Zhu Ping, Li Ju, Meng Deqian, Wu Xinhua, Zhang Zhongyuan, Wang Jiajia, Wang Kai, Gu Shaohua
Department of Endocrinology, The Affiliated Chuzhou Hospital of Traditional Chinese Medicine of Jiangsu College of Nursing, Huaian, 223200, China.
Department of Rheumatology and Immunology, The Huaian Clinical College of Xuzhou Medical University, Huaian, 223001, China.
Clin Rheumatol. 2025 Jun 11. doi: 10.1007/s10067-025-07532-7.
Current studies have demonstrated an association between osteoporosis (OP) and lipidome traits, yet the causal relationship between OP and lipidome remains controversial. Therefore, our aim is to explore the relationship between the lipidome and OP by calculation of genetic susceptibility.
This study utilized a two-sample Mendelian randomization (MR) approach which the instrument variables were derived from a large genome-wide database: lipidome (7174 Finnish individuals), osteoporosis (56,637 samples), fractures (426,795 samples), heel bone density (426,824 samples), whole-body bone density (56,284 samples), femoral neck bone density (32,735 samples), lumbar spine bone density (28,498 samples), and forearm bone density (8143 samples). The primary results were based on inverse variance weighting (IVW) with random effects.
Based on the IVW results, we identified 138 significant associations between lipidome traits and osteoporosis and its traits (P < 0.05). Among these, 8, 24, 27, 37, 17, 8, and 17 lipid species were significantly associated with femoral neck bone density, forearm bone density, fractures, heel bone density, lumbar spine bone density, osteoporosis, and whole-body bone density, respectively. Triglycerides were found to be significant protective factors for osteoporosis, forearm BMD, and lumbar BMD, whereas phosphatidylcholine was considered a prominent risk factor for osteoporosis, fractures, heel BMD, and lumbar BMD. The results of the heterogeneity test indicated that our IVW analysis was largely free of heterogeneity (P > 0.05). However, the pleiotropy test revealed significant pleiotropy between heel bone density and the measurement of triacylglycerol (56:6) (P < 0.05).
By applying MR methods, this study overcomes the biases inherent in traditional observational studies and provides novel mechanistic insights into lipid metabolism in op. Key Points • One hundred thirty-eight significant associations found. • Triglycerides protective for some bone densities, phosphatidylcholine a risk factor, phosphatidylethanolamine protective against fractures. • Different lipidomic traits associated with various bone measures and fracture risk.
目前的研究已证实骨质疏松症（OP）与脂质组特征之间存在关联，但OP与脂质组之间的因果关系仍存在争议。因此，我们的目的是通过计算遗传易感性来探索脂质组与OP之间的关系。
本研究采用两样本孟德尔随机化（MR）方法，其工具变量来自一个大型全基因组数据库：脂质组（7174名芬兰人）、骨质疏松症（56637个样本）、骨折（426795个样本）、足跟骨密度（426824个样本）、全身骨密度（56284个样本）、股骨颈骨密度（32735个样本）、腰椎骨密度（28498个样本）和前臂骨密度（8143个样本）。主要结果基于具有随机效应的逆方差加权（IVW）。
基于IVW结果，我们确定了脂质组特征与骨质疏松症及其特征之间的138个显著关联（P < 0.05）。其中，分别有8、24、27、37、17、8和17种脂质与股骨颈骨密度、前臂骨密度、骨折、足跟骨密度、腰椎骨密度、骨质疏松症和全身骨密度显著相关。发现甘油三酯是骨质疏松症、前臂骨密度和腰椎骨密度的显著保护因素，而磷脂酰胆碱被认为是骨质疏松症、骨折、足跟骨密度和腰椎骨密度的突出危险因素。异质性检验结果表明，我们的IVW分析在很大程度上没有异质性（P > 0.05）。然而，多效性检验显示足跟骨密度与三酰甘油（56:6）测量之间存在显著多效性（P < 0.05）。
通过应用MR方法，本研究克服了传统观察性研究中固有的偏差，并为OP中的脂质代谢提供了新的机制性见解。要点 • 发现138个显著关联。 • 甘油三酯对某些骨密度有保护作用，磷脂酰胆碱是危险因素，磷脂酰乙醇胺可预防骨折。 • 不同的脂质组特征与各种骨测量和骨折风险相关。
