Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

Abstract

Introduction: Osteonecrosis of the jaw (ONJ) is a clinically important, potentially painful and debilitating condition, which can affect the quality of life of cancer patients. Since 2003, ONJ appeared as a Bisphosphonate(BP)-related class effect, and the term Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) was widespread. Areas Covered: Under discussion in this review is the fact that ONJ cases have been reported after treatment including antiangiogenic agents and other “targeted therapy”, with and without BPs. Consequently, the comprehensive term Medication-Related Osteonecrosis of the Jaw (MRONJ) has been introduced. The clinical aspects and the prognosis of ONJ associated with these new drugs are still less reported, but basing on their pharmacodynamics, they could be different from the well-known BRONJ. Accordingly, recommendations largely in use for BRONJ should be extended to these new forms, but critically applied and with respect to the individual risk assessment. Expert Opinion: There is a high risk of underdiagnoses for ONJ due to a lack of awareness, and too much restrictive or incomplete diagnostic criteria; at the same time, with regard to ONJ associated to the new non –antiresorptive agents, described here, we observe the strong need to improve the defining of any distinguished feature in their diagnosis, prevention and therapy

Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors

“…The association of these drugs with antiangiogenic targeted therapies (sunitinib, bevacizumab) increases the risk to develop MRONJ (Fig. 7) [145,146] more often after oral surgery [147][148][149]. Few data of MRONJ are also reported with sorafenib, cabozantinib, alfibercept, and mTOR inhibitor monotherapy [124,147].…”

“…7) [145,146] more often after oral surgery [147][148][149]. Few data of MRONJ are also reported with sorafenib, cabozantinib, alfibercept, and mTOR inhibitor monotherapy [124,147]. MRONJ remains an underdiagnosed adverse event because of inadequate or restrictive diagnostic criteria [147] and because early lesions may have few symptoms.…”

Osteonecrosis of the jaws in patient received bisphosphonates and sunitinib separately: A case report

“…In contrast to other conventional chemotherapy, which is given in courses during a defined period, sunitinib therapy will last a longer period. [18]…”

“…It is a clinically devastating condition that can affect the cancer patients' quality of life. [1] The main predisposing factors for ONJ are surgical intervention and oral mucosa breakdown in patients encountering to radiotherapy and chemotherapy agents. [2] Primarily, it assumes as a bisphosphonate (BP)-related adverse effect but has been reported in patients receiving other anticancer treatment such as antiangiogenic and targeted therapy agents with and without BPs.…”

“…[2] Primarily, it assumes as a bisphosphonate (BP)-related adverse effect but has been reported in patients receiving other anticancer treatment such as antiangiogenic and targeted therapy agents with and without BPs. [1] Furthermore, the medication-related osteonecrosis of jaw has been recently named in medical literature and is matter of concern in novel drug therapy in cancer patients. Tyrosine kinase inhibitors (TKIs) are drugs with differentiated effects including tumor growth blockage and angiogenesis inhibition through multi-target mechanisms.…”