Efficacy and safety of botulinum toxin type A in distraction osteogenesis of the lower extremities: a meta-analysis of randomized controlled trials.

[BACKGROUND] To explore the efficacy and safety of botulinum toxin in patients who received distraction osteogenesis of the lower extremities.

[METHODS] We searched the PubMed, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials that administered botulinum toxin to individuals who underwent distraction osteogenesis of the lower limbs. The final search was conducted on July 6, 2021. Quality assessments were conducted using the Cochrane risk of bias tool and the Jadad scale. We performed random-effects meta-analysis to calculate the standardized mean differences (SMDs) and confidence intervals (CIs) of the pooled effect sizes, and subgroup analysis and meta-regression were performed for potential moderators.

[RESULTS] Our analysis of four randomized controlled trials, which enrolled a total of 257 participants, revealed that the difference in pain during the distraction phase was not statistically significant between groups (SMD, - 0.165; 95% CI, - 0.379 to 0.050, p = 0.133, I = 0.0%). The meta-regression analyses did not find any influence on the effect size, considering age (β = - 0.0092; p = 0.61) and the amount of lengthening (β = 0.0023; p = 0.99). Subgroup analysis did not reveal difference between different doses of botulinum toxin and single or multi-site study design. An analysis of two randomized controlled trials enrolling a total of 177 individuals demonstrated a limited effect of botulinum toxin in reducing postoperative pain (SMD, - 0.239; 95% CI, - 0.641 to 0.162, p = 0.24, I = 37.6%), total adverse events (SMD, - 0.207; 95% CI, - 0.505 to 0.090, p = 0.17, I = 0.0%), and infection of pin site (SMD, - 0.131; 95% CI, - 0.428 to 0.165, p = 0.39, I = 0.0%). No botulinum toxin-related adverse events were reported.

[CONCLUSIONS] The current evidence does not support the administration of botulinum toxin in patients who receive distraction osteogenesis of the lower limbs. However, we were unable to draw decisive conclusions because of the limitations of our meta-analysis. Future well-designed, large-scale randomized controlled trials are necessary to confirm our conclusions.