title: Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases.
abstract: BACKGROUND
  Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies.
  
  
  METHODS
  Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts.
  
  
  RESULTS
  Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab).
  
  
  CONCLUSIONS
  In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.
authors: Department of Urology, University of Montreal Montreal, Canada. Electronic address: fred.saad@umontreal.ca.
authors: F
authors: F
authors: Saad
authors: Cancer Research UK Clinical Centre, University of Leeds, Leeds, UK.
authors: J E
authors: JE
authors: Brown
authors: Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
authors: C
authors: C
authors: Van Poznak
authors: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.
authors: T
authors: T
authors: Ibrahim
authors: Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tiqva, Israel.
authors: S M
authors: SM
authors: Stemmer
authors: Department of Medicine, University of Arizona, Arizona Cancer Center, Tucson, USA.
authors: A T
authors: AT
authors: Stopeck
authors: Institute for Gynecologic Oncology, Center for Comprehensive Gynecology, Mannheim, Germany.
authors: I J
authors: IJ
authors: Diel
authors: The Cancer Institute Hospital of JFCR, Tokyo, Japan.
authors: S
authors: S
authors: Takahashi
authors: Carolina Urologic Research Center, Myrtle Beach.
authors: N
authors: N
authors: Shore
authors: Joan Karnell Cancer Center, Pennsylvania Hospital, Philadelphia, USA.
authors: D H
authors: DH
authors: Henry
authors: Internal Medicine Department, Pontifícia Universidade Católica do Rio Grande do Sul School of Medicine, Rio Grande do Sul, Brazil.
authors: C H
authors: CH
authors: Barrios
authors: Department of Blood Diseases, Hôpital Claude Huriez, Lille, France.
authors: T
authors: T
authors: Facon
authors: Northwest Medical Specialties Tacoma, USA.
authors: F
authors: F
authors: Senecal
authors: Department of Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors: K
authors: K
authors: Fizazi
authors: Global Biostatistical Sciences.
authors: L
authors: L
authors: Zhou
authors: Global Safety.
authors: A
authors: A
authors: Daniels
authors: Global Safety.
authors: P
authors: P
authors: Carrière
authors: Clinical Development, Amgen Inc., Thousand Oaks, USA.
authors: R
authors: R
authors: Dansey
mesh_terms: D000465:Algorithms; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000175:diagnosis* / Q000453:epidemiology* / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000556:secondary; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012307:Risk Factors; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid