Bisphosphonates

Question 1

Example of a Bisphosphonate

Answer 1

Alendronate

Question 2

How do Bisphosphonates work?

Answer 2

Bisphosphonates reduce bone turnover by inhibiting the action of osteoclasts, the cells responsible for bone resorption. Bisphosphonates have a similar structure to naturally occurring pyrophosphate, hence are readily incorporated into bone. As bone is resorbed, bisphosphonates accumulate in osteoclasts, where they inhibit activity and promote apoptosis. The net effect is reduction in bone loss and improvement in bone mass.

Question 3

Indications for Bisphosphonates

Answer 3

Alendronic acid is used as the first-line drug treatment option for patients at risk of osteoporotic fragility fractures.

Pamidronate and zoledronic acid are used in the treatment of severe hypercalcaemia of malignancy after appropriate intravenous rehydration.

For patients with myeloma and breast cancer with bone metastases, pamidronate and zoledronic acid reduce the risk of pathological fractures, cord compression and the need for radiotherapy or surgery.

Bisphosphonates are used first-line in the treatment of metabolically-active Paget’s disease, with the aim of reducing bone turnover and pain.

Question 4

Contraindications for Bisphosphonates

Answer 4

Bisphosphonates are renally excreted and should be avoided in severe renal impairment. They are contraindicated in the context of hypocalcaemia. Oral administration is contraindicated in patients with active upper gastrointestinal disorders. Because of the risk of jaw osteonecrosis, care should be exercised in prescribing bisphosphonates for smokers and patients with major dental disease.

Question 5

Side Effects of Bisphosphonates

Answer 5

Common: oesophagitis (when taken orally) and hypophosphataemia.

Rare:
Osteonecrosis of the jaw, which is more likely with high-dose IV therapy. Good dental care is important to minimise the risk of this.
Atypical femoral fracture, particularly in patients on long-term treatment.

Question 6

Interactions of Bisphosphonates

Answer 6

Bisphosphonates bind calcium. Their absorption is therefore reduced if taken with calcium salts (including milk), as well as antacids and iron salts

Question 7

Elimination of Bisphosphonates

Answer 7

Renal

Question 8

Patient information on Bisphosphonates

Answer 8

Alendronic acid tablets should be swallowed whole at least 30 minutes before breakfast or other medications, taken with plenty of water. The patient should remain upright for 30 minutes after taking to reduce oesophageal irritation.

Explain that you are recommending a medicine to help strengthen the bones to prevent fractures and/or lower calcium levels in the blood to improve symptoms. Explain that the tablets can cause inflammation of the gullet. To minimise this risk, give clear advice on how to take the tablets and ask them to report any symptoms of oesophageal irritation. Advise patients to see their dentist before and during bisphosphonate treatment. Emphasise the dose and frequency of bisphosphonate treatment to avoid overdosing errors.