Bone Abstracts

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 two cases of hypercalcaemia of malignancy refractory to treatment with pamidronate and corticosteroids but responsive to treatment with Denosumab and Zoledronic acid.

Case 1: Presenting problem: A 17-year-old boy with epidermolysis bullosa presented with advanced squamous cell carcinoma of the left leg and 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.

Management: The hypercalcaemia was initially managed with hyperhydration, prednisolone and intravenous pamidronate (1 mg/kg/dose×2 doses), following which only transient improvement was noted. Despite further aggressive management with these treatment options, serum calcium remained persistently elevated at 3.39 mmol/l. As he was symptomatic, a trial dose of subcutaneous Denosumab (60 mg) was given, following which the calcium fell to 2.86 mmol/l within 24 h and normocalcemia was sustained a week later.

Case 2: Presenting Problem: A 17-year-old girl with pelvic rhabdomyosarcoma was hypercalcemic (serum adjusted calcium, 3.19 mmol/l) with supressed PTH of 0.3 pmol/l and serum phosphate of 2.2 mmol/l. Serum 25 hydroxy Vitamin D was 28 nmol/l and renal profile was normal.

Management: The initial treatment comprised hyperhydration, furosemide, prednisolone and intravenous pamidronate, after which serum calcium remained persistently elevated at 4.04 mmol/l. At this point intravenous Zoledronic acid (2 mg) was administered, following which the serum calcium dropped to 2.79 mmol/l within 24 h and normocalcaemia was sustained for several weeks, with no adverse effects.

Discussion: Denosumab is a monoclonal antibody which neutralises RANKL (receptor activator of nuclear factor k-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.

Disclosure: The authors declared no competing interests.