Symptomatic hypocalcaemia after administration of denosumab and iron infusion in patients with normal and impaired renal function

Osteoporosis and iron deficiency anaemia are common coexisting comorbidities in an ageing population. To facilitate timely administration of disease-modifying therapy, denosumab and iron infusions are often given concurrently on the day of discharge from an inpatient admission following fracture. It is becoming increasingly recognised that close administration of both can result in profound hypocalcaemia and/or hypophosphataemia due to disruption of calcium, phosphate and bone remodelling homeostasis. Our case series describes three cases of clinically significant, symptomatic hypocalcaemia in the setting of this potential drug-drug interaction, with symptoms including atraumatic femoral fracture, subacute cognitive decline and non-sustained ventricular tachycardia. While most previous case reports described hypocalcaemia in patients with advanced chronic kidney disease, two out of three of our cases had normal renal function, and one patient developed hypocalcaemia despite having calcium and cholecalciferol supplementation before and after denosumab administration. The optimal safe period between administration of the two medications has not been clearly established; one of our patients developed electrolyte disturbances despite having the medications 10 weeks apart.