BMI-mediated association between pulmonary function and bone mineral density moderated by age: Integrated Mendelian randomisation and cross-sectional study

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with multiple systemic comorbidities, including osteoporosis. Emerging evidence suggests a strong link between impaired pulmonary function and reduced bone mineral density (BMD). However, the biological mechanisms underlying this association remain incompletely elucidated. METHODS: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) on 10 944 participants with complete data. Multivariate linear regression and restricted cubic spline analyses were used to evaluate the association between FEV1/FVC and BMD. Stratified and sensitivity analyses were conducted to validate the robustness of the findings. We used moderated mediation analysis to identify the role of BMI and age in the FEV1/FVC-BMD relationship, and employed Mendelian randomisation (MR) analysis with genome-wide association study (GWAS) data to infer causality. RESULTS: < 0.001). Sensitivity analyses confirmed robustness. CONCLUSION: Impaired pulmonary function is associated with lower BMD, with BMI as a partial mediator and age as a significant effect modifier. These findings point to a complex interplay between pulmonary function, metabolic health, and skeletal integrity in individuals with airflow limitation, suggesting that interventions targeting these interactions may offer strategies to mitigate osteoporosis risk.