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ObjectiveOur objective was to investigate the overall and sex-specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults.MethodsMale and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Aging completed standing knee radiographs and knee pain assessments. Participants were divided into three groups using Kellgren-Lawrence grade (KLG) of KOA severity (0-1, 2, or 3-4). Outcome measures included whole-body muscle mass, thigh fat-free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics.ResultsOverall, the presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (P trend < 0.036). Sex-specific analysis revealed reduced energetics only in female patients with KOA (P trend < 0.007) compared to female patients without KOA. In models adjusted for age, sex, race, nonsteroidal anti-inflammatory drug administration, site or technician, physical activity, height, and participants with abdominal adiposity with KLG 3 to 4 had greater MFI (mean 0.008%, 95% confidence interval [CI] 0.004%-0.011%) and lower leg power (mean -51.56 W, 95% CI -74.03 to -29.10 W) and specific power (mean -5.38 W/L, 95% CI -7.31 to -3.45 W/L) than those with KLG 0 to 1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power, and specific power.ConclusionMuscle health is associated with the presence and severity of KOA and differs by sex. Although muscle composition and power are lower in both male and female patients with KOA, regardless of pain status, mitochondrial energetics is reduced only in female patients.

BackgroundLower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established.MethodsCommunity-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007-2009) and Year 14 (2014-2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to 1.5).ResultsMen declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than -50%), those that maintained or increased step count had 3-8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2-3 and 2-4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores.ConclusionOlder men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.

BackgroundAdiposity increases risk for male lower urinary tract symptoms (LUTS), although longitudinal studies have produced conflicting results. No prior studies have evaluated longitudinal associations of changes in adiposity with concurrent LUTS severity among older men.MethodsWe used repeated adiposity measurements from dual-energy x-ray absorptiometry (DXA), body mass index (BMI), and American Urological Association Symptom Index (AUASI) measured at 4 study visits over a 9-year period among 5 949 men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Linear mixed effect models adjusted for age, health-related behaviors, and comorbidities were created to evaluate the association between baseline and change in visceral adipose tissue (VAT) area, total fat mass, and BMI with change in LUTS severity measured by the AUASI.ResultsA nonlinear association was observed between baseline VAT area and change in AUASI: men in baseline VAT tertile (T) 2 had a lower annual increase in AUASI score compared to men in T1 and T3 (T2 vs T1: β = -0.07; 95% CI -0.12, -0.03; p = .008; T3 vs T1: NS) but differences were small. No significant associations were observed between change in VAT area and change in AUASI score. Neither baseline tertiles nor change in total fat mass or BMI were associated with change in AUASI score.ConclusionsChanges in VAT area, total fat mass, and BMI were not associated with change in LUTS severity in this cohort. Thus, despite other health benefits, interventions targeting adiposity alone are unlikely to be effective for preventing or treating LUTS among older men.

ContextWhether repeated bone mineral density (BMD) screening improves fracture prediction in men is uncertain.ObjectiveWe evaluated whether a second BMD 7 years after the initial BMD improves fracture prediction in older men.MethodsAmong 3651 community-dwelling men (mean age 79.1 years) with total hip BMD at baseline and Year 7 (Y7), self-reported fractures after Y7 were confirmed by radiographic reports. Fracture prediction assessed using Cox proportional hazards regression and logistic regression with receiver operating characteristic curves for models based on initial BMD, BMD change, and the combination of initial BMD and BMD change (combination model).ResultsDuring an average follow-up of 8.2 years after Y7, 793 men experienced ≥ 1 clinical fractures, including 426 men with major osteoporotic fractures (MOF) and 193 men with hip fractures. Both initial BMD and BMD change were associated with risk of fracture outcomes independent of each other, but the association was stronger for initial BMD. For example, the multivariable hazard ratio of MOF in the combination model per 1 SD decrement in BMD was 1.76 (95% CI 1.57-1.98) for initial BMD and 1.19 (95% CI 1.08-1.32) for BMD change. Discrimination of fracture outcomes with initial BMD models was somewhat better than with BMD change models and similar to combination models (AUC value for MOF 0.68 [95% CI 0.66-0.71] for initial BMD model, 0.63 [95% CI 0.61-0.66] for BMD change model, and 0.69 [95% CI 0.66-0.71] for combination model).ConclusionRepeating BMD after 7 years did not meaningfully improve fracture prediction at the population level in community-dwelling older men.

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

BackgroundVitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent.MethodsIn an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses.ResultsAmong 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial.ConclusionsVitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

ObjectivesBack pain and poor mental health are interrelated issues in older men. Evidence suggests that socioeconomic status moderates this relationship, but less is known about the role of subjective social status (SSS). This study examined if the association between back pain and mental health is moderated by SSS.MethodWe used a sample of community-dwelling older men (≥65 years) from the Osteoporotic Fractures in Men Study (N = 5994). Participants self-reported their back pain severity and frequency over the past 12 months. SSS was assessed with the MacArthur Scale of SSS. Mental health was assessed with the SF-12 Mental Component Summary (MCS).ResultsSevere back pain was associated with lower SF-12 MCS scores (p = .03). Back pain frequency was not associated with SF-12 MCS scores. SSS moderated the back pain and mental health relationship. Among men with higher national or community SSS, the association between back pain severity and SF-12 MCS scores was not significant. However, among men with lower national or community SSS, more severe back pain was associated with lower SF-12 MCS scores (p's < .001). Among those with lower national or community SSS, greater back pain frequency was also associated with lower SF-12 MCS scores (p's < .05).ConclusionWhere one ranks oneself within their nation or community matters for the back pain and mental health relationship. Higher SSS may be a psychosocial resource that buffers the negative associations of severe and frequent back pain on mental health in older men.

BackgroundLower urinary tract symptoms (LUTS) are associated with frailty phenotype, a risk factor for functional decline. Our objective was to determine the association between baseline LUTS and 2-year risk of new functional limitation among older men.MethodsWe analyzed data from the Osteoporotic Fractures in Men (MrOS) study with baseline at Year 7 and follow-up through Year 9. Participants included 2716 community-dwelling men age ≥ 71 years without any baseline self-reported functional limitation. LUTS severity (American Urologic Association Symptom Index) was classified as none/mild (score 0-7), moderate (8-19), and severe (20-35). At baseline and follow-up, men reported their ability to complete several mobility, activities of daily living (ADLs), and cognition-dependent tasks. Risk was estimated for 3 incident functional limitation outcomes: (1) mobility (any difficulty walking 2-3 blocks or climbing 10 steps), (2) ADL (any difficulty bathing, showering, or transferring), and (3) cognition-dependent (any difficulty managing money or medications). We used Poisson regression with a robust variance estimator to model adjusted risk ratios (ARR) and 95% CIs controlling for age, site, and comorbidities; other demographic/lifestyle factors did not meet criteria for inclusion.ResultsOverall, the 2-year risk was 15% for mobility, 10% for ADLs, and 4% for cognition-dependent task limitations. Compared to none/mild LUTS, risk of incident mobility limitations was increased for moderate (ARR = 1.35, 95% CI: 1.12, 1.63) and severe LUTS (ARR = 1.98, 95% CI: 1.48, 2.64). Men were also at higher risk for incident ADL limitations if they reported moderate (ARR = 1.32, 95% CI: 1.05, 1.67) and severe LUTS (ARR = 1.62, 95% CI: 1.07,2.43). Results were somewhat attenuated after adjusting for the frailty phenotype but remained statistically significant. LUTS were not associated with incident cognition-dependent task limitations.ConclusionsLUTS severity is associated with incident mobility and ADL limitations among older men. Increased clinical attention to risk of functional limitations among older men with LUTS is likely warranted.

BackgroundMuscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat versus muscle fat to adverse outcomes have been unclear.MethodIn a large cohort of older men (N = 1 017), we measured muscle mass (D3-creatine dilution), muscle density (high-resolution peripheral quantitative computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual-energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years.ResultsIn combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% confidence interval: 0.74, 0.96), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively.ConclusionsMuscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

BackgroundCut-points to define slow walking speed have largely been derived from expert opinion.MethodsStudy participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.ResultsAmong 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as

BackgroundWhether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual-energy x-ray absorptiometry [DXA]), and these outcomes are inconsistent.MethodsMuscle mass measured by deuterated creatine (D3Cr) dilution and appendicular lean mass (ALM, by DXA) were assessed at the Year 14 Visit (2014-2016) of the prospective Osteoporotic Fractures in Men study (N = 1,425, age 77-101 years). Disability in activities of daily living (ADLs), instrumental ADLs, and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression, or proportional hazards models.ResultsIn age- and clinical center-adjusted models, the relative risks per decrement in D3Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for instrumental ADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age-, clinical center-, and weight-adjusted models, the relative risks per decrement in D3Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D3Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance.ConclusionsLow muscle mass as measured by D3Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.

BackgroundWe examined cross-sectional associations between dietary patterns, macronutrient intake, and measures of muscle mass and lean mass in older men.MethodsParticipants in the Osteoporotic Fractures in Men (MrOS) cohort (n = 903; mean ± SD age 84.2 ± 4 years) completed brief Block food frequency questionnaires (May 2014-May 2016); factor analysis was used to derive dietary patterns. The D3-creatine (D3Cr) dilution method was used to measure muscle mass; dual-energy x-ray absorptiometry (DXA) was used to measure appendicular lean mass (ALM). Generalized linear models were used to report adjusted means of outcomes by dietary pattern. Multiple linear regression models were used to determine associations between macronutrients and D3Cr muscle mass and DXA ALM. Multivariable models were adjusted for age, race, clinic site, education, depression, total energy intake, height, and percent body fat.ResultsGreater adherence to a Western dietary pattern (high factor loadings for red meat, fried foods, and high-fat dairy) was associated with higher D3Cr muscle mass (p-trend = .026). Adherence to the Healthy dietary pattern (high factor loadings for fruit, vegetables, whole grains, and lean meats) was not associated with D3Cr muscle mass or DXA ALM. Total protein (β = 0.09, 95% CI = 0.03, 0.14) and nondairy animal protein (β = 0.16, 95% CI = 0.10, 0.21) were positively associated with D3Cr muscle mass. Nondairy animal protein (β = 0.06, 95% CI = 0.002, 0.11) was positively associated with DXA ALM. Associations with other macronutrients were inconsistent.ConclusionsNondairy animal protein intake (within a Western dietary pattern and alone) was positively associated with D3Cr muscle mass in older men.

BackgroundDeclines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men.MethodsUsing repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.ResultsThe patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.ConclusionsOur description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

BackgroundDeclines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men.MethodsUsing repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.ResultsThe patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.ConclusionsOur description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

Our aim was to determine the association between objectively measured physical activity (PA) and bone strength of the distal limbs among older men. We studied 994 men from the MrOS cohort study (mean age 83.9) who had repeat (Year 7 and 14) 5-day activity assessment with at least 90% wear time (SenseWearPro3 Armband) and Year 14 measures using high resolution peripheral quantitative tomography (HR-pQCT) (Scanco). Total energy expenditure (TEE), total steps per day, peak cadence (mean of top 30 steps/min over 24 h) and time spent in a given level of activity: sedentary (reference,

PurposeIn younger men lower body mass is associated with fewer urinary symptoms, including incontinence and nocturia. However, lower body mass may have different implications in older men due to age associated muscle atrophy and decreased strength.Materials and methodsWe performed a prospective analysis of community dwelling men 70 to 79 years old in the multicenter Health ABC (Aging and Body Composition) study who underwent measurement of body mass on physical examination, composition using dual x-ray absorptiometry and strength according to grip and lower leg dynamometry. We evaluated associations with prevalent incontinence and nocturia on structured questionnaires as well as concurrent changes in urinary symptoms during 3 years using multivariate logistic regression.ResultsOf the 1,298 men analyzed 22% reported incontinence and 52% reported nocturia at baseline. Higher body mass index, fat mass and lower appendicular lean mass, and grip and quadriceps strength corrected for body mass index were associated with an increased prevalence of incontinence (each p

BackgroundPhysical performance and activity have both been linked to fall risk, but the way they are jointly associated with falls is unclear. We investigated how these two factors are related to incident falls in older men.MethodsIn 2,741 men (78.8 ± 5 years), we evaluated the associations between activity and physical performance and how they jointly contributed to incident falls. Activity was assessed by accelerometry. Physical performance was measured by gait speed, dynamic balance (narrow walk), chair stand time, grip strength, and leg power. Falls were ascertained by tri-annual questionnaires.ResultsMen were grouped into four categories based on activity and performance levels. The greatest number of falls (36%-43%) and the highest fall rate (4.7-5.4/y among those who fell) (depending on the performance test) occurred in men with low activity/low performance, but most falls (57%-64%) and relatively high fall rates (3.0-4.35/y) occurred in the other groups (low activity/high performance, high activity/high performance and high activity/low performance; 70% of men were in these groups). There were interactions between activity, performance (gait speed, narrow walk), and incident falls (p = .001-.02); predicted falls per year were highest in men with low activity/low performance, but there was also a peak of predicted falls in those with high activity.ConclusionsIn community-dwelling older men, many falls occur in those with the lowest activity/worst physical performance but fall risk is also substantial with better activity and performance. Activity/physical performance assessments may improve identification of older men at risk of falls, and allow individualized approaches to prevention.

BACKGROUND:To examine the associations between objective physical activity measures and subsequent health care utilization. METHODS:We studied 1,283 men (mean age 79.1 years, SD 5.3) participating in the Osteoporotic Fractures in Men Study. Participants wore a SenseWear® Pro Armband monitor for 1 week. Data was summarized as daily (i) step counts, (ii) total energy expenditure, (iii) active energy expenditure, and (iv) activity time (sedentary, ≥ light, ≥ moderate). The outcome measures of 1-year hospitalizations/duration of stay from Medicare data were analyzed with a two-part hurdle model. Covariates included age, clinical center, body mass index, marital status, depressive symptoms, medical conditions, cognitive function, and prior hospitalization. RESULTS:Each 1 SD = 3,092 step increase in daily step count was associated with a 34% (95% confidence interval [CI]: 19%-46%) lower odds of hospitalization in base model (age and center) and 21% (95% CI: 4%-35%) lower odds of hospitalization in fully adjusted models. Similar but smaller associations held for other physical activity measures, but these associations were not significant in fully adjusted models. Among those hospitalized, higher step count was associated with shorter total duration of acute/postacute care stays in the base model only. There was a fourfold significant difference (from model-based estimates) in predicted care days comparing those with 2,000 versus 10,000 daily steps in the base model, but only a twofold difference (not significant) in the full model. CONCLUSION:Daily step count is an easily determined measure of physical activity that may be useful in assessment of future health care burden in older men.

ContextBariatric surgery results in reduced muscle mass as weight is lost, but postoperative changes in muscle strength and performance are incompletely understood.ObjectiveTo examine changes in body composition, strength, physical activity, and physical performance following Roux-en-Y gastric bypass (RYGB).Design, participants, outcomesIn a prospective cohort of 47 adults (37 women, 10 men) aged 45 ± 12 years (mean ± SD) with body mass index (BMI) 44 ± 8 kg/m2, we measured body composition by dual-energy X-ray absorptiometry, handgrip strength, physical activity, and physical performance (chair stand time, gait speed, 400-m walk time) before and 6 and 12 months after RYGB. Relative strength was calculated as absolute handgrip strength/BMI and as absolute strength/appendicular lean mass (ALM).ResultsParticipants experienced substantial 12-month decreases in weight (-37 ± 10 kg or 30% ± 7%), fat mass (-48% ± 12%), and total lean mass (-13% ± 6%). Mean absolute strength declined by 9% ± 17% (P < 0.01). In contrast, relative strength increased by 32% ± 25% (strength/BMI) and 9% ± 20% (strength/ALM) (P < 0.01 for both). There were clinically significant postoperative improvements in all physical performance measures, including mean improvement in gait speed of >0.1 m/s (P < 0.01) and decrease in 400-m walk time of nearly a full minute.ConclusionsIn the setting of dramatic weight loss, lean mass and absolute grip strength declined after RYGB. However, relative muscle strength and physical function improved meaningfully and are thus noteworthy positive outcomes of gastric bypass.

ContextBariatric surgery results in reduced muscle mass as weight is lost, but postoperative changes in muscle strength and performance are incompletely understood.ObjectiveTo examine changes in body composition, strength, physical activity, and physical performance following Roux-en-Y gastric bypass (RYGB).Design, participants, outcomesIn a prospective cohort of 47 adults (37 women, 10 men) aged 45 ± 12 years (mean ± SD) with body mass index (BMI) 44 ± 8 kg/m2, we measured body composition by dual-energy X-ray absorptiometry, handgrip strength, physical activity, and physical performance (chair stand time, gait speed, 400-m walk time) before and 6 and 12 months after RYGB. Relative strength was calculated as absolute handgrip strength/BMI and as absolute strength/appendicular lean mass (ALM).ResultsParticipants experienced substantial 12-month decreases in weight (-37 ± 10 kg or 30% ± 7%), fat mass (-48% ± 12%), and total lean mass (-13% ± 6%). Mean absolute strength declined by 9% ± 17% (P < 0.01). In contrast, relative strength increased by 32% ± 25% (strength/BMI) and 9% ± 20% (strength/ALM) (P < 0.01 for both). There were clinically significant postoperative improvements in all physical performance measures, including mean improvement in gait speed of >0.1 m/s (P < 0.01) and decrease in 400-m walk time of nearly a full minute.ConclusionsIn the setting of dramatic weight loss, lean mass and absolute grip strength declined after RYGB. However, relative muscle strength and physical function improved meaningfully and are thus noteworthy positive outcomes of gastric bypass.

Sarcopenia has been described as the age-associated decrease in skeletal muscle mass. However, virtually every study of sarcopenia has measured lean body mass (LBM) or fat free mass (FFM) rather than muscle mass, specifically. In a number of published sarcopenia studies, LBM or FFM is referred to as muscle mass, leading to an incorrect assumption that measuring LBM or FFM is an accurate measure of muscle mass. As a result, the data on the effects of changes in LBM or FFM in older populations on outcomes such as functional capacity, disability, and risk of injurious falls have been inconsistent resulting in the conclusion that muscle mass is only weakly related to these outcomes. We review and describe the assumptions for the most commonly used measurements of body composition. Dual-energy X-ray absorptiometry (DXA) has become an increasingly common tool for the assessment of LBM or FFM and appendicular lean mass as a surrogate, but inaccurate, measurement of muscle mass. Other previously used methods (total body water, bioelectric impedance, and imaging) also have significant limitations. D3 -Creatine (D3 -Cr) dilution provides a direct and accurate measurement of creatine pool size and skeletal muscle mass. In a recent study in older men (MrOS cohort), D3 -Cr muscle mass was associated with functional capacity and risk of injurious falls and disability, while assessments of LBM or appendicular lean mass by DXA were only weakly or not associated with these outcomes. Inaccurate measurements of muscle mass by DXA and other methods have led to inconsistent results and potentially erroneous conclusions about the importance of skeletal muscle mass in health and disease. The assessment of skeletal muscle mass using the D3 -Cr dilution method in prospective cohort studies may reveal sarcopenia as a powerful risk factor for late life disability and chronic disease.

BackgroundThe association between diabetes and dementia may be explained in part by elevated levels of glycated peptides; we sought to determine whether serum-glycated peptides predicted cognitive decline in nondiabetic older adults.MethodsWe prospectively studied 525 community-dwelling nondiabetic women, mean age of 82 years, and analyzed baseline glycated peptides (serum level of fructosamine and glycated albumin). Cognitive outcomes included 5-year decline on the short Mini-Mental State Examination (sMMSE), Trails B, and performance on a battery of five other cognitive tests at the follow-up visit. Generalized linear models were adjusted for education, age, race, physical activity, body mass index, and vascular disease.ResultsWomen with higher level of fructosamine (upper two tertiles) had greater 5-year decline in Trails B performance compared with women in the lowest tertile (adjusted mean change = 67 vs 50 seconds, p = .046), but change in sMMSE was not different between groups. Higher fructosamine was also associated with worse cognitive function 5 years later: adjusted mean score for the California Verbal Learning Test-II Short Form was 22.7 versus 23.9 (p = .010) and for Category Fluency was 10.1 versus 11.1 (p = .003). Higher glycated albumin was also associated with worse performance on Category Fluency (10.1 vs 11.1, p = .003) but not on any other test.ConclusionsAmong older nondiabetic women, higher concentrations of glycated peptides may be associated with greater cognitive decline, especially in measures of executive function. These associations may present new opportunities for targeted prevention and therapeutic strategies in cognitive aging.

BackgroundLean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.ObjectivesTo determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.MethodsWe performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).ResultsSeven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.ConclusionsIn conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

BackgroundLean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.ObjectivesTo determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.MethodsWe performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).ResultsSeven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.ConclusionsIn conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Sarcopenia has been described as the age-associated decrease in skeletal muscle mass. However, virtually every study of sarcopenia has measured lean body mass (LBM) or fat free mass (FFM) rather than muscle mass, specifically. In a number of published sarcopenia studies, LBM or FFM is referred to as muscle mass, leading to an incorrect assumption that measuring LBM or FFM is an accurate measure of muscle mass. As a result, the data on the effects of changes in LBM or FFM in older populations on outcomes such as functional capacity, disability, and risk of injurious falls have been inconsistent resulting in the conclusion that muscle mass is only weakly related to these outcomes. We review and describe the assumptions for the most commonly used measurements of body composition. Dual-energy X-ray absorptiometry (DXA) has become an increasingly common tool for the assessment of LBM or FFM and appendicular lean mass as a surrogate, but inaccurate, measurement of muscle mass. Other previously used methods (total body water, bioelectric impedance, and imaging) also have significant limitations. D3 -Creatine (D3 -Cr) dilution provides a direct and accurate measurement of creatine pool size and skeletal muscle mass. In a recent study in older men (MrOS cohort), D3 -Cr muscle mass was associated with functional capacity and risk of injurious falls and disability, while assessments of LBM or appendicular lean mass by DXA were only weakly or not associated with these outcomes. Inaccurate measurements of muscle mass by DXA and other methods have led to inconsistent results and potentially erroneous conclusions about the importance of skeletal muscle mass in health and disease. The assessment of skeletal muscle mass using the D3 -Cr dilution method in prospective cohort studies may reveal sarcopenia as a powerful risk factor for late life disability and chronic disease.

Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity, and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high-resolution peripheral quantitative computed tomography (HR-pQCT) scans (Scanco Medical AG, Brüttisellen, Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal bone mineral density (aBMD) change from the year 7 to year 14 exam in three categories: "accelerated" loss, ≥10% loss at either the total hip or femoral neck (n = 299, 18.4%); "expected" loss,

Background:It is unknown whether subjective daytime sleepiness or objective napping could precede the risk of Parkinson's disease (PD) in the long term. Methods:We studied 2920 men (mean age 76 years) without a history of PD and followed them for 11 years. Excessive daytime sleepiness (EDS) was defined as having an Epworth Sleepiness Scale score >10. Objective naps were defined as ≥5 consecutive minutes of inactivity as measured by actigraphy, and napping duration was the accumulated time of naps outside the main sleep period. We used logistic regression to compare PD risk across four groups: no EDS& napping

ObjectivesTo determine the association between weight trajectory, health status, and mortality in older women.DesignCohort study.SettingStudy of Osteoporotic Fractures.ParticipantsOlder community-dwelling women (age: baseline (1986-88), mean 68, range 65-81; Year 20 (2006-08), mean 88, range 83-102 (N = 1,323)).MeasurementsBody weight measured repeatedly over 20 years (mean 8 times). Logistic and Cox proportional hazard models were used to evaluate whether 20-year weight trajectory measures were associated with hip fracture, falls, physical performance, and mortality.ResultsIn models adjusted for age, clinic, calcium use, Year 20 weight, walking speed, comorbidity score, smoking, self-reported health, and walking for exercise, women with moderate weight loss (>9.0 kg) over 20 years had a 74% greater risk of death (hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.37-2.20) in the 5 years after the Year 20 visit than those with no weight loss and more than twice the risk of hip fracture (HR = 2.56, 95% CI = 1.39-4.70). They were 3.6 times (odds ratio (OR) = 3.60, 95% CI = 1.86-6.95) as likely to have poor physical function at the Year 20 visit as women with no weight loss but no greater risk of 2 or more falls in the 1.5 years after the Year 20 visit. Weight variability and abrupt weight decline were not associated with adverse health oucomes (falls, fractures, mortality), but those in the highest quartile of variability were 2.3 times (OR = 2.26, 95% CI = 1.34-3.80) as likely to have poor physical function scores.ConclusionIn women surviving past 80 years of age, moderate weight loss over 20 years was associated with greater risk of hip fracture, poor physical function, and mortality but not of falls. Future work should separate voluntary from involuntary weight loss.

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.

We proposed the term "dysmobility syndrome" (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height2 30%, spine or hip T-score ≤ -2.5, grip strength

BackgroundThis study examines effects of mobility and multimorbidity on hospitalization and inpatient and postacute care (PAC) facility days among older men.MethodsProspective study of 1,701 men (mean age 79.3 years) participating in Osteoporotic Fractures in Men (MrOS) Study Year 7 (Y7) examination (2007-2008) linked with their Medicare claims. At Y7, mobility ascertained by usual gait speed and categorized as poor, intermediate, or good. Multimorbidity quantified by applying Elixhauser algorithm to inpatient and outpatient claims and categorized as none, mild-moderate, or high. Hospitalizations and PAC facility stays ascertained during 12 months following Y7.ResultsReduced mobility and greater multimorbidity burden were independently associated with a higher risk of inpatient and PAC facility utilization, after accounting for each other and traditional indicators. Adjusted mean total facility days per year were 1.13 (95% confidence interval [CI] = 0.74-1.40) among men with good mobility increasing to 2.43 (95% CI = 1.17-3.84) among men with poor mobility, and 0.67 (95% CI = 0.38-0.91) among men without multimorbidity increasing to 2.70 (95% CI = 1.58-3.77) among men with high multimorbidity. Men with poor mobility and high multimorbidity had a ninefold increase in mean total facility days per year (5.50, 95% CI = 2.78-10.87) compared with men with good mobility without multimorbidity (0.59, 95% CI = 0.37-0.95).ConclusionsAmong older men, mobility limitations and multimorbidity were independent predictors of higher inpatient and PAC utilization after considering each other and conventional predictors. Marked combined effects of reduced mobility and multimorbidity burden may be important to consider in clinical decision-making and planning health care delivery strategies for the growing aged population.

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.

We proposed the term "dysmobility syndrome" (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height2 30%, spine or hip T-score ≤ -2.5, grip strength

Our objective was to determine the associations of peripheral bone strength and microarchitecture with incident clinical and major osteoporotic fracture among older men after adjusting for major clinical risk factors. We used a prospective cohort study design with data from 1794 men (mean age 84.4 years) in the Osteoporotic Fractures in Men (MrOS) study. Eligible men attended the year 14 visit, had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia, DXA measured BMD, and were followed for mean 1.7 years for incident fracture. Failure load was estimated using finite element analysis. We used Cox proportional hazards models with standardized HR-pQCT parameters as exposure variables. Primary outcome was clinical fracture (n = 108). Covariates included either Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability calculated with BMD (FRAX-BMD), or individual clinical risk factors (CRF) including age, total hip BMD, race, falls, and prevalent fracture after age 50 years. Lower failure load was associated with higher risk of incident clinical fracture and incident major osteoporotic fracture. For clinical fracture with FRAX-BMD adjustment, the associations ranged from hazard ratio (HR) 1.58 (95% CI, 1.25 to 2.01) to 2.06 (95% CI, 1.60 to 2.66) per SD lower failure load at the diaphyseal tibia and distal radius. These associations were attenuated after adjustment for individual CRFs, but remained significant at the distal sites. Associations of volumetric BMD with these outcomes were similar to those for failure load. At the distal radius, lower trabecular BMD, number, and thickness, and lower cortical BMD, thickness, and area were all associated with higher risk of clinical fracture, but cortical porosity was not. Among community-dwelling older men, HR-pQCT measures including failure load, volumetric BMD, and microstructure parameters at peripheral sites (particularly distal radius) are robust independent predictors of clinical and major osteoporotic fracture. © 2018 American Society for Bone and Mineral Research.

ObjectivesTo determine the association of the frailty phenotype with subsequent healthcare costs and utilization.DesignProspective cohort study (Study of Osteoporotic Fractures (SOF)).SettingFour U.S. sites.ParticipantsCommunity-dwelling women (mean age 80.2) participating in SOF Year 10 (Y10) examination linked with their Medicare claims data (N=2,150).MeasurementsAt Y10, frailty phenotype defined using criteria similar to those used in the Cardiovascular Health Study frailty phenotype and categorized as robust, intermediate stage, or frail. Participant multimorbidity burden ascertained using claims data. Functional limitations assessed by asking about difficulty performing instrumental activities of daily living. Total direct healthcare costs and utilization ascertained during 12 months after Y10.ResultsMean total annualized cost±standard deviation (2014 dollars) was $3,781±6,920 for robust women, $6,632±12,452 for intermediate stage women, and $10,755 ± 16,589 for frail women. After adjustment for age, site, multimorbidity burden, and cognition, frail women had greater mean total (cost ratio (CR)=1.91, 95% confidence interval (CI)=1.59-2.31) and outpatient (CR=1.55, 95% CI=1.36-1.78) costs than robust women and greater odds of hospitalization (odds ratio (OR)=2.05, 95% CI=1.47-2.87) and a skilled nursing facility stay (OR=3.85, 95% CI=1.88-7.88). There were smaller but significant effects of the intermediate stage category on these outcomes. Individual frailty components (shrinking, poor energy, slowness, low physical activity) were also each associated with higher total costs. Functional limitations partially mediated the association between the frailty phenotype and total costs (CR further adjusted for self-reported limitations=1.32, 95% CI=1.07-1.63 for frail vs robust; CR=1.35, 95% CI=1.18-1.55 for intermediate stage vs robust women).ConclusionIntermediate stage and frail older community-dwelling women had higher subsequent total healthcare costs and utilization after accounting for multimorbidity and functional limitations. Frailty phenotype assessment may improve identification of older adults likely to require costly, extensive care.

Our objective was to determine the associations of peripheral bone strength and microarchitecture with incident clinical and major osteoporotic fracture among older men after adjusting for major clinical risk factors. We used a prospective cohort study design with data from 1794 men (mean age 84.4 years) in the Osteoporotic Fractures in Men (MrOS) study. Eligible men attended the year 14 visit, had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia, DXA measured BMD, and were followed for mean 1.7 years for incident fracture. Failure load was estimated using finite element analysis. We used Cox proportional hazards models with standardized HR-pQCT parameters as exposure variables. Primary outcome was clinical fracture (n = 108). Covariates included either Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability calculated with BMD (FRAX-BMD), or individual clinical risk factors (CRF) including age, total hip BMD, race, falls, and prevalent fracture after age 50 years. Lower failure load was associated with higher risk of incident clinical fracture and incident major osteoporotic fracture. For clinical fracture with FRAX-BMD adjustment, the associations ranged from hazard ratio (HR) 1.58 (95% CI, 1.25 to 2.01) to 2.06 (95% CI, 1.60 to 2.66) per SD lower failure load at the diaphyseal tibia and distal radius. These associations were attenuated after adjustment for individual CRFs, but remained significant at the distal sites. Associations of volumetric BMD with these outcomes were similar to those for failure load. At the distal radius, lower trabecular BMD, number, and thickness, and lower cortical BMD, thickness, and area were all associated with higher risk of clinical fracture, but cortical porosity was not. Among community-dwelling older men, HR-pQCT measures including failure load, volumetric BMD, and microstructure parameters at peripheral sites (particularly distal radius) are robust independent predictors of clinical and major osteoporotic fracture. © 2018 American Society for Bone and Mineral Research.

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual-energy X-ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral-fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.

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.IntroductionWe compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality.MethodsA 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.ResultsAmong 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

ObjectivesTo describe the natural history of frailty transitions in a large cohort of community-dwelling older men and identify predictors associated with progression to or improvement from states of greater frailty.DesignProspective cohort study.SettingSix U.S. sites.ParticipantsCommunity-dwelling men aged 65 and older (N = 5,086).MeasurementsFrailty was measured at baseline and an average of 4.6 years later. Frailty was defined as having three or more of the following components (low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed); prefrailty was defined as having one or two components. Separate multivariable logistic regression models were analyzed for progression and improvement in frailty status.ResultsOf the 5,086 men, 8% were frail, 46% were prefrail, and 46% were robust at baseline. Between baseline and follow-up, 35% progressed in frailty status or died, 56% had no change in frailty status, and 15% of prefrail or frail participants improved, although only 0.5% improved across two levels, from frail to robust. In multivariable models, factors associated with improvement in frailty status included greater leg power, being married, and good or excellent self-reported health, whereas presence of any instrumental activity of daily living (IADL) limitations, low albumin levels, high interleukin-6 levels, and presence of chronic obstructive pulmonary disease or diabetes mellitus were associated with lower likelihood of improvement in frailty status.ConclusionImprovement in frailty status was possible in this cohort of community-dwelling older men, but improvement from frail to robust was rare. Several predictors were identified as possible targets for intervention, including prevention and management of comorbid medical conditions, prevention of IADL disability, physical exercise, and nutritional and social support.

ObjectivesTo describe the natural history of frailty transitions in a large cohort of community-dwelling older men and identify predictors associated with progression to or improvement from states of greater frailty.DesignProspective cohort study.SettingSix U.S. sites.ParticipantsCommunity-dwelling men aged 65 and older (N = 5,086).MeasurementsFrailty was measured at baseline and an average of 4.6 years later. Frailty was defined as having three or more of the following components (low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed); prefrailty was defined as having one or two components. Separate multivariable logistic regression models were analyzed for progression and improvement in frailty status.ResultsOf the 5,086 men, 8% were frail, 46% were prefrail, and 46% were robust at baseline. Between baseline and follow-up, 35% progressed in frailty status or died, 56% had no change in frailty status, and 15% of prefrail or frail participants improved, although only 0.5% improved across two levels, from frail to robust. In multivariable models, factors associated with improvement in frailty status included greater leg power, being married, and good or excellent self-reported health, whereas presence of any instrumental activity of daily living (IADL) limitations, low albumin levels, high interleukin-6 levels, and presence of chronic obstructive pulmonary disease or diabetes mellitus were associated with lower likelihood of improvement in frailty status.ConclusionImprovement in frailty status was possible in this cohort of community-dwelling older men, but improvement from frail to robust was rare. Several predictors were identified as possible targets for intervention, including prevention and management of comorbid medical conditions, prevention of IADL disability, physical exercise, and nutritional and social support.

Prior data in women suggest that incident clinically undiagnosed radiographic vertebral fractures (VFs) often are symptomatic, but misclassification of incident clinical VF may have biased these estimates. There are no comparable data in men. To evaluate the association of incident clinically undiagnosed radiographic VF with back pain symptoms and associated activity limitations, we used data from the Osteoporotic Fractures in Men (MrOS) Study, a prospective cohort study of community-dwelling men aged ≥65 years. A total of 4396 men completed spine X-rays and symptom questionnaires at baseline and visit 2, about 4.6 years later. Incident clinical VFs during this interval were defined by self-reported clinical diagnosis plus community imaging showing a centrally adjudicated ≥1 increase in semiquantitative (SQ) grade in any thoracic or lumbar vertebra versus baseline study X-rays. Incident radiographic VFs (≥1 increase in SQ grade between baseline and visit 2 study X-rays) were categorized as radiographic-only (not clinically diagnosed) or radiographic plus clinical (also clinically diagnosed). Multivariable-adjusted log binomial regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs). Men with incident radiographic plus clinical VF were most likely to have back pain symptoms and associated activity limitation at follow-up. However, versus men without incident VF, those with incident radiographic-only VF also were significantly more likely at follow-up to report any back pain (70% versus 59%; PR, 1.2 [95% CI, 1.1 to 1.3]), severe back pain (8% versus 4%; PR, 1.9 [95% CI, 1.1 to 3.3]), bother from back pain most/all the time (22% versus 13%; PR, 1.7 [95% CI, 1.3 to 2.2]), and limited usual activity from back pain (34% versus 18%; PR, 1.9 [95% CI, 1.5 to 2.4]). Clinically undiagnosed, incident radiographic VFs were associated with an increased likelihood of back pain symptoms and associated activity limitation. Results suggest incident radiographic-only VFs often were symptomatic, and were associated with both new and worsening back pain. Preventing these fractures may reduce back pain and related disability in older men. © 2017 American Society for Bone and Mineral Research.

Prior data in women suggest that incident clinically undiagnosed radiographic vertebral fractures (VFs) often are symptomatic, but misclassification of incident clinical VF may have biased these estimates. There are no comparable data in men. To evaluate the association of incident clinically undiagnosed radiographic VF with back pain symptoms and associated activity limitations, we used data from the Osteoporotic Fractures in Men (MrOS) Study, a prospective cohort study of community-dwelling men aged ≥65 years. A total of 4396 men completed spine X-rays and symptom questionnaires at baseline and visit 2, about 4.6 years later. Incident clinical VFs during this interval were defined by self-reported clinical diagnosis plus community imaging showing a centrally adjudicated ≥1 increase in semiquantitative (SQ) grade in any thoracic or lumbar vertebra versus baseline study X-rays. Incident radiographic VFs (≥1 increase in SQ grade between baseline and visit 2 study X-rays) were categorized as radiographic-only (not clinically diagnosed) or radiographic plus clinical (also clinically diagnosed). Multivariable-adjusted log binomial regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs). Men with incident radiographic plus clinical VF were most likely to have back pain symptoms and associated activity limitation at follow-up. However, versus men without incident VF, those with incident radiographic-only VF also were significantly more likely at follow-up to report any back pain (70% versus 59%; PR, 1.2 [95% CI, 1.1 to 1.3]), severe back pain (8% versus 4%; PR, 1.9 [95% CI, 1.1 to 3.3]), bother from back pain most/all the time (22% versus 13%; PR, 1.7 [95% CI, 1.3 to 2.2]), and limited usual activity from back pain (34% versus 18%; PR, 1.9 [95% CI, 1.5 to 2.4]). Clinically undiagnosed, incident radiographic VFs were associated with an increased likelihood of back pain symptoms and associated activity limitation. Results suggest incident radiographic-only VFs often were symptomatic, and were associated with both new and worsening back pain. Preventing these fractures may reduce back pain and related disability in older men. © 2017 American Society for Bone and Mineral Research.

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

BackgroundThe association between various definitions of sarcopenia and hospitalization has not been evaluated in community-dwelling older men.MethodsWe used data from 1,516 participants at Visit 3 of the Osteoporotic Fractures in Men (MrOS) study who also had linked Medicare Fee-For-Service Claims data available. We examined the association between several sarcopenia definitions (International Working Group, European Working Group for Sarcopenia in Older Persons, Foundation for the NIH Sarcopenia Project, Baumgartner, and Newman) and hospitalization, using two-part ("hurdle") models, adjusted for age, clinical center, functional limitations, self-reported health, comorbidity, and cognitive function. Predictors included sarcopenia status (the summary definitions and the components of slowness, weakness, and/or lean mass); outcomes included hospitalization and cumulative inpatient days/year in the 3 years following the Visit 3 exam.ResultsAfter accounting for confounding factors, none of the summary definitions or the definition components (slowness, weakness, or low lean mass) were associated with likelihood of hospitalization, the rate ratio of inpatient days among those hospitalized, or the mean rate of inpatient days amongst all participants.ConclusionsSarcopenia was not associated hospitalization in community-dwelling older men. These results provide further evidence that current sarcopenia definitions are unlikely to identify those who are most likely to have greater hospitalization.

BackgroundMusculoskeletal pain is associated with increased fall risk among older men. However, the association of back pain, the most prevalent type of pain in this population, and fall risk is unknown.MethodsWe conducted a prospective investigation among 5,568 community-dwelling U.S. men at least 65 years of age from the Osteoporotic Fractures in Men Study (MrOS). Baseline questionnaires inquired about back pain and its location (such as low back), severity, and frequency in the past year. During 1 year of follow-up, falls were summed from self-reports obtained every 4 months. Outcomes were recurrent falls (≥2 falls) and any fall (≥1 fall). Associations of back pain and fall risk were estimated with risk ratios (RRs) and 95% confidence intervals (CIs) from multivariable log-binomial regression models adjusted for age, dizziness, arthritis, knee pain, urinary symptoms, self-rated health, central nervous system medication use, and instrumental activities of daily living.ResultsMost (67%) reported any back pain in the past year. During follow-up, 11% had recurrent falls and 25% fell at least once. Compared with no back pain, any back pain was associated with elevated recurrent fall risk (multivariable RR = 1.3, 95% CI: 1.1, 1.5). Multivariable RRs for 1, 2, and 3+ back pain locations were, respectively, 1.2 (95% CI: 1.0, 1.5), 1.4 (1.1, 1.8), and 1.7 (95% CI: 1.3, 2.2). RRs were also elevated for back pain severity and frequency. Back pain was also associated with risk of any fall.ConclusionsAmong older men, back pain is independently associated with increased fall risk.

ObjectiveTo investigate cross-sectional and longitudinal associations of diffuse idiopathic skeletal hyperostosis (DISH) and thoracic kyphosis in older persons.MethodsDISH and kyphosis were assessed in 1,500 men from the Osteoporotic Fractures in Men (MrOS) study and in 1,267 women from the Study of Osteoporotic Fractures (SOF). DISH was assessed using baseline lateral spine radiographs, and Cobb angle of kyphosis was measured from baseline and followup radiographs, a mean 4.6 years later in men, and 3.7 and 15 years later in women. Linear regression was used to analyze associations of DISH with baseline Cobb angle and with percent annualized change in Cobb angle. We tested for heterogeneity among studies.ResultsDISH was identified in 222 participants in MrOS (15%) and in 156 participants in SOF (12%). Participants with DISH in both cohorts had higher baseline Cobb angles (P  0.05) for men or women. Women with DISH had less kyphosis progression over 15 years (0.25% less annualized change in Cobb) than those without DISH.ConclusionPrevalent DISH is associated with greater kyphosis in older men and women, and is not significantly associated with a change in kyphosis over 4-5 years. However, in women followed over 15 years, DISH was associated with less progression of kyphosis. These results suggest that DISH influences kyphosis and may slow progression over the long term. Additional studies of DISH/kyphosis associations are warranted to understand the functional implications of this finding.

ObjectiveTo investigate cross-sectional and longitudinal associations of diffuse idiopathic skeletal hyperostosis (DISH) and thoracic kyphosis in older persons.MethodsDISH and kyphosis were assessed in 1,500 men from the Osteoporotic Fractures in Men (MrOS) study and in 1,267 women from the Study of Osteoporotic Fractures (SOF). DISH was assessed using baseline lateral spine radiographs, and Cobb angle of kyphosis was measured from baseline and followup radiographs, a mean 4.6 years later in men, and 3.7 and 15 years later in women. Linear regression was used to analyze associations of DISH with baseline Cobb angle and with percent annualized change in Cobb angle. We tested for heterogeneity among studies.ResultsDISH was identified in 222 participants in MrOS (15%) and in 156 participants in SOF (12%). Participants with DISH in both cohorts had higher baseline Cobb angles (P  0.05) for men or women. Women with DISH had less kyphosis progression over 15 years (0.25% less annualized change in Cobb) than those without DISH.ConclusionPrevalent DISH is associated with greater kyphosis in older men and women, and is not significantly associated with a change in kyphosis over 4-5 years. However, in women followed over 15 years, DISH was associated with less progression of kyphosis. These results suggest that DISH influences kyphosis and may slow progression over the long term. Additional studies of DISH/kyphosis associations are warranted to understand the functional implications of this finding.

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual-energy X-ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow-up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41-fold (95% confidence interval [CI] 1.23 to 1.63) higher aged-adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age-adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m2 ; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI. © 2017 American Society for Bone and Mineral Research.