Abstract
PurposeSwitch 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.MethodsThe 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.ResultsAmong 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.ConclusionOur results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.
Highlights
Bone metastases are common in advanced cancers, resulting in clinically important complications, such as cancerrelated pain, fractures, spinal cord compression, and hypercalcemia [1]
To reduce the potential bias in evaluating patient and treatment characteristics associated with the development of medication-related osteonecrosis of the jaw (MRONJ), we limited the study participants to those examined by dentists before starting bone-modifying agents (BMAs) treatments because poor oral health status has been reported as a significant risk factor for developing MRONJ [8–10]
Between Jul 2011 and Oct 2019, 1192 adult patients with cancer bone metastases were treated with denosumab and/or zoledronic acid (ZA)
Summary
Bone metastases are common in advanced cancers, resulting in clinically important complications, such as cancerrelated pain, fractures, spinal cord compression, and hypercalcemia [1]. Despite the effectiveness of BMAs, these medications can increase the risk of medication-related osteonecrosis of the jaw (MRONJ). Cancer Chemotherapy and Pharmacology (2021) 87:871–877 factors for MRONJ have been reported, including medication-, patient-, and oral health-related risk factors [8–10]. The risk of MRONJ in this patient population has not been fully evaluated. Both ZA and denosumab have been associated with MRONJ, but their pharmacological mechanisms are completely different. We hypothesized that the risk of MRONJ may additively increase after switching from ZA to denosumab. We evaluated whether switching from ZA increase risk for developing MRONJ in cancer patients with bone metastases, comparing it to that in patients who received ZA/denosumab alone
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