Zhang Kai, Wang Hongqiang, Wang Chuang, Liu Runze, Shi Xinge, Hu Weiran
Department of Spinal Cord Surgery, Henan Provincial People's Hospital, Zhengzhou, China.
People's Hospital of Zhengzhou University, Henan, China.
SAGE Open Med. 2025 Jul 29;13:20503121251360176. doi: 10.1177/20503121251360176. eCollection 2025.
Previous studies reported that many inflammatory factors have associations with osteoporosis. This study use Mendelian randomization (MR) analysis to explore the causal genetic relationship between 41 inflammatory factors and osteoporosis.
A bidirectional two-sample MR analysis was performed by employing five Mendelian randomization analysis methods including MR Egger regression, weighted median, inverse-variance weighted and weight mode methods. Summary statistics from the genome-wide association study (GWAS) of 41 inflammatory cytokines and osteoporosis were included in this study. This study examined the MR analysis results for heterogeneity and horizontal pleiotropy.
Using the inverse variance weighted (IVW) method, this analysis indicated that elevated monocyte chemotactic protein-1 (MCP-1) levels were potentially linked to a 22% increased likelihood of osteoporosis (Odds Ratio (OR) = 1.22, 95% CI: 1.04-1.43, = 0.014). Additionally, through the IVW approach, we observed that higher tumor necrosis factor-related apoptosis inducing ligand (TRAIL) levels were possibly associated with a 15% greater risk of osteoporosis (OR = 1.12, 95% CI: 1.03-1.29, = 0.012). Other 39 inflammatory cytokines don't have casual genetic association with osteoporosis. When this study use MR to estimate the influence of osteoporosis on inflammatory factors, none of the p-values with IVW method were lower than 0.05.
This is the first bidirectional MR analysis to explore the causal genetic relationship between inflammatory cytokines and osteoporosis. This study found that MCP-1 and TRAIL are probably the upstream factors correlated with osteoporosis, and no inflammatory cytokine was involved in osteoporosis development downstream.
既往研究报道，多种炎症因子与骨质疏松症相关。本研究采用孟德尔随机化（MR）分析，以探究41种炎症因子与骨质疏松症之间的因果遗传关系。
采用包括MR-Egger回归、加权中位数、逆方差加权和权重模式法在内的5种孟德尔随机化分析方法进行双向两样本MR分析。本研究纳入了41种炎症细胞因子和骨质疏松症的全基因组关联研究（GWAS）的汇总统计数据。本研究检验了MR分析结果的异质性和水平多效性。
采用逆方差加权（IVW）法，该分析表明单核细胞趋化蛋白-1（MCP-1）水平升高可能与骨质疏松症发生风险增加22%相关（优势比（OR）=1.22，95%置信区间：1.04-1.43，P=0.014）。此外，通过IVW方法，我们观察到肿瘤坏死因子相关凋亡诱导配体（TRAIL）水平升高可能与骨质疏松症风险增加15%相关（OR=1.12，95%置信区间：1.03-1.29，P=0.012）。其他39种炎症细胞因子与骨质疏松症无因果遗传关联。当本研究使用MR估计骨质疏松症对炎症因子的影响时，IVW法的所有P值均不低于0.05。
这是首次探索炎症细胞因子与骨质疏松症之间因果遗传关系的双向MR分析。本研究发现，MCP-1和TRAIL可能是与骨质疏松症相关的上游因素，且无炎症细胞因子参与骨质疏松症的下游发展。
