NSAID Use and Bone Healing: An Umbrella Review with a Reconstructed Meta-Analysis

This study combined an umbrella review of 16 prior systematic reviews/meta-analyses with a newly reconstructed meta-analysis of 38 primary studies to ask whether NSAIDs impair bone healing, and if so, in whom. Pooling roughly 82,000 NSAID-exposed and 756,000 unexposed patients, NSAID use was associated with higher odds of nonunion (OR 1.56, 95% CI 1.18-2.11), with the risk concentrated in adults, traumatic (not elective) fractures, long bones (not spine), and higher-dose regimens, while short courses of 14 days or less and pediatric patients showed no significant increase in risk.

AI summary · from the full text · reviewed by Pukhraj Gaheer, Medical Student, Queen's University before publishing

Why it mattersThis gives clerkship students and residents a risk-stratified framework for the common question of whether to give NSAIDs after a fracture, suggesting short low-dose courses are likely safe while caution is warranted with high-dose or prolonged use in adult long-bone fractures.

Presenting this at rounds? Start here

• ?The umbrella review found most source reviews were rated low or critically low quality by AMSTAR-2, and the reconstructed meta-analysis pooled RCTs, cohorts, and case-control studies with I2 as high as 83-93% for several key comparisons; how much should we trust pooled odds ratios built on such heterogeneous, largely observational data with likely confounding by indication (sicker or more severely injured patients may both need more analgesia and heal worse)?
• ?Given the nonsignificant finding for delayed union, no signal in pediatric patients, and no significant harm with short-term (<=14 day) use even in adults, how would you counsel a patient after an isolated long-bone fracture regarding a brief postoperative NSAID course for pain control?