Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease

Abstract

Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n = 48) and sham-operated group (n = 48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n = 36 each) and control group (n = 12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6 weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P < 0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P < 0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CfX/FRACP (P < 0.05). The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required. (C) 2015 Elsevier Inc. All rights reserved.