title: A model for the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw and teriparatide's potential role in its resolution.
abstract: OBJECTIVE
  The objective of this study was to present a comprehensive model for the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw (BON).
  
  
  METHODS
  Review of PubMed literature relevant to BON, bisphosphonates (BPs), and bone remodeling.
  
  
  RESULTS
  Six case reports of spontaneous resolution of BON lesions following administration of teriparatide (Forteo; Eli Lilly and Co., Indianapolis, IN) were identified. These reports suggest that osteoanabolic therapies may hold promise in BON management. Here we propose that BON pathogenesis is multifactorial and is the combined result of attenuated osteoblastic activity (owing to the patient's underlying disease, e.g., osteoporosis or multiple myeloma), BP-mediated osteoclast toxicity, and the resultant compromised osteoblast-osteoclast interactions during bone remodeling. Consequently, a vicious cycle of ineffective local remodeling results in the persistence of defective bone, compromised tissue perfusion, and if unresolved, ultimately leads to necrosis.
  
  
  CONCLUSIONS
  Our model for BON pathogenesis advocates for earlier therapeutic intervention in BON. The biological rationale for teriparatide's efficacy in BON justifies further investigation.
authors.affiliation: PGY1, General Practice Residency Program, New Jersey Dental School-UMDNJ, Newark, NJ 07101, USA.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Subramanian
authors.forename: Harold V
authors.initials: HV
authors.lastname: Cohen
authors.forename: Samuel Y P
authors.initials: SY
authors.lastname: Quek
mesh_terms: D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000188:drug therapy / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology / Q000503:physiopathology; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology; D019379:Teriparatide / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide