Influence of zoledronic acid on proliferation, migration, and apoptosis of vascular endothelial cells.

Bisphosphonates are commonly used to treat malignant tumours that originate in bone. In recent years, with the widespread application of these drugs in chemotherapy, reports have raised concerns about the development of osteonecrosis. Though the mechanism of bisphosphonate-related osteonecrosis of the jaw is not clear, vascular injury resulting from their use has been suggested as a possible cause. This study was designed to explore the influence of zoledronic acid, one of the most common bisphosphonates, on the function and viability of vascular endothelial cells in vitro to try to find possible mechanisms of the action bisphosphonates in osteonecrosis. Endothelial cell proliferation, migration, and apoptosis were examined with MTT assays, scratch tests, and flow cytometry in the presence of zoledronic acid in different concentrations. The relative expressions of protein were also examined by western blot assays, and the significance of the differences among concentrations of the drug were assessed statistically. Concentrations zoledronic acid of 15μmol-150μmol, can dose-dependently inhibit the activity of vascular endothelial cell proliferation and migration, and significantly up-regulate cell apoptosis (p<0.05). Zoledronic acid can inhibit the vascular endothelial cell activities of proliferation and migration, and can up-regulate cellular apoptosis, which suggests that direct inhibition of angiogenesis together with vascular impairment might contribute to the development of osteonecrosis of the jaw.