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There is limited wrist fracture information on men. Our goal was to calculate frequency and identify risk factors for wrist fracture in the Osteoporotic Fractures in Men (MrOS) study. We confirmed that fracture history and certain medications are predictors, and identified novel predictors including markers of kidney function and physical performance., Introduction: To calculate the incidence of wrist fractures and their risk factors in older community-dwelling men from the US Osteoporotic Fractures in Men (MrOS) study., Methods: Using triannual postcards, we identified incident wrist fractures (centrally confirmed by radiology) in men aged ≥ 65. Potential risk factors included the following: demographics, lifestyle, bone mineral density (BMD), selected medications, biomarkers, and physical function and performance measures. Both baseline and time-varying models were adjusted for age, race/ethnicity, MrOS geographic location, and competing mortality risks., Results: We observed 97 incident wrist fractures among 5875 men followed for an average of 10.8 years. The incidence of wrist fracture was 1.6 per 1000 person-years overall and ranged from 1.0 among men aged 65-69 to 2.4 among men age ≥ 80. Significant predictors included the following: fracture history after age 50 [hazard ratio (95% CI): 2.48 (1.65, 3.73)], high serum phosphate [1.25 (1.02, 1.53)], use of selective serotonin receptor inhibitor (SSRI) [3.60 (1.96, 6.63), decreased right arm BMD [0.49 (0.37, 0.65) per SD increase], and inability to perform the grip strength test [3.38 (1.24, 9.25)]. We did not find associations with factors commonly associated with wrist and other osteoporosis fractures like falls, diabetes, calcium and vitamin D intake, and alcohol intake., Conclusions: Among these older, community-dwelling men, we confirmed that fracture history is a strong predictor of wrist fractures in men. Medications such as SSRIs and corticosteroids also play a role in wrist fracture risk. We identified novel risk factors including kidney function and the inability to perform the grip strength test.

Unlabelled: Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors., Introduction: Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D., Methods: We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study., Results: IL-6 was lower in men with higher 25OHD (-0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) -0.07 to -0.38 μg/mL) and with higher 1,25(OH)2D (-0.20 μg/mL, 95 % CI -0.0004 to -0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D)., Conclusions: Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

Unlabelled: We investigated the value of routine laboratory testing for identifying underlying causes in older men diagnosed with osteoporosis. Most osteoporotic and nonosteoporotic men had ≥1 laboratory abnormality. Few individual laboratory abnormalities were more common in osteoporotic men. The benefit of routine laboratory testing in older osteoporotic men may be low., Introduction: To evaluate the utility of recommended laboratory testing to identify secondary causes in older men with osteoporosis, we examined prevalence of laboratory abnormalities in older men with and without osteoporosis., Methods: One thousand five hundred seventy-two men aged ≥65 years in the Osteoporotic Fractures in Men study completed bone mineral density (BMD) testing and a battery of laboratory measures, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), 25-OH vitamin D, total testosterone, spot urine calcium/creatinine ratio, spot urine albumin/creatinine ratio, creatinine-derived estimated glomerular filtration rate, 24-h urine calcium, and 24-h urine free cortisol. Using cross-sectional analyses, we calculated prevalence ratios (PRs) and 95 % confidence intervals (CI) for the association of any and specific laboratory abnormalities with osteoporosis and the number of men with osteoporosis needed to test to identify one additional laboratory abnormality compared to testing men without osteoporosis., Results: Approximately 60 % of men had ≥1 laboratory abnormality in both men with and without osteoporosis. Among individual tests, only vitamin D insufficiency (PR, 1.13; 95 % CI, 1.05-1.22) and high alkaline phosphatase (PR, 3.05; 95 % CI, 1.52-6.11) were more likely in men with osteoporosis. Hypercortisolism and hyperthyroidism were uncommon and not significantly more frequent in men with osteoporosis. No osteoporotic men had hypercalciuria., Conclusions: Though most of these older men had ≥1 laboratory abnormality, few routinely recommended individual tests were more common in men with osteoporosis than in those without osteoporosis. Possibly excepting vitamin D and alkaline phosphatase, benefit of routine laboratory testing to identify possible secondary causes in older osteoporotic men appears low. Results may not be generalizable to younger men or to older men in whom history and exam findings raise clinical suspicion for a secondary cause of osteoporosis.

Unlabelled: Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%)., Introduction: Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort., Methods: Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use., Results: At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry., Conclusions: Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

Summary: To determine whether there are race/ethnic differences in bone mineral density (BMD) by fracture history in men aged 65 years and older, we performed cross-sectional analysis in five large independent cohorts. Low BMD was associated with a higher prevalence of fracture in all cohorts, and the magnitude of the BMD differences by fracture status was similar across groups., Introduction: We aimed to determine whether there are race/ethnic and geographic differences in bone mineral density by fracture history in men aged 65 years and older., Method: The datasets included the Osteoporotic Fractures in Men (MrOS) Study (5,342 White, 243 African-American, 190 Asian, and 126 Hispanic), MrOS Hong Kong (1,968 Hong Kong Chinese), Tobago Bone Health Study (641 Afro-Caribbean), Namwon Study (1,834 Korean), and Dong-gu Study (2,057 Korean). The two Korean cohorts were combined., Results: The prevalence of self-reported non-traumatic fracture was US white, 17.1 %; Afro-Caribbean, 5.5 %; US African-American, 15.1 %; US Hispanic, 13.7 %; US Asian, 10.5 %; Hong Kong Chinese, 5.6 %, and Korean, 5.1 %. The mean differences in hip and lumbar spine BMD between subjects with fracture and without fracture were statistically significant in all cohorts except US African American and US Asian men. There was a significant race/ethnic interaction for lumbar spine BMD by fracture status (p for interaction = 0.02), which was driven by the small number of Hispanic men. There was no interaction for femoral neck or total hip BMD. There were no significant race/ethnic differences in the odds ratio of fracture by BMD., Conclusions: Low BMD was associated with a higher prevalence of fracture in all cohorts and the magnitude of the BMD differences by fracture status was similar across groups suggesting homogeneity in the BMD-fracture relationship among older men.

Unlabelled: We used a microsimulation model to estimate the threshold body weights at which screening bone densitometry is cost-effective. Among women aged 55-65 years and men aged 55-75 years without a prior fracture, body weight can be used to identify those for whom bone densitometry is cost-effective., Introduction: Bone densitometry may be more cost-effective for those with lower body weight since the prevalence of osteoporosis is higher for those with low body weight. Our purpose was to estimate weight thresholds below which bone densitometry is cost-effective for women and men without a prior clinical fracture at ages 55, 60, 65, 75, and 80 years., Methods: We used a microsimulation model to estimate the costs and health benefits of bone densitometry and 5 years of fracture prevention therapy for those without prior fracture but with femoral neck osteoporosis (T-score ≤ -2.5) and a 10-year hip fracture risk of ≥3%. Threshold pre-test probabilities of low BMD warranting drug therapy at which bone densitometry is cost-effective were calculated. Corresponding body weight thresholds were estimated using data from the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men (MrOS) study, and the National Health and Nutrition Examination Survey (NHANES) for 2005-2006., Results: Assuming a willingness to pay of $75,000 per quality adjusted life year (QALY) and drug cost of $500/year, body weight thresholds below which bone densitometry is cost-effective for those without a prior fracture were 74, 90, and 100 kg, respectively, for women aged 55, 65, and 80 years; and were 67, 101, and 108 kg, respectively, for men aged 55, 75, and 80 years., Conclusions: For women aged 55-65 years and men aged 55-75 years without a prior fracture, body weight can be used to select those for whom bone densitometry is cost-effective.

Unlabelled: In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss., Introduction: Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men., Methods: Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study-The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4., Results: Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm(2)) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss., Conclusion: Use of ACE inhibitors but not ARB may marginally increase bone loss in older men.

Unlabelled: In elderly man, low serum 25-hydroxyvitamin D (25(OH)D) was associated with a substantial excess risk of death compared to 25(OH)D values greater than 50-70 nmol/l, but the association attenuated with time., Introduction: The aim of the present study was to determine whether poor vitamin D status was associated with an increase in the risk of death in elderly men., Methods: We studied the relationship between serum 25(OH)D and the risk of death in 2,878 elderly men drawn from the population and recruited to the MrOS study in Sweden. Baseline data included general health and lifestyle measures and serum 25(OH)D measured by competitive RIA. Men were followed for up to 8.2 years (average 6.0 years)., Results: Mortality adjusted for comorbidities decreased by 5% for each SD increase in 25(OH)D overall (gradient of risk 1.05; 95% confidence interval 0.96-1.14). The predictive value of 25(OH)D for death was greatest below a threshold value of 50-70 nmol/l, was greatest at approximately 3 years after baseline and thereafter decreased with time., Conclusions: Low serum 25(OH)D is associated with a substantial excess risk of death compared to 25(OH)D values greater than 50-70 nmol/l, but the association attenuates with time. These findings, if causally related, have important implications for intervention in elderly men.

Unlabelled: A rib fracture history after age 45 was associated with a 5.4-fold increase in new rib fracture risk and a 2.4-fold increase in risk of any new clinical fracture in 155,031 postmenopausal women. A rib fracture history suggests osteoporosis and should be considered when evaluating patients for interventions to prevent fractures., Introduction: Until recently, little attention was paid to rib fracture as an osteoporosis marker. Emerging evidence suggests rib fracture may be an osteoporotic fracture in men and women. We report the 5-year independent association between baseline rib fracture histories and self-reported future fractures by age (decade) in the NORA cohort (155,031 postmenopausal women, 50-99 years)., Methods: Participants reported fracture history and responded to follow-up surveys at years 1, 3, or 6. Women with a baseline rib fracture history without other fractures were compared with women with no fracture., Results: At baseline, 4,758 (3.07%) women reported a rib fracture history without other fractures; 6,300 women reported 6,830 new clinical fractures, including wrist (2,271), rib (1,891), spine (1,136), hip (941), and forearm (591). Adjusted relative risk (ARR) values (95% confidence interval [CI]) for future fractures in women with rib fracture history versus women with no fracture history were 5.4 (4.8-6.1) at the rib, 2.1 (1.7-2.6) at the spine, and 1.4 (1.1-1.7) at the wrist, and not significant for forearm or hip fractures. Future fracture risk was at least doubled in women with a rib fracture history in all ages: ARR (95% CI) 3.4 (2.8-4.0) for ages 50-59, 2.5 (2.1-3.0) for ages 60-69, 2.0 (1.7-2.3) for ages 70-79, and 2.0 (1.6-2.6) for ages >80., Conclusions: Rib fracture, the second most common clinical fracture in women (after wrist fracture), predicted future fractures of the rib, wrist, and spine at all ages. Women presenting with rib fractures should be evaluated for appropriate management to prevent future fractures.

Summary: Women in POSSIBLE US™ who expressed greater treatment satisfaction at study entry were more likely to persist with osteoporosis therapy over a 1-year period. Lower satisfaction among women with moderate/severe side effects increased the risk of discontinuation/switching by 67%. Treatment satisfaction and side effect experience influence osteoporosis medication adherence., Introduction: Non-adherence is common among women using postmenopausal osteoporosis (PMO) medications. We describe the association between treatment satisfaction, measured with the Treatment Satisfaction Questionnaire for Medication (TSQM), and the risk of discontinuation/switching PMO medications using patient-reported data from a large, longitudinal cohort study., Methods: Data from 2,405 participants in the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™) Study were evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HR) for the association between treatment satisfaction at study entry and self-reported discontinuation/switching of pharmacologic PMO medications over a 1-year follow-up period. Logistic regression was used to evaluate relationships between treatment satisfaction, lifestyle behaviors, and compliance with bisphosphonate dosing instructions., Results: Median TSQM scores were highest (indicating greatest satisfaction) for the side effects domain [n = 1,182; median = 87.5 (Q1 = 75.0, Q3 = 100.0)] and lowest for global satisfaction [n = 2,340; median = 64.0 (Q1 = 55.7, Q3 = 77.7)]. Median scores decreased for the side effects and global satisfaction domains as patient-reported side effect severity increased. Women with higher satisfaction were less likely to discontinue/switch medications than women with lower scores (adjusted HRs for convenience 0.73, 95% CI = 0.63-0.85; effectiveness 0.82, 95% CI = 0.70-0.97; and global satisfaction 0.73, 95% CI = 0.63-0.85). Lower treatment satisfaction was particularly influential among women who reported moderate/severe side effects (HR = 0.60, 95% CI = 0.37-0.97)., Conclusions: Lower treatment satisfaction was associated with a 22% (1/0.82) to 67% (1/0.60) increased risk of discontinuation/switching osteoporosis medication during 1 year of follow-up.

Unlabelled: In this meta-analysis of all Merck-conducted, placebo-controlled clinical trials of alendronate, the occurrence of AF was uncommon, with most studies reporting two or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious AF was observed., Introduction: To explore the incidence of atrial fibrillation (AF) and other cardiovascular endpoints in clinical trials of alendronate., Methods: All double-blind, placebo-controlled studies of alendronate 5, 10, or 20 mg daily, 35 mg once-weekly, 35 mg twice-weekly, and 70 mg once-weekly of at least 3 months duration conducted by Merck were included in this meta-analysis. The primary method of analysis was exact Poisson regression. Estimated relative risk (RR) of alendronate versus placebo and the associated 95% confidence interval was derived from a model that included number of episodes with factors for treatment group and study and an offset parameter for number of person-years on study., Results: Of 41 studies considered, 32 met all criteria for inclusion in the analysis (participants-9,518 alendronate, 7,773 placebo). Estimated RR for all AF events was 1.16 (95% CI = 0.87, 1.55; p = 0.33). Most trials had two or fewer AF events. The RR of AF classified as a serious adverse event was 1.25 (95% CI = 0.82, 1.93; p = 0.33), but became 0.97 (95% CI = 0.51, 1.85) when the clinical fracture cohort of the Fracture Intervention Trial was excluded, indicating that results were driven by events in that study. Estimated RRs for other cardiovascular endpoints were less than 1., Conclusions: The incidence of atrial fibrillation was low in Merck clinical trials of alendronate and was not significantly increased in any single trial nor in the meta-analysis. Based on this analysis, alendronate use does not appear to be associated with an increased risk of atrial fibrillation.

Unlabelled: Radiographs and spinal bone mineral density (BMD) were evaluated from 342 elderly men regarding possible effects of diffuse idiopathic skeletal hyperostosis (DISH) on vertebral fractures and densitometry measurements. Prevalent vertebral fractures were more frequent among men with DISH compared to men with no DISH even after fracture prevalence was adjusted for BMD. Paravertebral calcifications should be considered in patients with DISH when interpreting BMD measurements because both dual X-ray absorptiometry (DXA) and quantitative CT (QCT) densitometry may not be reliable., Introduction: The purpose of this study is to evaluate the prevalence of DISH in older men and its association with vertebral fractures and with BMD determined by DXA and QCT., Methods: Lateral radiographs of the spine were analyzed in a sample of 342 men aged ≥ 65 years participating in the MrOS Study concerning the presence and grade of DISH and vertebral fractures. Lumbar BMD was measured by both DXA (areal, grams per square centimeter) and QCT (volumetric, grams per cubic centimeter). The association between DISH, BMD, and presence of fractures was studied using χ ( 2 ) and t tests., Results: DISH was present in 52% (178/342) of the men. Men with DISH were older (mean, 75.1 vs 73.3, p < 0.05) and more likely to have prevalent fractures (28% vs 20%, p < p = 0.09). BMD assessed with DXA (1.08 vs 1.00 g/cm(2), p ≤ 0.0001), but not with QCT (0.11 vs 0.11 g/cm3, p = 0.65), was significantly higher in men with DISH compared to men without DISH. Significantly lower BMD of men with both DISH and fractures compared to men with DISH but without fractures was only detected by QCT (-25%, 0.09 vs 0.12, p < 0.05). Both DXA BMD and QCT BMD were significantly higher in severe lumbar DISH (+22% and +31%, p < 0.0001), respectively., Conclusion: DISH was associated with a higher prevalence of vertebral fractures in elderly men. Lumbar ossifications related to DISH should be considered when interpreting BMD measurements to predict their fracture risk.

We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥ 65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p < 0.005)., Inroduction: Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans., Methods: We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥ 65 years in the Osteoporotic Fractures in Men Study., Results: SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p < 0.005)., Conclusion: None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

Summary: BMD was compared across race/ethnic groups. There were substantial race/ethnic differences in BMD even within African or Asian origin. Additional adjustment for body size greatly attenuated or reversed the differences between US Caucasian men vs Asian men. It illustrates the role of body size on the difference between these groups., Introduction: There is insufficient epidemiologic information about men's bone mineral density (BMD) levels across race/ethnic groups and geographic locations., Methods: In a cross-sectional design, we compared BMD in older men across seven race/ethnic groups in four countries. Femoral neck, total hip, and lumbar spine BMD were measured in men (age 65 to 78 years) from the Osteoporotic Fractures in Men (MrOS) Study (4,074 Caucasian, 208 African-American, 157 Asian, and 116 Hispanic men in USA), Tobago Bone Health Study (422 Afro-Caribbean men), MrOS Hong Kong Study (1,747 Hong Kong Chinese men), and the Namwon Study (1,079 South Korean men). BMD was corrected according to the cross-site calibration results for all scanners., Results: When compared with US Caucasian men, Afro-Caribbean and African-American men had, respectively, 8-20% and 6-11% higher age-adjusted mean BMD at all three bone sites. Hip BMD was similar in US Caucasian and Hispanic men, US Asian, Hong Kong Chinese, and Korean men had 3-14% lower BMD at all bone sites except femoral neck in Korean men. Additional adjustment for weight and height greatly attenuated or reversed the differences between US Caucasian men vs Asian men including US Asian, Hong Kong Chinese, and South Korean men. Among Asian groups, Korean men had higher femoral neck BMD and lower total hip BMD., Conclusion: These findings show substantial race/ethnic differences in BMD even within African or Asian origin and illustrate the important role of body size on the difference between Asian men and others.

Summary: In 5,541 community dwelling men, chronic obstructive pulmonary disease, or asthma was associated with lower bone mineral density (BMD) at the spine and total hip and an increased risk of vertebral and nonvertebral fractures independent of age, body mass index, and smoking. Men prescribed with corticosteroids had the lowest BMD., Introduction: It is unclear whether chronic obstructive pulmonary disease (COPD) is independently associated with BMD and fractures., Methods: In 5,541 men from the Osteoporotic Fractures in Men Study, history of COPD or asthma, current treatment with corticosteroids, BMD, bone loss after 4.5 years and fractures were ascertained., Results: Seven hundred fourteen (13%) men reported COPD or asthma, of which 103 were prescribed an oral steroid and 177 an inhaled steroid. Independent of confounders, men prescribed corticosteroids for COPD or asthma had the lowest BMD and a 2-fold increased risk of vertebral osteoporosis compared to men with no history of COPD or asthma (OR 2.13, 95% CI (confidence interval) 1.15-3.93 oral steroids; OR 2.05, 95% CI 1.27-3.31 inhaled steroids). During follow-up, BMD increased at the spine, but there was no difference in bone loss at the hip. However, men with COPD or asthma had a 2.6- and 1.4-fold increased risk of vertebral and nonvertebral fractures, respectively., Conclusion: Chronic obstructive pulmonary disease or asthma was associated with lower BMD at the spine and hip and increased risk of vertebral and nonvertebral fractures independent of age, clinic site, BMI, and smoking. A history of COPD or asthma may be a useful clinical risk factor to identify patients with osteoporosis.

Summary: We examined the association between peripheral arterial disease (PAD) and bone health in 1,332 adults. We found a weak association between PAD and osteoporosis and bone loss only in women, but the association was not independent of age. PAD was not associated with fractures in this community-based population., Introduction: Increased rates of osteoporosis have been reported in patients with cardiovascular disease, suggesting a link between osteoporosis and atherosclerosis., Methods: We examined the association between PAD and bone health in 1,332 adults who attended a research visit in 1992-1996, when the ankle-brachial index (ABI), bone mineral density (BMD), and spine X-rays were obtained. A total of 837 participants attended a follow-up visit in 1997-2000., Results: PAD defined by an ABI < or = 0.90 was present in 15.4% of the women and 13.3% of the men. Prevalence of osteoporosis was significantly higher in women with PAD compared to women without PAD (p < 0.05). During an average 4-year follow-up, women with PAD had a significantly higher rate of bone loss than women without PAD (p = 0.05). The associations were no longer significant after age adjustment. In men, PAD was not associated with osteoporosis, but men with PAD had lower BMD at the femoral neck than men without PAD (p = 0.03). PAD was not associated with osteoporotic fractures in either sex., Conclusion: We found a weak and age-dependent association between PAD and osteoporosis in women but not men. PAD was not associated with fractures in this community-based population.

Unlabelled: In women, but not men, lower 25-hydroxyvitamin D [25(OH)D] levels were associated with impaired performance on two lower extremity function tests in both cross-sectional and prospective analyses., Introduction: Preserved physical function may explain how 25(OH)D supplementation reduces falls and fractures., Methods: A total of 1,065 community-dwelling men and women (mean age 74.6 years) with 25(OH)D levels and performance on timed up and go (TUG) and timed chair stand (TCS) were seen in 1997-1999; 769 (72%) participants returned for follow-up. Associations were examined using generalized linear models., Results: 25(OH)D levels were higher in men than women, but the prevalence of vitamin D insufficiency defined as 25(OH)D <75 nmol/L was 14%. There were no baseline sex differences in TUG or TCS. However, after 2.5 years, decline in TCS and TUG was greater in women than men (11% vs. 3%; p < 0.001). Women in the lowest 25(OH)D quartile (<80 nmol/L) compared to the highest quartile had an accelerated rate of functional decline on the TUG and TCS independent of covariates. No significant associations were seen in men., Conclusion: In women, but not men, lower 25(OH)D levels were associated with impaired performance on two lower extremity function tests in both cross-sectional and prospective analyses. These results provide additional evidence that 25(OH)D is associated with physical function, which may explain how vitamin D supplementation reduces falls and fractures.

Unlabelled: Using data from 66,134 postmenopausal women enrolled in the National Osteoporosis Risk Assessment (NORA) study, more than half of whom were less than age 65, we identified 18 risk factors that independently predicted a significantly increased risk of falling and observed a graded increase in risk with an increasing number of risk factors., Introduction: This study was designed to identify predictors of falls in a large prospective study of community-dwelling, postmenopausal women, 58% of whom were less than 65 years old at baseline., Methods: We exclusively used survey data from 66,134 NORA participants who completed the baseline survey and three follow-up surveys over 6 years. Stepwise logistic regression was used to select potential fall predictors. A simple fall risk index was created by giving one point to each significant independent risk factor., Results: More than one third (38.2%) of participants reported at least one fall since baseline. The largest predictor of fall risk was history of falls (odds ratio [OR] = 2.7). In the multivariate analysis, 17 additional risk factors were significantly associated with incident falls (but with smaller OR), including age, college education, poor hearing, diabetes, personal or family history of fracture, hypothyroidism, and height loss. Of the 3,346 women with zero fall risk factors, 22.6% reported falling compared to 84.3% of the 51 women with >or=11 risk factors., Conclusions: This large cohort had sufficient power to identify 18 risk factors that independently predicted a significantly increased risk of falling with a graded increase in risk with increasing number of risk factors.

Unlabelled: Failure to take prescribed medication is common. The POSSIBLE US study is evaluating the impact of physician and patient characteristics on patient-reported compliance and persistence with osteoporosis medications. We report our study design and the baseline characteristics of 4,994 postmenopausal women recruited from primary care physician offices in 33 states., Introduction: The Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US) is a longitudinal cohort study of osteoporosis therapy in primary care., Methods: Between 2004 and 2007, 134 physicians (in 33 states) enrolled postmenopausal women initiating, changing, or continuing osteoporosis medications. After completing a baseline questionnaire, participants will provide data semi-annually for up to 3 years through 2008. Physicians provide patient data at baseline and routine follow-up visits. Participants from 23 sites also signed a release regarding administrative claims data for economic analyses and validation of self-reported data., Baseline Results: Four thousand nine hundred and ninety-four evaluable women were recruited from internal medicine (n = 1,784), family practice (n = 1,556), obstetrics/gynecology (n = 1,556), and from one rheumatology practice (n = 98). Mean participant age was 64.3 years (SD = 9.97); 89% were Caucasian; 59% had some college education. Sixty-three percent used a single osteoporosis agent, usually a bisphosphonate. For monotherapy patients, concordance between clinic- and patient-reported medication use was lowest for patients prescribed estrogen therapy (70%) or calcium/vitamin D (72%). Obstetrician/gynecologists enrolled younger women, who were more likely to use estrogen therapy than patients enrolled by other physicians. The 934 women (19%) prescribed only calcium/vitamin D were younger than women prescribed pharmacologic therapy., Conclusions: POSSIBLE US provides a unique foundation for evaluating longitudinal use of osteoporosis medications and related outcomes.

Unlabelled: Older men with reduced renal function are at increased risk of hip bone loss. Given the robustness of this association across different measures and a growing body of literature, our findings indicate that clinicians should take into account renal function when evaluating older men for osteoporosis risk and bone loss. Future randomized controlled trials should test whether interventions in this high risk population are effective in preventing bone loss and decreasing fracture incidence., Introduction: Studies examining whether kidney impairment, not requiring dialysis, is associated with osteoporosis have reported conflicting results., Methods: We tested the hypothesis that reduced renal function in older men as manifested by higher concentrations of cystatin C or lower levels of estimated glomerular filtration rate (eGFR) is associated with higher rates of bone loss. We measured serum cystatin C, serum creatinine and total hip bone mineral density (BMD) at baseline in a cohort of 404 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study and followed them prospectively for an average of 4.4 years for changes in BMD. Associations between renal function and change in hip BMD were examined using linear regression., Results: In multivariable analysis, the mean rate of decline in total hip BMD showed an increase in magnitude with higher cystatin C concentration (mean annualized percent change -0.29, -0.34, -0.37 and -0.65% for quartiles 1 to 4; p for trend=0.004). Similarly, adjusted rates of hip bone loss were higher among men with lower eGFR as defined by the modification of diet in renal disease formula (mean annualized percent change -0.58, -0.39, -0.37, and -0.31 for quartiles 1 to 4; p for trend=0.02), but not among men with lower eGFR as defined by the Cockcroft-Gault formula (mean annualized percent change -0.47, -0.44, -0.31 and -0.43 for quartiles 1 to 4; p for trend=0.48)., Conclusions: Older men with reduced renal function are at increased risk of hip bone loss. Our findings suggest that health care providers should consider renal function when evaluating older men for risk factors for bone loss and osteoporosis.

Unlabelled: We compared hip axis length (HAL) in 157 non-Hispanic white women, 292 African-American women, and 210 Mexican-American women. After adjusting for maximal hip girth, there were no residual differences in HAL by ethnicity. Differences in hip fracture risk seen between these groups cannot be explained by ethnic differences in HAL., Introduction: Hip axis length (HAL) has been reported to be an independent predictor of hip fracture. Significant ethnic differences in HAL have been noted, but no direct comparison has been made between African-American, Mexican-American, and non-Hispanic white women using the same protocol., Methods: We compared 157 non-Hispanic white women from the Rancho Bernardo Study, 292 women from the Health Assessment Study of African-American Women, and 210 women from the Skeletal Health of Mexican-American Women Project. A standardized questionnaire was used to obtain medical history; height, weight, waist girth, and hip girth were measured; and percentage body fat and HAL were obtained using dual energy X-ray absorptiometry. All HAL comparisons were adjusted for maximum hip girth to control for differences in size magnification by fan-beam absorptiometry., Results: Though there were ethnic differences in the unadjusted HAL measurement, after adjusting for hip circumference, there were no residual differences in HAL with regard to ethnicity: 10.7 cm in Mexican-American women vs. 10.8 in non-Hispanic white women and African-American women (p = 0.61)., Conclusions: There were no ethnic differences in HAL in women from the three ethnic groups. Differences in fracture risk among these groups cannot be explained by ethnic differences in HAL.

Unlabelled: No large-scale evaluations of osteoporosis screening tools have been done in men. OST and MOST were examined among 4658 US Caucasian and 1914 Hong Kong Chinese men. Both tools have high negative predictive values, accurately screening out men with low risk, and saving a third of DXA tests., Introduction: Prior investigations have studied the performance of osteoporosis screening tools in women, but no large-scale evaluations have been done in men., Methods: This study examines the performance of the Osteoporosis Self-assessment Tool (OST), the Male Osteoporosis Screening Tool (MOST), quantitative ultrasound index (QUI), and body weight as screening tools. Osteoporosis was defined by a dual-energy X-ray absorptiometry (DXA) measured bone mineral density (BMD) T-score < or =-2.5. Four thousand six hundred and fifty-eight US Caucasian and 1914 Hong Kong Chinese men, aged > or =65 years and community-dwelling, were included in the analysis. Receiver operating characteristic (ROC) analysis was used to compare the area under the ROC curve (AUC) between different screening tools., Results: MOST had a significantly larger AUC (> or =0.8) than OST, QUI, and body weight in detecting osteoporosis. Using the second tertile as cutoff, OST and MOST yielded sensitivities of around 90% and negative predictive values (NPVs) of >97%, accurately screening out Caucasian and Chinese men with low risk of osteoporosis., Conclusions: OST and MOST can effectively rule out osteoporosis for both Caucasian and Chinese men, and compared to referring men 65 years and older for BMD DXA testing, they save a third of DXA resources.

Unlabelled: The short-term association between wrist-fracture history and future fracture has not been simultaneously compared between younger and older postmenopausal women. This 3-year follow-up study of 158,940 women showed a similar future fracture risk in younger and older women with wrist-fracture history., Introduction: We examined the association between prior wrist fracture and future osteoporosis-related fractures within 3 years in younger and older postmenopausal women., Methods: In the National Osteoporosis Risk Assessment (NORA) study, 158,940 postmenopausal women, aged 50-98 (median 63) years, provided information on fracture history since age 45, and responded to follow-up surveys 1 or 3 years later when new fractures were queried. Cox regression models were used to obtain relative risk (RR) and 95% confidence interval (CI) estimates., Results: Of the 158,940 participants, 8,665 reported a history of wrist fracture at baseline; 4,316 women reported at least one new fracture within three years. The RR for any subsequent clinical fracture, adjusted for covariates and baseline BMD T-score, was 2.4 (2.0, 2.9) for younger and 2.1 (1.9, 2.3) for older women. A prior wrist fracture increased the risk of a future wrist fracture about 3-fold and doubled the risk of any osteoporotic fracture., Conclusions: Prior wrist fracture strongly predicts three-year risk of any future osteoporotic fracture for older and younger postmenopausal women, independent of baseline BMD and common osteoporosis risk factors. More consideration should be given to evaluating and managing osteoporosis in younger and older women with a history of wrist fracture, independent of their BMD.

Unlabelled: We examined the rate of clinical vertebral fractures, and the circumstances associated with the fractures, in a cohort of 5,995 US older men. Fractures were more common in the most elderly men, and were usually associated with falls and other low-energy trauma., Introduction: Little is known about clinical vertebral fractures in older men. We postulated that clinical vertebral fractures occur with falls, affect men with osteoporosis, and are more common as age increases., Methods: Five thousand nine hundred and ninety-five men aged > or =65 years were followed prospectively for an average of 4.7 years. Men with incident clinical vertebral fractures were compared to controls., Results: One percent (n = 61) sustained incident clinical vertebral fractures (2.2/1,000 person-years). The rate of fracture rose with age (0.7% in men 65-69 years and 5% > or =85 years). Fractured men were more likely frail (8.2% vs. 2.2%), more often fell (36.1% vs. 21%) and had lower total hip and lumbar spine BMD (all p values < or =0.002). In 73.8% of cases fractures were precipitated by no known trauma or by low-energy trauma, including falls in 57.3% Fractures were thoracic in 33% and lumbar in 56%. Men with an incident vertebral fracture were more likely to be osteoporotic (13% vs. 2%, p < 0.0001), but most men with incident fractures did not have osteoporosis., Conclusions: Incident clinical vertebral fractures were relatively common in older men and the rate increased after age 80 years. Fractures were usually associated with minimal trauma, most commonly a fall.

Unlabelled: The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women., Introduction: Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results., Methods: The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates., Results: Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score < or =-2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D., Conclusions: Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women.

Unlabelled: This study investigated osteoporosis management trends from 1998 to 2006 among 808 primary care physicians involved in the US-based NORA (National Osteoporosis Risk Assessment) study. These results suggest some significant improvements in osteoporosis management over the past eight years., Introduction: The purpose of this study was to investigate osteoporosis management trends among a large cohort of primary care physicians (PCPs) involved in the US-based NORA (National Osteoporosis Risk Assessment) study., Methods: In 2006, we undertook a resurvey of the 2,836 NORA PCPs who completed a baseline survey in 1998. Of the 2,199 PCPs for whom we had current contact information and who were still practicing, we collected usable surveys from 808 (37% response rate)., Results: From 1998 to 2006, more than double the percentage of NORA PCPs reported using BMDs "often" (35% vs. 87%). There was a doubling of the percentage of NORA PCPs who reported that a T-score of < or = -2.5 was the threshold indicating the presence of osteoporosis (34% vs. 67%). The percentage of NORA PCPs who reported using bone turnover markers to screen, diagnosis, or monitor osteoporosis almost tripled (19% vs. 55%). The percentage of patients prescribed or recommended hormone therapy dropped sixfold (67% to 11%), and the percentage of patients prescribed bisphosphonates increased fourfold from 15% to 59%., Conclusion: These results suggest some significant improvements in osteoporosis management over the past eight years.

Unlabelled: We examined the associations of metabolic syndrome (MS) with BMD, osteoporosis, and osteoporotic fractures in 417 men and 671 women from the Rancho Bernardo Study. After adjusting for BMI, MS was associated with lower, not higher BMD. Incidence of osteoporotic non-vertebral fractures was higher in participants with MS. MS may be another risk factor for osteoporotic fractures., Introduction: The metabolic syndrome (MS) is a cluster of risk factors, including abdominal obesity, high glucose, triglycerides, hypertension and low HDL levels, associated with cardiovascular disease morbidity. The association between components of the MS and bone mineral density (BMD) has been researched, but results are contradictory., Methods: We used multivariate regression models to examine the cross-sectional associations of MS defined by NCEP-ATP III criteria with BMD and osteoporosis, and the longitudinal association of MS with fractures in 420 men and 676 women from the Rancho Bernardo Study., Results: Prevalence of MS at baseline was 23.5% in men and 18.2% in women. In age-adjusted analyses, men and women with MS had higher BMD at total hip when compared to those without MS (p < 0.001 and p = 0.01, respectively). Men but not women with MS also had higher BMD at femoral neck (p = 0.05). After adjusting for BMI, these associations were reversed, such that MS was associated with lower and not higher BMD., Conclusion: Incidence of osteoporotic non-vertebral fractures was higher in participants with MS. MS may be another risk factor for osteoporotic fractures. The association of MS with higher BMD was explained by the higher BMI in those with MS.

Unlabelled: Using data from NORA, we used 18 potential risk factors in a classification and regression tree analysis to build two algorithms. These algorithms correctly identified postmenopausal women between the ages of 50 and 64 years who were at the highest risk of osteoporotic fracture within 36 months., Introduction: The objective was to develop algorithms that best predict short-term fracture risk (3 years) in postmenopausal women 50-64 years old., Methods: Data were from 91,652 women who responded to follow-up surveys as part of National Osteoporosis Risk Assessment (NORA) study. Peripheral bone mineral density (BMD) and risk factors obtained at baseline; incident osteoporotic fractures obtained from follow-up surveys. Eighteen risk factors were entered into a classification and regression tree analysis to build two algorithms, one with and one without BMD., Results: Two thousand and seven (2.2%) women reported new osteoporotic fractures. Prior fracture, a peripheral BMD T-score

Introduction: This study examined the distribution and determinants of serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) and their associations with bone mineral density (BMD) at the hip and spine in 414 older men (mean age 74 years) living in southern California., Methods: At a clinic visit (1997-2000), demographic and lifestyle information, fracture history, and medication use were recorded; venous blood for serum 25OHD and PTH was obtained; and BMD was measured at the hip and spine., Results: Only one man had vitamin D deficiency (25OHD <20 nmol/l), but 15.5% of the men had high parathyroid levels (PTH >or=65 pg/ml). The mean 25OHD and PTH levels were 109.0 nmol/l and 50.3 pg/ml, respectively. Overall, 21.5% used calcium and 9.7% used vitamin D supplements. Serum 25OHD decreased with age and was lowest in the winter; levels were higher in supplement users (vitamin D and/or calcium; p<0.01). Serum PTH did not vary by age or season, and it was lower in supplement users (p<0.01). After excluding 12 men who were outliers for serum 25OHD and PTH, there was no significant correlation between serum 25OHD and PTH (r=-0.05, p=0.3). In multiple adjusted models, serum 25OHD was positively associated with BMD at the hip (p=0.01) and spine (p=0.001). Serum PTH was moderately and inversely associated with BMD at the hip (p=0.04) but not at the spine (p=0.77)., Conclusion: We conclude that serum 25OHD is associated with bone health in older, community-dwelling men.

Introduction: Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones., Methods: To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study., Results: Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001)., Conclusions: These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.

Introduction: This study evaluates the effect of age and bone mineral density (BMD) on the absolute, excess, and relative risk for osteoporotic fractures at the hip, wrist, forearm, spine, and rib within 3 years of peripheral BMD testing in postmenopausal women over a wide range of postmenopausal ages., Methods: Data were obtained from 170,083 women, aged 50-99 years, enrolled in the National Osteoporosis Risk Assessment (NORA) following recruitment from their primary care physicians' offices across the United States. Risk factors for fracture and peripheral BMD T-scores at the heel, forearm, or finger were obtained at baseline. Self-reported new fractures at the hip, spine, rib, wrist, and forearm were obtained from questionnaires at 1- and 3-year follow-ups. Absolute, excess (attributable to low BMD), and unadjusted and adjusted relative risks of fracture were calculated., Results: At follow-up, 5312 women reported 5676 fractures (868 hip, 2420 wrist/forearm, 1531 rib, and 857 spine). Absolute risk of fracture increased with age for all fracture sites. This age-effect was most evident for hip fracture--both the incidence and the excess risk of hip fracture for women with low BMD increased at least twofold for each decade increase in age. The relative risk for any fracture per 1 SD decrease in BMD was similar across age groups (p>0.07). Women with low BMD (T-score <-1.0) had a similar relative risk for fracture regardless of age., Conclusions: At any given BMD, not only the absolute fracture risk but also the excess fracture risk increased with advancing age. Relative risk of fracture for low bone mass was consistent across all age groups from 50 to 99 years.

Introduction: Most of the research on osteoporosis has been conducted on women. Few studies have compared central and peripheral densitometry and their association with vertebral fractures in men. The present study was designed to compare peripheral bone mineral density (BMD) measurements with central BMD measurements, and to examine their association with radiographic spine fracture in men., Methods: We studied 402 community-dwelling men aged 45-92 years (mean: 70 years) from the Rancho Bernardo Study cohort who attended a clinic visit between 1988 and 1992 when BMD measurements of the midshaft radius, ultradistal wrist, lumbar spine, and total hip were obtained, and who returned for lateral X-rays of the thoracic and lumbar spine an average of 4 years later. Logistic regression, T-scores, and quintiles were used to analyze BMD and its association with vertebral fractures., Results: The prevalence of osteoporosis defined by the National Osteoporosis Foundation criteria (for women) was 14.2% at the spine and 13% at the hip. Because there are no validated definitions of osteoporosis based on the ability to predict fracture risk for peripheral densitometry, the frequency of overlap by bone site was calculated among men in the lowest quintile of each site. Of the 402 men, 82 men (20.3%) had at least two sites with BMD measurements in the lowest quintile. After an average of 4 years, 33 (8.2%) men had at least one radiographic vertebral fracture, and ten (2.5%) men had at least two vertebral fractures. Low BMD at the spine (with and without covariate adjustment) was associated with having one or more vertebral fractures, whether using NOF T-score-defined osteoporosis [Odds ratio (OR): 3.81; confidence interval (CI): 1.52, 9.57] or the lowest quintile versus all others (OR: 2.53; CI: 1.03, 6.19). After age and/or other covariate adjustments, neither BMD at the total hip nor at the peripheral sites was associated with spine fractures using either NOF women-based criteria or male quintiles from this cohort., Conclusion: Although different men had osteoporosis defined by quintiles at different sites, only low BMD at the spine was associated with vertebral fracture.

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50-97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l+/-35.0 nmol/l and 49.4 ng/l+/-23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels (p=0.04), and positively and independently associated with 25(OH)D levels (p=0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate (r=-0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.

Bone mass is a major determinant of fracture, but there have been few comprehensive studies of the correlates of bone mineral density (BMD) in older men. The objective of the current cross-sectional analysis was to determine the factors associated with BMD of the lumbar spine and proximal femur in a large population-based sample of older men enrolled in The Osteoporotic Fractures in Men Study, "Mr.OS." We enrolled 5,995 men 65 years of age or older, 89% Caucasian, in Mr.OS at six US clinical centers. Demographic, medical and family history and lifestyle information was obtained by interview and physical function and anthropometric data by examination. Spine and hip BMD was measured using dual-energy X-ray absorptimetry. The multivariable linear regression models predicted 19 and 10% of the overall variance in BMD of the femoral neck and spine, respectively. African-American men had 6 to 11% higher BMD than Caucasian men independent of multiple factors. Hip BMD declined with advancing age, while spine BMD increased. Body weight (per 10 kg) and self report of diabetes were each associated with 2 to 4% higher BMD, while history of a non-trauma fracture and current use of selective serotonin reuptake inhibitors, but not other antidepressants, were associated with at least 4% lower BMD. Both maternal and paternal histories of fracture were associated with 1.4-1.7% lower BMD. Osteoarthritis, physical activity, grip strength, alcohol intake, and dietary calcium were positively related to BMD, while a history of chronic lung disease, prostate cancer, and kidney stones was associated with lower BMD. Smoking, caffeine intake, and thiazide diuretics were not related to BMD in older men. A number of lifestyle and behavioral characteristics and medical conditions were associated with BMD in older men. Identification of these correlates could improve methods to identify men at risk for fracture and improve our understanding of fracture etiology.

Insulin-like growth factor-I (IGF-I) stimulates osteoblast function, inhibits collagen matrix degradation, and is positively associated with bone mineral density in most but not all studies. We previously reported that IGF-I was positively associated with BMD at the spine and hip in women but not men. Insulin-like growth factor binding protein-1 (IGFBP-1), a potent modulator of IGF-I, is expressed in normal osteoblasts and inhibits collagen gene expression in bone, but little is known about the relationship between IGFBP-1 and bone mineral density (BMD). We report a cross-sectional study of serum IGFBP-1 levels and BMD in 1,139 community-dwelling men and postmenopausal women (not using estrogen), aged 44-98. In both sexes, IGFBP-1 levels increased linearly with age (p<0.001) and decreased with body mass index (BMI) quartile (p<0.001). After adjusting for age and BMI, there was no significant association between IGFBP-1 and BMD at the hip or spine. IGF-I and IGFBP-1 were weakly and inversely associated with each other. These findings suggest that if there is an important role for IGFBP-1 in bone metabolism, it is mediated or confounded by weight. Studies are needed to further investigate the relationship between inhibitory components of IGF-1 and bone loss.

The objective of this work was to examine the prediction of incident hip fracture risk by composite indices of femoral neck strength, constructed from dual X-ray absorptiometry (DXA) scans of the hip. These indices integrate femoral neck size and body size with bone density, and reflect the structure's ability to withstand axial compressive forces and bending forces, and the ability to absorb energy in an impact. We studied a prospective cohort of community-dwelling women, 55 years or older at baseline, average age 72 years, that was established in 1988, with follow-up until 1998. Higher baseline values of each composite strength index were associated with lower risk of incident hip fracture in this cohort. After adjusting for age and body mass index, relative risks associated with each standard deviation increment in the composite indices were 0.39 for compression strength (95% confidence interval 0.25-0.60), 0.43 for bending strength (95% confidence interval 0.27-0.70), and 0.34 for impact strength (95% confidence interval 0.20-0.58). Larger bone size relative to body size was associated with lower risk of incident hip fracture. After adjusting for age, body mass index, and bone density, each standard deviation increment in femoral neck width normalized by body weight was associated with incident hip fracture relative risk of 0.38 (95% confidence interval 0.20-0.70). Our results suggest that composite indices of femoral neck strength, constructed from DXA measurements, have the potential to improve hip fracture risk assessment. This needs further exploration in larger cohorts and in different population sub-groups.

Recent studies reported an association between apolipoprotein E (ApoE) 4 and osteoporosis. We examined the association of ApoE 4 genotype with bone mineral density (BMD), bone loss and fracture risk in 596 men and 332 community-dwelling women aged 45-95 years. Women were postmenopausal and not using estrogen. At the baseline visit, BMD was measured at the ultradistal and midshaft radius using single photon densitometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Hip and lumbar spine BMD levels were remeasured 4 years later. Self-reported fractures were confirmed by radiology reports in 95% of cases. ApoE allele distribution did not vary by age; 25% of men and 20% of women had one ApoE 4 allele. There were no differences in BMD at the lumbar spine, total hip, ultradistal or midshaft radius in men or women with the ApoE 4 allele compared with men or women without the ApoE 4 allele. After an average 4 year interval, there were also no differences in the annualized percent change in BMD at the hip or lumbar spine in men or women with or without an ApoE 4 allele. One or more clinical fractures were reported by 55 men and 109 women. Fewer, not more, clinical fractures were reported in men and women with an ApoE 4 allele; these differences were not statistically significant (p = 0.21 and p = 0.62, respectively). These data do not support the hypotheses that there is an association between ApoE genotype and BMD, bone loss or osteoporotic fractures in older community-dwelling men or women.

There is a need for low-cost screening methods to detect low bone mass (osteopenia or osteoporosis) in postmenopausal women. The utility of quantitative ultrasonography (QUS) of the hand was assessed for osteoporosis screening using the WHO criteria. Bone mineral density (BMD) was measured in 206 postmenopausal Mexican-American women at the total hip and lumbar spine by dual-energy X-ray absorptiometry (DXA). The amplitude-dependent speed of sound (AD-SoS) was measured in the phalanges by QUS. Subjects identified by DXA as having osteopenia or osteoporosis had significantly lower AD-SoS values in comparison with normals. Estrogen users had significantly higher spine and hip BMD and AD-SoS values compared with non-estrogen users. The areas under the receiver operating characteristic (ROC) curves (AUC) for AD-SoS to screen for osteoporosis (T-score < or = -2.5) at the spine or hip were 0.73 for all subjects, 0.74 for estrogen users and 0.68 for non-estrogen users. The AUC for non-estrogen users to screen for osteopenia (T-score -1 to -2.5) was 0.77. Performance comparisons of AD-SoS with SCORE (a risk factor questionnaire) and body weight showed AUC values of 0.73, 0.69 and 0.65, respectively. QUS was the superior screening test when considering both the AUC and the shape of the ROC curves. For non-estrogen users, the group at higher risk for osteoporosis, QUS correctly identified 31% as normal, and 62% as having low bone mass and needing DXA referral; and the remaining 7% were false negatives. These data suggest phalangeal QUS can be effectively used for screening osteoporosis in postmenopausal women.

Understanding the determinants of adult bone mass may help to identify women for prevention of osteoporosis. We postulated that birth weight would predict low adult bone mass in old age. Subjects were 305 postmenopausal Caucasian women (mean age 70 years). Bone mineral content (BMC) and bone mineral density (BMD) were measured at the wrist, forearm, hip and lumbar spine. Birth weight was assessed by self-report. Birth weight was positively correlated with BMC at the forearm (r = 0.15), hip (r = 0.12) and lumbar spine (r = 0.18), and the age-adjusted mean BMC increased significantly from the lowest to the highest birth weight tertile. Adjusting for adult weight diminished this association at the forearm and hip, but not at the spine. Adjustment for multiple other covariates, including height, did not materially change these associations. Adult weight and height were significantly correlated with birth weight (r = 0.19 and r = 0.24, respectively). Birth weight was not independently correlated with BMD. Birth weight was thus positively correlated with adult weight and BMC 70 years later. These findings suggest that low birth weight may be a marker for future low bone mass and that different mechanisms exist for establishing the adult bone envelope (estimated by BMC) versus its density (estimated by BMD).

Osteoporosis is a major health problem in older women. A risk assessment tool, the Simple Calculated Osteoporosis Risk Estimation (SCORE), has been developed to identify postmenopausal women likely to have low bone mass who should be referred for bone densitometry. The objective of this study was to calculate the sensitivity, specificity and predictive values of SCORE in a community-dwelling sample of older women. A total of 1013 postmenopausal Caucasian women aged 44-98 years provided a standard medical history including history of osteoporotic fractures and medication use. Bone mineral density (BMD) was measured at the femoral neck using dual-energy X-ray absorptiometry. In accordance with the SCORE protocol, low BMD was defined as 2 or more standard deviations below the mean BMD in healthy young women. Among these older women (mean age = 72.5 years), 67% had low BMD. Using the recommended SCORE cutpoint of 6, the sensitivity of SCORE was 98% but the specificity was only 12.5%. The positive predictive value (PPV) and negative predictive value (NPV) were 69% and 75%, respectively, meaning that all but 5.5% of the women would be recommended for bone densitometry. Increasing the cutpoint of 11, based on ethnicity and the receiver operating characteristic (ROC) curve, reduced sensitivity to 80% but improved specificity to 46%. The PPV and NPV were 75% and 53%, respectively, meaning that bone scans would not be recommended for 28% of the women. However, 13% of the women with low BMD would be missed. Analyses restricted to women <74 years of age reduced the rate of recommended bone densitometry but increased the number of women with low BMD who would be missed. We conclude that SCORE has limited value as a method for appropriately referring older ambulatory women for bone densitometry.

Serum albumin has been found to be positively correlated with bone mass in small studies of ambulatory men or women with diagnosed osteoporosis. In this study the relation between serum albumin and bone mineral density (BMD) was examined in 1593 white, community-dwelling men and women aged 50-95 years. BMD was determined using single-photon absorptiometry (SPA) at the ultradistal radius and the midshaft radius, and using dual-energy X-ray absorptiometry (DXA) at the hip and spine. Albumin was measured from a fasting blood sample using the Technicon SMA 12 autoanalyzer. Mean albumin levels in both men and women decreased significantly with increasing age. All but four values were within the normal range (3.5-5.0 g/dl). BMD decreased with increasing age at all sites. In both sexes there was weak positive correlation between serum albumin and BMD in the unadjusted model (Pearson's r values < 0.3, p values < 0.005). After age adjustment, however, the relationship was no longer significant (Pearson's r values < 0.05, p values > 0.18). Men and women were divided into three sex-specific categories--osteoporotic, osteopenic and normal--based on World Health Organization criteria in relation to young adult means (normal, BMD > -1 SD; osteopenia, BMD between -1 SD and -2.5 SD; osteoporosis, BMD < -2.5 SD). Mean albumin values did not differ significantly across the three BMD categories in men or women. BMD levels stratified for albumin levels and calcium supplement status (a marker for osteoporosis awareness) also did not differ. Albumin levels were also not associated with a history of low-trauma fractures. In summary, there was no age-independent association between serum albumin within the normal range and low BMD or fractures in community-dwelling healthy older adults. We conclude that previously reported associations most likely reflect inadequate adjustment for the age-related decrease in albumin levels and the selection of very frail osteoporotic subjects.

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46-59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14-41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n = 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of -0.9% (0.4%) at the lumbar spine and -0.7% (0.6%) at the femoral neck (both p < 0.05 compared with women who remained premenopausal). In the women who became postmenopausal (n = 42) the mean annual changes in BMD were -2.5% (0.2%) at the lumbar spine and -1.7% (0.2%) at the femoral neck (both p < 0.0005), and in the women who remained post-menopausal (n = 60) they were -0.7% (0.2%) per year and -0.5% (0.3%) per year respectively (both p < 0.05), compared with women who remained premenopausal. In the 1-3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p < 0.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n = 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p < 0.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p < 0.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine.

NORA is an observational registry of postmenopausal US women with periodic collection of event and treatment data that will create a database including several hundred thousand subjects. It will utilize peripheral and central measurements of bone density and relate these to other risk factors, treatment patterns, and the natural history of osteoporosis. Initiated in the fall of 1997, the registry will be open to women throughout the United States who agree to complete baseline and on-going surveys. The database created by NORA will provide a resource that is unmatched in size and scope in the medical field and will allow for future research in a number of areas including patient outcomes, types of follow-up employed in clinical practice, diagnostic cost modelling, and osteoporosis therapy use (type, patient compliance, persistence and satisfaction). In addition, upon approval by the Steering Committee, women enrolled in the registry may be randomly selected to receive additional educational materials or questionnaires on a variety of topics of interest to specific researchers.