Evaluation of the immune state activation in patients affected by ONJ: preliminary data

Abstract

Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) is a serious adverse event characterized by non-healing necrotic bone tissue of mandible or maxilla. BPs target osteoclasts, inhibiting their action and blocking bone resorption, nonetheless an increased bone resorption in the oral cavity is associated to ONJ. One of the causes of ONJ is the dysregulation of the immune system, in particular the strong reduction of gamma/delta T cells circulating in peripheral blood (PB). The rate of circulating osteoclast precursors (OCPs) is altered in bone metastatic patients, suggesting a systemic alteration of osteoclast compartment, but we do not know wether it is altered in cancer patients affected by active lesion of ONJ induced by Zoledronic acid treatment. By flow cytometric analysis of patients’ and controls’ PB cells, we studied the presence of different T cell subsets, according to the expression of gamma/delta chains, CD4, CD8, CD25 and CD69 and of OCPs. We also evaluated the capability of PBMCs to spontaneously differentiate into osteoclasts _in vitro_, which is an index of pathological bone resorption. Our preliminary results confirmed in ONJ patients a marked reduction in gamma/delta T cells compared to their level befor patients started BP treatment. The subsets of activated T cells and OCPs were not significantly modified. In ONJ patients, _in vitro_ osteoclastogenesis was comparable to the one of healthy control, while before patients started BP treatment osteoclastogenesis was significantly increased. This result suggests that BPs correctly act in reducing the systemic activation of osteoclasts, associated to bone metastatic patients, as expected, but BPs fail to block osteoclast activity locally.