JAAOS - 2026-07-21 - Journal Article
NSAID Use and Bone Healing: An Umbrella Review with a Reconstructed Meta-Analysis.
Komargodski R, Kittany S, Abu-Kishk I, Beeri Berkovitch R, Epstein D, Matok I
Topics
Key Takeaway
NSAID exposure increases nonunion risk overall (OR 1.56, 95% CI 1.18–2.11), but short-term use ≤14 days was not associated with elevated risk, and the signal was absent in pediatric patients and spinal fusion.
Summary Depth
Choose how much analysis to show on this article page.
Summary
This umbrella review and reconstructed meta-analysis evaluated whether NSAIDs impair bone healing across subgroups defined by age, fracture type, dose, and duration. Pooling 38 primary studies, NSAID use was associated with increased nonunion risk (OR 1.56, 95% CI 1.18–2.11) but not delayed union (OR 1.58, 95% CI 0.65–3.67); risk was significant in adults (OR 1.67) but not pediatric patients (OR 0.77), higher in long-bone fractures than spinal fusion, and absent with ≤14-day exposure. Most included reviews were rated low or critically low quality by AMSTAR-2.
Key Limitation
The majority of included systematic reviews were rated low or critically low quality by AMSTAR-2, meaning the reconstructed meta-analysis inherits substantial heterogeneity and potential selection bias from its source literature.
Original Abstract
AIMS
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for perioperative analgesia, but effect on bone healing remains controversial. This umbrella review and reconstructed meta-analysis assessed whether NSAIDs impair bone healing and how risk varies by population, fracture type, dose, and duration.
METHODS
We conducted an umbrella review of systematic reviews/meta-analyses and a reconstructed meta-analysis of primary studies (PRIOR/PRISMA-compliant; PubMed, EMBASE, Web of Science, and Scopus to 9 November 2025). Two reviewers independently screened, extracted, and assessed quality (AMSTAR-2) and risk of bias. Overlapping cohorts were removed, and random-effects models were applied. Prespecified subgroups included age, clinical context (traumatic vs elective procedures), bone type (long bones vs spine), dose, and exposure duration (≤14 days).
RESULTS
Sixteen reviews (10 meta-analyses, six systematic reviews) were included; most suggested that NSAIDs increase impaired bone healing risk, particularly with higher doses or prolonged use, with minimal signal for short, low-dose perioperative regimens, especially in spinal fusion. Quality was low/critically low. The meta-analysis 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 (OR, 1.58, 95% CI, 0.65 to 3.67). Risk increased 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), was higher in long-bone fractures than in spinal fusion, trended upward with higher doses, and was not elevated with short-term (≤14 days) use. Risk also differed by clinical context, higher in traumatic versus elective procedures.
CONCLUSIONS
NSAID-related impairment of bone healing seems dose and context-dependent, with clinically important risk particularly in adults, long-bone fractures, and higher dose regimens. Short-term use (≤14 days) was not associated with increased nonunion risk. Risk seemed higher in traumatic fractures than in elective procedures. These findings support caution in higher risk scenarios, suggesting that short-duration NSAID use may be safe when avoiding higher dose exposure.