Iatrogenic Severe Hypocalcemia with the Use of High Dose Denusomab for Metastatic Bone Disease

Presentation Number: SAT 337
Date of Presentation: April 1st, 2017

Ayesha Jameel*, Ahmad A Chaudhary, Umair Iqbal and Madiha M Alvi
Bassett Medical Center, Cooperstown, NY


Use of osteoclast inhibitor denosumab (high dose 120 mg) significantly reduces risk of skeletal-related events (SREs) including fractures secondary to metastatic bone disease. Denosumab is a monoclonal antibody that inhibits the RANK ligand, a powerful bone-resorbing cytokine. The RANK pathway is critical in progression of bone metastasis. Severe hypocalcemia is a rare but potentially life-threatening outcome of this medication. It can be difficult to treat, especially with coexisting occult vitamin D deficiency as seen in patients with chronic kidney disease. Incidence of hypocalcemia is reported to be around 3 - 18%, and according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), only 3% are grade 3, grade 5 being death. We present a patient with metastatic prostate cancer who received denusomab with normal kidney functions and developed grade 4 hypocalcemia (serum calcium <6.0 mg/dL).
Clinical Case:
An 89-year-old male with recent diagnosis of prostate cancer with bone metastasis was given high-dose denusomab, after pre-treatment with vitamin D3 and calcium supplementation. Twelve days later he presented with generalized tremors, muscle cramps and myoclonic jerks. He had stable vital signs, normal mental status, but positive Chvostek’s and Trousseau’s signs. EKG showed normal sinus rhythm with prolonged QTc - 488 ms (n ≤ 440 ms). Laboratory analysis showed corrected serum calcium (SCa) 5.64 (pre-denosumab SCa 8.3; n 8.4–10.2 mg/dl); albumin 3.2 (n 3.5–5.0 g/dl); iCal 2.7 (n 4.2-5.4 mg/dL); Phos 2.0 (n 2.5-4.9 mg/dL), Magnesium 2.0 (n 1.5-2.5 mg/dL); Alkaline Phosphatase (ALP) 2470 (pre-denosumab ALP 3870; n 38-125 U/L); Intact PTH 487 (n 14-72 pg/mL). His electrolytes and kidney function were normal. He was started on calcium infusion and simultaneous high-dose oral supplements of calcium, calcitriol and cholecalciferol. Over the next 5 days the calcium levels stabilized to low normal range with improvement in his clinical symptoms. Calcium infusion was successfully weaned off and he was later discharged on oral therapy with a close outpatient follow up. 
Denusomab-induced hypocalcemia is usually prolonged and resistant to treatment potentially due to its long half-life (25 – 28 days) and elimination via the reticuloendothelial system. Predisposing risk factors include Vitamin D deficiency, inadequate oral calcium intake and high pre-treatment ALP levels as seen in this patient. Prior to initiation of osteoclast inhibitor therapy, serum calcium and vitamin D levels should be corrected. It is strongly recommended to closely monitor corrected serum calcium especially after first treatment in such patients.


Nothing to Disclose: AJ, AAC, UI, MMA