Efficacy of Adjuvant Treatment for Fracture Nonunion/Delayed Union: A Network Meta-Analysis of Randomized Controlled Trials

Background: Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis. Methods: A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions. Results: Thirty studies were included in analysis. For healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (Odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA+ACB (90%), and BMA alone (82%) showed relative advantages in healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (Standardized mean difference: -8.93; 95% confidence interval: -14.37, -3.48). LIUS (99%), BMA+PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Conclusions: Among the current intervention strategies, BMA and combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. However, large-scale, well-designed studies are still needed to confirm the results.Trial registration: retrospectively registered