Association of body fat distribution with bone mineral density: evidence from observational and mendelian randomization analyses.

Abstract

Although higher body weight is generally considered protective against low bone mineral density (BMD), the influence of body fat distribution on BMD remains unclear. We aimed to investigate whether specific adipose tissue depots have differential associations with BMD and to assess causality using Mendelian randomization (MR). We conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data to evaluate associations between regional fat depots (gynoid, android, visceral, abdominal subcutaneous fat, and total fat percentage) and BMD at total body, femoral neck, and lumbar spine. Multivariable linear regression was used to evaluate these relationships. To assess potential causal effects, we performed two-sample MR using genome-wide association study summary statistics for fat distribution traits and BMD. Gynoid fat was positively associated with BMD at the total body, femoral neck, and lumbar spine, while visceral and total body fat showed consistent inverse associations across these regions. Two-sample MR analysis supported a causal effect of gynoid fat on BMD but found no evidence of causality for visceral or total body fat. Gynoid fat shows a beneficial and causal effect on BMD, whereas the inverse associations observed for visceral and total body fat appear to be non-causal. These findings underscore the importance of considering fat distribution, not merely total body fat or weight, when evaluating bone health.