title: A novel model of bisphosphonate-related osteonecrosis of the jaw in rats.
abstract: OBJECTIVE
  To establish a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ) that realistically mimics major clinical manifestations of the disease.
  
  
  METHODS
  Female Sprague Dawley rats received intravenous zoledronate 80 μg/kg once a week via the tail vein. Three weeks after intravenous injection, maxillary first molars were extracted under general anesthesia. Then 1, 4 and 12 weeks after tooth extraction, the rats were euthanized, and the intact maxillas were harvested en bloc. Macroscopic analysis, histological analysis and cytokine analysis were performed. Untreated rats with tooth extraction were used as controls.
  
  
  RESULTS
  12 weeks after extraction, rats treated with zoledronate developed BRONJ-like disease, including characteristic features of impaired soft tissue healing, exposed necrotic bone or sequestra, increased inflammatory infiltrates, while the controls showed normal bone healing. 4 weeks after extraction, rats treated with zoledronate exhibited the decreased receptor activator of nuclear factor kappa-B ligand (RANKL) values, the increased osteoprotegerin (OPG) values and the remarkable decreased RANKL/OPG ratio when compared with the controls.
  
  
  CONCLUSIONS
  The rats treated with zoledronate can be considered a novel, reliable and reproducible animal model to better understand the pathophysiology and pathogenesis of BRONJ and to develop a therapeutic approach.
authors.affiliation: Department of Stomatology, Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Emergence, Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Stomatology, Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Stomatology, Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Stomatology, Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Shang
authors.affiliation: Department of Stomatology, Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles; D008437:Maxilla / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014945:Wound Healing; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D000077211:Zoledronic Acid
keywords: BRONJ; Bisphosphonates; OPG; RANKL; animal model; pathogenesis