3. Bone metabolism (Robson)

Question 1

What are osteoclasts and what is their function?

Answer 1

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

Question 2

What are osteoblasts and what is their function?

Answer 2

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

Question 3

What are osteocytes and what is their function?

Answer 3

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

Question 4

What are osteoprogenitor cells and what is their function?

Answer 4

These are mesenchymal cells that can differentiate into an osteoblast
Stimulated when bone formation is required - differentiate into osteoblasts
Found in the endostium

Question 5

How do osteoclasts move?

Answer 5

Have an ameboid like movement - have spikes which can sense the surrounding environment

Question 6

What do osteoclasts look like?

Answer 6

Large cells
Multinucleated
Sat in depressions in the bone

Question 7

What do osteoblasts look like?

Answer 7

Cuboidal like cells

Sat on the surface of the bone matrix

Question 8

What is the main type of collagen in bone?

Answer 8

Collagen type 1

Question 9

Which cells produce the collagen in bone?

Answer 9

Osteoblasts - produce the ECM i.e. collagen and proteoglycans

Question 10

What do osteocytes look like?

Answer 10

These are little black dots that look like pits

Question 11

What is the ECM of bone composed of?

Answer 11

Collagen type 1
Proteoglycans
Growth factors e.g. cytokines

Question 12

What are the different types of bone?

Answer 12

Lamellar bone

Woven

Question 13

What are the different types of lamellar bone and how do they differ?

Answer 13

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

Question 14

What is woven bone?

Answer 14

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

Question 15

Where is cortical bone found?

Answer 15

Found in the shaft of long bones

Question 16

Where is trabecular bone found?

Answer 16

Found at the ends of long bones

Also found in bones of pelvis, ribs, vertebrae, skull

Question 17

What is a Haversian canal?

Answer 17

This is a long canal/tube found within the centre of the cortical/compact bone

Contains blood vessels

Question 18

Which bone type has the highest rate of bone metabolism?

Answer 18

Trabeculae bone

Question 19

What is bone composed of?

Answer 19

35-40% is composed of the organic ECM - collagen type 1, proteoglycans, growth factors
60% is inorganic salts - calcium hydroxyapatite
5% is water

Question 20

What is the function of the collagen type 1 in bone?

Answer 20

Forms long fibres
Provides strong, tensile strength
Does not break

Question 21

Where is the calcium hydroxyapatite found in bone?

Answer 21

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)

Question 22

What are canaliculi?

Answer 22

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

Question 23

What is a lacuna?

Answer 23

This is a small space in bone containing an osteocyte

or in cartilage containing a chondrocyte

Question 24

What is ‘remodelling’ of bone and why is it done?

Answer 24

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

Question 25

Which bone undergoes renewal at a faster rate and why?

Answer 25

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

Question 26

What is sclerostin?

Answer 26

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

Question 27

What can act to inhibit the secretion of sclerostin?

Answer 27

If the bone is under mechanical stress - stress hormones can be released e.g. PTH This can inhibit the release of sclerostin - 'unhappy' osteoclasts

Question 28

What are RANK and RANKL?

Answer 28

RANK - receptor for RANKL on osteoclasts and their precursors RANKL - ligand that stimulates bone resorption - released by osteocytes (and osteoblasts)

Question 29

Outline the process of bone remodelling

Answer 29

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

Question 30

How does the appearance of bone change with bone remodelling?

Answer 30

Will see 'cement lines' between the old mineralised osteoid and the new unmineralised osteoid

Question 31

What cell is RANKL produced by and what cell does RANKL activate?

Answer 31

RANKL produced by osteocytes | RANKL stimulates osteoclasts

Question 32

How long does bone remodelling take from start to finish?

Answer 32

About three months

Question 33

What is the normal serum calcium level?

Answer 33

2.2-2.6mmol/L

Question 34

What is the recommended daily intake of calcium?

Answer 34

500-1300mg

Question 35

Where is the majority of the calcium in the body?

Answer 35

99.9% of calcium is in the skeleton

Question 36

What is the normal serum calcium level dependent on?

Answer 36

Intestinal absorption Renal excretion Skeletal mobilisation

Question 37

Why is the maintenance of serum calcium levels so important?

Answer 37

Calcium is used for a number of very important mechanisms e.g. contraction of the heart muscle, skeletal muscle contraction, neuronal regulation

Question 38

What is the source of calcium in emergencies i.e. if the serum calcium dips very low?

Answer 38

The skeleton

Question 39

What is the normal plasma concentration of phosphate?

Answer 39

0.8-1.5mmol/L

Question 40

What happens if there is a low calcium serum level i.e. below 2.2mmol/L?

Answer 40

Low serum calcium riggers the release of PTH

Question 41

What is the role of PTH in calcium maintenance?

Answer 41

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)

Question 42

What is the role of 1,25-dihydroxyvitamin D in calcium maintenance?

Answer 42

This acts to increase calcium absorption from the gut - should - can then signal back to stop the release of PTH

Question 43

When might Ca2+ reabsorption from the bone occur?

Answer 43

In cases of chronic low calcium

Question 44

What is calcitonin and what is it's role?

Answer 44

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

Question 45

Where is 1,25-hydroxyvitamin D made?

Answer 45

In the liver

Question 46

What is the effect of oestrogen on the bone?

Answer 46

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

Question 47

What is the effect of glucocorticoids on the bone?

Answer 47

Glucocorticoids negatively influence bone metabolism Gut - decrease calcium absorption Bone - increase bone resorption and decrease bone formation

Question 48

What is the adverse effect of long-term corticosteroid usage

Answer 48

Long term glucocorticoids | Result in osteoporosis formation

Question 49

What is the effect of menopause on bone metabolism?

Answer 49

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

Question 50

What is the effect of calcium supplements in the diet on PTH levels?

Answer 50

SO parathyroid glands release PTH when calcium levels are low Calcium supplements - increase calcium levels - PTH levels will fall

Question 51

Osteoprogenitor cells are what type of cells?

Answer 51

Mesenchymal cells

Question 52

Osteoprogenitor cells are found where in teh bone?

Answer 52

Endostium

Question 53

Osteoblasts/osteoclasts - which sits in depressions in the bone and which sits on surface of bone matrix?

Answer 53

Osteoclasts - depressions in bone | Osteoblasts - surface of bone matrix

Question 54

Cortical/compact lamellar bone makes up what percentage of the adult skeleton?

Answer 54

80%

Question 55

Cancellous bone makes up what percentage of the adult skeleton?

Answer 55

20%

Question 56

Haversian canals are found in which bone type?

Answer 56

Cortical lamellar

Question 57

What type of component is sclerostin?

Answer 57

Glycoprotein

Question 58

What cells release sclerostin?

Answer 58

Osteocytes

Question 59

When is sclerostin released?

Answer 59

When osteocytes are happy - no mechanical stress

Question 60

Function of sclerostin is?

Answer 60

Inhibition of bone formation

Question 61

Sclerostin release can be inhibited by?

Answer 61

Stress hormone PTH

Question 62

PTH released when?

Answer 62

When bones are under mechanical stress

Question 63

Main cell releasing RANKL is?

Answer 63

Osteocytes

Question 64

Function of RANKL?

Answer 64

Simulate resorption of bone

Question 65

What is osteoid?

Answer 65

New bone formation prior to mineralisation

Question 66

When is osteoid mineralised?

Answer 66

About one week after formation

Question 67

What are cement lines?

Answer 67

Lines formed and visible between new osteoid and old bone

Question 68

Effect of PTH on sclerostin?

Answer 68

PTH inhibits sclerostin production

Question 69

Functions of PTH in calcium maintenance x3

Answer 69

Reabsorption of calcium from the kidney Reabsorption of calcium from the bone Synthesis of 1,25-dihydroxyvitamin D (active form)

Question 70

Reabsorption of calcium at the kidney occurs at the expense of what?

Answer 70

Phosphate PO4

Question 71

How is calcium reabsorbed at the bone?

Answer 71

Increased activity and number of osteoclasts

Question 72

Serum calcium levels are <2.2mmol/L - which three areas is calcium reabsorbed from?

Answer 72

Kidney Bone Gut

Question 73

Calcitonin is released from which organ?

Answer 73

Thyroid gland

Question 74

When is calcitonin released?

Answer 74

When calcium levels are >2.6mmol/L

Question 75

Function of calcitonin is? x3

Answer 75

Inhibition of osteoclast activity and differentiation Increases calcium excretion from the kidney Inhibition of calcium reabsorption at the intestine

Question 76

Oestrogen has a positive or negative effect on bone metabolism?

Answer 76

Positive

Question 77

Function of oestrogen in bone metabolism x2

Answer 77

Increases calcium absorption at gut | Decreases bone resorption