Osteonecrosis of the jaw incidence and contributing risk factors in cancer patients treated with IV bisphosphonates: A Veterans Administration Healthcare study

Abstract

20511 Background: Intravenous bisphosphonates (IVB) can improve complications of bone metastases, but are associated with osteonecrosis of the jaw (ONJ). The incidence is speculated to be 3–13% with a variety of risk factors proposed. This study was designed to establish ONJ incidence (primary aim) and associated risk factors (secondary aim) in cancer patients treated with IVB. Methods: All cancer patients receiving at least one dose of IVB between January 1, 2001 and December 31, 2005 were eligible. ONJ was defined by high clinical suspicion and/or confirmatory radiography or jaw bone biopsy. Odds ratio (OR) were calculated using Fisher’s exact test. Spearman’s correlation coefficients (rs) were calculated by the Wilcoxon rank sum test. The distribution of time to ONJ development was estimated by the Kaplan-Meier method. Results: 260 of 263 eligible consecutive patients were available for analysis. Tumor types were diverse. Median age was 67 (range 41–94) and the majority were men. Median IVB dose per patient was 2 (range 1–80) with 69 receiving pamidronate, 152 zoledronic acid, and 39 receiving both during therapy. The overall incidence of ONJ was 4.2% (11/260). Patients with ONJ received more doses (median 22 vs 2;rs=0.23;p=0.0003) and had a longer duration of IVB treatment (median 805 vs 92 days;rs=0.26;p<0.0001) compared to those without ONJ. There was no difference between pamidronate or zoledronic acid (incidence 2.9% vs 2.6%;p=NS), but exposure to both agents increased the incidence (12.8%;p=0.03). IVB treatment beyond 24 months was associated with a significantly higher incidence (16.7% vs 2.2%;OR=7.85;p=0.002). ONJ development was also associated with dental trauma (OR=47.9;p<0.0001), but not with the use of chemotherapy (1.62;p=0.75), radiotherapy (0.85;p=0.77), hormonal therapy (1.23;p=0.75), corticosteroids (0.85;p=0.77), statins (0.29;p=0.13), or thrombophilia (2.02;p=0.39). Conclusions: ONJ is a rare, but serious complication of IVB use. Major risk factors for development include prolonged IVB treatment and dental trauma. Our findings support ASCO guideline recommendations to limit IVB therapy to 24 months. Further studies are needed to predict individual patient risk for ONJ. No significant financial relationships to disclose.