Effects of NSAID use on bone healing: A meta-analysis of retrospective case–control and cohort studies within clinical settings

Abstract

Introduction This meta-analysis aims to determine whether non-steroidal anti-inflammatory drug (NSAID) use is significantly associated with adverse bone healing outcomes within clinical settings, including trauma and elective spine settings. It will also explore bone healing outcomes with the type, route, dosage and duration of NSAID exposure and aims to demonstrate the effects of various other confounding factors on bone healing outcomes. Methods Electronic databases including MedLine, Embase and Cochrane were searched from January 1975 to December 2017. A distinct analysis of observational long bone and spine studies in adult populations was performed, assessing the effects of NSAID exposure on bone healing. Studies from paediatric population and randomised trials also underwent separate assessment in the synthesis. Meta-analysis was conducted in compliance with QUORUM and PRISMA guidelines. Results Quantitative assessment of observational studies suggested a significant risk of bone healing complications with NSAID exposure across each clinical group: long bone (p = 0.0004) and spine (p = 0.02). Analysis of paediatric studies revealed a non-significant association of poor outcomes with NSAID use (p = 0.36), while assessment of randomised trials demonstrated a statistically significant risk of complications following NSAID administration (p = 0.04). Meta-regression further suggested smoking to be a substantial confounder associated with adverse bone healing outcomes (p < 0.00001). Conclusion Inclusion of only fair and moderate-quality retrospective cohort and case–control studies in the current synthesis limits the clinical application of its findings and therefore warrants the need for further research. Thus, attempts to conduct high-quality prospective cohort and randomised trials to study the effects of NSAID use on bone healing would be very helpful and will provide a basis for more extensive research in future.

Pain Management Strategies After Orthopaedic Trauma: A Mixed-Methods Study with a View to Optimizing Practices

“…This may be due to the fact that pain management protocols do not automatically include NSAIDs and that clinicians may be reluctant to use them considering their effects on bone healing and the risk of bleeding after an injury. [84][85][86] As for cannabis, although most participants smoked it for recreational purposes, several also recognized its properties for pain relief and the improvement of associated symptoms. Previous studies have shown a marked interest (> 70%) in medical cannabis for patients after musculoskeletal injuries and orthopaedic procedures.…”

Does the use of NSAIDs for analgesia in fracture care contribute to delayed fracture healing?

“…A 2020 meta-analysis (11 retrospective cohort studies, n=12,962; single prospective double-blind randomized controlled trial [RCT], n=98; single prospective cohort within a RCT, n=190; single retrospective case-control, n=377; single case-control, n=2,815) explored if the use of NSAIDs during the bone healing process is associated with an increased risk of bone healing complications. 1 Observational studies and RCTs on long bone fractures and spinal fusion, which assessed the effects of perioperative NSAID exposure on bone healing outcomes in all ages and sexes, were included. In vitro and animal studies were excluded along with review articles and studies with undefined methodology and/or insufficient data for analysis.…”