Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®): Supportive care - Health Professional Information [NCI] - Oral Toxicities Not Related to Chemotherapy or Radiation Therapy
Table 5. Drugs and Biologics Used in Oncology and Reported to Be Associated With ONJ continued...
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.
When denosumab was compared to placebo in a study of men with nonmetastatic, high-risk, castration-resistant prostate cancer in which patients received treatment for at least 24 months, ONJ incidence was 4.6% in patients treated with denosumab; there were no cases of ONJ in the placebo group. Therefore, time on medication can be a factor in the development of ONJ.
Risk factors for ONJ include the following:
- Dental extractions.[Level of evidence: II]
- Ill-fitting dentures.
- Intravenous bisphosphonate (zoledronic acid, denosumab).[19,20][Level of evidence: I];[Level of evidence: I]
- Time on medication.[12,18,20]
- Multiple myeloma.
The incidence of ONJ may be reduced by the implementation of dental preventive measures before bisphosphonate therapy is initiated in solid-tumor patients with bone metastases.[22,23]
Diagnosis of ONJ
Diagnosis of ONJ can be clinically challenging. The most common clinical presentations are as follows:
- Classical: a cancer patient with skeletal metastasis who is receiving intravenous bisphosphonate or denosumab therapy and who presents with visible necrotic bone in the oral cavity. The site may be infected and painful; these conditions are the typical reason for referral to a dentist. Pain results both from inflammation of the soft tissues contiguous to the necrotic bone and from infection. Other symptoms typically occur in more advanced cases (e.g., paresthesia secondary to local neurologic involvement). Purulent secretion at the exposed area indicates active infection. Radiographic examination may demonstrate typical radiolucent and radiopaque areas associated with a bone sequestrum. Bone trabeculation may present with a moth-eaten appearance, suggesting ongoing bone destruction. Lesions can arise secondary to surgical dental treatments (e.g., dental extractions or periodontal surgery), significant dental infections, or trauma. Alternatively, ONJ can arise spontaneously, without any detectable trauma or predisposing treatment.
- Less common: a cancer patient receiving intravenous bisphosphonate or denosumab therapy who complains of pain that mimics periodontal or pulpal pathology. There is no clinically visible exposed necrotic bone, but a draining fistula or purulent secretion from the periodontal sulcus may exist. The involved teeth will typically be symptomatic upon palpation and percussion.
- Occasional: a cancer patient who complains of oral pain and discomfort, but a definitive diagnosis of ONJ cannot be made because no clinically exposed bone is evident. In these patients, the most likely clinical diagnosis should be addressed first. It is important to recognize that antiresorptive administration can result in bone pain, including to areas of the head and neck and jaws; this possible etiology for jaw symptoms should be considered as additional dental diagnoses are pursued. Routine clinical pulp testing and assessing for signs and symptoms of periodontal disease (e.g., pocket depths, bone loss, and bleeding on probing) should be performed. Radiographic examination should also be conducted. Although not yet definitively confirmed in the literature, the radiographic finding of sclerosing or absence of the lamina dura of the involved teeth may indicate the early presence of ONJ.[Level of evidence: III]
Endodontic and periodontal therapy should be performed first. The patient should be advised about the possibility of ONJ and should be educated about oral hygiene procedures. If dental extraction is indicated, the possibility of subclinical ONJ should be considered and explained to the patient. Thus, delay or absence of healing postextraction must be considered as risk for ultimate development of ONJ. Before the invasive procedure is performed, the risk of excessive bleeding and/or infection due to bone marrow suppression must be discussed with the patient's physician, and proper preventive measures should be formulated.