title: Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats.
abstract: BACKGROUND
  Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a pathologic condition of increasing frequency, with a poorly understood pathophysiology and which can be difficult to manage. The aim of this study was to find a reproducible experimental model that directly relates chronic bisphosphonate administration with the development of osteonecrosis with or without tooth extraction, with no other drug involved.
  
  
  METHODS
  Twenty male Wistar rats were divided into 4 groups (n = 5/group). Animals were injected over 9 weeks with zoledronic acid (0.1 mg/kg). In groups 1 and 2 three times a week intraperitoneally, and in group 3 once a week intravenously. A control group (group 4) received intraperitoneal injections of saline solution three times a week. After 8 weeks of treatment, 3 right upper jaw molars were extracted in groups 1, 3 and 4 and all rats were sacrificed 1 week later. The maxillae were histologically analyzed for presence of osteonecrosis foci, number of osteoclasts, vascularity, bone resorption status and presence of abscess. Radiographic examination was performed with a plain radiograph of each hemi-head.
  
  
  RESULTS
  We found that group 1 (dental extractions and highest cumulative dose of zoledronic acid) had the highest incidence of osteonecrosis (80%), absence of bone resorption (100%) and lowest number of osteoclasts (mean 7.9/field at 40×). Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study.
  
  
  CONCLUSIONS
  We offer a new animal model of BRONJ after zoledronic acid administration and dental extractions, achieving bone changes similar or superior to previous studies, highlighting the dental extraction as an important trigger factor.
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head of the Department: Miguel Burgueño), University Hospital La Paz, Madrid, Spain. Electronic address: p.barba.recreo@gmail.com.
authors.forename: Paula
authors.initials: P
authors.lastname: Barba-Recreo
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head of the Department: Miguel Burgueño), University Hospital La Paz, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Del Castillo Pardo de Vera
authors.affiliation: Cell Therapy Laboratory (Head of the Department: Prof. Damián García Olmo), Unidad de Invesigación, IdIPAZ, University Hospital La Paz, Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: García-Arranz
authors.affiliation: Department of Pathology, University Hospital La Paz, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Yébenes
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head of the Department: Miguel Burgueño), University Hospital La Paz, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Burgueño
mesh_terms: D000038:Abscess / Q000209:etiology / Q000473:pathology; D000539:Alveolar Process / Q000098:blood supply / Q000473:pathology; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology* / Q000473:pathology; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008437:Maxilla / Q000098:blood supply / Q000473:pathology / Q000601:surgery; D008963:Molar / Q000601:surgery; D010010:Osteoclasts / Q000473:pathology; D010026:Osteosclerosis / Q000209:etiology / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014081:Tooth Extraction / Q000009:adverse effects; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Bisphosphonates; Osteonecrosis of the jaws; Zoledronic acid