The effect of nonsteroidal anti-inflammatory drugs on bone healing in humans: A qualitative, systematic review

Study objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in postoperative pain management. While an increasing number of in vitro and animal studies point toward an inhibitory effect of NSAIDs on bone healing process, the few existing retro- and prospective clinical studies present conflicting data. Design: The aim of this qualitative, systematic review was to investigate the impact of perioperative use of NSAIDs in humans on postoperative fracture/spinal fusion healing compared to other used analgesics measured as fracture nonunion with radiological control. Patients/interventions: We performed a systematic literature search of the last 38 years using PubMed Embase and the Cochrane Controlled Trials Register including retro- and prospective clinical, human trials assessing the effect of NSAIDs on postoperative fracture/spinal fusion healing when used for perioperative pain management with a radiological follow up to assess eventual nonunion. Due to different study designs, drugs, dosages/exposition times and different methods to assess fracture nonunion, these studies were not pooled for a meta analysis. A descriptive summary of all studies, level of evidence, study quality and study bias assessment using different scores were used. Main results: Three prospective randomized controlled studies and thirteen retrospective cohort human studies were identified for a total of 12'895 patients. The overall study quality was low according to Jadad and Oxford Levels of Evidence scores. Conclusions: Published results of human trials did not show strong evidence that NDAIDs for pain therapy after fracture osteosynthesis or spinal fusion lead to an increased nonunion rate. Reviewed studies present such conflicting data, that no clinical recommendation can be made regarding the appropriate use of NSAIDs in this context. Considering laboratory data of animal, human tissue research and recommendation of clinical reviews, a short perioperative exposition to NSAIDs is most likely not deleterious. However, randomized, controlled studies are warranted to support or refute this hypothesis.