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

F. Saad, J. E. Brown, C. Van Poznak, T. Ibrahim, S. M. Stemmer, A. T. Stopeck, I. J. Diel, S. Takahashi, N. Shore, D. H. Henry, C. H. Barrios, T. Facon, F. Senecal, K. Fizazi, L. Zhou, A. Daniels, P. Carrière, R. Dansey

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1341-1347
Number of pages7
JournalAnnals of Oncology
Volume23
Issue number5
DOIs
Publication statusPublished - May 2012

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Keywords

  • Bone metastases
  • Denosumab
  • Osteonecrosis of the jaw
  • Zoledronic acid

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Saad, F., Brown, J. E., Van Poznak, C., Ibrahim, T., Stemmer, S. M., Stopeck, A. T., Diel, I. J., Takahashi, S., Shore, N., Henry, D. H., Barrios, C. H., Facon, T., Senecal, F., Fizazi, K., Zhou, L., Daniels, A., Carrière, P., & Dansey, R. (2012). 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. Annals of Oncology, 23(5), 1341-1347. https://doi.org/10.1093/annonc/mdr435