Denosumab and anti-angiogenetic drug-related osteonecrosis of the jaw: an uncommon but potentially severe disease

Abstract

Osteonecrosis of the jaw (ONJ) is a rare but serious lesion of the jaw characterized by exposed necrotic bone and is related to several drugs usually used for treating patients with advanced malignancies. Common therapies inducing ONJ are nitrogen-containing bisphosphonates (BPs), the human monoclonal antibody to the receptor activator of nuclear factor-kappa B ligand denosumab and some anti-angiogenic drugs, alone or in combination with BPs. The real incidence of ONJ is unknown. Several cases of ONJ in patients with cancer who underwent denosumab therapy have been reported and it seems that the overall incidence of denosumab-related ONJ is similar to that for BP-related in this population, ranging between 1-2%. The cell-surface vascular endothelial growth factor (VEGF) receptor plays a major role in cancer progression and can be targeted by drugs inhibiting the tyrosine kinase activator or other second messengers. Most angiogenesis inhibitors, such as the monoclonal antibody bevacizumab and the kinase inhibitor sunitinib, target the VEGF signaling pathway. Unfortunately, cases of bevacizumab-induced ONJ have been reported, especially in patients treated with bevacizumab and BPs in combination. There are only few studies reporting sunitinib-related ONJs. In patients with advanced cancer and malignancy-associated hypercalcemia undergoing BP, denosumab or bevacizumab therapy, enquiry into current dental health and dental examination is mandatory. Good oral hygiene, limiting of alcohol intake and stopping smoking should be suggested for all patients requiring such treatments.

Keywords: ONJ; Osteonecrosis of the jaw; bevacizumab; denosumab; review; risk factors; sunitinib.