Causal association between inflammatory factors and osteoporosis under the perspective of osteoimmunology: a two-sample Mendelian randomization study

Objective: To evaluate the causal relationship between inflammatory factors and osteoporosis (OP). Method: Obtain GWAS data for 41 inflammatory factors and bone density (BMD) from the GWAScatalog database, and obtain GWAS data for OP from the Finnish database. Two sample Mendelian randomization analysis was conducted using inverse variance weighted method (IVW), MR Egger regression method (MER), weighted median method (WME), simple median method, and weighted median method, with IVW method as the main analysis method. Evaluate the causal relationship between inflammatory factors and OP and BMD using beta and OR values. Further sensitivity analysis will be conducted to verify the reliability of the results. Cochran's Q statistical method will be used to evaluate heterogeneity, MR Egger regression test for level pleiotropy, and one method will be used to assess the impact of single nucleotide polymorphisms on the results. The results of this study indicate a causal relationship between inflammatory factors and OP and BMD. Among them, tumor necrosis factor related apoptosis inducing ligand (TRAIL) and monocyte chemoattractant protein 1 (MCP-1/MCAF) are positively correlated with the risk of OP occurrence; Tumor necrosis factor beta (TNF - β) is negatively correlated with BMD in individuals aged 0-15 years old; There is a negative correlation between interleukin-7 (IL-7) and BMD in individuals aged 15-30; There is a negative correlation between hepatocyte growth factor (HGF) and BMD in individuals aged 30-45; Macrophage inflammatory protein 1 alpha (MIP-1 alpha) and macrophage colony-stimulating factor (M-CSF) are negatively correlated with BMD in individuals aged 60 and above; MIP-1 α is negatively correlated with BMD across all age groups. In addition, there may be unknown inflammatory factors that pose potential threats to OP and BMD. Conclusion: The causal effects of 41 inflammatory factors on OP and BMD were comprehensively evaluated using Mendelian randomization method. The results showed a causal relationship between inflammatory factors and OP and BMD, suggesting that OP patients can intervene in the occurrence and development of OP by intervening in inflammatory factors in the early stages of the disease.