Denosumab: A New Agent in the Management of Hypercalcemia of Malignancy

Future Oncol. 2015;11(21):2865-71. doi: 10.2217/fon.15.232. Epub 2015 Sep 25.


Hypercalcemia of malignancy is an oncologic emergency due to tumoral factors that stimulate osteoclast-mediated bone resorption. It requires a combination of recommended treatments (i.e., hydration, bisphosphonate and calcitonin), which may be deleterious in patients with compromised cardiac or renal function or may not control serum calcium levels long term. Recurrent or refractory hypercalcemia may preclude the use of chemotherapeutic agents needed to effectively treat the underlying cancer, which is the cause of hypercalcemia. Denosumab, a fully human monoclonal antibody against RANKL, inhibits the maturation, function and survival of osteoclasts. An open-label, single-arm study of denosumab in patients with hypercalcemia of malignancy despite recent bisphosphonate treatment revealed positive results. Thus, the US FDA recently approved denosumab for the indication of hypercalcemia of malignancy, increasing the options available for patients with this debilitating and life-threatening condition.

Keywords: RANKL inhibition; cancer; denosumab; hypercalcemia of malignancy; treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use*
  • Clinical Trials as Topic
  • Denosumab / pharmacology
  • Denosumab / therapeutic use*
  • Disease Management
  • Humans
  • Hypercalcemia / drug therapy*
  • Hypercalcemia / etiology*
  • Neoplasms / complications*
  • Neoplasms / drug therapy*
  • Treatment Outcome


  • Bone Density Conservation Agents
  • Denosumab