Abstract
Background and Aim The association between obesity and osteoporosis (OP) remains complex and elusive. We elucidated the associations and identified the mediators between obesity/visceral adipose tissue (VAT) and bone mineral density (BMD) and OP in the UK Biobank population, as well as explored the causal associations between obesity/VAT and OP. Methods and Results We analyzed 38,026 UK Biobank participants. Multiple linear regression and logistic regression were used to investigate the association between obesity/VAT and both BMD and OP. Restricted cubic spline methods were used to assess nonlinear relationships. Mediation analysis assessed the mediating effects of biochemical indicators and inflammatory factors in obesity/VAT and OP. Mendelian randomization assessed the causal association between obesity/VAT and OP. The results showed a positive association between obesity/VAT and BMD at the vertebrae, femoral neck, and total body, as well as a negative association between obesity and the incidence of OP. Furthermore, nonlinear relationships were observed between VAT and both BMD and OP. Urate and phosphorus may exhibit a mediating trend in the relationship between obesity and OP. The Mendelian randomization results suggested a potential causal effect between obesity and OP, while VAT was associated with OP but without evidence of a causal link. Conclusions Our findings suggested that obesity and VAT were associated with a lower risk of OP and that urate and phosphorus demonstrated a potential mediating trend.</p>