Lecture 7

Question 1

Bone remodelling

Answer 1

1. Quiescent bone surface with osteocytes embedded in bone matrix
2. stimulus encourages bone remodelling
3. Osteoclast precursors are attracted to embedded osteocytes
4. Osteocytes differentiate to osteoclasts which reabsorb and degrade bone matrix
5. osteoblasts come into the area and lay down new bone matrix.

Question 2

osteoblasts

Answer 2

sit on bone surface. Produce bone matrix by first laying down collagen fibres (osteoid) then mineralising it with hydroxyapetite crystals. Once finished, can differentiate to osteocyte after it embeds itself into bone matrix. Derived from mesenchymal lineage. P1NP collagen component cleaved during matrix formation and serum levels in patients reflects bone formation.

Question 3

osteocytes

Answer 3

Mature bone cells derived from osteoblasts that become embedded in the bone matrix. They form an interconnected network via canaliculi which enables fluid flow that bends the cilia on osteocytes, making them key mechanosensors that detect mechanical loading on bone. Osteocytes regulate bone remodeling by controlling osteoclast and osteoblast activity.They secrete RANKL, which promotes osteoclast formation and activity, OPG which inhibits osteoclast development and they release sclerostin, which inhibits osteoblast activity.

Question 4

Importance of Ca

Answer 4

Neurotransmitter release and intracellular signal transduction. (regulates enzyme tertiary structure, muscle contraction, regulation of blood coagulation, maintains mechanical integrity)

Question 5

Hypocalcaemia

Answer 5

if left untreated: muscle spasms, seizures

Question 6

Hypercalcaemia

Answer 6

if left untreated: nausia, osteoporosis, kidney failure

Question 7

calcium deficiencies

Answer 7

need to be regulated without triggering CaPi precipitation and/or tissue calcification. Parathyroid and calcitriol are 2 key hormones for Ca regulation.

Question 8

Parathyroid gland

Answer 8

posterior surface of left/right lobes. there’s 4 of them. produces parathyroid hormone (PTH)

Question 9

PTH

Answer 9

PT cells detect Ca drop in serum ad release PTH to
- Act of the kidney to decrease Ca excretion
- Increase Ca release from bone through reabsorption
-stimulate calcitriol production in kidneys
When blood calcium is low, PTH production increases to release Ca from bone

Question 10

Calcitriol

Answer 10

comes from vit D. Comes from diet and UV rays. In liver, calcidiol is formed which goes to kidneys to form active calcitriol. Works synergistically with PTH to increase serum Ca by
- increasing intestinal Ca absorption
-supporting renal reabsorption of Ca
- signal via receptors on bone cells to increase bone reabsorption and decrease bone formation.

vitamin D supplements support bone health particularly if dietary Ca is low and UV is low.

Low vit D= low calcitriol = low serum Ca = increase PTH production = bone reabsorption = bone loss