Vitamin D in bone metabolism Flashcards
Why is vitamin D important?
- Ca & vit D important for achieveing peak bone mass.
- Important for Ca absorbtion in gut.
- Helps to prevent fractures, osteomalacia & secondary hyperparathyroidism
- Vit D supplementation helps w/ fall prevention & physical performance
Symptoms of vitamin D deficiency in adults & children?
Children & adults
- Fatigue
- Generalised muscle, joint & bone pain
- Muscle weakness - especially extremities & pelvic regions.
- Hyperalgesia - increased sensitivity to pain & an extreme response to pain.
- Fragility fractures
Children
- Bone deformities
- Muscle weakness
- Cardiac problems
Explain the regulation of vitamin D (hydroxylation).
- 2 inactive forms of vitamin D that exist:
- Vitamin D2 (ergocalciferol) - plant derived & consumed in food
- Vitamin D3 (cholecalciferol) - formed from the effect of UV-B sunlight on 7-dehydrocholesterol in skin. - Both bind to vitamin D binding protein in blood
- Vitamin D2 & D3 are hydroxylated to 25-hydroxyvitamin D in liver (25(OH)D)
- uses enzyme 25-hydroxylase - PTH stimulates vitamin D conversion in kidneys
- 25-hydroxyvitamin D is then hydroxylated in kidney to form active vitamin D form, 1,25-dihydroxyvitamin D (1,25(OH)2D)
- uses 1-⍺-hydroxylase - Conversion to 1,25-dihydroxyvitamin D, stimulates the conversion of more inactivated vitamin D2 or D3 into 25-hydroxyvitamin D to replace what was used.
What are the functions of 1,25-dihydroxyvitamin D?
- Maintains normal Ca absorption in the intestines
Inadequate absorbtion of Ca → low serum Ca → secondary hyperparathyroidism (PTH is trying to ↑ Ca levels) → PTH stimulates osteoclasts & bone resorption → osteopenia. - Bone mineralisation - stimulates Ca incorporation in the growth plate & bone (i.e. bone formation) MAIN EFFECT.
- Increases Ca & P absorption from food in gut. MAIN EFFECTS.
- helps body absorb Ca - Supresses gene transcription for PTH
- So promotes bone mineralisation.
Less 1,25-vitamin D = more PTH = more bone resorbtion.
5 . Stimulates resorption of bone - particularly when PTH is high.
- Stimulates (+ PTH) Ca reabsorption in the kidney (PCT). NOT BIG EFFECT
- Inhibits its own formation from 25 vitamin D.
- Stimulates its own breakdown (catabolism) into 1,24,25 vit D by stimulating FGF23.
- Reduces excretion of PTH from parathyroid glands.
- Stimulates FGF23
Why is vitamin D so important in calcium and phosphate metabolism?
- If plasma Ca goes down, 1,25-dihydroxy vitamin D increases Ca reabsorbtion in the gut
- If plasma Ca goes up, it increases excretion of urinary Ca
- 1,25-dihyroxyvitamin D supresses PTH = suppresses bone resorbtion.
- Lack of Phosphate→ induces decrease in Ca + decreases efficacy of 1-⍺-hyroxylase → decreases 1,25(OH)2D → decreases gut’s ability to absorb Ca.
- Calcitonin ensures that the calcium in bone stays in bone.
What is the role of PTH in Vitamin D metabolism?
Stimulates the conversion of 25 vitamin D → 1,25 vitamin D in the kidney by activating the 1-⍺-hydroxylase enzyme
This conversion stimulates more vit D uptake from food to replace the 25 vit D.
What does FGF23 do?
Stimulates excretion of phosphate in the urine - MAIN EFFECT
Stimulates breakdown of 1,25 vitamin D & 25 vitamin D into non-active metabolites.
What are some sources of vitamin D?
- Skin synthesis- summer
- oily fish
-meat - eggs
- milk & cheese
- fortified spreads
- fortified cereals
- Recommended = 12 micrograms/day
- Most people are deficient.
What are some causes of vitamin D deficiency?
1.Low sunshine exposure - elderly housebound people or concealing dress style.
2. Low dietary supply
3. Malbsobtion disorders - Crohn’s or coeliacs disease.
4. Obesity- vitamin D likes to sit in fat tissue = not available to the liver or kidney..
5. Kidney or liver disease
6. Neonatal or infancy:
- Low maturnal status = low neonatal reserves.
- Prolonged breast feeding & cow’s milk.
Name the groups of people at high risk of vitamin D deficiency
- Dark skin (at high & low lattitudes) - can produce same amount of vit D but takes longer because pigment slows UVB through the skin.
- Concealing dress style
- Little UVB exposure e.g. mobility issues reduces time outside
- Obesity - vitamin D sits in fat
- Frail elderly - limited opportunity to be outside or vitamin D loss in kidney.
- Exclusively breast-fed babies
- Renal disease, GI disorders, coeliac disease, ICU patients, severe liver disease, cystic fibrosis, TB, HIV.
- Inflammation increases the risk of vitamin D deficiency.
Clinically, which type of vitamin D do you measure to get someone’s vitamin D level?
Need to measure 25 vitamin D. conc.
- 1,25 vit D is not measured clinically because plasma vit D is only weakly related to function & health outcomes.
- A lot of 1,25 vit D is hydroxylated in other tissues e.g. placenta, breast, bone, intestine so 1,25 is broken down = not reflected in the plasma.
below 25 nmol/L= deficient
25-50 nmol/L= insufficient
50 nmol/L= sufficient
What does a Ca & vitamin D deficiency cause?
secondary hyperparathryoidism
PTH constantly high = bone resorption = bone loss.
- Osteoporosis
Rickets & osteomalacia
Increased risk of falls w/ IV vitamin D
