Department of Pharmacy, Kobe City Medical Center General Hospital, 2-2-1, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
Support Care Cancer. 2021 Aug;29(8):4763-4772. doi: 10.1007/s00520-021-06018-x. Epub 2021 Feb 1.
This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ.
The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline.
Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024).
The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.
本研究旨在评估在开始使用地舒单抗或唑来膦酸(骨修饰剂)治疗骨转移之前接受牙科检查的患者中,临床特征与药物相关性颌骨坏死(MRONJ)发展之间的关联。此外,还评估了发生 MRONJ 的患者的临床结局以及 MRONJ 缓解的时间。
回顾性分析 2012 年 1 月至 2016 年 9 月期间接受地舒单抗或唑来膦酸治疗骨转移的癌症患者的病历。如果患者在基线时未进行牙科检查,则将其排除在外。
在 374 例纳入患者中,34 例(9.1%)发生了 MRONJ。地舒单抗组的 MRONJ 发生率明显高于唑来膦酸组(27/215 [12.6%] vs. 7/159 [4.4%],P=0.006)。多变量 Cox 比例风险回归分析显示,地舒单抗治疗、年龄较大、以及在开始使用 BMA 治疗前后拔牙与发生 MRONJ 显著相关。接受地舒单抗治疗的患者 MRONJ 缓解时间明显短于接受唑来膦酸治疗的患者(中位 26.8 个月 vs. 未达到;P=0.024)。
本研究结果表明,在接受骨转移治疗的患者中,地舒单抗治疗、年龄>65 岁、以及在开始使用 BMA 治疗前后拔牙与发生 MRONJ 显著相关。然而,地舒单抗引起的 MRONJ 比唑来膦酸引起的 MRONJ 缓解更快。