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.

Figure 1

BRONJ: Empty lacunae are seen in the centre of the bone while towards the surface some lacunae display their osteocytes

Figure 2

BRONJ: Haemorrhage and chronic inflammatory cells infiltrate

Figure 3

BRONJ: Chronic inflammatory cells infiltrate

Figure 4

BRONJ: Osteoclasts, lymphocytes and plasma cells

Figure 5

Bisphosphonates: mechanisms of anti-angiogenesis

Figure 6

Bisphosphonate effects on oral keratinocytes