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BackgroundLower urinary tract symptoms (LUTS) are associated with frailty phenotype, a risk factor for functional decline. Our objective was to determine the association between baseline LUTS and 2-year risk of new functional limitation among older men.MethodsWe analyzed data from the Osteoporotic Fractures in Men (MrOS) study with baseline at Year 7 and follow-up through Year 9. Participants included 2716 community-dwelling men age ≥ 71 years without any baseline self-reported functional limitation. LUTS severity (American Urologic Association Symptom Index) was classified as none/mild (score 0-7), moderate (8-19), and severe (20-35). At baseline and follow-up, men reported their ability to complete several mobility, activities of daily living (ADLs), and cognition-dependent tasks. Risk was estimated for 3 incident functional limitation outcomes: (1) mobility (any difficulty walking 2-3 blocks or climbing 10 steps), (2) ADL (any difficulty bathing, showering, or transferring), and (3) cognition-dependent (any difficulty managing money or medications). We used Poisson regression with a robust variance estimator to model adjusted risk ratios (ARR) and 95% CIs controlling for age, site, and comorbidities; other demographic/lifestyle factors did not meet criteria for inclusion.ResultsOverall, the 2-year risk was 15% for mobility, 10% for ADLs, and 4% for cognition-dependent task limitations. Compared to none/mild LUTS, risk of incident mobility limitations was increased for moderate (ARR = 1.35, 95% CI: 1.12, 1.63) and severe LUTS (ARR = 1.98, 95% CI: 1.48, 2.64). Men were also at higher risk for incident ADL limitations if they reported moderate (ARR = 1.32, 95% CI: 1.05, 1.67) and severe LUTS (ARR = 1.62, 95% CI: 1.07,2.43). Results were somewhat attenuated after adjusting for the frailty phenotype but remained statistically significant. LUTS were not associated with incident cognition-dependent task limitations.ConclusionsLUTS severity is associated with incident mobility and ADL limitations among older men. Increased clinical attention to risk of functional limitations among older men with LUTS is likely warranted.

BackgroundMuscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat versus muscle fat to adverse outcomes have been unclear.MethodIn a large cohort of older men (N = 1 017), we measured muscle mass (D3-creatine dilution), muscle density (high-resolution peripheral quantitative computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual-energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years.ResultsIn combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% confidence interval: 0.74, 0.96), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively.ConclusionsMuscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

BackgroundMuscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat vs. muscle fat to adverse outcomes have been unclear.MethodsIn a large cohort of older men (N= 1017), we measured muscle mass (D3 creatine dilution), muscle density (high resolution peripheral computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years.ResultsIn combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% CI: 0.74, 0.70), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively.ConclusionsMuscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as

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.

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.

ContextObservational studies show discordant links between endogenous testosterone levels and cardiovascular diseases (CVD).ObjectiveWe assessed whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CVD in community-dwelling elderly men.Design setting and participantsProspective study of incident CVD among 552 men ≥ 65 years in the MrOS Sleep Study without prevalent CVD and no testosterone therapy at baseline.OutcomesFasting serum levels of total testosterone and estradiol were measured using liquid chromatography-mass spectrometry, and SHBG by chemiluminescent substrate. The association of sex hormones and SHBG with incident coronary heart disease (CHD), cerebrovascular (stroke and transient ischemic attack) and peripheral arterial disease (PAD) events were assessed by quartile and per SD increase in proportional hazards models.ResultsAfter 7.4 years, 137 men (24.8%) had at least 1 CVD event: 90 CHD, 45 cerebrovascular and 26 PAD. The risk of incident CVD events was not associated with quartiles of baseline sex hormones or SHBG (all P ≥ 0.16). For +1 SD in total testosterone, the multivariate-adjusted hazard ratio was 1.04 (95% CI, 0.80-1.34) for CHD, 0.86 (0.60-1.25) for cerebrovascular, and 0.81 (0.52-1.26) for PAD events. When analyzed as continuous variables or comparing highest to low quartile, levels of bioavailable testosterone, total estradiol, testosterone/estradiol ratio and SHBG were not associated with CVD events.ConclusionsIn community-dwelling elderly men, endogenous levels of testosterone, estradiol, and SHBG were not associated with increased risk of CHD, cerebrovascular, or PAD events. These results are limited by the small number of events and should be explored in future studies.

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. [ABSTRACT FROM AUTHOR]

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.

BackgroundThere is growing interest in the area of "wearable tech" and its relationship to health. A common element of many of these devices is a triaxial accelerometer that can yield continuous information on gross motor activity levels; how such data might predict changes in health is less clear.MethodsWe examined accelerometry data from 2,976 older men who were part of the Osteoporotic Fractures in Men (MrOS) study. Using a shape-naive technique, functional principal component analysis, we examined the patterns of motor activity over the course of 4-7 days and determined whether these patterns were associated with changes in polysomnographic-determined sleep and cognitive function (Trail Making Test-Part B [Trails B], Modified Mini-Mental State Examination [3MS]), as well as mortality over 6.5-8 years of follow-up.ResultsIn comparing baseline to 6.5 years later, multivariate modeling indicated that low daytime activity at baseline was associated with worsening of sleep efficiency (p < .05), more wake after sleep onset (p < .05), and a decrease in cognition (Trails B; p < .001), as well as a 1.6-fold higher rate of all-cause mortality (hazard ratio = 1.64 [1.34-2.00]). Earlier wake and bed times were associated with a decrease in cognition (3MS; p < .05). Having a late afternoon peak in activity was associated with a 1.4-fold higher rate of all-cause mortality (hazard ratio = 1.46 [1.21-1.77]). Those having a longer duration of their daytime activity with a bimodal activity pattern also had over a 1.4-fold higher rate of cardiovascular-related mortality (hazard ratio = 1.42 [1.02-1.98]).ConclusionsPatterns of daily activity may be useful as predictive biomarkers for changes in clinically relevant outcomes, including mortality and changes in sleep and cognition in older men.

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual-energy X-ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral-fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.

Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual-energy X-ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm2); expected loss (n = 2768; change between 0 g/cm2 and -0.034 g/cm2]); and accelerated loss (n = 545; change 1 SD below mean change or worse [≤-0.034 g/cm2]). Multivariate proportional hazards models adjusted for potential confounders estimated the risk of all-cause mortality over 8.1 ± 2.8 years following visit 2. Mortality was centrally adjudicated by physician review of death certificates. At visit 1, mean age was 72.9 ± 5.5 years. Men who maintained BMD were less likely to die during the subsequent follow-up period (33.7%) than men who had accelerated BMD loss (60.6%) (p < 0.001). Compared to men who had maintained BMD, those who had accelerated BMD loss had a 44% greater risk of mortality in multivariate-adjusted models (HR, 1.44; 95% CI, 1.23 to 1.68). Compared to men who had maintained BMD, there was no significant difference in mortality risk for men with expected loss of BMD (36.9% died) (multivariate HR, 1.00; 95% CI, 0.89 to 1.13). Further adjustment for visit 1 or visit 2 BMD measurement did not substantially alter these associations. Results for total hip BMD were similar. In conclusion, accelerated loss of BMD at the hip is a risk factor for mortality in men that is not explained by comorbidity burden, concurrent change in weight, or physical activity.

Introduction: Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods: This study was undertaken by the growth hormone (GH) scientific study group in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives, and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with growth hormone deficiency (GHD) was compiled. Each member was asked to determine the: (1) importance of the data field and (2) ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect. Results: A total of 246 items were compiled and 27 were removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GHD on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months, and 9 every 12 months. Conclusion: In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the MDS requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting GH. [ABSTRACT FROM AUTHOR]

The association between vitamin D status and diabetes risk is inconsistent among observational studies, and most of the available studies have been with women. In the present study we investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and incident type 2 diabetes (T2D) in older men (≥65years old) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study enrolled from March 2000 to April 2002. Baseline 25(OH)D levels were available in 1939 subjects without prevalent T2D. Clinical information, body mass index (BMI) and other factors related to T2D were assessed at the baseline visit. Incident diabetes, defined by self-report and medication use, was determined over an average follow-up of 6.4years. At baseline, participants were, on average, 73.3 (±5.7) years old, had a mean BMI in the overweight range (27.2kg/m(2)±3.6) and had total serum 25(OH)D of 26.1ng/ml (±8.3). Incident diabetes was diagnosed in 139 subjects. Cox regression analysis showed a trend toward a protective effect of higher 25(OH)D levels with a lower risk of T2D (HR 0.87, 95% CI: 0.73-1.04 per 1 SD increase of 25(OH)D). After adjusted for BMI and other potential confounders, the relationship between 25(OH)D levels and incident diabetes was further attenuated (HR 1.03, 95% CI 0.85-1.25). No significant difference in the incidence of diabetes emerged after analyzing study subjects according to baseline 25(OH)D quartiles. In conclusion, 25(OH)D levels were not associated with incident T2D in older men.

BackgroundVariations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes.MethodsData were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates.ResultsAt baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis.ConclusionsVariations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.

ObjectiveTo evaluate the associations between definitions of sarcopenia and clinical outcomes and the ability of the definitions to discriminate those with a high likelihood of having these outcomes from those with a low likelihood.DesignOsteoporotic Fractures in Men Study.SettingSix clinical centers.ParticipantsCommunity-dwelling men aged 65 and older (N = 5,934).MeasurementsSarcopenia definitions from the International Working Group, European Working Group on Sarcopenia in Older Persons, Foundation for the National Institutes of Health Sarcopenia Project, Baumgartner, and Newman were evaluated. Recurrent falls were defined as two or more self-reported falls in the year after baseline (n = 694, 11.9%). Incident hip fractures (n = 207, 3.5%) and deaths (n = 2,003, 34.1%) were confirmed according to central review of medical records over 9.8 years. Self-reported functional limitations were assessed at baseline and 4.6 years later. Logistic regression or proportional hazards models were used to estimate associations between sarcopenia and falls, hip fractures, and death. The discriminative ability of the sarcopenia definitions (vs reference models) for these outcomes was evaluated using area under the receiver operating characteristic curve or C-statistics. Referent models included age alone for falls, functional limitations and mortality, and age and bone mineral density for hip fractures.ResultsThe association between sarcopenia according to the various definitions and risk of falls, functional limitations, and hip fractures was variable; all definitions were associated with greater risk of death, but none of the definitions materially changed discrimination based on the AUC and C-statistic when compared with reference models (change ≤1% in all models).ConclusionSarcopenia definitions as currently constructed did not consistently improve prediction of clinical outcomes in relatively healthy older men.

Aims/hypothesisDiabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.MethodsThe MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.ResultsIn models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).Conclusions/interpretationMen with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.

Data suggest that clinical applications of human induced pluripotent stem cells (hiPSCs) will be realized. Nonetheless, clinical applications will require hiPSCs that are free of exogenous DNA and that can be manufactured through Good Manufacturing Practice (GMP). Optimally, derivation of hiPSCs should be rapid and efficient in order to minimize manipulations, reduce potential for accumulation of mutations and minimize financial costs. Previous studies reported the use of modified synthetic mRNAs to reprogram fibroblasts to a pluripotent state. Here, we provide an optimized, fully chemically defined and feeder-free protocol for the derivation of hiPSCs using synthetic mRNAs. The protocol results in derivation of fully reprogrammed hiPSC lines from adult dermal fibroblasts in less than two weeks. The hiPSC lines were successfully tested for their identity, purity, stability and safety at a GMP facility and cryopreserved. To our knowledge, as a proof of principle, these are the first integration-free iPSCs lines that were reproducibly generated through synthetic mRNA reprogramming that could be putatively used for clinical purposes.

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 (β =-0.17, p < 0.001) and higher D3Cr muscle mass, although this was of borderline significance (β = 0.07, p = 0.05). Replacing 30-min of ST for LPA was associated with lower FM (β =-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. [ABSTRACT FROM AUTHOR]

Multiple studies have shown clear evidence of vitamin D’s anti-tumor effects on prostate cancer cells in laboratory experiments, but the evidence has not been consistent in humans. We sought to examine the association between vitamin D and prostate cancer risk in a cohort of older men.We conducted a prospective case-cohort study nested within the multicenter Osteoporotic Fractures in Men (MrOS) study. Baseline serum 25-OH vitamin D was measured in a randomly selected sub-cohort of 1,433 men ≥65 years old without a history of prostate cancer and from all participants with an incident diagnosis of prostate cancer (n = 297). Cox proportional hazards models were used to evaluate the associations between quartiles of total 25-OH vitamin D and incident prostate cancer, as well as Gleason score.In comparison with the lowest quartile of 25-OH vitamin D, the hazard ratio for the highest quartile of 25-OH vitamin D was 1.22 (CI 0.50–1.72, p = 0.25), no trend across quartiles (p = 0.94) or association with Gleason score was observed. Adjustment for covariates did not alter the results.In this prospective cohort of older men, we found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer.

The association between vitamin D levels and incident fractures in older men is uncertain. To test the hypothesis that low serum 25-hydroxyvitamin D [(25(OH)D] levels are associated with an increased risk of fracture, we performed a case-cohort study of 436 men with incident nonspine fractures, including 81 hip fractures, and a random subcohort of 1608 men; average follow-up time 5.3 years. Serum vitamin D(2) and vitamin D(3) were measured on baseline sera using mass spectrometry and summed for total vitamin D. Modified Cox proportional hazards models were used to estimate the hazard ratio (HR) of fracture with 95% confidence intervals (CIs). Multivariable models included age, clinic, season, race, height, weight, and physical activity. The mean (SD) total 25(OH)D was 24.6 (7.8) ng/mL in nonspine fracture subjects, 21.5 (7.9) ng/mL in hip fracture subjects, and 25.2 (7.8) ng/mL in controls (nonspine fracture subjects versus nonpatients, p = .14; hip fracture subjects versus controls, p < .0001). 25(OH)D levels were unrelated to nonspine fractures. One SD decrease in total 25(OH)D was associated with an increased risk of hip fracture (multivariate HR = 1.60; 95% CI 1.18-2.17). Compared with men in the top quartile of total 25(OH)D (> or =28), the HR of hip fracture was 2.36 (95% CI 1.08-5.15) for men in the lowest quartile (

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment.