Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect

Abstract

Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ). However, the etiopathogenic mechanisms of this pathological condition are poorly understood. Although, several pathways have been proposed for BRONJ occurrence, no single model can explain all morphological changes observed at the macro- and microscopic level. Recent research suggests that BPs may promote an anti-angiogenic effect which contributes directly to the clinical features associated with BRONJ. Remarkably, the anti-angiogenic effect promoting BRONJ might be in keeping with the anti-neoplastic action of BPs. The current review, presents clinical diagnostic criteria. In addition, based on our own experience we describe the histopathological criteria for diagnosis of BRONJ and the possible pathways which may lead to this frustrating pathological condition.

Risk factors influencing the duration of treatment with bisphosphonates until occurrence of an osteonecrosis of the jaw in 963 cancer patients

“…On a cellular level, switching BPs in the course of treatment might make sense, as the BPs act at different points in the mevalonate pathway and have various potential to cause other biochemical effects, not only on osteoclast/osteoblast interaction but also on inhibiting angiogenesis or tissue regeneration (Sharma et al 2013). In light of our results on the similar potential of ibandronate and zoledronate to promote an ONJ within the same time frame, it might make sense to start off with or switch to a BP of an earlier generation such as pamidronate if other aspects of the patient's quality of life allow for it.…”

Bisphosphonate Related Osteonecrosis of the Jaw: An Update

“…In 2012 Reid and Cornish [5] reviewed 2408 cases of BRONJ and reported that incidence of BRONJ after administration of IV BPs in cancer patients was 89 % while rest 11 % had only received oral BPs. In contrast to the above report Sharma et al [6] in 2013 reported that the incidence rate of BRONJ after IV administration of bisphosphonates has been documented from 0 to 28 % and not more than 4 % in cases of oral BPs administration.…”

“…In the IORN cases numerous osteoclasts could be detected close to vital bone. In 2013 Sharma et al reported that BRONJ was characterized by presence of osteocyte-depleted bone lacunae which was more commonly seen in the deeper layers of the bone while lacunae located towards the surface of the bone lamellae will lose the osteocytes at a later stage [6,46]. Recently specimens of BRONJ/IORN tissues show necrotic bone surrounded by many bacterial colonies.…”

Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model

“…The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results. (Yamada et al, 2009;Anavi-Lev et al, 2013;Sharma et al, 2013). Therefore, it seems that stimulating angiogenesis locally could be an effective management strategy.…”