Denusomab

Denosumab is a monoclonal antibody directed against the receptor activator of nuclear factor- KappaB ligand (RANKL). It reduces osteoclast differentiation and bone resorption. It can be administered subcutaneously. [2]

Denosumab has a lower risk of acute kidney injury than bisphosphonates, and so requires less monitoring, and may be preferred as a first line treatment for hypercalcaemia of malignancy in patients with renal impairment. It may also be used in combination with bisphosphonates. [5]

Potential adverse effects of denosumab include skin infections, acute osteonecrosis of the jaw, and hypocalcaemia in patients with vitamin D deficiency. Rebound hypercalcaemia has been observed in patients taking denosumab. [2]

In June 2018, the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued a safety alert following a pooled analysis of four phase 3 studies of denosumab in patients with advanced malignancies involving bone. [2, 11] New primary malignancies were reported more frequently among patients receiving denosumab than those receiving zoledronic acid (cumulative incidence of new primary malignancy at 1 year was 1.1% for denosumab and 0.6% for zoledronic acid). No treatment-related patterns for individual cancers or cancer groupings were identified. It is not known whether there is an increased risk of new primary malignancy when denosumab is prescribed for the treatment of hypercalcaemia of malignancy. [2]