Metabolomic evaluation of air pollution-related bone damage and potential mediation in Women's Health Initiative participants

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 Women's Health Initiative (WHI) participants with plasma samples. Whole-body, TH, FN, and spine BMD were determined using DXA at enrollment and follow-up visits (years 1, 3, 6, and 9 visits; Y1, Y3, Y6, Y9, respectively). Geocoded, participant address-specific, daily particulate matter nitrogen oxide (NO), nitrogen dioxide (NO₂), particulate matter ≤10 μm (PM₁₀), and sulfur dioxide (SO₂) concentrations were averaged over 1-, 3-, and 5-yr periods before plasma sampling for metabolomic assessments (at baseline and Y1 visit). The averages were then integrated using masked WHI participant identifiers. Statistical analyses included multivariable-adjusted linear mixed models, pathway analyses, and mediation modeling. At all averaging periods, NO, NO₂, and SO₂, but not PM₁₀, were associated with taurine, inosine, and C38:4 phosphatidylethanolamine (PE). We found a partial potential mediation of C38:4 PE in the association between 1-yr average NO and LS BMD (p-value:. 032). This is the first study suggesting phospholipids may partially mediate air pollution-related bone damage in postmenopausal women.