Exploring the Causal Relationship between Ibuprofen Use and Osteoarthritis Risk: A Mendelian Randomization Study
1
Institute of Biochemistry, Medical Faculty, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany
2
Division of Molecular and Experimental Surgery, Translational Research Center, Universitätsklinikum Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany
3
Muscle Research Center, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2024, 13(9), 748; https://doi.org/10.3390/biology13090748
Submission received: 19 August 2024
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Revised: 16 September 2024
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Accepted: 20 September 2024
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Published: 23 September 2024
(This article belongs to the Section Medical Biology)
Simple Summary
This study investigated whether using the common painkiller ibuprofen increases the risk of developing osteoarthritis, a joint disease that causes pain and stiffness. We used two-sample Mendelian randomization, which helped us understand the relationship between drugs and disease by examining genetic data. We analyzed data from multiple studies to see if people with certain genetic markers linked to ibuprofen use were more likely to develop osteoarthritis. Our findings suggest that ibuprofen use may indeed increase the risk of developing osteoarthritis. This finding is important because ibuprofen, while effective in relieving pain, may have long-term effects on joint health. These insights may help doctors make better decisions about the use of ibuprofen in patients at risk of developing osteoarthritis.
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.
Keywords:
ibuprofen; osteoarthritis; Mendelian randomization; GWAS; causal inference
