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

BackgroundDeclines 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.MethodsUsing 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.ResultsThe 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.ConclusionsOur 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

Stored elastic energy powers the 60-μm extension of the Limulus polyphemus sperm actin bundle

During the 5 s of the acrosome reaction of Limulus polyphemus sperm, a 60-μm-long bundle of scruin-decorated actin filaments straightens from a coiled conformation and extends from the cell. To identify the motive force for this movement, we examined the possible sources of chemical and mechanical energy and show that the coil releases ∼10−13 J of stored mechanical strain energy, whereas chemical energy derived from calcium binding is ∼10−15 J. These measurements indicate that the coiled actin bundle extends by a spring-based mechanism, which is distinctly different from the better known polymerization or myosin-driven processes, and that calcium initiates but does not power the reaction

Circumstances of clinical fracture events with advancing age in older men.

To characterize fracture circumstances by age at time of fracture among community-dwelling older men, we analyzed incident clinical fractures in the Osteoporotic Fractures in Men study. Participants were contacted every 4 mo to identify fractures confirmed by radiographic reports. Fractures were classified as fall- or non-fall-related and further categorized by degree of trauma: minimal (fall from ≤ standing height), moderate (fall on stairs, steps or curb), or severe (fall from > standing height) for fall-related fractures; and minimal (eg, coughing), moderate (eg, collisions with objects during normal activity without falling), or severe (eg, motor vehicle accident) for non-fall-related fractures. Of 2351 clinical fractures in 1424 men during an average follow-up of 9.9 yr, 12.7% occurred at age <75 yr, 15.7% at age 75-79 yr, 26.1% at age 80-84 yr, and 45.5% at age ≥85 yr. A total of 1891 fractures (80.4% of all fractures) were the result of a fall. The proportion of fall-related fractures steadily rose with increasing age at time of fracture, ranging from 65.8% in men <75 yr rising to 84.7% in men ≥85 yr (p < .001). Most fall-related fractures (76.4%) were due to minimal trauma; the proportion of all fractures due to a fall with minimal trauma steadily rose with increasing age (p < .001). In contrast, approximately half of non-fall-related fractures (53.5%) were due to severe trauma. The proportion of all fractures due to severe trauma (whether fall-related or not) declined with advancing age (p < .001). In conclusion, the most frequently occurring fracture circumstance in older men was a fall from ≤standing height. This circumstance was increasingly common with advancing age occurring in 7 of every 10 fractures in men ≥85 yr, while a fracture (fall-related or not) due to severe trauma was less common with advancing age. Findings have implications for development of fracture prevention strategies in older men

Dietary Intake, D3Cr Muscle Mass, and Appendicular Lean Mass in a Cohort of Older Men.

BackgroundWe examined cross-sectional associations between dietary patterns, macronutrient intake, and measures of muscle mass and lean mass in older men.MethodsParticipants in the Osteoporotic Fractures in Men (MrOS) cohort (n = 903; mean ± SD age 84.2 ± 4 years) completed brief Block food frequency questionnaires (May 2014-May 2016); factor analysis was used to derive dietary patterns. The D3-creatine (D3Cr) dilution method was used to measure muscle mass; dual-energy x-ray absorptiometry (DXA) was used to measure appendicular lean mass (ALM). Generalized linear models were used to report adjusted means of outcomes by dietary pattern. Multiple linear regression models were used to determine associations between macronutrients and D3Cr muscle mass and DXA ALM. Multivariable models were adjusted for age, race, clinic site, education, depression, total energy intake, height, and percent body fat.ResultsGreater adherence to a Western dietary pattern (high factor loadings for red meat, fried foods, and high-fat dairy) was associated with higher D3Cr muscle mass (p-trend = .026). Adherence to the Healthy dietary pattern (high factor loadings for fruit, vegetables, whole grains, and lean meats) was not associated with D3Cr muscle mass or DXA ALM. Total protein (β = 0.09, 95% CI = 0.03, 0.14) and nondairy animal protein (β = 0.16, 95% CI = 0.10, 0.21) were positively associated with D3Cr muscle mass. Nondairy animal protein (β = 0.06, 95% CI = 0.002, 0.11) was positively associated with DXA ALM. Associations with other macronutrients were inconsistent.ConclusionsNondairy animal protein intake (within a Western dietary pattern and alone) was positively associated with D3Cr muscle mass in older men

Body Weight, BMI, Percent Fat and Associations with Mortality and Incident Mobility Limitation in Older Men

How different measures of adiposity are similarly or differentially related to mobility limitation and mortality is not clear. In total, 5849 community-dwelling men aged ≥65 years (mean age: 72 years) were followed mortality over 10 years and self-reported mobility limitations (any difficulty walking 2-3 blocks or with climbing 10 steps) at six contacts over 14 years. Baseline measures of adiposity included weight, BMI and percent fat by DXA. Appendicular lean mass (ALM, by DXA) was analyzed as ALM/ht2. Proportional hazards models estimated the risk of mortality, and repeated measures generalized estimating equations estimated the likelihood of mobility limitation. Over 10 years, 27.9% of men died; over 14 years, 48.0% of men reported at least one mobility limitation. We observed U-shaped relationships between weight, BMI, percent fat and ALM/ht2 with mortality. There was a clear log-linear relationship between weight, BMI and percent fat with incident mobility limitation, with higher values associated with a greater likelihood of mobility limitation. In contrast, there was a U-shaped relationship between ALM/ht2 and incident mobility limitation. These observational data suggest that no single measure of adiposity or body composition reflects both the lowest risk of mortality and the lowest likelihood for developing mobility limitation in older men

Objective measures of moderate to vigorous physical activity are associated with higher distal limb bone strength among elderly men

Our aim was to determine the association between objectively measured physical activity (PA) and bone strength of the distal limbs among older men. We studied 994 men from the MrOS cohort study (mean age 83.9) who had repeat (Year 7 and 14) 5-day activity assessment with at least 90% wear time (SenseWearPro3 Armband) and Year 14 measures using high resolution peripheral quantitative tomography (HR-pQCT) (Scanco). Total energy expenditure (TEE), total steps per day, peak cadence (mean of top 30 steps/min over 24 h) and time spent in a given level of activity: sedentary (reference, <1.5 metabolic equivalents of task [METs]), light (1.5 to <3 METs), or moderate to vigorous physical activity(MVPA: ≥3 METs) were calculated as mean over the two time points. Estimated failure load was determined from HR-pQCT data using finite element analysis. We used standardized variables and adjusted for potential confounders using linear regression. The means ±SDs for daily activity were: 2338 ± 356 kcal/d [TEE]; 5739 ± 2696 steps/day [step count], 60 ± 20 cpm [peak cadence], 67 ± 28 min/d [light activity], and 85 ± 52 min/d [MVPA]. Higher TEE, step count, and peak cadence were each associated with higher failure load of the distal radius (effect sizes respectively: 0.13 [95% CI: 0.05, 0.20], 0.11 [95% CI: 0.04, 0.18], and 0.08 [95% CI: 0.01, 0.15]) and higher failure load of the distal tibia (effect sizes respectively 0.21 [95% CI: 0.13, 0.28], 0.19 [95% CI: 0.13, 0.26], 0.19 [95% CI, 0.13, 0.25]). Time spent in MVPA vs. time sedentary was related to bone strength at both sites after adjustment, whereas time spent in light activity vs. time sedentary was not. TEE was associated with compartmental area and BMD parameters at distal tibia, but only area parameters at the distal radius. In summary, MVPA over a 7-year period of time may have a modest association with bone strength and geometry among older men

Hospitalization-Associated Change in Gait Speed and Risk of Functional Limitations for Older Adults

BACKGROUND: Hospitalization-associated functional decline is a common problem for older adults, but it is unclear how hospitalizations affect physical performance measures such as gait speed. We sought to determine hospitalization-associated change in gait speed and likelihood of new limitations in mobility and activities of daily living (ADLs). METHODS: We used longitudinal data over 5 years from the Health, Aging and Body Composition Study, a prospective cohort of black and white community-dwelling men and women, aged 70-79 years, who had no limitations in mobility (difficulty walking 1/4 mile or climbing 10 steps) or ADLs (transferring, bathing, dressing, and eating) at baseline. Gait speed, and new self-reported limitations in mobility and ADLs were assessed annually. Selected participants (n = 2,963) had no limitations at the beginning of each 1-year interval. Hospitalizations were self-reported every 6 months and verified with medical record data. Generalized estimating equations were used to examine hospitalization-associated change in gait speed and odds of new limitations over each 1-year interval. Fully adjusted models included demographics, hospitalization within the past year, health conditions, symptoms, body mass index, and health-related behaviors. RESULTS: In fully adjusted models, any hospitalization was associated with decrease in gait speed (-0.04 m/s; 95% confidence interval [CI]: -0.05 to -0.03) and higher odds of new limitations in mobility or ADLs (odds ratio = 1.97, 95% CI: 1.70-2.28), and separately with increased odds of new mobility limitation (odds ratio = 2.22, 95% CI: 1.90-2.60) and new ADL limitations (odds ratio = 1.84, 95% CI: 1.53-2.21). Multiple hospitalizations within a year were associated with gait speed decline (-0.06 m/s; 95% CI: -0.08 to -0.04) and greater odds of new limitations in mobility or ADLs (odds ratio = 2.96, 95% CI: 2.23-3.95). CONCLUSIONS: Functionally independent older adults experienced hospitalization-associated declines in gait speed and new limitations in mobility and ADLs

The Causal Effect of Vitamin D Binding Protein (DBP) Levels on Calcemic and Cardiometabolic Diseases: A Mendelian Randomization Study

Background: Observational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy- vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease. Methods and Findings: We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age-and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n=2,254). DBP had a strong observational and causal association with 25OHD levels (p=3.2x10(-19)). While DBP levels were observationally associated with calcium and body mass index (BMI),these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p=1.00; n=46,186); fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,] ;p=0.22; n=46,186); BMI (0.00 kg/m(2) [95% CI -0.01, 0.01]; p=0.80; n=127,587); bone mineral density (0.01 g/cm(2) [95% CI -0.01, 0.03]; p=0.36; n=32,961); mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]); p=0.36; n=28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97, 1.04]; p=0.92; n=12, 389/62, 004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p=0.31; n=2,233/64, 762); or type 2 diabetes (OR = 1.01 [95% CI 0.97, 1.05]; p=0.76; n=9, 580/53, 810). Conclusions: DBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP

Association of dietary patterns with the gut microbiota in older, community-dwelling men.

BackgroundWhile the gut microbiota is relatively stable through adulthood, its composition is influenced by various host and environmental factors, including changes in health, gastrointestinal processes (e.g., transit time, gastric acidity), medication use, and diet. The association of habitual diet, in the form of a posteriori-derived dietary patterns, and microbiota composition has not been adequately studied, particularly in older men.ObjectiveThe objective was to investigate the association of dietary patterns with the composition and diversity of the gut bacterial microbiota in community-dwelling, older men.MethodsThis cross-sectional study included 517 men who were participants in the Osteoporotic Fractures in Men (MrOS) Study (≥65 y of age at baseline in 2000-2002) and who provided a stool sample and completed an FFQ at MrOS Visit 4 in 2014-2016. Dietary patterns were derived by factor analysis. 16S ribosomal RNA target gene sequencing was performed and taxonomy assignments were derived using the Greengenes database. Linear regression and permutational multivariate analysis of variance (PERMANOVA) considered variations in alpha and beta diversity by dietary pattern, and a model that implements a 0-inflated Gaussian distribution of mean group abundance for each taxa (metagenomeSeq) assessed taxonomic variations by dietary pattern.ResultsIn multivariable-adjusted models, greater adherence to the Western pattern was positively associated with families Mogibacteriaceae and Veillonellaceae and genera Alistipes, Anaerotruncus, CC-115, Collinsella, Coprobacillus, Desulfovibrio, Dorea, Eubacterium, and Ruminococcus, while greater adherence to the prudent pattern was positively associated with order Streptophyta, family Victivallaceae, and genera Cetobacterium, Clostridium, Faecalibacterium, Lachnospira, Paraprevotella, and Veillonella. The relative abundance of the dominant gut bacterial phyla, Bacteroidetes and Firmicutes, did not differ between participants with greater adherence to the Western pattern, compared with those with greater adherence to the prudent pattern. Dietary patterns were not associated with measures of alpha diversity, but beta diversity measures were significantly associated with both Western and prudent patterns.ConclusionsWe observed significant associations between dietary patterns and measures of gut microbial composition in this sample of community-dwelling, older men

Mortality risk reduction differs according to bisphosphonate class: A 15-year observational study

Summary: In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Introduction: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. Methods: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. Results: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48–0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66–1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031–0.70)] for n-BP vs. etidronate]. Conclusion: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival