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Denosumab and Hypocalcemia

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Severe hypocalcemia associated with denosumab (Xgeva or Prolia) in metastatic castration-resistant prostate cancer has been reported on the European Urology website (25/2/2015)


Some practice points for physicians have been recommended here. 


  • Bone is the most frequent site of metastatic disease in prostate cancer, which can lead to skeletal-related events (SREs) such as pathologic fracture and cord compression.
  • Denosumab is approved by the US Food and Drug Administration (and the TGA / PBS in Australia) for use in solid tumors with bone metastases to prevent or delay SREs such as new fracture and the need for radiotherapy to bone.
  • The authors' case series suggested that a higher prevalence of severe and often prolonged hypocalcemia requiring hospitalization may occur in patients with metastatic castration-resistant prostate cancer in clinical practice. Hypophosphatemia was also commonly identified in cases of severe hypocalcemia.
  • Increased disease burden and vitamin D deficiency were discernible risk factors. Patients with albumin-corrected calcium levels in the low normal range may also be at risk.
  • Hospitalization for aggressive calcium and vitamin D replacement, calcitriol therapy, and correction of other electrolyte imbalances is encouraged for patients who experience severe hypocalcemia while receiving treatment.


Denosumab (Xgeva or Prolia) is a unique monoclonal antibody inhibiting 'RANKL', as distinct from zoledronic acid, which is a second generation bisphosphonate, also widely used for bone protection in the context of extended androgen deprivation (ADT) and/or bone metastases. a clinical comparison of these two drugs can be found in this section of The Forum.


Patients about to use or already using denosumab should discuss the issues raised above with their prescribing doctors, and should ensure that serum calcium and phosphate are being adequately monitored. 




Alan B

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.....a little more information on hypocalcemia (low calcium) with bone protection drugs.


This effect can also occur with the bisphosphonate drugs - both infused zoledronic acid and oral alendronate - but at lower frequency than with denosumab.


Vitamin D serum levels should be added to calcium and phosphorus blood monitoring for users of any of these drugs - before and during use. Discuss with your doctor if this is relevant to you.


Alan B 

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