From the Guidelines
Evinity (denosumab) is associated with a risk of osteonecrosis of the jaw (ONJ), with an incidence rate of approximately 1-2% in cancer patients receiving the higher 120 mg dose, as reported in the most recent study 1. The risk increases with longer duration of treatment, with most cases occurring after 2-3 years of therapy. Additional risk factors that significantly increase ONJ risk include:
- Invasive dental procedures (particularly extractions)
- Poor oral hygiene
- Periodontal disease
- Ill-fitting dentures
- Cancer diagnosis (especially multiple myeloma or metastatic disease)
- Concurrent chemotherapy
- Corticosteroid use
- Smoking To minimize risk, patients should:
- Undergo comprehensive dental evaluation before starting Evinity
- Complete necessary dental work prior to treatment initiation
- Maintain excellent oral hygiene
- Avoid invasive dental procedures during therapy when possible ONJ risk is related to Evinity's mechanism of action as a RANKL inhibitor, which suppresses bone turnover and remodeling, potentially impairing the jaw's ability to heal after trauma or infection due to its high bone turnover rate and exposure to oral bacteria, as supported by studies 1. The NCCN Guidelines for MM recommend bisphosphonates (category 1) or denosumab for all patients receiving therapy for symptomatic MM regardless of documented bone disease, with a baseline dental examination and monitoring for ONJ in all patients receiving a bone-modifying agent 1. It is essential to weigh the benefits of Evinity against the potential risks, particularly in patients with a history of dental problems or those undergoing invasive dental procedures, as noted in the studies 1. The most recent and highest quality study 1 provides the best evidence for the incidence of ONJ in patients receiving Evinity, and its findings should be prioritized in clinical decision-making.
From the Research
Incidence of Osteonecrosis of the Jaw
- The incidence of osteonecrosis of the jaw (ONJ) in patients with osteoporosis is estimated to be 1-90 per 100,000 patient-years of exposure 2.
- In the oncology patient population, the incidence of ONJ appears to be related to dose and duration of exposure, and prevalence has been estimated to be as high as 18.6% 2.
- A study found that the incidence of ONJ was 1.8% (2/110), 6.3% (6/99), 4.9% (4/82), 5.6% (3/54), and 3.4% (1/29), respectively in the first, second, third, fourth, and fifth year of bone resorption inhibitor (BRI) exposure 3.
- Another study found that the incidence of ONJ per 10,000 observed patient-years was 28.3 in patients receiving denosumab and 4.5 in patients with bisphosphonate-associated ONJ, yielding a rate ratio of 6.3 (95% confidence interval [CI] 2.1 to 22.8), p < 0.001 4.
Risk Factors for Osteonecrosis of the Jaw
- Risk factors for ONJ include the presence of periodontal disease, oral surgical procedures with extractions or implants, radiation therapy, chemotherapy, diabetes, glucocorticoid use, and smoking 2.
- Antiangiogenic agents appear to contribute to the risk of ONJ, however, data at this time are limited and further evidence is required prior to confirming a causal relationship 2.
- Previous bisphosphonate therapy before switching to denosumab may be an additional risk factor for ONJ development 4.
Comparison of Denosumab and Bisphosphonates
- A study found that the risk of ONJ was higher in patients receiving denosumab therapy compared with bisphosphonates (hazard ratio 3.49,95% CI 1.16 to 10.47, p = 0.026) 4.
- Another study found that the incidence of ONJ was 1.8% (52/5723) in patients receiving denosumab and 1.3% (37/5723) in patients receiving zoledronic acid (P = 0.13) 5.