Vitamin D Metabolism and Associated Diseases

Question 1

What are the 2 main forms of Vit D and where are they found?

Answer 1

• Vit D3 (in animals)

- Vit D2 (in plants)

Question 2

How is vitamin D synthesised?

Answer 2

-Reaction of 7-dehydrocholesterol with UV radiation
Need UV wavelength of 290-300nm.
-Cholecalciferol found which goes to liver where it is hydroxylated to 25-hydroxycholecalciferol by enzyme 25-hydroxylase.
-In the kidney, it then acts as substrate for 1 alpha hydoxylase, forming active Vit D 1.25DHCC.

Question 3

How does Vit D respond to low Ca and how?

Answer 3

• It increases to:
• Maintain skeletal Ca balance by promoting intestinal Ca absorption, increaseing oseoclast numbers.
• Binds to Vit D receptor, becoming a TF that modulates expression of transport proteins involved in Ca absorption in intestine.

Question 4

What is the problem with excess Vit D?

Answer 4

• Hypercalcaemia can cause nausea, vomiting
• It is rare to have the toxic effects of too much Vit D as we can consume decent amounts
• But may progress to bone pain, kidney disorders eg. Ca stone formation

Question 5

What are the problems with Vit D deficiency?

Answer 5

• Osteomalacia (once epiphysis is fused)

- Rickets (if epiphysis still present)

Question 6

What characterises osteomalacia?

Answer 6

-Impaired mineralisation of bone, leads to accumulation of unmineralised bone matrix called osteoid.

Question 7

What characterises rickets?

Answer 7

-Newly formed bone of growth plate does not mineralise, causing it to become thick, wide and irregular.

Question 8

What are potnetial primary and secondary causes of rickets?

Answer 8

• Primary: Asian immigrants (eat chapatis)
• Elderly housebound
• Lack of sunlight exposure
• Bizzare diets
• Seconday: partial gastrectomy
• Small bowel malabsorption
• Pancreatic disease
• Chronic renal disease
• Anticonvulsants

Question 9

What are the clinical features of osteomalacia?

Answer 9

• Often asymptomatic
• Bone pain; localised or generalised
• Bone tenderness
• Proximal muscle weakness
• Will cause decrease in BMD

Question 10

What are the currnet proven roles for Vit D in treatment?

Answer 10

• Osteomalacia/vit D deficiency treatment.

- Decrease hip fractures in elderly and housebound

Question 11

What are some potential causes of rickets?

Answer 11

• Vit D dependant rickets (4 types)
• Hypophosphatasia (phosphate problems)
• Fat malabsorption
• Renal tubulopathies

Question 12

What causes the 4 different types of vitamin D dependant rickets?

Answer 12

• 1A: caused by hydroxylation at alpha 1
• 1B: 25-hydroxylase deficiency
• 2A: defect on vit. d receptor gene
• 2B; due to abnormal expression of a hormone response element binding protein that interferes with normal function of Vit D receptor

Question 13

What does FGF have to do with rickets?

Answer 13

Its expression can sometimes play a role in causing rickets

Question 14

Describe some potential treatments for rickets?

Answer 14

• Current: additional phosphate, adequate Vit D, avoid calciuria and elevated PTH
• New- burosumab

Question 15

What are endocrine effects from Ca of Vit D?

Answer 15

• Rickets

- Osteomalacia

Question 16

What are non-endocrine effects not from Ca of Vit D?

Answer 16

• May result in other diseases:
• Cancer
• Type 1 diabetes
• Peridontal diseases

Question 17

What different levels of molecules can be expected in serum of osteoporosis patient?

Answer 17

• Ca = normal
• Phosphate = normal
• Alkaline phophatase = normal
• 250H Vit D = normal or low
• PTH = normal

Question 18

What different levels of molecules can be expected in serum of osteomalacia patient?

Answer 18

Ca = low or normal

• Phosphate = low or normal
• Alkaline phosphatase = normal or high+
• 250 H Vid D = low
• PTH = high

Question 19

What different levels of molecules can be expected in serum of primary hyperparathyroidism patient?

Answer 19

Ca= high
Phospahte = normal or low
Alkaline phosphatase = normal or high
250H Vit D = normal or low
PTH = high