Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®): Supportive care - Health Professional Information [NCI] - Oral Toxicities Not Related to Chemotherapy or Radiation Therapy
Bisphosphonate-associated Osteonecrosis (BON)
Bisphosphonates are potent inhibitors of osteoclasts. They are used in cancer patients with skeletal metastasis, including breast, prostate, or lung cancer; and in patients with multiple myeloma. Bisphosphonates are also used to treat hypercalcemia of malignancy. (Refer to the PDQ summary on Hypercalcemia for more information.) Bisphosphonates reduce the risk of fracture and skeletal pain, improving the quality of life of patients with malignant bone disease. (Refer to the PDQ summary on Pain for more information.)
Bisphosphonate osteonecrosis (BON) is an oral complication of bisphosphonate therapy in cancer patients. First reported in 2003,[3,4] BON is defined as the unexpected appearance of exposed necrotic bone anywhere in the oral cavity of an individual who is receiving a bisphosphonate and who has not received radiation therapy to the head and neck. The exposed bone persists for 6 to 8 weeks despite the provision of standard dental care. It is also possible that symptoms of dental and/or periodontal disease may be present, without visible exposed bone. The occurrence of BON is based on cases reported in the literature, and occurrence ranges between 1% and 10% for patients receiving the intravenous formulation (pamidronate and zoledronic acid) and less than 1% for patients taking oral bisphosphonate.[6,7]
A study evaluating the literature until December 2008 found that the prevalence of BON 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 seem to 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, the prevalence of cases of BON when 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 BON in other parts of the head and neck and skeleton.[10,11,12]
Osteonecrosis of the jaw (ONJ) incidence, risk factors, and outcomes were assessed in an analysis of three phase III trials in patients who had metastatic bone disease secondary to solid tumors or myeloma and who were receiving antiresorptive therapies. Patients were assigned to receive either subcutaneous injections of denosumab (120 mg) or intravenous administration of zoledronic acid (4 mg) every 4 weeks. Oral examinations were performed at baseline and every 6 months. Oral adverse events were adjudicated by a panel of dental experts. Of 5,723 patients enrolled, 89 (1.6%) were diagnosed with ONJ; 37 received zoledronic acid, and 52 received denosumab. Tooth extraction was reported for two-thirds of patients with ONJ. As of October 2010, ONJ resolved in 36% of patients (29.7% for zoledronic acid and 40.4% for denosumab). A combined analysis of these trials found that ONJ was an infrequent event, management was mostly conservative, and healing occurred in more than one-third of the patients. Bone-targeted therapy may help reduce the rate of ONJ and improve outcomes.