# Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Use Is Associated With an Increased Risk of Femoral Osteonecrosis in Migraine Patients: A Retrospective, TriNetX Database-Based Study

## TL;DR

This study found that using NSAIDs for migraines is linked to a higher risk of femoral osteonecrosis, a condition caused by reduced blood flow to the femur.

## Contribution

The study is the first to show a significant association between NSAID use for migraines and femoral osteonecrosis using a large database.

## Key findings

- NSAID use in migraine patients was associated with a 3.6-fold increased risk of femoral osteonecrosis.
- The risk was significantly elevated in both male and female subgroups.
- The results were statistically significant across all analyzed cohorts.

## Abstract

Background and objective

Many patients across the United States suffer from migraines, which can be extremely painful and often require therapeutic management. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications for migraine treatment. However, these drugs may carry a potential risk of femoral osteonecrosis, as NSAID use can contribute to microthrombi formation in certain blood vessels and reduced blood flow. Therefore, further research is needed to determine whether the use of these anti-migraine medications is associated with an increased risk of developing femoral osteonecrosis. This study aimed to evaluate whether the use of common NSAIDs for the treatment of migraine is associated with an increased risk of osteonecrosis of the femur.

Methods

A retrospective analysis was conducted using the TriNetX database. The first cohort included patients aged 18 to 50 who had a diagnosis of migraine, no history of femoral neck fractures, and were prescribed any of the following NSAID medications: naproxen, aspirin, diclofenac, or ibuprofen. The second cohort consisted of patients from the TriNetX database who had migraines but were not prescribed any of the specified NSAID medications and had no history of femoral neck fractures. Comparable cohorts were also created and stratified by sex. Propensity score matching was performed to assess the most common risk factors associated with femoral osteonecrosis. The relative risk and odds ratio (OR) for outcomes of femoral osteonecrosis were compared between the two cohorts.

Results

Our findings revealed that across the overall cohort, as well as the male-only and female-only cohorts, there was a statistically significant difference in osteonecrosis outcomes between migraine patients who used NSAIDs and those who did not, indicating clinical significance. In the generalized cohort, anti-migraine medication use was associated with a significantly increased risk of femoral osteonecrosis (risk ratio (RR) = 3.606, 95% confidence interval (CI): 3.112-4.179; OR = 3.609, 95% CI: 3.114-4.182; p < 0.0001). Similarly, stratified analyses showed significant findings in males (RR = 3.897, 95% CI: 2.986-5.086; OR = 3.902, 95% CI: 2.989-5.094) and females (RR = 3.441, 95% CI: 2.872-4.122; OR = 3.443, 95% CI: 2.874-4.124; all p < 0.0001).

Conclusions

These findings are concerning, given the widespread use of NSAIDs for migraine management, as they may contribute to reduced blood flow to the femur and eventual ischemia.