Bone Metabolism Flashcards

1
Q

2 types of bone

A

Lamellar
Woven

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2
Q

Subtypes of lamellar bone

A

Cortical/compact
Cancellous/trabecular/spongy

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3
Q

When is woven bone present

A

Immaturity
Healing
Pathology

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4
Q

What structures make up compact bone

A

Osteons

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5
Q

How much of adult bone mass is cortical and trabecular bone

A

Cortical - 80%
Trabecular - 20%

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6
Q

Does lamellar or woven bone form faster

A

Woven

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7
Q

Organic components of bone

A

T1collagen
proteoglycans
growth factors
cytokines
osteoid

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8
Q

Main inorganic component of bone

A

Calcium hydroxyapatite

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9
Q

Why is calcium hydroxyapatite deposited in blocks along collagen in bone not in a continuous layer

A

Allows flexibility and bending in collagen to decr brittleness

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10
Q

Bone cells

A

Osteoprogenitor cells
Osteoblasts
Osteocytes
Osteoclasts

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11
Q

What lineage are osteoclasts from

A

Macrophage lineage

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12
Q

What cells can osteoprogenitor cells become

A

Osteoblasts (then become osteocytes)
Chondrocyte (under specific conditions)

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13
Q

What type of stress do osteocytes sense in bone

A

Mechanical

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14
Q

What does osteocyte death signal for

A

Remodelling

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15
Q

Reasons for bone remodelling

A

Renew bone before deterioration
Redistribute bone matrix along mechanical stress lines

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16
Q

Is trabecular or cortical bone formed faster

A

Trabecular

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17
Q

Which cells produce sclerostin

A

Healthy osteocytes

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18
Q

Which signal does sclerostin give and to which cells

A

Inhibitory signal to surface osteoblasts to stop being active and being lining cells

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19
Q

How does damage to bone cause bone formation

A

Osteocytes damages -> stop sclerostin production -> osteoblasts activate

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20
Q

What does ephrinB2/ephrinB4 signalling cause and which cells is it between

A

Clast inhibition, blast activation
Bidirectional Between osteoclasts and osteoblasts

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21
Q

Process of bone remodelling

A

Clast attaches to bone -> acid and enzymes break down bone -> proteins and minerals cross Clast and released into interstitial fluid

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22
Q

What happens to proteins and minerals released from osteoclasts after bone remodelling

A

Used to mineralise new bone

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23
Q

Serum calcium range

A

2.2-2.6 mmol/l

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24
Q

What form of calcium is usable by cells

A

Free ionised

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25
Q

What maintains serum calcium

A

GI absorption
Renal excretion
Skeletal mobilisation

26
Q

Recommended daily calcium intake

A

500-1300mg

27
Q

What hormone is released when serum calcium is low

A

PTH

28
Q

How does PTH affect serum calcium

A

Decr Ca excretion from kidney
Incr GI Ca absorption
Incr Ca efflux from bone

29
Q

Normal plasma phosphate

A

0.8-1.5mmol/l

30
Q

Why is phosphate serum concentration less tightly regulated than calcium concentration

A

Less important for body processes

31
Q

Which hormone modulates phosphate absorption and secretion

A

PTH

32
Q

How does PTH increase Ca resorbtion from bone

A

Incr Clast activity and number

33
Q

How does PTH increase Ca absorbtion from the gut

A

Increase 1,25-dihydroxyvitamin D synthesis

34
Q

How does PTH increase osteoclast activity and number

A

Binds to receptor on osteoblasts -> blasts produce RANKL -> RANKL activates clasts and Clast precursors

35
Q

Which cells produce FGF23

A

Osteoblasts
Osteocytes

36
Q

Effects of FGF23

A

Incr serum phosphate excretion from kidney
Stop 1,25 (OH)2D production by inhibiting 1 alpha hydroxylase
Decr PTH secretion

37
Q

What is the principal phosphaturic hormone

A

FGF23

38
Q

What do receptor does FGF23 bind to on the kidney and parathyroid

A

Klotho

39
Q

FGF23/Klotho axis

A

PTH induces FGF23 production by osteocytes and osteoblasts -> FGF23 binds to Klotho on parathyroid and kidney -> inhibits PTH secretion, increases PO4 excretion, decreases alpha1dehydroxylase to decrease 1,25vitD

40
Q

Which hormone regulates cellular phosphate conc and 1,25 vit D metabolism

A

FGF23

41
Q

Osteoid

A

Unmineralised bone matrix

42
Q

What does the cement line show

A

Line between mineralised and unmineralised bone

43
Q

What happens to lacunae formed by osteoclasts breaking down bone

A

Filled with osteoid by osteoblasts

44
Q

How long before osteoid laid down by osteoblasts is mineralised

A

1 week

45
Q

How does PTH increase bone resorption

A

Bind to osteoblasts -> blasts make RANKL -> RANKL binds to Clast precursor -> incr Clast maturation + differentiation

46
Q

Do TNF-alpha, IL-1, IL-11, and PGE2 inhibit or induce PTH

A

Induce

47
Q

Does estrogen inhibit or induce PTH

A

Inhibit

48
Q

What 2 substances are needed for osteoclast formation

A

RANKL
M-CSF

49
Q

What stimulates calcitonin release

A

Serum Ca>2.25 mmol/L

50
Q

Calcitonin actions

A

Inhibit osteoclast differentiation and activity
Incr Ca excretion from kidney
Inhibit Ca absorption in intestines

51
Q

Why is a pt with a removed thyroid gland given PTH but not calcitonin

A

calcitonin has much weaker effect on bone metabolism

52
Q

What is the prohormone for active vitamin D

A

25 OH vitamin D

53
Q

Where is 1,25 vitamin D made

A

Kidney

54
Q

Action of 1,25 vitamin D on bone metabolism

A

Stim Ca absorption from gut
Stimulate bone resorption
Prepare bone ECM for mineralisation

55
Q

How does 1,25 vit D make bone matrix pH correct for mineralisation

A

Stimulates production of alkaline phosphatase matrix vesicles

56
Q

Which hormones increase and decrease serum calcium

A

Incr - PTH
Decr - calcitonin

57
Q

What can prolonged corticosteroid treatment and oestrogen decr at menopause lead to

A

Osteoporosis

58
Q

Do oestrogen and glucocorticoids increase or decrease gut Ca absorption

A

Oes Incr
Gluc decr

59
Q

How does oestrogen effect osteoclasts

A

Inhibit

60
Q

Do glucocorticoids and oestrogen increase or decrease bone reabsorption

A

Oestrogen decr
Glucocorticoid incr

61
Q

How does FSH affect monocytes and osteoclasts

A

Upregulate RANK in osteoclasts
Indirectly incr monocyte Il1, TNF, and IL6 secretion