Denosumab should be the treatment of choice for bisphosphonate refractory hypercalcaemia of malignancy

BMJ Case Rep. 2014 Jan 30;2014:bcr2013202861. doi: 10.1136/bcr-2013-202861.


Denosumab, a fully humanised monoclonal antibody, is licensed for treatment of postmenopausal osteoporosis, hormone ablation-induced bone loss and for prevention of skeleton-related events in patients with bone metastases from solid tumours. In pivotal phase 3 randomised trials, denosumab caused profound hypocalcaemia in patients with normocalcaemia despite oral calcium and vitamin D supplementation. This significant hypocalcaemic effect can be exploited to treat hypercalcaemia of malignancy (HCM). Recent reports from the USA suggest that denosumab is an effective treatment of HCM. According to our knowledge, we report the first two cases in UK with bisphosphonate refractory hypercalcaemia who responded to denosumab injections. Our first case gained 7 months of stabilisation of hypercalcaemia following prolonged admissions with life-threatening levels, while our second case achieved rapid normalisation of serum calcium levels for the first time in 14 months. We conclude that denosumab should be the treatment of choice for patients with bisphosphonate refractory hypercalcaemia.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma, Clear Cell / complications
  • Adenocarcinoma, Clear Cell / secondary*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bone Neoplasms / complications
  • Bone Neoplasms / secondary*
  • Carcinoma, Papillary / complications
  • Carcinoma, Papillary / secondary*
  • Carcinoma, Renal Cell / complications
  • Carcinoma, Renal Cell / secondary*
  • Denosumab
  • Diphosphonates
  • Female
  • Humans
  • Hypercalcemia / drug therapy*
  • Hypercalcemia / etiology
  • Kidney Neoplasms / complications
  • Kidney Neoplasms / pathology*
  • Middle Aged
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / pathology*
  • Paraneoplastic Syndromes / drug therapy*
  • Paraneoplastic Syndromes / etiology
  • RANK Ligand / antagonists & inhibitors*


  • Antibodies, Monoclonal, Humanized
  • Diphosphonates
  • RANK Ligand
  • Denosumab

Supplementary concepts

  • Humoral Hypercalcemia Of Malignancy