Published: 8 June 2018


Hypocalcaemia – a Risk with Zoledronic Acid

Prescriber Update 39(2): 24-25
June 2018

Key Messages

  • Hypocalcaemia is a common adverse reaction of zoledronic acid.
  • Measure serum calcium levels and treat pre-existing hypocalcaemia before administering zoledronic acid.
  • Give adequate calcium and vitamin D to all patients receiving zoledronic acid.
  • Monitor serum calcium levels and related metabolic parameters after starting zoledronic acid therapy.
  • Be cautious when administering zoledronic acid with medicines known to cause hypocalcaemia.

Zoledronic acid (zoledronate), is a bisphosphonate used for prevention of skeletal-related events in patients with advanced malignancies involving bone, and treatment of tumour-induced hypercalcaemia, Paget’s disease and osteoporosis1 .


Hypocalcaemia has been reported in 5–10% of patients treated with zoledronic acid infusion2 . Because zoledronic acid rapidly reduces bone turnover, transient hypocalcaemia may develop after administration, due to reduced bone contribution to the calcium pool. Transient hypocalcaemia is usually seen after the first infusion of zoledronic acid3 .

Although most cases are mild and asymptomatic, severe hypocalcaemia presenting with cardiac arrhythmias and neurologic events (seizures, tetany, and numbness) has been reported. In some instances, the hypocalcaemia may be life-threatening4 . Severe hypocalcaemia can occur within one day to several months after starting therapy2 .

Between May 2009 and December 2017, the Centre for Adverse Reactions Monitoring (CARM) received 10 reports of hypocalcaemia with zoledronic acid. One case was fatal. Zoledronic acid was the sole suspect medicine in nine of the cases. Baseline serum calcium level was reported to be normal in five of the cases while it was not reported in the remaining five cases.

Risk factors

Patients with low pre-treatment calcium level, co-administration of corticosteroids5 , inadequate calcium intake, Paget’s disease2 , low parathyroid reserve, vitamin D deficiency3 , and concomitant use of aminoglycosides, calcitonin or loop diuretics4 are at increased risk of developing severe hypocalcaemia following zoledronic acid infusion.

Reducing the risk of hypocalcaemia

The risk of hypocalcaemia can be reduced by:

  • measuring serum calcium and correcting pre-existing hypocalcaemia before starting therapy3,4
  • adequately supplementing patients with calcium and vitamin D during therapy3,4
  • monitoring serum calcium (albumin-corrected) levels and related metabolic parameters such as phosphate, magnesium and serum creatinine, after initiating zoledronic acid infusion3,4 .

Please report any adverse reactions to zoledronic acid to CARM (

  1. New Zealand Formulary. 2018. New Zealand Formulary v71: Zoledronic acid 1 May 2018 URL: (accessed 1 May 2018).
  2. UpToDate. 2018. Zoledronic acid: Drug information. URL: (accessed 30 April 2018).
  3. Novartis. 2016. Aclasta New Zealand Data Sheet 13 December 2016. URL: (accessed 10 May 2018).
  4. Novartis New Zealand Limited. 2016. Zometa New Zealand Data Sheet 23 May 2016. URL: (accessed 30 April 2018).
  5. Hanamura M, Iwamoto T, Soga N, et al. 2010. Risk factors contributing to the development of hypocalcemia after zoledronic acid administration in patients with bone metastases of solid tumor. Biol Pharm Bull 33(4): 721–4.
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