ENDO - Clinical Pharmacology of Bisphosphonates, Parathyroid Hormones and Analogues

Question 1

Describe the role and regulation of calcium in the human body.

Answer 1

• Skeletal and smooth muscle contraction
• Functionality of endocrine and exocrine glands - Modulates cAMP and co-factor for lots of intracellular enzymes
• Involved in blood clotting

Mostly stored in bone as crystals
- 2% found in plasma
- 1% PPB
- 1% FREE and ACTIVE

Question 2

Summarise bone turnover in the body.

Answer 2

• Bone is dynamic up to 10 % of the total bone is being remodelled at any one time
• Trabecular bone has a higher turnover than cortical bone
• Osteoclast resorb bone and osteoblast make new bone

Question 3

Describe bone turnover in close detail.

Answer 3

See Slide 7

Question 4

(a) What are the 3 main causes of hypercalcaemia?

(b) What can moderate and severe hypercalcaemia lead to?

Answer 4

• Increased reabsorption from bone
• Increased absorption from the gut
• Decreased excretion through the kidney

Moderate hypercalcaemia leads to renal stones and damage. Severe leads to coma

Question 5

What are the 2 major causes of hypocalcaemia?

Answer 5

• PTH deficiency - Idiopathic hypoparathyroidism and surgical parathyroid gland removal
• Vitamin D deficiency - Dietary deficiency, limited sunlight and renal failure (1𝛼hydroxylation)

Question 6

How are mild, severe, chronic and acute severe cases of hypocalcaemia treated?

Answer 6

• Mild: oral calcium supplements must be taken between meal to avoid binding to phosphate and oxalate found in food stuffs
• Severe: vit D supplements. Usually large doses of ergocalciferol (vit D2)
• In chronic cases calcium supplements may be given also as carbonate or citrate salts
• Acute severe: as a result of parathyroidectomy must be treated IV with calcium either as gluconate, gluceptate or a chloride salt

Question 7

How can hypoparathyroidism be treated? PART 1

Answer 7

• TREATMENT: alfacalcidol
• PTH not use as replacement therapy
• Ergocalciferiol in large doses could be used but there is a risk of hypercalcaemia

Question 8

How can hypoparathyroidism be treated? PART 2

Answer 8

• Due to renal deficiency in hydroxylation of vit D in hypoparathyroidism there is a delayed onset of action (2-4 weeks) of ergocalciferiol
• Calcitriol onset of action 1-2 days (rapid)
• Choice of drug depends on kidneys ability to hydroxylate D2 – D3