Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients

Abstract

Aim: The aim of this study is to replicate both clinical and histological presentation of bisphosphonate induced osteonecrosis of the jaws (BONJ) in an animal model of the disease state. Successful recapitulation of a BONJlike indication in an animal model will be useful for studying pathogenesis, as well as prevention and treatment strategies for BONJ. Materials and Methods: Eighty (80) rats were prospectively and randomly divided into two groups; control group(40) and study group(40). All animals in study group, injected with a dose of 1 mg/kg dexamethasone (DX) subcutaneously on day 7, 14, or 21; and 1, 2, or 3 doses of 7.5 µg/kg zoledronic acid (ZA) subcutaneously administered to coincide with the last day of DX. Half of the animals from each group underwent extraction of the left mandibular molars and the remaining animals underwent extraction of the left maxillary molars under pentobarbital-induced general anesthesia. All animals were euthanized twenty-eight (28) days following tooth extractions. Results: The amount of new bone trabecules as significantly decreased in bisphosphonate-dexamethasone (BP-DX) treated sockets. Difference between both groups was found statistically significant (p=0,0001). There's no foreign body reaction in sockets of both groups and no significance difference observed for fibrosis (p=0,306). The necrosis scores were significantly higher in BP-DX treated sockets (p=0,015). The inflamation scores were significantly higher for study group (p=0,0001). Conclusion: This study provides preliminary observations for the development of an animal model of BONJ. But we think that there is need for other studies have only BP treated group and larger study population.

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

“…Considering the current discussion of MRONJ clinical stage classification a very interesting fact was observed in this study 21,22 . In a literature review of experimental models on MRONJ 15 , authors considered 10 small animal models [23][24][25][26][27][28][29][30][31][32] , and 5 large animal models 15,[33][34][35][36][37] . In all studies, when used as the extraction inducing factor, premolars and molars were used [23][24][25][26][27][28][29][30][31][32] .…”

“…In a literature review of experimental models on MRONJ 15 , authors considered 10 small animal models [23][24][25][26][27][28][29][30][31][32] , and 5 large animal models 15,[33][34][35][36][37] . In all studies, when used as the extraction inducing factor, premolars and molars were used [23][24][25][26][27][28][29][30][31][32] . From 10 studies with rodents, which were used different induction protocols, only 5 revealed MRONJ lesions clinically detected 24,26,28,29,32 , however, in 9 studies, osteonecrosis was detected microscopically [23][24][25][26][27][28][29][30]32 .…”

“…In all studies, when used as the extraction inducing factor, premolars and molars were used [23][24][25][26][27][28][29][30][31][32] . From 10 studies with rodents, which were used different induction protocols, only 5 revealed MRONJ lesions clinically detected 24,26,28,29,32 , however, in 9 studies, osteonecrosis was detected microscopically [23][24][25][26][27][28][29][30]32 . Only one study did not reveal this information 31 .…”

Jawbone Changes in Sodium Zoledronic Acid- and Dexamethasone-Treated Rats

“…In healthy rats, the covering epithelium is observed 17 days after tooth extraction, and complete closure is observed after 28 days 18,19) .…”

Systemic Supplement with Resveratrol Increased Bone Formation in Rats’ Alveolar Socket

“…Placebo injections were conducted in control group rats. Rats had standard diet during the experiment time of 28 days (Ali-Erdem et al, 2011). After 28 days of treatment, subjects were sacrificed and histological samples were collected from center second molar sockets.…”