Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates

Ana O. Hoff, Béla B. Toth, Kadri Altundag, Marcella M. Johnson, Carla L. Warneke, Mimi Hu, Ajay Nooka, Gilbert Sayegh, Valentina Guarneri, Kimberly Desrouleaux, Jeffrey Cui, Andrea Adamus, Robert F. Gagel, Gabriel N. Hortobagyi

Research output: Contribution to journalArticlepeer-review


Introduction: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The: incidence and risk factors associated with this disorder have not been clearly defined. Materials and Methods: We conducted a retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and 2004. Our goals were to estimate the frequency, understand the clinical presentation, and identify risk factors associated with ONJ development. Results: Sixteen of 1338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. The median dose and duration of treatment with Pamidronate or zoledronic acid were significantly higher in patients with ONJ (p <0.0001). Multivariate Cox proportional hazards regression analysis identified treatment with zoledronic acid (hazards ratio [HR], 15.01; 95% CI: 2.41-93.48; p = 0.0037), treatment with Pamidronate followed by zoledronic acid (HR, 4.00; 95% CI: 0.86-18.70; p = 0.078), and dental extractions (HR, 53.19; 95% CI: 18.20-155.46; p <0.0001) as significant risks for ONJ in breast cancer. In multiple myeloma, dental extractions (HR, 9.78; 95% CI: 3.07-31.14; p = 0.0001) and osteoporosis (HR, 6.11; 95% CI: 1.56-23.98; p = 0.0095) were significant risk factors while controlling for bisphosphonate therapy. Thirteen of 29 patients were followed for a median of 17.1 mo (range, 7-67 mo); lesions healed in 3 patients during this period. Conclusions: ONJ is an uncommon but long-lasting disorder that occurs mainly in breast cancer and multiple myeloma patients treated with intravenous bisphosphonates. High cumulative doses of bisphosphonates, poor oral health, and dental extractions may be significant risk factors for ONJ development. ONJ resolved in 23% of patients with conservative therapy.

Original languageEnglish
Pages (from-to)826-836
Number of pages11
JournalJournal of Bone and Mineral Research
Issue number6
Publication statusPublished - Jun 2008


  • Bisphosphonates
  • Bone metastasis
  • Breast cancer
  • Multiple myeloma
  • Osteonecrosis of the jaw
  • Osteoporosis

ASJC Scopus subject areas

  • Surgery


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