Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Profound hypocalcaemia following Denosumab for metastatic prostate carcinoma; an under-recognised and potentially fatal complication (#284)

Thomas Chesterman 1 , Anthony Zimmermann 1 , Peak Mann Mah 1 , Parind Vora 1
  1. Department of Endocrinology, Northern Adelaide Local Health Network, Elizabeth Vale, South Australia, Australia

Introduction

Denosumab has been demonstrated to be superior to Zoledronic acid for prevention of skeletal related events in patients with bone metastases from solid tumours.1 The safety profiles of both agents are comparable however hypocalcaemia is more frequent with Denosumab.2

Cases

We describe two patients with metastatic prostate cancer who required treatment for severe, symptomatic hypocalcaemia following Denosumab.

Case 1

A 76 year old man from a nursing home presented with confusion, agitation, fever and acute kidney injury. He was found to have severe hypocalcaemia (corrected total plasma calcium 1.64mmol/L). His plasma calcium level eventually normalised with a combination of aggressive intravenous and oral calcium replacement, calcitriol and thiazide diuretic therapy.

Case 2

A 74 year old man presented with lethargy and anorexia. Serum biochemistry revealed hypocalcaemia (corrected total plasma calcium 1.86mmol/L), hypophosphataemia, hypokalaemia and hypomagnesaemia. Medical history was notable for excessive alcohol intake, and poor nutritional status was thought to be a major contributor to his electrolyte abnormalities. He was commenced on oral potassium, phosphate and magnesium replacement and an increased dose of calcium carbonate and vitamin D. Three days later his hypocalcaemia worsened (corrected plasma calcium 1.29mmol/L). He required a continuous intravenous calcium infusion for over a week, magnesium infusion and high doses of calcitriol to eventually normalise his plasma calcium level.  

Discussion

Hypocalcaemia is an increasingly recognised adverse effect of Denosumab.2 While most cases are mild, severe and fatal cases have been reported.3 We discuss risk factors for the development of hypocalcaemia and review recommendations for the prevention and management of hypocalcaemia secondary to Denosumab.

  1. Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. European Journal of Cancer. 2012 Nov 30;48(16):3082-92.
  2. Body JJ, Bone HG, De Boer RH, Stopeck A, Van Poznak C, Damião R, Fizazi K, Henry DH, Ibrahim T, Lipton A, Saad F. Hypocalcaemia in patients with metastatic bone disease treated with denosumab. European Journal of Cancer. 2015 Sep 30;51(13):1812-21.
  3. XGEVA® (denosumab) prescribing information, Amgen.