Current situation and future issues of antiresorptive agent-related osteonecrosis of the jaw

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is characterized by refractory bone exposure, has recently emerged as a serious side effect of bisphosphonate (BP) treatment. BRONJ was first thought to be due to administration of high doses of intravenous BP to treat metastatic bone lesions or multiple myeloma. However, more recent studies have indicated that BRONJ also frequently occurs in patients receiving low doses of BP for the treatment of osteoporosis. In addition, patients treated with denosumab, a human monoclonal antibody against receptor activator of nuclear factor-kappa B ligand (RANKL) whose antiresorptive effects differ from those of BP, may develop osteonecrosis of the jaw. Since both BP and denosumab are associated with osteonecrosis of the jaw (ONJ), antiresorptive agent-related ONJ (ARONJ) has been suggested as a comprehensive term. Although the pathophysiology of BRONJ remains unclear and the number of affected patients is increasing in Japan, significant improvements have been made with respect to risk reduction strategies and treatment. Despite the publication of the first position paper on BRONJ in Japan in 2010, an increase of the number of patients of BRONJ is hypothesized to result from an increase in the long-term use of BP. Previous findings have suggested that inadequate preventive measures including restriction of tooth extraction may be responsible for increases in BRONJ incidence.