Inflammatory factors and osteoporosis: a bidirectional Mendelian randomized study

Purpose: Osteoporosis (OP) poses a significant risk to the elderly population, which is rapidly increasing worldwide. Prior research has linked various inflammatory cytokines to the development of OP. This study employs Mendelian randomization (MR) to investigate the causal relationships between 41 inflammatory cytokines and OP, utilizing genetic variants as instrumental variables to clarify direct effects rather than mere associations. Methods: Genome-wide association studies summarize data of osteoporosis comprising 399,054 individuals (8,017 cases and 391,037 controls) for OP from Release 10 of FinnGen Biobank. The IEU OpenGWAS offered the GWAS data on 41 factors related to inflammation. MR is a statistical approach to minimize bias when analyzing whole genome sequencing data. This method offers a straightforward yet powerful framework that leverages genetic information to investigate various facets of human biology. Results: The results obtained from the inverse variance weighting (IVW) method suggest that lower circulating levels of interleukin-9 and higher levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interleukin-18 are potentially linked to an increased risk of OP. Furthermore, our analysis using reverse Mendelian randomization did not reveal any evidence that osteoporosis influences the levels of these inflammatory cytokines. This finding reinforces the notion that the relationship between these cytokines and osteoporosis may be primarily causal, rather than bidirectional. Conclusion: These findings indicate that TRAIL, IL-18, and IL-9 may play an essential role in developing OP. Further investigation is necessary to determine if these biomarkers have the potential to be utilized in the prevention or treatment of OP.