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

Gynoid fat was positively associated with bone mineral density at multiple skeletal sites in cross-sectional analysis.

• Positive associations were found between gynoid fat and BMD at the total body, femoral neck, and lumbar spine.
• Data were drawn from the National Health and Nutrition Examination Survey (NHANES).
• Multivariable linear regression was used to evaluate these relationships after adjustment for covariates.
• The association was consistent across all three BMD measurement sites examined.

Visceral fat and total body fat percentage showed consistent inverse associations with BMD across all measured skeletal regions.

• Inverse associations were observed for both visceral fat and total body fat percentage with BMD at total body, femoral neck, and lumbar spine.
• These inverse associations were consistent across all three skeletal regions assessed.
• The analysis used NHANES cross-sectional data with multivariable linear regression.
• Android fat and abdominal subcutaneous fat were also evaluated as regional fat depots in the analysis.

Two-sample Mendelian randomization supported a causal effect of gynoid fat on BMD.

• Two-sample MR was performed using genome-wide association study summary statistics for fat distribution traits and BMD.
• MR analysis provided evidence supporting causality for the gynoid fat–BMD relationship.
• The MR approach used genetic instruments derived from GWAS summary statistics to minimize confounding.
• This causal finding distinguished gynoid fat from other fat depots examined.

Mendelian randomization found no evidence of causality for visceral fat or total body fat on BMD, suggesting their observed inverse associations are non-causal.

• Despite inverse observational associations, MR analysis did not support a causal effect of visceral fat on BMD.
• Similarly, no causal effect of total body fat on BMD was identified through MR.
• The divergence between observational and MR findings suggests confounding or reverse causation may explain the inverse associations for visceral and total body fat.
• Two-sample MR used GWAS summary statistics for both fat distribution traits and BMD outcomes.

The study evaluated five regional fat depots in relation to BMD at three skeletal sites using a combination of observational and Mendelian randomization methods.

• Fat depots assessed included gynoid fat, android fat, visceral fat, abdominal subcutaneous fat, and total fat percentage.
• BMD was measured at total body, femoral neck, and lumbar spine.
• Cross-sectional analysis was conducted using NHANES data.
• Causal inference was assessed through two-sample MR using GWAS summary statistics.