Bisphosphonate — Intravenous (Annual) Pregnancy: Contraindicated — bisphosphonates accumulate in bone; fetal harm possible

Zoledronic Acid (Rheumatology — Osteoporosis)

Brand names: Aclasta, Zometa

Adult dose

Dose: 5 mg IV infusion (Aclasta) once yearly

Route: Intravenous infusion over at least 15 minutes

Frequency: Once yearly (osteoporosis); once every 2 years (Paget's disease)

Max: 5 mg per infusion (Aclasta); 4 mg per infusion (Zometa — oncology dosing)

Ensure adequate hydration before infusion. Check renal function and calcium before each infusion. Do NOT give if eGFR <35 mL/min (Aclasta). Pre-treat with 500 mg calcium + 400 IU vitamin D for at least 2 weeks before infusion to prevent hypocalcaemia.

Paediatric dose

Route:

Not licensed for paediatric osteoporosis in UK — seek specialist paediatric bone health opinion

Dose adjustments

Renal

Contraindicated if eGFR <35 mL/min — acute renal failure can occur. Ensure adequate hydration; avoid in dehydrated patients

Hepatic

No dose adjustment required

Clinical pearls

MHRA 2011 and 2020: Osteonecrosis of the jaw (ONJ) — dental examination and any necessary dental work should be completed BEFORE starting. During treatment, avoid invasive dental procedures; if unavoidable, consider treatment holiday (bisphosphonate holiday for 2–3 months around procedure, though benefit is debated)
MHRA 2011: Atypical femoral fractures — warn patients to report thigh, hip, or groin pain; bilateral risk; X-ray both femurs if unilateral AFF diagnosed
HORIZON pivotal fracture trial (NEJM 2007): 5 mg zoledronic acid IV annually reduced vertebral fractures by 70%, hip fractures by 41% — landmark trial establishing annual IV bisphosphonate efficacy
Post-infusion acute phase reaction: not an allergic reaction; prostaglandin-mediated; pre-dose paracetamol 1 g and hydration reduce severity
Drug holiday: after 5 years IV zoledronic acid, consider holiday in low-risk patients; high-risk patients (prior hip/vertebral fracture) should continue or switch to alternative

Contraindications

eGFR <35 mL/min
Hypocalcaemia — must be corrected before infusion
Pregnancy and breastfeeding
Hypersensitivity to bisphosphonates

Side effects

Post-infusion acute phase reaction — fever, flu-like illness, myalgia, arthralgia in 30% within 24–72 hours (especially first dose); self-limiting 1–3 days; paracetamol recommended
Hypocalcaemia — risk highest in vitamin D-deficient patients; mandatory pre-treatment with calcium and vitamin D
Osteonecrosis of the jaw (ONJ) — rare but serious; much higher risk in oncology doses (Zometa); risk with dental procedures; dental check before starting
Atypical femoral fractures (AFFs) — thigh pain warning sign; X-ray both femurs
Renal toxicity — infusion rate matters; must be given over ≥15 minutes
Uveitis/scleritis — rare inflammatory ocular complication

Interactions

Aminoglycosides — additive nephrotoxicity; avoid concurrent use
NSAIDs — increased nephrotoxicity; caution
Loop diuretics — hypocalcaemia risk; ensure adequate calcium supplementation

Monitoring

Serum creatinine and eGFR before each annual infusion
Serum calcium and vitamin D levels
Dental review before initiation
Thigh pain assessment (AFFs)
DXA scan every 2 years

Reference: BNFc; BNF 90; HORIZON Trial (NEJM 2007); MHRA DSU 2011 (ONJ/AFFs); NICE TA204 (Osteoporosis); SPC Aclasta. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways