Bone Metabolism Flashcards
1
Q
What are the two types of bone
A
lamellar
woven
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
3
Q
what is the majority of the bone in the body made up of
A
lamellar bone
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
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
6
Q
what type of bone allows generation of new bone
A
Lamellar bone = cancellous/trabecular/spongy bone type
7
Q
What are the two types of bone marrow
A
- red and yellow bone marrow
8
Q
what bone marrow is the majority of bone marrow
A
Yellow bone marrow
9
Q
what is yellow bone marrow made out of
A
adipocytes and fibroblasts
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
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
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.
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
14
Q
Describe what compact bone looks like
A
- circular osteon
- blood vessels run down the centre
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
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
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
18
Q
describe what the inorganic part of the bone matrix is made out of
A
- 95% calcium hydroxyapatite
19
Q
list the 4 types of cells found in bone
A
- osteoprogenitor cell
- osteoblast
- osteocyte
- osteoclast
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
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
22
Q
What is an osteocytes
A
Osteocytes are a more mature osteoblast which has become incased in the osteoid material the osteoblast produced
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
24
Q
what do osteoclasts do
A
- the osteoclasts come from the haempoietic red bone marrow linage
- these cause the reabsorption of bone
25
what does death of osteocytes cause
Death of osteocytes signals remodelling-
26
what are the reasons for remodelling
1) renews bone before deterioration
| 2) redistributes bone matrix along mechanical stress lines.
27
how much quicker does trabecular bone turn over than cortical bone
1) renews bone before deterioration
| 2) redistributes bone matrix along mechanical stress lines.
28
what are the differences between trabecular bone and cortical bone
Trabecular bone
- larger surface area
- responds quicker to stresses on the bone
29
What is sclerostin
Sclerostin secreted glycoprotein that inhibits bone formation by osteoblasts
30
what causes the activation and inhibition of osteoblasts
- Inhibited by PTH and mechanical stress
| - increased by calcitonin
31
what happens if there is a mutation in the sclerotin gene
sclerosteosis autosomal recessive disorder characterised by bone overgrowth.
32
describe the interactions between the osteoclasts and osteoblasts
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
what happens if you don't remodel the bone
- 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
describe how bone remodelling happens
- 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
describe how osteoblast secretes new osteoid
- osteoblasts fill lacuna with osteoid
| - the osteoid is then mineralised approximately 1 week later
36
what antibiotic is fluorescences by osteoid
tetracycline
37
how long does bone remodelling take
Bone remodelling approximately takes about 3 months
38
what cells is responsible for bone formation and reabsorption
Bone formation = osteoblasts
Resorption = osteoclasts
39
describe the levels of calcium in different parts of the body
- 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
what does the maintenance of normal serum calcium depends on
intestinal absorption
renal excretion
skeletal mobilisation
41
what is the recommended daily intake of calcium
500-1300mg
42
how much calcium is excreted a day
Kidneys approx 200mg/day
Gut approx 600-800mg/day in stools
43
where is the phosphate in the body
80-90% in skeleton 10% in blood and plasma
44
What is the normal phosphate concentration
Normal plasma concentration 0.8 -1.5mmol/L
45
what is phosphate absorption linked to
- calcium metabolism
46
what monitors phosphate and calcium absorption
PTH
47
what organs absorb and excrete calcium
gut and kidneys
48
What does PTH promote
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
describe RANKL on osteoblasts and osteoclasts
- Osteoblasts produce RANKL
| - Osteoclasts and their precursors have RANK receptors
50
what stimulates PTH
low serum calcium
51
what does 1,25(OH)2 do
1,25 (OH)2 vitamin D3 increases Ca2+ absorption from gut.
52
where is 25 (OH)2 vitamin D produced
liver
53
what is 1,25 (OH)2 vitamin D
Kidneys
54
What does osteoclasts formation require
Osteoclast formation requires RANKL and M-CSF produced by osteoblasts and stromal cells
55
what does RANKL stand for
Receptor activator of nuclear factor kappa-B ligand
56
What does M-CSF stand for
Macrophage colony-stimulating factor.
57
What does OPG stand for
osteoprotegrin (decoy receptor for RANKL)
58
describe how RANKL stimulation works
- 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
what produces calcitonin
- C parafollicular cells within he thyroid gland
60
what causes the production in calcitonin
= increase in plasma calcium serum levels
| Ca2+ >2.25mmol/L
61
What does calcitonin do
inhibits osteoclast differentiation and activity
increases Ca2+ excretion from kidney
Inhibits Ca2+ absorption by intestines
62
what is the most potent form of vitamin D
1,25 DIhydroxy vitamin D
63
How is 25(OH) Vitamin D (prehormone) made from
- diet
| - UV light on precursors in skin
64
what is the daily requirement of vitamin D
400IU/day
65
what does vitamin D do
Strongly stimulates Ca2+ absorption from gut
Stimulates bone resorption in same way as PTH
66
What is vitamin D3 (1,25-(OH)2) involved in
- preparing the ECM for mineralisation
- production of pro-collagen type 1
- production of alkaline phosphatase matrix vesicles
67
what stimulates 1,25 -(OH)2 Vitamin D3
Elevated PTH
Decreased calcium
Decreased serum phosphate
68
what inhibits PTH
Elevated serum calcium
Elevated 1,25(OH)2D in kidney
69
what inhibits 1,25-(OH)2 Vitamin D3
Decreased PTH
Elevated serum calcium
Elevated serum phosphate
70
how does PTH effect the intestines
No direct effect
| Acts indirectly on bowel by stimulating 1,25(OH)2D in kidney
71
How does PTH affect the kidney
Stimulates 25(OH)D-1αOHase in proximal tubular cells to make 1,25(OH)2D
Increases reabsorption of calcium
Promotes excretion of phosphate
72
How does PTH effect the bone
increases bone resorption indirectly by proliferation and differentiation of osteoclasts
73
how does 1,25-(OH)2 Vitamin D3 effect the intestine
Strongly stimulates intestinal absorption of calcium and phosphate
74
how does calcitonin effect calcium reabsorption in the intestine
Inhibits Ca2+ absorption by intestines
75
how does calcitonin effect calcium reasborption in the kidney
- increases renal calcium excretion
76
How does calcitonin effect calcium reabsorption in the bone
Inhibits bone resorption by direct inhibition of osteoclast differentiation and activity
77
how does oestrogen effect calcium reabsorption
gut - increased Ca2+ absorption
bone - decreased re-absorption (inhibit osteoclasts)
At menopause loss of bone mass - osteoporosis
78
How does glucocorticoids affect calcium reabsorption
gut - decrease Ca2+ absorption
bone - increased re-absorption/decreased formation
Prolonged corticosteroid treatment – osteoporosis
79
How does progesterone effect calcium reabsorption
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
