title: Development of a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ).
abstract: 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.
authors: Department of Oral Biology, Georgia Health Sciences University, College of Dental Medicine, Augusta, GA, USA.
authors: Karen L
authors: KL
authors: Marino
authors: Ibrahim
authors: I
authors: Zakhary
authors: Rafik A
authors: RA
authors: Abdelsayed
authors: Jared A
authors: JA
authors: Carter
authors: Jack C
authors: JC
authors: O'Neill
authors: Rania M
authors: RM
authors: Khashaba
authors: Mohammed
authors: M
authors: Elsalanty
authors: Mark R
authors: MR
authors: Stevens
authors: James L
authors: JL
authors: Borke
mesh_terms: D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000378:metabolism / Q000473:pathology*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004164:Diphosphonates / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles / Q000009:adverse effects*; D011726:Pyridinium Compounds / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014081:Tooth Extraction; D020390:Tooth Socket / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D011726:Pyridinium Compounds; D042461:Vascular Endothelial Growth Factor A; D000077211:Zoledronic Acid; D003094:Collagen