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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.

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research.

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.

Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual-energy X-ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm2); expected loss (n = 2768; change between 0 g/cm2 and -0.034 g/cm2]); and accelerated loss (n = 545; change 1 SD below mean change or worse [≤-0.034 g/cm2]). Multivariate proportional hazards models adjusted for potential confounders estimated the risk of all-cause mortality over 8.1 ± 2.8 years following visit 2. Mortality was centrally adjudicated by physician review of death certificates. At visit 1, mean age was 72.9 ± 5.5 years. Men who maintained BMD were less likely to die during the subsequent follow-up period (33.7%) than men who had accelerated BMD loss (60.6%) (p < 0.001). Compared to men who had maintained BMD, those who had accelerated BMD loss had a 44% greater risk of mortality in multivariate-adjusted models (HR, 1.44; 95% CI, 1.23 to 1.68). Compared to men who had maintained BMD, there was no significant difference in mortality risk for men with expected loss of BMD (36.9% died) (multivariate HR, 1.00; 95% CI, 0.89 to 1.13). Further adjustment for visit 1 or visit 2 BMD measurement did not substantially alter these associations. Results for total hip BMD were similar. In conclusion, accelerated loss of BMD at the hip is a risk factor for mortality in men that is not explained by comorbidity burden, concurrent change in weight, or physical activity.

BackgroundAutonomic dysfunction contributes to atrial fibrillation (AF).ObjectiveWe hypothesized that polysomnogram (PSG)-based heart rate variability (HRV) autonomic function biomarkers are associated with incident AF and these associations are modified by measures of sleep disordered breathing (SDB).Methods2350 participants of a multi-center prospective study (Outcomes of Sleep Disorders in Older Men Study) without baseline AF underwent sleep studies with incident adjudicated AF follow up (8.0 ± 2.6 years). Cox proportional hazard models were used to analyze sleep study-ECG spectral HRV indices [low and high frequency power (LF, HF), LF/HF] and time domain indices [mean of normal to normal beats (MNN), short and long term variability (STV, LTV) and STV/LTV] and premature atrial contractions (PACs) and incident AF (HR and 95% CI). Statistical interactions between HRV and SDB were examined. Models were adjusted for age, race, body mass index, waist circumference, cardiac medications, co-morbid diseases, alcohol use and study site.ResultsLower LF/HF and lower LF were associated with higher AF incidence (LF/HF Q1 vs. Q4: 1.46, 1.02-2.08, LF Q1 vs. Q4: 1.46, 1.02-2.10). Higher STV/LTV was associated with an increased risk of AF (p-trend= 0.028). The highest PAC quartile had a 3-fold increased AF risk (2.99, 1.94-4.62) compared to the lowest quartile. A significant interaction of obstructive apnea was observed in the LF-AF relationship (0.045).ConclusionsSleep-related reduced sympathovagal balance (LF/HF) and increased atrial ectopy are independently associated with future AF; a relationship modified by obstructive apnea.

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.

BackgroundPrior studies have only considered one measurement of physical performance in its relationship to fractures and mortality. A single measurement is susceptible to large within-person changes over time, and thus, may not capture the true association between physical performance and the outcomes of interest.MethodsUsing data from the Study of Osteoporotic Fractures, we followed 7,015 women enrolled prior to age 80 years who had outcome information beyond this age. Trajectories of walking speed (m/s) and chair stand speed (stands/s) were estimated up to the last visit prior to age 80 years using mixed-effects linear regression. Physical performance at age 80 (PF_age80) was assessed at the last visit prior to age 80 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression and multivariate models adjusted for all other covariates.ResultsGreatest walking speed decline and chair stand speed decline were both associated with higher risk of hip fracture (HR: 1.28; 95% CI: 1.03, 1.58 and HR: 1.26; 95% CI: 1.03, 1.54, respectively), but not nonspine fractures. Greatest walking speed decline and chair stand speed decline were both associated with a significant 29% (95% CI: 17-42%) and 27% (95% CI: 15-39%) increased risk of mortality, respectively.ConclusionsGreatest declines in walking speed and chair stand speed were both associated with an increased risk of hip fracture and mortality independent of PF_age80 and other important confounders. Both physical performance change and the single physical performance measurement should be considered in the etiology of hip fracture and mortality.

ObjectivesTo evaluate the relationship between life-space mobility (extent, frequency, independence of movement) and mortality in older women.DesignProspective cohort study.SettingFour U.S. clinical sites.ParticipantsWomen (N = 1,498) aged 75 to 102 (mean 87.6) followed from 2006 to 2015.MeasurementsLife-space during the past 4 weeks was assessed in an interview, scored from 0 (daily restriction to bedroom) to 120 (daily trips outside town without assistance), and categorized (0-20, 21-40, 41-60, 61-80, 81-120). All-cause mortality was the primary outcome; noncancer, cardiovascular, cancer, and noncardiovascular noncancer mortality were secondary outcomes.ResultsOver a mean 5.2 years, 842 (56.2%) women died. Unadjusted risk of all-cause mortality was 82.6% in women with the lowest level of life-space (0-20 points) and 36.2% in those with the highest level (81-120 points). In multivariable proportional hazards models, there was a strong relationship between less life-space and greater risk of all-cause mortality (Ptrend < .001). Women with the lowest level of life-space (0-20 points) had a risk of all-cause mortality that was 2.4 times as high (95% confidence interval (CI) = 1.5-4.0) as that of women with the highest level (81-120 points); women with life-space scores between 21 and 60 had a risk of all-cause mortality that was 1.5 times as high as that of women with the highest level. Each standard deviation decrease in life-space was associated with a 1.2 times greater (95% CI = 1.1-1.4) risk of all-cause mortality. Women unable to travel beyond their neighborhood without assistance had a risk of all-cause mortality that was 1.4 times (95% CI = 1.1-1.7) as high as that of women who could travel beyond their neighborhood without assistance. Results were similar for noncancer, cardiovascular, and other mortality and did not change after controlling for underlying disease or living arrangement.ConclusionLife-space scores of 60 or less were associated with mortality in older women independent of other strong risk factors.

The association between vitamin D status and diabetes risk is inconsistent among observational studies, and most of the available studies have been with women. In the present study we investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and incident type 2 diabetes (T2D) in older men (≥65years old) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study enrolled from March 2000 to April 2002. Baseline 25(OH)D levels were available in 1939 subjects without prevalent T2D. Clinical information, body mass index (BMI) and other factors related to T2D were assessed at the baseline visit. Incident diabetes, defined by self-report and medication use, was determined over an average follow-up of 6.4years. At baseline, participants were, on average, 73.3 (±5.7) years old, had a mean BMI in the overweight range (27.2kg/m(2)±3.6) and had total serum 25(OH)D of 26.1ng/ml (±8.3). Incident diabetes was diagnosed in 139 subjects. Cox regression analysis showed a trend toward a protective effect of higher 25(OH)D levels with a lower risk of T2D (HR 0.87, 95% CI: 0.73-1.04 per 1 SD increase of 25(OH)D). After adjusted for BMI and other potential confounders, the relationship between 25(OH)D levels and incident diabetes was further attenuated (HR 1.03, 95% CI 0.85-1.25). No significant difference in the incidence of diabetes emerged after analyzing study subjects according to baseline 25(OH)D quartiles. In conclusion, 25(OH)D levels were not associated with incident T2D in older men.

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.

ObjectiveTo determine the risk of all-cause and disease-specific mortality among older women with hip osteoarthritis (OA) and to identify mediators in the causal pathway.MethodsData were from the Study of Osteoporotic Fractures, a US population-based cohort study of 9,704 white women age ≥65 years. The analytic sample included women with hip radiographs at baseline (n = 7,889) and year 8 (n = 5,749). Mortality was confirmed through October 2013 by death certificates and hospital discharge summaries. Radiographic hip OA (RHOA) was defined as a Croft grade of ≥2 in at least 1 hip (definite joint space narrowing or osteophytes plus 1 other radiographic feature).ResultsThe mean ± SD followup time was 16.1 ± 6.2 years. The baseline and year 8 prevalence of RHOA were 8.0% and 11.0%, respectively. The cumulative incidence (proportion of deaths during the study period) was 67.7% for all-cause mortality, 26.3% for cardiovascular disease (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease mortality, and 27.8% for all other mortality causes. RHOA was associated with an increased risk of all-cause mortality (hazard ratio 1.14 [95% confidence interval 1.05-1.24]) and CVD mortality (hazard ratio 1.24 [95% confidence interval 1.09-1.41]) adjusted for age, body mass index, education, smoking, health status, diabetes, and stroke. These associations were partially explained by the mediating variable of physical function.ConclusionRHOA was associated with an increased risk of all-cause and CVD mortality among older white women followed up for 16 years. Dissemination of evidence-based physical activity and self-management interventions for hip OA in community and clinical settings can improve physical function and might also contribute to lower mortality.

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD.

Recent studies indicate that obesity is not protective against fracture in postmenopausal women and increases the risk of fracture at some sites. Risk factors for fracture in obese women may differ from those in the nonobese. We aimed to compare the ability of FRAX with and without bone mineral density (BMD) to predict fractures in obese and nonobese older postmenopausal women who were participants in the Study of Osteoporotic Fractures. Data for FRAX clinical risk factors and femoral neck BMD were available in 6049 women, of whom 18.5% were obese. Hip fractures, major osteoporotic fractures, and any clinical fractures were ascertained during a mean follow-up period of 9.03 years. Receiving operator curve (ROC) analysis, model calibration, and decision curve analysis were used to compare fracture prediction in obese and nonobese women. ROC analysis revealed no significant differences between obese and nonobese women in fracture prediction by FRAX, with or without BMD. Predicted hip fracture risk was lower than observed risk in both groups of women, particularly when FRAX + BMD was used, but there was good calibration for FRAX + BMD in prediction of major osteoporotic fracture in both groups. Decision curve analysis demonstrated that both FRAX models were useful for hip fracture prediction in obese and nonobese women for threshold 10-year fracture probabilities in the range of 4% to 10%, although in obese women FRAX + BMD was superior to FRAX alone. For major osteoporotic fracture, both FRAX models were useful in both groups of women for threshold probabilities in the range of 10% to 30%. For all clinical fractures, the FRAX models were not useful at threshold probabilities below 30%. We conclude that FRAX is of value in predicting hip and major osteoporotic fractures in obese postmenopausal women, particularly when used with BMD.

BackgroundResults of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline.MethodsThe study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score.ResultsWomen with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05-2.42) for women with 25(OH)D

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.