Exploring the Causal Relationship between Ibuprofen Use and Osteoarthritis Risk: A Mendelian Randomization Study

Area of Science:

• Pharmacogenomics
• Rheumatology
• Genetic Epidemiology

Background:

• Osteoarthritis (OA) is a common joint disorder causing pain and stiffness.
• Ibuprofen (IBU) is widely used for pain relief, but its long-term effects on OA risk are unclear.

Purpose of the Study:

• To investigate the potential causal relationship between ibuprofen use and osteoarthritis risk.
• To assess if genetic predisposition to ibuprofen metabolism influences OA development.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using four osteoarthritis genome-wide association study (GWAS) datasets.
• Single-nucleotide polymorphisms (SNPs) associated with ibuprofen metabolism served as instrumental variables.
• Inverse variance weighted (IVW) and weighted median methods were employed for causal inference, with MR-Egger regression and Cochran's Q statistics used to assess pleiotropy and heterogeneity.

Main Results:

• MR analysis indicated a significant causal association between ibuprofen use and an increased risk of osteoarthritis.
• Meta-analysis of IVW and weighted median results yielded an odds ratio (OR) of 1.116 (95% CI = 1.063-1.170) for OA risk.
• Low pleiotropy and minimal heterogeneity confirmed the robustness of the findings.

Conclusions:

• The study provides strong evidence supporting a causal link between ibuprofen use and elevated osteoarthritis risk.
• Ibuprofen may potentially accelerate OA progression while providing symptomatic relief.
• Clinical practice should consider the long-term joint health implications of ibuprofen use.