Bone Metabolism

Question 1

How do osteoclasts appear on a slide

Answer 1

Multinucleated
Large
Sparse

Question 2

What do osteocytes do

Answer 2

Determine the status of piece of bone, decide whether it needs removal and remodelling

Question 3

What cells are immature osteocytes

Answer 3

Osteoblasts

Question 4

What type of bone marrow makes up the majority at birth

Answer 4

Red

Question 5

Where does red bone marrow remain

Answer 5

Spongy bones of vertebrae, ribs, sternum, cranium and epiphyses

Question 6

Name the 2 overall types of bone

Answer 6

Lamellar

Woven

Question 7

2 types of lamellar bone?

Answer 7

Cortical/ compact

Cancellous/ trabeculae/ spongy

Question 8

What % of adult bone mass is cortical bone

Answer 8

80

Question 9

What is the purpose of the Haversian canal system

Answer 9

All columns form around the outside so weight pushes on these columns
Deals with stress that comes from above

Question 10

Which bone type has greater surface area? By how much?

Answer 10

Trabecullae bone 10* bigger surface area

Question 11

When is woven bone used

Answer 11

Fracture healing

Question 12

How is collagen laid down in woven bone and what is the consequence of this

Answer 12

Randomly laid down collagen, so weaker structure

Question 13

What % of bone is organic

Answer 13

35-40%

Question 14

What type of collagen makes up bone

Answer 14

Type 1

Question 15

What are the 3 organic components of bone

Answer 15

Type 1 collagen
Proteoglycans
Growth factors

Question 16

What type of strength do proteoglycans provide

Answer 16

Compressive

Question 17

What are the non organic components of bone

Answer 17

Calcium hydroxyapatite

Water

Question 18

Describe how calcium hydroxyapatite coats the collagen

Answer 18

In blocks, leaving gaps of exposed collagen to ensure there is some bendability

Question 19

What are osteoclasts derived from

Answer 19

Haemopoietic stem cells

Question 20

What are osteoblasts derived from

Answer 20

Osteoprogenitor cell (mesenchymal stem cell)

Question 21

What structure enables osteocytes to detect any bends

Answer 21

Branches

Question 22

What is the overall signal for bone remodelling

Answer 22

Osteocyte death

Question 23

What bone type is quicker to form

Answer 23

Trabecular

Question 24

Why does trabecular bone form faster than cortical

Answer 24

Larger surface area

Responds to stresses on the bone quicker

Question 25

Give 2 reasons for bone remodelling

Answer 25

- Renews bone before deterioration | - Redistributes bone matrix along mechanical stress lines

Question 26

What is sclerostin

Answer 26

A glycoprotein that inhibits bone formation by osteoblasts. Secreted by osteocytes

Question 27

What inhibits sclerostin release

Answer 27

PTH and mechanical stress

Question 28

What increases sclerostic release

Answer 28

Calcitonin

Question 29

What is sclerosteosis

Answer 29

A mutation in the sclerostin gene causes autosomall recessive disorder characterised by bone overgrowth

Question 30

What is romosozumab

Answer 30

An antibody to sclerostin currently being trailed as a way to increase bone density

Question 31

Describe the role of osteoclasts in bone remodelling

Answer 31

- Crawls across surface seeking out damage - Attaches to bone in leak proof seal - Releases protein digesting enzymes to break down collagen - Releases acid to dissolve bone minerals

Question 32

What ph is required to dissolve bone minerals

Answer 32

5

Question 33

What happens to the calcium broken down/ released by osteoclasts

Answer 33

Cross osteoclast to exit into the interstitial fluid

Question 34

What happens in bone remodelling once old bone has been destroyed

Answer 34

New osteoblast produced, moving into gap where osteoclast was Secrete collagen and protein matrix, becomes embedded and surrounded Fill lacuna with osteoid

Question 35

At what stage does new osteoid become mineralised

Answer 35

After about a week

Question 36

3 phases of bone remodelling

Answer 36

Rest Resorption Formation

Question 37

State the distribution of calcium in the body

Answer 37

99% skeleton 1% cells, blood and body 0.1% ECM

Question 38

What are normal serum calcium levels

Answer 38

2.2-2.6mmol/L

Question 39

How much free ionised calcium should there be in the body

Answer 39

1.0-1.25mmol/L

Question 40

What 3 things does maintenance of normal serum calcium depend upon

Answer 40

Intestinal absorption Renal excretion Skeletal mobilisation

Question 41

What is the RDI of calcium

Answer 41

500-1300mg

Question 42

How much calcium is secreted by the kidneys a day

Answer 42

200mg/day

Question 43

How much calcium is secreted by the gut a day

Answer 43

600-800/day in stools

Question 44

Describe the distribution of phosphate in the body

Answer 44

80-90% in skeleton | 10% plasma

Question 45

What are normal plasma concentrations of phosphate

Answer 45

0.8-1.5mmol/L

Question 46

What hormone is used to modulate absorpton and excretion of phosphate and calcium

Answer 46

Parathyroid hormone

Question 47

What is the stimulus for PTH release

Answer 47

Low plasma calcium levels

Question 48

How does PTH act upon the kidney

Answer 48

Promotes calcium reabsorption and phosphate excretion

Question 49

How does PTH act on the bone

Answer 49

Calcium reabsorption increasing the number and activity of osteoclasts

Question 50

How does PTH increase nimber and activity of osteoclasts

Answer 50

``` Osteoblasts have PTH receptor Receptor is activated Osteoblasts produce RANKL Osteoclasts have RANKL receptors Number and activity increases ```

Question 51

What is the effect of PTH of 1,250dihydroxyvitamin D synthesis

Answer 51

Increases it

Question 52

How does 1,25dihydroxyvitamin D affect calcium metabolism

Answer 52

Increases calcium absorption from the gut

Question 53

What molecules are required for osteoclast formation

Answer 53

RANKL and M-CSF

Question 54

What cells produce RANKL and M-CSF

Answer 54

Osteoblasts and stromal cells

Question 55

What does RANKL stand for

Answer 55

Receptor activator of nuclear factor kappa b ligand

Question 56

What does M-CSF stand for

Answer 56

Macrophage colony stimulating factor

Question 57

What is OPG

Answer 57

Osteoprotegrin | This is a decoy receptor for RANKL

Question 58

What expresses ephrin B2 ligand

Answer 58

Osteoclasts

Question 59

What expresses ephB4 receptor

Answer 59

Osteoblasts

Question 60

What is the effect of PTH on ephrin B2

Answer 60

Increases ephrinB2 expression

Question 61

Does oestrogen stimulate or inhibit RANLK

Answer 61

Inhibit

Question 62

When is calcitonin released

Answer 62

When serum calcium >2.25mmol/L

Question 63

3 effects of calcitonin release

Answer 63

- Inhibits osteoclast differentiation and activity - Increased calcium excretion from kidney - Inhibits calcium absorption by intestines (opposite PTH)

Question 64

Where do we get vit D from

Answer 64

Diet | UV light

Question 65

What is normal daily requirement for vitamin D

Answer 65

400IU/ day

Question 66

Where is the active form of vitamin D made

Answer 66

Kidney

Question 67

What is the role of vitamin D in bone formation and remodelling

Answer 67

Prepares the ECM for mineralisation by produces pro-collagen type 1 and producing alkaline phosphatase matrix vesicles

Question 68

How does oestrogen effect calcium metabolism

Answer 68

- Increased absorption in gut - Decreased reabsorption in bone - Inhibits osteoclasts

Question 69

What disease, common at menopause, is caused by decreased oestrogen or prolonged steroid use

Answer 69

Osteoporosis

Question 70

What is the effect of glucocorticoids on calcium metabolism

Answer 70

Decreased absorption in gut | Increased reabsorption/ decreased formation in bone

Question 71

What hormone may be used to treat menopausal osteoporosis

Answer 71

Progesterone