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NSAID Exposure and Risk of Nonunion: A Meta-Analysis of Case–Control and Cohort Studies

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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for postoperative pain control. However, concerns regarding the potential deleterious effects of NSAIDs on bone healing have compelled many physicians to avoid NSAIDs in patients with healing fractures, osteotomies, and fusions. We systematically reviewed and analyzed the best clinical evidence regarding the effects of NSAID exposure on bone healing. Medline, Embase, and Cochrane electronic databases were searched for prospective and retrospective clinical studies of fracture, osteotomy, and fusion studies of patients with NSAID exposure and nonunion as an outcome. Study quality was assessed using the Newcastle–Ottawa Scale. Data on study design, patient characteristics, and risk estimates were extracted. Pooled effect estimates were calculated. Subanalyses were performed by bone type and by NSAID dose, duration, and route of administration. In the initial analysis of 11 cohort and case-control studies, the pooled odds ratio for nonunion with NSAID exposure was 3.0 (95% confidence interval 1.6–5.6). A significant association between lower-quality studies and higher reported odds ratios for nonunion was observed. When only higher-quality studies were considered, seven spine fusion studies were analyzed, and no statistically significant association between NSAID exposure and nonunion was identified (odds ratio = 2.2, 95% confidence interval 0.8–6.3). There was no increased risk of nonunion with NSAID exposure when only the highest-quality studies were assessed. Randomized controlled trials assessing NSAID exposure in fracture, fusion, and osteotomy populations are warranted to confirm or refute the findings of this meta-analysis of observational studies.

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Acknowledgments

The authors wish to thank Dr. M. Stoto (Harvard University) and Dr. J. Street (University of British Columbia) for their guidance. Ethical review board approval was not required for this review study.

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Authors and Affiliations

  1. Harvard School of Public Health, Harvard University, Boston, MA, USA

    Emily R. Dodwell, Julius Gene Latorre, Emilio Parisini, Elisabeth Zwettler & Divay Chandra

  2. Department of Orthopaedic Surgery, University of British Columbia, 3114-910 West 10th Avenue, Vancouver, BC, V5Z 4E3, Canada

    Emily R. Dodwell & Kishore Mulpuri

  3. Harvard Medical School and Children’s Hospital, Harvard University, Boston, MA, USA

    Brian Snyder

  4. 4th Medical Department and LBI of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, Vienna, Austria

    Elisabeth Zwettler

  5. Center for Nano Science and Technology of ITT at PoliMI, Milan, Italy

    Emilio Parisini

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  1. Emily R. Dodwell
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Correspondence to Emily R. Dodwell.

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Dodwell, Parisini, Zwettler and Latorre contributed equally to this work.

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Dodwell, E.R., Latorre, J.G., Parisini, E. et al. NSAID Exposure and Risk of Nonunion: A Meta-Analysis of Case–Control and Cohort Studies. Calcif Tissue Int 87, 193–202 (2010). https://doi.org/10.1007/s00223-010-9379-7

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