Bone and calcium metabolism

• Bone is made up of:

  • Proteins and collagen - give the bone ability to be stretched without fracturing
  • Calcium and phosphate crystals (mineral portion) - gives bone density and rigid strength making it resistant to bending
• Bone osteoblasts:

  • Makes collagen, proteins and ALP (enzyme)
  • All form a scaffold
  • Calcium and phosphate crystallise on this scaffold
  • Results in bone formation
• Bone osteoclasts:

  • Break down and resorb bone tissue
  • Releases calcium and phosphate back into blood
• Bone ALP and liver ALP are different enzymes but standard blood tests cannot differentiate - special isoenzyme blood test can be done but history and examination should indicate the underlying cause
• Calcium metabolism:

  1. We get calcium through our diet
  2. Calcium is absorbed from intestines
  3. Filtered by kidneys but majority reabsorbed back into blood
  4. 2% is within the blood - level regulated tightly
  5. 98% is within the bone - strengthens and acts as a store that can be released into blood when needed
• Calcium levels in blood and bone controlled by:

  • Calcitriol (active vitamin D3)
  • PTH
  • Calcitonin - produced by thyroid gland to decrease calcium
• Vitamin D metabolism:

  1. Small amount through diet - most through sunlight exposure
  2. Vitamin D precursor in the skin (inactive), UV light exposure turns this into an inactive form of vitamin D3 = cholecalciferol
  3. Cholecalciferol goes to the liver and is converted to calcifediol (inactive)
  4. Calcifediol goes to the kidney and is turned into calcitriol - active form of vitamin D
• Forms of vitamin D3:

  • Cholecalciferol - inactive form made from precursor in skin
  • Calcifediol (25-hydroxyvitamin D3) - inactive form made from cholecalciferol in the liver - what blood tests measure
  • Calcitriol - active form made from calcifediol in the kidney
• Calcitriol (active vit D3) effect on calcium and phosphate:

  • Main site of action is the GI tract - increases calcium and phosphate absorption
  • Also increases reabsorption of calcium and phosphate from the kidneys
  • Causes bone resorption, bone mineralization and is important for bone regulation
  • Overall effect is to increase extracellular levels of calcium and phosphate
• Vitamin D and bone resorption:

  • Vitamin D binds to receptors of osteoblasts causing cytokine release (E.g. RANK ligand)
  • These activate osteoclasts causing bone resorption, releasing calcium and phosphate into blood
• Vitamin D and increased bone mineralisation:

  • Increased calcium and phosphate absorption from the GI tract and kidneys results in more calcium and phosphate in the blood
  • Bind together and form new bone
• Vitamin D and bone regulation:

  1. Activates osteoclasts to break down old bone
  2. Increases calcium and phosphate levels in blood to make new bone
• PTH effect on calcium and phosphate:

  • Works in 2 ways to increase blood calcium levels:
  • Kidneys
  • Bone
• PTH effect on the kidneys:

  • Increases activity of the enzyme in the kidney that converts inactive vitamin D3 into active vitamin D3 - calcitriol, leading to osteoclast activation and increased calcium and phosphate absorption from GI tract
  • PTH also increases renal reabsorption of calcium and increases renal excretion of phosphate - as there is more calcium than phosphate in the blood it won't all precipitate into bone resulting in more sustained increased blood calcium levels (calcium and phosphate tend to bind together, so need to excrete phosphate)
• PTH effect on bone:

  • Stimulates osteoclasts
  • Bone resorption releases calcium and phosphate levels in plasma
• Calcitonin effect on calcium and phosphate:

  • Thyroid gland detects high levels of calcium - produced calcitonin
  • Has opposite effect to PTH
  • Effect on kidneys - decreases reabsorption of calcium and phosphate
  • Effects on bone - decreases osteoclast activity meaning less calcium and phosphate released into plasma