Bisphosphonate-Related Osteonecrosis of the Jaw: Epidemiology and Risk factors

Objective: To evaluate the frequency, risk factors and clinical presentation of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in cancer patients treated with intravenous bisphosphonate (BP). Patients and Methods: We performed a retrospective analysis of 576 patients treated with pamidronate and/or zoledronate between January 2003 and December 2007 at the University of Minnesota Masonic Cancer Center and Park Nicollet Institute. Results: Eighteen of 576 identified patients (3.1%) developed BRONJ including 8 of 190 (4.2%)patients with breast cancer, 6 of 83 (7.2%) patients with multiple myeloma, 2 of 84(2.4%) patients with prostate cancer, 1 of 76 (1.3%) patients with lung cancer, 1 of 52(1.9%) patients with renal cell carcinoma and in none of the 73 patients with other malignancies. Ten patients (55%) developed BRONJ following tooth extraction, while 7 (39%) developed it spontaneously. The mean number of BP infusions (38.1±19.06 vs 10.5±12.81, p<0.0001) and duration of BP treatment (months, 44.3±24.34 vs 14.6±18.09,p<0.0001) was significantly higher in BRONJ patients compared to patients without BRONJ. Multivariate Cox proportional hazards regression analysis revealed that diabetes(HR=3.40; 95% CI=1.11-10.11; 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 ofzoledronate infusions (HR=1.07; 95% CI=1.03-1.11; p=0.001) significantly increased therisk of developing BRONJ. Conclusion: Increased cumulative doses and long-term intravenous 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. 4-2010-->