title: Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats.
abstract: OBJECTIVE
  This study aimed to investigate the role of progressive periodontal disease in inducing bisphosphonate-related osteonecrosis of the jaws (BRONJ) using an ovariectomized (OVX) rat model mimicking human intracortical remodeling process.
  
  
  METHODS
  Thirty 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, zoledronic acid (ZA) or vehicle control was administered intraperitoneally for 12 weeks. On the same day of injection, a cotton ligature was placed subgingivally around the first left lower molar to induce periodontitis. All animals were sacrificed 12 weeks after injection. The entire mandibles were harvested for micro-computed tomography (micro-CT) and histological examinations.
  
  
  RESULTS
  Micro-CT examination showed that ligature placement caused significant alveolar bone loss both in ZA (0.63 ± 0.13 vs. 0.38 ± 0.06 mm, P < 0.001) and in control (0.88 ± 0.19 vs. 0.40 ± 0.06 mm, P < 0.001) groups. Whereas in the ZA group, bone loss was attenuated compared with the control group (P < 0.01); the bone mineral density in the ZA group (1.00 ± 0.02 g/cm(3)) was significantly higher than that in vehicle control group (0.96 ± 0.03 g/cm(3), P < 0.001). Histological examination found necrotic bone tissue with extensive, empty lacunae in two of 15 rats in ZA group, but in none of the control group.
  
  
  CONCLUSIONS
  Bisphosphonates inhibit alveolar bone resorption in progressive periodontal disease, which might benefit the management of periodontitis, but increase the risk of developing BRONJ.
authors.affiliation: Discipline of Oral Diagnosis & Polyclinics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
authors.forename: Chun Lei
authors.initials: CL
authors.lastname: Li
authors.affiliation: Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Weijia William
authors.initials: WW
authors.lastname: Lu
authors.affiliation: Discipline of Oral Biosciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Chaminda Jayampath
authors.initials: CJ
authors.lastname: Seneviratne
authors.affiliation: Discipline of Oral Diagnosis & Polyclinics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
authors.forename: Wai Keung
authors.initials: WK
authors.lastname: Leung
authors.affiliation: Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Zwahlen
authors.affiliation: Discipline of Oral Diagnosis & Polyclinics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
authors.forename: Li Wu
authors.initials: LW
authors.lastname: Zheng
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology* / Q000517:prevention & control*; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D010510:Periodontal Diseases / Q000150:complications* / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: bisphosphonate-related osteonecrosis of the jaws; ovariectomy; periodontitis; rat; zoledronic acid