Abstract
Objective: This study utilized Mendelian randomization to elucidate the causal relationship between Phosphatidylcholine (O-17:0_15:0) levels and osteoporosis, exploring the mediating roles of inflammatory factors and immune cells.
Methods: The genetic information of osteoporosis patients was obtained from the Finnish FinnGen project, with supplementary data including sequencing results for 179 liposome, 91 inflammatory factors, and 713 immune cells sourced from GWAS summary datasets. In this study, we analyzed liposome profiles as the exposure and osteoporosis as the outcome, with inflammatory factors and immune cells being examined as mediating factors. Two-sample Mendelian randomization, employing the inverse variance weighted method, and mediation analyses were conducted to assess the impact of Phosphatidylcholine on osteoporosis through inflammatory and immune pathways. Analyses of heterogeneity and pleiotropy was also conducted to assess the complexity and potential biases in the causal relationship between identified liposome and osteoporosis.
Results: Our analysis has unveiled a significant positive causal relationship between the levels of Phosphatidylcholine (O-17:0_15:0) in serum and the risk of osteoporosis. Notably, it was observed that the levels of Phosphatidylcholine (O-17:0_15:0) in serum contribute to the downregulation of tumor necrosis factor (TNF) and the activation of CD16-CD56 positive natural killer (NK) cells, both of which are protective factors against osteoporosis. This dual mechanism underscores the complex interplay between liposome and bone health, providing new insights into the pathophysiology of osteoporosis and highlighting potential targets for therapeutic intervention. Sensitivity analyses confirmed the robustness of these findings, showing no evidence of pleiotropy or reverse causation.
Conclusion: This study provides compelling evidence that Phosphatidylcholine (O-17:0_15:0) levels causally affect osteoporosis risk, with significant mediation effects observed through both inflammatory and immune mechanisms. These findings offer new insights into the complex interplay between lipid metabolism, inflammation, and immune regulation in osteoporosis, suggesting potential targets for therapeutic intervention in bone-related diseases.