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 D 3 synthesis. Biological evidence documents 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 fractures history at enrollment (2006-2010) and analyzed their environmental exposure data (2007-2010). Air pollution measurements included the annual averages of air particulate matter (PM 2.5 , PM 2.5-10 , and PM 10 ), nitrogen oxides (NO 2 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 eight-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 for 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 PM 10 , 20% for NO 2 , and 17% for NO x , respectively, with a 4-6% 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).