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© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society Objective: To examine rest–activity circadian rhythm (RAR) and cognitive decline in older men. Design: Longitudinal. Setting: Osteoporotic Fractures in Men (MrOS) and ancillary Outcomes of Sleep Disorders in Men (MrOS Sleep) studies. Participants: MrOS and MrOS Sleep participants (N=2,754; mean age 76.0 ± 5.3). Measurements: The Modified Mini-Mental State examination (3MS) was used to assess cognition at baseline (2003–05) and follow-up examinations (2005–06 and 2007–09). Wrist actigraphy was used to measure 24-hour activity counts at baseline. RAR variables included amplitude (strength of activity rhythm), mesor (mean activity level), pseudo F-statistic (overall circadian rhythm robustness), and acrophase (time of daily peak activity). Results: After an average of 3.4 ± 0.5 years, men with lower amplitudes, mesors, and pseudo F-statistics had greater decline in 3MS performance (amplitude: –0.7 points Q1 vs –0.5 points Q4, p

© 2018 American Society for Bone and Mineral Research We proposed the term “dysmobility syndrome” (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height2 30%, spine or hip T-score ≤ –2.5, grip strength

© 2017, International Osteoporosis Foundation and National Osteoporosis Foundation. The full acknowledgments are as follows: Acknowledgments We are grateful to Dr. Julia Hippisley-Cox and Dr. Stephen Hippisley-Cox for advice regarding use of their open source code for the QFracture risk assessment tool. We thank Carrie Gartland for her assistance with manuscript preparation.

© 2017, International Osteoporosis Foundation and National Osteoporosis Foundation. Abstract: Summary: Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and three externally generated fracture risk tools had similar accuracy to identify older men who developed osteoporotic fractures. Risk tools with femoral neck BMD performed better than those without BMD. The externally developed risk tools were poorly calibrated. Introduction: We compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality. Methods: A comparative ROC curve analysis assessed the ability of the QFracture, FRAX® and Garvan fracture risk tools, and femoral neck bone mineral density (BMD) T score with or without age to identify incident fracture in community-dwelling men aged 65 years or older (N = 4994) without hip or clinical vertebral fracture or antifracture treatment at baseline. Results: Among risk tools calculated with BMD, the discriminative ability to identify men with incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC 0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI 0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73), FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67, 0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk scores calculated with BMD compared with QFracture (P

© 2017 American Society for Bone and Mineral Research 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.

© 2016 American Society for Bone and Mineral Research 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

© 2016, Society of General Internal Medicine. Background: Although older adults are disproportionately affected by painful musculoskeletal conditions and receive more opioid analgesics than persons in other age groups, insufficient evidence is available regarding opioid harms in this age group. Objective: To examine longitudinal relationships between opioid use and falls, clinical fractures, and changes in physical performance. We hypothesized that opioid use would be associated with greater risks of falling and incident clinical fractures and greater declines in physical performance. Design: We analyzed data from the Osteoporotic Fractures in Men Study (MrOS), a large prospective longitudinal cohort study. Participants completed baseline visits from 2000 to 2002 and were followed for 9.1 (SD 4.0) years. Participants: MrOS enrolled 5994 community-dwelling men ≥ 65 years of age. The present study included 2902 participants with back, hip, or knee pain most or all of the time at baseline. Main Measures: The exposure of interest was opioid use, defined at each visit as participant-reported daily or near-daily use of any opioid-containing analgesic. Among patients, 309 (13.4 %) reported opioid use at one or more visits. Participants were queried every 4 months about falls and fractures. Physical performance scores were derived from tests of grip strength, chair stands, gait speed, and dynamic balance. Key Results: In the main analysis, the adjusted risk of falling did not differ significantly between opioid use and non-use groups (RR 1.10, 95 % CI 0.99, 1.24). Similarly, adjusted rates of incident clinical fracture did not differ between groups (HR 1.13, 95 % CI 0.94, 1.36). Physical performance was worse at baseline for the opioid use group, but annualized change in physical performance scores did not differ between groups (−0.022, 95 % CI −0.138, 0.093). Conclusions: Additional research is needed to determine whether opioid use is a marker of risk or a cause of falls, fractures, and progressive impairment among older adults with persistent pain.

© 2015, The American Geriatrics Society. Objective To evaluate the associations between definitions of sarcopenia and clinical outcomes and the ability of the definitions to discriminate those with a high likelihood of having these outcomes from those with a low likelihood. Design Osteoporotic Fractures in Men Study. Setting Six clinical centers. Participants Community-dwelling men aged 65 and older (N = 5,934). Measurements Sarcopenia definitions from the International Working Group, European Working Group on Sarcopenia in Older Persons, Foundation for the National Institutes of Health Sarcopenia Project, Baumgartner, and Newman were evaluated. Recurrent falls were defined as two or more self-reported falls in the year after baseline (n = 694, 11.9%). Incident hip fractures (n = 207, 3.5%) and deaths (n = 2,003, 34.1%) were confirmed according to central review of medical records over 9.8 years. Self-reported functional limitations were assessed at baseline and 4.6 years later. Logistic regression or proportional hazards models were used to estimate associations between sarcopenia and falls, hip fractures, and death. The discriminative ability of the sarcopenia definitions (vs reference models) for these outcomes was evaluated using area under the receiver operating characteristic curve or C-statistics. Referent models included age alone for falls, functional limitations and mortality, and age and bone mineral density for hip fractures. Results The association between sarcopenia according to the various definitions and risk of falls, functional limitations, and hip fractures was variable; all definitions were associated with greater risk of death, but none of the definitions materially changed discrimination based on the AUC and C-statistic when compared with reference models (change ≤1% in all models). Conclusion Sarcopenia definitions as currently constructed did not consistently improve prediction of clinical outcomes in relatively healthy older men.

© 2015 American Society for Bone and Mineral Research.Trabecular bone score (TBS) has been shown to predict major osteoporotic (clinical vertebral, hip, humerus, and wrist) and hip fractures in postmenopausal women and older men, but the association of TBS with these incident fractures in men independent of prevalent radiographic vertebral fracture is unknown. TBS was estimated on anteroposterior (AP) spine dual-energy X-ray absorptiometry (DXA) scans obtained at the baseline visit for 5979 men aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) Study and its association with incident major osteoporotic and hip fractures estimated with proportional hazards models. Model discrimination was tested with Harrell's C-statistic and with a categorical net reclassification improvement index, using 10-year risk cutpoints of 20% for major osteoporotic and 3% for hip fractures. For each standard deviation decrease in TBS, there were hazard ratios of 1.27 (95% confidence interval [CI] 1.17 to 1.39) for major osteoporotic fracture, and 1.20 (95% CI 1.05 to 1.39) for hip fracture, adjusted for FRAX with bone mineral density (BMD) 10-year fracture risks and prevalent radiographic vertebral fracture. In the same model, those with prevalent radiographic vertebral fracture compared with those without prevalent radiographic vertebral fracture had hazard ratios of 1.92 (95% CI 1.49 to 2.48) for major osteoporotic fracture and 1.86 (95% CI 1.26 to 2.74) for hip fracture. There were improvements of 3.3%, 5.2%, and 6.2%, respectively, of classification of major osteoporotic fracture cases when TBS, prevalent radiographic vertebral fracture status, or both were added to FRAX with BMD and age, with minimal loss of correct classification of non-cases. Neither TBS nor prevalent radiographic vertebral fracture improved discrimination of hip fracture cases or non-cases. In conclusion, TBS and prevalent radiographic vertebral fracture are associated with incident major osteoporotic fractures in older men independent of each other and FRAX 10-year fracture risks, and these data support their use in conjunction with FRAX for fracture risk assessment in older men.

© 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. Introduction For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals. Methods A prospective cohort study of 5,415 community-dwelling men aged ≥65 years without hip or clinical vertebral fracture or antifracture treatment at baseline was conducted. Participants had concurrent BMD and fracture follow-up between 2000 and 2009, and additional fracture follow-up through 2014. Data were analyzed in 2015. Time to incident osteoporosis (lowest T-score ≤ -2.50) for men without baseline osteoporosis, and time to hip or clinical vertebral fracture or major osteoporotic fracture for men without or with baseline osteoporosis, were estimated. Results Nine men (0.2%) with BMD T-scores >-1.50 at baseline developed osteoporosis during follow-up. The adjusted estimated time for 10% to develop osteoporosis was 8.5 (95% CI=6.7, 10.9) years for those with moderate osteopenia (lowest T-score, -1.50 to -1.99) and 2.7 (95% CI=2.1, 3.4) years for those with advanced osteopenia (lowest T-score, -2.00 to -2.49) at baseline. The adjusted times for 3% to develop a first hip or clinical vertebral fracture ranged from 7.1 (95% CI=6.0, 8.3) years in men with baseline T-scores > -1.50 to 1.7 (95% CI=1.0, 3.1) years in men with baseline osteoporosis. Conclusions Men aged 65 years and older with femoral neck, total hip, and lumbar spine BMD T-scores >-1.50 on a first BMD test were very unlikely to develop osteoporosis during follow-up. Additional BMD testing may be most informative in older men with T-scores ≤-1.50.

© 2014 American Society for Bone and Mineral Research. While accentuated kyphosis is associated with osteoporosis, it is unknown whether it increases risk of future fractures, independent of bone mineral density (BMD) and vertebral fractures. We examined the associations of baseline Cobb angle kyphosis and 15 year change in kyphosis with incident non-spine fractures using data from the Study of Osteoporotic Fractures. A total of 994 predominantly white women, aged 65 or older, were randomly sampled from 9704 original participants to have repeated Cobb angle measurements of kyphosis measured from lateral spine radiographs at baseline and an average of 15 years later. Non-spine fractures, con firmed by radiographic report, were assessed every 4 months for up to 21.3 years. Compared with women in the lower three quartiles of kyphosis, women with kyphosis greater than 53° (top quartile) had a 50% increased risk of non-spine fracture (95% CI, 1.10-2.06 after adjusting for BMD, prevalent vertebral fractures, prior history of fractures, and other fracture risk factors. Cobb angle kyphosis progressed an average of 7° (SD = 6.8) over 15 years. Per 1 SD increase in kyphosis change, there was a multivariable adjusted 28% increased risk of fracture (95% CI, 1.06-1.55) that was attenuated by further adjustment for baseline BMD (HR per SD increase in kyphosis change, 1.19; 95% CI 0.99-1.44). Greater kyphosis is associated with an elevated non-spine fracture risk independent of traditional fracture risk factors in older women. Furthermore, worsening kyphosis is also associated with increased fracture risk that is partially mediated by low baseline BMD that itself is a risk factor for kyphosis progression. These results suggest that randomized controlled fracture intervention trials should consider implementing kyphosis measures to the following: (1) further study kyphosis and kyphosis change as an additional fracture risk factor; and (2) test whether therapies may improve or delay its progression.

A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged ≥65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score. Total hip bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Incident nonspine fractures were centrally adjudicated. After adjustment for age, body mass index (BMI), total hip BMD, fall history, prior fracture, smoking status, comorbidities, race, and clinical center, the risk of nonspine fracture (n = 805) was increased among men with higher AAC (hazard ratio [HR] quartile 4 [Q4] [AAC score ≥9] versus quartile 1 [Q1] [0-1], 1.36; 96% confidence interval [CI], 1.10-1.68). This association was due to an increased risk of hip fracture (n = 178) among men with higher AAC (HR Q4 versus Q1, 2.33; 95% CI, 1.41-3.87). By contrast, the association between AAC and the risk of nonspine, nonhip fracture was weaker and not significant (HR Q4 versus Q1, 1.22; 95% CI, 0.96-1.55). The findings regarding higher AAC and increased risk of fracture were not altered in additional analyses accounting for degree of trauma, estimated glomerular filtration rate, presence of lumbar vertebral fractures (which may bias AAC assessment), preexisting cardiovascular disease, ankle brachial index, or competing risk of death. Thus, in this large cohort of elderly men, greater AAC was independently associated with an increased risk of hip fracture, but not with other nonspine fractures. These findings suggest that AAC assessment may be a useful method for identification of older men at high risk of hip fracture. © 2014 American Society for Bone and Mineral Research.

Background :Results 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.Methods :The 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. Results :Women 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

OBJECTIVES: To determine whether objectively measured sleep quality predicts 5-year incident instrumental activity of daily living (IADL) impairment and decline in grip strength and gait speed in older women. DESIGN: Prospective cohort. SETTING: Participants' homes, Study of Osteoporotic Fractures sites. PARTICIPANTS: Eight hundred seventeen women with a mean age of 82.4 at baseline. MEASUREMENTS: Participants completed 4.1 ± 0.7 nights of wrist actigraphy at baseline and measures of IADL impairment, grip strength, and gait speed at baseline and 5-year follow-up. RESULTS: After 5 years of follow-up, approximately 41% of participants had incident impairment in one or more IADLs. The quartile of women with the shortest total sleep time (TST) had 93% greater odds of incident IADL impairment than the longest sleepers (adjusted odds ratio (AOR) = 1.93, 95% confidence interval (CI) = 1.25-2.97). Similarly, the quartile of women with the lowest sleep efficiency (SE) had 65% greater odds of impairment than those with the highest (AOR = 1.65, 95% CI = 1.06-2.57). Women in the shortest TST quartile had twice the odds of declining grip strength as those with the longest TST (AOR = 1.97, 95% CI = 1.17-3.32). Finally, women in the quartiles with the most wake after sleep onset (WASO) and the lowest SE had approximately 90% greater odds of grip strength decline than those with the least WASO (AOR = 1.90, 95% CI = 1.11-3.24) and SE (AOR = 1.92, 95% CI = 1.12-3.29). CONCLUSION: Findings indicate that shorter sleep duration, greater WASO, and lower SE are risk factors for functional or physical decline in older women. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

OBJECTIVES: To evaluate the associations between visual field loss and nonspine fractures. DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: Four thousand seven hundred seventy-three community-dwelling white and African-American women aged 65 and older with no previous history of hip fracture at the time of recruitment. MEASUREMENTS: Radiographically confirmed hip and nonspine, nonhip fractures identified from September 1997 to April 2008. Visual field loss was measured using a Humphrey Field Analyzer suprathreshold screening test of the peripheral and central vision of each eye and was classified into an ordinal rating of no, mild, moderate, or severe binocular visual field (BVF) loss. RESULTS: For hip and nonspine, nonhip fractures and in unadjusted and covariate-adjusted analyses, the highest incidence of fractures was seen in women with the most-severe BVF loss. In covariate-adjusted analysis, women with mild, moderate, and severe BVF loss had a 49% (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.18-1.88), 25% (HR=1.25, 95% CI=0.87-1.80), and 66% (HR=1.66, 95% CI=1.19-2.32) greater risk, respectively, for hip fractures than women without BVF loss. Similarly, women with mild visual field loss had a 12% (HR=0.88, 95% CI=0.75-1.04) lower risk for nonspine, nonhip fractures, whereas women with moderate and severe visual field loss had a 18% (HR=1.18, 95% CI=0.92-1.52) and 59% (HR=1.59, 95% CI=1.24-2.03) greater risk of nonspine, nonhip fractures than women without BVF loss. CONCLUSION: BVF loss is independently associated with hip and nonspine, nonhip fractures in older female volunteers. © 2009, The American Geriatrics Society.

OBJECTIVES: To determine whether bone mineral density (BMD) is associated with age-related maculopathy (ARM) risk in older women. DESIGN: Cross-sectional analysis at Year 10 (1997/98) of the Study of Osteoporotic Fractures (SOF). SETTING: Four clinical centers in the United States. PARTICIPANTS: One thousand forty-two randomly sampled SOF participants who attended the Year 10 clinic visit. MEASUREMENTS: ARM status was determined from fundus photographs using a modification of the Wisconsin Age-Related Maculopathy Grading System 6-level severity scale used in the National Health and Nutrition Examination Survey III. Total hip BMD was measured at Year 10 using dual-energy x-ray absorptiometry. Information on potential confounders, including age, reproductive hormone exposures, body mass index, smoking, alcohol consumption, nutrition, education, diabetes mellitus, hypertension, and physical activity, was ascertained with questionnaires. RESULTS: The prevalence of ARM was 50% (46% had early ARM and 4% had late ARM). After potential confounder adjustment, greater BMD was associated with lower odds of ARM (odds ratio (OR) per 1 standard deviation increase in BMD=0.82, 95% confidence interval (CI)=0.70-0.96). Women in the highest quartile of BMD had lower odds of ARM than those in the lowest quartile (OR=0.63, 95% CI=0.41-0.97) and those in the lowest three quartiles combined (OR=0.66, 95% CI=0.48-0.91). CONCLUSION: Higher levels of BMD may be associated with lower risk for ARM. The underlying mechanism is unknown, although BMD may be a marker for lifetime endogenous estrogen exposure. Future studies are needed to replicate these findings and further investigate the nature of the relationship between BMD and ARM. © 2007, The American Geriatrics Society.

OBJECTIVES: To examine the relationship between binocular visual field loss and the risk of incident frequent falls in older white women. DESIGN: A multicenter, prospective cohort study. SETTING: Four clinic centers within the United States in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: Four thousand seventy-one community-dwelling white women aged 70 and older participating in the Study of Osteoporotic Fractures. MEASUREMENTS: Primary outcome was incident frequent falls, defined as two or more falls within 1 year. Primary risk factors were binocular visual field loss, distance visual acuity in the better eye, and contrast sensitivity at low spatial frequency in the better eye. RESULTS: Of 4,071 women, 409 (10%) had severe binocular visual field loss at the eye examination, and 643 (16%) experienced frequent falls within 1 year after their eye examination. Severe binocular visual field loss was significantly associated with frequent falls when adjusting for age, study site, and cognitive function (odds ratio=1.50, 95% confidence interval=1.11-2.02). The data showed a trend for increasing odds of two or more falls with greater binocular visual field loss (P