Department of Spinal Surgery, Southern Central Hospital of Yunnan Province, Honghe, China.
Department of Spinal Surgery, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, China.
Front Endocrinol (Lausanne). 2024 Sep 3;15:1439255. doi: 10.3389/fendo.2024.1439255. eCollection 2024.
Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density.
We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results.
MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively.
Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.
成纤维细胞生长因子 21（FGF21）是一种调节机体代谢的分泌蛋白。近年来，大量观察性研究发现 FGF21 与骨密度和骨质疏松密切相关，但它们之间的因果关系尚不清楚。因此，本研究采用两样本中介孟德尔随机化（MR）分析探讨 FGF21 与骨质疏松症和骨密度之间的因果关系。
我们利用公开的全基因组关联研究（GWAS）的遗传数据进行了两样本中介 MR 分析，该研究包括炎症细胞因子 FGF21 的遗传变异与全身骨密度、足跟骨密度、前臂骨密度、股骨颈骨密度、骨质疏松症。主要分析方法采用逆方差加权（IVW）来研究暴露与结局之间的因果关系。此外，还采用加权中位数、简单中位数法、加权中位数法和 MR-Egger 回归进行补充说明，并进行敏感性分析以评估结果的可靠性。
MR 结果表明，FGF21 过表达降低骨密度：全身骨密度（OR=0.920，95%CI：0.876-0.966），P=0.001）、足跟骨密度（OR=0.971，95%CI（0.949-0.993）；P=0.01）、前臂骨密度（OR=0.882，95%CI（0.799-0.973）；P=0.012）、股骨颈骨密度（OR=0.952，95%CI（0.908-0.998），P=0.039）；此外，还增加了骨质疏松症的风险（OR=1.003，95%CI（1.001-1.005），P=0.004）。敏感性分析支持这些结果的可靠性。FGF21 过表达对骨质疏松症的影响可能通过 2 型糖尿病和基础代谢率介导，介导效应分别为 14.96%和 12.21%。
本研究提示 FGF21 过表达可能导致骨密度降低，增加骨质疏松症风险，FGF21 对骨质疏松症的影响可能通过 2 型糖尿病和基础代谢率介导。本研究可为分析骨质疏松症的潜在机制提供参考，对骨质疏松症的防治具有重要意义。
