Exposure to Multiple Air Pollutants and the Risk of Fractures: A Large Prospective Population-Based Study

Atmospheric chemistry studies suggest air pollution impedes ultraviolet B photons and thus reduces cutaneous vitamin D₃ synthesis. Biological evidence shows that inhaled pollutants disrupt circulating 25-hydroxyvitamin D (25[OH]D) metabolism and ultimately impact bone health. The hypothesis is that higher air pollution concentrations are associated with a higher risk of fractures, mediated by lower circulating 25(OH)D. The study included participants of the UK Biobank who were free of fracture history at enrollment (2006 to 2010) and analyzed their environmental exposure data (2007 to 2010). Air pollution measurements included the annual averages of air particulate matter (PM_2.5 , PM_2.5-10 , and PM₁₀ ), nitrogen oxides (NO₂ and NO_x ), and a composite air pollution score. Multivariable Cox proportional hazard models were used to assess the associations of the individual pollutants and the score with fracture risks. Mediation analyses were conducted to assess the underlying role of serum 25(OH)D in such associations. Among 446,395 participants with a median of 8-year follow-up, 12,288 incident fractures were documented. Participants living in places with the highest quintile of air pollution score had a 15.3% increased risk of fractures (hazard ratio [95%CI]: 1.15[1.09,1.22]) compared to those in the lowest, and 5.49% of this association was mediated through serum 25(OH)D (p_mediation  < 0.05). Pollutant-specific hazard of top-to-bottom quintiles was 16% for PM_2.5 , 4% for PM_2.5-10 , 5% for PM₁₀ , 20% for NO₂ , and 17% for NO_x , with a 4% to 6% mediation effect of serum 25(OH)D concentrations. The associations of the air pollution score with fracture risks were weaker among female participants, those who drank less alcohol, and consumed more fresh fruit than their counterparts (p_interaction  < 0.05). © 2023 American Society for Bone and Mineral Research (ASBMR).