Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults.

BACKGROUND: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent. METHODS: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses. RESULTS: Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial. CONCLUSIONS: Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Sarcopenia and Cardiovascular Diseases.

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be particularly important among those with chronic disease states. Early recognition of sarcopenia is important because it can provide an opportunity for interventions to reverse or delay the progression of muscle disorder, which may ultimately impact cardiovascular outcomes. Relying on body mass index is not useful for screening because many patients will have sarcopenic obesity, a particularly important phenotype among older cardiac patients. In this review, we aimed to: (1) provide a definition of sarcopenia within the context of muscle wasting disorders; (2) summarize the associations between sarcopenia and different cardiovascular diseases; (3) highlight an approach for a diagnostic evaluation; (4) discuss management strategies for sarcopenia; and (5) outline key gaps in knowledge with implications for the future of the field.

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.

D3Creatine Dilution as a Direct, Non-invasive and Accurate Measurement of Muscle Mass for Aging Research.

Initial definitions of sarcopenia included the age-associated loss of skeletal muscle mass that was presumed to be associated with late-life reduced functional capacity, disability and loss of independence. Because no method for determination of muscle mass was available for large cohort studies of aging men and women, lean body mass determined by dual X-ray absorptiometry or bioelectrical impedance was used as a surrogate measure of muscle mass. The data from these studies showed either no or a poor relationship between LBM and functional capacity and health related outcomes, leading to the conclusion of many that the amount of muscle may not be associated with these age-associated outcomes. It was assumed that some undefined index of muscle quality is the critical contributor. These studies also consistently showed that muscle strength is lost more quickly than lean mass. Total body muscle mass can now be measured directly, accurately and non-invasively using the D3creatine (D3Cr) dilution method. D3Cr muscle mass, but not DXA derived LBM, is strongly associated with functional capacity, falls and insulin resistance in older men and women. In addition, D3Cr muscle mass is associated with risk of disability, hip fracture and mortality. New and emerging data demonstrate that low muscle mass may serve as a diagnostic criterion for sarcopenia.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

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 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 six U.S. sites. The primary back pain measure used baseline and year five back pain questionnaire data to characterize participants as having: no back pain; non-persistent back pain; infrequent persistent back pain; or frequent persistent back pain. Secondary measures of back pain from year five questionnaire included disabling back pain phenotypes. The main outcomes measured were all-cause and cause-specific mortality. RESULTS: After the year five 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 adjusting 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 mortality and other mortality, but we observed no association of back pain with cancer mortality. Secondary back pain measures including back-related disability were associated with increased mortality risk that remained statistically significant in fully-adjusted models. CONCLUSION: While frequent persistent back pain was not independently associated with mortality in older men, additional secondary disabling back pain phenotypes were independently associated with increased mortality. Future investigations should evaluate whether improvements in disabling back pain effect general health and well-being or mortality.

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.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

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.

Relation Between Dietary Protein Intake and Gut Microbiome Composition in Community-Dwelling Older Men: Findings from the Osteoporotic Fractures in Men Study (MrOS).

BACKGROUND: Little is known about the association of specific nutrients, especially proteins, on age-related gut dysbiosis. OBJECTIVES: To determine the associations between the quantity and sources (vegetable and animal) of dietary protein intake and gut microbiome composition in community-dwelling older men. METHODS: We performed a cross-sectional analysis on 775 older men from the Osteoporotic Fractures in Men Study (MrOS) (age 84.2 ± 4.0 y) with available dietary information and stool samples at visit 4 (2014-2016). Protein intake was estimated from a brief FFQ and adjusted to total energy intake. The gut microbiome composition was determined by 16S (v4) sequencing (processed by DADA2 and SILVA). A total of 11,534 amplicon sequence variants (ASVs) were identified and assigned to 21 phyla with dominance of Firmicutes (45%) and Bacteroidetes (43%). We performed α-diversity, ß-diversity, and taxa abundance (by Analysis of Compositions of Microbiomes with Bias Correction [ANCOM-BC]) to determine the associations between protein intake and the gut microbiome. RESULTS: Median protein intake was 0.7 g/(kg body weight · d). Participants with higher energy-adjusted protein intakes had higher Shannon and Chao1 α-diversity indices (P < 0.05). For ß-diversity analysis, participants with higher protein intakes had a different center in weighted and unweighted UniFrac Principal Co-ordinates Analysis (PCoA) compared with those with lower intake (P < 0.05), adjusted for age, race, education, clinical center, batch number, fiber and energy intake, weight, height, and medications. Similarly, higher protein consumptions from either animal or vegetable sources were associated with higher gut microbiome diversity. Several genus-level ASVs, including Christensenellaceae, Veillonella, Haemophilus, and Klebsiella were more abundant in participants with higher protein intakes, whereas Clostridiales bacterium DTU089 and Desulfovibrio were more abundant in participants with lower protein intake (Bonferroni corrected P < 0.05). CONCLUSIONS: We observed significant associations between protein intake and gut microbiome diversity in community-living older men. Further studies are needed to elucidate the mediation role of the gut microbiome on the relation between protein intake and health outcomes in older adults.

Muscle Steatosis and Fibrosis in Older Adults, From the AJR Special Series on Imaging of Fibrosis.

The purpose of this article is to review steatosis and fibrosis of skeletal muscle, focusing on older adults. Although CT, MRI, and ultrasound are commonly used to image skeletal muscle and provide diagnoses for a variety of medical conditions, quantitative assessment of muscle steatosis and fibrosis is uncommon. This review provides radiologists with a broad perspective on muscle steatosis and fibrosis in older adults by considering their public health impact, biologic mechanisms, and evaluation using CT, MRI, and ultrasound. Promising directions in clinical research that employ artificial intelligence algorithms and the imaging assessment of biologic age are also reviewed. The presented imaging methods hold promise for improving the evaluation of common conditions affecting older adults including sarcopenia, frailty, and cachexia.

Subjective social status moderates back pain and mental health in older men.

OBJECTIVES: Back pain and poor mental health are interrelated issues in older men. Evidence suggests that socioeconomic status moderates this relationship, but less is known about the role of subjective social status (SSS). This study examined if the association between back pain and mental health is moderated by SSS. METHOD: We used a sample of community-dwelling older men (≥65 years) from the Osteoporotic Fractures in Men Study (N = 5994). Participants self-reported their back pain severity and frequency over the past 12 months. SSS was assessed with the MacArthur Scale of SSS. Mental health was assessed with the SF-12 Mental Component Summary (MCS). RESULTS: Severe back pain was associated with lower SF-12 MCS scores (p = .03). Back pain frequency was not associated with SF-12 MCS scores. SSS moderated the back pain and mental health relationship. Among men with higher national or community SSS, the association between back pain severity and SF-12 MCS scores was not significant. However, among men with lower national or community SSS, more severe back pain was associated with lower SF-12 MCS scores (p's < .001). Among those with lower national or community SSS, greater back pain frequency was also associated with lower SF-12 MCS scores (p's < .05). CONCLUSION: Where one ranks oneself within their nation or community matters for the back pain and mental health relationship. Higher SSS may be a psychosocial resource that buffers the negative associations of severe and frequent back pain on mental health in older men.

Lean mass, grip strength, and hospital-associated disability among older adults in Health ABC.

INTRODUCTION: Older adults with cognitive impairment, including those with Alzheimer's disease and related dementias, are particularly at risk for hospitalization and hospital-associated disability. Understanding of key risk factors for hospital-associated disability is limited. Sarcopenia, age-related declines in muscle mass and strength, is common in older adults with cognitive impairment and may be an important risk factor for hospital-associated disability. METHODS: Using data from the Health ABC Study, we examined associations of pre-hospitalization appendicular lean mass (ALM) and grip strength with the development of a new activity of daily living (ADL) disability at the next annual assessment after hospitalization. RESULTS: Grip strength, but not ALM, was negatively associated with increased risk of hospital-associated ADL disability, and this association was greater among those with cognitive impairment compared to those without. DISCUSSION: Lower grip strength may be an important risk factor for hospital-associated ADL disability in older adults, particularly those with cognitive impairment.

Oxylipins Associated with D3-Creatine Muscle Mass/Weight and Physical Performance among Community-Dwelling Older Men.

Poor physical function is highly prevalent with aging, and strongly associated with D3-creatine muscle mass/weight. Using metabolomics, we previously identified several triglycerides consisting mostly of polyunsaturated fatty acids that were higher in older adults with good mobility. Here, we sought to further investigate polyunsaturated fatty-acid-related metabolites, i.e., oxylipins, and their associations with D3-creatine muscle mass/weight, gait speed, grip strength, and the Short Physical Performance Battery among 463 older men from the Osteoporotic Fractures in Men Study (MrOS). Oxylipins were measured in fasting serum using liquid chromatography-mass spectrometry. Muscle mass was estimated using D3-creatine dilution and adjusted for body size. We used linear regression to determine oxylipins associated with D3-creatine muscle mass/weight and physical performance, while adjusting for age, education, physical activity, Western dietary pattern, fish oil supplementation, and multiple comparisons. Among 42 oxylipins, none were associated with grip strength and 3 were associated with the Short Physical Performance Battery. In contrast, 18 and 17 oxylipins were associated with D3-creatine muscle mass/weight and gait speed, respectively. A subset of associations between oxylipins and gait speed were partially attenuated by D3-creatine muscle mass/weight. Higher levels of fatty acid alcohol and ketone oxylipins tended to be most strongly associated with gait speed and D3-creatine muscle mass/weight, potentially reflecting anti-inflammatory activity from these select oxylipins in MrOS older men.

Individual and joint trajectories of change in bone, lean mass and physical performance in older men.

BACKGROUND: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men. METHODS: Using repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations. RESULTS: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data. CONCLUSIONS: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

Associations between novel jump test measures, grip strength, and physical performance: the Osteoporotic Fractures in Men (MrOS) Study.

BACKGROUND/AIMS: Weight-bearing jump tests measure lower extremity muscle power, velocity, and force, and may be more strongly related to physical performance than grip strength. However, these relationships are not well described in older adults. METHODS: Participants were 1242 older men (mean age 84 ± 4 years) in the Osteoporotic Fractures in Men (MrOS) Study. Jump peak power (Watts/kg body weight), force (Newton/kg body weight) at peak power, and velocity (m/s) at peak power were measured by jump tests on a force plate. Grip strength (kg/kg body weight) was assessed by hand-held dynamometry. Physical performance included 400 m walk time (s), 6 m usual gait speed (m/s), and 5-repeated chair stands speed (#/s). RESULTS: In adjusted Pearson correlations, power/kg and velocity moderately correlated with all performance measures (range r = 0.41-0.51; all p < 0.001), while correlations for force/kg and grip strength/kg were weaker (range r = 0.20-0.33; all p < 0.001). Grip strength/kg moderately correlated with power/kg (r = 0.44; p < 0.001) but not velocity or force/kg. In adjusted linear regression with standardized ßs, 1 SD lower power/kg was associated with worse: 400 m walk time (ß = 0.47), gait speed (ß = 0.42), and chair stands speed (ß = 0.43) (all p < 0.05). Associations with velocity were similar (400 m walk time: ß = 0.42; gait speed: ß = 0.38; chair stands speed: ß = 0.37; all p < 0.05). Force/kg and grip strength/kg were more weakly associated with performance (range ß = 0.18-0.28; all p < 0.05). CONCLUSIONS/DISCUSSION: Jump power and velocity had stronger associations with physical performance than jump force or grip strength. This suggests lower extremity power and velocity may be more strongly related to physical performance than lower extremity force or upper extremity strength in older men.

Urinary Incontinence and Nocturia in Older Men: Associations with Body Mass, Composition and Strength in the Health ABC Study.

PURPOSE: In younger men lower body mass is associated with fewer urinary symptoms, including incontinence and nocturia. However, lower body mass may have different implications in older men due to age associated muscle atrophy and decreased strength. MATERIALS AND METHODS: We performed a prospective analysis of community dwelling men 70 to 79 years old in the multicenter Health ABC (Aging and Body Composition) study who underwent measurement of body mass on physical examination, composition using dual x-ray absorptiometry and strength according to grip and lower leg dynamometry. We evaluated associations with prevalent incontinence and nocturia on structured questionnaires as well as concurrent changes in urinary symptoms during 3 years using multivariate logistic regression. RESULTS: Of the 1,298 men analyzed 22% reported incontinence and 52% reported nocturia at baseline. Higher body mass index, fat mass and lower appendicular lean mass, and grip and quadriceps strength corrected for body mass index were associated with an increased prevalence of incontinence (each p <0.05). Higher body mass index and greater fat mass were also associated with an increased nocturia prevalence (each p <0.05). Concurrent 5% or greater decrease in body mass or fat mass was not associated with lower odds of new or worsening incontinence or nocturia, whereas a 5% or greater decrease in maximum grip strength was associated with higher odds of new or worsening incontinence. CONCLUSIONS: Older men with a higher body mass index and greater fat mass are more likely to report prevalent incontinence and nocturia. However, late life decreases in strength but not increases in body mass or fat mass were associated with a concurrent increase in urinary incontinence.

Recent Progress in Sarcopenia Research: a Focus on Operationalizing a Definition of Sarcopenia.

PURPOSE OF REVIEW: To discuss recent progress in sarcopenia research and to highlight controversies in the field particularly around reaching consensus on a definition of sarcopenia. RECENT FINDINGS: Accordingly, this review begins with a discussion of the increasing awareness of this condition; briefly describes evolving definitions of sarcopenia; suggests a framework for consistent terminology for sarcopenia; discusses outstanding issues in the definition of sarcopenia; and reviews the association between sarcopenia and adverse outcome in older adults. In addition, the role of sarcopenia in other diseases is discussed. The field of sarcopenia continues to hold considerable promise and work continues to resolve outstanding concerns in this field with a unifying consensus definition on the horizon.