Abstract
Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.
Highlights
Being reported in 2003 (Marx, 2003), medication-related osteonecrosis of the jaws (MRONJ) is one of the potential adverse effects after BPs treatment and has received greater attention more than any other side effects of BPs
Given the fact that clinically peripheral bone seldom went through surgical intervention than that in oral cavity, we aim to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs
Soft tissue fenestrations were observed in four cases (4/24) in the maxilla, and four (4/24) in the mandible in zoledronic acid (ZA)-treated group, while two cases (2/24) in the mandible in control group
Summary
Being reported in 2003 (Marx, 2003), medication-related osteonecrosis of the jaws (MRONJ) is one of the potential adverse effects after BPs treatment and has received greater attention more than any other side effects of BPs. Various assumption and hypotheses have been proposed regarding the etiology of MRONJ, including inhibition of osteoclast activity and over-suppression of bone turnover, suppression of angiogenesis, oral infection, and cell toxicity [4, 5]. These hypotheses could not thoroughly explain the exclusive site of occurrence of ONJ. Some studies showed that the high bone turnover rate of jaw bones, together with the increased bone remodeling due to dental surgical operations, resulted in the development of osteonecrosis in this specific site [6]. Others found that turnover rate of the jawbones was not changed in patients with zoledronic acid or denosumab treatment [7,8,9]
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