6.6.2 Bisphosphonates and other drugs affecting bone metabolism

Oral bisphosphonates are absorbed very poorly; therefore counselling should be given to the patient as to how and when administration is most appropriate.

All oral bisphosphonate should be taken in combination with calcium & vitamin D (see section 9.6 Vitamins), the patient should be offered the product they like the best to achieve concordance.

Patient information leaflet: Your osteoporosis medication explained

Prescribers are reminded to check that an annual infusion of zoledronic acid has not been given, prior to commencing oral bisphosphonates.

Please refer to formulary guidance: Management of osteoporosis

MHRA Drug Safety Update (Nov 2009): The risk of developing osteonecrosis of the jaw with oral bisphosphonates seems to be low. The risk of is substantially greater for patients receiving I/V bisphosphonates for cancer indications than for patients receiving oral bisphosphonates for osteoporosis of Paget's disease. To minimise risk all patients should have a dental check-up before bisphosphonate treatment. All other patients who start bisphosphonates should have a dental examination only if they have poor dental status. During treatment, patients should maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or swelling.

MHRA Drug Safety Update (June 2011): Atypical femoral fractures have been reported rarely with bisphosphonate therapy, mainly in patients receiving long-term treatment for osteoporosis. They are often bilateral; therefore the contralateral femur should be examined in patients who have sustained a femoral shaft fracture. Discontinuation of therapy in patients suspected to have an atypical femur fracture should be considered while they are evaluated, and should be based on an assessment of the benefits and risks of treatment for the individual. During treatment, patients should be advised to report any thigh, hip, or groin pain. Any patient who presents with such symptoms should be evaluated for an incomplete femur fracture. The optimum duration of treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of bisphosphonate therapy for individual patients, particularly after 5 or more years of use.

Alendronic acid
  • Tablets 10mg (£1.83)
  • Weekly tablets 70mg (£0.74 = 4 tablets)

Indications and dose

  • Treatment of postmenopausal osteoporosis, 10mg daily or 70mg once weekly
  • Treatment of osteoporosis in men, 10mg daily
  • Prevention and treatment of corticosteroid-induced osteoporosis in postmenopausal women not receiving hormone replacement therapy, 10mg daily


  1. Alendronic acid 70mg is a 'special container' pack of four tablets. These should not be prescribed on weekly prescriptions as the pack cannot be split by the pharmacy to provide one tablet.
  2. Severe oesophageal reactions (oesophagitis, oesophageal ulcers, oesophageal stricture and oesophageal erosions) have been reported; patients should be advised to stop taking the tablets and to seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain
  3. Alendronate is not recommended for patients with renal impairment, GFR less than 35mL/minute
  • Tablets 5mg, 30mg (£18.85 = 5mg)
  • Weekly tablets 35mg (£0.85 = 4 tablets)

Indications and dose

  • Paget's disease of bone, 30mg daily for 2 months; may be repeated if necessary after at least 2 months
  • Treatment of postmenopausal osteoporosis to reduce risk of vertebral or hip fractures, 5mg daily or 35mg once weekly
  • Prevention of osteoporosis (including corticosteroid-induced osteoporosis) in postmenopausal women, 5mg daily
  • Treatment of osteoporosis in men at high risk of fractures, 35mg once weekly


  1. Oesophageal reactions: Patients should be advised to stop taking the tablets and to seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain
  2. The use of risedronate sodium is contraindicated in patients with severe renal impairment, avoid if GFR less than 30mL/minute
Ibandronic acid
  • Injection 1mg/ml (£44.68 = 2ml vial)


  • Treatment of postmenopausal osteoporosis


  • Intravenous injection over 15–30 seconds, 3mg every 3 months


  1. Ibandronic acid should be used with caution in patients with renal impairment – please consult the manufacturer's information for further information.
Sodium clodronate
  • Capsules 400mg (£139.83 = 120)
  • Tablets 520mg (£152.59 = 60)
  • Tablets 800mg (£146.43 = 60)


  1. Consultant initiation only
  2. Clodronate is eliminated mainly via the kidneys. Please refer to the manufacturers information for guidance regarding dose alterations.
Disodium pamidronate
  • Injection 15mg vial, 30mg vial, 60mg vial, 90mg vial


  1. IV disodium pamidronate is licensed to treat hypercalcaemia, osteolytic lesions and bone pain linked to bone/ skeletal metastases and that related to Paget's disease.
  2. Disodium pamidronate may be used in the treatment of osteoporosis (unlicensed). The required dose is diluted in 0.9% sodium chloride to a concentration of not more than 60mg in 250ml and given at a rate not exceeding 1mg per minute.
Zoledronic Acid
  • Zometa® concentrate for IV infusion 800 micrograms/mL, 5ml (4mg) vial
  • Aclasta® I/V infusion 50 micrograms/ml 100ml bottle

Monoclonal antibodies

  • Subcutaneous injection, pre-filled syringe 60mg per mL (£183.00 = 1ml syringe) (for South Devon patients this is provided by specialist service at Torbay Hospital)
  • Injection 70mg per ml 1.7ml (120mg) vial

Indications and dose

  • Prevention of osteoporotic fragility fractures in postmenopausal women, in line with NICE TA204, subcutaneous injection, 60mg every 6 months
  • Prevention of skeletal-related events in adults with bone metastases from breast cancer and from solid tumours other than prostate, in line with NICE TA265, by subcutaneous injection, 120mg every 4 weeks


  1. See here for the NEW Devon CCG Specialised Medicines Service Guideline for Denosumab (Prolia®) for osteoporosis (Western Locality)
  2. To avoid unnecessary out of pocket expenses, practices or pharmacies should order Prolia® direct from Movianto: www.prolia.co.uk/HCP/how_to_order_prolia.html
  3. MHRA Drug Safety Update (Oct 2012) The following precautions should be followed to minimise the risk of hypocalcaemia with denosumab:
    1. Denosumab 120mg (for cancer indications) should not be used in patients with severe, untreated hypocalcaemia
    2. Denosumab 60mg (for osteoporosis indications) should not be used in patients with hypocalcaemia, regardless of severity (the contraindications vary between the two doses, because their indications are different)
  4. NICE TA204: Denosumab for the prevention of osteoporotic fractures in postmenopausal women (October 2010)
  5. NICE TA265: Denosumab for the prevention of skeletal-related events in adults with bone metastases from solid tumours (October 2012)
  6. MHRA Drug Safety Update (Feb 2013): Atypical femoral fractures have been reported rarely in patients with postmenopausal osteoporosis receiving long-term (2.5 years or longer) treatment with denosumab 60mg in a clinical trial. During denosumab treatment, patients presenting with new or unusual thigh, hip or groin pain should be evaluated for an incomplete femoral fracture. Discontinuation of denosumab therapy should be considered if an atypical femur fracture is suspected, while the patient is evaluated
  7. MHRA Drug Safety Update July 2015 and MHRA Drug Safety Update June 2017:
    • Before prescribing denosumab or intravenous bisphosphonates:
      1. give patients the patient reminder card for their medicine
      2. explain the risk of osteonecrosis of the jaw, and osteonecrosis of the external auditory canal, and advise patients on precautions to take
      3. do not prescribe denosumab 120mg (cancer indication) to patients with unhealed lesions from dental or oral surgery
      4. advise patients to report any problems with their mouth or teeth, any ear pain, discharge from the ear, or an ear infection during denosumab treatment
      5. please continue to report suspected side effects to denosumab, bisphosphonates or any other medicines on a Yellow Card.


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