title: Osteonecrosis of the jaw onset times are based on the route of bisphosphonate therapy.
abstract: OBJECTIVE
  Osteonecrosis of the jaw (ONJ) has been reported to be associated with patients receiving bisphosphonate (BP) therapy. There are many reports that suggest that the time of exposure to BPs is a significant risk factor for ONJ and that the greatest risk occurs after dentoalveolar surgery. The aim of this study was to retrospectively investigate the duration of BP therapy and related events before the onset of ONJ based on an intravenous (IV) or oral route of administration.
  
  
  METHODS
  We conducted a retrospective cohort study of patients referred to our institution to identify the onset of ONJ based on the exposure to BP therapy and associated triggers (ie, dentoalveolar surgery or spontaneous occurrence) based on the route of BP administration. Demographic data (ie, age, gender, and race), medical diagnosis related to BP therapy, and information as to whether the BP therapy was continued at the time of ONJ diagnosis were also collected.
  
  
  RESULTS
  We reviewed the records for 114 patients with a history of ONJ. We divided patient cohorts by route of BP administration, with 76 patients having a history of IV BP therapy and 38 patients having a history of oral BP therapy. The overall onset of ONJ was earlier in the IV BP group (median, 3 years) compared with the oral BP group (median, 5 years). There was no statistical difference in the duration to occurrence of ONJ associated with dental extraction compared with spontaneous occurrence for both the IV and oral BP groups.
  
  
  CONCLUSIONS
  The median onset of ONJ for patients undergoing IV BP therapy occurs earlier than the median onset for patients undergoing oral BP therapy, and there was no difference in onset occurring spontaneously and after dental extraction. The significance of these findings suggests that patients who receive IV BP therapy should be closely evaluated after the initiation of BP therapy. The lack of evidence suggesting greater onset after dental extraction may provide clinical support for dentoalveolar surgery that is indicated for patients with a history of BP therapy. Research focusing on the clinical circumstances and physiologic events during early antiresorptive therapy may provide insight as to the critical risk factors.
authors.affiliation: Department of Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, NY 10010, USA. kef3@nyu.edu
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Fleisher
authors.forename: Anu
authors.initials: A
authors.lastname: Jolly
authors.forename: Uma Deepthi Chippada
authors.initials: UD
authors.lastname: Venkata
authors.forename: Robert G
authors.initials: RG
authors.lastname: Norman
authors.forename: Deepak
authors.initials: D
authors.lastname: Saxena
authors.forename: Robert S
authors.initials: RS
authors.lastname: Glickman
mesh_terms: D000284:Administration, Oral; D000368:Aged; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000503:physiopathology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019647:Oral Surgical Procedures / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates