Bevacizumab, a vascular endothelial growth factor inhibitor, promotes orthodontic tooth movement in an experimental rat model

Abstract

Objective: This study aimed to evaluate the impact of bevacizumab on orthodontic tooth movement (OTM) in Wistar rats. Materials and methods: The OTM model was constructed by placing an orthodontic coil spring between the maxillary first molar and anterior tooth. Bevacizumab (Avastin®; 10 mg/kg twice per week) was started one week before the OTM and continued for 3 weeks. After 1 and 2 weeks, OTM distance and anterior tooth mobility were measured. Thereafter, the maxilla was dissected for micro-CT microarchitectural analysis, followed by histological analysis, and tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the distributions of collagen fibers type-I and –III (Col-I and Col-III) were evaluated using Picro-Sirius red staining. Results: Orthodontic force prompted bone resorption and formation on the pressure and tension sides, respectively. Bevacizumab therapy resulted in a 42% increase of OTM, particularly after 2 weeks. Furthermore, bevacizumab disturbed the morphometric structure at both pressure and tension sites. The histological evaluation indicated about 35–44% fewer osteoblasts in the bevacizumab group, especially at the tension side, whereas the proportion of TRAP-positive osteoclasts at the pressure side was 34–37% higher than the control. The mature Col-I was reduced at the tension site by 33%, whereas the Col-III/Col-I ratio was enhanced by 20–44% at pressure and tension sites, after 2 weeks, in the bevacizumab group. Conclusion: Anti-vascular bevacizumab therapy accentuates OTM in rat model, possibly through the enhancement of bone resorption, at the pressure side, and the reduction of bone formation, at the tension side as well as dysregulation of collagen fibers distribution.

Keywords

• Angiogenesis inhibitors
• Bevacizumab
• Orthodontics
• Orthodontic extrusion
• Tooth movement