Metabolomic Evaluation of Air Pollution-related Bone Damage and Potential Mediation

Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from WHI participants with plasma samples. Whole-body, total hip, femoral neck, and spine BMD at enrollment and follow-up (Y1, Y3, Y6). Daily particulate matter NO, NO₂, PM₁₀ and SO₂ were averaged over 1-, 3-, and 5-year periods before metabolomic assessments. Statistical analyses included multivariable-adjusted linear mixed models, pathways analyses, and mediation modeling. NO, NO₂, and SO₂, but not PM₁₀, were associated with taurine, inosine, and C38:4 phosphatidylethanolamine (PE), at all averaging periods. We found a partial mediation of C38:4 PE in the association between 1-year average NO and lumbar spine BMD (p-value: 0.032). This is the first study suggesting that a PE may partially mediate air pollution-related bone damage in postmenopausal women.