Association Between Muscle Mass Determined by D3 -Creatine Dilution and Incident Fractures in a Prospective Cohort Study of Older Men.

The relation between a novel measure of total skeletal muscle mass (assessed by D3 -creatine dilution [D3 Cr]) and incident fracture is unknown. In 1363 men (mean age 84.2 years), we determined D3 Cr muscle mass; Fracture Risk Assessment Tool (FRAX) 10-year probability of hip and major osteoporotic (hip, humerus, vertebral, forearm) fracture; and femoral neck bone mineral density (BMD) (by dual-energy X-ray absorptiometry [DXA]). Incident fractures were centrally adjudicated by review of radiology reports over 4.6 years. Correlations adjusted for weight and height were calculated between femoral neck BMD and D3 Cr muscle mass. Across quartiles of D3 Cr muscle mass/weight, proportional hazards models calculated hazard ratios (HRs) for any (n = 180); nonspine (n = 153); major osteoporotic fracture (n = 85); and hip fracture (n = 40) after adjustment for age, femoral neck BMD, recurrent fall history, and FRAX probability. Models were then adjusted to evaluate the mediating influence of physical performance (walking speed, chair stands, and grip strength). D3 Cr muscle mass was weakly correlated with femoral BMD (r = 0.10, p < 0.001). Compared to men in the highest quartile, those in the lowest quartile of D3 Cr muscle mass/weight had an increased risk of any clinical fracture (HR 1.8; 95% confidence interval [CI], 1.1-2.8); nonspine fracture (HR 1.8; 95% CI, 1.1-3.0), major osteoporotic fracture (HR 2.3; 95% CI, 1.2-4.6), and hip fracture (HR 5.9; 95% CI, 1.6-21.1). Results were attenuated after adjustment for physical performance, but associations remained borderline significant for hip and major osteoporotic fractures (p ≥ 0.05 to 0.10). Low D3 Cr muscle mass/weight is associated with a markedly high risk of hip and potentially other fractures in older men; this association is partially mediated by physical performance. © 2022 American Society for Bone and Mineral Research (ASBMR).

Effects of melatonin on sleep disturbances in multiple sclerosis: A randomized, controlled pilot study.

BACKGROUND: Sleep disturbances are commonly reported by people with multiple sclerosis (PwMS). However, optimal management of sleep disturbances is uncertain, and objective studies of sleep quality in PwMS are scarce. OBJECTIVES: To determine the effect of exogenous melatonin on sleep quality and sleep disturbances in PwMS. METHODS: Thirty adult PwMS reporting sleep difficulties were recruited in a randomized, controlled, double-blind cross-over study. They took either melatonin or placebo for 2 weeks, and the opposite for the following 2 weeks. During weeks 2 and 4, an actigraph was used to capture mean total sleep time and sleep efficiency. Patient-reported outcomes (PROs) were collected at weeks 0, 2 and 4. RESULTS: Melatonin use significantly improved mean total sleep time (p = 0.03), with a trend towards higher sleep efficiency (p = 0.06). No PROs were significantly different; there was a trend for melatonin use to decrease mean Insomnia Severity Index score (p = 0.07), improve Pittsburgh Sleep Quality Index sleep quality component (p = 0.07), and improve NeuroQoL-Fatigue (p = 0.06). No other PROs showed differences between melatonin and placebo; nor did step count measured by actigraphy (all p > 0.45). CONCLUSION: These results provide preliminary evidence that melatonin, a low-cost, over-the-counter supplement, could improve objective measures of sleep quality in PwMS.

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

BACKGROUND: We examined cross-sectional associations between dietary patterns, macronutrient intake, and measures of muscle mass and lean mass in older men. METHODS: Participants 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. RESULTS: Greater 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 (ß = 0.09, 95% CI = 0.03, 0.14) and nondairy animal protein (ß = 0.16, 95% CI = 0.10, 0.21) were positively associated with D3Cr muscle mass. Nondairy animal protein (ß = 0.06, 95% CI = 0.002, 0.11) was positively associated with DXA ALM. Associations with other macronutrients were inconsistent. CONCLUSIONS: Nondairy animal protein intake (within a Western dietary pattern and alone) was positively associated with D3Cr muscle mass in older men.

The Importance of Muscle Versus Fat Mass in Sarcopenic Obesity: A Re-evaluation Using D3-Creatine Muscle Mass Versus DXA Lean Mass Measurements.

BACKGROUND: The combination of sarcopenia and obesity has been associated with physical impairment in older people. However, previous research has relied on assessments of lean mass as a surrogate for muscle mass. We postulate that inaccurate measures of muscle mass may have obscured the role of obesity in sarcopenia and related outcomes. Our aim was to clarify the interactions of muscle and fat with physical performance and adverse outcomes using an accurate measure of muscle mass. METHODS: In a longitudinal study of >1,300 older men (mean age 84 years), we compared a direct measurement of muscle mass (D3 creatine dilution; D3Cr) with an approximation of muscle mass (appendicular lean mass [ALM] by dual-energy x-ray absorptiometry [DXA]) and their associations with measures of physical performance (gait speed, chair stand time) and adverse outcomes (incident injurious falls and mobility problems). We measured percent fat mass by DXA. RESULTS: Low D3Cr muscle mass was strongly associated with decreased performance and increased risk of adverse outcomes. Increased fat mass had little association after accounting for D3Cr muscle mass. In contrast, DXA ALM was minimally associated with performance or adverse outcomes, and fatness remained associated with both outcomes after accounting for DXA ALM. CONCLUSIONS: When an accurate assessment of muscle mass (rather than lean mass) is used, reduced muscle mass is highly associated with important outcomes and the negative effects of adiposity are minimal, suggesting that obesity has little relevance for the understanding of important adverse health outcomes of sarcopenia in older men.

Association of change in muscle mass assessed by D3 -creatine dilution with changes in grip strength and walking speed.

BACKGROUND: Muscle mass declines with age. However, common assessments used to quantify muscle mass are indirect. The D3 -creatine (D3 Cr) dilution method is a direct assessment of muscle mass; however, longitudinal changes have not been examined in relation to changes in other measures of muscle mass, strength, and performance. METHODS: A convenience sample of 40 men from the Osteoporotic Fractures in Men Study (mean age = 83.3 years, standard deviation = 3.9) underwent repeat assessment of D3 Cr muscle mass, dual-energy X-ray absorptiometry (DXA) lean mass, grip strength, and walking speed at two time points approximately 1.6 years apart (2014-2016). One-sample t-tests and Pearson correlations were used to examine changes in DXA total body lean mass, DXA appendicular lean mass/height2 , DXA appendicular lean mass/weight, D3 Cr muscle mass, D3 Cr muscle mass/weight, grip strength, walking speed, and weight. RESULTS: D3 -creatine muscle mass, D3 Cr muscle mass/weight, grip strength, and walking speed all significantly declined (all P < 0.01). The change in DXA measures of lean mass was moderately correlated with changes in D3 Cr muscle mass. There was no significant correlation between the change in DXA measures of lean mass and change in walking speed (all P > 0.05). The change in D3 Cr muscle mass/weight was moderately correlated with change in walking speed (r = 0.33, P < .05). The change in grip strength was weakly correlated with the change in DXA measures of lean mass and D3 Cr muscle mass (r = 0.19-0.32). CONCLUSIONS: The results of our study provide new insights regarding the decline in muscle strength and D3 Cr muscle mass. The D3 Cr method may be a feasible tool to measure declines in muscle mass over time.

Strong Relation Between Muscle Mass Determined by D3-creatine Dilution, Physical Performance, and Incidence of Falls and Mobility Limitations in a Prospective Cohort of Older Men.

BACKGROUND: Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass. METHODS: Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 years). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 m); and dual x-ray absorptiometry (DXA) lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls. RESULTS: Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (odds ratio [OR] Q1 vs Q4: 2.49, 95% confidence interval [CI]: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95% CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend < .001 for all. Results for incident recurrent falls were in the similar direction (p = .156). DXA lean mass had weaker associations with the outcomes. CONCLUSIONS: Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility, and incident injurious falls in older men.

Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS).

Almost 30% of hip fractures occur in men; the mortality, morbidity, and loss of independence after hip fractures are greater in men than in women. To comprehensively evaluate risk factors for hip fracture in older men, we performed a prospective study of 5994 men, primarily white, age 65+ years recruited at six US clinical centers. During a mean of 8.6 years of 97% complete follow-up, 178 men experienced incident hip fractures. Information on risk factors including femoral neck bone mineral density (FNBMD) was obtained at the baseline visit. Cox proportional hazards models were used to calculate the hazard ratio (HR) with 95% confidence intervals; Fine and Gray models adjusted for competing mortality risk. Older age (≥75 years), low FNBMD, currently smoking, greater height and height loss since age 25 years, history of fracture, use of tricyclic antidepressants, history of myocardial infarction or angina, hyperthyroidism or Parkinson's disease, lower protein intake, and lower executive function were all associated with an increased hip fracture risk. Further adjustment for competing mortality attenuated HR for smoking, hyperthyroidism, and Parkinson's disease. The incidence rate of hip fracture per 1000 person-years (PY) was greatest in men with FNBMD T-scores <-2.5 (white women reference database) who also had 4+ risk factors, 33.4. Men age ≥80 years with 3+ major comorbidities experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age <70 years with zero comorbidities. Older men with low FNBMD, multiple risk factors, and multimorbidity have a high risk of hip fracture. Many of these assessments can easily be incorporated into routine clinical practice and may lead to improved risk stratification. © 2016 American Society for Bone and Mineral Research.

Social-cognitive correlates of protective drinking behaviors and alcohol-related consequences in college students.

Although heavy episodic drinkers are at risk to experience alcohol-related consequences, studies show that a large percentage of student drinkers do not experience problems as a result of their drinking. The present study was a more in-depth examination of factors beyond just drinking quantity and frequency to explain why students experience consequences. The current research examined the relationship between the use of protective behaviors, alcohol use, and alcohol related consequences, as well as the relationship between attitudinal and cognitive predictors of engaging in protective behaviors when drinking. We hypothesized there would be a significant direct effect of protective behaviors on consequences after taking into account the effect of alcohol use and that cognitive predictors, including perceived self-efficacy, perceived effectiveness, and subjective norm, would be associated with the attitude and frequency of engaging in protective behaviors. Results supported both hypotheses, indicating good model fit for all models and significant paths between constructs (p's<.05). These findings extend the literature on protective behaviors by providing insight as to their utility in preventing harm and why students choose to engage in these behaviors. Implications for interventions are also discussed.