3. Bone metabolism (Robson) Flashcards
What are osteoclasts and what is their function?
Cells which destroy the bone - secretes digestive enzymes which act to break down the bone - relatives of the macrophage
These sit in depressions in the bone and move around and seek out damaged areas of bone to move it
What are osteoblasts and what is their function?
Move in and have a role once the osteoclasts have done their role
Produce the ECM of the bone i.e. collagen type 1 and proteoglycans- this mineralises the bone
These then become embedded within the bone - are now osteocytes
What are osteocytes and what is their function?
These are the osteoblasts that have now become embedded within the bone
These look after the bone - can still make components of the ECM
These maintain the bone - sense stress and can send out distress signals if the bone is damaged
What are osteoprogenitor cells and what is their function?
These are mesenchymal cells that can differentiate into an osteoblast
Stimulated when bone formation is required - differentiate into osteoblasts
Found in the endostium
How do osteoclasts move?
Have an ameboid like movement - have spikes which can sense the surrounding environment
What do osteoclasts look like?
Large cells
Multinucleated
Sat in depressions in the bone
What do osteoblasts look like?
Cuboidal like cells
Sat on the surface of the bone matrix
What is the main type of collagen in bone?
Collagen type 1
Which cells produce the collagen in bone?
Osteoblasts - produce the ECM i.e. collagen and proteoglycans
What do osteocytes look like?
These are little black dots that look like pits
What is the ECM of bone composed of?
Collagen type 1
Proteoglycans
Growth factors e.g. cytokines
What are the different types of bone?
Lamellar bone
Woven
What are the different types of lamellar bone and how do they differ?
Cortical/compact:
80% of adult skeleton - strong and able to carry the weight of muscles - strengthens the skeleton - very organised bone - formed into little haversion canals (columns)
Cancellous/trabecular/spongy:
Organised bone but with spaces inbetween - provides flexibility - can twist and bend under pressure - lightens the skeleton - filled with bone marrow - 20% of the adult skeleton - very important for the production of red blood cells
What is woven bone?
This is immature bone that is only found in small amounts within the skeleton - this is converted to lamellar bone
Present if there is a pathological process or if healing a fracture or in growing children’s bones
Good for joining the ends of bones together during formation
Random collagen organisation – mechanically weak - forms quickly
Where is cortical bone found?
Found in the shaft of long bones
Where is trabecular bone found?
Found at the ends of long bones
Also found in bones of pelvis, ribs, vertebrae, skull
What is a Haversian canal?
This is a long canal/tube found within the centre of the cortical/compact bone
Contains blood vessels
Which bone type has the highest rate of bone metabolism?
Trabeculae bone
What is bone composed of?
35-40% is composed of the organic ECM - collagen type 1, proteoglycans, growth factors
60% is inorganic salts - calcium hydroxyapatite
5% is water
What is the function of the collagen type 1 in bone?
Forms long fibres
Provides strong, tensile strength
Does not break
Where is the calcium hydroxyapatite found in bone?
This crystallises on the surface of bone - does not coat the bone but forms little blocks of
This allows the collagen to still bend and move a small amount (rather than coating the bone in the salt)
What are canaliculi?
These are little black processes that come off of the osteocyte - these allow the osteocyte to sense the environment and communicate with neighbours i.e. osteocyte from other levels
These can monitor the level of bend and stress of the bone - any distress
What is a lacuna?
This is a small space in bone containing an osteocyte
or in cartilage containing a chondrocyte
What is ‘remodelling’ of bone and why is it done?
This is the renewal of bone before it deteriorates and breaks from e.g. the age of the bone
Also allows the redistribution of bone matrix along lines of mechanical stress e.g. during exercise - need to put a lot more bone into certain part of the skeleton to strengthen that part
Which bone undergoes renewal at a faster rate and why?
Trabecular bone renews 3-10 times faster than cortical bone
This bone is under a lot more stress - weaker and spongey and responds to stress much quicker - breaks more easily
What is sclerostin?
This is a glycoprotein released from osteocytes if they are ‘happy’ i.e. there is no mechanical stress
Sclerostin inhibits bone formation - prevents the osteoclasts from making more bone
What can act to inhibit the secretion of sclerostin?
If the bone is under mechanical stress - stress hormones can be released e.g. PTH
This can inhibit the release of sclerostin - ‘unhappy’ osteoclasts
What are RANK and RANKL?
RANK - receptor for RANKL on osteoclasts and their precursors
RANKL - ligand that stimulates bone resorption - released by osteocytes (and osteoblasts)
Outline the process of bone remodelling
Occurs if osteocyte sclerostin release is inhibited
RANK receptor on the osteclast precursors is stimulated and osteoclasts are stimulated - ameboid movement
Osteoclasts form a channel which starts to dissolve section of bone matrix - clamp down and create a leakproof seal
Osteoclasts then release protein-digesting enzymes to break down the collagen fibres and acid to dissolve bone minerals
Ca2+ and other useful components are passed out into the interstitial fluid to prevent wastage
This then leaves an empty space - the osteoblasts (formed from osteoprogenitor cells) then fill this with osteoid (unmineralised bone matrix)
The osteoid is then mineralised with calcium salt about one week later
How does the appearance of bone change with bone remodelling?
Will see ‘cement lines’ between the old mineralised osteoid and the new unmineralised osteoid
What cell is RANKL produced by and what cell does RANKL activate?
RANKL produced by osteocytes
RANKL stimulates osteoclasts
How long does bone remodelling take from start to finish?
About three months
What is the normal serum calcium level?
2.2-2.6mmol/L
What is the recommended daily intake of calcium?
500-1300mg
Where is the majority of the calcium in the body?
99.9% of calcium is in the skeleton
What is the normal serum calcium level dependent on?
Intestinal absorption
Renal excretion
Skeletal mobilisation
Why is the maintenance of serum calcium levels so important?
Calcium is used for a number of very important mechanisms e.g. contraction of the heart muscle, skeletal muscle contraction, neuronal regulation
What is the source of calcium in emergencies i.e. if the serum calcium dips very low?
The skeleton
What is the normal plasma concentration of phosphate?
0.8-1.5mmol/L
What happens if there is a low calcium serum level i.e. below 2.2mmol/L?
Low serum calcium riggers the release of PTH
What is the role of PTH in calcium maintenance?
PTH released if there is low serum calcium
PTH promotes Ca2+ reabsorption from the kidney and PO4 excretion
Ca2+ reabsorption from the bone - increased number and activity of osteoclasts (in extreme cases)
Synthesis of 1,25-dihydroxyvitamin D (active vit D)
What is the role of 1,25-dihydroxyvitamin D in calcium maintenance?
This acts to increase calcium absorption from the gut - should - can then signal back to stop the release of PTH
When might Ca2+ reabsorption from the bone occur?
In cases of chronic low calcium
What is calcitonin and what is it’s role?
Calcitonin is released from the thyroid gland when Ca2+ serum levels rise above 2.2mmol/L
This acts to inhibit osteoclast differentiation and activity, increases Ca2+ EXCRETION from the kidney and inhibits Ca2+ absorption by intestines
Where is 1,25-hydroxyvitamin D made?
In the liver
What is the effect of oestrogen on the bone?
Oestrogen positively influences bone metabolism
Gut - increases calcium absorption to maintain serum calcium levels
Bone - decreases bone resorption so inhibits the activity of osteoclasts - less likely to develop osteoporosis
What is the effect of glucocorticoids on the bone?
Glucocorticoids negatively influence bone metabolism
Gut - decrease calcium absorption
Bone - increase bone resorption and decrease bone formation
What is the adverse effect of long-term corticosteroid usage
Long term glucocorticoids
Result in osteoporosis formation
What is the effect of menopause on bone metabolism?
Menopause - decreased oestrogen levels so reduced serum calcium levels - require calcium from the bones
SO there is an increased osteoclast activity - can lead to onset of osteoporosis
What is the effect of calcium supplements in the diet on PTH levels?
SO parathyroid glands release PTH when calcium levels are low
Calcium supplements - increase calcium levels - PTH levels will fall
Osteoprogenitor cells are what type of cells?
Mesenchymal cells
Osteoprogenitor cells are found where in teh bone?
Endostium
Osteoblasts/osteoclasts - which sits in depressions in the bone and which sits on surface of bone matrix?
Osteoclasts - depressions in bone
Osteoblasts - surface of bone matrix
Cortical/compact lamellar bone makes up what percentage of the adult skeleton?
80%
Cancellous bone makes up what percentage of the adult skeleton?
20%
Haversian canals are found in which bone type?
Cortical lamellar
What type of component is sclerostin?
Glycoprotein
What cells release sclerostin?
Osteocytes
When is sclerostin released?
When osteocytes are happy - no mechanical stress
Function of sclerostin is?
Inhibition of bone formation
Sclerostin release can be inhibited by?
Stress hormone PTH
PTH released when?
When bones are under mechanical stress
Main cell releasing RANKL is?
Osteocytes
Function of RANKL?
Simulate resorption of bone
What is osteoid?
New bone formation prior to mineralisation
When is osteoid mineralised?
About one week after formation
What are cement lines?
Lines formed and visible between new osteoid and old bone
Effect of PTH on sclerostin?
PTH inhibits sclerostin production
Functions of PTH in calcium maintenance x3
Reabsorption of calcium from the kidney
Reabsorption of calcium from the bone
Synthesis of 1,25-dihydroxyvitamin D (active form)
Reabsorption of calcium at the kidney occurs at the expense of what?
Phosphate PO4
How is calcium reabsorbed at the bone?
Increased activity and number of osteoclasts
Serum calcium levels are <2.2mmol/L - which three areas is calcium reabsorbed from?
Kidney
Bone
Gut
Calcitonin is released from which organ?
Thyroid gland
When is calcitonin released?
When calcium levels are >2.6mmol/L
Function of calcitonin is? x3
Inhibition of osteoclast activity and differentiation
Increases calcium excretion from the kidney
Inhibition of calcium reabsorption at the intestine
Oestrogen has a positive or negative effect on bone metabolism?
Positive
Function of oestrogen in bone metabolism x2
Increases calcium absorption at gut
Decreases bone resorption
