Chennuru S, Koduri J, Baumann M A
Department of Medicine, Division of Hematology/Oncology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA.
Intern Med J. 2008 Aug;38(8):635-7. doi: 10.1111/j.1445-5994.2007.01580.x. Epub 2008 Feb 17.
The bisphosphonate zoledronic acid is commonly prescribed to prevent skeletal complications in patients with multiple myeloma or metastatic cancer. Although symptomatic hypocalcaemia is a potential risk of treatment, it has been thought to be uncommon.
After seeing several episodes of symptomatic hypocalcaemia following zoledronic acid administration, we undertook a review to determine the incidence of this complication in our population and to attempt to identify risk factors.
We reviewed the records of all patients receiving zoledronic acid in two teaching hospitals over a 2-year period. Findings collected included the indication for treatment, whether dosing was adjusted for creatinine clearance, coadministered medications, serum chemistries and clinical course.
Of 120 patients who received a total of 546 zoledronic acid infusions, hypocalcaemia developed related to 55 infusions (10%) in 42 patients (35%). Symptomatic hypocalcaemia requiring i.v. supplementation occurred in 10 patients (8%), in spite of appropriate dose adjustment for creatinine clearance and despite prophylactic administration of oral calcium and vitamin D. More patients who became hypocalcaemic developed impairment of creatinine clearance during zoledronic acid treatment than in the group that remained normocalcaemic. Hypomagnesaemia was found in all patients who developed hypocalcaemia who had serum magnesium measured.
Hypocalcaemia was common in our patient group following zoledronic acid treatment. Because of the prolonged elimination half-life of this agent (146 h), renal impairment occurring during a number of days after administration may increase risk. Hypomagnesaemia may further increase risk by blunting compensatory increase in parathyroid hormone secretion.
双膦酸盐唑来膦酸常用于预防多发性骨髓瘤或转移性癌症患者的骨骼并发症。尽管症状性低钙血症是治疗的潜在风险,但一直被认为并不常见。
在观察到数例唑来膦酸给药后出现症状性低钙血症的病例后,我们进行了一项回顾性研究,以确定该并发症在我们患者群体中的发生率,并试图识别风险因素。
我们回顾了两家教学医院在两年期间所有接受唑来膦酸治疗的患者的记录。收集的资料包括治疗指征、是否根据肌酐清除率调整剂量、联合使用的药物、血清化学指标及临床病程。
120例患者共接受了546次唑来膦酸输注,其中42例患者(35%)的55次输注(10%)出现了与唑来膦酸相关的低钙血症。尽管根据肌酐清除率进行了适当的剂量调整,且预防性给予了口服钙和维生素D,但仍有10例患者(8%)出现了需要静脉补充钙剂的症状性低钙血症。与血钙正常的患者组相比,发生低钙血症的患者在唑来膦酸治疗期间出现肌酐清除率损害的更多。在所有检测血清镁的发生低钙血症的患者中均发现了低镁血症。
在我们的患者群体中,唑来膦酸治疗后低钙血症很常见。由于该药物的消除半衰期较长(146小时),给药后数天内出现的肾功能损害可能会增加风险。低镁血症可能会通过抑制甲状旁腺激素分泌的代偿性增加而进一步增加风险。