4 - Bone Metabolism Flashcards
What are the 2 types of bone
Lamellar
Woven
What are the 2 types of lamellar bone
Cortical/compact
Cancellous/trabecular/spongey
Feature of lamellar bone
Has a layered organisation
Features of cortical//compact bone
Makes up the outside of a bone to give strength and structure
80% of total bone mass
Cancellous/trabecular bone
Thin in diaphysis and most in head/neck, lighter
20% of total bone mass
10x SA of cortical bone
Features of Woven bone
Random collagen organisation
Mechanically weak and forms quickly
Immature
Used in healing and can be pathological
What bone marrow fills bone in adults
Yellow bone marrow
lies in the medullary cavity
Where is bone marrow in adults
In spongy bones of vertebrae, rib, sternum, cranium and epiphyses of long bones
Composition of bone matrix
35-40% organic = Type 1 collagen, proteoglycans, growth factors
70% inorganic = 95% Calcium hydroxyapatite
5% water
Osteoprogenitor cell
In the outer membrane
Can become an osteoblast
Osteoblast
Cells that form new bone
Osteocyte
Detects stresses in the ECM and produces bone collagen to maintain the bone matrix
Osteoclast
Large cells that dissolve the bone
Canaliculi
Canals that connect osteocytes together
Haversian Canals
Tubes which form a network and contain blood vessels
What signals remodelling
Death of osteocytes
Reasons for remodelling
Renews bone before deterioration
Redistributes bone matrix along mechanical stress line
What is Sclerostin
A secreted glycoprotein
Inhibits osteoblasts to prevent bone formation
What inhibits and increases Sclerositin
PTH and mechanical stress inhibits sclerostin
Calcitonin increases
What secretes sclerostin
Osteocytes
they secrete sclerostin when not under mechanical stress to prevent new bone formation
What is Ephirin B2
A ligand expressed by osteoclasts
What is Eph B4
A receptor expressed on osteoblasts
What increases Ephrin B2 expression
PTH
What happens when the ephrinb2 ligant attaches to the ephb4 receptor
• Generates bidirectional anti-osteoclastogenic and pro-osteoblastogenic signals.
• Inhibits osteoclast precursor differentiation and enhances osteoblast differentiation.
MORE BONE
Stages of bone remodelling
1) Osteoclast attaches to bone forming a leak proof seal
2) Osteoclast secretes HCL, and protein-digesting enzymes
3) The protein digesting enzymes break down collagen fibres
4) The Acid dissolves bone minerals
5) Proteins and minerals cross osteoclast to exit into interstitial fluid to be reused
6) Osteoclast will unclamp and then clamp again along the bone and forms a groove behind it
7) Osteoblasts produced fill lacuna with osteoid
8) The osteoid secretes collagen and protein
9) The osteoid is mineralised approx 1 week later
What can be used as a bone marker to measure if mineralisation was taking place
Tetracycline
How much calcium in adult body
1100g
How much of calcium in our body is in our skeleton
1%
Serum calcium level
- 2- 2.6mmol/L
8. 5-10.5 mg.dL
How much serum calcium is free ionised calcium
1.0-1.25mmol/L
What is free ionised calcium
The physiologically important component which is free and active
What does maintenance of normal serum calcium depend on
Intestinal absorption
Renal excretion
Skeletal mobilisation
Recommended daily intake of calcium
500-1300mg
Calcium extcreted
Kidneys - 200mg/day
Gut - 600-800mg/day in stools
How much phosphate in the adult body
500-800g
Hydroxyapatite
80-90% in skeleton and 10% in blood/plasma
Normal plasma conc of phosphate
0.8-1.5mmol/L
What stimulates PTH to be secreted from the parathyroid gland
Low plasma ca2+
What does PTH promote
Ca2+ reabsorption from kidney
PO4 excretion (more PO4 excreted and less Ca)
Ca2+ reabsorption from bone (does this by increasing the no of osteoclasts)
Synthesis of 1,25-dihydroxyvitamin D (1,25 (OH)2 vitamin D3). (RANKL inducer)
How does PTH increase the number and activity of osteoclasts
PTH/vitamin Dis released
PTH binds to PTH receptors on osteoblasts
This causes the RANK-L to be produced
RANK-L binds to RANK receptor on osteoclast
Causes osteoclast activity
What does 1,25 (OH)2 vitamin D3). do
increase Ca2 absorption from the gut
induces RANKL
What is M-CSF
Macrophage colony stimulating factor
Osteoclast needs this to be activated
What produces MCSF and RANKL
Osteoblasts
Stromal cells
What is OPG (Osteoprotegrin)
A RANKL inhibitor
IT is a decoy receptor for RANKL so RANKL will bind however osteoclasts are not activated
What is released when plasma levels of Ca2+ are too high
Calcitonin
When Ca2+ >2.25mmol/L
What does calcitonin do
inhibits osteoclast differentiation and activity
increases Ca2+ excretion from kidney
Inhibits Ca2+ absorption by intestines
What is the Vitamin D requirement a day
400IU/day
What can 1,25 (OH)2 vitamin D3 do?
Strongly stimulates Ca2+ absorption from gut
Stimulates bone resorption in same way as PTH
Production of pro-collagen type I
Productionof alkaline phosphatase matrix vesicles
How does oestrogen affect bone metabolism
In the gut it increases Ca2+ absorption
In the bone it causes decreased reabsorption (inhibits osteoclasts)
How does glucocorticoids affect bone metabolism
In the gut they decrease ca2+ absorption
In the bone they increase reabsorption + decreases formation
Prolonged corticosteroid treatment can cause osteoporosis
How does progesterone affect bone metabolism
Increases bone density
Where is calcitonin released from
Thyroid gland
