Osteonecrosis of the mandible due to anti-angiogenic agent, bevacizumab

Abstract

Osteonecrosis of the jaw (ONJ) is defined by areas of tissue breakdown and exposure of bone in the maxillofacial region that fail to heal within 8 weeks after identification by a health provider in a patient who has not received radiation of the jaws. The disease affects the quality of life and produces significant morbidity in afflicted patients. ONJ is correlated with such risk factors as treatment with bisphosphonates, dental extraction-related trauma, chemotherapy, corticosteroids, renal osteodystrophy and infections. Although the use of bisphosphonates is associated with osteonecrosis of the jaw, the pathophysiology of bisphosphonate-associated ONJ is still unknown. It has been assumed that bisphosphonates lead to the inhibition of capillary angiogenesis and disturbances in the activities of both osteoblasts and osteoclasts, thereby impairing bone remodelling. Currently, inhibitors of angiogenesis used in the treatment of cancer patients are implicated in isolated cases of ONJ. This manuscript reports a case of ONJ in a female patient who received bevacizumab (Avastin®, Roche), a humanised monoclonal antibody that recognises and blocks vascular endothelial growth factor (VEGF)-A. The anti-angiogenic agent, bevacizumab, may increase the risk of osteonecrosis of the jaw. This agent inhibits VEGF and, therefore, also presumably represses the vascularisation of the jaw, which leads to healing complications. Due to increasing use of bevacizumab, patients receiving this agent should be closely monitored for possible side effects.