Department of Pharmacy, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Department of Oral and Maxillofacial Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.
Cancer Chemother Pharmacol. 2021 Jun;87(6):871-877. doi: 10.1007/s00280-021-04262-w. Epub 2021 Mar 31.
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.
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.
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.
Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.
由于 denosumab 对颌骨和残留 ZA 活性的附加作用，从唑来膦酸（ZA）转换为 denosumab 可能会增加药物相关性颌骨坏死（MRONJ）的风险。我们评估了接受 ZA、denosumab 或 ZA 至 denosumab 治疗骨转移的患者发生 MRONJ 的风险。
回顾性分析接受 denosumab 或 ZA 治疗骨转移的癌症患者的病历。未在基线时进行牙科检查的患者被排除在外。主要终点是评估 ZA 至 denosumab 组发生 MRONJ 的风险。次要终点是 MRONJ 的概率和危险因素与 MRONJ 发生时间之间的关系。
在这项研究的 795 名患者中，有 65 名（8.2%）发生了 MRONJ。ZA 至 denosumab 组的 MRONJ 发生率明显高于 ZA 组[7/43（16.3%）比 19/350（5.4%），p=0.007]。多变量 Cox 比例风险回归分析显示，denosumab 治疗[风险比（HR），2.41；95%置信区间（CI），1.37-4.39；p=0.002]、ZA 至 denosumab 治疗（HR，4.36；95%CI，1.63-10.54，p=0.005）、ZA 或 denosumab 开始后拔牙（HR，4.86；95%CI，2.75-8.36；p<0.001）和同时使用抗血管生成药物（HR，1.78；95%CI，1.06-2.96；p=0.030）是 MRONJ 的显著危险因素。
我们的结果表明，从 ZA 转换为 denosumab 会显著增加骨转移患者发生 MRONJ 的风险。
