RANK Ligand Inhibitor (Anti-resorptive) Pregnancy: Contraindicated — animal studies show skeletal malformations. Women of childbearing age: effective contraception required during and for 5 months after last dose.

Denosumab

Brand names: Prolia (osteoporosis 60mg), Xgeva (oncology 120mg)

Adult dose

Dose: Osteoporosis (Prolia): 60mg SC every 6 months. Prevention of skeletal-related events in bone metastases (Xgeva): 120mg SC every 4 weeks (with additional 120mg on days 8 and 15 of first month for giant cell tumour).

Route: Subcutaneous injection

Frequency: Every 6 months (Prolia); every 4 weeks (Xgeva)

Max: 60mg per 6-month dose (Prolia); 120mg per 4-weekly dose (Xgeva)

RANK-L inhibitor — blocks osteoclast activation. Unlike bisphosphonates, does not accumulate in bone — effects reverse within 12 months of stopping (rebound vertebral fractures reported on discontinuation). Ensure calcium and vitamin D supplemented. Can be used in severe renal impairment (eGFR <30) — advantage over bisphosphonates.

Paediatric dose

Route: Subcutaneous injection

Frequency: Every 6 months

Max: Individualised

Xgeva licensed from age 12 years for giant cell tumour of bone and bone metastases. Prolia not licensed in children. Seek specialist paediatric oncology/endocrinology opinion.

Dose adjustments

Renal

No dose adjustment required — can be used in any degree of renal impairment including dialysis. Monitor calcium closely in severe renal impairment (high risk of hypocalcaemia).

Hepatic

No dose adjustment required.

Clinical pearls

Rebound fracture risk on stopping: do NOT stop denosumab without transitioning to a bisphosphonate — vertebral fracture risk is paradoxically high in the 12 months after stopping due to rapid reversal of antiresorptive effect
FREEDOM trial: 68% reduction in vertebral fractures vs placebo over 3 years
Preferred in renal impairment (eGFR <35) where bisphosphonates are contraindicated
ONJ and atypical fracture warnings apply — same dental precautions as bisphosphonates

Contraindications

Hypocalcaemia (must correct before starting)
Hypersensitivity to denosumab
Pregnancy

Side effects

Hypocalcaemia (particularly in renal impairment or vitamin D deficiency — most serious side effect)
ONJ (similar risk to bisphosphonates)
Atypical femoral fractures
Infections (skin infections/cellulitis — RANK-L also expressed on immune cells)
Rebound vertebral fractures on discontinuation

Interactions

Immunosuppressants — additive infection risk
Other antiresorptives — do not combine

Monitoring

Calcium (before each injection and 2 weeks after — especially in CKD)
Vitamin D level
DEXA scan every 2 years
Dental review before starting
Transition plan on stopping (to bisphosphonate)

Reference: BNFc; BNF 90; NICE TA204; FREEDOM Trial (NEJM 2009). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways