Learning from experience. Proposal of a refined definition and staging system for BRONJ.

It is the authors' belief that the internationally accepted definition of bisphosphonate-related osteonecrosis of the jaws (BRONJ) (Ruggiero et al., 2009) has several limitations that prevent clinicians from being confident with the diagnosis of the disease. Following recognition of the non-exposed BRONJ clinical variant (Lazarovici et al., 2009), we all become aware that the presence of "exposed necrotic bone in the oral cavity", as outlined in the AAOMS case definition, is just one of the possible clinical manifestations of BRONJ and cannot be inclusive of all BRONJ patients. As "bone exposure" is certainly not the initial sign of BRONJ in most cases and a minimum of 6-8 weeks persistence is required to confirm the clinical suspicion, final diagnosis is usually delayed for several weeks or months. Thus, it has been almost impossible to look into the early phases of BRONJ to date. This can also explains, at least in part, why the disease is often refractory to the medical and surgical treatments commonly used. We believe that most likely clinicians will benefit from a BRONJ definition which contains only robust information, without considering any definite clinical picture nor a binding timeframe (i.e. 6-8 weeks). As qualified members of the "Expert panel of the Italian Society for Maxillofacial Surgery (SICMF) and the Italian Society of Oral Pathology and Medicine (SIPMO) on Bisphosphonate-Related Osteonecrosis of the Jaws”, we are submitting to the attention of the scientific community the following definition of BRONJ: "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". Along with this new definition of BRONJ, we set-up and propose a diagnostic work-up to be used to reach the final diagnosis.