title: Bisphosphonates inhibit bone remodeling in the jaw bones of rats and delay healing following tooth extractions.
abstract: OBJECTIVE
  This study aimed to evaluate the impact of concurrent administration of clinically relevant doses of zoledronic acid (ZA) and dexamethasone (DX) on bone healing after tooth extraction (EXO).
  
  
  METHODS
  Forty-four Sprague-Dawley rats (6-8 month old) were randomized into five groups: ZA + DX = weekly injection of ZA with DX for 7 weeks; WD = ZA with DX for 3 weeks then DX alone for 4 weeks; C = control saline for 7 weeks; ZA = ZA alone for 7 weeks and DX = DX alone for 7 weeks. ZA was administered at 0.13 mg/kg/week and DX at 3.8 mg/kg/week and body weights recorded at the time of injection. All rats underwent extraction (EXO) of the mandibular and maxillary first molars at 3 weeks and were euthanized at 7 weeks. The extracted and non-extracted sides of both jaws were harvested for micro-CT analyses.
  
  
  RESULTS
  All rats, particularly those injected with ZA, exhibited weight gain till EXO followed by decline then recovery. ZA + DX group demonstrated highest fractional bone to tissue volume (BV/TV) in the non-extracted side. ZA + DX rats exhibited also highest volume and surface of sequestra. Only sequestra volume was statistically higher in the WD group compared to C group.
  
  
  CONCLUSIONS
  Combined treatment with ZA and DX over a prolonged period inhibits bone remodeling and increased sequestra formation to a greater extent than either drug alone. Trauma caused by these sequestra cutting through the mucosa could play a key role in the development of BRONJ by potentially facilitating infection. ZA withdrawal may promote bone-remodeling reactivation following EXO.
authors.affiliation: Division of Restorative Dentistry, Faculty of Dentistry, McGill University, Montreal, QC, Canada; Bone Engineering Labs, Research Institute, McGill University Health Center, Montreal, QC, Canada.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Jabbour
authors.affiliation: Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, McGill University, Montreal, QC, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: El-Hakim
authors.affiliation: Bone Engineering Labs, Research Institute, McGill University Health Center, Montreal, QC, Canada; Department of Medicine and Surgery, Faculty of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Henderson
authors.affiliation: Division of Restorative Dentistry, Faculty of Dentistry, McGill University, Montreal, QC, Canada; Department of Dental Materials and Prosthodontics, Faculty of Dentistry of Ribeirão Preto, University of Sao Paulo, Brazil. Electronic address: rubens.albuquerque@mcgill.ca.
authors.forename: Rubens F
authors.initials: RF
authors.lastname: de Albuquerque
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014081:Tooth Extraction; D014945:Wound Healing; D055114:X-Ray Microtomography
chemical_list: D004164:Diphosphonates
keywords: Bisphosphonates; Cancer treatment; Corticosteroid; Jaw bone; Necrosis; Sequestra; Tooth extraction