Use of photodynamic therapy, beta-tricalcium phosphate and doxycycline in the alveolar repair of rats induced by osteonecrosis: microtomographical and laser confocal microscopy analysis

Abstract

Bisphosphonates are anti-resorptive drugs used in the treatment of skeletal disorders, such as osteoporosis, but their prolonged use may induce osteonecrosis of the jaw (MRONJ), which represents a challenging treatment for dentistry. The aim of this project will be to evaluate the preventive effect of therapies on MRONJ during the alveolar repair process in rats. For this, 360 wistar rats will be used, which will be treated with 04 applications of 0.035 mg / kg of zoledronic acid (ZOE) through the caudal vein with 15 days intervals between applications and subsequently have their right lower molars removed. After extraction, the animals will continue treatment with ZOE in the same protocol until euthanasia. The animals will be divided into seven groups according to the treatment of the dental socket: GS (Sham - ZOE will apply), GC (blood clot only), G² (²-tricalcium phosphate), GD (10% doxycycline), GP (photo-dynamic therapy), GD² (10% doxycycline + ²-tricalcium phosphate), GP² (photo-dynamic therapy + ²-tricalcium phosphate), GPD (photo-dynamic therapy + 10% doxycycline), GPD² (photo-dynamic therapy + 10% doxycycline + ²-tricalcium phosphate). . For in vivo analysis, in the calcified cuts will be used 72 animals, where after 36 days from the date of extraction, the animals will be euthanized for evaluation by 1) application of fluorochromes (calcein and alizarin) followed by confocal laser microscopy analysis. and 2) microtomographic analysis.