Calcium

  • 99% in bone, 1% in blood
  • Obtained through diet (mainly dairy products), absorption controlled by vitamin D.
 

Calcium Regulation

  • Controlled by Parathyroid hormone, secreted from the parathyroid gland.
  • An increase in PTH, will cause an increase in calcium levels in the blood. This occurs my two main mechanisms:
    • Decreasing calcium secretion by the kidneys – This results in a increased secretion of phosphate ions
    • Increasing calcium absorption from bone, by action on osteocytes
Cell
Info
Function
Osteoblast
Found on the surface of bone. Constantly active, and depositing new bone tissue.
Produce osteoid – which is a collagen based material, which makes up the raw material of bone. These cells also help mineralise the bone to give it its strength.normal bone is about 30% osteoid, and 70% mineral salts (mainly calcium and phosphate).  There is a reduction in number of osteoblasts with age
Osteoclast
Found within the bone matrix. Constantly active and reabsorbing bone tissue
Remove bone tissue, and allow bone remodelling. Usually, at any one time, 1% of bone is being reabsorbed by osteoclasts. When when the bone is reabsorbed, the products of the reabsorption do not go straight into the ECF, instead they are trapped behind the osteocyctic membrane system.
Osteocyte
Essentially an osteoblast that has become trapped in the bone matrix. Found throughout bone, but most importantly, help form the osteocytic membrane system. This is a thin membrane that covers the bone, and separates bone from extracellular fluid.
Through the osteocytic membrane system, helps to regulate the concentration of solutes in the fluid around bone. PTH acts on these cells to increase the amount of calcium pumped out of the bone fluid system.

Normal bone formation

  1. Osteoid is made by osteoblasts. Consists of 95% collagen, and hyaluronic acid, and peptidoglycans. Collagen fibres tend to run lengthways in bone. Osteoid is very similar to cartilage, however, its structure allows salts to rapidly precipitate within it.
  2. Mineralisation – the main salt that forms contain both calcium and phosphate, and is called hydroxyapatite. Initially the crystals that form are not hydrozyapatitie, but over weeks and months, they will gradually be converted to this form. The precursor forms are knwon as amourphous crystals. These crystals can be rapidly reabsorbed if calcium is needed in the circulation.
    1. Calcium and phosphate will naturally form crystals once their concentrations are over a certain level. In normal ECF and other fluids, there are inhibitors of crystal formation that prevent calcium and phosphate forming crystals, despite their high concentration. In the fluid around bone behind the oesteocytic membrane system, these inhibitors are not present.
 

Normal Bone reabsoprtion

This is constantly occurring, and happens on about 1% of bone at any one time. Osteocytes have a ruffled border which is in direct contact with the bone matrix. They secrete:
  • Enzymes – which break down the osteoid
  • Acid – including lactic acid, which breaks down the mineral crystals
Osteoclasts also phagocytose fragments of bone crystal to help break them down, before releasing the products.
 
Ongoing process
Normally (except when we are growing) bone deposition and bone absorption occur at the same rate. Osetoclasts will absorb bone in little cylindrical ‘tunnels’ a few mm in length. This process takes about 3 weeks. Osteoblasts will the deposit bone matrix in concentric layers around the central lamina, until they encroach on a blood vessel, that is often at the centre of one of these holes. The areas around the blood vessel is known as the Haversian canal. The new area of bone that has been deposited is known as an osteon, and this process takes several months.
 

Why does bone remodelling occur?

  • It allows the alteration of bone strength in relation to the weight bearing the bone has to perform
  • It allows reshaping of the bone in relation to stress patterns
  • Old organic material in bone degenerates, making old bone weaker than new bone
    • In children, rates of remodelling are fast – and they have strong bones
    • In the elderly, rates are much slower, and bones are more brittle
 

Fractures

At the site of a fracture, osteoprogenitor cells will rapidly differentiate to form large numbers of osteoblasts, to aid the rapid reformation of bone. An organic matrix between the two bone ends will quickly be formed. This is known as a callus. This will then gradually be mineralised over the following weeks and months.
Stress on a bone site increases the rate of new bone formation. Surgeons can manipulate this effect, and in some fractures, the bones are held together strongly to create the impression of stress, so the fracture will heal more quickly.
 
 

Vitamin D regulation

Vitamin D has two important effects:
  • Increasing calcium absorption from the GI tract
  • Alteration of bone deposition and absorption
However, it does not exhibit either of these effects directly, and has to be converted to another substance first.
 
Production of vitamin D3(aka cholecalciferol)
There are various vitamin D coumpounds, and they all perform roughly the same function. The most important is D3.
Vitamin D is produced when 7-dehydrocholesterol in the skin, comes into contact with UV light. It can also be absorbed in the diet.
  • Conversion in the liverD3 is converted to 25- hydrocycalciferol in the liver. This product is slightly active. This has several benefits:
    • Regulates the level of active vitamin in the blood – even with very high vitamin D intake/production, there is a limit as to how much the liver can convert, thus it stops levels getting too high.
    • Is not stored for very long – again limiting the amount of the active substance in the blood. Vitamin D on the other hands, can be stored for months.
  • Conversion in the kidney – from 25-h, to 1,25-dihydroxycalciferol. This is the most active product, 1000 time more active than 25-h.
    • This production is dependent on PTH – in the absence of PTH, it does not occur.
 

Regulation of vitamin D levels

  • 1,25-dhc in the kidneys production is directly related to calcium concentration in the plasma. The higher the calcium concentration, the less 1,25-dhc is produced. This leads to reduced absorption of calcium from the GI tract, and increased secretion by the kidney, as secondary effects of reduced vitamin D3 activity.
 

Effect on bone

  • Moderate levels of 1,25-dhc cause increased bone mineralisation
  • Very high levels of 1,25-dhc cause bone absoprtion
 
For more info on calcium regulation, and bone remodelling, see osteoporosis

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