The Robust Bidirectional Association Between Chronic Lung Disease and Incident Osteoporosis: A Two-Stage Individual Participant Data Meta-Analysis of Three International Longitudinal Cohorts (HRS, SHARE, and ELSA)

Abstract Background: The association between chronic lung disease (CLD) and osteoporosis (OP) is well-recognized, but the direction and magnitude of this relationship remain debated, particularly in aging populations. We aimed to quantify the bidirectional association between CLD (including COPD and asthma) and incident OP using a two-stage individual participant data (IPD) meta-analysis of three large longitudinal cohorts. Methods: We harmonized and analyzed individual-level data from the Health and Retirement Study (HRS, USA), the Survey of Health, Ageing and Retirement in Europe (SHARE, Europe), and the English Longitudinal Study of Ageing (ELSA, UK), all comprising adults aged greater than or equal to[≥]50 years. In the first stage, Cox proportional hazards models were fitted separately in each cohort to estimate hazard ratios (HRs) for the forward (CLD[->]OP) and reverse (OP[->]CLD) associations, adjusting for a comprehensive set of confounders (demographics, lifestyle, comorbidities, functional status). In the second stage, cohort-specific log HRs were pooled using fixed-effect meta-analysis. Heterogeneity was assessed with the I-squared statistic. Results: A total of 40,050 participants were included across the three cohorts. The pooled HR for incident OP among individuals with baseline CLD was 1.37 (95% confidence interval [CI] 1.24-1.51), with similar estimates for COPD (HR 1.47, 95% CI 1.27-1.69) and asthma (HR 1.35, 95% CI 1.22-1.50). For the reverse association, baseline OP was associated with increased risk of incident CLD (pooled HR 1.16, 95% CI 1.05-1.29), COPD (HR 1.28, 95% CI 1.11-1.47), and asthma (HR 1.17, 95% CI 1.05-1.30). Heterogeneity was low across all analyses (I2[≤]7.5%). Conclusion: This two-stage IPD meta-analysis provides robust evidence of a bidirectional relationship between CLD and OP in older adults. These findings underscore the need for integrated screening and management of both conditions in aging populations.