Impact of Central Obesity on Bone Mineral Density Across Life Stages: A Genetic Epidemiology and Cross-Sectional Study

Introduction: This study aimed to investigate the association and causality between central obesity and bone mineral density (BMD). Methods We utilized linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) to assess genetic correlations and causal relationships between waist circumference adjusted for BMI (WCadjBMI) and total body less head BMD (TB-BMD). Additionally, a cross-sectional analysis of 7,452 participants evaluated the relationship between A body shape index (ABSI) and TB-BMD using weighted multivariable linear regression and smooth curve fitting. Results LDSC and MR analysis confirmed a negative relationship between WCadjBMI and TB-BMD (β=-0.16; 95% CI: -0.26, -0.07). The cross-sectional study indicated that an increase of 0.01 ABSI corresponded to a decrease of 0.035 TB-BMD (g/cm ² ), with this negative effect being particularly pronounced in males and older adults. An inflection point was identified at ABSI = 0.076: below this threshold, ABSI positively correlated with pelvis BMD, whereas above it, the association became negative. Conclusions Central obesity is significantly negatively related to BMD. Maintaining ABSI within 0.058–0.078 is crucial for individuals in bone mass accrual (20–30 years) and stabilization (30–45 years) periods. In contrast, managing central obesity in people experiencing early bone loss (45–60 years) presents greater complexity and warrants further investigation.