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NSAID Use and Bone Healing: An Umbrella Review with a Reconstructed Meta-Analysis
Rinat Komargodski1, Sewar Kittany, Ibrahim Abu-Kishk
1From the School of Pharmacy (Komargodski, Kittany, Matok), Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, the Pharmacy Services (Komargodski), Shamir Medical Center (Assaf Harofeh), Zerifin, Affiliated to Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv, the Pediatric Intensive Care Unit (Abu-Kishk, Beeri Berkovitch), Shamir Medical Center (Assaf Harofeh), Zerifin, Affiliated to Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv, and the Pediatric Orthopedic Unit (Epstein), Shamir Medical Center (Assaf Harofeh), Zerifin, Affiliated to Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv.
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.
