ESPE Abstracts (2015) 84 P-2-223

Refractory Hypercalcaemia of Malignancy: Responsiveness to Denosumab and Zoledronate

Dinesh Giria, Renuka Ramakrishnana, James Haydena, Lynda Brooka, Urmi Dasa, M Zulf Mughalb, Peter Selbyc, Poonam Dharmaraja & Senthil Senniappana


aAlder Hey Children’s Hospital, Liverpool, UK; bRoyal Manchester Children’s Hospital, Manchester, UK; cManchester Royal Infirmiry, Manchester, UK


Background: Hypercalcaemia secondary to malignancy is rare in children and adolescents. Parathyroid hormone related peptide (PTH-rP) secreted by malignant cells increases bone resorption and renal calcium retention causing hypercalcaemia. We report 2 cases of hypercalcaemia of malignancy refractory to treatment with pamidronate and corticosteroids but responsive to treatment with Denosumab and Zoledronic acid.

Case 1: A 17-year-old boy with epidermolysis bullosa and advanced squamous cell carcinoma of the left leg presented with symptomatic hypercalcaemia (serum adjusted calcium, 4.2 mmol/l). PTH was suppressed at 0.7 pmol/l. Serum 25 hydroxy vitamin D level was 31 nmol/l (normal range >50 nmol/l). PTH-rP and 1, 25 dihydroxy vitamin D levels were elevated at 2.1 pmol/l (0.0–1.8) and 173 pmol/l (43–143) respectively. The hypercalcaemia was initially managed with hyperhydration, prednisolone and i.v. pamidronate (1 mg/kg per dose×two doses), following which only transient improvement was noted. As symptomatic hypocalcaemia persisted (serum calcium 3.39 mmol/l), a trial dose of subcutaneous Denosumab (60 mg) was given, following which the calcium fell to 2.86mmol/l within 24 h and normocalcemia was sustained a week later.

Case 2: A 17-year-old girl with pelvic rhabdomyosarcoma was hypercalcaemic (serum adjusted calcium, 3.19 mmol/l) with suppressed PTH of 0.3 pmol/l. Serum 25 hydroxy vitamin D was 28 nmol/l and renal profile was normal. The initial treatment comprised hyperhydration, furosemide, prednisolone and intravenous pamidronate (1 mg/kg). As symptomatic hypercalcaemia persisted (serum calcium 4.04 mmol/l), intravenous Zoledronic acid (2 mg) was administered, following which the serum calcium dropped to 2.79 mmol/l within 24 h with sustained normocalcemia.

Conclusion: Denosumab is a monoclonal antibody, which neutralises RANKL (receptor activator of nuclear factor κ-B ligand), inhibiting the function of osteoclasts thereby preventing generalized bone resorption. Zoledronic acid blocks osteoclast resorption and has a more potent calcium-lowering effect than pamidronate. These two drugs widen the treatment options for patients with resistant hypercalcaemia of malignancy.

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