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Frequency and Risk Factors Associated With Osteonecrosis of the Jaw in Cancer Patients Treated With Intravenous Bisphosphonates
Author(s) -
Hoff Ana O,
Toth Béla B,
Altundag Kadri,
Johnson Marcella M,
Warneke Carla L,
Hu Mimi,
Nooka Ajay,
Sayegh Gilbert,
Guarneri Valentina,
Desrouleaux Kimberly,
Cui Jeffrey,
Adamus Andrea,
Gagel Robert F,
Hortobagyi Gabriel N
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080205
Subject(s) - medicine , zoledronic acid , osteonecrosis of the jaw , bisphosphonate , multiple myeloma , breast cancer , incidence (geometry) , retrospective cohort study , proportional hazards model , hazard ratio , surgery , osteoporosis , risk factor , cancer , confidence interval , physics , optics
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.