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.
Authors
- Charles Kooperberg (ORCID: https://orcid.org/0000-0002-7986-8560)
- Raji Balasubramanian (ORCID: https://orcid.org/0000-0002-1488-1692)
- Carolyn Crandall (ORCID: https://orcid.org/0000-0001-9441-0198)
- Eric A. Whitsel (ORCID: https://orcid.org/0000-0003-4843-3641)
- Feng Gao (ORCID: https://orcid.org/0000-0002-1641-2101)
- Jeff D. Yanosky
- Vrinda Kalia (ORCID: https://orcid.org/0000-0003-2244-6663)
- Diddier Prada (ORCID: https://orcid.org/0000-0002-6517-156X)
- Kathryn M. Rexrode (ORCID: https://orcid.org/0000-0003-3387-8429)
- Andrea Ramírez Varela (ORCID: https://orcid.org/0000-0003-2685-9617)
- Claudia María García-Cuellar (ORCID: https://orcid.org/0000-0001-8080-5797)
- Andrea Baccarelli (ORCID: https://orcid.org/0000-0002-3436-0640)
- David Cantú de León (ORCID: https://orcid.org/0000-0002-0229-7931)
- Alex P. Reiner (ORCID: https://orcid.org/0000-0002-1427-4470)
- Duanping Liao (ORCID: https://orcid.org/0000-0001-7405-6152)
- Jonathan González-Ruíz (ORCID: https://orcid.org/0000-0003-4323-4061)
- James D. Stewart (ORCID: https://orcid.org/0000-0002-2776-6570)
- Carol R. Horowitz
- Hui‐Chen Wu
Institutions
- Brigham and Women's Hospital (US)
- Pennsylvania State University (US)
- Harvard University (US)
- University of California, Los Angeles (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Instituto Nacional de Cancerología (MX)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Journal of Bone and Mineral Research
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1093/jbmr/zjaf059
- Citations
- 3
- Primary Topic
- Air Quality and Health Impacts
- Type
- article
- Field-Weighted Citation Impact
- 3.60
Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Cancer Institute