A Retrospective Study Evaluating Frequency and Risk Factors of Osteonecrosis of the Jaw in 576 Cancer Patients Receiving Intravenous Bisphosphonates

Abstract

To evaluate the frequency, risk factors, and clinical presentation of bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ). We performed a retrospective analysis of 576 patients with cancer treated with intravenous pamidronate and/or zoledronate between January, 2003 and December, 2007 at the University of Minnesota Masonic Cancer Center and Park Nicollet Institute. Eighteen of 576 identified patients (3.1%) developed BRONJ including 8 of 190 patients (4.2%) with breast cancer, 6 of 83 patients (7.2%) with multiple myeloma, 2 of 84 patients (2.4%) with prostate cancer, 1 of 76 patients (1.3%) with lung cancer, 1 of 52 patients (1.9%) with renal cell carcinoma, and in none of the 73 patients with other malignancies. Ten patients (59%) developed BRONJ after tooth extraction, whereas 7 (41%) developed it spontaneously (missing data for 1 patient). The mean number of BP infusions (38.1 ± 19.06 infusions vs. 10.5 ± 12.81 infusions; P<0.001) and duration of BP treatment (44.3 ± 24.34 mo vs. 14.6 ± 18.09 mo; P<0.001) were significantly higher in patients with BRONJ compared with patients without BRONJ. Multivariate Cox proportional hazards regression analysis showed that diabetes [hazard ratio (HR)=3.40; 95% confidence interval (CI), 1.14-10.11; P=0.028], hypothyroidism (HR=3.59; 95% CI, 1.31-9.83; P=0.013), smoking (HR=3.44; 95% CI, 1.28-9.26; P=0.015), and higher number of zoledronate infusions (HR=1.07; 95% CI, 1.03-1.11; P=0.001) significantly increased the risk of developing BRONJ. Increased cumulative doses and long-term BP treatment are the most important risk factors for BRONJ development. Type of BP, diabetes, hypothyroidism, smoking, and prior dental extractions may play a role in BRONJ development.