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Locomotor 2 > Bone Metabolism > Flashcards

Bone Metabolism Flashcards

1
Q

What are the two types of bone

A

lamellar

woven

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2
Q

what are the two types of lamellar bone and describe there percentage amount of the adult skeleton

A
  • Cortical/compact bone (80% of total bone mass of an adult)

- Cancellous/trabecular/spongy bone (20% total bone mass of an adult) but has 10 times more surface area of compact bone

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3
Q

what is the majority of the bone in the body made up of

A

lamellar bone

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4
Q

What does lamellar bone do

A
  • gives a strong stable skeleton that holds the skeleton up and gives the shape of the body
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5
Q

describe the two types of lamellar bone

A

Cortical/compact bone
- is present on the outside of the bone and is strong

cancellous/trabecular/spongy bone

  • is on the inside and is more prevalent in the epiphysis and the shaft of the long bones
  • has more flexible and responds to the stress that the skeleton is put under
  • allows generation of new bone
  • has bone marrow in it
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6
Q

what type of bone allows generation of new bone

A

Lamellar bone = cancellous/trabecular/spongy bone type

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7
Q

What are the two types of bone marrow

A
  • red and yellow bone marrow
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8
Q

what bone marrow is the majority of bone marrow

A

Yellow bone marrow

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9
Q

what is yellow bone marrow made out of

A

adipocytes and fibroblasts

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10
Q

what is then red bone marrow made out of

A
  • usually present in the epiphysis

- this is where the haemopoietic stem cells are present

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11
Q

what bones is red marrow present in

A

. Red bone marrow remains in spongy bones of vertebrae, ribs, sternum, cranium and epiphyses of long bones

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12
Q

describe what happens to the bone marrow at birth

A

At birth virtually all bone marrow is red bone marrow immediately postnatally conversion begins to yellow bone marrow starts peripherally and moves towards central axial skeleton.

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13
Q

what is woven bone good for

A
  • can be formed quickly it is good for growing skeletons

- can be converted into lamellar bone

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14
Q

Describe what compact bone looks like

A
  • circular osteon

- blood vessels run down the centre

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15
Q

describe what woven bone looks like

A

Random collagen organisation - light bounces of the collagen fibres in different directions so gives a more randomised pattern of polarised light

Mechanically weak

Forms quickly

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16
Q

describe the composition of the matrix of bone

A

Organic (35-40%)

  • type 1 collagen (90% tensile strength)
  • proteoglycans (compressive strength)
  • growth factors/cytokines/osteoid

inorganic (60%)
- 95% calcium hydroxyapatite

5% is water

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17
Q

Describe what the organic part of the matrix of the bone is made out of

A
  • type 1 collagen (90% tensile strength)
  • proteoglycans (compressive strength)
  • growth factors/cytokines/osteoid
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18
Q

describe what the inorganic part of the bone matrix is made out of

A
  • 95% calcium hydroxyapatite
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19
Q

list the 4 types of cells found in bone

A
  • osteoprogenitor cell
  • osteoblast
  • osteocyte
  • osteoclast
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20
Q

What do osteoprogenitor cells do

A
  • these are stem cells that live in the periosteum or endosteum of the bone and can become chondrocytes or fibroblasts,
  • can become osteoblast
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21
Q

What do osteoblasts do

A
  • Cubodial cells
  • sits of the surface of the bone
  • makes the organic component of the osteoid
  • as more osteoid gets secreted around the osteoblasts they become an osteocyte
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22
Q

What is an osteocytes

A

Osteocytes are a more mature osteoblast which has become incased in the osteoid material the osteoblast produced

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23
Q

What does an osteocyte do

A
  • they have long canaliculi which are projections that allow communications between the osteocytes
  • can measure the amount of bend or stretch the bone is undergoing by how much the canaliculi deform
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24
Q

what do osteoclasts do

A
  • the osteoclasts come from the haempoietic red bone marrow linage
  • these cause the reabsorption of bone
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25
Q

what does death of osteocytes cause

A

Death of osteocytes signals remodelling-

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26
Q

what are the reasons for remodelling

A

1) renews bone before deterioration

2) redistributes bone matrix along mechanical stress lines.

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27
Q

how much quicker does trabecular bone turn over than cortical bone

A

1) renews bone before deterioration

2) redistributes bone matrix along mechanical stress lines.

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28
Q

what are the differences between trabecular bone and cortical bone

A

Trabecular bone

  • larger surface area
  • responds quicker to stresses on the bone
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29
Q

What is sclerostin

A

Sclerostin secreted glycoprotein that inhibits bone formation by osteoblasts

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30
Q

what causes the activation and inhibition of osteoblasts

A
  • Inhibited by PTH and mechanical stress

- increased by calcitonin

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31
Q

what happens if there is a mutation in the sclerotin gene

A

sclerosteosis autosomal recessive disorder characterised by bone overgrowth.

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32
Q

describe the interactions between the osteoclasts and osteoblasts

A

Ephrin B2 ligand is a membrane bound ligand and is found on osteoclasts

  • the receptor EphB4 is found on osteoblasts
  • when these two factors come together and are bidirectionally signalling
  • they prevent the osteoclast from differentiating and becoming mature and signals the osteoblast to differentiate and secrete more bone
33
Q

what happens if you don’t remodel the bone

A
  • it becomes very old and if we don’t remove the dead osteocytes the bone becomes brittle and breaks
  • this redistributes the bone matrix
34
Q

describe how bone remodelling happens

A
  • the osteoclast attaches to the bone forming a leak proof seal
  • releases hydrochloric acid
  • protein digesting enzymes breakdown collagen fibres
  • acid dissolves the bone minerals
  • bone proteins and minerals such as calcium cross the osteoclast to exit into interstitial fluid
35
Q

describe how osteoblast secretes new osteoid

A
  • osteoblasts fill lacuna with osteoid

- the osteoid is then mineralised approximately 1 week later

36
Q

what antibiotic is fluorescences by osteoid

A

tetracycline

37
Q

how long does bone remodelling take

A

Bone remodelling approximately takes about 3 months

38
Q

what cells is responsible for bone formation and reabsorption

A

Bone formation = osteoblasts

Resorption = osteoclasts

39
Q

describe the levels of calcium in different parts of the body

A
  • 99% of calcium is in the skeleton, 1% in cells, blood and body fluids (ECF=0.1%)
  • Serum calcium level 2.2-2.6mmol/L
  • Free ionised calcium 1.0-1.25 mol/L = 0.05% of total Ca2+
40
Q

what does the maintenance of normal serum calcium depends on

A

intestinal absorption

renal excretion

skeletal mobilisation

41
Q

what is the recommended daily intake of calcium

A

500-1300mg

42
Q

how much calcium is excreted a day

A

Kidneys approx 200mg/day

Gut approx 600-800mg/day in stools

43
Q

where is the phosphate in the body

A

80-90% in skeleton 10% in blood and plasma

44
Q

What is the normal phosphate concentration

A

Normal plasma concentration 0.8 -1.5mmol/L

45
Q

what is phosphate absorption linked to

A
  • calcium metabolism
46
Q

what monitors phosphate and calcium absorption

A

PTH

47
Q

what organs absorb and excrete calcium

A

gut and kidneys

48
Q

What does PTH promote

A

Ca2+ reabsorption from kidney and PO4 excretion,

Ca2+ reabsorption from bone - increases number and activity of osteoclasts

synthesis of 1,25-dihydroxyvitamin D (1,25 (OH)2 vitamin D3).

49
Q

describe RANKL on osteoblasts and osteoclasts

A
  • Osteoblasts produce RANKL

- Osteoclasts and their precursors have RANK receptors

50
Q

what stimulates PTH

A

low serum calcium

51
Q

what does 1,25(OH)2 do

A

1,25 (OH)2 vitamin D3 increases Ca2+ absorption from gut.

52
Q

where is 25 (OH)2 vitamin D produced

A

liver

53
Q

what is 1,25 (OH)2 vitamin D

A

Kidneys

54
Q

What does osteoclasts formation require

A

Osteoclast formation requires RANKL and M-CSF produced by osteoblasts and stromal cells

55
Q

what does RANKL stand for

A

Receptor activator of nuclear factor kappa-B ligand

56
Q

What does M-CSF stand for

A

Macrophage colony-stimulating factor.

57
Q

What does OPG stand for

A

osteoprotegrin (decoy receptor for RANKL)

58
Q

describe how RANKL stimulation works

A
  • Osteoblasts produced RANKL after stimulation via PTH
  • this causes the osteoclast precursor to mature and become an active osteoclast
  • this increases the bone reabsorption
59
Q

what produces calcitonin

A
  • C parafollicular cells within he thyroid gland
60
Q

what causes the production in calcitonin

A

= increase in plasma calcium serum levels

Ca2+ >2.25mmol/L

61
Q

What does calcitonin do

A

inhibits osteoclast differentiation and activity

increases Ca2+ excretion from kidney

Inhibits Ca2+ absorption by intestines

62
Q

what is the most potent form of vitamin D

A

1,25 DIhydroxy vitamin D

63
Q

How is 25(OH) Vitamin D (prehormone) made from

A
  • diet

- UV light on precursors in skin

64
Q

what is the daily requirement of vitamin D

A

400IU/day

65
Q

what does vitamin D do

A

Strongly stimulates Ca2+ absorption from gut

Stimulates bone resorption in same way as PTH

66
Q

What is vitamin D3 (1,25-(OH)2) involved in

A
  • preparing the ECM for mineralisation
  • production of pro-collagen type 1
  • production of alkaline phosphatase matrix vesicles
67
Q

what stimulates 1,25 -(OH)2 Vitamin D3

A

Elevated PTH

Decreased calcium

Decreased serum phosphate

68
Q

what inhibits PTH

A

Elevated serum calcium

Elevated 1,25(OH)2D in kidney

69
Q

what inhibits 1,25-(OH)2 Vitamin D3

A

Decreased PTH

Elevated serum calcium

Elevated serum phosphate

70
Q

how does PTH effect the intestines

A

No direct effect

Acts indirectly on bowel by stimulating 1,25(OH)2D in kidney

71
Q

How does PTH affect the kidney

A

Stimulates 25(OH)D-1αOHase in proximal tubular cells to make 1,25(OH)2D

Increases reabsorption of calcium

Promotes excretion of phosphate

72
Q

How does PTH effect the bone

A

increases bone resorption indirectly by proliferation and differentiation of osteoclasts

73
Q

how does 1,25-(OH)2 Vitamin D3 effect the intestine

A

Strongly stimulates intestinal absorption of calcium and phosphate

74
Q

how does calcitonin effect calcium reabsorption in the intestine

A

Inhibits Ca2+ absorption by intestines

75
Q

how does calcitonin effect calcium reasborption in the kidney

A
  • increases renal calcium excretion
76
Q

How does calcitonin effect calcium reabsorption in the bone

A

Inhibits bone resorption by direct inhibition of osteoclast differentiation and activity

77
Q

how does oestrogen effect calcium reabsorption

A

gut - increased Ca2+ absorption

bone - decreased re-absorption (inhibit osteoclasts)

At menopause loss of bone mass - osteoporosis

78
Q

How does glucocorticoids affect calcium reabsorption

A

gut - decrease Ca2+ absorption

bone - increased re-absorption/decreased formation

Prolonged corticosteroid treatment – osteoporosis

79
Q

How does progesterone effect calcium reabsorption

A

Adding progesterone cream to osteoporosis therapy increased bone density by around 10% in 1st 6 months to rate of 3-5% annually stabilises at levels of 35 year old
Balancing progesterone may be key to reversing osteoporosis

Locomotor 2 (30 decks)

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