A CASE OF DENOSUMAB-INDUCED HYPOCALCEMIA

A SEVERE AND PROLONGED CONSEQUENCES

Abstract

INTRODUCTION

Denosumab is known to cause abnormalities in calcium homeostasis. The majority of such cases have been described in patients with underlying metastatic cancer, chronic kidney disease or vitamin D deficiency. History of bariatric surgery could also compound the effect of hypocalcemia necessitating intravenous treatment and prolong high dose oral supplementation.

CASE
We present a 61-year-old female with a 6-day history of progressive worsening limbs numbness, tingling sensation and intermittent muscle cramp. She had gastric sleeve surgery done 20 years ago. Her regular medication includes calcium, vitamin D and iron supplement. Further history taking uncovered a history of denosumab treatment for osteoporosis 1 week ago at a private hospital.

Biochemistry revealed severe hypocalcemia with adjusted calcium of 1.33 mmol/l, mild hypophosphatemia at 0.65 mmol/l, with normal magnesium and renal function. ECG showed prolonged QT interval. PTH level was high at 34.6 pmol/l and 25-OH-vitamin D was insufficient at 33 mmol/l.

She required multiple courses of intravenous calcium gluconate bolus and infusion due to retractable severe hypocalcemia while titrating up her oral supplement in the ward. She was discharged after 8 days with serum calcium around 1.90 mmol/l. At clinic follow up 5 days later, her serum calcium decreased again to 1.64 mmol/l requiring further IV calcium infusion and oral supplement adjustment.

After 2 months, she still requires high dose replacement with 1.5ug calcitriol twice daily, 1g calcium carbonate thrice daily and vitamin D3 replacement to maintain normocalcemia..

CONCLUSION
This case report highlights the importance of screening for risk factors for iatrogenic hypocalcemia before initiating denosumab treatment particularly for patients with a history of bariatric surgery. Vitamin D should be adequately replaced prior to treatment and serum calcium levels should be closely monitored post treatment.