The effect of coffee consumption on three main bone disorders: a Mendelian randomization trial.

Introduction: Despite a large number of observational studies examining the effect of coffee consumption(CC) on bone disorders(BDs), particularly, osteoarthritis(OA), osteoportic fracture(OF), and rheumatoid arthritis(RA), the conclusions are highly controversial. Thus, it is essential to examine the causal association between CC and BDs.

Materials and methods: Mendelian randomization (MR) analysis was performed to assess the causal influence of CC on OF, RA, and OA. The main endpoint was the odds ratio (OR) of the inverse variance weighted (IVW) approach. In addition, the weighted median (WM), MR-Egger regressions, MR-pleiotropy residual sum and outlier (MR-PRESSO) and multivariable MR (MVMR) were included in sensitivity analyses. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks.

Results: Primary MR analysis based on the IVW method suggested that changes in CC alter risk of OF (OR = 1.383, 95%CI 1.079-1.853, P = 0.039), RA(OR: 1.623, 95%CI 1.042-2.527, P = 0.032) and HOA (hip osteoarthritis, OR = 1.536, 95% CI 1.044-2.259, P = 0.021). However, these causal relationships were not robust in sensitivity analyses. In contrast, there is a positive causal relationship between increased CC and the risk of KOA (knee osteoarthritis, OR: 2.094, 95%CI: 1.592-2.754, P = 1.41 × 10^-7), as evidenced by the IVW using random effect. A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy.

Conclusion: Based on our MR analysis, increased CC was causally linked to an increase in the risk of KOA. Genetic predictions suggested that CC reduction may have benefits for bone health.