Bone Metabolism Flashcards
How do osteoclasts appear on a slide
Multinucleated
Large
Sparse
What do osteocytes do
Determine the status of piece of bone, decide whether it needs removal and remodelling
What cells are immature osteocytes
Osteoblasts
What type of bone marrow makes up the majority at birth
Red
Where does red bone marrow remain
Spongy bones of vertebrae, ribs, sternum, cranium and epiphyses
Name the 2 overall types of bone
Lamellar
Woven
2 types of lamellar bone?
Cortical/ compact
Cancellous/ trabeculae/ spongy
What % of adult bone mass is cortical bone
80
What is the purpose of the Haversian canal system
All columns form around the outside so weight pushes on these columns
Deals with stress that comes from above
Which bone type has greater surface area? By how much?
Trabecullae bone 10* bigger surface area
When is woven bone used
Fracture healing
How is collagen laid down in woven bone and what is the consequence of this
Randomly laid down collagen, so weaker structure
What % of bone is organic
35-40%
What type of collagen makes up bone
Type 1
What are the 3 organic components of bone
Type 1 collagen
Proteoglycans
Growth factors
What type of strength do proteoglycans provide
Compressive
What are the non organic components of bone
Calcium hydroxyapatite
Water
Describe how calcium hydroxyapatite coats the collagen
In blocks, leaving gaps of exposed collagen to ensure there is some bendability
What are osteoclasts derived from
Haemopoietic stem cells
What are osteoblasts derived from
Osteoprogenitor cell (mesenchymal stem cell)
What structure enables osteocytes to detect any bends
Branches
What is the overall signal for bone remodelling
Osteocyte death
What bone type is quicker to form
Trabecular
Why does trabecular bone form faster than cortical
Larger surface area
Responds to stresses on the bone quicker
Give 2 reasons for bone remodelling
- Renews bone before deterioration
- Redistributes bone matrix along mechanical stress lines
What is sclerostin
A glycoprotein that inhibits bone formation by osteoblasts. Secreted by osteocytes
What inhibits sclerostin release
PTH and mechanical stress
What increases sclerostic release
Calcitonin
What is sclerosteosis
A mutation in the sclerostin gene causes autosomall recessive disorder characterised by bone overgrowth
What is romosozumab
An antibody to sclerostin currently being trailed as a way to increase bone density
Describe the role of osteoclasts in bone remodelling
- Crawls across surface seeking out damage
- Attaches to bone in leak proof seal
- Releases protein digesting enzymes to break down collagen
- Releases acid to dissolve bone minerals
What ph is required to dissolve bone minerals
5
What happens to the calcium broken down/ released by osteoclasts
Cross osteoclast to exit into the interstitial fluid
What happens in bone remodelling once old bone has been destroyed
New osteoblast produced, moving into gap where osteoclast was
Secrete collagen and protein matrix, becomes embedded and surrounded
Fill lacuna with osteoid
At what stage does new osteoid become mineralised
After about a week
3 phases of bone remodelling
Rest
Resorption
Formation
State the distribution of calcium in the body
99% skeleton
1% cells, blood and body
0.1% ECM
What are normal serum calcium levels
2.2-2.6mmol/L
How much free ionised calcium should there be in the body
1.0-1.25mmol/L
What 3 things does maintenance of normal serum calcium depend upon
Intestinal absorption
Renal excretion
Skeletal mobilisation
What is the RDI of calcium
500-1300mg
How much calcium is secreted by the kidneys a day
200mg/day
How much calcium is secreted by the gut a day
600-800/day in stools
Describe the distribution of phosphate in the body
80-90% in skeleton
10% plasma
What are normal plasma concentrations of phosphate
0.8-1.5mmol/L
What hormone is used to modulate absorpton and excretion of phosphate and calcium
Parathyroid hormone
What is the stimulus for PTH release
Low plasma calcium levels
How does PTH act upon the kidney
Promotes calcium reabsorption and phosphate excretion
How does PTH act on the bone
Calcium reabsorption increasing the number and activity of osteoclasts
How does PTH increase nimber and activity of osteoclasts
Osteoblasts have PTH receptor Receptor is activated Osteoblasts produce RANKL Osteoclasts have RANKL receptors Number and activity increases
What is the effect of PTH of 1,250dihydroxyvitamin D synthesis
Increases it
How does 1,25dihydroxyvitamin D affect calcium metabolism
Increases calcium absorption from the gut
What molecules are required for osteoclast formation
RANKL and M-CSF
What cells produce RANKL and M-CSF
Osteoblasts and stromal cells
What does RANKL stand for
Receptor activator of nuclear factor kappa b ligand
What does M-CSF stand for
Macrophage colony stimulating factor
What is OPG
Osteoprotegrin
This is a decoy receptor for RANKL
What expresses ephrin B2 ligand
Osteoclasts
What expresses ephB4 receptor
Osteoblasts
What is the effect of PTH on ephrin B2
Increases ephrinB2 expression
Does oestrogen stimulate or inhibit RANLK
Inhibit
When is calcitonin released
When serum calcium >2.25mmol/L
3 effects of calcitonin release
- Inhibits osteoclast differentiation and activity
- Increased calcium excretion from kidney
- Inhibits calcium absorption by intestines
(opposite PTH)
Where do we get vit D from
Diet
UV light
What is normal daily requirement for vitamin D
400IU/ day
Where is the active form of vitamin D made
Kidney
What is the role of vitamin D in bone formation and remodelling
Prepares the ECM for mineralisation by produces pro-collagen type 1 and producing alkaline phosphatase matrix vesicles
How does oestrogen effect calcium metabolism
- Increased absorption in gut
- Decreased reabsorption in bone
- Inhibits osteoclasts
What disease, common at menopause, is caused by decreased oestrogen or prolonged steroid use
Osteoporosis
What is the effect of glucocorticoids on calcium metabolism
Decreased absorption in gut
Increased reabsorption/ decreased formation in bone
What hormone may be used to treat menopausal osteoporosis
Progesterone
