Bisphosphonates are analogues of pyrophosphate, a molecule which decreases demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis.

Clinical uses

• prevention and treatment of osteoporosis
• hypercalcaemia
• Paget's disease
• pain from bone metatases

Adverse effects

• oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
• osteonecrosis of the jaw
  • substantially greater risk for patients receiving IV bisphosphonates in the treatment of cancer than for patients receiving oral bisphosphonates for osteoporosis or Paget's disease
  • poor dental hygiene/prior dental procedures are also a risk factor
  • the BNF advises that 'all patients with cancer and patients with poor dental status should have a dental check-up ... before bisphosphonate treatment'
  • initial investigation of choice if suspected would be an orthopantomogram - also known as a panoramic dental X-ray
• increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate
• acute phase response: fever, myalgia and arthralgia may occur following administration
• hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant

The BNF suggests the following counselling for patients taking oral bisphosphonates

'Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an empty stomach at least 30 minutes before breakfast (or another oral medication); patient should stand or sit upright for at least 30 minutes after taking tablet'

Hypocalcemia/vitamin D deficiency should be corrected before giving bisphosphonates. However, when starting bisphosphonate treatment for osteoporosis, calcium should only be prescribed if dietary intake is inadequate. Vitamin D supplements are normally given.

The duration of bisphosphonate treatment varies according to the level of risk. Some authorities recommend stopping bisphosphonates at 5 years if the following apply:

• patient is < 75-years-old
• femoral neck T-score of > -2.5
• low risk according to FRAX/NOGG