A Meta-analysis of Randomized Controlled Trials of Adjunctive Biophysical Stimulation for Bone Regeneration Across Distraction Osteogenesis, Limb Reconstruction, and Delayed Union.

Background: Impaired bone regeneration remains a major challenge in orthopedic reconstruction, particularly in distraction osteogenesis, limb reconstruction, and delayed union, where prolonged healing increases treatment burden and complication risk. Adjunctive biophysical stimulation, including low-intensity pulsed ultrasound and pulsed electromagnetic field stimulation, has been investigated as a noninvasive strategy to improve bone-healing outcomes, but evidence in reconstructive orthopedic settings remains limited and heterogeneous. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020. PubMed/MEDLINE, Scopus, and Web of Science were searched from database inception to March 21, 2026. Eligible studies evaluated adjunctive low-intensity pulsed ultrasound or pulsed electromagnetic field stimulation in distraction osteogenesis, limb reconstruction, or delayed union using comparative control groups. Random-effects meta-analysis was performed for clinically comparable outcomes. Fixation-normalized healing outcomes were pooled as mean differences, radiographic healing outcomes as standardized mean differences, and methodological quality was assessed using RoB 2. Results: Seven randomized controlled trials met eligibility criteria for qualitative synthesis. Two studies contributed to quantitative pooling of fixation-normalized healing efficiency, demonstrating significantly shorter healing duration with adjunctive intervention compared with control (mean difference, -16.78 days/cm; 95% CI, -22.72 to -10.83; P < 0.001; I² = 0%). Three studies contributed to radiographic meta-analysis, showing a significant benefit favoring adjunctive biophysical stimulation (SMD, 0.40; 95% CI, 0.07-0.74; P = 0.02; I² = 42.1%). Secondary clinical burden and safety outcomes were not suitable for quantitative pooling because of heterogeneous reporting. Six studies were judged as having some concerns and one as high risk of bias. Conclusions: Adjunctive biophysical stimulation was associated with favorable healing-related outcomes in selected distraction osteogenesis, limb reconstruction, and delayed-union settings. However, the evidence base remains limited by small study numbers, methodological heterogeneity, and inconsistent outcome reporting, supporting the need for larger contemporary randomized trials.