Denosumab is a fully human monoclonal antibody, which inhibits bone resorption by specifically targeting RANK Ligand in the bone matrix, thus mimicking the body’s natural bone protection. 10 year safety and efficacy data for hip and vertebral fracture reduction in postmenopausal osteoporosis now available.

 

Indication for treatment

Postmenopausal women with bone mineral density (BMD) t-score < -2.5 and ≥ -4.0 for whom oral bisphosphonates are unsuitable due to contraindication, intolerance or inability to comply with the administration.

 

Preparation available - Prolia

Recommended dosage and administration

  • Denosumab 60 mg by single subcutaneous injection into the thigh, abdomen or back of arm every 6 months.
  • Cost: £183 per injection (annual cost £366)
  • Prescribe on standard GP10 prescription
  • Generally long-term as bone density falls on discontinuation with potential rebound increased fracture risk. If stopping treatment consider other pharmacological measures to prevent this. Recommend review fracture risk every 3 -5 years.
  • As the benefits wear off quickly, Denosumab or alternative treatment should be administered within 4 weeks of when due.
  • Renal impairment – No dose adjustment however increased risk hypocalcaemia
  • Hepatic impairment – Has not been studied, avoid until further data available
  • Drug Interactions – No interaction studies performed- in view of specific mode of action the potential for pharmacodynamic interactions is considered to be low.
  • Contra-indications:
    • Hypocalcaemia*
    • Hypersensitivity to active substance or any of the excipients
    • Pregnancy and lactation (until further data available)
      *Note-
      - -Contra-indications –
      Hypocalcaemia*
      Hypersensitivity to active substance or any of the excipients Pregnancy and lactation (until further data available)

Note 

  • Correct calcium and vitamin D deficiency before starting treatment
  • Co-prescribe calcium and vitamin D supplements such as Adcal D3 2 caplets twice a day unless hypercalcaemia or other contra-indication.
  • Prolonged, profound hypocalcaemia can occur in renal impairment – use with caution if eGFR < 60mmol/l and repeat serum calcium 2 weeks after each injection.
  • Avoid if eGFR 30mmol/l or less or dialysis.

 

Side effects

  • Generally very well tolerated.
  • Minor nausea, dizziness, fatigue, headache, rash, arthralgia.
  • Small increased risk of skin, urinary and upper respiratory tract infections however Denosumab is not immunosuppressant – no requirement for prior infection screening,vaccination (unless other indication) or to be stopped in the presence of active infection.
  • Risk of osteonecrosis of the jaw and atypical fracture is likely to be equivalent to Bisphosphonates.

Specialist responsibilities

  1. Assessment at osteoporosis clinic to formulate management plan on an
    individual patient basis.
  2. The decision to treat with Denosumab.
  3. To advise patient and send letter to General Practitioner advising plan.
  4. Further advice to General Practitioner at request.
  5. Review of patient at any stage at request of General practitioner if
    problems arise. (Routine follow up at osteoporosis clinic is not required
    unless other medical issues requiring follow up there.)
  6. To inform Primary Care as appropriate of any new data that becomes
    available regarding Denosumab.

Primary care responsibilities

  1. To identify patients where treatment may be appropriate - see positioning of Denosumab in treatment pyramid (appendix 1).
  2. Check serum eGFR, calcium and vitamin D along with other screening bloods for osteoporosis if not already checked, ideally prior to referral.
  3. Exclude myeloma.
  4. Refer osteoporosis clinic – referral pathway attached (appendix)

    Following receipt of letter from osteoporosis clinic advising initiation of Denosumab -

  5. Ensure calcium and vitamin D status adequate.
  6. Arrange prescription – ordinary prescription.
  7. Administration of subcutaneous injection (likely to be by practice nurse).
  8. Check serum calcium 2 – 4 weeks after initial injection and after each injection if eGFR < 60 mmol/l (in view of increased risk hypocalcaemia).
  9. 6 monthly review of patient to ensure no adverse effects or change in clinical scenario then arrange repeat administration of subcutaneous
    Denosumab 60mg as appropriate.
  10. Check serum calcium and eGFR prior to each injection to ensure remains sufficient and no new renal impairment.
  11. Check vitamin D annually pre injection if supplement compliance uncertain.
  12. Aim to treat long-term as long as no contraindication arises (such as
    progressive renal impairment).
  13. Consider referral back to osteoporosis clinic / sci-gateway advice request if further fractures despite treatment > 2 years or problems arise.

Positioning of denosumab in treatment pyramid

 

Denosumab Protocol

 

Patient leaflet

Click here for patient leaflet

Editorial Information

Last reviewed: 16/10/2023

Next review date: 16/10/2025

Author(s): Anne Drever.

Version: 1.1