Bone Metastases

Question 1

Bisphosphonates

Aldendronic acid

Common indications

Answer 1

1. Aldendronic acid is used as the first-line drug treatment option for a patient at risk of osteoporosis fragility fractures.
2. Pamidronate and zoledronic acid are used in the trea.tment of severe hypercalcaemia of malignancy after appropriate IV rehydration
3. For a patient with myeloma and breast cancer with bone metastases, pamidronate and zoledronic acid reduce the risk of pathological fractures, cord compression and t.he need for radiotherapy or surgery
4. Bisphosphonates are used first-lin.e in the treatment of metabolically active paget’s disease, with the aim of reducing bone turnover and pain

Question 2

Bisphosphonates

Aldendronic acid

MOA

Answer 2

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

Question 3

Bisphosphonates

Aldendronic acid

Adverse effects

Answer 3

• 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 an atypical femoral fracture, particularly in patients on long-term treatment

Question 4

Bisphosphonates

Aldendronic acid

Warnings

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 an active upper GI disorder
• Because of the risk of jaw osteonecrosis, care should be exercised in prescribing bisphosphonates for smokers and patients with major dental disease

Question 5

Bisphosphonates

Aldendronic acid

Interactions

Answer 5

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

Question 6

Bisphosphonates

Aldendronic acid

Communication

Answer 6

• Explain that you are recommending 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 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

Question 7

Bisphosphonates

Aldendronic acid

Monitoring

Answer 7

• In osteoporosis, check and replace calcium and vit D before treatment
• Monitor efficacy using dual-energy X-ray absorptiometry (DEXA) scans every 1-2 years to check bone density is stable or increasing
• For hypercalcaemia, monitor efficacy by symptom enquiry and reduction in calcium levels
• In the treatment of myeloma, bone metastases and Paget’s disease
• Enquire about symptoms and bone complications
• For safety, be alert to symptoms of oesophagitis, osteonecrosis of the jaw and atypical femoral fractures, and monitor calcium and phosphate