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SYSTEMATIC REVIEW article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1428240

Do NSAIDs Affect Bone Healing Rate, Delay Union, or Cause Non-union: An Updated Systematic Review and Meta-Analysis

Provisionally accepted
Po-Yao Chuang Po-Yao Chuang Tien-Yu Yang Tien-Yu Yang Yao-Hung Tsai Yao-Hung Tsai Kuo-Chin Huang Kuo-Chin Huang *
  • Chiayi Chang Gung Memorial Hospital, Chiayi City, Taiwan

The final, formatted version of the article will be published soon.

    Nonsteroidal anti-inflammatory drugs (NSAIDs) may potentially result in delayed or non-union of fractures by inhibiting prostaglandin synthesis. However, studies have provided conflicting results. This systematic review and meta-analysis aimed to gather and synthesize current evidence on the potential influence of NSAIDs on bone healing.We searched the PubMed, Embase and Cochrane CENTRAL databases for relevant studies published up to July 25, 2023. Specific keywords were: "NSAID," "nonsteroidal anti-inflammatory drug," "cyclooxygenase-2 inhibitor," "bone healing," "non-union," "pseudoarthrosis," "delayed union," and "atrophic bone". Prospective, retrospective, and case-controlled studies assessing the correlation between NSAID use and bone healing outcomes were eligible for inclusion. The leave-one-out approach was used to test the robustness of the meta-analysis results. Twenty studies with a total of 523,240 patients were included in the analysis. The mean patient age ranged from 6.7 to 77.0 years, and follow-up duration ranged from 3 to 67 months.Meta-analysis revealed no significant difference in non-union or delayed union between NSAIDs user and non-user (pooled adjusted odds ratio [OR] = 1.11, 95% confidence interval [CI]: 0.99-1.23). The initial analysis identified a significant association between NSAID usage and an increased risk of reoperation. However, this association became insignificant upon conducting sensitivity analyses (crude OR = 1.42, 95% CI: 0.88-2.28). In conclusions, NSAIDs may have a minimal impact on non-union or delayed union risks, though interpretative caution is advised due to the limited number of studies and the absence of specific focus on NSAID types and dosages.

    Keywords: Nonsteroidal anti-inflammatory drugs (NSAIDs), Cyclooxygenase-2 (COX-2) inhibitor, bone healing, Non-union, Delayed union

    Received: 13 May 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Chuang, Yang, Tsai and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kuo-Chin Huang, Chiayi Chang Gung Memorial Hospital, Chiayi City, Taiwan

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