TeacherOfMedicine: Bisphosphonates

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.

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.

Common side effects include oesophagitis (when taken orally) and hypophosphataemia.
A rare but serious adverse effect of bisphosphonates is osteonecrosis of the jaw, which is more likely with high-dose IV therapy. Good dental care is important to minimise the risk of this.
Another rare but important adverse effect is atypical femoral fracture, particularly in patients on long-term treatment.

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.

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

TeacherOfMedicine