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Objective: A national survey was conducted to determine the extent of use of compounded hormone therapy(C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the USFood and Drug Administration (FDA-HT users).Methods: This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal orexperiencing the menopause transition. The sample was weighted slightly by age, region, education, and race toreflect population attributes based on US Census data.Results: Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT.C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason forusing HT was vasomotor symptoms ( 70%). Nonapproved indications for using HT were selected more often byC-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reportedamong the 738 FDA-HT users. Significance was not determined because of small numbers.Conclusions: This survey indicates substantial use of C-HT across the country and the possibility of higher ratesof endometrial side effects with such products. There is a need for standardized data collection on the extent of use ofcompounded hormones and their potential risks.

Objective: A national survey was conducted to determine the extent of use of compounded hormone therapy(C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the USFood and Drug Administration (FDA-HT users).Methods: This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal orexperiencing the menopause transition. The sample was weighted slightly by age, region, education, and race toreflect population attributes based on US Census data.Results: Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT.C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason forusing HT was vasomotor symptoms ( 70%). Nonapproved indications for using HT were selected more often byC-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reportedamong the 738 FDA-HT users. Significance was not determined because of small numbers.Conclusions: This survey indicates substantial use of C-HT across the country and the possibility of higher ratesof endometrial side effects with such products. There is a need for standardized data collection on the extent of use ofcompounded hormones and their potential risks.

The associations between objective measures of sleep duration and bone outcomes in older men are unknown. No consistent, significant association was identified between sleep duration and bone mineral density (BMD) in the current analysis. However, future research should determine if vitamin D status modifies this relationship.IntroductionPrior studies, predominantly in women, reported that long and short self-reported sleep duration are associated with lower BMD. Associations between actigraphy-determined sleep duration and BMD or bone turnover markers (BTMs) in older men are unknown.MethodsMen in The Osteoporotic Fractures in Men (MrOS) Study with wrist actigraphy and concurrent BMD assessment but without comorbidities affecting bone health were included. Sleep duration was considered as a continuous (N = 1926) and dichotomized variable where men were classified as getting the recommended (7-8 h/night; N = 478) or short (< 6 h/night; N = 577) sleep. The cross-sectional association between BMD, BTMs, and sleep duration was examined using a t test or linear regression, where appropriate, in unadjusted and adjusted models.ResultsThere were no clinically or statistically significant differences in BMD at the L-spine, total hip, or femoral neck between men getting the recommended vs. short sleep duration, using actigraphy or self-reported sleep duration (all p ≥ 0.07). When sleep duration was considered as a continuous variable, femoral neck BMD was higher in men with longer self-reported sleep duration (β = 0.006 ±0.003, p = 0.02), but this was not significant after further adjustment. In men with low 25OHD (< 20 ng/mL), longer actigraphy-determined sleep duration was associated with higher total hip BMD (β = 0.016 ± 0.008; p = 0.04). Sleep duration and BTMs were not associated.ConclusionSleep duration was not associated with hip or L-spine BMD or BTMs in older men. Future research should determine if vitamin D status or other factors modify this relationship.

ObjectivesOur aim was to determine the association between protein intake (overall and by source) and all-cause and cause-specific mortality among older men.DesignProspective cohort study.Setting5790 ambulatory community-dwelling older men from multicenter Osteoporotic Fractures in Men (MrOS) study.MeasurementsTotal energy and protein intake, and protein intake by source (dairy, non-dairy animal, plant) were assessed using a 69-item food frequency questionnaire. We included up to 10-year follow-up with adjudicated cardiovascular, cancer and other mortality outcomes. We used time-to-event analysis with protein exposures, mortality outcome, and adjusted for possible confounders including age, center, education, race, smoking, alcohol use, physical activity, weight, total energy intake (TEI), and comorbidities. Hazard ratios were expressed per each unit=2.9% TEI decrement for all protein intake variables.ResultsThe mean (SD) baseline age of 5790 men was 73.6 (5.8) y. There were 1611 deaths and 211 drop-outs prior to 10 years, and 3868 men who were alive at the 10-year follow-up. The mean (SD) total protein intake was 64.7 (25.8) g/d, while the mean (SD) intake expressed as percent of total energy intake (%TEI) was 16.1 (2.9) %TEI. Lower protein intake was associated with an increased risk of death, with unadjusted HR=1.11 (95% CI: 1.06, 1.17) and adjusted HR=1.09 (95% CI: 1.04, 1.14) and the associations for protein intake by source were similar. The adjusted HR for cancer mortality was HR=1.13 (95% CI: 1.03, 1.25) while the association for CVD mortality was HR=1.08 (95% CI: 0.99, 1.18).ConclusionsLow protein intake, irrespective of source, was associated with a modest increase in risk of all-cause and cause-specific mortality among older men. Special consideration should be given to level of protein intake among older adults.

We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength.PurposeComposite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT.MethodsWe used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women.ResultsAdjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample.ConclusionsMeasuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.

Methodological limitations preclude determination of the association between sleep duration and bone mineral density (BMD) from existing literature. This was the first study to use objective sleep duration to determine its association with BMD. Nocturnal sleep duration, assessed objectively (actigraphy) or subjectively (questionnaire), was not independently associated with BMD in postmenopausal women.IntroductionBoth long and short self-reported sleep durations are associated with low bone mineral density (BMD) in men and women. The association between sleep duration measured by actigraphy and BMD in postmenopausal women is unknown.MethodsThe Study of Osteoporotic Fractures (SOF) ancillary sleep study was used to determine the association between sleep duration and BMD at the total hip and femoral neck in postmenopausal women ≥ 75 years old. Sleep duration was assessed by wrist actigraphy (average 4 nights) and questionnaire. BMD was compared between postmenopausal women with short (

In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD. INTRODUCTION:Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical atherosclerosis to bone health is not certain. METHODS:We followed 3385 participants from the Cardiovascular Health Study (mean age 74.7 ± 5.3 years) with a median time to fracture of 12.1 years who underwent baseline carotid artery and aortic wall ultrasound scanning and ankle brachial blood pressure index (ABI) determinations. A subset underwent bone mineral density (BMD) testing. RESULTS:There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture [(HR 1.18 [1.04, 1.35]), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk. CONCLUSION:Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD.

Weight loss in men in late life was associated with lower bone strength. In contrast, weight gain was not associated with a commensurate increase in bone strength. Future studies should measure concurrent changes in weight and parameters of bone strength and microarchitecture and evaluate potential causal pathways underlying these associations. INTRODUCTION:Our aim was to determine associations of weight loss with bone strength and microarchitecture. METHODS:We used data from 1723 community-dwelling men (mean age 84.5 years) who attended the MrOS study Year (Y) 14 exam and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans at ≥ 1 skeletal sites (distal tibia, distal radius, or diaphyseal tibia). Weight change from Y7 to Y14 exams (mean 7.3 years between exams) was classified as moderate weight loss (loss ≥ 10%), mild weight loss (loss 5 to

Among older men, characteristics that predict longitudinal changes in trabecular bone score (TBS) are different from characteristics that predict changes in bone mineral density (BMD). Most notably, weight loss is strongly associated with concomitant loss in BMD but with concomitant increases in TBS, when measured on Hologic densitometers. INTRODUCTION:Our objective was to compare and contrast predictors of changes in TBS, total hip BMD, and lumbar spine BMD. METHODS:Our study population was 3969 Osteoporotic Fractures in Men (MrOS) cohort participants (mean age 72.8 years) with repeat measures of TBS, lumbar spine and total hip BMD, body mass index (BMI) less than 37 kg/m2, and no use of bisphosphonate or glucocorticoid medications. TBS was scored (Med-Imaps Software version 2.1) and BMD measured on Hologic densitometers. RESULTS:One thousand four hundred forty-four men had a TBS decrease > 0.04 units (estimated least significant change for TBS), 795 men had a TBS increase > 0.04 units, and 1730 men had TBS change ≤ 0.04 units over mean follow-up of 4.6 years. Older age was not associated with TBS change, but was associated with greater decline in lumbar spine and total hip BMD. Compared to stable weight, > 10% weight loss was strongly associated with an increase in TBS [effect size = 1.24 (95% CI 1.12, 1.36)] and strongly associated with a decrease in total hip BMD [- 1.16 (95% CI - 1.19, - 1.03)]. Other predictors discordant for longitudinal changes of TBS and BMD included baseline BMI, walk speed, and ACE inhibitor use. CONCLUSIONS:Predictors of changes in TBS are different from predictors of changes in lumbar spine and total hip BMD. At least when assessed on Hologic densitometers, weight loss is associated with subsequent declines in spine and total hip BMD but subsequent increase in TBS. Faster walk speed may protect against loss of hip BMD, but is not associated with longitudinal changes of TBS.

ObjectiveTo determine normative values for weight-bearing, countermovement leg extension ("jump") tests in the oldest men and characteristics of those not completing vs. completing tests.Design2014-16 cross-sectional exam.SettingSix U.S. sites from the Osteoporotic Fractures in Men (MrOS) Study.ParticipantsCommunity-dwelling men (N=1,841) aged 84.5±4.2 (range: 77-101) years.InterventionsN/A.MeasurementsJump tests on a force plate measured lower-extremity muscle peak power/kg, velocity and force/kg at peak power, with normative values for 5-year age groups and by limitations in moderate-intensity activities of daily living (ADLs) and climbing several flights of stairs.ResultsJump completion was 68.9% (N=1,268/1,841) and 98% (1,242/1,268) had ≥1 analyzable trial/participant. Exclusions primarily were due to poor mobility and/or balance: 24.8% (456/1,841) prior to and 6.4% (N=117/1,841) after attempting testing. Peak power was 20.8±5.3 W/kg, with 1.2±0.3 m/s for velocity, and 16.7±1.9 N/kg for force at peak power. Each 5-year age group >80 years had subsequently 10% lower power/kg, with 30% lower power/kg at >90 vs. ≤80 years (all p90 vs. ≤80 years (all p80 years. Future research should examine age- and functional-related declines in jump measures related to physical performance decline, falls, fractures, and disability.

Dairy protein but not plant protein was associated with bone strength of the radius and tibia in older men. These results are consistent with previous results in women and support similar findings related to fracture outcomes. Bone strength differences were largely due to thickness and area of the bone cortex.IntroductionOur objective was to determine the association of protein intake by source (dairy, non-dairy animal, plant) with bone strength and bone microarchitecture among older men.MethodsWe used data from 1016 men (mean 84.3 years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study, completed a food frequency questionnaire (500-5000 kcal/day), were not taking androgen or androgen agonists, and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia. Protein was expressed as percentage of total energy intake (TEI); mean ± SD for TEI = 1548 ± 607 kcal/day and for total protein = 16.2 ± 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as dependent variables and adjusted for age, limb length, center, education, race/ethnicity, marital status, smoking, alcohol intake, physical activity level, corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis medications.ResultsHigher dairy protein intake was associated with higher estimated failure load at the distal radius and distal tibia [radius effect size = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while higher non-dairy animal protein was associated with higher failure load at only the distal radius. Plant protein intake was not associated with failure load at any site.ConclusionThe association between protein intake and bone strength varied by source of protein. These results support a link between dairy protein intake and skeletal health, but an intervention study is needed to evaluate causality.

BackgroundSubclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear.ObjectiveTo investigate the association between subclinical thyroid dysfunction and bone loss.MethodsIndividual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach.ResultsAmongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site.ConclusionAmongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

In this prospective cohort of 4462 older adults, incident atrial fibrillation (AF) was not statistically significantly associated with subsequent risk of incident fracture.IntroductionAF is associated with stroke, heart failure, dementia, and death, but its association with fracture is unknown. Therefore, we examined the association of incident AF with the risk of subsequent fracture in the Cardiovascular Health Study (CHS) cohort.MethodsOf the CHS participants aged ≥65 years, 4462 were followed between 1991 and 2009, mean follow-up 8.8 years. Incident AF was identified by annual study electrocardiogram (ECG), hospital discharge diagnosis codes, or Medicare claims. Fractures of the hip, distal forearm, humerus, or pelvis were identified using hospital discharge diagnosis codes or Medicare claims. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between incident AF (time-varying) and the risk of subsequent fracture. We also evaluated whether AF was associated with risk of sustaining a fall.ResultsCrude incident fracture rate was 22.9 per 1000 person-years in participants with AF and 17.7 per 1000 person-years in participants without AF. Individuals with incident AF were not at significantly higher risk of hip fracture (adjusted HR = 1.09, 95 % CI 0.83-1.42) or fracture at any selected site (adjusted HR = 0.97, 95 % CI 0.77-1.22) or risk of sustaining a fall (adjusted HR = 1.00, 95 % CI = 0.87-1.16) compared with those without AF.ConclusionIn this cohort of older, community-dwelling adults, incident AF was not shown to be associated with falls or hip or other fractures.

UnlabelledVitamin 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.IntroductionVitamin 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.MethodsWe 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.ResultsIL-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).ConclusionsAssociations 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.

UnlabelledSoluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture.IntroductionSoluble CD14, a proinflammatory cytokine, is primarily derived from macrophages/monocytes that can differentiate into osteoclasts. The purpose of this study was to examine the relationship between sCD14 levels and osteoporotic fractures.MethodsIn the Cardiovascular Health Study, 5462 men and women had sCD14 levels measured at baseline. Incident hip fractures (median follow-up time 12.5 years) and incident composite fractures (defined as the first hip, pelvis, humerus, or distal radius fracture, median follow-up 8.6 years) were identified from hospital discharge summaries and/or Medicare claims data. Cox proportional hazards models were used to model the association between sCD14 levels and time to incident hip or composite fracture, overall and as a function of race and gender.ResultsIn unadjusted models, there was a positive association between sCD14 levels (per 1 standard deviation increase, i.e., 361.6 ng/mL) and incident hip (HR, 1.26; 95 % CI, 1.17, 1.36) and composite (HR, 1.20; 95 % CI, 1.12, 1.28) fractures. When models were fully adjusted for demographics, lifestyle factors, and medication use, these associations were no longer significant. However, in whites, the association of sCD14 levels with hip fractures remained significant in fully adjusted models (HR, 1.11; 95 % CI, 1.01-1.23). Associations of sCD14 levels with hip and composite fracture did not differ between men and women.ConclusionsIn this large cohort of community-dwelling older adults, higher sCD14 levels were associated with an increased risk of incident hip fractures in whites.

Activity rhythm disturbances and depression often co-occur among older adults. However, little is known about how activity rhythm disturbances themselves co-occur, or how disturbances to multiple aspects of the activity rhythm relate to depression over time. In this study, we performed a Latent Class Analysis to derive sub-groups of older men [total n = 2933, mean age = 76.28, standard deviation (SD) = 5.48] who shared similar patterns of activity rhythm disturbances (defined as extreme values of modeled activity rhythm parameters). We found eight sub-groups with distinct combinations of activity rhythm disturbances: one had all normative activity rhythm parameters (32.09%), one had only lower activity (10.06%), three had earlier activity (totaling 26.96%) and three had later activity (totaling 30.89%). Groups with similar timing were distinguished depending on whether the relative length of the active period was shorter and/or if the activity rhythm had lesser amplitude/robustness. We next examined whether the derived activity rhythm sub-groups were associated with different rates of change in depression symptom levels over an average of 5.5 (0.52 SD) follow-up years. The sub-group with lower activity only had faster increases in depressive symptoms over time (compared with the group with normative rhythm parameters), but this association was accounted for by adjustments for concurrently assessed health status covariates. Independent of these covariates, we found that four activity rhythm disturbance sub-groups experienced faster depressive symptom increases (compared with the normative sub-group): These included all three sub-groups that had later activity timing and one sub-group that had earlier activity timing plus a shorter active period and a dampened rhythm. Low activity rhythm height/robustness with normal timing therefore may mark depression risk that is attributable to co-occurring disease processes; in contrast, having late or combined early/compressed/dampened activity rhythms may independently contribute to depression symptom development. Our findings suggest that activity rhythm-related depression risk is heterogeneous, and may be detected when multiple aspects of rhythm timing are delayed or when early timing is accompanied by compressed/dampened activity rhythms. Future studies should consider how distinct combinations of altered activity rhythm timing and height/robustness develop and conjointly determine health risks. Further research is also needed to determine whether/how activity rhythms can be modified to improve depression outcomes.

BackgroundThe ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.DesignAn analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.MethodsSubjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.ResultsIn predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p

Objective-To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization. Research design and methods-The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at

SummaryThe Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.IntroductionThis study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.MethodsWHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).ResultsAmong women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.ConclusionThough based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Background: Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aime

UnlabelledTo examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.IntroductionThe purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups.MethodsA nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)).ResultsEach 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) 90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNFα soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c)

SummaryHip geometry measurements of outer diameter and buckling ratio at the intertrochanter and shaft of the hip dual energy X-ray absorptiometry (DXA) scan predicted incident hip fracture in postmenopausal women. These associations, independent of age, body size, clinical risk factors, and conventional areal bone mineral density, suggest hip geometry plays a role in fracture etiology and may aid in improving identification of older women at high fracture risk.IntroductionThis study examined whether hip geometry parameters predicted hip fracture independent of body size, clinical risk factors, and conventional femoral neck bone mineral density (aBMD) and whether summary factors could be identified to predict hip fracture.MethodsWe studied 10,290 postmenopausal women from the Women's Health Initiative. Eight thousand eight hundred forty-three remained fracture free during follow-up to 11 years of follow-up, while 147 fractured their hip, and 1,300 had other clinical fractures. Hip structural analysis software measured bone cross-sectional area, outer diameter, section modulus, average cortical thickness, and buckling ratio on archived DXA scans in three hip regions: narrow neck, intertrochanter, and shaft. Hazard ratios were estimated using Cox proportional hazards models for individual parameters and for composite factors extracted from principal components analysis from all 15 parameters.ResultsAfter adjustment for age, body size, clinical risk factors, and aBMD, intertrochanter and shaft outer diameter measurements remained independent predictors of hip fracture with hazard ratios for a one standard deviation increase of 1.61 (95% confidence interval (CI), 1.25-2.08) for the intertrochanter and 1.36 (95% CI, 1.06-1.76) for the shaft. Average buckling ratios also independently predicted incident hip fracture with hazard ratios of 1.43 (95% CI, 1.10-1.87) at the intertrochanter and 1.24 (95% CI, 1.00-1.55) at the shaft. Although two composite factors were extracted from principal components analysis, neither was superior to these individual measurements at predicting incident hip fracture.ConclusionsTwo hip geometry parameters, intertrochanter outer diameter and buckling ratio, predict incident hip fracture after accounting for clinical risk factors and aBMD.

IntroductionThe purpose of the study was to test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels.MethodsWe conducted a nested case-control study within the Women's Health Initiative HT Trials. The sample included 231 hip fracture case-control pairs and a random sample of 519 all fracture case-control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history, and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture were identified over an average follow-up of 6.53 years.ResultsThere was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture, including hip fracture, compared to placebo.ConclusionThe effect of HT on fracture reduction is independent of estradiol and SHBG levels.

SummaryMany falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women.IntroductionPhysical and lifestyle risk factors for falls and population attributable risks (PAR) were examined.MethodsWe conducted a 4-year prospective study of 8,378 community-dwelling women (mean age = 71 years, SD = 3) enrolled in the Study of Osteoporotic Fractures. Data on number of falls were self-reported every 4 months. Fall rates were calculated (# falls/woman-years). Poisson regression was used to estimate relative risks (RR).ResultsPhysical risk factors (p < or = 0.05 for all) included tall height (RR = 0.89 per 5 in.), dizziness (RR = 1.16), fear of falling (RR = 1.20), self-reported health decline (RR = 1.19), difficulty with Instrumental Activities of Daily Living (IADLs) (RR = 1.12, per item), fast usual-paced walking speed (RR = 1.18, per 2 SD), and use of antidepressants (RR = 1.20), benzodiazepines (RR = 1.11), or anticonvulsants (RR = 1.62). Protective physical factors (p < or = 0.05 for all) included good visual acuity (RR = 0.87, per 2 SD) and good balance (RR = 0.85 vs. poor). Lifestyle predicted fewer falls including current smoking (RR = 0.76), going outdoors at least twice weekly but not more than once a day (RR = 0.89 and vs. twice daily). High physical activity was associated with more falls but only among IADL impaired women. Five potentially modifiable physical risk factors had PAR > or = 5%.ConclusionsFall interventions addressing modifiable physical risk factors with PAR > or = 5% while considering environmental/behavioral risk factors are indicated.

ObjectiveThis case-cohort study was designed to examine whether total hip bone mineral density (BMD) is independently associated with breast cancer over and above its association with other determinants, including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin.MethodsOur study population was selected from a cohort of 8,203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992, at which time BMD was assessed, and blood samples were obtained. A total of 109 women developed breast cancer during four years of follow-up; 173 other randomly selected women from the larger cohort were also selected. Cox proportional hazards with robust variance adjustment was used for these analyses.ResultsRelative to women in the lower fourth of the BMD distribution, the risk associated with being in the upper fourth was 2.6 (95% confidence interval (CI) 1.1-5.8). After adjusting for serum hormone levels, the corresponding relative risk was 2.5 (95% CI 0.9-5.2). With body mass index and number of years since menopause added to the multivariate analysis, the relative risk decreased to 1.4 (95% CI 0.5-4.0).ConclusionsBMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates.