Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently Than Bisphosphonates Alone

Background: The use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ). Antiangiogenic agents are used with increasing frequency and may induce the risk of ONJ, especially when administered concurrently with bisphosphonates.

Patients And Methods: We retrospectively reviewed data of 116 patients receiving bisphosphonates, 78 zoledronic acid and 38 ibandronic acid, with or without antiangiogenic agents for osseous metastases from various tumors in our department from June 2007 to June 2008.

Results: ONJ developed in: 2 patients with breast cancer and 1 with colon cancer receiving concurrently bisphosphonates and bevacizumab, 1 patient with renal cell carcinoma receiving sunitinib and zoledronic acid concurrently, and 1 patient with prostate cancer receiving zoledronic acid without antiangiogenic agents. The incidences of ONJ among patients receiving bisphosphonates with or without antiangiogenic agents were 16 and 1.1%, respectively. The difference was statistically significant (p = 0.008). The treatment duration of bisphosphonates did not differ significantly between the 2 groups.

Conclusions: The combination of bisphosphonates and antiangiogenic factors induces ONJ more frequently than bisphosphonates alone. These preliminary observations should be evaluated in large cohorts of patients and in prospective studies.