The Potential Role of Angiogenic Osteoclast Inhibition in the Occurrence of Bisphosphonate-related Osteonecrosis of the Jaw

Abstract

Bisphosphonate-related osteonecrosis of the jaw is a serious complication of systemic bisphosphonate administration, the mechanism of which remains unclear. Many hypotheses regarding pathophysiology are discussed, including the most commonly cited: suppression of bone remodeling and suppression of angiogenesis, but none of these would explain all the unique features of bisphosphonaterelated jaw osteonecrosis. Bisphosphonates are potent inhibitors of osteoclasts, and recent studies have shown that osteoclasts are important for bone angiogenesis. Therefore, we hypothesize that bisphosphonates inhibit osteoclastic stimulation of angiogenesis, thereby contributing to the occurrence of osteonecrosis of the jaws. This theory would partially explain the pathophysiology of bisphosphonate-related osteonecrosis of the jaw to the unfathomable.