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
• 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: