Bisphosphonate (IV) Pregnancy: Contraindicated — bisphosphonates persist in bone; potential fetal skeletal effects. Women of childbearing age: effective contraception required.

Zoledronic Acid

Brand names: Aclasta (once yearly), Zometa (oncology dosing)

Adult dose

Dose: Osteoporosis (Aclasta): 5mg IV once yearly. Paget's disease: 5mg IV single dose. Hypercalcaemia of malignancy (Zometa): 4mg IV over 15 minutes (repeat after ≥7 days if inadequate response). Bone metastases prevention: 4mg IV every 3–4 weeks.

Route: Intravenous infusion

Frequency: Once yearly (osteoporosis); every 3–4 weeks (oncology); single dose (Paget's/hypercalcaemia)

Max: 5mg per year (osteoporosis); 4mg per infusion (oncology)

Infuse over minimum 15 minutes (Zometa) or 15 minutes (Aclasta) — must be adequately hydrated before infusion. Ensure calcium and vitamin D supplements given (oral) before and after infusion. Preferred when oral bisphosphonates not tolerated or when adherence is concern.

Paediatric dose

Route: IV infusion

Frequency: Annually or as per specialist plan

Max: Individualised

Used under specialist supervision in osteogenesis imperfecta and other paediatric metabolic bone diseases. Seek specialist paediatric endocrinology opinion.

Dose adjustments

Renal

Aclasta (osteoporosis): do not use if eGFR <35. Zometa (oncology): dose reduce based on eGFR — manufacturer table required (3mg if eGFR 30–39; 3.5mg if 40–49; 4mg if ≥60).

Hepatic

No dose adjustment required.

Clinical pearls

Acute phase reaction: prophylaxis with paracetamol 1g oral before and for 3 days after infusion reduces severity significantly — counsel all patients
Pre-infusion checklist: eGFR ≥35, calcium and vitamin D supplemented, hydrated, dental review completed, no active infection
ONJ risk is higher in oncology patients (monthly dosing, underlying cancer, poor dentition) than osteoporosis patients (annual dosing)
HORIZON trial: once-yearly zoledronate reduced vertebral fractures by 70% and all-cause mortality by 28% in post-fracture patients

Contraindications

eGFR <35 (osteoporosis indication)
Hypocalcaemia (must correct before infusion)
Pregnancy
Hypersensitivity to zoledronic acid or other bisphosphonates

Side effects

Acute phase reaction — flu-like symptoms within 24–72h of first infusion (fever, myalgia, bone pain, fatigue); usually resolves within 3 days; less with subsequent infusions
Hypocalcaemia (particularly if vitamin D deficient — ensure replete before infusing)
ONJ (risk higher with more frequent oncology dosing)
Atypical femoral fractures (long-term)
Renal impairment (with rapid infusion or dehydration)
Uveitis (rare)

Interactions

Aminoglycosides — additive hypocalcaemia and nephrotoxicity
Thalidomide, nephrotoxic drugs — additive renal risk
Loop diuretics — additive hypocalcaemia

Monitoring

eGFR before each infusion
Calcium and phosphate before infusion
Vitamin D levels
DEXA scan every 2 years
Dental assessment
Symptom review (atypical bone pain)

Reference: BNFc; BNF 90; NICE CG146; HORIZON Trial (NEJM 2007). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways