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BackgroundLow grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.AimWe examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.MethodsParticipants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).ResultsMean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.ConclusionsGrip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength

IntroductionHyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.MethodsMen aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity.ResultsDuring a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend

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.

Hyperkyphosis (HK), or accentuated forward spinal curvature, commonly affects older people, although its causes are not completely understood. We tested whether a measure of bone quality, trabecular bone score (TBS), is associated with HK in 1997 older men, and determined that men with degraded TBS were more likely to have HK.IntroductionWhile vertebral fractures and low bone mineral density (BMD) contribute to kyphosis progression, it is unknown whether the trabecular bone score (TBS) may provide additional information on bone quality that could influence the degree of kyphosis. We hypothesized that degraded TBS would be associated with hyperkyphosis (HK) defined as a Cobb angle > 50°.MethodsUsing data from 1997 participants of the Osteoporotic Fractures in Men (MrOS) Study who had baseline TBS and Cobb angle kyphosis measured, we investigated whether men with degraded TBS were more likely to be hyperkyphotic, even after adjustment for BMD and prevalent vertebral fractures.ResultsMen were an average age of 74 ± 6 (mean ± SD) years with a mean kyphosis angle of 38.6 ± 11.5°, 295 (15%) were classified as hyperkyphotic, and 416 (21%) had degraded TBS. Compared with men with TBS > 1.2, men with degraded TBS were more likely to have HK (OR: 1.47, 95% CI: 1.06-2.06, p = 0.02) after adjusting for age, clinic, race, BMI, hip BMD, and prevalent vertebral fracture. If spine instead of hip BMD was included in the model, the odds ratio decreased to 1.35 (95% CI: 0.97-1.89, p = 0.08).ConclusionsOlder men with degraded TBS are more likely to have HK not explained by underlying vertebral fractures.

IntroductionLimited evidence exists on the impact of age and comorbidity on biopsy rates and findings among older women.Materials and methodsWe used data from 170,657 women ages 66-94 enrolled in the United States Breast Cancer Surveillance Consortium (BCSC). We estimated one-year rates of biopsy by type (any, fine-needle aspiration (FNA), core or surgical) and yield of the most invasive biopsy finding (benign, ductal carcinoma in situ (DCIS) and invasive breast cancer) by age and comorbidity. Statistical significance was assessed using Wald statistics comparing coefficients estimated from logistic regression models adjusted for age, comorbidity, BCSC registry, and interaction between age and comorbidity.ResultsOf 524,860 screening mammograms, 9830 biopsies were performed following 7930 exams (1.5%) within one year, specifically 5589 core biopsies (1.1%), 3422 (0.7%) surgical biopsies and 819 FNAs (0.2%). Biopsy rates per 1000 screens decreased with age (66-74:15.7, 95%CI:14.8-16.8), 75-84:14.5(13.5-15.6), 85-94:13.2(11.3,15.4), ptrend

BackgroundThe cost-effectiveness of screening mammography beyond age 75 years remains unclear.ObjectiveTo estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden.DesignMarkov microsimulation model.Data sourcesSEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium.Target populationU.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS).Time horizonLifetime.PerspectiveNational health payer.InterventionScreening mammography to age 75, 80, 85, or 90 years.Outcome measuresBreast cancer death, survival, and costs.Results of base-case analysisExtending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer.Results of sensitivity analysisCosts per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography.LimitationNo randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs.ConclusionAlthough annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer.Primary funding sourceNational Cancer Institute and National Institutes of Health.

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend

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

BackgroundPrevious reports suggested risk of death and breast cancer varied by comorbidity and age in older women undergoing mammography. However, impacts of functional limitations remain unclear.MethodsWe used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare linked database (1999-2015) who had screening mammogram at ages 66-94 years. We estimated risk of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items and was categorized as an ordinal variable (0, 1, and 2+). Fine and Gray proportional sub-distribution hazards models were applied with breast cancer and death treated as competing events. Risk estimates by FRI scores were adjusted by age and NCI comorbidity index separately and stratified by these factors.ResultsOverall, 9,252 women were diagnosed with breast cancer, 406 died of breast cancer, and 41,640 died from non-breast cancer causes. The 10-year age-adjusted invasive breast cancer risk slightly decreased with FRI score [FRI = 0: 4.0%, 95% confidence interval (CI) = 3.8-4.1; FRI = 1: 3.9%, 95% CI = 3.7-4.2; FRI ≥ 2: 3.5%, 95% CI = 3.1-3.9). Risk of non-breast cancer death increased with FRI score (FRI = 0: 18.8%, 95% CI = 18.5-19.1; FRI = 1: 24.4%, 95% CI = 23.9-25.0; FRI ≥ 2: 39.8%, 95% CI = 38.8-40.9]. Risk of breast cancer death was low with minimal differences across FRI scores. NCI comorbidity index-adjusted models and stratified analyses yielded similar patterns.ConclusionsRisk of non-breast cancer death substantially increases with FRI score, whereas risk of breast cancer death is low regardless of functional status.ImpactOlder women with functional limitations should be informed that they may not benefit from screening mammography.

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

To estimate the association of self-reported poor sleep in multiple dimensions with health care costs in older men. Participants were 1,413 men (mean [SD] age 76.5 [5.7] years) enrolled in both the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study and Medicare Fee-for-Service. Poor sleep was characterized at the baseline MrOS Sleep visit on five dimensions (satisfaction, daytime sleepiness, timing, latency, and duration). Health care costs and utilization were ascertained over 3 years of follow-up using Medicare Claims. Median (interquartile range [IQR]) annualized total health care costs (2018 US dollars) rose from $3,616 (IQR 1,523-7,875) for those with no impaired sleep dimensions to $4,416 (IQR 1,854-11,343) for men with two impaired sleep dimensions and $5,819 (IQR 1,936-15,569) for those with at least three impaired sleep dimensions. After multivariable adjustment, the ratio of total health care costs (CR) was significantly higher for men with two (1.24, 95% confidence interval [CI] 1.03- to 1.48) and men with at least three impaired sleep dimensions (1.78, 95% CI 1.42 to 2.23) vs. those with no impaired sleep dimensions. After excluding 101 men who died during the 3-year follow-up period, these associations were attenuated and not significant (CR 1.22, 95% CI 0.98 to 1.53 for men ≥3 impaired sleep dimensions vs. none). Self-reported poor sleep on multiple dimensions is associated with higher subsequent total health care costs in older men, but this may be due to higher mortality and increased health care costs toward the end of life among those with poor sleep health.

BackgroundPotential benefits of screening mammography among women ages 75 years and older remain unclear.MethodsWe evaluated 10-year cumulative incidence of breast cancer and death from breast cancer and other causes by Charlson Comorbidity Index (CCI) and age in the Medicare-linked Breast Cancer Surveillance Consortium (1999-2010) cohort of 222 088 women with no less than 1 screening mammogram between ages 66 and 94 years.ResultsDuring median follow-up of 107 months, 7583 were diagnosed with invasive breast cancer and 1742 with ductal carcinoma in situ; 471 died from breast cancer and 42 229 from other causes. The 10-year cumulative incidence of invasive breast cancer did not change with increasing CCI but decreased slightly with age: ages 66-74 years (CCI0 = 4.0% [95% CI = 3.9% to 4.2%] vs CCI  ≥ 2 = 3.9% [95% CI = 3.5% to 4.3%]); ages 75-84 years (CCI0 = 3.7% [95% CI = 3.5% to 3.9%] vs CCI  ≥ 2 = 3.4% [95% CI = 2.9% to 3.9%]); and ages 85-94 years (CCI0 = 2.7% [95% CI = 2.3% to 3.1%] vs CCI  ≥ 2 = 2.1% [95% CI = 1.3% to 3.0%]). The 10-year cumulative incidence of other-cause death increased with increasing CCI and age: ages 66-74 years (CCI0 = 10.4% [95% CI = 10.3 to 10.7%] vs CCI ≥ 2 = 43.4% [95% CI = 42.2% to 44.4%]), ages 75-84 years (CCI0 = 29.8% [95% CI = 29.3% to 30.2%] vs CCI ≥ 2 = 61.7% [95% CI = 60.2% to 63.3%]), and ages 85 to 94 years (CCI0 = 60.3% [95% CI = 59.1% to 61.5%] vs CCI  ≥ 2 = 84.8% [95% CI = 82.5% to 86.9%]). The 10-year cumulative incidence of breast cancer death was small and did not vary by age: ages 66-74 years = 0.2% (95% CI = 0.2% to 0.3%), ages 75-84 years = 0.29% (95% CI = 0.25% to 0.34%), and ages 85 to 94 years = 0.3% (95% CI = 0.2% to 0.4%).ConclusionsCumulative incidence of other-cause death was many times higher than breast cancer incidence and death, depending on comorbidity and age. Hence, older women with increased comorbidity may experience diminished benefit from continued screening.

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,

Determine the association of poor multidimensional sleep health with health-care costs and utilization. We linked 1,459 community-dwelling women (mean age 83.6 years) participating in the Study of Osteoporotic Fractures Year 16 visit (2002-2004) with their Medicare claims. Five dimensions of sleep health (satisfaction, daytime sleepiness, timing, latency, and duration) were assessed by self-report. The number of impaired dimensions was expressed as a score (range 0-5). Total direct health-care costs and utilization were ascertained during the subsequent 36 months. Mean (SD) total health-care costs/year (2017 dollars) increased in a graded manner across the sleep health score ranging from $10,745 ($15,795) among women with no impairment to up to $15,332 ($22,810) in women with impairment in three to five dimensions (p = 0.01). After adjustment for age, race, and enrollment site, women with impairment in three to five dimensions vs. no impairment had greater mean total costs (cost ratio [CR] 1.34 [95% CI = 1.13 to 1.60]) and appeared to be at higher risk of hospitalization (odds ratio (OR) 1.31 [95% CI = 0.96 to 1.81]). After further accounting for number of medical conditions, functional limitations, and depressive symptoms, impairment in three to five sleep health dimensions was not associated with total costs (CR 1.02 [95% CI = 0.86 to 1.22]) or hospitalization (OR 0.91 [95% CI = 0.65 to 1.28]). Poor multidimensional sleep health was not related to outpatient costs or risk of skilled nursing facility stay. Older women with poor sleep health have higher subsequent total health-care costs largely attributable to their greater burden of medical conditions, functional limitations, and depressive symptoms.

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.

Previous studies examining the association of cognitive impairment and dementia with fracture outcomes in older adults have usually used standard approaches that did not take into account the competing risk of mortality. However, ignoring mortality may not provide accurate estimates of risk of fracture because dementia in older adults strongly predicts death, making mortality a competing risk. A total of 1491 women (mean age 87.6 years) participating in the prospective Study of Osteoporotic Fractures (SOF) Year 20 exam were cognitively assessed and followed to ascertain vital status (deaths verified by death certificates) and hip fractures (confirmed by radiographic reports). Cognitive status was categorized as normal, mild cognitive impairment (MCI), or dementia, based on a standardized evaluation. Absolute probability of hip fracture by category of cognitive function was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of hip fracture by cognitive function category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average follow-up of 5.6 years, 139 (9.3%) women experienced a hip fracture and 990 (66.4%) died before experiencing this outcome. Among women with dementia, the risk of hip fracture was 11.7% (95% confidence interval [CI] 7.3-17.2) at 5 years and 18.6% (95% CI 9.1-30.9) at 10 years using traditional survival analysis versus 7.9% (95% CI 5.1-11.6) at 5 years and 8.8% (95% CI 5.8-12.8) at 9.8 years using a competing risk approach. Results were similar for women with MCI. Women with MCI and dementia have a higher risk of hip fractures than women with normal cognition. However, not taking into account the competing risk of mortality significantly overestimates the risk of hip fracture in women in the ninth and tenth decades of life with cognitive impairment. © 2018 American Society for Bone and Mineral Research.

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.

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.

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

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.

Finite element model can estimate bone strength better than BMD. This study used such a model to determine its association with hip fracture risk and found that the strength estimate provided limited improvement over the hip BMDs in predicting femoral neck (FN) fracture risk only.IntroductionBone fractures occur only when it is loaded beyond its ultimate strength. The goal of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of DXA scans, with incident hip fracture as a single condition or with femoral neck (FN) and trochanter (TR) fractures separately in older men.MethodsThis prospective case-cohort study included 91 FN and 64 TR fracture cases and a random sample of 500 men (14 had a hip fracture) from the Osteoporotic Fractures in Men study during a mean ± SD follow-up of 7.7 ± 2.2 years. We analysed the baseline DXA scans of the hip using a validated plane-stress, linear-elastic FE model of the proximal femur and estimated the femoral strength during a sideways fall.ResultsThe estimated strength was significantly (P

The ability of bone mineral density (BMD) and other risk factors to predict fracture risk is well-established for as long as 5 to 10 years. However, their value to predict risk over a longer term has not been directly studied. We investigated whether a single assessment of femoral neck BMD and fracture history can predict fracture risk over 20 to 25 years. We used data from the Study of Osteoporotic Fractures (SOF) that assessed BMD and risk factors in 7959 women age ≥67 (mean = 73.4) in 1988-1990. Follow-up for fractures continued for 25 years for hip fracture, and for 20 years for any nonvertebral fracture. Using age-adjusted proportional hazards models, we analyzed the relationships between a single baseline assessment of femoral neck BMD, fracture history and age, and 20-25-year fracture incidence. The 25-year cumulative incidence of hip fracture was 17.9%; 20-year incidence of any nonvertebral fracture was 46.2%. The 25-year hip fracture incidence was highest in those ≥80 years old (22.6%) compared to 13.9% in women aged 80 years. History of hip fracture predicted hip fractures only slightly better than history of nonvertebral fracture (RH = 1.6 [95% CI, 1.1 to 2.2] versus RH = 1.4 [95% CI, 1.2 to 1.5], respectively). Fracture history remained strongly predictive up to 25 years. We conclude that a single BMD and fracture history assessment can predict fracture risk over 20 to 25 years. Long-term risk of hip fracture remains extremely high in the oldest age groups, supporting risk assessment and consideration of treatment even in the oldest, highest-risk women.© 2017 American Society for Bone and Mineral Research.

The association of weight loss with health care costs among older women is uncertain. Our study aim was to examine the association of objectively measured weight change with subsequent total health care (THC) costs and other health care utilization among older women. Our study population included 2,083 women (mean age 80.2 years) enrolled in the Study of Osteoporotic Fractures and U.S. Medicare Fee for Service. Weight loss and gain were defined, respectively, as ≥5% decrease and ≥5% increase in body weight, and weight maintenance as

UNLABELLED: 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. INTRODUCTION: Our 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. METHODS: We 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. RESULTS: Higher 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. CONCLUSION: The 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.

Hyperkyphosis commonly affects older persons and is associated with morbidity and mortality. Many have hypothesized that hyperkyphosis increases fall risk. Within this prospective study of older adults, kyphosis was significantly associated with incident falls over 1 year. Measures of hyperkyphosis could enhance falls risk assessments during primary care office visits.IntroductionTo determine the association between four measures of kyphosis and incident and injurious falls in older persons.MethodsCommunity-dwelling adults aged 65 and older (n = 72) residing in southern California were invited to participate in a prospective cohort study. Participants had kyphosis assessed four ways. Two standing measures included a flexicurve ruler placed against the back to derive a kyphotic index and the Debrunner kyphometer, a protractor used to measure the kyphotic angle in degrees. Two lying measures included the blocks method (number of 1.7 cm blocks needed to achieve a neutral head position while lying supine) and traditional Cobb angle calculation derived from DXA based lateral vertebral assessment. Baseline demographic, clinical, and other health information (including a timed up and go (TUG) test) were assessed at a clinic visit. Participants were followed monthly through email or postcard for 1 year, with falls outcomes confirmed through telephone interview.ResultsMean age was 77.8 (± 7.1) among the 52 women and 20 men. Over 12 months, 64% of participants experienced at least one incident fall and 35% experienced an injurious fall. Each standard deviation increase in kyphosis resulted in more than doubling the adjusted odds of an incident fall, even after adjusting for TUG. Odds of injurious falls were less consistent across measures; after adjusting for TUG, only the blocks method was associated with injurious falls.ConclusionsEach kyphosis measure was independently associated with incident falls. Findings were inconsistent for injurious falls; the blocks measure suggested the strongest association. If these findings are replicated, the blocks measure could be incorporated into office visits as a quick and efficient tool to identify patients at increased fall risk.

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.

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

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.

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.

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

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.

UNLABELLED: Spine fracture prevalence is similar in men and women, increasing from 90 %) individuals were unaware of their spine fractures, lateral spine imaging is needed to identify these women and men. Spine fracture prevalence was threefold higher in individuals meeting NOF criteria for spine imaging (∼1 in 7 undergoing VFA). Identifying spine fractures as part of comprehensive risk assessment may improve clinical decision making.

Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003-2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003-2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow-up, 20.0% of men had an incident clinical fracture. In multivariate-adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate-adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (-1.8% more annualized loss than in men with ACR

Visceral adipose tissue (VAT) measured by computed tomography (CT) is related to insulin resistance, lipids, and serum inflammatory markers. Our objective was to compare the strength of the associations of VAT measured using dual-energy X-ray absorptiometry (DXA-VAT) and CT (CT-VAT) with insulin resistance, serum lipids, and serum markers of inflammation. For 1117 men aged 65 and older enrolled in the Osteoporotic Fractures in Men Study, the cross-sectional associations of DXA-VAT and CT-VAT with homeostasis model assessment of insulin resistance (homa2ir), C-reactive protein, and high-density lipoprotein (HDL) cholesterol were estimated with regression models and compared using a Hausman test. Adjusted for age and body mass index, DXA-VAT was moderately associated with homa2ir (effect size 0.38, 95% confidence interval [CI]: 0.28-0.47) and modestly associated with HDL cholesterol (DXA effect size -0.29, 95% CI: -0.38 to -0.21). These associations were significantly greater than those for CT-VAT with homa2ir (0.30, 95% CI: 0.24-0.37; p value for effect size difference 0.03) and CT-VAT with HDL cholesterol (-0.22, 95% CI: -0.29 to -0.15; p value for difference 0.005). Neither DXA-VAT nor CT-VAT was associated with C-reactive protein after adjustment for age and body mass index (DXA-VAT effect size 0.14, 95% CI: -0.04 to 0.32; CT-VAT effect size 0.08, 95% CI: -0.08 to 0.25; p value for difference 0.35). DXA-VAT has similar or greater associations with insulin resistance and HDL cholesterol as does CT-VAT in older men, confirming the concurrent validity of DXA-VAT. Investigations of how well DXA measurements of VAT predict incident cardiovascular disease events are warranted.

Determine the associations of sleep disturbances with hospitalization risk among older women. One thousand eight hundred and twenty-seven women (mean age 83.6 years) participating in Study of Osteoporotic Fractures Year 16 (Y16) examination (2002-2004) linked with Medicare and/or HMO claims. At Y16 examination, sleep/wake parameters were measured by actigraphy (total sleep time [TST], sleep efficiency [SE], sleep latency [SL], and wake after sleep onset [WASO]) and subjective sleep measures (sleep quality [Pittsburgh Sleep Quality Index] and daytime sleepiness [Epworth Sleepiness Scale]) were assessed by questionnaire. Measures except TST were dichotomized based on clinical thresholds. Incident hospitalizations were determined from claims data. Nine hundred and seventy-six women (53%) had ≥1 hospitalization in the 3 years after the Year 16 examination. Reduced SE (odds ratio [OR] = 2.39, 95% confidence interval [CI] 1.69-3.39), prolonged SL (OR = 1.41, 95% CI 1.11-1.78), greater WASO (OR = 1.57, 95% CI 1.28-1.93), shorter TST (OR = 1.98, 95% CI 1.42-2.77) and poorer sleep quality (OR = 1.33, 95% CI 1.07-1.65) were each associated with a higher age and site-adjusted odds of hospitalization; associations were attenuated after multivariable adjustment for traditional prognostic factors with the OR for reduced SE (OR = 1.60, 95% CI 1.08-2.38) and shorter TST (OR = 1.63, 95% CI 1.12-2.37) remaining significant. Among women who were hospitalized, greater WASO (rate ratio [RR] = 1.20, 95% CI 1.04-1.37) and poorer sleep quality (RR = 1.18, 95% CI 1.02-1.35) were each associated with a greater age and site-adjusted RR of inpatient days, but associations did not persist after multivariate adjustment. Older women with sleep disturbances have an increased risk of hospitalization partially attributable to demographics, poorer health status, and comorbidities.

Dietary protein is a potentially modifiable risk factor for fracture. Our objectives were to assess the association of protein intake with incident fracture among older men and whether these associations varied by protein source or by skeletal site. We studied a longitudinal cohort of 5875 men (mean age 73.6 ± 5.9 years) in the Osteoporotic Fractures in Men (MrOS) study. At baseline, protein intake was assessed as percent of total energy intake (TEI) with mean intake from all sources = 16.1%TEI. Incident clinical fractures were confirmed by physician review of medical records. There were 612 major osteoporotic fractures, 806 low-trauma fractures, 270 hip fractures, 193 spine fractures, and 919 non-hip non-spine fractures during 15 years of follow-up. We used Cox proportional hazards models with age, race, height, clinical site, TEI, physical activity, marital status, osteoporosis, gastrointestinal surgery, smoking, oral corticosteroids use, alcohol consumption, and calcium and vitamin D supplements as covariates to compute hazard ratios (HRs) with 95% confidence intervals (CIs), all expressed per unit (SD = 2.9%TEI) increase. Higher protein intake was associated with a decreased risk of major osteoporotic fracture (HR = 0.92; 95% CI, 0.84 to 1.00) with a similar association found for low-trauma fracture. The association between protein and fracture varied by protein source; eg, increased dairy protein and non-dairy animal protein were associated with a decreased risk of hip fracture (HR = 0.80 [95% CI, 0.65 to 0.98] and HR = 0.84 [95% CI, 0.72 to 0.97], respectively), whereas plant-source protein was not (HR = 0.99 [95% CI, 0.78 to 1.24]). The association between protein and fracture varied by fracture site; total protein was associated with a decreased risk of hip fracture (HR = 0.84 [95% CI, 0.73 to 0.95]), but not clinical spine fracture (HR = 1.06 [95% CI, 0.92 to 1.22]). In conclusion, those with high protein intake (particularly high animal protein intake) as a percentage of TEI have a lower risk of major osteoporotic fracture. © 2016 American Society for Bone and Mineral Research.

BackgroundThis study examines effects of mobility and cognition on hospitalization and inpatient days among women late in life.MethodsProspective study of 663 women (mean age 87.7 years) participating in the Study of Osteoporotic Fractures Year 20 examination (2006-2008) linked with their inpatient claims data. At Year 20, mobility ascertained by Short Physical Performance Battery categorized as poor, intermediate, or good. Cognitive status adjudicated based on neuropsychological tests and classified as normal, mild cognitive impairment, or dementia. Hospitalizations (n = 182) during 12 months following Year 20.ResultsReduced mobility and poorer cognition were each associated in a graded manner with higher inpatient health care utilization, even after accounting for each other and traditional prognostic indicators. For example, adjusted mean inpatient days per year were 0.94 (95% confidence interval [CI] 0.52-1.45) among women with good mobility increasing to 2.80 (95% CI 1.64-3.89) among women with poor mobility and 1.59 (95% CI 1.08-2.03) among women with normal cognition increasing to 2.53 (95% CI 1.55-3.40) among women with dementia. Women with poor mobility/dementia had a nearly sixfold increase in mean inpatient days per year (4.83, 95% CI 2.73-8.54) compared with women with good mobility/normal cognition (0.84, 95% CI 0.49-1.44).ConclusionsAmong women late in life, mobility limitations and cognitive deficits were each independent predictors of higher inpatient health care utilization even after considering each other and conventional predictors. Additive effects of reduced mobility and poorer cognition may be important to consider in medical decision making and health care policy planning for the growing population of adults aged ≥85 years.

BackgroundAlthough there are several consensus definitions of sarcopenia, their association with health care utilization has not been studied.MethodsWe included women from the prospective Study of Osteoporotic Fractures with complete assessment of sarcopenia by several definitions at the Study of Osteoporotic Fractures Year 10 (Y10) exam (1997-1998) who also had available data from Medicare Fee- For-Service Claims (N = 566) or Kaiser Encounter data (N = 194). Sarcopenia definitions evaluated were: International Working Group, European Working Group for Sarcopenia in Older Persons, Foundation for the NIH Sarcopenia Project, Baumgartner, and Newman. Hurdle models and logistic regression were used to assess the relation between sarcopenia status (the summary definition and the components of slowness, weakness and/or lean mass) and outcomes that included hospitalizations, cumulative inpatient days/year, short-term (part A paid) skilled nursing facility stay in the 3 years following the Y10 visit.ResultsNone of the consensus definitions, nor the definition components of weakness or low lean mass, was associated with increased risk of hospitalization or greater likelihood of short-term skilled nursing facility stay. Women with slowness by any criterion definition were about 50% more likely to be hospitalized; had a greater rate of hospitalization days amongst those hospitalized; and had 1.8 to 2.1 times greater likelihood of a short-term skilled nursing facility stay than women without slowness. There was the suggestion of a protective association of low lean mass by the various criterion definitions on short-term skilled nursing facility stay.ConclusionEstimated effects of sarcopenia on health care utilization were negligible. However, slowness was associated with greater health care utilization.

BackgroundThe causes of age-related hyperkyphosis (HK) include osteoporosis, but only 1/3 of those most severely affected have vertebral fractures, suggesting that there are other important, and potentially modifiable causes. We hypothesized that muscle mass and quality may be important determinants of kyphosis in older persons.MethodsWe recruited 72 persons >65 years to participate in a prospective study designed to evaluate kyphosis and fall risk. At the baseline visit, participants had their body composition measures completed using Dual Energy X-ray Absorptiometry (DXA). They had kyphosis measured in either the standing [S] or lying [L] position: 1) Cobb angle from DXA [L]; 2) Debrunner kyphometer [S]; 3) architect's flexicurve ruler [S]; and 4) blocks method [L]. Multivariable linear/logistic regression analyses were done to assess the association between each body composition and 4 kyphosis measures.ResultsWomen (n = 52) were an average age of 76.8 (SD 6.7) and men 80.5 (SD 7.8) years. They reported overall good/excellent health (93%), the average body mass index was 25.3 (SD 4.6) and 35% reported a fall in the past year. Using published cut-offs, about 20-30% were determined to have HK. For the standing assessments of kyphosis only, after adjusting for age, sex, weight and hip BMD, persons with lower TLM were more likely to be hyperkyphotic.ConclusionsLower TLM is associated with HK in older persons. The results were stronger when standing measures of kyphosis were used, suggesting that the effects of muscle on thoracic kyphosis are best appreciated under spinal loading conditions.

ObjectivesTo determine whether slow gait speed increases the risk of costly long-term nursing home residence when accounting for death as a competing risk remains unknown.DesignLongitudinal cohort study using proportional hazards models to predict long-term nursing home residence and subdistribution models with death as a competing risk.SettingCommunity-based prospective cohort study.ParticipantsOlder women (mean age 76.3) participating in the Study of Osteoporotic Fractures who were also enrolled in Medicare fee-for-service plans (N = 3,755).MeasurementsGait speed was measured on a straight 6-m course and averaged over two trials. Long-term nursing home residence was defined using a validated algorithm based on Medicare Part B claims for nursing home-related care.ResultsParticipants were followed until long-term nursing home residence, disenrollment from Medicare plan, death, or December 31, 2010. Over the follow-up period (median 11 years), 881 participants (23%) experienced long-term nursing home residence, and 1,013 (27%) died before experiencing this outcome. Slow walkers (55% of participants with gait speed

Trabecular bone score (TBS) has been proposed as a dual-energy X-ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m2 . Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS-VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS-VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI

To determine the proportion of incident radiographic vertebral fractures (vfx) also diagnosed as incident clinical vfx in older men and vice-versa, we used data from 4398 community-dwelling men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study. Incident radiographic vfx were identified by comparing baseline and follow-up lateral thoracic and lumbar spine study films (average 4.6 years between films) using a semiquantitative (SQ) method and defined as a change in SQ reading of ≥1 at a given vertebral level from baseline to follow-up study radiograph. Participants were contacted triannually to ascertain incident clinical vfx; community spinal imaging studies were obtained and clinical vfx were confirmed when the study radiologist determined that the community imaging study showed a new deformity of higher grade than was present in the same vertebra on the baseline study radiograph. A total of 237 incident radiographic vfx were identified in 197 men, whereas 31 men experienced 37 confirmed incident clinical vfx. Of incident radiographic vfx, 13.5% were also clinically diagnosed as incident fractures, with clinical diagnoses made for 16.3% of the radiographic vfx with SQ grade change ≥2. Of incident clinical vfx, 86.5% were identified as incident radiographic vfx, most of them with SQ grade change ≥2. In summary, less than 15% of incident radiographic vfx were also clinically diagnosed, whereas the majority of incident clinical vfx were identified as severe radiographic vfx. These results in men supplement those previously published for women and suggest a complex relationship between clinical and radiographic vfx in older adults. Published 2016.(†) American Society for Bone and Mineral Research.

BackgroundVertebral fractures (VFx) are the most common osteoporotic fracture and are associated with higher risk of impaired function, additional fractures and death. The purpose of this analysis was to test the hypotheses that VFx are also associated with greater inpatient healthcare utilization.MethodsWe studied 4709 Caucasian women enrolled in the Study of Osteoporotic Fractures (SOF) and merged SOF cohort data with Medicare claims or Kaiser encounter data. To be included in this analysis, women had to be enrolled in Medicare Fee for Service or Kaiser as of 1/1/1991 and have radiographic information on VFx status at SOF Visit 3 (1991-92). VFx status was assessed using quantitative morphometry on lateral thoracic and lumbar spine radiographs. Prevalent VFx were defined as any height ratio>3 standard deviations below normal. Women were considered to have a clinical VFx if they reported a new diagnosis of VFx and a clinical radiographic report that confirmed that a VFx was present. Any hospitalization and the number of annualized days of hospitalization were identified through inpatient claims or encounter data. Specific hospitalizations for 5 major common reasons for hospitalizations were also examined.ResultsOver 5-years, 2632 (55.9%) women were hospitalized. In multivariate adjusted models, women with a prevalent radiographic VFx were 21% (95% CI, 2-44%) more likely to be hospitalized for any reason. This association was independent of a number of risk factors including smoking. The annualized rate of inpatient day was, however, similar, 1.67 and 1.48 among women with and without a VFx, respectively, p=0.49. Women with an incident clinical VFx were more likely to be hospitalized including women without evidence of a prevalent radiographic VFx (odds ratio (OR)=5.33; 95% confidence interval (CI)=1.81-15.71) and women with a prevalent radiographic VFx (OR=2.13; 95% CI, 1.05-4.33). Women with a VFx were more likely to be hospitalized specifically for hip fracture or chronic obstructive pulmonary disease (COPD) but not stroke, myocardial infarction or congestive heart failure. The association with COPD was attenuated to non-significance after adjusting for smoking.ConclusionOur results extend the potential public health impact of radiographic and clinical VFx to include an increased risk of any hospitalization.

BackgroundThis study examines the effects of mobility and cognition on mortality risk in women late in life.MethodsA prospective study was conducted among 1,495 women (mean age 87.6 years) participating in the Study of Osteoporotic Fractures Year 20 examination (2006-2008). Mobility (ascertained by Short Physical Performance Battery [SPPB]) was categorized as poor (SPPB 0-3, n = 312), intermediate (SPPB 4-9, n = 799), or good (SPPB 10-12, n = 384). Cognitive status (adjudicated based on neuropsychological tests) was classified as normal (n = 873), mild cognitive impairment (n = 354), or dementia (n = 268). Deaths (n = 749) were identified from Year 20 through July 31, 2014 (average follow-up 4.9 years).ResultsThere was not strong evidence of an interaction between mobility and cognition for prediction of mortality risk (p interaction term .16). Compared to women with good mobility, mortality risks were increased among women with intermediate mobility (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02-1.57) and those with poor mobility (HR 1.64, 95% CI 1.24-2.16) after consideration of cognition and other mortality risk factors. Similarly, mortality risks were higher among women with mild cognitive impairment (HR 1.46, 95% CI 1.21-1.76) and those with dementia (HR 1.88, 95% CI 1.54-2.31) compared to women with normal cognition after consideration of mobility and other mortality risk factors.ConclusionsAmong women late in life, 5-year mortality risk was substantially increased among women with deficits in mobility even after accounting for cognition and traditional prognostic indicators. Similarly, deficits in cognition were associated with increased 5-year mortality despite consideration of mobility and conventional risk factors.

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

SummaryThere are many ways to measure thoracic kyphosis ranging from simple clinical to more complex assessments. We evaluated the correlation among four commonly used kyphosis measures: Cobb angle, Debrunner kyphometer, kyphotic index, and the blocks method. Each measure was correlated with the others, confirming high clinical and research applicability.IntroductionThe purpose of this study was to assess the associations among four commonly used measures of thoracic kyphosis in older adults.MethodsSeventy two men and women aged 65-96 were recruited from the San Diego community. Four kyphosis measures were assessed in the same person during a baseline clinic visit. Two measures were done in the lying (L) and two in the standing (ST) position: (1) Cobb angle calculated from dual X-Ray absorptiometry (DXA) images (L), (2) Debrunner kyphometer (DK) angle measured by a protractor (ST), (3) kyphotic index (KI) calculated using an architect's flexicurve ruler (ST), and (4) the blocks method involving counting the number of 1.7 cm-thick blocks required to achieve a neutral head position while lying flat on the DXA table (L). Spearman rank correlation coefficients were used to determine the strength of the association between each kyphosis measure.ResultsUsing the Cobb angle as the gold standard, the blocks method demonstrated the lowest correlation (r(s) = 0.63, p

To examine the degree of trauma in major osteoporotic fractures (MOF) in men versus women, we used data from 15,698 adults aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5994 men) and the Study of Osteoporotic Fractures (SOF) (9704 women). Participants were contacted tri-annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self-reported trauma. Trauma was classified as low (fall from ≤ standing height; fall on stairs, steps, or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist, and humerus fractures. Mean fracture follow-up was 9.1 years in SOF and 8.7 years in MrOS. A total of 14.6% of the MOF in men versus 6.3% of the MOF in women were classified as high trauma (p < 0.001); men versus women more often experienced fractures resulting from severe trauma as well as from fall > standing height. High-trauma fractures were more significantly common in men versus women at the hip (p = 0.002) and wrist (p < 0.001) but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high-trauma fracture among men versus women was 3.12 (95% confidence interval [CI] 1.70-5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (odds ratio [OR] = 3.34, 95% CI 1.04-10.67) and those with wrist fracture (OR = 5.68, 95% CI 2.03-15.85). Among community-dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. © 2015 American Society for Bone and Mineral Research.

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