Publications

Zoledronic acid: May be less tolerable for elderly patients

Published: 5 March 2026
Prescriber Update 47(1): 9–11
March 2026

Key messages

Elderly patients receiving zoledronic acid infusions are at higher risk of adverse reactions and may experience more severe adverse reactions or find them more disabling than younger people.
In particular, acute phase reactions are noted as a cause of concern in reports to the New Zealand Pharmacovigilance Database.
Consider the following prior to the zoledronic infusion.

Inform the patient that acute phase reactions are common and usually resolve in a few days. However, patients should seek medical attention if symptoms are serious or prolonged.
Ensure the patient is adequately hydrated and measure their serum creatinine. Maintain adequate hydration following the infusion.
Treat pre-existing hypocalcaemia with adequate intake of calcium and vitamin D.

Background

Zoledronic acid is a bisphosphonate given as an intravenous infusion to treat various bone diseases such osteoporosis, Paget’s disease¹, tumour-induced hypercalcaemia and to prevent skeletal-related events in advanced malignancy involving the bone.²

Elderly patients receiving zoledronic acid infusions are at higher risk of adverse effects , including acute phase reactions, renal adverse events and hypophosphataemia and hypocalcaemia. Reasons for this include age-related decline in renal function, complex co-morbidities and polypharmacy.^1,2

Elderly patients may also experience more severe adverse reactions or find them more disabling than younger people, as noted in recent reports to the New Zealand Pharmacovigilance Database.

Acute phase reactions

Acute phase reactions (also known as post-dose symptoms) are a constellation of symptoms including fever, joint pain and swelling, myalgia, influenza-like illness and gastrointestinal symptoms (abdominal pain, vomiting and diarrhoea) that usually occur within the first three days after zoledronic administration.^1,2 Ocular inflammation, such as uveitis, can rarely occur.^1,3,4

These reactions are possibly due to a transient and rapid release of pro-inflammatory cytokines from the activation of T-cells following administration of zoledronic acid.⁵

Prior to infusion, inform the patient that acute phase reactions commonly occur, particularly following the first infusion. Symptoms are usually mild to moderate and resolve within a few days of onset.^1,2 Advise patients to seek medical attention if the symptoms are serious or prolonged.

Administering paracetamol shortly after the zoledronic acid infusion may reduce symptoms.^1,6

Promptly refer patients that develop symptoms of ocular inflammation (eg, eye redness, eye pain, light sensitivity, blurred vision) to an ophthalmologist for examination and treatment.⁷

Renal adverse events

Renal impairment can occur following administration of zoledronic acid, particularly if the patient has pre-existing renal impairment or additional risk factors, including age.¹

To minimise the risk of renal impairment in elderly patients:

ensure the patient is adequately hydrated¹ prior to and after the infusion (especially if acute phase reactions cause dehydration)
use caution if the patient is also taking medicines that can impair renal function, such as nephrotoxic medicines and diuretics^1,8
measure the patient’s serum creatinine prior to infusion and calculate their creatinine clearance.^1,8 Refer to the respective product data sheet for when zoledronic acid should not be given.

Hypocalcaemia and hypophosphatemia

Elderly patients are at risk of developing low serum calcium and phosphate levels following zoledronic acid infusion.¹ Cardiac arrythmias and neurological events are a potential consequence of severe hypocalcaemia.²

Administration of zoledronic acid is contraindicated in patients with hypocalcaemia. Pre-existing hypocalcaemia must be treated by adequate intake of calcium and vitamin D before initiating therapy with zoledronic acid.^1,2

New Zealand case reports

From 1 January 2016 to 31 December 2025, there were 428 cases reported to the New Zealand Pharmacovigilance Database where zoledronic acid was suspected to cause an adverse reaction. There were 355 reports in females, 69 in males and 4 where gender was not reported. Age was reported in 413 cases, with a median age of 70 years (range 15 to 94 years).

Cases reported in elderly patients

There were 290 cases reported in elderly patients aged 65 years and older, including 219 serious reports.

Acute phase reactions: there were 220 reports describing acute phase reactions, including 159 serious reports. The most frequently reported reactions were arthralgia (53 reports), myalgia (40), influenza-like illness (36), headache (34) and pyrexia (29).
Renal adverse events: there were 22 reports of renal adverse events, including 14 reports of acute renal failure and 6 reports of renal impairment.
Hypocalcaemia and hypophosphataemia: there were 17 reports of hypocalcaemia and 9 reports of hypophosphataemia, including 3 cases where both hypocalcaemia and hypophosphataemia were reported.

References

Sandoz New Zealand Limited. 2025. Aclasta New Zealand data sheet 23 January 2025. URL: www.medsafe.govt.nz/profs/datasheet/a/Aclastainf.pdf (accessed 13 January 2026).
Viatris Ltd. 2024. Zoledronic acid Viatris New Zealand data sheet 7 November 2024. URL: www.medsafe.govt.nz/profs/datasheet/z/ZoledronicAcidinf.pdf (accessed 13 January 2026).
Murdoch R, Mellar A, Horne AM, et al. 2023. Effect of a three-day Course of dexamethasone on acute phase response following treatment with zoledronate: A randomized controlled trial. Journal of Bone and Mineral Research 38(5): 631–8. DOI: https://doi.org/10.1002/jbmr.4802 (accessed 8 January 2026).
Thangavelu T, Johnson-Rabbett B, Magar RR, et al. 2018. Severe systemic inflammatory response syndrome with multi-organ failure following zoledronic acid infusion. AACE Clinical Case Reports 4(1): 26–9. DOI: https://doi.org/10.4158/EP161734.CR (accessed 8 January 2026).
Zincir Ercin DO and Ercin D. 2022. Evaluation of intravenous zoledronic acid-induced acute-phase response in the emergency department: Zoledronic acid acute in emergency department. Journal of Surgery and Medicine 6(8): 772–7. DOI: 10.28982/josam.1036910 (accessed 8 January 2028).
New Zealand Formulary (NZF). 2026. NZF v164: Zoledronic acid 1 February 2026. URL: https://nzf.org.nz/nzf_4035 (accessed 8 February 2026).
Medsafe. 2011. Reminder: Keeping an eye on bisphosphonates. Prescriber Update 32(3): 24. URL: www.medsafe.govt.nz/profs/puarticles/BisphosphonatesSept2011.htm (accessed 13 January 2026).
Rosen HN. 2025. Bisphosphonate therapy for the treatment of osteoporosisem. In: UpToDate 110 March 2025. URL: www.uptodate.com/contents/bisphosphonate-therapy-for-the-treatment-of-osteoporosis (accessed 13 January 2026).