3. Bone metabolism (Robson) Flashcards

1
Q

What are osteoclasts and what is their function?

A

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

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2
Q

What are osteoblasts and what is their function?

A

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

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3
Q

What are osteocytes and what is their function?

A

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

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4
Q

What are osteoprogenitor cells and what is their function?

A

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

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5
Q

How do osteoclasts move?

A

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

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6
Q

What do osteoclasts look like?

A

Large cells
Multinucleated
Sat in depressions in the bone

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7
Q

What do osteoblasts look like?

A

Cuboidal like cells

Sat on the surface of the bone matrix

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8
Q

What is the main type of collagen in bone?

A

Collagen type 1

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9
Q

Which cells produce the collagen in bone?

A

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

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10
Q

What do osteocytes look like?

A

These are little black dots that look like pits

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11
Q

What is the ECM of bone composed of?

A

Collagen type 1
Proteoglycans
Growth factors e.g. cytokines

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12
Q

What are the different types of bone?

A

Lamellar bone

Woven

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13
Q

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

A

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

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14
Q

What is woven bone?

A

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

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15
Q

Where is cortical bone found?

A

Found in the shaft of long bones

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16
Q

Where is trabecular bone found?

A

Found at the ends of long bones

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

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17
Q

What is a Haversian canal?

A

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

Contains blood vessels

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18
Q

Which bone type has the highest rate of bone metabolism?

A

Trabeculae bone

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19
Q

What is bone composed of?

A

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

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20
Q

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

A

Forms long fibres
Provides strong, tensile strength
Does not break

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21
Q

Where is the calcium hydroxyapatite found in bone?

A

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)

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22
Q

What are canaliculi?

A

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

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23
Q

What is a lacuna?

A

This is a small space in bone containing an osteocyte

or in cartilage containing a chondrocyte

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24
Q

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

A

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

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25
Q

Which bone undergoes renewal at a faster rate and why?

A

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

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26
Q

What is sclerostin?

A

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

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27
Q

What can act to inhibit the secretion of sclerostin?

A

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

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28
Q

What are RANK and RANKL?

A

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

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29
Q

Outline the process of bone remodelling

A

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

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30
Q

How does the appearance of bone change with bone remodelling?

A

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

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31
Q

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

A

RANKL produced by osteocytes

RANKL stimulates osteoclasts

32
Q

How long does bone remodelling take from start to finish?

A

About three months

33
Q

What is the normal serum calcium level?

A

2.2-2.6mmol/L

34
Q

What is the recommended daily intake of calcium?

A

500-1300mg

35
Q

Where is the majority of the calcium in the body?

A

99.9% of calcium is in the skeleton

36
Q

What is the normal serum calcium level dependent on?

A

Intestinal absorption
Renal excretion
Skeletal mobilisation

37
Q

Why is the maintenance of serum calcium levels so important?

A

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

38
Q

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

A

The skeleton

39
Q

What is the normal plasma concentration of phosphate?

A

0.8-1.5mmol/L

40
Q

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

A

Low serum calcium riggers the release of PTH

41
Q

What is the role of PTH in calcium maintenance?

A

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)

42
Q

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

A

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

43
Q

When might Ca2+ reabsorption from the bone occur?

A

In cases of chronic low calcium

44
Q

What is calcitonin and what is it’s role?

A

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

45
Q

Where is 1,25-hydroxyvitamin D made?

A

In the liver

46
Q

What is the effect of oestrogen on the bone?

A

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

47
Q

What is the effect of glucocorticoids on the bone?

A

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

48
Q

What is the adverse effect of long-term corticosteroid usage

A

Long term glucocorticoids

Result in osteoporosis formation

49
Q

What is the effect of menopause on bone metabolism?

A

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

50
Q

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

A

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

51
Q

Osteoprogenitor cells are what type of cells?

A

Mesenchymal cells

52
Q

Osteoprogenitor cells are found where in teh bone?

A

Endostium

53
Q

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

A

Osteoclasts - depressions in bone

Osteoblasts - surface of bone matrix

54
Q

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

A

80%

55
Q

Cancellous bone makes up what percentage of the adult skeleton?

A

20%

56
Q

Haversian canals are found in which bone type?

A

Cortical lamellar

57
Q

What type of component is sclerostin?

A

Glycoprotein

58
Q

What cells release sclerostin?

A

Osteocytes

59
Q

When is sclerostin released?

A

When osteocytes are happy - no mechanical stress

60
Q

Function of sclerostin is?

A

Inhibition of bone formation

61
Q

Sclerostin release can be inhibited by?

A

Stress hormone PTH

62
Q

PTH released when?

A

When bones are under mechanical stress

63
Q

Main cell releasing RANKL is?

A

Osteocytes

64
Q

Function of RANKL?

A

Simulate resorption of bone

65
Q

What is osteoid?

A

New bone formation prior to mineralisation

66
Q

When is osteoid mineralised?

A

About one week after formation

67
Q

What are cement lines?

A

Lines formed and visible between new osteoid and old bone

68
Q

Effect of PTH on sclerostin?

A

PTH inhibits sclerostin production

69
Q

Functions of PTH in calcium maintenance x3

A

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

70
Q

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

A

Phosphate PO4

71
Q

How is calcium reabsorbed at the bone?

A

Increased activity and number of osteoclasts

72
Q

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

A

Kidney
Bone
Gut

73
Q

Calcitonin is released from which organ?

A

Thyroid gland

74
Q

When is calcitonin released?

A

When calcium levels are >2.6mmol/L

75
Q

Function of calcitonin is? x3

A

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

76
Q

Oestrogen has a positive or negative effect on bone metabolism?

A

Positive

77
Q

Function of oestrogen in bone metabolism x2

A

Increases calcium absorption at gut

Decreases bone resorption