NSAID Use and Bone Healing: An Umbrella Review with a Reconstructed Meta-Analysis.
Rinat Komargodski, Sewar Kittany, Ibrahim Abu-Kishk et al.
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In 30 seconds
This umbrella review and reconstructed meta-analysis examined whether NSAID exposure is associated with impaired bone healing and whether risk varies by patient group, procedure, dose, and duration. It included 16 systematic reviews and pooled 38 primary studies. NSAID exposure was associated with higher nonunion risk (OR, 1.56, 95% CI, 1.18 to 2.11), but not clearly with delayed union. Associations varied across populations and clinical contexts: risk was higher in adults and long-bone fractures, while short-term use (≤14 days) was not associated with increased nonunion risk.
Key findings
- NSAID exposure was associated with higher nonunion risk (OR, 1.56, 95% CI, 1.18 to 2.11).
- The association with delayed union was unclear (OR, 1.58, 95% CI, 0.65 to 3.67).
- Nonunion risk was higher in adults (OR, 1.67, 95% CI, 1.25 to 2.47), but not in pediatric patients (OR 0.77, 95% CI 0.58 to 1.02).
- Risk was higher in traumatic fractures than elective procedures; short-term use (≤14 days) was not associated with increased nonunion risk.
Why it matters
NSAIDs are commonly used for perioperative analgesia, and their potential effect on bone healing remains clinically relevant. These findings suggest that any association with nonunion may depend on patient population, injury or procedure context, dose, and duration rather than applying uniformly. The review also reports low or critically low quality among included reviews, so the estimates warrant cautious interpretation.
What to keep in mind
The included reviews were mostly low or critically low quality, and the reconstructed meta-analysis pooled primary studies with differing populations and clinical contexts.