Abstract
<title>Abstract</title> <p>Background Body mass index (BMI) is positively associated with bone mineral density (BMD) but does not capture heterogeneity in skeletal muscle and visceral adiposity among individuals of similar body size. Whether BMI-relative variation in these body composition compartments provides distinct and incremental information on BMD beyond BMI remains unclear. Methods This retrospective cross-sectional study included 1,393 adults aged ≥ 45 years who underwent body composition assessment and dual-energy X-ray absorptiometry during the same health examination visit. Sex-specific BMI-residualized SMI and VFA were derived from natural cubic spline models and standardized within sex. Multivariable linear regression evaluated associations with lumbar spine, femoral neck, and total hip BMD. Incremental explanatory value beyond BMI and clinical covariates was assessed using changes in adjusted R² (ΔAdjusted R²), with 95% confidence intervals estimated from 5,000 bootstrap resamples. Results Higher BMI-residualized SMI was consistently associated with higher BMD at the lumbar spine (β = 0.037, 95% CI 0.028–0.046), femoral neck (β = 0.027, 95% CI 0.021–0.034), and total hip (β = 0.029, 95% CI 0.023–0.036; all P < 0.001). Higher BMI-residualized VFA showed weaker inverse associations with BMD at all three sites. Adding BMI-residualized SMI increased adjusted R² by 3.92–4.09 percentage points in the total population and by 3.45–5.23 percentage points in sex-stratified analyses, with all bootstrap 95% CIs remaining above zero. In contrast, incremental gains associated with BMI-residualized VFA were substantially smaller and were not consistently supported across bootstrap resamples. Conclusions Among middle-aged and older adults, skeletal muscle variation not captured by BMI was consistently associated with BMD and accounted for additional variation across clinically relevant skeletal sites. In contrast, BMI-relative visceral adiposity showed weaker and less stable incremental explanatory value. These findings suggest that skeletal muscle assessment may complement BMI when characterizing body composition-related heterogeneity in BMD.</p>