Development of a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

The purpose of this study was to develop a rat model predictive of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats were randomized into 2 groups, control and experimental. The experimental group received 2 intravenous injections of zoledronate (20 μg/kg)....

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Bibliographic Details
Published in:	The Journal of oral implantology Vol. 38 Spec No; no. S1; pp. 511 - 518
Main Authors:	Marino, Karen L, Zakhary, Ibrahim, Abdelsayed, Rafik A, Carter, Jared A, O'Neill, Jack C, Khashaba, Rania M, Elsalanty, Mohammed, Stevens, Mark R, Borke, James L
Format:	Journal Article
Language:	English
Published:	United States Allen Press Inc 01-10-2012
Subjects:	Animals Bisphosphonate-Associated Osteonecrosis of the Jaw - metabolism Bisphosphonate-Associated Osteonecrosis of the Jaw - pathology Bone density Bone Density - drug effects Bone Density Conservation Agents - adverse effects Bones Collagen - drug effects Collagen - metabolism Dentistry Diphosphonates - adverse effects Disease Disease Models, Animal Female Imidazoles - adverse effects Pyridinium Compounds - metabolism Random Allocation Rats Rats, Sprague-Dawley Rodents Surgery Tomography Tooth Extraction Tooth Socket - drug effects Tooth Socket - metabolism Tooth Socket - pathology Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Wound healing Wound Healing - drug effects X-Ray Microtomography
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Summary:	The purpose of this study was to develop a rat model predictive of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats were randomized into 2 groups, control and experimental. The experimental group received 2 intravenous injections of zoledronate (20 μg/kg). The mesial root of the right mandibular first molar was extracted. Rats were euthanized at 0, 4, and 8 weeks. Bone mineral density (BMD), collagen breakdown (pyridinium [PYD]), vascular regeneration (VEGF), and histology were examined. A trend toward higher PYD values was suggested in control vs experimental groups after wounding. Serum VEGF increased significantly after wounding for both control and experimental groups. After 8 weeks, VEGF continued to rise for the experimental group only. In the extraction socket area, BMD was significantly lower after wounding in control vs. zoledronate-treated rats. Histology sections from experimental groups showed bacteria and bone necrosis. Consistent findings of BRONJ features similar to those in humans were observed after zoledronate treatment.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0160-6972 1548-1336
DOI:	10.1563/aaid-joi-d-11-00057