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

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.

A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery

“…The debate is ongoing, but it has recently been demonstrated that ketorolac did not predispose to pseudoarthrosis in an adolescent idiopathic scoliosis surgical population [23]. Likewise, Dodwell et al [24] reviewed NSAID for postoperative pain treatment in seven high-quality retrospective studies in spine surgery and did not find an increased risk of pseudoarthrosis from shortterm NSAID use during a 12-month follow-up period. On the other hand, NSAIDs have demonstrated significant analgesic properties with reduced need of opioids followed by reduced levels of PONV [25].…”

Will My Tibial Fracture Heal? Predicting Nonunion at the Time of Definitive Fixation Based on Commonly Available Variables

“…Pro [32] NSAID use at admission Pro [13,27] Con [17,35] NSAID use at discharge Pro [13,27] Con [17,35] Opioid use at admission Pro [12] Opioid use at discharge Pro [12] Human immunodeficiency virus Pro [24] Con [20] Hepatitis C None Diabetes Pro [13,21,27] ASA score Pro [16] Smoking status Pro [13,21,31,36] Con [29,35] Alcohol use Pro [10,13,21] AO classification Pro [30] Con [2,22] ISS score Pro [30] TRISS score Pro [30] ICU days None * Pro articles support a correlation between nonunion and the variable; Con articles show that the variable has no correlation with nonunion; GSW = gunshot wound; NSAID = nonsteroidal anti-inflammatory drug; ASA = American Society of Anesthesiologists; AO = Arbeitsgemeinschaft für Osteosynthesefragen; ISS = Injury Severity Score; TRISS = Trauma and Injury Severity Score; ICU = intensive care unit.…”

Pubic Ramus Stress Fracture: Case Report

“…Hareket sırasında ağrının olmaması kemiğin iyileştiğinin belirtisidir. Deneysel hayvan çalışmalarında non streoid anti inflamatuvar ilaçların stres kırığının iyileşmesini geciktirdiği gösterilmiştir (13). Bifosfonat kullanımının etkinliği randomize kontrollü çalışmalar ile desteklenememiştir.…”