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ABSTRACTS P-185 to P-235 POSTER PRESENTATIONS
Posters will be on display throughout the symposium, but will be attended by their presenting authors as follows: Odd numbers on Friday 11:00 - 12:00, Sunday 11:00 - 12:00
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Osteoporosis: Evaluation and Treatment OSTEOPOROSIS: MISSED OPPORTUNITIES IN AN IMPORTANT TARGET GROUP M. G. Smith*, P. Dunkow, D. M. Lang South Manchester University Hospital NHS Trust, Wythenshawe Hospital, Manchester, UK Introduction: All patients seen in a hospital fracture clinic with an osteoporotic fracture should be advised of the diagnosis of osteoporosis and their primary care team informed of the need for follow-up. We undertook a retrospective study to assess the percentage of patients with an osteoporotic distal radial fracture that had any subsequent investigation or treatment for osteoporosis. Methods: All patients over 50 years old who sustained a distal radial fracture after a simple fall, and a subsequent fractured neck of femur were identified over a 7-year period. Evidence of any treatment for, or investigation of, osteoporosis between the initial radial fracture and subsequent neck of femur fracture was recorded. Results: 74 patients met the above criteria: 7 male and 67 female, median age 83 (54 to 99). Eight percent of cases were on treatment for osteoporosis at time of their osteoporotic wrist fracture. A further 8% had evidence of treatment for, or investigation of, osteoporosis commenced by time of their femoral neck fracture. 84% of patients received no advice, investigation or treatment. Discussion and Conclusion: As orthopaedic surgeons we have a duty to inform the primary care team of the need to follow-up patients with osteoporotic fractures. There is a significant reduction in patient morbidity and mortality, and cost benefit to health service providers when osteoporosis is treated in target groups. Significant efforts need to be made to increase the percentage of patients that receive investigation of, or treatment for osteoporosis following an osteoporotic distal radial fracture. SOYBEAN ISOFLAVONES AND RALOXIFEN IN POSTMENOPAUSAL WOMEN WITH BONE MASS LOSS M. A. Bazarra-Castro1*, A. Bazarra-Fernández2 1University of Santiago de Compostela, Spain 2University of La Coruña. Health Sciences Dept., Spain Statement of purpose: Determining if there are differences in using soybean isoflavones and raloxifen on bone mass loss in postmenopausal women. Statement of method: we studied for 20 months 24 women who were 45 to 62 years old at base line, were within 1 and 10 years of menopause, and had a bone mineral density at the lumbar spine between 150 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 women, 12 were assigned to therapy with soybean isoflavones 80 mg and 12 were treated with raloxifene HCL 60 mg. The SPSS programme was used for statistical analysis. Summary of 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 statistically significant difference was found among the groups as bone mineral density at the lumbar spine. Conclusions: It is necessary to carry out a wider study but it seems that raloxifene HCL contribute advantages versus isoflavones therapy to decrease the bone mass loss in postmenopausal women at least at lumbar spine. BONE MINERAL DENSITY AND NEW GEOMETRY PARAMETERS ASSESSMENT IN CLINICAL PRACTICE T. O. Chernova Endocrinology Research Center, Moscow, Russia During the past decades the implementation of bone densitometry in clinical practice made it possible to assess BMD in health and disease and to monitor the treatment. The new modalities of assessment of upper neck regions and AHA appeared in densitometry practise. PURPOSES: 1) To assess the clinical value of dual-femur acquisition in comparison with single-femur acquisition and the clinical value of spine densitometry in cases of bone deformities; 2) To assess the perspectives of upper neck regions and AHA in clinical practice. METHODS: About 9000 patients were examined over the period of 6 years. We assessed all parameters of BMD and body composition using DEXA (Lunar Expert XL, USA). 2.500 patients were assessed using the new densitometer Prodigy Oracle (Lunar GE, USA). CONCLUSIONS: 1) There were clinically insignificant differences between dominant and non-dominant proximal femur DEXA results. Dual-femur assessment is very important in special cases of problems with one femur or spine deformities and in cases of early diagnostics of osteopenia among risk population. The obtained data show that in cases of kyphosis, scoliosis, etc the spine acquisition has no clinical significance and is not acceptable for the therapy monitoring; 2) Upper neck region is very informative and BMD in this region is lowest, as in case of Wards region, 3) Body composition is a perspective research in the assessment and therapy monitoring of obesity along with the possible future implementation in the research of aging, insulin resistance and meno- and andropause treatment. 4) The implementation of new AHA determination is extremely interesting and its significance has to be determined. HOW TO IMPROVE THE BONE STRENGTHENING EFFECT OF EXERCISE C. H. Turner*, I. Alam, S. Tanaka School of Medicine, Indiana University, Indianapolis, USA Stochastic resonance, in which noise enhances the response of a nonlinear system to a weak signal, has been observed in various biological sensory systems. We speculated that bone formation in response to mechanical loading could be enhanced by adding noise (vibration) to a standard exercise regimen. To test this hypothesis, three different loading regimens were applied to the ulnae of mice: (1) high amplitude, low frequency sinusoidal loading at 2 Hz with an amplitude of 3 N to simulate exercise; (2) low amplitude, broad frequency vibration with frequency components 0- 50 Hz and 0.3 N of mean amplitude; (3) the sinusoidal wave combined with vibration (S+V) to invoke stochastic resonance. The simulated exercise regimen induced new bone formation on the periosteal surface of the ulna, however the addition of vibration noise with exercise enhanced the osteogenic response by almost 4-fold. Vibration by itself had no effect on bone formation. It was concluded that adding low magnitude vibration greatly enhanced bone formation in response to loading, suggesting a contribution of stochastic resonance in the osteogenic response. These findings demonstrate that the bone strengthening effects of exercises can be improved substantially if vibration is added to the exercise regimen.
SKELETAL CALCIUM/PHOSPHORUS RATIO AS A DIAGNOSTIC INDEX FOR BONE DISORDERS M. Tzaphlidou School of Medicine,University of Ioannina, Ioannina, Greece Although the major elements in bone are calcium and phosphorus, most chemical measurements of the skeleton are optimized for detecting calcium. Usually, measurements for calcium or phosphorus are performed independently. The calcium/phosphorus ratio is not often calculated. In vitro measurements for calcium and phosphorus concentrations were performed in intact cortical and trabecular bone samples from the femoral neck and iliac crest of healthy women aged from 15 to 55 years. For these measurements neutron activation analysis was used. Calcium/phosphorus ratios were calculated by using the mean concentration values found in calcium and phosphorus separately. In all cases, the standard deviation and coefficient of variation for calcium/phosphorus ratio was lower than those for calcium and phosphorus separately. This points to a specificity for the calcium/phosphorus ratio which is better than those of calcium and phosphorus concentrations and this ratio may be therefore provide greater reliability for diagnosis of bone disorders than the calcium and phosphorus values. In vivo, neutron activation estimation of calcium in bone needs high radiation doses while for phosphorus there is only a theoretical possibility. Nowadays, we can measure bone calcium/phosphorus ratio in vivo by X-ray absorptiometry. The calcium/phosphorus ratio of the right radius was measured in 20 osteoporotic females, aged 56 to 72 years. The diagnosis of osteoporosis was based on clinical findings. A mean calcium/phosphorus ratio of 1.29 was found. This ratio was significantly lower (p<0.01) than that of 1.71 from 50 normal adult females, aged 44 to 68 years. The coefficient of variation for the in vivo measurements was 2.3%. Up to now the most common way to evaluate the risk of fracture upon osteoporosis was based on the assessment of bone mineral density by dual X-ray absorptiometry. However, recent reports indicate that the data obtained by this method are not sufficiently accurate. In this respect, bone calcium/phosphorus ratio can be used as a clinical indicator. TWO-YEAR TREATMENT WITH RALOXIFENE PLUS CALCIUM AND VITAMIN D3 SUPPLEMENTATION CONTRIBUTES TO INCREASED BONE MINERALIZATION IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS G. Boivin1*, K. D. Harper2, S. Sarkar2, K. V. Pinette2, P. Lips3, S. M. Ott4, P. J. Meunier1 1INSERM Unite 403, Lyon, France 2Lilly Research Laboratories, Indianapolis, Indiana, USA 3Vrije Universiteit Medical Centre, Amsterdam, The Netherlands 4University of Washington, Seattle, Washington, USA The selective estrogen receptor modulator (SERM) raloxifene has been shown to increase BMD and reduce the risk of vertebral fracture in postmenopausal women with osteoporosis (Delmas, JCEM 2002). In this study, we report the results of the first prospective longitudinal study to evaluate the mean degree of mineralization of bone (MDMB) in a subpopulation of patients enrolled in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial who had consented to participate in the biopsy study (Ott, JBMR 2002). Patients were randomly assigned to one of three treatment groups: placebo (n=24), raloxifene 60 mg/day (RLX60, n=22) or raloxifene 120 mg/day (RLX120, n=18), and all patients received calcium (500 mg) and vitamin D3 (400-600 IU) supplementation for the duration of the study. Iliac crest biopsies were taken at baseline (prior to the initiation of the study) and following two years of treatment. Quantitative microradiography (Boivin & Meunier, CTI 2002) was used to analyze the biopsy specimens, revealing a mean percent increase in MDMB following treatment with RLX60 of 7.6%, 6.5% and 7.0% for cortical, trabecular and total (cortical + trabecular) bone respectively, compared to baseline. A similar increase in MDMB was observed following treatment with RLX120. However, the numerical increases in MDMB following raloxifene treatment were not found to be significantly different from the calcium and vitamin D3 supplemented placebo group. The mean percent increase in MDMB for the placebo group was 4.9%, 5.4% and 5.0% for cortical, trabecular and total bone respectively, compared to baseline. When compared to placebo, raloxifene treatment shifted the sample distribution to higher values of mineralization. RLX60 increased the mineral content of cortical, trabecular and total bone by 36%, 16%, and 29% respectively. Estimated increases in mineral content were determined using an ANCOVA model adjusted for differences in baseline mineralization. There are data to support that the increase in distribution to higher levels of MDMB, and the overall percent increase in MDMB compared to baseline following RLX treatment, closely resembles the degree of mineralization of physiologic premenopausal bone. CORRECTING FOREARM BONE MINERAL DENSITY MEASUREMENT FOR AGE AND WEIGHT INCREASES ITS VALIDITY IN THE DIAGNOSIS OF OSTEOPOROSIS D. Picard*, J. P. Brown, M. Couturier, L. Rosenthall, J. Lévesque, M. Dumont, L-G. Ste-Marie, A. Tenenhouse, S. Dodin Quebec Osteoporosis Study Group, Canada Peripheral bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has already been shown as an accurate method for the diagnosis of osteoporosis, especially in distant areas, where central DXA is not available. The aim of this study was to evaluate the increased ability of peripheral BMD to predict central BMD after being corrected for two clinical factors that can affect bone mass, age and weight. We determined BMD of the spine (s), femoral neck (fn) (1 Hologic, 3 Lunar), as well as proximal (pfa) and distal forearm (dfa) with Norland pDXA in 831 women aged 20 to 85 years. The sBMD and fnBMD were converted to a Hologic base and t- score were then derived using data from the Canadian Multicentre Osteoporosis Study (CaMos). Regression analyses were then applied on the gold t-score (the lowest between s and fn) where age, weight and subsequently the forearm t-scores were retained as the main predictors. Forearm t-scores were then corrected according to the regression formula obtained. The performance of forearm DXA and corrected forearm DXA as a diagnostic test for osteoporosis was evaluated by ROC curves where a positive case was defined as a t-score <= -2.5 either on s or fn. The optimal cutoff points were selected on the basis of highest sensitivity and specificity. Results are presented in the table below.The main improvement of correcting the forearm t-scores is observed through a reduction of the false positives by 13% and 23% respectively for pfa and dfa. Furthermore, most of the false positives are in fact osteopenics as only 7 and 4 respectively for pfa and dfa present a central t-score > -1. Hence, this study suggests that correcting forearm t-scores for age and weight, improves their validity in the diagnosis of osteoporosis, especially through a substantial reduction of the proportion of subjects falsely identified as osteoporotics.
LS BMD INCREASE ACCOUNTS FOR ONLY A FRACTION OF THE VERTEBRAL FRACTURE REDUCTION AT 1 YEAR: RESULTS FROM THE VERT AND HIP TRIALS OF RISEDRONATE N. B. Watts1*, T. D. Johnson2, Z. Li2, C. Kasibhatla2 1University of Cincinnati Bone Health and Osteoporosis Center, Cincinnati, USA 2Procter & Gamble Pharmaceuticals, Mason, USA The objective of this analysis was to establish and quantify the relationship between changes in LS BMD and vertebral fracture risk in a population of osteoporotic women taking risedronate. The analysis included patients from the VERT and HIP studies, who were enrolled either on the basis of low LS BMD (T-score < -2.0) and at least one prevalent vertebral fracture (VERT-NA) or two prevalent vertebral fractures (VERT-MN) or FN T-score < -4 or -3 with at least one nonskeletal risk factor for hip fracture (HIP studies). Patients were randomized to receive either placebo or risedronate 2.5 mg or 5 mg daily. In addition patients also received 1000 mg/day calcium supplementation and vitamin D, if baseline levels were low. The Cox regression analysis was used to estimate the overall treatment effect and the treatment effect explained by LS BMD at 1 year. Only patients who had a post-baseline BMD measurement prior to 1 year and a known fracture status were included in the analysis. There were 70 patients who had an incident vertebral fracture, out of a total of 1739. The overall risk reduction over 1 year is 60% (CI: 54-65). The proportion of fracture risk reduction explained by LS BMD increase over 1 year was estimated to be 7%. In conclusion this analysis showed that LS BMD increase only weakly contributes to vertebral fracture risk reduction at 1 year. TWO YEAR VERTEBRAL FRACTURE RISK REDUCTION WITH RISEDRONATE 35 MG ONCE-A-WEEK N. B. Watts1*, R. Lindsay2, Z. Li3, C. Kasibhatla3, J. Brown4 1University of Cincinnati Bone Health and Osteoporosis Center, Cincinnati, USA 2Regional Bone Center, Helen Hayes Hospital, West Haverstraw, USA 3Procter & Gamble Pharmaceuticals, Mason, USA 4Centre de Recherche du CHUQ, Quebec, Canada A large active-controlled clinical trial demonstrated the non-inferiority of the once- a-week dose form of risedronate compared to the daily dose at 1 year. The primary endpoint of this trial was change in lumbar spine BMD over 1 year with safety evaluated over 2 years. To assess vertebral fracture risk reductions in the absence of a placebo group, historical controls were generated matching patients from the risedronate Phase III vertebral fracture studies to patients in the Once-a-Week (OaW) trial. Important baseline characteristics were matched between the historical placebo group and the 35 mg once-a-week group (mean lumbar spine T-score: -3.17 to -3.03; mean age: 67.6 to 68.1; % w/ prevalent fractures: 34.8% to 35.7%). The vertebral fracture risk reduction with risedronate 35 mg OaW was statistically significant over 2 years compared with the matched historical placebo group (vertebral fracture incidence: historical placebo, (n=114) 10.5%, 35 mg risedronate OaW (n=403) 1.5%, relative risk=0.13, 95% CI:0.04-0.38). A similar vertebral fracture risk reduction was also observed with risedronate 50 mg OaW. Previously, we demonstrated that vertebral fracture risk was significantly reduced over 1 year using the same placebo control (RR=0.23, 95% CI:0.05-0.91, p=0.018) for the 35 mg once- a-week dose. These results and the results over the first year of the study support the anti-fracture efficacy of risedronate OaW treatment in postmenopausal women with osteoporosis. These results also suggest that appropriately matched historical controls may be useful to derive anti-fracture efficacy when placebo arms in prospective clinical trials are unavailable. BONE HISTOLOGY AND HISTOMORPHOMETRY IN A 2-YEAR RISEDRONATE STUDY COMPARING DAILY AND WEEKLY DOSING R. R. Recker1*, E. W. Sod2, Z. Li2, A. A. Chines2 1Creighton University Osteoporosis Research Center, Omaha, USA 2Procter & Gamble Pharmaceuticals, Mason, USA The risedronate once-a-week study compared the efficacy of daily 5 mg to 35 and 50 mg once-a-week treatments in postmenopausal osteoporotic women. The primary endpoint of the non-inferiority study was changes in lumbar spine BMD at 1 year with safety evaluated over 2 years. Both weekly doses were non-inferior to 5 mg daily in lumbar spine BMD. As part of the safety evaluation, iliac crest biopsies were obtained in a subset of patients at baseline (n=109) and year 2 (n=86). No histological abnormalities were observed in any of the risedronate-treated groups, suggesting normal bone quality even at the highest tested dose of 50 mg once- a-week. Double tetracycline labeled surfaces were observed in all endpoint biopsies. Trabecular and cortical bone structural parameters were generally unchanged and similar among the treatment groups. Bone turnover was significantly and similarly reduced in all groups by approximately 65%. All groups showed increased formation periods (FP) with significant changes in the 5 mg daily and 35 mg weekly groups. Consistent with previous 5 mg/d data, median mineralizing surface was approximately 1.5% in all groups after 2 years of therapy. Median change in mineral apposition rate (MAR) was positive in all groups and reached statistical significance in the weekly dose groups. Although wall thickness was unchanged in all groups, increased MAR and FP is suggestive of an anabolic effect of risedronate. This is the first study demonstrating daily and weekly risedronate regimens produce similar results at the bone tissue, BMU, and cellular levels. These bone biopsy results, in combination with the non-inferiority of lumbar spine BMD in both weekly regimens, supports the selection of 35 mg once-a-week as an alternative to 5 mg daily risedronate. PHITOESTROGENS EFFICACY ON BONE LOSS RISK M. Valente Dpt. Obs. and Gyn. 'La Sapienza' Rome, Italy The first choice for prevention of Osteoporosis in Perimenopausal women with normal bone mass or Osteopenia would be HRT, because it has so many other beneficial effects for women of this age. However new prospects for overcoming this choice to take advantage of the skeletoprotective actions have opened up with the development of the efficacy studies on Phitoestrogens(Pe) treatments. The controversy over hormone replacement therapy as been fuelled as much by myths and fears as by scientific data. In a debate still clouded by uncertainties about cardiovascular benefits versus cancer risks, at least remain the alternative option of Pe. We have made a revue on Phitoestrogen therapy and his efficacy about Osteoporosis risk and we support with our personal studies on Pe against HRT after two years on treatment with a dosage of soy isoflavones + calcium and vit.D 3 + equisetum and lactobacillus (± 120 mg/die) against HRT ( E2 2mg./die + 0.5 mg. trimegestone). COMPARATIVE EFFECTS OF TREATMENT WITH ETIDRONATE AND ALENDRONATE ON BONE RESORPTION, BACK PAIN, AND ACTIVITIES OF DAILY LIVING IN ELDERLY WOMEN WITH VERTEBRAL FRACTURES J. Iwamoto1*, T. Takeda1, D. Ichimura2, M. Uzawa3 1Keio University School of Medicine, Tokyo, Japan 2National Defense Medical College, Saitama, Japan 3Keiyu Orthopaedic Hospital, Gunma, Japan Objectives: To compare the effects of treatment with etidronate and alendronate on bone resorption, back pain, and activities of daily living (ADL) in elderly women with vertebral fractures. Design: Fifty elderly women, 63-84 years of age, with back pain due to osteoporotic vertebral fractures were randomly divided into two groups with 25 patients in each group: cyclical etidronate treatment group (200 mg/day for 2 weeks per 3 months) and alendronate treatment group (5 mg/day, daily). Urinary cross-linked N-telopeptides of type I collagen (NTx) level measured by enzyme-linked immunosorbent assay, back pain evaluated with face scale score, and ADL score (disability) determined with a questionnaire were assessed before and 3 and 6 months after the start of treatment. Results: No significant differences in these parameters were found between the two groups before treatment (unpaired t-test). Urinary NTx level, face scale score, and ADL score decreased significantly in both groups (all P<0.0001, one-way ANOVA). Although the reduction in urinary NTx level was significantly greater in the alendronate group than in the etidronate group (P<0.0001, two-way ANOVA), the reduction in face scale score was transiently significantly greater in the etidronate group than in the alendronate group (P<0.001, unpaired t-test). However, changes in ADL score did not significantly differ between the two groups (two-way ANOVA). Conclusion: Although back pain was reduced and ADL was improved in both treatment groups of elderly women with clinical vertebral fractures, the mechanism for the reduction in back pain differs somewhat between the two treatment groups. A double-blind placebo-controlled study is needed to confirm the therapeutic effects of these agents on back pain and deterioration of ADL. BONE HISTOMORPHOMETRY AND BONE MARKERS IN WOMEN AGED 20-39 YEARS WITH OSTEOPOROSIS A. Sawicki1,2*, A. Debinski1, Z. Polowiec2, D. Bryk3, J. Pachecka3 1Mineral Metabolism and Bone Disease Dept., National Food and Nutrition Institute 2Warsaw Osteoporosis and Calcium Metabolism Centre 'Osteomed', Poland 3Depatment of Biochemistry and Clinical Chemistry, Medical Univesity Warsaw, Poland Osteoporosis is a significant health problem for women especially after menopause, but without known risk factors osteoporosis also occurs in young women. The aim of the study was assessment of bone histomorphometry and biochemical bone markers in young women. Twenty five women aged between 20-39 (X ±SD=32.1 ±6.5)years without known risk factors of osteoporosis underwent transiliac bone biopsy following tetracycline- labelling and bone markers studies. All of them had t-score of bone mineral density below 2.5 measured by DEXA-method (Hologic QDR4500A). none of them had hyperparathyroidism, renal disease, malabsorption and/or long-term corticosteroid tretment or other osteoporosis risk factors. Histomorphometric assessment of their bone including: trabecular volume, osteoid volume, osteoclast surface,and osteoblast surface according to ASMBR were done. Normal values of static histomorphometric parameters were obtained from 13 women aged 20-39 years without osteopathy who diet suddenly in trafic accidents. Serum osteocalcin and serum deoxypyridinoline concentration were measured by ELISA-method. Normal values of markers concentration were obtained from 56 health women aged 20-49(X ±SD=33.0 ±9.4)years. Mean bone volume was significantly decreased (15.80 ±3.83 vs. 32.30 ±1.07; p<0.001), the mean osteoid volume and mean osteoclast surface was significantly increased (3.97 ±2.72 vs. 1.98 ±0.45: p<0.01: 2.60 ±1.28 vs. 1.49 ±0.54; p<0.01 respectively). No significant difference in mean osteoblast surface was found (2.84 ±2.22 vs. 3.50 ±0.79; NS). In study group mean concentratin of serum deoxypyridinoline was significantly higher then in control group (6.24 ±2.66 nmol/L vs. 3.81 ±0.62 nmol/L; p<0.001). No significant difference in serum osteocalcin concentration was found (10.35 ±4.02 vs. 10.89 ±3.80; NS) Conclusions: osteoporosis in women in there thrities and fourts is characterised by uncoupling between increased bone resorption without changed of osteoblast activity. Uncoupling between resorption and formation can be reason of osteoporosis in youn women. The study was supported by State Committee for Scientific Research, grant no. 4PO5B11614 BONE MINERAL DENSITY AND BIOCHEMICAL MARKERS OF BONE METABOLISM IN TYPE 1 DIABETES MELLITUS A. P. Shepelkevich*, T. V. Mokhort, J. V. Tolcachev Belarussian State Medical University, Minsk, Belarus In order to investigate the relationship between the decrease of bone density and the altered mineral metabolism in type 1 diabetes mellitus (type 1 DM), 159 patients (68 men and 91 women; age 32,31+0,72 yr; duration of disease 11,92+0,64 years) were studied. Bone mineral density was measured by dual energy X-ray absorptiometry (DEXA), markers of bone formation [serum alkaline phosphatase (ALP) and serum osteocalcin] and bone resorption [urinary excretion of calcium and of the cross-linked N-telopeptide of type 1 collagen, both corrected for the excretion of creatinine] were measured in the diabetic patients and in 30 healthy controls, matched for sex, age, height, weight and body mass index (BMI). In 28 % of the diabetic men and 36 % of the diabetic women osteopenia of the femoral neck and/or the lumbar spine (T-value < or = -1 SD) was present. There was significantly higher mean cross-linked N-telopeptide of type 1 collagen (38%) levels in the patients with femoral neck osteopenia than in those without osteopenia at this site, suggesting increased bone resortion. The serum osteocalcin levels were lower (p<0,05) in the patients with femoral neck osteopenia than in those without osteopenia, that suggested lowering bone formation. There were no differences in the mean serum ALP, urinary excretion of calcium levels between the diabetic patients and the controls, nor between the diabetic patients with and without femoral neck osteopenia. Bone mineral density (BMD) negatively correlated with plasma levels of glycosylated hemoglobin (HbA1c). Our data demonstrate that at least in type 1 DM patients, osteopenia is the consequence of a lowered bone formation with a predominance of bone resorption over formation. BONE MINERAL DENSITY IN LONG-TERM SURVIVORS OF HIGHLY-MALIGNANT OSTEOSARCOMA G. Holzer1*, P. Krepler1, M. A. Koschat2, S. Grampp3, M. Dominkus1, R. Kotz1 1Department of Orthopaedics, University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria 2New York University, 44 West Fourth Street, New York, NY 10012-1126, USA 3Department of Radiology, Osteoradiology, University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria This study presents evidence of the long-term effects on bone mineral density (BMD) in long-term survivors of highly-malignant osteosarcoma treated with the chemotherapy protocols of the German-Swiss-Austrian Osteosarcoma Study Group (COSS) which includes high-dose methotrexate. Forty-eight subjects (mean age: 31 ± 4.2 years, mean follow-up: 16 ± 2.2 years) participated in the study. BMD of lumbar spine and proximal femur of the non- operated side were measured by dual energy X-ray absorptiometry. A questionnaire was administered to determine personal and life style factors as well as patients' medical history and medication. In the sample, ten patients were osteoporotic, twenty one osteopenic, and seventeen normal according to WHO definition. Eighteen patients reported bone fractures after receiving chemotherapy. The sample had statistically significantly lower BMD levels for all sites measured. In conclusion, long-term survivors of highly-malignant osteosarcoma treated with one of the COSS protocols showed lower BMD values that are statistically as well as medically significant. RATIONAL SCREENING FOR OSTEOPOROSIS IN THE PRIMARY CARE SETTING R. Hren1*, B. Salobir2, M. Cokolic3, A. Kocijancic4 1University of Ljubljana, Ljubljana, Slovenia 2VA Hospital dr. Peter Drzaj, Ljubljana, Slovenia 3Teaching Hospital Maribor, Maribor, Slovenia 4Clinical Center, Ljubljana, Slovenia Early identification of postmenopausal women with osteoporosis by means of bone mineral density (BMD) measurement is a prerequisite for reducing the incidence of osteoporotic fractures. Primary care physicians have a leading role in referring such patients, however, given the cost of the BMD measurement, efficient screening criteria remain to be determined. Currently available criteria (e.g., SCORE, ORAI) are very broad with low specificity. Objective of our study is to assess simple decision rules that could enhance identifying patients with high risk of fracture while concurrently minimizing number of unnecessary measurements. In the study, 357 primary care physicians (GPs and gynecologists) referred their patients to BMD measurements based on the following decision rules: women (i) should be postmenopausal for at least 5 years, (ii) should have body mass index (BMI) less than 26 kg/m2, and (iii) should have never been diagnosed with osteoporosis. BMD of lumbar spine and/or hip was measured by dual-energy x-ray absorptiometry (DXA) in 5 centers. Results of BMD measurements were expressed in terms of the T- score and were forwarded to the primary care physicians. In the study, 2339 postmenopausal women were enrolled; by the end of the study, 327 physicians (92%) reported results on 2196 women (94%). 1332 women of 2196 (61%) were identified as osteoporotic, 637 (29%) as osteopenic, and 227 (10%) had normal BMD. Approximately 30% of patients with osteoporosis suffered from previous low-trauma fracture. Among all women, the prevalence of osteoporosis was 34% for ages less than 55 years, 50% for ages 55-59 years, and 69% for ages above 60 years. The number of DXA measurements needed to detect one osteoporotic patient among women older than 60 years and with BMI <24.5 kg/m2 was 1.32. Results of our study suggest that three simple decision rules provide efficient guidance for BMD measurement referrals. Moreover, these decision rules proved to be efficient in the primary care setting. Since a vast majority of women enrolled in the program (90%) had either osteopenia or osteoporosis, it can be expected that these decision rules primarily apply to identification of patients who are at relatively high risk of fracture. These rules should be thus recognized as the initial judicious tool for identifying patients with osteoporosis in the primary care setting, which should be later supplemented by other broader criteria. ULTRASOUND TESTS IN DIAGNOSTIC OF LOCAL DIABETIC OSTEOPENIA A. P. Shepelkevich Belarussain State Medical University, Minsk, Belarus Localized lesions at the foot skeleton are a serious and well recognized complication of diabetes mellitus which may impair the clinical outcome of the patients remarkably. The presence of localized lesions at the hand skeleton related to diabetes mellitus is less acknowledged and its clinical relevance is less obvious. Materials and methods: 38 type 1 DM patients (age 34,9 SD 10,2 years, diabetes duration 9,7 SD 7,9 years, HbA1c 8,4 SD 1,5%) and 30 healthy controls, matched for sex, age, height, weight and body mass index (BMI) were studied. All type 1 DM patients and controls quantitative ultrasound (QUS) of the calcaneal bone and QUS of the hand phalanges were performed. The ultrasonometry variables, speed of sound (SOS), broad ultrasound attenuation (BUA), and the stiffness index (SI) were compared in the results of two methods: QUS of the calcaneal bone and QUS of the hand phalanges. Results: We observed a statistically significant difference between the methods in the next ultrasonographic parameters: BMD (0,56 vs 0,52 and 0,56 vs 0,55, p<0,01), QUI (99,2 vs 95,1 and 106,3 vs 98,4, p< 0,01), BUA (83,3 vs 73,8 AND 86,1 vs 74,3, p<0,01). Diabetic osteopenia was reveal in 54 % with the QUS of the calcaneal bone and 28 % with the QUS of the hand phalanges. Conclusion: Our results indicate a possible role QUS for the diagnostic of local diabetic osteopenia. Finally, QUS of the calcaneal bone is more early/specific method in discriminating of local diabetic osteopenia. 3-D SYNCHROTRON MICRO-CT ALLOWS UNIQUE INSIGHT OF CHANGES IN BONE QUALITY WITH RISEDRONATE THERAPY E. L. Ritman1*, B. Borah2, T. E. Dufresne2, R. J. Phipps2, J. P. Sacha2, S. M. Jorgensen1, D. A. Reyes1, R. T. Turner1 1Mayo Clinic, Rochester, USA 2Procter & Gamble Pharmaceuticals, Mason, USA With the increased awareness that the effectiveness of anti-resorptive therapies in reducing fractures is partly mediated by changes in bone quality, there is an on-going search for new technologies to describe and quantify such changes. With high- resolution Synchrotron 3-D Micro-CT, we have investigated changes in local trabecular micro-architecture and degree of mineralization of bone biopsies from risedronate treated osteoporotic women. Paired transiliac bone biopsies obtained at baseline and after 3 years of treatment with placebo (n = 8) or risedronate 5 mg daily (n = 11) were scanned at the Synchrotron Light Source X2B beam line micro-CT scanner at Brookhaven. The monochromatic radiation allows for quantification of material radio opacity (density) and its 3-D distribution by calibrating the gray level values with a phantom of multiple concentrations (g/cc) of K2HPO4. The high resolution (4 micron) images provided quantitative delineation of the under-mineralized or low-density bone (mean 0.864; range 0.565 - 0.942 g/cc) from the high-density bone (mean 1.041; range 0.942-1.475 g/cc). There was a significant reduction of the low-density bone fraction (%low density bone/total bone) with concomitant increase of the high-density fraction in the risedronate treated biopsies relative to baseline (p = 0.0001). The composite histograms calibrated with the phantom provided a distribution of the degree of mineralization in each treatment cohort. Risedronate increased the peak densities by 5.1% (p < 0.001) relative to baseline, indicating an increase in the degree of mineralization. The changes for the placebo group in the low or high-density bone fractions as well as in the degree of mineralization were not significantly different from baseline. Further, surface topology analysis showed a reduction of surface roughness (presumably osteoclastic erosions) with risedronate treatment relative to baseline. The observed changes with risedronate are likely due to reduced bone turnover and may contribute to improved bone quality, and reduction in fracture risks. NON-INVASIVE AND IN VIVO 3D-EVALUATION OF BONE STRUCTURES IN THE HUMAN FOREARM; A STEP TOWARD AN INDIVIDUAL FRACTURE RISK PREDICTION M. Neff1*, M. A. Dambacher2, L. Qin3, P. Ruegsegger1 1Center for Osteoporosis, Zürich, Switzerland 2University Clinic Balgrist, Zürich, Switzerland 3Chinese University of Hongkong, PR.China Non-invasive and in vivo 3D-Evaluation of Bone Structures in the Human Forearm; a step toward an individual fracture risk prediction Till now in vivo only bone mass was available quantitatively. The non invasive evaluation of bone structures, which play an important role in the fracture risk prediction, was made qualitatively using high resolution 2D-CT-images. Recently quantitative 3D structure analysis became available in vivo with the help of 3D-QCT (Densiscan 3D, Scanco Medical AG, Zürich, Switzerland). Methods: The new device has a 2-dimensional detector array in combination with a 0.15 x 12mm line-focus x-ray tube (effective energy 40keV), enabling the simultaneous acquisition of stacks of 110 tomograms perpendicular to the bone axis. The radial resolution is <160µm (10% MTF, isotropic voxel size 90µm) and axial <200µm (10%MTF). The first stack of tomograms is taken 7mm proximal from the endplate of the distal radius delivering a coverage of a region of about 10mm. The data acquisition time is about 2 minutes and the skin radiation dose for a whole examination (scout view included) 2.5mGy. With automatic repositioning the reproducibility is <±1% (for structure elements) in mixed collectives. Results: In praxi it is now possible to quantify microarchitectural features as number of trabeculae, trabecular and cortical thickness, trabecular spacing and endosteal surface; in addition the volumetric BMD of trabecular and cortical bone. Conclusions: Such a characterization gives not only a better insight into the pathogenesis for the prevention and treatment (e.g. with Risedronate) of the primary and secondary osteoporosis; it also improves individual fracture risk prediction; e.g. with the help of finite element analysis. OSTEOCALCIN IN HUMAN URINE: IDENTIFICATION OF MULTIPLE OSTEOCALCIN FRAGMENTS AND DEMONSTRATION OF THEIR DISTINCT CLINICAL PERFORMANCE K. K. Ivaska1*, J. Hellman2, J. Likojärvi1,2, S. M. Käkönen2, P. Gerdhem3, K. Åkesson3, K. J. Obrant3, K. Pettersson2, H. K. Väänänen1 1Institute of Biomedicine, Department of Anatomy, University of Turku, Turku, Finland 2Department of Biotechnology, University of Turku, Turku, Finland 3Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden Osteocalcin (OC) is a bone matrix protein of 49 amino acids. It is synthesized by osteoblasts and OC in circulation is currently considered as a marker of bone turnover. OC is rapidly cleared by glomerular filtration into urine and it has been detected also in urine samples. The detailed structure, origin and clinical significance of urine OC are still mainly unknown. We have isolated and identified nine fragments of OC from urine samples of healthy individuals. Urine OC fragments consisted of 18-27 amino acid residues from the middle region of OC. Fragments were abundant and large enough to be detected with simple and convenient two-step assays based on monoclonal antibodies and time-resolved fluorescence detection. Longer fragments were abundant in all the samples tested (N = 6) and most of them had amino acid Gly7 in their N-terminus. The most predominant was the one consisting of residues 7-31. Additional OC fragments starting from residue Asp14 were detected in the samples of children and young adults. Immunoassays for the determination of different urine OC fragments were evaluated by measuring samples from 37 females, all 75 years of age, together with other markers of bone turnover, serum tartrate-resistant acid phosphatase 5b and intact OC. The assay for total urine OC, which measures both Gly7- and Asp14- fragments, had the best clinical performance when correlation to bone mineral density (BMD) assessed at femoral neck was evaluated (r = -0.68, p < 0.0001). Also, a significant (p = 0.0003) difference in BMD was observed between the quartiles of this assay, in contrast to non-significant differences observed with other evaluated assays. Thus, Asp14- and Gly7- OC fragments in urine appear to reflect different aspects of bone metabolism and the measurement of them separately or in combination may have potential applications in diagnostics related to disorders of bone metabolism. DESCRIPTIVE ANALISIS OF THE CALCANEAL QUANTITATIVE ULTRASOUND VALUES IN 5195 POSTMENOPAUSAL WOMEN ATTENDED IN PRIMARY CARE CENTERS F. Marín1*, F. Teruel2, R. Julián3, E. Mira4, M. Borge5, E. Sampedro6 for the ECOSAP investigators 1Department Medical Research, Lilly S.A., Madrid, Spain 2CS Txantrea, Pamplona, Spain 3CS Peñagrande, Madrid, Spain 4CS Los Angeles, Alicante, Spain 5CS Arturo Eyres Sur, Valladolid, Spain Objetives: Quantiative ultrasound (QUS) assessment is a safe, simple and effective method for evaluating bone status. The aim of the study was to describe the calcaneal QUS values of a large cohort of postmenopausal women consecutively attended in Primary Care Centers in Spain. Secondly, the prevalence of osteoporosis was evaluated applying the WHO criteria to QUS values in this population. Subjects and Methods: Transversal, descriptive, multicenter study. 5195 women >65 year-old (mean+SD: 72'3+5'3 years) attended for any medical reason, between March 2000 and June 2001, in 58 Primary Care Centers distributed throughout the spanish peninsula, were included in the study. Subjects with known metabolic or neoplastic bone diseases, with the exception of osteoporosis, were excluded. An informed consent to participate was required. QUS was performed at the right heel with a Sahara bone sonometer. To calculate T-scores, the national reference values for this equipment were used(1). For the diagnosis of osteoporosis, the WHO criterion for dual-energy X-ray absorptiometry (DXA) technology was applied: i.e.; T-score <-2,5 SD. Results: see Table.The prevalence of osteoporosis was of 12.8%, 5.1%, 13.8% and 12.4% using the T-scores of the Estimated Heel BMD, BUA, SOS and QUI respectively. Conclusions: The prevalence of osteoporosis applying the WHO cut-off value for DXA to QUS values is clearly below the expected prevalence in this age group (between 25-50% depending on the measurement site). BUA T-score values were notably higher than the rest of the QUS parameters, and it seems of less value to evaluate the bone status. QUS specific T-scores thresholds for the diagnosis of osteoporosis are needed to facilitate adequate clinical decision making when using this technique. 1Osteoporos Int (2002):13:487
BASELINE CHARACTERISTICS AND REASONS FOR INITIATING OSTEOPOROSIS TREATMENT: RESULTS FROM THE SPANISH COMPLIANCE OSTEOPOROSIS STUDY IN POSTMENOPAUSAL OSTEOPOROSIS (PROCUOS) C. Turbi1*, G. Herrero Beaumont2, J. C. Acebes2, G. Graña3, A. Torrijos4 11 Lilly Spain, Eli Lilly and Company. Alcobendas, Madrid, Spain 2Fundación Jiménez Díaz, Madrid, Spain 3Hospital Juan Canalejo, A Coruña, Spain 4Hospital La Paz, Madrid, Spain OBJECTIVES: To describe baseline characteristics and to evaluate the reasons for initiating osteoporosis treatment in postmenopausal women. MATERIAL AND METHODS: PROCUOS is an observational, prospective, multicenter and comparative study. Postmenopausal women (PW) with increased risk of osteoporotic fractures, aged >55 years, and who had not been on any therapy with bone active agents for at least 3 months were enrolment in the study, and commenced raloxifene 60 mg/day or alendronate 10 mg/day therapy. Primary objective was to evaluate compliance with raloxifene compared to alendronate treatment for a minimum of 12 months in PW with increased risk of osteoporotic fractures, as evaluated by the treating physician. Secondary objectives were to evaluate factors involved in non-compliance and patient satisfaction with osteoporosis treatment. Here, we present baseline characteristics and treatment choices at baseline as determined by the treating physician. Reasons for treatment choice were determined using the risk factors for osteoporosis fractures from National Osteoporosis foundation and by the diagnosis of osteopenia, osteoporosis and established osteoporosis following the WHO criteria. RESULTS: A total of 902 postmenopausal women were included, 476 patients in the raloxifene group (mean age: 63.5 years old) and 426 patients in the alendronate group (mean age: 65.4). The age range in both treatment groups was 55-89 years. Mean age of menopause in both treatment groups was 48.3 years. The percentage of women with surgical menopause in both groups was 13.9%. 56.2% of the patients were recruited in public centers, 38.6% in private centers and 5.2% in mixed centers. 69.6% of the patients did not receive any antiresorptive treatment prior to this study. In the pooled population, the main reasons for study treatment was osteoporosis (45.9%), established osteoporosis (23.9%) and osteopenia (17.1%). Reasons for treatment initiation are shown in Table 1. CONCLUSIONS: In postmenopausal women, the primary reason for initiating osteoporosis treatment is still based on the diagnosis of osteopenia, osteoporosis, and established osteoporosis following WHO criteria.
REASONS FOR DISCONTINUATING OSTEOPOROSIS TREATMENT: RESULTS FROM THE SPANISH COMPLIANCE OSTEOPOROSIS STUDY IN POSTMENOPAUSAL OSTEOPOROSIS (PROCUOS) C. Turbi1*, G. Herrero Beaumont2, J. C. Acebes2, R. Miguelez3, S. Garcia4 1Lilly Spain, Eli Lilly and Company. Alcobendas, Madrid, Spain 2Fundación Jiménez Díaz, Madrid, Spain 3Hospital de Móstoles, Madrid, Spain 4Hospital Universitario Puerta del Mar, Cádiz, Spain OBJECTIVES: To evaluate reasons for discontinuing osteoporosis treatment in postmenopausal women MATERIAL AND METHODS: PROCUOS is an observational, prospective, multicenter, comparative and non-interventional open label study. Postmenopausal women with increased risk of osteoporotic fractures, aged 55 years or over, who had not been on any therapy with bone active agents for at least 3 months and who after enrollment in the study, initiated raloxifene 60 mg/day or alendronate 10 mg/day treatment, as determined by the treating physician. We analyzed the proportion of women who had been on previous treatment at least 3 months before enrollment in the study and the reasons for discontinuation. RESULTS: A total of 628 (69.6%) patients did not receive any antiresorptive treatment prior to this study. A total of 274 (30.4%) women included in the study had previously been treated for osteoporosis (Table 1). Treatment-related side effects were most often the reason for stopping HRT (27.3%) and alendronate (45.1%). In those patients who were treated with CT and ET, the main reason for discontinuation was patient concern (26.6% and 23.5%, respectively). Two women stopped raloxifene treatment because of patient concern, one stopped because advice of the doctor and the other women stopped without reason(Table 2). CONCLUSIONS: We conclude that the reasons for non-adherence differ by treatment type. Although small sample size, the most common reasons for patients not adhering to HRT and alendronate therapy were side effects, as has been previously reported.
EFFICACY OF FOSAMAX VS. EVISTA COMPARISON TRIAL (EFFECT-INTERNATIONAL): RESULTS AT 6 MONTHS P. Sambrook1, P. Geusens2, V. Keraudren3, K. Gaines3, A. Leung3, M. Melton3* 1Royal North Shore Hospital, Sydney, Australia 2Biomedical Research Institute-LUC, Diepenbeek, Belgium 3Merck & Co., Inc., Whitehouse Station, NJ USA This multinational study was designed to compare the efficacy of alendronate and raloxifene when used for treatment of osteoporosis in postmenopausal women. We presented here the 6 month results from this 12 month study. This study population comprised 487 postmenopausal women at 50 centers in 15 countries representative of Eastern and Western Europe, Asia-Pacific, and South America. Patients were randomly assigned in a 1:1 ratio to receive alendronate 70 mg once weekly (Fosamax, Merck & Co., Inc.) and raloxifene placebo daily or raloxifene 60 mg daily (Eli Lilly) and alendronate placebo once weekly. This interim analysis assessed the response in markers of bone turnover at 6 months. The markers measured were urinary NTx and serum BSAP. The mean age of women enrolled was 62 years (range 42 to 90 years). 79% were Caucasian. They were on average 15 years post menopause. At 6 months, the decrease in urinary NTx from baseline in the alendronate group was 68.1%, compared to a decrease of 28.6% in the raloxifene group (P<0.001). The decrease in serum BSAP from baseline in the alendronate group was 43.8%, compared to a decrease of 11.1% in the raloxifene group (P<0.001). For both urinary NTx and serum BSAP, changes from baseline within treatment group were significant for both treatments (P<0.001 for both alendronate and raloxifene). This study is planned to continue through a 12 month treatment duration. The 6 month results presented here indicate that weekly alendronate provides larger decreases in bone turnover than does daily raloxifene, and is therefore a more potent antiresorptive agent when used for treatment of osteoporosis in postmenopausal women. NORMAL VALUES OF FOREARM BONE BMD AND INCIDENCE OF PRIMARY OSTEOPOROSIS IN CHINESE WOMEN Y. Jiang1*, L. Miao1, Z. G. Ji1, X. Xie2, C. Y. Wang1, S. Cao1, Q. Xiang3, N. Su3, C. Y. Li3, Z. H. Liu3 1Central Hospital of China Petroleum and Natural Gas Corporation Group, Langfang, HeBei Province, 065000, P.R.China 2Denmark Hilleroed Hospital 3China-Japan Friendship Hospital, Beijing,100029, P.R.China In this study we obtained the normative reference data of forearm BMD in Chinese women using a new computerised radiogrammetric analysis system (Pronosco X- posure system),which generates a BMD estimate(DXR-BMD)through scanning of a plain radiogaph of the hand and forearm.DXR-BMD data were obtained in 354 normal Chinese women aged 20-79 years.The peak BMD was found in women between 30-39 years of age(estimated peak BMD=0.5569,SD=0.027,occurring at age 30-39).The incidence of osteoporosis diagnosed on the basis of pcak BMD minus 2.0 SD in this study population was similar to the prevalence of primary osteoporosis in Chinese women reported by others using osteodensitometry.We conclude that the Pronosco X-posure system can can provide simple, accurate and inexpensive assessment of bone mineral status, making it valuable in the diagnosis of osteoporosis, especially in developing countries. Key words: Women Forearm Bone mineral density, Incidence, Computerised radiogrammetric analysis system Normal values of forearm bone BMD and incidence of primary osteoporosis in Chinese women
RESEARCH OF NORMAL POPULATION'S PHALANGEAL BONE DENSITY IN THE SUBURBS OF BEIJING BY RADIOGRAPHIC ABSORPTIONETRY Z. H. Liu1*, D. King2, Q. Xiang3, N. Su3, C. Y. Li3, X. J. Ma1, X. S. Wang4, C. M. Ma4 1Beijing Eastern Asia-Pacific Bone and Mineral Research Center, 100102, Box9910, Beijing, P.R.China 2Alara Incorporated, U.S.A. 3Sino-Japanese Friendship Hospital, Beijing, 100029, China 4Epidemic Prevention Station of Langfang City, HeBei Province, 065000, P.R.China Preface: MetriScan Bone Densitometer is a popular portable osteoporosis diagnostic instrument to estimate phalangeal BMD. We conducted this research to develop a normative database for the Chinese people. Method:Metriscan is an independent desktop bone density measuring device which uses radiographic absorptiometry(RA)to estimate the corresponding BMD value and T-score. As a result,osteoporosis can be diagnosed and fracture risk can be predicted.Grouping:we selected 8 groups of ordinary people aging from 10 to 89. Each group has 50 people with men and women counted separately.To obtain more accurate estimate of peak bone mass, age groups from 20 to 29 and from 30 to 39 include 125 people each. People who have taken osteoposis drugs or who have suffered from diabetes, ovariotomy, etc. are excluded from the selected groups. Result: for women, peak bone mass appears in the age group from 30 to 39 and from 29 to 35. As age increases, bone mass loss is evident with considerable regularity. The other hand, for men, peak bone mass appears in the age group from 30 to 39 and 25 to 32. As age increases, loss of bone mass slows down. Discussion:A.The brand new MetriScan integrating Radiographic Absorptiometry and Digital Graph Analysis is suitable for osteoporosis diagnosis for the Chinese people. Before SPA came into being, X-ray was used to diagnose osteoporosis. Affected by many factors, osteoporosis was diagnosed only when bone mass loss reached 30 to 50 percent. Digitalization and RA technology brought a new member to the early-stage osteoporosis diagnostic instrument family. The result obtained by using MetriScan to measure the normal group from Northern China is similar to that obtained by a task team headed by Prof.Liu Zhong-hou using SPA to measure bone density of the forearm(radius and ulna)1/3 of 40,000 people. B. MetriScan is an independent bone density diagnostic instrument with a low price. As it is easy to operate, it is suitable for small hospitals.In big hospitals, Metriscan is supplementary to DEXA. CLINICAL ANALYSIS OF 156 OLD PATIENTS WITH HIP FRACTURE T. C. Shen*, H. W. Jiang, X. F. Xu Department of Orthopedics, Affiliated Hospital of Zhengjiang Medical College, JiangSu Province, P.R.China Objective: To report the treatment of hip bone fracture in the senile patients, to analyse its characteristics and key points in diagnosis and treatment. Methods: All 156 cases over 60 years(age ranged from 60 to 93)with hip fracture were treated from January 1997 to December 1999. With male 55 cases, average 71.8 years, female 101 cases, average 73.1 years. Bone fracture types include the femoral neck fracture (94cases), among those, male(20), female(74); The femoral intertrochanteric fracture (62 cases), male(35), female (27). 41 cases were treated with non-operational methods; 115 patients received operational treatment, among them 45 cases were treated with internal fixation, 68 cases were replaced with artificial femoral head, 2 cases were ablated femoral head and neck. Some were given drugs of osteoporosis. Results: 110 cases were followed up from 0.5 to 3.5 years. Two cases were venous thrombosis in low limbs after operation, two cases had femoral head ischemia and necrosis, the moving and slipping of internal fixation were 2 cases, and the internal fixation break-up was one case, pain caused by artificial femoral head sinking were 4 cases, the death shortly after operation were 2 cases (died of cardiac infarction and respiratory infection), 97 cases got satisfactory result (88.2%). Conclusion 1. Hip bone fractures are mostly seen in senile woman (64.7%); while less in senile male (35.3%), which related to the osteoporosis after menopause in female. Femoral neck fractures are mostly seen in senile female, while femoral intertrochanteric fractures are mostly seen in senile male, when over 70 years, the hip bone fracture occurs more frequently than before, which is related to the osteoporosis, it shows that the bones fracture occurrence rate increases with the age, the danger of it increases too. 2. The hip bone fracture in the senile man belongs to that of osteoporosis, but the femoral intertrochanteric fracture has obvious injury history. The femoral neck fracture is often with slight force (torsion), so we should make a right diagnose and try to prevent omitting or mistaking, which will have a negative effect. 4. We should treat the osteoporosis together with fracture, which is of great significance in relieving bone pain, promoting bone healing and preventing hip bone from re-breaking up. Key words: Aged, Hip fracture, Osteoporosis THREE-YEARS TREATMENT WITH RISEDRONATE PRESERVES BONE QUALITY E. P. Paschalis1*, R. J. Phipps2 1Hospital for Special Surgery, New York, USA 2Procter & Gamble Pharmaceuticals, Mason, USA Factors such as bone microarchitecture and bone quality in addition to bone mineral density (BMD) are important determinants of fracture risk. Treatment of postmenopausal osteoporotic subjects with risedronate (1- and 3-yr) reduces vertebral fractures while concomitantly preserving bone microarchitecture and increasing BMD. In this analysis we compared the effects of placebo and 3-yr risedronate treatment on bone quality, specifically mineral crystallinity/maturity and collagen cross-link ratio (pyr/deH-DHLNL) via Fourier transform infrared microscopic imaging (FTIRI), in paired human iliac crest biopsies. Paired iliac crest biopsies were obtained from 19 postmenopausal osteoporotic subjects at baseline and after 3-y treatment with placebo (n=8), or risedronate (5mg/day orally; n=11). The biopsies were embedded in methylmethacrylate, and the trabecular bone region was analyzed by FTIRI in ~4 um thick sections for determination of mineral crystallinity (bone mineral crystallite size in the crystallographic c-axis), and collagen cross-links ratio. Attention was focused to trabeculae devoid of resorbing surfaces. Three images per section were acquired (each image 400 x 400 um 2 area or >2000 pixels with a spatial resolution of 7 um). Crystallinity was compared before and after treatment (t-test). Values are mean ± standard deviation Three-yr risedronate treatment had no significant effect on mineral crystallinity or collagen cross-link (pyr/deH-DHLNL) ratio of trabecular bone. Crystallinity before and after treatment was 0.995 ± 0.107 and 0.927 ± 0.059, respectively. Collagen cross- link ratio before and after treatment was 1.605 ± 0.404 and 1.609 ± 0.859, respectively. In contrast, in subjects treated for 3-yr with placebo there were statistically significant increases in both the mineral crystallinity (0.924 ± 0.06 vs. 1.218 ± 0.04) and collagen cross-link ratio (1.4 ± 0.2 vs. 1.9 ± 0.04). This lack of an increase in both mineral crystallinity and collagen cross-link ratio coupled with increased BMD and preservation of microarchitecture suggests that risedronate suppresses osteoclastic activity relatively more than osteoblastic activity. These results contrast to the previously reported increase in mineral crystallinity seen with other antiresorptive therapies (ibandronate and hormonal replacement therapy). DO THE IOF CASE FINDING CRITERIA IDENTIFY OSTEOPOROTIC WOMEN FOR BONE DENSITOMETRY AS ACCURATELY AS THE CLINICAL DECISION RULES SCORETM, OST AND ORAI? B. R. Christoffersen1*, C. L. Tofteng1, N. Nissen2, P. Vestergaard3, O. Bärenholdt4, S. P. Nielsen4, L. Mosekilde3, B. Abrahamsen2 1Osteoporosis Unit, Hvidovre Hospital, Copenhagen, Denmark 2Department of Endocrinology, Odense University Hospital, Odense, Denmark 3Department of Endocrinology, Aarhus County Hospital, Aarhus, Denmark 4Department of Diagnostic Imaging , Hilleroed Hospital, Hilleroed, Denmark Several clinical decision rules (CDR) have been developed to guide the clinician in deciding whether to refer postmenopausal women for DXA. SCORETM, OST and ORAI are all validated in several, mainly North American cohorts. The purpose of the present analysis was to investigate how accurately these CDRs perform in comparison with the current IOF case finding criteria in predicting a T- score =< -2.5 at the femoral neck or lumbar spine. Study population: 2016 healthy women with recent menopause, aged 43-58, median 50.5 years interviewed at baseline within The Danish Osteoporosis Prevention Study. Methods: BMD was measured at the hip and lumbar spine using cross calibrated Hologic QDR-1000 and -2000 densitometers. NHANES III and Hologic young adult reference ranges for femoral neck and spine were used. Data sufficient for calculation of the CDR and IOF-scores were available in 2009 women. The IOF criteria were operationalised as follows: -Menopause < 45y -Secondary amenorrhoea >1y -Corticosteroid therapy > 7.5 mg/day >1y -Maternal hip fracture -BMI < 19 kg/ m2 -Fragility fracture >45y (wrist, hip, spine, rib, humerus, pelvis) -Hyperthyroidism, hyperparathyroidism, immobilization >1 month, renal failure. A positive IOF-score was defined as at least one positive answer. Results: The prevalence of T=<-2.5 was 4.5%. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) are shown in the table below. At their recommended cut-offs, the CDRs have significantly higher predictive values than the IOF criteria. No association between the IOF criteria and the presence of osteoporosis could be established. Though the CDRs had low PPV, they raised the prevalence of osteoporosis among women eligible for DXA by up to 82%. Conclusions: Despite weak diagnostic accuracy, all of the CDRs are superior to the IOF criteria in selecting women for densitometry in this relatively young age group.
PRIOR USE OF HORMONE REPLACEMENT THERAPY (HRT) AND THE EFFECTS OF RALOXIFENE ON THE RISK OF VERTEBRAL FRACTURE IN POSTMENOPAUSAL WOMEN WITH AND WITHOUT PREVALENT VERTEBRAL FRACTURES D. Agnusdei1*, P. M. Kulkarni1, J. L. Stock1, M. Wong1, O. Johnell2 1Lilly Research Laboratories, Indianapolis, Indiana, USA 2Universitetssjukhuset MAS, Malmo, Sweden The objective of this analysis is to determine the effects of raloxifene on the risk of vertebral fracture (VF) in postmenopausal women with osteoporosis, with or without prevalent VF, who used HRT prior to enrollment in the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) study. Of the 7682 women who reported their status of prior HRT use, 2235 women used HRT before enrolling in MORE. Separate logistic regression models analyzed the relationships between prior HRT use and VF risks. At baseline, women who previously used HRT were younger and more likely to have a family history of osteoporosis than women who did not use HRT. Raloxifene 60 mg/d significantly decreased VF risk by 54% in women who had prior HRT use [relative risk (RR) 0.46 (95% confidence interval (CI) 0.32, 0.67)], and by 29% in women who did not use HRT previously [RR 0.71 (95% CI 0.58, 0.86)]. In women without prevalent VF, raloxifene 60 mg/d reduced the VF risk by 38% [RR 0.62 (95% CI 0.41-0.95)] in those who did not use HRT previously, and by 71% [RR 0.29 (95% CI 0.13-0.63)] in those who had previously used HRT. The significant interactions between prior use of HRT and VF risk reduction in the overall analysis population (P=0.05) and in women without prevalent VF (P=0.09), suggest a possible differential effect of raloxifene 60 mg/d on VF risk in women with and without prior HRT use. However, in women with prevalent VF, who are at higher risk of new VF, raloxifene 60 mg/d decreased the VF risk by 46% [RR 0.54 (95% CI 0.36-0.81)] in those with prior HRT use, and by 29% [RR 0.71 (95% CI 0.57-0.88)] in those with no prior history of HRT use. The interaction effect was not significant (P=0.27), suggesting that raloxifene 60 mg/d decreases VF risk to a similar extent in women with prevalent VF, irrespective of prior HRT use. In summary, raloxifene 60 mg/d significantly reduces VF risk in postmenopausal women with osteoporosis, irrespective of prior HRT use. Women without prevalent VF who had previously used HRT may experience further reductions in VF risk. COMPARISON OF FRACTURE, CARDIOVASCULAR, AND BREAST CANCER EVENT RATES AT 3 YEARS IN POSTMENOPAUSAL WOMEN WITH PREVALENT VERTEBRAL FRACTURES FROM THE PLACEBO GROUP OF THE MORE STUDY S. L. Silverman1*, P. Delmas2, P. M. Kulkarni3, J. L. Stock3, M. Wong3, L. Plouffe Jr3 1University of California Los Angeles, Los Angeles, California, USA 2University Claude Bernard, Lyon, France 3Lilly Research Laboratories, Indianapolis, Indiana, USA Osteoporosis, cardiovascular events, and breast cancer are 3 major health concerns affecting postmenopausal women. Treatment selection should weigh the relative occurrence rates for these diseases. The current analysis examines the number of women with at least one new fracture, cardiovascular, or breast cancer event at 3 years in the placebo group of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial who had a prevalent vertebral fracture [n=938, mean age 69 ±6 (SD) years]. All women were given daily calcium and vitamin D supplements. Spinal radiographs and mammograms determined vertebral fractures and breast cancer, respectively, at 2 and 3 years. At each clinic visit, subjects were asked if they had any symptoms suggestive of fracture or diagnoses of cardiovascular or breast cancer events, which were recorded as adverse events. Adjudication boards confirmed the radiographic diagnoses and self-reports to determine new cases of fracture, cardiovascular, and breast cancer events, which are reported as rates per 1000 patient-years (Table). In these women with prevalent vertebral fractures, the occurrence of any fracture was the most common event, as expected. The rate of vertebral or clinical vertebral fracture was greater than that for hip fracture, cardiovascular, or breast cancer events. Furthermore, even though these women were at high risk of subsequent fractures, the likelihood of any cardiovascular event was approximately 3 times greater than hip fracture. In conclusion, the relative importance of clinically significant skeletal and extra-skeletal events should be considered when choosing an agent for maintenance of postmenopausal health. These data would be useful in formulating decisions regarding prevention and treatment strategies for this population.
STUDY OF CORRELATION OF BONE MASS BETWEEN DIFFERENT REGIONS IN AXIAL AND PERIPHERICAL SKELETON E. López Gavilanez1*, A. Segale Bajaña2, K. Sánchez Castro3, F. Vera Vargas4 1Endocrinology Service of National Police Hospital No-2, Guayaquil, Ecuador 2Internal Medicine Service of National Police Hospital No-2, Guayaquil, Ecuador 3Endocrinology Service of APROFE, Guayaquil, Ecuador 4North Medical Unite of IESS, Guayaquil, Ecuador The objective of our study is to stablish if a correlation exists between the axial and peripherical values of bone density in postmenopausal women. PATIENTS, MATERIALS AND METHODS: We measured the bone density in 250 women. In the Group 1(n=107 postmenopausal women) we measured the bone density in extreme distal (RD) and ultradistal of the radius (RUD) with a team Osteometer DTX 200, and simultaneously in Lumbar Spine (LS) and Femoral Neck (FN) with a team DEXA (Hologic 1.500). In the Group 2 (n=143 women) we measure the bone density in the end distal (RD) of the radius and simultaneously in the Calcaneus (C) with a team Lunar PIXI. The values of the bone density are expressed as units of T score. We performed a test of lineal correlation and we calculate the respective regression equation. The statistical significance is expressed as a value of p <0,05. RESULTS: The average age was 58,6 ±10,2 years. Time of menopause: 13 ±7 years.The results of the correlations among the different regions are showed in the following chart. CONCLUSIONS:We found a significant correlation, between the bone density in peripherical skeleton and the values found in axial skeleton in women who were studied. However the correlation and determination coefficients are moderate, that makes difficult to predict the values found in one region from the measurement in another.
PERFORMANCE OF A NEW 10S SCAN MODE ON A DXA FAN BEAM BONE DENSITOMETER - AP SPINE AND HIP BMD CORRELATION C. C. Ruth1*, L. A. Wierzbowski1, T. L. Kelly1, K. E. Wilson1, S. M. Nattrass2 1Hologic, Inc., Bedford, USA 2Puget Sound Osteoporosis Center, Seattle, USA A new scanning mode, Express (Hologic, Inc.), has been developed for the Hologic Discovery QDRTM Series bone densitometer for AP Spine and Hip BMD measurements. Express scanning allows BMD assessment in 10 seconds with 30% less dose compared with the previous 30 second 'Fast' scanning mode. The Express scanning mode also has improved image processing utilizing a dynamic noise reduction algorithm which produces consistent image quality over a wide range of patient thickness. Correlation of the new mode with the previous default scanner mode is essential for use of reference data and for follow-up of patients measured after an upgrade. Sixty women (age range 21 to 70, spine BMD range 0.63 to 1.27 g/cm2) underwent left hip and AP spine scans using both the Fast mode and the Express 10 second mode. A linear regression analysis was used to measure the correlation between the two modes for spine (L1-L4), total hip, and femoral neck regions. None of the intercepts were statistically different from zero, so the slopes reported below use an intercept restricted to zero. The slopes were not statistically different than unity. The Standard Estimate of Error (SEE) was slightly higher for the hip than the spine however all the SEE's reported are lower than the SEE's typically found in fan beam vs. pencil beam correlation. Bland-Altman analyses of the difference between Express BMD and Fast BMD vs. patient thickness and average BMD revealed no significant relationships. In conclusion, the correlation between the new 10 second Express mode and the 30 second Fast mode is excellent. The Express mode offers improved image quality at 30% less dose and may prove more cost effective by increasing patient throughput.
NEW BONE FORMATION INDUCED BY TERIPARATIDE (RHPTH 1- 34) IS MAINTAINED BY RALOXIFENE OR ESTROGEN IN OVARIECTOMIZED RATS H. U. Bryant1*, M. Sato1, Y. L. Ma1, G. L. Evans2, R. T. Turner2 1Lilly Research Laboratories, Indianapolis, Indiana, USA 2Mayo Clinic, Rochester, Minnesota, USA Teriparatide (TPTD) administered once daily (SC) stimulates new bone formation and increases bone mass in ovariectomized (OVX) rats. However, following cessation of TPTD injections, bone mass declines with time. As the discontinuation of TPTD is associated with increased resorption activity, anti-resorptive agents should blunt the loss of TPTD-induced bone gain. In order to evaluate the ability of estrogen receptor based anti-resorptives to maintain bone formed after TPTD exposure, the effects of raloxifene (a selective estrogen receptor modulator) or ethynyl estradiol (EE) were evaluated in OVX rats previously treated with TPTD. 6-month-old virgin Sprague Dawley rats were OVX and permitted to develop osteopenia for 2 months, after which a 2-month TPTD (80 microg/d; SC) regimen was initiated. The TPTD regimen produced marked increases in bone mineral density of both the distal femur and proximal tibia (58%). Following the 2 month TPTD exposure period, animals were either: 1) continued on TPTD for 2 more months, 2) discontinued from TPTD, 3) switched to raloxifene (3 mg/kg/d; PO) or estrogen (17 alpha-ethynyl estradiol; EE - 0.1 mg/kg/d; PO) for 2 months. Animals maintained on TPTD showed a continued increase in bone mass (8%), while animals discontinued from TPTD exhibited a drop in bone mass (23%). Switching to raloxifene or EE prevented the bone loss in the withdrawal group. Dynamic histomorphometric analysis of the proximal tibia revealed a marked increase in bone turnover rate (25%) following discontinuation of TPTD, which was prevented by either raloxifene or EE. Bone formation activity was elevated both by OVX and TPTD treatment, and was restored to levels observed in the sham controls by both raloxifene and EE. Serum osteocalcin levels paralleled these effects on bone formation activity, with raloxifene demonstrating even a less suppressive effect than EE. In a corollary study, pretreatment of OVX rats with raloxifene for a 2 month period, had no untoward effects on the bone formation response induced by TPTD in OVX rats. These studies demonstrate that estrogen receptor based anti-resorptives, such as raloxifene, are an attractive option for the maintenance of bone built with TPTD anabolic regimens. INCREASE OF VASCULAR ENDOTELIAL GROWTH FACTOR (VEGF) AND DECREASE OF PAIN BY ELECTRICAL STIMULATION WITH HIGH VARIABILITY IN FREQUENCY AND AMPLITUDE (LORENZ PAT-PEND). A CLINICAL STUDY IN OSTEOPOROTIC PATIENTS WITH VERTEBRAL FRACTURES M. Bevilacqua*, L. Baruffaldi, L. Foddis, R. Toscano, G. Baldi, T. Vago, V. Righini Sacco University Hospital, Milan, Italy Background and Aims. Administration of exogenous Vascular Endothelial Growth Factor (VEGF) is a promising new treatment to achieve neo-angiogenesis in critical limb and myocardial ischemia and to increase bone mass. Animal studies (rats) show that endogenous VEGF can be produced in the skeletal muscle by electrical long-term (8 hrs) stimulation, with low frequency and low amplitude signals. In humans VEGF can be increased by genetically modified plasmid injections into the ischemic muscle. Plasma level of VEGF after plasmid injections shows, however, minimal increases (2-5 pg/ml). We have devised a new electrical system (Lorenz pat-pend) which employs continuous changes in both frequency and amplitude of electrical current to treat limb ischemia, diabetic neuropathy and pain. These signals don't induce muscle contraction. This study was designed to investigate a possible effect of the electrical stimulation on pain and VEGF in osteoporotic patients. Materials and Methods. Ten patients with vertebral fractures and 10 control subjects were treated with electrical stimulation, appling electrical current signals direcly on the site of vertebral crush through adhesive cutaneous electrodes. After 5 and 10 minutes of electrical stimulation, we measured VEGF plasma levels, platelet number, blood gases and hemodynamic changes. Pain was evaluated with VAS before and after the electrical stimulation. Results. After the first 3 applications of Lorenz, pain consistently decreased in all patients (VAS: 8 to 4; p<0,01). VEGF levels nearly doubled after 5 and 10 minutes of electrical stimulation in patients and in controls. No effect of stimulation was observed on platelet count, blood gases and systemic hemodynamics. Conclusion. This procedure is a simple and practical method to decrease pain and to increase endogenously VEGF levels. Further studies are necessary to evaluate the metabolic effect on bone. NERIDRONATE, BONE MINERAL DENSITY AND TURNOVER IN POSTMENOPAUSAL OSTEOPOROSIS: EFFECT OF DOSING INTERVAL P. Filipponi1*, S. Cristallini1, G. Policani1, B. Frediani2, M. F. Schifini1, P. Garinei1, S. Morlunghi1 1Umbertide Regional Hospital, Center for Metabolic Bone Diseases, Perugia, Italy 2Institute of Reumathology, University of Siena, Italy Neridronate (NER), a nitrogen-containing bisphosphonate developed by Abiogen Pharma (Italy), was tested to evaluate its reliability in the treatment of postmenopausal osteoporosis. In a randomised, placebo-controlled 2-year study, 49 postmenopausal women, aged 49-72 years, with low bone mineral density (BMD) were randomly assigned to one of 2 different treatment groups with intramuscular NER: a) NER, 25 mg every 2 weeks, n=25; b) NER 25 mg/day for 6 consecutive days every 3 months, n=23. 22 postmenopausal women were used as control. Both control and NER patients received calcium and vitamin D supplement. BMD was measured with Lunar Expert every 3 months at lumbar spine (L1-4) and proximal femur. Bone turnover was evaluated by bone specific ALP (bAp) and by urinary type 1 collagen C-telopeptide (CTx), using commercial kits. Results. Intramuscular NER caused an increase in L1-4 and proximal femur BMD in all patients treated (L1-4: A=9.2±1.1; B=7.9±1.2. Total F: A=4.5±0.7; B=3.8±1.2) ). There was a sharp increase during the first 6 months of treatment but a positive trend was still evident after 2 year. Markers of bone turnover reached a nadir at 2-3 months, with a median decrease of 35-40%: suppression persisted at 24 months with both regimens. Decrease in bone turnover was faster with the 3-month regimen (B), without return towards baseline between administrations. No alteration in biochemical tests were observed, including those relating to renal function. Localized pain at the site of injection was the most frequent complain in 15 patients. Acute-phase reaction, with a slight increase in body temperature and arthromyalgia was observed in 5 patients. Conclusion. A powerful inhibitor of bone resorption, NER, at doses of 150 mg every 3 months, significantly increases BMD at spine and hip. No significant differences in BMD and turnover were observed between 2-week and 3-month regimens. Intramuscular intermittent NER could be a valid option in the treatment of osteoporosis, expecially in women with a low compliance for oral bisphosphonate administration. SUSTAINED SUPPRESSION OF A MARKER OF BONE FORMATION (PINP) IN POSTMENOPAUSAL WOMEN TREATED WITH ALENDRONATE FOLLOWING 18-MONTH TREATMENT WITH HRPTH 1-34 J. J. Stepan*, M. Weichetova Faculty of Medicine, Charles University, Prague, Czech Republic Background: Alendronate increases BMD and decreases fracture incidence over 4 yr. During yr 6 and 7, 3.3%/yr of women taking alendronate had a clinical vertebral fracture (JCEM 2000;85:3109) compared to 1.1%/yr of morphometric fractures in the first 3 yr (NEJM,1995,333;1437). In the women taking alendronate for 3 yr, the mineralisation of bone was 11% higher and the activation frequency was 91% lower than in patients on placebo (Bone 2000;27:687). Aim. The aim of this study was to compare markers of bone remodeling in premenopausal women and in women with postmenopausal osteoporosis treated with hrPTH for 18 mo followed by alendronate (ALN) for 24 mo. Methods. The study involved 85 healthy premenopausal women and 24 women with postmenopausal osteoporosis who participated in the clinical trial with hrPTH (7 on placebo, 9 on 20 ug and 6 on 40 ug of PTH). After discontinuation of the trial, all patients were treated with ALN (10 mg/day) for 24 mo. Serum aminoterminal propeptide of type I collagen (PINP) was measured by a radioimmunoassay (Orion Diagnostica) and serum type 1 collagen crosslinked C-telopeptide (S- betaCTX) using the Elecsys (Roche). Results. 2 yr treatment with ALN decreased serum CTX by 52% (mean 169 ng/l, 1 SD range 81-350 ng/l) below the mean premenopausal values (mean 322 ng/l, 1 SD range 254-408 ng/l) (p < 0.01) and serum PINP by 46% (mean 18.8 ug/l, 1 SD range, 10-33 ug/l) below the mean premenopausal values (mean 35.1 ug/l, 1 SD range, 24-52 ug/l) (p < 0.01). No significant differences in the concentrations of the markers of bone remodeling were found between patients previously treated with hrPTH or placebo. Conclusion. ALN therapy following 18 mo hrPTH suppressed bone turnover to lower than premenopausal range. The effect was persistent over 2 yr of therapy. Further investigation is needed to assess the impact of such effect on the fracture risk.
GLUCOCORTICOID INDUCES LOW TURN OVER OSTEOPOROSIS IN GROWING MINIPIGS S. Akahoshi1*, S. Ikeda1, Y. Morishita2, H. Tsutsumi3, M. Ito4, A. Shiraishi5, S. Arita1, M. Nagashima1, A. Sakai1, T. Nakamura1 1Department of Orthopaedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan 2Chugai Pharmaceutical Co. Ltd, Tokyo, Japan 3Chugai Research Institute for Medical Science,INC. 4Department of Radiology, Nagasaki University School of Medicine, Nagasaki, Japan 5Product Research Laboratory, Chugai Parmaceutical Co. Ltd., Tokyo, Japan The purpose of the present experiment was to evaluate osteoporotic changes in the skeleton by glucocorticoids in young Gottingen minipigs, an otherwise often used animal model for human disease. Fifteen gottingen minipigs were used to 3 experimental groups when they were 8 months old: Baseline control group (BC , n=5),Control group (C, n=5) ,Glucocorticoid group (GC , n=5). Group GC received prednisolone for 6 months at 5th times/week , dose of 0.5mg/kg body weight . Body weight , serum Ca , urine Ca , serum BAP , serum OC , urine NTX were measured at 0, 4,12, 24 weeks. Group BC were sacrificed at day 0. Group C and GC were sacrificed at 24 weeks. BMC and BMD were measured by DXA and pQCT. Three-dimensional microarchitecture was measured by micro-CT. Ultimate compressive load was obtained by the materials-testing machine . Lumber body specimen were assessed histomorphometrically. All of serum BAP , serum OC , urine NTX levels in group GC significantly decreased compared with level of them in group C. Histomorphometrically, BFR/BS decreased. BMD value of lumber vertebra significantly decrease mesured by DXA and pQCT. BV/TV,Tb.Th decreased and BS/BV,SMI,TBPf increased in group GC by micro CT. These data suggested glucocorticoid induced osteoporosis is low turnover. In conclusion glucocorticoid induced osteoporosis in growing gottingen minipigs showed low turn over osteoporosis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
