Genetic variants and physical activity interact to affect bone density in Hispanic children.

BACKGROUND: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study. METHODS: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD. RESULTS: We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p < 0.05). Higher PRS was associated with a lower total body BMD (ß = - 0.040 ± 0.009, p = 1.1 × 10- 5) and lumbar spine BMD (ß = - 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (ß = - 0.015 ± 0.006, p = 0.02; ß = 0.008 ± 0.01, p = 0.4, respectively). DISCUSSION: The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed. CONCLUSIONS: Bone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.

Safety and efficacy of lumen-apposing metal stents versus plastic stents to treat walled-off pancreatic necrosis: systematic review and meta-analysis.

Background and study aims Lumen-apposing metal stents (LAMS) are increasingly used for drainage of walled-off pancreatic necrosis (WON). Recent studies suggested greater adverse event (AE) rates with LAMS for WON. We conducted a systematic review and meta-analysis to compare the safety and efficacy of LAMS with double-pigtail plastic stents (DPPS) for endoscopic drainage of WON. The primary aim was to evaluate stent-related AEs. Methods In October 2019, we searched the Ovid (Embase, MEDLINE, Cochrane) and Scopus databases for studies assessing a specific LAMS or DPPS for WON drainage conducted under EUS guidance. Safety outcomes were AE rates of bleeding, stent migration, perforation, and stent occlusion. Efficacy outcomes were WON resolution and number of procedures needed to achieve resolution. A subanalysis including non-EUS-guided cases was performed. Results Thirty studies including one randomized controlled trial (total 1,524 patients) were analyzed. LAMS were associated with similar bleeding (2.5 % vs. 4.6 %, P =  0.39) and perforation risk (0.5 % vs. 1.1 %, P =  0.35) compared to DPPS. WON resolution (87.4 % vs. 87.5 %, P =  0.99), number of procedures to achieve resolution (2.09 vs. 1.88, P =  0.72), stent migration (5.9 % vs. 6.8 %, P =  0.79), and stent occlusion (3.8 % vs. 5.2 %, P =  0.78) were similar for both groups. Inclusion of non-EUS-guided cases led to significantly higher DPPS bleeding and perforation rates. Conclusions LAMS and DPPS were associated with similar rates of AEs and WON resolution when limiting analysis to EUS-guided cases. Higher bleeding rates were seen in historical studies of DPPS without EUS guidance. Additional high-quality studies of WON treatment using consistent outcome definitions are needed.

Correction to: Comparison of 8-year knee osteoarthritis progression in 2 siblings: a case-based review.

The original version of this article was revised due to a retrospective Open Access order.

Comparison of 8-year knee osteoarthritis progression in 2 siblings: a case-based review.

Because the pathophysiology of knee osteoarthritis is poorly understood, optimal evidence-based clinical management is uncertain. Sibling comparison studies can help inform a clinical model to guide preventive care. We compared the 8-year clinical outcomes in 2 sisters with a family history of osteoarthritis, normal BMI, and absence of knee pain at baseline. Both patients had Kellgren-Lawrence grade 1 in the affected knee at the time of twisting knee injuries leading to osteoarthritis diagnoses at age 50 (patient 1) and 51 (patient 2). Patient 1 developed a chronic right knee effusion, and progressed to Kellgren-Lawrence grade 3 bilaterally by the time she had a right total knee replacement at age 58. Patient 2 had subchondral fractures of the right knee with transient effusion, which healed after 1 year of partial weight-bearing with crutches and subsequent daily use of knee sleeves. Patient 2 had Kellgren-Lawrence grade 0 bilaterally upon surveillance imaging at age 58. The terms "osteoarthritis and knee and diagnostic imaging and subchondral bone and pathophysiology" were searched in the PubMed database to identify original research articles to inform a clinical model consistent with the patients' outcomes. A fluid model of osteoarthritis was the best explanatory model for the discordant clinical trajectories of the age-matched siblings. Patient recommendations are presented based on these findings.

Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children.

CONTEXT: Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied. OBJECTIVE: We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children. METHODS: We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1030 Hispanic children (4-19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry. RESULTS: Significant heritability were observed for BMC and BMD at multiple skeletal sites ranging between 44 and 68% (P < 2.8 × 10-9). Significant evidence for linkage was found for BMD of pelvis and left leg on chromosome 7p14, lumbar spine on 20q13 and left rib on 6p21, and BMC of pelvis on chromosome 20q12 and total body on 14q22-23 (logarithm of odds score > 3). We found genome-wide significant association between BMC of right arm and rs762920 at PVALB (P = 4.6 × 10-8), and between pelvis BMD and rs7000615 at PTK2B (P = 7.4 × 10-8). Exome-wide association analysis revealed novel association of variants at MEGF10 and ABRAXAS2 with left arm and lumber spine BMC, respectively (P < 9 × 10-7). CONCLUSIONS: We identified novel loci associated with BMC and BMD in Hispanic children, with strongest evidence for PTK2B. These findings provide better understanding of bone genetics and shed light on biological mechanisms underlying BMD and BMC variation.

Correction to: Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study.

Owing to an oversight by the authors, the acknowledgments were incomplete.

Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study.

Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and three externally generated fracture risk tools had similar accuracy to identify older men who developed osteoporotic fractures. Risk tools with femoral neck BMD performed better than those without BMD. The externally developed risk tools were poorly calibrated. INTRODUCTION: We compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality. METHODS: A comparative ROC curve analysis assessed the ability of the QFracture, FRAX® and Garvan fracture risk tools, and femoral neck bone mineral density (BMD) T score with or without age to identify incident fracture in community-dwelling men aged 65 years or older (N = 4994) without hip or clinical vertebral fracture or antifracture treatment at baseline. RESULTS: Among risk tools calculated with BMD, the discriminative ability to identify men with incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC 0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI 0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73), FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67, 0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk scores calculated with BMD compared with QFracture (P < 0.0001). Calibration was good for the internally generated BMD T score predictor with or without age and poor for the externally developed risk tools. CONCLUSION: In untreated older men without fragility fractures at baseline, an age plus femoral neck BMD T score classifier identified men with incident hip fracture as accurately as more complicated fracture risk scores.

Screening for Osteoporosis in Older Men: Operating Characteristics of Proposed Strategies for Selecting Men for BMD Testing.

BACKGROUND: The optimal approach for selecting men for bone mineral density (BMD) testing to screen for osteoporosis is uncertain. OBJECTIVE: To compare strategies for selecting older men for screening BMD testing. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 4043 community-dwelling men aged ≥70 years at four US sites. MAIN MEASURES: BMD at the total hip, femoral neck, and lumbar spine using dual-energy x-ray absorptiometry (DXA). Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating curve (AUC) of the Osteoporosis Self-Assessment Tool (OST) and Fracture Risk Assessment Tool (FRAX) without BMD to discriminate between those with and without osteoporosis as defined by World Health Organization (WHO) diagnostic criteria, and between those recommended and not recommended for pharmacologic therapy based on the National Osteoporosis Foundation (NOF) guidelines. KEY RESULTS: Among the cohort, 216 (5.3%) had a BMD T-score ≤ -2.5 at the femoral neck, total hip, or lumbar spine, and 1184 (29.2%) met criteria for consideration of pharmacologic therapy according to NOF guidelines. The OST had better discrimination (AUC 0.68) than the FRAX (AUC 0.62; p = 0.004) for identifying T-score-defined osteoporosis. Use of an OST threshold of <2 resulted in sensitivity of 0.83 and specificity of 0.36 for the identification of osteoporosis, compared to sensitivity of 0.59 and specificity of 0.59 for the use of FRAX with a cutoff of 9.3% 10-year risk of major osteoporotic fracture. CONCLUSIONS: The OST performs modestly better than the more complex FRAX in selecting older men for BMD testing to screen for osteoporosis; the use of either tool substantially reduces the proportion of men referred for BMD testing compared to universal screening. Of 1000 men aged 70 and older in this community-based cohort, the use of an OST cutoff of <2 to select men for BMD testing would result in 654 men referred for BMD testing, of whom 44 would be identified as having osteoporosis, and nine with osteoporosis would be missed.

Time to Clinically Relevant Fracture Risk Scores in Postmenopausal Women.

BACKGROUND: Clinical practice guidelines recommend use of fracture risk scores for screening and pharmacologic treatment decisions. The timing of occurrence of treatment-level (according to 2014 National Osteoporosis Foundation guidelines) or screening-level (according to 2011 US Preventive Services Task Force guidelines) fracture risk scores has not been estimated in postmenopausal women. METHODS: We conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores in postmenopausal women aged 50 years and older, prior to receipt of pharmacologic treatment and prior to first hip or clinical vertebral fracture. RESULTS: In 54,280 postmenopausal women aged 50 to 64 years without a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of rare incidence of treatment-level scores. In 6096 women who had FRAX scores calculated with bone mineral density, the estimated unadjusted time to treatment-level FRAX ranged from 7.6 years (95% confidence interval [CI], 6.6-8.7) for those aged 65 to 69, to 5.1 years (95% CI, 3.5-7.5) for those aged 75 to 79 at baseline. Of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years. CONCLUSIONS: Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.

Impact of Competing Risk of Mortality on Association of Weight Loss With Risk of Central Body Fractures in Older Men: A Prospective Cohort Study.

To determine the association of weight loss with risk of clinical fractures at the hip, spine, and pelvis (central body fractures [CBFs]) in older men with and without accounting for the competing risk of mortality, we used data from 4523 men (mean age 77.5 years). Weight change between baseline and follow-up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow-up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan-Meier versus 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6-fold higher adjusted risk of CBF (HR 1.59; 95% CI, 1.06 to 2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16; 95% CI, 0.77 to 1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their long-term fracture probability and relative fracture risk. © 2016 American Society for Bone and Mineral Research.

Time to Osteoporosis and Major Fracture in Older Men: The MrOS Study.

INTRODUCTION: For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals. METHODS: A prospective cohort study of 5,415 community-dwelling men aged ≥65 years without hip or clinical vertebral fracture or antifracture treatment at baseline was conducted. Participants had concurrent BMD and fracture follow-up between 2000 and 2009, and additional fracture follow-up through 2014. Data were analyzed in 2015. Time to incident osteoporosis (lowest T-score ≤ -2.50) for men without baseline osteoporosis, and time to hip or clinical vertebral fracture or major osteoporotic fracture for men without or with baseline osteoporosis, were estimated. RESULTS: Nine men (0.2%) with BMD T-scores >-1.50 at baseline developed osteoporosis during follow-up. The adjusted estimated time for 10% to develop osteoporosis was 8.5 (95% CI=6.7, 10.9) years for those with moderate osteopenia (lowest T-score, -1.50 to -1.99) and 2.7 (95% CI=2.1, 3.4) years for those with advanced osteopenia (lowest T-score, -2.00 to -2.49) at baseline. The adjusted times for 3% to develop a first hip or clinical vertebral fracture ranged from 7.1 (95% CI=6.0, 8.3) years in men with baseline T-scores > -1.50 to 1.7 (95% CI=1.0, 3.1) years in men with baseline osteoporosis. CONCLUSIONS: Men aged 65 years and older with femoral neck, total hip, and lumbar spine BMD T-scores >-1.50 on a first BMD test were very unlikely to develop osteoporosis during follow-up. Additional BMD testing may be most informative in older men with T-scores ≤-1.50.

Bone Density Screening and Re-screening in Postmenopausal Women and Older Men.

Clinical practice guidelines universally recommend bone mineral density (BMD) screening to identify osteoporosis in women aged 65 years and older. Risk assessment is recommended to guide BMD screening in postmenopausal women under age 65. Insufficient data are available to inform standard ages to start and stop BMD screening in postmenopausal women. Based on longitudinal studies of incident osteoporosis and fracture in postmenopausal women, an initial BMD test should be ordered for all women aged 65, and the frequency of re-screening should be based on age and BMD T score (more frequent testing for older age and lower T score). Although clinical practice guidelines recommend BMD screening according to risk factors for fracture in postmenopausal women under age 65, no standard approach to risk assessment exists. Minimal evidence is available to guide osteoporosis screening in men, but some experts recommend initiation of BMD screening in men at age 70.

Subchondral insufficiency fracture of the knee: a non-traumatic injury with prolonged recovery time.

Subchondral insufficiency fractures are non-traumatic fractures that occur immediately below the cartilage of a joint. Although low bone density may be present concurrently, it is not the underlying cause of subchondral insufficiency fractures in the majority of patients. Patients with subchondral insufficiency fracture characteristically have unremarkable plain radiographs, while MRI examination may reveal extensive bone marrow oedema and subchondral bone collapse. This article presents a 51-year-old postmenopausal woman, a physician, who had subchondral insufficiency fractures of the knee associated with prolonged standing during clinical work. She was treated with partial weight bearing on crutches until 14 months after the injury, viscosupplementation at 4 months to treat osteoarthritis and teriparatide treatment to improve bone healing at 7 months. By 26 months after the injury, she tolerated independent walking with a fabric knee support but still experienced mild posterolateral knee pain and numbness on prolonged standing.

DXA Utilization Between 2006 and 2012 in Commercially Insured Younger Postmenopausal Women.

Reimbursement for dual-energy X-ray absorptiometry (DXA) scans in the outpatient setting has declined significantly since 2006. Research through 2011 has suggested reimbursement reductions for DXA scans have corresponded with an overall decreased utilization of DXA. This study updates utilization estimates for DXAs through 2012 in patients with commercial insurance and compares DXA rates before and after reimbursement changes. We evaluated DXA utilization for women aged 50-64 yr from Marketscan Commercial Claims and Encounter database between January 2006 and December 2012 based on CPT codes. We estimated utilization rates per 1000 person years (PY). We also used segmented regression analysis of monthly rates to evaluate the change in utilization rates after a proposed reimbursement reduction in July 2009. In women aged 50-64 yr, 451,656 DXAs were performed in 2006, a rate of 144 DXAs per 1000 PY. This rate increased to 149 DXAs per 1000 PY in 2009 before decreasing to 110 DXAs per 1000 PY or 667,982 scans in 2012. DXA utilization increased by 2.24 per 1000 PY until July 2009 then declined by 12.98 DXAs per 1000 persons, resulting in 37.5 DXAs per PY fewer performed in 2012 compared with 2006. Since July 2009 a significant decline in DXA utilization occurred in a younger postmenopausal commercially insured population. This decline corresponds with a time period of reductions in Medicare DXA reimbursement.

Comparison of fracture risk prediction by the US Preventive Services Task Force strategy and two alternative strategies in women 50-64 years old in the Women's Health Initiative.

CONTEXT: The United States Preventive Services Task Force (USPSTF) recommends osteoporosis screening for women younger than 65 years whose 10-year predicted risk of major osteoporotic fracture (MOF) is at least 9.3% using the Fracture Risk Assessment Tool. In postmenopausal women age 50-64 years old, it is uncertain how the USPSTF screening strategy compares with the Osteoporosis Self-Assessment Tool and the Simple Calculated Osteoporosis Risk Estimate (SCORE) in discriminating women who will and will not experience MOF. OBJECTIVE: This study aimed to assess the sensitivity, specificity, and area under the receiver operating characteristic curve of the three strategies for discrimination of incident MOF over 10 years of follow-up among postmenopausal women age 50-64 years. SETTING AND DESIGN: This was a prospective study conducted between 1993-2008 at 40 US Centers. PARTICIPANTS: We analyzed data from participants of the Women's Health Initiative Observational Study and Clinical Trials, age 50-64 years, not taking osteoporosis medication (n = 62 492). MAIN OUTCOME MEASURES: The main outcome was 10-year (observed) incidence of MOF. RESULTS: For identifying women with incident MOF, sensitivity of the strategies ranged from 25.8-39.8%, specificity ranged from 60.7-65.8%, and AUC values ranged from 0.52-0.56. The sensitivity of the USPSTF strategy for identifying incident MOF ranged from 4.7% (3.3-6.0) among women age 50-54 years to 37.3% (35.4-39.1) for women age 60-64 years. Adjusting the thresholds to improve sensitivity resulted in decreased specificity. CONCLUSIONS: Our findings do not support use of the USPSTF strategy, Osteoporosis Self-Assessment Tool, or SCORE to identify younger postmenopausal women who are at higher risk of fracture. Our findings suggest that fracture prediction in younger postmenopausal women requires assessment of risk factors not included in currently available strategies.

Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study.

OBJECTIVES: To quantify incremental effects of applying different criteria to identify men who are candidates for drug treatment to prevent fracture and to examine the extent to which fracture probabilities vary across distinct categories of men defined by these criteria. DESIGN: Cross sectional and longitudinal analysis of a prospective cohort study. SETTING: Multicenter Osteoporotic Fractures in Men (MrOS) study in the United States. PARTICIPANTS: 5880 untreated community dwelling men aged 65 years or over classified into four distinct groups: osteoporosis by World Health Organization criteria alone; osteoporosis by National Osteoporosis Foundation (NOF) but not WHO criteria; no osteoporosis but at high fracture risk (at or above NOF derived FRAX intervention thresholds recommended for US); and no osteoporosis and at low fracture risk (below NOF derived FRAX intervention thresholds recommended for US). MAIN OUTCOME MEASURES: Proportion of men identified for drug treatment; predicted 10 year probabilities of hip and major osteoporotic fracture calculated using FRAX algorithm with femoral neck bone mineral density; observed 10 year probabilities for confirmed incident hip and major osteoporotic (hip, clinical vertebral, wrist, or humerus) fracture events calculated using cumulative incidence estimation, accounting for competing risk of mortality. RESULTS: 130 (2.2%) men were identified as having osteoporosis by using the WHO definition, and an additional 422 were identified by applying the NOF definition (total osteoporosis prevalence 9.4%). Application of NOF derived FRAX intervention thresholds led to 936 (15.9%) additional men without osteoporosis being identified as at high fracture risk, raising the total prevalence of men potentially eligible for drug treatment to 25.3%. Observed 10 year hip fracture probabilities were 20.6% for men with osteoporosis by WHO criteria alone, 6.8% for men with osteoporosis by NOF (but not WHO) criteria, 6.4% for men without osteoporosis but classified as at high fracture risk, and 1.5% for men without osteoporosis and classified as at low fracture risk. A similar pattern was noted in observed fracture probabilities for major osteoporotic fracture. Among men with osteoporosis by WHO criteria, observed fracture probabilities were greater than FRAX predicted probabilities (20.6% v 9.5% for hip fracture and 30.0% v 17.4% for major osteoporotic fracture). CONCLUSIONS AND RELEVANCE: Choice of definition of osteoporosis and use of NOF derived FRAX intervention thresholds have major effects on the proportion of older men identified as warranting drug treatment to prevent fracture. Among men identified with osteoporosis by WHO criteria, who comprised 2% of the study population, actual observed fracture probabilities during 10 years of follow-up were highest and exceeded FRAX predicted fracture probabilities. On the basis of findings from randomized trials in women, these men are most likely to benefit from treatment. Expanding indications for treatment beyond this small group has uncertain value owing to lower observed fracture probabilities and uncertain benefits of treatment among men not selected on the basis of WHO criteria.

Associations between Body Composition, Hormonal and Lifestyle Factors, Bone Turnover, and BMD.

BACKGROUND: The relative importance of body composition, lifestyle factors, bone turnover and hormonal factors in determining bone mineral density (BMD) is unknown. We studied younger postmenopausal women to determine whether modifiable or nonmodifiable risk factors for osteoporosis have stronger associations with BMD. METHODS: In multivariable linear regression models, we tested associations between non-bone body composition measures, self-reported measures of physical activity and dietary intake, urinary N-telopeptide (NTx), sex hormone concentrations, and BMD in 109 postmenopausal women aged 50 to 64 years, adjusting for current hormone therapy use and clinical risk factors for low BMD. Lean mass, fat mass and areal BMD (aBMD) at the lumbar spine, femoral neck, total hip and distal radius were measured using dual energy X-ray absorptiometry. RESULTS: Higher body weight and self-reported nonwhite race were independently associated with higher aBMD at the lumbar spine, femoral neck, total hip and distal radius. Lean and fat mass were not independently associated with aBMD. Older age and higher urinary NTx were independently associated with lower aBMD at the distal radius but not at weight-bearing sites. Sensitivity analyses demonstrated lack of an independent association between total daily protein or calorie intake and BMD. CONCLUSIONS: BMD, weight and race were the most important determinants of aBMD at all sites. Older age and higher bone turnover were independently associated with lower aBMD at the distal radius. In a limited analysis, self-reported physical activity, dietary protein and calorie intake were not associated with aBMD after adjustment for the other variables.