Anti-RANKL Monoclonal Antibody Pregnancy: Contraindicated — fetal harm (RANKL essential for lymph node and bone development)

Denosumab

Brand names: Prolia (60 mg — osteoporosis), XGEVA (120 mg — bone metastases)

Adult dose

Dose: Osteoporosis (Prolia): 60 mg SC every 6 months. Bone metastases/giant cell tumour (XGEVA): 120 mg SC every 4 weeks.

Route: Subcutaneous

Frequency: Every 6 months (Prolia) or monthly (XGEVA)

Max: 60 mg per 6 months (Prolia); 120 mg per month (XGEVA)

FREEDOM trial: superior fracture reduction vs placebo. Do NOT discontinue without transitioning to bisphosphonate — rebound vertebral fracture risk on cessation. Calcium + vitamin D supplementation required.

Paediatric dose

Route: N/A

Frequency: N/A

Max: Not licensed in children (Prolia). XGEVA approved for giant cell bone tumour and bone metastases only.

Prolia not for use in children with open growth plates — hypocalcaemia risk

Dose adjustments

Renal

No dose adjustment required; hypocalcaemia more common in severe renal impairment — monitor calcium closely

Hepatic

No dose adjustment required

Clinical pearls

Calcium and vitamin D must be supplemented throughout treatment — denosumab suppresses RANKL-mediated osteoclast activity, calcium demand on skeleton increases
Dental review mandatory before starting — inform dentist patient is on denosumab; invasive dental procedures should be avoided during treatment
Rebound fractures: multiple vertebral fractures reported within 18 months of stopping — always transition to bisphosphonate on discontinuation
FREEDOM trial: 68% reduction in vertebral fractures, 40% hip fractures vs placebo over 3 years

Contraindications

Hypocalcaemia (must correct before starting)
Unhealed dental extractions (ONJ risk — dental assessment before starting)
Pregnancy

Side effects

Hypocalcaemia (significant — especially with renal impairment or vitamin D deficiency)
Atypical femoral fractures (rare — as with bisphosphonates)
Osteonecrosis of the jaw (ONJ — higher risk with XGEVA high doses)
Back pain
Serious infections (cellulitis, hospitalisation)
Rebound vertebral fractures on discontinuation

Interactions

No significant pharmacokinetic interactions — monoclonal antibody

Monitoring

Serum calcium (1 week and 1 month after each injection; ongoing in renal impairment)
Vitamin D levels before each injection
Dental hygiene
Atypical thigh pain (atypical fracture)
Bone pain

Reference: BNFc; BNF; FREEDOM Trial (Cummings et al, NEJM 2009); NICE TA204; Prolia SPC. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways