Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, China.
Gansu Province Orthopaedic Clinical Medicine Research Center, Lanzhou, China.
Biol Res Nurs. 2025 Jan;27(1):91-100. doi: 10.1177/10998004241279934. Epub 2024 Aug 30.
This study aimed to explore the relationship between circulating metabolites and postmenopausal osteoporosis (PMOP) and to assess the mediating role of inflammatory factors. 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. 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, = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. 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.
本研究旨在探讨循环代谢物与绝经后骨质疏松症（PMOP）之间的关系，并评估炎症因子的中介作用。利用全基因组关联研究（GWAS）的汇总数据，采用孟德尔随机化方法，对循环代谢物与 PMOP 之间的关系进行了两样本 MR 分析。此外，还采用两步 MR 方法来量化炎症因子对循环代谢物影响 PMOP 的中介作用。研究结果表明，某些代谢物与 PMOP 的风险之间存在显著关联，特别是非常大 VLDL 颗粒中游离胆固醇与总脂质的比值（OR：1.399，95%CI：1.002-1.954， = 0.048）和 IL-16（OR：0.773，95%CI：0.608-0.983， = 0.036）。IL-16 被发现部分介导了循环代谢物对 PMOP 的影响，其介导效应为 10.4%。本研究强调了循环代谢物和炎症因子在 PMOP 发病机制中的关键作用。建立了循环代谢物与 PMOP 之间的因果关系，IL-16 介导了部分效应。这些发现为 PMOP 的早期检测、个性化医疗和治疗靶点的识别提供了临床应用的前景。
