Associations of long-term exposure to ambient air pollution with fracture risk and bone mineral density: A cohort study of 0.5 million Chinese adults.

BACKGROUND: Evidence regarding the effects of air pollution on bone damage remains limited and inconclusive. We aimed to investigate the individual and combined associations of long-term exposure to ambient air pollutants with fracture risk and bone mineral density (BMD). METHODS: This study included 490,172 participants from the China Kadoorie Biobank who were free of prior fractures at baseline, among whom 32,545 received calcaneus BMD measurement using quantitative ultrasound in the second or third resurveys. Annual mean concentrations of particulate matter with diameters≤ 2.5μm (PM2.5), ≤ 10μm (PM10), nitrogen dioxide (NO2), and warm-season ozone (O3) were assigned to participants based on the geographic locations of recruitment clinics in their communities, using 1 × 1 km resolution. Incident fracture cases were defined as the first occurrence of fracture at any anatomical site, excluding those least likely due to osteoporosis and most likely due to severe trauma or cancer. Time-varying Cox proportional hazard models and linear mixed models were used to examine individual associations between air pollutant exposure and incident fracture risk, and longitudinal changes in BMD, respectively. Principal component analysis and quantile-based g-computation were applied to evaluate the combined effects of air pollutants and the relative contributions of each pollutant. Mediation analyses were performed to investigate the potential mediating role of BMD in the associations between pollutant and fracture risk. FINDINGS: During a median follow-up of 12.0 years, 15,614 fractures were identified. Long-term exposure to PM2.5 and warm-season O3 was associated with an increased risk of any fracture, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.09 (1.05, 1.13) and 1.08 (1.04, 1.12), respectively, per 10 µg/m3 increase in concentration. For each unit increase in the principal component score for air pollutants, the HR (95%CI) for any fracture was 1.08 (1.03, 1.13). PM2.5 contributed most to the elevated fracture risk (70%), followed by warm-season O3 (30%). Higher levels of air pollution were associated with lower BMD, with BUA, SOS, SI, and T-score lowering by 0.263 (95%CI: 0.220, 0.305), 0.265 (0.225, 0.306), 0.299 (0.264, 0.334), and 0.311 (0.274, 0.347) (in units of standard deviation) for per principal component score increment, respectively. The decline in the latter three BMD measures accounted for 5.80-8.59% of the association between pollutants and fracture risk. INTERPRETATION: Long-term co-exposure to PM2.5, PM10, NO2, and warm-season O3 was associated with lower BMD and increased fracture risk, with reduced BMD potentially acting as a modest partial mediator. PM2.5 consistently exhibited the greatest contribution to the associations between air pollutants and both fracture risk and BMD. Our findings suggest that adherence to fine particulate matter control and enhanced pollutant synergism may play an important role in bone health promotion in aging populations.