Anti-RANKL Monoclonal Antibody Pregnancy: Not recommended for use in pregnant women or in women of child-bearing potential not using contraception; there are no or limited data in pregnant women and animal studies have shown reproductive toxicity. Women should be advised not to become pregnant during and for at least 5 months after treatment. It is unknown whether denosumab is excreted in human milk - a decision on whether to abstain from breast-feeding or from therapy should take account of the benefit of each.

Denosumab

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

Denosumab is a subcutaneously administered monoclonal antibody used to treat osteoporosis at high fracture risk and to prevent skeletal complications of bone metastases, with different formulations and frequencies for each indication. In orthopaedics it is encountered chiefly as antiresorptive therapy for fragility-fracture prevention.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 60 mg

Route: Subcutaneous injection into the thigh, abdomen or upper arm, as a single injection; administration should be performed by an individual adequately trained in injection techniques

Frequency: Once every 6 months

Patients must be adequately supplemented with calcium and vitamin D. Patients should be given the package leaflet and the patient reminder card. The optimal total duration of antiresorptive treatment for osteoporosis (including both denosumab and bisphosphonates) has not been established; the need for continued treatment should be re-evaluated periodically on an individual patient basis, particularly after 5 or more years of use. Elderly (age 65 and over): no dose adjustment required. Hepatic impairment: safety and efficacy have not been studied. Product basis for this extraction is the 60 mg pre-filled syringe (osteoporosis / bone loss presentation, Acvybra 60 mg); the 120 mg oncology presentation used for skeletal-related events has a separate SPC and a different regimen and is NOT covered here. Paediatric: should not be used in children aged under 18 years because of safety concerns of serious hypercalcaemia and potential inhibition of bone growth and lack of tooth eruption; data for children aged 2 to 17 years are described in SPC sections 5.1 and 5.2.

Dose adjustments

Renal

No dose adjustment is required in patients with renal impairment. However, patients with severe renal impairment (creatinine clearance below 30 mL/min) or receiving dialysis are at greater risk of developing hypocalcaemia, with severe and fatal cases reported - ensure adequate calcium and vitamin D intake and monitor calcium regularly. No data are available in patients on long-term systemic glucocorticoid therapy with GFR below 30 mL/min.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Hypocalcaemia

Side effects

Pain in extremity and musculoskeletal pain (very common)
Urinary tract infection and upper respiratory tract infection (common)
Sciatica, constipation, abdominal discomfort (common)
Rash, eczema, alopecia (common); cellulitis, diverticulitis, ear infection, lichenoid drug eruptions (uncommon)
Hypocalcaemia, drug hypersensitivity, anaphylactic reaction, osteonecrosis of the jaw and atypical femoral fractures (rare)

Interactions

Concomitant glucocorticoid treatment is an additional risk factor for hypocalcaemia
Osteonecrosis of the jaw risk is increased by concomitant therapies including corticosteroids, chemotherapy, angiogenesis inhibitors and radiotherapy to the head and neck
Note: SPC section 4.5 was not captured in the retrieved bundle - clinician to check the full interaction section

Clinical monograph

How it works

It binds and neutralises RANK ligand, preventing activation of RANK on osteoclasts, thereby inhibiting osteoclast formation and function and reducing bone resorption.

Prescribing in practice

Correct hypocalcaemia before each dose and ensure adequate calcium and vitamin D, as denosumab can cause significant hypocalcaemia, particularly in renal impairment.
Stopping denosumab causes a rapid rebound increase in bone turnover with risk of multiple vertebral fractures, so doses must be given on schedule and a plan for alternative antiresorptive cover is needed if it is discontinued.
It is associated with osteonecrosis of the jaw and atypical femoral fractures — encourage dental health before and during treatment and review the SPC, noting the osteoporosis and oncology products differ in strength and frequency.

Monitoring

Check calcium (and renal function) before dosing and after starting, and remain alert for jaw symptoms and new thigh or groin pain during treatment.

Counselling the patient

Take your calcium and vitamin D as advised and do not miss your scheduled injections.
Tell your clinician before stopping treatment, as missing doses can lead to spinal fractures.
Maintain good dental hygiene and report jaw pain or non-healing mouth sores, and any new thigh or groin pain.

Evidence & guidelines

NICE recommends denosumab as an option for osteoporosis in selected patients, and the MHRA has warned about rebound vertebral fractures after stopping and the risk of osteonecrosis of the jaw.

Reference: FREEDOM Trial (Cummings et al, NEJM 2009); NICE TA204; Prolia SPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways