Effect of Zoledronic Acid on Maxillary Alveolar Bone Coverage in Rice Rats With and Without Dental Trauma

Bisphosphonates are a class of drug widely used in both human and veterinary medicine for the treatment of pathologies affecting bone remodeling. Currently they represent the most commonly prescribed therapy for osteoporosis, with over 5 million prescriptions filled in the United States every year. Over the last decade the use of high dose nitrogen-containing bisphosphonates (BPs) has become increasingly popular in the multimodal approach to oncologic conditions. This class of medication has been shown to slow the progression of certain tumor cells from penetrating healthy bone tissues as well as slowing tumor cell proliferation. In addition BPs have been shown to significantly reduce the discomfort associated with metastases in some patients. Unfortunately, as the use and dosing of BPs has increased, so has the clinical complication associated with their use. Most notably, a condition known as bisphosphonate related osteonecrosis of the jaw (BRONJ) has emerged over the last ten years. While this condition has been linked to multiple risk factors, high dose BP usage and trauma in the oral cavity have been shown to be the primary events that precede the development of BRONJ lesions. BRONJ is a disabling and painful condition affecting both the maxilla and mandible. To date this condition is poorly understood, and consequently current treatment options are inconsistently effective.The overall purpose of this study was to develop a reliable animal model of BRONJ that can be used by researchers to advance the understanding of the pathophysiology of this disease. Because no grossly visible lesions were observed in these animals, we focused our efforts on exploring the role of two factors that have been implicated in the pathogenesis of BRONJ: periodontal disease and dental trauma. High-resolution micro computed tomography (µCT) was used to quantify the effects of a potent intravenous nitrogen-containing BP, zoledronic acid (ZA), on maxillary alveolar bone loss in an established rat model of periodontal disease. The role of trauma was determined by comparing data from sites adjacent to and remote from dental extractions. A statistically significant decrease in alveolar bone loss around maxillary molars both adjacent to and distant from dental extraction was identified. The magnitude of this effect was found to be associated with severity of initial bone loss. The more severe the initial degree of bone loss, the less of a protective effect BP has on disease progression. While no grossly visible BRONJ lesions were identified in our animal model, this study serves as a foundation for studying the effect of ZA on maxillary alveolar bone. Ongoing work on this project will include a detailed microscopic assessment of the tissue response in ZA-treated extraction sites and a comparison of histomorphometric data from the maxillary alveolar bone and trabecular bone in the appendicular skeleton.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Comparative and Veterinary Medicine

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Callard, Jason Scott

Contributors dc:contributor

• Allen, Matthew

• Biology
• Biomedical Research
• Dentistry
• Medicine
• Zoledronic Acid
• Bisphosphonates
• Bisphosphonate Related Osteonecrosis of the Jaw
• BRONJ
• Rice Rats

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1366108637

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1366108637