Switching from Zoledronic Acid to Denosumab Increases the Risk for Developing Medication-related Osteonecrosis of the Jaw in Patients with Bone Metastases

Purpose: Switch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases.

Methods: The medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing MRONJ in the ZA-to-denosumab group. Secondary endpoints were probability of MRONJ and the relationship between risk factors and the time to the development of MRONJ.

Results: Among the 795 patients included in this study, 65 (8.2%) developed MRONJ. The incidence of MRONJ was significantly higher in the ZA-to-denosumab group than in the ZA group [7/43 (16.3%) vs. 19/350 (5.4%), p = 0.007]. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment [hazard ratio (HR), 2.41; 95% confidence interval (CI), 1.37-4.39; p = 0.002], ZA-to-denosumab treatment (HR, 4.36; 95% CI, 1.63-10.54, p = 0.005), tooth extraction after starting ZA or denosumab (HR, 4.86; 95% CI, 2.75-8.36; p < 0.001), and concomitant use of antiangiogenic agents (HR, 1.78; 95% CI, 1.06-2.96; p = 0.030) were significant risk factors for MRONJ.

Conclusion: Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.