The risk of osteoporosis in COPD: An analysis of sex differences and mediating effects based on NHANES

Chronic obstructive pulmonary disease (COPD) and osteoporosis are significant public health concerns, often co-occurring due to shared risk factors such as ageing, smoking, and systemic inflammation, as well as treatment-related factors such as long-term glucocorticoid use. However, large-scale studies exploring these associations, their sex-specific effects, and mediating factors remain limited. A total of 8,274 participants aged ≥50 years from NHANES cycles 2005-2018 were included. COPD and osteoporosis were identified based on self-reported diagnoses, with Bone Mineral Density (BMD), measured by Dual-energy X-ray Absorptiometry (DXA), used as a sensitivity outcome. Weighted logistic regression analyzed the association between COPD and osteoporosis. Interaction and stratified analyses explored effect modification by sex, BMI, prednisone use, vitamin D, and race. Exploratory mediation analysis examined the indirect effects of prednisone, sleep problems, and vitamin D. COPD was significantly associated with osteoporosis risk (OR = 2.24, P < 0.001). A nominal sex interaction was observed (unadjusted P = 0.03), with a stronger association in males (adjusted OR = 4.85, 95% CI: 2.49-9.42, P < 0.001) than females (adjusted OR = 1.86, 95% CI: 1.30-2.65, P < 0.001). Exploratory mediation analyses suggested that prednisone use (mediated 5.1%) and sleep problems (mediated 9.3%) accounted for portions of the association, while vitamin D level did not show meaningful mediation. Sensitivity analyses confirmed an association between COPD and lower BMD (β = -0.032, P < 0.001), with significant mediation by prednisone (2.2%, P = 0.034). COPD is significantly associated with osteoporosis, with a stronger relative effect observed in males. Exploratory findings suggest potential mediation by prednisone use and sleep disorders. These results highlight the importance of integrated bone health management in COPD patients, with particular attention to sex-specific risks and modifiable factors such as glucocorticoid exposure and sleep quality.