femur (regions including neck, greater trochanter, Ward triangle, proximal diaphysis, and total), frontal lumbar spine, and total body were measured using a Norland Medical Systems XR36 pencil-beam dual-energy X-ray absorptiometry (DXA) system. Performance times for the swimming, bicycling, and marathon components of the event were documented. Statistical analysis was performed using Minitab version 12 software. RESULTS:
REGION Total Neck Trochanter Ward MINIMUM T MAXIMUM T MEAN T MINIMUM Z MAXIMUM Z MEAN Z 1.89 2.99 2.81 3.78 3.13 1.93 2.18 0.38 0.007 0.58 0.34 1.9 0.85 0.51 1.78 2.32 3.3 2.42 2.83 1.45 0.35 1.44 0.29 0.385

These results indicate an association of an allelic variant at the VDR locus with muscle strength in elderly men in their sixth and seventh, but not eighth decade, independent of BMI, suggesting that the effect of the VDRP on muscle strength declines with age as previouly described for the inuence of VDRP on BMD. The difference in allelic patterns on muscle strength in men and women might be explained by the effect of sex steroids on the expression of VDRP. Further studies are indicated on the effect of VDRP on muscle strength with age and dependency on sex steroids.

123 (115). DOES RALOXIFENE REDUCE NON-VERTEBRAL FRACTURE RISK IN WOMEN WITH VERY LOW BMD: RESULTS FROM THE MORE STUDY D. M. Black, T. Blackwell, B. Ettinger, S. Sarkar, K. Harper, K. Ensrud, S. Cummings, 1University of California, San Francisco, CA; 2Kaiser Permanente, Oakland, CA; 3Eli Lilly & Co., Indianapolis, IN; 4University of Minnesota, Minneapolis, MN, USA Recent studies have suggested that, among women without vertebral fractures (VFx), bisphosphonates reduce non-vertebral fracture risk more effectively in those with lowest BMD. For example, FIT recently showed that, among women with VFx, the reduction in non-vertebral fractures with alendronate was only 14% overall compared to 36% in the subgroup of women with T<2.5. To address whether this is also true for raloxifene, a selective estrogen receptor modulator, we analyzed data from the Multiple Outcomes of Raloxifene (MORE) trial in which 7705 women were randomized to placebo, raloxifene 60 or 120 mg and followed for 3 years. The analysis was limited to the 4805 women without baseline VFx. A total of 356 non-vertebral and 128 spine fractures occurred in this subset. We compared the effect of raloxifene on all non-vertebral and incident spine (morphometric) fractures within tertiles of baseline femoral neck (FN) BMD. The results showed no evidence that the effect of raloxifene varied by initial BMD. We conclude that, among women without existing VFx, raloxifene shows no greater reduction in non-vertebral fractures in women with lower BMD. Whether these results represent a more general distinction between SERMS and bisphosphonates remains to be determined.
Effect of raloxifene in 4805 women without baseline vertebral fractures:

CONCLUSION: According to World Health Organization (WHO) crteria, although osteopenia and osteoporosis occur among world-class male triathletes over 45 years of age, prevalence is extremely low. As a group, T- and Z- scores fall within the normal range for the regions of greatest clinical importance (total, neck, trochanter). These results are compatible with the intense physical training regimens of these older men, and emphasize the importance of exercise in the prevention of age-related bone loss throughout life.

122 (114). INFLUENCE OF VDR POLYMORPHISM ON MUSCLE STRENGTH IN ELDERLY MEN H. A. Bischoff1, W. Dick1, P. Geusens2, L. Michiels3, R. Theiler4, H. B. Sta helin5, 1Orthopedics, University Basel, Switzerland; 2Dept. of Rheumatology, Academic Hospital, Maastricht, The Netherlands; 3Biomedical Research Institute, Limburg University Center, Diepenbeek, Belgium; 4Rheumatology, University Basel, Switzerland; 5Geriatrics, University Basel, Switzerland Muscle strength has been related to vitamin D receptor polymorphism (VDRP) in elderly non-obese women with increased muscle strength in bb genotype compared to BB genotype. The purpose of this study was to investigate this relationship in 212 ambulatory elderly men (mean age: 76.8; age range: 6695). Muscle strength was measured as leg extension power in watts (LEP) and was 12% higher for BB genotype compared bb genotype (p = 0.04). After correction for body mass index (BMI) this association remained signicant. However; effect of VDR genotype on muscle strength was lost in subjects older than 80 years (ANOVA: age 580: p = 0.025; > 80: p = 0.85). LEP declined with age (r = 0.48, p50.0001) and was positively correlated with both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (r = 0.24; p = 0.0004 / r = 0.14; p = 0.045). No association was found between the VDRP and vitamin D metabolites or biochemical markers of bone turnover.

Baseline FN BMD Tertile T-score Low Middle High Overall <2.6 2.12.6 >2.1

Non-vertebral fractures
RR 95% CI

Spine fractures
RR 95% CI

1.05 0.67 0.93 0.87

(0.75, (0.47, (0.62, (0.71,

1.47) 0.94) 1.39) 1.07)

0.48 0.81 0.42 0.53

(0.28, (0.43, (0.22, (0.38,

0.82) 1.50) 0.78) 0.75)

124 (116). OCCURRENCE OF OSTEOPOROSIS IN BULGARIA A STUDY OF THE BULGARIAN LEAGUE FOR THE PREVENTION OF OSTEOPOROSIS A-M. Borissova, R. Kovatcheva, A. Shinkov, M. Vukov, R. Shigarminova, 1Medical University, Soa, Bulgaria; 2National Centre for Information In Medicine, Soa, Bulgaria The Bulgarian League for the Prevention of Osteoporosis (BLPO) performed a bone density measurement in three Bulgarian cities. 627 women were included, mean age 48.4, 295 (47.1%) had menstrual cycle and 332 (52.9%) were postmenopausal. Osteopenia or osteoporosis was observed in 269 (42.8%), 102 (37.9%) menstruating and 167 (62.1%) postmenopausal (p<0.001). Bone density was signicantly lower in the postmenopausal group (p<0.001). Fractures after the age of 40 were reported by 38

(6.2%) women 27 (8.76%) postmenopausal and 12 (4.35%) menstruating (p<0.01). The T-score showed a positive correlation with the fracture risk (p<0.05). Of all postmenopausal women only 36 (10,8%) used HRT 1/3 had surgical and 2/3 had natural menopause, and 80% were married and 20% divorced. Single women and widows and subjects with secondary education did not apply HRT. Of all postmenopausal women only 14 (4,21%) had been on HRT for more than one year. Conclusions: Osteopenia or osteoporosis were observed in 42,8% of the middle-aged Bulgarian females. Of them 6,2% had a fracture after the age of 40. Only 4,21% of postmenopausal women in Bulgaria have been receiving HRT for more than one year.

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During a six day period, 226 consecutive adult women were screened in village clinics in St. Lucio, Coyolito, and San Isidro located in the Department of Yoro, Honduras. The Spanish version of the Simple Calculated Osteoporosis Risk Estimation (SCORE), Merck & Co., Inc. was given. Heights and weights were measured. Sixty-six postmenopausal women were identied. There was a history of one broken wrist and one broken hip in this group. There was no signicant difference in the mean heights among postmenopausal women by decade (p = 0.84). Twenty-four women had score totals 512. In a 1998 study of postmenopausal American women a score total of 512 correlated with osteopenia or osteoporosis. In the absence of any hormone replacement therapy, there appears to be a low prevalence of fractures of the hip, wrist, and spine among these postmenopausal women and possibly in the Honduran rain jungle region.

125 (117). INTERSITE RELATIONSHIPS OF BONE MINERAL DENSITY (BMD) IN ELITE FEMALE TRIATHLETES G. J. Boyd, E. M. Kwong, G. F. Rocha, M. Look, G. Nakamoto, M. A. Mikus, L. Musial, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate bone mineral density in elite female triathletes with particular reference to intersite relationships. METHODS: 139 elite female athletes (age 2269, mean=39) years participating in the 1999 Ironman World Championship Triathalon in Kona, Hawaii were prospectively enrolled. Whole body DXA, non-dominant proximal femoral DXA and frontal lumbar spine DXA was performed using a Norland XR36 pencil beam table top scanner. Detailed history regarding diet, exercise and lifestyle habits, medical problems, family and personal fracture history, and menstrual function was obtained on each subject. Performance times in the event swim, cycling tour, and marathon were also recorded. RESULTS: Regression analysis demonstrated a statistically signicant correlation (p<0.001) between whole body BMD vs total/regional femoral BMD, however, whole body BMD vs total spine BMD (p = 0.86), as well as total/regional femoral BMD vs total spine BMD (p = 0.88) did not correlate. Subsequently, BMD of individual spine segments was analyzed and compared to both whole body BMD and total/regional femoral BMD. BMD at the L2 and L3 levels directly correlated (p<0.001) with both whole body BMD and total/regional femoral BMD, whereas BMD at the L4 level did not correlate with either whole body BMD or total/ regional femoral BMD (p = 0.77 and p = 0.89, respectively). CONCLUSIONS: In elite female triathletes a statistically signicant relationship is demonstrated between whole body BMD and total/regional femoral BMD. Total spine BMD does not correlate with either whole body BMD or total/regional femoral BMD. BMD at L2 and L3 is signicantly correlated with whole body and total/regional femoral BMD, and the absence of such correlation at the L4 level (as well as visual inspection of DXA scan images) suggests a relatively high prevalence of degenerative disease in the lower lumbar spine among this population. This association implies that excessive physical exercise in women may predispose to low back problems, or that the presence of the latter does not preclude high performance triathlon participation.
SCORE Totals for Postmenopausal Honduran Women Age 4150 5160 6170 7182 N 24 16 20 6 Mean Total 5.71 9.88 13.05 17.67 SD 3.32 2.92 4.51 3.88

127 (119). VALIDATION OF HISTORY OF OSTEOPOROTIC AND NON OSTEOPOROTIC FRACTURES PROVIDED BY PARTICIPANTS OF THE SEMOF-STUDY, A PROSPECTIVE COHORT STUDY ON 7800 ELDERLY WOMEN J. Burnand, J. Cornuz, M A. Krieg, P. Burckhardt, for the SEMOF Study Group, University Hospital, Lausanne, Switzerland INTRODUCTION: The validation of the self-reported clinical events through mailed follow-up questionnaires is crucial to ensure quality of the obtained epidemiologic data. METHODS: Between December 1997 and September 1999, 7800 women aged 6882 were enrolled in the SEMOF Study (Swiss Evaluation of the Methods of Measurement of Risk of Osteoporotic Fracture), an ongoing prospective study comparing different bone ultrasound measurements for predicting fracture risk. The occurrence of fracture has been recorded by a selfadministered questionnaire sent every 6 months. The data provided by the participants are compared with the information obtained from the participants' physicians (74% response rate). RESULTS: The physicians1 conrmation of the rst 161 fractures reported by the participants is shown in table:

Type of fracture Hip Wrist Vertebrae Other Total

Number of fractures reported by women 18 46 24 73 161

Number of fractures conrmed by physicians 15 (83%) 43 (93%) 20 (80%) 63 (86%) 141 (88%)

126 (118). LOW PREVALENCE OF POSTMENOPAUSAL FRACTURES IN THE HONDURAN RAIN JUNGLE W. Bronson1, J. McMillen2, S. Gondring3, E. Brooks4, W. Gondring5, 1Heartland Health Systems, (HHS), St. Joseph, MO, USA; 2HHS; 3St. Joseph, MO, USA; 4Missouri Western State College, St. Joseph, MO, USA; 5HHS, The purpose of this investigation was to estimate the prevalence of postmenopausal hip, wrist, and vertebral fractures in an isolated indigenous population of women in a rain jungle.

Among the 73 fractures classied by the participants in ``other'' category, 5, 2 and 1 fractures were mentioned as hip, wrist and vertebral fractures by the physicians, respectively. Rheumatologic symptoms were the most diagnosis for these non-conrmed fractures. CONCLUSION: 89% of osteoporotic fractures (hip, wrist and vertebrae) and 88% of all fractures have been conrmed by physicians. This high conrmation rate means that participants provide reliable information.

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128 (120). BLOOD PRESSURE AND SODIUM INTAKE AS RISK FACTORS FOR HIGH URINARY CALCIUM LOSSES IN A MULTIETHNIC POPULATION F. P. Cappuccio, A. M. Blackwood, D. G. Cook, G. A. Sagnella, Departments of Medicine and Public Health Sciences, St George's Hospital Medical School, London, UK Background. Hypertension is associated with increased urinary calcium (UCa) excretion. A high sodium intake increases both UCa and blood pressure (BP). This may explain the higher risk of kidney stones and bone demineralisation seen in hypertensives. It is not clear whether this effect is modied by gender or ethnicity. We examined the relationships between BP, urinary sodium (UNa), gender and ethnic origin with both daily and fasting UCa excretions in a population-based study. Methods. Out of 1,577 individuals taking part in a crosssectional survey, 743 were considered for the analysis (407 women). They were all untreated, provided a complete 24h urine collection, and had all measurements of anthropometry, BP, UNa and UCa. They were 277 whites, 227 of blacks and 239 South Asians. Comparisons were also carried out in the 690 participants who also provided 3h-fasting urine collections. Results. After adjustment for confounders including age and gender, 24h UCa was signicantly and independently associated with ethnic origin, BP and UNa. Adjusted mean UCa was 4.62 (0.11) mmol/d (m[se]) in whites, 3.33 (0.12) in South Asians and 3.16 (0.13) in blacks (p<0.001). A 100 mmol higher UNa predicted a 1.04 mmol higher daily UCa and a 20 mmHg higher systolic BP predicted a 0.28 mmol higher Uca (both p<0.001). The slopes were not signicantly different by ethnic group. Adjusted means for fasting Uca were 1.64 [0.05] in mmol/min in whites, 1.08 [0.06] in South Asians and 1.13 [0.06] in blacks (p<0.001). The degree of association with both BP and UNa also did not vary. Conclusions. BP, salt intake and ethnic origin are independent predictors of UCa in an unselected population. These relationships are unlikely to be the result of differences in Ca intake or intestinal absorption, suggesting that they may reect differences in renal tubular handling. The estimated effects of either BP or Na intake on UCa, sustained over many years, may contribute to increased bone mineral loss.

women who fractured their hip, and those that did not, may be the lower level of 2-OHE1 relative to 16a-OHE1.

130 (122). OSTEOPOROSIS MANAGEMENT AFTER LOW IMPACT DISTAL FOREARM FRACTURE IN POSTMENOPAUSAL WOMEN M. T. Cuddihy, S. E. Gabriel, C. S. Crowson, L. J. Melton, III, Mayo Clinic and Mayo Foundation, Rochester, MN, USA The purpose of this investigation was to describe the use of osteoporosis therapeutic interventions (OTI) among postmenopausal women who sustained a low impact trauma distal forearm fracture (DFF). Methods: Using the population-based resources of the Rochester Epidemiology Project, we assembled a cohort of postmenopausal women in Olmsted County, MN, who experienced a DFF between 19931997. We investigated OTI given and adherence up to 12 months after DFF date. Types of OTI offered after DFF were: ``Rx'' (Estrogen, bisphosphonates, raloxifene or calcitonin) or ``NP'' (nonpharmacologic advice). Results: 370 postmenopausal women had a DFF due to low impact trauma (fall from standing height or less) whose mean age was 70.5 years (range 45100). Only 30% of women were offered OTI after DFF. No signicant difference was detected between OTI offered to women after a rst osteoporotic fracture vs those with history of fractures (p = 0.12). Adherence to initial OTI advice was only 44% at one year. Discussion: These data demonstrate underutilization of known effective osteoporosis therapeutic interventions among postmenopausal women with osteoporotic fractures. Additional research is needed to explore the barriers underlying such underutilization.

Table 1: Type of OTI Offered After Low Impact DFF: Fracture Hx Yes No % of total Rx Advice 24% 12% 16% NP Advice 3% 1% 2% On Rx Before DFF 8% 14% 12% Total 129 241 370

129 (121). ESTROGEN METABOLITES AND HIP FRACTURE: A PROSPECTIVE STUDY J. Cauley, J. Zmuda, T. Klug, S. Cummings, D. Bauer, L. Kuller, 1 Universities of Pittsburgh and California; 2Immuna-Care, Inc., Bethlehem, PA, USA 16a-hydroxyestrone (16a-OHE1) has been described as an estrogen agonist, while 2-OHE1 may have anti-estrogenic activity. To test the hypothesis that serum concentrations of 2-OHE1, 16aOHE1 and their ratio predict the risk of hip fracture in older women, we performed a prospective case-cohort study. A total of 54 women experienced an incident hip fracture, over an average follow-up of 62 years. We randomly chose 94 controls; all women were white; age 565 years, not receiving estrogen and participating in the Study of Osteoporotic Fractures. Estrogen metabolites (pg/ml) were measured in serum collected at the baseline examination and stored at 708C. Monoclonal antibodybased enzyme immunoassays were used (ESTRAMET 2 and 16, ImmunaCare, Inc.). We calculated the relative risk(RR) of hip fracture across tertiles of the metabolites and their ratio. All analyses are adjusted for age and obesity. The median (range) concentration of 2-OHE1 was lower in the fracture cases, 69 (20 217) compared with controls, 82 (20266), p = 0.09. There were no differences in 16a-OHE1 in cases, 112 (28398) vs. controls, 118 (35464), p = 0.82. The 2-OHE1:16a-OHE1 ratio was lower in cases, 0.51 than controls, 0.74, p = 0.13. Women with the highest 2:16 ratio had a signicantly reduced risk of hip fractures compared to women with lowest ratio, (RR=0.32; 95% CI, 0.12 to 0.82). An important difference in estrogen metabolism among 131 (123). DIETARY RISK FACTORS FOR HIP FRACTURE: THE BLUE MOUNTAINS EYE STUDY R. G. Cumming, R. Q. Ivers, P. Mitchell, A. Peduto, University of Sydney, Sydney, NSW, Australia This study was designed to examine dietary risk factors for hip fracture in a longitudinal study of an older population. Baseline data collected for the Blue Mountains Eye Study included a detailed interview and dietary questionnaire in 3654 residents aged 49 years and older. Hip fractures occurring during 5 year follow-up (n=60) were identied by self-report (conrmed by radiology reports) and/or review of medical records at the local hospital. All hip fractures were conrmed radiologically by a specialist radiologist. Analysis of hip fractures was carried out for median follow-up of 5 years. Dietary variables were ranked in quintiles for analysis, and included intake from diet (energy adjusted) and supplements. For most variables examined there was no consistent relationship between increased intake and risk of hip fracture (age and sex adjusted). The trend p value for increasing quintiles of protein intake was 0.1, for vitamin A p = 0.7, for vitamin C p = 0.5, for zinc p = 0.7, and sodium p = 0.5. There was some evidence for an association between increasing calcium intake and decreased risk of hip fracture, although this was not signicant (trend p = 0.1). For increasing quintiles of calcium intake the odds ratios (OR) and 95% condence intervals

(95%CI) were OR 1.0 (referent), 1.1 (95%CI 0.42.9), 0.8 (95%CI 0.32.2), 0.6 (95%CI 0.21.7), 0.5 (95% CI 0.11.7).

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134 (126). FRACTURES AND THE LOSS OF QUALITY OF LIFE: A COMPARISON OF AMERICAN AND DUTCH EXPERT PANELS C.E.D.H. De Laet1, J. van Busschbach1, M. van der Klift1, P. Lips2, H.A.P. Pols1, For The Dutch Osteoporosis Consensus Committee, 1 Erasmus University Medical School, Rotterdam; 2Vrije Universiteit Amsterdam, The Netherlands Osteoporosis has little impact on mortality but can have an important impact on health related quality of life (QOL). Therefore, costeffectiveness analyses of osteoporosis have to take into account changes in health perception and associated loss of Quality Adjusted Life Years (QALY). Relatively little experimental data are available, however, and for its recent review the American National Osteoporosis Foundation (NOF) avoided this problem by using an expert panel for the evaluation of the loss of QOL. In this study a Dutch expert panel evaluated the same postfracture conditions. In addition, the total burden of disease attributable to osteoporosis was evaluated. The list of postfracture conditions from NOF was evaluated by a Dutch panel using the time trade-off method. Total QALY loss was recalculated for rst and subsequent years for both the American and the Dutch evaluations. Total burden of illness was evaluated assuming average mortality after all but hip fractures, but assuming an increased mortality after hip fracture. The Dutch evaluations of QALY loss in the rst and subsequent years after fracture were consistently lower than the US evaluations. Assuming average health pre-fracture the QALY loss due to hip fracture was evaluated at 0.28 for the rst year (0.47 in the NOF report) and at 0.12 for subsequent years (vs. 0.17). For wrist fracture this was 0.03 vs. 0.05 for rst and 0.002 vs. 0.006 for subsequent years. For vertebral fractures this was 0.04 vs. 0.05 for rst year and 0.02 vs. 0.05 for subsequent years. Average loss of life in the population due to osteoporosis in general was evaluated for women at 23 days. Average loss of health related QOL was evaluated at 0.33 QALY's. This Dutch evaluation of health related QALY loss is systematically lower than the American evaluation. While wrist fractures appear to have little impact on overall burden of illness, the impact of vertebral fractures is proportionally higher than expected due to the long term QOL effects.

132 (124). VERTEBRAL OSTEOPHYTOSIS AND VERTEBRAL DEFORMITIES IN ELDERLY POPULATION SAMPLE Selma Cvijetic1, Kristina Potocki2, 1Institute for Medical Research and Occupational Health, Zagreb, MD, Croatia; 2Clinical Hospital Rebro, Zagreb, MD, Croatia We investigated the association between vertebral osteophytosis and vertebral deformities in the elderly population sample and the inuence of some risk factors on spinal osteophytosis and deformities. Population sample of 280 women and 263 men, all Zagreb residents, older than 45 years participated in the study. Radiographs of thoracic and lumbar spine were evaluated for the presence of osteophyte formation and vertebral deformities. Osteophyte size was graded on a scale from 0 to 4. Vertebral deformities were determined by semiquantitative method of McCloskey. Data were analyzed using chi-square test and discriminate analysis. The prevalence of vertebral osteophytosis was 47.9% in men (36.5% in the thoracic and 21.3% in the lumbar spine) and 56.0% in women (36.0% in the thoracic and 23.9% in the lumbar spine). The prevalence of vertebral deformities was 8.3% in men (5.3% in the thoracic and 3.4% in the lumbar spine) and 12.5% in women (7.9% in the thoracic and 5.4% in the lumbar segment). There was a signicant association between deformities and osteophytosis on the lumbar segment of the spine (p = 0.0240 men, p = 0.0152 women). Analyzing the inuence of several risk factors, age was found to be the most associated with both vertebral deformities and osteophytosis. Obesity was signicantly associated with osteophytosis. Since we found a signicant association between vertebral osteophytosis and deformities in the lumbar segment and no relationship in the thoracic segment, it implicates different etiologies of vertebral deformities in the thoracic and lumbar spine.

133 (125). ASSOCIATION BETWEEN NON-TRAUMA MORTALITY AND OSTEOPOROSIS IN ELDERLY WOMEN P. Dargent, S. H. Lee, V. Ringa, G. Bre art, for the EPIDOS Group, INSERM Unit 149, Villejuif, France Results of the SOF study (Lancet 1991;338:355358) suggested that low BMD in elderly women could be a marker for poor underlying health, which has important implications for preventive health care. We investigated the possible association between several indicators of osteoporosis and mortality in the 7598 women aged 575 years who were enrolled in the EPIDOS study (mean age 80.53.8). Baseline indicators of osteoporosis included femoral neck BMD measured by DXA (Lunar DPX-Plus), ultrasound parameters (Lunar Achilles), loss of height, and fracture history. During a mean of 3.9 (0.9) years of follow-up, 741 nontraumatic deaths occurred. After adjustment for age and follow-up time using Cox models, nontrauma mortality was signicantly associated with low BMD (RR= 1.14 for 1SD; 95% CI 1.06 1.22), low BUA (1.26 for lowest quartile; 1.06 1.50), low SOS (1.17 for lowest quartile; 0.99 1.40), and loss of height (1.29 for 5 cm; 1.17 1.43). These indicators of osteoporosis were signicantly associated (p50.001) with several other signicant predictors of mortality (IADL incapacities, gait speed, calf circumference, subjective health, cognitive functions). Adjustment for these variables eliminated the association between mortality and BMD, BUA, and SOS. Only loss of height remained signicantly associated with an increased risk of mortality (1.20; 1.06 1.35). Low BMD and ultrasound measures are associated with increased mortality in elderly women, probably because they are markers of ill health and frailty.

135 (127). INCIDENCE OF HIP FRACTURES IN OSLO, NORWAY: NO CHANGE DURING THE LAST DECADE J. A. Falch, C. M. Lofthus, E. K. Osnes, T. S. Kaastad, I. S. Kristiansen, L. Nordsletten, I. Stensvold, H. E. Meyer, Aker Hospital, University of Oslo, Oslo, Norway The incidence of hip fractures in Oslo has shown a secular increase during the past decades. The aim of the present study was to estimate the current incidence of hip fractures in Oslo. Using the electronic diagnosis registers and the lists of the operating theatre for the hospitals in Oslo with somatic care, all patients with the ICD 9-code 820.X (hip fracture) from May 1, 1996 through April 30, 1997 were identied. Medical records for all the identied patients were retrieved and the diagnosis veried. Using the population of Oslo on January 1, 1997 (Statistics Norway, 1997) as the population at risk, the age-and sex-specic annual incidence rates were calculated. These rates were compared to those for 1978/79 and 1988/89. A total of 1,316 hip fractures were included (78% women). The age-adjusted fracture rates per 10 000 for the age group 50 years and older were 118.0 and 44.0 in 1996, 124.3 and 44.9 in 1988/89, and 104.5 and 35.8 in 1978/79 for women and men, respectively. Compared to 1996, the rates in 1988/89 were 5% higher in women (n.s.) and 2% higher in men (n.s.). In 1978/79 the rates were 11% lower in women (p<0.02) and 19% lower in men (p<0.05). The present study shows that the incidence of hip fractures in Oslo has not changed signicantly during the last decade. It is still the highest ever reported.

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136 (128). COMPARISON OF RISK FACTORS FOR VERTEBRAL FRACTURE BETWEEN WOMEN IN URBAN AND RURAL AREAS S. Fujiwara1, M. Shiraki2, N. Masunari1, F. Kasagi2, Y. Shiraki3, C. Aoki3, K. Naito1, 1Departments of Clinical Studies; 2Statistics, Radiation Effects Research Foundation, Hiroshima; 3Research Institute and Practice for Involutional Disease, Nagano, Japan This study compares the risk factors for vertebral fracture (VF) between women living in urban and rural areas. Subjects were 666 women (age 65.99.6 yrs) in Hiroshima City selected for a longitudinal epidemiological study based on the 1950 Japanese National Census, and 484 women in Nagano (age 63.510.4 yrs) who had undergone bone mineral density (BMD) measurements at health checkup. One third of the Nagano women were farmers, while 47% in Hiroshima were housewives and less than 2% farmers. The 1150 women were followed by BMD measurements and spine X-rays for more than two years. None were receiving treatment for osteoporosis. Diagnosis of VF was standardized for Hiroshima and Nagano. Poisson regression analysis showed that the risk of new VF was related to age, BMD, and previous VF (Table). After adjusting for age, relative risk of VF was similar for the two groups, around 1.3 by 1 SD decrease in BMD. However, the relative risk for VF among women with previous VF was higher in women in Nagano than in Hiroshima. The difference in risk among women with VF between urban and rural areas may be due to occupational differences in the two groups. In conclusion, after adjusting for age, the relationship between BMD and subsequent VF was similar in urban and rural areas, but the contribution of previous VF on new VF may differ by occupation or daily activity. RESULTS:
BMD vs SOF P Head Chest Midriff Pelvis L Leg R Leg L Arm R Arm 0.002 0.000 0.167 0.003 0.000 0.000 0.000 0.000 R2 (adj) % 6.7 26.8 0.7 6.1 40.0 36.0 18.6 28.8 BMC vs SOF P 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000


R2 (adj) % 26.1 46.9 80.6 36.1 64.0 63.7 69.7 69.2

LEFT vs RIGHT LEG P BMC AREA SOFT TISSUE BMD 0.000 0.000 0.000 0.000 R2 (adj) % 94.6 86.3 95.0 87.8

LEFT vs RIGHT ARM P 0.000 0.000 0.000 0.000 R2 (adj) % 75.5 63.1 78.2 67.8

Table. Relative risk for VF in the two areas Risk factors Urban (Hiroshima) Age (10 yrs) Spine BMD (1 SD) Previous VF 1.82 1.28 1.88 Relative risk Rural (Nagano) 1.55 1.35 2.53

CONCLUSION: Both BMC and BMD are signicantly correlated with total soft tissue distribution in most regions of the body among elite female triathletes. However, correlation coecients for BMD were higher in biomechanically active regions (chest, legs, arms. In contrast to previous studies demonstrating relatively constant ratios between BMD/BMC and muscle mass in the extremities, neither was signicantly related to individual soft tissue components (lean versus fat) of the arms/legs in these high performance female athletes. Relative symmetry of bone and soft tissue composition in the arms and legs is present.

138 (130). BONE MINERAL DENSITY IN ADOLESCENTS WITH IDIOPATHIC SCOLIOSIS S. Gatto, R. Gimigliano, G. Iolascon, Orthopedics Dept., II University of Naples, Italy The purpose of our study is to assess an association of osteopenia/osteoporosis with idiopathic scoliosis and if osteoporosis plays a rule in primary etiology of spinal deformity. Burner (1982) demonstrated this association using Singh Index. Cook (1987), using DPA, found a signicant reduction in BMD. METHODS. BMD was measured in 49 patients (31 females and 18 males) with idiopathic scoliosis. Adolescents were aged from 10 to 17 y.o. and Cobb angle ranged from 258 to 478. No orthosis was used before BMD measurements. Bone mass was measured by DEXA technique both spinal and femoral sites. Our results were compared with normal values published by Kroger (1993). RESULTS. 15 males and 26 females showed low BMD (Zs: 52 S.D.) at spinal and femoral sites. Low bone mass was indipendent from curve severity and was more important in femoral neck. CONCLUSIONS. Scoliosis was associated with osteopenia/ osteoporosis in 83% of our adolescents. Low bone mass, probably, is not secondary to the scoliosis because it is present also, and mostly, in femoral neck. Osteoporosis, probably, plays a rule in the onset of vertebral body deformity and therefore in curve irreducibility. Low bone mass has no rule in scoliosis primary etiology because body deformity cannot explain all pathological ndings of vertebra in these patients. Further studies need to investigate about this association.

137 (129). REGIONAL DISTRIBUTION OF BONE MINERAL AND SOFT TISSUE COMPOSITION IN ELITE FEMALE ATHLETES R. Garcia, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate the relationship between regional distribution of bone mineral density (BMD)/content (BMC) and soft tissue mass (lean versus fat components) in a unique population of elite female endurance athletes. METHODS: 139 female triathletes competing in the 1999 Ironman World Championship Triathlon held at Kona, Hawaii were randomly recruited from the qualifying competitors. Ages ranged from 2269 (mean 39) years of age. Body weight ranged from 93176 (mean=125) pounds. Detailed information regarding dietary/medical history, exercise/lifestyle habits, and menstrual function was elicited from each participant. Performance times in the swimming, bicycling, and marathon components of the event were also recorded. Regional bone mineral and soft tissue composition was assessed using a Norland XR36 pencil-beam dual-energy X-ray absorptiometry system. Statistical analysis was performed using Minitab version 12 software.

139 (131). BONE MINERAL DENSITY IN ADOLESCENTS WITH JUVENILE KYPHOSIS S. Gatto, R. Gimigliano, G. Iolascon, Orthopedics Dept., II University of Naples, Italy The purpose of our study is to assess an association of osteopenia/osteoporosis with juvenile kyphosis and if osteoporosis plays a rule in primary etiology of spinal deformity. Bradford(1976) and Burner(1982) demonstrated this association using Singh Index and postulated that transitory osteoporosis is a primary etiology of Scheurmann's kyphosis. METHODS. BMD was measured in 47 patients (17 females and 30 males). The wedge body deformity was present in 28 patients (15 with Scheuermann's signs and 13 without). 19 patients had no structural deformity. Adolescents were aged from 10 to 17 y.o.. No orthosis was used before BMD measurements. Bone mass was measured by DEXA technique at spinal and femoral sites. Our results were compared with normal values published by Kroger (1993). RESULTS. 23 males (76%) and 11 females (65%) showed low BMD (Zs: 52 S.D.) at spinal and femoral sites. Low bone mass was indipendent from etiology and curve severity and was more important in femoral neck. CONCLUSIONS. Kyphosis was associated with osteoporosis in 76% of males and, 65% of females. Low bone mass, probably, is not secondary to the kyphosis because it is present also, and mostly, in femoral neck. Osteoporosis could determine wedge deformity but not other Scheuermann signs. Furthermore low bone mass is present also in absence of vertebral deformity. Further studies need to investigate about this association.

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xed and irreversible anteroexion of the thoracic spine in 46% of patients. These ndings open new perspectives for therapy, which should not only aim to prevent inammation, but also to prevent vertebral wedging. Insofar osteoporosis is involved in the development of severe wedging of vertebrae, prevention of bone loss should be considered.

141 (133). RISK FACTORS FOR OSTEOPOROSIS IN TURKISH WOMEN A. Gokman1, U. Sec ckin1, H. Bodur1, O. H. Gu ndu z1, G. Pekcan2, 1 Dept. of Physical Medicine and Rehabilitation, Ankara Numune Education and Research Hospital; 2Dept. of Dietetics, Samanpazari, Hacettepe University, Ankara, Turkey We evaluated the relationships between bone mineral density (BMD) and nutrition, calcium (Ca) intake, age, number of pregnancy, age at menopause, menopausal period, lactation period, body weight, and height, body mass index (BMI), and physical activity level. 151 subjects were evaluated in a randomized manner. There were signicant differences between age, number of alive children, menopause period and the two groups which are designed according to the BMD's of L1-L4 lumbar spine and Ward's triangle. In groups with lower BMD values, patients had more alive children, longer menopausal periods and higher average age. There were signicant differences between the number of pregnancy, lactation period, fat intake, meal frequency and the BMD of the Ward's triangle. Patients with higher BMD values had higher BMI, higher body weight and physical activity levels. Patients with low BMD values had a tendency towards having more pregnancies, longer lactation periods and more fat intakes. We didn't nd any relationship between Ca intake and BMD values. This could be due to insufcient Ca intake in our subjects.

140 (132). VERTEBRAL WEDGING AND SPINAL DEFORMITY IN ANKYLOSING SPONDYLITIS P. Geusens1,2, J. Vanhoof2, D. Vosse1, D. van der Heijde1, J. Raus2, Sj. van der Linden1, 1Department of Rheumatology, Academic Hospital, Maastricht University, The Netherlands; 2 Biomedical Research Institute DWI, Limburg University Centre, Diepenbeek, Belgium Fixed anteroexion of the spine is one of the irreversible clinical complications in ankylosing spondylitis (AS) that can seriously affect quality of life. Thoracic hyperkyphosis has been related to the severity of AS and to osteoporosis. However, the underlying anatomical changes in vertebral shape have not yet been related in detail to the clinical changes in spinal stature in AS. We therefore studied the changes in shape of vertebrae in 69 patients with AS (21 women and 48 men), having different degrees of kyphosis as measured by wall-occiput distance (WOD). Lateral xrays of the thoracic spine (T7-T12) were measured for anterior (Ha) and posterior height (Hp) of the vertebrae. Severe vertebral wedging was dened as Ha/Hp <0.80. Severe vertebral wedging was found in 36 vertebrae in 22 (32%) of patients (range 1 to 4). In the vertebrae from T7 to T12, WOD was associated with wedging of the vertebrae [R=0.509 (p<0.01)]. In patients with WOD >1 cm, 46% had at least one severely wedged vertebra compared to 13% in patients with WOD <1 cm (p<0.05). A greater proportion of patients with a WOD of >10 cm had one or more severely wedged vertebrae compared to patients with WOD of 0 cm [59% versus 13% respectively of patients (p<0.001)]. Patients with 1 or more severely wedged vertebrae had a higher mean WOD than patients without severely wedged vertebrae [12 cm versus 6 cm respectively (p<0.01)]. The mean WOD increased signicantly with the number of severely wedged vertebrae in men and women (6 cm among those without severely wedging, up to 23 cm among those with >2 severely wedged vertebrae, p = 0.001 for trend). There were no signicant differences between men and women. We conclude that in patients with AS and WOD >1 cm, severe wedging of the thoracic vertebrae contributes signicantly to the

142 (134). PREVALENCE OF OSTEOPOROTIC VERTEBRAL FRACTURES IN FRENCH ELDERLY WOMEN FROM EPIDOS STUDY F. Grados1, C. Roux2, J. F. Vergnol1, C. Marcelli3, P. DargentMolina4, P. J. Meunier5, P. Fardellone1, 1Rheumatology CHU Amiens; 2CEMO CHU Cochin, Paris; 3Rheumatology CHU Caen; 4 INSERM U 149 Paris; 5INSERM U 403 Lyon, France The prevalence of osteoporotic vertebral fractures was evaluated in 770 randomly selected women participants of the Epidos study. Epidos is a multicenter study performed in ve French centers (Amiens, Lyon, Paris, Montpellier, Toulouse) among 7598 healthy female volunteers aged 7595 years living at home. Anteroposterior and lateral radiographs of the thoracic and lumbar spine were reviewed by two trained rheumatologists using the semiquantitative (SQ) method described by Genant et al (JBMR 1993;8:113748). Vertebral deformities that could be related to causes other than osteoporosis (i.e Scheuermann's disease or osteoarthritis) were not taken into account. The nal analysis was made on 745 women after exclusion of 25 women whose spine radiographs were incomplete or of poor quality. The mean age was 80.13.4 years. We veried in 39 women that the concordance of SQ method was excellent. The interobserver agreement was 98% with a corresponding kappa score of 0.95. Vertebral fractures related to osteoporosis were found in 170 women: 22.8% (95% CI = 19.825.8%). The prevalence of vertebral fractures rose with age from about 18.2 per 100 women 7579 years old to 25.8 per 100 in those 80 years of age and over. We concluded that the prevalence of osteoporotic vertebral fractures is high in French elderly women living at home.

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143 (135). THE INFLUENCE OF ESTROGENS ON BONE MASS IN WOMEN WITH BREAST CANCER P. Hadji, G. Emons, K.-D. Schulz, Philipps University Marburg, Marburg, Germany This study was aimed to evaluate the relation between bone mass and breast cancer and to investigate if cumulative exposure to estrogens could explain this association. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and Stiffness index (SI) of the Os calcaneus were measured in 2492 women, mean age 54.4 years. 242 patients had a history of breast cancer, while 2250 women had not. Due to the signicant group differences, we randomly formed an equally sized sample of healthy women who were matched for confounding variables such as age, BMI, cumulative exposure to estrogens and others. Women with breast cancer were older, showed a higher weight, BMI, number of parity and lactation, and a longer exposure to estrogens. SOS and SI were signicantly higher in women with breast cancer even after matching for confounding variables (p<0.001). Odds ratios for the risk of breast cancer were 1.0, 1.6, 3.4 and 2.9 from the lowest to the highest quartile of SI (p for trend <0.001). Women with breast cancer have higher bone mass than controls, even after matching for confounding variables. Women in the higher quartiles of bone mass are at higher risk for breast cancer. Although the link of bone mass and breast cancer is not fully understood, factors other than cumulative exposure to estrogens must play a role. 144 (136). PRIMARY PREVENTION OF OSTEOPOROSIS WITH SPECIAL PATIENT-EDUCATIONAL PROGRAM FOR CHILDREN sz, Rheumatology Unit Kutvolgyi Clinical Dept., K. Hala Semmelweis University Budapest, Hungary The peak-bone mass is genetically determined. This genetic program is inuenced by environmental factors, such as suitable nutrition, lack of harmful habits, and appropiate sport activity throutout the life. Since osteoporosis /OP/ cannot be cured even now all efforts have to be done forprimary prevention that has to be started as young as possible. Age suited educational program is necessary to increase the knowladge and awareness of OP. 450 children aged 517 years were involved in the study. The author presented the main facts of OP in 45 min sessions at schools. After the class children were encouraged to draw anything they picked from the presentation. 177 drawings were made. The bests were exhibited and awarded on Osteoporosis Day 1999. After the age of 13 yrs children dislike to draw. Therefore an introductory and assessement questionnaire were developed for high-school children. The goal was to assess their original knowladge on OP and what they have learned from the presentation. The evaluation of drawins made by kindergarden and primary school-children showed that they already knew quite a few information on OP, and the targeted presentation helped them to organiz the data and form positive opinions for prevention. Presentations at high schools provided an emotional strategy for older children to reorganize their everyday lifestyle aiming to reach the highest peak-bone mass. The evaluation of questionnaires were statistically analized. 145 (137). RESULTS OF A NATIONAL SURVEY ON RISK FACTORS FOR OSTEOPOROSIS IN URUGUAY J. Herna ndez, A. Ronco, V. Chijani, R. Souto, G. Gonza lez, C. mez, M. Albanese, L. Uboldi, R. Tejeiro, A. Ramagli, L. Tuso, E. Go Bairo, M. Moyano, B. Mendoza, C. Belzarena, S. Lima, Study Group On Osteopatic, 1Uruguayan Society of Rheumatology, Montevideo, Uruguay The rst nationwide survey on selected risk factors for osteoporosis has been carried out in Uruguay, in order to know

their prevalence and to furtherly enhance the prevention of the disease. During the period June-August / 1999 a number of 3,500 fourty-years-old and above patients (84% women) who went to medical examination for control or under symptomatic conditions to general practitioners or specialists received a short questionnaire form queries about education, lifestyle, selected consuptions and medial issues. Patients came from the whole country (62% from Montevideo, the capital city), from both healtcare systems (81% from the pre-paid system) and were ethnically rather representative of the general population (97% white). A risk score was calculated on the basis of answers, with a range of 424 points. The threshold of susceptibility to osteoporosis was established in 12 points, as in the original MedGuide version. While 67% of women fell into the risk group, only 16% of men did it (OR= 4.01. 99% CI 2.99 5,46). Main ndings are herewith presented and discussed.

146 (138). ORTHOPEDIC PATIENTS WITH COGNITIVE IMPAIRMENT HAVE INCREASED HIP FRACTURE RISK AND MORTALITY K. Hinds, J. B. Lauritzen, Department of Orthopedic Surgery, Hvidovre Hospital, University of Copenhagen, Denmark Aim To evaluate cognitive impairment as a prognostic risk factor for hip fracture and mortality. Design & patients A total of 1,590 patients more than 74 years of age were consecutively included in the study after admittance to one of two orthopedic departments in Copenhagen. The patients participated in a hip protector trial, and for analyses related to hip fracture risk 642 controls were included. At inclusion all patients were interviewed and examined. Cognitive impairment was evaluated using a short questionnaire. During follow-up hip fractures and deaths were recorded. Multivariate survival analysis (Cox proportional hazard model) was used. Results In the cohort 32 % (95% CI: 3034%) (503/1,590) were cognitively impaired. The overall annual mortality was 20% (437 deaths / 2,172 person-years). The mortality rate for cognitively impaired was 41 % and for non-impaired 13 %, SMR 3.2 (2.73.9). Adjusted for the effects of gender, age, medical conditions and nursing home the SMR was 2.5 (2.03.2). Annual hip fracture risk for cognitively impaired was 5.9% versus 2.8% for non-impaired; relative risk 2.1 (1.04.5), adjusted for gender, age, fall tendency and smoking. Conclusion Cognitive impairment is a common occurrence among elderly orthopedic patients, and leads to increased risk of hip fracture and mortality.

147 (139). DETERMINANTS OF BONE MINERAL DENSITY AND QUANTITATIVE ULTRASOUND INDEX IN WOMEN WITH RHEUMATOID ARTHRITIS M. C. Hochberg, J. C. Scott, W. Yap, University of Maryland School of Medicine, Baltimore, MD, USA The objective was to determine whether measures of disease activity and severity are independently associated with bone mineral density (BMD) and quantitative ultrasound index (QUI) in women with rheumatoid arthritis (RA). A convenience sample of 100 women with RA (mean [SD] age 58.6 [12.2] years, height 160.2 [5.6] cm, and weight 72.6 [17.2] kg) completed a detailed osteoporosis risk factor questionnaire identical to that used in the Study of Osteoporotic Fractures and the Stanford Health Assessment Questionnaire Disability Index (HAQDI), had BMD measured at the right hip and total body with a Hologic QDR2000 and QUI measured at the right heel with a Hologic Sahara, and underwent a 28-joint count performed by a trained nurse. Multiple regression analyses were performed to adjust for factors known to be associated with bone mass. Mean (SD) BMD (g/cm2) at the

femoral neck, greater trochanter, total hip and total body was 0.67 (0.14), 0.92 (0.20), 0.78 (0.19) and 1.06 (0.12), respectively; mean (SD) QUI was 80.7 (22.9). Signicant predictors of BMD by site follow: Femoral neck: age, weight, height Trochanter: age, weight, height, HAQDI Total hip: weight, height, menopausal status Total body: weight, menopausal status The only signicant predictors of QUI were age and height. Neither the number of painful/tender joints or swollen joints, nor the current use of prednisone or methotrexate, were signicantly associated with BMD at any site or QUI. These data suggest that, in women with RA, measures of disease activity and severity have little eect on BMD and bone microarchitecture over and above factors known to be associated with bone mass.

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was conducted in 43 Italian out-patients centers. Medical history and a life-style questionnaire was recorded in 799 hundred ninety-nine postmenopausal women (age range 6080 years, median 67) at their rst Osteoporosis work-out were administered: a validated food frequency questionnaire was planned for calcium intake measurement. Each woman self-administered a 3item daily based calcium intake score sheet. The nutritional analysis showed a 784 mg/day median calcium dietary intake; a geographic subanalysis indicated a signicantly lower calcium intake in Southern Italy (710 mg/day vs. 810 and 835 mg/day respectively in Northern and Central Italy, p<0.001). This data mainly reects different regional habits in cheese consumption (p<0.01): however the proportion of dietary calcium coming from milk and dairy products was about 70% without signicant geographic patterns. The following table shows the proportion of subjects with different ranges of Ca intake in the 3 major geographic areas. Low calcium intake was associated with Activities of Daily Living impairment (p<0.01): lower Ca intake levels were detected in diabetic patients (p<0.05). The 3-item calcium score was signicantly correlated with calcium intake levels measured by the extended food-frequency questionnaire (p<0.0001). In conclusion, this study conrms the relevance of dietary calcium insufciency in Italian elderly population: this emphasizes the need of wide-scale educational programs to correct one of the major determinants of senile osteoporosis. We validated an easy-to-use tool to be tested on a large scale in GPs' ofces to stimulate physicians and patients awareness on this public health issue.

148 (140). CHANGES IN BONE DENSITY IN JAPANESE WOMEN OVER THREE YEARS AND DETERMINANTS OF THE BONE LOSS M. Iki, A. Morita, Y. Ikeda, H. Aihara, S. Kagamimori, Y. Kagawa, T. Matsuzaki, H. Yoneshima, F. Marumo, for JPOS Study Group, Kinki U Schl Med, Osaka-Sayama, Japan This study aimed to clarify the changes in bone mineral density (BMD) of several skeletal sites in Japanese women of various age and to investigate the determinants of these changes. We randomly selected 50 women each from 5-year age stratied populations (1579 year) according to the resident registration in each of 3 areas located north, middle and south parts of Japan. The follow-up study was conducted 3 years after the baseline. Both studies comprised bone densitometry of the spine, hip (QDR4500A, Hologic) and distal forearm (pDXA, Norland/Stratec), and interviews on medical histories and lifestyle factors. In total, 1651 women underwent the baseline study and 1137 completed the both studies. Among 1137 women, 1000 had never had any diseases or administration of drugs which may affect bone mass and were analyzed further. Signicant bone loss in the spine was observed in the subjects aged 4574 at baseline and that in the femoral neck was in those under 25 or over 40 years. The greatest loss was seen just after menopause in the spine and neck and in the subjects aged 75 or older in the femoral neck. We found signicant differences in BMD change in most sites examined among the study areas. These differences reduced after allowing for the effects of height, weight, BMD at baseline, habitual exercise, dietary calcium intake, and consumption of fermented soybean on the BMD change but still remained signicant. The regional differences in BMD change were attributed partly to the difference in physique and lifestyles. Other unknown factors, however, operated in generating such differences in Japan.

All No. of cases Calcium Intake 0500 mg/day 5011000 mg/day 10011500 mg/day >1500 mg/day 799 25% 50% 20% 5%

North 333 24% 49% 23% 5%

Center 206 24% 47% 23% 6%

South 260 28% 54% 15% 3%

150 (142). LIFESTYLE FACTORS HAVE ONLY A MODEST INFLUENCE IN PREDICTING INCIDENT VERTEBRAL DEFORMITY : RESULTS FROM THE EUROPEAN PROSPECTIVE OSTEOPOROSIS STUDY (EPOS) A. A. Ismail, J. D. Finn, M. Lunt, C. Cooper, D. Felsenberg, O. Johnell, J. Reeve, A. J. Silman, T. W. O'Neill, the EPOS Study Group, ARC Epidemiology Unit, Manchester University, UK Background: Little is known about risk factors for incident vertebral deformity. The aim of this analysis was to determine, in women, whether lifestyle factors inuence susceptibility to incident vertebral deformity. Methods. Women aged 50 years and over were recruited from population registers in 15 European countries for participation in a screening survey of vertebral osteoporosis (European Vertebral Osteoporosis Study). Subjects underwent an interviewer administered questionnaire and lateral spinal radiographs using a standard protocol. The questionnaire included questions about smoking, alcohol, milk consumption (at ages 1525yrs, 2550 yrs, and 50 years+) and physical activity. Paired spinal radiographs were evaluated morphometrically. An incident vertebral deformity was dened as a vertebra which fullled criteria for a prevalent deformity on the second lm, and in which there was evidence of a change of 20% or more in vertebral height (anterior, middle or posterior) between lms. Poisson regression was used to determine the inuence of lifestyle factors on the risk of incident vertebral deformity. Results. 3,569 women, mean age 62.1 years (SD= 7.5) had duplicate spinal radiographs performed (median 3.7 yrs apart).

149 (141). DIETARY CALCIUM INSUFFICIENCY IN ELDERLY FREE-LIVING WOMEN: AN ITALIAN MULTICENTER STUDY G. Isaia1, R. Giorgino2, on behalf of the Italian Multicenter Study Group, 1Turin, Italy; 2Rome, Italy Few studies are available at national level on dietary calcium intake in elderly Italian people: the aim was to measure the prevalence of dietary calcium insufciency and its major determinants in postmenopausal free-living women. On a period between Feb. 15th and March 15th 1999, an observational study

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After adjustment for age and centre, none of the lifestyle factors studied were associated with a statistically signicant increase in the risk of incident vertebral deformity : walking (per day : 530 mins vs 530 mins) relative risk (RR)=0.8, smoking (ever vs never) RR=1.2, milk consumption (per day: 51 glass vs 51 glass) RR=0.81.0 (depending on consumption at different ages), alcohol (number of days per week : 5 days vs 51 day) RR=1.5. Conclusion: Lifestyle factors appear to have limited impact in determining susceptibility to incident vertebral deformity in postmenopausal women.

153 (145). SOCIAL FACTORS PREDICT FRAGILITY FRACTURES IN AN MIDDLE-AGED POPULATION. A POPULATION-BASED STUDY OF 33,000 MEN AND WOMEN O. Johnell, A. Holmberg, P. Nilsson, J. A. Nilsson, G. Berglund, Department of Orthopaedics and Department of Medicine, Malmo University Hospital, Malmo, Sweden Several risk factors have been identied for osteoporotic fractures. Less attention has been paid to social predictors for fractures. The purpose of this investigation was to study biological, social and life style predictors in a population Malmo Preventive Study. Baseline variables were obtained from 22,444 men and 10,902 women with a participation rate of 72%. Mean age men 46 and women 48 years. The follow-up was up to 18 years. The fractures were recorded from the les of the Department of Diagnostic Radiology and the rst incidence fragility fracture was identied. Social data were obtained from a questionnaire and the Swedish Population and Housing Census. In a stepwise logistic regression the following signicant relations were found for incidence fragility fractures: Men alcohol problem OR 1.54 (1.271.86), manual work OR 1.35 (1.20 1.52), unmarried OR 1.33 (1.141.56), divorced OR 1.31 (1.101.55) and for continuous risk factors per SD change: Body mass index 0.88 (0.830.94), gamma GT 1.10 (1.041.17). For women we only found the following signicant relations: Body mass index 0.92 (0.860.99), gamma GT 1.08 (1.011.14). Besides known risk factors, social factors could be important especially in middleaged men.

151 (143). HEALTH AND VITAMIN D STATUS IN OSTEOPOROTIC PATIENTS WITH AND WITHOUT VERTEBRAL FRACTURE T. Jalava, B. Mawer, S. Sarna, L. Pylkkanen, J. A. Kanis, E. McCloskey, University of Shefeld, UK We have examined differences in several measures of skeletal and non-skeletal health in 677 patients with osteoporosis (PMOP, n=483; women with secondary osteoporosis, n=110 and osteoporotic men, n=84). Of these, 55% had prevalent vertebral fractures at entry. Patients with fractures were older (67.9 years vs 64.3 years, p<0.0001), had a higher number of concomitant diseases (p<0.0009) and treatments (p<0.0001), a higher ESR (p = 0.032) and poorer renal function (p = 0.0097). Finally, the serum calcium (p = 0.006) and 25-OHD3 were lower (21.2 vs 25.0 ng/ml, p = 0.0001). Over 3.2 years, mortality was higher in secondary (8.2%) and male (11%) osteoporosis than in PMOP (3.9%). A multivariate Cox regression analysis revealed that increased mortality was associated with prevalent vertebral fractures (HR 3.9, 95%CI 1.311.5), low (<9ng/ml) 25-OHD3 (4.4, 1.74.9) and more concomitant treatments (1.3, 1.11.4). Higher serum albumin was associated with lower mortality (0.9, 0.81.0). When the multivariate analysis was restricted to PMOP alone, only prevalent vertebral fractures were associated with an increased mortality (10.3, 1.380.1). It is unclear whether the association between low 25OHD3 and mortality, particularly in secondary and male osteoporosis, is causative or simply reects general illhealth.

154 (146). RELATIVE RISK OF HIP FRACTURE ACCORDING TO WHO CRITERIA FOR OSTEOPOROSIS J. A. Kanis, O. Johnell, A. Oden, B. Jonsson, C. De Laet, A. Dawson, Centre for Metabolic Bone Diseases, University of Shefeld Medical School, Shefeld, UK In the assessment of patients it is appropriate to quantify fracture risk in relation to the risk of the general population. By contrast, the predictive value of bone mineral density (BMD) is commonly expressed as an increase in fracture risk per standard deviation difference in BMD. For example, hip fracture risk increases 2.6-fold per standard deviation difference in femoral neck BMD. Thus, an individual with a Z-score of 1 has a 2.6-fold increase in risk compared to an individual with a Z-score of 0 (RRmean). The risk of fractures with BMD is non-linear however, whereas BMD at each age is normally distributed. For this reason an average BMD (eg Z-score = 0) is associated with a lower than average risk of fracture. The aim of this paper is to characterise risk, based on BMD to the risk of the general population (RRpop) rather than RRmean based on mathematical modelling using the NHANES reference material applied to the population of Sweden. Women at the age of 50 years at the threshold for osteoporosis (T-score = 2.5 SD) had a RRmean of 4.6 decreasing to 0.98 at the age of 85 years. By contrast, the RRpop was 2.9 and decreased with age to 0.62 at the age of 85 years. In men at the age of 50 years the RRmean was 14.6 and the RRpop 4.6 and fell to 9.2 and 2.9 respectively at the age of 85 years. The use of relative risks applied to average bone mineral density overestimates the impact of osteoporosis in the community. The use of RRpop gives relative risks that are 27 and 32% of values for RRmean in women and men respectively. Similar transformations for other fractures and other technologies will be required to assess risks in individuals to effectively target interventions.

152 (144). IS GENERAL HEALTH RELATED TO OSTEOPOROTIC FRACTURES? A POPULATION-BASED STUDY O. Johnell, A. Holmberg, P. Nilsson, J. A. Nilsson, G. Berglund, Department of Orthopaedics and Department of Medicine, Malmo University Hospital, Malmo, Sweden The purpose of this investigation is to study general health issues in relation to different osteoporotic fractures in both sexes. In Malmo Preventive Study 10,902 women and 22,444 men were examined. The mean age for men was 46 years and women 48 years. The participants were followed-up to a maximum time of 18 years. The fractures were recorded prospectively and during the follow-up 1,700 had any fragility fracture. The questions in this study were: Have you got full health? (health) Have your appetite changed? (appetite) Do you often wake up? (wake up). A logistic regression model was used adjusting for age. Only low energy fractures were selected. For individuals with fracture of the distal end of the forearm there was no signicance, neither in men nor in women. For hip fractures there was a signicance for health RR = 0.66 and wake up 1.76. For women there was only signicance for health 0.57. For clinical vertebral fractures in men there was a signicance for all questions: appetite 2.70, health 0.52, wake up 2.30, for women only wake up was signicant 1.76. It seems that there is a difference between different osteoporotic fractures in relation to these health questions and also a difference between the sexes.

155 (147). HIP FRACTURE INCIDENCE RATES IN SINGAPORE 19911998 L. Koh, S. M. Saw, J. Lee, K. H. Leong, J. Lee, National Working Committee On Osteoporosis, Singapore The purpose of this population-based study was to determine the incidence rates of hip fracture among Singapore residents aged 50 years and above. Information was obtained from a centralized database system which captured admissions with the primary diagnosis of a closed hip fracture (ICD9 codes 820, 820.0, 820.2 and 820.8, n = 12,927) from all health-care establishments in the country from 1991 to 1998 inclusive. After removing duplicates, hospital transfers, readmissions and non-acute care admissions, the total number of hip fractures was 9,406. The age-standardized hip fracture rates per 100 000 (standardized to USA population 1985) for 19918 were 152 in men and 402 in women, 1.5 and 5 times higher than corresponding rates in the 1960s respectively. From 1991 to 1998, hip fracture rates increased annually by 0.7% in men and 1.2% in women. Age-standardized hip fracture rates among the three major racial groups were as follows:
Chinese* Male Female 168 (158,178) 410 (395,425) Malay* 71 (54,88) 264 (225,303) Indian* 128 (105,152) 361 (290,432)

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predisposes to the latter, or that its presence does not preclude triathlon participation.

157 (149. OSTEOPOROTIC VERTEBRAL FRACTURES IN PATIENTS WITH CROHN'S DISEASE L. Landgraf1, D. Felsenberg1, S. Ljunghall2, G. Bianchi Porro2, R. Stockbrugger2, M. Vatn2, 1Univ. Hospital B. Franklin, Berlin, Germany; 2Steering Committee of The Matrix Study Group Objective: To study the prevalence of vertebral fractures in patients with Crohn's Disease (CD), where osteoporosis is a common problem. Methods: Baseline values were analysed in a trial conducted at 34 European centres. In total 137 women (mean age 37.2 years) and 136 men (mean age 36.5 years) with CD were randomized to receive treatment with budesonide or prednisolone. Vertebral fractures (fx) were assessed by one radiologist using the ``EVOS'' criteria. Results: 60 vertebral (45 wedge and 15 concavity) fractures were found in 39 (14%) of 273 patients. In men, the prevalence of vertebral fractures was similar in all age groups; in women, it increased signicantly with age (P=0.0042; linear regression). Conclusion: In this predominantly young study population with CD, the vertebral fracture rate was strikingly high, both in men and women, a problem deserving further clinical attention.

*rates (95% condence intervals)

Hip fracture rates in Singapore have risen rapidly over the past 3040 years. Signicant racial dierences in hip fracture rates are present within the same community.
Patients Patients with fx Women Women with fx Men Men with fx

Total 273 39 (14%) 137 17 (12%) 136 22 (16%)

Age 1730 111 12 (11%) 50 3 (6%) 61 9 (15%)

3140 64 8 (13%) 36 4 (11%) 28 4 (14%)

4150 48 8 (17%) 28 4 (14%) 20 4 (20%)

5160 34 6 (18%) 16 3 (19%) 18 3 (17%)

6169 16 5 (31%) 7 3 (43%) 9 2 (22%)

156 (148). INTERSITE RELATIONSHIPS OF BONE MINERAL DENSITY IN OLDER ELITE MALE TRIATHLETES E. M. Kwong, G. F. Rocha, M. Look, M. A. Mikus, L. Musial, G. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California San Diego School of Medicine, La Jolla, CA, USA OBJECTIVE: To investigate relationships among bone mineral density (BMD) and content (BMC) measurements at the lumber spine, proximal femur, and whole body in high performance male triathletes over forty-ve years of age. METHODS: 95 clite male athletes of aged 45 to 76 (mean 54) years competing in the 1999 Ironman World Championship Triathlon in Kona, Hawaii were recruited as subjects at the site of the competition. BMD and BMC at the lumber spine (L2-L4), proximal femur, and whole body were assessed using a Norland XR36 pencil-beam tabletop dual-energy X-ray absorptiometry system. Detailed histories regarding diet, exercise/lifestyle habits and medical history were elicited from each participant. Event performance times in the swim, cycling tour, and marathon were recorded. Data analysis employed Minitab release 12 statistical software. RESULTS: Regression analysis indicated a signicant correlation between whole body BMD and proximal femoral BMD (p50.0001). BMD correlations between whole body and total lumber spine (p = 0.390) and between promimal femur and total lumber spine (p = 0.602) were not statistically signicant. However, when both whole body and proximal femur BMD were compared to individual lumber spine levels L2 and L3, signicant relationships were found (p50.0001). In contrast, when compared to L4, the correlations were again insignicant (p = 0.449 and 0.839, respectively). CONCLUSIONS: Among elite male triathletes over 45 years of age, signicant intersite relationships exist between total body, proximal femoral, and upper lumbar spine BMD. The failure of BMD in the total lumbar spine and L4 alone to correlate with other skeletal sites suggests a relatively high prevalence of degenerative spinal disease in the low back among this population. This implies that intense physical activity among older men either

158 (150). LIFE COURSE PREDICTORS OF ULTRASONIC HEEL MEASUREMENT IN A CROSS-SECTIONAL STUDY OF WOMEN FROM SOUTHEAST ASIA D. S. Lauderdale1, T. Salant1, K. L. Han2, P. Tran2, 1University of Chicago; 2Weiss Health Center, Chicago, IL, USA We conducted a cross-sectional study of bone mineral density (BMD) estimated from ultrasonic calcaneal measurement in women born in Southeast Asia and now living in Chicago. The study addressed three questions: was there a trend towards low estimated BMD? what factors before and after immigration were associated with BMD? and were factors which reected the environment before age 18 equally associated with BMD for postmenopausal and premenopausal women? An interviewer administered a bilingual questionnaire collecting immigration, reproductive and lifestyle data for 213 women (age 2080) born in Vietnam, Cambodia or Laos. Average age at immigration was 39. Postmenopausal Southeast Asian women had lower estimated mean BMD than reference values for white women. Four summary indicators of the childhood and adolescent environment were predictive: education, remembered age at menarche, height, and coastal birth. These factors were more strongly associated with estimated BMD for premenopausal (multiple-partial R2=0.21) than postmenopausal (R2=0.06) women. Adjusting for these factors and age, young adult exposures were also associated: early rst birth (lower BMD), farming at age 18 (higher BMD), and age at immigration (inverse association). Consistent with other studies, smoking and physical inactivity were associated with lower BMD. Distinctive proximal factors vegetarian diet (lower BMD) and betel nut use (higher BMD) were weakly associated.

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Although early life factors inuenced BMD, modiable risk factors were also predictive.

in a test of balance (1.8; 1.12.9), low level of physical activity (2.2; 1.14.4), history of fall in the past 6 months (1.1; 0.62.0 for the rst year to 3.0; 1.56.1 for the fourth year of follow-up). The effect of these fall-related predictors varied according to the level of BMD: in osteoporotic women (BMD T-score 42,5), they were signicantly associated with HF, whereas in non osteoporotic women they were not. These results suggest that programs aimed at preventing HF should target, in priority, women who have both types of risk factors.

159 (151). PREVALENCE OF LOW BONE MASS IN THE PROXIMAL FEMUR AMONG WORLD-CLASS FEMALE TRIATHELETES P. Lee, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate the prevalence of low bone mass in the proximal femur among elite, high performance athletic women. METHODS: 139 females were randomly recruited from the 500 participants competing in the 1999 Ironman World Championship Triathlon at Kona, Hawaii. Subject age ranged from 1669 (mean 39) years. Detailed information regarding diet, exercise regimen, medical problems, lifestyle habits, personal/family fracture history, and menstrual function were obtained from all study participants. Bone mineral density (BMD) and content (BMC) of the proximal femur (regions including neck, greater trochanter, Ward triangle, proximal diaphysis, and total), frontal lumbar spine, and total body were measured using a Norland Medical Systems XR36 pencil-beam dual-energy X-ray absorptiometry (DXA) system. Performance times for the swimming, bicycling, and marathon components of the event were documented. Statistical analysis was performed using Minitab version 12 software. RESULTS: The mean BMC and BMD of the femoral neck were 4.46 g and 0.96 (range: 0.71 to 0.97) g/cm2, respectively; trochanter values were 9.0 g and 0.75 (range: 0.45 to 1.01) g/cm2, respectively; diaphyseal values were 17.4 g and 1.12 (range: 0.75 to 1.58) g/cm2, respectively. Standardized total femoral BMC and BMD were 32042 mg and 992 (range: 1348 to 691) mg/cm2, respectively. Mean total femoral T-score was 0.52 (range: 2.15 to 2.19); mean Z-score was 0.811 (range: 1.34 to 3.19). Mean T- and Z-scores for the femoral neck were 0.54 (range: 3.26 to 2.07) and 0.0619 (range: 1.52 to 2.9), respectively. Mean T-and Z-scores for the trochanter were 0.29 (range: 2.77 to 2.21) and 0.202 (range: 1.99 to 3.27). CONCLUSION: In contrast to previous studies which have focused on amateur female athletes competing in a single sport, we conclude that these world-class triathlete women generally do not suffer from low bone mass or osteoporosis in the proximal femur. Relative preservation of bone mass in this population may be related to optimized dietary and training regimens that maintain body fat at a reasonable level (mean: 12.9%), and thus, their ability to produce sufcient estrogen.

161 (153). PREVALENCE OF OSTEOPROSIS IN PATIENTS REFERRED FOR BONE DENSITOMETRY IN SRILANKA S. Lekamwasam, Faculty of Medicine, University of Ruhuna, Sri Lanka This study estimates the prevalence of osteoporosis at different skeletal sites in 236 patients, who underwent Duel Energy Absoptiometry for the rst time in Sri Lanka. Method: 236 patients, who were suspected to have osteoporosis were scanned using Norland Eclipse Densitometer. Asian Reference data set provided by manufactures was used to estimate the T score. The diagnosis of osteoporosis was made using WHO criteria based on the T score. Results: 90% of patients were women and 83% of them were postmenopausal. The Mean age of the population was 55 (+11.2) yrs, their height 148 (+21.7) cm, weight 51 (+11.9) kg and BMI 22 (+4.8). Osteoporosis was detected in 29% of patients at distal radius and ulna, 42% at proximal radius and ulna, 55% at proximal radius, 48% at lumbar spine and 17% at the neck of femur. Discussion: High % of post-menaopasal women would have contributed to osteoporosis of lumbar spine detected in 48%. Unlike in western countries, the highest prevalence of osteoporosis was seen at the proximal radius. This raises the possibility of associated vitamin D and Calcium deciency in the etiology. Further studies are required to prove this possibility, which will have direct relevance on the prevention and treatment of osteoporosis in Asian countries.

162 (154). DEFINITION OF INCIDENT VERTEBRAL DEFORMITY IN POPULATION STUDIES : CASES SHOULD ALSO SATISFY CRITERIA FOR A PREVALENT DEFORMITY M. Lunt, A. A. Ismail, C. Cooper, D. Felsenberg, O. Johnell, J. Kanis, T. W. O'Neill, J. Reeve, A. J. Silman, the European Prospective Osteoporosis Study Group, ARC Epidemiology Unit, Manchester University, UK Background: Several morphometric criteria have been proposed to dene incident vertebral deformities, however, there are few data comparing their relative performance. The aim of this study was to compare the performance of two established morphometric methods. Methods: The subjects who took part in the analysis were recruited from population registers for participation in a prospective study of osteoporosis the European Prospective Osteoporosis Study (EPOS). At baseline subjects had an interviewer administered questionnaire, lateral spine x-rays and a subsample had BMD assessment. Repeat spinal x-rays were performed a mean of 3.8 years later. Radiographs were assessed morphometrically and clinically by an experienced radiologist. Incident deformities were dened using 2 morphometric criteria: a) a change in vertebral height by more than 20% since baseline, b) a new prevalent deformity (using the McCloskey method). A discriminant function was developed using several risk factors including BMD, which differentiated between subjects in whom both methods agreed were normal and those both agreed had incident deformities. This function was then applied to the subjects who were positive by only one denition.

160 (152). RISK FACTORS FOR FRACTURES OF PROXIMAL HUMERUS S. H. Lee, P. Dargent, G. Bre art, for the EPIDOS Group, INSERM Unit 149, Villejuif, France Fracture of the proximal humerus is one of the major osteoporotic fractures, yet it has seldom been studied. Two types of factors (related to bone fragility or to falls) were evaluated to identify risk factors for humeral fractures (HF), as well as to examine possible interactions between them. 6901 women aged 75 years and older had a baseline examination including femoral neck bone mineral density (BMD), calcaneal ultrasound parameters (speed of sound SOS and broadband ultrasound attenuation BUA), personal and maternal history of fractures, as well as physical capacity, mobility, neuromuscular and visual function assessements. During a mean of 3.6 (0.8) years of follow-up, 165 humeral fractures occurred. Using Cox regression models, we identied three bone fragility-related risk factors low BMD (RR= 1.4 for 1SD; 95% CI 1.11.7), low SOS (1.3 for 1SD; 1.01.6), maternal history of hip fracture (1.8; 1.03.0), and four fall-related risk factors pain in the ankle or foot (1.4; 1.02.1), bad performance

Results: Paired spinal radiographs were available in 3500 women and 3000 men. Using the discriminant function there was no signicant difference between subjects positive only by method a and those positive only by method b, although there were more subjects positive by method b. The risk factor prole of subjects who were positive by only one denition was more similar to subjects agreed to be normal than to subjects agreed to have an incident deformity. If only subjects satisfying both criteria were regarded as having incident deformities, the number of subjects with deformities not diagnosed as having a clinical fracture (according to the radiologist) dropped from 56 (method a) or 201 (method b) to 22, whilst the number with clinical fractures dropped from 188 (method a) or 202 (method b) to 184. Conclusions: In this analysis, using data from a population survey, there was no difference in the risk factor characteristics of subjects classied as having an incident deformity by two established morphometric criteria. A combination of these criteria was more strongly associated with the potential risk factors and the clinical evaluation than either method separately.

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O at least in one region; 4) The 31.53 % of the patients has OP at least in one region; 5) The T is the most preserved region, which is shown N in a 66.15 % of the examined patients; 6) It doesn't exist an affection sequence in which R should precede FN; 7) The weight dissociates the R from the T.

164 (156). COMPARATIVE PREDICTIVE ABILITY OF SKELETAL MEASUREMENTS FOR FRAGILITY FRACTURE E. V. McCloskey, D. de Takats, J. Bernard, K. Pande, R. Ashford, M. Beneton, T. Jalava, J. Kenraali, L. Pylkkanen, J. A. Kanis, University of Shefeld, UK We wished to compare the predictive abilities of a number of densitometric and ultrasound techniques for fragility fractures. In an interim analysis of a prospective double-blind, placebocontrolled study of hip fracture prevention, 4348 women aged at least 75 years underwent a variety of skeletal assessments at entry. They were then randomised to receive clodronate 800mg daily or placebo. The present analysis remains blinded to treatment. During a median follow-up of 15 months, a total of 195 validated fragility fractures were documented, including 51 hip fractures. The age and weight adjusted odds ratio for fracture for each 1SD decrease in measurement was computed by logistic regression (Table). All of the assessments showed signicant predictive ability for any fragility fractures. The relative performance of total hip BMD appears superior to the other assessments.

163 (155). INCIDENCE OF OSTEOPOROSIS IN A WOMAN POPULATION OF BUENOS AIRES CITY Z. Man, P. Antunez, TIEMPO Medical Center, Buenos Aires, Argentina In order to determine the incidence of spinal and hip Osteoporosis (OP) and Osteopenia (O) in a group of women ([,]]) without obvious risk factors in our city, a random selected group of 280 postmenopausal [,] from 46 to 82 years old (y) has been evaluated densitometrically (dtm), measuring Bone Mineral Density (BMD) in lumbar spine (R), Femoral Neck (FN) and Trochanter (T). There have been excluded from the research those [,] with early menopause (less than 45 years old), hyper or hypothyroidism, hyper or hypoparathyroidism, renal failure, Cushing syndrome or adrenal deciency, kidney stones, severe gastrointestinal pathologies, cerebral-vascular injure, pathological fractures, Paget disease, multiple mieloma or other cancers, hypopituitarism or GH decit, hyperprolactinemia; drugs (for more than 2 months): any drug used for OP treatment, corticoids, T4, heparine or oral anticoagulants, diuretics, high doses of AINE or raloxiphene. The 130 patients (age X = 60, 4612,1 y) which did not present any of the above mentioned OP risk factors, were asked about number of y from menopause (MY) and their Body Mass Index (BMI) was calculated. The patients were classied according to: a) BMD: Normal (N = T up to 0.99), O (O = T from 1 to 2.49) or OP (OP = T >2.49); b) MY: 1 to 4.9; 5 to 9.9; 10 to 19.9 and >20; c) BMI: Normal Weight (NW, >24.9), Overweight (OW, from 25 to 29.9) and Obesity (OB, >30). Results (respectively R/FN/T,): N-N-N, 31 [,], 23.84%; O-O-O, 16 [,], 12.3%; OP-OP-OP, 6 [,]], 4.61%; O-N-N, 11 [,], 8.46%; OPN-N, 2 [,], 1.53%; OP-O-O, 10 [,], 7.69%; OP-O-N, 12 [,], 9.23%; O-OP-O, 3 [,], 2.3%; N-O-N, 13 [,], 10%; O-O-N, 17 [,], 13.07%; OP-OP-O, 8 [,], 6.15%; N-O-O, 1 [,], 0.76%. a) Neither NW [,] with >5 YM nor any [,] >20 YM had the 3 dtm measured regions N; b) None of the OW or OB [,], independently of YM, had OP in the 3 zones, only NW [,] presented OP in the 3 zones; c) None of the NW [,] had R with O or OP with N hip (FN and T); d) None of the [,] had FN OP with R and T N, but 3 [,] showed FN OP with R and T O and 13 [,] FN O with R and T N; e) None of the [,] with > 20 YM had N FN; f) OB [,] only change T after 10 YM; g) Only 2 [,] shown OP in R with hip (FN and T) N; h) In all YM groups were found [,] with OP-O-N, O-N-N and O-O-N, but only 1 [,] had N R with hip (FN and T) O; i) It has been found that more [,] OW or OB showed BMD dissociation between R and T. Conclusions: 1) The 23.84 % of postmenopausal [,] didn't present O or OP, but neither any [,] YM >5 nor any [,] YM >20 has the 3 regions N; 2) Only a 4.61 % of postmenopausal [,], all NW, have OP in R, FN and T; 3) The 41.61 % of the patients presented

Measurement Total hip BMD Forearm BMD Heel BUA Tibial SOS

Any OP fracture 1.6 1.4 1.2 1.2 (p<0.0001) (p<0.0001) (p = 0.0038) (p = 0.0082)

Hip fracture 2.1 1.7 1.3 1.1 (p<0.0001) (p<0.0001) (p = 0.0062) (p = 0.4404)

165 (157). INCIDENCE OF HIP AND DISTAL FOREARM FRACTURES AMONG URBAN POPULATION IN RUSSIA E. E. Mikhailov, L. I. Benevolenskaya, S. G. Anikin, E. A. Besedina, U. A. Doroshenko, O. B. Ershjva, E. V. Zhuravleva, O. M. Lesnyak, L. V. Menshikova, E. N. Otteva, Institute of Rheumatology RAMS, Moscow, Russia Retrospective multicentral study among the population aged 50 year and over from 12 Russian cities in the period of 19921997 was aimed at the study of hip and distal forearm fractures incidence. Total numbers of the examined population was 1,394,250 persons (M=529, 796; F=864, 454). Among males hip fracture incidence varied from 25.7 to 176.2/100 000 which averagely is 78.8/100 000. Fracture incidence among females in the majority of the cities statistically signicant prevailed over that among males and varied from 61.4 to 259.5 being in average 105.9/100 000. Fracture incidence grew with age with maximal values in age groups >70 y/o. Distal forearm fractures incidence among males varied from 71.2 to 1247.3 which averagely is 235.1/ 100 000 for all period of observation. Fracture incidence of this localisation among females statistically signicant prevailed over that among males and varied from 242.4 to 1213.3 which averagely is 684.9/100 000. Three groups of cities were isolated: with high, medial and low fractures incidence. The differences between groups were statistically reliable. Analysis of fractures dynamics during the studies years enabled us to reveal the statistically signicant increase of fractures incidence of both localisations for the last years.

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166 (158). OBSERVATIONAL STUDY ON ARTHROSIS AND OSTEOPOROSIS: RESULTS FROM 1880 WOMEN O. Moreschini, S. Conte, M. Nocente, University of Rome ``La Sapienza'' Orthopaedic Department, Italy Abstract. We studied the possible relationship between Osteoartrhitis (OA), Osteoporosis (OP), and correlated risk factors, in a cohort of female subjects over 45 years. Severe OA was dened as a variation of grade 4, in acccordance with the criteria described by Kellgren and Lawrence; OP was diagnosed by means of densitometric examination performed with double X-ray mineralometric techniques (DEXA). Complete data, including anthropometric charateristics, gonadal function, eating habits during both adolescence and adult age, smoking, physical intensity of working activities, articular and somatic pain and disability, were available in 1880 women (mean age 65.28 years). Statistical analysis was made. Our results show an inverse correlation between bone density distribution in terms of the degree of OA, (r = 0.89; p = 0.042) regardless of the age factor. We found an highly signicant difference (p50.01) in body weight, number of children, body mass index, articular pain (always higher in the OA group) and quality of life (lower in the severe OA group). No signicant differences (p > 0.05) were observed for height, menarchal age, period of breastfeeding, eating habits during adolescence and adulthood, comsumption of alcohol or coffee, smoking, somatic pain. Our study conrms the existence of a marked inverse correlation between OA and OP, particularly in the most severe clinical and diagnostic conditions. To conclude, far from presuming a denite pathological cause linking these two conditions, we consider the factor ``presence of severe OA'' as an additional diagnostic element for management of post-menopausal osteoporosis.
RHOA Osteophytes MJS 1.5 mm
*P<.05 **P<.01

% new RHOA (OR) by Age-adj. BMD Quartile Q1 2.3% (1.0) 2.7% (1.0) 2.7% (1.0) Q2 2.5% (1.2) 3.6% (1.4) 2.2% (0.8) Q3 3.2% (1.6) 3.9% (1.5)* 2.6% (1.0) Q4 4.7% (2.3)** 4.7% (1.9)** 2.6% (1.0)

168 (160). REGIONAL BONE MINERAL DENSITY AND SOFT TISSUE COMPOSITION IN OLDER ELITE MALE ATHLETES D. Nguyen, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To assess the relationships among regional bone mineral density (BMD), bone mineral content (BMC) and lean versus fat soft tissue composition in highly trained athletic men over 45 years of age. METHODS: 95 elite male athletes ranging in age from 45 to 76 (mean 54) years who competed in the 1999 Ironman World Championship Triathlon in Kona, Hawaii were examined. Total body and regional BMC and BMD, as well as total and regional soft tissue mass (including lean versus fat components) were measured using a Norland XR36 pencil-beam tabletop dualenergy X-ray absorptiometry scanner. Dietary/medical history, exercise/lifestyle habits, and personal/family fracture history, along with performance times in the swim, cycling tour, and marathon components of the event, were documented for each participant. Statistical analysis of data was performed using Minitab version 12 software. RESULTS: Signicant correlation was found between (BMC) and soft tissue (lean plus fat) mass in all body regions, with the strongest relationship in the abdomen (p50.0001, R-Sq = 77.8%). However, BMC in the arms and legs was not statistically related to either fat or lean mass individually in these areas. Correcting for skeletal size, BMD correlated signicantly with total soft tissue mass only in the chest, legs, and arms (p ranging from <0.0001 to <0.005). No statistical relationship was found between regional BMD and separate fat versus lean tissue components. BMC, BMD, bone size, and total soft tissue mass of the right versus left extremities were signicantly correlated (p50.0001), indicating symmetry. CONCLUSIONS: BMC correlates well with total soft tissue mass in all regions of the body among older male triathletes. However, the BMD:soft tissue relationship is signicant only in the biomechanically active regions of the body (chest, arms, legs), suggesting an inuence of their intense physical training. In contrast to previous studies demonstrating relatively constant ratios between BMD/BMC and muscle mass in the extremities, this investigation suggests that BMD/BMC in the arms and legs is related to total soft tissue mass as opposed to lean versus fat components separately among older elite male athletes.

167 (159). HIGH BMD INCREASES THE RISK OF NEW HIP OA IN ELDERLY WOMEN, BUT OSTEOPOROSIS IS NOT PROTECTIVE M. Nevitt, N. Lane, M. Hochberg, E. Williams, for the SOF Research Group, Universities of California, San Francisco; 2 Baltimore, Maryland, USA In cross-sectional studies women with radiographic hip OA (RHOA) have increased BMD at the hip and peripheral sites. We performed a prospective study of the relationship between baseline BMD, prevalent vertebral fractures (PVFX), and new RHOA among women age 565 in the Study of Osteoporotic Fractures (SOF). AP pelvis x-rays were obtained 8.0 (SD 0.4) years apart in 5,987 women, 73% of survivors. Paired x-rays were assessed blinded to order for individual radiographic features (IRFs) of hip OA and measurement of minimal joint space (MJS). Total hip BMD was assessed by DXA (Hologic QDR 1000) and radius BMD by SPA (Osteon Osteoanalyzer). PVFX were assessed by morphometry from lateral spine x-rays. In women without RHOA at baseline, we calculated odds ratios (OR) for the association of age-adjusted quartiles of BMD and PVFX with new RHOA ([get] 2 new IRFs), new osteophytes and new MJS 41.5 mm. Logistic regression was used to estimate ORs in a hipbased analysis, with GEE to account for within subject correlation, adjusted for age, estrogen use, weight, height, physical activity, and smoking. Women with high hip BMD had a greater risk of new RHOA and osteophytes, but not loss of joint space, a marker for severe OA. Results were similar for radius BMD. In contrast, women with 2 or more (vs. none) PVFX had an increased risk of RHOA, osteophytes and loss of joint space. We conclude that high BMD is a risk factor for an osteotrophic variant of RHOA in elderly women. However, osteoporosis may increase the risk of developing severe hip OA with loss of joint space.

169 (161). EXERCISE AND MILK INTAKE ARE DETERMINANTS OF BONE MASS IN ELITE MALE MILITARY CADETS J Nieves, M Zion, J Rufng, R Lindsay, F Cosman, Helen Hayes Hospital, NY, USA Peak bone mass is clearly related to genetic and lifestyle factors. A sample of 557 male cadets entering the United States Military Academy (USMA) had multiple bone density assessments to determine the relative importance of milk intake and physical activity on bone mass at various skeletal sites. Dietary intakes of calcium, salt, caffeine and physical activity over the year preceding entry to the USMA were assessed by written questionnaire. Calcium intake was almost solely determined by

milk intake in this population. A Lunar DPX-IQ Dual x-ray absorptiometry (DXA) was used to assess bone density (BMD) at the lumbar spine and total hip in a randomly chosen subset of 131 male cadets. A peripheral DXA (Lunar) was used to assess heel BMD in 557 male cadets and a peripheral pQCT (Norland) was used to measure tibial bone content and cortical thickness in 503 male cadets. On average the cadets had spine, hip and heel BMD values that were one standard deviation above the manufacturers young normal reference population. Higher milk intakes (3 cups/day or more) were signicantly related to greater total tibial content (p = 0.01); cortical thickness (p = 0.02) and heel BMD (p = 0.05). There was also a trend toward higher BMD of the spine and hip in those with higher milk intakes. In male cadets, intense physical activity in the past year (exceeding 12 hours per week) was associated with signicantly higher bone mass throughout the skeleton including the spine, hip, heel and tibia (3 and 6% higher; all p<0.02) as compared to cadets with less intense levels of physical activity. Salt and caffeine were not associated with bone mass. In conclusion, males with bone mass at the high end of normal, can still maximize bone mass at all skeletal sites by high levels of exercise and adequate calcium intake through milk consumption.

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dietary/medical history, exercise/lifestyle habits, and personal/ family fracture history. Performance times in the swimming, bicycling, and marathon components of the event were also recorded. Statistical analysis was performed using Minitab version 12 software. RESULTS: Height ranged from 5975 (mean 69) inches. Weight ranged from 129193 (mean 159) pounds. Maximum lifetime weight averaged 175, with a high of 230, pounds. Total body BMC ranged from 23683918 (mean 3109) grams. Total body BMD ranged from 0.8591.235 (mean 1.080) grams/cm2. Total soft tissue mass ranged from 55.682.1 (mean 69.7) kilograms. Lean body mass ranged from 35.169.3 (mean 51.6) kilograms. Fat body mass ranged from 4.720.8 (mean 11.1) kilograms. Corrected percentage body fat ranged from 4.025.6 (mean 12.5) %. Total body BMC was signicantly correlated with total soft tissue mass (p50.0001, R-Sq = 29.6%). Total body BMD was signicantly correlated with total soft tissue mass (p50.0001, RSq = 14.0%). However, neither total body BMC nor BMD was predicted by lean versus fat components of total body soft tissue composition (p = 0.657, p = 0.14 for BMC, p = 0.393, p = 0.107 for BMD, respectively). Lean body mass was not signicantly related to fat body mass (p = 0.287). CONCLUSIONS: Older elite male triathletes as a group do not differ signicantly from the general population in terms of total body BMC and BMD, despite intense physical training regimens. Similarly, percentage body fat is not below the generally accepted ideal range of 1020% for the general population of men. Total body BMC and BMD are predicted by total soft tissue mass, but not by lean or fat body mass independently.

170 (162). GENETIC CONTRIBUTION TO BONE MINERAL DENSITY VARIATION AT MAJOR SKELETAL SITES IN TWINS T. Niu1, J. Ni2, C. Chen1, D. Chen,1,2, B. Wang,1,2, X. Liu2, S. R. Cummings3, C. J. Rosen4, X. Xu,1,2,5, 1Program for Population Genetics, Harvard Schl Pub Hlth, Boston, MA; 2Inst. for Biomed, Anhui Med. Univ., Hefei, China; 3Dept. of Med., UCSF, San Francisco, CA; 4Maine Ctr. for Osteoporosis Res. & Education, Bangor, ME; 5Channing Lab, Dept. of Med., BWH, Harvard Med. Schl., Boston, MA, USA Twin studies offer unique opportunities in estimating the genetic component of quantitative traits. We measured bone mineral density (BMD) using DEXA at various skeletal sites and for the total body in 605 twin pairs in Anqing, China. Estimates of heritability for age-, sex-, smoking status-, and body mass index (BMI) -adjusted BMD of head, arms, legs, trunk, rib, pelvis, spine, and total body were 0.65, 0.82, 0.71, 0.75, 0.73, 0.45, 0.78 and 0.58, respectively for twins under age 18, and were 0.60, 0.53, 0.70, 0.70, 0.67, 0.75, 0.45, and 0.66 for twins at least 18 years old. The intrapair difference of BMI was found to be a signicant predictor of the intrapair difference of age- and sex-adjusted BMD of trunk, rib, pelvis, and total body among adult MZ twins (P<0.001). This study suggests that the variance of BMD at various anatomical sites is largely genetically determined in both children and adults. Furthermore, our results demonstrate that BMI is a signicant predictor of BMD values at various skeletal sites examined.

172 (164). BMD IN CALCANEUS IN 1392 18 YEAR OLD MEN IN RELATION TO MUSCLE STRENGTH C. Nyman, O. Johnell, K. Landin-Wilhelmsson, L. Hulthen, R. Kullenberg, L. Samuelsson, R. Lorentzon, E. Norjavaara, D. Mellstro m, 1Dept of Geriatrics, Internal Medicine and Radiophysics, University of Gothenburg, The National Service Administration, Regional Ofce, Gothenburg; 2Dept of Orthopaedics, Umea and Malmo, AstraZeneca, Lund, Sweden BMD is a predictor of fractures and survival in men. Most studies show a close relation between BMD and muscle strength in men. The question is if BMD is a predictor of muscle strength and endurance corrected for anthropometric factors and years of training. Most (96 per cent) of 18 year old men in Sweden participate in a two days test of functional capacity and tness for the compulsary military service. BMD in right calcaneus was measured with DXA. Calscan. A questionnaire included nutritional habits, physical activity, life style factors and heredity. BMD in calcaneus correlated to heigth (r = 0.14), weight (r = 0.21), years of training (r = 0.39), muscle strength (r = 0.33), oxygen uptake (r = 0.21) and endurance test (r = 0.40). In a covariance analysis BMD remainded signicant in a model with age, heigth, weight and years of training as a predictor for muscle strength. In summary BMD in calcaneus was an independent predictor of muscle strength and endurance in a community based population of 18 year old men.

171 (163). TOTAL BODY CALCIUM AND BODY COMPOSITION IN OLDER ELITE MALE TRIATHLETES C. T. Norred, E. M. Kwong, G. F. Rocha, M. Look, M. A. Mikus, L. Musial, G. Nakamoto, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To evaluate total body bone mineral content (BMC)/ density (BMD) and soft tissue composition among elite male triathletes over age 45 years, with reference to regional distribution and interrelationships. METHODS: 96 male triathletes ranging in age from 4576 (mean 54) years participating in the 1999 Ironman World Championship Triathlon at Kona, Hawaii were prospectively recruited. Dualenergy X-ray absorptiometry studies of the total body, frontal lumbar spine, and proximal femur were performed on each subject using a Norland XR36 pencil-beam tabletop scanner. Questionnaire data solicited from each participant included

173 (165). A METHOD OF CALCULATING THE LONG-TERM PROBABILITY OF FRACTURE A. Oden, J. A. Kanis, O. Johnell, D Mellstro m, B. Jonsson, C. De Laet, A. Dawson, Consulting Statistician Romelanda, Sweden Whereas hip BMD provides diagnostic criteria for osteoporosis, treatment thresholds depend upon other factors including absolute risk and the cost effectiveness of interventions. Absolute risks are preferable to relative risks and 10-year risks are considered appropriate for the development of practice guide-

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lines. In this paper we have devised a method of determining long-term risks. The easiest way of determining the long-term risk of fracture is to follow a cohort for a given period of time but this is not always feasible. A more appropriate approach is to estimate the fracture and death hazards separately with varying follow up periods and without restriction to time by the use of Poisson regression models. The general relationship between the probability on one side and the two hazard functions on the other one is then applied in order to calculate the probabilities for different subgroups. Adjustments of the death hazards to future hazards or to other countries are possible by this method as well as adjustments to the general level of the fracture hazard of the country. The relative importance of risk variables such as bone mineral density (reected by beta coefcients in regression models) is probably more stable from country to country than the general level of the risk of a country. In many cases the estimations of the two hazard functions can be done with a greater accuracy than the estimation say, of the ve years probability by logistic regression. For example, a low bone mineral density gives a higher risk of death which to some extent makes the bone mineral density less important for the probability than for the hazard function. In addition, the data after these ve years can be used. This methodology has been applied to the Gothenberg population in Sweden to examine the effects of age, sex, bone mineral density, body mass index and other risk factors on the ten year probability of hip fracture.

Population and method: From the longitudinal population study of the elderly in Gothenburg, 1628 individuals (944 women) with a mean age from start of 77.6 years (range 7085 years), were included. Bone mineral density was measured with DPAtechnique in calcaneus. The occurrence of hip fractures was ensured by coordination with the medical register of the National Board of Health and Welfare and x-ray archives. A Poison model was used to study the impact of time after BMD measurement to predict hip fractures. Results: The total follow up time was 12.223.8 years. The number of patients with hip fracture were 216. Mean value of BMD was 0.381 g/cm2 and SD was 0.137. The predictive power of a bone density measurement declined during a period of 10 years with a relative risk per SD from &1.5 year one to 1.2 the nal year. The study indicates that gender has no signicant importance for the risk of hip fracture if bone density was included in the model and smokers and subjects with low BMI had an independent increased risk for hip fracture. Conclusion: This study demonstrates that a bone density measurement in calcaneus is a strong independent predictor for future hip fracture also at age 80. It also indicates that the predictive power signicantly decrease during a period of 10 years after the measurement.

176 (168). HIGH CHOLESTEROL LEVELS ARE ASSOCIATED WITH LOW BONE DENSITY IN POSTMENOPAUSAL WOMEN P. Orozco, I. Hurtado, ABS Gotic & Universitat de Barcelona & Unitat Recerca Experimental, Barcelona, Spain Recent studies suggest that osteoporosis and cardiovascular risk factors may be associated. Objective: To evaluate the lumbar and femoral bone density (by DXA) in early postmenopausal women aged 553 years with normal (5240 mg/dl) and high cholesterol levels (>240 mg/dl). Patients: 55 women (32 normal and 23 with high cholesterol), with no treatment that interfere lipids or bone metabolism. All were no heavy smoker, no sedentary, no early menopause. Results: Women with high cholesterol had lower BMD than those with normal cholesterol. Both group had similar age, time since menopause, weight, height, blood pressure, but calcium intake was lower in those with high cholesterol.
Cholesterol (mg/dl) <240 >240 X (SD) n=32 X (SD) n=23 Tscore L2 L4 Tscore neck Tscore troch Tscore inter Tscore F-tot Tscore Ward's Cholesterol Years since mp BMI (kg/m2) Calcium intake 1.0 (1.4) 0.7 (0.9) 0.4 (1.4) 0.2 (1.3) 0.1 (1.3) 1.0 (1.4) 207 (24) 5 (2) 27.4 (2.2) 1213 (426) 1.6 (0.7) 1.1 (0.8) 0.7 (1.1) 0.6 (1.0) 0.8 (1.0) 1.6 (0.8) 275 (27) 5 (2) 27.3 (1.6) 928 (281) p

174 (166). EXCESS COSTS: OSTEOPOROTIC FRACTURES IN VETERANS A. Ohldin, K. Kiefe, University of Alabama, Birmingham, AL, USA Background: Osteoporosis affects over 20 million Americans. Complications of osteoporosis such as hip and other fractures result in signicant incremental health care costs. Hip fractures account for 300 000 hospital admissions and annual cost estimates range from $15 billion to $30 billion. The majority of hip fractures are attributed to osteoporosis. The prevalence of osteoporosis and associated fractures are expected to increase among the aging Veteran population. Osteoporotic hip fractures are associated with one-year excess mortality of 1020%. Less than one third of elders with hip fractures return to their previous level of function. Purpose: Identify frequency and incremental medical costs associated with hip fractures among Veterans. Methods: Medical cost inferences based on VA and Medicare discharge and cost data. Results: Hip fractures annually result in 11 million dollars of excess costs to Veterans and the VA. Conclusions: Osteoporotic hip fractures are preventable. Use of primary and secondary preventive measures, in the VA, represent an opportunity for substantial cost savings and enhanced quality of life.

0.02 0.07 0.4 0.02 0.02 0.06 0.0001 0.7 0.9 0.007

175 (167). DOES THE PREDICTIVE VALUE FOR HIP FRACTURE OF A CALCANEAL BONE MINERAL MEASUREMENT CHANGE WITH TIME? J. O Olsson1, J A. Kanis2, A. Oden3, O. Johnell4, C. Johansson1, A. Rundgren1, D. Mellstro m1, 1Dept. of Geriatrics, University of Gothenburg, Sweden; 2Metabolic Bone Diseases, Shefeld University, Shefeld, UK; 3Dept. of Statistics, Chalmers Gothenburg, Sweden; 4Dept. of Orthopaedics, Malmo, Sweden Bone mineral density measurement predicts future hip fracture, with a relative risk per SD from 1.5 to 2.6 depending on site of measurement in a metaanalyse. The question is, if a single BMD measurement among elderly could predict hip fracture after 510 years.

Conclusions: These data suggest that women with hypercholesterolemia have lower bone density, but other confounding factors like nutrition should be considered.

177 (169). RISC FACTORS FOR OSTEOPOROSIS IN CITIZENS OF BELGRADE , N. Vujasinovic - Stupar, D. Palic-Obradovic , G. N. Pilipovic , Institute of Rheumatology, Radunovic, P. Vukojevic, S. Brankovic Belgrade, Yugoslavia We examined 667 citizens of Belgrade, randomly selected from the population register to estabilsh risc factors for osteoporosis.

The study was carried out in Institute of rheumatology in Belgrade and bone mineral density (BMD) of lumbar spine were performed, using a Lunar DPX-L device. There were 541 female aged between 20 and 78 years (mean 48.6011,84) and 126 male aged between 20 and 77 (mean 50,8915.09). Osteopenia was found in 26.6% women and 28.6% men, and osteoporosis in 9,1 % and 8.7% women and men, respectively. Analysis have been done using Chi square test, T-test for independent samples and ANOVA. Study conrmed that age and menopause have signicant effect on BMD. Also, in this study the other factors were found to be of substantial importance for bone mass: sedentary life (recreation end sport activity, as well as hard work have positive corelation with BMD), low calcium intake (intake of diary products every day has positive corelation with BMD), low sun exposure, low BMI, surgical treatment especially early oophorectomy, malignancy, thyreoid disases, joint disease and extensive smoking. The most of these risc factors could be modied for prevention of osteoporotic fractures.

Thursday, June 15, 2000

signicant, concerning both the accurence rate of osteopenia and osteoporosis and severity of bone affection (T and Z score) of lumbar spine (p = 0.007), as well as of the neck of the femur (p = 0.035). The incidence of osteopenia and osteoporosis increases with the duration of the underlying disease, with duration of corticosteroid therapy and the presence of other serious diseases may also have been involved. The region of the lumbar spine was signicantly more frequently affected than the neck of the femur. Conclusions: Management of patients with SLE should involve prevention of the development of osteopenia, particularly in women of menopausal age, in the presence of several risk factors of osteoporosis, especially in long-term therapy with corticosteroids and a prolonged course of underlying disease with frequent ares of disease activity.

178 (170). THE INCIDENCE OF VERTEBRAL DEFORMITY IN HUNGARIAN MEN AND WOMEN Gyula Poor1, Csaba Kiss1, Dieter Felsenberg2, Terence W. O'Neill3, Marianne Szilagyi1, Alan J. Silman3, 1National Institute of Rheumatology, Budapest, Hungary; 2Steglitz Medical Centre, Freie Universitat Berlin, Berlin, Germany; 3ARC Epidemiology Research Unit, University of Manchester, Manchester, UK There is no reliable vertebral fracture incidence data in Hungary. We studied prospectively 223 women and 198 men aged >50 for a mean of 5.1 years in Budapest. Baseline and follow-up lateral Xray of the spine (T4-L4) was digitised centrally. Film pairs with candidate fractures were submitted for reevaluation by skeletal radiologist. Data were examined for inconsistencies and database cleaning in the statistical centre. Mc Closkey -Kanis 3 SD deformities were identied on the second X-ray and incidence dened by a 53 SD vertebral hight reduction. Clinical fractures were judged on new endplate infraction and vertebral shape change. There were 17 incident deformities in 9 women and 12 in 6 men compatible with osteoporosis. Adjusted to age 65, 1.21 (0.65 1.42, 95% CI) woman suffered an incident deformity per 100 years follow up and 0.61 (0.420.79, 95% CI) men suffered an incident deformity per 100 years follow up.

180 (172). AGE-RELATED BONE LOSS IN NORMAL POPULATION OF UKRAINE: DATA OF ULTRASOUND BONE DENSITOMETRY V. V. Povoroznyuk, Institute of Gerontology, AMS Ukraine, MD, Ukraine The bone tissue state in the residents of Ukraine, subjects of both sexes, was studied. The total of 1866 persons (1364 women and 502 men; 2089 years old) were included. Patients with diseases inuencing their bone tissue metabolism were excluded from the study. The heel bone examinations were performed by means of an ultrasound bone densitometer 5Achilles+4 (Lunar Corp., Madison, WI). The speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and a calculated 5Stiffness4 index (SI, %) were measured. It was found out that the ultrasound parameters characterizing state of spongy bone tissue, and its density decrease after the age of 45 years old in women and after the age of 70 years old in men (g. 1). Fig.1. SI values in population of Ukraine associated with age and sex Note: *p50.05; **p50.01; ***p50.,001 compared to the age group of 3539 years old; #p50.05; ##p50.01; ###p50.001 compared to women. SI lower than the fracture threshold was found in: 2.4% men; 13.4% women in age group of 5059 years; 9.6% men; 24.6% women in age group of 6069; 22.6% men; 50.0% women in age group of 7079 years, 20.,1% men; 53.3% women in age group of 8089 years. Thus, in the process of aging ultrasound parameters characterizing bone tissue state decrease signicantly and number of the examined with indices lower than the fracture threshold increases.

179 (171). BONE DENSITY EVALUATION IN SYSTEMIC LUPUS ERYTHEMATOSUS Z. Pospisil, P. Horak, V. Scudla, L. Faltynek, IIIrd Department of Internal Medicine, University of Olomouc, Czech Republic Background: The actual accurrence of osteopenia in patients with SLE has not been established as yet and the causes have not been adequately elucidated. Objective: To assess the accurrence rate of osteopenia in women with SLE, the severity of skeletal damage (ostepenia, osteporosis) in the region of lumbar spine and in the neck of femur, to determine and assess causal relationships involve in the development of osteopenia. Patients and methods: The study is based on the analysis of a group of 26 women (9 in the productive, 17 in postmenopausal age). Their degree of bone tissue mineralisation was measured using the method of double-energy x-ray absorbtiometry (LUNAR DPX-L). Results: In young women of productive age skeletal affection was but rarely observed, ostepenia was present in 4/9 (44%), while none of them had osteoporosis. In women of postmenopausal age ostepenia was recorded in 7/17 (41%), osteoporosis in 6/17 (35%), only 4/17 (24%) had a normal densitometric nding. The differences observed between two groups were statistically

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181 (173). ULTRASOUND DENSITOMETRY OF THE CALCANEUS IN CHILDREN AND ADOLESCENTS OF UKRAINE V. V. Povoroznyuk, Institute of Gerontology, AMS Ukraine, MD, Ukraine The bone tissue state in children and adolescents of Ukraine, subjects of both sexes, was studied. The purpose of this study is to determine normal values in Ukrainian children and adolescents. The total of 577 healthy children and adolescents (205 males and 372 females; 718 years old) were examined by means of 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. Ultrasound parameters increased with age in both sexes (g.1). It was found out that the ultrasound parameters characterizing state of spongy bone tissue and its density increase during the age of 1014 years. Results of linear regression analysis revealed a signicant correlation between ultrasound parameters and beight (SOS = 1413+0.99 x Height; r = 0.45; R2=20.2; p<0.001; BUA = 7.0+0.62 x Height; r = 0.60; R2=36.1; p<0.001; SI = 0.69 x Height 19,6; r = 0.60; R2=36.1; p<0.001). Using the method of step-by-step multiple regression, mathematical models for determination of the structural-functional age of bone system (SFA BS) in children and adolescents are worked out: SFA BS (males) = 9.01 x H +0.06 x W +0.04 x BUA7.7 (r = 0.88; R2=78%; p<0.0001); SFA BS (females) = 8.02 x H +0.05 x W 0.008 x SOS13.9 (r = 0.78; R2=61%; p<0.0001), where: H height (m), W weight.

measured by current mean steroid dose 7.8 mg vs. 4.1 mg and mean lupus damage score [excluding osteoporosis] 1.7 vs. 1.1, and personal characteristics as measured by mean BMI 29.0 kg/ m2 vs. 26.5 kg/m2 and mean daily calcium intake 910 mg vs. 1185 mg. Mean unadjusted LS BMD was 0.996 g/cm2 and 0.966 g/cm2 in C and A-A lupus women, respectively (p = 0.000). A-A lupus women had signicantly lower LS BMD compared with C lupus women in multiple regression analysis, after controlling for BMI, lupus damage score and menopause. A-A lupus women compared with C lupus women had lower LS BMD equivalent to 1SD. Race was not protective for LS BMD in A-A lupus women and may indeed be a risk factor. Therefore, preventive measures must be incorporated into the care of all lupus patients, irrespective of race.

183 (175). DETERMINANTS OF SIZE OF INCIDENT SPINE DEFORMITIES J. Reeve, M. Lunt, G. Armbrecht, T. O'Neill, A. J. Silman, D Felsenberg, the EPOS Study Group, Institute of Public Health, Cambridge, UK Background: The personal impact of a vertebral fracture depends partly on its size. To help understand the biological mechanisms underlying the development of disabling spinal osteoporosis we have investigated the determinants of fracture size in a large European population-based prospective study (EPOS). Methods: 3800 women and 3300 men were followed in 31 European centres. Lateral spine radiographs were taken a mean of 3.7 years apart. Bone mineral density (BMD) measurements were made, using DXA, at the spine or hip in all but 9 centres. Paired digital lm images were adjusted to the same magnication and each candidate fracture was subjected to rigorous QA. Incident deformities were dened by the McCloskey-Kanis algorithm on the second lm (6 point method) and had at least one height reduced by 20% between lms. 66 men and 142 women had at least 1 incident deformity, for each of which loss of height (LOH) was calculated as the percentage reduction in the sum of the three vertebral heights. Clinical fractures were classied as wedge(we), concave(co), biconcave(bi) or crush(cr). Backwards stepwise regression was used to determine a parsimonious model for LOH. Results: LOH increased with age (4%/decade), previous bi or cr and was not signicantly different between men and women. LOH also increased by 2% /0.1g.cm2 decrease in BMD. Models including BMD accounted for >30% of the variance in LOH. When LOH for all newly fractured vertebrae was summed and made the dependent variable, the model retained the same determinants and the variance accounted for increased to 70%. LOH for theworst new fracture was more than 2-fold greater in subjects with a pre-existing bi or cr deformity (mean 30 vs 13% P<0.001). Conclusions: Second fracture size, like second fracture risk, is predicted independently of BMD by a previous fracture. Meticulous radiological evaluation of spine lms is crucial in the prognosis and management as well as in the diagnosis of vertebral osteoporosis.

Fig. 1. SI values in children and adolescents associated with age and sex Note: *p50.05; ** p50.01; *** p50.001 in comparison with the 10 year-old males and females In summary, basic preventive measures against the development of ``future'' osteoporosis in children need to be carried out during the period from 1015 years.

182 (174). AFRICAN-AMERICAN(A-A) WOMEN WITH LUPUS HAVE A GREATER RISK OF LOWER LUMBAR SPINE (LS) BONE MINERAL DENSITY (BMD) THAN CAUCASIAN(C) WOMEN WITH LUPUS R. Ramsey-Goldman, D. Dunlop, C. F. Huang, E. Koch, C. McCray, S. Cunanan, S. Spies, S. Manzi, Northwestern University, IL, and University of Pittsburgh, PA, USA A-A women are aficted with lupus 34x more frequently than C women. However, little is known about the bone health of A-A women with lupus. The objectives of this study were to measure LS BMD by DXA and to estimate the effect of risk factors for low BMD in A-A and C women with lupus. 179 women [139 C and 40 A-A] were studied to date. There were signicant differences (p = 0.05) between A-A and C lupus women in disease severity as

184 (176). PREVALENCE OF LOW BONE MASS AND DEGENERATIVE SPINAL DISEASE IN OLDER HIGH ENDURANCE MALE TRIATHLETES G. F. Rocha, E. M. Kwong, M. L. Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA OBJECTIVE: To investigate bone mineral content (BMC), bone mineral density (BMD) and resulting mean T-scores and Z-scores at the lumber spine of high endurance male triathletes 45 years of age and over. METHODS: 95 high endurance male athletes ages 4576 (mean 54) years competing in the 1999 Ironman World Championship

Triathlon in Kona, Hawaii were randomly recruited as subjects at the competition site. BMD, BMC, T-scores, and Z-scores of the lumber spine (L2-L4) were assessed using a Norland XR36 pencil-beam tabletop dual-energy X-ray absorptiometry (DXA) system. Detailed information regarding dietary/medical history, exercise/lifestyle habits, and personal/family fracture record were obtained from each participant. Event performance times in the swimming, cycling tour, and marathon components of the event were recorded. Data analysis employed Minitab release 12 statistical software. RESULTS: Visual and quantitative analysis of total lumbar spine and individual levels (L2-L4) indicated a relatively high prevalence of degenerative spinal disease. Mean BMC values for L2-L4 were 0.333, 0.329, and 0.41 g, respectively. Average BMD values for L2-L4 were 0.017, 0.016, and 0.161 g/cm2, respectively. Mean Tscores for L2-L4 were 0.57, 0.39, and 0.95, respectively. Average Z-scores for L2-L4 were 0.031, 0.145, and 0.319, respectively. CONCLUSION: Among high endurance male triathletes over 45 years of age, DXA results suggest a relatively high prevalence of degenerative spinal disease in the lower back. This implies that intense physical activity among older males either predisposes to the latter, or that its presence does not preclude world-class triathlon participation. According to World Health Organization (WHO) criteria, the prevalence of low bone mass and osteoporosis in this population is extremely low; as a group, vertebral Tand Z-scores fall within the normal range even at levels unaffected by signicant degenerative changes. These results are compatible with the intense physical training regimens of these older men, and emphasize the importance of exercise in the prevention of age-related bone loss throughout life.

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In conclusion, more attention should be paid by the experts on osteoporosis to the education of primary care physicians about the management of the disease.

186 (178). WORKSHOPS IN OSTEOPOROSIS IN PRIMARY CARE: EXPERIENCE OF ONE YEAR J. A. Roman, C. Ferna ndez, A. Fuertes, J. Milla n, L. Abad, Hospital Universitario Dr. Peset, Valencia, Spain PURPOSE: In order to improve the knowledge, management and control of osteoporosis of Primary Care (PC) physicians we organize four workshops in our area and evaluate the results obtained after the workshops. METHODS: All of workshops have a rst part of theory and a second practice section. 20 PC physicians participated in the workshops, each of them selected three consecutive postmenopausal females (n=60) for the evaluation. Risk factors, daily dietary calcium intake, previous fractures, bone resorption markers (Urinary Calcium/Creatinine, Ca/Cr and Deoxypyridinoline/Creatinine, D-pyr/Cr, after 12 hours fasting) and bone mineral density (BMD) measurements were analyzed in all women. RESULTS: Risk factors: only 8 women performed daily exercise, 28% have an estimated calcium daily dietary intake 5500 mg/day. 90% of patients had non-specic pain in any part of the squeleton. 24% had a previous fracture, from which 33% had more than one fracture site (Colles and vertebral). 36% (n=22) had hypercalciuria and 61.6% had high turnover, dened as at least one of the bone resorption markers raised (Ca/Kr in 40% and D-pyr/Cr in 44%). BMD results (n=54): normal in 32, osteopenia in 16 (30%) and osteoporosis in 6 (11%). In patients with hip fracture the mean t-score was 2.7 (mean age: 80 years). DISCUSION: We have found osteoporosis in 11% of postmenopausal females attending a PC clinic, most of them with non-specic esqueletal pain. Previous fractures, low calcium diet, hypercalciuria and high bone turnover were the factors more frequently founded between these women.

185 (177). AWARENESS, ATTITUDES AND OPINIONS ON OSTEOPOROSIS OF PRIMARY CARE PHYSICIANS WORKING IN THE METROPOLITAN AREA OF ROME E. Romagnoli1, S. Minisola2, 1Ospedale San Giovanni Battista; 2 Dipartimento di Scienze Cliniche, Universita degli Studi La Sapienza-, Rome, Italy This study was aimed to determine the awareness and opinions of family physicians regarding prevention, diagnosis and treatment of osteoporosis. One hundred out of 115 family physicians were randomly selected among the 2562 primary care physicians working in the large metropolitan area of Rome. The doctors were asked to complete a survey including ten closed-ended questions. As far as the level of awareness is concerned, approximately one-third of the physicians (38%) do not know that the WHO has established precise criteria for diagnosis of osteoporosis in caucasian females; moreover, thirty-seven percent of doctors believes that the disease, in the elderly, is not relevant in respect to other chronic diseases. Thirty-six percent of physicians make the diagnosis of osteoporosis exclusively on the basis of BMD results. Seventeen percent of doctors never use BMD for diagnosing the disease. Forty-seven percent rely on BMD as well as on X-ray of the spine and/or reported symptoms. Once the presence of osteoporosis is suspected, fty-three percent of doctors require the measurement of biochemical markers of bone turnover. As far as the choice of treatment is concerned, 44% of the doctors start therapy autonomously, according to the suggestions of editorials in journals (38%) and/or pharmaceutical advertising (18%). Answers related to the follow-up of treatment have been briey grouped for the sake of clarity as correct or inadequate, according to widely accepted criteria. Fifty-six percent of physicians appropriately rely on BMD measurement, with or without other parameters, after at least twelve months of treatment; the remaining 44% either request BMD before 12 months of treatment or evaluate the response to the treatment by means of unaccepted criteria. Regarding the issue of biochemical markers of bone turnover 35% of doctors assess them within six months after starting therapy.

187 (179. PELVIC INSUFFICIENCY FRACTURES IN OSTEOPOROSIS S. Samdani, B. Lachmann, W. Nagler, New York Presbyterian Hospital, New York, NY, USA Pelvic insufciency fractures (PIF) are a commonly overlooked cause of hip and low back pain that can occur without trauma. PIF are a type of stress fracture that can occur with repetitive stress to already weakened or abnormal bone. Insufciency fractures often occur in bone with decreased mineralization and elastic resistance, with postmenopausal osteoporosis as the main risk factor. It is estimated that 40% of Caucasian women in the United States will sustain at least one osteoporotic fracture after the ago of 50. The lifetime risk of fracture among women aged 50 and older may be as high as 70% if all skeletal sites are included. Other predisposing factors for pelvic inaufciency fractures include prolonged corticosteroid use, rheumatoid arthricis, renal disease, and local irradiation. The clinical presentation is often variable. Patients often complain of severe low back, groin, or hip pain accompanied by difculty or inability to ambulate. Diagnosis can be challenging as initial imaging studies are often negative in the rst two to four weeks following onset of symptoms. Sensitivity of early lms may be as low as 15%. Technitium99 bone scintigraphy typically reveals increased radiotracer uptake at the site of the fracture and is nonspecic and may be diagnostic within 24 hours of symptom onset. Increased uptake of bone scans can occur with almost any increase in osteoblastic activity often seen with trauma from a fall, infections, neoplasms, and bone infarcts. Computed tomography conrms the diagnosis and can be helpful to rule cut a malignancy. Magnetic resonance imaging is considered to be the most sensitive and specic test.

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Diagnosis of pelvic insufciency fractures is often based on high clinical suspicion, a thorough physical exam, and the appropriate conrmatory imaging study. We conduoted a retrospective chart review of 90 patients with pelvic insufciency fractures. The review assessed initial presentation, past medical history, ndings on physical exam, and diagnostic imaging studies obtained. We also reviewed overall morbidity and functional status of patients after such fractures and will discuss clinical ndings, radiological ndings, and functional outcome at discharge. Through our extensive review, we documented that the majority of patients with pelvic insufciency fractures can be treated conservatively without surgical intervention and can safely weight bear as tolerated with use of an assistive device with good functional outcome.

Conclusion: Average calcium intake is quite high in sub-urban Sri Lankan men and women. The intake declines at the old age. The main source of calcium is dried sh and sprats.

190 (182). THE EFFECT OF DIETARY CALCIUM ON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN Y. Suzuki1, S. J. Whiting1, P. D. Chilibeck2, K. S. Davison2, 1 College of Pharmacy and Nutrition, Saskatoon, SK, Canada; 2 College of Kinesiology, University of Saskatchewan, Saskatoon, SK, Canada The objective of this study was to examine the effect of usual dietary intake of calcium (Ca), vitamin D (vD), and retinol on BMD at various bone sites in postmenopausal women. Dietary intake was determined by using food frequency and diet history questionnaires. Subjects were 58 women, mean (SD) age was 57(7.2)y, 7.9(7.1)y since menopause (YSM). Subjects' mean total intake of Ca was 1163 mg, of vD was 9 mg, and of retinol was 0.71 mg. There was a negative correlation between age (or YSM) and BMD, as well as between weight (or BMI) and BMD. There was a positive correlation between total Ca intake and BMD at hip (r = 0.294, P<0.05), femoral neck (r = 0.364, P<0.01), trochanter (r = 0.270, P<0.05), and wards (r = 0.306, P<0.05). There was a positive correlation between total vD and BMD (r = 0.287, P<0.05) and between total retinol and BMD (r = 0.229, P<0.1) at trochanter. Ca, vD, and retinol intakes were correlated with each other. Stepwise multiple linear regression showed a major effect of age or YSM and weight or BMI at most bone sites except total body. It also showed the positive effect of total Ca on BMD at cortical bone sites such as hip (5.9 %), femoral neck (9.8 %), wards (6.8 %), and total body (5.5 %). There was a positive effect of total retinol on the BMD at trochanter (6.8 %). There was no dietary effect on BMD at the spine, which is mostly trabecular. Our study showed the positive effect of total dietary Ca on BMD of postmenopausal women and supported the hypothesis that the effect of Ca is mostly on cortical bone rather than on trabecular bone.

188 (180). INFLUENCE OF THE MENTAL STATE OF OLD PEOPLE ON OSTEOPOROTIC FEMORAL FRACTURES O. V. Semenova, A. V. Urivaev, O. B. Ershova, V. G. Evstratov, Yaroslavl Center of Osteoporosis, Yaroslavl Medical Institute, Yaroslavl, Russia A number of mental states parameters of 116 patients suffering from fractures (average age 69,419, 07) and 84 (average age 71, 5710, 56) people without fractures have been examined. The study was carried out for the purpose fo evaluation of mental state of old people as one of the factors in osteoporotic femoral fractures. To achieve this the psycho diagnostic (Mini-MentalStatus Test, MMST) was utilized. This test is a screening method for founding cognitive deviations of people of advanced age). The test contained 30 questions. The highest number of points being 30. The average rating for patients suffering from fractures was 25, 914, 67 and for the people without fractures 27, 832, 36. The difference proved to be statistically correct, p = 0.02. Low rating as per the results of the MMST was discovered with patients who had deviations in realization of movement process, which in its turn causes falls and fractures. On the whole the results of the test prove importance of optimal state of old people the nervous activity in prevention of falls.

189 (181). SRI JAYAWARDENEPURA COMMUNITY SURVEY OF OSTEOPOROSIS; DIETARY CALCIUM INTAKE S. H. Siribaddana, U. Hewage, D. J.S. Fernando, 1Department of Medicine, Sri Jayawardenepura University, Nugegoda, Sri Lanka Introduction: Risk of osteoporosis in any given person is dependent on peak bone mass. Although genetic factors contribute mainly to the peak bone mass exercise and calcium intake are modiable contributing factors. Methods: 988 ambulatory persons, aged 21 to 80 years were randomly selected from electoral list in a suburban area. Calcium intake was calculated from semi-quantitative food frequency questionnaire. Results:
Males Age Number Mean/mg SD/mg Main contributor (mg) Females Age Number Mean/mg SD/mg Main contributor (mg) 2130 75 1382 600 Sprats (383) 2130 143 1458 578 Sprats (387) 3140 58 1359 638 Sprats (391) 3140 144 1481 534 Sprats (407) 4150 54 1635 543 Sprats (425) 4150 159 1452 469 Sprats (448) 5160 44 1336 546 Sprats (358) 5160 166 1456 536 Sprats (368) 6170 33 1355 524 Sprats (329) 6170 70 1372 492 Sprats (340) 7180 13 1214 384 K'murunga (312) 7180 24 1301 463 Sprats (351)

191 (183). DIRECT MEDICAL COSTS OF OSTEOPOROTIC PROXIMAL FEMUR FRACTURES M. Tamulaitiene, V. Alekna, I. Diliunaite-Breiviene, National Osteoporosis Center, Institute of Experimental and Clinical Medicine, Vilnius, Lithuania The aim of this study was to determine the direct medical costs of the osteoporotic proximal femur fracture in Lithuanian population. A 1-year retrospective study was carried out applying it to all the patients over 50 years old with osteoporotic hip fractures treated in traumatological-orthopaedical departments in 3 Vilnius hospitals in 1998. The direct medical cost of hip fracture includes acute hospital care and subsequent restore treatment, i.e. rehabilitation expenses. Cost of acute hospital care mainly depends on the method of surgical treatment. The total direct medical costs for hip fracture were calculated, where acute hospital care costs represented the larger proportion. On the contrary, evaluation of the mean cost per fracture showed that larger proportion was formed by rehabilitation expenses. The most expensive method of proximal hip fracture treatment is the prosthetic replacement followed by extended rehabilitation program. The largest proportion of the direct medical costs was formed by costs of treating hip fracture by internal xation with or without rehabilitation.

192 (184). SCREENING FOR LOW BONE MASS IN CROHN'S DISEASE: INCIDENCE OF OSTEOPENIA AND OSTEOPOROSIS IN 500 UNSELECTED CASES R. Tanger, B. Weidmann, H. Malchow, J. D. Ringe, Leverkusen, Germany Patients with Crohn's disease have an increased risk of osteoporosis and associated fractures compared to a healthy population. The prevalence of different clinical stages and the correlation with different contributing risk factors, however, has not been studied in a large cohort of affected patients including those with a mild course of the disease. Methods: Bone mineral density (BMD) was measured by DEXAtechnique at the lumbar spine and femoral neck in 500 unselected patients with established Crohn's Disease. The mean age of the patients was 35.1 years (range: 10.1 80.3). The average duration of disease was 8.2 years (range: 0 43.8). Lateral x-rays of the spine were performed in cases with back pain or signicantly reduced BMD at the lumbar spine (T-score 52.5 SD). A vertebral fracture was diagnosed if loss of anterior, median or posterior height of 20 % or more was observed. Accompanying risk factors for bone loss (e.g. dosage and duration of corticoids, disease activity, vitamin D levels, previous operation, smoking habits) were recorded. Results: Normal values of BMD (T-score above 1.0) were found at the lumbar spine in 275 cases (= 55.0%) and at the femoral neck in 252 patients (= 50.4%). Osteopenia or preclinical osteoporosis (T-score 1.0 to 2.5) was documented in 157 (= 31.4%), and 196 patients (= 39.2%), and established osteoporosis (T-score below 2.5) in 68 (= 13.6%) and 52 patients (= 10.4%) at the two measuring sites, respectively. 30 patients (6.0%) had severe osteoporosis with one or more vertebral fractures (range: 14 63 years). There was a signicant correlation between BMD and duration of disease, (n = 500), cumulative dose of corticoids (n = 104) and tobacco consumption (n = 106). Conclusion: We conclude that in unselected patients with Crohn's disease preclinical and established osteoporosis can be expected at an average rate of 41% and 18%, respectively. Screening for osteoporosis with osteodensitometry and preventive measures are mandatory. Patients with long-term disease, a high cumulative dose of corticoids, and smoking are at particularly high risk. Further studies on contributing risk factors and longitudinal measurements of BMD with and without intervention are of high interest.

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cycling tour, and marathon components of the event were also documented. Data analysis was performed using Minitab version 12 statistical software. RESULTS: Total body BMC ranged from 16753528 (mean 2631) grams. Total body BMD ranged from 0.771.218 (mean 1.024) g/cm2. Mean values for lean body mass, fat body mass, and percentage body fat were 48.8 kg, 11.2 kg, and 12.9%, respectively. Total body BMC (p50.0001, R-Sq = 48.9%) and BMD (p50.0001, R-Sq = 27.2%) correlated signicantly with total soft tissue mass. However, total body BMC was not statistically related to lean body mass (p = 0.16), fat body mass (p = 0.71), or percentage body fat (p = 0.45). Similarly, total body BMD was not statistically related to lean body mass (p = 0.082), fat body mass (p = 0.75), or percentage body fat (p = 0.89). Of the two soft tissue components, lean body mass appeared to be more strongly related to BMC and BMD than did fat body mass. CONCLUSIONS: In contrast to previous studies relating body composition to physical activity levels among amateur women athletes, the elite female triathletes in this investigation generally did not suffer from extremely low bone mass or osteoporosis. This difference may be explained by maintenance of percentage body fat at a reasonably high level (mean = 12.9% versus generally accepted ideal range of 1530% for women) despite intense physical training, with the skeletal risk:benet ratio of the latter thus being acceptable.

194 (186). EVALUATION OF BONE MASS AND OSTEOPOROSIS SUSCEPTIBILITY IN THE LUMBAR SPINE OF ELITE FEMALE TRIATHLETES D. J. Theodorou, S. J. Theodorou, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate the effects of endurance athletic training on bone mineral density (BMD) and content (BMC) in the spine of high performance female athletes, and to develop potential recommendations for levels of physical exercise compatible with optimal skeletal health in women. METHODS: Frontal spine (L2-L4), proximal femoral, and total body BMC and BMD measurements were performed in 139 randomly recruited female participants in the 1999 Ironman World Championship Triathlon at Kona, Hawaii athletes, using a Norland XR36 dual-energy X-ray absorptiometry (DXA) system. Age ranged from 1669 (mean 39) years. Body weight ranged from 93176 (mean 125) pounds. Height ranged from 5171 (mean 64) inches. Questionnaire data elicited from each subject included dietary/medical information, exercise/lifestyle habits, personal/ family fracture history, and menstrual function. Performance times in the swim, cycling tour, and marathon components of the event were recorded. Data analysis was performed using Minitab version 12 statistical software. RESULTS: Average BMD values for the L2, L3, L4 and L2-L4 regions were 1.064, 1.082, 1.022 and 1.108 g/cm2, respectively. Corresponding mean T-scores were 0.46, 0.09, 0.63, and 70.51, while mean Z-scores were 0.085, 0.125, 0.385, 0.13, respectively. Although in individual athletes or vertebrae increased bone loss could be identied, BMD values in the population as a whole were within normal limits according to World Health Organization (WHO) criteria. Visual inspection of DXA scan images and statistical analysis of BMD values by level documented a high prevalence of degenerative disease in the lower lumbar spine among these female triathletes. CONCLUSIONS: In contrast to prior investigations of physical activity versus bone mass among amateur female athletes, worldclass triathlete women generally maintain acceptable levels of bone mass in the spine. This may be secondary to relative preservation of body fat (mean 12.9% versus generally accepted ideal range of 1530% for women) and hence sufcient estrogen levels. Degenerative spine disease in elite female athletes may be

193 (185). TOTAL BODY CALCIUM AND SOFT TISSUE COMPOSITION IN ELITE FEMALE TRIATHLETES V. A. Tatsis, E. M. Kwong, G. F. Rocha, M. L. Look, A. M. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate total body calcium, lean body mass, and percentage body fat in elite female athletes, with reference to interrelationships among the various components of body composition. METHODS: 139 high performance female endurance athletes competing in the 1999 Ironman World Championship Triathlon held at Kona, Hawaii were randomly recruited from the qualifying eld. Age ranged from 1669 (mean 39) years. Height ranged from 5171 (mean 64) inches. Weight ranged from 93176 (mean 125) pounds. Maximum lifetime weight ranged from 101198 (mean 137) pounds. Total body bone mineral content (BMC) and density (BMD), lean body mass, fat body mass, and percentage body fat were measured using a Norland XR36 pencil-beam tabletop dual-energy X-ray absorptiometry system. Questionnaire data elicited from each subject included dietary/medical history, exercise/lifestyle habits, personal/family fracture background, and menstrual function record. Performance times in the swim,

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related to intense physical training regimens, and/or does not preclude high performance triathlon participation.

falls is a less discriminating criterion when screening for risk of hip fracture than bone density.

195 (187). VERTEBRAL OSTEOPOROTIC DEFORMITY: ASSOCIATION WITH RISK FACTORS N. V. Toroptsova, L. I. Benevolenskaya, Institute of Rheumatology RAMS, Moscow, Russia Aim: To study the prevalence of vertebral deformities in women with osteopenia aged 55 and elder and establish risk factors for them. Methods: 697 women with osteopenia (T-score less than 2 SD in one vertebrae measured by DEXA, Hologic 4500A) were examined by X-ray and deformities were evaluated by morphometric analysis of T4-L5 on the lateral images. Also, we selected a group of age matched women (N=110) with osteopenia in L1-L4 (without vertebral deformities) and performed a case-control study to evaluate the inuence of some factors on development of vertebral fracture. Results: Spine osteoporotic fractures were revealed in 107 patients (15.3%). The deformity of 1 vertebrae occurred in 44.8% of pts, 2 in 26.7% pts, 3-in 20.4% pts, 4 and > in 8.6% pts. Mean value of BMD was 0.7360.0095 (g/cm2) for L1-L4 in women with osteoporotic deformities. In control group mean value of BMD was 0.7260.0077 (g/cm2). We analysed some individual factors, including medical and family history, and revealed an association between osteoporotic spine deformities and body mass index (BMI): patients with higher BMI signicantly more often had osteoporotic vertebral fractures (p<0.05). No other factors had associations with deformities of vertebrae in this case-control study. Conclusion: Our data presents the prevalence of osteoporotic deformities in women with osteopenia. The analysis of some factors revealed association between BMI and osteoporotic fractures.

197 (189). DESCRIPTIVE STUDY OF OSTEOPOROTIC FRACTURES AND HIP FRACTURE RISK EVALUATION OF SUBJECTS WITH PAST MINOR FRACTURES P. A. Vendittoli1, D. Major2, A. Simpson2, S. Jean2, J. P. Brown1, Centre Hospitalier Universitaire De Quebec, Universite Laval; 2 Service de Depistage Provincial PARLAB Ste-Foy, QC, Canada

Osteoporotic fractures, especially hip fractures, represent a major health problem in terms of morbidity, mortality and cost. Since the availability of new treatments for osteoporosis, a better understanding of the disease is needed to dene the indications for treatment. A descriptive study of all osteoporotic fractures was done on a population aged 45 years old and older from 1980 to 1997 (2.5 million individuals, 1997). During the follow-up period there was a total of 220, 120 fractures (hip, wrist, proximal humerus and ankle). The incidence of fracture was stable over time. The wrist fracture was the most frequent (42.2%) followed by the hip fracture (32.5%). Although the proportion of fracture sites were similar for both sexes, 75% of the fractures occurred in females. The peak incidence of wrist fracture is between 4565 years old. The hip fracture follows an exponential curve of incidence after 65 years of age. The mortality 1 year after a hip fracture is increased by 1427% for men and 913% for women after 60 years of age. Men and women aged 45 years old and older have a risk for hip fracture after a minor fracture of 2.317.3 time the risk of people without previous minor fracture. Because actual medical osteoporosis treatment is effective and minor fractures represent a signicant risk for future hip fracture, all these patients should be evaluated for osteoporosis and receive the appropriate treatment.

196 (188). SCREENING FOR RISK OF HIP FRACTURE IN THE ELDERLY N. M. Van Schoor, L. M. Bouter, P. Lips, EMGO-Institute, Vrije Universiteit, Amsterdam, The Netherlands A randomized clinical trial is performed to examine whether external hip protectors can reduce the number of hip fractures in Dutch elderly persons at high risk of fracturing a hip. Elderly persons from nursing homes, homes and apartment houses for the elderly are included when having a: (1) broadband ultrasound attenuation (BUA) 440 or (2) 40 5BUA 460 and at least 2 risk factors for falls or (3) 60 5BUA 470 and at least 3 risk factors for falls. Risk factors for falls: one or more falls in the past, dizziness, stroke, impaired mobility, low physical activity, urinary incontinence, and cognitive impairment. Recently 248 elderly persons were screened for risk of hip fracture. 40.3% of these persons sustained a fall in the previous half year, 42.7% reported dizziness, 18.1% reported a stroke, 50.4% had low physical activity, 30.7% had impaired mobility, 54.8% reported urinary incontinence and 47.8% had cognitive impairment. 195 of the 248 screened persons had a bone density below 70 dB/MHz; 32 persons with a low bone density were excluded because they had too few risk factors for falls. 53 persons were excluded because their bone density was too high. The mean number of risk factors for falls in the bone density groups with a BUA 440; 40 5BUA 460, 60 5BUA 470 and BUA >70 was respectively 3.9; 3.3; 3.3 and 3.1. It appears that persons in homes for the elderly have a high risk for falls. This study suggests that the number of risk factors for

198 (190). RELATIONSHIP BETWEEN MUSCLE STRENGTH IN FUNCTIONAL MOVEMENTS, ACTIVITIES OF DAILY LIVING AND BONE MINERAL DENSITY IN OSTEOPOROTIC WOMEN L. A. Verbruggen, A. Lenaerts, W. Duquet, C. Pauwels, T. Mets, 1 University Hospital VUB; 2Free University Brussels, Brussels, Belgium Potential relationships were investigated in osteoporotic women between muscle strength in functional leg extension movements and handgrip, ability to perform activities of daily living (ADL), and bone mineral density (BMD) by lumbar QCT or calcaneal ultrasound. The following evaluations were made in 103 outpatients (age 60 to 93 years): power and force of leg extension at 2 speeds using a linear isokinetic dynamometer (Aristokin1 Lode, Netherlands), handgrip strength using a Martin vigorimeter, lumbar BMD by QCT, broadband ultrasound attenuation (BUA) of the calcaneus, and the Lawton-Instrumental-ADL (IADL) scale. The IADL scale weakly but signicantly correlated with extensor strength (r 0.270.29, p<0.001) and with QCT (r 0.28, p<0.001). Furthermore, using age as a controlling variable, leg extension strength correlated with lumbar BMD (r 0.390.43, p<0.001) and to a lesser extent with handgrip strength (r 0.24 0.31, p<0.01). The latter also weakly correlated with BUA of the calcaneus (r 0.28, p<0.005). The use of a linear isokinetic dynamometer allows to measure force and power in functional movements involving more than one articulation, such as leg extension: its relevance was conrmed by signicant correlations with handgrip strength, ability to perform ADL, and BMD in this group of osteoporotic women.

199 (191). AVERAGE TOTAL LIFETIME ALCOHOL INTAKE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN J. Wactawski-Wende, M. Trevisan, R. Brennan, S. G. Grossi, R. J. Genco, C. Klemenz, University at Buffalo, Buffalo, NY, USA This study assesses the relationship between average total lifetime alcohol intake and bone mineral density (BMD) in 608 Caucasian postmenopausal women from Buffalo, NY participating in a larger study of the relationship between BMD and periodontal disease, an ancillary study of the NIH Women's Health Initiative. After consent, all women completed questionnaires on health history and risk exposure, and had a physical exam. BMD of the hip (total femur region) was assessed by dual energy X-ray absorptiometry (DXA; Hologic QDR4500). BMD was dichotomized for logistic regression analyses (lowest tertile vs. highest 2 tertiles). Alcohol intake (mean daily ounces total alcohol) was the primary independent variable of interest. Other factors assessed in the analysis were: age at interview, cigarette smoking (ever), education (4high school, college, graduate school), body mass index (BMI), diabetes (ever), thyroid disease (ever), physical activity (daily hours standing), fracture 5 age 40 (ever), and years of estrogen deciency (years since menopause-years of estrogen replacement therapy). Alcohol intake was found to be signicantly associated with higher BMD (OR=1.84, p = .0486). Other factors found to be related independently with higher BMD included: no history of adult fracture (OR=2.23, p = .0003), higher BMI (OR=1.18, p = .0000), younger age (OR=1.08, p = .0001), and fewer years without estrogen (OR=1.03, p = .0086). This study supports the hypothesis that moderate lifetime alcohol intake is associated with higher BMD of the total femur, even after controlling for factors known or suspected to be associated with bone mineral density.

Thursday, June 15, 2000

201 (193). OSTEOPOROSIS: PREVALENCE IN TAIWANESE WOMEN T. S. Yang, C. R. Chen, Department of Ob/Gyn, Veterans General Hospital Taipei and National Yang-Ming University, Taipei, Taiwan Objectives: this paper aims to clarify the bone mass values in the Taiwanese female population and to further analyze the close relationship among the bone mass values // body height // body weight and BMI (body mass index). We also assess the number and proportion of Taiwanese women considered to have osteoporosis according to the WHO diagnostic guideline. Method: A total of 4689 female subjects were recruited. All bone mass measurements were performed by means of dual energy X-ray densitometry: DXA (Lunar, DPX-L,USA) at two sites: lumbar vertebrae L2-L4 and femoral neck. These values are expressed with reference to the mean bone mineral density values, height, weight and BMI of the group aged 3039 years. Results: the study revealed respectively that there is no clear relationship between the bone mineral density and the body height // body weight nor BMI. The diagnostic value for osteoporosis is set at 0.827 g/cm2 for lumbar vertebrae and 0.605 g/cm2 for femoral neck. According to the dening values of lumbar vertebrae, the prevalence of osteoporosis in the different age groups is detailed as follow: 4049 years, 8.24%; 5059 years, 8.62%; 6069 years, 14.14%; 7079 years, 14.25%; >80 years, 16.07%. Those diagnosed to have osteoporosis by femoral neck is detailed as follow: 4049 years, 5.24%; 5059 years, 5.27%; 60 69 years, 11.16%; 7079 years, 17.30%; >80 years, 24%. The whole proportion for osteoporosis included 10.08% for lumbar vertebrae and 7.45% for femoral neck. Conclusion: there is no close relationship among the bone mineral density // body height // body weight nor BMI in Taiwanese female population, which coincides with most of the recent reports' results. The prevalence of osteoporosis is also lower in comparing with the females of western societies, and this may be related to the alimentary habits, life style, cultural background and ethnicity. Nevertheless, the acceptance rate of HRT in the Taiwanese female population is also lower, which is calculated to be no more than 5%. The maintenance of traditional culture and habits and the HRT policy propagation will both be the tasks to be accomplished in the future.

200 (192). THE RELATIONSHIP OF BONE MINERAL DENSITY TO ORAL BONE LOSS IN POSTMENOPAUSAL WOMEN J. Wactawski-Wende, S. G. Grossi, E. Hausmann, R. Dunford, R. J. Genco, C. Klemenz, M. Trevisan, University at Buffalo, Buffalo, NY, USA This study assesses the relationship between bone mineral density (BMD) and oral bone loss in 608 Caucasian postmenopausal women from Buffalo, NY participating in a study of BMD and periodontal disease, an ancillary study of the NIH Women's Health Initiative. After consent, women completed questionnaires on health history, risk exposures and had a physical exam. Oral bone loss was dened as mean loss of alveolar crestal height (ACH) dichotomized for logistic regression analyses (worst ACH tertile vs. best tertiles). BMD of the total femur (lowest vs. highest 2 tertiles) was the primary independent variable of interest and was assessed by dual energy X-ray absorptiometry (DXA; Hologic QDR4500). Other factors assessed included: age at visit, cigarette smoking (ever), education (4high school, college, graduate school), body mass index (BMI), diabetes (ever) and years estrogen deciency (years since menopause years on estrogen). Lower ACH was signicantly associated with lower BMD (OR=1.81, p = .0134). Other factors independently associated with lower ACH included: older age (OR=1.11, p = .0000) and ever smoking cigarettes (OR=1.84, p = .0033). This study supports the hypothesis that lower BMD is associated with loss of oral bone even after controlling for factors known or suspected to be associated with either ACH or BMD. This study is one of the largest to date and supports previous ndings by us and others that lower BMD is related to oral bone loss, that may lead to tooth loss. Additional research is needed to better understand this relationship.

202 (194). A SEVEN-YEAR FOLLOW UP STUDY OF BONE LOSS IN A RURAL JAPANESE COMMUNITY: THE MIYAMA STUDY N. Yoshimura, K. Sakata, T. Hashimoto, Wakayama Medical College, Wakayama, Japan Purpose: To assess the rate of bone loss and characterise its determinants among general inhabitants of Miyama village, a rural Japanese community. Method: A cohort of 1543 residents consisting of all inhabitants aged 4079 was established in 1989, using the resident registration of December 1988. A total of 400 individuals, comprising 200 males and 200 females, were then recruited randomly from following age strata; 4049, 5059, 6069, 7079 (giving a total of 50 subjects in each age-sex group.) They were performed the interviewer-administered questionnaire survey including information on past medical history, physical activity, calcium intake, a menstrual history and so on. The follow up study was performed three and seven years later. Subjects participating in the baseline study were recontacted. Dual energy X-ray absorptiometry (DXA: Lunar DPX) was used for the measurement of bone mineral density (BMD) in both the initial and follow-up studies. Results: A total of 148 men and 170 women participated the follow up study (79.5%). The annual rates of change of lumbar spine BMD between 1990 and 1993 in men in their 40's, 50's, 60's and 70's were 0.20%, 0.06%, 0.34% and 0.31% per year respectively. Rates in women were 0.43%, 1.45%, 0.72% and 0.69%. Annual rates of change in BMD from 1993 to 1997 among

Thursday, June 15, 2000

men in their 40's, 50's, 60's and 70's were 0.16%, 0.81%, 0.44% and 0.17% respectively. Those among women were 1.03%, 70.72%, 0.31% and 0.26%. The rates of change of lumbar spine BMD was also assessed by classied by menstrual status. Menstrual status at baseline was related signicantly to change in bone density. Conclusion: The fastest bone loss was observed on women in their 50's. Menstrual function were suggested to be important determinant of bone loss.

Conclusions: An increased fracture risk can be found up to 10 years prior to surgery in primary hyperparathyroidism. The fracture risk is normalised after surgery.



C. E. D. H De Laet1, M. van der Klift1, A. Hofman2, H. A. P. Pols,2,3, Institute for Medical Technology Assessment; 2Dept of Epidemiology and Biostatistics; 3Dept of Internal Medicine, The Erasmus University Medical School, Rotterdam, The Netherlands

203 (195). EPIDEMIOLOGICAL CHARACTERISTICS OF HIP AND WRIST FRACTURES IN METROPOLITAN AND RURAL HOSPITALS OF CAMEROON M. R. D. Zebaze, E. T. Magny, C. Djeumen, L. M. Ebah, G. T. Mbonda, S. Eko, S. Mba, Medicine, University of Yaounde, Yaounde, Cameroon Purpose: to assess the occurrence of hip and wrist fractures in Cameroon, Africa. Osteoporosis and related fractures are reported rare in Africa. To assess this concept, a two years retrospective study in two rural and two urban hospitals were taken. All patient admitted for fractures, age 35 and above were recruited. We found 70 (13.6% of all fractures) hip and wrist fractures in urban hospitals and 6 (15%) in rural's both being the third cause of admissions for fractures. They affect mostly postmenopausal women and were due to minimal low-energy trauma like falling 61.4% of them. 8.3% of all fractures were hip and wrist fractures due to fall, a gure of which is high being the third cause of admission for fracture. Using the 1997 report on the population in Cameroon, the minimal age-specic incidence rate per 100 000 for the 35 years and above based on the discharged diagnosis alone in the two urban hospitals were 7; which is not negligible. Our study shows that the problem of involutional bone disorders is important in Africa. This challenges the concept of rarity of osteoporosis in Africa and may change the view of this disease in this part of the world.

The American National Osteoporosis Foundation (NOF) proposed a fracture risk assessment (all fractures) for women based on data from the Study of Osteoporotic Fractures (SOF) using 5 risk indicators. However, this prediction algorithm was not validated elsewhere. In this study we tested the selected risk indicators in the female population from the Rotterdam Study. We assessed the performance of the proposed risk indicators for (low body weight, current smoking status, fracture history and parental history of fracture) with and without bone mineral density (BMD) measurement at their proposed thresholds, in the female population of the Rotterdam Study. Incident hip fractures and other peripheral fractures were reported and veried during follow-up. At baseline, the risk factors proposed by the NOF including BMD were measured. Prior fracture, however, was only assessed for the 5 years preceding baseline. All relative risks (RR) were corrected for age, with and without correction for BMD. Valid follow-up of fractures was obtained for 4268 women, and for 3078 of those we also had valid baseline BMD data. Average follow-up was 3.9 years for all non-vertebral fractures (338 fractures) and over 6 years or hip fractures (166 fractures). From the 5 risk indicators selected for the NOF guidelines, only prior fracture and BMD carried a similar and signicant relative risk for the risk of any fracture. The RR for all non-vertebral fractures for BMD was 1.5 (2.2 for hip fractures). For all non-vertebral fractures the RR for prior fracture was 1.4 corrected for age and 1.3 corrected for both age and BMD. Both relative risks were signicant but lower than in the NOF guidelines. The relative risks for the other risk indicators, however, were lower than in the NOF report and not signicantly different from 1. Risk indicators derived from only one study overestimate predictive power. Validation in other populations is needed before a risk indicator or a risk score can be used with condence.

Plenary Session 4: Fracture Risk (Thursday, June 15, 15001700)

204. FRACTURE RISK BEFORE AND AFTER SURGERY FOR PRIMARY HYPERPARATHYROIDISM P. Vestergaard, C. L. Mollerup, V. G. Frokjaer, P. Christiansen, M. Blichert-Toft, L. Mosekilde, 1Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus, Denmark Aim: To study fracture risk before and after surgery in patients with primary hyperparathyroidism. Design: Case-control study with historical follow-up. Material and methods: 674 patients primary hyperparathyroidism (median age 61, range 1389 years, 74% women, 90% adenomas, 25% with previous kidney stones at the time of surgery) with operated between January 1 1979 and December 31 1997 and 2021 age and gender matched normal controls. The occurrence of fractures in the patients was compared to that of the controls. Results: There was an increased relative risk of fractures before (RR=1.8, 95% CI: 1.32.3) but not after surgery (RR=1.0, 95% CI: 0.81.3) among the patients. The fracture risk was increased for fractures of the vertebrae, the distal part of the lower leg/ankles, and the non-distal part of the forearm. The increase in fracture risk began approximately 10 years before surgery followed by a lower but still signicant level within the last ve years immediately prior to surgery. 206. BMD CHANGES AFTER 1 YEAR PREDICT BMD CHANGES AFTER 4 YEARS M. McClung, P. D. Ross, R. D. Wasnich, C. Christiansen, D. Hosking, D. Thompson, M. Daley, J. Yates, for the EPIC Research Group, 1Oregon Osteoporosis Center, Portland, OR, USA; 2Hawaii Osteoporosis Center, Honolulu, HI, USA; 3Center for Clinical and Basic Research, Ballerup, DK; 4City Hospital, Nottingham, UK; 5 Merck & Co., Inc., Rahway, NJ, USA Many women experience declines in bone mineral density (BMD) after menopause. However, it is not obvious how short-term changes (1 year) relate to changes over longer periods. We explored this issue using data from 373 women ages 4559 (>6 months postmenopause) in the placebo group of the Early Postmenopausal Interventional Cohort (EPIC) Study, a randomized, controlled trial of alendronate. At baseline, these women had a mean age of 53 years, and were an average of 6 years postmenopause. During 4 years of followup, the mean (SD) change in BMD was 2.9%, 1.9%, 2.8%, 4.6%, and 6.3% at the spine, hip, total body, forearm, and ultradistal wrist, respectively. In general, BMD changes measured over 1 year provided a good indication of the total BMD changes over 4 years. The subset of 122 women who lost 02% (mean = 1.0%) at the spine during year 1 had a total 2.8% decrease in spine BMD at the end of 4 years. Women with extreme changes at year 1 tended

to have subsequent BMD changes that were less extreme; however, the total changes after 4 years remained more extreme than the average for other women. For example, those who lost >4% (n = 41; mean = 5.2%) at the spine during year 1 had an average 5.7% decrease in spine BMD at the end of 4 years (twice the losses compared to women with decreases of 02% at year 1). These data suggest that the BMD change measured at 1 year is a good indicator of long-term changes, on average. However, the ability of short-term changes to predict long-term changes in individuals may not be as good.

Thursday/Friday, June 16, 2000

after baseline. Fracture rates (per 100 person years) were twice as high in the NOF Tx group compared to the non-NOF Tx group. Both devices identied approximately 30% of the women as meeting NOF criteria. The fracture rates and odds ratios for the NOF groups were similar when based on either forearm or heel BMD sites. We conclude that peripheral BMD measurements identify similar proportions of women eligible for treatment of OP and yield comparable estimates of fracture risk based on the NOF treatment guidelines.


Forearm (pDEXA) 30.5 19,718 5.0 2.8 1.8 1.5, 2.2

Heel (SXA) 28.5 29,421 5.3 2.6 2.0 1.8, 2.4

207. HIP FRACTURE IN ASIA WHAT IS THE SCALE OF THE PROBLEM AND HOW SHOULD IT BE PREVENTED? E. M. C. Lau , P. Suriwongpaisal , J. K. Lee , S. Das De , M. R. Festin2, A. Khir2, T. Torralba2, A. Sham1, P. Sambrook2, 1 Department of Community and Family Medicine, The Chinese University of Hong Kong; 2Asian Osteoporosis Study Group Objectives The Asian Osteoporosis Study was conducted in four Asian countries to study the incidence of hip fracture and to identify risk factors for public health strategies for its prevention. Methods National hospital discharge surveys on hip fracture were conducted in 1997, and a casecontrol study was conducted on 451 men and 725 women with hip fracture and an equal number of age-matched community controls. Results Incidence rates (per 100 000 population) of hip fracture (Age-adjusted to 1997 US white population) are as follows:
Men/women Hong Kong 189/453 Singapore 180/417 Malaysia 90/291 Thailand 125/356
1 2 2 2

NOF Tx Group: % Number Fx Rate Non-NOF Tx Gp:Fx Rate Odds Ratio 95% CI for Odds Ratio

209. INCREASED RISK OF NEW VERTEBRAL FRACTURE WITHIN 1 YEAR OF AN INCIDENT VERTEBRAL FRACTURE R. Lindsay1, N. Watts2, Ch. Roux3, J. Brown4, I. Barton5, K. Flowers6, C. Cooper7, 1West Haverstraw, NY, USA; 2Atlanta, GA, USA; 3Paris, France; 4Ste-Foy, Quebec, Canada; 5Staines, UK; 6 Cincinnati, OH, USA; 7Southampton, UK We examined data from 2725 postmenopausal women enrolled in the control groups of 3 large clinical trials of 3 years duration in order to determine the effect of an incident vertebral fracture on the risk of a new fracture within 1 year. Baseline and annual radiographs conrmed prevalent and incident fractures, respectively. Patients received calcium (1000 mg/day), and were supplemented with vitamin D if baseline levels were low. The mean age of patients was 76 years and 57% had baseline (prevalent) vertebral fractures. Of the 381 patients who experienced an incident fracture, overall 19.2% fractured again within 1 year following the rst incident fracture. Fracture incidence within 1 year of an incident fracture increased as a function of the number of prevalent fractures. For example, in patients with 1 prevalent fracture, 11.5% experienced an additional fracture within 1 year of an incident fracture. For patients with 2 or more prevalent fractures, 24.0% had another incident fracture within 1 year of the rst incident fracture. In conclusion, patients taking only calcium and Vitamin D can rapidly fracture again (within 1 year) following an incident fracture. As fractures begin to cluster, risk for additional fracture increases and can lead to decreased quality of life. The immediate risk to these patients suggest a need for a therapy that can provide a rapid reduction in vertebral fracture risk.

Adjusted relative risk (RR) and population attributable risk (PAR%) for hip fracture in Singapore, Malaysia, Thailand and Philippines are as follows:
Men RR Fell twice in last year Cigarette smoking Alcoholism Calcium intake (<498g/day) No regular load-bearing activities A history of stroke 2.9 1.4 1.7 1.6 3.8 3.1 PAR (%) 9.3 19.5 6.1 30.5 55.6 7.4 Women RR PAR (%) 2.6 0.8 2.7 2.0 1.9 5.5 8.9 NA 2.2 40.1 33.9 13.3

Conclusion The incidence rates of hip fracture in Asian countries varied by 50100%. Hip fracture may be preventable by maintaining physical activity, calcium intake, preventing falls and stroke and avoidance of cigarette smoking and alcoholism in developing Asian countries.

208. USE OF THE NOF GUIDELINES WITH PERIPHERAL DENSITOMETRY TO PREDICT FRACTURES P. Miller, E. Siris, K. G. Faulkner, T. Abbott, D. Furman, J. Panish, E. Barrett-Connor, M. Berger, A. Santora, L. Sherwood, Colorado Center for Bone Research, Lakewood, CO, USA NORA is a longitudinal observational study of US women designed to study osteoporosis (OP). Study participants were ambulatory, postmenopausal women with no prior diagnosis of OP or BMD test in the past year. Heel (SXA) or forearm (pDEXA) density data and risk assessment questionnaires were collected from 167,892 Caucasian women at baseline. These women were classied into two groups: those who met the NOF treatment guidelines (NOF Tx group: T-score 52.0 or 51.5 with a risk factor) and those who did not (non-NOF Tx group). For 52,050 of these women, prospective self-reported fracture data were captured by follow-up surveys completed an average 8 months

Plenary Session 5: Secondary Osteoporosis (Friday, June 16, 08001000)

210. ASSOCIATION OF BMI AND DEPRESSION IN AN ELDERLY POPULATION J. A. Robbins1, C. H. Hirsch1, R. Whitmer1, J. Cauley2, T. B. Harris3, 1U. C. Davis, Sacramento, CA; 2U. of Pittsburgh, Pittsburgh, PA; 3National Institute of Aging, Bethesda, MD, USA Background Low bone mineral density (BMD) is a major risk factor for fractures. It has been suggested that low BMD may be associated with depression, but results have been inconsistent. Few studies have been community based or addressed the problem in both men and women or in races other than Caucasian.

Friday, June 16, 2000

Methods Using data from 1,566 Cardiovascular Health Study (CHS) participants, total hip BMD, after adjustment for multiple co-variates, was compared with the Center for Epidemiological Studies 10-item Depression Scale (CES-Dm). Risk factors for osteoporosis were compared in depressed (CES-Dm 510) and non-depressed participants. Potential correlates were entered into a regression model. Results Sixteen percent of participants showed depressive symptomatology. Mean BMD was 40 mg/cm2 lower in those with depression (p<0.001). Higher CES-Dm scores were associated with lower BMD (p<0.5) when adjusted for BMI, age, Kcals of activity, estrogen use, gender, race, smoking and drinking. When stratied by race, this remained true for Caucasians (p<0.01), African-Americans (p<0.05), and Caucasian women (p<0.001). Further stratication yielded the results in the table, listed as parameter estimates, (bS).
Table. Relationship of Depression and BMD mg/cm2. Adjusted for covariates ALL Risk Factor CES-D BMI AGE KCAL ESTRGN # PKYRS ALCOH 3.81*** 13.98*** 4.24*** 0.01* 0.35* 2.27*** Women (903) Men (649)

212. INHALED CORTICOSTEROIDS AND RISK OF FRACTURES T. P. Van Staa, H. Leufkens, C. Cooper, 1Utrecht University, The Netherlands; 2Procter & Gamble Pharmaceuticals, 0; 3Medical Research Council, Southampton, UK The objective of this study was to describe the fracture risks of inhaled corticosteroids. Information was obtained from the General Practice Research Database in the UK which contains medical records of general practitioners. Inhaled corticosteroid users aged 18 years or older were compared to matched control patients and bronchodilators users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users and 170,818 control patients. The relative rates of non-vertebral, hip and vertebral fractures during inhaled corticosteroid treatment compared to control were 1.15 (95% condence interval 1.101.20), 1.22 (1.041.43) and 1.51 (1.221.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (non-vertebral RR = 1.00). With a standardised daily dose of less than 300 mg beclomethasone per day, hip fracture risk was 0.95 (0.671.34) relative to control, rising to 1.06 (0.801.40) at doses of 300 up to 700 mg, and 1.77 (1.312.40) at doses of 700 mg per day or more. These results suggest that users of inhaled corticosteroids have an increased risk of fractures albeit this excess risk may be partly related to the severity of respiratory disease.

Caucasian (716) Af. American Caucasian (536) Af. American 2.92** 13.37*** 5.57*** 0.0008 62.4*** 0.01 2.56** 0.79 11.86*** 6.21** 0.006 62.0 0.21 1.79 2.52 15.61*** 5.11*** 0.006* 0.20 3.05** 3.47 17.85*** 4.18 0.009 1.25 0.73

*p<0.05, **p<0.01, ***p<0.001, #Only used in models with only women

Conclusions: A signicant association was found between BMD and depressive symptoms after adjustment for osteoporosis risk factors. We postulate that there may be an unmeasured third factor, such as an endogenous steroid, which is responsible for both low BMD and depression.

213. THE EFFECTS OF A SINGLE PAMIDRONATE INFUSION PRIOR TO LIVER TRANSPLANTATION ON BONE LOSS: A RANDOMISED CONTROLLED SINGLE-BLIND TRIAL M. Ninkovic, S. A. Love, B. Thom, S. Skingle, J. S. Wright, G. J.M Alexander, J. E. Compston, Department of Medicine, University of Cambridge School of Clinical Medicine and Metabolic Bone Unit, Addenbrooke's Hospital, Cambridge, UK Osteoporosis is a common complication of liver transplantation. Increased rates of bone loss have been demonstrated after transplantation and fractures occur in up to one-third of patients in the rst post-operative year. Since bone loss occurs early after transplantation and is characterised by increased bone turnover, administration of an anti-resorptive agent prior to transplantation provides a rational strategy for prevention of bone loss. We investigated the effects of a single intravenous infusion of pamidronate (60mg) on bone loss during the rst year after liver transplantation in patients with chronic liver disease. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry on an Hologic QDR4500. 99 adult patients (50 male) were randomised to treatment with pamidronate, 60 mg as a single infusion prior to transplantation or no treatment. Pre-operatively, 34% of the patients were osteoporotic and 51% osteopenic as dened by WHO criteria. In the lumbar spine, no signicant bone loss was detected in either group nor were there any signicant differences in BMD at the three time points between the two groups. In the femoral neck, signicant bone loss occurred during the rst three months (3.7 and 3.6% respectively compared with baseline, p<0.001 and <0.005 respectively). Signicant bone loss versus baseline values was also demonstrated at 6 months (p<0.001 and <0.01 respectively) and at 1 year (p<0.005 and <0.04). No signicant differences were seen between the pamidronate and untreated groups at any time point. These results demonstrate that pamidronate, in the regimen used, does not have signicant effects on BMD in the spine or femoral neck following liver transplantation. The absence of bone loss in the spine may reect the use of lower doses of glucocorticoids in recent years.

211. VISUAL IMPAIRMENT AND RISK OF HIP FRACTURE R. Q. Ivers, R. G. Cumming, P. Mitchell, A. Peduto, 1University of Sydney, Sydney, NSW, Australia The aim of this investigation was to examine the associations between visual impairment and risk of hip fracture in a longitudinal study of eye disease in an older population. Baseline data collected for the Blue Mountains Eye Study included a detailed interview and eye examination including refraction, measurement of visual acuity, contrast sensitivity and visual eld in 3654 residents aged 49 years and older. Eye disease was graded from photographs according to well dened protocols. Hip fractures occurring during 5 year follow-up (n=60) were identied by self-report (conrmed by radiology reports) and/or review of medical records at the local hospital. All hip fractures were conrmed radiologically by a specialist radiologist. Several vision variables were associated with risk of hip fracture in the rst two years of follow-up: corrected visual acuity worse than 20/60 in the best eye (adjusted odds ratio (OR) 9.0, 95% condence interval (CI) 1.650.3); any posterior subcapsular cataract in the worst eye (adjusted OR 3.9, 95% CI 1.113.5); ve or points missing in the visual eld (adjusted OR 5.9, 95% CI 1.131.8). At 5 years follow up no vision variable was signicantly associated with increased risk of fracture. Older people at risk of hip fracture should have their eyes tested every 2 years, and have refractive error and cataract treated promptly to reduce their risk of hip fracture.

214. USE OF ORAL CORTICOSTEROIDS INCREASES RISK OF FRACTURE M. Steinbuch1, R. Burge2, A. Thompson3, T. Youket4, 1Mason, OH, USA; 2Mason, OH, USA; 3Kansas City, MO, USA; 4Mason, OH, USA The objective of this study was to assess the risk of fracture in patients exposed to oral corticosteroids (OCS). The data source for the analysis was the MEDSTAT MarketScan1 administrative claims database. The OCS population was dened as members 1864 years of age continuously enrolled for at least one year prior to and one year after date of initial pharmacy claim for an OCS during a 24-month capture period (19951996). The comparison population was selected from all members with a claim for a non-corticosteroid. One comparison member was selected for each OCS member and individually matched on age (2 years), sex, and date of rst claim (3 months). The day supply for each script was dened as the reported day supply or 31 days, whichever was greater, to adjust for variation in dose tapering. Measurements of exposure included: average daily dose (high, low), duration (590, 590 days), and pattern of use (single, intermittent, continuous). Osteoporosis-related fractures were observed up to time of fracture (hip, vertebral, wrist, nonvertebral, any), disenrollment date, or 31 December 1997, whichever occurred rst. A total of 17,957 OCS users and 17,957 comparison members were analyzed. The total person-years of observation for any fracture was 32,986 and 34,206 in the exposed and unexposed groups, respectively. The prednisone-equivalent average daily dose for OCS exposure was 7.5 mg (median=4.8 mg). Based on a Cox model, the adjusted relative risk estimates for fractures associated with OCS exposure were as follows: hip (RR=1.87, 95% condence interval [CI]=1.22.9); vertebral (RR=2.92, 95% CI=2.04.3); and wrist (RR=1.03, 95% CI=0.81.4). The combination of duration of OCS exposure and pattern of use demonstrated a signicant 5-fold and 5.9-fold increased risk of hip and vertebral fracture, respectively, among continuous OCS users with 590 days exposure compared to those unexposed to OCS. These data suggest a rapid deleterious effect on trabecular-rich bone which has not been previously recognized.

Friday, June 16, 2000

Plenary Session 6: Nutrition and Bone Disease

216. A META ANALYSIS OF CALCIUM SUPPLEMENTATION FOR THE PREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS B Shea, C J Rosen, G Guyatt, A Cranney, P Tugwell, D Black, the Osteoporosis Research Advisory Group (ORAG), 1McMaster University; 2University of Ottawa; 3UCSF; 4St. Joseph Hospital, Introduction: Calcium supplementation is considered essential in the prevention of bone loss for most postmenopausal women. Moreover, calcium is added to standard anti-osteoporosis treatments such as the bisphosphonates, estrogens, and calcitonin, to optimize bone gain and prevent fractures. However, observational studies and some controlled trials have produced conicting results leading to controversy concerning the efcacy of calcium supplementation alone in preventing fractures or bone loss in postmenopausal women. ORAG (The Osteoporosis Research Advisory Group) has worked with the Cochrane Collaboration to perform evidence based analyses of randomized controlled trials (RCTs) for several osteoporosis treatments. Methods: We performed a meta-analysis of trials with calcium supplementation alone and excluded studies of calcium and vitamin D (i.e. >400 IU per day) in postmenopausal women. We established apriori hypotheses to explore reasons for large differences in results between studies (heterogeneity), utilized three reviewers to rate methodologic quality and used an evidence based method to perform searches of RCT of calcium in women older than 45 years of age who were postmenopausal, and who were followed for at least one year with bone densitometry. Results: Sixty six (66) published papers addressed the relationship of calcium intake and BMD of which 22 were RCTS. Seven were excluded for various reasons leaving 15 RCTs which fullled pre-set criteria and for which the primary author provided additional data. Five (5) of the RCTs reported fractures as an outcome. Eighteen hundred and six (1806) patients were enrolled in the 15 trials, 953 receiving calcium supplementation. Pooled differences in percentage change in bone density from baseline between treatment (calcium) and control at two years are as follows (95% CI): TBBMD: +2.05% (0.243.86%), LS BMD: +1.66% (0.922.39%), FN-BMD: +1.60% (0.782.4%); radial BMD: +1.91% (0.333.5%). The RR for vertebral fractures was 0.77 (0.541.09) and for non-vertebral fractures was 0.86 (0.43 1.72). Conclusion: We conclude that calcium supplementation alone has a small positive effect on BMD at all skeletal sites but the number of events is too small to meaningfully address the impact on fractures.

215. THYROID HORMONE REPLACEMENT IS NOT RELATED TO INCREASED RISK OF OSTEOPOROSIS Martin Stenstrom, Jan-Oloph Olsson, Dan Mellstro m, Dept of Geriatric Medicine, University of Gothenburg, Gothenburg, Sweden Hyperthyroidism causes increases in bone turnover and reduced bone mass especially in elderly woman. Thyroxine (T4) stimulate directly bone resorption. A major clinical concern has been the issue of exogenous thyroid hormone replacement and osteoporosis, The purpose of this study was to examine bone mass in postmenopausal women with treatment with thyroxine and controls. BMD was measured in the forearm with DXA (Osteometer 200). The study population setting was a simultaneus screening of breastcancer and osteoporosis in 10 364 women aged 49 to 69 years, The population of thyroxine treated women was 6,9 per cent. There were no differences in BMD between treated or not treated women. The inuence of a great variety of variables from a health questionnaire and treatment with thyroxine was tested with a logistic regression model. A history of earlier fractures, treatment with peroral cortisone and antihypertensive drugs, smoking and a higher current BMI was signicantly more frequent in women with treatment with thyroxine compared to controls. Conclusion: Thyroxine treatment was not related to reduced BMD.

217. CAN VITAMIN D SUPPLEMENTATION REDUCE THE RISK OF FRACTURE IN THE ELDERLY? A RANDOMISED CONTROLLED TRIAL H. E. Meyer, J. A. Falch, E. Kvaavik, G. B. Smedshaug, A. Tverdal, J. I. Pedersen, National Health Screening Service, Oslo, Norway The purpose of this randomised controlled trial was to study if a daily supplement of vitamin D3 could reduce the risk of hip fracture and other osteoporotic fractures in institutionalised elderly. The study was performed in nursing home residents in two Norwegian cities. It was of importance to make a simple study design in order to facilitate its use in the great number of wards involved. The intervention group received 5 ml ordinary cod liver oil daily containing 10mg vitamin D3 and the control group 5 ml cod liver oil where vitamin D was removed. The participants, the nursing staff, and the investigators were blinded to which type of cod liver oil the participants were given. During the study period of two years, hip fracture, other non-vertebral fractures and deaths were registered. The fracture diagnoses were validated in hospital discharge letters or x-ray descriptions.

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A total of 1,144 residents from 51 nursing homes were included in the study. Mean age at baseline was 85 years and 3/4 of these were women. The intervention ended summer 1999. The study participants contributed with a total of approximately 1,700 observation years, giving the study a 80% power to detect a 42% reduction in hip fracture incidence and a 30% reduction in all nonvertebral fractures at the 5% signicance level. The fracture validation will soon be completed, and will be followed by analysis of fracture data on the intention-to-treat basis. Main results from the study will be presented and discussed.

remodeling and histomorphometry analysis of the secondary spongiosa and cortex of the tibia were also investigated. Plasma IGF-I and testosterone were determined, as well as seminal vesicles weight taken as the reection of testosterone effects. At 12 weeks, a marked decrease in IGF-I was observed with the lowest protein diet: 67529, 66823, 65735 and 34929* ng/ml (meansSEM; *p<0.05 vs 15% by ANOVA) in rats fed 15, 7.5, 5 and 2.5% casein, respectively. The effect was still more pronounced after 24 weeks. In contrast, at 12 weeks no effect on testosterone was observed. Only at 24 weeks testosterone was inuenced: 1306251, 998169, 707109* and 49465* pg/ml (*p<0.05 vs 15%), in rats fed 15, 7.5, 5 and 2.5% casein, respectively. The early fall in IGF-I was associated with decreased bone formation and the late depressed testosterone with an increment of bone turnover. The repercussion on BMD, US and tissues weights observed at 24 weeks are tabulated below:
Protein Intake PT BMD (mg/cm2) PT US (N) Seminal vesicle (mg) Muscle (g)
Bone Mass Diagnosis

218. VITAMIN D AND CALCIUM SUPPLEMENTATION REDUCES FALLS IN ELDERLY WOMEN VIA IMPROVEMENT OF BODY SWAY AND NORMALISATION OF BLOOD PRESSURE: A PROSPECTIVE, RANDOMIZED, AND DOUBLE-BLIND STUDY H. W. Minne1, M. Pfeifer1, B. Begerow1, D. Nachtigall2, C. Hansen2, 1Institute of Clinical Osteology ``Gustav Pommer'' and Clinic ``DER FUERSTENHOF''Bad Pyrmont, Germany; 2 Strathmann AG, Hamburg, Germany The risk of fractures increases with age. This is a result of increasing bone fragility due to osteoporosis but it is also a result of an increasing number of falls. Consequently, therapeutic interventions should either increase bone mass and bone quality or decrease the risk of falling. The effects of eight weeks of supplementation with vitamin D and calcium on body sway, blood pressure, and biochemical measures of bone metabolism were studied. The sample consisted of 148 women (mean [SD] age, 741 years) with a 25-hydroxy-cholecalciferol level below 50 nmol/l. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured 25hydroxyvitamin D, intact parathyroid hormone, markers of bone turnover, and blood pressure before and after treatment. Falls and fractures among the participants were followed over a oneyear period. Statistical evaluation was carried out using SAS for Windows, version 6.10 (CCDRD, Berlin, Germany). Compared to calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72 percent (p<0.0001), a decrease in parathyroid hormone of 18 percent (p = 0.0432), a decrease in body sway of 9 percent (p = 0.0435), a decrease in systolic blood pressure of 9 percent (p = 0.0165), and a decrease in heart rate of 5 percent (p = 0.0219). The mean number of falls per subject during a one year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves body sway, normalizes blood pressure, reduces secondary hyperparathyroidism and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.

15.0% 2663 15611 30913 7.720.25

7.5% 2706 13721 30520 7.550.21

5.0% 2614 1405 22742 5.740.98*

2.5% 2348** 1145* 19914* 5.560.16*

Similar eects on midshaft tibia and femoral neck BMD were observed. Thus, bone loss occurred in male rats pairfed an isocaloric low protein diet at skeletal sites formed by cortical and/ or trabecular bone. This was associated with alteration of bone mechanical properties. A dose-dependent decrease of muscle weight was also observed. In conclusion, isocaloric protein undernutrition induces bone loss in adult male rats, through mechanisms involving an early drop in IGF-I and in bone formation followed by hypogonadism and increased bone turnover. This could be reminiscent to osteoporosis pathogenesis in male elderly.

220 (196). BONE MINERAL DENSITY IN CHILDREN WITH ASTHMA RECEIVING LONG-TERM TREATMENT WITH INHALED BUDESONIDE L Agertoft, S Pedersen, Department of Pediatrics, Kolding Hospital, Kolding, Denmark The aim of our study was to assess the effects of long-term treatment with inhaled budesonide (BUD) on total body bone mineral density (BMD), total body bone mineral capacity (BMC), total bone calcium (TBC), and body composition in children with asthma. Dual energy X-ray absorptiometry (DEXA) was performed in 157 asthmatic children treated with inhaled BUD at a mean daily dose of 504 mg (range: 189 to 1,322 mg) for 3 to 6 years (mean, 4.5 years). Measurements were compared with those of 111 agematched children also suffering from asthma but who had never been treated with exogenous corticosteroids for more than 14 d (control group). There were no statistically signicant differences between the two groups in BMD (BUD = 0.915 g/cm2 controls = 0.917 g/cm2), BMC (BUD = 1,378 g, controls = 1,367 g), TBC (BUD = 524 g, controls = 519 g), or body composition (lean body weight BUD = 27,600 g, controls = 26,923 g; % body fat BUD = 20.1%, controls = 20.3%). Furthermore, there was no correlation between any of these parameters and duration of treatment, accumulated or current dose of budesonide. Three to six years of treatment with inhaled budesonide at an average daily dose of 504 mg has no adverse effect on total BMD, total BMC, TBC, or body composition in children with chronic asthma.

219. BONE LOSS INDUCED BY ISOCALORIC PROTEIN UNDERNUTRITION IN ADULT MALE RATS IS ASSOCIATED WITH EARLY DECREASED IGF-I AND LATE HYPOGONADISM P. Ammann, A. Toromanoff, S. Bourrin, J. P. Bonjour, R. Rizzoli, Division of Bone Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland Hypogonadism and protein undernutrition can contribute to the pathogenesis of osteoporosis in elderly. We have shown that protein undernutrition could affect both sex hormone status and IGF-I system in adult female rats. To investigate whether protein undernutrition could inuence gonadal function and/or the IGF-I system in males, we evaluated the time-dependent effects of isocaloric diets with various levels of protein content (15, 7.5, 5 and 2.5% casein) in pairfed 7 month-old adult male rats. Bone mineral density (BMD), and ultimate strength (US) were measured at the level of the femur, proximal tibia (PT) and midshaft tibia, together with lower limb muscle mass. Markers of bone

221 (197). EVALUATION OF THE BONE MINERAL DENSITY OF THE LOWER EXTREMITIES OF THE HEMIPLEGIC PATIENTS Fatma Atalay1, Oya Gulec1, Gulcin Kaymak Karatas1, Jale M. Tan1, 1Department of Physical Medicine and Rehabilitation, Gazi University Faculty of Medicine, Ankara, Turkey In stroke patints, there is a risk for osteoporosis due to immobilization. In this study bone mineral densities of both lower extremities of hemiplegic patients were evaluated and its relationship with immobilisation were investigated. Bilateral tibial bone mineral densities of 18 men and 14 women, a total of 32 patients were measured by quantitative ultrasound and speed of sound(SOS) , t and z scores were estimated. The participants were questioned for demographic properties, risk factors for osteoporosis and for menopause durations in women. Spastisity and Rivermead Mobility Indexes were assessed and their relationships between bone mineral density parameters were evaluated. Mean age of participants was determined as 58, 19, 2 years and mean duration of illness was 24, 118, 5 months. No signicant differences was found in SOS, t and z scores between hemiplegic and normal extremities in total patients. In men, no signicant correlation was found between age, duration of illness and SOS, t and z scores of both extremities. In women, there was not any correlation between age, menopause duration and bone mineral density parameters, but there was a strong correlation between illness duration and bone mineral density parameters in both hemiplegic and normal sides.

Friday, June 16, 2000

with areal BMD of the total body (TB), total hip (TH) and its subregions, and lumbar spine (LS; Prodigy, Lunar). Subjects were girls aged 1113 years enrolled in an intervention study to evaluate the effects of supplementation with calcium, vitamin D, and cheese on the acquisition of bone mass during pre-puberty (the CALEX study). The median of the CVs for duplicate determination of BUA was 1.2% in 103 girls. Correlations (Spearman rho) between bone mass and anthropometric parameters in 61 girls are shown in the table below. BUA was weakly associated with BMD of the total body, the hip and all its subregions, but not the spine. Both BUA and BMD measurements were associated with height, weight, body mass index (BMI), and age to a similar degree. Further study is required to determine whether the differences between calcaneal BUA and axial BMD are due to the measurement technique or to differences in bone mass acquisition at different skeletal sites. QUS appears to be a promising technique for evaluating bone mass in children.


TH BMD 0.321 0.814

LS BMD 0.236* 0.755 0.737

Height 0.204 0.471 0.335 0.504

Weight 0.445 0.495 0.432 0.527 0.764

BMI 0.494 0.407 0.423 0.386 0.348 0.860

Age 0.250 0.317 0.326 0.392 0.621 0.420 0.129*

* not signicant; all others p<0.05

222 (198). DIAGNOSTIC VALUE OF A SINGLE DENSITOMETRY Marek Bolanowski, Department of Endocrinology and Diabetology, Wroclaw Medical University, Wroclaw, Poland Nowadays bone densitometry has been available in clinical practice and its consequence are many confusing results. Moreover, descriptions of a measurement without personal contact with patient are not uncommon. In some cases the result of a single, sometimes by chance, densitometry can provide a false conclusion and therapeutic decision when interpreted without sufcient knowledge of an individual clinical picture and/or methodological conditions. The purpose of the study was to compare densitometric results using different methods in healthy men. Following densitometric analyses were carried out: forearm (SPA, SXA, pDEXA, pQCT), lumbar spine (DEXA, QCT), hip (DEXA), total body (DEXA), tibia (QUS), os calcis (QUS), phalanx (QUS). The results were compared according to age, race and sex matched normal population values. A considerable dispersion in the results of densitometry was shown. Especially methods used in screening studies (SPA, SXA, QUS) provided results lower in contrast to results obtained by standard methods (DEXA, QCT). It suggests to be very careful when interpreted or described the result of a single densitometry without personal contact with patient and his history, or without sufcient knowledge of densitometric methods. 224 (200). CAN COMMERCIALLY AVAILABLE PHANTOMS BE USED FOR UNIVERSAL FOREARM BMD CROSSCALIBRATION? X. G. Cheng, J. A. Shepherd, C. F. Njeh, T. Fuerst, J. Toschke, M. Grigorian, H. K. Genant, Osteoporosis & Arthritis Research Group, University of California, San Francisco, CA, USA There is a need for phantoms to monitor machine precision and to cross-calibrate between peripheral DXA devices for large multicenter trials. We evaluated seven commercially available phantoms on ve DXA scanners. The European Forearm Phantom II (EFPII), the Computerized Imaging Reference Systems (CIRS) 400, 600 and 800 phantoms, the Osteometer DTX200 phantom, the Norland pDEXA phantom, and the Lunar PIXI phantom, were scanned ve times with repositioning. The DXA scanners were the Aloka DCS600EX, the Hologic QDR4500A, the Osteometer DTX200, the Norland pDEXA, and the Lunar PIXI. In addition, 100 female subjects (2178 yrs) were scanned on each densitometer as part of an in vivo cross calibration study. CVs are shown in the table. The gure shows the distribution of in vivo PIXI T-scores compared to each phantom. Precision varied due to phantom-specic repositioning issues. A combination of these phantoms could be used to cover the clinical BMD range for monitoring precision and accuracy in multi-center trials.


S. Cheng1, H. Suominen1, A. Koistinen1, F. Tylavsky2, H. Kroger3, University of Jyvaskyla, Jyvaskyla, Finland; 2University of Tennessee, Memphis, TN, USA; 3University of Kuopio, Kuopio, Finland

Relatively little is known about the association between quantitative ultrasound (QUS) parameters and bone mineral density (BMD) in children. We have compared calcaneal broadband ultrasound attenuation (BUA; QUS2, Metra Biosystems)

Friday, June 16, 2000

Device Aloka Holo. Osteo. PDXA PIXI 400 2.3 2.2 2.2 2.4 1.8 600 3.1 1.9 1.2 1.1 1.9 800 1.7 1.4 0.9 2.1 1.1 DTX 1.0 0.9 0.6 0.7 0.5 EFPII na 2.6 0.5 0.7 1.0 PDXA 1.2 1.7 0.7 0.9 1.1 PIXI 1.0 0.9 0.6 1.1 0.4

Results: Both BUA and SI were decreased in patients with Cushing's syndrome (P<0.01) but not SOS (P=0.08). BMD was also strongly decreased in Cushing's syndrome both at the LS and FN (P<0.001). The sole marker of bone turnover statistically signicantly different between the 2 groups was OC: 3.53.4 ng/ mL versus 6.42.9 ng/mL (P<0.01). The areas under the ROC curves (AUC) were 0.722 (BUA), 0.729 (SI), 0.898 (BMDLS), 0.812 (BMDFN) and 0.829 (OC) respectively. AUC was signicantly higher for BMDLS than for both BUA ans SI (P<0.05). Conversely AUC were not statistically signicantly different for BMDFN and for both BUA and SI. Odds-ratios [and 95% condence interval -CI-] per 1 control standard deviation decrease were: 1.9 [1.13.3] for BUA, 1.7 [95% CI: 12.9] for SI, 7.8 [95% CI: 2.623.7] for BMDLS, 4.7 [95% CI: 1.812.1] for BMDFN and 2.9 [95% CI: 1.36.3] for OC. Odds ratios for SOS and other markers of bone turnover were not statistically signicant. Conclusion: QUS of bone seems a relevant tool for assessing bone involvement in Cushing's syndrome. QUS does have a lower sensitivity as compared with DXA however. The new markers of bone turnover (PINP, PICP and ICTP) assessed in this study do not seem of interest.

225 (201). AGE RELATED INCIDENCE OF AORTIC CALCIFICATION AND OSTEOPHYTE IN KOREAN AGEING PEOPLE W. H. Choi, C. B. Lee, Y. S. Park, T. H. Kim, University of Hanyang, Hangdangdong, Seoul, Korea There are two basic clinical indication for performing bone density. The one is accurate measurement of BMD in order to identify patients with low bone mass and increased risk of fracture, the other one is precise monitoring of patients place on therapy to determine its effect. But most of popular bone mineral densimeter, DEXA system which has limited value for evaluation of old people who has common osteophyte and aortic calcication in anterioposterior scan. There are no known data about incidence of osteophyte and aortic calcication in ageing people. We used computed tomography (Siemens, somatom plus4) and simultaneous caliblation phantom(K2HPO4) and software QCT pro (Mindways, CA) with 3 dimensional evaluation. We evaluated 128 patient who visited to osteoporosis clinic at Hanyang university hospital in Seoul, Korea. We dened osteophyte that detected bony overgrowth around the any region of L1 to L2 area. Aortic calcication dened any radioopaque calcied region in the same level of aorta and renal atery. The incidence of osteophyte were 35% at 50th decade, 62% at 60th decade, 68% at 70th decade and more than 95% at 80th decade. The incidence of aortic calcication were 20% at 50th decade, 42% at 60th decade, 50% at 70th decade and more than 95% at 80th decade. Both are present lower than 5% at 50th decade, but 37% at 60th decade, 40% at 70th decade and more than 95% at 80th decade. Some patient could not evaluate the follow up DEXA result after year treatment of antiresorptive agents. This clinical problem might be considered ageing change of osteophyte and or aortic calcication. To overcome this limitation, 3 dimensional QCT method would be useful for alternative method.

227 (203). THE ITALIAN EPIDEMIOLOGICAL STUDY ON THE PREVALENCE OF OSTEOPOROSIS (E.S.O.P.O.) G. Crepaldi1, S. Adami2, G. Isaia3, P. Filipponi4, O. DiMunno5, S. Maggi1, R. Giorgino6, A. Menotti7, The E.S.O.P.O Study Group , 1 Padua; 2Verona; 3Turin; 4Perugia; 5Pisa; 6Rome, Italy; 7 Minneapolis, USA Aim of the study is to measure the prevalence of osteopenia and osteoporosis among general population across all Italian regional areas. The study (starting Feb. 1st 2000 and ending May 31st 2000) involves about 90 hospital and university sites: the recruitment will be supported by 1800 General Practitioners who will invite by mail or by phone 25 000 women (aged 4079 yrs) and 20 000 men (aged 6079 yrs). Subjects will be randomly selected from GPs' database. A 66% redemption rate is expected in order to allow a nal sample of 30 000 subjects. The sample has been calculated based on published cohort data. Each subject will undergo an ultrasound densitometry at the heel on a Lunar Achilles Express device for Stiffness Index measurement. Recent studies have shown that Stiffness Index T-scores measured by the Achilles are entirely congruent with those of axial BMD. Based on WHO criteria, Stiffness and axial BMD identify the same proportion (20%) of postmenopausal women as osteoporotic. A life-style and risk-factor questionnaire (partially drawn by the EVOS study) will be administered to each subject: blood pressure and BMI will be also measured. The primary endpoint of ESOPO will be to estimate the proportion of subjects with Stiffness Index >1 SD (osteopenia) and >2.5 SD (osteoporosis) below the young adult mean in each decade: the secondary endpoint is to conrm and/ or identify any potential determinant of both conditions. A precision error test trial will be also performed in each center to measure Stiffness Index CV in vivo both intra- and inter-observer. A specic software has been developed for data collection: an interim-analysis has been planned on early April in order to allow a preliminary presentation at the WCO meeting.

226 (202). QUANTITATIVE ULTRASOUND OF BONE AND NEW MARKERS OF BONE TURNOVER IN CUSHING'S SYNDROME B. Cortet, F. Blanckaert, A. Racadot, M. d'Herbomez, X. Marchandise, D. Dewailly, C. Cortet, University-Hospital of Lille, Lille cedex, France Purpose: Quantitative ultrasound (QUS) of bone is a valuable tool in the assessment of postmenopausal osteoporosis. QUS and new markers of bone turnover have been poorly assessed in Cushing's syndrome however. Patients and Methods: 22 patients with Cushing's syndrome (19 females, 3 males, mean age: 3810 years) were studied and compared to 35 control patients age- and sex-matched (mean age for controls: 3911 years, P=0.8). The following variables were measured in both groups: QUS at the heel (Achilles, Lunar): BUA, SOS ans stiffness index (SI), bone mineral density (BMD) both at the lumbar spine (LS) and femoral neck (FN) by dualenergy X-ray absorptiometry (DXA, QDR 2000, Hologic), serum markers of bone turnover: osteocalcin (OC), procollagen type INand C-terminal propeptides (PINP and PICP), procollagen type IC-terminal telopeptide (ICTP).

228 (204). BUA AND SOS VALUE OF THE CALCANEUS IN ELDERLY WOMEN DEPENDS ON MECHANICAL LOAD OF THE SOLE E Csupor1, P Soos2, L Basch3, P Vargha4, S Meszaros4, C Horvath4, 1Health Service of Budavar, St. Janos Hosp, Sensitiv LTD, lst Dept of Med., Semmelweis University, Budapest, Hungary The advantage of the quantitative ultrasound (QUS) is measuring parameters inuenced not only by mineral density but also by structure and qualitiy of the bone. For this reason, to study the

role of mechanical load of sole to the heel QUS parameters seemed to be promising. SOS, BUA and QUI (Sahara, Hologic) were measured at both calcaneus in 84 elderly women (age 679.1 ys). The pressure to the right and left sole were also examined by podoscope. Patients were grouped as pressing dominantly the right or left sole or pressing equally both sides. The difference in right-left side for BUA, SOS and QUI was calculated. Results: mean, (95% cond. limits), *p<0.0002 Our results suggest the role of mechanical load in determining the speed and attenuation measured at the calcaneus.

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and femur, there is renewed interest in small, low-cost devices for BMD measuring in the peripheral skeleton like forearm. It's also good place for estimation of bone microstructure, thanks to small amount of soft tissues. One could remember that radial fractures are common in osteoporotic patients. The sim of this study was to estimate the value of measurements of the forearm in diagnosing osteoporosis in comparison to lumbar spine and proximal femur densytometric measurements. Application of computerised assessement of bone structure on Xrays is described. Bone mineral measurement was performed in 600 patients. Forearm measurements were carried out using the DTX200 (Osteometer) in both ``distal'' and ``ultradistal'' regions. Measurements of the lumbar spine and proximal femur were performed on the DPX-IQ (Lunar) densytometer. Signicant correlation between peripheral results, proximal femur and lumbar spine was found. Diagnosis of osteoporosis was also wellcorrelated in peripheral and axial measurements (about 89 %). Radiographs of distal radial methaphysis, femoral neck and calcaneus were selected for the research. All the radiographs had been made in ordinary X-ray rooms. The elaborated method allows for a quantitative bone structure measurement on radiographs of different types: distal radius, femoral neck, and calcaneus radiographs as well as on experimental radiographs. The only condition of this method is good quality of the radiograph and access to image recording device CCD camera or scanner. In the previously performed resarch, measurement precision as well as certain norm range for distal radius. We conclude that measurements of bone mineral density in the foreann is valuable method in diaguosing asteoporosis. On the basis of the computerised analyses of radiographx it is possible to obtain quantitative measurement of bone structure. Bone mineral density was assessed by using of DTX100 and DTX200. Measurements are carried out in distal (mainly cortical bone) and ultradistal (trabecular bone) regious. We found high correlation between bone mineral density measurements in the forearm, proximal femur and lumbar spine with correlation coefcient (r) range from 0.66 to 0.8. Using WHO denition diagnosis of osteoporosis based on forearm densitometry was conrmed or excluded in 90% cases in comparison to proximal femur and lumbar spine densitometry. Measurement of BMD in forearm is very efcient, precise and low cost method in diagnosis of osteoporosis. There are also possibilities to estimate of bone structure in the forearm basing on digitalised radiogram. Such programs Trabecula and Densyt are dedicared for evaluation of both trabecular and cortical bone structure, mainly trabecular quantity, width, density. Basing on PC computer and standarised radiogram patients with deteriorated bone structured can be distinguished from patients with normal bone structure.

equal load n BUA SOS QUI 42 0.54 (2.50; 1.41) 2.,69 (0.62; 5.99) 19.12 (54.18; 15.95)

right dom. 27 5.81* (3.24; 8.37) 12.08* (8.55; 15.61) 7.35* (5.08; 9.62)

left dom. 15 9.90* (14.2; 5.56) 13.74* (18.68; 8.8) 9,68* (13.08; 6.3)

229 (205). COMPUTER AIDED HISTOMORPHOMETRIC ANALYSIS OF VERTEBRAL BODIES E. Czerwinski1, A. Gadek1, L. Wojnar2, 1Depat. of Orthopaedics, Jagiell. University, Krakow; 2Inst. of Mat. Sc., Kracow University of Technology, Poland The aim of study was elaboration of a automatic method of histomophometric analysis of trabecular bone samples using computer aided image analysis. Transverse sections of decalcied vertebral bodies has been chosen for examination. Digital images of the sections analysed have been stored in a PC computer. memory using the frame grabber. Further analysis has been performed using the specialised software for image analysis Aphelion v. 2.4. Independent analysis of the RGB channels and automatic shade correction allowed was used. This introductory processing has been followed by binarisation and measurements of selected parameters. Application of the procedures offered by image analysis has enabled fast and objective evaluation of histomorphometric parameters of the trabecular structure. The method proposed has high sensitivity an offers good repeatability of the results, even in the case of samples with poor contrast. The results of introductory tests indicates that this method can be applied in a fully automatic mode within various elds of view of a single specimen. Good repeatability of the results and high efciency in measurements makes this method an interesting alternative for classical histomorphometric analysis.

230 (206). RADIUS BONE MINERAL DENSITY MEASUREMENTS AND STRUCTURE ANALYSIS IN DIAGNOSIS OF OSTEOPOROSIS E. Czerwinski, R. T. Kukielka, A. Len, Dept. of Orthopaedics, Medical Coll. of Jagiellonian University, Kopernika, Krakow, Poland However bone mineral density is widerly accepted criterion for osteoporosis, but is not sufcient for bone quality and fractures risk assessment. Apart from BMD the bone structure is also or even more important. The DXA method is currently considered the golden standard in diagnosing osteoporosis. According to WHO criteria the values of T-scores in any site justies the diagnosis of osteoporosis. Because of the perceived high cost of DEXA studies of the spine

231 (207). CALCANEAL ULTRASOUND -INFLUENCE OF ACTIVITY AND COMPARISON WITH STANDARD DEXA MEASUREMENTS IN A GENERAL CLINICAL PRACTICE R. D. Danese, A. A. Licata, B. Richmond, C. Deal, Cleveland Clinic Foundation, Cleveland, Ohio, USA Calcaneal ultrasound (US) is a rapid and inexpensive modality for screening osteoporosis in daily ofce practice. But questions remain about its precision, correlation with standard DEXA procedures, and applicability to WHO criteria. We compared its results to routine DEXA testing and evaluated the performance of this tool pre and post exercise. Fifty women were evaluated with ultrasound (Hologic Sahara) at their scheduled DEXA testing (Lunar 4500). The mean (s.d.) age, height, weight, and years since menopause were 60.3(1.2) y, 1.61 (0.06) m, 65.6(9.6) kg. and 12.9 (9.3) y, resp.

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Ultrasound correlation
Neck r-value p-value 0.40 0.005 Trochanter 0.59 <0.009 Ward 0.32 0.026 Total Hip 0.37 0.012 Spine 0.42 0.006

233 (209). DXA INSUFFICIENCY IN PRIMARY DIAGNOSIS OF OSTEOPOROSIS R. Dreher, M. Hesse, G. Lingg, G. Sommer, 1Hospital for Rheumatic Diseases, Bad Kreuznach; 2Hospital Evaluation Systems, Kaiserslautern, Germany Aims: To dene osteoporotic patients by triple bone mineral density (BMD) measurements. To compare DXA and QCT BMD measurement values. Methods: BMD measurements were performed by LUNAR lumbar DXA (LDXA) and femoral neck DXA (FNDXA) measurements and additionally by QCT measurements of lumbar vertebrae (General Electric 3000 single energy scanner) in women (n = 250), women 5170 years (n = 141), women >70 years (n = 109) and men (n = 74), men 5170 years (n = 60), men >70 years (n = 14). 1. Denition of osteoporosis on the basis of absolute BMD values for women/ men: LDXA 50,90/ 50,93mg/ cm2 and/or FNDXA 50.73/ 50.80mg/cm2 and/or QCT lumbar vertebrae 591.5mg HAE (Hydroxy Apatite Equivalent), the same for women and men. 2. Comparison of numbers and percentages of osteoporotic patients depending on the BMD measurement methods and age of patients. 3. Comparison of triple BMD absolute values by Spaerman correlation coefcients between QCT-LDXA, QCT-FNDXA and FNDXA-LDXA. 4. Spaerman correlation coefcients betwen BMD values and number of grade 3 lumbar vertebrae fractures. Results: Numbers (n) and percentages (%) of osteoporosis by triple BMD measurements (LDXA, FNDXA, QCT) women, 5170 years (n=141); LDXA (n=38/27%), FNDXA (n=43/31%), QCT (n=93/ 66%), women, >70 years (n=109); LDXA (n=35/32%), FNDXA (n=51/47%), QCT (n=96/88%) men, 5170 years (n=60); LDXA (n=10/17%), FNDXA (n=27/45%), QCT (n=39/65%), men, >70 years (n=14); LDXA (n=5/36%), FNDXA (n=9/64%), QCT (n=13/ 93%). Spearman correlation coefcients of BMD values women, 5170 years; QCT vs LDXA (r = 0.56, p = 0.000), QCT vs FNDXA (r = 0.51, p = 0.000), LDXA vs FNDXA (r = 0.56, =0.000) women, >70 years: QCT vs LDXA (r = 0.44, p = 0.000), QCT vs FNDXA (r = 0.45, p = 0.000), LDXA vs FNDXA (r = 0.50, p = 0.000) men, 5170 years: QCT vs LDXA (r = 0.49, p = 0.000), QCT vs FNDXA (r = 0.45, p = 0.000), LDXA vs FNDXA (r = 0.27. p = 0,19), men, > 70 years; QCT vs LDXA (r = 0,67, p = 0.003), QCT vs FNDXA (r = 0.91, p = 0.000), LDXA vs FNDXA (r = 0.61, p = 0.010) Spearman correlation coefcients between grade 3 lumbar vertebrae fractures (G 3 LF) and BMD values, all patients: G 3 LF vs QCT (r = 0.44, p = 0.000), G 3 LF vs FNDXA (r = 0.31, p = 0.000), G3 LF vs LDXA (r = 26, p = 0.000) Conclusion: If only DXA techniques are used in patients with various underlying rheumatological diseases, osteoporosis will often be overlooked. FNDXA is only moderately correlated with LDXA and lumbar QCT with the exception of elderly men, where FNDXA correlates strongly with the QCT values of the lumbar spine. Grade 3 lumbar vertebrae fractures correlate best with lumbar QCT values.

Only 4% of pts had US t-scores below2.5 s.d., but 20.5% had DEXA scores below 2.5 s.d. at the spine, 21.7% at the femoral neck, 28.8% at wards triangle, 4.4% at the trochanter, and 5% at the total hip. 42% of patients had US t-scores below 1.0 s.d.. 18 subjects were evaluated before and after a 12 mile ``walk for osteoporosis''. Mean US t-scores were 70.033(95% CI, 0.48 to 0.42) before the walk and 0.24 (95% CI, 70.73 to 0.24) afterwards (p = 0.008). Pre-walk, 16.6% had t-scores below ~1.0 compared to 33% post walk. Those with (-) scores at the outset (mean 0.70 [range 1.06 to 0.33]) showed worse values after the walk (mean 0.94 [range 1.27 to 0.60] p = 0.01). US with this machine failed to detect the same frequency of osteoporosis as routine dexa when using standard WHO critical cuto criteria (i.e., 2.5 s.d. t-score). Prior activity inuenced these measurements and falsely lowered values. Conclusion: WHO criteria cannot be used to screen for osteoporosis when using this specic machine. Minor physical activity may aect precision and increase the false positive rate.

232 (208). ESTIMATION OF THE RISK OF HIP FRACTURE IN TWO DIFFERENT POPULATIONS: THE EPIDOS AND SOF STUDIES P. Dargent, M. Nevitt, L. Palermo, F. Poitiers, G. Bre art, for the EPIDOS And SOF Research Groups, 1University of California, San Francisco; 2INSERM, Paris, France Differences in age- and BMD-specic fracture risks across geographic populations are an obstacle to generalizable screening and treatment guidelines for osteoporosis. The goal of this analysis was to assess whether differences in hip fracture rates between cohorts of French and American women could be explained by differences in the distribution of BMD and age. We used data from two large, prospective cohort studies of BMD and hip fracture in France (EPIDOS) and the US (SOF). This analysis included only women between 75 and 89 years of age with baseline hip BMD; 6510 women in EPIDOS (mean age 80.43.4 years) and 4448 women in SOF (78.03.1 years). Women had hip BMD assessed by DXA at baseline (Lunar DPX in EPIDOS and Hologic QDR1000 in SOF). We used published equations (JBMR 1997; 12:13 16) to convert manufacturer-specic values for total hip BMD into standardized units (sBMD). Follow-up for hip fracture was truncated at 4 years in each cohort. In SOF, 140 hip fractures occurred during 3.7 ( 0.7) years while in EPIDOS, 245 hip fractures occurred during 3.6 (0.8) years. Crude rates of hip fracture per 1000 woman-years were 27% higher in EPIDOS (10.7; 9.4 11.9) than in SOF (8.4; 7.0 9.8). The mean age-standardized sBMD was higher in SOF than EPIDOS up to age <83 (746.2 and 727.5 mg/cm2, respectively, p50.001), but was lower in SOF after age 583 (686.2 and 693.9 mg/cm2, p = 0.21). In both cohorts, the risk of hip fracture showed nearly identical strong associations with sBMD and age in Cox proportional hazards models. In combined models, adjustment for sBMD and age eliminated study differences in risk of hip fracture (RR for SOF vs. EPIDOS: 1.12; 95% CI: 0.911.39). There were no signicant sBMD or age by study interactions. In conclusion, the 4-year age- and hip BMD-specic risks of hip fracture are similar for women in the EPIDOS and SOF cohorts. This suggests that simple screening and treatment guidelines utilizing risk of hip fracture in risk groups dened by age and hip BMD may have similar validity in the US and France. Studies are needed to test the generalizability of fracture risk estimates across other geographic areas.

234 (210). INTERRELATIONSHIPS BETWEEN BONE MASS, SERUM PTH LEVELS AND BONE TURNOVER IN PATIENTS ON CHRONIC MAINTENANCE HEMODIALYSIS C. Dumitrache, D. Grigorie, Elena Neacsu, Carmen Barbu, M. Grabovschi, C. I. Parhon Institute of Endocrinology, Nephrology Department of the Carol Davila Hospital, Bucharest, Romania The aim of the study was to assess the pattern of bone loss in the axial and appendicular skeleton and its relationships with serum PTH levels and bone turnover in patients on chronic hemodialysis. We measured the total body bone mineral density by DEXA in 15 patients (6 women and 9 men) with a mean of 7.4 years (range:118 years) of chronic hemodialysis. Mean value of Z score was signicantly decreased in the arms (Z=2.21). There was no correlation between bone mineral density measured at any region

and serum levels of intact PTH (IRMA), intact serum osteocalcin or total alkaline phosphatase. We found a signicant inverse relationship between bone loss (Z score) and serum levels of iPTH (r = 0.6, p<0.05) and years of hemodialysis (r = 0.58, p<0.05), respectively. We found a signicant increase in mean values of serum iPTH (782.4 pg/ml) and osteocalcin (155.23 ng/ml) levels. In conclusion, 1) the cortical bone loss is signicant and is due to chronic renal failure, 2) signicant increase in serum PTH levels and bone turnover markers suggests that long-term hemodialysis produces a high-turnover bone loss, 3) secondary hyperparathyroidism is pathogenically involved in the bone loss, 4) the incidence of high-turnover renal osteodystrophy seems to be high among chronic renal failure patients treated by hemodialysis.

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(T-score: 2.66) for the femoral wards, 0.5770.174 (T-score: 71.75) for the femoral trochanter and 0.9030.137 (T-score: 72.04) for total body. Repeated bone scan and BMD after 6 months of therapy with oral Vit-D, calcium and proper sun exposure demonstrated a signicant increase (P<0.00) in BMD and healing of pseudofracture. Conclusion: Measurements of BMD in patients with osteomalacia are of value and recommended in the initial assessment of the degree of osteopenia. Bone scintigraphy is valuable in demonstrating the site and extent of stress fractures as well as diagnosis.

235 (211). BONE MINERAL DENSITY AND BONE SCINTIGRAPHY IN CHILDREN AND ADOLESCENTS WITH OSTEOMALACIA M. El Desouki, N. Al Jurayyan, King Khalid University Hospital, Riyadh, Saudi Arabia In order to demonstrate the role of bone mineral density (BMD) measurements and bone scan in the management of patients with osteomalacia, radioisotope bone scintigraphy using Tc99m Methyline Diphosphonate (MDP) and BMD measurements of the lumbar spine and femur by means of Dual X-ray Absorptiometry (DXA) were performed at the time of diagnosis, and six months after therapy in 26 Saudi patients (17 females and 9 males). Their mean age was 13.5 years (range, 516). BMD measurements were compared with those of normal Saudi subjects matched for age and sex. Bone scan showed an increase in tracer uptake throughout the skeleton (``superscan'') in all children and demonstrated multiple stress fractures in eight. The mean BMD for the lumbar spine was 0.53 gm/cm2 (Z-score, 3.1) and for the femoral neck 0.55 gm/cm2 (Z-score, 2.8). Repeated bone scan and BMD after 6 months of therapy with oral Vitamin D, calcium and proper sun exposure, demonstrated signicant increase (P<0.001) in BMD and healing of pseudofractures. In conclusion, as a non-invasive method with minimal radiation exposure, measurements of BMD in children with osteomalacia are to be recommended in the initial assessment of the severity of osteopenia and in the follow up to monitor the response to therapy. Bone scintigraphy is valuable in demonstrating the site and severity of stress fractures.

237 (213). BONE SCINTIGRAPHY AND BONE DENSITOMETRY IN CHILDREN WITH OSTEOPETROSIS M. El Desouki, N. Al Jurayyan, A. Al Herbish, S. Al Rasheed, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Bone scintigraphy and dual x-ray absorptiometry were performed in 18 children (8 males, 10 females) with clinical and radiologic diagnoses of osteopetrosis in order to demonstrate the scintigraphic features of this rare disorder and to measure the bone mineral density. Their mean age was 9 years (range, 3 16 years). Bone scintigraphy demonstrated characteristic features of a widened metaphysis of all long bones that showed increased tracer uptake, particularly in the distal femur and proximal tibia. Dual x-ray absorptiometry of the lumbar spine, three femoral sites, and total body showed a marked increase in bone mineral density. The mean values for bone density of the lumbar spine and greater trochanter were markedly elevated than were other sites. Compared with a normal group matched for age and gender, the increase in bone mineral density was 181 % for the lumbar spine and 193% for the greater trochanter. The authors concluded that bone imaging and bone densitometry are useful in establishing the diagnosis of osteopetrosis by demonstrating increase tracer uptake in the widened metaphysis and increased bone density. Bone densitometry may be of prognostic value in followup, especially in monitoring the response to therapy.

238 (214). OSTEOPOROSIS IN POSTMENOPAUSAL SAUDI WOMEN USING DUAL X-RAY BONE DENSITOMETRY 236 (212). BONE MINERAL DENSITY (DXA) AND BONE SCAN IN ADULT SAUDI FEMALE PATIENTS WITH OSTEOMALACIA M. El Desouki, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Objectives: This prospective study was conducted to demonstrate the role of bone mineral density (BMD) and bone scan in the management of patients with osteomalacia. Patients and Methods: Bone scans using 99m Tc-Methylene Diphosphonate (MDP) and BMD of the total body, lumbar spine and femur using Dual X-ray Absorptiometry (DPA), Lunar Radiation Corp., Wisconsin) were performed at the time of diagnosis, and 6 months after treatment in 96 Saudi female patients, aged between 18 and 73 years (mean 42 yr) with clinical and biochemical diagnosis of Osteomalacia. BMD measurements were compared with that of normal Saudi female subjects. Results: Bone scan showed the features of ``Superscan'' in all patients and demonstrated multiple stress fractures in twenty seven. In 19 patients with chronic bone pain and the diagnosis was made by bone scan as the rst modality. The BMD (mean SD in gm/cm2) was 0.7810.156 (T-score: 3.01) for the lumbar spine, 0.6660.177 (T-score: 2.44) for the femoral neck, 0.5620.190 M. El Desouki, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Objective: A pilot study to evaluate prevalence of osteopenia and osteoporosis in postmenopausal Saudi women. Patients and Methods: Lumbar spine bone density was measured in 483 postmenopausal Saudi women 5262 years of age (average 55 years), using dual x-ray absorptiometry (DXA). Results: The results of the bone mineral density (BMD) in gm/ cm2 was compared to the peak bone density (PBD) in young healthy Saudi females (T-score) and to age matched group (Zscore). Based on the denition of WHO the T-score value was considered for analysis. Accordingly, 203 (42%) patients were normal (mean BMD of 1.0980.109, mean T-score of 0.513 SD; Z-score of 0.434), 164 (34%) with osteopenia (mean BMD of 0.8930.134, mean T-score of 2.36 SD; Z score of 1.05), and 116 (24%) patients with osteoporosis (mean BMD of 0.7950.142, mean T-score of 3.2 SD; Z score of 1.76). Conclusion: Osteopenia and Osteoporosis are not uncommon among postmenopausal Saudi women and should be considered a matter of public concern. Bone densitometry should be used to classify patients, identify those who need therapy. Further studies are needed to investigate the secondary causes of osteoporosis and to determine the Vitamin-D level.

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239 (215). INTERPRETATION OF PROXIMAL FEMORAL DUALENERGY X-RAY ABSORPTIOMETRY (DXA) SCANS: REGIONOF-INTEREST CONTROVERSIES LAID TO REST S. Farooki, R. J. Smith, K. Hoyte, D. Clain, D. J. Sartoris, Department of Radiology, University of California School of Medicine, San Diego, CA, USA PURPOSE: To critically examine the variability in bone mineral content (BMC) and density (BMD) among the various manufacturer-specied regions-of-interest (ROI) in the proximal femur in order to develop guidelines for DXA scan interpretation in the clinical detection and management of osteoporosis. METHODS: We retrospectively reviewed the proximal femoral DXA reports of 1227 patients from August 1998 August 1999 (81 males; 1146 females, average age 58.7. BMD and T-scores calculated for the femoral neck, Ward's triangle, greater trochanter, and the total proximal femur were compared with one another using analysis of variance (ANOVA) for determination of statistical signicance. All scans were performed on a Lunar DPX-IQ pencil-beam DXA system. Statistical analysis was performed using Minitab version 12 software. RESULTS: The distribution of the lowest T-scores for subregions was: 67.7% (831/1227) Ward's triangle, 9.6% (118/1227) neck, 6.2% (76/1227) trochanter, 7.3% (90/1227) total proximal femur, and 9.2% with multiple subregions being equal. The mean T-scores for Ward's triangle, femoral neck, greater trochanter, and total proximal femur were 1.54, 1.08, 0.59, and 0.99, respectively, and there was a statistically signicant difference between the T-score means (F = 784.72, p50.001 with repeated measures ANOVA). There was a very high degree of correlation between T-scores in Ward's triangle and femoral neck (Pearson's correlation coefcient r = 0.93) and an intermediate degree between the total proximal femur and Ward's triangle (r = 0.88), total and neck (r = 0.89), and total and trochanter (r = 0.87). There was a low correlation between Ward's triangle and greater trochanter (r = 0.77) and between neck and trochanter (r = 0.78). CONCLUSIONS: The lowest T-score among the major ROIs should always be used for diagnosis. However, Ward's triangle should not be used for diagnosis or follow-up due to its uniformly low T-scores and small sample volume. Our data show that only the femoral neck or the greater trochanter should be used for diagnosis of osteoporosis. For follow up examinations, either the greater trochanter or the total proximal femur could be used.


of 65-year-old men that would be classied as osteoporotic for each measurement. Differences in age-related T-scores for each skeletal site are shown below. At age 65, the mean T-score ranged from 0.6 for total hip, to 1.9 for QCT spine. Prevalence estimates were 3% at the total hip, 4% for DXA spine, 5% for the forearm, 6% for ultrasound heel, 8% for femoral neck, and 27% for spinal QCT. We conclude that T-score discrepancies exist in men as have been previously reported for women. These discrepancies raise important concerns about the use of BMD measures in assessing fracture risk in men.
1. Faulkner KG, von Stetten E, Miller P 1999 Discordance in patient classication using T-scores. J Clin Densitometry 2(3):343350


241 (217). ANY PERIPHERAL FRACTURE OCCURRING AT ANY AGE IS ASSOCIATED WITH DECREASED BONE MINERAL DENSITY IN POST-MENOPAUSAL WOMEN C. Fiorano-Charlier, A. Ostertag, J P Aquino, M. C. de Vernejoul, C. Baudoin, Inserm U349, Centre Viggo Petersen, Hopital Lariboisiere, Paris, France Women who experienced any peripheral fractures at any age are they at risk of osteoporosis? For this purpose, we selected among a cohort of 503 women, 460 women (mean ageSD: 656) without vertebral or femoral neck fractures and without previous treatment with bisphosphonate or uoride. Among them, 49 women (10%) had a total of 60 wrist fractures at a mean age of 4917 years (WF) and 74 (16%) had a peripheral fracture at another site (OPF) (ribs, humerus, tibia, feet ankles . . .) at a mean age of 4918 years. These two fractured groups and the 337 women without any previous fractures (NF) had the same age, weight, height, nutritional calcium, prevalence of femoral neck fracture in the family and proportion (40%) and duration (77 years) of HRT use. Wrist fracture group and other peripheral fracture group had a decreased bone mineral density at both the lumbar spine (WF: 0.990.15, OPF: 0.980.16, NF: 1.070.17 g/cm2, p<0.0001) and the femoral neck (WF: 0.770.09, OPF: 0.770.10, NF: 0.820.11 g/cm2, p<0.0001). Women who had a wrist fracture before menopause (n=13, age at the fracture: 2513, Z-score at the lumbar spine: 0.600.82) were comparable with women who had a wrist fracture after menopause (n=35, age at the fracture: 587, Z-score: 0.090.89). Both were decreased compared to women without fractures (Z-score: 0.210.90). The same differences were observed at the femoral neck and for the other peripheral fractures. Conclusion: 1) Women with any previous peripheral, fractures besides wrist fractures, have an increased osteoporotic risk. 2) peripheral fractures occurring before menopause are associated with a decreased bone mineral density. This suggest that these pre-menopausal women had a dcreased peak bone mass at the ime of the fracture.



K G Faulkner1, E von Stetten2, E Orwoll3, 1Synarc, Portland, OR; Hologic Inc., Bedford, MA; 3Oregon Health Sciences University, Portland, OR, USA Recently it has been acknowledged that signicant T-score differences exist at various skeletal sites in Caucasian women (1). At the heel, few women have T-scores below 2.5, while most postmenopausal women will fall below this level with lateral DXA or QCT. As a result, a single T-score criterion cannot be universally applied to all BMD measurements and skeletal sites in women. However, potential normative database discrepancies have not yet been fully investigated in men. In this study, we compared the prevalence of osteoporosis in men (based on a 2.5 SD criterion compared to young normal Caucasian males) at different skeletal sites using manufacturer's normative data. We determined the expected mean T-score for a 65-year-old male at the heel (ultrasound), femoral neck (DXA), total hip (DXA), spine (DXA and QCT), and forearm (DXA). Assuming a normal distribution of T-scores, we computed the expected percentage

242 (218). MONITORING THERAPY RESPONSE WITH BONE DENSITOMETRY AND QUANTITATIVE ULTRASOUND IN WOMEN PARTICIPATING IN A REHABILITATION PROGRAM M. G. Glu er1, H. Minne2, A. Lazerescu2, M. Pfeifer2, B. Begerow2, er1, W. Polla hne2, 1Universitatsklinik CAU T. Schlotthauer2, C. Glu Kiel; 2Institut fur klinische Osteologie, Bad Pyrmont, Germany We investigated if therapy effects of a 2-year rehabilitation program can be demonstrated by Bone Densitometry (Hologic QDR) and Quantitative Ultrasound (QUS, Lunar Achilles). All women had been diagnosed with postmenopausal osteoporosis. Depending on their disease status they got recommendations for adequate drug. Women of group A (n=19, age 67.48.4) actually took mild medications (calcium, Vitamin D), while women of group B (n=48, age 62.46.6) took stronger treatments (bisphosphonates, hormones). After two years women of both groups gained bone mineral density (BMD) but their QUS parameters (SOS Speed of Sound and BUA Broadband Ultrasound Attenuation) were reduced (see table). Women in the strong treatment group gained more BMD and lost less in QUS parameters. Whether loss in QUS parameters was due to lack of treatment effect or was caused by download drift needs to be claried. Our results demonstrate the effectiveness of the rehabilitation program in increasing the BMD of the patients.

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Var BMD Lumbar spine BMD Total hip BMD Whole body SOS Calcaneus BUA Calcaneus

Mild treatment 2.7%* 0% n.s. 1.6%* 0.7%** 1.8% n.s.

Strong treatment 6.8%*** 3.2%*** 4.4%*** 0.4%** 0.9% n.s.

244 (220). CORRELATION OF BONE AREA WITH MUSCLE AREA IN LOWER LIMBS M. Hartard, A. Arians, D. Jeschke, M. Schwaiger, Working Group of MusculoSkelatal Interactions, Universities of Munich, Germany Positive correlations of bone mass to muscle mass, of bone mass to muscle force or of bone strength to muscle force have been corroborated many times over. The goal of this cross-sectional study was to correlate cross sectional areas of muscle and bone of the right lower limb. In nearly 300 healthy subjects of both sexes (9- 80 years) the cross sectional areas were determined from peripheral quantitative computed tomography (pQCT) using a STRATEC XCT 2000. Images were taken at 4%, 14%, 38% and 66% of tibia length, starting at the distal ankle joint of the right limb. Muscle cross sectional areas at 66% of tibia length correlated highly (R2=0,8) with pQCT derived bone cross sectional areas at 38% of tibia length. The high age-, gender- and motivation-unrelated correlation between the cross sectional areas of bone and muscle supports the hypothesis that muscle could be a leading variable estimating bone health. The strong correlation of cross sectional areas of bone and muscle might be valuable as a tool for diagnosis of bone diseases.

Signicant change: *p50.05; **p50.01; ***p50.001

243 (219). BONE STRUCTURE EVALUATION WITH MEASURES OF COMPLEXITY W. Gowin1, P. Saparin1, P. Kurths2, D. Felsenberg1, 1Univ. -Hosp. B. Franklin, Free Univ. Berlin, Germany; 2Inst. of Physics, Univ. Potsdam, Germany Objective: The purpose of this study was to develop parameters based on physical complexity to evaluate the architectural composition of human vertebral trabecular bone. Methods: 50 L3 and 57 L4 specimen (age:2492) were examined by QCT (BMD: 18144 mg/ml) and HRCT in axial 1mm slices. The method was developed on 1 mm slices and later transferred to the QCT-slices. The images were encoded with symbols using symbolic dynamics. 5 measures of complexity were derived from the data. The parameters describe the architectural composition (IGE), the regional complexity (SCI), the disorder of composition (SDI), the homogeneity, and the relation to the marrow space of the trabecular network. Results: The gures show IGE, SCI, and SDI in relation to BMD. D = L3, & = L4, osteopenia = 80100 mg/ml. The trabecular network of normal vertebrae has a orderly complex and differentiated composition, whereas osteoporotic lumbar vertebrae are much simpler composed. Osteopenic and mild osteoporotic vertebrae appear to be in a compositional transition with increased disorder of the trabeculae. In contrast to BMD, we found no age dependency for the structural parameters SCI, IGE, and SDI. Conclusion: The structural measures are remarkably sensitive to architectural composition and show no dependency of age in adult lumbar vertebrae.

245 (221). ULTRASOUND AND DEXA BONE MEASUREMENT IN FEMALE RHEUMATOID ARTHRITIS PATIENTS COMPARED WITH RANDOMLY SELECTED SUBJECTS IN THE POPULATION. PRELIMINARY RESULTS G Haugeberg1, R E Orstavik1, T Uhlig1, T K Kvien1, J A Falch2, J I Halse3, 1Oslo City Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo; 2Dept. of Internal Medicine, Aker Hospital, Oslo; 3 Osteoporosis Clinic, Oslo, Norway Background and Objective: The risk of vertebral fractures in rheumatoid arthritis (RA) patients seems to be less dependent on bone mass than in primary osteoporosis, suspecting a poorer bone quality in RA patients. Quantitative ultrasound is suggested to measure aspects of bone quality. The aim was to examine bone mass in female RA patients compared with randomly selected subjects in the population measured in spine and hip with dual energy x-ray absorptiometry (DEXA) and in the heel with quantitative ultrasound. Methods: A total of 28 female RA patients randomly selected from a RA register and 28 age matched female controls recruited

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randomly from the population were examined. Mean disease duration for the RA patients was 17.6 yrs and 35% were rheumatoid factor positive. Bone mineral density (BMD) measurements were performed in spine and in the hip using DEXA (Lunar Expert). Speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness were measured at the heel using quantitative ultrasound (Lunar Achilles+). The associations between DEXA and ultrasound measurements in the two groups were tested using Pearson's correlation coefcients. Results: No difference in age (61.9 vs. 61.8 yrs, P=0.96) and weight (64.5 vs. 68.8 kg, P=0.12) were found between the RA patients and the controls. No statistically signicant differences in BMD (g/cm2) were found between RA patients and the controls at the spine (1.04 vs 1.07, p = 0.56) and the hip (femoral neck: 0.80 vs. 0.84, P=0.29; total hip: 0.85 vs. 0.88, P=0.39). In RA patients a statistically signicant reduction was found in SOS (1493 vs. 1516 m/s, P=0.007) and Stiffness (67.2 vs. 75.9, P=0.043) but not in BUA (103.5 vs. 106.9 dB/MHz, P=0.30). The correlation coefcients (Pearson's r) between quantitative ultrasound (Stiffness) and DEXA (BMD in hip and spine) in RA were 0.59*, 0.65* and 0.44* for femoral neck, total hip and spine and for the controls 0.58*, 0.62* and 0.47*, respectively (*all P<0.02). Conclusion: A statistical signicant reduction was found for ultrasound (SOS and Stiffness) but not for BUA or BMD in RA patients compared with controls. Studies evaluating both DEXA and quantitative ultrasound and risk of fracture in RA patients are needed.

medical students. Peak bone mass is considered to be an important predictor for future fractures. Physical activity is, besides heredity, one of the main determinants of the observed variance in peak bone mass. Material and Methods: One-hundred and twenty-four healthy, non-smoking, Caucasian medical students, 62 women, 254 years (meanSD) and 62 men, 284 years, were investigated. Bone mineral density (BMD; total body, lumbar spine, and hip) and body composition were determined by DEXA (Lunar DPX-L). The current level (hrs/w) and type (hi, medium, and low) of impact loading activities were registered. Results: There were no differences in the amount or the participation rates in different impact loading activities between female and male students. In the female students, no association was found between current physical activity and BMD. A signicant positive association (r = 0.31, p = 0.014) was observed between age and fat mass. Using stepwise multiple regression, body weight was the only determinant of total body (b = 0.43, p = 0.001), trochanter (b = 0.37, p = 0.003), and lumbar spine BMD (b = 0.40, p = 0.001), while lean body mass was the only predictor of femoral neck BMD (b = 0.26, p = 0.038). In male students, the current level of high impact loading was positively correlated to BMD on all locations (r = 0.290.42, p 0.0010.023) and lean body mass (r = 0.27, p = 0.035). A signicant decrease in hip BMD (r = 70.330.37, p = 0.030.09) was observed with age. Age and fat mass was positively correlated (r = 0.25, p = 0.047). After stepwise multiple regression, lean body mass was a predictor (b = 0.390.45, p = 0.0010.004) of BMD on all locations, but the level of physical activity also predicted total body and hip BMD (b = 0.260.30, p = 0.0080.028). Conclusions: In female medical students, the level of current physical activity is not related to BMD. Body weight is the main predictor of BMD. In male students, high impact activities are related to BMD and lean body mass is the major determinant of BMD.

246 (222). PREDICTION OF PERIPROSTHETIC BONE LOSS AFTER HIP ARTHROPLASTY BY DEXA OF THE SPINE T. H. Hennigs, University of Frankfurt/M, Germany A periprosthetic bone loss occurs after total hip arthroplasty (THA) attributed to initial operative irritation, immobilization and stress shielding. Recent studies showed only a weak correlation between the BMD of the proximal femur and the amount of the postoperative bone loss. The aim of our study was to evaluate the predictive capacity of DEXA for the periprosthetic bone loss. In 38 subjects (f+m) aged 2265, with un-cemented THA, without suspected conditions affecting bone metabolism, we measured the BMD (Hologic, 4500 A) of the spine (L1-L4), the periprosthetic femur and the contralateral femur in the rst week and one year after surgery. Regions of interest (ROI) were dened according to Gruen. ROI 7 (calcar femoris) showed the highest amount of bone loss with a range up to 60 %. We found a high correlation between this bone loss and the BMD of the lumbar spine (r = ~0.74): with decreasing lumbar BMD (T-score) (x), the relative bone loss (y) was increasing (y = 0.7x2 6.1x + 19.1). The correlation of the BMD of the periprosthetic femur or of the contralateral femur with the bone loss was much weaker (r = 0.35 and 0.39, resp.). We conclude, that the predictive capacity for the early periprosthetic bone loss is much higher in the DEXA measurement of the lumbar spine than in that of the ipsi- or contralateral femur. A preoperative assessment of the expected bone loss is possible and represents a valuable aid in the planning and postoperative treatment of THA, mainly in supposed healthy candidates.

248 (224). QUANTITATIVE ULTRASOUND OF PHALANGES IN PATIENTS WITH END-STAGE RENAL FAILURE TREATED WITH HEMODIALYSIS C Horvath, S Meszaros, E Hosszu, J Szucs, N Szedelyi, G Deak, I Mucsi, 1st Dept Medicine, 2nd Dept Pediatrics, Semmelweis University, Budapest, Hungary End-stage renal failure is frequently resulted in low bone density and fractures. The aim of this study was to evaluate the ability of bone ultrasonometry to detect bone disease due to renal failure in comparison to bone densitometry. 32 patients (18 men and 21 women, age 54.114,3 ys) with end-stage renal failure treated with hemodialysis and 21 age- and sex-matched controls were studied. All patients were normocalcemic with a slightly increased serum PTH level. Bone densitometry was performed at lumbar spine and femoral neck (XR26, Norland) as well as at forearm (NK364, Gamma). Speed of ultrasound transmitting the phalanges (SOS) was also measured (DBM Sonic 1200, IGEA). Negative correlations were found between SOS and age and positive correlations between SOS and femur or radius BMD. In women the SOS positively correlated to bone-specic alkaline phosphatase, too. Our results suggest the phalangeal ultrasound to be a useful method in the diagnosis of renal bone disease. Results:
women patients LBMD FBMD RBMD SOS 0.937** 0.724** 0.724 1888.7* controls 1.078 0.895 0.778 1997.0 men patients 1.100 0.811* 1.180 1909.9** controls 1.090 0.942 1.220 2024.0

247 (223). BONE MINERAL DENSITY, BODY COMPOSITION, AND PHYSICAL ACTIVITY IN MEDICAL STUDENTS M. Hogstrom, H. Alfredson, R. Lorentzon, K. Thorsen, 1Sports Medicine, Department of Surgical and Perioperative Science, Umea University; 2Department of Musculoskeletal Research, National Institute for Working Life, Umea, Sweden The purpose was to examine the relationship between bone mineral density, body composition, and physical activity in

(p<0.05*, p<0.01**)

249 (225). AGE-RELATED DECREASE IN BONE ULTRASONOMETRY IN DENSITY-ADJUSTED WOMEN E Hosszu, V Ferencz, S Meszaros, E Csupor, E Toth, K Bors, E V McCloskey2, C Horvath, 12nd Dept Pediatrics, 1st Dept Medicine, Semmelweis University, Budapest, Hungary; 2WHO Collaborating Centre for Metabolic Bone Diseases, University of Shefeld, Shefeld, UK A growing body of evidences suggest that bone ultrasonometry (QUS) reects not only density but also non-mass properties of the bone. To test this hypothesis QUS was done in young and middle-aged women with the same bone mineral density. Patients: Y 22 healthy young women (age 21.72.1 ys) and for comparison: S 25 women (age 48.35.3 ys) adjusted for spine BMD, F 20 women (age 48.86.2 ys) adjusted for femur BMD, R 24 women (age 48.17.7 ys) adjusted for radius BMD, respectively. All women were premenopausal. Methods: BMD measurement was performed by DEXA at lumbar spine and femoral neck (DPX-L, Lunar) and by SPA at forearm (NK364, Gamma). Heel ultrasonometry was also done (Sahara, Hologic) and BUA, SOS, QUI and estimated heel BMD (eBMD) were calculated. Results: *p<0.01, **p<0.001
S BMD F BMD R BMD BUA SOS QUI eBMD 1.270.03 1.060.03 0.860.02 85.93.4 15977.5 119.14 0.680.03

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In conclusion, DXR provides a densitometry equivalent measurement of the distal forearm and hand and seems to offer new information on the structure of cortical bone. This may prove useful in the evaluation of bone loss, fracture risk and treatment effect.

251 (227). LONG-TERM EFFECT OF INHALED BUDESONIDE ON BONE METABOLISM IN ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) m2, C-G Lo fdahl3, 1University Hospital, O. G. Johnell1, R. Karlstro 2 Malmo, Sweden; AstraZeneca R&D, Lund, Sweden; 3University Hospital, Lund, Sweden on behalf of the EUROSCOP steering committee To assess the long-term effect of inhaled budesonide on bone metabolism, two groups of patients were investigated in two randomized trials. 165 asthmatic patients (86 F, 1859 years) were treated with Pulmicort Turbuhaler1 (BUD) at daily doses adjusted according to the severity of the disease, or non-steroid reference therapy for 2 years. 912 patients (254 F, 2565 years) with chronic obstructive pulmonary disease (COPD) were treated with BUD 800 mg/day or placebo for 3 years. In 161 COPD patients and in all asthmatics, BMD (lumbar spine and femoral neck) was measured at baseline, after 6 months, and at yearly intervals. In 653 COPD patients and in all asthmatics, the frequency of vertebral fractures was assessed at baseline and at the end of the treatment period. No statistically signicant difference in BMD and in the frequency of vertebral fractures was recorded between patients treated with Pulmicort Turbuhaler1 and control patients. After long-term treatment with BUD, no signicant effect could be detected on BMD or frequency of vertebral fractures in asthmatic patients or in patients with COPD compared with control patients.
Estimated differences between groups for change (%) in BMD over 2 years. Asthmatic patients BUD vs. Control L2-L4 Fem. Neck Est diff. Lower Limit CI 1.46 2.00 Upper Limit CI 0.76 0.60 p-value


1.060.03 69.43.5* 15525.5** 93.93.3** 0.520.03** 62.33.3** 15405.7** 85.73.2** 0.460.02** 0.840.01 66.03.3** 15485.7** 90.63.4** 0.500.03**

All QUS parameters correlated negatively with age and positively with spine or hip BMD. Conclusion: our results suggest that changes in bone quality/ structure occured with ageing can be responsible for the QUS differences between young and middle-aged women. Bone ultrasound reects denitely more than density alone.

0.35 0.70

0.5380 0.2900

250 (226). HORMONE REPLACEMENT THERAPY AND BISPHOSPHONATE TREATMENT EVALUATED BY NEW QUALITATIVE MEASURES OF CORTICAL BONE L. Hyldstrup, J. T. Jrgensen, L. Baeksgaard, T. K. Srensen, Dept. of Endocrinology, Hvidovre Hospital, University of Copenhagen, and Pronosco A/S, Denmark To evaluate longitudinal changes in BMD following treatment with HRT or bisphosphonate (BP), 121 postmenopausal women (75 controls, 32 using HRT and 14 on BP) were measured twice over 2 years with digital X-ray radiogrammetry (DXR) by Pro-nosco Xposure System and DXA of the spine, hip and forearm. Longitudinal changes in DXA-BMD were compared to changes in DXRBMD, cortical thickness of the 2nd metacarpal (MT2), porosity of cortical bone and striation of the distal radius. The expected annual reduction in BMD in the control group was detected by BMDspine (0.8%,p<.02), BMDhip (1.6%, p<.001), BMDforearm (1.5%, p<.001), DXR-BMD (0.8%, p<.001), and MT2 (1.1%, p<.001). In the HRT group only signicant reductions were seen in DXA-BMDhip, (1.0%, p<.01) and distal forearm (71.0%, p<.02), while striation increased (p<0.05). Comparing the HRT group with the untreated, the reduction in MT2 was signicantly smaller. In the BP group, only cortical porosity was signicantly reduced (p<.025). Comparing changes in the BP group with an age-matched subsample of controls, both DXRBMD, MT2, and porosity of cortical bone differed signicantly (p<.01, p<.05, p<.05, respectively), while the DXA measurements did not.

Estimated differences between groups for change (%) in BMD over 3 years. COPD patients L2-L4 Fem Neck 0.52 0.87 1.91 2.58 0.88 0.85 0.4667 0.3205

252 (228). BONE MINERAL DENSITY IN WOMEN WITH COLLES' FRACTURE. A CASE CONTROL STUDY E. Kanterewicz, A. Yanez, A. Perez-Pons, I. Codony, L. Del Rio, Hospital General De Vic and Cetir Medical Center, Barcelona, Spain Colles' fracture in postmenopausal women has been linked with lumbar and femoral osteoporosis. However, the direction of the association has not been not clearly established. Objectives: To evaluate the association between Colles' fracture and low bone mineral density (BMD). Methods: We undertook a case-control study including 58 postmenopausal patients with recent Colles' fracture and 83 population-based controls of similar age and menopausal status. Age of participants ranged from 45 to 80 years. BMD was measured by DXA (Lunar Expert) at the non-fractured wrist, lumbar spine and hip. WHO criteria (t-score <2.5 SD) were used to dene osteoporosis.

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Results: Cases were, on average, older than controls (mean age 65.8 years vs. 58.7, p<0.05). Mean body mass index (BMI) was the same in both groups (27.2 kg/m2). BMD was signicantly lower in cases than controls for all three areas (p<0.001). Osteoporosis was more prevalent in cases than in controls at wrist (60% vs. 35%, p<0.001), lumbar spine (47% vs. 20%, p<0.005) and total hip (19% vs. 6%, p<0.005). Osteoporosis (at lumbar spine and/or hip) remained signicantly associated with Colles' fracture: (OR 2.3, 95% Cl 1.15.1) after adjusting for age and BMI in a multivariate analysis. Conclusions: Colles' fracture in postmenopausal women is associated with osteoporosis in other areas commonly affected by osteoporosis as well as osteoporosis of the forearm.

Tanner stage, weight and shoe size, but dietary CA was not. In contrast, for BUA, neither dietary CA or level of WBA were signicant predictors after controlling for anthropomorphic parameters. The results of this cross-sectional study suggest, that prior to puberty, the level of WBA seems more important than dietary CA in the determination of QUS parameters.

255 (231). EVALUATION OF DUAL-X-RAY ABSORPTIOMETRY AND QUANTITATIVE ULTRASOUND IN POLISH WOMEN P. Leszczyn ski, J. K. Lacki, S. H. Mackiewicz, Department of Rheumatology, University School of Medicine, Poznan, Poland

253 (229). T-SCORE IS USEFULL TO DETERMINE PROBABILITY OF RISK OF VERTEBRAL FRACTURES BY QCT IN ELDERLY PATIENTS S. Kudlacek, O. Freudenthaler, J. Weissbo ck, H. Resch, B. Schneider, R. Willvonseder, Med. Dep. Barmherzige Bruder & Ludwig Boltzmann, Inst. of Aging Research, Vienna, Austria Bone mineral density determined by the DEXA (Dual X Ray Absortiometry) method is expressed as T-Score and/or Z-Score. T-Score has been accepted to classify osteoporosis of postmenopausal females. QCT has remained the gold standard of bone mineral density measurement but it is uncertain if T-Score classication can be adopted from results obtained by the DEXA methode. We have determined bone density by QCT and vertebral fractures in 534 postmenopausal females (60.98 years, median 60; 4083). Statistical analysis was performed to evaluate the predictive value of fracture probability between QCT (mg/cc), T-Score and Z-Score. ROC analysis and differences of AUC (area under curve) were calculated by a non-parametric contrast test. We found an overlap of QCT, T-Score and Z-Score in women beow age 55. When the whole study population including women up to 83 years was calculated, QCT and T-Score were superior. Occurence of vertebral fractures can be explained by T-Score and QCT (mg/cc) in 90%, by Z-Score in 77% (p50.0001). Our results demonstrate that T-Score classication is suitable for the QCT method to determine probability of fracture risk. If the same score classication can be adopted remains uncertain.

Objective: The aim of our study was to analyze BMD of the forearm, lumbar spine, hip and BUA and SOS of the calcaneus in Polish women. Materials and methods: A sample of 297 healthy women, average age 55.010.3 yrs (range 27 to 81 yrs) were involved in the study. BMD of the forearm was measured by DXA using DTX 200 and QUS parameters by DTU-ONE (all systems produced by Osteometer Medi-Tech A/S Denmark). BMD of lumbar spine and hip were measured by DXA using ECLIPSE densitometer (NORLAND Medical Systems, Inc., Fort Atkinson, WI). Results: Average BMD values of the forearm (BMDF), lumbar spine (BMDL) and hip (BMDH) were: 0.4080.069g/cm2, 0.9200.139 g/cm2, 0.7660.105 g/cm2 (respectively). Average BUA and SOS values were: 48.48.3 db/MHz and 154212 m/s (respectively). We have found signicant correlation between BUA and BMDF, BMDL, BMDH (r = 0.477, r = 0.398, r = 0.421; respectively) and between BMDF, BMDL, BMDH and SOS (r = 0.379, r = 0.422, r = 0.392; respectively). Conclusion: QUS and DXA correlate relatively closely but it is questionable whether the combination of these measurements improve the discrimination of women with increased risk of fractures.

256 (232). LUMBAR VERSUS THORACIC VERTEBRAL FRACTURE LOADS AND CORRELATION WITH IN-SITU AND EX-SITU DXA E.-M. Lochmu ller, D. Bu rklein, N. Krefting, J. Grimm, R. Mu ller, F. Eckstein, C.-C. Glu er, Universitatsfrauenklinik, LMU Munchen, Germany The purpose of this study was to determine the correlation of mechanical failure loads in the thoracic and lumbar spine, and to assess their association with DXA of the lumbar spine in-situ (including soft-tissues) as well as ex-situ. We studied 130 specimens (7910 yrs), measuring the BMC of L 24 with DXA in situ (AP) and ex situ (lateral and AP). Two segments of the thoracic (Th 57 and Th 911) and one of the lumbar spine (L 24) were tested as a functional unit in an axial compression test (400 mm/min). The failure load (but not the failure stress) of Th 6 was signicantly lower than that of Th 10 and L 3. In men, the fracture loads were signicantly higher than in women, also after adjusting for the vertebral cross-sectional area. The correlation of the fracture loads of Th 6 and 10 was r = 0.86, and those of Th 6 and Th 10 with L 3 0.65 and 0.71, respectively. Measuring the BMC in lateral (but not in AP) projection under ex-situ conditions improved the prediction of lumbar, but not of thoracic failure loads, compared with the AP in situ measurements (Table 1). The study shows that lateral ex situ DXA of the lumbar spine predicts lumbar failure loads with higher accuracy than in situ measurements. However, the prediction of thoracic failure loads is similar for both types of measurements.

254 (230). PREDICTING BONE MASS IN PREADOLESCENT GIRLS C. K. Kwoh, E. Trapl, L. Morgan, G. Warner, Case Western Res. U. and DVAMC, Cleveland, OH, USA We examined predictors of bone mass in a cohort of 8 to 10 year old girls. Bone mass was assessed using quantitative heel ultrasound (QUS). Bone mass parameters included Bone Ultrasound Attenuation (BUA), Speed of Sound (SOS) and a calculated stiffness index (STIFF). Girls with chronic diseases or on medications known to affect bone mass were excluded. Assessment included, height, weight, Tanner stage, dietary calcium intake by 3-day food diary (CA), and level of weight bearing activity (WBA). The mean age of the 160 girls was 9.30.6 years (meansd) and 91% were white. Forty percent were in pre-puberty or early puberty and 88% were in mid-puberty. Anthropomorphic characteristics were height 1.40.07 m, weight 36.59.0 kg, and lean body mass 28.97.7 kg. Mean bone mass parameters were 94.411 for BUA, 153823 for SOS, and 73.712 for STIFF. Mean dietary CA by food diary was 1090442 mg/day and mean WBA was 2.95.2 hours/week. Level of WBA (by tertiles) was a signicant predictor of SOS and STIFF after controlling for

Table 1: Correlation (r) of BMC vs. failure load L3 L24 in situ AP L24 ex situ AP L24 ex situ lat 0.73*** 0.66*** 0.84*** Th10 0.74*** 0.69*** 0.74*** Th 6 0.68*** 0.69*** 0.68***

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muscle strength in the model. The question is whether BMD is a proxy for another variable like muscle strengths?

259 (235). BONE MINERAL DENSITY (BMD) OF TOTAL BODY (TB) AND LUMBAR SPINE (LS) DURING PUBERTY. A CROSSSECTIONAL STUDY O. D. Messina1, A. M. Armatta2, G. L. Araujo1, C. Bianculli2, J. C. Barreira1, J. A. Maldonado Cocco1, 1Rheumatology; 2Pediatrics Services, Hospital Dr. Cosme Argerich, Buenos Aires, Argentina Objective. To establish regional normative values for TB and LSBMDs and total body bone mineral content (BMC) derived from healthy children of both sexes, according to pubertal development. Method. 100 Females and 100 Males, aged 10 to 20 years were studied; 20 at each stage were sexmatched. Pubertal stage (by Tanner 5-grading scale) and anthropometric measures were recorded. Posteroanterior LS-BMD, TB-BMD and TB-BMC were measured by DEXA (Lunar DPX L). Results. Mean values and SD in early and late puberty were respectively: LS-BMD F: 0.814 (0.120) g/cm2 and 1.154 (0.107) g/cm2; M:0.740 (0.111) g/cm2 and 1.114 (0.121) g/cm2; TBBMD F: 0.914 (0.072) g/cm2 and 1.102 (0.065) g/cm2; M: 0.918 (0.058) g/cm2 and 1.184 (0.087) g/cm2; TB-BMC F: 1442 (264) g and 2181 (288) g; M: 1518 (339) g and 2922 (404) g. Increments on either BMDs and BMC in F among Tanner stages 1234 and in M among Tanner stages 12 and 345 were statistically signicant. Higher mean LS-BMD values were shown in F at stages 3 and 4 than in M at same pubertal stages (p<0.05), reecting the impact on trabecular bone of the earlier female gonadal maturition and menarche. However, males showed higher TB-BMD at stage 5 (p<0.05) and higher TB-BMC at stages 2 and 5 (p<0.05) than females at same pubertal stages. High correlations were determined between TB-BMD and weight in M (r: 0.81) and between TB-BMC and weight in both sexes (F r: 0.85, M r: 0.90) and height in M (r: 0.84). Conclusions. A large amount of the observed changes on LSBMD, TB-BMD and TB-BMC during puberty is accounted for by growth and pubertal development, showing marked sex differences.

257 (233). A STUDY OF LUMBAR BONE MINERAL DENSITY AND ITS MORPHOLOGICAL EXAMINATION E. Matsuyama, Y. Sen, Nara Medical University, Kashihara, Nara, Japan The purpose of the present study is to investigate the sexual difference in the morphology of the lumbar vertebrae including not only the vertebral body itself but the posterior elements, and to analyze the relation between the morphological change and BMD. All the subjects who consisted of 220 female and 86 male underwent roentgenography and the BMD measurement using DXA method. The BMD of the lumbar vertebrae ranging from L2 to L4 showed little statistical difference between men and women. The measured values of area, width, and height were greater in men than in women, because of the difference in physical constitution. In morphology of the lumbar vertebrae, it was natural that all the parameters except the interpedicular distance should be smaller in women than in men, because of their physical constitution. In order to compare the morphology of the lumber vertebrae, it should be corrected by the size of the skeletal structure. Therefore we used the relative values to compare between each parameter. From the results of this study, we concluded that the difference between men and women in the size of the bony structure was natural and that the shape of the vertebrae was the most important factor in the vertebral morphology. The cross section of the vertebral body to the height of the vertebral body was smaller in women, and the posterior elements were relatively larger in women than in men, in spite of smaller size of the vertebral body. However, it is important that the absolute value of the posterior elements was smaller in women. Moreover, it is suggested that the real BMD is higher in women than in men.

258 (234). IS BMD RELATED TO COGNITIVE FUNCTION? A POPULATION-BASED STUDY D. Mellstro m, C. Nyman, K. Landin-Wilhelmsson, L. Hulten, L. Samuelsson, R. Lorentzon, E. Norjavara, O. Johnell, Dept Geriatrics and Internal Medicine, University of Gothenburg, The National Service Administration Regional Ofce, Gothenburg, Depts Orthopedic, Unica and Malmo , Astrazereca, Lund, Sweden BMD is useful to predict fractures as well as mortality. Our question is whether BMD is related to cognitive functionintelligence quotient (IQ)? At 18 years of age all men in Sweden must perform a 2-day test before selection to compulsory military service. 96% attend this test. The test consists of several parts: questionnaire, anthropometric measurements, physical tests (muscle strengths, oxygen uptake etc) and cognitive function. We added a BMD measurement of the right calcaneus, DXACalscan. 3,015 men were included. Mean age 18.3 (0.3), weight 73.1 (11.0) kg, height 180.4 (6.7)cm. IQ was signicantly correlated to height (r = 0.14), BMD (r = 0.05), muscle strength (r = 0.10), endurance test (r = 0.15). In a covariance analysis BMD remained signicant in a model with age, height and weight. For quintiles of IQ BMD was 0.62, 0.64, 0.64, 0.65, 0.64. In young men the signicant correlation with BMD remained also after controlling for age, height, weight, but was not signicant after including

260 (236). DIFFERENCES IN BMD BY USING DIFFERENT DENSITOMETERS OR BY MEASURING DIFFERENT SITES OF SPINE IN OSTEOPOROTIC VERTEBRAL FRACTURES W. N. Moon1, H. J. Oh2, 1Orthopedic Surgery, Sungkjunkawn Univ.; 2Family Medicine, Sungkyunkawn Univ., Samsung Cheil Hospital, Seoul, Korea Purpose: This study was done to see whether types of DEXA and levels of lumbar vertebrae show any differences in making standard values of lumbar bone mineral density (BMD) in osteoporotic vertebral fracture. Materials and Methods: Sixty osteoporotic vertebral fracture out of 462 postmenopausal patients were subdivided into QDR group and DPX group according to densitometers (QDR 39 patients, DPX 21 patients). The BMD was compared between two groups. The difference between BMD measured in L3 and that measured in L24 was analyzed by student t-test. Results: There was no difference between BMD of L3 and L24 standard level (p>0.05). The mean BMD measured by QDR and DPX using L24 standard were 0.6670.127g/cm2 and 0.7560.123g/cm2 respectively and showed statistically signicant difference (p = 0.012). Conclusion: The type of bone mineral densitometer should be taken into consideration in follow-up of osteoprosis patients and

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the L3 standard level might have no superiority over the conventional L24 standard level in measuring BMD in osteoporotic vertebral fracture patients. 263 (239). QUANTITATIVE ULTRASOUND AT THE HAND PHALANGES AND ANTHROPOMETRIC PARAMETERS IN POLISH NORMAL CHILDREN AGED 813 YEARS: A PROSPECTIVE STUDY


261 (237). RELATIONSHIPS OF SPINAL BMD AND REPRODUCTIVE HISTORY IN POSTMENOPAUSAL KOREAN WOMEN H. J. Oh, W. N. Moon, H. K. Yoon, I. K. Han, Sungkyunkwan University, Seoul, Korea The purpose of this study was to determine the associations of spinal BMD and reproductive risk factors including YSM, weight, BMI and gravidity and numbers of delivery of Korean menopausal women. We have evaluated general characteristics, spinal BMD, and reproductive histories those were assessed by simple questionnaires of 625 peri and postmenopausal women. Our results revealed that: 1) In simple correlation analysis, BMD was associated positively with weight (r = 0.261, P<0.01) but negatively with YSM (r = 0.47, P<0.001). 2) After controlling age, BMI and YSM, spinal BMD was negatively correlated with numbers of delivery (r = 0.159, P<0.001). 3) YSM, weight, number of delivery and age were revealed as important factors that predicting spinal BMD by multiple stepwise regression analysis. These results could suggest that YSM is one of the most important factor that predicting BMD. And numbers of delivery also might affect BMD in postmenopausal women.

W. Pluskiewicz, Z. Halaba, Silesian School of Medicine, Zabrze, Poland In the prospective study 288 normal Polish children (146 girls and 142 boys) aged 813 y. were evaluated. The time interval between the 1st and 2nd examination was 12 months 1 month. Following anthropometric parameters were measured: height, length of the trunk with lower limbs, length of the trunk, length of the lower and upper limbs and lateral reach. Bone status was assessed using quantitative ultrasound (QUS) at the proximal phalanges II-V of the hand using DBM Sonic 1200 (Igea, Italy). Amplitude dependent Speed of Sound (Ad-SoS [m/s]) was established. CV% was 0.64. sCV% was 7.13%. Results: In girls the growth rate of height and the growth rate of the length of the lower limbs diminishes from 10 year while the growth rate of Ad-SoS and the growth rate of the length of the trunk increases from 11 year. In boys we did not observe the increase of the growth rate of AdSoS and the length of the lower limbs while the growth rate of height and the length of the trunk increases from 11 year. Among all studied children we have observed positive signicant correlation only between the growth of Ad-SoS and the growth of height r = 0.58, p = 0.009 and the growth of the lateral reach r = 0.52, p = 0.022. Menstruating girls had higher values of Ad-SoS than non menstruating but these differences were signicant only in the group of 12 years (p = 0.009). Concluding, QUS at the hand phalanges is able to detect skeletal changes during childhood and adolescence in Polish normal children.

262 (238). BONE MINERAL DENSITY IN PATIENTS WITH ANOREXIA NERVOSA J. M. Olmos, J. Mene ndez-Arango, J. L. Pen a, J. Mart nez, J. A. Amado, J. Gonza lez-Mac as, Dpto. Medicina Interna Y (*), S. Psiquiatria Hospital Universitario Marque s de Valdecilla, Santander, Spain Objectives: A) To evaluate spinal and femoral bone mineral density (BMD) in patients with anorexia nervosa (AN) and its relation with clinical data. B) To determine the course of BMD in AN patients after two years of follow-up. Patients and methods: We studied 25 women with AN (DSM-IV) aged 1536 years (mean SD; 275). Mean body mass index (BMI) was 15.42.3 Kg/m2 and duration of AN was 5.53.4 years. BMD was determined in lumbar spine (LS) and femoral neck (FN) by dual-energy-X-ray absorptiometry (Hologic QDR, 1000). Clinical and densitometric studies were repeated in 8 patients two years later. 38 healthy women (265 years) with a normal BMI (202 Kg/m2) were utilized as a control group. Results:
BMD (g/cm2) Spine A.Nervosa Controls p 0.8190.124 1.0090.097 <0.001 Femoral neck 0.7200.125 0.8390.110 <0.01

264 (240). PATHOGENESIS OF COLLES' FRACTURE S. Pors-Nielsen, Xiong Xie, O. Ba renholdt, Hillerd Hospital, Denmark This investigation was undertaken after it was observed that Colles' fracture often occurs in women with normal lumbar spine and hip BMD. Problem: Why do Colles' fractures occur where they do? (in our hands from 7 to 20 mm from the joint gap). Or: Are there any specic features of the cross-sectional geometry or volumetric density at that site? Material: 70 consecutive post-menopausal women with Colles' fracture, mean age (SD) 64.1 (13.1) and 34 pre-menopausal women without fractures ever, mean age 49 (9.7) years. Methods: 1) Multilayer CT with Scanco Densiscan 1000 using a dedicated software was done at an ultradistal site rich in trabecular bone including the typical Colles fracture site, and a more proximal site rich in cortical bone (non-fractured arm measured). Precision error: less that 0.1% for standards measured daily over 152 days. 2) Transaxial quantitative ultrasonometry (tQUS) was done with Sunlight Omnisense , measuring speed of sound (SOS) along the long axis of long bones. Results: Moving proximally mean trabecular volumetric density (TVD) started to decline one cm from the joint gap in both groups; mean cortical thickness of non-fracture and fracture cases started to diverge at the same site. The following variables were lower (p<0.001) in the fracture cases: Mean ultradistal TVD, mean ultradistal and proximal cortical volumetric density (CVD), mean ultradistal and proximal cortical thickness. Cross-sectional total bone area and cortical bending moment of inertia were identical in the two groups, suggesting that the deforming force of Colles' fracture has a transaxial direction (fall on outstrched arm), resulting in a crush fracture, and that it is not a bending force. SOS correlated with mean CVD, mean cortical crosssectional area, and mean cortical thickness at the cortical rich proximal site. However, pQCT and tQUS did not correlate

Both spinal and femoral BMD were inversely correlated with the duration of AN (r = 0.43; p<0.05 and r = 70.41; p<0.05 respectively). BMI was slightly increased (1.31.2 kg/m2) in patients after 2 years of follow-up. However, BMD decreased in LS and remained unchanged in FN. Conclusions: A) Women with, AN have a reduced spinal and femoral BMD that is correlated with the duration of the disease. B) Bone loss in LS persisted in patients followed during two years, in spite of the stabilization of BMI.

sufciently well to justify individual prediction of one from the other. Conclusions: 1) The deforming force in Colles' fracture is a transaxial one; 2) Colles' fracture is a crush fracture; 3) Specic cross-sectional properties of the distal radius are characteristic of Colles' fracture.

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8 boys (mean age 14.60.5 years; height 1.550.03 m; weight 44.92.8 kg) with scoliotic disease of III and IV degree of severity; II group 9 girls (mean age 13.90.6 years; height 1.670.03 m; weight 48.64.2 kg). Control group (CG) was made up by girls standardized by age, sex etc. To evaluate the structuralfunctional state of bone tissue ultrasound densitometer ``Achilles+'' (Lunar Corp., Madison, WI) was used. Speed of ultrasound spreading (SOS, m/sec), broadband ultrasound attenuation (BUA, dB/MHz) and Stiffness, index of bone tissue (SI, %) were determined. Compared to CG the most consi-derable changes in structural-functional state of bone tissue were revealed in patients with scoliotic disease of III and IV degree of severity (girls SOS: I group 15565 m/sec; CG 15765 m/sec; p<0.05; BUA: I group 97.51.8 dB/MHz; CG 110.12.0 dBMHz; p<0.001; SI: I group 80.81.8%; CG 94.82.2%; p<0.001; boys SOS: I group 15407 m/sec; CG 15745 m/sec; p<0.05; BUA: I group 93.93.3 dB/MHz; CG 109.62,4 dB/MHz; p<0.001; SI: I group 73.74.0%; CG 94.22.2%; p<0.001). Ultrasonometry data considerably deteriorated in girls with progression of the disease's severity: SOS: I-II degree 15597 m/sec; III-IV degree 15565 m/sec; BUA: I-II degree 109.73.9 dB/MHz; III-IV degree 97.51.8 dB/MHz; SI: I-II degree 90.63.9%; III-IV degree 80.81.8%; p<0.001. Thus, we have revealed considerable structural-functional disorders of bone tissue in patients with scoliotic disease of IIIIV degree of severity. Disorders become more pronounced with progression of the disease. Decrease in bone density, deterioration of its quality in children and adolescents with scoliotic disease make it necessary to control its state constantly by means of densitometry and to carry out the appropriate medical and prophylactic measures.

265 (241). ABILITY OF A COMBINATION OF pDXA MEASUREMENTS OF THE OS CALCIS AND FOREARM TO SCREEN WOMEN AT MENOPAUSE FOR OSTEOPOROSIS J. M. Pouilles, F. A. Tre mollieres, J. Gauchiran, C. Ribot, Menopause & Bone Disease Unit, Dept of Endocrinology, CHU Rangueil, Toulouse cedex, France Axial DXA is currently considered the gold standard for the evaluation of osteoporosis. However, peripheral BMD measurements by pDXA using lower cost and portable devices are being increasingly used for screening. The aim of this study was to evaluate the usefulness of combining in a same patient two peripheral measurements (os calcis and distal forearm) using a new pDXA densitometer (PIXI, Lunar) in identifying postmenopausal women with axial osteoporosis. 362 healthy postmenopausal women (mean age 546 yrs [range 4069]) had BMD measured the same day at the lumbar spine (LS) and femoral neck (FN) by DXA (DPX-IQ, Lunar) and at the os calcis and forearm by pDXA. Moreover, 228 ``young'' normal women aged 2039 yrs were measured for T-score calculation. The shortterm precision of the PIXI densitometer assessed in 10 subjects was 1.5 % both for the os calcis and forearm. 23% of the women were classied as being osteoporotic (Tscore 42.5) using LS and/or FN BMD measurements as compared to only 5.2% and 6% at the os calcis and forearm, respectively. 25% of women with axial osteoporosis had a normal peripheral T-score (5 1 SD) at the os calcis and 29% of those osteoporotic women had a normal forearm T-score. The pDXA Tscore threshold value that allowed to detect 95% of women with axial osteoporosis (either LS or FN) was similar for the os calcis and forearm and was 0. Twenty two to 34% of the women were above this cut-off at the os calcis and forearm, respectively and thus could be excluded from further axial measurement. Combining the two peripheral sites slightly improved the performance of screening in increasing to 43% the number of women who would not need further axial measurement. Of the women recommended for axial measurement, only 10% had a normal LS and/or FN T-score (5 1) (false positives). The results of this study suggest that the ability of pDXA measurements to screen early postmenopausal women with axial osteoporosis is poor but might be enhanced when combining 2 peripheral sites.

267 (243). ULTRASOUND DENSITOMETRY INDICES AMONG WOMEN WITH COLLES' FRACTURE IN POSTMENOPAUSAL PERIOD V. Povoroznjuk1, V. Fischenko2, V. Kostuk2, 1Institute of Gerontology AMS Ukraine; 2Medical University of Vinnytcya, Ukraine This research was aimed at studying the bone tissue state among women with Colles' fracture with aid of the ultrasound densitometry method. The total of 41 healthy postmenopausal women 4274 years old (62.17.5) having Colles' fracture in their anamnesis (CF) were examined by ultrasound bone densitometer ``Achilles+'' (Lunar Corp., Madison, WI). The control group included postmenopausal women without any osteoporotic fractures in their anamnesis (WF), being standardized by age, BMI, etc. The speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and a calculated ``Stiffness'' index (SI, %) were measured. The main risk factors for the osteoporotic Colles' fracture turned out to be a menarche after 15 years, an early and late menopause. 29.3% of patients with Colles' fractures had a bone tissue stiffness index coinciding with the limit of fracture risk or under it. There was no revealed relation between the age and the ultrasound densitometry indices among women of posmenopausal age without fractures. Only 12.5% of patients with Colles' fractures were noticed to have a normal bone tissue. The ultrasound parameters were veritably lower among postmenopausal women with CF than among WF (SOS: CF 152428.4; WF 154324.3, p50.05; BUA: CF 10217.8; WF 10912.0, p<0.05; SI: CF 7614.9; WF 3513.5, p<0.05; all values are the mean SD). It is caused by the decrease of bone tissue mineral density, it's accelerated aging, and the development of osteopaenia and osteoporosis. The most tangible differences in these indices were noticed among the elderly patients. Colles' fracture indicates osteopaenia and osteoporosis in postmenopausal period. In summary, ultrasound densitometry is an effective screening method to reveal the women of risk group having future osteoporotic Colles' fracture in postmenopausal period.

266 (242). STRUCTURAL-FUNCTIONAL STATE OF BONE IN PATIENTS WITH PRONOUNCED FORMS OF SCOLIOTIC DISEASE V. V. Povoroznyuk1, V. Ya. Fishchenko2, D. V. Ulyeshohenko2, V. A. Ulyeshchenko, 1Institute of Gerontology, S. Ukraine; 2Ukrainian Scientic Research Institute of Traumatology and Orthopedics, Health Ministry of Ukraine, Ukraine Studying of etiology and pathogenesis of scolictic disease plays a leading role in the problem of its treatment. Many national and foreign authors payed great attention to it in their works but a number of unresolved problems still remain. One of them is to assess the inuence of structural-functional state of the bone on the development of scoliotic disease. To study the structuralfunctional state of bone in children and adolescents with scoliotic disease depending on the degree of disease's severity, 82 patients aged 1116 years were examined. People examined were divided into the following groups; I group 25 girls (mean age 14.70,4 years; height 1.590.02 m; weight 49.01.9 kg) and

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268 (244). INTERPRETATION OF BONE DENSITY RESULTS IN YOUNG WOMEN J. Przedlacki, M. Wieliczko, W. Tlustochowicz, J. MatuszkiewiczRowinska, K. Ostrowski, National Center of Osteoporosis, Medical University of Warsaw, Warsaw, Poland The purpose of this investigation was to evaluate the interpretation of DXA results in young women (age up to 45 y, Young-Adult). The BMD result depends on sex, age as well as on the bone volume, so T-score which is taken as criterion of diagnosis of osteoporosis is simplied parameter only (does not depend on body weight, when Z-score depends on it). BMD was measured in 39 women aged 39.36.6 y (2045 y) with low body weight 47.52.8 kg (38-arbitrary taken 50 kg) using Lunar DPX-L equipment in lumbar spine region. BMI was 18.91.4 (15.223.2). The indication for bone densitometry was prophylaxis of osteoporosis in 19, bone pain in 12, X-ray suspicion of osteoporosis in 10, bone fractures in 3, other in 3 women. Bone fractures were recognised in 5 women. Osteoporosis was diagnosed in 4, osteopenia in 17 and normal result in 18 women on the basis of T-score value (traditional way). When Zscore was taken as the criterion of diagnosis, osteoporosis was recognised in 2, osteopenia in 9 and normal result in 28 women. The diagnosis was changed in 12 women. We conclude that in young women (aged up to 45 y) the diagnosis of bone mineral disturbances (osteoporosis among others) ought to be based on Z-score value and not on T-score value. Z-score value ought to be taken as their own peak bone mass parameter.




Fat free mass 15.80 kg (79.39 % of body weight) 15.36 kg (79.9 % of body weight) Fast mass 4.10 kg (20.60 % of body weight) 4.19 kg (21.1 % of body weight)

We have observed a mildly increased fat mass vs normal for age and sex, both on anthropometric remarks and DEXA. The nutritional support so far settled seems to have produced an overall correct growth in terms of total BC in this child after 3 years of NTBC therapy. We believe that anthropometry and DEXA represent useful tools to monitor dietary intake or therapy and their impact on BC in children with HT.

270 (246). SIMULTANEOUS DUAL-FEMUR SOFTWARE IN CLINICAL PRACTICE USING DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA): VALIDATION OF SYMMETRY F. Sarter, J. Felt, G. J. Boyd, D. Clain, D. Feiger, D. Schneider, D. J. Sartoris, University of California School of Medicine, San Diego, CA, USA PURPOSE: To investigate the clinical value of simultaneous dualfemur acquisition software using DXA, with particular reference to degree of side-to-side symmetry, and to generate specic recommendations concerning scanning the dominant versus non-dominant femur at institutions where such advanced software is currently unavailable. METHODS: Approximately 400 male and female patients with clinical risk factors for low bone mass referred for two-site (spine, proximal femur) DXA were included in the study population. All subjects underwent femoral densitometry utilizing simultaneous dual-femur acquisition software installed on a Lunar DPX-IQ pencil-beam tabletop DXA system. Bone mineral content (BMC), projected area (cm2), bone mineral density (BMD), % young normal mean, T-score, % age-matched mean, Z-score, neckshaft angle, and regional % body fat were recorded for the right versus left sides, with bone regions-of-interest including the femoral neck, Ward triangle, greater trochanter, proximal diaphysis, and total proximal femur. Average values for BMD, % young normal mean, T-score, % age-matched mean, and Z-score were also documented, along with side-to-side differences. Statistical analysis with particular reference to symmetry was performed using Minitab version 12 software. RESULTS: Patients ranged in age from 2793 (mean 63) years, with height ranging from 6074 (mean 65.5) inches and weight ranging from 90263 (mean 142) pounds. Representative ranges and mean values (total proximal femur) for the various measured parameters were as follows:
%FAT R MIN R MAX R MEAN L MIN L MAX L MEAN 5.7 34.4 19.9 8.3 36.0 21.0 N-ANGLE 49.0 61.0 54.0 49.0 62.0 55.2 BMD 0.42 1.194 0.844 0.501 1.199 0.853 %YOUNG 39.0 110.0 83.5 50.0 110.0 84.3 T-SCORE 5.2 0.8 1.38 4.2 0.9 1.31 %AGE 46.0 118.0 95.3 65.0 119.0 96.3 Z-SCORE 3.8 1.4 0.34 2.5 1.02 0.88

269 (245). TOTAL BODY COMPOSITION IN A CHILD WITH HEPATORENAL TYROSINAEMIA D. Rigante1, P. Ranieri2, E. Holme3, G. Segni1, P. Caradonna2, 1 Department of Pediatrics; 2Department of Internal Medicine and Geriatrics, Universita Cattolica Sacro Cuore, Rome, Italy; 3 Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden An adequate nutritional support is rstly reected on a balanced total body composition (BC), especially for inborn errors of metabolism receiving benet from dietetic regimens: therefore the evaluation of total BC and of fat/lean mass distribution are essential for assessing a personalized diet or optimizing therapy. Hepatorenal tyrosinaemia (HT; fumarylacetoacetase deciency, McKusick 276700) is an inherited metabolic disorder (incidence 1: 100.000), characterized by hepatic cirrhosis, renal tubular dysfunction and acute porphyria. Children with HT improve remarkably with low Phe/Tyr medical foods and specic therapy with NTBC [2-(2-nitro4-triuoro-methylbenzoyl)1,3-cyclohexanedione]. We report a case of a 6 year and 3/12old female child, who -at the age of 3 years, after having reached normal developmental milestones- presented signs related to invalidating rickets, which led to the diagnosis of HT. Since then the child has been treated with a Phe/Tyr restricted diet (daily intake of proteins: 1.35 g/kg), Maxamaid X-Phen Tyr-SHS (75 g/day) and NTBC (1 mg/kg/day). She actually has a weight of 21.3 kg (508 centile), a height of 113.5 cm (25508 centile) and total BC has been evaluated with (1) anthropometric measurements of wrist, mid-arm, arm, waist, hip, thigh, mid-thigh, calf circumferences and triceps, biceps, subscapular, abdominal, sovrailiac, anterior/posterior thigh, calf skinfold thicknessess according Brook's equation (software Master Ver. 1.1 Dietosystem) and (2) dual energy X-ray absorptiometry (DEXA, Hologic QDR 2000) at the lumbar spine (L2-L4) and at the femoral neck. The results are shown in the following table:

No signicant dierence was found between regional % body fat, BMD, % young normal mean, T-score, % age-matched mean, and Z-score for the two sides (p = 0.19 to 0.65). Signicant asymmetry was found between neck-shaft angle on the two sides (p = 0.0036). The right-left dierence in BMD ranged from 00.229 (mean 0.036) g/cm2. CONCLUSION: The results of this investigation generally support previous studies indicating clinically insignicant differences between dominant versus non-dominant proximal femur DXA results. However, dual-femur acquisition may be necessary in certain patients where signicant side-to-side asymmetry may occur. Such situations may be encountered in the setting of

severe scoliosis, hemiparesis or hemiparalysis, unilateral arthritis of the hip joint, leg-length discrepancy, and a variety of congenital/developmental deformities.

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ment exists such that standardization is necessary for diagnostic uniformity.

R^2 Values

DTX200 0.77

PDEXA 0.73 0.61

PIXI 0.85 0.78 0.82

QDR4500 0.82 0.74 0.92 0.89

X-Posure 0.64 0.57 0.51 0.68 0.57

271 (247). RESULTS OF THREE YEARS OF BONE DENSITY TESTING IN SOUTHEASTERN MICHIGAN L. Scheiber, L. Torregrosa, P. Bereziuk, Henry Ford-Wyandotte Hospital, Wyandotte, MI, Objective: The purpose of this study was to analyze three years of bone density testing performed in southeastern Michigan. Methods: Henry Ford-Wyandotte Hospital acquired a Hologic QDR 1000 and opened an osteoporosis testing center in April of 1996. In the rst three years of operation ninety-ve physicians referred 4,147 patients to the center for a central bone density test. Of those tested 3,955 were women and 192 were men. Results: Using NOF/WHO criteria for the diagnosis of osteoporosis, of the 3,890 consecutive Caucasian women ages 19 to 94 yo scanned, 1,696 or 44% were osteoporotic, 1,579 or 40% were osteopenic, and 615 or 16% were normal. Of the 1,696 Caucasian women that were osteoporotic 333 or 19% were under sixty years of age. Of the 1,579 osteopenic women, 649 or 41% were under sixty years of age. In the group of women seventy years of age and over 62% were osteoporotic and 32% were osteopenic, only 6% were normal. One hundred ninety Caucasian men between the ages of 24 to 92 yo were scanned. Of these, 78 or 41% were osteoporotic, 73 or 38% were osteopenic and 39 had a normal scan. Fifty-one African Americans were scanned. Of the forty-nine African American women tested seventeen or 35% were osteoporotic, twenty-two or 45% were osteopenic and ten had a normal scan. Two African American men tested, both were osteopenic. Twelve Hispanic women were tested with three being osteoporotic, eight being osteopenic and one normal. Four Asian women were tested with one osteoporotic, two being osteopenic and one normal. Conclusion: In our community osteoporosis is clearly not a disease isolated to our Caucasian senior citizens. DXA scanning has facilitated early identication and treatment of osteoporosis and osteopenia in our community in a variety of races and in individuals ranging from 19 years old to 94 years of age.


273 (249). PREDICTION OF FRACTURES IN THE EARLY POSTMENOPAUSAL PERIOD; USE OF DUAL ENERGY X-RAY ABSORPTIOMETRY (DXA) AND QUANTITATIVE ULTRASOUND (QUS) A. Stewart, D. M. Reid, Osteoporosis Research Unit, Dept of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK QUS has been shown to be a predictor of osteoporotic fractures in the elderly. Studies in younger women are rare. 1000 women underwent QUS measurement using a Walker Sonix UBA 575, measuring broadband ultrasound attenuation (BUA) in 19901 and DXA scan of spine (L2-L4) and hip. Beginning Dec. 1997 these women were asked for a follow-up scan, and completed a questionnaire with regard any fractures they had sustained since baseline. 81 women have a fracture of any site/trauma from a total of 742 attending for follow-up. Relative risks (RR) (adjusted for age, body mass index and years postmenopause) were calculated and are as follows (RR with 95% CI for one SD): BUA 1.52 (1.171.96), L2L4 1.70 (1.282.26), Neck 1.47 (1.111.94). Combining both DXA and QUS slightly improved the RR's (L2L4*BUA 1.80 (1.362.39), Neck*BUA 1.70 (1.282.26)). If we examine the fractures which have occurred only at the site of wrist, ankle or hip and repeat the adjusted RR we nd the values are as follows: BUA 1.49 (1.052.13), L2L4 1.70 (1.162.49), Neck 1.47 (1.002.15), L2L4*BUA 1.79 (1.212.63), Neck*BUA 1.68 (1.142.49). ROC analysis showed areas under the curve (AUC) ranging from 0.56 To 0.62 but there was no signicant difference in the AUC's. In conclusion DXA and BUA can predict those who have fractures in the early postmenopausal period regardless of trauma level.

272 (248). IS THERE A NEED FOR FOREARM BMD STANDARDIZATION? A DIAGNOSTIC COMPARISON OF SIX DENSITOMETERS J. A. Shepherd, X. G. Cheng, C. F. Njeh, T. Fuerst, M. Grigorian, J. O. Toschke, H. K. Genant, Osteoporosis & Arthritis Research Group, University of California, San Francisco, CA, USA As part of an effort understand the differences in devicedependent osteoporotic diagnosis, 101 women, aged 20 to 80 (ca. 16 per decade) were scanned on six forearm bone densitometers: the Aloka DCS600EX, the Hologic QDR4500A, the Lunar PIXI, the Osteometer DTX200, the Pronosco X-Posure, and the Norland pDEXA. The scans were analyzed using the manufacturers' suggested methods. Comparisons were confounded due to large differences in the ROI size and placement. The number of ROIs reported for a single scan by each device varied from one to 12. The magnitude of BMD change versus age for similar ROIs compared well. The table contains the R^2 values for either the only available ROI (radius+ulna), the most distal radius+ulna ROI (QDR4500, pDEXA), or the distal radius (DCS600). Comparative linear regression slopes of the T-scores differed by less than 10% to over 50%. There was no general rule found to predict agreement of T-scores based on ROI or manufacturer most likely due to the inter-relationship of ROI denitions and reference populations. In conclusion, systemic and device-dependent T-score disagree-

274 (250). THE PREVALENCE OF LOW BONE MINERAL DENSITY IN ELDERLY MEN RESIDING IN NURSING HOMES N. Toofanny, J. Voytas, M. E. Maddens, D. Kowalski, William Beaumont Hospital, Royal Oak, MI, USA Nursing home residents are at high risk of developing fractures. Little attention has been given to the possibility of low bone mineral density in men. We studied the prevalence of osteopenia and osteoporosis and evaluated the associated fracture risk in elderly men residing in nursing homes. Ninety three men aged 64 to 101 years were recruited from ve skilled nursing facilities. Using the Lunar PIXI Bone Densitometer (version 1.43), bone mineral density of the right calcaneus was measured. Charts were reviewed to determine age, current use of medications known to affect bone density, and history of falls and fractures over the previous 12 months. Using the Lunar criteria equivalent for osteopenia and osteoporosis (T-score 0.6 to 1.6 for osteopenia and below 1.6 for osteoporosis), 49 (53%) had osteoporosis and 21 (23%) had osteopenia. Of the 37 men (40%) who had a history of falls, 19 (51%) suffered at least one fracture and of these, 17 (89%) were either osteopenic or osteoporotic. Of the 71 men (76%) who were osteopenic or osteoporotic, 11 (16%) were on some type of bone strengthening agent. In conclusion, this high

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prevalence of low bone mineral density in male nursing home residents and the associated increased fracture risk calls for further studies to delineate proper evaluation and management of bone loss in elderly male nursing home residents.

signicantly older than the others. Neither back pain nor use of walking aid was related to KI. Am scale (0~5), Ai scale (0~4), As scale (0~4) and ADL scale all decreased signicantly with age and KI. After adjusting for age and use of walking aid, KI was associated negatively and signicantly with Am scale, As scale and ADL scale (p<0.001, p<0.05 and p<0.01). Conclusion: The present results suggested that progression of kyphosis was associated with decrease in higher level ADL in elderly women.

275 (251). GLUCOCORTICOID-INDUCED CORTICAL BONE POROSITY IN POSTMENOPAUSAL PATIENTS WITH ASTHMA H. Tsugeno, B. Goto, M. Okamoto, S. Harada, T. Mifune, Y. Hosaki, F. Mitsunobu, K. Ashida, Y. Tanizaki, 1Misasa Med Branch, Okayama Univ Med School, Tottori, Japan; 2Calcium Research Institute, Osaka, Japan In a previous study, we demonstrated that chronic administration of systemic glucocorticoids decreases cortical bone mineral density (BMD) and induces development of pathologic fractures in asthmatic patients. To investigate cortical bone porosity, we studied cortical bone volume, BMD, bone strength, and fractures in patients with asthma in this report. A total of 82 postmenopausal asthmatic patients were enrolled in the study. Vertebral fractures were diagnosed via plain spinal radiograms. Peripheral quantitative computed tomography (pQCT) was used to measure cortical BMD, relative cortical volume, and Strength Strain Index (SSI). Multiple regression analysis and other statistical analyses were performed. Lifetime cumulative dose of glucocorticoids was related to cortical BMD, relative cortical volume, SSI, and the number of vertebral fractures. The cortical volume-density relationship appeared to remain constant regardless of systemic glucocorticoid administration. The number of vertebral fractures correlated highly with cortical BMD, relative cortical volume, and SSI at the radius. In conclusion, systemic glucocorticoid administration decreases cortical bone density, cortical bone volume, and bone strength. Glucocorticoid administration appears to be responsible for the process of cortical bone porosity at both endosteal and intracortical sites. Given that both cortical bone density and volume provide bone strength, cortical bone porosity was seen to contribute to glucocorticoid-induced bone strength loss and fractures.

277 (253). BONE DENSITOMETRY IN CHILDREN WITH DIFFERENT TECHNIQUES; DISCREPANCIES AND INTERPRETATION C. van Kuijk1, R. R. van Rijn2, M. H. Lequin2, I. M. van der Sluis3, S. M.P.F. de Muick Keizer-Schrama3, S. G.F. Robben2, 1Department of Radiology, Academic Medical Centre, Amsterdam; 2 Departments of Pediatric Radiology and Pediatric Endocrinology, Academic Children's Hospital, Sophia, Rotterdam, The Netherlands Introduction: Several different techniques for bone densitometry in children are used in clinical practice. These techniques include planar X-ray measurements (DXA); volumetric measurements (QCT and volumetric radiographic absorptiometry (RA); and ultrasound measurements (QUS). Questions can be raised with regard to the applicability of these techniques in a pediatric population. We therefore compared several techniques in a healthy Dutch Caucasian population and compared them with existing data from our own population and from the literature. Methods: In our study we have enrolled 278 Dutch Caucasian boys, (range 5.0 to 19.5 years), and 294 Dutch Caucasian girls, (range 5.2 to 19.9 years). Radiographs of the hand were made for determination of skeletal age and for volumetric RA. Tibial QUS was performed in these patients, In a previous study a similar population was used for DXA measurements. Results: Tibial QUS showed an increase of speed of sound with increasing age, comparable to DXA ndings. However, volumetric RA showed a stable low density until puberty, with a rapid increase during the pubertal years. The latter nding is consistent with QCT data as reported in the literature as well as data from (calculated) volumetric DXA. Discussion: True bone density seems to be low and stable until puberty; a nding that explains the incidence of greenstick fractures in this population. During puberty there is a rapid increase in true density. Normal values generated by planar techniques (e.g. DXA) and also with tibial QUS show both changes in bone density and bone size, which renders these techniques difcult to interpret in clinical practice.

276 (252). ASSOCIATION BETWEEN KYPHOSIS AND ACTIVITY OF DAILY LIVING IN JAPANESE ELDERLY WOMEN I. Tsuritani, R. Honda, F. Sun, Y. Noborisaka, M. Ishizaki, Y. Yamada, Department of Hygiene, Kanazawa Medical University, Uchinada, Ishikawa, Japan To determine the inuence of kyphosis, which could be caused by osteoporosis, on QOL, we investigated the relationships between kyphosis and, higher level activity of daily living (ADL) and back pain in elderly women in a community. Subjects: 128 women, aged 6588, participating in a physical function survey conducted by the local community. Methods: Kyphosis index (KI) was calculated as the maximum horizontal length of the upper back bow divided by the vertical one, using exicurve measurement. Height at age 20 years, use of walking aid (including stick) and degree of back pain during last one year were inquired about by interview. Higher level ADL was assessed by an Index of Competence developed by Tokyo Metropolitan Institute of Gerontology, and the questionnaire was composed of questions about ability of 13 kinds of actions in daily life: 5 for self-maintenance (Am), 4 for intellectual activity (Ai) and 4 for social role (As). The answers were counted `1' for ``Yes'' and `0' for ``No'', and the total was calculated as ADL scale (0~13). Statistical analysis was used by ANCOVA. Results: Mean[SD] of KI was 0.102{0.042] in the subjects. KI increased signicantly with age (r = 0.479, p<0.001). There was a signicant correlation between self-reported height loss and KI (r = 0.378, p<0.001). 13 women who used a walking aid, were

278 (254). COMPARISON OF QUANTITATIVE ULTRASOUND PARAMETERS OF THE OS CALCIS BETWEEN YOUNG ATHLETES AND AGE-AND SEX-MATCHED NONATHLETHIC CONTROLS B. Wu nsche1, K. Wu nsche2, H. Fa hnrich2, R. Venbrocks1, W. Kaiser2, 1Clinic of Orthopaedics; 2Institute of Radiology, Friedrich-Schiller-University Jena, Germany Aim: Effective primary preventive treatment of Osteoporosis has to begin obtaining a higher peak bone mass in childhood and adolescence also by physical activity. The aim of our investigation was to examine differences between the Ultrasound Bone parameters Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS) in athletes and nonathletic controls. Method: Parameters of athletes going in for football, wrestling, judo and athletics were compared with those parameters of a large normal healthy population. The right heel was measured using the Bone Sonometer ``SAHARA'' (Hologic).

Results: # p50.05 (Mann-Whitney-U test).
sports / age football/ 1116 control-group athletics/1115 control-group judo/ 1116 y. control-group wrestling/1217 control-group no. 39 857 17 752 21 680 16 770 SOS (m/s) 1581.522.8 1562.228.7 # 1588.526.8 1561.028.2 # 1577.018.0 1560.328.0 # 1567.721.3 1561.028.5 BUA (dB/MHz) 1.712.3 2.914.1 # 7.117.8 2.013.4 # 6.311.2 3.214.5 5.714.6 4.215.0

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phalanges Digit II-V in 43 patients with recent (<3 weeks) hip fracture (21 cases of cervical hip fractures, 22 cases of trochanteric fractures). The DBM Sonic 1200 (Igea, Italy) was used, double measurements at the non-dominant hand were performed. QUS results of the hip fracture group were compared to german reference data (Osteop Int 1998 (5)). There was no signicant difference in the compared hip fracture groups concerning age, body height, weight and body mass Index. Table 1: QUS parameters for hip fracture patients and controls expressed in Mean 1SD and in Z-scores of patients compared with controls *=p<0.01 vs. controls SOS through the nger phalanges was signicant ly lower in patients with hip fractures than in controls. SOS did not differ signicantly between the two hip fracture groups (T-Test n.s.) however there was a trend towards lower SOS values in patients with trochanteric hip fractures. We conclude that QUS at the nger phalanges is a valid method to diagnose generalized osteoporosis.

Signicant higher values of SOS and BUA were found in athletes of football and athletics, no signicant dierence was seen in athletes of judo and wrestling. Conclusion: High-impact weight-bearing activity like football and athletics appears benecial for bone accretion because of evaluation of signicant higher quantitative bone parameters in these athletes. This difference is not so well dened in more brawn-intensive physical activity with a high static muscle-load.

Trochanteric SOS (m/s) Z-Score (SD) 1778114* 2.44

Cervical 179094* 2.21

Controls 190552

279 (255). SEX-RELATED DIFFERENCES OF QUANTITATIVE ULTRASOUND PARAMETERS OF THE OS CALCIS IN CHILDREN AND ADOLESCENTS hnrich1, S. Vogt1, B. Wu nsche2, W. A. Kaiser1, K. Wu nsche1, H. Fa 1 Institute of Radiology; 2Clinic of Orthopaedics, Friedrich-SchillerUniversity Jena, Germany Objective: In earlier investigations standard values of Broadband Ultrasound Attenuation (BUA) und Speed of Sound (SOS) in healthy children and adolescents were evaluated. Are sex related differences in the age range from 618 years detectable? Method: BUA and SOS were measured in 3299 healthy children and teenagers (1623 girls and 1676 boys). age range 618 years, using the bone densitometer ``SAHARA'' from Hologic. Children with diseases inuencing bone metabolism were excluded. Results: BUA values were signicantly higher in 9 and 11 years old boys than in girls. Between the age groups 13, 14, 15, 16 and 17 years BUA was signicantly higher in girls than in boys. SOS was nearly constant during ageing for both sexes. SOS values were signicantly higher in 7 years and 13, 14, 15, 16 and 17 years old girls than in boys. Conclusion: The above mentioned differences are probably caused by the different onset of puberty, the different onset of growth phases and the effects of estrogen or related factors on muscle-bone relationship. This corresponds to the studies of Rubin et al, [1993] and Ferretti et al, [1998]. The observed signicant sex-related differences in our study support the hypothesis that quantitative ultrasound bone densitometry is sensitive to detect small changes of bone mineral density in childhood and adolescence. 281 (257). CALCANEAL ULTRASOUND AND PHALANGEAL DXA COMPARED TO DXA OF THE HIP AND SPINE FOR OSTEOPOROSIS DETECTION D. M. Bachman, P. E. Crewson, Metrowest Medical Center, Framingham, MA, USA Peripheral screening devices are attractive alternatives to axial dual x-ray absorbtiometry because of portability and lower expense. We evaluated the ability of two such devices to detect osteoporosis diagnosed by spine and hip DXA. 453 Caucasian women (mean age 61) consecutively scheduled for spine and hip DXA on a Lunar DPX-L had heel ultrasound on a Lunar Achilles and 180 also had phalangeal DXA measured on a Shick Accudexa. T scores (standard deviation from young adult mean) were determined using each device's data base. By either spine, hip or both, 48% were osteopenic (T 1.0 to 2.49) and 26% were osteoporotic (T less than 2.5). For the osteoporotic group, 43% were less than 2.5 by ultrasound stiffnes index and 24% by phalangeal DXA. If a cutpoint of 1.0 was used, 55% and 32% of osteoporotic patients were detected.. On the other hand, 9% of heel measurements and 8% of digit measurements were at least 1.0 S.D. less than the spine and hip measurements. We conclude that while peripheral screening studies will detect some people with osteoporosis, the number is substantially less than those detected by axial DXA. We found heel ultrasound more sensitive than nger DXA at all age groups. Sole reliance on these peripheral devices would identify fewer people as being at risk for osteoporotic fracture and would be likely to alter treatment recommendations for many patients.

Osteoporosis Diagnosis
280 (256). QUANTITATIVE ULTRASOUND (QUS) AT THE FINGER PHALANGES IN PATIENTS WITH CERVICAL AND TROCHANTERIC HIP FRACTURES F. E. Alenfeld, U. Baldin, D. Felsenberg, 1Osteoporosis and Arthritis Research Group, University Hospital Benjamin Franklin, Germany; 2Free University Berlin, Germany The purpose of this study was to investigate whether QUS measurements at the nger phalanges enable to separate patients with hip fractures from age matched controls and trochanteric from cervical hip fractures. We measured speed of sound through the distal metaphysis of the proximal nger 282 (258). FRACTAL ANALYSIS OF TRABECULAR BONE TEXTURE ON RADIOGRAPHS: EFFECTS OF AGE ON MICROARCHITECTURAL CHANGES C. L. Benhamou, S. Poupon, L. Pothuaud, R. Niamane, R. Harba, E. Lespessailles, Institut de Prevention et de Recherche sur I'Osteoporose, Orleans, France We have previously developed and validated a fractal analysis of texture on plain radiographs. Bone alterations are characterized by a fractal dimension (D) increase. We have studied a population of 627 control women from 21 to 93 years. Calcaneus x-rays were performed following standardized conditions, and radiographic

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Osteometer BioTech A/S). Using HUS, 47% had a T-score of 572.0 (range 2.0 to 4.6) and were classied as osteoporotic, 34% ranged from 1.0 to 1.8 and were classied as normal and 17% ranged from 1.0 to 2.0 and were classied as intermediate. Correlation between Osteosal and ELISA was 0.87 but neither correlated with HUS. Those with normal HUS were re-assured and given life-style advice but those with Osteosal >2.0 were prescribed calcium and vitamin D. The osteoporotic group were treated with bisphosphonates and/or calcium and vitamin D. Osteosal measurements were repeated at 3 months to monitor response, 80% showed a signicant reduction in value. The intermediate group were referred for DXA. HUS and Osteosal in the clinic enables a rapid, relatively cheap and effective osteoporosis risk evaluation of elderly patients. Osteosal enables treatment decisions and monitoring of responses at earlier time points. Point of care tests using HUS and bone markers enables an effective and cost-efcient one-stop clinical service.

lms scanned to obtain texture images. Fractal analysis was applied and results expressed by H exponent (H=2-D). Subjects were classied by range of 10 years, from 2030 years to 90100 years (Figure). This study suggests that fractal evaluation is able to characterize age induced changes with an increase in H for young subjects followed by a decrease in H after 40 years.

283 (259). PREVALENCE OF OSTEOPOROSIS IN A GENERAL POPULATION G. K. R. Berntsen1, V. Fnneb2, A. J. Sgaard3, I. Njolstad4, A. Tollan5, J. H. Magnus6, 1Univ of Troms, Norway; 2Univ of Troms, Norway; 3Univ of Oslo, Norway; 4Univ of Troms, Norway; 5Central Hospital, Hamar, Norway; 6Univ of Troms, Norway Our objective was to determine the osteoporosis prevalence by currently suggested denitions in a general population. We invited all men aged 5574, women aged 5074 and 510% representative samples of remaining age groups aged 25 or more years, living in Troms to forearm bone densitometry with SXA. In all 3062 men and 4558 women aged 2584 years (response rate 80.3%) took part. Osteoporosis denitions:1) WHO1 BMD <2.5 standard deviations (SD) below female peak BMD. 2) WHO2: BMD <72.5SD below mean pre-menopausal BMD. 3) NHANES: BMD <72.5SD below male peak BMD. 4) Age-specic: BMD 51 SD below the 10 year age- and sex-group BMD mean. 5) UK consensus: Osteoporosis diagnosis by either NHANES or Agespecic criteria. We applied WHO1, WHO2 and Age specic criteria to women, and WHO1, NHANES, Age specic and UK consensus criteria to men. Prevalences were standardised to WHO European standard population. Depending on denition, osteoporosis was found in 24%32% of all women aged 550 and in 220% of all men aged 550. The WHO1-denition for women and the UK consensus denitions for men yielded the highest prevalences. Of women aged 570 years, 65% were osteoporotic and only 10% had normal BMD (WHO1). Medicalisation of elderly women may be an important adverse effect of the WHO osteoporosis denition.

286 (262). COMPARISON OF THE FEMORAL GEOMETRIC VALUES MEASURED BY X RAY RADIOGRAMS AND DEXA IN MALE AND FEMALE CASES H. T. Calis1, M. Eryavuz1, M. Calis2, G. Can3, H. Sayman4, Physical Therapy and Rehabilitation Departmant, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; 2 Physical Therapy and Rehabilitation Departmant, Sisli Etfal Education and Research Hospital, Istanbul, Turkey; 3Public Health Departement, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; 4Nucleer Medicine Departement, University Cerrahpasa Medical Faculty, Istanbul, Turkey

285 (261). OSTEOPOROSIS RISK ASSESSMENT USING POINTOF-CARE TECHNOLOGY R. Branton1, M Buxton-Thomas, B. Gray, C. Mangion, D. Percival1, C. Moniz, 1King's College Hospital, London, UK; 2 Provalis Diagnostics, Flintshire, UK Heel ultrasonography (HUS) performed in a clinic offers a more cost-efcient osteoporosis risk assessment compared to DXA, especially in elderly women with bony or calcication artefacts. We studied the use of HUS (Achilles, Lunar) and biochemical markers in an Osteoporosis Clinic. 86 elderly women (mean age 75yrs, 7090) were measured prior to consultation. Each provided a second-void, fasting urine sample on which CTx was tested by OsteosalTM (Provalis Diagnostics Ltd) a rapid point of care test. A T-score above +2.5 indicated increased bone resorption. Urine samples were also measured for CTx using ELISA (CrossLapsTM,

Femoral geometric measurements are suggested to be important in the evaluation of the risk of hip fracture. In this study, femoral geometric measurements of 34 males and 34 postmenauposal females were examined and compared. None of them have had any hip fracture in their lives and all of them were older than 50 ages. In all cases bilateral hip axis length (HAL), femoral neck axis length (FNAL), acetabular width (AW), femoral head width (FHW), femoral neck width (FNW), femoral shaft width (FSW), intertrochanteric width (ITW), medial femoral neck cortical bone thickness, medial femoral shaft cortical bone thickness, lateral femoral shaft cortical bone thickness, femoral neck-shaft angle in degrees(N-SA) were measured on AP plain pelvic Xray radiograms and manual HAL, FNW, FSW, ITW,N-SA on Hologic QDR 4500 Dual Energy X-ray Absorbtiometry (DEXA) and automatic HAL values on DEXA were detected. There was no signicant difference between the mean age of male (63.088.2) and female(63.008.01) cases (p = 0.964). Statistically, mean heigth of female (156.237.5) cases was signicantly lower than male cases (169.086.5) (p<0.05). Radiographic measurements of HAL, FNAL, AW, FHW, FNW, FSW, ITW and measurements of HAL (manual and automatic), FNW, FSW, ITW on DEXA were signicantly lower in females (p<0.001). There was no statistically signicant difference between the male and female cases in relation to medial femoral neck cortical bone thickness, medial femoral shaft cortical bone thickness, lateral femoral shaft cortical bone thickness and N-SA measurements on radiograms and N-SA values on DEXA.

287 (263). QUANTITATIVE ULTRASOUND AND BONE TURNOVER IN THE PREDICTION OF VERTEBRAL FRACTURE C. Cepollaro, S. Gonnelli, B. Rossi, D. Bruni, S. Martini, C. Pondrelli, M. S. Campagna, C. Gennari, Institute of Internal Medicine, University of Siena, Italy It is well known that bone fracture depends on both bone density and bone structure. Also bone turnover play a role in the assessment of fracture risk, in fact it has been demonstrated that high bone turnover independently predicts fracture risk. It

has been shown that Quantitative Ultrasound (QUS) is able to predict femoral and vertebral fracture. Few studies are present in literature about the relationship between QUS and bone turnover. The aim of this study was to evaluate the ability of QUS and bone turnover alone or in combination in the prediction of vertebral fracture. In 89 postmenopausal women, 38 of those with (61.28.7 years) and 51 without (62.26.2) vertebral fracture we measured bone density at lumbar spine (BMD-LS) and at femoral neck (BMD-FN) by DXA (Hologic 4500) and broadband ultrasound attenuation (BUA) at the calcaneus by QUS2 (Metra Biosysiem). In all patients we also assessed markers of bone turnover: total alkaline phosphatase (T-ALP) and bone alkaline phosphatase (BALP, Hybretech) to evaluate bone formation and urinary hydroxyproline (HOP/Cr) and a-Cross-Laps (Osteometer Biotech) to evaluate bone resorption. The precision of QUS2, evaluated by measuring 5 healthy subjects and 5 osteoporotic women daily for 5 days, showed a coefcient of variation of 1.4% and 1.3% respectively and a standardized coefcient of variation of 1.8% and 1.7% respectively in healthy subjects and in osteoporotic patients. All densitometric and ultrasonographic parameters were signicantly lower in postmenopausal women with vertebral fractures with respect to those without vertebral fractures. BUA signicantly correlates with bone density and with markers of bone turnover. BUA, B-ALP and a-Cross-Laps independently predict vertebral fractures; the combination of BUA and B-ALP and of BUA and a-Cross-Laps improves the ability to assess fracture risk. We can conclude that: QUS2 presents good characteristics of precision and signicantly correlates with bone mineral density and markers of bone turnover. The relationship of markers and BUA in the prediction of fracture risk are not only independent, but also additive.

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easy to use instrument. Further validation is needed to apply this framework to other populations.

289 (265). VERTEBRAL MORPHOMETRY AND RISK OF VERTEBRAL FRACTURES D. Diacinti, S. Minisola, E. Tomei, E. D'Erasmo, GF. Mazzuoli, Department of Clinical Sciences, University ``La Sapienza''Rome, Italy The purpose of this study was to evaluate if a new morphometric index is to able to predict vertebral fracture risk. Materials and methods: in 130 postmenopausal women (mean age 6510; range 4674 years) who came to our Mineral Metabolism Centre lateral spine lms were obtained at base line and after two years. The lms were digitized by means of a scanner and then was performed the vertebral morphometry from T4-L5 using specied software (QR-Verona). The computer automatically calculated the anterior, middle and posterior vertebral bodies heights (Ha, Hm, Hp), the ratios of heights of single vertebra (Ha/Hp, Hm/Hp, Hp/Hpp), as well as the sum of vertebral body heights (AHs, MHs and PHs). At baseline the vertebra was considered fractured if any of the three ratios was <3SD the corrisponding reference ratio of fertile women. A new fracture was dened as a reduction of 20% (4mm.), in the height of any vertebral body between baseline and follow-up. Lumbar bone mineral density (LS-BMD) was measured by dual-energy xray absorptiometry using the Hologic QDR4500 densitometer (Hologic, USA). Osteoporosis was dened as a LS-BMD <2.5SD the mean value in fertile women (WHO). Results: at base line 35/130 (26.9%) women had AHs <2.5SD the normal fertile value, 18/35 (51.4%) had vertebral fractures; 48/ 130 (36.9%) had LS-BMD <2.5SD, 14/48 (29.1%) were fractured. After two years became fractured 8/17 (47%) of the women not fractured at base line but with AHs <2.5SD and 12/34 (35.3%) women with LS-BMD <2.5SD at base line. Conclusion: vertebral morphometry, detecting minor asymptomatic vertebral deformities, allows to identify women with increased risk of further fracture.

288 (264). COMBINATION OF RISK INDICATORS TO ESTIMATE HIP FRACTURE RISK IN WOMEN C. E. D. H. De Laet, H. A. P. Pols, J. A. Kanis, A. Dawson, O. Johnell, A. Oden, Erasmus University Medical School, Rotterdam, The Netherlands Although BMD is a well-established risk indicator for hip fractures it is generally recognised that other risk indicators contribute independently to hip fracture risk. The purpose of this study was to provide a framework for their combination based on data from the Rotterdam Study. Based on available evidence we used 4 putative risk indicators for hip fracture risk. To obtain reasonable prevalences for each of the 16 combinations of risk indicators we used moderate threshold values. For low-weight the threshold was set at the median weight, for tall height this was set at the highest quartile. Other indicators were a previous fracture in the previous 5 years and use of a walking aid. The additional risk of having a low BMD (dened as a Z score below 0.5) was assessed and its prevalence determined in each of the combinations of risk indicators. The analysis was done for both the total population and also stratied by 10-year age groups. The relative risks (risk indicators adjusted for each other) were 1.7 for low weight, 2.4 for tallness, 1.8 for use of a walking aid and 1.2 for previous fracture. Prevalence was 14 % for the use of a walking aid and 16 % for a previous fracture. Adding BMD into the model the relative risk for low BMD was 3.5 and the relative risk for having a low weight decreased to 1.3. The relative risks for the other indicators remained similar. When the relative risk for hip fracture for individuals having none of the 4 risk indicators was dened as 1, the relative risks for individuals in the 16 combinations of risk indicators varied from 1 to 9, and the average risk for the total population was 2. Only 25% of the population had a higher than average risk. In the groups with 3 or more risk indicators the prevalence of low BMD was 60%, much higher than the expected 30 %. Several risk indicators, measuring different determinants of hip fracture risk, can be combined in an

290 (266). HEARING LOSS AS A COMPLICATION OF PAGET'S DISEASE OF BONE J. Donath, B. Fornet, M. Krasznai, Gy. Poor, National Institute of Rheumatology and Physiotherapy, Haynal Imre University of Health, Oto-Rhyno-Laryngology Clinic, Budapest, Hungary Background: Hearing loss has long been known to be a complication of Paget's disease of bone. The aim of this study was to investigate the hearing loss in Paget's disease and treating the patients with pamidronate and tiludronate. Methods: 65 patients with Paget's disease were examined /30 men, 35 women, age range 4997/. Imaging included radiography/n=65/, bone scintigraphy/n=65/ and QCT scan /n=10/. The quantitative bone scintigraphy/QBS/ was performed in 27 cases and the results were expressed as a ratio of the affected bone and normal uptake of TC99mMDP before and after the treatment with bisphosphonates. Results: 28 skull involvements were documented in 65 patients and 10 had hearing loss. The bone scintigraphy showed increasing uptake of the petrous pyramids /n=5/. The QCT showed involvement of the middle ear ossicles /n=5/, ossication of the stapedius tendon /n=1/, narrowing of the external auditory meatus /n=1/ and involvement of the petrous pyramids /n=5/. After bisphosphonate treatment the patients recognised an improvement in hearing sensitivity. In QBS the activity of petrous pyramids were decreased. Conclusion: QCT imaging is a well suited for demonstrating the complication of the disease.

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QBS may be a useful technique for evaluating of the effects of the treatment. Early diagnosis and bisphosphonate treatment may be a way to control hearing loss as a complication of Paget's disease.

293 (269). THE DETECTION OF FRACTURE RISK IN PRIMARY CARE A. Fairney1, M. W. van den Brekel1, A. Keyede2, P. Kyd1, S. Illife2, D. A. Percival3, R. Branton3, 1Metabolic Medicine, Imperial College School of Medicine, St. Mary's, UK; 2Lonsdale Medical Centre London, Flintshire, UK; 3Provalis Diagnostics, Flintshire, UK Strategies to prevent osteoporotic fractures could be facilitated by provision of bone density services in the community, together with near patient measurements of bone turnover1. Patients living in the community were invited to visit the Health Centre for a forearm bone density measurement (BMD) (DTX 200, Osteometer) and to provide a sample of urine. Urine CTelopeptide was measured by OsteosalTM immunochromatographic test (Provalis Diagnostics Ltd, Flintshire, UK), corrected for creatinine and results expressed as Osteosal T-scores. This was compared with the urine C-Telopeptide CrossLapsTM (Osteometer, Denmark CTx). Of 105 subjects, (39M, 66F) mean age 71 years (range 6089) 33% had normal BMD (N), 40% osteopenia (OPEN), and 27% osteoporosis (OPOR), (WHO criteria). OsteosalTM results correlated with laboratory CTx (p<0.0005). Urine CTx, though not OsteosalTM, was higher in OPOR subjects compared to N or OPEN (p<0.0001). In primary care, the combination of forearm BMD and bone turnover measurements may help to identify those at risk of fracture who require preventative treatment. 1Garnero P, et al. Osteoporos Int. 1998;8:5639.

291 (267). A SCREENING INSTRUMENT FOR ASSESSING OSTEOPOROSIS RISK IN ADULTS WITH DEVELOPMENTAL DISABILITY B. Dunford, S. Cottrell, J. Bodsh, J. McKee, Western Carolina Center, Morganton, NC, USA The prevalence of osteoporosis in individuals with developmental disability has not been clearly quantied. Currently available diagnostic tools such as central or peripheral scans are somewhat invasive and expensive to perform. The instrument developed is an initial attempt to create a non-invasive screening tool to identify those individuals with developmental disability who are at risk for developing osteoporosis, who may then be referred for further diagnostic testing, then a treatment plan developed to meet the specic needs of the individual. This screening instrument accounts for clinical issues specic to the population with developmental disability (non-ambulatory status and exposure to various anti-epileptic drugs). This instrument was validated in 360 individuals living in a residential intermediate care facility for the developmentally disabled (mean age 40.1 years, 41% female, 43% nonambulatory). Signicant risk factors identied were increasing age, history of fractures, history of treatment with phenytoin and/or phenobarbital, less ambulatory ability, and decreased body weight. The weighting of the individual questions on the instrument were based on the results of a multiple regression analysis from the facility sample tested. This screening instrument has utility for either sex and should identify those at risk for developing osteoporosis allowing for early intervention to postpone, minimize, or prevent bone demineralization.

n N OPEN OPOR 35 42 28

BMD T-score 0.22 (0.14) 1.79 (0.06) 3.42 (0.12)

OsteosalTM T-score 0.86 (0.27) 0.64 (0.21) 1.34 (0.29)

CTX mg/mmol 110 (14)* 132 (12)* 252 (26)

Mean (SEM), *p<0.0001 vs. OPOR.

292 (268). CORRELATION BETWEEN KNEE OSTEOARTHRITIS AND BONE MINERAL DENSITY OF THE LUMBAR SPINE, PROXIMAL FEMUR AND DISTAL RADIUS G. Durlanik, F. Sahin, F. Merdol, B. Kuran, Dept. of Physical Medicine and Rehabilitation, Sisli Etfal Teaching and Research Hospital, Istanbul, Turkey The aim of this study was to determine the possible inverse relation between osteoporosis (OP) and osteoarthritis (OA) by evaluating the association between bone mineral density (BMD) and knee OA. BMD's in proximal femur, lumbar spine and distal radius were measured by LUNAR-DEXA. Knee OA was assessed by a weight bearing anteroposterior radiograph and graded on a severity scale of 4 according to Kellgren-Lawrence. We compared the bone densities of each OA group with those without knee OA. Among a study population of 300 postmenopausal women (age range 4286 years) 220 had radiologically diagnosed knee OA. The t scores according to the stages of knee OA were as follows: 294 (270). THE ABILITY OF AN IMAGING QUANTITATIVE ULTRASOUND SYSTEM TO DISCRIMINATE SUBJECTS WITH OSTEOPOROTIC FRACTURE FROM CONTROLS B. Fan, M. Grigorian, M. Chen, C. F. Njeh, T. Fuerst, I. Saeed, D. Hans, H. K. Genant, Osteoporosis and Arthritis Research Group, University of California, San Francisco, CA, Quantitative ultrasound (QUS) has emerged as a promising tool in identifying individuals at risk of sustaining a fragility fracture. The aim of this study was to assess the ability of an imaging calcaneal QUS system (UBIS 5000, DMS, France) to identify women with osteoporotic fracture. The study group consisted of 52 healthy women (mean age 718.14 yr.) with no risk factors associated with osteoporosis and 51 women (mean age 766.02 yr.) with osteoporotic fracture of spine or hip. All women had calcaneal QUS and Hologic 4500 (Hologic, USA) was used for bone mineral density (BMD) measurement of the lumbar spine and hip. The ttest was used to calculate the difference between the two groups. Both QUS parameters and BMD of the hip and spine differentiated signicantly between the fracture and control group (P<0.01). Odds ratios (OR) per standard deviation were computed by using the logistic regression analysis. We also calculated the area under the curve (AUC) by using CLABROC software. The OFs, AUC and 95% condence intervals (CI) are given in the table. After adjustment for age all the parameters still remain signicant except BMD of the neck. Our results suggest that the QUS parameters can discriminate the fracture subjects from controls as well as bone density of the hip and spine.

Stage 1 No: Lumbar t score Neck t score D. Radius t score 21 2.52 1.65 2.32

Stage 2 98 2.45 1.63 2.43

Stage 3 88 1.77 1.31 2.11

Stage 4 13 1.62 1.53 2.10

This is an on going study. The early ndings suggest that postmenopausal patients have moderate degrees of knee OA and as the severity of OA increases, the t scores of the lumbar spine decreases correspondingly.

Parameters BUA SOS BMD_spine BMD_neck Odds ratios (95% CI) 2.52 1.87 2.10 1.93 (1.54, (1.21, (1.32, (1.21, 4.13) 2.90) 3.34) 3.10) AUC(95% CI) 0.73 0.66 0.71 0.68 (0.63, (0.56, (0.61, (0.58, 0.82) 0.77) 0.81) 0.77)

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clinical risk factors for osteoporosis were no more likely than those with no risk factors to receive clinical preventive services (counseling and screening). In multivariate analyses, those less likely to have been counseled about universal preventive measures were in their 40s, premenopausal, in good/fair/or poor health, or had an annual income less than $50 000. More likely to have been counseled were women who had visited a health care provider for menopausal symptoms. Current osteoporosis practices appear to be oriented towards management of identied osteoporosis, rather than primary or secondary prevention. Much work remains to be done to fully implement guidelines for primary prevention of osteoporosis, as well as new screening guidelines.

295 (271). HEEL BMD AND THE NOF CRITERIA PREDICT FRACTURES IN BOTH CAUCASIAN AND NON-CAUCASIAN WOMEN K. G. Faulkner, T. Abbott, D. Furman, J. Panish, E. Siris, P. Miller, E. Barrett-Connor, M. Berger, A. Santora, L. Sherwood, Participants in NORA are ambulatory, postmenopausal women with no prior diagnosis of osteoporosis or BMD test in the past year. Heel density data (SXA) and risk assessment data were collected from 102,101 women at baseline. Women were classied into 2 groups: those who met National Osteoporosis Foundation (NOF) treatment guidelines (NOF Tx group: T-score 52.0 or 51.5 with a risk factor) and those who did not (NOF non-Tx group). For 32,497 of these women, self-reported prospective fracture data were captured by follow-up surveys completed an average 8 months after baseline. The % of women meeting treatment criteria varied from 18.05% for African Americans to 39.46% for Asians. Fracture rates (per 100 person years) in the Tx group was 2 to 6 times higher than the non-Tx group, depending on ethnicity. The NOF criteria were particularly strong predictors of fracture in African American and Asian women. We conclude that the NOF criteria based on heel BMD assessments can identify women of various ethnicities at increased risk for fracture.

297 (273). BIOLOGICAL AGE, BALANCE, MUSCLE STRENGTH, VISUAL ACUITY AND BONE MASS IN 75-YEAR-OLD WOMEN P. Gerdhem, K. Ringsberg, H. Magnusson, K. Akesson, K. Obrant, Department of Orthopaedics, Malmo University Hospital, Malmo, Sweden The purpose of this investigation was to evaluate a method of estimating biological age, and to correlate it to known risk factors for osteoporotic fractures. Biological age may be an underestimated factor for fracture risk but lacks denition and no measurement of it exists. Patients and methods: 993 women, all 75 years old. Biological age was assessed as follows: each woman was given a subjective fragility score from 1100 within 15 seconds from rst sight. 4 investigators took part in the scoring. 957 women were scored independently by 2 investigators. A modied Romberg balance test was performed. Visual acuity (VA) and thigh strength (TS) was measured. Bone mineral density (BMD) of the hip and spine was measured with a Lunar DPX-L scan. Statistics was calculated with the Pearson product moment correlation or the Spearman rank correlation. Results: Biological age as assessed by two independent observers had a good correlation (r varying between 0.51 and 0.59, p<0.001) The correlation (r-value) between biological age and balance varied between 0.28 and 0.53 (p = 0.0013- p<0.0001). The r-value between biological age and TS varied between 0.22 and 0.30 (p = 0.02- p<0.0001). No correlation existed between biological age and VA or between biological age and BMD. Conclusion: Biological age, as measured in our study, can quite well predict balance, an important risk factor for falling and subsequent fracture, and the correlation between independent observers is good. It is not possible to anticipate a patients BMD by estimating her biological age.

Ethnicity Tx Group: % Age (Mean) T-score (Mean) Fx Rate Non-Tx Gp: Fx Rate Odds Ratio 95% CI

African American 18.05 70.8 2.01 9.7 1.6 6.3 2.2, 18.5

Caucasian 28.51 69.9 2.05 5.3 2.7 2.0 1.7, 2.4

Hispanic 31.4 69.6 2.08 4.7 2.4 2.1 0.8, 5.1

Asian 39.5 68.1 2.11 6.4 1.8 3.8 1.0, 14.6

296 (272). MISSED OPPORTUNITIES FOR OSTEOPOROSIS PREVENTION IN CLINICAL PRACTICE T. C. Gallagher1, O. Geling2, J. FitzGibbons3, F. Comite4, 1 University of Illinois, Champaign, IL, USA; 2University of Illinois, Champaign, IL; 3Yale University, New Haven, CT; 4Yale University, New Haven, CT, USA Adherence to osteoporosis clinical practice guidelines was assessed in a randomly-selected sample of 1,004 female members (age 4069) of a network-based managed care arrangement in the Northeastern U.S. Guidelines recommend that all women receive counseling regarding universal preventive measures (calcium, weight-bearing exercise, smoking cessation), those with selected risk factors receive bone mineral density testing, and those with identied osteoporosis receive advice regarding available treatments. Osteoporosis practices were below the recommended level. This was true for counseling regarding universal preventive measures (only 49% of the sample ever discussed osteoporosis with a health care provider), BMD screening (only 18% of women age 65+ advised regarding BMD screening), and treatment (74% of those with identied osteoporosis advised of pharmaceutical treatments). Women with

298 (274). CUT-OFF VALUES FOR VERTEBRAL FRACTURE BY PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (PQCT) IN JAPANESE WOMEN I. Gorai1, K. Nonaka2, H. Kishimoto3, H. Sahata4, Y. Fujii5, T. Fujita5, 1Yokohama City University, Yokohama, Japan; 2Nishimoto Sangyo Co., Ltd., Tokyo, Japan; 3Sanin Rosai Hospital, Tottori, Japan; 4Nayoro Orthopedic Clinic, Hokkaido, Japan; 5Calcium Research Institute, Hyogo, Japan In spite of the benets of bone mass measurement by DXA, the use of DXA has limitations. It is unable to assess a true geometry of a bone and totally approximate to estimate bone strength. It cannot discriminate between the trabecular and cortical components of bone. The purpose of this study is to determine reference values of total bone density (BD), trabecular bone density (TBD) and polar strength strain index (pSSI) in Japanese female population measured by pQCT (XCT960 Rev. 5.10 or 5.16s, Stratec Medizinteknik GmbH, pforzheim, Germany), and nd out cut-off values of BD, TBD and pSSI that could most efciently differentiating those subjects with vertebral fractures from those without them. Total of 5,942 healthy Japanese women aged 20 to

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89 years entered this study. All the subjects gave informed consent before the study. Six hundred and twenty-one women were extracted from 5,942 subjects for radiographic examination of the thoracic and lumbar spine at the time of pQCT measurement to determine cut-off values of BD, TBD and pSSI for vertebral fractures. The backgrounds of the extracted population did not differ signicantly from those of the whole population. All the subjects were divided into each ve-year-age group according to their ages. The TBD showed a plateau until the ages of 4044 years, which corresponds to the young adult mean (YAM) values of lumbar spine, femoral neck and radius BMDs measured by DXA. The TBD decreased signicantly thereafter. The pSSI did not change signicantly from age group of 1519 years to that of 5054 years, and decreased slightly in age groups of 5059 and 6064 years and markedly thereafter. The cut-off values for the discrimination of vertebral fractures were obtained by the calculation of sensitivities, specicities and area under the curve (AUC) using receiver operating characteristics (ROC) analysis (Table). These ndings suggest that different thresholds are needed among different variables.
Table. YAM and cut-off value for vertebral fractures n BD (mg/cm3) TBD (mg/cm3) pSSI (mm3) 1,298 1,298 928 YAMSD 405.461.7 195.840.9 322.569.7 Cut-off value (SD, %YAM) 283.8 (2.0, 70%) 117.5 (1.9, 60%) 193.5 (1.9, 60%)

lesser trochnters. In osteoporotics, the zones of Apparent Cortical Defect was denitely wider than in non-osteoporotics. Modulus of section (mm3) (Z1s, Z1i, Z2s, Z2i, Z3 and Z4) divided by distance from the center Z/d indicating mechanical fracture threshold, was at the minimum in Z1 and Z3. In osteoporotics, Z1s/d1, Z1i/d1 and Z3/d3 were 11.6, 0.8 and 30.9 respectively, always signicantly lower in the former than non-osteoporotics (62.2, 18.5, 48.8) (p<0.01). The zones of Apparent Cortical Defect demonstrated for the rst time correspond to the well-known sites of frequent occurrence of intra-and extracapsular fractures. In control subjects in the 40s, no zones of Apparent Cortical Defect were found.

300 (276). CLINICAL PERFORMANCE OF THE QUS2: A PORTABLE, GEL-COUPLED, SCANNING CALCANEAL ULTRASONOMETER S. L. Greenspan1, S. Cheng2, P. D. Miller3, E. S. Orwoll4, the QUS 2 PMA Trial Investigators, 1University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2University of Jyvaskyla, Jyvaskyla, Finland; 3Colorado Center for Bone Research, Lakewood, CO, USA; 4Oregon Health Sciences University, Portland, OR, USA We recruited Caucasian women 2584 years of age to evaluate the clinical performance of the QUS2 calcaneal ultrasonometer (Metra Biosystems): normative database (n=794), precision (n=79), low bone mass and fracture discrimination (n=528, aged 5084 years). Mean calcaneal BUA was constant in healthy women from 2554 years of age and decreased with increasing age thereafter. The mean (SD) BUA in 171 women aged 2534 years was 89.0 (12.4) dB/MHz. Short-term (within day) precision, with and without repositioning of the heel, and long-term (over 16 weeks) precision yielded comparable results (BUA SD of 2.12.4 dB/MHz, CV of 2.52.9%). BUA was signicantly correlated with BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS) (r = 0.60.7, p<0.0001) in 698 women. Prevalence of osteoporosis in our population (WHO criteria) was 20%, 17%, 21%, and 24% for BUA, TH BMD, FN BMD, and LS BMD, respectively. Age-adjusted values for a 1SD reduction in BUA, TH BMD, and FN BMD predicted prevalent clinical fractures (spine, forearm, and hip) with signicant (p<0.05) odds ratios of 2.3, 2.0, and 2.1, respectively. Areas under the ROC curves for ageadjusted bone mass values predicting prevalent fracture were 0.62 for BUA, 0.59 for TH BMD, 0.60 for FN BMD, and 0.57 for LS BMD; all statistically equivalent. We conclude that the QUS2 calcaneal ultrasonometer exhibits reproducible clinical performance and is equivalent to BMD of the hip and spine for identifying women with osteoporosis and fracture discrimination.

299 (275). QUANTITATIVE BIOMECHANICAL MEASUREMENT OF PROXIMAL FEMUR BY RECONSTRUCTION OF HELICAL COMPUTED TOMOGRAM B. Goto, J. Maeda, Y. Fujii, T. Nakamura, T. Fujita, Calcium Research Institute Osaka, Japan Three-dimensional reconstructiion was carried out on the helical computed tomogram with 3mm slice/ second using GEYokogawa Lemage SX-E at 120 kv, 200mA, in the proximal femur of 17 subjects 67 and 77 years of age, 12 with and 5 without osteoporosis by the lumbar BMD. On extraction of cortical bone with CT number >300, belt-like zones with no detectable cortical bone by this method(Apparent Cortical Defect) were always found, one surrounding the neck beneath femoral head and the other on the dorsal half of the plane containing the greater and

301 (277). DOES OSTEOPOROSIS CLASSIFICATION USING HEEL BMD AGREE ACROSS MANUFACTURERS? M. Grigorian, J. A. Shepherd, X. G. Cheng, C. F. Njeh, J. O. Toschke, H. K. Genant, Osteoporosis & Arthritis Research Group, University of California San Francisco, San Francisco, CA, USA In this study, we evaluated the agreement between two heel DXA devices on BMD and T-scores. A total of 99 healthy females aged 21 to 78 years (ca. 16 per decade) had their non-dominant heel BMD measured using the PIXI (Lunar Inc.) and APOLLO (Norland Medical) DXA machines. The PIXI ROI is the inner 50% area of a circle inscribed on three perimeter markers on the calcaneus. The APOLLO ROI is 30 mm long by the calcaneal width starting 6 mm from the distal end. The mean BMD values were 0.492 and 0.607 g/cm2 and the mean T-scores were 0.07 and 0.25 for the PIXI and APOLLO respectively. Both the BMD and T-score inter-machine relationships were highly correlated but showed signicant nonidentity slopes and non-zero offsets.

Furthermore, using Bland-Altman analysis, we found that the difference in BMD between the two devices tended to increase as BMD decreases (p<0.003). Classifying all patients using the NOF guidelines resulted in an 84% agreement. Normalizing the reference peaks and SDs using the study's 20 39 aged subjects removed the systematic T-score disagreement. In conclusion, the PIXI and APOLLO are highly correlated. Differences in BMD values may be solely due to the ROI denitions. Additional T-score disagreement highlighted differences in the manufacturers' reference populations and T-score methods.

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wrist fractures); and 102 age-matched controls (mean age 60.58). All of them were free of any drugs which could affect bone metabolism. The age-adjusted odds-ratio per standard deviation decrease of calcaneal BMD was calculated to assess the prediction of osteoporotic fracture. The correlation of calcaneal BMD with age was 0.36 in the combined population. The difference between the peak BMD and that of normal 70year-old women was 17%, or a T-score of about 1.0. Fracture cases averaged 12% lower BMD than controls (Z-score 0.6), and the odds-ratio was close to 2. Calcaneal BMD predicted osteoporotic fracture comparably to axial BMD in other studies, even though the T-score decrease with age is less than that for spine or femur BMD. This conrms other reports showing that the WHO denition of osteoporosis is not valid for calcaneal BMD.

Independent Variable PIXI-BMD PIXI T-score

n 99 99

r2 0.84 0.84

SE 0.032 0.263

Intercept 0.216 0.208

Slope 0.81 0.55

Calcaneal BMD Mean

T-Score SD 0.09 0.1 0.09

ODDS Ratio

302 (278). INTERRELATIONSHIPS BETWEEN SERUM LEVELS OF BONE RESORBING CYTOKINES, BONE MINERAL DENSITY AND BONE TURNOVER IN TYPE I OSTEOPOROTIC PATIENTS D. Grigorie, E. Neacsu, C. Barbu, M. Dumitrache, M. Grigorie, C. Dumitrache, 1``C.I. Parhon'' Institute of Endocrinology; 2Ana Aslan Institute of Geriatrics and Gerontology, Bucharest, Romania We measured markers of bone turnover, serum levels of resorbtive cytokines (IL1alpha, IL1ra and TNF alpha) and serum calciotropic hormones levels in 50 women in early postmenopause. Compared to premenopausal subjects, mean value of VMD (0.913 g/sqcm) was signicantly lower (p<0.001) in postmenopausal women. Mean levels of serum intact osteocalcin (23.6 pg/ml), crosslaps value (403.9 mcg/mmol creat.) and serum IL1 alpha (5.77 pg/ml) and IL1ra (496 pg/ml) were signicantly higher (50%, 41%, 32.3%, 44% respective, p<0.05) in postmenopausal women compared with controls. A signicant correlation was found between VMD and crosslaps values (r = 0.35, p50.05). Serum levels of TNF alpha correlated signicantly with serum intact osteocalcin (r = 0.42, p<0.02), serum IL 1 alpha (r = 0.33, p<0.05) and IL 1 ra (r = 0.42, p<0.01). Postmenopausal women with very low levels of serum estradiol (<5 pg/ml) had a signicantly higher mean IL 1 alpha serum levels compared with postmenopausal subjects with higher serum estradiol levels (> 5 pg/ml). Mean values of serum Ca, serum intact (184) PTH, serum (25-OHD) and serum TNF alpha levels did not signicantly change during menopause. Conclusions: 1) in early postmenopause, trabecular bone loss is correlated with the level of bone resorbtion; 2) our data suggest that the high serum levels of resorbtive cytokines could be responsible for the high bone turnover and trabecular bone loss in early postmenopause.

Young Adults Controls Osteoporotic

0.524 0.483 0.424

0 0.5 1.1

NA 1.93

304 (280). DIFFERENCE BETWEEN T-SCORE OF LUMBAR SPINE AND HIP AS AN INDICATOR FOR PERIMENOPAUSAL BONE LOSS T. H. Hennigs, University of Frankfurt/M, Germany The aim of this study was to examine an index (Im) for the postmenopausal bone loss comparing the bone mineral density of the lumbar spine and the hip. The BMD was represented by the DEXA T-score (Hologic 4500A). The index Im = Scorelumbar 7 Scorehip. The investigation included white healthy women, without suspected conditions affecting bone metabolism, divided into three groups: premenopausal (PREM) (n = 48, mean age 42.3, range 3058 years), postmenopausal with Hormone Replacement Therapy (HRT) (POSTH) (n = 43, 56.5, 4665) and postmenopausal without HRT (POST) (n = 63, 56.5, 3965). The results show that the onset and degree of menopausal bone loss can be determined by the Im calculated from the difference between the T-scores of the vertebra with the lowest score (Lmin) and the neck of the femur. We found signicant differences between mean Im of POST (1.0340.826) vs. PREM (0.3160.704) (P<<0.001) and POST vs. POSTH (0.2550.588) (P<<0.001). There was no difference between POSTH and PREM. Furthermore, we found a strong correlation: with increasing number (x) of years since menopause (YSM), the Im in POST was decreasing in a linear mode: Im = 0.102 x 0.274 (SD0.59) (r = 0.70). There was no similar correlation in the POSTH group (r = 0.17). We conclude that in healthy perimenopausal women the Im multiplied by 10 and corrected by 3 is approximately equal to the number of years since menopause (10 Im(TLmin Tneck) 3 = YSM). This new Im-score allows a dynamic approach to the results of BMD measurement even during the rst patient visit.

303 (279). CAN WE USE THE PIXI DENSITOMETER IN MASS SCREENING FOR OSTEOPOROSIS?: A POPULATION-BASED STUDY D. Hans, C. Perron, G. Conicella, M. Barada, C. Gumy, D. O. Slosman, Nuclear Medicine Div., Geneva University Hospital, Geneva, Switzerland Some clinicians propose using peripheral densitometry (pDXA) for mass screening. The purposes of this study were to investigate the PIXI as a screening tool by checking its ability to discriminate osteoporotic fractures versus controls. In the mass-screening environment of the last Geneva fair, more than 400 women were scanned at the calcaneum in less than a week using the PIXI densitometer (Lunar Corp., Madison, WI). All volunteers had a detailed questionnaire, using which we extracted 3 sub-groups: 54 young adults (mean age 326); 34 patients with osteoporotic fracture (mean age 619; hip, spine,

305 (281). EVALUATION OF AN OSTEOPOROSIS SELFREFERRAL PROGRAM A. B. Hodsman, N. Platt, S. Baker, L. Nicholson, B. Nicholson, Department of Medicine and the Lawson Research Institute, University of Western Ontario, London, ON, Canada In an effort to identify women at risk for osteoporosis, an Osteoporosis Self-Referral Program (OSRP) was developed for a fee of $30 Canadian. Clients attended a one hour group class led by a Nurse Practitioner, were informed about risk factors, completed a SCORE1 questionnaire, and underwent calcaneal

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ultrasound (U/S). Risk was communicated as low, medium or high, based on published tertiles for U/S BUA in women over age 65 years (cut-points at 72.5 and 58 ml/sec, Hologic Sahara). A telephone survey was developed to identify 5 domains of information provided by the OSRP. 517 clients were contacted, at least 6 months post-OSRP, and 271 completed the survey. Ages ranged from <50 yrs (n=72), 5065 yrs (n=136), to >65 yrs (n=53), of whom 20% were high, 30% medium, and 50% low risk for osteoporosis. Results: Over 80% could: dene osteoporosis, list >2 signs/ symptoms, list >2 risk factors and describe both U/S and DEXA BMD tests. Reported diet calcium increased in those with previously low intake (p = 0.005). Sedentary clients exercised more (p = 0.05). Compared to lower risk groups, high risk clients were more likely to speak to their doctor about DEXA (p = 0.03). 50% of high risk clients vs. only 7% low risk clients had arranged for DEXA tests (p<0.001). 60% of high risk clients were either on estrogen or bisphosphonates vs low or medium risk clients, of whom 4050% were already on estrogen. Conclusion: The unusually high estrogen use suggests a wellmotivated client base. However, the OSRP led to effective education of its clients, and targeted appropriate responses in both the clients and their primary physicians.

Material and Methods: 103 consequtively admitted women aged 698.6 years were included in the study and were exposed to a new x-ray of the spine. The x-rays were subsequently descriebed by trained radiologists and hence the lateral exposures were digitized to classify the degree of vertebral compression. The results were compared by calculations of Kappa coefcients. Results:

Conclusion: Only a minor fraction of cases could demonstrate an agreement between the clinical radiological evaluation of vertebral fractures and the digitzed parameters of vertebral compression.

306 (282). AN INTERVENTION STUDY TO EXAMINE KNOWLEDGE AND ATTITUDE TOWARDS CHANGE IN OSTEOPOROSIS PREVENTION J. Im1, D. J. Sartoris1, J. O.F. Reimann2, 1University of California San Diego, San Diego, CA, USA; 2San Diego State University, San Diego, CA, USA The purpose of this intervention study was to promote osteoporosis awareness and prevention among young adult females. In this intervention study an osteoporosis lecture and a bone mineral density (BMD) measurement were utilized to determine knowledge and attitude towards change regarding osteoporosis prevention. Twenty-eight Caucasian and Asian women ranging from 18 to 29 years of ages were included in the study. Each participant completed two question-naires. The two questionnaires consisted of knowledge and attitude towards change concerning osteoporosis. In addition to the two surveys, participants in the intervention group were provided with a bone mineral density (BMD) measurement and an osteoporosis lecture. The Statistical Program for Social Sciences (SPSS) was used for data analysis. Specically, independent sample t-tests, paired sample t-tests, and descriptive analyses were performed to conduct data analysis. Results suggest an increase in knowledge and attitude towards change among individuals who were provided with a lecture and a BMD measurement compared to those who did not receive any intervention. Also, there was a signicant difference in knowledge and attitude towards change between the pre- and post-test results among individuals who received the intervention.

308 (284). A NEUROMUSCULAR TEST BATTERY FOR ADULTS K. Kerschan-Schindl3, E. Uher3, S. Grampp1, A. Kaider2, V. FialkaMoser3, E. Preisinger3, 1Dept. of Radiology; 2Dept. of Medical Computer Sciences; 3Dept. of PM&R, University of Vienna, Austria The aim of this study was to examine the practicability of a short neuromuscular test battery in elderly women suffering from osteoporosis. The number of postmenopausal fractures and the history in regard of agility and falls were assessed in 42 women with a mean age of 70.05.1 years. The women performed neuromuscular tests and bone mineral density (BMD) of the spine and femoral neck were measured. 13.21.3 months later, 39 women appeared for the follow-up assessment. During the observation period ve women fell once and one woman fell twice; only two vertebral and no non-vertebral fractures occurred. Neuromuscular performance did not change within this observation period. The median changes in BMD between the two assessments were clinically not relevant. Comparing patients suffering from established osteoporosis with osteoporotic patients without a history of postmenopausal fractures showed that they did not differ in regard of age, neuromuscular performance, BMD, and fear of falling. This neuromuscular test battery is a feasible and practicable tool because it is brief and economical. However, its efcacy as a predictor of fractures has to be tested in studies with a long-term follow-up.

309 (285). INTERNAL QUALITY CONTROLS OF ULTRASOUND OF BONE (ACHILLES PLUS) IN THE SEMOF STUDY: THE INFLUENCE OF THE WATERBATH TEMPERATURE M. A. Krieg, J. Cornuz, L. Sandini, P. Burckhardt, for the SEMOF Study Group, University Hospital, Lausanne, Switzerland

307 (283). RADIOLOGICAL VERTEBRAL FRACTURE: FACT OR FALLACY? J.-E. B. Jensen, H. A. Srensen, Department of Endocrinologi, H:S Hvidovre Hospital, University Hospital of Copenhagen, Denmark Vertebral fractures are seriours complications to osteoporosis found in nearly 25% of all Danish women. A 20% reduction in the vertebral hight is considered dianostic for a vertebral fracture. The purpose of this study was to compare the common clinical evaluation of X-rays with a semi-automatic digitized measurement of vertebral compression.

Background: Stability of the devices should be measured when using quantitative ultrasound. During the inclusion phase of the SEMOF study (Swiss Evaluation of the Methods of Measurement of Risk of Osteoporotic Fracture) on 7800 elderly women, 10 Achilles+ devices (Lunar), used in 10 centers, were checked through a standardized quality control (QC) program, i.e. by repeated measurements with a local phantom provided by the manufacture. Method: QC included measure of: water temperature (wt), water SOS (wSOS), phantom temperature (pt), phantom BUA (pBUA) and phantom SOS (pSOS). It was performed 56 to 98 time in each of the 10 centers.

Results: wSOS was highly correlated with wt (r = 0.870.99). The correlation with pt was better for pSOS (r = 0.830.99) than for pBUA (r = 0.640.94). -In vitro long-term precision of Achilles+ before (CV%) and after adjusted by pt (adjCV%), from 10 centers:
CV% BUA SOS 1.23 0.39 range 0.691.79 0.280.48 adjCV% 0.61 0.13 range 0.400.84 0.050.23

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312 (288). COMPARISON OF FRACCIONAL CALCIUM ABSORPTION FROM CALCIUM CARBONATE AND CALCIUM CITRATE ON ACHLORHYDRIC PATIENTS A. Marino, J. R. Talbot, G. Rodriguez, J. R. Zanchetta, E. Roldan, Metabolic Research Institute; 2School of Medicine; 3Del Salvador University; 4Dept. Clin. Pharmacology of Gador, Buenos Aires, Argentina

Conclusion: wSOS was highly correlated with wt, and pSOS and pBUA with pt. Long-term precision of BUA and SOS was improved after correction by temperature. However, specic standardized phantoms have to be developed in order to compare the different devices used in a multicenter study.

310 (286). OSTEOPOROSIS IN AN INTERNAL MEDICINE SERVICE OF A UNIVERSITARY GENERAL HOSPITAL IN SPAIN J. A. Lopez-Herce, A. Del Castillo, J. Portugal, Hospital General Universitario Gregorio Maranon, Madrid, Spain OBJECTIVES To study the incidence, the level of suspicion for diagnosis and treatment of osteoporosis. METHODS We have retrospectively reviewed all discharged charts of the patients who entered in 1997 in our Internal Medicine Service. Men over 55 years old and women over 45 years old. We have studied if the patients had been diagnosed or treated of osteoporosis previously, during their staying in the hospital, or when they were discharged. RESULTS More than 25% of the patients had radiological signs of osteoporosis, but they were not diagnosed nor treated for it. Some of these patients had been receiving yatrogenic treatments with corticoids, haparin or thyroxin. Only 1% of the patients were diagnosed of osteoporosis during their stay in the hospital. CONCLUSIONS The osteoporosis is a clinical entity underdiagnosed and undertreated.

Although the knowledge of calcium absorption performance is crucial to the understanding of calcium and bone status it has been neglected by most workers on the bone eld, regardless of the fact that its efciency decreases linearly after 50 years of age. Recently it has been reported that calcium citrate may have a better bioavailability than other calcium salts probably because calcium-citrate complexes can be absorbed by both ionizedtranscellular and citrate-induced paracellular mechanisms. The aim of this study was to compare the calcium absorption efciency from calcium carbonate and citrate salts on patients with functional achlorhydria induced by atrophic gastritis. Two fractional calcium absorption tests (a2) were performed to each of nine 604-year-old females. After a 12-h fast, serum samples were drawn at baseline and one hour after the oral administration of 20 mg of elemental calcium as carbonate (CBD) or citrate (Mission/Gador) plus 5 uCi of Ca45. Five patients started the absorption test taking calcium carbonate rst and calcium citrate two weeks later; the remaining 4 patients started with calcium citrate and then switched to calcium carbonate. Fractional calcium citrate absorption was signicantly higher than that of calcium carbonate: (a2SD = 0.4390.092 vs 0.8030.062, p<0.001). Our study conrms that calcium citrate its better absorbed than calcium carbonate in achlorhydric patients. Since the active calcium absorption decreases in the elderly in favour of the passive mechanism, the higher bioavailability of calcium citrate observed in our study, may be explained by the positive inuence of both calcium and citrate ion on calcium kinetics. Since achlorhydria is also a common disorder in elderly persons, calcium carbonate should not be used as a supplement in individuals with any type of achlorhydria (drug-, disease- or age-related) in the assessed conditions.

311 (287). SCREENING FOR OSTEOPOROSIS IN LONG-TERM SURVIVORS OF BREAST CANCER S. M. Mahon, Saint Louis University, St. Louis, MO, USA Purpose: Improved treatment of breast cancer has created a population of survivors who are at risk for osteoporosis due to treatment with chemotherapy, early menopause, and long-term estrogen deciency. At least 500 000 women at age 50 are breast cancer survivors with an additional 20 000 women added each year. Methods: A mailed survey to a random sample of 668 outpatient oncology nurses (n=320, response rate=48%) was conducted to determine practices for osteoporosis screening in long-term survivors. Results: On average, 22.5% report that patients with breast cancer have height measured annually. This recommendation is most likely initiated by the physician (n=119, 40.5%) or the nurse (n=116, 39.5%). 68.1% of the respondents report there is no formal program for bone health education. When this education is done; it is most often initiated by a physician (n=165, 54.6%) or a nurse (n=89, 29.5%). On average, only 19% have BMD done and is most often initiated by a physician (n=248, 81.8%). BMD was available at 221 (69.1%) of the institutions. Conclusions: These results suggest that education about risks, means of prevention, and screening for osteoporosis are not routinely discussed or implemented with long-term survivors of breast cancer. Increased awareness of osteoporosis and the implementation of protocols to assure screening and treatment are carried out could ultimately decrease the morbidity and mortality associated with this treatment and disease-related complication.

313 (289). THE COMPARISON OF DUAL X-RAY ABSORPTIOMETRY AND SPINE X-RAYS DATA IN POSTMENOPAUSAL WOMEN L. A. Martchenkova, A. V. Dreval, N. M. Milov, Moscow Regional Research Clinical Institute, Moscow, Russia The purpose of this study was to evaluate the efcacy of axial and peripheral dual X-ray absorptiometry (DXA) in predicting vertebral deformities in postmenopausal women. The bone mineral density (BMD) measurement and standard thoracic and lumbar spine Xrays were performed at 64 postmenopausal women aged 4570 yrs. BMD at lumbar spine (L1-L4), femoral neck, Ward's triangle and trochanter were assessed utilizing a Lunar DPX absorptiometer. Wrist BMD was measured by an Osteometer DTX200. The positive correlation between BMD (T-score, %) of the lumbar spine and all proximal femur sites were revealed (r = 0.590.92, p<0.05), and there was no signicant correlation between wrist BMD and BMD of the other skeletal sites (r = 0.010.37, p>0.05). 38% of women with lumbar T-score 52.5 SD had osteoporotic vertebral deformities in the lumbar spine and 76% had ones in the thoracic spine. Nobody of women with normal lumbar BMD had vertebral deformities in lumbar spine, but 28% of them had thoracic vertebral fractures. All the women with wrist T-score 52.5 SD had vertebral deformities in the thoracic spine. Conclusions: The lumbar spine DXA data objectively assesses only the risk of fractures in the lumbar spine, but does not predict thoracic vertebral deformities. The wrist DXA data does not give any information about spinal and proximal femur BMD, nevertheless osteoporosis in wrist indirectly testies to vertebral deformities.

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314 (290). DECREASED BONE MINERAL DENSITY AFTER BONE MARROW TRANSPLANTATION G. Massenkeil1, C. Fiene1, O. Rosen1, R. Michael2, W. Reisinger3, R. Arnold1, 1Dept. of Internal Medicine, Div. of Oncology/ Hematology; 2Clinic for Nuclear Medicine; 3Institute of Radiology, University Hospital Charite, Berlin, Germany Purpose of this investigation: To study the changes in bone metabolism and bone mineral density (BMD) after bone marrow transplantation (BMT). Material and Methods: 42 patients were followed prospectively after BMT. Median age 36 years (range 1758), 24 males, 18 females. 38/42 suffered from leukemia (12 ALL, 11 AML, 14 CML, 1 MDS), 1 aplastic anemia, 2 NHL, 1 breast cancer. 38 patients underwent allogeneic BMT after TBI and chemotherapy, 25/38 had a related and 13/38 had an unrelated donor. 4 patients received an autologous transplantation. GvHD prophylaxis consisted of CSA, MTX and in addition prednisone in MUD. BMD was measured by computerized tomography of the lumbar spine (CT) and sonography of the calcaneus (US) before, 6 and 12 months after BMT. Deoxypyridinium (DPD) and pyridinium (PYD) were analysed by ELISA and RIA and vitamine D was measured by RIA. Serum and urine analyses were performed before BMT and weekly thereafter for six weeks, and 6 and 12 months postBMT. Results: BMD Z-scores in CT decreased after BMT from .0.48 to .1.14 after 6 and .1.01 after 12 months. Z-scores in US decreased from .0.03 to .0.89 and .0.77 after 5 and 12 months, respectively. 8/42 (19%) patients developed osteoporosis (BMD below .2.5) Bone metabolism showed pathologically increased DPD and PYD values at baseline: DPD:10.0 nmol/mmol crea (normal 2.5 6.5) and PYD 79.05 nmol/mmol crea 1637). After BMT values normalized within 2 weeks both rising again to pathologic serum concentrations with hematopoietic reconstitution. Despite vitamine D supplementation, the initially normal serum values of 1,25 (OH), D3 and 25 (OH)D3 fell to pathologically low values after BMT and did not recover within the rst 6 weeks after BMT. Conclusions: BMT patients frequently have decreased BMD even before conditioning. Conditioning, BMT and GvHD prophylaxis add further damage to the bone. Diagnosis, pervention and therapy of osteoporosis should be included in patients' care after BMT.

``discordance'' in T scores at different skeletal sites), the optimal T-scores for diagnosing osteoporosis were calculated for both techniques. 89 women, mean age 698, range 3386 years, were studied. There were signicant correlations between QUS and central site BMDs (total hip r = 0.55, spine r = 0.47), between PIXI and central sites BMDs (total hip r = 0.56, spine r = 0.61), and between QUS and PIXI (r = 0.66) [p<0.001]. There were no signicant differences between areas under the ROC curves for QUS (0.670.04) and PIXI (0.720.04) [p = 0.4]. The optimal T score cut-offs for diagnosing osteoporosis were T= 2.4 for QUS (stiffness) and T= 1.7 for heel PIXI. These are similar to the T-score equivalents for these techniques suggested by the manufacturers, based on equivalent prevalence of osteoporosis using hip BMD as the standard (T= 2.5 for Achilles Plus and T= 1.6 for heel PIXI). Using the calculated optimal cut-offs the sensitivity, specicity, false positive and negative rates for QUS in diagnosing osteoporosis were 65%, 66%, 16% and 19% respectively, and those for PIXI were 69%, 68%, 15% and 17% respectively. In conclusion, QUS (Achilles plus) and BMD (PIXI) measurements at the calcaneus site had similar ability in diagnosing osteoporosis. The optimal T-score thresholds for these peripheral devices, calculated from the ROC curves, were T2.4 and T1.7 respectively.

316 (292). CONSISTENCY AND CHANGES IN T-SCORE CATEGORIES OVER 4 YEARS AMONG EARLY POSTMENOPAUSAL WOMEN M. McClung, P. D. Ross, C. Christiansen, D. Hosking, D. Thompson, J. Yates, for the EPIC Research Group, 1Oregon Osteoporosis Center, Portland, OR; 2Merck & Co., Inc., Rahway, NJ, USA Many clinicians use WHO criteria for osteoporosis and low BMD (T-scores 42.5 and 1.0 to 2.5, respectively). We examined the proportions of women who shifted from one category to another during a 4 yr period, using spine, hip, and total body BMD from 373 women ages 4559 (>6 months postmenopause) in the placebo group of the Early Postmenopausal Interventional Cohort (EPIC) Study, a randomized, controlled trial of alendronate. Enrollment of women with osteoporosis was limited by study design to <10%, so the proportion with osteoporosis at baseline may not be representative of the community. Nevertheless, this cohort is appropriate for examining changes among BMD categories over time. The women were given general recommendations about calcium intake and exercise for bone loss prevention, but calcium supplements were not provided. At baseline, 6.4% of women were classied as osteoporotic, and 48.5% had low BMD, based on spine BMD. At the hip and total body, 4.3 and 3.8% were osteoporotic, and 41.3 and 50.5% had low BMD, respectively. At the end of 4 years, the proportions of women with osteoporosis (T 42.5) had increased to 9.4, 5.9, and 7.1%, based on spine, hip, and total body BMD, respectively. Among the 181 women initially classied with low BMD at the spine, 17 became osteoporotic within the subsequent 4 years, and 157 remained in the low BMD category. All of the 17 women who became osteoporotic had T-scores 41.9 at baseline, close to the 2.5 cutoff. The shift to osteoporosis will accelerate; the proportion of all women with spine T-scores between 2.5 and 2.0 increased from 9.7% at baseline to 15.0% after 4 years. We conclude that the WHO classications remain relatively stable over 4 years, although the proportion of women with osteoporosis increases substantially within 4 years due to progressive bone loss. The aim of prevention is therefore to preserve bone mass and thereby minimize the risk of developing osteoporosis.

315 (291). COMPARISON OF HEEL BONE MINERAL DENSITY AND QUANTITATIVE ULTRASOUND MEASUREMENTS IN DIAGNOSING OSTEOPOROSIS T. Masud, D. Pearson, D. Jordan, O. Sahota, D. J. Hosking, City Hospital, Nottingham, UK Bone mineral density (BMD) and quantitative ultrasound (QUS) measurements at peripheral sites are increasingly being used for the diagnosis of osteoporosis and assessment of fracture risk. The aim of this study was to compare heel QUS with heel BMD in diagnosing osteoporosis using conventional central (hip and spine) dual-energy x-ray absorptiometry (DXA) as the standard method. Women who were consecutively referred for bone densitometry from the bone clinic were studied. QUS (stiffness) and BMD of the left heel were measured by the same trained operator using the Achilles Plus and PIXI (peripheral DXA) [Lunar] machines respectively. BMD of the hip and spine were measured using the Lunar Expert DXA machine. Receiver operating characteristic (ROC) curves were plotted for QUS and PIXI using EMD at any central site (total hip, femoral neck or lumbar spine) as the ``standard'' method for diagnosing osteoporosis (employing the WHO T 2.5 criteria). As the WHO criteria cannot automatically be applied to all peripheral techniques (because of the occurrence of

317 (293). EVALUATION OF HEEL DENSITOMETRY BY PIXI FOR THE DIAGNOSIS OF OSTEOPOROSIS IN PATIENTS WITH AND WITHOUT NON-SPINE FRACTURES S. Meszaros, E. Csupor, E. Hosszu, K. Bors, E. Toth, C. Horvath, 1st Dept Medicine, Semmelweis University, Budapest, Hungary Precision error and diagnostic utility of the heel bone densitometry was evaluated in this study. BMD was measured in 106 women (2868 ys) and 44 men (2372 ys) at heel (PIXI, Lunar), at lumbar spine and hip (DPX-L, Lunar), at radius (NK364, Gamma). Heel ultrasound (Sahara, Hologic) was also done. Fractures have occured in 30 women and 20 men. In vitro precision error of heel BMD by multiple phantom measurements was found 0.41% and 0.26%, with or without reposition, respectively. In vivo precision error in healthy volunteers and in patients with spinal osteoporosis was found 1.0% and 2.81%, respectively. Heel BMD negatively correlated with age in women (r = 0.348, p50.0001) but not in men. Positive correlations were found for BMD between heel and other sites (r = 0.5070.680) and between heel BMD and heel SOS or BUA (r = 0.5460.777), in both sexes. Patients were grouped as normals or osteopenics or osteoporotics based on T-score at spine or hip or radius. Heel BMD in women differentiated normals from patients with osteopenia or osteoporosis, based on any site. In males the normals were differentiated from patients with low density but osteopenia was not separated from osteoporosis. For heel BMD the difference between patients with and without previous non-spine fractures was signicant in female but not in male patients, while heel ultrasound resulted in signicant difference between the fractured and non-fractured groups of both sexes. Our results suggest the heel densitometry to be an effective tool for the diagnosis of osteoporosis in women with or without fractures. However, more investigations seem to be needed for using this method in osteoporosis of the males.

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in creatinine values induces a secondary hyperparathyroidism that may inuence the changes in femoral bone mass.

319 (295). QUANTITATIVE ULTRASOUND AT PHALANXES IN THE DIAGNOSIS OF OSTEOPOROSIS IN MEN A. Montagnani, S. Gonnelli, C. Cepollaro, M. Mangeri, S. Pacini, L. Gennari, B. Lucani, C. Gennari, Institute of Internal Medicine, University of Siena, Italy Previous studies in women have shown that Quantitative ultrasound parameters (QUS) could be useful in the diagnosis of osteoporosis and in discriminating between fractured and unfractured women. Instead, to date few experiences exist about QUS application in the diagnosis of male osteoporosis. The aim of the present study was to investigate the usefulness of QUS at phalanxes in male osteoporosis. We studied 88 osteoporotic men (59.311.0 yrs; 32 with- and 56 without osteoporotic fractures) and 120 healthy men (59.89.1 yrs). In all subjects we measured bone mineral density (BMD) at lumbar spine and at femur by DXA (QDR 4500, Hologic, USA) and ultrasound parameters at phalanxes by DBM Sonic 1200 (IGEA, Italy). This device gives amplitude-dependent speed of sound (AD-SoS) and other parameters characterising US graphic trace (Fast wave amplitude-FWA, Signal dynamic-SDy, Bone transmission time-BTT and Ultrasound bone prole index-UBPI). DBM Sonic is characterised by a good precision, i.e. 0.3% for AD-SoS. All QUS parameters were signicantly (P<0.001) lower in osteoporotic patients than in healthy subjects, showing a moderate relationship with BMD values at lumbar and femoral level. As expected, axial and femoral BMD was signicantly lower in fractured group. Among QUS parameters only AD-SoS and BTT showed a signicant difference between fractured and unfractured patients (1938.189.9 m/s vs 1995.3103.8 m/s and 1.4 ms vs 1.7 ms, respectively). Moreover, a ROC curves analysis showed a good ability of all QUS parameters in discriminating between osteoporotic and healthy subjects, whereas only BTT and AD-SoS showed a signicant, even if moderate, sensitivity in distinguishing between osteoporotic patients with or without fracture. In conclusion our study points out that: in males as well as in women QUS parameters at phalanxes are able to distinguish between osteoporotic and healthy subjects; moreover, BTT and AD-SOS could be useful in discriminating between fractured and unfractured men. Therefore, QUS at phalanxes could be considered a useful tool in the management of male osteoporosis.

318 (294). BONE DISEASE AFTER LIVER TRANSPLANTATION (LT). A THREE-YEAR PROSPECTIVE STUDY A. Monegal, M. Navasa, N. Guan abens, P. Peris, F. Pons, J. M. mez, Hospital Mart nez de Osaba, J. Ordi, J. Rodes, J. Mun oz-Go Clinic, Barcelona, Spain Aims: To determine the risk factors and the incidence of bone fractures and to assess the evolution of bone mass and turnover after LT. Patients and Methods: Three years prospective study in 45 LT patients (16m/29f), age 50.88 years. The follow-up was 2 years in 34 patients and 3 years in 30 patients. For all patients vertebral and femoral bone mineral density, spinal X-ray (rst year) and serum levels of Ca, P, osteocalcin, intact PTH, 25 OH-D and testosterone (men) were evaluated before and 3, 6, 12, 18, 24 and 36 months after LT. Histomorphometric analysis was done in bone biopsies obtained in 24 patients before and 6 months after LT. Results: 15 patients (33%)developed fractures after LT. Elder patients (p<0.05) and those with densitometric criteria of osteopenia or osteoporosis were more prone to develop fractures (p<0.05). Serum PTH, osteocalcin, 25 OH-D, testosterone and creatinine levels increased after LT. PTH correlated with creatine (R:0.7, p<0.000) and osteocalcin (R:0.5, p<0.05) values. Bone mass decreased during the rst 6 months and reached to baseline values at the lumbar spine at the second year, with posterior but signicant (p<0.05) increase at the femoral neck. Long-term evolution of femoral BMD correlated with PTH levels (R:0.6, p<0.01). Six months after LT bone histomorphometric data showed an increase in bone formation parameters. Conclusions: LT patients, specially those with osteopenia or osteoporosis showed a high incidence of fractures. Bone mineral density decreased in the short-term period and improved, initially at the lumbar spine and later at femur, according to histomorphometric evidences of an increase in bone formation. The increase

320 (296). QUANTITATIVE ULTRASOUND DOES NOT REFLECT MECHANICALLY-INDUCED DAMAGE IN CANCELLOUS BONE P. H.F. Nicholson, M. L. Bouxsein, Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA This study assessed the sensitivity of quantitative ultrasound (QUS) to reductions in the elastic modulus (E) of cancellous bone due to mechanical damage, in the absence of changes in apparent density or architecture. Ultrasonic velocity and attenuation were measured using an in-house imaging system in 46 cancellous bone cores from the human calcaneus (mean age=82 yrs, range=5099). Cores were tested mechanically to a) determine E prior to damage, b) induce damage by applying specied strains in excess of the yield strain, and c) measure E post-damage. Four groups were used: a control group subjected to a non-destructive 0.7% maximum strain (em), and three damage groups subjected to increasing strain levels (em = 1.5%, 3.0%, 4.5%). QUS measurements were made before and after mechanical testing. At baseline (i.e., before damage was induced), QUS measurements were strongly correlated to bone density (r2=0.85 70.93, p<0.01) and to E (r2=0.710.75, p<0.01). QUS measurements were unaffected by mechanically induced damage despite

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highly signicant reductions in E of up to 72%. These results demonstrate that current QUS measures do not intrinsically reect the elastic properties of cancellous bone. This is consistent with QUS properties being determined by other factors (apparent density and/or architecture) which are normally strongly associated with elastic properties, but only when bone is mechanically intact. Hence clinical QUS cannot be expected to detect bone fragility in the absence of accompanying changes in bone density or structure.

and DXA of the lumbar spine and femoral neck (Lunar DPX-IQ or Expert). QUS was `Positive' if the calcaneal Stiffness 470. Using these criteria the population was stratied into two groups based on Stiffness. The prevalence of axial osteoporosis, (T42.5) in either the lumbar spine or femoral neck, is shown for the QUS subgroups for the whole population and for women over 60 yrs. Achilles stiffness 470 identies a subgroup in whom further assessment by DXA is justied. Pre-screening using Stiffness can stratify the population into `low risk' and `at risk' groups for axial osteoporosis.
Whole Population Women over 60 n Prevalence of axial osteoporosis (%) 53 8

321 (297). EXCELL, EXCELLplus, REFINEMENTS OF PROVEN DXA TECHNOLOGY J. M. Paucek, L. N. Harrold, Norland MedicalSystems, Inc., Fort Atkinson, WI, USA Norland Medical Systems implemented enhancements to central densitometers, to reduce scan times without compromising precision or accuracy. A clinical study was undertaken to validate the performance of these enhancements with respect to previous scanner characteristics. Two Norland scanners, an Eclipse and Excellplus, were used to perform in vitro phantom and in vivo human scanning. Systems were calibrated according to manufacturer recommendations. 15 volunteers were recruited. Experienced technologists were used for all scanning and analysis. Scan results were as expected, and consistent with previous published results, demonstrating the Excell offers signicantly reduced scan times wile retaining continuity with earlier Norland DXA densitometers.
US70 US>70

Prevalence of axial osteoporosis (%) 43 4

74 126

57 39

323 (299). PHALANGEAL OSTEOSONOGRAPHY IN WRIST FRACTURE DISCRIMINATION R. Rotini1, L.Catamo1, F. Noia1, R. Cadossi2, F. de Terlizzi2, G. Fontanesi1, 1Rizzoli Orthopaedic Institute, 1st Division, Bologna; 2 IGEA Biophysics Laboratory, Carpi, MO, Italy In this study we evaluated a group of 50 postmenopausal women with low energy forearm fractures and a group of 266 women that responded to a public call and that have been measured with ultrasound. Measurements were performed at the distal metaphysis of the proximal phalanxes of the hand by the DBM Sonic Bone Proler using an ``automatic acquisition mode''. The reproducibility of the methodology was for AD-SoS CV%=0.64% and for UBPI CV%=2.38. The table shows the characteristics of both groups of women and the results of the US measurements. We calculated the ROC curves for age-matched subgroups of subjects (100 controls and 50 fractured) and the AUC were respectively 0.750.04 for AD-SoS and 0.740.04 for UBPI. Our results show that ultrasound investigation at the phalanxes performed with the ``automatic acquisition mode'' is reproducible and efciently discriminates between subjects with wrist fractures and a population-based control group. The method provides a good reproducibility. The automatic modality of the DBM Sonic Bone Proler is easy to learn and doesn't require a skilled operator.


SCAN SPEED HIGH SPEED 260 mm/SEC HIGH SPEED, 260 mm/SEC 260 mm/SEC HIGH SPEED, 20 mm/sec 30 mm/sec


1.1 % 1.4% 1.5% 1.23% 0.8%

322 (298). THE UTILITY OF THE ACHILLES STIFFNESS PARAMETER FOR PRE-SCREENING FOR AXIAL OSTEOPOROSIS N. Pocock, N. Culton, G. Gilbert, M. Hoy, R. Babichev, J. Chu, J. Freund, St Vincent's, Liverpool; 2Bankstown Hospitals, Sydney, Australia Population screening for axial osteoporosis may aid in limiting the increasing health costs of osteoporotic fractures if it could be provided on a mass scale. The radiation exposure, and size of dual energy X-ray absorptiometry (DXA), generally requiring that scanners be sited within medical centers, limits their utility for mass population screening. While quantitative ultrasound (QUS), is radiation free and portable making it ideal for mass screening, previous studies have reached conicting conclusions, due often to the different emphasis placed on the low specicity of QUS in detecting low axial bone mineral density (BMD), despite its demonstrated role as an independent predictor of fracture risk. However even as a screen for low axial BMD, low specicity may be acceptable, if high sensitivity can be achieved given the safety, low cost and potential for widespread availability of QUS. The current study assessed the utility of QUS as a mass pre-screening tool to stratify the population into a `low risk' group for axial osteoporosis, and an `at risk' group, with a high prevalence of axial osteoporosis, who warrant further assessment by DXA. Two hundred females were studied using heel QUS (Lunar Achilles)

AD-SoS UBPI Number Age Age at (units) (yrs) menopause (m/s) (yrs) Control group Avg. and std. 266 Wrist fractured Avg. and std. 50 60.9 9.1 65.4 6.9 43.0 17.0 47.6 5.7 1915 111 1786 91 0.41 0.25 0.17 0.13

324 (300). OSTEOPENIC DEGENERATIVE LUMBAR SPINAL STENOSIS IN FEMALE SUBJECTS H. Sari, U. Akarirmak, C. Do nmez, D. Onel, Cerrahpasa Medical Faculty, Physical Medicine and Rehabilitation Department, Istanbul University, Istanbul, Turkey The aim of this study was to investigate the possible role of osteoporosis in the pathogenesis of Lumbar Spinal Canal Stenosis(LSS)

Methods: Bone mineral density was measured by Quantitative Computerized Tomography(Q-CT) Spinal Canal Stenosis was diagnosed by clinical ndings and CT measurement. Lumbar axial shortening was measured on magnied lateral topograms. Results: 32 women with LSS and 72 age matched controls were included in the study. 18 patients were under 50 years of age (56%). 16 patients were premenopausal (50%). Discal bulging in 29 patients (90%) and hypertrophy of facet joints were the must frequent CT ndings Conclusion: There was a signicant decrease in BMC in LSS subjects compared to controls in the age matched group especially in young, menstruating women (n=18.56%). Thus it could be considered that osteoporosis may be the prime mover in some patients.

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Etiology of the pregnancy-associated osteoporosis is not clear. In our group this is more commonly seen older patients with their rst pregnancies. We suggest pregnant women with back and/or hip problems during their third trimester or in postpartum period needs to be investigated for pregnancy-associated osteoporosis.

1 H MRS is an easy adjunct to spine MRI and may be used to (1) quantify major tissue components of vertebrae and to (2) determine bone strength. The technique can measure the entire volume of all lumbar vertebrae and will add 15 minutes to a routine MRI. We measured lipid-water-ratios (LWR), percent fat volumes (PFV), and linewidth. Nomograms for normal subjects (age 1587; 50 M/46 F) were compiled. In 83 subjects we correlated 1H MRS data with MRI signs of bone weakening (fractures, etc.). DXA data of 24 vertebrae (11 subjects) were compared with 1H MRS data. There was a linear rise of LWR and PFV with age. LWR's of younger subjects (2039 yrs = LWR 0.31) were markedly lower than those of older people (>80 yrs = LWR 1.38). Males showed a higher LWR than females. Subjects with MRI evidence of bone weakening had a higher percent fat volume. Comparison with DXA showed an inconsistent relationship between bone mineral density and percent fat volume. In conclusion, bone stability is likely determined by multiple factors. 1 H MRS may provide important additional information about bone strength.

325 (301). SEVERE IMMOBILIZING OSTEOPOROSIS AND CARBAMAZEPINE-INDUCED HYPERCORTISOLISM H-E Sarnighausen, K Goitom, M Engelbach, T Pohlmann, P Kann, K Lichtwald, J Beyer, Department of Internal Medicine and Endocrinology, University Hospital of Mainz, Germany The purpose of this investigation was to observe a 77-year-old male patient with hypercortisolism of unknown origin and immobilizing osteoporosis, diagnosed two years ago. A postoperative epilepsia appeared after an operation of a meningioma in 1972. He has not experienced any seizures within the last 6 years due to a treatment with carbamazepine. The patient has been diagnosed 6 years ago with carcinoma of the prostate and was orchidectomized. Methods/Results: AP 304 U/1, g-GT 67 U/1, and an elevated value of cortisol was found in the evening, pathologic overnight dexamethasone suppression test, suppressed cortisol in the second half of dexamethasone long test which was determined over a period of ve days, FSH was elevated, and the testosterone level was low, hyperglycemic suppressed hGH. No tumor was found in the CT-scan and endosonography of adrenals. Discussion: No sign for adrenal, pituitary or ectopic cortisol production. Lowered efcacy of the pituitary feedback of cortisol shown by the elevated cortisol in the evening by carbamazepine [J Clin Endocr Metab 1992;74(2):406 12]. Carbamazepine induces liver-cytochrome-p450-induction and accelerates the metabolism of dexamethasone [Horm Metab Res 1998;30:38997]. No correlation of bone density and carbamezepine was found [J Pediatr 1995 Aug; 127(2):25662]. In this case the osteoporosis is probably caused by postoperative hypogonadism.

328 (304). OSTEOPOROSIS PREVENTION COUNSELING DURING ANNUAL HEALTH MAINTENANCE EXAMS Sarina Schrager, Department of Family Medicine, University of Wisconsin, Madison, WI, USA Objective: The purpose of this study was to determine how often primary care providers discussed osteoporosis prevention and adequate calcium intake with healthy women during annual health maintenance exams. Methods and Results: 447 women ages 1865 were interviewed at eight family practice clinics around the state of Wisconsin immediately following a health maintenance exam. 46% reported discussing osteoporosis with their provider during the visit and 51% reported discussing calcium intake. A total of 61% reported discussing either osteoporosis or calcium intake during the visit. Female providers were signicantly more likely to discuss either osteoporosis prevention or calcium intake with women. As a woman got older, she was more likely to discuss both of these issues. Conclusion: Osteoporosis prevention counseling occurs slightly more than half of the time during primary care health maintenance exams. Provider education and institutional changes may increase the frequency of this counseling.

326 (302). PREGNANCY-ASSOCIATED OSTEOPOROSIS: SEVEN CASES OF PREGNANCY-ASSOCIATED OSTEOPOROSIS DISCUSSED T. Sarpel, E. Kozanoglu, R. Guzel, K. Goncu, Dept. of Physical Medicine and Reh., Cukurova University, Medicine Faculty, Adana, Turkey Osteoporosis has been described in pregnant women who developed vertebral and/or hip fractures in their last trimester or shortly after delivery. The etiology of this phenomenon is not known. During the last two years we had 7 cases with pregnancy associated osteoporosis. Osteoporosis was documented with radiographic ndings and by bone densitometry test. Also in each case other osteoporosis causing factors were eliminated. These cases presented with acute low back and/or hip pain. Mean age was 28.5 (2035), and 57% of the cases osteoporosis occurred during the rst pregnancy. Vertebral compression fractures were observed in all cases, in one patient there was a hip fracture. All patients were treated with either bisphosphonates and/or vitamin D metabolites. The response to the treatments will be discussed.

329 (305). LONGITUDINAL ANALYSIS OF DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS IN FRACTURE PATIENTS C. Simonelli, HealthEast Medical Research Institute, St. Paul, MN, USA The purpose of our study was to determine the rate of diagnosis and treatment of osteoporosis following hospital admission for low-impact fracture. A chart review and one year follow-up survey of 301 postmenopausal patients was completed. Retrospective

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analysis indicated this population was at high risk for osteoporosis and fracture. Despite this, osteoporosis was noted on the hospital chart in only 26% of patients. Calcium and/or vitamin D use marginally increased from 13.6% on admission to 16.2% on discharge. Only 39% of women discussed osteoporosis with their physician, 10% had BMD testing and only 26% received medication for osteoporosis. Quality of life deteriorated post fracture; 8.4% suffered additional fractures and 77.5% did not return to their pre-fracture functionality. The one-year mortality was 13%. On the positive side, 86% of those started on osteoporosis treatment remained on therapy for a year. Conclusion: These patients were at high risk for fracture but most were not evaluated or treated for osteoporosis. There was clear deterioration of quality of life post fracture. When physicians chose to intervene and prescribe osteoporosis medication, most of the women followed their instructions.

trabecular and cortical bone loss. In osteoporotic patients two different patterns of bone loss were seen (1) Accelerated (type I) trabecular bone loss where low DBD was accompanied by low RI (T-score <1.0); and (2) Balanced (type II) trabecular and cortical bone loss where DBD was low but RI remained normal. CONCLUSION of this study is that RI can differentiate type I osteoporotics with 44% multiple spine fractures from type II osteoporotics with only 9% multiple fractures.

332 (308). MULTI-SITE ULTRASONOMETRY METHOD FOR IMPROVED DIAGNOSTICS IN OSTEOPOROSIS A. M. Tatarinov1, A. P. Sarvazyan2, 1Riga Technical University, Riga, Latvia; 2Artann Laboratories, Lambertville, NJ, USA Mono-site QUS usually doesn't discern changes of bone material and architectural properties. To provide distinctive diagnostics of osteoporosis of different etiology and manifestation, an approach, utilizing multi-site tests, has been proposed. The idea is to compare changes of ultrasound parameters in different skeletal area, having prevalence of bulk substance (cortex), spongy tissue and combined spongy and cortical layers. For this purpose an experimental set up was built, compiling through mode and linear array probes, compact controller and mini-PC. Ultrasound velocity and attenuation frequency slope were measured in short (heel), at (ilium) and long (ulna, tibia) bones. In phantom studies inuence of contributions of mineral content, porosity and thickness of cortex on the said parameters have been investigated. First clinical trials involved a limited group of females with and without osteoporosis symptoms and demonstrated varied combinations of changes of ultrasound velocity in the sites with compact and spongy bone. Thus, in cases of chronic renal failure strong lowering was noted in the all mentioned sites. In arthritis patients moderate decrease of velocity in heel and ilium was usually accompanied by tends to increase in cortex of long bones. In the most cases of postmenopausal osteoporosis expressed decrease of velocity was registered in heel and ilium with no marked changes in long bones.

330 (306). PERIPHRAL DEXA: AN ECONOMIC ALTERNATIVE TO CENTRAL DEXA Amolak Singh, Houman Kiani, University of Mis souri Hospital, Columbia, MO, USA Peripheral DEXA (PD) measuring appendicular bone mineral density can be helpful in conditions such as hyperparathyroidism. We wondered, if PD can be useful in detecting osteoporosis in patients who can not afford Central DEXA (spinal and hip DEXA). Limited value of the PD in predicting axial skeletal osteopenia is well known; however the PD is relatively inexpensive and may be appealing to the under-priviledged population. Four hundred and forty eight (448) patients underwent PD. There were 402 females and 46 males. The PD was performed using a low cost device called PIXI (Lunar Corporation). We performed 212 calcaneus and 236 forearm (distal radius and ulna) PD studies. Signicant osteopenia was dened as a T score greater than 1.2. The severity of the osteopenia was graded as mild if T score was more than 1.2 but under 2.0, moderate if T score was more than 2.0 but less than 3.0, and severe if T score was more than 3.0. Signicant osteopenia was found in 173 of 448 (39%) individuals with age ranging 2197 years (mean age: 6313). Of those with osteopenia, the severity was mild in 91 (53%), moderate in 61 (35%), and severe in 21 (12%) of patients. The calcaneus and forearm measurements were equally effective in screening. The osteoporosis was more common in females (39%) than males (33%). The older patients exhibited more severe osteopenia. The PD may be useful when Central DEXA is cost-prohibitive.

333 (309). DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA) SCAN INTERPRETATION: LOOKING BEYOND THE NUMBERS D. J. Theodorou1, S. J. Theodorou1, D. J. Sartoris1, L. J. Deftos2, D. Resnick1, 1Department of Radiology; 2Department of Medicine, Veterans Affairs Medical Center and University of California, School of Medicine, San Diego, CA, USA Purpose: To investigate DXA scan image ndings that deviate from anticipated anatomical landmarks and require a sophisticated approach to patient positioning, scan analysis, and/or bone mineral density (BMD) determination, with the goal of optimizing interpretation of computer-generated printouts by clinicians and radiology technologists through radiographic correlation and critical appraisal of numeric data on DXA scan images. Patients and Methods: The DXA scan (Lunar DPX, Lunar Corp., WI) images of 1425 patients referred for 2-site (spine and hip) BMD measurement over a 4-year period were reviewed for various artifacts and pathologic processes, and their possible inuence on BMD results. Results: A wide spectrum of incidental DXA scan image ndings were identied including degenerative disease of the lumbar spine in 46 (3.2%) cases, fractures in 41 (2.8%) cases, scoliosis in 32 (2.2%) cases, osteoarthritis of the hip in 14 (0.9%) cases, metal artifacts in 13 (0.9%) cases, soft tissue calcication in 10 (0.7%) cases, spinal fusion in 8 (0.5%) cases, improper positioning of regions of interest in 7 (0.4%) cases, metastatic disease in 5 (0.3%) cases, osteonecrosis of the femoral head in 4 (0.2%) cases, and Paget's disease in 2 (0.1%) cases.

331 (307). RADIUS INDEX: FOREARM BONE DENSITY RATIO AS MARKER FOR TYPE I AND TYPE II OSTEOPOROSIS Manmohan Singh, University of Illinois at Chicago, IL, USA PURPOSE of this study is to differentiate Type I (postmenopausal) osteoporosis that results from rapid bone loss after menopause and affects metabolically active trabecular bone, from type II (age-related) osteoporosis, which affects both cortical, and trabecular bone tissues. METHODS involve the use of a Norland 278 SPA densitometer to measure bone density at 5-mm (55% trabecular) bone site in distal radius (DBD), and 2/3rd (95% cortical) bone site in mid radius (MBD). DBD/MBD ratio, called radius index (RI), was calculated to identify women with rapid trabecular bone loss. Two groups were tested: (1) Normals: 1192 Caucasian women in good health, aged 2089 years; and (2) Osteoporotics: 186 consecutive patients in an osteoporosis clinic. RESULTS indicate that DBD in normal population declines signicantly from 40654 mg/cm2 (meanSD) in age group 2029 to 28148 mg/cm2 in age group 8089. However, this bone loss did not signicantly change the RI (577% in age group 2029 versus 579% in age group 8089) because of balanced

Conclusion: DXA provides imaging performance that approximates radiographic quality, and may document abnormalities whose recognition is critical to optimal interpretation of BMD results. However, in many cases, the scan quality is insufcient to establish a specic diagnosis of ancillary ndings; therefore, radiographic or other imaging correlation may be necessary.

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0.830.36 g/cm2 and controls 1.10.21 g/cm2. Correlations for % wedging concavity and compression (n = 20) for HtL1 r = 0.31, 0.16 and 0.08 respectively and HtL2 r = 0.18, 0.37 and 0.02 respectively. These were not signicant. THtL differed in osteoporotics with and without vertebral deformity and with controls. THtL was not signicantly related to vertebral morphometric abnormality in this small sample.

334 (310). NORMAL VERTEBRAL DIMENSIONS IN SERIAL MEASUREMENTS OF VERTEBRAE: A METHOD USING MRI E. Thomas, Ph. de Reffye, M. C. Picot, F. Blotman, C. Cyteval, Montpellier, France Much clinical research on osteoporosis is aimed at documenting a reduction in vertebral fractures rate, but there is disagreement about dening normality. Most methods for measuring vertebral body dimensions use lateral radiographs. We investigate on the reliability of magnetic resonance imaging (MRI) for normal references determination. A validation study was performed on cadaver by comparing vertebral body volume measured with MRI (sagittal acquisition in T1 weighted sequence) and immersion. The digital data were converted to a work station and transfered to a high performance graphic system (corpus 20001). After manual segmentation, software processing of geometrical measures allows to determine the volume of each vertebral body. MRI was then performed from T9 to L5 in a population of 80 women with no vertebral collapse. All vertebrae measurements were standardized relative to each other, mean and standard deviation of their volume and medial area were derived by using a statistical tting procedure. The validation study conrmes reproducibility and accuracy of MRI (intraclass correlation coefcient 0.95). There is a strong correlation between volume and medial area of vertebral bodies (Pearson's correlation coefcient 0.95) and constant relationship between medial area of vertebral bodies for each subject (coefcient of variation 5.6%). The notion of normal vertebral body dimensions will allow comparison with osteoporotic vertebrae and could be useful for treatments monitoring.

336 (312). FACTOR OF RISK FOR SPINE FRACTURE NORMAL CHINESE MEN AND WOMEN IN TAIWAN Rong-Sen Yang1, Tang-Kue Liu1, Yi-Hsiong Hang1, Poon-Ung Chieng2, Keh-Sung Tsai3, 1Departments of Orthopaedics; 2 Radiology; 3Laboratory Medicine, College of Medicine, National Taiwan University, Taiwan INTRODUCTION: To investigate the potential risk of fracture, we assessed the factor of risk (f) of spine fracture in healthy Chinese in Taiwan. SUBJECTS AND METHODS: 603 females and 223 males aged 1872 years were included in this study. They were divided into either young (age <65 years) or old group (age 565 years). The bone mineral content (BMC) and projection area of lumbar spine was measured by a Norland XR26 DXA machine. The estimated strength (L) of lumbar spine was calculated from the regression equation (Carter et al.) and the estimated spinal load (F) for a person bending over with back horinzontal, either with hand free (F0) or lifting 200N weight (F200), was calculated from force diagram (William and Lissner). f was dened as the quotient of F/ L. RESULTS: The results showed an age-related decrease of BMD (p<0.001) in both genders corrected for weight and height. The f for F0 and F200 in the old females was signicantly larger than those of young females, whereas no signicant difference between the young males and old males. By multiple linear regression analysis, f for F0 and F200 increased signicantly with aging corrected for weight and height only in young females (p<0.0001). However, the increment was not signicant with aging in both old groups, whereas f for F0 and F200 for the old females were signicantly larger than old males (for F0, 0.530.10 vs. 0.640.13, p<0.001, for F200, 0.910.16 vs. 1.110.22, p<0.0001). DISCUSSION AND CONCLUSION: This study incorporated the body status and bone mineral content for estimation of the risk of fracture. Such a method may provide a more comprehensive estimation of fracture risk of spine during daily activities.

335 (311). HEIGHT LOSS AND VERTEBRAL DEFORMITY IN CLINICAL OSTEOPOROSIS S. E. W. Walsh, S. J. Iqbal, P. R. M. Jones, M. Haddaway, M. Davies, R. Dhingsa, K. Brooke-Wavell, T. Davies, 1From The Loughborough University, Loughborough, UK; 2Leicester Royal Inrmary, Leicester, UK; 3The Robert Jones & Agnes Hunt Orthopaedic & District Hospital, Oswestry, UK Osteoporosis can produce vertebral deformities with total height loss (THtL) and kyphosis. Can THtL be related to the level of vertebral deformity? We studied 49 osteoporotics, 43 F, 6 M, mean age 6512.9, 49 F controls aged 6410.3. Recalled peak height (RPkHt) was obtained by a questionnaire and current height (CHt) and armspan (ASPN) were measured using a portable stadiometer. Height loss was calculated from: RPkHTt CHt = height loss 1 (HtL1) and from ASPN CHt = HtL2. Lateral (T4 L5) spinal x-rays were used to undertake vertebral morphometry for % wedging, concavity and compression indices using a computerised image analysis system. Lumbar spinal (L2-L4) bone mineral density (BMD) was measured. The correlations between: ASPN and RPkHt r = 0.93 p <0.05, and % HtL1 and % HtL2 r = 0.39 p <0.05. HtL2 was signicantly different in osteoporotics with vertebral deformity (results in meanSD) THtL 7.64.6 cms to those without vertebral deformity THtL 3.64.1 cm and controls THtL 4.63 cms. The BMD was signicantly different in osteoporotics with vertebral deformity (mean SD) 0.780.13 g/cm2 and those without vertebral deformity

Osteoporosis Genetics
337 (313). THE RELATIONSHIP BETWEEN DIFFERENT GENOTYPES OF COLLAGEN TYPE I a 1 (COLIA 1) AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN Fatma Atalay, Oya Sahin, Volkan Seyrantepe, Gazi University Medical Faculty, Dept Physical Medicine and Rehabilitation, Ankara, Turkey Objective: This study aimed to investigate the relationship between different genotypes of collagen type I a 1 (COLIA 1) and bone mineral density (BMD) in postmenopausal women. Material-method: 50 postmenopausal women with no history of seconder osteoporosis and no usage of any medication that was effective on bone metabolism except oral calcium replacement were included to the study. BMD was determined by dual-energy x-ray absorptiometry (DEXA) at lumber spine and right hip. We looked for presence of signicant difference of bone mineral density between cases with different genotypes for the binding site for the transcription factor Sp1 in COLIA 1 gene. Result: BMD values, T and Z-scores of the lumbar spine were found to be the highest in `SS' genotype, they were reduced in

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`Ss' genotype and were lower in `ss' homozygotes. However, the differences between genotypes were not signicant for BMD values of the lumbar spine and proximal femur, T and Z-scores of the lumbar spine and femoral neck. Conclusion: We conclude that determination of the genotype according to the polymorphism, dened in COLIA 1 gene is not enough for prediction of BMD. Until the studies that are going on moleculer genetics will result, BMD of the lumbar spine and proximal femur is thought to preserve being the most appropriate way of diagnosing osteoporosis and determining the fracture risk.

genetic contribution to the pathogenesis of both female and male osteoporosis has been recognized. Previous studies examining the relationship between candidate gene polymorphisms, such as estrogen receptor (ER) or vitamin D receptor (VDR) genes, and BMD have been performed on women, with conicting results. However there are no comparable published data for men. In this study 240 elderly men, recruited by direct mailing (age range 55 88 years) were followed for two years. Femoral and Lumbar BMD (DEXA, Hologic QDR), bone ultrasound parameters at the os calcis (Lunar Achilles), serum testosterone (T), serum estradiol (E2), sex hormone binding globulin (SHBG), 25OH-vitamin D (25OHD), dehydroepiandrosterone (DHEA), and bone turnover markers (a-crosslaps and bone alkaline phosphatase) were evaluated for each man. Polymorphisms at the ERa (Pvu II, Xba I and TAn repeats), ERb (Alu I), VDR (Fok I) and aromatase (TTTAn repeats) genes were evaluated after PCR amplication of the polymorphic sites. No signicant relationships of serum T, SHBG, DHEA or E2 levels with bone ultrasound parameters and femoral BMD were observed, even though a serum E2 weakly correlated with BMD at the Ward's triangle (r = 0.28, P=0.06). A similar correlation was observed between lumbar BMD and serum E2 levels (r = 0.34, P=0.05). Interestingly, the rates of bone loss at the lumbar spine and Ward's triangle resulted signicantly higher in men with a low number of TTTA repeats at the aromatase gene than in those with a higher number of repeats (P=0.01, ANOVA), while the rates of bone loss at the femoral neck were signicantly higher in men with the ``ff'' VDR genotype than in those with ``Ff'' or ``FF'' genotype (P=0.04, ANOVA). Bone alkaline phosphatase levels resulted signicantly higher in men with a low number of TTTA repeats at the aromatase gene than in those with a higher number of repeats (P=0.03, ANOVA). Taken all together, these results conrm a direct role of estrogens on bone in males and suggest that different genes may be involved in age-related bone loss at trabecular and cortical bone.

338 (314). A FUNCTIONAL POLYMORPHIC VARIANT IN THE IL 6 GENE PROMOTER ASSOCIATED WITH LOW BONE RESORPTION IN POSTMENOPAUSAL WOMEN S. L. Ferrari1, P. Garnero2, Le Ahn-Luong3, H. Montgomery3, S. Humphries3, S. Greenspan,1,4, 1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; 2INSERM Unit 403 and Synarc, Lyon, FR; 3Rayne Institute, Univ. College London Medical School, London, UK; 4Univ. of Pittsburgh Medical Center, Pittsburgh, PA, USA It has been recently demonstrated that a G174/C allelic variant in the Il6 gene promoter is functional in vitro and in vivo, and that subjects with the CC genotype have decreased circulating IL6 levels. The purpose of this study was to investigate the relationship between IL6 gene polymorphisms, markers of bone turnover and bone mineral density (BMD) in postmenopausal women. Healthy, community-dwelling women (n=434; >90% Caucasian), older than 65 yrs (meanSD, 71.75.7 yrs), were genotyped: CC, 68 (16%), GC, 204 (47%) and GG, 162 (37%). Osteocalcin and serum C-telopeptide of type I collagen (CTx) were measured. BMD was evaluated at the proximal femur and wrist by dual-energy X-ray absorptiometry (DXA). Age, height, weight, BMI, and calcium and vitamin D intakes did not differ among genotypes. CTx was signicantly lower in CC as compared to GC and GG subjects: 0.2750.02, 0.3250.01 and 0.3560.02 ng/ml, respectively (meansem; p = 0.006). The risk of having high bone resorption, i.e. CTx >0.506 ng/ml (the mean +1SD in premenopausal women), decreased with the number of C alleles: odds ratios (95% condence interval) 0.65 (0.411.0; p = 0.06) and 0.37 (0.180.73; p = 0.005) in GC and CC subjects, respectively. In contrast, osteocalcin did not differ among IL6 genotypes. Mean BMD values were 5% higher at the trochanter and Ward's triangle, and 3% higher at the total hip, ultradistal radius and ulna in CC as compared with GG subjects. However, age-adjusted BMD differences approached statistical signicance only at the trochanter (p = 0.09). In conclusion, functional allelic variants in the IL6 gene promoter are associated with bone resorption rates in postmenopausal women. Several arguments support the reliability of these ndings, including the size of each genotypic group and the magnitude of CTx differences between groups. Nevertheless, there were no statistically signicant BMD differences among IL6 genotypes. This might reect the multiple factors which determine BMD at that age, including the persisting inuence of peak bone mass. Further studies will establish whether IL6 gene polymorphisms can predict postmenopausal bone loss.

340 (316). EVIDENCE THAT COL1A1 GENOTYPE BUT NOT VITAMIN D RECEPTOR GENOTYPE (VDR) MAY CONTRIBUTE TO THE HERITABILITY OF BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN (PMW) IN GREECE E. A. Georgiadis, C. Billi, A. E. Georgiadis, L. Florentin, Osteoporosis Center and Molecular Biology and Cytogenetics Center of LITO Gynecol Hospital, Athens, Greece The purpose of this study was to assess whether BMD is related to the COL1A1 and VDR genotype in Greek PMW. We have studied 140 PMW (Mean age 536 ys and similar body mass index). 70 of them had osteoporosis at Hip and/or Lumbar spine (LS) (according to WHO criteria) and 70 were normal after BMD mesurements using an Hologic 1000 QDR bone densitometer. Polymorphism of VDR gene was investigated by PCR using TaqI restriction enzyme and the alleles were characterised (TT, Tt, tt). Polymorsm of Col1a1 gene was investigated by PCR using Bal I restriction enzyme and the alleles were characterised (SS, Ss, ss). The presence of a restriction site was labeled as T or s allele, whereas the absence was labeled as t and S. Our results showed that the proportion of VDR alleles between osteoporotic and normal PMW was approximately the same and the T genotype was not found to correlate with low bone mass. On the contrary the proportion of the alleles of COL1A1 between the two groups (Normals = ss 1% and Osteoporotics = ss 20%) were statistically different (p <0.001) by ANOVA and the possession of `s' allele was associated with lower BMD at LS and/or hip. Conclusion: There is strong association of COL1A1 gene polymorphism and osteoporosis in the Greek PMW and the `ss' genotype may contribute to the inherited pathological component of BMD.

339 (315). BONE LOSS AND BONE TURNOVER IN AGED MEN: HORMONAL AND GENETIC DETERMINANTS L Gennari1, S. Gonnelli2, L Becherini1, L. Masi1, A. Montagnani2, G. Bargagli2, R. Monaco2, M. B. Franci2, M. L Brandi1, C. Gennari2, 1 Endocrine Unit, University of Florence, Italy; 2Institute of Internal Medicine, University of Siena, Italy Predictors of osteoporosis in men are not yet clearly dened. Although there are several environmental inuences on BMD, a

341 (317). ASSOCIATION OF COLLAGEN Ia1 SP1 POLYMORPHISM WITH DIFFERENCES IN SPEED OF SOUND IN THE CALCANEUS IN POSTMENOPAUSAL WOMEN P. Kann, , Y. Fang , A. P. Bergink , A. Hofman , P. L.A. van Daele1, J. P.T.M. van Leeuwen1, J. Beyer3, A. G. Uitterlinden,1,2, H. A.P. Pols,1,2, 1Dept. of Internal Medicine III; 2Dept. of Epidemiology and Biostatistics, Erasmus University, Rotterdam, The Netherlands; 3Dept. of Internal Medicine, Endocrinology and Metabolic Diseases, Johannes Gutenberg University, Mainz, Germany Bone mineral density and fracture risk are under genetic control. An association of the G to T polymorphism of the Sp1 binding site of the collagen I a 1 gene with the risk for fractures has been reported previously. This association is only in part explained by differences in bone mineral density. Thus, the relationship between the Sp1 collagen I a 1 polymorphism and skeletal factors other than BMD was analyzed. A parameter characterizing bone material properties and bone stability is the modulus of elasticity which is a determinator of ultrasound transmission velocity (UTV) in bone. In a population based sample of 740 women of the age between 55 and 80 years (mean age 64.96.5 years) we determined collagen I a 1 genotype and UTV in the calcaneus. UTV in the ``GG'' genotype group was 152231 m/s, in the ``GT'' group 151930 m/s, and in the ``TT'' group 1508 m/s (p = .014: ANOVA adjusted for age, height and weight). Calculation of allele-dose-effect showed a mean decrease of UTV 4,312 m/s per each copy of allele ``T'' (p = .016 adjusted for age, height and weight). The differences remained signicant after adjustment for bone mineral density measured at the femoral neck. Linear regression analysis showed a progressive negative slope of the regression line of UTV over age from ``GG'' over ``GT'' to ``TT'' genotype. These data suggest that collagen I a 1 polymorphism is associated to the modulus of elasticity of bone as determined in vivo by acustical measurement independent of bone mineral density.
1,3 1 2 2

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343 (319). A SYSTEMATIC CANDIDATE-GENE APPROACH FOR THE GENETIC DETERMINANTS OF OSTEOPOROSIS H. Orimo1, T. Hosoi1, T. Suzuki2, A. Hada3, S. Inoue4, M. Emi5, 1 Tokyo Metropolitan Geriatric Hospital; 2Tokyo Metropolitan Institute for Gerontology; 3Asahikawa Medical School; 4Univ. of Tokyo; 5Nippon Medical School, Japan We have been focusing on candidate-gene approach among the strategies to investigate the genetic aspects of osteoporosis. Considering the multi-factorial nature of osteoporosis, various genes should be considered systematically. We listed a panel of candidate genes for osteoporosis, which consists of about 30 genes and is being expanded. We used the polymorphic markers in or adjacent to these genes. At rst, association studies between BMD and polymorphic markers were conducted in the healthy un-related postmenopausal women(n=400500). And then the affected sib-pair analysis (approx. 200 pairs) was done using the markers which gave positive results in the association study. In additon, single-nucleotide polymorphisms (SNPs) were searched in the loci of interest. So far, interleukin 6 (IL6) and transforming growth factor alpha genes gave positive results in sib-pair analysis and some novel SNPs were indendied in the promotor region and exons of IL6 gene. We are elucidating the biological signicance of these polymorphisms in the candidate genes.

344 (320). COLLAGEN TYPE I a 1 GENE POLYMORPHISM IN IDIOPATHIC OSTEOPORIS IN MEN P. Peris, L. Alvarez, J. Oriola, N. Guan abens, A. Monegal, M. J. Mart nez de Osaba, J. Jo, F. Pons, A. M. Ballesta, J. Munoz. mez, Metabolic Bone Diseases Unit, Hospital Clinic, University Go of Barcelona, Spain Aims: To analyze the distribution of S/s alleles in collagen 1 a 1 Sp polymorphism (COLIA1) and their relationship with bone metabolism parameters and bone turnover in men with idiopathic osteoporosis. Methods: 35 men (aged 50.410.3 yrs) with idiopathic osteoporosis were studied. Serum osteocalcin (BGP), 25-OHvitamin D and PTH were determined. The COLIA1 Sp1 genotypes (SS, Ss, ss) were assessed by restriction enzyme digestion (Bal 1) of PCR amplied DNA extracted from whole blood. The results were compared with a control group of 60 men (aged 47.417.6 yrs). Results:

342 (318). ABSENCE OF THE HIGH RISK `s' ALLELE ASSOCIATED WITH OSTEOPOROSIS AT THE INTRONIC SP1 BINDING-SITE OF COLLAGEN I a 1 GENE IN SOUTHERN CHINESE A. W. C. Kung, I. Lambrinoudaki, Dept. of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC The Sp1 polymorphism in the rst intron of the collagen Ia1 gene was recently described to be associated with low bone mineral density (BMD) and increased fracture risk in Caucasion populations. The impact of this gene was assessed in a southern Chinese population. 181 women, aged 51.18.8 years were evaluated for the Sp1 polymorphism. 22% of the women were classied as having osteoporosis on the basis of a T-score at the lumbar spine or the hip below 2.5 with or without a prevalent fracture. Genotype analysis was performed by PCR amplication and restriction enzyme digestion. Single-strand conformational polymorphism analysis (SSCP) was performed in 65 randomly selected samples to search for any polymorphic site in the PCR amplied region. The results showed that no restriction enzyme site could be identied in any of the 181 samples analyzed. Moreover SSCP analysis revealed no polymorphism in the PCR amplied region of the rst intron of the collagen Ia1 gene. In conclusion, the `s' allele, associated with low BMD and increased fracture risk in Caucasians, is non-existent or very rare in the southern Chinese population. The absence of this `high risk' allele may in part account for the reduced fracture risk observed in the Chinese in comparison to Western populations.

allelic frequency S Controls (60) Patients (35) 107 (89%) 50 (71%) p = 0.004 s 13 (11%) 20 (29%)

genetic frequency SS 48 (80%) 17 (48%) p = 0.006 Ss 11 (18%) 16 (46%) ss 1 (2%) 2 (6%)

The distribution of genotypes in controls was in Hardy Weinberg equilibrium. No dierences were observed between SS vs Ss+ss patients or controls in regard to the BGP, PTH and 25-OH vitamin D values. Except for allelic and genetic frequency in COLIA1 polymorphims, no signicant dierences in parameters of bone metabolism were found between patients and controls. Conclusion: In men with idiopathic osteoporosis there is a high prevalence of s allele and Ss genotype not related with other parameters of bone metabolism.

Friday/Saturday, June 17, 2000

345 (321). LACK OF ASSOCIATION BETWEEN IL1RA GENE POLYMORPHISM AND BONE DENSITY IN HUNGARIAN POSTMENOPAUSAL WOMEN I. Takacs, E. Bajnok, Z. Nagy, G. Speer, M. Kucsera, L. Kiss, Z. Bori, C. Horvath, P. Lakatos, Department of Medicine, Semmelweis University, Budapest, Hungary Interleukin1 receptor antagonist protein (IL1ra) inhibits the bone-resorptive effects of IL1 and other cytokines. Genetic polymorphism of IL1ra gene might have an impact on the effectiveness of IL1ra protein, and thus it may inuence bone density. In this study, we examined whether IL1ra gene polymorphism is associated with decreased bone mass in 286 Hungarian postmenopausal women (age range:4075). From this cohort, 98 osteoporotic (OP) patients (mean age: 56.5+7.1) were compared with 81 (mean age: 54.3+5.5) healthy control (C) women. Bone mineral density (BMD) was measured at the lumbar spine (L24) and femoral neck using DEXA method. PCR was used to amplify polymorphic 86 bp variable number tandem repeat within intron 2 of the IL1ra gene. Five alleles were identied in the 286 studied subjects. There were three common genotypes: A1A1 (53.2%), A1A2 (34.9%), A2A2 (8.1%). There was no signicant difference in the allele frequencies of the OP (A1:76.5%, A2:22.4%) and C (A1:69.7%, A2:27.8%) groups. No signicant effect of IL1ra genotype on BMD was observed either in the whole population or in the subgroups. Our data do not support the idea that IL1ra gene polymorphism have an impact on bone mass in postmenopausal women.

for their potential association with postmenopausal osteoporosis. In all subjects the polymorphic variants FokI, ApaI, TaqI and BsmI (for VDR), AluI (for CTR), and XbaI and PvuII (for ESR) were determined using a polymerase chain reaction (PCR) and endonuclease digestion. Osteoporosis was diagnozed by dualenergy X-ray absorptiometry (T-score of <2.5, i.e., more than 2.5 SD below the peak bone mass value in the young adult reference population). A signicant difference between healthy and osteoporotic women was observed in ESR XbaI polymorphism (Pearson's X2=10.457, p = 0.0054): prevalence of XX homozygotes was 4.6% in osteoporotic vs 27.3% in healthy women. No differences were, however, found between osteoporotic and healthy subjects in the remaining investigated genes. This nding supports the conclusion that ESR gene polymorphism XbaI is associated with low bone mineral density in postmenopausal women. This would contribute to the early detection of the female population at high risk for postmenopausal osteoporosis, thus allowing application of adequate preventive and therapeutic treatment.

Plenary Session 7: Treatment 1 (Saturday, June 17, 0800-1000)

348. HORMONE REPLACEMENT THERAPY (HRT) IMPROVES BOTH ALVEOLAR AND POSTCRANIAL BONE DENSITY R. Civitelli, T. Pilgram, M. Dotson, J. Muckerman, N. Lewandowski, E. Kardaris, J. Hauser, S. Cohen, M. Vannier, N. Yokoyama-Crothers, C. Hildebolt, Washington University School of Medicine; 2Barnes-Jewish Hospital, St. Louis, Missouri, USA To test whether the protective effect of HRT on postmenopausal bone loss results in improved oral bone density, we randomized 134 postmenopausal women (age 596.2; 13.711.4 years since menopause) to receive either HRT (PremproTM or Premarin1 0.625mg qD) or placebo for 3 years in a prospective, double-blind study. All subjects also received daily calcium (1000mg) and vitamin D (800IU) supplements and had yearly dental cleanings. An intention-to-treat analysis was performed at 3 years on all subjects enrolled (91 completed the study). Bone density increased in the HRT group and did not change in the placebo group at the proximal femur (neck, +2.05.5 vs. 0.25.7%; total, +3.66.8 vs. +0.24.7%, p<0.02). Group differences were not signicant at the spine (+1.05.1% vs. +0.26.2%; p>0.10), perhaps because of the high prevalence of DJD in these women. Alveolar crest height (ACH) and alveolar bone mass (ABM) were measured from digital images of dental radiographs as indices of alveolar bone loss. Both improved in the two arms of the study, suggesting that good dental care and calcium/vitamin D supplementation are very important for oral bone density. However, the increase in ABM was twice as large in the HRT than in the placebo group (1.82.9% vs. 0.92.0%; p<0.04), whereas a non-signicant trend was observed for ACH (5.011.6% vs. 3.57.3%; p>0.10). Importantly, changes in proximal femur bone density were signicantly correlated with changes in ABM and ACH only in the HRT arm. We propose that improved oral bone density constitutes an additional therapeutic benet of HRT in postmenopausal women.

346 (322). DETERMINANTS OF BONE MASS IN CHILDREN 46 YEARS M. Willing, J. Torner, T. Burns, J. Warren, K. Janz, S. Levy, University of Iowa, Iowa City, IA, USA Our work has focused on characterizing biologic variation in bone development in healthy children, with the goal of understanding the contribution of genetic, environmental and life-style characteristics to bone mass. A cohort of 305 children (145 boys, 160 girls, ages 4.3 to 6.5 years; mean 5.2 years) was recruited to the present study, which includes bone mineral density (BMD) and content (BMC) measurements of the total body, lumbar spine, and femoral neck, as well as genetic studies. We examined allelic variation at loci for the type I collagen genes (COL1A1, COL1A2), osteocalcin, osteonectin, osteopontin, and the vitamin D (VDR), estrogen and androgen receptors. BMD had a wide distribution (hip 0.4090.736 g/cm2; spine 0.3820.685 g/cm2; whole body 0.6090.850 g/cm2). Measurements of body size, including body mass index (BMI) and height, as well as age and gender had signicant associations with bone measures. After adjusting for these factors, preliminary analysis suggests a genetic effect of both osteocalcin (C/T promoter polymorphism)and VDR (translation initiation site polymorphism) genotype on hip BMD (p50.05). Data for COL1A1 was suggestive, but did not reach statistical signicance (p50.10). Our data suggest that genes involved in bone formation and bone matrix structure may be important determinants of bone mass in children. Initial data will be reevaluated when the entire cohort (n=450) becomes available.

347 (323). POSTMENOPAUSAL OSTEOPOROSIS ASSOCIATED WITH XBAI POLYMORPHIC SITE IN THE ESTROGEN RECEPTOR GENE ofkova kova I. Z , K. Zajic , R. Bahbouh, Institute of Endocrinology, Prague, Czech Republic In this study genes for the vitamin D receptor (VDR), calcitonin receptor (CTR) and estrogen receptor (ESR) were analyzed in healthy (n=33) and osteoporotic, but otherwise normal (n=65) Czech postmenopausal women aged 62.38.9 years (meanSD)

349. NORETHINDRONE ACETATE HAS AN ADDITIVE EFFECT ON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN TREATED WITH ETHINYL ESTRADIOL J. P. Symons, N. J. Kempfert, J. A. Simon, J. C. Gallagher, 1ParkeDavis Pharmaceutical Research, Ann Arbor, MI, USA; 2Women's Health Research Center, Laurel, MD, USA; 3Creighton University, Omaha, NE, The purpose of this study was to further investigate the additive effect of norethindrone acetate (NA) on bone mineral density

(BMD) in postmenopausal women. It has been previously demonstrated that ethinyl estradiol (EE) alone can maintain lumbar spine trabecular BMD. When NA was added to EE there was an increase in BMD compared to EE alone after 2 years of continuous administration. Signicant differences in BMD were observed between 5 mcg of EE alone compared to a combination of 1 mg NA/5 mcg EE suggesting an additive effect of NA when combined with EE. To further investigate this association 942 postmenopausal women were enrolled in a placebo-and positivecontrolled clinical trial. All subjects received 100 mg calcium supplementation daily. Women were randomized to 1 of the 8 following treatment groups: placebo, 5 mcg EE, 10 mcg EE, 0.25 mg NA/5 mcg EE, 1 mg NA/5 mcg EE, 0.5 mcg NA/10 mcg EE, 1 mg NA/10 mcg EE, and 0.625 mg conjugated equine estrogen/2.5 mg medroxyprogesterone acetate. Lumbar spine and hip BMD were measured at baseline and after 6 and 12 months of treatment. All subjects will have completed the investigation by mid-January 2000 and the data will be available for analysis shortly thereafter. It is hypothesized that the addition of NA will increase BMD relative to both EE alone or placebo. These results will be presented. The relative merits of NA compared with other progestins will likewise be established.

Saturday, June 17, 2000

postmenopausal osteoporosis given intermittent intravenous Neridronate (50 mg every two months for 12 months). 43 women served as controls. In the treated patients bone alkaline phosphatase decreased by 1822% p<0.0001) within 4 months, remaining unchanged thereafter. Plasma Lp(a) rose progressively up to 5954% (p<0.0001) at the end of the study. A similar trend was observed for plasma HDL cholesterol (+1815% p<0.0001 at 1 year). Moderate changes were also observed for plasma LDL (7514% p<0.05), Apo AI (+611% p<0.001) and Apo B (614% p<0.05). The serum bone alkaline phosphatase levels were negatively related to Lp(a) (r = 0.19 p<0.05). We also studied the lipid prole in 7 patients after three-monthly Clodronate i.v. infusion (300 mg/day for 5 days) over 6 months. Lp(a) and HDL cholesterol increased by 1925% (p = 0.09) and by 713% (n.s.), respectively. The results of this study show a surprising interconnection between bisphosphonate therapy and lipid metabolism. This interconnection open a new horizon in our understanding of skeletal metabolism. It is somewhat associated with the following known ndings: 1. Apo(a) [a major component of Lp(a)] is a member of kringle containing proteins, including plasminogen activator, which is an osteoblast responsive element to PTH and other cytokines. 2. The sequence of Apo(a) gene contains several IL6 responsive elements.

350. COST EFFECTIVENESS OF TREATMENTS FOR HIP FRACTURE TARGETTED TO THE GENERAL FEMALE POPULATION J. A. Kanis, A. Dawson, A. Oden, O. Johnell, C. De Laet, B. Jonsson, Centre for Metabolic Bone Diseases, University of Shefeld Medical School, Shefeld, UK Current strategies to tackle osteoporosis depend on identifying individuals at high risk and thereafter targeting treatments that are cost effective. From a health economic viewpoint, hip fractures are the dominant complication, the risk of which increases exponentially with age. The aim of the present study was to determine whether age was a sufcient risk factor such that treatments could be targeted effectively to the general population. We used an established Markov model applied to the female population of Sweden using a 5 year intervention that reduced the risk of hip fracture by 35% during the treatment period, and an effect that reversed to pre-treatment risk during the next 5 years. Cost effectiveness was critically dependent upon the age (i.e. absolute risk) and costs of intervention. Reasonable cost effectiveness ($2030,000/QALY gained; direct costs only) was shown even with relatively high intervention costs ($625 per annum) for women at an average risk of hip fracture at the age of 85 years or more. For the cheapest interventions ($63 per annum) cost effectiveness could be found from the age of 53 years. We conclude that segments of the apparently healthy population may be advantaged by treatment without the necessity for screening procedures. Since the identication and treatment of individuals at higher than average risk (e.g. prior fragility fracture) would be even more cost effective; these data provide a sound basis on which to build rational screening strategies, particularly in the elderly.

352. INTERVENTION STUDY WITH HIP PROTECTORS IN ORTHOPEDIC PATIENTS WITH HIP FRACTURES K. Hinds, J. B. Lauritzen, 1Department of Orthopedic Surgery, Hvidovre Hospital; 2University of Copenhagen, Denmark Objective To evaluate the effect of hip protectors on risk of subsequent hip fractures among elderly orthopedic patients admitted with hip fractures. Design Open prospective case cohort study among elderly orthopedic patients more than 74 years of age admitted to orthopedics with falls or fractures. A total of 303 patients with fractures at Hvidovre Hospital were offered three sets of hip protectors (SAFEHIP) and 244 patients at Bispebjerg Hospital were controls. Patients were followed from 1 to 1 year. p = 0.05, one alfa. Results The annual rate of second hip fractures in the control group was 4.6 %. Primary acceptance of hip protectors was 65 %. Based on intention to treat analysis the relative risk (RR) was 0.83,ns. Based on primary acceptance the RR was 0.73, ns (n 196) and based on continued use referred to still possessing hip protectors the RR was 0.64, ns (n 110). For those who used hip protectors regularly or every day the RR was 0.0, p = 0.03 (n 60). Conclusion Hip protectors demonstrated a signicant protective effect against second hip fracture among hip fracture patients who wore hip protectors on a regular basis and eliminated hip fractures in this subgroup. Based on intention to treat the RR was reduced by 17%. For those who were registered as having and still possessed hip protectors the RR for a new hip fracture was reduced by 36%.

353. SCREENING FOR OSTEOPOROSIS: 57 YEAR DATA ON HRT ADHERENCE, BONE LOSS AND FRACTURES RATES 351. INTRAVENOUS BISPHOSPHONATE THERAPY INCREASES LP (a) AND HDL CHOLESTEROL PLASMA LEVELS V. Braga, D. Gatti, G. C. Guidi, S. Adami, C. O.C. Valeggio, University of Verona, Italy Lipoprotein(a) [Lp(a)] is a low density lipoprotein-like particle with athero-thrombotic properties. Lp(a) can 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 44 women with D. J. Torgerson1, A. Stewart2, D. M. Reid2, 1Dept of Health Studies, York University; 2Osteoporosis Research Unit, Department of Medicine & Therapeutics, University of Aberdeen, UK Between 19913 2051 women aged 4549, selected at random, were invited to have their BMD measured. The lowest 25% of BMD at either the hip or spine were encouraged to take HRT to prevent fractures. In 1998/9 the women were recalled to have their BMD re-measured and to assess HRT adherence. 1501 (73%) were remeasured of whom 538 were current HRT and 334 were past users (median length of use for current users 5.0 years).

Saturday, June 17, 2000

54% (n=117), 42% (n = 138) and 30% (n = 283) of women with low BMD at both sites, one site or neither site respectively were current HRT users (p50.001 for trend). 1154 women (77%) had lost bone at the spine, whilst 347 gained bone or stayed the same. Of current HRT users 39% (n= 212) gained bone or stayed the same compared with only 14% (n=135) of never or ex-users (p50.001). HRT users with low BMD at baseline lost an average of 0.7% of BMD at the spine compared with 7.4% of BMD for women with low BMD who were not using HRT (p<0.001). 65 women out of 645 had suffered a fracture with current HRT users having a 30% lower fracture rate compared with all other women (p = 0.21). In conclusion, about seven years after BMD measurement about 50% of women with low BMD were still using HRT and this was associated with a 7% difference in BMD, and a nonsignicant 30% reduction in fracture rates compared with non HRT users.

femoral neck compared to men with shorter repeats (lowest tertile) (0.7360.14 vs 0.7740.13; p<0.05). The prevalence of osteoporosis (T score 42.5) was also greater in the highest compared with lowest tertile of CAG repeat size (16.1% vs 5.5%; p<0.01), equivalent to an odds ratio (OR) of 3.57 (95% C.I.: 1.54, 8.29). This association was attenuated (OR: 2.70; 95% C.I.: 1.14, 6.43) after adjusting for the signicantly lower body weight of men with longer repeat size. These results suggest that the AR CAG repeat polymorphism is a novel molecular marker of osteoporosis susceptibility in older men, and that this effect may be mediated in part through body weight.

356. BIOAVAILABLE ESTRADIOL MAY BE AN IMPORTANT DETERMINANT OF OSTEOPOROSIS IN MEN. THE MINOS STUDY P. Szulc1, F. Munoz1, B. Claustrat2, P. Garnero1, F. Marchand3, F. Duboeuf1, P. D. Delmas1, 1INSERM Research Unit 403, Lyon, France; 2Hopital Neuro-Cardiologique, Lyon, France; 3SSMB, Montceau Les Mines, France Experimental data suggest that estradiol may play an important role in bone metabolism in men, but clinical evidence is limited. In a cohort of 596 men aged 51 85 yrs, we measured bone mineral density (BMD) of the spine, hip, total body (HOLOGIC QDR 1500) and forearm (OSTEOMETER DTX 100), serum levels of sex streoid hormones (total and free testosterone fT, total estradiol E2 and bioavailable estradiol bioE2, androstendione, sex hormone binding globulin) and levels of markers of bone turnover (serum osteocalcin OC, bone alkaline phosphatase BAP, N-terminal extension propeptide of type I collagen PINP, b-isomerized Cterminal telopeptide of collagen type I bCTX as well as urinary excretion of bCTX, free and total deoxypyridinoline fDPyr, tDPyr). An age-related decrease was found for bio-E2 (r = 0.16, p = 0.0001) but not for total E2. E2 and bio-E2, bur not other hormones, were correlated with BMD after adjustment for age and body weight (e.g.: total hip BMD r = 0.16, p<0.001 and r = 0.14, p<0.002 respectively). In age- and body weight-adjusted models, bio-E2, but not other hormones, was negatively correlated with bone markers (e.g.: OC r = 0.13, p<0.002, serum and urinary bCTX r = 0.18, p = 0.0001 and r = 0.13, p<0.002, respectively). In the age- and body weight-adjusted multiple regression models, bio-E2 contributed signicantly to the explanation of the variability of all the markers. In summary, we have found in a cross-sectional analysis of a cohort of men that low levels of bio-E2 are associated with high bone turnover and low BMD. These data suggest that low E2 levels may be an important mechanism of osteoporosis in men.

Plenary Session 8: Males (Saturday, June 17, 1030-1230)

354. BONE MINERAL DENSITY AND PREDICTION OF MORTALITY IN MEN: THE ROTTERDAM STUDY M. van der Klift1, C. E.D.H. de Laet1, J. M. Geleijnse2, A. Hofman2, H. A.P. Pols3, 1Institute of Medical Technology Assessment; 2 Departments of Epidemiology; 3Internal Medicine, Erasmus University Rotterdam, The Netherlands Recent studies have shown an inverse relationship between bone mineral density (BMD) and mortality. However, most studies only investigated this relationship in women. Our aim was to model the relation between BMD and all cause mortality in men. In the Rotterdam Study, follow-up till 31st March 1997 was complete for 2445 men aged 55 and over for whom BMD data were available. During an average follow-up time of 4.7 years, 340 men deceased. We calculated Z-scores from the BMD, which was measured at the femoral neck. Cox' proportional hazards was used to t the model. An average BMD (Z-score of zero) was used as reference. A cubic model best tted the relationship under study, also after adjusting for age and body mass index. Our model shows that the risk of mortality exponentially increases when BMD is below average. Similar results were found when separate curves were made for diabetics and non diabetics, smokers (ever or never), and tertiles of BMI. Analysis were repeated excluding subjects who had suffered hip fractures, adjusting for the number of drugs used and for lower limb disability, respectively, which resulted in similar risk estimates. Our results suggest that in men a non-linear relationship between BMD and mortality exists, independent of comorbidity and impaired mobility.

355. ANDROGEN RECEPTOR CAG REPEAT POLYMORPHISM: A NOVEL MOLECULAR MARKER OF OSTEOPOROTIC RISK IN MEN J. M. Zmuda1, J. A. Cauley1, L. H. Kuller1, A. B. Newman1, J. Robbins2, T. Harris3, R. E. Ferrell1, 1Universities of Pittsburgh, Pittsburgh, PA; 2California, Davis; 3The National Institute On Aging, Bethesda, MD, USA Androgenic effects on bone are mediated through the androgen receptor (AR), a ligand activated transcription factor. The AR gene contains a CAG repeat polymorphism in exon 1 that codes for a polyglutamate sequence of variable length. This polymorphism inuences AR trans-activation, with longer CAG repeats conferring reduced transcriptional activation of androgen target genes. We tested the hypothesis that longer AR CAG repeats are associated with osteoporotic risk in 508 Caucasian men (age 565 yrs) who were participants in the population-based Cardiovascular Health Study. Men with longer CAG repeats (highest tertile) had lower bone mineral density (BMD) at the

357. GENDER DIFFERENCE IN MORTALITY AFTER HIP FRACTURE L. E. Wehren, W. Hawkes, J. R. Hebel, S. I. Zimmerman, D. Orwig, J. Magaziner, Univ of MD, Baltimore, MD, USA Mortality during the 1 to 2 years after hip fracture has been shown to be higher among men than women. Is this due to differences in age, medical comorbidity, functional limitation, metabolic derangement, or another factor? We investigated this in a cohort of 804 community dwelling men and women in the Baltimore Hip Studies who sustained hip fracture and were followed for 2 years. Men were younger (79.57.6 yr vs 81.67.3 yr), had more baseline comorbidiy (3.62.2 vs 3.22.0 conditions), and had longer hospitalization after fracture (17.211.3 vs 14.38.3 days), but had no difference in baseline physical or instrumental activities of daily living and experienced fewer post-operative complications (1.41.4 vs 3.22.0) than women. There were no differences in type of fracture or surgical procedure, time to surgery or baseline hemoglobin and hematocrit; however, men had higher ASA scores (2.90.6 vs 2.70.6) and were more likely to have chest

X-ray abnormalities (47.3% vs 37.3%). Men lived signicantly shorter times (517.2292.7 vs 624.4230.0 days); only 57.6% of men were alive at 24 months, compared to 76.7% of women. In logistic regression modeling, the unadjusted odds ratio (OR) for male survival was 0.428 (95% CI 0.292, 0.628); adjustment for age, comorbidity, complications, ASA score, chest X-ray abnormalities, and length of stay produced only a small change in this OR, to 0.492 (95% CI 0.320, 0.755), so that these factors, although signicantly associated with survival, do not explain the observed gender difference. The increased vulnerability of men who fracture their hips deserves further careful study.

Saturday, June 17, 2000

mass in women. There is little data addressing its association with fracture risk in men. Aim: To analyse the associations & linkage of the Sp1 polymorphism in the COL1A1 gene & VDR genotype with BMD & hip fracture risk in elderly men. Method: 100 men aged over 50 with low trauma hip fracture and equal matched controls were prospectively recruited. Whole blood for genetic studies was collected at rst visit; in cases this was within 48 hours of the fracture. BMD was measured by DXA (Hologic QDR1000) at both the lumbar spine and femur in all controls and 62 cases; in cases this was within 1 week of fracture. Col1A1 Sp1 and VDR Bsml genotyping was performed using standard techniques. Result: Fracture cases were older, had lower weight, BMI & BMD compared to controls (p<0.01). Smoking habits, alcohol consumption, dietary calcium intake and steroid usage were similar in the two groups. Cases had signicantly more co morbid conditions like Parkinsons, dementia, poor vision and stroke reducing mobility (p<0.01). The frequency distribution of the VDR and Col1a1genotypes was similar in cases and controls: (cases Vs controls VDR 15.8% Vs 16% for BB, 48.4% Vs 55% for Bb and 35.8% Vs 29% for bb; Col1a1 70.2% Vs 64% for SS, 27.7% Vs 32% for Ss and 2.1% Vs 4% for ss). Between group comparison by ANOVA showed no differences in age, BMI, BMD, vitamin D, parathyroid, androgens (total testosterone, free testosterone, free androgen index, oestrogens (total and free oestradiol), osteocalcin & urinary deoxypyridinoline among the three VDR and Col1a1genotypes. Repeat analysis comparing these variables between men having the less favourable allele B (genotypes BB & Bb) with those without it (homozygous bb) showed no difference. No differences were seen in men with the unfavourable s gene (genotypes ss & Ss) compared to those homozygous for SS. Conclusion: Our results indicate that VDR and Col1a1 gene polymorphism is not related to risk of low trauma hip fracture in elderly men. There is no relation to BMD, calciotropic hormones, sex steroids and bone markers.

358. SPINE BONE MINERAL DENSITY PREDICTS VERTEBRAL DEFORMITY LESS WELL IN MEN THAN WOMEN: DATA FROM THE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY (CAMOS) D. T. Drinkwater1, W. P. Olszynski2, T. M. Murray3, 1University of Saskatchewan, Saskatoon, SK, Canada; 2Saskatoon Centre of CaMos; 3University of Toronto, Toronto, ON, Canada CaMos is a population-based prospective cohort study which represents an age, gender and region specic sample of noninstitutionalized Canadians. This study allows us to look at the prevalence of vertebral deformities (VDF) and investigate the relationship of VDF to bone mineral density (BMD), especially in older men. The number, type and severity of VDF for men and women, aged 5096y, were evaluated from spinal X-rays. BMD at the lumbar spine L1-L4 (LS) and femoral neck (FN) was assessed using dual-energy X-ray absorptiometry. Of 1745 men and 4383 women we found [mean (SD); n, %]:
# VDF 0 1 2 3 4 5+ LS BMD (g/cm2) Men Women* 1.041(.173) 1374, 78.7% 1.037(.176) 252, 14.4% 0.934(.185) 71, 4.1% 1.044(.183) 27, 1.5% 0.937(.194) 13, 0.7% 0.834(.151) 8, 0.5% 0.921(.162) 3363, 76.7% 0.897(.174) 670, 15.3% 0.834(.175) 204, 4.7% 0.835(.180) 90, 2.1% 0.731(.193) 24, 0.5% 0.738(.195) 32, 0.7% FN BMD (g/cm2) Men Women* 0.798(.124) 1374, 78.7% 0.770(.122) 252, 14.4% 0.717(.121) 71, 4.1% 0.740(.145) 27, 1.5% 0.717(.158) 13, 0.7% 0.642(.120) 8, 0.5% 0.702(.117) 3363, 76.7% 0.665(.113) 670, 15.3% 0.630(.116) 204, 4.7% 0.619(.103) 90, 2.1% 0.546(.100) 24, 0.5% 0.533(.154) 32, 0.7%

Osteoporosis Pathophysiology
360 (324). MAGNITUDE AND DETERMINANTS OF VITAMIN D INSUFFICIENCY AND DEFICIENCY IN ELDERLY FEMALE OUTPATIENTS: AN ITALIAN MULTICENTER STUDY S. Adami1, R. Giorgino2, on behalf of the Italian Multicenter Study Group, 1Verona, Italy; 2Rome, Italy Previous studies have shown high prevalence of hypovitaminosis D in elderly Mediterranean people: in Italy, available data are limited to selected areas. Over a period between Feb. 15th and March 15th 1999, an observational study was conducted in 43 Italian hospital and university out-patients centers. A medical history and a life-style questionnaire were administered to 799 postmenopausal women (age range 6080 years, median 67) at their rst Osteoporosis work-out. A blood sample was taken for centralized 25(OH)D and PTH assays. 25(OH) levels 412 ng/ml dened Vitamin D insufciency (VDI): 45 ng/ml dened a Vitamin D deciency (VDD) status. Overall, 74% of the patients showed 25(OH)D levels 412 ng/ml: 28% of the total patients were decient. In 570 years old subgroup, the prevalence of VDI and VDD were respectively 78% and 36%. A signicant square negative correlation was observed between 25(OH)D and PTH levels (p = 0.003; r2=0.13). Low sun exposure was mildly associated with VDI (p = 0.05): increased PTH levels (p<0.01) were seen in patients with reduced sun exposure. Vitamin D deciency was strongly associated with Activities of Daily Living impairment: specic ADLs i.e. difculty in using stairs (p<0.05), walking at least 400 m (p<0.05), carrying a heavy thing (p<0.001), going in and out of bed (p<0.05), managing nances (p<0.05), doing heavy housework (p<0.01) were associated with low

*p<0.05, women dierent from men at each site

There was a progressive decline in BMD with increasing number of VDF for both men (LS: r = 0.09, FN: r = 0.17, p<0.01) and women (LS: r = 0.17, FN: r = 0.23, p<0.01). At both sites, for the same number of VDF, BMD values were greater for men than women, although the dierences are less at the FN site. LS BMD was not as highly correlated with VDF as was FN BMD in both groups, possibly the result of trauma or osteophytes. We conclude that in older men FN BMD appears to be a more reliable predictor of VDF than LS BMD.

359. POLYMORPHISM AT COL1A1, VITAMIN D RECEPTOR GENE & RISK OF LOW TRAUMA HIP FRACTURE IN ELDERLY MEN Ira Pande1, S. H. Ralston2, D. L. Scott3, A. D. Woolf1, 1 Rheumatology Unit, Truro; 2Dept of Medicine & Therapeutics, Aberdeen; 3Rheumatology Unit, London, UK Background: BMD is under strong genetic control. Polymorphisms in the vitamin D receptor (VDR) & the collagen type 1a1(COL1A1) gene account for some of the variation in bone

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25(OH)D levels. Patients with an history of chronic diseases showed an higher prevalence of VDI (76% vs 69%, p<0.05). More interestingly, diabetic patients had a very signicantly higher prevalence of VDI (87% vs. 72%, p<0.0001): 39% of diabetic patients were Vitamin D decient. An history of cerebro-vascular diseases was strongly associated with VDI: 87% and 53% of these patients showed 25(OH)D levels respectively 412 and 45 ng/ml (both p<0.0001 vs. controls). Twenty-three women (3% of the total population) reported an hip fracture: 90% of them showed 25(OH)D levels 412 ng/ml and 50% were vitamin D decient. In conclusion, this study conrm the wintertime high prevalence of VDI and VDD in elderly free-living subjects: even if this observation is limited to a time of the year corresponding to 25(OH)D levels nadir, it seems that hypovitaminosis D affects overall QoL beyond its detrimental effects on bone health. Further studies need to be done to explore the potential mechanism behind the signicant association of diabetes and cerebrovascular diseases with low 25(OH)D levels.

[25(OH)D] estimated by RIA (INCSTAR Inc.) and serum iPTH estimated by two-site binding IRMA assay (DPC Inc.). BMD was estimated by dual energy X-Ray absorptiometry (DXA) (HologicQDR 4500A). Results: Only 19/75 (25.3%) of the subjects had serum 25 (OH) D concentration above 15 ng/ml. 37/75 (56%) had severe vitamin D deciency. Mean of sunlight exposure in our subjects was 11.35 6.8 minutes per day (range: 525 min/day) involving face and arms upto elbow. There was strong correlation between the duration of sun exposure and 25-hydroxy vitamin D level (r = 0.731, p<0.001). Secondary hyperparathyroidism was found in 7/15 subjects. There was signicant linear correlation between serum 25(OH) vitamin D concentration and iPTH. BMD of spine and appendicular bone was signicantly lower in healthy Indians when compared with Caucasians normals. There was signicant positive correlation between serum 25-hydroxy vitamin D concentration and BMD of ward's triangle and femoral neck (r = 0.50, p = 0.020 and r = 0.46, p = 0.037 respectively). Conclusions: Despite adequate sunlight throughout the year, hypovitaminosis D is frequent in Indian normals. Low vitamin D levels are associated with secondary hyperparathyroidism and lower BMD at femoral neck predisposing Indians at higher risk of hip fracture.

361 (325). A COMPARISON OF BONE QUALITY IN PAST AND MODERN POPULATIONS S. C. Agarwal,1,3, M Dumitriu3, M. D. Grynpas,2,3, 1Department of Anthropology, Department of Laboratory Medicine and Pathobiology, U of Toronto, SLRI of Mount Sinai Hospital, As osteoporosis has become a growing health concern, there has been steady interest to investigate the prevalence of the disease in the past. Although a number of studies have shown low bone mass in past populations, few have shown fragility fracture. In order to examine age and sex-related changes in bone quality in the past as compared to modern populations, a study was made of trabecular bone architecture in a British historic skeletal collection. X-rays of 5mm thick coronal sections from lumbar vertebrae were taken from 55 adult individuals (m=24, f=31) divided into three age categories (1829, 3049, 50+ yrs), and examined using image analysis to evaluate parameters related to trabecular bone structure and connectivity. A signicant agerelated loss in the amount (TBV%) and connectivity of bone was found between the youngest and the two older age groups, and loss appeared to be greater in males than females. These patterns contrast with those shown in modern populations that exhibit continuing loss between middle and old age, and greater loss in females. We speculate that the early age loss may be related to nutritional deciency, while ``lifestyle'' factors such as physical activity, parity and prolonged periods of lactation may explain the low prevalence of fragility fracture and maintenance of bone connectivity in the oldest age groups.

363 (327). A LARGE ANIMAL MODEL OF OSTEOPOROSIS: THE OVARECTOMIZED AND CORTICOID TREATED SHEEP P. Augat, C. Gohl, A. Ignatius, S. Iwabu, L. Claes, Orthopedic Research and Biomechanics, University of Ulm, Germany To create persisting osteopenic bone in a large animal, 24 skelettally mature merino sheep (mean age: 6.1 yrs0.8 yrs) were randomly assigned to ovarectomy alone (OVX), ovarectomy combined with glucocorticoid treatment (OVX+GLU) (0.45 mg Methylprednisolon per kg body weight for 6 months), or no treatment (CONTROL). Bone biopsies were harvested 6 months after ovarectomy and onset of treatment from the proximal tibia to assess trabecular bone. The biopsies were scanned for bone mineral density by Quantitative Computed Tomography (XCT960, Stratec) and tested mechanically in uniaxial compression. The BMD of the bone biopsies was signicantly decreased in the OVX+GLU group (p50.01, Dunnett's test) but not in the OVX group (p>0.1; Figure). The elastic modulus decreased by 5% in the OVX group (p>0.1) and by 53% in the OVX+GLU group (p<0.1). Ovarectomy in combination with glucocorticoid treatment gen-

362 (326). LOW SERUM 25-HYDROXY VITAMIN D A POSSIBLE CAUSE FOR LOW BMD AT PROXIMAL FEMUR IN HEALTHY INDIANS V. Arya1, A. Mithal2, 1Department of Endocrinology, Nizam's Institute of Medical Sciences, Hyderabad, India; 2Indraprastha Apollo Hospital, New Delhi, India Osteoporotic fractures are more common amongst Indians and occur earlier than Caucasian counter part. Subclinical vitamin D deciency is known to increase bone resorption and it is considered as a risk factor for osteopenia and fractures. There is lack of data regarding the determinant of hip fractures in Indians. Thus, to determine the association between BMD and vitamin D status this prospective study was undertaken. Material and methods: We studied 75 young healthy volunteers (56 females, 19 males) for daily sun exposure, vitamin D status and bone mineral density. Sample for serum intact parathormone (iPTH) was collected in 15 volunteers. 25-hydroxy vitamin D

erates osteopenia of trabecular bone in sheep and may serve as a new large animal model for the study of osteoporosis.

364 (328). B12 DEFICIENCY ITS ROLE IN THE DEVELOPMENT OF OSTEOPOROSIS J. Beynon, C. Murray, S. Vasishta, Dept. of Adult Medicine, St. Woolos Hospital, Newport, UK Pernicious anaemia (PA) and B12 deciency have previously been identied as a risk factor for osteoporosis and its associated fractures. The pathophysiologic process is mediated through a suppression of osteoblastic activity due to the

deciency in B12. These data highlight that the role of PA and B12 deciency as a risk factor for osteoporosis should not be forgotten. To determine the prevalence of B12 deciency in patients with osteoporosis the following study was undertaken. Over a 3-month period the authors reviewed the case notes of patients attending the bone clinic. Patients were included in the study if they had osteoporosis conrmed by bone density measurement (BMD). The following data were collected on each patient: Basic demographic data, past medical history, fracture history, baseline blood count and B12 level, current therapy with B12, BMD measurement. Within this unit normal B12 reference range is 176760 ng/l. The data was stratied by age, B12 level and fracture history. 263 patients were included (19 men, 244 women). The number of patients in each age range with B12 values of 5176ng/l is as follows: 3714 (21.4%) aged 55 years or less, 15/82 (18.2%) aged 56 65,20/110 (18.1%) aged 66 75,6/ 57 (10.5%) aged 76 or above. Of the 44 patients with low B12 values 22 had sustained a previous fracture. In only one patient was another condition identied which would account for the low B12 value. None of the patients with a low B12 value had a haemoglobin value below 11g/dl. In this patient population the level of previously unidentied B12 deciency was in the order of 16.7%. There have been no large scale studies to show that B12 replacement improves BMD and reduces fracture risk. However as B12 deciency has been shown to suppress osteoblastic activity, enhancing B12 levels should reverse this action and consequently lead to an improvement in BMD. We would therefore recommend B12 levels be measured as part of the diagnostic workup in patients with osteoporosis as it is an easily treatable.

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368 (332). RELATIONSHIP BETWEEN AWAKENING SALIVARY CORTISOL AND BONE QUALITY IN PREMENOPAUSAL WOMEN K. Brooke-Wavell1, A. Clow2, P. Evans2, S. Ghazi-Noori2, F. Hucklebridge2, 1Dept. Human Sciences, Loughborough University; 2Psychophysiology and Stress Research Group, University of Westminster, Cortisol levels show diurnal variation, peaking 30 minutes after awakening then declining to lower levels for the remainder of the day. Negative associations between 24 hour or basal cortisol levels and bone density have been reported, but the relationship between cortisol levels during the awakening peak and bone density has not been studied. We thus examined this relationship in a group of premenopausal women. Subjects were 40 healthy, eumenorrhoeic, non-smoking women aged mean (SE) 30.7 (1.5) y. Saliva samples were collected on awakening and 30 and 240 (n=32) minutes thereafter. Broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus. Salivary cortisol concentrations at 0, 30 and 240 minutes after awakening were 4.7 (0.5), 8.6 (0.8) and 4.3 (1.1) nmol/l. After adjustment for body mass, BUA and SOS were positively correlated with awakening cortisol concentrations but not those later in the day (r = 0.36*, 0.40* and 0.09 for BUA and 0.27, 0.36* and 0.05 for SOS at 0, 30 and 240 minutes after waking respectively, *P<0.05). In contrast to previous reports that cortisol levels at other times of day are related to poorer bone density, our ndings suggest that high cortisol levels on awakening are associated with better bone quality.


369 (333). REDUCING SODIUM INTAKE REDUCES URINARY CALCIUM LOSSES IN THE ELDERLY F. P. Cappuccio, A. M. Blackwood, G. A. Sagnella, N. D. Markandu, C. Carney, G. A. MacGregor, BPU, Department of Medicine, St George's Hospital Medical School, London, UK Background. High salt intake is associated with reduced peak bone mass in young girls and a high rate of bone mineral loss in postmenopausal women. It is also associated with increased urinary calcium losses. However, it is not clear whether this is a causative effect and whether it may be quantitatively compatible with a negative calcium balance. Methods. Forty-seven untreated elderly individuals (24 men, 42 whites, mean age 66.85.3 years, range 6078) completed a 2month double-blind randomised placebo-controlled study of modest salt restriction with slow sodium and placebo to give a salt intake of either 10g (equivalent to the usual amount for the UK and many western populations) or 5g. Results. On the higher sodium intake urinary calcium excretion was 5.19 (SD 2.41) mmol/day with a urinary sodium excretion of 177 (49) mmol/day. With modest sodium reduction, urinary calcium fell to 4.06 (2.12) mmol/day (p<0.001) with a urinary sodium excretion of 94 (50) mmol/day. A reduction in sodium intake of 83 mmol/day was associated with a reduction in urinary calcium excretion of 1.13 (95% CI: 0.741.52) mmol/day. Urinary sodium excretion was strongly and directly associated with urinary calcium excretion on both the high (r = 0.591; p<0.001) and the reduced (r = 0.475; p<0.001) sodium intake. The changes in urinary calcium per 100 mmol/day changes in sodium excretion were similar on the high (2.32 [0.64] mmol/day) and on the reduced (2.53 [0.51] mmol/day) sodium intake. The changes in calcium excretion were directly associated with the changes in sodium excretion (r = 0.530; p<0.001). It was estimated that a change in 100 mmol/day of sodium excretion would predict 1.19 (0.28) mmol/day changes in urinary calcium excretion. Conclusions. The higher the sodium intake, the higher the urinary calcium losses in an elderly population. A modest reduction in salt intake causes a signicant reduction in urinary


367 (331). ESTROGEN INCREASES CARTILAGE FORMATION AND FRACTURE HEALING STRENGTH IN OVX RATS M. E. Bolander, J. T. Bronk, G. Sarkar, Mayo Clinic and Mayo Foundation, Rochester, MN, USA The protective effect of estrogen (E2) on bone mass in postmenopausal women is well documented; however, the effect of estrogen depletion on fracture repair has not been evaluated. We report that E2 replacement improves fracture healing in OVX rats. Fractures were made in 120 six-month old rats. Of 90 OVX animals, 60 were given E2 replacement. Animals were killed at times representing specic stages of fracture healing; specimens were taken for histology, evaluation of gene expression, and mechanical testing. OVX animals without E2 replacement had signicantly weaker fracture calluses, and decreased cartilage formation on histology (p<0.05). Evaluation of gene expression showed a 13-fold increase in the expression of estrogen receptor during fracture healing, to a level 70% of that found in the rat uterus. Cartilage-related genes, including type II collagen and aggrecan were expressed at lower levels in the callus from OVX animals. Intramembranous bone formation was also decreased in OVX animals, but histology and evaluation of gene expression suggested this was secondary to abnormal endochondral ossication. E2 administration normalized cartilage formation, cartilage gene expression, and mechanical properties of the fracture callus. These studies suggest that fracture repair is abnormal in osteoporotic women. Estrogen replacement appears to normalize the fracture healing process.

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calcium losses in older people. This might be equivalent to a bone mineral density loss of 1.5% per year. A high salt intake, at least in the short term, is directly responsible for inappropriate urinary calcium losses in older people who are at much greater risk of developing bone demineralisation. Our results may have important implications for a nutritional approach to the prevention of osteoporosis and bone fractures in older people.

meters decreased with F content (p<0.05); however, this variation was not observed in histological sections. In conclusion, life-long uoride ingestion does not appear to alter the mechanical properties of human bone, although there may be a subtle effect on the architecture and mineralization. Jewish General Hospital and McGill University, Montreal, Canada.

370 (334). LOW S-ESTRADIOL LEVELS ARE PREVALENT IN MALES DIAGNOSED WITH PRIMARY OSTEOPOROSIS C. G. Carlsen, T. H. Srensen, E. F. Eriksen, University Department of Endocrinology, Aarhus Amtssygehus, Aarhus, Denmark Recent studies suggest that estrogens may be more powerful regulators of bone remodeling in adult males than androgens. We therefore investigated estrogen and androgen status in 54 males diagnosed with primary osteoporosis in our clinic over a period of 3 years. The diagnosis was based on the presence of either low energy fractures or a BMD t-score 52.5 in the spine or hip. The subjects underwent extensive clinical examination and biochemical testing in order to exclude secondary osteoporosis. 15 (28%) were classied as secondary osteoporosis (3(5.5%) displayed primary hypogonadism). 39(mean age 58.3 years) were classied as primary osteoporosis. 21 exhibited one or more vertebral fractures, 30 a lumbar BMD t-score 52.5 and 24 a hip BMD t-score 52.5. S-estradiol was assessed using sensitive assays (detection limits 40 pM). Among the 39 males with primary osteoporosis, mean S-testosterone was slightly elevated, with a median value of 19 nM (normal mean for men 5070 years is 14.6 nM (range 8.425.4 nM)). Circulating S-estradiol levels were, however, low in a large fraction of the material. 14 of 39 patients (36%) displayed S-estradiol levels below the normal range (48 165 pM; p<0.001). These results indicate that estrogen deciency is much more prevalent than androgen deciency in male osteoporosis. Estrogen deciency constitutes a dominating pathogenetic factor underlying low bone mass in males diagnosed with primary osteoporosis using currently recommended screening tests. Future screening tests for male osteoporosis should therefore include assessment of S-estradiol.

372 (336). THE QUEST (QUALITATIVE EFFECTS OF SALMONCALCITONIN THERAPY) STUDY: AN UPDATE OF THE BASELINE DATA C. Chesnut1, A. Shields1, P. Schmeer1, S. Majumdar2, D. Newitt2, P. Richardson3, A. Kriegman3, L. Mindeholm3, 1Osteoporosis Research Group, University of Washington, Seattle, WA; 2UCSF, San Francisco, CA; 3Novartis, East Hanover, NJ/Basel, Switzerland The QUEST study is a 2 year phase IV double-blind randomized controlled clinical trial designed to dene the mechanism of action of nasal spray salmon calcitonin vs. placebo in reducing fracture (Chesnut C. et al, 2000), utilizing multiple innovative technologies for assessing at multiple skeletal sites the interrelationship between bone quantity (BQUANT): DXA/US; bone quality (BQUAL): bone biopsy histomorphometry/micro CT/high resolution magnetic resonance imaging (MRI); and bone turnover: serum/urine NTx. Currently under analysis in the enrolled 91 postmenopausal osteoporotic (conrmed fractures by x-ray) women are 1) baseline (BL) assessment of the relationship between BQUANT (DXA/US) and BQUAL (MRI) at the same anatomical site (os calcis), 2) BL assessment of BQUAL in terms of trabecular bone architecture and structure as measured at multiple anatomical sites with differing technologies (iliac crest: bone biopsy histomorphometry and micro CT, hip: MRI, os calcis: MRI), and 3) the relationship of BQUANT (DXA/US) and BQUAL (histomorphometry/ micro CT/MRI) to severity of disease in terms of vertebral fracture severity. Our underlying hypotheses in terms of the ongoing BL analyses are that 1) BQUANT and BQUAL are discordant at the os calcis, 2) BQUAL is concordant in terms of trabecular structure across multiple sites and techniques, and 3) BQUAL will be a greater determinant of disease severity than BQUANT. Data currently analyzed will be presented.

371 (335). DOES LIFE-LONG INGESTION OF FLUORIDATED WATER ALTER BONE QUALITY IN HUMANS? D. Chachra, H. Limeback, A. E. Gross, C. H. Hutchison, D. Zukor, M. Schwartz, M. D. Grynpas, University of Toronto and Mt. Sinai Hospital, Toronto, Canada The purpose of this study is to assess the effects of life-long ingestion of subclinical amounts of uoride on the quality of human bone (including chemical composition, mechanical properties, mineralization, and architecture) as a surrogate for its effect on fracture risk. Femoral heads were obtained during total hip arthroplasty from 39 patients from Toronto (where municipal water has been uoridated at 1 ppm for >30 years) and 20 from Montreal (where water is not uoridated). The F content of cancellous bone from each specimen was determined by neutron activation analysis (Toronto mean: 1035(1922264) ppm F; Montreal mean 643(2951200) ppm F; p<0.01). Cylinders (6mm 6 6mm) of cancellous bone were subjected to compressive mechanical testing, but no relationship was found between mechanical properties and F content. The microhardness, which is related to the mineralization, was measured at a number of sites; at one of them, it was found to correlate linearly and positively with the F content (R2=0.304; p<0.001). Image analysis of radiological sections indicated that some connectivity para-

373 (337). PULMONARY FUNCTION CHANGES IN SPINAL OSTEOPOROTIC PATIENTS A. Co mlekci2, A. Alacacioglu1, B. Pamuk1, E. Ceylan3, A. Y. Goktay4, A. Akkoclu3, S. Yesil2, 1Dept. of Internal Medicine; 2 Division of Endocrinology; 3Dept. of Pulmonary Medicine; 4Dept. of Radiology, Inciralti, Dokuz Eylul Univ. Medical School, Izmir, Turkey Osteoporotic patients may have impaired quality of life for several reasons. However few data are present on the degree of the severity of vertebral deformity due to vertebral fractures on pulmonary function. We have investigated the effects of the degree of vertebral deformity on spirometry and lung volumes on 55 osteoporotic patients patients, 51 female, 4 male, mean (SD) age 62.48.2 years). Patients having previous history of pulmonary disease, smoking and diabetes were not included in study. Severity of osteoporosis was determined by calculation of the spine deformity index (SDI) (SDI-total and SDI-anterior) on lateral radiograph of the spine as described before. Although there was no signicant difference in spirometry and lung volumes between patients having SDI41 and SDI>1, there were signicant negative correlations between SDI and vital capacity (VC), FEF2575, RV/TLC, ERV (p<0.05) in patients with SDI>1.

These data suggest that osteoporotic patients having no pulmonary complaint may have subclinical pulmonary changes due to the degree of severity of vertebral deformity.

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In conclusion, bone turnover is increased in up to 46% of institutionalized patients suffering from E. TAP and to a lesser extent BAP constitute the best predictors of BMD in institutionalized patients treated by ACT.
Tot. Ca mg/dl NV 8.810.4 P gG T TAP BAP 25OHD 1,25(OH)2D iPTH uNTX/cr mg/dl IU/l IU/l mg/l ng/ml pg/ml pg/ml nM/mM 2.44.4 444 65215 2.914.5 1040 1845 1060 365 69 53 166 51 12.4 4.6 24.3 18.4 27.0 15.6 27 13 69 41

374 (338). CITRATE LEVEL IN OSTEOPOROTIC WOMEN TREATED WITH ESTROGEN AND ALENDRONATE P. D'Amelio1, M. Beccattini2, G. P. Pescarmona2, G. C. Isaia1, 1 Department of Internal Medicine; 2Department of Genetic, Biology and Biochemistry, University of Turin, Italy The aim of our work is to investigate the behaviour of plasma citrate in women with postmenopausal osteoporosis and treated with HRT or Alendronate. Basal citrate level was detected in 28 women with postmenopausal osteoporosis (T-score 52.5 S.D.). 16 patients where treated with HRT and 8 with Alendronate and the citrate level was measured (using a spectrofotometric method) at 3 and 6 months of therapy. The citrate were compared to each other using the Student's T-test. Our results are shown in the table:
HRT (16) mean Basal' 3 months' 6 months' 127 mmol/L 102 mmol/L 110mmol/L S.D. 26 18 27 ALENDRONATE (8) mean 107 mmol/L 122 mmol/L 122 mmol/L S.D.' 26 29 29 P NS

Mean 9.22 3.15 SD 0.32 0.63

376 (340). LOW MINERAL BONE DENSITY IN PROFESSIONAL SCUBA DIVERS o, C. F. Costa Dias, J. A. Pereira da Silva, J. E. Fonseca, H. Canha Resende, M. Viana Queiroz, 1Rheumatology Unit, Santa Maria Hospital, Lisbon, Portugal Scuba diving is associated with a 90 % reduction in effective weight and with the loss of a weight bearing effect on joints (due to a loss of contact with the ground). These conditions are very similar to the continuous weightlessness exposure that occurs in spaceight, which is clearly associated with signicant bone mass loss. In addition to this, the increase in blood CO2, observed frequently in diving, can also cause an inhibition of osteoblasts and an increase in bone resorption. All these arguments are consistent with the hypothesis of a bone mass reduction in frequent scuba diving. Objectives: Evaluate the bone mass and osteoporotic risk factors in a population of professional scuba divers. Material and methods: 66 professional scuba divers, working in the portuguese navy, randomly selected, all male, with a mean age of 33.56.5 years and a mean diving time of 3179319591 minutes, during the last ve years, were submitted to a bone mineral density (BMD) measurement with DXA and queried about osteoporotic risk factors. Results: The mean vertebral (L1-L4) BMD was 1.070.14 g/cm2 (Tscore + 0.171.12) and the mean femoral (neck) BMD was 0.950.12 g/cm2 (Tscore 0.291.06). 16.7% had a BMD 1 SD below the reference population in trabecular bone (L1-L4), 22.8% had a BMD 1 SD below the reference population in cortical bone (femoral neck) and 3% a BMD 2,5 SD below the reference population in cortical bone (25.8% had a BMD 1 SD below the reference population in cortical bone). No signicant differences were found between the osteopenic and the normal groups concerning the amount of alcohol, coffee and calcium consumption, age, body mass and diving time. Nevertheless, a signicantly higher weight bearing physical activity was found in the group with normal BMD (p = 0.017, comparing differences in cortical bone). Curiously, a higher tobacco consumption was found in the normal BMD group (p = 0.006, comparing differences in trabecular bone). Conclusion: We have found a reduction of BMD in professional scuba divers, mainly in cortical bone (25.8%) but also in trabecular bone (16.7%). The major additional factor inuencing the BMD was weight bearing physical activity.

The variation of citrate were signicant considering the HRT group: basal/3 months p = 0.0045, basal/6months p = 0.009, 6 months/3months p = NS, wile in the Alendronate group citrate did not change. Our data show that citrate signicantly decrease after 3 month of HRT and remains unchanged after 6 months, while it is not inuenced by Alendronate. Citrate level seems to be greatly inuenced by estrogen therapy, these data led us to suppose the importance of estrogen in determining Krebs cycle and our work suggests the citrate as a possible ``new marker'' of short term ecacy of HRT and of patient's compliance.

375 (339). METABOLIC ACTION ON BONE OF ANTICONVULSANT THERAPY IN INSTITUTIONALIZED PATIENTS SUFFERING FROM EPILEPSY J. P. Devogelaer, M. Divry, T. De Barsy, Depts Rheumatology and Neurology, St Luc University Hospital, Brussels, and Lennox Institute, Ottignies, Belgium Anticonvulsant therapy (ACT) has been for a long time a wellaccepted cause of disturbed bone metabolism (BM), mostly osteomalacia (OM), in patients suffering from epilepsy (E). We have assessed the parameters of BM in 30 institutionalized patients (A 45.2 (10.4); 16 F, 14 M). BMDs of the lumbar spine (L) and of the hip were measured by DXA using a QDR 4500 (Hologic, Inc.). The results (M SD) are summarized in the table. There was an excellent correlation between bone-specic alkaline phosphatase (BAP) and total (T) AP (r2 = 0.58; p50.0001), BAP and urinary (U) NTX/cr (r2 = 0.53; p50.0001) and between TAP and uNTX/cr (r2 = 0.56; p50.0001). Ten percent of patients had a serum Ca level lower than the inferior limit of normal (N) versus 13%, 31% and 35% for P, 25OHD, and 1,25(OH)2D, respectively. Seventy percent of patients had their gGT level higher than the superior limit of N, vs 16%, 28%, 3% and 46% for TAP, BAP, iPTH and uNTX/cr, respectively. Z-scores of the BMD of the spine and of the total hip amounted to 0.83 (1.27) and 1.34 (0.72), respectively. There was a negative correlation between L-BMD and TAP (r2 = 0.33; p50.001), and BAP (r2 = 0.17; p50.05), trochanter and TAP (r2 = 0.12; p50.05) and BAP (r2 = 0.11; p = 0.05).

377 (341). BONE DENSITY IN PREMENOPAUSAL WOMEN WITH ENDOMETRIOSIS AND DURING TREATMENT OF ENDOMETRIOSIS L. Diveky1, M. Hudecova1, P. Payer1, K. Holoman1, M. Krizko1, P. Suska1, 1Dept. Ob/Gyn, Comenius University, Bratislava, Slovakia OBJECTIVE: To investigate the impact of endometriosis on bone density and to evaluate the effect of add-back treatment of medrogestone on bone mineral density (BMD) under conditions

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of estrogen withdrawal in women with endometriosis who were treated with Decapeptyl depot. METHODS: We compared BMD in three groups of 40 premenopausal women. The patients were examined for endometriosis by laparoscopy or laparotomy because of benign gynecological pathology. Endometriosis was diagnosed in 20 patients. They were divided to two groups. A-group (n=10) was treated by Triptorelin combined with either placebo or 10 mg/d Medrogestone (group-B, n=10) for six months. C-group contained remaining 20 women without endometriosis. RESULTS: Lumbar spine BMD was measured at 0 and 6 month. Patients in both groups (A and B) had a similar and signicant decrease in BMD after six moths (4.5%, p50.01). Bone density of the lumbar spine in month ``0'' were: A-group 0.8870.335 Bgroup 0.9300.34; C-group 0.8950.29; Statistical analysis was performed by means of Student ``t''-test; signicance was set up at p<0.05. CONCLUSION: No signicant correlation was observed between any bone density measurement and severity of endometriosis. Add-back treatment with medrogestone at 10mg/d does not prevent lumbar bone density loss in premenopausal women under estrogen deprivation. For denitive practice conclusions, a bigger study is needed.

capacity FFBH 050% OR = 2.09, functional capacity FFBH 50 70% OR = 1.34 n.s. Severity the disease (OR compared with slight disease): asymptomatic disease OR = 1.19 n.s., moderate disease OR = 2.15, severe disease OR = 3.6, very servere disease OR 7.2 Disease duration (OR compared with disease duration 52 years): 310 years OR = 1.17 n.s., >10 years OR = 1.80 Erythrocyte sedimentation rate (OR compared with ESR 530 mmW): ESR 30 50 mmW OR = 1.17 n.s., ESR > 50 mmW OR = 1.30 n.s. C-reactive Protein (OR compared with CRP 520 mg/l): CRP 2030 mg/l OR 1.34 n.s., CRP >30mg/l OR = 1.14 n.s. Steroid treatment >1 year (OR compared with no steroids) 57.5 mg/l OR = 1.80, >7.5 mg/l OR = 1.83 Conclusion: Inammatory rheumatological diseases, severity of the disease, disease duration and steroid treatment are associated with an elevated risk for osteoporosis.

379 (343). EVIDENCE FOR CONTINUED BONE LOSS AFTER CARDIAC TRANSPLANTATION A CROSS SECTIONAL STUDY IN 53 PATIENTS A. Fahrleitner, G. Prenner, D. Kniepeiss, K. H. Tscheliessnigg, L. Stach, C. Piswanger-Solkner, G. Leb, H. Dobnig, Dept. of Internal Medicine, Dept of Surgery, Div. of Endocrinology, Div. of Transplantation, Karl Franzens University, Graz, Austria, Europe It is well known that cardiac transplant recipients have a high prevalence of osteoporosis (OPO) before transplantation and usually demonstrate signicant bone loss following cardiac tranplantation (CTX) with a maximum in the rst postoperative year. The aim of this study was to evaluate bone mineral and fracture status in long-term survivors after CTX. We studied 53 patients with an average of 555 (SE) mos after CTX. In all patients a hip DXA, a standardized spinal X-ray and laboratory tests were performed. None of the patients were on osteoprotective therapy and all received a triple immunosuppressive medication. WHO-dened OPO at the hip was diagnosed in 42% (n=22) of patients, 36% (n=19) had one or more vertebral fractures (3.5#/pat), 74% (n=39) had renal impairment, 62% (n=33) 28 HPT and 30% of all males (n=12) had evidence of primary hypogonadism. Patients with vertebral fractures had signicantly reduced Zand T-scores at the hip (1.140.22 vs.0.400.21 and 2.70.22 vs.1.760.24, p<0.02) when compared to non-fractured subjects. Fractured patients tended also to have higher creatinine-, PTHand serum cross laps levels but were comparable in mean time since CTX to unfractured individuals. To further analyze time effects on bone mineral status we grouped patients into categories A (1224 mos), B (2548 mos) and C (49148 mos) according to time since CTX and could demonstrate a fall in mean z-score (neck) from 0.430.2 to 0.520.3 and 0.910.27 (NS). In addition, patients belonging to group C had lower z-scores (trochanter) when compared to group A (1.00.24 vs.0.260.2, p<0.04) and higher creatinine-, PTH-, cross laps- and lower testosterone values than in the early posttransplantation period. This cross-sectional study suggests that bone loss extends over the immediate post-operative period and that additional long-term complications such as renal impairment, 28 HPT and hypogonadism may contribute to further worsening of bone status.
Men (n=40) Age Z-score femoral neck Z-score trochanter T-score femoral neck T-score trochanter Serum PTH Serum cross laps Serum osteocalcin 25-OH vitamin D3 56.50.2 0.80.2 0.50.2 2.20.2 1.10.2 9511 4881453 495 201.8 Women (n=13) 60.21.4 0.30.2 0.40.2 1.90.2 1.30.3 13641 67761548 6220 153.2 p-value men vs. women NS NS NS NS NS NS NS NS NS Normal range

378 (342). RHEUMATOLOGICAL DISEASES AS RISK FACTORS FOR OSTEOPOROSIS R. Dreher, G. Lingg, J. Listing, A. Zink, 1Hospital for Rheumatic Diseases, Bad Kreuznach; 2Epidemiology Department, German Rheumatism Research Center, Berlin, Aims: To compare different rheumtological diseases as risk factors for osteoporosis. To dene patients functional capaclty, severity of the disease, disease duration and inammatory activity as risk factors for osteoporosis. Methods: In cooperation with the National Database of the German Cooperative Arthritis Center Berlin, the database of the Hospital for Rheumatic Diseases Bad Kreuznach was crosssectionally evaluated for osteoporosis in women >50 years with various underlying rheumatological diseases. Osteoporosis was dened as values for bone mineral density 2.5 SD. or more below the young mean in LDXA or SDXA (LUNAR) or below 122 mg HAE (Hydroxy Apatite Equivalent) in lumbar QCT (General Electric 3000 single energy scanner). Logistic Regression analysis models with osteoporosis (yes/no) as the dependent variable and various rheumatological diseases, age, functional capacity FFBH (Hannover questionnaire score for function), severity of disease (asymptomatic, slight, moderate, severe, very severe) disease duration (52 years, 310 years, >10 years, ESR (mmW), Creactive protein (mg/l) and steroid treatment >1 year >7.5mg/d, <7.5mg/d) as covariables were calculated in respect of the risk for osteoporosis (odds ratio) associated with a given number of independent variables. Results: Osteoporosis (number of women with osteoporosis: number of total women, %) in women >50 years, dependent on the underlying rheumatological disorder: Connective Tissue Diseases (17/103, 16.5%), Polymyalgia Rheumatica (54/173, 31.2%), RF pos. Rheumatoid Arthritis (329/ 953, 34.5%), RF neg. Rheumatoid Arthritis (142/595, 23.9%). Osteoarthritis (141/1158, 12.2%). Ankylosing Spondylitis (12/35, 34.3%). Low Back Pain Syndrome (76/408, 18.6%) Risk factors for osteoporosis calculated as odds ratios (OR) in logistic regression analysis models adjusted for age Underlying rheumatological diseases (OR for osteoporosis compared with osteoarthritis): 1) Connective Tissue Diseases OR = 1.85, 2) Polymyalgia Rheumatica OR = 2.65), 3) RF pos. Rheumatoid Arthritis OR = 3.45, 4) RF neg. Rheumatoid Arthritis OR = 2.56, 5) Ankylosing Spondylitis OR = 5.13. Functional capaclty (Hannover questionnaire score (FFBH%) for function. OR compared with FFBH = 70100%): functional

1065 pg/ml 14654565 pmol/l 1030 ng/ml 945 ng/ml

380 (344). LONGITUDINAL CHANGES OF BONE TURNOVER AND BONE LOSS ACCROSS THE MENOPAUSE. THE OFELY STUDY P. Garnero,1,2, E. Sornay-Rendul, F. Munoz1, P. D. Delmas1, 1 INSERM Unit 403, Lyon, France; 2Synarc, Lyon, France Crossectional studies indicate an increase of both bone formation and bone resorption after the menopause. Whether bone turnover increases before menopause is still unclear, because of the lack of longitudinal studies. In this study, a measurements of markers of bone formation [serum osteocalcin (OC) and bone alkaline phosphatase (BAP)] and of bone resorption [urinary C-telopeptide of type I collagen (CTX] and of FSH was performed annually in 257 healthy untreated women (mean age, 41.4 yr) followed prospectively for a mean (SD) of 5.1 (1.2) yr (range 26 yr). At baseline, 186 women (w) were classied as premenopausal (FSH levels <16.7 UI/l, mean age 39 yr), and 71 as perimenopausal (FSH levels >16.7 UI/l with or without irregular menses, mean age 48 yr). During follow-up, 44 premenopausal w. became perimenopausal, 13 premenopausal w. became postmenopausal (absence of menses for at least 1 yr) and 33 perimenopausal w. became postmenopausal. In the whole population, increased levels of FSH were associated with a higher bone turnover (r = 0.27, p = 0.005 and r = 0.22, p = 0.02 for CTX and osteocalcin respectively). Among w. who remained premenopausal, levels of bone formation markers remained unchanged and urinary CTX slightly decreased with time. In w. who remained perimenopausal during the study (mean follow-up: 4.3 yr), bone turnover progressively increased with time (0.76 ng/ml/yr, p = 0.003 and 0.29 ng/ml/yr, p = 0.06, for OC and BAP respectively). In w. who became perimenopausal, levels of serum OC, BAP and urinary CTX increased and the mean levels were respectively 17% (p<0.0001), 11% (p<0.0001) and 21% (p = 0.03) higher than the premenopausal values in the same subjects. Bone turnover markers further increased after established menopause with values 2035% higher than perimenopausal values in the same subjects (p<0.001). No signicant change of bone mineral density at the mid radius was observed in women who remained premenopausal, perimenopausal or who became perimenopausal during the study. In contrast women who changed from a perimenopausal to a postmenopausal status had a signicant bone loss of 0.4% per year which was correlated with increased baseline levels of CTX (r = 0.41; p<0.03). In conclusion this longitudinal study indicates that bone turnover begins to increase before the menopause, during the perimenopausal period, and that this increase precedes bone loss

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for women with three or more pregnancies, but higher if nulliparity. For women with pure trabecular bone mass in the three lower quintiles (<274 mg/cm3), being nulliparous and/or having a ratio of apo B to A1 in the top tertile (>0.67), the prevalence of fast bone-loser women is 79 %. The initial values in the cohort study conrm these results, the trabecular bone mass (means in mg/cm3) at radius being by non-biased groups:

Apo-ratio >0.72 and/or Apo-ratio 40.72 and one or nulliparous more pregnancies Women N Mean (SEM) (11) (9) N 41 38 =.12 Mean 236 256 (SEM) (8) (10) P <.05 n.s.

without HRT 36 208 with HRT 37 247 P (two-tailed) <.01

With growing postmenopausal years, only in women without HRT trabecular bone masses decrease and the apo-ratios increase continuously. Conclusions. There is good evidence that bone metabolism is inuenced by lipid metabolism. With the ending of menstruation, in women with insufciently developped trabecular bone (bone mass 5median) the high ratio of apolipoproteins B to A1 is a special risk factor for osteoporosis, suggesting an association with atherosclerotic disease.

382 (346). BONE LOSS IN EARLY, ACTIVE RHEUMATOID ARTHRITIS: EFFECTS OF CORTICOSTEROIDS, GENDER AND MENOPAUSAL STATUS IN THE COBRA TRIAL P. Geusens,1,2 A. C. Verhoeven2, M. Boers3, J. M. te Koppele4, W. H. van der Laan4, H. M. Markusse5, S. van der Linden1, 1 Rheumatology Dept, Academic Hospital, Maastricht University, The Netherlands; 2Biomedical Research Institute, LUC, Diepenbeek, Belgium; 3Clinical Epidemiology & Biostatistics, VU University Hospital, Amsterdam; 4TNO Prevention & Health, Vascular and Connective Tissue Research Division, Leiden; 5 Rheumatology Dept., Zuider Hospital, Rotterdam, The Netherlands The degree of bone loss in rheumatoid arthritis (RA) is still a matter of debate. Many clinical studies use mixed patient groups of men and women with variable disease duration and intensity of steroid therapy. In a double blind randomized trial, a group of patients with early, active RA was treated with sulfasalazine (SSZ, n=79) or a combination of sulfasalazine + methotrexate + prednisolone (60 mg/d in week 1 tapered to 7.5 mg maintenance dose in week 7) during 6 months, followed by sulfasalazine alone (COMB, n=76) (Lancet 1997; 350: 30918). All had supplements of calcium (500 mg/day) and, if vitamin D decient, with vitamin D (400 IU/day). Mean (95% C.I.) lumbar bone density changes over 56 weeks were 1.3% (2.3, 0.4) in the COMB group and 0.3% (71.4, 0.8) in the SSZ group (p = 0.15). In the femoral neck, bone density changes over 56 weeks were 1.9% (3.1, 0.7) versus 1.3% (2.5, 0.1) (both p>0.2). In a multiple regression analysis, including treatment, gender and menopausal status as factors, bone loss was signicantly dependent on menopausal status. Premenopausal women (n=33) lost no bone. Postmenopausal women without hormonal replacement therapy (HRT) (n=27) lost signicant amounts of bone at all sites after 56 weeks, up to 3.5 (6.1, 0.9) after SSZ and 4.5% (77.9, 71.0) after COMB in the femoral neck. This appeared more rapidly in the SSZ group but more pronounced in the COMB group, although differences between groups were not signicant. Women in the COMB group on HRT (n=8) lost little or no bone after 56 weeks except in the femoral neck [3.3% (5.9, 0.7)]. Only men in the COMB group (n=22) lost bone, and only in the spine [after 56 weeks 2.2% (4.1, 0.3)].

381 (345). LIPOPROTEINS INFLUENCING MENOPAUSAL BONE LOSS R. Gass, E. Bally, ISPM, Epidem., University of Zurich, Zurich, Switzerland For the prevention of osteoporosis we have to identify causal cofactors. Methods. In a prospective two-year study the bone mass and loss of 70 healthy women, on average 52 years old and not taking hormones, were measured one to four years after natural menopause by peripheral QCT (type Densiscan); additionally, in a cohort study the bone mass in women aged 560 years with several years (range 1 to 20) after menopause, the half of these 152 measured women being treated with estrogens (HRT). Results. Regarding the annual change of the pure trabecular bone mass at the ultradistal radius in the two-year study, the prevalence of fast bone-loser women (trabecular bone loss >3.8 % per year) is 34 %, the distribution of the bone loss rates being bimodal. The logistic regression shows: the lower the trabecular bone mass and the higher the ratio of apolipo-proteins B to A1, the greater is the probability that the particular woman has an accelerated bone loss; moreover, this risk is independently lower

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We conclude that in women with early active RA, postmenopausal status is a risk factor for signicant bone loss in the spine and hip, irrespective of antirheumatic treatment regimen. HRT protected against bone loss, except in the femoral neck. In men, short-term corticosteroid therapy is a risk factor for bone loss in the spine only.

385 (349).CHOICES FOR BETTER BONE HEALTH: A SELFMANAGEMENT PROGRAM FOR OSTEOPOROSIS D. T. Gold, S. L. Silverman, B. E. Miller, 1Duke University Medical Center, Durham, NC, USA; 2University of California At Los Angeles, CA, USA; 3Procter and Gamble, Cincinnati, OH, USA Osteoporosis (OP) has psychosocial as well as physical consequences; in addition, poor patient compliance with medication, exercise, and calcium often occur. Traditional patient education about OP has focused on a simple transfer of information and has had minimal impact on behavioral change. Based on a needs assessment and focus groups, we have developed a patient self-management course for OP called CHOICES for Better Bone Health. This course empowers patients to become active members of their OP healthcare teams. CHOICES is based on the 5 Cs of self-management: Comprehending the problems of OP; Choosing OP management strategies; Committing to those management strategies; Communicating about OP and its management to family, friends, and health care providers; and Coping with the challenges of OP. CHOICES is a ve-session course, and each class is facilitated by a trained patient (Manager) and allied health care professional (Management Partner). Course content includes background information on OP, assessment of bone health, OP medications, management strategies for diet, exercise, calcium/Vitamin D intake, the psychosocial outcomes of OP, partnering with health care providers, and fashion for people with OP. Key messages include, ``It's never too late to begin prevention or treatment of OP,'' ``You can manage your bone health,'' and ``You have a choice of therapies.'' CHOICES will be available nationally in Fall, 2000 and can be modied to meet cultural and regional needs. Evaluation outcomes will include the effect on health-related quality of life and adherence to medication/exercise regimens and life style changes.

383 (347). DECREASED PHYSICAL ACTIVITY IS RELATED TO INCREASED BONE RESORPTION IN HEALTHY AMBULATORY ELDERLY WOMEN, INDEPENDENT OF VITAMIN D STATUS P. Geusens,1,2, J. Vanhoof1, K. Declerck1, H. Bischoff3, J. Raus1, Sj van der Linden2, 1Biomedical Research Institute DWI, Limburg University Center, Diepenbeek, Belgium; 2Department of Rheumatology, Academic Hospital, Maastricht University, The Netherlands; 3Department of Orthopaedics, Rheumatology and Geriatrics, University Basel, Switzerland Immobility may lead to signicant bone loss. Physical activity decreases with age and after fracture. Increased bone resorption associated with lower mobility has been found in institutionalised elderly, but is not documented in elderly ambulatory women. Physical performance, muscle strength and urinary pyridinoline excretion (PYR) were measured in 340 healthy elderly ambulatory women. Mean PYR was 27% higher in less mobile women compared to mobile women as evaluated by their ability to rise from a chair (44 nM/mg creatinine versus 34 nM/mg creatinine respectively, p<0.0001). Mean PYR was 30% higher in women with limited daily activities as compared to physically still active women (44 nM/mg creatinine versus 34 nM/mg creatinine, p = 0.001). Mean PYR was 15% higher in women with a history of fracture compared to women without a history of fracture (39 nM/mg creatinine versus 34 nM/mg creatinine, p<0.05). PYR was not related to vitamin D status. Bone density in the hip was modestly related to PYR (r = 0.114, p<0.05) and to muscle strength (r = 0.174, p<0.05) but not to vitamin D status. We conclude that, in ambulatory healthy elderly women, decreased mobility is associated with increased bone resorption that is associated with low bone density in the hip, independent of vitamin D status.

386 (350). BONE CHANGES DUE TO BISPHOSPHONATE TREATMENT IN A MODEL OF ASEPTIC LOOSENING M. D. Grynpas1, M. Kasra1, R. A. Kandel1, L. White2, A. Binnington3, 1Depts of Lab Medicine and Pathobiology and Radiology, U of Toronto & Mount Sinai Hospital; 2Ontario Veterinary College, University of Guelph, The aim of this work was to study the bone changes induced by the bisphosphonate zoledronate (Zln) in a canine model of aseptic loosening of hip implant. Between 10 and 20% of hip replacements are revisions of failed primary implants. The reason is aseptic loosening caused by polyethylene (PE) and other wear debris leading to inammation and bone resorption. Bisphosphonates should prevent the bone resorption that leads to implant loosening. In this study, 30 adult male dogs were given an uncemented titanium femoral prosthesis and a cemented acetabular cup. The femoral components contained multiple horizontal grooves led with micron size PE particles in clotted blood. Each group of 10 dogs received weekely s.c. injections of: vehicle in group 1 (control), 2mg/kg Zln (low dose) in group 2 and 10mg/kg (high dose) in group 3. The dogs were allowed full postoperative ambulation and were sacriced after 26 wks. The operated legs were x-rayed preoperatively at 1 day and at 2, 4, and 6 months postoperatively. The membranes surrounding the implant were harvested and examined histologically. They consisted of hyalinized brous tissue with PE fragments and inltration by histiocytes and occasional lymphocytes. There was no histological differences between the 3 groups. There was diffuse and localized periosteal new bone formation seen radiographically mainly in the high dose group and to a lesser extent in the low dose group and occasionally in the control group. Mechanical testing was done on 4 longitudinal rectangular strip of each femur. These 4-point bending tests showed that elastic modulus and bending stress increased signicantly with increased dose of Zln. These results indicate that Zln

384 (348). HIGH LEVELS OF DEPRESSION ARE ASSOCIATED WITH HIGH LEVELS OF FREE TESTOSTERONE IN POSTMENOPAUSAL WOMEN M. G. Glu er1, A. D. Lazerescu2, H. W. Minne2, B. Begerow2, M. hne2, 1Universitatsklinik CAU Pfeifer2, T. Schlotthauer2, W. Polla zu Kiel; 2Institut fur klinische Osteologie, Bad Pyrmont, Germany Severity of depression may be inuenced by hormones, i.e. estrogen deciency in women. We investigated 225 postmenopausal osteoporotic women (age 63.387.71), assessing hormonal status, depression (Hautzinger & Bailer 1992) lumbar spine bone density (BMD, Hologic QDR 2000) and fracture status (SDI, Spine Deformity Index). Hormones included 25-OH-D (Nichols Inst., FRG), LH, FSH, SHBG, free testosterone (LIA, Chiron Diagnostics, FRG), and 17b-estradiol (measurable in 113 women only, FIA, Wallac-ADL, FRG). The sample was subdivided by median into groups with high (18.96.1) and low (5.92.7) depression scores. Free testosterone was signicantly elevated in the group with high depression scores (2.01.7 pmol/l vs. 1.51.3 pmol/l, p<0.01) even when controlled for age and fracture status (p<0.02). SHBG (p<0.087) and SDI (p<0.12) showed somewhat higher levels while 25-OH-D (p<0.056) and 17b-estradiol (p<0.23) were somewhat lower. LH, FSH and BMD did not show signicant differences. Results on fracture status agree with previous reports. The weak association of female hormones may have been caused by small sample size and the low levels in elderly women. The strong difference in free testosterone should be investigated further and, if conrmed, therapeutic implications should be elucidated.

treatment increases the mechanical properties of bone and increases periosteal new bone formation in this model of aseptic loosening.
Fem.neck Total hip Spine L24 Baseline 0.847 (0.159) 0.871 (0.157) 1.102 (0.202) At 2 yrs 0.835 (0.172) 0.867 (0.159) 1.092 (0.189)

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BMD reduction (95%CI) 0.011 (0.023, 0.002) 0.007 (0.016, 0.002) 0.010 (0.022, 0.002)

387 (351). BONE REMODELING UNDER A LOW-DOSE ORAL CONTRACEPTIVE M. Hartard, P. Bottermann, D. Jeschke, M. Schwaiger, Working Group of MusculoSkelatal Interactions, Universities of Munich, Germany Epidemiological investigations of the Royal College of General Practitioners document a 20% greater risk of bone fracture in women who have taken contraceptives (OC) for a long time. These results indicate that further investigations are needed. The objective of this exploratory 24-months controlled study was to observe bone mass and bone metabolism under a low-dose OC (30 mg estradiol and 75 mg gestodene) in women aged from 2535 years. After being off OC for at least 4 months, 24 women decided to take OC, 25 participated in the control. No differences existed between the groups at any time with regard to the anthropometric, nutritional and performance data. The groups were comparable with regard to the data of electrolytes, hormones, bone metabolism and bone mass (DPX: L24 and right collum). After two years sign. lower serum levels for alkaline phosphatase (p<0.05), osteocalcin (p<0.0001), pyridinoline (p<0.005) and deoxypyridinoline (p<0.05) in the OC group, even signicant differences between the groups (p<0.05) for osteocalcin could be observed. Both groups did not show any bone mass changes. There is a largely balanced bone remodeling unaffected by OC in this age group. This brings about sufciently quick and extensive repairs. These observations could be evaluated in terms of reduced bone remodeling and it cannot be ruled out that lowdose OC's reduce the repair capacity of bone in young women.

Conclusion: Only minimal bone loss was observed during two years in this group of female RA-patients receiving counselling and prevention/treatment of osteopenia and osteoporosis according to clinical judgement.

389 (353). OSTEOPOROSIS PREVENTION AMONG TEENS Linda L. Hightower, Community Medical Center, Missoula, Montana, USA The purpose of this investigation was to develop a program to educate teens about the prevention of osteoporosis. Initially, research was done to understand the future affects of current teen practices in relation to nutrition and exercise. A presentation was written based on NOF recommendations about information teens need and information gathered from some teens themselves. During presentations in classrooms, a pre- and postsurvey was done to evaluate the students' knowledge about osteoporosis. An evaluation was done allowing students to anonymously voice suggestions for additions or subtractions and evaluate how this information might affect their lives. Results showed that most students understand that osteoporosis causes bones to be more fragile but they believe that it only affects elderly women and that there is no prevention or treatment. They were very positive about the information and said they would recommend that their friends receive this same information. In conclusion, teens not only need this information to prevent osteoporosis, but they want to hear it.

388 (352). NO SIGNIFICANT LOSS OF BONE: A TWO YEAR FOLLOW-UP OF 173 FEMALE PATIENTS WITH RHEUMATOID ARTHRITIS G. Haugeberg1, T. K. Kvien1, T. Uhlig1, R. E.Orstavik1, J. A. Falch2, J. I. Halse3, 1Oslo City Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo; 2Dept. of Internal Medicine, Aker Hospital, Oslo; 3 Osteoporosis Clinic, Oslo, Norway Objective: To examine longitudinal changes in bone mass in female Caucasian rheumatoid arthritis (RA) patients managed in a regular clinical setting with combined rheumatologist/general practitioner care. Method: A total of 173 female RA patients age 2070 yrs, recruited from a RA-register (completeness 85%), underwent bone density measurements at baseline and after two years. All patients were at baseline adviced about life-style, calcium and vitamin D supplementation, and they received hormone replacement therapy or bisphosphonates according to clinical judgement. The following baseline characteristics were recorded: mean age 53.6 yrs (SD 11.1), mean disease duration 12.8 yrs (SD 9.6), 66.5% post-menopausal, 28.3% current users of estrogen, 54% Waaler positive, mean MHAQ 1.59 (SD 0.42), and 30.8% never, 23.1% previous and 46.2% current users of prednisolone. Bone mineral density (BMD) measurements in hip (femoral neck and total hip) and spine (L24) using DXA (Lunar Expert-XL) were performed. The long time phantom coefcient of variation (CV%) was 0.8% and the in-vivo reproducibility of BMD measurements (assessed from duplicate measurements in 31 healthy females) was 1.5% at the femoral neck, 1.5% at the total hip, and 2.2% at the lumbar spine (L24). Results: In the two year period a 1.3% reduction in BMD was found in femoral neck, 0.8% in total hip and 0.9% in spine L24. As shown in the table below no statistically signicant BMD (g/cm2) reduction was found over the two year period.

390 (354). MALDESCENDED TESTIS AND SUBSEQUENT DEVELOPMENT OF OSTEOPOROSIS IN MALES S. J. Iqbal, M. Quinn, S. Muhlbayer, Dept of Chemical Pathology, Leicester Royal Inrmary, Leicester, UK In men osteoporosis can by caused by hypogonadism, the actiology of which can be varied. Can maldescent of testis be a cause? Case 1. An Asian, 49 yrs presented with height loss (HtL) of 2 1/ 2 ins, kyphosis and gynaccomastia. Lateral spinal x-rays (LSPXR) showed mild wedging and spinal bone mineral density (BMD); (L2-L4) was 0.560 g/cm2 (T score 5.6). PMH included orchidopexy and later orchidectomies at 31 and 36 yrs. FSH 55 iu/L (110), LH 9.5 iu/L (1.09.0), testosterone <0.7 nmol/L (1030), SHBG 5 nmol/L (15 40). He also had severe myopathy with coexisting nutritional osteomalacia. Adjusted calcium 1.75 mmol/L, alk phos 803 iu/L, phosphate 0.94 mmol/L, 25(OH)VitD <5 mg/L, PTH 88 pmol/L. Case 2. A male, 55 yrs, with IgG paraprtoeinaemia developed severe back pain, kyphosis and HtL 8/9 ins over the past 3 years. PMH included inguinal operations at age of 46 and 49. Results; FSH 28, LH 12, testosterone 3.0, SHBG 71. LSPXR showed multiple severe wedge fractures. Spinal BMD unmeasurable because of kyphosis. Case 3. An Asian, 48 yrs presented with back pain. PMH included R hernia repair at 12 yrs. FSH 5.8, LH 1.7, testosterone 5.4, SHBG 15. LSPXR showed no wedging, BMD (L2-L4) 0.948 g/ cm2 (T score 2.4), pituitary MRI scan NAD. Case 4. A patient 80 yrs, presented with back pain. LSPXR showed wedging T9,L1, L3, BMD (L2-L4) 0.805 g/cm2 (T score 73.6), FSH 40, LH 97, testosterone 2.8, SHBG 82. Testes were not in the scrotum but in inguinal pouches.

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All these men presented with sparse/absent male body hair, with one or both testis which were atrophic or absent and had not fathered any children. They were treated with Testosterone. Males with maldescended testis require monitoring of testosterone levels, with replacement therapy if necessary, to prevent osteoporosis.

and p50.05), more modest in the ERT treated women at the VB (0.60.1 SD, p50.001) but not at the FN (0.40.2 SD, p50.05). VB and FN width were not signicantly reduced in the recovered women (0.30.2 SD, p = 0.1, 0.30.2 SD, p = 0.2 respectively). In untreated women, VB and FN volumetric BMD decits were 1.60.1 SD and 1.10.1 SD (both p50.001), more modest in ERT treated women (1.20.2 SD, 0.60.2 SD, both p50.001) and least in recovered women (0.60.1 SD, 0.50.2 SD, both p50.05). Bone fragility in AN is due to reduced bone size and reduced volumetric BMD. These decits may be largely reversed following ERT or recovery from illness.

391 (355). LACK OF CORTICOSTEROID EFFECT ON TRABECULAR BONE DENSITY OVER 18 MONTHS IN SYSTEMIC LUPUS ERYTHEMATOSUS A. A. Kalla, L. Bewerunge, S. Swanevelder, A. B. Fataar, 1 Rheumatic Diseases, University of Cape Town; 2Nuclear Medicine Department, Medical Research Council, Cape Town, South Africa Aim: To study the longitudinal effects of corticosteroid therapy in patients with systemic lupus erythematosus (SLE). Methods: Patients meeting the ACR criteria for SLE were followed up at the Lupus Clinic at Groote Schuur Hospital. Normal volunteers and patients had dual x-ray absorptiometry (DXA) measurement of the hip and lumbar vertebrae with the Hologic QDR 1000 on 2 occasions, approximately 18 months apart. Patients with SLE were monitored with respect to current daily dose and cumulative dose since rst DXA measurement. None of the subjects were receiving substances that could interfere with bone metabolism. In the SLE group, exclusions were made for male sex, chronic renal failure, dialysis, pregnancy, epilepsy, immobilization and menopause. Results: There were 56 patients with SLE and 41 normal controls. The mean age of the SLE group was 32 (SD7) years and mean disease duration 74 (SD62) months. The mean age of the controls was 34 (SD9) years. The 2 groups were comparable for height and weight. The patients with SLE had lower bone mineral density (BMD) than controls at each cross-sectional comparison. However, there was no signicant change over 18 months in either the SLE patients or the normal controls (p>0.50), at any of the femoral or lumbar sites of measurement. There were 26 patients receiving corticosteroid (CS) therapy at the time of study. The mean daily dose of prednisone was 12 (range 245) mg and the mean cumulative dose over the study period was 7.019 (range 1.02921.973) grams. The mean duration of CS therapy was 32 (SD12) months. When the CS-treated subgroup was analyzed for change in BMD, no signicant change was seen at any of the sites (p>0.20). The body mass index increased signicantly, suggesting compliance with therapy. Conclusions: Bone loss in premenopausal SLE is due to the underlying disease and is not accelerated by corticosteroid therapy. Systemic lupus erythematosus may be associated with factors protecting against CS-induced bone loss. Other potential mechanisms for bone loss in SLE need to be studied in order to effectively prevent fractures in later life.

393 (357). HIGH PREVALENCE OF VERTEBRAL FRACTURES IN PATIENTS WITH CROHN'S DISEASE EVALUATED BY QUANTITATIVE MORPHOMETRY J. Klaus1, J. Bruckel1, M. Steinkamp1, M. Reinshagen1, G. Adler1, A. Rieber2, C. V. Tirpitz1, 1Department of Internal Medicine I, University of Ulm; 2Department of Radiology, University of Ulm, Ulm, Germany Background and aims: Osteopenia and osteoporosis are frequent in Crohn's disease (CD). However, there are no data that show the association of decreased bone mineral density (BMD) and vertebral compression fractures in these patients. The aim of this study was to examine the prevalence of vertebral fractures in CD patients with decreased BMD. Methods: 258 CD patients were screened including osteodensitometry by dual energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4) and total upper femur. In 92 CD patients (55 female) with osteopenia or osteoporosis at the lumbar spine, both, DXA and X-ray examinations of the thoracic and lumbar spine were available. The assessment of fractures included the visual reading of the X-rays and the quantitative morphometry (QM) of the vertebral bodies (T4-L4) according to the criteria of the European Vertebral Osteoporosis Study (EVOS). Results: From the 92 CD patients (aged 36,27 years, range 17 67), 29 patients (31,5%) showed osteoporosis (T-score 52.5) and 63 (68.5%) osteopenia (T-score 51,> 2.5). 72 CD patients showed preclinical osteopenia and osteoporosis with no prevalent vertebral changes whereas in 20 (21.7%) (13 female) CD patients the QM revealed one or more vertebral deformities (fxd.) or fractures (fx.). 7 out of the 20 patients only showed fxd., and 13 (14.13%) (11 female) patients had criteria of fx. In these 20 CD patients a total of 25 fx. (14 of the thoracic and 11 of the lumbar spine) and 11 fxd. (8 thoracic and 3 lumbar) were detected. Only in 4 patients the fx. were clinically evident (9 fx., two of them considered to be caused by minimal inadequate trauma). The fx. in the other 16 patients were clinically undetected. There was no signicant difference considering BMD between the preclinical and manifest cases (lumbar T-score 2.090,65 vs. 2.490.94, n.s., hip T-score 1.981.18 vs. 1.800.79, n.s., respectively). There was a signicant difference regarding BMD at the hip comparing the 7 patients with fxd. to the 13 patients with fx. (lumbar T-score 1.950.42 vs. 2.261.05, n.s., hip T-score 1.210.94 vs. 2.41.09, p<0.05, respectively). Conclusions: In patients with Crohn's disease (CD) and low BMD (T <1) the prevalence of vertebral fractures or deformities i.e. manifest osteoporosis was unexpectedly high. By detailed morphological analysis of X-rays (quantitative morphometry) we were able to demonstrate 25 fractures and 11 deformities in 20 out of 92 (21.7%) mostly asymptomatic patients.

392 (356). ESTROGEN REPLACEMENT THERAPY AND RECOVERY FROM ANOREXIA NERVOSA: RESTORATION OF AXIAL AND APPENDICULAR BONE SIZE AND DENSITY K. M. Karlsson, S. Weigall, Y. Duan, E. Seeman, Department of Endocrinology, University of Melbourne, Melbourne, Australia The purpose of the study was to evaluate if anorexia nervosa (AN) is associated with reduced bone size and reduced volumetric bone mineral density (BMD) and if estrogen replacement therapy (ERT) or recovery from AN is associated with restoration of size and BMD. Using DEXA, we measured bone size and volumetric BMD of the third lumbar vertebral body (VB) and femoral neck (FN) in 77 women with AN, 58 women with AN receiving ERT, 26 women recovered from AN, and 205 controls. Results were expressed Z scores (meansem). In untreated women, decits in VB and FN width were 1.00.1 SD and 0.30.1 SD (p50.001

394 (358). COMPARED TRABECULAR BONE ARCHITECTURE IN MEN AND WOMEN E. Legrand, D. Chappard, I. Degasne, M. F. Basle , M. Audran, Service de Rhumatologie, CHU, Angers, France We have shown that trabecular bone connectivity is a major and independant determinant of vertebral fracture in men with mild

osteoporosis (OP) (1). The purpose of the present study was to compare trabecular bone microarchitecture in osteoporotic men and women. Methods: spine and hip bone density (BMD) and transilliac bone biopsy were obtained in 31 male patients with idiopathic OP, 10 male patients with hypogonadism induced-OP and 29 women with postmenopausal OP. Histomorphometric analysis was done on a Leica quantimet image processor and the followings measures were performed: trabecular bone volume (BV/TV), trabecular thickness (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).
Results Women Post menopausal n = 29 Age (years) Spine BMD (gr/cm2) Hip BMD (gr/cm2) BV/TV (%) Tb Th (mm) Tb N ICI Star Volume (mm3) Free-end (%) Node (%) 60.4 0.64* 0.63* 14.1 109.8 1.27 2.6 17.3 16.0 23.9 Men Idiopathic n = 31 49.8 0.73 0.71 13.5 105.6 1.3 2.4 17.9 17.8 24.4 Hypogonadism n = 10 59.5 0.70 0.70 12.8 118 1.1** 4.6** 16.2 29.1** 18.9

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tibiae, in regions where the cortical bone predominates and in regions with cancellous bone predominance. The increase in bone density is accompanied by an increase of the bone strength.

396 (360). VITAMIN D STATUS IN YOUNG FEMALES DURING GROWTH V. Matkovic1, N. E. Badenhop-Stevens1, J. D. Landoll1, E. J. Ha1, S. L. Mobley1, B. Hollis2, L. Nagode1, 1The Ohio State University, Columbus, OH; 2University of South Carolina, Charleston, SC, The purpose of this study was to evaluate the relationship between vitamin D status and serum parathyroid hormone (PTH) in a group (N=341) of young healthy teenage females from central Ohio (ages 11.80.8 y), participants of a long-term study of skeletal development during puberty. Serum 25(OH)D3 was measured by a radioimmunoassay (RIA) with 125I-labeled tracer (Hollis et al. Clin Chem 39/3,529,1993) and intact PTH was measured using Nichols RIA kits with a method previously described (Nussbaum et al, Clin Chem 33:1364, 1987). Calcium intake data were established based on the compliance with calcium supplements and detailed assessment of dietary calcium consumption utilizing food records. The results indicate a strong seasonal variation in serum vitamin D level with the peak serum concentration during the month of July with nadir during the winter season. Serum concentration of PTH was opposite to 25(OH)D3 with the highest levels being during winter season and the lowest during the summer months. Serum PTH was inversely related to circulating 25(OH)D3 (r = 0.329, p<0.0001) (Figure below). When the subjects were separated into a high- (~1500 mg/d) and a low (~800 mg/d) -calcium intake groups, the observed association between PTH and vitamin D was only present in the low-Ca intake group, during both, summer and winter season. The study suggests that 25(OH)D3 may be important for skeletal health during growth particularly when Ca intake is low.

*p<0.05 versus men. **p<0.05 versus idopathic male OP and versus women.

These results strongly suggest that, despite a higher BMD, architectural changes are equivalent in men with idiopathic OP and post menopausal women. By contrast trabecular bone microarchitecture seems to be profoundly altered in men with hypogonadism-induced OP. (1) E Legrand M Audran. Trabecular bone microarchitecture, bone mineral density and vertebral fractures in male osteoporosis. J Bone Miner Res 2000; 15(1) in press.

395 (359). DENSITOMETRIC AND BIOMECHANICAL STUDY OF THE EFFECT OF CHRONIC VENOUS STASIS ON THE RAT TIBIA G. P. Lyritis1, C. K. Yiannakopoulos1, Th. Karachalios1, K. Kalogera1, M. Katsiri1, A. Galanos1, 1Laboratory for the Research of the Musculoskeletal System, Athens, Greece The purpose of our study was to conduct an experiment that would elucidate the effects of chronic venous stasis on the rat bone using densitometric and biomechanical methods. We studied the effect of venous stasis on the rat tibia after ligation of the common femoral vein in 15 adult, 3 month old, male Wistar rats. The bone mineral density (BMD) and the bone mineral content (BMC) have been measured in vivo immediately after the operation and after 8 weeks by dual energy X-ray absorptiometry (DEXA). The special small animal software has been used. Five regions of interested have been designed (ROI 15). The coefcients of variation was 0.67, 0.89, 1.15, 1.23 and 4.07 respectively. The BMD and the BMC exhibited statistically signicant increase in all regions of interest, except for the distal tibial epiphysis. The mean percent of BMD increase was for the ve ROI's 10.236%, 17.649.47%, 15.9712.26%, 14.6914.68%, 5.2612.13% respectively. The biomechanical properties of both tibiae have been examined using a destructive three point bending test. The biomechanical examination revealed statistically signicant increase of all the measured biomechanical parameters. We conclude that the chronic veous stasis causes signicant increase of the bone density in the rat

397 (361). FRACTURE RISK AND USE OF ORAL STEROIDS J. W. Meyer, Ingenix Intnl., Eden Praire, MN, USA Objective To assess the fracture risk associated with oral steroid (OS) exposure. Methods Data were obtained from claims of subjects, 1864 years, of 8 United Healthcare health plans. OS claims in 199596 were classied by patterns of use and daily prednisoneequivalent dose. A control group was matched on minimum enrollment duration, age, & gender. Subjects were followed until age 65, fracture, disenrollment, or up to 3.5 years. Adjusted relative risks (RR) were estimated using Cox proportional hazard models.

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Results 36, 271 OS users and 14, 421 controls were included; 58% were female, mean age was 42, and mean enrollment was 68 and 75 months. Prednisone was the most commonly prescribed OS (69%) and the most common OS conditions were inammatory skin disorders, arthropathies, and nervous system disorders. Patterns of OS use were 50.7% single OS claims (SNGL), 41.6% intermittent use (INT), and 7.7% continued use (CNTD). Mean daily dose was 8.2 mg/day. Subjects with CNTD and 53 OS claims had a RR=2.6 for hip and RR=3.0 for vertebral fractures versus unexposed subjects. SNGL use had a RR=1.9 for hip fractures. Users of 59.5 mg/day OS daily dose had a RR=2.5 for hip and RR=1.7 for vertebral fractures. OS exposure was related to other non-vertebral/open fractures (SNGL RR=1.2; INT RR<1.0; CNTD RR=1.5; 3.59.5 mg/day OS dose RR=0.9) [All RRs: P<0.05] Summary Continued and extended OS use had the greatest increase in risk of hip and vertebral fracture. A separate dose dependent hip and vertebral fracture risk was evident. OS exposure did not increase forearm fracture risk.

among TBI patients. We wanted to know if serum CTX levels at baseline (T0) were able to predict the extent of the bone loss at the heel after 6 months (T6) of VS. We explored 36 TBI patients (29M/7F; age 3312) using ultrasonic Hologic SAHARA device at T0 and T6. Serum CTX was measured by ELISA at T0 (Cis Bio Osteometer CROSSLAPS, N<8500 pmol/l). At T0 the time elapsed since injury was 10.14.7 weeks. Glasgow Coma Score at the time of injury was 5.91.6 (48 for all the patients, normal=15) and at T0 was 9.72.9. The VS was only transient in 12 patients (group A) who were able to walk again at T6 while the 24 other patients (group B) were still in VS. Results of ultrasonic parameters at T6 are expressed as mean percentage (and standard deviation) of measurements at T0.

QUI T6 WHOLE GROUP p, T6 vs T0 r with CTX r2 GROUP A GROUP B p, A vs B 84% (12) <0.05 0.62 0.38 89% (6) 81% (13) <0.05

BUA T6 82% (12) <0.05 0.64 0.41 87% (9) 80% (13) <0.05

SOS T6 98.4% (1.3) <0.05 0.52 0.27 99% (0.7) 98.2% (1.4) <0.05

398 (362). OSTEOPOROSIS AFTER TRAUMATIC BRAIN INJURY (TBI) COMPLICATED BY TRANSIENT VEGETATIVE STATE (VS) E. Meys, P. Rigaux, B. Veys, D. Darriet, N. Benabid, B. Sutter, F. Danze, Groupe Hopale, Berck/Mer, France We have previously shown persistent VS is a risk factor to develop disuse osteoporosis at the lower limb. We wanted to know if bone loss was also observed after recovery of transient VS and if the forearm and the heel were affected to the same extent. We explored 51 TBI male patients (age 3210 years) who suffered from transient VS and 51 male controls (338 years) using DXA Lunar PIXI device. The time elapsed since injury was 3938 months. At the time of the study all the patients were able to walk despite paralytic after-effects among 16 of them. The duration of VS was 1814 weeks but was longer in paralysed patients (2914 weeks, p<0.0001). Results are expressed as mean bone loss and T score in comparison with the normative values given by the manufacturer. According to the WHO criteria 1/3 of the patients are osteopenic and 1/3 are osteoporotic. The bone loss is mainly observed at the heel, is more severe among paralysed patients and is strongly correlated with the duration of VS (r = 0.7 at the heel). The paralysed forearm is also affected which suggests a negative effect on bone of muscle weakness by itself. We conclude TBI patients despite brain recovery may be osteoporotic.

Serum CTX levels are increased (152996672) and are higher in group B (175236622) than in group A (108524105, p<0.0001). We conclude serum CTX at baseline is able to predict the severity of the bone loss measured by ultrasound at the heel after TBI complicated by 6 months of VS.

400 (364). THE PSYCHOLOGICAL IMPACT OF A DIAGNOSIS OF OSTEOPOROSIS C. Murray1, J. Beynon1, J. Board2, 1Dept. of Adult Medicine; 2Dept of Psychology, St. Woolos Hospital, Newport, Osteoporosis is a chronic condition affecting everyday activities. As well as the physical aspects of the condition one needs to consider its psychological impact. The emotional implications of long-term chronic illnesses are well known, the psychological impact of osteoporosis has attracted little attention. A district general hospital has developed a comprehensive osteoporosis and bone density service tailored to meet individual patient needs. The following study was undertaken to examine the psychological impact of a diagnosis of osteoporosis: a) identifying the patients' response and feelings at being given a diagnosis of osteoporosis; b) did a prior diagnosis of osteoporosis affect these feelings; c) were patients' reactions inuenced by the presence of a family member; d) what did patients understand by the diagnosis of osteoporosis. Patients who attended the one stop shop clinic, in which they have a bone density measurement followed immediately by a clinical assessment and nurse specialist interview, were invited to participate in the study. 14 consecutive female patients with bone density conrmed osteoporosis agreed to take part. An independent clinical psychologist conducted a questionnaire-based interview lasting one-hour in the patients' home, one to three weeks following clinic attendance. 7 of the 14 patients expressed distress at receiving the diagnosis, using emotional language to describe their feelings ``I was devastated'' ``it hit me like a sledge hammer''. These feelings were not related to whether they had previously been given a diagnosis of osteoporosis. All patients understood the diagnosis of osteoporosis. Patients' reactions were not inuenced by the presence of a family member. This preliminary study indicates that the diagnosis of osteoporosis has a psychological impact on patients. This does not itself inuence patients' ability to absorb and retain information. However this study highlights that osteoporosis services need to offer psychological as well as physical support to patients.

GROUP Control Control TBI TBI Paralysed Paralysed Paralysed Paralysed

SITE Forearm Heel Forearm Heel Healthy forearm Paralysed forearm Healthy heel Paralysed heel

BONE LOSS 5 % 0 5 % 20 % 1 % 12 % 24 % 35 %

T SCORE 0.5 0 0.5 1.4 0.1 1.2 1.7 2.4




399 (363). SERUM CTX PREDICTS THE BONE LOSS AT THE HEEL AFTER SIX MONTHS OF VEGETATIVE STATE (VS) E. Meys, P. Rigaux, B. Veys, D. Darriet, N. Benabid, F. Bianchi, F. Danze, Groupe Hopale, Berck/Mer, France Persistent VS after traumatic brain injury (TBI) is a important risk factor to develop disuse osteoporosis. We have previously shown using serum CTX the occurence of a high bone resorption rate

401 (365). VITAMIN D INSUFFICIENCY AND DECREASED BONE MASS IN JAPANESE FEMALE COLLEGE STUDENTS K. Nakamura, M. Nashimoto, M. Yamamoto, Niigata University School of Medicine, Niigata, Japan Vitamin D insufciency, a risk factor for osteoporosis, has been well investigated in elderly women, but little information has been available in younger ages. The purposes of this study were to determine serum 25-hydroxyvitamin D levels [25(OH)D, an index of vitamin D nutritional status] in Japanese young girls, and to test whether there is an association between 25(OH)D and bone mass. Subjects were 77 Japanese female junior college students aged 1924 years. The investigation was conducted in April in 1998 and 1999. Serum 25(OH)D was measured with high-performance liquid chromatography. Bone mass of the calcaneus was evaluated with quantitative ultrasound densitometry. The mean 25(OH)D concentration was 34.2 nmol/L (SD 12.1). The proportion of subjects with 25(OH)D less than 30 nmol/L, a cut-off value for vitamin D insufciency, was 31/77 (40.3%). Simple linear regression analysis showed that there was a signicant linear relationship between 25(OH)D and bone mass (r2=0.098, p = 0.0069). The association held even after adjusting for weight (partial r2=0.098, p = 0.0023). Body weight was also associated with bone mass (partial r2=0.105, p = 0.0034). These results suggest that vitamin D insufciency may be prevalent in healthy young girls, and that low levels of 25(OH)D in young girls may adversely affect bone mass.

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403 (367). BONE MASS DENSITY AND SEX STEROIDS IN GREEK HEALTHY MALE INDIVIDUALS F. G. Papadopoulou1, K. Kalothetou1, G. Koliakos2, Th. Konstantinidis1, E. Nikopoulou1, D. Doukidis1, G. Krassas1, 1Dept of Endocrinology and Metabolism, PANAGIA Hospital, Thessaloniki, Greece; 2Dept of Biological Chemistry, Medical School of the Aristotle University of Thessaloniki, Greece Osteoporosis is an increasingly recognized disorder in men but pathogenesis of the disease remains obscure. The aim of this study was to investigate the circulating levels of gonadal and adrenal sex steroids in healthy male individuals as well as the possible correlation of these steroids with bone mass. For the purpose of this study 363 healthy male individuals were recruited from factory and hospital workers. Mean age was 51.38.7yr (30 75) and mean BMI was 27.53.7 (18.147.9) kg/m2. Bone mass density (BMD) was evaluated by DEXA at 4 skeletal sites, lumbar spine (LS), femoral neck (FN), trochanter (Tr) and Ward's triangle (WT). Blood samples were taken for the measurement of dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), free testosterone (FT) and 17 b estradiol (E2). All measurements were done by radioimmunoassay. Data were analysed using Kolmogorov Smirnov, student t-test and Spear-man test. Results: Forty four out of 363 (12%) individuals had reduced BMD, with T score 42.5 in the LS and/or FN. Mean DHEA, DHT, FT and E2 values in the whole group have as follows: 8.811.7 (ng/ml), 338.9328.5 (pg/ml), 16.05.0 (pg/ml) and 40.628.2 (pmol/lt). Serum DHEA was positively related to BMD at LS (r = 0,127, p = 0.027), DHT was positively related to BMD at FN (r = 0.094, p = 0.05), while E2 was negatively related to BMD at 3 sites, i.e. FN r = 0.329, p = 0.001), Tr (r = 0.245, p = 0.000) and WT (r = 0.200, p = 0.03). No association was found between FT and BMD at any site. In conclusion it seems that testosterone had no relevant inuence on BMD, while DHEA, DHT and E2 seem to have a metabolic effect on bone mass.

402 (366). EFFECTIVENESS OF EDUCATION AND/OR NTx RESULTS AS AN MEANS OF ENCOURAGING COMPLIANCE TO ALENDRONATE S. Nattrass, S. Silverman, B. Drinkwater, 1PacMed Clinics, Seattle, WA, USA; 2Osteoporosis Medical Center, Los Angeles, CA, USA Patient compliance with medication is frequently insufcient for optimal results. This 12 month study was designed to determine whether an early indication of successful treatment (NTx), intensive patient education, or the combination of the two would be effective in encouraging patient compliance with an Alendronate prescription. 240 postmenopausal women with a DXA T score <2.0 of spine or hip were randomly assigned to one of four groups: 1) NTx (baseline & 3 months), 2) Monthly osteoporosis educational materials, 3) Combination of 1 & 2, or 4) Control. An initial prescription for Alendronate was provided by the patients' primary care provider. Rells were available at 13 month intervals. Patients returned at 12 months for a DXA and to complete a questionnaire. Compliance was measured by number of months women continued to use the drug. Results: There were no differences between groups at baseline. 74.4% lled the original prescription; 54% took the drug for 12 months. There were no differences between groups in compliance. Reasons for non-compliance were: chose HRT, 7.9%; adverse effects, 9.6%; cost, 4.6; personal reasons, 6.2%. 7.5% were lost to follow up.
Table. Number of months on medication (Mean and SE)

404 (368). SERUM LEPTIN LEVELS ARE ASSOCIATED WITH BONE MASS IN NON-OBESE WOMEN J. A. Pasco, M. J. Henry, M. A. Kotowicz, G. R. Collier, M. J. Ball, G. C. Nicholson, Department of Medicine, Geelong Hospital, The University of Melbourne, Geelong, Victoria, Australia In vitro studies have demonstrated that leptin directly stimulates osteoblast differentiation (Endocrinology 1999;140:1630). As both serum leptin and bone mass are correlated with body fat, our hypothesis was that circulating leptin may be a regulator of bone mass in vivo. We investigated 214 healthy, non-obese women (age 2091 yr; BMI 1630 kg/m2). Bone mineral content (BMC), projected bone area and body fat mass were measured by dual energy X-ray absorptiometry and fasting serum leptin by radioimmunoassay (4.18.2% inter-, 5% intra-assay precision). A signicant positive association was observed between leptin (natural log) and BMC (adjusted for age, weight, body fat mass and bone area) at the spine (lateral projection), Ward's triangle, the trochanter and whole body (partial r2=0.0190.036; all p<0.05). Similar trends were observed at the femoral neck and PA-spine. With bone mineral density the dependent variable (adjusted for age, weight and body fat mass), the association was signicant at the lateral spine (partial r2=0.030; p=0.011), of borderline signicance at the proximal femur sites (partial r2=0.0120.017; p=0.0580.120) and not signicant at other sites. The weight and body fat mass adjustments suggest the relationship is independent of mechanical loading and other humoral factors asscciated with adipose tissue, supporting the hypothesis that circulating leptin may be a mediator in the regulation of bone mass.

Analysis Intent to treat On 1012 months

Group 1 7.63 (0.73) 11.81 (0.09)

Group 2 7.70 (0.69) 11.73 (0.15)

Group 3 8.71 (0.68) 11.92 (0.05)

Group 4 7.45 (0.74) 11.75 (0.12)

p nsd nsd

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405 (369). VITAMIN D DEFICIENCY IN PATIENTS SUFFERING FROM CHRONIC PANCREATITIS J. Payer, Z. Killinger, S. Aleryany, H. Kratochvilova, P. Ondrejka, University Hospital, Bratislava, Slovakia Chronic pancreatitis is a longlasting inammatory disease manifested clinically in the advanced stage by malabsorption syndrome. Its manifestations include also changes in the calcium metabolism and the occurrence of osteoporosis and osteomalacia or their combination. The objective of the study was to assess the vitamin D3 blood concentration in patients with chronic pancreatitis. The group comprised 15 patients (8 men and 7 women), median age 45.0 years. The authors found a signicantly reduced serum concentration of vitamin D3 (p<0.01) in patients with chronic pancreatitis. They assume that vitamin D deciency is one of the decisive causes of bone complications in prolonged pancreatitis. Supplementation with vitamin D or its metabolites is then a necessary part of preventive and therapeutic provisions.

satisfactory results. Long-term clinical outcome was better in patients with pure compression fractures, without signicant sagittal alterations. In severe deformities consequent to compression-exion fractures, the sagittal axis appears anteriorly dislocated. A new load balance seems to be achieved by means of an increase of lumbar-sacral lordosis and patients with mild arthrotic alterations seem to have a higher capacity to adapt. Therefore, clinical-functional recovery in elderly patients with thoracolumbar fractures seems to depend on the ability of the lumbar-sacral spine to adapt to the kyphotic deformity by varying its lordotic qurvature and establishing a new sagittal load axis. Achievement of this new equilibrium, hindered by spinal stiffness due to old-age and arthrosis, is not easy: long-term clinical outcome is worse in patients who fail to do so.

408 (372). DIURETICS ALTER THE DIURNAL RHYTHM OF SERUM PTH, CALCIUM, AND PHOSPHATE L. Rejnmark, P. Vestergaard, L. Heickendorff, F. Andreasen, L. Mosekilde, Aarhus Bone and Mineral Research Group and Centre of Clinical Pharmacology, Aarhus University Hospital, Denmark Aim: The effect of loop and thiazide diuretic, alone or in combination, on the diurnal rhythm of serum PTH, 1,25dihydroxyvitamin D, and on serum and urinary calcium and phosphate. Fifty postmenopausal women were randomly allocated to 7 days of treatment with either Bendroumethiazide (BFMT) 10 mg/day (n=14), Bumetanide (BU) 2 mg/day (n=13), BFMT 10 mg/day plus BU 2 mg/day (n=11), or placebo (n=12). The diurnal rhythm of each variable was evaluated on the 7th day of treatment. Results: In all four groups, all parameters showed a signicant (with-in group) diurnal variation. Treatment caused a betweengroup difference in the diurnal rhythm of S-PTH (p<0.001), S-Ca (p = 0.002), S-Ph (p = 0.001), and urinary calcium (p<0.001). In the BU-group the S-PTH level (8.50.9 pmol/l) was signicantly above the level in the placebo-group (4.40.4 pmol/l, p<0.001). From 10 a.m. (time of tablet ingestion) to 2 p.m., S-PTH increased 9816% in the BU-group, whereas the increase in the placebo-group was 198% (p<0.001). Conclusion: Treatment with BFMT and/or BU has a major inuence on the diurnal rhythm of parameters of the calciumphosphate homeostasis. BU may cause secondary hyperparathyroidism.

406 (370). BONE TURNOVER MARKERS AND SEX HORMONES IN MEN WITH IDIOPATHIC OSTEOPOROSIS P. Pietschmann, J. Grisar, S. Kudlacek, S. Spitzauer, W. Woloszczuk, R. Willvonseder, M. Peterlik, Krankenhaus Barmherzige Bruder, Ludwig Boltzmann Institutes of Aging Research and Experimental Endocrinology, University of Vienna, Vienna, Austria In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention. Since little is known about the pathophysiology of osteoporosis in men, we determined various biochemical parameters of bone metabolism and sex hormones in 31 men with idiopathic osteoporosis and 35 age matched control subjects. In the men with osteoporosis a signicantly increased urinary excretion of deoxypyridinoline as well as increased serum levels of the c-terminal telopeptide of type I collagen were found. While serum levels of osteocalcin, the bone specic isoenzyme of alkaline phosphatase and carboxyterminal propeptide of type I collagen were not signicantly different in the patients and controls, serum bone sialoprotein levels were signicantly decreased in the patients. Moreover, in men with idiopathic osteoporosis increased levels of sex hormone binding globulin and a signicant decrease of both estradiol concentrations and the free androgen index were seen. We conclude that in men with idiopathic osteoporosis bone resorption is increased and exceeds bone formation. The excessive bone resorption seen in idiopathic male osteoporosis may be due to decreased estradiol and increased sex hormone binding globulin levels.

409 (373). HYPERPARATHYROIDISM: NEGATIVE DETECTION WITH SSBI AND POSITIVE WITH THALLIUM D. Salica1, E. E. Schulz2, 1Healing Bone and Mineral Institute, Cordoba, Argentina; 2Loma Linda University, Loma Linda, CA, USA The purpose of this study is to show that Tl201/Tc99 (Tl/Tc) subtraction parathyroid scan (PTS) may be necessary to localize enlarged parathyroids (PT)in patients clinically hyperparathyroid (HPT), with elevated Ca and PTH, and a negative SSBI PTS, a common event in osteoporosis. We are doing almost exclusively SSBI, in the last few years, for suspected PT adenoma, hyperplasia or carcinoma. Reviewing the cases interpreted by author ES where the rst study was SSBI (n=43), we found 7 cases of (-)SSBI but clinically HPT, that had a follow up Tl/Tc scan, excluding those with previous neck surgeries and implants. Six had (+)Tl/Tc (3 had a single area and 3 had multiple areas) and 1 was negative as the SSBI. Four out of the six (+)Tl/Tc patients were taken to surgery and all four had enlarged PT. Discussion: It can be argued that our SSBI/PTS technique can be improved to achieved greater sensitivity using color and subtraction as we do for Tl/Tc. Most cases however were clearly (-)SSBI and strikingly (+)Tl. We believe that in some cases for

407 (371). THE POST-TRAUMATIC SPINE IN ELDERLY PATIENTS: VARIATIONS OF SAGITTAL CONTOUR AND CLINICAL-FUNCTIONAL CORRELATIONS A. Ramieri, O. Moreschini, M. Nocente, Orthopaedic and Traumatology, University ``La Sapienza'', Rome, Italy In elderly patients vertebral fractures, single or multiple, with spinal deformity are common. Treatment is generally conservative in orthopedic vest but does not guarantee correction of deformity. Forty-six cases of single, non-neurological, thoracolumbar fracture (D10-L3), were treated by means of 1216 weeks in a plastic brace: they were aged between 65 and 82 (median 73). Lesions were classied as compression or compression-exion with involvement of the anterior column or both the anterior and middle columns as suggested by Denis. Initial and long-term radiographic deformity (range 1542 months median 33) was assessed using Farcy's Sagittal Index while long-term clinical evaluation was based on Knight's classication of pain and functional limitation. The majority of patients (60%) had

some reason the results between SSBI and Tl can be totally different. Conclusion: Negative SSBI parathyroid scans with clinical evidence of HPT probably need a Tl/Tc study to achieve grater sensitivity for presurgical detection of enlarged parathyroids.

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energy X-ray absorptiometry(DXA) was different between rheumatoid arthritis(RA) with a mean age of 60.0 years and non-RA with a mean age of 65.4 years. We measured BMD by DXA in 74 patients with RA and 124 patients with non-RA. All patients were postmenopausal and treated with non-steroidal anti-inammatory drugs. And we investigate the relation to BMD, age, weight, height, stage, class and disease duration. As a result no signicant differences were found in BMD with RA and non-RA. There were signicant correlation between lumber BMD and age (r = 0.346, p<0.005), weight (r = 0.444, p<0.0001). But there were non-correlation between BMD and stage, class, disease duration associated with RA. By Multiple linear regression analysis, age and weight only were signicant predictors of lumber BMD (R=0.550, P<0.01, n=74). In conclusion local bone loss in RA is generalized, but general bone loss is likely to be related to loss of mobility or muscle atrophy associated with RA.

410 (374). ARE DEFICITS IN VOLUMETRIC BONE DENSITY IN WOMEN WITH FRACTURES DUE TO REDUCED ACCRUAL OR EXCESSIVE BONE LOSS?: INSIGHTS FROM THEIR DAUGHTERS E. Seeman, A. Tabensky, Y. Duan, Austin & Repatriation Medical Centre, The University of Melbourne, Heidelberg, Vic., Australia Spine areal bone mineral density (aBMD) is reduced in women with spine fractures and their daughters. Femoral neck (FN) aBMD is reduced in women with hip fractures and their daughters. About 1520% of the decit in spine aBMD in women with spine fractures is explained by smaller bone size (Duan et al, in press). Women with hip fractures have increased FN volume so that the decit is underestimated by ~10% (Duan et al, submitted). The residual decit after accounting for reduced bone size, ie the decit in volumetric (v)BMD, may be due to reduced accrual and/or excessive bone loss. Any decit in premenopausal daughters must be due to reduced peak accrual. We asked: (i) is BMC and aBMD reduced in daughters after accounting for bone size? (ii) is vBMD reduced? (iii) what is the decit in vBMD in the mothers? We studied 45 women with hip fractures (age 76 yrs, range 56 89) and 59 of their daughters (age 47yrs, range 2570), and 29 women with vertebral fractures (age 69 yrs, range 5490) and 41 of their daughters (age 43 yrs, range 2464). BMC, aBMD were determined using dual x-ray absorptiometry (Lunar DPX-L). vBMD was derived using the Carter method. Results: age, height and weight adjusted Z scores (meansem).
Spine Fx Mothers (n=29) FN BMC FN aBMD FN Volume FN vBMD L3 BMC L3 aBMD L3 Volume L3 vBMD 0.250.22 0.460.20* 0.540.32 0.670.21** 0.960.15{ 0.930.17{ 0.590.14{ 0.990.17{ Spine Fx Daughters (n=41) 0.150.15 0.040.15 0.150.13 0.040.15 0.190.18 0.280.16 0.030.17 0.400.15** Hip Fx Mothers (n=45) 0.320.16 0.750.14{ 1.340.28{ 1.150.11{ 0.180.15 0.070.14 0.210.21 0.130.16 Hip Fx Daughters (n=59) 0.180.12 0.020.13 0.420.12{ 0.310.13* 0.380.14** 0.260.11* 0.360.17* 0.060.12

412 (376). GEOMETRIC MEASUREMENTS OF FEMORAL DIMENSIONS AND THEIR RELATION TO HIP FRACTURE RISK Vesile Sepici1, Ercan Dincel2, Oya Sahin1, Ismail Sanli2, Behcet Sepici2, 1Department of Physical Medicine and Rehabilitation, Gazi University Medical Faculty; 2Department of I.Orthopaedic Surgery, S.B. Ankara Hospital, Ankara, Turkey Objective: In this study, we aimed to evaluate whether geometric measurements of femoral dimensions were associated with femoral strength and hip fracture risk. Subjects and methods: 9 patients (3 men, 6 women, mean age: 766.16) with fracture of proximal femur related with osteoporosis due to minor traumas and 10 healthy controls (3 men, 7 women, mean age 735.16) were included to the study. The hip axis length (HAL-the distance from below the lateral aspect of the greater trochanter to the inner pelvic brim), the femoral length (FL-the distance along the line of the hip axis from the lateral aspect of the femur to the line joining the superior and inferior extremes of the hip joint) and femoral width (FW-the shortest distance across the femoral neck, at right angles to the line of the hip axis) were measured on antero-posterior pelvic radiographs by two different observers. Two summary ratios were dened as HAL/FW and FL/ FW. The differences between patients and controls were compared. Results: There was no difference in the mean age of the subjects. The mean hip axis length was longer in patient group, but the difference was not signicant. We also found no signicant association between other femoral dimension measurements and the risk of hip fracture (p>0.05). Conclusion: It was concluded that further controlled studies with increased number of cases were required to assess the effects of geometric measurements of femoral dimensions on femoral strength and hip fracture risk. Increasing the number of the cases would also allow to evaluate racial differences in femoral dimensions and risk of hip fracture.

*p50.05, **p50.01, {p50.001 compared to zero.

Mothers with spine fractures had low bone size, mass and vBMD. Their daughters had low vertebral vBMD, not bone size, suggesting the decit in the mother may be the result of reduced peak accrual in the smaller bone. Women with hip fractures had increased FN size (so normal BMC) but low vBMD. Their daughters also had increased FN size and reduced vBMD. We conclude that vBMD and size dier in the fracture types, and low vBMD may be partly due to low peak since the daughters had reduced vBMD by 3050% of the decit in the mothers, consistent with the genetic hypothesis.

413 (377). BONE DENSITY VS INTERNAL ARCHITECTURE OF HIP (SINGH INDEX) AS PREDICTOR OF BONE STRENGTH Manmohan Singh, University of Illinois at Chicago, IL, USA PURPOSE of this in vitro study was to assess the relative importance of bone density and bone architecture in determining hip fracture risk. METHOD involved scanning 65 cadaver femurs, submerged in water to simulate soft tissues, using Norland 2600 DPA unit to measure bone mineral density (BMD). BMD values were obtained for total area and nine equal segments of proximal femur. Total BMD ranged from 352 to 983 mg/cm2 (mean = 658135 SD). Xrays were donez to obtain Singh index (SI) readings, which ranged from 1 to 6 (5.031.36 SD). Femurs were then mounted on MTS 812 materials testing machine and loaded to failure under axial

411 (375). BONE MINERAL DENSITY IN RHEUMATOID ARTHRITIS WITH POSTMENOPAUSE Y. Sen1, E. Matuyama2, 1Department of Orthopedic Surgery, Nara National Hospital, Nara City; 2Department of Orthopedic Surgery, Nara Medical University, Kashihara City, Nara, Japan The purpose of this investigation was to evaluate whether the bone mineral density (BMD) of lumbar spine as determined dual

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compression. Breaking loads ranged from 1967 to 10224 N (57231896 SD). Resulting fracture lines consistently simulated clinical fractures of femoral neck. The head and trochanter fragments were then ashed for mineral content. RESULTS of regression analysis showed the following correlations:
breaking load ash density (head) ash density (troch) vs BMD vs BMD vs BMD r = 0.58 r = 0.74 r = 0.87 vs SI vs SI vs SI r = 0.73 r = 0.58 r = 0.60

had more bone change. Weight, weight change during pregnancy, dietary calcium intake, and less physical activity were not signicantly associated with bone change. This study provides evidence of a non-pathological bone mass loss with pregnancy as measured with bone ultrasound. The amount of change would be consistent with the demands of fetal mineralization as well as the continuing mineralization of the maternal skeleton among the younger primiparas.


CONCLUSIONS of the study: (1) bone mineral content (i.e. ash density) correlated best with BMD, (r = 0.87); (2) bone strength (i.e. breaking load) correlated better with SI (r = 0.73) than with BMD (r = 0.58), (3) Three segments of femur overlying primary tensile trabeculae had BMD that correlated best with breaking strength (r = 0.62, 0.51, and 0.56). It was signicant to note that SI grades depend on changes observed in the same group of trabeculae.

P. Szulc1, F. Munoz1, F. Marchand2, F. Duboeuf1, P. D. Delmas1, INSERM Research Unit 403, Lyon, France; 2SSMB, Montceau Les Mines, France

414 (378). BLOOD LEAD CONCENTRATION DURING PREGNANCY AND BONE LOSS M. F. Sowers1, T. Scholl2, M. Jannausch3, John Bogden4, University of Michigan, Ann Arbor, MI, USA; 2University of Medicine & Dentistry of New Jersey, Stratford, NJ, USA; 3 University of Michigan, Ann Arbor, MI, USA; 4University of Medicine & Dentistry of New Jersey, Newark, NJ, USA

Bone is the sink for heavy metals, such as lead, that can be liberated by bone turnover. We evaluated whether bone loss in pregnancy, measured with ultrasound, was associated with an increase in bone lead concentrations. Bone ultrasound was measured at entry to prenatal care and at seven weeks postpartum in 252 pregnant women, aged 1234 years. Blood lead was measured at entry to care, the 28-week prenatal visit and at parturition using atomic absorption spectrometry. Osteocalcin concentrations were also measured using radioimmunoassay in specimens collected in the same time frames. The average blood lead concentrations at entry to care were 1.27 mg/dl0.78. While there was, on average, a 3.6% change in ultrasound bone mass in pregnancy, there was no signicant changes in blood lead concentrations. Likewise, there was no association between serum osteocalcin concentrations and blood lead concentrations. There are several possible explanations. The turnover of bone in pregnancy may be insufcient to liberate substantial amounts of sequestered lead or prevention efforts may have reduced the amount of sequestered lead levels among women this age.

We evaluated bone loss in a cohort of 588 men aged 5185 yrs followed prospectively during 3 years. Bone mineral density (BMD) of spine, hip, total body was measured using HOLOGIC QDR 1500 device and BMD of forearm using OSTEOMETER DTX 100 device. We found a bone loss at the level of total hip (0.611.20 %/yr, p = 0.0001), of the distal and ultradistal sites of forearm (0.551.11 and 0.451.58 %/yr, p = 0.0001), and of the whole body BMC (0.441.19 %/yr, p = 0.0001). Lumbar spine BMD increased (0.281.66 %/yr, p<0.001) mainly due to an increase of BMD in the men with osteoarthritis (OA) (0.501.73 %/yr, p<0.001) whereas it was stable in men without OA. The rate of bone loss increased with age at all the skeletal sites. In men more than 70 yrs of age, the bone loss rate was higher than before this age (e.g.: distal forearm BMC 0.520.91 vs 0.250.82 %/yr, p<0.002; femoral neck BMD 0.531.31 vs 0.171.33 %/yr, p<0.01). The rate of bone loss was not related to the current body weight, however, it was correlated with the change of body weight since the age of 25 yrs (after adjustment for age) at the level of the hip (r = 0.11, p = 0.01) and of the whole body (r = 0.12, p<0.01) and with the weight change during the follow-up (hip: r = 0.15, p<0.001). Men who gained less than 4 kg of body weight since the age of 25 yrs (rst quartile) had a higher rate of bone loss than those who gained more than 4 kg (total hip 0.791.12 vs 0.520.76 %/yr, p<0.01). In the stepwise regression, the change of fat mass during the follow-up (and not that of lean body mass) was the major determinant of the rate of bone loss at the level of the total hip (r = 0.15, p<0.001) and at the level of lumbar spine in men without OA. In summary, we could demonstrate signicant bone loss over 3 years at various skeletal sites in a cohort of healthy men. Bone loss is more pronounced after the age of 70 yrs and in those who show little weight gain especially little gain of fat tissue. These data suggest that peripheral estrogen production in fat tissue might reduce bone loss in elderly men.

417 (381). CALCIUM LOAD TEST IN OSTEOPOROSIS 415 (379). BONE LOSS IN PREGNANT ADOLESCENTS AND ADULT WOMEN M. F. Sowers1, T. Scholl2, M. Jannausch3, 1University of Michigan, Ann Arbor, MI, USA; 2University of Medicine & Dentistry of New Jersey, Stratford, NJ, USA; 4University of Michigan, Ann Arbor, MI, USA To determine the amount of bone change in pregnancy, bone ultrasound measures were taken at entry to prenatal care and at seven weeks postpartum in 252 pregnant women, aged 1234 years. After adjusting for variation in time at entry to care and time between delivery and the postpartum bone measurement, there was signicantly lower bone ultrasound at the postpartum visit (73.6% less, on average, p<0.0001). Women who were nulliparous or still-growing adolescents had signicantly greater bone loss (p<0.001). Women with higher baseline bone ultrasound also R. Tanakol, M. Akyildiz, H. Boztepe, F. Alago l, Istanbul Faculty of Medicine, Endocrinology, Turkey The purpose of this investigation is to detect the value of calcium load test in the differentiation of various causes of hypercalciuria in the pathogenesis of osteoporosis and also the relationship between cAMP suppressibility and BMD. A 2-hr urine sample after an overnight fast and after 1 g of calcium by mouth were tested for calcium, PTH, urinary cyclic AMP (UcAMP) and creatinine. 21 patients (Group I, age: 5111 yrs) with BMD <72.5 SD T-score and 12 healthy subjects (Group II, 479 yrs) with BMD 1SD T-score were studied. Bone formation and resorption parameters were not different between the groups. In Group I, UcAMP increased from a fasting value of 3.41.4 nmol/ 100 ml GFR to 4.75.3 after 1g Ca load, while it decreased from 4.21.4 to 3.31.2 (p = 0.04) in Group II (NS between groups). In group I, urinary Ca increased from a basal fasting level of 0.14

mg/mgCr to 0.220.1 after oral Ca load. In Group II, basal fasting level of urinary Ca (0.070.04 mg/mgCr) was signicantly lower than group I (p = 0.05) which increased to 0.190.0 (NS). Resorptive hypercalciuria was detected in 1 and absorptive hypercalciuria in 11 of the cases. No case with renal hypercalciuria was found. Only 3 patients had nonsuppressible PTH levels, as 11 patients had nonsuppressible UcAMP after the Ca load. The results suggested higher bone resorption in patients with osteoporosis despite the presence intact PTH levels within normal ranges. UcAMP may provide a more reliable index of parathyroid function than intact PTH in Ca loading test.

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patient population) while there was a borderline signicant increase in fractures of the feet and toes (RR=2.3, 95% CI: 1.0 5.0). Conclusions: There was a temporary increase in fracture risk within the rst two years following diagnosis of primary idiopathic myxoedema.

420 (384). CAUSES OF OSTEOPENIA IN CHILDHOOD AND EFFECT OF SUPPLEMENTATION THERAPY ON BONE MINERAL DENSITY il, J. Varvar ovska , E. Benese, Department of Bone V. Vyskoc Disease IInd Clinic of Internal Medecine, Orthopedic Clinic, University Hospital PLZEN, E. Benese, Authors present classication of osteopenias and osteoporosis in childhood according to aetiology. They studied 46 children with spine osteopenia associated with different diseases. The children suffering from secondary osteoporosis due to osteogenesis imperfecta, glucocorticoids or other metabolic bone diseases were excluded. 46 studied children had base-line Z score values 1.49 in spine, 1.21 in hip, neck and 0.61 in distal radius. They received appropriate dosis of Calcium (0.51.0 g) and Vigantol daily. After completing 2 years of therapy bone densitometry and markers of bone resorption were assessed. Subsequently bone density increase per year was evaluated. The 18 children without calcium therapy were assigned as a control group. They had no osteopenia in hip and forearm and their base-line Z score in spine was 1.58 comparable with the group of treated children. After a 2-year period of follow-up the intervention group had 7.1% of bone density increase in spine (control group 6.3%), in neck 4.1% (control group 0.5%), in distal radius 4.2% (control group 2.24%). The markers of bone resorption showed that the intervention group had signicant decrease of parathormone after therapy (36 to 18), osteocalcin (122.8 to 83.0) as well as crosslinks (1908 to 243). In the control group there were no signicant changes in markers of bone resorption (parathormone 45.7 to 34, osteocalcin 80.7 to 72.3, crosslinks 917 to 386). No urolithiasis or heterotopic ossications were observed in any child. The result of the study allow to conclude that the therapy modies only bone density in the regions with importantly decreased bone density but does not raise bone density substantially when compared with the control group. Similar conclusions were drawn in Scandinavian studies.

418 (382). FRACTURE RISK IN PATIENTS TREATED FOR HYPERTHYROIDISM P. Vestergaard1, L. Rejnmark1, J. Weeke2, L. Mosekilde1, 1 Department of Endocrinology and Metabolism, Arhus Amtssygehus, Aarhus, Denmark; 2Department of Medicine M, Aarhus Kommunehospital, Denmark Aim: To study fracture risk and risk factors for fractures in patients with hyperthyroidism. Material: A total of 864 patients with diffuse toxic goitre or toxic nodular goitre and 1000 randomly selected controls from the background population received a standard questionnaire. Results: Among the patients 621 (72%) and among the controls 654 (65%) returned the questionnaire (p<0.01). Within the rst ve years before the diagnosis the patients had the same fracture risk as the controls (RR=1.1, 95% CI: 0.81.5). After the diagnosis, fracture risk was elevated among the patients (RR=1.7, 95 % CI: 1.22.3), especially in the age group 50 years or older (RR=2.2, 95% CI: 1.53.3). Fracture risk was elevated for fractures of the spine (RR=5.7, 95% CI: 1.423.8) and the forearm (RR=3.1, 95% CI: 1.66.2), but not at other skeletal sites. Treatment with radioactive iodine alone was associated with an increased fracture risk (OR=2.7, 95% CI: 1.26.0), a risk that was not present in patients who had received methimazole (RR=1.5, 95% CI: 0.73.2). Conclusions: Our study demonstrated an increased fracture risk in hyperthyroidism, a fracture risk that was present with radioactive iodine treatment alone, but not in subjects that had received both radioactive iodine and methimazole or other types of antithyroid therapy.

419 (383). FRACTURES IN PATIENTS WITH PRIMARY IDIOPATHIC MYXOEDEMA P. Vestergaard, J. Weeke, H. C. Hoeck, H. K. Nielsen, J. Rungby, L. Rejnmark, P. Laurberg, L. Mosekilde, Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus, Denmark Aim: To study fracture risk and risk factors for fractures in patients with primary idiopathic myxoedema. Material: A self-administered questionnaire was issued to 628 patients with primary idiopathic levothyroxine substituted myxoedema and 1000 randomly selected controls from the background population. Results: A total of 412 patients (65.6%) and 654 controls (65.4%, p = 0.98) returned the questionnaire. The patients were older than the controls (median 57 years, 43 years, 2p<0.01). Overall fracture risk was increased in patients compared to controls (Relative risk: RR=1.6, 95% CI: 1.12.3). The increase was temporary and limited to the period within the rst two years following the diagnosis of myxoedema (RR=2.9, 95% CI: 1.94.3). Before the diagnosis and more than two years after the diagnosis the fracture risk in patients did not deviate from that of the controls. The increase in fracture risk was only signicant in the age group above 50 years (RR=1.9, 95% CI: 1.23.0), and was limited to the forearms (RR=3.0, 95% CI: 1.46.3 for the entire 421 (385). IMPORTANCE OF DENSITOMETRY BEFORE TOTAL ENDOPROTHESIS APPLICATION AND POSSIBILITIES OF PHARMACOLOGIC PREVENTION OF ENDOPROTHESIS LOOSENING V. Vyskocil1,2, K. Koudela1, O. Topolcan3, 1Department of Orthopedic Surgery; 2Department of Bone Disease; 3Department of Medicine II, Charles University Hospital PLZEN, Czech Republic 259 patients were examined by means of densitometry before application of total hip and knee endoprothesis, 212 patients before total hip endoprothesis and 47 patients before knee total endoprothesis (TEP). Patients' mean age was 62 years, the youngest patient was 26, the oldest one 82 years old. All BMD measurements were performed by using dual-energy x-ray absorptiometry, using Hologic QDR 2000. Measurements were obtained at the posteroanterior lumbar spine and hip, mostly at the left hip, in cas of right hip operation at the right hip. All patients before operation had following values of hip BMD expressed in T score percentage: left total hip 87%, trochanter 62%, intertrochanteric area 84%, femoral neck 58%, Ward's triangle 83%, right total hip

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59%, trochanter 56%, intertrochanteric area 57%, femoral hip 62% and Ward's triangle 57%. WHO classication and its criteria for osteoporosis were accomplished in following groups of patients: the left area 725% patients for the total hip, 31% for trochanter, 37% for intertrochanteric area, 25% for femoral hip, the right area 730% patients for total hip, trochanter 35%, intertrochanteric area 735%, femoral neck 721% patients. T score values in spine were inuenced by severe spondylosis which is common in elderly people: L1 90% (range 52153%), L2 area 88.9% (range 54147%), L3 area 85.3% (range 52152%), L4 area 84.4% (range 56-155%), total L14 85.1% (range 57140%). Patients accomplishing criteria for osteopenia were treated with calcium supplementation, patients with osteoporosis were treated according to their results of markeers of bone metabolism and risk factors. Densitometry in all patients was checked up after 13 years of therapy and compared to x-ray ndings where the position of TEP was followed and possible loosening stated. Authors discussed the possibilities of pharmacologic prevention from TEP detachment (loosening).

primary osteoporotic patients and dependence of BMD changes, risk of fractures and changes of markers of bone metabolism on the patients' age.

423 (387). PROTECTION FROM OVARIECTOMY-INDUCED BONE LOSS BY OSTEOPONTIN DEFICIENCY IS INDEPENDENT OF MOUSE STRAIN H. Yoshitake1, D. T. Denhardt2, S. R. Rittling2, M. Noda1, 1Dept Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan; 2Dept Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA Osteopontin is one of the most abundant non-collagenous matrix proteins in bone. It is produced by both osteoblasts and osteoclasts and has been implicated in regulation of bone resorption based on in vitro studies. We have recently observed that bone loss induced by ovariectomy in mice was reduced in osteopontin-decient mice with C57B16/129sv back ground. As it is known that bone metabolism could vary depending on the genetic background of the mice, we examined whether ovariectomy of the mice with pure genetic back ground of 129 could make any difference in terms of the effects of osteopontindeciency on ovariectomy-induced bone resorption. Three to four months old female wild or osteopontin-decient mice with 129 background were either ovariectomized or sham operated. After four weeks of the surgery, uterine weight was signicantly reduced in both wild type and osteopontin-decient mice. Body weight was not changed during the four weeks in either sham operated or ovariectomized mice regardless of the genetic background. Micro computed tomography analyses indicated that the bone volume in the proximal end of the tibiae was signicantly reduced in 129 wild type mice, however, this reduction in the cancellous bone volume was less in the osteopontin-decient 129 mice. These observations are similar to those in mice with C57B16/129sv background and further conrmed that the effects of osteopontin-deciency on the reduction of bone loss due to ovariectomy are not restricted in mice with a particular genetic background.

422 (386). OSTEOPOROSIS TREATMENT AND COMPARISON OF DIFFERENT MEDICAMENTS INFLUENCING BONE MINERAL DENSITY AND MARKERS OF BONE METABOLISM Vaclav Vyskocil, Department of Bone Disease, Charles University Hospital PLZEN, Czech Republic 1500 patients treated for osteoporosis in the course of the last 5 years (19951999) were followed up. Patients suffering from secondary osteoporosis and corticosteroid induced osteoporosis were excluded from the study as well as those ones with spondylosis and spondylarthrotic progression in spine and coxarthrosis in hip. Patients participating in the study were divided into 7 main groups according to their treatment: calcium /Ca/ and vitamin D, HRT, alendronate /ALN/, calcitonin /CT/, clodronate, uorides and the last 7th group without therapy. Particular medicaments as ALN and CT were assigned conformably to used adjuvant substitution in 4 subgroups (calcium, ergocalciferol, cholecalciferol, rocaltrol). The complete group of patients was composed of 1306 females and 194 males, their mean age was 60.8 and mean period of treatment was 15.4 months (1224 months after the applied therapy). Changes of BMD measured in spine and hip in adults aged 1865 years were compared with people older than 65 years or patients suffering from degenerative diseases of spine, forearm and hip. Differences of BMD in spine were evaluated in L14, in hip total hip and neck. Initial T score was 2.05 in spine, 1.76 in hip and 2.53 in neck. Structure of study subjects according to their medication was as follows: 23% patients without treatment, 14.8% with only calcium preparations, 37.4% with ALN, 18.6% with CT, HRT in 3.4% patients, uorides 2.2% and clodronate 0.6% patients. Simultaneously changes of bone formation and resorption were assessed and values of parathormon, osteocalcin, procollagen I and crosslinks before and after treatment were compared. Percentage changes of spine BMD (compared to baseline value) were at month 12 +2.15% for HRT, 3.69% for ALN, +1.85% for CT, +2.44% for uorieds (but a large dispersion was present), +0.6% for clodronate, 0.41% for Ca, hydroxiapatite + 1.84%, the last group without therapy decrease of BMD 2.43%. Total hip BMD showed increase of + 1.56% in HRT, 1.4% in ALN group, 0.89% for CT, 2.55% for uorieds (but also a wide range of results), clodronate nonsignicant decrease of 0.34%, Ca +0.29%, hydroxiapatit +0.84%, the group without treatment decrease 71.85%. Neck proved BMD increase +1.32% for HRT, +1.39% for ALN, +0.07% for CT, 0.11% for uorides, Ca +0.93%, hydroxiapatite +1.42%, but signicant decrease for clodronate 2.42% and the group without treatment also decrease 1.5%. The author observed the effectivity of different therapies in

424 (388). PREDICTIVE VALUE OF BIOAVAILABLE TESTOSTERONE FOR BONE MINERAL DENSITY IN NORMAL WOMEN ofkova I. Z , R. Bahbouh, M. Hill, Institute of Endocrinology, Prague, Czech Republic In the cross-sectional study performed on 147 healthy or osteoporotic, but otherwise normal premenopausal women aged 40.19.9 years (n=39) or postmenopausal women aged 61.98.9 years (n=108) associations between serum ovarial or adrenal sexual steroids and bone mineral density (BMD) were investigated. Serum estradiol, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS) and androstenedione and sex hormone binding globulin (SHBG) correlated positively with BMD at the spine or hip as total testosterone levels with BMD at the spine. However, only SHBG values (but not steroid confounders) correlated with serum cross-linked telopeptide of type I collagen and osteocalcin levels. After adjustment for age, body mass index and serum estrogen or androgen levels the predictive importance of bioavailable testosterone (testosterone/SHBG) for BMD at the spine or hip and estradiol for BMD at the spine was demonstrated. The difference in bioavailable testosterone levels between osteoporotic and healthy women were demonstrated in the postmenopausal (but not in the premenopausal) subgroup. The ndings document a signicant predictive value of bioavailable testosterone for BMD and outline a possible pathogenetic importance of this androgen in postmenopausal osteoporosis.


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427 (391). RISEDRONATE RAPIDLY REDUCES FRACTURE RISK IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS S. Adami1, O. Srensen2, R. Eastell3, E. Sod4, S. Horlait5, N. Watts6, 1Verona, Italy; 2Copenhagen, Denmark; 3Shefeld, UK; 4 Cincinnati, OH, USA; 5Staines, UK; 6Atlanta, GA, USA The primary role of osteoporosis treatment is fracture prevention. The effectiveness of risedronate (RIS) in reducing the risk of vertebral fracture in osteoporotic women was evaluated in 2 randomized, double-blind, placebo-controlled trials. VERT-MN (Multinational Europe and Australasia) included women with 52 vertebral fractures; VERT-NA (North America) included those with 1 prevalent vertebral fracture and a T-score 42 or 2 prevalent vertebral fractures. A total of 3864 women were randomized to receive RIS (2.5 or 5 mg/d), or placebo for 3 years. All received calcium (1 g/d) and those vitamin D decient at baseline received 4500 IU/d. Patients were at least 5 years postmenopause (mean = 24 years) with a mean age of 69 years. The median number of fractures at baseline was 3 for VERT-MN and 2 for VERT-NA. Quantitative and semi-quantitative methods of analysis were utilized to determine incident vertebral fractures. After one year of RIS treatment, a signicant reduction was observed in new vertebral fracture incidence, ranging from 61% to 65% for RIS 5mg vs. control (p<0.001). The anti-fracture effect was slightly greater in the more severely osteoporotic group (52 prevalent fractures) as the fracture risk reduction ranged from 65% to 74% for RIS 5mg vs. control (p<0.001). These results indicate that risedronate rapidly reduces the risk of vertebral fractures, within the rst year of treatment. It is important for physicians to treat with a therapy that rapidly reduces vertebral fracture risk.

Osteoporosis Treatment
425 (389). CYCLIC ADMINISTRATION OF INTRAVENOUS NERIDRONATE INCREASES BONE MASS BOTH IN GROWING AND ADULT PATIENTS WITH OSTEOGENESIS IMPERFECTA S. Adami1, D. Gatti1, E. Fracassi1, V. Braga1, F. Corallo1, F. Antoniazzi2, 1Rheumatological Rehabilitation University Hospital Valeggio S/M, Italy; 2Pediatric Unit, University of Verona, Italy In an ongoing clinical trial involving patients affected by Osteogenesis Imperfecta (O.I.) we are administering neridronate 2 mg per kg of body weight up to a maximum of 100 mg intravenously every three months. Here we report the densitometric data in 39 patients who completed the rst 12 months of therapy. The study group includes 17 males and 22 females. 14 patients were under 17 years of age (range: 616 y.o.) and 25 over 20 years old (range 2168 y.o.). The types of Osteogenesis Imperfecta were: type 1 (n. 26), type 3 (n. 5), type 4 (n. 8). In the growing patients (aged <17 y.) BMC rose signicantly at both the spine and total hip (+41.2% and 48.6% respectively). The corresponding BMD increases were lower (+ 27.9% and 28.8%) for an 10% enlargement of the projected area. In the patients aged >20 y. BMC and BMD values increased signicantly both at the spine (2.4% to 3.4%) and at the hip (2.5% to 2.6%). Intermittent intravenous neridronate induced extraordinary increases in bone mass in young growing individuals with O.I. Here we have shown for the rst time that I.V. bisphosphonate therapy increases signicantly bone mass also in adult patients.

428 (392). QUALITY OF LIFE IN OSTEOPOROTIC TURKISH WOMEN TREATED WITH ALENDRONATE 426 (390). EFFECTS OF TWO INTERMITTENT ALENDRONATE REGIMENS IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS M. Rossini, D. Gatti, V. Braga, G. James, S. Adami, Ospedale di Valeggio, University of Verona, Italy A large proportion of patients have bone mass values for which a therapeutic intervention is considered necessary but the accepted aim might be the sole preservation of the actual bone mass. Aim of this study was to investigate effects of two intermittent alendronate regimens in the treatment of non-severe forms postmenopausal osteoporosis. 124 postmenopausal women (age range 5275 years) with a bone mineral density (BMD) at the femoral neck 2 SD below the mean values of young healthy individuals, and without a history of previous osteoporotic fracture, were randomly assigned either to calcium/ vitamin D supplements alone or associated with 2 different intermittent oral alendronate regimens: 20 mg once a week (weekly group) or 10 mg daily for one month out of three (cyclical group). After 1 year in both active groups we observed a signicant increase of BMD at both the spine (+2.22.6 and +2.52.9%), and femoral neck (+1.64.8 and +1.52.2%) for weekly or cyclical regimen, respectively. This was associated with a signicant diminution of both serum bone-specic alkaline phosphatase (25 and 28%) and urinary NTX (40 and 30%). In the control group BMD decreased signicantly at the lumbar spine. The compliance to treatment and its tolerability was excellent in both alendronate arms. In conclusion, intermittent alendronate at cumulative doses (and costs) 3 times lower than those currently recommended for osteoporosis treatment is very well accepted and is able to signicantly increase BMD at the spine and femoral neck. These regimens can be clinically useful in the long-term treatment of non severe forms postmenopausal osteoporosis, particularly in women with low compliance for continuous administration. G. Akyu z1, N. Eskiyurt2, D. Ouoglu1, S. Aki2, O. Kayhan1, A. Oncel2, 1Department of Physical Medicine and Rehabilitation, Marmara University, School of Medicine, Istanbul, Turkey; 2 Department of Physical Medicine and Rehabilitation, Istanbul Unviersity, School of Medicine, Istanbul, Turkey Osteoporosis is a metabolic bone disease characterized by decrease of bone density and increase susceptibility to fracture. The aim of this study is to investigate relationships between pain and subjective aspects of quality of life. Sixtyfour patients with osteoporosis were included to our study. Patient's mean age were 63.66.8 (5074) and menopause duration were 168.2 years. Their vertebral and femoral bone mineral density were measured before and after treatment by Dual X-Ray Absorptiometry (DXA). Mean vertebral T score were 3.350.7; and mean femoral neck T score were 2.20.6. All patients were taken alendronate (10 mg/day) plus calcium (1000 mg/day) for 1 year. The assessment was carried out using visual analog scale (VAS), face scale, Mc Master Health Index Questionnaire (MHIQ) and Beck Depression Index (BDI). Differences between before and after therapy were found statistically signicant in all evaluation parameters (p<0.05). As a result, we suggest that alendronate therapy is effective in patients with osteoporosis to relieve pain and increase quality of life.

429 (393). THE EFFECTS OF INDOMETHACIN AND IBUPROFEN ON HORMONE-DEFICIENT BONE DENSITY LOSS IN AN OVARIECTOMIZED MATURE RAT MODEL C. G. Ambrose, G. R. Gogola, M. Brennan, University of Texas Health Science Center, Houston, Texas, USA The goals of this study were to determine the effect of commonly available NSAIDs in preventing hormone-decient bone loss, and

Saturday, June 17, 2000

to correlate the mechanical strength of bone after exposure to NSAIDs with the bone mineral density as obtained from DXA measurements. Bilateral ovariectomy or sham operations were performed on 48 mature female Sprague-Dawley rats. 12 rats were sacriced for baseline measurements. The rest were divided into three treatment groups and underwent daily gavage for 8 weeks with one of three suspensions: ibuprofen (30 mg/kg/day), indomethacin (2 mg/kg/day), or the suspension vehicle alone (1ml/day). Bone density of the lumbar spine and the distal femur was measured on each rat initially and at 8 weeks. Bone strength was determined by three-point bending of the femoral midshaft, and bending of the femoral neck after sacrice at 8 weeks. In the control group a 10.5% BMD loss was measured in the lumbar spine and a 9.8% loss was measured in the distal femur. The strength of the femoral neck, but not the femur mid-shaft, was signicantly lower (p = 0.04) in ovariectomized animals when compared to sham-operated animals. The ibuprofen-treated animals had a signicant loss of BMD in the lumbar spine, but not the distal femur. The femoral neck strength was signicantly lower in ovariectomized animals when compared to sham-operated animals. In the indomethacin treated animals, there were no signicant differences between the ovariectomized and the sham-operated animals in any of the measured parameters.

431 (395). BIOMECHANICAL EVALUATION OF A BIORESORBABLE POLYMER FOR THE AUGMENTATION OF SCREW OSTEOSYNTHESIS IN OSTEOPOROTIC CANCELLOUS BONE P. Augat, A. Ignatius, M. Ohnmacht, P. Pokinskyj, H. J. Kock, L. Claes, 1Institute of Orthopedic Research and Biomechanics, University of Ulm, Germany; 2Merck Biomaterial GmbH, Darmstadt, Germany The purpose of this study was to assess the efcacy of a new resorbable polymer to improve the anchorage of osteosynthesis materials in cancellous bone. The new resorbable polymer is based on Alkylen-bis (dilactoyl) methacrylat. Bending strength and pullout strength of cancellous bone screws were tested in 48 bovine and 24 human osteoporotic vertebral bodies. Removal torque was tested in the diaphysis of 8 human femora. Strength measurements of bone screws augmented with the new polymer cement were compared to nonaugmented screws and screws augmented with PMMA. Removal torque of the polymer augmented screw increased by 77% (p<0.05) compared with non-augmented screws. In bovine vertebrae augmentation increased the pullout strength by 88% for the new cement and by 92% for PMMA (p<0.001). Pull-out strength in human osteoporotic vertebrae was increased by 118% (p<0.01). Bending strength was increased after augmentation in bovine vertebrae (115%, p<0.01; PMMA: 90%) and in human osteoporotic vertebrae (114%, p<0.08). Augmentation by the new polymer signicantly enhanced anchorage and attachment of bone screws in cancellous bone. While the mechanical properties of the new polymer were comparable to PMMA, its biodegradable properties may comprehend some advantages for osteosynthesis applications in osteoporotic patients.

430 (394). RALOXIFENE AND HORMONE REPLACEMENT THERAPY LOWER ATHEROGENIC LIPOPROTEINS TO THE SAME EXTENT IN HEALTHY POSTMENOPAUSAL WOMEN P. W. Anderson1, D. A. Cox1, A. Sashegyi1, S. Paul1, B. W. Walsh2, S. L. Silfen1, 1Lilly Research Laboratories, Indianapolis, IN; 2 Brigham and Women's Hospital, Boston, MA, Background: Non-HDL cholesterol (nonHDL-C) is a measure of all atherogenic, apolipoprotein B-containing lipoproteins in serum, and is predictive of cardiovascular events in women. Raloxifene (RLX) and hormone replacement therapy (HRT) lower LDL-C, but their effects on nonHDL-C have not been compared. Objective: To determine the effect of RLX and HRT on nonHDL-C serum levels in postmenopausal women. Methods: 390 women aged 45 72 years were randomized to either placebo, RLX (60 mg/d or RLX 120 mg/d), or continuous combined HRT. Total-C and HDL-C were measured in serum at baseline and after 3 and 6 months. NonHDL-C was calculated as Total-C minus HDL-C. Results: All active treatments decreased serum nonHDL-C signicantly compared with placebo at both 3 and 6 months (see table). The effect of all treatments to lower nonHDL-C compared with placebo was greatest in women with hypercholesterolemia (Total C >240 mg/dL) at baseline. Conclusion: Raloxifene and HRT lower the serum nonHDL-C concentration, a global measure of atherogenic serum lipoproteins, by the same magnitude in postmenopausal women, particularly among those with hypercholesterolemia.

432 (396). FEASABILITY OF A TREATMENT WITH HIGH FREQUENCY VIBRATION FOR THE PREVENTION OF BONE AND MUSCLE LOSS IN ELDERLY WOMEN P. Augat, C. Becker, S. Scheible, U. Lindemann, T. Nikolaus, L. Claes, Institute of Orthopedic Research and Biomechanics and Bethesda Geriatric Hospital, University of Ulm, Germany Cyclic ground based vibration has previously shown to induce bone formation in sheep and increase muscle force in young athletes. This study was performed to test the feasibility of applying ground-based vibration in elderly women. Fifty-three postmenopausal, healthy women (age 55 yrs to 75 yrs, mean age 67 yrs) were enrolled in the study. At study entrance and at completion functional performance was assessed by a functional reach test, a ve-chair stand test, and measurement of walking velocity. Force and power of the lower extremity was assessed by isokinetic force measurements (Cybex). All study participants were subjected to 5 minutes of vertical ground based vibration, oscillating at 30 Hz, two times a week for a period of 8 weeks. Forty-three women (81%) completed the study. While 4 women discontinued on own request, 6 women (11%) had to cancel because of minor problems that might have been associated with the vibration treatment. Functional reach increased by 11% (p<0.01), time for the ve chair test decreased by 19% (p<0.01), walking velocity increased by 2% (n.s.), and isokinetic moment increased by 10% (p<0.01). The study showed a high acceptance of vibration treatment in a possible target population for osteoporosis treatment. It furthermore suggested its effectiveness in the prevention of muscle loss.

Median Change from Baseline 3 months Placebo RLX 60mg/d RLX 120mg/d ccHRT
*p<0.001 vs. placebo.

6 months 0.03 0.39 0.43 0.40 (0.63%) (10.1%)* (9.1%)* (9.3%)*

0.01 0.39 0.44 0.34

(0.23%) (9.2%)* (10.1%)* (9.1%)*

433 (397). COMBINED ALENDRONATE AND TIBOLONE IS MORE EFFICACIOUS THAN EITHER MEDICATION ALONE IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS A. Avramides, D. G. Goulis, J. Sarris, Ch. Balaris, S. Delaroudis, A. Kiroudi, M. Tzoiti, Department of Endocrinology, Hippocration Hospital, Thessaloniki, Greece The purpose of this study was to evaluate the effectiveness of alendronate or tibolone as well as their combination (alendronate+tibolone) in women with established postmenopausal osteoporosis. We carried out a 24-month, randomized, control-matched study of the use of alendronate 10 mg (group A, n=50), tibolone 2.5 mg (group B, n=50) or their combination (group C, n=25) in 45 to 69 year-old women with postmenopausal osteoporosis. The mean (SE) bone density of the lumbar spine increased by 2.21.2 percent and 1.91.1 percent in the alendronate and tibolone group respectively (p<0.01 vs. control). It increased by 3.81.9 percent in the combination group (p<0.01 vs. groups A and B) whereas it decreased by 0.30.3 percent in the control group. Similar changes were found regarding the femoral-neck bone density. There were no differences in adverse effects among the three groups. We conclude that the combined use of alendronate and tibolone results in greater increase in bone density than either medication alone in white women with postmenopausal osteoporosis.

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435 (399). RISEDRONATE THERAPY INCREASES TOTAL HIP BMD IN POSTMENOPAUSAL WOMEN INDEPENDENT OF INITIAL HIP BMD STATUS C. L. Benhamou1, C. Chesnut2, Ch. Roux3, R. Wasnich4, S. Goemaere5, M. Greenwald6, T. Diamond7, S. Adami8, D. Ethgen9, R. Eastell10, 1Orleans, France; 2Seattle, WA, USA; 3Paris, France; 4 Honolulu, HI, USA; 5Ghent, Belgium; 6Palm Springs, CA, USA; 7 Kogarah, NSW, Australia; 8Verona, Italy; 9Mason, OH, USA; 10 Shefeld, UK The risedronate (RIS) osteoporosis clinical program enrolled over 15,000 patients with varying osteoporosis severity, based on a combination of low BMD (spine or hip) and/or prevalent vertebral fractures. One large study, the Hip Intervention Program (HIP) enrolled 9331 elderly postmenopausal women at risk for hip fracture. Two other studies (VERT-MN [multinational Europe and Australasia], and VERT-NA [North America]) enrolled 3684 patients based on the presence of vertebral fracture status. Patients in all 3 studies received RIS (2.5 or 5 mg) or placebo daily for 3 years, 1g calcium daily, and vitamin D supplementation if levels were 540 nmol/L. Total hip BMD in all 3 studies was measured at those study centers using Hologic densitometers, so data were available for a subset of patients. Signicant BMD increases for RIS 5mg vs. baseline and control were observed at the proximal femur beginning at the earliest measurement (6 months) and continued for the duration of the study. Consistent increases in total hip BMD were observed for RIS 5mg vs. control across the 3 studies. Total hip BMD increases at 3 years for all centers were: 3.9%, 5.2%, and 3.1% for RIS 5mg vs. control in the HIP, VERT-MN, and VERT-NA studies, respectively (p<0.001 for the comparison in all 3 studies). In conclusion, risedronate treatment produces rapid and consistent increases in total hip BMD compared to control patients receiving 1g calcium and vitamin D. These effects are observed in women independent of their baseline hip BMD status. These consistent increases are sustained over 3 years of treatment.

434 (398). USING IN POSTMENOPAUSAL WOMEN WITH BONE MASS LOSS RALOXIFENE AND ALENDRONATE A. Bazarra1, A. Castro2, M. Suarez, 1Health Sciences and Medicine Dept, University of the Coruna, Spain Objective: Determining if the combined use of raloxifene hydrocloride and alendronate inuences on bone mass loss in postmenopausal women. Material and method: We studied for 6 months 21 women who were 44 to 64 years old at base line, were within 2 and 11 years of menopause, and had a bone mineral density at the lumbar spine between 145 mg/cc and 50 mg/cc measured by the QBMAP system with a spiral CT Picker PQ-S densitometer at L2, L3, L4 and L5. Of all the women, 10 were assigned to 60 mg of raloxifene hydrocloride, 800 IU of vitamin D3 and 1 g of calcium carbonate supplementation. 11 were treated with 10 mg of alendronate, 60 mg of raloxifene hydrocloride, 800 IU of vitamin D3 and 1 g of calcium carbonate supplementation. The SPSS programme was used for statiscal analysis. Results: The characteristics of the women recruited for both groups were similar. Mean mineral bone density at the lumbar spine was between 1 and 3 DS below the mean value for 30 years old normal premenopausal women. After a treatment of 6 months no statistically signicant difference was found among both groups as for the bone mineral density at the lumbar spine. However, the group with alendronate increased a litle more the bone mineral density. Conclusions: It is necessary to carry out a wider and longer study but it seems that the combination of raloxifene hydrocloride and alendronate contribute advantages to decrease the bone mass loss in postmenopausal women, at least, at lumbar spine. Osteoporosis is a multifactorial disease, maybe its best treatement and prevention is combining several drugs and attitudes. It would be good to test several adjusted doses to decrease side effects.

436 (400). EVALUATION OF POWER: A MULTISITE COMMUNITY BASED EDUCATIONAL PROGRAM FOR OLDER ADULTS WITH OSTEOPOROSIS L. Bernick1, T. Izukawa1, A. Stephens2, 1Baycrest Centre for Geriatric Care, Toronto, ON, Canada; 2North York General Hospital, Toronto, ON, Canada The evaluation of a six-week, multi-site program aimed to empower older adults with osteoporosis, improve their quality of life and prevent falls will be presented. The collaborative program is provided by nurses, physicians, physiotherapists and dieticians, from four organizations, and includes culturally sensitive screening, education, nutrition and exercise services to community dwelling elders. The formative evaluation included a review of the program structure and process using the logic model and descriptive statistical analysis of data from focus groups, satisfaction questionnaires, knowledge pre and posttests, demographic data and treatment recommendations. The results indicated that the majority of the participants (N=187) had completed the program (90%); were female (97%) and a mean age of 73 years; had fallen within the last two years (35.5%); and had osteoporosis on average for two years. Calcium supplements (46%), Vitamin D (55.8%) and bone resorption-inhibiting drugs (22.4%) were recommended for the participants. They reported an increase in their calcium intake and daily exercise, life style changes and improved knowledge. This program has been between three health care organizations, a pharmaceutical company and public health. This unique collaboration has contributed to the success of this program.

Saturday, June 17, 2000

437 (401). PRETREATMENT BMD AND VERTEBRAL FRACTURE STATUS AS WELL AS CHANGE IN OSTEOCALCIN ARE ALL PREDICTORS FOR THE RISK OF INCIDENT VERTEBRAL FRACTURE DURING RALOXIFENE THERAPY N. H. Bjarnason, C. Christiansen, T. Duong, P. D. Delmas, for the MORE Study Group, We have previously shown that a short-term change in bone turnover is associated with a long-term decrease in vertebral fracture risk during raloxifene treatment. However, a possible inuence of baseline risk factors such as BMD and vertebral fracture status was not assessed. The MORE study randomised 7705 osteoporotic women to daily treatment with either placebo, raloxifene 60 mg or 120 mg. Spine X-rays were obtained pre-treatment and after 3 years and were analysed blinded. In a subset of about 1/3 of the participants, a fasting blood sample was collected before randomisation and at 6, 12, 24 and 36 months for bone marker analysis. BMD assessments were performed yearly. Using logistic regression to model the risk of suffering at least 1 vertebral fracture, we performed multi-variable analyses including age, baseline spine BMD, prevalent vertebral fracture status and percent change at 1 year in osteocalcin for the pooled raloxifene groups (N=1584). The results are given as odds ratios per 1 std increase in each parameter. Results from analyses of additional bone markers will also be presented. The strongest predictor for incident vertebral fractures was the presence of prevalent vertebral fractures, with an odds ratio of 3.34 (CI: 2.115.31, p<0.0001). Odds ratio for baseline spine BMD was 0.66 (CI: 0.530.83, p = 0.0003) with a std of 0.133 g/cm2 and odds for change in osteocalcin was 0.81 (CI: 0.680.96, p = 0.0168) with a std of 28.7%. Thus, if the osteocalcin change during raloxifene therapy exceeds 28.7%, the likelihood of incident vertebral fracture over 3 years decreases with 19%. Age was only borderline signicant in the multi-variable analyses. Our data show that the presence of vertebral fracture and brnd are very important risk factors for the development of new fractures, even during treatment. Importantly, the predictive value of on-treatment change in bone turnover is signicant after adjustment for strong risk factors such as pre-treatment prevalent vertebral fractures, BMD and age.


439 (403). INCREASING AGE AND FEMALE GENDER ARE ASSOCIATED WITH DELAYED UNION OF HUMERAL SHAFT FRACTURES M. E. Bolander, J. T. Bronk, G. Sarkar, D. M. Ilstrup, L. J. Melton III, Mayo Clinic and Mayo Foundation, Rochester, MN, USA Age and gender inuence skeletal formation and remodeling, but their effects on the time taken for fracture healing are unknown. We report a retrospective analysis of 115 patients with closed fractures of the humeral diaphysis (shaft). The time required for healing was based on clinical criteria and was analyzed on the basis of fracture characteristics, patient age, and gender. For some analyses patients were divided into four groups: 1) young (15 years or under); 2) adult (1630); 3) mature (2155); and 4) old (55 or older). Fractures were transverse in 41% of patients and oblique or spiral in 45%; one third were comminuted. Fractures occurred after falls (50%), motor vehicle accidents (30%) or other trauma (20%). Neither time to healing nor nonunion rate was signicantly affected by the etiology, location, or conguration of the fracture. The time until clinical union increased with age in all patients (p<0.0001); additionally, fractures in women took signicantly longer to heal than fractures in men of comparable age (p<0.0001). The incidence of fracture nonunion was increased in women compared to men (14.0% vs 5.2%, p = 0.066). Older patients, especially older females, require increased time for fracture healing than younger patients, and as a result are at potentially greater risk than younger patients for developing complications during fracture healing.

438 (402). THE EARLY ANTIFRACTURE EFFICACY OF ALENDRONATE IN WOMEN WITH OSTEOPOROSIS: RESULTS FROM FIT D. Black1, D. Bauer1, D. Thompson2, M. Hochberg3, for the FIT Research Group, 1Univ. of California, San Francisco, CA; 2Merck & Co., Rahway, NJ; 3Univ. of Maryland, Baltimore, MD, USA We investigated the effect of alendronate (ALN) on fracture incidence in 3658 women from the Fracture Intervention Trial (FIT) with one or more prevalent vertebral fracture (VFx) at baseline and women without a prevalent VFx but with femoral neck Tscores 42.5 (WHO threshold for osteoporosis). In this group of women, ALN was effective in reducing the risk of any clinical fracture (RR = 0.70 (0.59, 0.82)), non-vertebral fracture (RR = 0.73 (0.61, 0.87)), symptomatic spine fractures (RR = 0.55 (0.36, 0.82)), hip fracture (RR = 0.47 (0.26, 0.79)) and wrist fracture (RR = 0.70 (0.49, 0.98)). The cumulative incidence curves for any clinical fracture, symptomatic vertebral fracture and hip fracture began to diverge as early as 6 months. For each of these fractures the effect was consistent (tended to increase) over time. We observed a 59% (p = 0.030) reduction in symptomatic spine fracture at 12 months, a 63% (p = 0.014) reduction in hip fracture by 18 months, and a 27% (p = 0.017) reduction in any clinical fracture at 18 months. Conclusion: In women with either existing VFx or with femoral neck BMD T-score 42.5, alendronate was effective in reducing the risk of any clinical fracture, non vertebral fractures, symptomatic spine fractures, hip fractures and wrist fracture. The effect of alendronate was evident very early.

440 (404). RISEDRONATE IS WELL-TOLERATED IN PATIENTS WITH OSTEOPOROSIS INCLUDING THOSE OVER 80 YEARS OF AGE M. Bolognese1, D. Mclntyre2, I. Fogelman3, W. Olszynski4, H. Beck-Nielsen5, H. Mulder6, I. Barton7, T. Ernst8, A. Chines9, 1 Gaithersburg, MD, USA; 2South Brisbane, QLD, Australia; 3 London, UK; 4Saskatoon, SK, Canada; 5Odense, Denmark; 6 Rotterdam, Netherlands; 7Staines, UK; 8Mason, OH, USA; 9 Mason, OH, USA As part of a 15,066 patient clinical program, the tolerability of risedronate (RIS) was assessed in placebo-controlled studies of up to 3 years' duration. Patients were not excluded because of underlying medical condition or concomitant medication use

(history of GI disorder or NSAID/aspirin use). Approximately 4000 patients were 580 years of age at enrollment, a population traditionally excluded from clinical trials. Patients were randomly assigned to receive RIS 2.5 or 5mg, or placebo, all as lm-coated tablets. The proportions of patients reporting adverse events (AEs) or upper GI AEs were similar in the RIS 5mg and placebo groups, as were the percentages of patients discontinuing due to AEs (table).

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persistent bone mass improvement. The aim of the study was to assess the effects of our exercise program (developed in Institute of Rheumatology) on BMD. The patients with low BMD exercised 3 times a week (for 4 weeks), and after that period patients continued regularly exercise at home. BMD was measured by dual x-ray absorptiometry (Lunar DXA system). Group of 24 pts exercised without taking any drugs for osteoporosis, mean age 57.38 (4673) years and mean BMD 0.9150.12 gr/cm2 with average T score 2.400.98. The rst control DXA was done after average period of 10.3 months. BMD was increased to mean 0.9250.10 gr/cm2 (1.5%), and T score to 2.280.88 (3.7%), (n.s.). Second control DXA was done in sixteen patients (out of 24) who discontinued exercising at home during next year. BMD in this group decreased from 0.9230.07 gr/cm2 at the end of rst year to 0.9040.06 gr/cm2 (2.1%); (t=2.21; p<0.05), after average period of 11.7 months. Our result suggests that exercise have a positive effect on BMD even without any medicaments. It is necessary to continue exercise because when pts stoped exercising, BMD decreased signicantly to lower values compared to values at the beginning.

Age 580 Years Placebo (N=1821) n (%) Any AEs Withdrawals due to AEs Upper GI (UGI) AEs Most common UGI AEs Abdominal pain Dyspepsia 1651 (91) 290 (16) 419 (23) 189 (10) 160 (8.8) RIS 5 mg (N=1812) n (%) 1649 (91) 301 (17) 416 (23) 174 (9.6) 171 (9.4)

Age 580 Years Placebo (N=1313) n (%) 1154 (88) 274 (21) 265 (20) 99 (7.5) 94 (7.2) RIS 5 mg (N=1292) n (%) 1137 (88) 249 (19) 241 (19) 84 (6.5) 84 (6.5)

The frequencies of the most common treatment-related GI AEs were also similar between treatment groups and importantly there was no evidence of increased incidence of clinical adverse events or intolerance in patients 580 years of age. These ndings, collected from more than 15,000 patients (approximately 4000 of whom are 580 years of age) across a wide range of osteoporosis disease severity, support that risedronate is a well-tolerated therapy with a favorable safety prole.

443 (407). LOW BONE MASS BUT NOT QUANTATIVE ULTRASOUND OR BONE MARKERS ARE ASSOCIATED WITH VERTEBRAL FRACTURES IN OLDER MEN J Cauley, J Zmuda, L Palermo, M Nevitt, Universities of Pittsburgh and California, San Fransisco, To test the hypothesis that bone mineral density (BMD), quantitative ultrasound (QUS), and bone turnover markers are associated with prevalent vertebral fractures (VFx) in a community based population of older men, we recruited 306 white men, mean age 73 years. Prevalent VFx were identied with morphometry. A vertebra was considered fractured if any of the vertebral height ratios were > 3 Standard Deviations (SD) below the mean for that vertebral level. BMD was measured using DXA (QDR) and heel ultrasound with Sahara QUS device (Hologic, Inc., Waltham, MA). Osteocalcin and N-Telopeptides (NTx) were measured by Endocrine Science (Calabassas Hills, CA). 14% of men (n=43) had a VFx. We calculated the age-adjusted odds ratio (95% Condence Interval (CI)) of prevalent fracture for 1 SD decrease in the parameter using logistic regression. One SD decrease in BMD was associated with an increased prevalence of VFx (Table). There was no association with QUS or either bone marker. We conclude that low BMD is a signicant correlate of VFx in older men.

441 (405). THE EFFICACY OF CALCITRIOL IN OSTEOPOROTIC PATIENTS WITH ASTHMA RECEIVING INHALED CORTICOSTEROIDS P. Borman1, Y. G. Kutsal1, F. Kalyoncu2, 1Department of Physical Medicine and Rehabilitation; 2Chest Diseases, Samanpazari, University of Hacettepe, Ankara, Turkey The aim of this study was to evaluate the efcacy of calcitriol (Rocaltrol1) in a group of asthmatic women suffering from inhaled corticosteroid(cs) induced osteoporosis. 21 osteoporotic patients who were receiving treatment with inhaled cs with a mean dose of 1.62.31 mg BDP/day, for a mean duration of 4.80.92 years, were included to the study. The patients were randomly allocated into two groups treated with either 0.25 mg calcitriol (n=11) twice daily or 1000 mg calcium (n=10) alone for one year. The patients receiving calcium had signicantly greater bone loss at the lumbar spine (0.820.12/0.780.11 g/cm2), while the mean values of lumbar BMD remained unchanged (0.810.13/0.810.11 g/cm2) in the patients receiving calcitriol. One new fracture occurred in the calcium supplement group. No side effects of the drugs were observed in the two groups. These results suggest that calcitriol may be a useful agent to prevent inhaled cs induced osteoporosis in patients suffering from asthma. Long-term studies including more patients should follow to conrm these preliminary ndings.

Skeletal Parameter Total Hip (g/cm2) Lumbar Spine (g/cm2) BUA (dB/MHz) SOS (m/s) NTx (nM BCE/mM Cr) Osteocalcin (ng/ml)

SD 0.15 0.18 17.1 32.4 19.4 3.8

OR (95% CI) 1.81 1.46 1.23 1.14 1.05 1.10 (1.24,2.63) (1.03,2.06) (0.86,1.78) (0.79,1.64) ( (0.80,1.51)

442 (406). INFLUENCE OF EXERCISE ON BONE MINERAL DENSITY , N. Pilipovic , P. Vukojevic, N. Vujasinovic -Stupar, D. S. Brankovic , Institute of Rheumatology, Belgrade, Yugoslavia Palic-Obradovic We studied the inuence of exercise program on bone mass and the role of exercise in the prevention and treatment of osteoporosis. Exercise intervention may provide modest increas in bone mineral density (BMD), but must be sustained for

444 (408). THE HETEROGENEITY IN BONE MINERAL DENSITY AND BIOCHEMICAL MARKERS OF BONE TURNOVER IN RESPONSE TO HORMONE REPLACEMENT O. Chaki, I. Gorai, H. Yoshikata, R. Kikuchi, F. Hirahara, Yokohama City University, Yokohama, Japan In order to analyze the heterogeneity in response of lumbar spine and femoral neck bone mineral density(L- and FN-BMD) to estrogen replacement therapy (HRT) and in suppression of biochemical markers of bone metabolism and bone-resorbing

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cytokines, 31 postmenopausal women, aged 4063 yrs (mean age, 55.05.0 yrs) were treated with continuous combined HRT for 2 yrs. Six markers of bone formation, bone-specic alkaline phosphatase (B-AlP), AlP, intact osteocalcin (I-OC), OC, N-mid OC and N-terminal OC (N-OC) and three markers of bone resorption, serum and urinary type I collagen C-telopetide breakdown products (CTx), and cross-linked N-telopeptides of type I collagen (NTx) were measured at baseline and 1, 3 and every 3 months after treatment whereas L- and FN-BMD were determined at baseline, and 6, 12, 18, and 24 months after HRT. We divided the whole population into two groups, because of a small number of the subjects, instead of quartiles, based on years since menopause (YSM), baseline L- and FN-BMD and biochemical markers at entry, and responsiveness for BMD at 24 months. The percentage changes in L-BMD did not correlate with those in FN-BMD at each treatment period. L-BMD of late postmenopausal women with more than 6 YSM increased more than that of early postmenopausal women within 5 YSM during 24 months of treatment. Serum and urinary CTx, B-AlP, N-mid OC and N-OC showed a nadir at earlier period in late postmenopause than in early postmenopause. Women with low baseline bone mass showed a signicantly higher increase in L-BMD (p<0.05) and a signicantly less decrease in FN-BMD (p<0.05) than those with high baseline bone mass. With no signicant differences in baseline biochemical markers except for B-AlP between the two groups, HRT signicantly suppressed NTx and N-OC in women with low baseline L-BMD (p<0.05) more than in those with high baseline L-BMD. NTx, I-OC, OC, N-mid OC, N-OC, AlP and B-AlP at nadir (at 6 to 24 months) were signicantly suppressed more in women with a favorable response in L-BMD (p<0.05) than in those with a minimal response, demonstrating that biochemical markers have a variation in treatment period at which each marker reached a nadir and in magnitude of suppression of each marker. Moreover, N-mid OC at 1 month, and AlP and NTx at 6 months in women with a favorable response in L-BMD showed a signicant suppression (p<0.05) before they reached a nadir compared to those with a minimal response. We conclude that there is a heterogeneity in bone density and in biochemical markers in response to HRT.
Ex (n=13) Thigh BMD CSAbone CSAmuscles BMRT Lower leg BMD CSAbone CSAmuscles BMRT Ex (n=12) EsEx (n=10)

Co (n=15)

0.33 0.92* 4.83** 4.23 1.10* 0.12 7.24 7.89

0.15 0.52 4.18* 3.62 0.54 0.66 4.33 5.37

0.61 0.94* 7.40*** 7.19* 2.01** 0.43 10.46** 12.73**

0.21 0.27 1.45 4.01 0.95 0.51 4.74 5.68

*p<0.05, **p<0.01, ***p<0.001 compared to the control.

446 (410). VAGINAL PREMARIN1 VS. REPLENS1 IN WOMEN WITH PRE-EXISTING VAGINAL ATROPHY RECEIVING ORAL PLACEBO OR RALOXIFENE: EFFECTS ON SUBJECTIVE ENDPOINTS A. Ciaccia1, L. Nachtigall2, P. Sulak3, R. Basson1, H. Heath1, L. Plouffe1, A. Parsons4, 1Lilly Research Laboratories, Indianapolis, IN; 2New York, NY; 3Scott and White Clinic, Temple, TX; 4 University of South Florida, Tampa, FL, Objective: Compare the effects of vaginal Premarin1 and Replens1 vaginal moisturizer on self-reported symptoms in women with pre-existing vaginal atrophy who are receiving concomitant oral placebo or raloxifene. Design: 187 naturally postmenopausal women with at least 2 signs of genitourinary atrophy were randomly assigned to receive double-blind oral placebo or raloxifene 60 mg/day and open-label vaginal Premarin (0.5 g/day; PRM) or Replens (REP). Women described the presence and severity of vaginal symptoms (including vaginal dryness, itching, painful urination, urinary urgency, vaginal bleeding, and painful intercourse) based on a 4-point scale (1=none, 2=mild, 3=moderate, 4=severe). Results: Mean age and years postmenopause at entry were 59 and 9.5, respectively. There were no treatment group differences for any of the symptoms at baseline. After 3 months, almost all measurements in each treatment group decreased, indicating an overall improvement in symptoms. The changes from baseline for itching, painful urination, vaginal bleeding, and painful intercourse were not signicant within each group or across groups. Vaginal dryness rating improved in each group (p<0.043), with no signicant therapy group differences. Urinary urgency was improved in the Placebo/PRM and raloxifene/REP groups, but there were no signicant differences between PRM and REP. There were no signicant differences between raloxifene and placebo for any symptom. Conclusion: PRM and REP treatments are associated with similar improvement in vaginal atrophic symptoms. These effects were not inuenced by concomitant RLX therapy.

445 (409). EFFECTS OF HORMONE REPLACEMENT THERAPY AND HIGH-IMPACT PHYSICAL EXERCISE ON BONE/MUSCLE RATIO IN POSTMENOPAUSAL WOMEN S. Cheng, S. Sipila, J. Puolakka, H. Suominen, Dept. of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland The purpose of this one-year intervention trial was to evaluate the effects of hormone replacement therapy (HRT) and high-impact physical exercise on bone/muscle ratio in postmenopausal women. Eighty healthy women aged 5057, with <5 years after onset of the menopause and with no previous HRT were randomly assigned to one of the four groups: estrogen (Es), exercise (Ex), estrogen + exercise (EsEx) and control (Co). The HRT was conducted (double-blind) for 1-year using combined estradionoretisteron acetate (Kliogest). The exercise groups participated in a 1-year progressive training program consisting of jumping and bounding activities. Two supervised sessions per week were performed with subjects additionally undertaking a series of exercises at home 4 days/week. A QCT scanner (Siemens Somatom DR) with a program (BonAlyse) was used to calculate bone mineral density (BMD, g/cm3), cross-sectional area (CSA, mm2) and the bone/muscle ratio (BMRT) from the middle region of the thigh and lower leg. The percentage (%) changes in BMD, CSA and BMRT after the 1-year period are given in the Table. Our results suggest that the alteration of the bone/muscle ratio is mainly due to the contribution of the change in muscle CSA and the combined effects of HRT and high-impact physical exercise may exceed the effects of HRT alone.

447 (411). TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN PATIENTS WITH IMPAIRED FAST GLUCOSE Miro Cokolic, Rok Hren, 1Department of Endocrinology and Diabetology, Internal Clinic, General Hospital Maribor, Maribor, Slovenia; 2Institute of Mathematics, Physics, and Mechanics, University of Ljubljana, Ljubljana, Slovenia Impaired fast glucose (IFG) designates a metabolic stage between normal glucose homeostasis and diabetes. The aim of this study was to monitor blood glucose level and bone mineral density (BMD) in patients with IFG that are treated for postmenopausal osteoporosis. Methods: Six women with IFG (serum levels of glucose 6.0 to 7.0 mmol/l) and postmenopausal osteoporosis (T-score below 2.5)

were enrolled in a one-year prospective study. The patients were 62 to 71 years old (mean: 68 years) and 9 to 28 years (mean: 18 years) after the menopause. They were treated with alendronate (10 mg/d) in combination with 500-mg elemental calcium. The BMD in the lumbar spine (L2-L4) and left hip were measured in all patients using dual energy X-ray densitometry (Hologic QDR2000+) at the start of the treatment and at 3 months, 6 months, and 12 months after the treatment. The serum levels of glucose, Ca, and creatinine were taken at the same time intervals. Results: Serum levels of glucose remained relatively unaltered throughout the treatment, with an average values of 6.3 mmol/l (range 6.06.6 mmol/l) in the beginning of the treatment and 6.3 mmol/l (range 6.16.4 mmol/l) at 12 months after the treatment. In 12 months, the BMD increased on average by 2.4% (range 0.0 6.5%) in the lumbar spine (L2-L4) and by 2.4% (range 0.54.6%) in the left hip. Levels of Ca and creatinine remained within normal limits during the treatment. No clinical side effects were observed during the study. Conclusions: Our results suggest that alendronate administration can provide clinically relevant benets in postmenopausal women with osteoporosis and IFG.

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the question is raised whether administration of DHEA counteracts defects associated with aging. Two hundred and eighty healthy individuals (70 women70 men, 6069 y old, and 70 women70 men 7079 y old) were given DHEA, 50 mg, or placebo (pl), orally, daily for one year in a double blind, placebo-controlled study. We measured hip and forearm BMD before and after 12 months (mo) of treatment, and biological markers of bone turnover, serum osteocalcin (Oc) and bone alkaline phosphatase (bAP) for bone formation, and serum Cross-laps (CTx) for bone resorption, before and after 6 and 12 mo of treatment. In men, no effect of DHEA was recorded, whether on BMD or on biochemical markers, except an increase in bAP (+32%; p<0.05) at 12 mo in the older DHEA-treated men. However, signicant differences in BMD change (data given as median in mg/cm2 [1st;3rd quartiles]) between placebo- and DHEA-treated women were observed at several sites, the femoral neck (pl:9 [16;+18]; DHEA: +13 [+1;+13]; p<0.05) and Ward's triangle (pl:23 [40;+6]; DHEA: +4 [19;+25]; p<0.05) in the 6069 y women and the upper (pl:10 [19;+5]; DHEA:+4 [8;+14]; p<0.05) and total radius (pl:11 [20; +5]; DHEA:+2 [5;+10]; p<0.05) in the 7079 y women. Furthermore, serum CTx was decreased by 11% (p<0.05) and 26% (p<0.01) at 6 mo and 12 mo respectively, only in the 7079 y DHEA-treated women while serum Oc and bAP were unchanged. Considering the 7079 y women with the serum sDHEA levels in the lowest quartile at baseline, the decrease of serum CTx was even larger (43% at 6 mo and 35% at 12 mo; p<0.01 in each case) and was accompanied by a delayed decrease of serum Oc (5% at 6 mo, not signicant and 35% at 12 mo, p<0.01). These results suggest that treatment with oral DHEA at a daily dose of 50 mg has favourable effects on bone health in women, specially in those 70 y old and over, but not in men. Whether or not these effects are due to the formation of active estrogen(s) and/or androgen(s) deserves further studies.

448 (412). EFFECT OF CONTINUOUS TRANSDERMALESTRADIOL AND NORETHISTERONE ACETATE VS ESTRADIOL TRANSDERMAL HRT ON BONE MARKERS IN POSTMENOPAUSAL WOMEN C. Cooper1, D. F. Archer2, 1Southampton General Hospital, Southampton, UK; 2Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA OBJECTIVE: To compare the effects of three doses of continuous combined transdermal estradiol/norethisterone acetate (E2/ NETA) versus E2 alone on bone markers in healthy postmenopausal women. METHODS: A total of 625 postmenopausal women were enrolled in this 52-week, randomized, double-blind, multicenter study. Subjects were assigned to one of four treatment regimens: transdermal E2 50 mg/day or transdermal E2/NETA delivering E2 50 mg/day and NETA 140, 250 or 400 mg/day. Markers of bone formation (serum bone-specic alkaline phosphatase, total osteocalcin) and bone resorption (urinary N- and C-telopeptide) were obtained at baseline and weeks 24 and 52. RESULTS: Reductions in bone formation and bone resorption for the E2/NETA 50/250 and 50/400 groups were comparable to those in the E2 group. The decrease in the E2/NETA 50/140 group was signicantly (P<0.05) less than with the E2 group for Ctelopeptide/creatinine ratio, N-telopeptide/creatinine ratio, and osteocalcin. At baseline, bone turnover was higher than the normal premenopausal range; with E2/NETA and E2, the markers approached the normal premenopausal range. CONCLUSIONS: After 1 year of treatment, markers of bone formation and resorption improved with all three doses of E2/ NETA. This improvement with transdermal E2/NETA 50/250* and 50/400 treatment groups was comparable to that with transdermal E2. *trademark: ESTALIS1

450 (414). PARATHYROID HORMONE IN COMBINATION WITH ESTROGEN DRAMATICALLY REDUCES VERTEBRAL FRACTURE RISK F. Cosman, J. Nieves, C. Formica, L. Woelfert, V. Shen, R. Lindsay, Helen Hayes Hospital, West Haverstraw, New York, NY, USA Our best pharmacological agents for osteoporosis treatment prevent approximately fty percent of osteoporotic fractures. Thus, there is a need for an agent which can further augment bone mass and reduce fracture risk more substantially. Therefore, we embarked on a trial investigating the utility of PTH in combination with established hormone therapy in women with osteoporosis. Fifty-two women who had been on HRT for at least one year were enrolled in this trial in which 25 were randomly assigned to remain on HRT alone and 27 were assigned to remain on HRT and also receive daily subcutaneous PTH (134) 400 units (25 mg). Bone mineral density measurements at the spine and hip and biochemical determinations of bone turnover were obtained every six months. Lateral thoracic and lumbar spine x-rays were obtained at baseline and after three years in all patients. Subjects were also followed for one year after discontinuation of PTH, with bone density measurements and biochemistry obtained at 6 and 12 months after discontinuation. In the group receiving HRT alone, bone density and biochemical turnover variables remained stable throughout the three year treatment trial and one year follow up. Subjects in the PTH+HRT group increased bone mass by 12.81.4% (p<0.001) in the spine, and 4.40.6% (p = 0.001) in the total hip. One year follow-up bone density did not change signicantly at the hip but there was a modest loss at the spine. (1.8% loss at spine p = 0.07; 1.3% loss at total hip p = 0.39). Biochemical variables of bone turnover in the PTH+HRT group increased to a peak of 1650% above baseline by year 1 and remained above baseline for the 3 years. Levels returned to baseline by 1 year after discontinuation of PTH. There were 12 incident fractures in the HRT only group and 2 incident fractures

449 (413). EFFECT OF ONE YEAR DHEA TREATMENT OR PLACEBO ON BONE MINERAL DENSITY (BMD) AND BONE TURNOVER: THE DHEage STUDY C. Cormier1, J C. Souberbielle2, J. Raison3, C. Kindermans2, F. Forette4, E E. Baulieu5, 1Rhumatologie A, Hopital Cochin; 2 Physiologie, Hopital Necker; 3Endocrinologie-Nutrition, Hopital Hotel Dieu; 4Fondation National De Gerontologie, AP-HP, Paris; 5 INSERM U444; 6Le Kremlin-Bicetre, France The secretion and the blood levels of the adrenal steroid DHEA and its sulfate ester (sDHEA) decrease profoundly with age, and

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in the PTH+HRT group using a 15% height reduction cut point (p = 0.001). Using a 20% height reduction cut point, there were 7 fractures in the HRT group but 0 in the PTH+HRT group (p = 0.003). 37.5% of women in the HRT group vs 8.3% in the PTH+HRT group had incident fractures using the 15% cut point, and 25% vs 0% had fractures in their respective groups using the 20% cut point (both p<0.02). We conclude that the majority of the PTH induced bone mass increment is maintained with continued HRT 1 year after discontinuation of PTH. Furthermore, parathyroid hormone in combination with hormone therapy is an effective means of dramatically increasing bone mass throughout the skeleton and specically reducing vertebral fracture occurrence, dramatically more so than estrogen alone.

the mean age of women in the studies ranged from the mid 60s to the low 70s. Women in the Chapuy study were much older. The dropout rates across the studies ranged from a low of 2% in the Black study to a high of over 45% in the Chapuy study. Except for the Lufkin and Chapuy studies, the duration of the studies was 2 years or more. The table below reports the results from the studies. A `+' in the BMD column indicates a percent change in BMD less than 5%, a `++' indicates a change of more than 5%. A ``Yes in the fracture columns indicates a signicant (p<0.05) reduction in fracture risk. In summary, a signicant increase in BMD, and a signicant reduction in morphometric fractures of the vertebrae has been found for almost all of the therapies included in our analyses. However, a signicant reduction of hip-fractures and other non-spine fractures has only been shown for Vit-D and alendronate. In addition, alendronate was the only therapy that also caused a signicant reduction in clinical fractures of the vertebra and the wrist. Thus, in postmenopausal women with low BMD and existing vertebral fracture, alendronate appears to be the most effective therapy to prevent osteoporotic fractures at multiple sites.

451 (415). COMPARISON OF INTRANASAL AND TRANSDERMAL 17 b-ESTRADIOL ON BONE LOSS IN POSTMENOPAUSAL WOMEN AT 1 YEAR P. D. Delmas1, C. Ribot2, B. Pornel3, A. Cyganek4, H. S. The5, P. Garnero6, J. Villero-Anuarbe7, 1E. Herriot Hospital, Lyon, France; 2 Rangueil Hospital, Toulouse, France; 3Brussels Menopause Center, Belgium; 4University Medical School, Warsaw, Poland; 5 Den Helder, The Netherlands; 6Inserm U, Lyon, France; 7Hospital Reina Soa, Cordoba, Spain Objectives: to compare the efcacy of intranasal estradiol (S21400: Aerodiol1) and a reference patch on bone turnover and bone loss. Design and methods: Multinational study of 56 weeks duration with a 16-week randomised cross-over treatment period (S21400 300mg/d or Estraderm TTS1 50: 2 patches/ week continuously, 12 weeks with 2 parallel arms then a 4-week cross-over treatment period), followed by 40 weeks treatment with S21400 or reservoir patch according to patient's choice. Bone mineral density (BMD) was assessed at spine and hip using a dual X-ray absorptiometry (DXA) at baseline and after 56 weeks. Urinary type I collagen Ctelopeptides (CTX), serum osteocalcin (OC) and bone alkaline phosphatase (B-ALP) were assessed at baseline and after 12, 28 and 56 weeks of therapy. Results: 358 postmenopausal women aged 51.5 (4.5) years were included. After 12 weeks, mean CTX decreased by 31% and 28% in S21400 and patch groups respectively. Groups of longest treatment duration were compared at week 56. Due to the patient choice at W16, 232 were assigned to the S21400 group and 126 to the patch group. BMD increased signicantly (P<0.001 vs baseline in both groups) at the spine and hip. The percentage increase (mean-SD) was 2.1 (3.0) at the spine in both groups and 1.2 (2.4) compared to 1.1 (2.2) at the hip in S21400 and patch groups respectively. CTX, OC and B-ALP signicantly (P<0.001) decreased from baseline to W56 in both groups. At that time bone metabolism was normalised with a signicant decrease from baseline (P<0.001) of all markers: 56% and 53% for CTX, 24% and 25% for OC in S21400 and patch groups respectively. Conclusion: Pulsed estrogen therapy 300mg/d was as effective in normalising bone turnover and preventing bone loss after one year as a reference reservoir patch delivering 50mg/d.



BMD* Vertebral Fractures

Clinical Fractures

Morphometric Clinical Non Spine Hip Wrist Etidronate (423) Calcitonin (208) Vitamin D (213) Vitamin D (3270) Estrogen (78) Alendronate (994) Alendronate (2027) Watts Overgaard Dawson Chapuy Lufkin Liberman Black ++ + + + ++ ++ ++ Yes Yes Yes No Yes Yes Yes No No No No No No Yes No No Yes Yes No No Yes No No No Yes No No Yes No No No No No No Yes

453 (417). THREE YEARS PREVENTION OF POSTMENOPAUSAL OSTEOPENIA WITH ALFACALCIDOL DEXA ASSESSMENT OF EFFICACY 1, V. Radenkovic 1, R. Filipov1, H. 1, S. Milenkovic A. Dimic 2, B. Simic 2, 1Institute for Prevention, Treatment and Milovanovic Rehabilitation of Rheumatic and Cardiovascular Patients ``Niska Banja'' In Niska Banja Pharmaceutical Industry, 2``Zdravlje'' Leskovac, Yugoslavia We performed three years prospective study on the effects of management of postmenopausal osteopenia with active metabolite of vitamin D3-alfacalcidol. Hundred postmenopausal women aged 50 to 69 years were enrolled in the study. Inclusion criterion was bone mineral density (BMD) below normal values (T score less than 1, greater than 2.5) and the absence of the disease or treatment with medicament negatively inuencing BMD. BMD was evaluated using Lunar DPX densitometer before entering the study and every six months during the study. Basic parameters of phospho-calcic metabolism (blood and urinary calcium and phosphorus, alkaline phosphatase) were evaluated in the same manner. Treated group consisted of 53 women taking 0.5 micrograms of alfacal-cidol, and control group (without the treatment) consisted of 47 women with average age and postmenopausal status comparable to treated group. Alfacalcidol showed efcacy in controlling postmenopausal osteopenia BMD in treated group increased in the rst year, stagnated in the second and slightly decreased in the third year, compared to constant BMD loss in the control group. The efcacy was greater in older age (60 to 69 years). During the study only mild adverse events as temporary hypercalcaemia and renal calculosis were noted in 2% of patients. It can be concluded that alfacalcidol should be used to prevent postmenopausal osteoporosis in women with low BMD, especially in older age.

452 (416). EVIDENCE BASED MEDICINE IN OSTEOPOROSIS: A REVIEW OF SELECTED CLINICAL TRIALS H. P. Dimai1, S. Sieghart2, K. Klaushofer3, 1University Hospital, Graz, Styria, AUT; 2Kaiserin-Elisabeth Hospital, Vienna, AUT; 3 Ludwing Boltzmann Institute of Osteology, Vienna, AUT We conducted a review of several studies to determine the efcacy of several therapies in preventing boss loss, vertebral fractures and clinical fractures in postmenopausal women with low BMD and with existing vertebral fractures. Only published randomized studies in which both BMD and fractures are included as endpoints are included in the analyses. In general,

454 (418). THE EFFECTIVENESS OF OSSIN IN THE POSTMENOPAUSAL OSTEOPOROSIS A. V. Dreval1, L. B. Lazebnik2, L. A. Martchenkova1, R. S. Tischenina1, B. I. Minchenko1, C. B. Malitchenko2, L. B. Bondar2, 1 Moscow Regional Research Clinical Institute; 2Russian Medical Academy of Postgraduate Traning, Moscow, Russia The purpose of this investigation was to compare the clinical efcacy of Ossin (GRUNENTHAL) and other methods of therapy of the postmenopausal osteoporosis. 49 females aged 5168 years with postmenopausal osteoporosis received Ossin (sodium uoride 34.8 mg/day), or HRT, or combination of intramuscular calcitonin (50 MU/day) with lalpha-OH-D3 (0.5 mcg/day) for 6 month. The bone mineral density (BMD) was measured utilizing DEXA. Intensiveness of the back pane and laboratory follow-up (serum alkaline phosphatase, calcium and phosphorus) were also assessed. Results of treatment:
Ossin n=15 Lumbar BMD, % Proximal femur BMD, % Serum akaline phosphatase, U/l Serum calcium, mmol/l Serum phosphorus, mmol/l Back pane, units
*p<0.05, **p<0.01.

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456 (420). COMPARISON OF ALENDRONATE, CALCITONIN AND CALCIUM TREATMENTS IN POST-MENOPAUSAL OSTEOPOROSIS N. Dursun, E. Dursun, S. Yalc, University of Kocaeli, Kocaeli, Turkey The present study was planned to assess the safety, tolerability, and efcacy on bone mineral density (BMD), pain, quality of life and fracture risk of alendronate, calcitonin and calcium treatments. 84 Post-menopausal women with lumbar spine BMD 2 SD or more below the young adult mean were randomly assigned to one of 3 groups. Twenty-nine patients received oral alendronate 10 mg and calcium 1000 mg (alendronate group), 28 patients nasal salmon calcitonin 100 IU and oral calcium 1000 mg (calcitonin group), 27 patients oral calcium 1000 mg (calcium group) daily for one year. BMD was assessed by Dual Energy X-ray Absorbsiometry, pain by a Visual Analogous Scale (VAS), quality of life by Nottingham Health Prole. Both at 6 and 12 months mean increases in BMD were signicantly (p = 0.02, p<0.001) greater in the alendronate group than those of the other two groups at lumbar spine. No signicant difference was found between the groups at the femoral neck (p = 0.72, p = 0.72), trochanter (p = 0.44, p = 0.53) and Ward's triangle (p = 0.58, p = 0.78). Both at 6 and 12 months mean decreases in VAS were signicantly (p<0.001, p<0.001) greater both in the alendronate and calcitonin groups than that of the calcium group. No statistically signicant difference was found in any parameters of quality of life in the calcium group (p<0.05) but in calcitonin and alendronate groups (p>0.05). New vertebral fractures were seen 29.4% of the alendronate, 38.3% of the calcitonin, and 41.6% of the calcium groups, representing no statistical diference (p = 0.75). No side effects were seen in any of the patients during the follow-up.

HRT n=22 +3.80 +1.93 29.8* 0.12 0.32* 0.01

Calc.+1alpha-OH-D3 n=12 +1.61 +0.90 23.6 0.04 0.16* 1.3*

+7.06* +2.40 +15.0* 0.06* 0.17** 2.1*

Conclusion: in postmenopausal osteoporotic patients Ossin signicantly increases spinal BMD, stimulates the bone formation, improves the bone pain, and decreases calcium and phosphorus serum levels.

455 (419). KYPHOPLASTY FOR VERTEBRAL COMPRESSION FRACTURES S. Dudeney, I. Lieberman, F. Phillips, 1Cleveland Clinic, Cleveland, OH; 2University of Chicago, Chicago, IL, PURPOSE: To evaluate the early experience with inatable balloon tamp reduction and cement augmentation, ``Kyphoplasty'', in the treatment of osteoporotic vertebral compression fractures. BACKGROUND: Kyphoplasty involves the percutaneous penetration of the vertebral body with a cannula, followed by insertion of an inatable balloon tamp. The tamp restores the vertebral body back to its original height, while creating a cavity to be lled with bone cement. Cement injection is done under low pressure to reduce leakage. PATIENTS & METHODS: Forty-Seven consecutive kyphoplasty procedures were performed in 23 patients. The commonest indication was painful osteoporotic vertebral compression fractures. Mean duration of symptoms was 3.5 months. Painful levels were identied by correlating the exam with MRI ndings. The levels treated ranged from T7 to L5, the majority at the thoracolumbar junction. Pre and post-operative x-rays were compared to calculate the percentage height restored. Outcome data was obtained by comparing preoperative and latest postoperative SF36 data. RESULTS: There were no major complications related directly to use of this technique. The mean percentage height restored by the procedure was 39%. SF36 bodily pain scores improved from 13.6 to 47 (p = 0.004). Physical function improved from 28.7 to 55.3 (p = 0.02). CONCLUSIONS: Kyphoplasty is well tolerated and associated with improvement of pain, function, as well as restoration of vertebral body height.

457 (421). TIBOLONE TREATMENT PREVENTS TRABECULAR BONE LOSS IN THE VERTEBRA AND LONG BONES AND MAINTAINS CORTICAL BONE STRENGTH IN OVARIECTOMISED RATS WITH ESTABLISHED BONE LOSS A. G. H. Ederveen, H. J. Kloosterboer, Department of Pharmacology, N.V. Organon, The Netherlands Tibolone (Org OD 14) is a tissue specic 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 at ve 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 signicant decreases in bone density of the distal femur and BT/TV in the proximal tibia and lumbar vertebrae. A six-month treatment with tibolone prevented further loss of trabecular bone in the proximal tibia and in the lumbar vertebrae L1-L2. With the highest dose even a 13% increase in BT/TV was found as compared to start of treatment but this did not reach statistical signicance. In these osteopenic rats, tibolone prevented the signicant 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 tumover as indicated by the decrease in

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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 preservation of cortical bone quality.

by site (esophagus, stomach, duodenum). The table below indicates the incidence of AEs in these patient subpopulations.
Incidence of Upper GI Adverse Events Subpopulation History of Upper GI Disease NSAID/Aspirin Users H2/PPI Users N 3900 6336 2043 Placebo 29.0% 25.0% 50.0% RIS 5mg 29.5% 25.0% 51.5%

458 (422). SECONDARY PREVENTION IN OSTEOPOROSIS B. J. Edwards1, L. Taft2, 1Northwestern University; 2Northwestern Memorial Hospital, Chicago, IL, USA This purpose of this program is to identify and treat osteoporosis when fractures motivate a hospital admission. This disease is often under diagnosed, therefore this population of fracture patients are at increased risk of subsequent fractures. Baseline data (1998) demonstrated only 20% of inpatients with osteoporosis related fractures were treated, while only 10% of those seen in the ambulatory setting were treated. Funding was obtained from the Illinois Department of Public Health, and the Northwestern Memorial Foundation. This is the result of the rst six months of program development. The program counts with the participation of the Division of Geriatrics, Endocrinology and Rheumatology, and the Department of Orthopedics. Osteoporosis Consults are performed on all patients with fractures, x-ray evidence of osteopenia is gathered and risk factors assessed. Consultants discuss treatment options with the patients and the clinical nurse specialist carries out education. Outpatient follow-up is arranged and communication is carried out with the primary attending. To date over 50 fracture patients have been evaluated and treated. Fractures patients seen in the outpatient setting (100) have been hesitant to follow-up with the Osteoporosis Program, this may be due to a lack of awareness and further public education should be undertaken. Secondary osteoporosis is very common in this population (25%) chronic renal, pulmonary diseases and steroid use. Patients will have follow-up provided and an outcome analysis will be performed in the future. This program may serve as a model to increase awareness and provide secondary prevention in osteoporosis.
Fractures Hip fractures Extremity TJR Age 77 67 62 Prior Dx 20% 25% 29% Prior Rx 10% 20% 15% Xray osteopenia 80% 42% 43%

As shown from the table, in patients with a history of upper GI disease, use of NSAIDs/aspirin or use of H2 blockers/PPIs the incidence of overall upper GI adverse events was similar between the RIS 5mg group and placebo. Overall, endoscopy ndings were similar in the 3 treatment groups among the 497 patients with endoscopy. A `normal' nding was reported most frequently (58%) at all anatomic sites in all treatment groups. Gastric ulcers were the next most common observation (24%) and occurred with similar frequency across groups. In summary, risedronate was well-tolerated in patients at risk of upper GI disease or irritation, and was not associated with an increase in endoscopically-veried upper GI lesions.

460 (424). ALENDRONATE IN THE TREATMENT OF OSTEOPOROSIS IN MEN: MONITORING BY QUANTITATIVE ULTRASOUND SONOGRAPHY (QUS) AND FAN-BEAM X-RAY ABSORPTIOMETRY B. Frediani, A. Allegri, L. Storri, S. Bisogno, P. Falsetti, F. Baldi, C. Ridol, R. Marcolongo, Institute of Rheumatology, University of Siena, Italy Osteoporosis in men is an important clinical condition. We conducted an open, controlled study of 24 months duration, with the aim of evaluating the effect of Alendronate on Bone Mineral Density (BMD) and Stiffness (SI). 60 men, aged 3579 yr (mean:61 yr), with osteoporosis (femoral neck T-score<2,5) were enrolled and received either placebo (PBO, n=30, calcium 500mg per day) or Alendronate (ALN, n=30, 10mg per day). SI was measured by QUS (Lunar-Achilles+); BMD was assessed by fanbeam DXA (Lunar-Expert) of lumbar spine, hip and total-body. Longitudinal precision of BMD and SI has been assessed in PBO group. We obtained a normalized coefcient of variation (nCV) dividing short-term CV by annual decrease of BMD or SI and we calculated the Lowest Signicant Difference (LSD= 3 nCV). In the PBO group SI and BMD decreased signicantly; in ALN group SI and BMD increased signicantly. Mean percent change in BMD (or SI) and mean change in Tscore from baseline to 24 months

459 (423). GASTROINTESTINAL SIDE EFFECTS AND ENDOSCOPIC FINDINGS SIMILAR BETWEEN RISEDRONATE AND PLACEBO-TREATED PATIENTS I. Fogelman1, L. Moreland2, G. Woodson3, D. Mellstro m4, E. Boling5, W. Riskin6, D. Strauss7, K. Stevens7, M. Manhart7, 1 London, UK; 2Birmingham, AL, USA; 3Decatur, GA, USA; 4 Goteborg, Sweden; 5Rancho Cucamonga, CA, USA; 6Hollywood, FL, USA; 7Mason, OH, USA As part of the overall clinical program, the tolerability of risedronate (RIS) was evaluated by collecting adverse events (AEs) in 15,066 patients (>98% postmenopausal women) randomized to risedronate (2.5 or 5mg daily) or placebo daily for up to 3 years' duration. Patients were not excluded because of underlying gastrointestinal (GI) disorders or concomitant use of medications, e.g., NSAIDs, aspirin, H2 blockers, or proton pump inhibitors (PPIs). Endoscopy was performed at the investigator's discretion in 497 patients with GI complaints and was evaluated

PBO BMD-SI Os Calcis Spine (L2-L4) Femur Neck Total Body 3.2* 2.8* 3.6* 1.9* T 0.31 0.20 0.22 0.17

ALN BMD-SI 6.8*8 6.3*8 3.4*8 2.8*8 T 0.59 0.48 0.28 0.29 LSD 3.5

3.0 2.9


*p<0.01 vs baseline; 8p<0.01 vs PBO.

Depending on the skeletal regions evaluated, 50 to 70% of patients treated with ALN had a densitometric increase greater than LSD.

Decreased PBO Os Calcis Spine (L2-L4) Femur Neck Total Body 50.0 46.7 66.7 33.3 ALN 0 0 0 0 Unmodied PBO 50.0 53.3 33.3 66.7 ALN 33.3 30.0 43.3 50.0 Increased PBO 0 0 0 0 ALN 66.7 70.0 56.7 50.0

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sis; b) quantitative ultrasound measurement of os calcis is as useful for monitoring the effects of therapy as axial X-ray absorptiometry.

462 (426). EFFECT OF HEATED OYSTER SHELL WITH ALGAL INGREDIENT (ADVA-CAL) ON OSTEOPOROSIS T. Fujita, Y. Fujii, B. Goto, A. Miyauchi, T. Takagi, S. Ohgitani, Calcium Research Institute, Osaka and National Sanatorium Hyogo Chuo Hospital, Hyogo, Japan Calcium is better absorbed from Adva-Cal, oyster shell and seaweed Cystophyllum fusiforme heated in vacuo at 800C than from calcium carbonate as shown by the greater increase of urinary calcium excretion 1~4 hours after oral dose of 1000 mg and the rise of plasma ionized calcium, and more pronounced PTH suppression after ingestion of 300~600 mg calcium as AdvaCal than after ingestion of the same amount of calcium from milk or calcium citrate malate. Supplementation with 900 mg/day Ca as Adva-Cal increased spinal bone mineral density in anteriorposterior direction measured by DXA in 2 years, in osteoporotic elderly women with a mean age of 80 in a prospective doubleblind study over the same amount of calium supplied as calcium carbonate or placebo. In younger pre-and postmenopausal women with osteoporosis or osteopenia, 900 mg/day Ca as Adva-Cal increased distal radial trabecular bone and diaphyseal cortical bone desity measured by pQCT in 4 months, whereas placebo, the same amount of Ca as calcium carbonate or the same amount as heated oyster shell without algal ingredient had no effect. The increase of bone mineral density was more pronounced upon administration with etidronate, 200~400 mg daily for 2 weeks of 2 months. Adva-Cal appears to be effective to increase BMD in osteoporosis and osteopenia alone and in conjunction with other drugs.

In conclusion: a) Alendronate (10 mg per day) is eective in male osteoporosis; b) ultrasonometry of os calcis is as useful for monitoring the eects of therapy as axial X-ray absorptiometry.

461 (425). EFFECTS OF ALENDRONATE ON HEEL STIFFNESS AND AXIAL BMD IN PREVENTION AND THERAPY OF GLUCOCORTICOIDS INDUCED OSTEOPOROSIS B. Frediani, A. Allegri, L. Storri, S. Bisogno, P. Falsetti, F. Baldi, C. Ridol, R. Marcolongo, Institute of Rheumatology, University of Siena, Italy 120 patients, aged 3472, receiving continuously glucocorticoids (60 women with osteopenia: T-score <-land>2.5; 60 women with osteoporosis: T-score <2.5), were enrolled into an open study of 24 months duration, with the aim of evaluating the effect on Stiffness (SI) and the effect on Bone Mineral Density (BMD) of Alendronate (ALN: 10 mg per day) or Placebo (PBO: calcium 500 mg per day). SI was measured by os calcis ultrasonometry (Lunar-Achilles+); BMD was assessed by fan-beam X-ray absorptiometry (Lunar-Expert) of lumbar spine, hip and totalbody. Longitudinal precision of BMD and Stiffness has been assessed in PBO group. We obtained a normalized coefcient of variation (nCV) dividing short-term CV by annual decrease of BMD or SI and we calculated the Lowest Signicant Difference (LSD= 3 nCV). In the PBO groups SI and BMD decreased signicantly; in ALN groups SI and BMD increased signicantly. Mean percent change (BMD or SI) from baseline to 24 months
Osteopenia PBO Os Calcis Spine (L2-L4) Femur Neck Total Body 6.2* 5.0* 4.8* 4.3* ALN 3.3*8 2.2*8 1.28 1.08 Osteoporosis PBO 5.6* 4.7* 4.3* 4.0* ALN 4.2*8 3.3*8 1.58 1.88 LSD 2.0 1.9 2.3 1.6

463 (427). MEDICAL CARE COSTS ASSOCIATED WITH POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY N. I. Gavin1, R. L. Ohsfeldt2, J. M. Thorp3, J. W. Bray1, 1Research Triangle Institute, Research Triangle Park, NC; 2Eli Lilly and Company, Indianapolis, IN; 3University of North Carolina School of Medicine, Chapel Hill, NC Objective: This study was conducted to quantify components of medical care costs attributable to postmenopausal hormone replacement therapy (HRT). Methods: 77,252 patient-years of data over the years 198997 were obtained from Saskatchewan Health for 5762 women aged 55 or older who received HRT during 199094 and an equal number controls matched on age, residence, and marital status. Medical care costs for a minimum of 3 and maximum of 7 years after the index date for each woman were aggregated into components of annual costs. A regression model was used to estimate the association between the logarithm of annual costs and patterns of HRT use, controlling for prior patient medical care costs, marital status, rural/urban residence, and year. Results: compared to never-HRT-users, HRT users had higher annual total and medical management costs. Excess medical management costs ranged from $200 to $500 per annum (1997 Canadian dollars). These excess costs were related to excess rates of uterine and breast-related procedures. Osteoporosis and CHD-related costs were lower among HRT users than never-HRT users. These cost offsets ranged from $100 to $150 per annum. Conclusion: postmenopausal HRT appears to generate excess medical costs associated with its uterine and breast side effects. These medical management costs should be incorporated into future analyses of the cost-effectiveness of postmenopausal HRT.

*p<0.01 vs baseline; 8p<0.01 vs PBO.

Depending on the skeletal regions evaluated, 30 to 73% of patients treated with ALN had a densitometric increase greater than LSD.

Decreased PBO Os Calcis Spine (L2-L4) Femur Neck Total Body 93.3 86.7 66.6 73.3 ALN 0 0 0 0

Unmodied PBO 6.7 13.3 33.3 26.6 ALN 26.6 30.0 70.0 50.0

Increased PBO 0 0 0 0 ALN 73.3 70.0 30.0 50.0

Moreover we examined the inuence of glucocorticoid cumulative dose (GCD) on the eect of ALN. ALN increase SI and BMD irrespective of GCD. In conclusion: a) Alendronate (10 mg per day) is effective in prevention and in therapy of glucocorticoid induced osteoporo-

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464 (428). WHICH IS THE LEAST EFFECTIVE TRANSDERMAL ESTRADIOL DAILY DOSE FOR PREVENTING OF BONE LOSS IMMEDIATELY AFTER OOPHORECTOMY? COMPARISON OF HEEL ULTRASONOMETRY AND SPINE DXA DATA FROM A 2YEAR RANDOMIZED PROSPECTIVE STUDY R. Giorgino, P. Paparella, D. Lorusso, S. Mancuso, Catholic University, Rome, Italy The majority of available data on estrogen bone density effects in oophorectomized women are often biased by the lack of homogeneity of the populations in terms of time since surgery and bone turnover rate. Aim was to identify the least effective dosage of transdermal estradiol to prevent post-oophorectomy bone loss in healthy women. Eighty fertile women (age ranging 4353 years, serum FSH and E2 levels within premenopausal range), underwent hysterectomy and prophylactic oophorectomy for uterine broids. By the rst week after surgery, patients were randomized to receive alternatively 25, 50, 75. 100 mg/day transdermal estradiol continuously for two years. Duplicate calcaneus Ultrasonometry was performed on a Lunar Achilles at baseline and at 6 months intervals: spine BMD was measured by DEXA. Two-year data are available for 10, 15, 13 and 11 patients respectively in 25, 50, 75, 100 mg/day treated groups. A signicant decrease of both Stiffness Index and Lumbar Spine BMD was observed in 25 mg (open circles, *) and 50 mg treated groups (open squares, &) in the rst year after surgery: no further changes were deiected during the following period. In 75 mg (closed circles, *) and 100 mg E2 treated groups (closed squares, &), premenopausal Stiffness Index and Spine BMD were maintained during the 2 years of observation. In both groups, QUS Stiffness Index changes were signicantly greater than spine DXA in magnitude as shown by the AUC comparison (p<0.05 in each group). In conclusion, 75 mcg/day transdermal estradiol should be considered as the minimum effective dosage to prevent trabecular bone loss at least in the rst year after oophorectomy. Moreover, quantitative ultrasonometry is a valid alternative to DEXA spine BMD measurement for monitoring bone changes in the early period after oophorectomy.

465 (429). TREATMENT WITH ZOLEDRONATE OR SDZ PTS 893 RESTORES TRABECULAR ARCHITECTURE IN OVX MICE M. Glatt, Novartis Pharma AG, Bone Metabolism Unit, Basel, Switzerland The anti-osteoporotic effects of a highly potent anti-resorptive bisphosphonate and a bone anabolic PTH-derivative were tested in estrogen-decient DBA1 mice. For this purpose DBA1 mice were ovariectomized at the age of 6 weeks. Six weeks later, treatment was started and continued for another 4 weeks. 10 mg/kg BW of the bisphos-phonate zoledronate was injected s.c. once weekly, whereas 50 mg/kg BW of the PTH analogue SDZ PTS 893 was injected s.c. 5x/week. At the end of the experiment, animals were sacriced and tibiae, femorae and lumbar vertebrae dissected free and stored in 70% ethanol until microtomography was conducted at 9x9x9 mm3 nominal voxel resolution. In an additional experiment SDZ PTS 893 treatment was followed by a 4 week recovery period to determine whether the effects were reversible. Both zoledronate and SDZ PTS 893 signicantly increased bone volume fraction and this effect was accompanied by corresponding changes in other parameters such as Tb.N, Tb.Th, Tb.Sp and BS/BV. The most pronounced effects were found in the tibia, followed in descending order by femur and vertebra. The anabolic effects of SDZ PTS 893 were partially lost during the recovery period showing that in mice the maintenace of PTH-induced new bone would require continuous treatment.

466 (430). LONG TERM TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH CALCITONIN, ALENDRONATE, OR ALPHACALCIDIOL G. Gu ls ,en Demirel, N. Paker, H. Yilmaz, Istanbul Physical Medicine and Rehabilitation Centre, Istanbul, Turkey We compare the effect on the bone mineral density (BMD) measured with DEXA in postmenopausal women treated for three years with calcitonin or alendronate or vitamin D. A group of 378 postmenopausal women with established or densitometric osteoporosis (2 score <2.00) were randomly distributed in three groups. Hundred-thirty patients (mean age 56.74.6 years) were treated with salmon calcitonin (100 IU daily by nasal route), 114 patients (mean age 59.55.7 years) were treated with alendronate (5mg/day), 134 patients (mean age 61.25.3 years) were treated with alphacalcidiol (0.50 mcg/day). Every case received a suplement with 500mg of calcium. Before treatment, at one, two, and three years, they were studied densitometrically with the DEXA method on the level of the lumbar spine, and the proximal femur. Biochemical markers of bone formation and resorption were measured. The increase of BMD in lumbar spine was signicantly greater in women treated with alendronate compared to other groups in the rst two years, but not in the third year. The BMD in femur neck showed a statistically signicant increase only in the rst year in those treated with alendronate compared to other groups. Salmon calcitonin use is effective in relieving pain and bone resorption compared to other groups. This is the preliminary report of our ongoing study.

467 (431). ALENDRONATE INCREASES LUMBAR SPINE BONE MINERAL DENSITY IN PATIENTS WITH CROHN'S DISEASE. A DOUBLE BLIND CONTROLLED STUDY K. V Haderslev1, L. Tjellesen1, H. A. Srensen2, M. Staun1, 1 Rigshospitalet; 2Hvidovre Hospital, Copenhagen, Denmark Low bone-mineral density is a common complication of Crohn's disease and may lead to increased morbidity and mortality due to fractures. We investigated the effect of treatment with the

bisphosphonate alendronate-sodium on bone mass and markers of bone remodeling in patients with Crohn's disease. A 12-month double blind, randomized, placebo-controlled trial was performed to study the effect of 10-mg daily of alendronate. A total of 32 patients (9 men, 16 premenopausal and 7 postmenopausal women) with a bone-mass T-score below 1 of the hip or lumbar spine were studied. Exclusion criteria included active Crohn's disease (Van Hees index >150) and previous small bowel resections exceeding 100 cm. The main outcome measure was the difference in the mean percent change in bone mineral density of the lumbar spine measured by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in bone mineral density of the hip and biochemical markers of bone turnover, i.e., s-osteocalcin, urine pyridinoline and urine deoxypyridinoline excretion. The mean (SE) of the lumbar spine bone mineral density showed an increase of 4.61.2 percent in the alendronate group compared with a decrease 0.91.0 percent in patients who received placebo (P50.01). Bone mineral density of the hip increased by 3.31.5 percent in patients who received alendronate treatment compared with a smaller increase of 0.71.1 percent in the placebo group (P = 0.08). Biochemical markers of bone turnover decreased signicantly in the alendronate group (P50.001). Alendronate was well tolerated and there was no difference in adverse events between treatment groups. We conclude that treatment with alendronate 10 mg daily signicantly increased bone mineral density in patients with Crohn's disease and was safe and well tolerated.

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therapy decreases. As part of an evaluation study of screening women between the ages of 50 and 75 for osteoporosis in primary care, women already on HRT were not excluded. We report the ndings of those women, with particular emphasis on dosage and continuation of therapy after screening. 699 women were invited to attend the surgery for wrist BMD measurement using an Osteometer DTX 200, and to complete a validated clinical and risk factor questionnaire. 479 women (68.5%) responded and were scanned. 100 women were already on HRT (20.9%) of whom 66% were below age 60. All women with a T score <1.5 were reviewed. 27 were on HRT, 9 below age 60 with a predominant risk factor of an early (before age 45) menopause. Above age 60 early menopause and past fragility fracture were equally dominant. 4 women had a T score <2.5 who were not previously know to have osteoporosis. All the women except two, regardless of age, have continued on HRT therapy, 5 at an increased dose. 3 are taking additional bisphosphonate. The only signicant event has been a vertebral fracture in a woman of 53 with a previous fragility fracture, who stopped her HRT. Screening for osteoporosis appears to be a valuable aid to compliance with therapy in the presence of risk factors, particularly over the age of 60 when most women stop HRT.

470 (434). EFFECT OF VITAMIN D IN PATIENTS WITH DECLINING VERTEBRAL BONE MINERAL DENSITY DESPITE STABLE BISPHOSPHONATE THERAPY J. D. Adachi, G. A. Heckman, A. Papaioannou, McMaster University, Hamilton, ON, Canada Objective: To assess vitamin D supplementation in patients with osteoporosis (OP) not responding to stable bisphosphonate therapy. Methods: We analyzed the records of those OP patients being followed at our tertiary care centre who were taking stable bisphosphonate therapy and in whom lumbar spine BMD was measured annually for three years. Patients who took vitamin D 1000 IU daily were assigned to the intervention group, while control group patients did not. We compared the annual rates of change of lumbar spine (LS) bone mineral density (BMD) in the 2 groups. Results: In the intervention group, LS BMD declined by 0.99% in the year before vitamin D was started and rose 0.68% in the subsequent year. The difference of 1.67% was signicant (p = 0.008). The control group gained 1.65% the rst year and 0.88% the second, a change of 0.77% (p = 0.099). Baseline serum vitamin D levels were similar in both groups. Conclusion: Vitamin D 1000 IU daily can reverse the decline in LS BMD in patients not responding to stable bisphosphonate therapy.

468 (432). THE EFFECT OF LONG-TERM HORMONE REPLACEMENT THERAPY ON QUANTITATIVE ULTRASONOMETRY P. Hadji, G. Emons, K.-D. Schulz, Philipps University Marburg, Marburg, Germany This study was aimed to investigate the impact of a long-term hormone replacement therapy (HRT) on Quantitative Ultrasonometry. 2006 healthy peri-/post-menopausal women (mean age 52.210.3 years) were recruited in 5 German centers: 611 women (30%) had taken HRT, 1395 (70%) had not. About 90% of the HRT users were current users, the remaining 10% had recently stopped HRT (mean 1.5 4 months). Speed of sound, broadband ultra-sound attenuation and the stiffness index were compared in: (a) all users and non-users of HRT, (b) in HRT users and non-user controls matched for age, weight, height and body mass index, and (c) HRT users grouped in relation to the duration of HRT use and their matched controls. Women taking HRT had signicantly higher values (p<0.001) than non-users for all ultrasound variables, even after age, weight, height and body mass index had been controlled for. Women who had taken HRT for >3 years had signicantly higher values (p<0.001) than matched control women for all ultrasonometry variables, differences increased with the duration of use. Our results on a large cohort of healthy women showed that Quantitative Ultrasonometry differentiates HRT users from nonusers even after adjustment for confounding variables. These differences increased with the duration of HRT use. Therefore, QUS could be useful in both clinical trials and patient management.

471 (435). SIGNIFICANT REDUCTION OF PERIPROSTHETIC BONE LOSS BY AN EARLY, SHORT-TERM ALENDRONATE TREATMENT T. H. Hennigs, University of Frankfurt/M, Germany Bone loss around total hip arthroplasty (THA) is well recognized and occurs with all types of implants whether cemented or uncemented mainly in the rst six months after THA. The aim of our study was to show that a short but very early therapy of alendronate is efcient to prevent this bone loss. We randomized 44 subjects (f+m) aged 3361 with un-cemented THA and a lumbar BMD below normal average (T-score <0) but without suspected conditions affecting bone metabolism. A: Treatment with 10 mg/d alendronate oral over 10 weeks after the operation (n = 21), C: no treatment as the control-group (n = 23). The primary efcacy endpoint was the periprosthetic BMD in the Gruen zones (ROI) measured by DEXA (Hologic, 4500 A) after the 2., 4, 6, and 12. month, compared with the value measured in the rst week

469 (433). ARE WE PRESCRIBING ENOUGH HRT IN PRIMARY CARE? M. R. Harvey, S. Davidson, Cuckeld Medical Practice, Cuckeld, UK It is suggested that HRT provides adequate prevention for the development of osteoporosis when taken at least between the ages of 5060. After the age of 60 continuing compliance with

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after surgery. Even after two months there was a signicant difference between the two groups (ROI17): A 2.0% vs. C 4.2% (p<0.02), which was increasing during the follow up: A 1.2% vs. C 5.4% (p<0.01). The ROI 7 (calcar) showed the highest amount of bone loss and the highest difference: A 4.7%, C 14.7% (p<0.01), however, during the next months also in the group A the bone loss increased, but the difference remained still signicant: A 16.8% vs C 26.0% (p<0.029). Alendronate appears to reduce signicantly the periprosthetic bone loss due to the initial turnover of the operative irritation and underloading. The later remodeling due to stress shielding is not affected adversely by this mode of therapy.

474 (438). EFFECT OF CALCITRIOL ON BONE MINERAL DENSITY (BMD) IN CHINESE PREMENOPAUSAL WOMEN ON CHRONIC STEROID THERAPY A. Y. Y. Ho, I. Lambrinoudaki, D. T. M. Chan, C. S. Lau, R. W. S. Wong, S. S. C. Yeung, A. W. C. Kung, Dept. of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC The effect of chronic steroid therapy on BMD in premenopausal women with normal menstrual cycles and its treatment was evaluated in 81 lupus patients. They were randomly allocated to three groups: 1: 0.5mg calcitriol and 1200mg calcium daily, 2: 1200mg calcium and placebo calcitriol and 3: placebo. Baseline T-score at the lumbar spine was > 1 in 56.8% and 52.5 in 3.7% of the patients. At the end of two years, patients in the calcitriol group exhibited a signicant increase of 2.12.4% in the BMD at the lumbar spine when compared to baseline value (p<0.05). However this change was not signicantly different from the respective change in either the calcium (0.42.9%) or the placebo group (0.33.5%). No signicant changes were observed in any of the treatment groups in the BMD at the hip or at the radius. Alkaline phophatase remained stable in the calcitriol group but increased in both the calcium and placebo group. In conclusion, the benecial effect of calcitriol treatment in these premenopausal women was small, at least when it was instituted late in the course of steroid therapy. (This study is partly supported by Roche Pharmaceutical Company, Hong Kong Ltd.)

472 (436). THE EFFECTIVENESS AND TOLERABILITY OF ALENDRONATE IN CASE OF POSTMENOPAUSAL OSTEOPOROSIS S. Hepgu ler, S. Ozvurmaz, C. Oztu rk, K. Capaci, R. Aks ,it, Ege University Med. Faculty Physical Therapy and Rehab. Dept., Izmir, Turkey Aim of this study was to determine the effectiveness and tolerability of alendronate. 68 postmenopausal women with ages between 4177 years (59.198.08) were included in the study. According to DEXA, rutine blood, urine, liver functional tests, alkalene phosphotase, urea, creatinine, serum calcium and phoshorus, urine calcium, deoxypyridinoline as bone markers were investigated for all patients. Alendronate was given once a day with the treatment regimen including elementary calcium daily and Vit D monthly. At 12th month, signicant density increase was obtained in all patients' lumbar vertebrae, femoral neck and trochanter. Alkalene phosphotase, deoxypyridinoline values comparing to initial changed signicantly at 6th 12th months. At the end of the rst year, the bone mineral densities in lumbar vertebrae, femur neck and trochanter were found to be signicantly increased and this increase was at the rate of %4.5 in L1 4 vertebraes, %3.83 in femoral neck, %4.77 in femoral trochanter and %2.22 in wards triangle. Cessation of the treatment was not needed in cases of gastrointestinal side effects which were detected in 2 patients. As a result, alendronate is an effective drug in the treatment of postmenopausal osteoporosis.

475 (439). EFFECT OF CALCIUM AND VITAMIN D SUPPLEMENTATION ON BONE LOSS IN POSTMENOPAUSAL CHINESE WOMEN: A COMPARATIVE STUDY O. R. Huang, J. H. Lu, Q. Zhou, Y. J. Liu, Q. H. Wang, Center of Osteoporosis Prevention and Treatment, Shanghai Sixth People's Hospital, Shanghai, China Objective: To determine the effect of calcium and vitamin D supplementation on bone turnover and bone loss in postmenopausal Chinese women. Methods: Seventy-nine postmenopausal Chinese women, aged 5269 years, were divided into two groups. Group A: 34 cases, menopause duration 410 years, and group B: 45 cases, menopause duration >10 years. Both groups were administered 1.0g calcium and 400 IU vitamin D per day for one year. At baseline and at 12 months after treatment, the bone mineral density (BMD) of the lumbar spine (L24) and proximal femur was measured by dual-energy X-ray absorbtionmetry, and at baseline and at 3, 6, 12 months, serum and urinary markers of calcium metabolism were also examined. Results: After 12 months, in group B, the percentage change rates of BMD at the sites of femoral neck, trochanter, Ward's triangle and L24 were increased 1.58%, 2.10%, 4.26%, 1.33% respectively, P<0.05% for femoral neck, and P<0.001% for others; while in group A, the percentage change rates of the BMD at intertrochanteric sites were signicantly reduced (P<0.05), at other sites were insignicantly changed. As compared two groups, the percentage change rates of the BMD at trochanter, intertrochanter, Ward's triangle in group B were higher than those in group A (P<0.05). In both groups, the serum PTH and AKP levels all were signicantly decreased from baseline, there was no signicant difference between two groups at 12 months. U-pyridinoline/creatine (Pyd/Cr) ratios were changed 42.5% and 22.6% at 12 months, there was signicant difference between two groups (P<0.01). Conclusions: By 1.0 g calcium and 400 IU vitamin D supplementation, PTH secretion and bone turnover were signicantly inhibited, and the BMD of the hip in postmenopausal Chinese women with more than 10 years' menopause duration,

473 (437). THE EFFECTIVENESS OF ALENDRONATE IN THE PREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS S. Hepgu ler, H. Toprak, K. Capaci, C. Oztu rk, R. Aks ,it, Ege University Med. Faculty Physical Therapy and Rehab. Dept., Izmir, Turkey The aim of this study was to determine the preventive effect of alendronate, a spesic inhibitor of bone resorbtion, in postmenopausal osteoporosis. Twenty-one postmenopausal osteopenic women with ages between 3170 years (mean 56.338.82) and whose T scores were found to be between 1.00 and 2.50 in DEXA tests were included in the study. Rutine blood, urine, liver functional tests, alkalene phosphotase, urea, creatinine, serum calcium and phoshorus, urine calcium, deoxypyridinoline as bone markers were investigated. Alendronate was given every other day with the treatment regimen including elementary calcium daily and Vit D monthly. At 12th month, statistically signicant density increase was obtained in all patients' lumbar vertebrae, femoral neck and trochanter (p<0.05) and this increase was at the rate of %10.72 in L14 vertebraes, %2.85 in femoral neck, %7.56 in femoral trochanter and %2.48 in wards triangle. Alkalene phosphotase, deoxypyridinoline values comparing to initial changed signicantly at 6th 12th months. During the study, because of gastrointestinal side effects two patients and because of allergic reactions one patient had to stop the treatment. As a result, alendronate is an effective drug in the prevention of postmenopausal osteoporosis.

but not in whom with not more than 10 years' menopause duration, were signicantly increased.

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478 (442). EFFECTS OF RALOXIFENE AND ALENDRONATE ON BONE MINERAL DENSITY AND BONE TURNOVER MARKERS IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS O. Johnell1, Y. Lu2, E. Seeman3, J. Reginster4, W. Scheele2, Universitetssjukhuset MAS, Malmo, Sweden; 2Eli Lilly and Company, Indianapolis, USA; 3Austin & Repatriation Medical Centre, Heidelberg, Australia; 4Polycliniques Universitaires L. Brull, Liege, Belgium

476 (440). ORAL CALCITONIN PREPARATION WAS NOT PROVED EFFECTIVE IN THE YOUNG JAPANESE MALES. THE PHASE I PILOT STUDY A. Itabashi1,2, K. Nemoto1,2, M. Tsuboi2, T. Kohno3, M. Koida3, K. Iwamitsu4, 1Saitama Medical School, Saitama; 2NS Clinic, Tokyo; 3 Setsunan University, Osaka; 4Towa Pharmaceutical Company, Osaka, Japan Calcitonin is a potent inhibitor of osteoclastic bone resorption and has been used for the treatment of osteoporosis, Paget's disease and hypercalcemia of malignancy. Nasal calcitonin is available in US and EU countries while only injectable form is approved in Japan. Oral salmon calcitonin manufactured by Cortecs is a unique product. Salmon calcitonin is emulcied with phospholipids and gelatine-capsulated. It is dissolved in the intestine and absorbed into lymphatic system. If proved effective, it will be a very useful preparation. We conducted a phase I study in Japan. Forty healthy young Japanese males were recruited after informed consent. Each group, consisted of eight candidates, took 200IU, 400IU, 800IU, 1600IU of oral salmon calcitonin or placebo before breakfast. Plasma salmon calcitonin concentrations were serially measured using very high sensitive salmon calcitonin EIA developed by Kohno. Urinary crosslaps (CTx) and deoxypyridinoline (DPD) were also measured. Even after the ingestion of the highest dose, salmon calcitonin was not detected in the plasma. Neither urinary CTx nor DPD excretion was suppressed greater than those in the placebo group as a diurnal variation. Our assay system has been validated in the case of nasal salmon or eel calcitonin preparations. These disappointing results show that oral salmon calcitonin preparation developed by Cortecs has not been proved effective in the short term phase I pilot study in the Japanese young males.

Both raloxifene RLX) and alendronate ALN) increase bone mineral density (BMD), decrease bone turnover and prevent new vertebral fractures. The purpose of this randomized, double-blind study is to assess the effects of placebo (PL, N=81), RLX 60mg/d (N=82), ALN 10 mg/d (N=83), or RLX+ALN (N=84) in postmenopausal women with osteoporosis. BMD and the bone turnover markers N- and C-telopeptide normalized to creatinine (NTx/Cr, CTx/Cr), osteocalcin (OC), and bone-specic alkaline phosphatase (BSAP), were assessed at baseline, 6 and 12 months. Overall differences among groups and changes within groups were estimated by ANOVA and t-test respectively. Possible interactions in the effects of RLX and ALN were tested by two-way ANOVA. Correlation between BMD and bone markers was estimated by Spearman's coefcient. Within-group statistical signicance at p<.05 is denoted by *. At 12 months, all changes in BMD and bone markers were different between each active treatment group and PL, and between RLX and RLX+ALN (p<0.05). The increase in femoral neck BMD was greater in the RLX+ALN group compared with ALN (p<0.02). The effects of RLX and ALN are additive, since interaction effects between RLX and ALN were not statistically signicant at P=0.10. Changes in lumbar spine BMD were correlated with changes in BSAP and CTx/Cr at 6 months in the RLX group, and with OC at both time points in the ALN and RLX+ALN groups. RLX+ALN may reduce bone turnover more than RLX or ALN alone, resulting in greater BMD increment. Whether this difference reects better fracture risk reduction is unknown.

Mean Percentage Change from Baseline to 12-Month Endpoint PL RLX 2.1* 1.7* 17.8* 31.2* 25.5* 24.4* ALN 4.3* 2.7* 40.9* 49.5* 38.8* 45.3* RLX+ALN 5.3* 3.7* 54.3* 69.3* 48.8* 48.4*

477 (441). THE POWER PROGRAM: AN EVIDENCE-BASED SELF-MANAGEMENT PROGRAM FOR OSTEOPOROSIS IN THE ELDERLY T. A. Izukawa1, L. Bernick1, A. Stephens2, 1Baycrest Centre for Geriatric Care, University of Toronto, Toronto, ON, Canada; 2 North York General Hospital, Toronto, ON, Canada Osteoporosis as a chronic illness ts well into the self-management concept. We will review the literature on self management and present a model for a self management program for individuals living with osteoporosis. The POWER (Promoting Osteoporosis Wellness through Education, exercise and Resources/research) program is a short term, community-based self-management program aimed at Seniors diagnosed with osteoporosis. It is evidence-based, and emphasizes the client's role in managing their condition, through education, skills and assistance with some areas of personal planning and goalsetting. Aspects of the program that follow the self management philosophy include the general education, nutrition education and exercise education components, along with specic advice on lifestyle modication and an emphasis on injury prevention planning. The program is taught by an interdisciplinary team. Evaluation has been built in. Another unique aspect of the program has been the partnership between a community hospital, a teaching and complex continuing care hospital, ethnic-based community health and skilled nursing home facilities and the Dept. of Public Health, in conjunction with sponsorship by private companies and government funded agencies. This unique model may be an indication of the future direction of health care provision for seniors with chronic illnesses.

Lumbar Spine BMD Femoral Neck BMD NTx/Cr CTx/Cr OC BSAP

0.06 0.31 26.9* 4.4 5.0 10.6*

479 (443). EFFECT OF ALENDRONATE AND COMBINED HORMONE REPLACEMENT THERAPY IN TAIWANESE POSTMENOPAUSAL OSTEOPOROTIC WOMEN Jung-Fu Chen1, Jao-San Huang2, Jen-Der Lin2, 1Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Kaohsiung; 2Taoyuan, Taiwan, R.O.C. PURPOSE Osteoporosis becomes to be a serious health problem for Taiwanese older women and effective treatments are needed. This study is to evaluate the effect of alendronate and combined hormone replacement on the different site of bone mineral density (BMD). PATIENTS AND METHOD Seventy-three Taiwanese postmenopausal women, age (meanSE, 661), with established osteoporosis (T 42.5) were enrolled. Patients were divided into three groups, including the control group (n=25) received 900 mg elemental calcium, the alendronate group (n=32) received alendronate (10mg) daily and calcium, the combined therapy group (n=16) received alendronate (10 mg), premarin (0.625 mg), provera (5 mg) and calcium daily. BMD was measured by dual-

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energy X-ray absorptiometry (Norland XR36) at the lumber spine and femoral neck before treatment and one year after, compared for baseline and percentage changes inbetween. RESULTS The difference of BMD in the alendronate group who increased in the lumber spine by 6.9% and the femoral neck by 3.8%. For patients who received combined alendronate and hormone therapy, the increase were 8.8% and 3.8% in lumber spine and femoral neck. The groups with calcium alone decreased 1.5% and 0.7% in lumber spine and femoral neck respectively. The women receiving alendronate had signicant BMD increase in lumber spine (p<0.00), and femoral neck (p = 0.36) compared with control group, and the women receiving combined therapy had also signicant BMD increase in lumber spine (p<0.00) and femoral neck (p = 0.39) compared with control group after 1 year of therapy. CONCLUSION This study conrmed alendronate to be an very effective treatment for Taiwanese postmenopausal osteoporotic women, and additive effect of combined alendronate and hormone replacement therapy was seen in selected subgroups.

groups in which the rst group was the base group, the second group was sham operated, and the other groups were surgically ovariectomized. After 24 hours of ovariectomy, they were either untreated (ovx) or S.C. injected with 17-b estradiol (E2) 30 mcg/ kg/24hours or low-dose calcitonin (LDC) (Miacalcic1amp, by Novartis-Pharma used) 10 IU/kg/48 hours or high-dose calcitonin (HDC) 20 IU/kg/48 hours. At the end of the six-week period, bone density was measured by DEXA, and all animals were sacriced. Plasma was collected to measure osteocalcin (OC), estrogen, parathormon (PTH), calcium (Ca) and inorganic phosphate (iP) levels. The femurs of the rats were harvested for histomorphometric evaluation. While serum estrogen levels were signicantly lower in all the groups compared with the base group, the levels of OC, PTH, and Ca did not differ. ip levels were signicantly low in OVX and E2 groups. BMD of the spine and proximal femur was found to be substantially low in OVX group. BMD of the spine seemed to be restored both E2 and LDC and HDC treatments. Although there was also an increase in BMD of proximal femur, it was not achieved statistical support. Histomorphometric evaluation revealed that relative trabecular volume was signicantly high in LCT and HCT groups. However, relative and absolute osteoid volume did not differ as expected. In conclusion, calcitonin treatment restores bone lost in ovariectomized rats, and these results in the animal model if estrogen depletion suggest that calcitonin provides an important alternative therapy in postmenopausal osteoporosis.

480 (444). EFFECT OF COMBINATION THERAPY WITH ETIDRONATE AND ALFACALCIDOL AFTER ALFACALCIDOL THERAPY ALONE ON SPINE, RADIUS AND CALCANEUS BONE MINERAL DENSITY IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN H. Katagri, H. Hagino, R. Teshima, Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan Few data are available on the effects of combination therapy for thetreatment of osteoporosis. The aim of this study was to investigate the effects of a combination of cyclical etidronate and alfacalcidol on spine, radius and calcaneus bone mineral density (BMD) in postmenopausal osteoporotic women having been treated with alfacalcidol alone. We examined this therapy among 13 postmenopausal osteoporotic women having been treated with alfacalcidol alone for more than 5 years. Etidronate (200 mg/day) was administered orally for 14 days, beginning 10 to 12 weeks after discontinuation of alfacalcidol. Alfacalcidol (0.5 m g/day) was administered orally for the subsequent 10 weeks. Treatment cycles were repeated about eight times for two years. Lumbar spine and distal radius BMD were measured by DXA three times; two years before starting, at baseline (just starting) and at one years of this treatment. The measurement of calcaneus BMD was performed using SXA. The mean increase in lumbar spine BMD was 4.4%/yr after this treatment, which was signicantly different from the previous alfacalcidol therapy alone, where there was a 3.7%/yr change. The distal radius BMD increased 6.3%/yr, which was signicantly greater than the 0.9%/yr increase before this treatment. The calcaneus BMD increased 3.7%/yr, while before this treatment the BMD decreased 2.6%/yr. These data indicate that a combination of cyclical etidronate and alfacalcidol is better than alfacalcidol alone in terms of changes in BMD at all measurement sites. Further studies are needed to determine if the combination is more effective than cyclical etidronate alone.

482 (446). INTRAVENOUS PAMIDRONATE THERAPY IN OSTEOPOROSIS J. Kekow1, W. Flach2, T. Linde1, 1Clinic of Rheumatology, University of Magdeburg, Vogelsang/Magdeburg; 2Department of Laboratory Medicine, Vogelsang, Germany Oral bisphosphonates are frequently used to treat osteoporosis. In patients experiencing adverse GI effects from oral administration, parenteral bisphosphonates are recommended. We report on 25 patients (15 women, 10 men) treated with intravenous (i.v.) pamidronate after failure of ether oral alendronate or etidronate therapy as dened by a lack of BMD increase under oral bisphosphonate therapy for at least 1 year. The group c