Association of body composition with all-cause mortality among U.S. adults with osteoporosis or osteopenia: a population-based study.

BACKGROUND: Adults with osteopenia or osteoporosis have increased risks of adverse outcomes; however, mortality risk varies substantially and may be influenced by body composition. Evidence for the joint impact of low muscle mass and percentage-based adiposity in this population remains limited. OBJECTIVES: To examine the independent and combined associations of low muscle mass and obesity with all-cause mortality among U.S. adults with osteopenia or osteoporosis and to characterize the dose-response relationship between total fat mass and mortality. METHODS: We performed a retrospective cohort analysis of NHANES cycles with concurrent whole-body DXA (appendicular lean mass and total fat mass) and site-specific BMD assessments (1999-2006, 2013-2014, and 2017-2018). Eligible participants with osteopenia or osteoporosis and mortality linkage were included (unweighted n = 3,918). Low muscle mass (LMM) was defined by DXA-derived appendicular lean mass index (ALMI; men < 7.0 kg/m², women < 5.5 kg/m²), while obesity was operationally defined by DXA body fat percentage (FM%; men > 30%, women > 42%) instead of body mass index (BMI). Survey-weighted Cox models and restricted cubic splines were utilized. RESULTS: Over a median follow-up of 14.8 years, 1,095 deaths occurred. In fully adjusted models, low muscle mass was associated with higher mortality (HR = 1.59, 95% CI: 1.30-1.95). Jointly, both low muscle mass alone (HR = 1.70, 95% CI: 1.30-2.23) and low muscle mass with obesity (HR = 1.45, 95% CI: 1.13-1.87) were associated with higher mortality compared with the normal phenotype, whereas obesity alone was not; notably, the isolated low muscle mass phenotype exhibited a higher point estimate than the combined phenotype. For total fat mass, with Q1 as reference, intermediate quartiles exhibited significantly lower risk (Q2: HR = 0.71, 95% CI: 0.57-0.88; Q3: HR = 0.68, 95% CI: 0.54-0.87), while Q4 showed a similar but non-significant downward trend (HR = 0.64, 95% CI: 0.50-1.03). CONCLUSIONS: Among U.S. adults with osteopenia or osteoporosis, low muscle mass was a robust predictor of all-cause mortality. Adiposity defined by body fat percentage was not independently associated with mortality, and fat mass demonstrated a nonlinear pattern with the lowest risk at intermediate levels. These findings support incorporating muscle assessment and refined adiposity measures into risk stratification beyond BMD alone. CLINICAL TRIAL REGISTRATION: Not applicable.