Department of Endocrinology, Austin Health, Melbourne, Vic., Australia.
Department of General Medicine, Royal Melbourne Hospital, Melbourne, Vic., Australia.
Clin Endocrinol (Oxf). 2020 Jun;92(6):495-502. doi: 10.1111/cen.14169. Epub 2020 Feb 16.
Denosumab is often used in men with advanced prostate cancer to prevent skeletal-related events, but can be associated with severe hypocalcaemia. Our objective was to review the pathophysiology, identify risk factors and provide recommendations for prevention and management of denosumab-associated hypocalcaemia.
We reviewed the literature regarding denosumab-associated severe hypocalcaemia, defined as necessitating hospitalization for intravenous calcium treatment, in the context of prostate cancer.
Men with prostate cancer with severe denosumab-associated hypocalcemia.
We identified 20 men with prostate cancer with severe denosumab-associated hypocalcemia, including the present case. Median age (range) was 70 years (45-86). All had skeletal metastases and presented with symptomatic hypocalcemia 16 days (4-35) after the initial (n = 18) or second (n = 2) denosumab treatment, with a serum total calcium of 1.36 mmol/L (1.13-1.91). The key risk factor was presence of active osteoblastic metastases, evidenced by elevated serum alkaline phosphatase, 838 U/L (58-2620) and supportive imaging. Other risk factors reported in some men included vitamin D deficiency (<50 nmol/L), 25-OH vitamin D 44 nmol/L (22-81), renal impairment, serum creatinine 103 μmol/L (62-1131) and hypomagnesaemia, 0.82 mmol/L (0.29-1.20). Men received intravenous calcium infusions for 16 days (1-90), and median total intravenous elemental calcium requirements were 3.17 g (0.47-26.65).
Denosumab treatment in men with metastatic prostate cancer can be associated with life-threatening hypocalcaemia requiring prolonged hospitalization for intravenous calcium treatment. Modifiable risk factors should be corrected before denosumab administration. In men with active osteoblastic metastases, consideration should be given to delay denosumab treatment until underlying disease activity is controlled, and/or be administered with close monitoring and proactive treatment with calcium and calcitriol.
地舒单抗常用于治疗晚期前列腺癌患者以预防骨骼相关事件，但可能会导致严重低钙血症。本研究旨在探讨地舒单抗相关低钙血症的病理生理学、识别危险因素，并为其预防和管理提供建议。
我们回顾了与前列腺癌相关的地舒单抗引起的严重低钙血症的文献，将其定义为需要住院进行静脉补钙治疗的情况。
患有前列腺癌且发生严重地舒单抗相关低钙血症的男性。
我们共纳入了 20 例患有前列腺癌且发生严重地舒单抗相关低钙血症的男性患者，包括本研究中的病例。中位年龄（范围）为 70 岁（45-86 岁）。所有患者均有骨骼转移，在初始（n=18）或第二次（n=2）地舒单抗治疗后 16 天（4-35 天）出现症状性低钙血症，血清总钙为 1.36mmol/L（1.13-1.91）。关键的危险因素是存在活跃的成骨转移，这表现为碱性磷酸酶升高，为 838U/L（58-2620）和支持性影像学证据。在一些患者中，其他报告的危险因素包括维生素 D 缺乏（<50nmol/L）、25-羟维生素 D 44nmol/L（22-81）、肾功能损害、血清肌酐 103μmol/L（62-1131）和低镁血症，为 0.82mmol/L（0.29-1.20）。男性接受了 16 天的静脉补钙治疗（1-90 天），中位总静脉用元素钙需求量为 3.17g（0.47-26.65）。
在患有转移性前列腺癌的男性中使用地舒单抗治疗可能会导致危及生命的低钙血症，需要长时间住院进行静脉补钙治疗。在使用地舒单抗之前，应纠正可纠正的危险因素。对于存在活跃成骨转移的患者，应考虑延迟地舒单抗治疗，直到控制基础疾病活动，或在密切监测下进行地舒单抗治疗，并积极用钙和骨化三醇进行治疗。
