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.

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.

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.

Replacing sedentary time for physical activity: Does intensity matter for body composition in oldest-old adults?

To assess the independent and combined relationships among objectively measured sedentary time (ST), light intensity PA (LPA), and moderate-to-vigorous intensity PA (MVPA) with muscle mass and fat mass (FM) and how theoretical displacement of these inter-dependent behaviours relates to body composition in oldest-old men. A total of 1046 men participating in the year 14 visit of the prospective Osteoporotic Fractures in Men (MrOS) cohort study with complete data for accelerometry, dual x-ray absorptiometry, and deuterated creatine dilution (D3Cr) muscle mass were included in the analysis (84.0 ± 3.8 yrs.). Single, partition, and isotemporal substitution models were used to assess the interrelationships between PA intensities and ST with body composition measures, while controlling for relevant confounders. Replacing 30-min of ST with 30-min of MVPA was associated with lower FM (ß =-0.17, p < 0.001) and higher D3Cr muscle mass, although this was of borderline significance (ß = 0.07, p = 0.05). Replacing 30-min of ST for LPA was associated with lower FM (ß =-0.15, p < 0.001), but there was no effect on D3Cr muscle mass (p > 0.05). Exchanging ST with any intensity of PA is associated with benefits for FM in oldest-old adult men, although substitution with MVPA may be more beneficial than LPA for maintaining/improving skeletal muscle mass.

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.

A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss.

Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long-term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.

Optimizing exoskeleton assistance to improve walking speed and energy economy for older adults.

BACKGROUND: Walking speed and energy economy tend to decline with age. Lower-limb exoskeletons have demonstrated potential to improve either measure, but primarily in studies conducted on healthy younger adults. Promising techniques like optimization of exoskeleton assistance have yet to be tested with older populations, while speed and energy consumption have yet to be simultaneously optimized for any population. METHODS: We investigated the effectiveness of human-in-the-loop optimization of ankle exoskeletons with older adults. Ten healthy adults > 65 years of age (5 females; mean age: 72 ± 3 yrs) participated in approximately 240 min of training and optimization with tethered ankle exoskeletons on a self-paced treadmill. Multi-objective human-in-the-loop optimization was used to identify assistive ankle plantarflexion torque patterns that simultaneously improved self-selected walking speed and metabolic rate. The effects of optimized exoskeleton assistance were evaluated in separate trials. RESULTS: Optimized exoskeleton assistance improved walking performance for older adults. Both objectives were simultaneously improved; self-selected walking speed increased by 8% (0.10 m/s; p = 0.001) and metabolic rate decreased by 19% (p = 0.007), resulting in a 25% decrease in energetic cost of transport (p = 8e-4) compared to walking with exoskeletons applying zero torque. Compared to younger participants in studies optimizing a single objective, our participants required lower exoskeleton torques, experienced smaller improvements in energy use, and required more time for motor adaptation. CONCLUSIONS: Our results confirm that exoskeleton assistance can improve walking performance for older adults and show that multiple objectives can be simultaneously addressed through human-in-the-loop optimization.

Associations Between Walking Speed and Gut Microbiome Composition in Older Men From the MrOS Study.

BACKGROUND: Gut dysbiosis has been linked to frailty, but its association with early mobility decline is unclear. METHODS: First, we determined the cross-sectional associations between walking speed and the gut microbiome in 740 older men (84 ±â€…4 years) from the MrOS cohort with available stool samples and 400 m walking speed measured in 2014-2016. Then, we analyzed the retrospective longitudinal associations between changes in 6 m walking speed (from 2005-2006 to 2014-2016, calculated by simple linear equation) and gut microbiome composition among participants with available data (702/740). We determined gut microbiome composition by 16S sequencing and examined diversity, taxa abundance, and performed network analysis to identify differences in the gut microbiome network of fast versus slow walkers. RESULTS: Faster 400 m walking speed (m/s) was associated with greater microbiome α-diversity (R = 0.11; p = .004). The association between a slower decline in 6 m walking speed and higher α-diversity (R = 0.07; p = .054) approached borderline significance. Faster walking speed and less decline in walking speed were associated with a higher abundance of genus-level bacteria that produce short-chain fatty acids, and possess anti-inflammatory properties, including Paraprevotella, Fusicatenibacter, and Alistipes, after adjusting for potential covariates (p < .05). The gut microbiome networks of participants in the first versus last quartile of walking speed (≤0.9 vs ≥1.2 m/s) exhibited distinct characteristics, including different centrality measures (p < .05). CONCLUSIONS: Our findings suggest a possible relationship between gut microbiome diversity and mobility function, as indicated by the associations between faster walking speed and less decline in walking speed over 10 years with higher gut microbiome diversity in older men.

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.

A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.

The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 - 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 - 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.

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.

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: mediation analysis in SPRINT.

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. CONCLUSION: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

The benefit of intensive (<120 mmHg) blood pressure (BP) treatment, reduction in all-cause mortality (ACM), was attenuated when mediated through non-fatal major adverse cardiovascular events. This was driven by cardiovascular mortality (CVM). The harm of intensive BP treatment, increase in ACM, was amplified when mediated through serious adverse events. This was driven by non-CVM. Current reporting of treatment effects in cardiovascular trials does not allow for expansion of the lens to focus on important occurrences after the index event.

Associations of Lean Mass, Muscular Strength, and Physical Function with Trabecular Bone Score in Older Adults.

INTRODUCTION/BACKGROUND: Trabecular bone score (TBS) is an indirect measurement of bone quality and microarchitecture determined from dual-energy X-ray absorptiometry (DXA) imaging of the lumbar spine. TBS predicts fracture risk independent of bone mass/density, suggesting this assessment of bone quality adds value to the understanding of patients' bone health. While lean mass and muscular strength have been associated with higher bone density and lower fracture risk among older adults, the literature is limited regarding the relationship of lean mass and strength with TBS. The purpose of this study was to determine associations of DXA-determined total body and trunk lean mass, maximal muscular strength, and gait speed as a measure of physical function, with TBS in 141 older adults (65-84 yr, 72.5 +/- 5.1 yr, 74% women). METHODOLOGY: Assessments included lumbar spine (L1-L4) bone density and total body and trunk lean mass by DXA, lower body (leg press) and upper body (seated row) strength by one repetition maximum tests, hand grip strength, and usual gait speed. TBS was derived from the lumbar spine DXA scan. Multivariable linear regression determined the contribution of proposed predictors to TBS. RESULTS: After adjusting for age, sex, and lumbar spine bone density, upper body strength significantly predicted TBS (unadjusted/adjusted R2= 0.16/ 0.11, ß coefficient =0.378, p=0.005), while total body lean mass index showed a trend in the expected direction (ß coefficient =0.243, p=0.053). Gait speed and grip strength were not associated with TBS (p>0.05). CONCLUSION: Maximum strength of primarily back muscles measured as the seated row appears important to bone quality as measured by TBS, independent of bone density. Additional research on exercise training targeting back strength is needed to determine its clinical utility in preventing vertebral fractures among older adults.

Association of Subjective and Objective Measures of Sleep With Gut Microbiota Composition and Diversity in Older Men: The Osteoporotic Fractures in Men Study.

BACKGROUND: Growing evidence suggests bidirectional links between gut microbiota and sleep quality as shared contributors to health. Little is known about the relationship between microbiota and sleep among older persons. METHODS: We used 16S rRNA sequencing to characterize stool microbiota among men (n = 606, mean [standard deviation] age = 83.9 [3.8]) enrolled in the Osteoporotic Fractures in Men (MrOS) study from 2014 to 2016. Sleep was assessed concurrently by a questionnaire (Pittsburgh Sleep Quality index [PSQI]), and activity monitor to examine timing (acrophase) and regularity of patterns (F-statistic). Alpha diversity was measured using Faith's phylogenetic diversity (PD). Beta diversity was calculated with robust Aitchison distance with matrix completion (RPCA) and phylogenetic-RPCA (PRPCA). Their association with sleep variables was tested with partial distance-based redundancy analysis (dbRDA). Predictive-ratio biomarkers associated with sleep measurements were identified with CoDaCoRe. RESULTS: In unadjusted analyses, men with poor sleep (PSQI >5) tended to have lower alpha diversity compared to men with normal sleep (Faith's PD, beta = -0.15; 95% confidence interval [CI]: -0.30 to 0.01, p = .06). Sleep regularity was significantly associated with RPCA and PRPCA, even after adjusting for site, batch, age, ethnicity, body mass index, diabetes, antidepressant and sleep medication use, and health behaviors (RPCA/PRPCA dbRDA; p = .033/.002). In taxonomic analysis, ratios of 7:6 bacteria for better regularity (p = .0004) and 4:7 for worse self-reported sleep (p = .005) were differentially abundant: some butyrate-producing bacteria were associated with better sleep characteristics. CONCLUSIONS: Subjective and objective indicators of sleep quality suggest that older men with better sleep patterns are more likely to harbor butyrate-producing bacteria associated with better health.

The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts.

OBJECTIVE: Metabolic dysregulation frequently co-occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA. METHODS: In two parallel cross-sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2 ) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics. RESULTS: Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37-15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39-3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men. CONCLUSION: In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.

Lower Leg Power and Grip Strength Are Associated With Increased Fall Injury Risk in Older Men: The Osteoporotic Fractures in Men Study.

BACKGROUND: Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries. METHODS: In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6-m usual; narrow walk) and chair stands speed. RESULTS: Of men with ≥1/4 follow-ups (N = 5 178; age 73.4 ± 5.7 years), 40.4% (N = 2 090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p < .0001), with lower quartiles at significantly increased risk versus highest Q4 except for grip strength Q3 versus Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95% confidence interval [CI]: 1.12-1.26) and 16% higher per SD lower grip strength/kg (95% CI: 1.10-1.23). In models including both leg power/kg and grip strength/kg, odds ratios (ORs) were similar and independent of each other and physical performance (leg power/kg OR per SD = 1.13, 95% CI: 1.06-1.20; grip strength/kg OR per SD = 1.11, 95% CI: 1.05-1.17). CONCLUSIONS: Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.