Low Intensity Pulsed Ultrasound for Accelerating Distraction Osteogenesis: A Systematic Review of Experimental Animal Studies

Abstract

The purpose of this report is to review systematically all studies performed regarding the influence of low intensity pulsed ultrasound (LIPUS) on bone regeneration in animals during distraction osteogenesis (DO). Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist structure, a systematic search using PubMed and EMBASE electronic databases was undertaken utilizing the key words "distraction osteogenesis" and "low intensity ultrasound". Human trials, review articles, case reports and non-English language publications were excluded. Data items were extracted from each eligible study, regarding the study design, risk of bias, results and whether or not LIPUS accelerated bone regeneration. The search identified 40 relevant articles, 15 of which were included for full review. Included studies were characterized by a high risk of bias and considerable variations in study design was observed. However, most studies which reported LIPUS in an intensity of 30-40 mW/cm 2 accelerated bone formation via endochondral ossification, thus shortening the consolidation period when applied during distraction and early consolidation periods. According to the current review, application of LIPUS during DO shows promise in accelerating bone formation and density during DO, that bears no adverse effects, thus shortening the consolidation period. Optimal timing of LIPUS application is during the distraction and early consolidation phases. The preferred intensity should be between 30-40 mW/cm 2. Histological analysis indicates influence via endochondral ossification. Thus, the effect of LIPUS on chondrocytes should be further investigated in order to decipher the exact molecular and cellular influence of LIPUS on enhancement of bone formation. These findings should be used in future clinical protocols and raise potential directions for future research regarding the molecular mechanisms underlying the influence of LIPUS on bone formation.