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Methods: Utilizing summary-level data from genome-wide association studies (GWAS) and employing a Mendelian Randomization approach, a two-sample MR analysis was conducted to assess the relationship between circulating metabolites and PMOP. Additionally, a two-step MR was used to quantify the mediating impact of inflammatory factors on the effect of circulating metabolites on PMOP. Results: The results revealed a significant association between certain metabolites and the risk of PMOP, notably the ratio of free cholesterol to total lipids in very large VLDL particles (OR: 1.399, 95% CI: 1.002-1.954, p = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, p = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. Conclusion: This study underscores the crucial role of circulating metabolites and inflammatory factors in PMOP pathogenesis. A causal relationship between circulating metabolites and PMOP was established, with IL-16 mediating some effects. These findings hold promise for clinical applications in early detection, personalized medicine, and the identification of therapeutic targets for PMOP.<\/jats:p>","DOI":"10.1177\/10998004241279934","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T10:58:35Z","timestamp":1725015515000},"page":"91-100","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["IL-16 Mediates the Effect of Circulating Metabolites on Postmenopausal Osteoporosis: A Two-Step, Multivariable Mendelian Randomization Study"],"prefix":"10.1177","volume":"27","author":[{"given":"Yi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China"},{"name":"Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China"},{"name":"Gansu Province Intelligent Orthopedics Industry Technology Center, Lanzhou, 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