F Saad1, J E Brown2, C Van Poznak3, T Ibrahim4, S M Stemmer5, A T Stopeck6, I J Diel7, S Takahashi8, N Shore9, D H Henry10, C H Barrios11, T Facon12, F Senecal13, K Fizazi14, L Zhou15, A Daniels16, P Carrière16, R Dansey17. 1. Department of Urology, University of Montreal Montreal, Canada. Electronic address: fred.saad@umontreal.ca. 2. Cancer Research UK Clinical Centre, University of Leeds, Leeds, UK. 3. Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, USA. 4. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. 5. Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tiqva, Israel. 6. Department of Medicine, University of Arizona, Arizona Cancer Center, Tucson, USA. 7. Institute for Gynecologic Oncology, Center for Comprehensive Gynecology, Mannheim, Germany. 8. The Cancer Institute Hospital of JFCR, Tokyo, Japan. 9. Carolina Urologic Research Center, Myrtle Beach. 10. Joan Karnell Cancer Center, Pennsylvania Hospital, Philadelphia, USA. 11. Internal Medicine Department, Pontifícia Universidade Católica do Rio Grande do Sul School of Medicine, Rio Grande do Sul, Brazil. 12. Department of Blood Diseases, Hôpital Claude Huriez, Lille, France. 13. Northwest Medical Specialties Tacoma, USA. 14. Department of Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France. 15. Global Biostatistical Sciences. 16. Global Safety. 17. Clinical Development, Amgen Inc., Thousand Oaks, USA.
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. PATIENTS AND 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.
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. PATIENTS AND 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.
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