Abstract
Background: Non-steroidal anti-inflammatory drugs (NSAID) have excellent anti-inflammatory and analgesic properties and are extensively used to treat post-traumatic or surgical musculoskeletal pain. Although an extensive literature exists on the administration of NSAID on animal bone healing, no systematic review and meta-analysis have yet been conducted to on the subject. Such work is important as it can identify the key histomorphometric and biomechanics characteristics during the process of fracture healing and provide comparative information regarding different factors that may affect this process after NSAID administration.Methods: We performed a systematic review and meta-analysis of animal studies to estimate the effect of NSAID administration after bone fracture on healing outcomes. We searched eight databases without limiting the search to starting date up to August 1, 2017 for articles on fractured bone healing in animal models in which NSAID were administered.Results: Out of 5,818 articles screened, 45 were included and three common bone healing outcomes were analysed: biomechanical properties (maximum force to break, stiffness, and work-to-failure), micro-computed tomography (µ-CT), and histomorphometric measurements. The studies were generally of low-quality scores because crucial information, especially concerningrandomization, blinding, and allocation concealment, was poorly reported. Our results show that the negative effects of NSAID after bone fracture on certain biomechanical properties of the healing bones was not statistically significant in mice compared with other animals, in females compared with males, and in younger compared with older animals.Conclusion: The findings suggest that NSAID should be administered with caution in patients with bone fractures or in those who undergo certain orthopedic surgical procedures until prospective human clinical studies can be conducted.Systematic review registration: the protocol published and registered in SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) in 2017, https://www.radboudumc.nl/getmedia/757ec408-7a9e-4635-8233-ae951effea54/Non-Steroidal-Anti-inflammatory-Drugs-and-bone-healing-in-animal-Models-Systematic-Review-and-Meta-Analysis.aspx