Complementary and Alternative Therapies for Genitourinary Syndrome of Menopause : An Evidence Map.

BACKGROUND: Women seeking nonhormonal interventions for vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM) may seek out complementary and alternative medicine or therapies (CAMs). PURPOSE: To summarize published evidence of CAMs for GSM. DATA SOURCES: Ovid MEDLINE, EMBASE, and CINAHL from inception through 11 December 2023. STUDY SELECTION: Randomized controlled trials (RCTs) 8 weeks or more in duration that evaluated the effectiveness or harms of CAMs for postmenopausal women with GSM and reported 1 or more outcomes of interest, with sample sizes of 20 or more participants randomly assigned per group. DATA EXTRACTION: Data were abstracted by 1 reviewer and verified by a second. DATA SYNTHESIS: An evidence map approach was used to organize and describe trials. Studies were organized by type of intervention, with narrative summaries for population, study characteristics, interventions, and outcomes. Fifty-seven trials were identified that investigated 39 unique interventions. Studies were typically small (n < 200), and most were done in Iran (k = 24) or other parts of Asia (k = 9). Few trials evaluated similar combinations of populations, interventions, comparators, or outcomes. Most studies (k = 44) examined natural products (that is, herbal or botanical supplements and vitamins), whereas fewer reported on mind and body practices (k = 6) or educational programs (k = 7). Most studies reported 1 or 2 GSM symptoms, mainly sexual (k = 44) or vulvovaginal (k = 30). Tools used to measure outcomes varied widely. Most trials reported on adverse events (k = 33). LIMITATIONS: Only English-language studies were used. Effect estimates, risk of bias, and certainty of evidence were not assessed. CONCLUSION: There is a large and heterogeneous literature of CAM interventions for GSM. Trials were small, and few were done in North America. Standardized population, intervention, comparator, and outcomes reporting in future RCTs are needed. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42023400684).

Hormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause : A Systematic Review.

BACKGROUND: Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM). PURPOSE: To evaluate effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers for treatment of GSM symptoms. DATA SOURCES: Medline, Embase, and CINAHL through 11 December 2023. STUDY SELECTION: Randomized controlled trials (RCTs) of at least 8 weeks' duration enrolling postmenopausal women with at least 1 GSM symptom and reporting effectiveness or harms of hormonal interventions or vaginal moisturizers. DATA EXTRACTION: Risk of bias and data extraction were performed by one reviewer and verified by a second reviewer. Certainty of evidence (COE) was assessed by one reviewer and verified by consensus. DATA SYNTHESIS: From 11 993 citations, 46 RCTs evaluating vaginal estrogen (k = 22), nonestrogen hormones (k = 16), vaginal moisturizers (k = 4), or multiple interventions (k = 4) were identified. Variation in populations, interventions, comparators, and outcomes precluded meta-analysis. Compared with placebo or no treatment, vaginal estrogen may improve vulvovaginal dryness, dyspareunia, most bothersome symptom, and treatment satisfaction. Compared with placebo, vaginal dehydroepiandrosterone (DHEA) may improve dryness, dyspareunia, and distress, bother, or interference from genitourinary symptoms; oral ospemifene may improve dryness, dyspareunia, and treatment satisfaction; and vaginal moisturizers may improve dryness (all low COE). Vaginal testosterone, systemic DHEA, vaginal oxytocin, and oral raloxifene or bazedoxifene may provide no benefit (low COE) or had uncertain effects (very low COE). Although studies did not report frequent serious harms, reporting was limited by short-duration studies that were insufficiently powered to evaluate infrequent serious harms. LIMITATIONS: Most studies were 12 weeks or less in duration and used heterogeneous GSM diagnostic criteria and outcome measures. Few studies enrolled women with a history of cancer. CONCLUSION: Vaginal estrogen, vaginal DHEA, oral ospemifene, and vaginal moisturizers may improve some GSM symptoms in the short term. Few long-term data exist on efficacy, comparative effectiveness, tolerability, and safety of GSM treatments. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42023400684).

Life-space mobility and cognition in community-dwelling late-life women: A cross-sectional analysis.

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.

Fall Trajectories in Older Men: Trajectories of Change by Age and Predictors for Future Fall Risk.

BACKGROUND: Very little is known about specific trajectories or patterns of falls over time. Using the well-characterized cohort of the Osteoporotic Fractures in Men Study (MrOS), we classified individuals by fall trajectories across age and identified predictors of group assignment based on characteristics at baseline. METHODS: Using an analysis sample of 5976 MrOS participants and 15 years of follow-up data on incident falls, we used group-based trajectory models (PROC TRAJ in SAS) to identify trajectories of change. We assessed the association of baseline characteristics with group assignment using one-way analysis of variance (ANOVA) and chi-square tests. Multivariable logistic regression was used to analyze the outcome of the high risk fall trajectory groups compared to the low risk groups. RESULTS: Changes in rates of falls were relatively constant or increasing with five distinct groups identified. Mean posterior probabilities for all five trajectories were similar and consistently above 0.8 indicating reasonable model fit. Among the five fall trajectory groups, two were deemed high risk, those with steeply increasing fall risk and persistently high fall risk. Factors associated with fall risk included body mass index, use of central nervous agents, prior history of diabetes and Parkinson's disease, back pain, grip strength, and physical and mental health scores. CONCLUSIONS: Two distinct groups of high fall risk individuals were identified among five trajectory groups, those with steeply increasing fall risk and persistently high fall risk. Statistically significant characteristics for group assignment suggest that future fall risk of older men may be predictable at baseline.

Long-term Trajectories of Low Back Pain in Older Men: A Prospective Cohort Study With 10-Year Analysis of the Osteoporotic Fractures in Men Study.

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.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

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

Neighborhood Socioeconomic Deprivation and Health Care Costs in Older Community-Dwelling Adults: Importance of Functional Impairment and Frailty.

BACKGROUND: Low neighborhood socioeconomic status is associated with adverse health outcomes, but its association with health care costs in older adults is uncertain. OBJECTIVES: To estimate the association of neighborhood Area Deprivation Index (ADI) with total, inpatient, outpatient, skilled nursing facility (SNF), and home health care (HHC) costs among older community-dwelling Medicare beneficiaries, and determine whether these associations are explained by multimorbidity, phenotypic frailty, or functional impairments. DESIGN: Four prospective cohort studies linked with each other and with Medicare claims. PARTICIPANTS: In total, 8165 community-dwelling fee-for-service beneficiaries (mean age 79.2 years, 52.9% female). MAIN MEASURES: ADI of participant residence census tract, Hierarchical Conditions Category multimorbidity score, self-reported functional impairments (difficulty performing four activities of daily living), and frailty phenotype. Total, inpatient, outpatient, post-acute SNF, and HHC costs (US 2020 dollars) for 36 months after the index examination. KEY RESULTS: Mean incremental annualized total health care costs adjusted for age, race/ethnicity, and sex increased with ADI ($3317 [95% CI 1274 to 5360] for the most deprived vs least deprived ADI quintile, and overall p-value for ADI variable 0.009). The incremental cost for the most deprived vs least deprived ADI quintile was increasingly attenuated after separate adjustment for multimorbidity ($2407 [95% CI 416 to 4398], overall ADI p-value 0.066), frailty phenotype ($1962 [95% CI 11 to 3913], overall ADI p-value 0.22), or functional impairments ($1246 [95% CI -706 to 3198], overall ADI p-value 0.29). CONCLUSIONS: Total health care costs are higher for older community-dwelling Medicare beneficiaries residing in the most socioeconomically deprived areas compared to the least deprived areas. This association was not significant after accounting for the higher prevalence of phenotypic frailty and functional impairments among residents of socioeconomically deprived neighborhoods.

Hip Fracture Risk Assessment Tools for Adults Aged 80 Years and Older.

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.

Associations of empirically derived dietary patterns and cognitive performance in older men: Results of the Osteoporotic Fractures in Men (MrOS) study.

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.

Association of back pain with all-cause and cause-specific mortality among older men: a cohort study.

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.

Difference between kidney function by cystatin C versus creatinine and association with muscle mass and frailty.

BACKGROUND: A higher difference in estimated glomerular filtration rate by cystatin C versus creatinine (eGFRDiff = eGFRCys - eGFRCreat) is associated with decreased frailty risk. Since eGFRCreat is influenced by muscle more than eGFRCys, muscle mass may explain this association. Previous work could not account for this when considering regional muscle measures by imaging. Deuterated creatine (D3Cr) dilution measures whole body muscle mass (kilograms). We aimed to determine whether eGFRDiff is associated with D3Cr muscle mass and whether muscle mass explains the association between eGFRDiff and frailty. METHODS: Cross-sectional analysis within the multicenter MrOS Study at Year 14 (visit 4). 490 men of the original cohort of 5994 MrOS participants (aged ≥65 at enrollment) were included. Exposure was eGFRDiff (= eGFRCys - eGFRCreat), calculated using CKD-EPI equations 2012/2021. Primary outcome was D3Cr muscle mass. Secondary outcome was phenotypic pre-frailty (one or two criteria) and frailty (≥three criteria) including the following: weight loss, weakness, slow gait, physical activity, poor energy. The association of eGFRDiff with D3Cr muscle mass was examined by linear regression, that with prefrailty / frailty by multinomial logistic regression. RESULTS: Mean ± SD age was 84 ± 4 years, eGFRCreat 68 ± 16, eGFRCys 52 ± 16, eGFRDiff -15 ± 12 mL/min/1.73 m2 and D3Cr muscle mass 24 ± 4 kg. For each SD increment in eGFRDiff, D3Cr muscle mass was 1.4 kg higher on average, p < 0.0001 (fully adjusted). Higher eGFRDiff was associated with lower odds of frailty (OR = 0.63 95% CI [0.45;0.89]), but this was partially attenuated and insignificant after additionally adjusting for D3Cr muscle mass (OR = 0.85 95% CI [0.58; 1.24]). CONCLUSIONS: Higher eGFRDiff is associated with lower odds of frailty among late-life men. D3Cr muscle mass accounts for some of this association. This suggests that non-GFR determinants of creatinine and cystatin C, such as muscle mass, play a role in explaining the association of eGFRDiff with frailty. Future studies are needed to confirm.

Physical function trajectory after wrist or lower arm fracture in postmenopausal women: results from the Women's Health Initiative Study.

Long-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older. INTRODUCTION: Physical functioning trajectory following lower arm or wrist fracture is not well understood. PURPOSE: This study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age. METHODS: We performed a nested case-control study of prospective data from the Women's Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining. RESULTS: Mean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19-1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29-1.88); age 70-79 years aOR 1.29 (95% CI 1.09-1.52); age < 70 years aOR 1.15 (95% CI 0.86-1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level. CONCLUSIONS: Women with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experience declines in physical functioning than women without such fractures, independent of baseline physical functioning level.

Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older.

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.

Osteoporosis.

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. Evidence-based screening strategies improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started, choice of medication, and duration of treatment maximizes the benefits of fracture prevention while minimizing potential harms of long-term drug exposure.

The Vitamin D Metabolite Ratio Is Associated With Volumetric Bone Density in Older Men.

CONTEXT: Serum 25-hydroxyvitamin D (25(OH)D) is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in bone mineral density (BMD) and fracture risk. OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown. METHODS: We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength in the distal radius and tibia, assessed by HR-pQCT in 545 older men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD and estimated failure load (EFL, a marker of bone strength) at the distal radius and tibia. RESULTS: The mean age was 84 ± 4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60 mL/min/1.73 m2. In adjusted models, each twofold higher VMR was associated with a 9% (3%, 16%) higher total vBMD and a 13% (5%, 21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes. CONCLUSION: Among older men, a higher VMR was associated with greater vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.

Breaking Up Sedentary Time Reduces Recurrent Fall Risk, but Not Incident Fracture Risk in Older Men.

Apart from physical activity volume, frequent breaks from sedentary bouts and active bouts may differentially reduce fall and fracture risk. We assessed the longitudinal relationship between frequency of breaks from time spent sedentary and frequency of active bouts with recurrent falls and fractures. The sample included 2918 men aged 79.0 ± 5.1 years with free-living activity (SenseWear Armband) at the Osteoporotic Fractures in Men Study (MrOS) year 7 (2007-2009) visit. Men were divided into quartiles by the number of breaks from sedentary bouts (sedentary bout: 5+ minutes sedentary; <1.5 metabolic equivalents of task [METS]) and separately by active bout frequency (active bout: 5+ minutes of activity; ≥1.5 METS). Recurrent falls (2+ falls/year) and fractures were ascertained by self-report; fractures were radiographically confirmed. Generalized estimating equations estimated the recurrent fall odds, with restricted cubic splines applied to assess nonlinear relationships. Cox proportional hazards models estimated fracture risk. Over 4 years of follow-up after year 7, 1025 (35.1%) men were fallers. Over 8.40 ± 4.10 years of follow-up, 640 (21.9%) men experienced a fracture. There was a significant nonlinear U-shaped relationship between number of breaks from sedentary bouts and recurrent falls (p < 0.001); compared with men with few breaks from sedentary bouts (1.4-<13.6), the odds of recurrent falls were lower with a moderate number (13.6-<17.0, odds ratio [OR] = 0.82, 95% confidence interval [CI] 0.66, 1.01; 17.0-<20.4, OR = 0.79, 95% CI 0.64, 0.99), but not with the highest number of breaks from sedentary bouts (20.4-34.6, OR = 1.01, 95% CI 0.81, 1.27). Results remained borderline significant after adjusting for total sedentary time. Men with the highest compared with the lowest number of breaks from sedentary bouts had a lower fracture risk, but the association was attenuated after adjustment for total sedentary time. No associations were observed for active bout frequency. In conclusion, breaking up extended periods of sedentary time reduces fall risk regardless of total sedentary time. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Advantages and Disadvantages of Random Forest Models for Prediction of Hip Fracture Risk Versus Mortality Risk in the Oldest Old.

Targeted fracture prevention strategies among late-life adults should balance fracture risk versus competing mortality risk. Models have previously been constructed using Fine-Gray subdistribution methods. We used a machine learning method adapted for competing risk survival time to evaluate candidate risk factors and create models for hip fractures and competing mortality among men and women aged 80 years and older using data from three prospective cohorts (Study of Osteoporotic Fractures [SOF], Osteoporotic Fracture in Men study [MrOS], Health Aging and Body Composition study [HABC]). Random forest competing risk models were used to estimate absolute 5-year risk of hip fracture and absolute 5-year risk of competing mortality (excluding post-hip fracture deaths). Models were constructed for both outcomes simultaneously; minimal depth was used to rank and select variables for smaller models. Outcome specific models were constructed; variable importance was used to rank and select variables for inclusion in smaller random forest models. Random forest models were compared to simple Fine-Gray models with six variables selected a priori. Top variables for competing risk random forests were frailty and related components in men while top variables were age, bone mineral density (BMD) (total hip, femoral neck), and frailty components in women. In both men and women, outcome specific rankings strongly favored BMD variables for hip fracture prediction while frailty and components were strongly associated with competing mortality. Model discrimination for random forest models varied from 0.65 for mortality in women to 0.81 for hip fracture in men and depended on model choice and variables included. Random models performed slightly better than simple Fine-Gray model for prediction of competing mortality, but similarly for prediction of hip fractures. Random forests can be used to estimate risk of hip fracture and competing mortality among the oldest old. Modest gains in performance for mortality without hip fracture compared to Fine-Gray models must be weighed against increased complexity. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Performance of Fracture Risk Assessment Tools by Race and Ethnicity: A Systematic Review for the ASBMR Task Force on Clinical Algorithms for Fracture Risk.

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.