Pathophysiology of BRONJ: Drug-related osteoclastic disease of the jaw

Since the first article about bisphosphonate-related osteonecrosis of the jaw (BRONJ) was published in 2003, clinical and basic research for BRONJ has continued worldwide to understand this novel disease. Several organizations have proposed the definition, diagnostic criteria, risk factors, and treatment strategy for BRONJ. Recently, some new drugs used for cancer patients such as bevacizumab and sunitinib have also been reported to be involved in osteonecrosis of the jaw (ONJ). Because ONJ appears to be initially derived from osteoclast inhibition, a new category of diseases named as “drug-related osteoclastic disease of the jaw” may be assumed. Considering the accumulated knowledge related to BRONJ, including osteoclast biology, bisphosphonate pharmacology, animal experiments, and clinicopathological findings, a perspective of BRONJ from the pathophysiological viewpoint is proposed in this review.

▸ The recent findings and perspectives for BRONJ are reviewed. ▸ A hypothesis about the pathophysiology of BRONJ are proposed. ▸ Osteoclasts play a critical role in the self-defense of the jaw. ▸ BRONJ may be classified into a new category of diseases, “drug-related osteoclastic disease of the jaw”. ▸ We should prepare for the challenges from new drugs-related new diseases of the jaw.