Table 5. Drugs and Biologics Used in Oncology and Reported to Be Associated With ONJ continued...
With the approval of a new antiresorptive medication, denosumab, a fully humanized monoclonal antibody that targets RANKL and that has indications similar to those of the bisphosphonates, additional reports confirmed that this new drug can also cause ONJ. Subsequently, the introduction of antiangiogenic medications in clinical trials in oncology revealed that these agents can also be associated with ONJ development, either as single drugs or when used in combination with antiresorptives. When antiangiogenics are used in combination with bisphosphonates, the risk of ONJ increases significantly.
Thus, osteonecrosis of the jaw is no longer a problem exclusively associated with the use of bisphosphonates; it is also associated with the use of other drugs such as the monoclonal antibody denosumab and antiangiogenics such as bevacizumab and sorafenib. For this reason, it is proposed that the nomenclature that refers to this pathology be changed to ONJ, meaning osteonecrosis of the jaw that is associated with medications.
ONJ is an oral complication of antiresorptive therapy in cancer patients. First reported in 2003,[1,2,3] ONJ is defined as the unexpected appearance of exposed necrotic bone anywhere in the oral cavity of an individual who is receiving drugs that have been associated with ONJ (bisphosphonates, denosumab, and antiangiogenics) and who has not received radiation therapy to the head and neck. The exposed bone persists for at least 6 to 8 weeks, despite the provision of standard dental care. It is also possible that symptoms of dental disease, periodontal disease, or both may be present, without visible exposed bone. The occurrence of ONJ is based on cases reported in the literature, and occurrence ranges from between 1% and 10% for patients receiving the intravenous formulation (pamidronate and zoledronic acid) to less than 1% for patients taking oral bisphosphonates.[10,11]
A study evaluating the literature until December 2008 found that the prevalence of ONJ can vary according to study design and the type of bisphosphonate used. For example, studies in which patient evaluation and follow-up are conducted by dental professionals have an overall prevalence of 7.3%, whereas survey studies of large populations of patients have a prevalence of less than 1%. If the prevalence is calculated on the basis of type of bisphosphonate used, then the prevalence of cases of ONJ in which a combination of zoledronic acid and pamidronate is used over the course of therapy can be as high as 24.5%. The mandible is affected in approximately 68% of cases, the maxilla in about 28% of cases, and both jawbones in approximately 4% of cases. However, there have been reports of evidence of ONJ in other parts of the head and neck and skeleton.[14,15,16]