title: The starting point for bisphosphonate-related osteonecrosis of the jaw: Alveolar bone or oral mucosa? A randomized, controlled experimental study.
abstract: OBJECTIVE
  Although over a decade has passed since first introduction of BRONJ, the exact pathophysiology of this disease is still unclear. The present experimental study aimed to determine whether the oral mucosa or alveolar bone serves as the starting point for BRONJ development.
  
  
  METHODS
  Sixty male Wistar rats were randomly assigned into study and control groups (each, n = 30), and received intraperitoneal injection of 0.06 mg/kg zoledronate and saline, respectively, once a week for 12 weeks. At the end of the week 4 of the experiment, all 60 rats underwent unilateral mandibular first molar extraction. A 4 mm defect was made in the contralateral canine alveolar mucosa. At the end of the experiment, rats were sacrificed, and the three areas of interest including extraction, soft tissue defect, and the non-intervention (canine area on the same side of extraction) sites were assessed clinically for presence of bone exposure/fistula, and histologically for status of bone remodeling (only at extraction site) and osteonecrosis.
  
  
  RESULTS
  In the study group, the frequency of bone exposure/fistula was 80%, 0%, and 0%; and the rate of histological bone necrosis was 83.3%, 20%, and 0%; at the extraction, soft tissue defect, and non-intervention sites, respectively. No clinical and histological sign of bone necrosis was found in the control group. Normal bone remodeling was observed in 0% and 100% of the extraction sockets in the study and control groups, respectively.
  
  
  CONCLUSIONS
  Injury to alveolar bone was a stronger trigger for BRONJ development compared to oral mucosal damages.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hamadan University of Medical Sciences, Hamadan, Iran; Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zandi
authors.affiliation: Department of Pathology, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: pejmanjanbaz@yahoo.com.
authors.forename: Pejman
authors.initials: P
authors.lastname: Janbaz
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Malekzadeh
authors.affiliation: Department of Biostatistics, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Amini
mesh_terms: D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology / Q000473:pathology*; D006801:Humans; D007568:Jaw / Q000187:drug effects / Q000473:pathology; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology*; D017208:Rats, Wistar
keywords: Animal study; Bisphosphonate; Jaw; Osteonecrosis; Pathophysiology