Dr Gagel has served as a speaker and received research support from Novartis Pharmaceuticals. Drs Hortobagyi and Hoff received research support from Novartis Pharmaceuticals. All other authors state that they have no conflicts of interest.
Frequency and Risk Factors Associated With Osteonecrosis of the Jaw in Cancer Patients Treated With Intravenous Bisphosphonates
Version of Record online: 4 FEB 2008
Copyright © 2008 ASBMR
Journal of Bone and Mineral Research
Volume 23, Issue 6, pages 826–836, June 2008
How to Cite
Hoff, A. O., Toth, B. B., Altundag, K., Johnson, M. M., Warneke, C. L., Hu, M., Nooka, A., Sayegh, G., Guarneri, V., Desrouleaux, K., Cui, J., Adamus, A., Gagel, R. F. and Hortobagyi, G. N. (2008), Frequency and Risk Factors Associated With Osteonecrosis of the Jaw in Cancer Patients Treated With Intravenous Bisphosphonates. J Bone Miner Res, 23: 826–836. doi: 10.1359/jbmr.080205
- Issue online: 4 DEC 2009
- Version of Record online: 4 FEB 2008
- Manuscript Revised: 20 DEC 2008
- Manuscript Accepted: 31 JAN 2008
- Manuscript Received: 14 AUG 2007
- osteonecrosis of the jaw;
- breast cancer;
- multiple myeloma;
- bone metastasis;
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.