Current Controversies in Classification, Management, and Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with oral and intravenous bisphosphonate therapy that adversely affects the quality of life, producing significant morbidity. Since the first description of bone necrosis in patients receiving bisphosphonate therapy in 2003 [1], hundreds of studies were published about this topic and various national and international medical societies have published protocols and guidelines. Nevertheless, there are still many controversies regarding the classification, management, and prevention of BRONJ. Even the definition of BRONJ is still debated and changed with the progress of knowledge and experience. According to the original definition of the AAOMS (American Association of Oral and Maxillofacial Surgery) [2, 3] " Patients may be considered to have BRONJ if all of the following three characteristics are present: (1) Current or previous treatment with a bisphosphonate; (2) Exposed bone in the maxillofacial region that has persisted for more than eight weeks; and (3) No history of radiation therapy to the jaws. " Following recognition of the nonexposed BRONJ clinical variant, it became clear that the presence of exposed necrotic bone in the oral cavity is just one of the possible clinical manifestations of BRONJ and is not found in all BRONJ patients. In 2012 the SICMF (Italian Society for Maxillofacial Surgery) and the SIPMO (Italian Society of Oral Pathology and Medicine) proposed a new definition [4]: " Bisphosphonate related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction described as the progressive destruction and death of bone that affects the mandible or maxilla of patients exposed to the treatment with nitrogen-containing bisphosphonates, in the absence of a previous radiation treatment. " Recently, this definition was robustly supported by a cross-sectional study on a large population of European patients with exposed and non-exposed bisphosphonate-associated ONJ; where, according to the traditional definition, only 76% of ONJ were diagnosed, and diagnosis in the remaining 24% could not be adjudicated, as they had several abnormal features relating to the jaws but no visible necrotic bone. [5] In parallel, it was demonstrated, in a large multicentre retrospective study, that the severity of ONJ (i.e. the extent of bony disease) as main guide to its management, can be correctly identified if measured by computed tomography (CT), more accurately than by clinical inspection and radiography as proposed by several staging systems, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system [6]. Very recently the …