title: Bisphosphonate-related osteonecrosis of the jaw in patients with oral bisphosphonate exposure: clinical course and outcomes.
abstract: OBJECTIVE
  To characterize the spectrum and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurring with oral bisphosphonate therapy.
  
  
  METHODS
  We assembled a retrospective cohort of patients who had developed oral BRONJ according to the 2009 American Association of Oral and Maxillofacial Surgeons criteria and received care within Kaiser Permanente, Northern California, during 2004 to 2011. Patients with intravenous bisphosphonate exposure were excluded. The demographic factors, comorbidities, pharmacologic exposure, maxillofacial findings, and outcomes were ascertained from the clinical and radiologic records.
  
  
  RESULTS
  We identified 30 cases of oral BRONJ (median age 77 years, 87% women). All had received oral bisphosphonate for osteoporosis/osteopenia (median duration 4.4 years, interquartile range 1.9 to 6.6). More than one half (57%) had comorbidities or relevant drug exposure, including rheumatoid arthritis, diabetes, glucocorticoid therapy, and disease-modifying antirheumatic medications. Extractions preceded BRONJ in 17 patients and trauma in 3; 10 developed BRONJ spontaneously. Overall, 83% had healed within 3 to 52 months, although the relative rate of healing varied by antecedent factor and/or the presence of comorbid conditions/exposures. Nearly all patients with trauma-related and spontaneous BRONJ healed within 1 year (median 7.0 and 7.5 months, respectively) compared with those developing BRONJ after extraction, in whom the median time to healing was 18 months (P < .0001). Patients with relevant comorbidities had a lower probability of healing (P = .0002) and a longer median time to healing (20 months) than patients without comorbidities (7.5 months).
  
  
  CONCLUSIONS
  We found that postextraction patients and those with comorbid conditions/exposures showed refractory BRONJ with prolonged healing times. Practitioners should be aware that the BRONJ clinical course and outcome varies depending on the antecedent factor and comorbidity status.
authors.affiliation: Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, Oakland, CA 94611, USA. Felice.O’Ryan@kp.org
authors.forename: Felice S
authors.initials: FS
authors.lastname: O'Ryan
authors.forename: Joan C
authors.initials: JC
authors.lastname: Lo
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology* / Q000601:surgery; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy; D002908:Chronic Disease; D015331:Cohort Studies; D003646:Debridement; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D000077557:Ibandronic Acid; D008297:Male; D008875:Middle Aged; D010014:Osteolysis / Q000209:etiology; D010024:Osteoporosis / Q000188:drug therapy; D010026:Osteosclerosis / Q000209:etiology; D012189:Retrospective Studies; D014081:Tooth Extraction; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D018501:Antirheumatic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005938:Glucocorticoids; D000077557:Ibandronic Acid; D019386:Alendronate