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

**Authors:** Yongzhi Jian, Yanmin Lyu, Said Hashemolhosseini

PMC · DOI: 10.3390/biology13090748 · 2024-09-23

## TL;DR

This study suggests that using ibuprofen may increase the risk of developing osteoarthritis, a joint disease, based on genetic data analysis.

## Contribution

The study provides new evidence of a causal link between ibuprofen use and increased osteoarthritis risk using Mendelian randomization.

## Key findings

- Ibuprofen use is associated with a 11% increased risk of osteoarthritis (OR = 1.116).
- Results were consistent across multiple genetic analysis methods with low pleiotropy and heterogeneity.
- Findings suggest ibuprofen may worsen joint health over time despite pain relief.

## Abstract

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.

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.

## Linked entities

- **Chemicals:** ibuprofen (PubChem CID 3672)
- **Diseases:** osteoarthritis (MONDO:0005178)

## Full-text entities

- **Diseases:** joint disorder (MESH:D007592), stiffness (MESH:C566112), pain (MESH:D010146), OA (MESH:D010003)
- **Chemicals:** IBU (MESH:D007052)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11428583/full.md

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Source: https://tomesphere.com/paper/PMC11428583