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

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

Bone loss following a fracture could increase the risk of future fractures. In this study, we found that elderly women who had an upper body fracture or multiple fractures lost more bone at the hip than those who did not fracture. This suggests a possible systemic bone loss response initiated by fracture.IntroductionA prior fracture is one of the strongest predictors of subsequent fracture risk, but the etiology of this phenomenon remains unclear. Systemic bone loss post-fracture could contribute to increased risk of subsequent fractures. Therefore, in this study, we investigated whether incident fractures, including those distant to the hip, are associated with accelerated loss of hip bone mineral density (BMD) in elderly women.MethodsWe analyzed data from 3956 Caucasian women aged ≥ 65 years who were enrolled in the Study of Osteoporotic Fractures and completed hip BMD measurements at study visit 4 (year 6) and visit 6 (year 10). Clinical fractures between visits 4 and 6 were ascertained from triannual questionnaires and centrally adjudicated by review of community radiographic reports. Subjects provided questionnaire information and clinical variables at examinations for known and potential covariates. Generalized linear models were used to calculate average annual percent change in total hip BMD between visits 4 and 6 for each incident fracture type and for upper body and lower body fractures combined. A subset of women (n = 3783) was analyzed for annual total hip BMD change between study visits 4 and 5 and between study visits 5 and 6 to evaluate change in total hip BMD during these 2-year intervals.ResultsWomen with incident upper body fracture or incident lower body fracture exhibited reductions in total hip BMD of 0.89 and 0.77% per year, respectively, while women who did not fracture exhibited reductions in total hip BMD of 0.66% per year during the 4-year period. Accelerated loss of hip BMD was isolated to the 2-year time interval that included the fracture. Loss of total hip BMD was not affected by the number of days from fracture to follow up DXA.ConclusionsSystemic bone loss following fracture may increase the risk of future fractures at all skeletal sites. There is a need for improved understanding of mechanisms leading to apparent accelerated bone loss following a fracture in order to reduce subsequent fracture risk.

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

There was no association of plasma DPP-4 activity levels with bone mineral density (BMD), body composition, or incident hip fractures in a cohort of elderly community-dwelling adults.IntroductionDipeptidyl peptidase IV (DPP-4) inactivates several key hormones including those that stimulate postprandial insulin secretion, and DPP-4 inhibitors (gliptins) are approved to treat diabetes. While DPP-4 is known to modulate osteogenesis, the relationship between DPP-4 activity and skeletal health is uncertain. The purpose of the present study was to examine possible associations between DPP-4 activity in elderly subjects enrolled in the Cardiovascular Health Study (CHS) and BMD, body composition measurements, and incident hip fractures.MethodsAll 1536 male and female CHS participants who had evaluable DXA scans and plasma for DPP-4 activity were included in the analyses. The association between (1) BMD of the total hip, femoral neck, lumbar spine, and total body; (2) body composition measurements (% lean, % fat, and total body mass); and (3) incident hip fractures and plasma levels of DPP-4 activity were determined.ResultsMean plasma levels of DPP-4 activity were significantly higher in blacks (227 ± 78) compared with whites (216 ± 89) (p = 0.04). However, there was no significant association of DPP-4 activity with age or gender (p ≥ 0.14 for both). In multivariable adjusted models, there was no association of plasma DPP-4 activity with BMD overall (p ≥ 0.55 for all) or in gender stratified analyses (p ≥ 0.23). There was also no association of DPP-4 levels and incident hip fractures overall (p ≥ 0.24) or in gender stratified analyses (p ≥ 0.39).ConclusionPlasma DPP-4 activity, within the endogenous physiological range, was significantly associated with race, but not with BMD, body composition, or incident hip fractures in elderly community-dwelling subjects.

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

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

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.

Background: Screening and monitoring for chronic kidney disease (CKD) could lead to earlier interventions that improve clinical outcomes. Purpose: To summarize evidence about the benefits and harms of screening for and monitoring and treatment of CKD stages 1 to 3 in adults. Data Sources: MEDLINE (1985 through November 2011), reference lists, and expert suggestions. Study Selection: English-language, randomized, controlled trials that evaluated screening for or monitoring or treatment of CKD and that reported clinical outcomes. Data Extraction: Two reviewers assessed study characteristics and rated quality and strength of evidence. Data Synthesis: No trials evaluated screening or monitoring, and 110 evaluated treatments. Angiotensin-converting enzyme inhibitors (relative risk, 0.65 [95% CI, 0.49 to 0.88]) and angiotensin II-receptor blockers (relative risk, 0.77 [CI, 0.66 to 0.90]) reduced end-stage renal disease versus placebo, primarily in patients with diabetes who have macroalbuminuria. Angiotensin-converting enzyme inhibitors reduced mortality versus placebo (relative risk, 0.79 [CI, 0.66 to 0.96]) in patients with microalbuminuria and cardiovascular disease or high-risk diabetes. Statins and [beta]-blockers reduced mortality and cardiovascular events versus placebo or control in patients with impaired estimated glomerular filtration rate and either hyperlipidemia or congestive heart failure, respectively. Risks for mortality, end-stage renal disease, or other clinical outcomes did not significantly differ between strict and usual blood pressure control. The strength of evidence was rated high for angiotensin II-receptor blockers and statins, moderate for angiotensin-converting enzyme inhibitors and [beta]-blockers, and low for strict blood pressure control. Limitations: Evidence about outcomes was sometimes scant and derived from post hoc analyses of subgroups of patients enrolled in trials. Few trials reported or systematically collected information about adverse events. Selective reporting and publication bias were possible. Conclusion: The role of CKD screening or monitoring in improving clinical outcomes is uncertain. Evidence for CKD treatment benefit is strongest for angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers, and in patients with albuminuria combined with diabetes or cardiovascular disease. Primary Funding Source: Agency for Healthcare Research and Quality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain. PURPOSE: To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED. DATA SOURCES: English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned. STUDY SELECTION: Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED. DATA EXTRACTION: Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities. DATA SYNTHESIS: Data, primarily from short-term trials (

OBJECTIVE: To determine the efficacy and safety of treatments for nursing home residents with urinary incontinence (UI). PATIENTS AND METHODS: A systematic review was conducted of randomized controlled trials published from January 1985 through May 2008. Data sources were MEDLINE and Cochrane Library databases, proceedings of the 3rd International Consultation on Incontinence, and reference lists of retrieved clinical trials and review articles. Trials were eligible if they consisted of nursing home or long-term institutionalized residents with UI. Eligible trials compared interventions for improving UI with controls, including comparisons of UI outcomes and/or adverse events between randomized groups. RESULTS: Fourteen unique clinical trials, consisting of 1161 patients, met inclusion criteria. Treatments included antimuscarinic medications, oral estrogen plus progesterone, and behavioral interventions (eg, prompted voiding). Compared with usual care, prompted voiding alone or prompted voiding plus exercise reduced daytime incontinence and increased appropriate toileting. Efficacy outcomes indicated that neither prompted voiding plus exercise nor prompted voiding plus oral estrogen and progesterone was superior to prompted voiding alone for incontinence management. Prompted voiding plus oxybutynin slightly reduced incontinence compared with prompted voiding plus placebo. CONCLUSION: In nursing home residents with UI, prompted voiding alone and prompted voiding with exercise were associated with modest short-term improvement in daytime UI. Results do not clearly support an independent effect of exercise in improving UI. Oxybutynin may provide small additional benefit when used with prompted voiding. There appears to be no role for oral estrogen in UI treatment. Long-term clinical trials of prompted voiding alone, prompted voiding with exercise, and antimuscarinic medications should be conducted with targeted nursing home residents who have UI. These trials should include measures of UI, patient quality of life, and cost outcomes. [ABSTRACT FROM AUTHOR]

Background: A standard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults. However, the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain.Methods: To determine whether a standard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index (BMI), we ascertained frailty status in a cohort of 6724 women>or=69 years and followed them prospectively for incident falls, fractures, and mortality. Frailty was defined by the presence of three or more of the following criteria: unintentional weight loss, weakness, self-reported poor energy, slow walking speed, and low physical activity. Incident recurrent falls were defined as at least two falls during the subsequent year. Incident fractures (confirmed with x-ray reports), including hip fractures, and deaths were ascertained during an average of 9 years of follow-up.Results: After controlling for multiple confounders such as age, health status, medical conditions, functional status, depressive symptoms, cognitive function, and bone mineral density, frail women were subsequently at increased risk of recurrent falls (multivariate odds ratio=1.38, 95% confidence interval [CI], 1.02-1.88), hip fracture (multivariate hazards ratio [MHR]=1.40, 95% CI, 1.03-1.90), any nonspine fracture (MHR=1.25, 95% CI, 1.05-1.49), and death (MHR=1.82, 95% CI, 1.56-2.13). The associations between frailty and these outcomes persisted among women>or=80 years. In addition, associations between frailty and an increased risk of falls, fracture, and mortality were consistently observed across categories of BMI, including BMI>or=30 kg/m2.Conclusion: Frailty is an independent predictor of adverse health outcomes in older women, including very elderly women and older obese women. [ABSTRACT FROM AUTHOR]

Background: The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this association.Methods: Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time.Results: There were 305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278 seconds. Compared with women with sleep efficiency > or = 70%, those with <70% had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio [MOR] = 1.61; 95% confidence interval [CI], 1.20-2.16; Trails B > 278 MOR = 1.96; 95% CI, 1.43-2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13-1.33; Trails B > 278 MOR = 1.13; 95% CI, 1.04-1.24), as was higher WASO (per half hour: MMSE < 26 MOR = 1.15; 95% CI, 1.06-1.23; Trails B > 278 MOR = 1.24; 95% CI, 1.15-1.34). Women who napped > or = 2 hours per day had a higher risk (MMSE < 26 MOR = 1.42; 95% CI, 1.05-1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26-2.40). There was no significant relationship for total sleep time.Conclusion: Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus and lower weight are both associated with osteoporotic fractures, but the roles of variability and trajectory are less clear. The associations of these factors among older adults with dysglycemia, who are at highest risk of fracture, with fracture risk and BMD remain uncertain. We followed 775 men and 1080 women from the Cardiovascular Health Study (mean age 77.4 years) with abnormal oral glucose tolerance testing in 1989-1990. We measured their weights yearly through 1994-1995 and derived intra-individual mean weight, weight slope, and weight variability. We also used growth mixture modeling to derive 4 latent BMI trajectories over time. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CI for subsequent hip fracture through 2015 and linear regression models to estimate cross-sectional associations with BMD of the hip. Each 10 kg higher mean weight was associated with a lower risk of subsequent hip fracture overall (HR 0.81; CI, 0.70-0.94) and among women (HR 0.76; CI, 0.64-0.91) and with higher BMD (p <.001). Higher weight variability was directly associated with incident hip fracture among women (HR 1.18; CI, 1.03-1.35). Compared with a stable trajectory, a "progressive overweight" trajectory was associated with lower risk of hip fracture (HR 0.66; CI, 0.44-0.99). An uncommon trajectory of "accelerating obesity" was associated with higher BMD. Among older adults with dysglycemia at high risk for fracture, lower mean weight is associated with higher fracture risk, but variability and trajectory may also contribute. These results highlight the complex effects of weight in older age., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Frailty defined by the Cardiovascular Health Study (CHS) phenotype is associated with higher healthcare expenditures in community-dwelling Medicare beneficiaries after accounting for claims-based cost indicators. However, frailty assessment using the CHS phenotype is often not feasible in routine clinical practice. We evaluated whether frailty identified by the simple Study of Osteoporotic Fractures (SOF) phenotype is associated with subsequent incremental costs after accounting for claims-derived cost indicators., Methods: Prospective study utilizing data from four cohort studies of older adults linked with Medicare claims composed of 8264 community-dwelling fee-for-service beneficiaries (4389 women, 3875 men). SOF Frailty Phenotype (three components: weight loss, poor energy, and inability to rise from chair five times without using arms) and CHS Frailty Phenotype (operationalized using five components) derived from cohort data. Participants were classified as robust, prefrail, or frail using each phenotype. Multimorbidity index (CMS Hierarchical Conditions Categories score) and Kim frailty indicator (approximating the deficit accumulation index) derived from claims. Annualized total and sector-specific healthcare costs ascertained for 36 months after frailty assessment., Results: Average annualized total healthcare costs (2023 US dollars) were $15,021 in women and $15,711 in men. After accounting for claims-based multimorbidity and frailty indicators, average incremental costs of SOF phenotypic frailty (two or three components) versus robust (none) were $7142 in women and $5961 in men, only modestly lower than incremental costs of CHS phenotypic frailty ($9422 in women, $6479 in men). SOF phenotypic frailty in both sexes was associated with higher subsequent expenditures in the inpatient, skilled nursing facility, and home healthcare sectors., Conclusions: As observed with CHS phenotypic frailty, SOF phenotypic frailty is associated with higher subsequent total and sector-specific expenditures after accounting for claims-derived indicators. The parsimonious SOF phenotype can be readily assessed in space-constrained and time-limited practice settings to improve identification of older adults at high risk of costly care., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Life-space mobility captures the daily, enacted mobility of older adults. We determined cross-sectional associations between life-space mobility and cognitive impairment (CI) among community-dwelling women in the 9th and 10th decades of life., Methods: A total of 1375 (mean age 88 years; 88% White) community-dwelling women enrolled in a prospective cohort of older women. Life-space score was calculated with range 0 (daily restriction to one's bedroom) to 120 (daily trips leaving town without assistance) and categorized (0-20, 21-40, 41-60, 61-80, 81-120). The primary outcome was adjudicated CI defined as mild cognitive impairment or dementia; scores on a 6-test cognitive battery were secondary outcomes., Results: Compared to women with life-space scores of 81-120 and after adjustment for demographics and depressive symptoms, the odds of CI was 1.4-fold (OR 1.36, 95% CI 0.91-2.03) higher for women with life-space scores of 61-80, twofold (OR 1.98, 95% CI 1.33-2.94) higher for women with life-space scores of 41-60, 2.6-fold (OR 2.62, 95% CI 1.71-4.01) higher for women with life-space scores of 21-40, and 2.7-fold (OR 2.71, 95% CI 1.27-5.79) higher for women with life-space scores of 0-20. The association of life-space scores with adjudicated CI was primarily due to higher odds of dementia; the odds of dementia versus normal cognition was eightfold (OR 8.63, 95% CI 3.20-23.26) higher among women with life-space scores of 0-20 compared to women with life-space scores of 81-120. Lower life-space scores were associated in a graded manner with lower mean scores on tests of delayed recall (California Verbal Learning Test-II delayed recall) and language and executive function (phonemic fluency, category fluency, and Trails B). Life-space score was not associated with scores on tests of attention and working memory (forward and backward digit span)., Conclusions: Lower life-space mobility is associated in a graded manner with CI among community-dwelling White women in the 9th and 10th decades of life., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Although low back pain (LBP) may persist or recur over time, few studies have evaluated the individual course of LBP over a long-term period, particularly among older adults. Based on data from the longitudinal Osteoporotic Fractures in Men (MrOS) Study, we aimed to identify and describe different LBP trajectories in older men and characterize members in each trajectory group. A total of 5 976 community-dwelling men (mean age = 74.2) enrolled at 6 U.S. sites were analyzed. Participants self-reported LBP (yes/no) every 4 months for a maximum of 10 years. Latent class growth modeling was performed to identify unique LBP trajectory groups that explained variation in the LBP data. The association of baseline characteristics with trajectory group membership was assessed using univariable and multivariable multinominal logistic regression. A 5-class solution was chosen; no/rare LBP (n = 2 442/40.9%), low frequency-stable LBP (n = 1 040/17.4%), low frequency-increasing LBP (n = 719/12%), moderate frequency-decreasing LBP (n = 745/12.5%), and high frequency-stable LBP (n = 1 030/17.2%). History of falls (OR = 1.52), history of LBP (OR = 6.37), higher physical impairment (OR = 1.51-2.85), and worse psychological function (OR = 1.41-1.62) at baseline were all associated with worse LBP trajectory groups in this sample of older men. These findings present an opportunity for targeted interventions and/or management to older men with worse or increasing LBP trajectories and associated modifiable risk factors to reduce the impact of LBP and improve quality of life., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined., (© 2024. The Author(s).)

Objective: We evaluated whether more severe back pain phenotypes-persistent, frequent, or disabling back pain-are associated with higher mortality rate among older men., Methods: In this secondary analysis of a prospective cohort, the Osteoporotic Fractures in Men (MrOS) study, we evaluated mortality rates by back pain phenotype among 5215 older community-dwelling men (mean age, 73 years, SD = 5.6) from 6 sites in the United States. The primary back pain measure used baseline and Year 5 back pain questionnaire data to characterize participants as having no back pain, nonpersistent back pain, infrequent persistent back pain, or frequent persistent back pain. Secondary measures of back pain from the Year 5 questionnaire included disabling back pain phenotypes. The main outcomes measured were all-cause and cause-specific death., Results: After the Year 5 exam, during up to 18 years of follow-up (mean follow-up = 10.3 years), there were 3513 deaths (1218 cardiovascular, 764 cancer, 1531 other). A higher proportion of men with frequent persistent back pain versus no back pain died (78% versus 69%; sociodemographic-adjusted HR = 1.27, 95% CI = 1.11-1.45). No association was evident after further adjustment for health-related factors, such as self-reported general health and comorbid chronic health conditions (fully adjusted HR = 1.00; 95% CI = 0.86-1.15). Results were similar for cardiovascular deaths and other deaths, but we observed no association of back pain with cancer deaths. Secondary back pain measures, including back-related disability, were associated with increased mortality risk that remained statistically significant in fully adjusted models., Conclusion: Although frequent persistent back pain was not independently associated with risk of death in older men, additional secondary disabling back pain phenotypes were independently associated with increased mortality rate. Future investigations should evaluate whether improvements in disabling back pain affect general health and well-being or risk of death., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to examine associations between empirically derived dietary pattern scores and cognition, as well as risk of cognitive decline, over an average of 4.6 (± 0.3) years in older men., Materials and Methods: This analysis was conducted as part of the Osteoporotic Fractures in Men (MrOS) prospective cohort study. Diet was assessed at Visit 1 (3/2000-4/2002) by food frequency questionnaire, and dietary patterns (Western and Prudent) were derived by factor analysis. The analytic cohort comprised 4231 community-dwelling American men who were aged 65 years or more. Cognitive function was assessed with the Modified Mini-Mental State exam (3MS) and the Trails B test at Visit 1 and at Visit 2 (3/2005-5/2006). Associations between dietary pattern score and cognition and risk of cognitive decline were estimated using mixed effects regression models. Model 1 was adjusted for age, clinic site and total energy intake (TEI). Model 2 was further adjusted for calcium and vitamin D supplement use, body mass index (BMI), physical activity, smoking, diabetes and hypertension (Western diet group) and education, calcium and vitamin D supplement use, depression, BMI, physical activity, smoking and stroke (Prudent diet group)., Results: Adherence to the Western dietary pattern was associated with higher 3MS scores and shorter Trails B test time at Visit 1 in Model 2. Adherence to the Prudent dietary pattern was associated with higher 3MS scores in Model 1 but not Model 2. There were no independent associations between dietary pattern scores and risk of cognitive decline 4.6 (± 0.3) years later at Visit 2., Conclusion: The results do not support a robust protective effect of the Prudent dietary pattern on cognition in the MrOS cohort. Associations between the Western dietary pattern and better cognitive scores should be interpreted with caution. Further research is needed to understand the complex interactions between dietary patterns and cognition in older men., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Published by Elsevier B.V.)

This study examined if the amino acids phenylalanine or tyrosine contribute to risk of hip fracture or frailty in older adults. We determined that neither phenylalanine nor tyrosine are important predictors of hip fracture or frailty. We suggest advice on protein intake for skeletal health consider specific amino acid composition., Purpose: Protein is essential for skeletal health, but the specific amino acid compositions of protein may have differential associations with fracture risk. The aim of this study was to determine the association of serum levels of the aromatic amino acids phenylalanine and tyrosine with risk for incident hip fractures over twelve years of follow-up and cross sectional associations with frailty., Methods: We included 131 older men and women from the Cardiovascular Health Study (CHS) who sustained a hip fracture over twelve years of follow-up and 131 men and women without an incident hip fracture over this same period of time. 42% of this cohort were men and 95% were Caucasian. Weighted multivariable Cox hazards molecules were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher serum level of phenylalanine or tyrosine. Relative risk regression was used to determine the cross-sectional association of these amino acids with Freid's frailty index., Results: Neither serum levels of phenylalanine (HR 0.85 (95% CI 0.62-1.16) or tyrosine (HR 0.82 (95% CI 0.62-1.1) were significantly associated with incident hip fractures or cross sectionally with frailty (frail compared with prefrail/not frail) (HR 0.92 (95% CI 0.48-1.76) and HR (0.86 (95% CI 0.46-1.61) respectively., Conclusion: Phenylalanine and tyrosine are not significant contributors to hip fractures or frailty in older men and women., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Importance: While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain., Objective: To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction., Design, Setting and Participants: Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024., Main Outcomes and Measures: Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles., Results: A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk., Conclusions and Relevance: In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.

Background: Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks., Methods: Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture., Results: Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture., Conclusion: Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years., (© 2024 The American Geriatrics Society.)

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5 K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 × 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Stressful life events, such as loss of a partner, loss of a pet or financial problems, are more common with increasing age and may impact the experience of pain. The aim of the current study is to determine the cross-sectional and prospective association between stressful life events and low back pain reporting in the Osteoporotic Fracture in Men Study, a cohort of older men aged ≥65 years., Methods: At a study visit (March 2005-May 2006), 5149 men reported whether they had experienced a stressful life event or low back pain in the prior 12 months. Following that visit, data on low back pain patients were gathered through triannual questionnaires every 4 months for 1 year. Multivariable logistic regression analyses estimated the association of stressful life events with recent past low back pain or future low back pain., Results: N = 2930, (57%) men reported at least one stressful life event. The presence of a stressful life event was associated with greater odds of any low back pain (OR = 1.42 [1.26-1.59]) and activity-limiting low back pain (OR = 1.74 [1.50-2.01]) in the same period and of any low back pain (OR = 1.56 [1.39-1.74]) and frequent low back pain (OR = 1.80 [1.55-2.08]) in the following year., Conclusion: In this cohort of men, the presence of stressful life events increased the likelihood of reporting past and future low back pain., Significance: Stressful life events such as accident or illness to a partner are common in later life and may impact the experience of pain. We present cross-sectional and prospective data highlighting a consistent association between stressful life events and low back pain in older men. Further, there is evidence to suggest that this relationship is upregulated by an individual's living situation. This information may be used to strengthen a biopsychosocial perspective of an individual's pain experience., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Objective: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily., Methods: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included., Conclusion: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies., (© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

In this study, we aimed to evaluate the association of innate and adaptive immune cell subsets in peripheral blood mononuclear cells (PBMCs) with hip fracture. To conduct this study, we used data from the Cardiovascular Health Study (CHS), a U.S. multicenter observational cohort of community-dwelling men and women aged ≥ 65 years. Twenty-five immune cell phenotypes were measured by flow cytometry from cryopreserved PBMCs of CHS participants collected in 1998-1999. The natural killer (NK), γδ T, T helper 17 (Th17), and differentiated/senescent CD4 + CD28 - T cell subsets were pre-specified as primary subsets of interest. Hip fracture incidence was assessed prospectively by review of hospitalization records. Multivariable Cox hazard models evaluated associations of immune cell phenotypes with incident hip fracture in sex-stratified and combined analyses. Among 1928 persons, 259 hip fractures occurred over a median 9.7 years of follow-up. In women, NK cells were inversely associated with hip fracture [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.60-0.99 per one standard deviation higher value] and Th17 cells were positively associated with hip fracture [HR 1.18, 95% CI 1.01-1.39]. In men, γδ T cells were inversely associated with hip fracture [HR 0.60, 95% CI 0.37-0.98]. None of the measured immune cell phenotypes were significantly associated with hip fracture incidence in combined analyses. In this large prospective cohort of older adults, potentially important sex differences in the associations of immune cell phenotypes and hip fracture were identified. However, immune cell phenotypes had no association with hip fracture in analyses combining men and women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The American Society of Bone and Mineral Research (ASBMR) Professional Practice Committee charged an ASBMR Task Force on Clinical Algorithms for Fracture Risk to review the evidence on whether current approaches for differentiating fracture risk based on race and ethnicity are necessary and valid. To help address these charges, we performed a systematic literature review investigating performance of calculators for predicting incident fractures within and across race and ethnicity groups in middle-aged and older US adults. We included English-language, controlled or prospective cohort studies that enrolled US adults aged >40 years and reported tool performance predicting incident fractures within individual race and ethnicity groups for up to 10 years. From 4838 identified references, six reports met eligibility criteria, all in women. Just three, all from one study, included results in non-white individuals. In these three reports, non-white women experienced relatively few major osteoporotic fractures (MOFs), especially hip fractures, and risk thresholds for predicting fractures in non-white women were derived from risks in the overall, predominantly white study population. One report suggested the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) overestimated hip fracture similarly across race and ethnicity groups (black, Hispanic, American Indian, Asian, white) but overestimated MOF more in non-white than White women. However, these three reports were inconclusive regarding whether discrimination of FRAX or the Garvan calculator without BMD or of FRAX with BMD for MOF or hip fracture differed between white versus black women. This uncertainty was at least partly due to imprecise hip fracture estimates in black women. No reports examined whether ratios of observed to predicted hip fracture risks within each race or ethnicity group varied across levels of predicted hip fracture risk. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Branched chain amino acids (BCAA) are building blocks for protein, an essential component of bone. However, the association of plasma levels of BCAA with fractures in populations outside of Hong Kong or with hip fractures in particular is not known. The purpose of these analyses was to determine the relationship of BCAA including valine, leucine, and isoleucine and total BCAA (SD of the sum of Z-scores for each BCAA) with incident hip fractures and bone mineral density (BMD) of the hip and lumbar spine in older African American and Caucasian men and women in the Cardiovascular Health Study., Design: Longitudinal analyses of association of plasma levels of BCAA with incident hip fractures and cross-sectional BMD of the hip and lumbar spine from the Cardiovascular Health Study., Setting: Community., Participants: A total of 1850 men (38% of cohort) and women; mean age 73 years., Main Outcome Measures: Incident hip fractures and cross-sectional BMD of the total hip, femoral neck, and lumbar spine., Results: In fully adjusted models, over 12 years of follow-up, we observed no significant association between incident hip fracture and plasma values of valine, leucine, isoleucine, or total BCAA per 1 SD higher of each BCAA. Plasma values of leucine but not valine, isoleucine, or total BCAA, were positively and significantly associated with BMD of the total hip (P = .03) and femoral neck (P = .02), but not the lumbar spine (P = .07)., Conclusions: Plasma levels of the BCAA leucine may be associated with higher BMD in older men and women. However, given the lack of significant association with hip fracture risk, further information is needed to determine whether BCAAs would be novel targets for osteoporosis therapies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)