Muscle mass assessed by the D₃-creatine dilution method and incident self-reported disability and mortality in a prospective observational study of community-dwelling older men

Background: Whether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual-energy x-ray absorptiometry [DXA]), and these outcomes are inconsistent. Methods: Muscle mass measured by deuterated creatine (D₃Cr) dilution and appendicular lean mass (ALM, by DXA) were assessed at the Year 14 Visit (2014–2016) of the prospective Osteoporotic Fractures in Men study (N = 1,425, age 77–101 years). Disability in activities of daily living (ADLs), instrumental ADLs, and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression, or proportional hazards models. Results: In age- and clinical center-adjusted models, the relative risks per decrement in D₃Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for instrumental ADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age-, clinical center-, and weight-adjusted models, the relative risks per decrement in D₃Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D₃Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance. Conclusions: Low muscle mass as measured by D₃Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.