Denosumab-induced Prolonged Hypocalcemia: A Case Study

This article is part of Endocrinology Advisor‘s coverage of the 26th American Association of Clinical Endocrinologists (AACE) Annual Scientific Sessions & Clinical Congress, taking place in Austin, Texas. Our staff will report on medical research and technological advances in diabetes, obesity, and thyroid conditions, conducted by experts in the field. Check back regularly for more news from AACE 2017.

At the 26th American Association of Clinical Endocrinologists (AACE) Annual Scientific Sessions & Clinical Congress, held May 3-7, 2017 in Austin, Texas, physicians from Henry Ford Health System in Detroit, Michigan, presented a case study of a patient treated for severe hypocalcemia due to treatment with denosumab.¹

The human monoclonal antibody denosumab increases bone density and reduces osteoclastogenesis and bone resorption. It is typically prescribed at 60 mg every 6 months for osteoporosis treatment, or at 120 mg every 4 weeks for “prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors,” the researchers wrote.

Previous research found severe hypocalcemia in 15% of patients treated with denosumab.² Risk factors for denosumab-induced hypocalcemia, according to the current investigators, “include osteoblastic metastases, high PSA levels, high alkaline phosphatase levels, renal dysfunction and vitamin D deficiency.” The focus of their case study was an 83-year-old male patient with castration-resistant prostate cancer metastatic to bone who had prolonged hypocalcemia resulting from denosumab use.

The patient had received subcutaneous injection of denosumab 120 mg 8 days before presenting to the emergency department with generalized weakness and altered mental status. Clinical examination showed no presence of Chvostek’s sign or Trousseau’s sign, and lab results were as follows:

• Corrected calcium: 5.4 mg/dL (8.7-10.1 mg/dL)
• Creatinine: 1.6 mg/dL
• Glomerular filtration rate: 45 ml/min/1.73m² (>60 ml/min/1.73m²)
• Parathyroid hormone: 419 pg/mL (15-65 pg/mL)
• Alkaline phosphatase: 237 IU/L (0-140 IU/L)
• Magnesium: 1.7 mg/dL (1.8-2.3 mg/dL)
• Phosphorus: 2.5 mg/dL (2.5-4.5 mg/dL)
• 25-hydroxy vitamin D: 41 ng/mL (>20 ng/mL)
• Prostate-specific antigen (PSA): 163.5 ng/mL (<4.0 ng/mL)

In addition, prolongation of the corrected QT (QTc) interval was observed on electrocardiogram.

When multiple intravenous boluses of calcium gluconate failed to significantly improve serum calcium levels, the patient was admitted to the intensive care unit. Following a 36-hour continuous infusion of calcium gluconate, serum calcium and ionized calcium increased to 7.2 mg/dL (8.6-10.4 mg/dL) and 1.0 mmol/L (1.0-1.35 mmol/L), respectively.

The patient returned to the hospital twice in the 5 weeks post-discharge due to asymptomatic hypocalcemia, despite daily supplementation with ≥3 g of oral calcium carbonate and 4 mcg of calcitriol. Calcium levels again improved with continuous calcium infusion, and 7 weeks after denosumab was administered the patient required daily supplementation with 4 g of oral calcium carbonate, 10 mcg of oral calcitriol, and 2000 IU of vitamin D3.

The researchers emphasized the importance of monitoring and correcting levels of calcium and vitamin D before denosumab is administered, and the supplementation of both nutrients during and after administration of the drug. “Prolonged calcium infusion and high dose calcitriol may be required to correct severe hypocalcemia,” they noted. 

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Reference

1. Das LMV, Gopie S, Rao S, Lahiri S, Bhan A. Denosumab-induced prolonged hypocalcemia: need for high-dose calcium and calcitriol supplementation. Abstract 508. Presented at: 26th American Association of Clinical Endocrinologists Annual Scientific Sessions & Clinical Congress. May 3-7, 2017; Austin, TX.
2. Autio KA, Farooki A, Glezerman IG, et al. Severe hypocalcemia associated with denosumab in metastatic castration-resistant prostate cancer: risk factors and precautions for treating physicians. Clin Genitourin Cancer. 2015;13(4):e305-e309. doi:10.1016/j.clgc.2014.11.008