Sex- and age-specific effects of fat distribution on bone mineral density.
BACKGROUND BMI cannot distinguish fat distribution and may mask the true effects of different fat depots on bone mineral density (BMD).To investigate sex- and age-specific associations between fat distribution and BMD and its mediating role in age-related bone loss. MATERIALS AND METHODS This study analyzed 927 individuals undergoing low-dose chest CT. Visceral (VAT) and subcutaneous adipose tissue (SAT) at L2, VAT/SAT ratio, VAT%, and L1-L2 BMD were quantified. Multivariable regression, restricted cubic splines, and mediation analysis were used to assess sex- and age-stratified associations between fat distribution and BMD. RESULTS Compared with younger participants, males aged >45 years had higher VAT but lower SAT, whereas females aged >45 had higher VAT and SAT. After adjustment, VAT was inversely associated with BMD across all sex-age groups, with stronger associations in females (β -0.33 vs -0.20 at ≤45 years; -0.27 vs -0.16 at >45 years). SAT was inversely associated with BMD only in females aged ≤45. VAT% was associated with greater odds of low bone mass only in males (OR 1.30, P = 0.03). Exploratory mediation analyses identified significant indirect associations through VAT in males (P < 0.001) and females (P = 0.006), and through the VAT/SAT ratio in males only (P = 0.028). CONCLUSIONS Higher VAT was associated with lower BMD in females, whereas a higher VAT% was associated with lower BMD primarily in males aged >45 years. These cross-sectional findings highlight sex-specific associations between fat distribution and BMD.