Abstract
This study explored the potential causal relationship between ibuprofen (IBU) use and the risk of developing osteoarthritis, a prevalent joint disorder characterized by pain and stiffness. We conducted a two-sample MR analysis using four distinct OA GWAS datasets as outcomes and single-nucleotide polymorphisms (SNPs) associated with IBU metabolism as exposures. The inverse variance weighted (IVW) and weighted median methods were utilized to assess the causal association by meta-analysis, while pleiotropy and heterogeneity were evaluated using MR-Egger regression and Cochran's Q statistics. The MR analysis provided strong evidence for a causal association between IBU use and an increased risk of OA. A meta-analysis of the IVW and weighted median results across all datasets demonstrated an OR = 1.116 (95% CI = 1.063-1.170) and an OR = 1.110 (95% CI = 1.041-1.184). The consistency of the results obtained from different methods enhanced the reliability of the findings. Low pleiotropy and minimal heterogeneity were observed, further validating the results. The study supports a causal link between IBU use and an increased risk of OA, suggesting that IBU may accelerate the progression of OA while relieving symptoms. These findings highlight the importance of cautious use of IBU in clinical practice, especially considering its potential impact on long-term joint health.