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Old 06-11-2012
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Question Vitamin D mechanism of action on bone


I was wondering if anyone could help me figure out Vitamin D's effect on bone. My understanding is that Vitamin D increases bone reabsorption and increases Ca+ and Po3 levels in the blood.

However, I also read that low Vitamin D can cause rickets/osteomalacia because "it is needed for mineralization of bone." What exactly is mineralization of bone? Does that mean putting in the Ca/Phos into the protein matrix? What exactly does Vitamin D do on the bone? If it increases bone reabsorption, then wouldn't a lack or Vitamin D mean you would have less bone reabsorption and thus more dense bones? How does vitamin D deficiency cause soft bones exactly if it is normally involved in bone reabsorption?

Thanks for your help!
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Old 06-11-2012
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First of all it's bone resorption and not "bone reabsorption".

Vitamin D does increase bone resorption by causing osteoblasts to secrete RANKL which will activate osteoclasts. But on the other hand it decreases the PTH secretion leading to decrease in bone resorption.
It also stimulates Ca+2 re absorption from the gut and decrease in PO4 lose in the urine. It's important to understand that it is very important to decrease PO4 lose in the urine simply because in order to form hydroxylapatite you need both PO4 and calcium.
The overall outcome is that there is bone turnover with increase in the bone mass even although osteoclast are activated this is crucial because in order to form new strong bone you need to get rid of the older wakened bone (bone remodelling mediated by osteoclasts), the best example is in the disease osteopetrosis that although there is more bone mass which is formed, the bones are more fragile and that is because it's not the mass is important but the bone remodeling which is mediated by osteoclasts (which are activated by vitamin D indirectly).
Ofcourse excessive activation of osteoclasts like done by PTH will cause bone lose (i would add that even this is only when there is high amount of PTH, because actually low amount of PTH prompts bone formation this is best seen in the drug triparatide which is an analogous of PTH it's used in low doses in treatment of osteoporosis)
but the "beauty" about vitamin D is that it finds the right balance so to say

Bone mineralization is depositing Calcium and Phosphate in the matrix they join together and with OH to form hydroxylapatite which becomes carbonated to give us the bone mineral.

It's a very difficult topic that not everything is still known i doubt USMLE will dig to deeply in the topic. But know about RANKL and also about OPG (osteoprotegerin) questions might be seen about them.

with regards,
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The above post was thanked by:
ejhasan (06-11-2012)


Biochemistry-, Musculoskeletal-, Physiology-

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