Bone Metabolism

Question 1

What is lamellar bone?

Answer 1

It’s mature bone, either of the cortical or trabecular form.

Question 2

What is woven bone?

Answer 2

Immature bone that is formed in response to damage or may be pathological

Question 3

What percentage of total bone mass is made up of cancellous/trabecular bone?

Answer 3

20%

Question 4

What percentage of total bone mass is made up of cortical/compact bone?

Answer 4

80%

Question 5

How does the collagen organisation differ between lamellar and woven bone?

Answer 5

In woven bone there is random collagen organisation which makes it mechanically weak in comparison to the ordered structure of lamellar bone.

Question 6

Describe the composition of the extracellular matrix of bone

Answer 6

•	35-40% organic
o	Type 1 collagen for tensile strength
o	Proteoglycans for compressive strength
o	Growth factors, cytokines and osteoid
•	60% inorganic 
o	Contains a large amount of calcium hydroxyapatite on top of the collagen fibres 
•	5% consists solely of water.

Question 7

What type of collagen is ordinarily present in bone?

Answer 7

Type 1

Question 8

What are the main organic components of bone matrix?

Answer 8

Type 1 collagen, proteoglycans, growth factors, cytokines and osteoid

Question 9

What is the main inorganic component of bone matrix?

Answer 9

Calcium hydroxyapatite (on top of collagen fibres)

Question 10

Which cells secrete sclerostin?

Answer 10

Osteocytes

Question 11

What is the function of sclerostin?

Answer 11

Inhibits bone formation by osteoblasts

Question 12

What is the function of osteocytes?

Answer 12

To sense mechanical stress on bone by detecting death and a need for remodelling; in response to stress stop secreting sclerostin (due to action of PTH)

Question 13

How does calcitonin affect sclerostin production by osteocytes?

Answer 13

Upregulates secretion and therefore inhibits bone formation by osteoblasts

Question 14

How does PTH affect sclerostin production by osteocytes?

Answer 14

Inhibits sclerostin production in response to mechanical stress; this signals for osteoblasts to deposit bone

Question 15

What are osteoblasts?

Answer 15

A form of mesenchymal cell which replace (deposit) more bone matrix (osteoid)

Question 16

What are osteoclasts?

Answer 16

Macrophage-like cells from red bone marrow that work to dissolve and digest the bone matrix

Question 17

What are osteoprogenitor cells?

Answer 17

Bone marrow stem cells.

Question 18

What are canaliculi?

Answer 18

These allow chemical communication between osteocytes to decide whether remodelling is required in response to stress

Question 19

What are osteocyte lacunae?

Answer 19

The ‘pit’ or ‘lake’ in which individual osteocytes sit

Question 20

Outline the process of bone remodelling

Answer 20

1. Osteoclast attached to bone to form a leak-proof seal
2. Protein-digesting enzymes break down the collagen fibres
3. Acid secreted dissolves the bone minerals
4. Bone proteins and minerals (mainly Ca2+) to cross the osteoclast and exitinto the interstitial fluid
5. Osteoblasts then fill the lacuna with osteoid, and the osteoid is mineralised approximately a week later

Question 21

What does serum calcium depend upon?

Answer 21

Intestinal absorption, renal excretion and skeletal mobilisation

Question 22

What is normal serum calcium?

Answer 22

2.2-2.6mmol/L (8.5-10.5mg/dL)

Question 23

What is the recommended daily intake of calcium?

Answer 23

500-1,300mg

Question 24

How is calcium excreted?

Answer 24

Calcium is excreted by kidneys (~200mg/day) and gut (~600-800mg/day in stools)

Question 25

What are normal serum phosphate levels?

Answer 25

0.8-1.5mmol/L

Question 26

Which hormones are involved in 'bone maintenance'?

Answer 26

Vitamin D, oestrogen, progesterone

Question 27

Which hormones are involved with increased bone degradation?

Answer 27

Calcitonin, PTH, glucocorticoids (steroids)

Question 28

Outline the effect of PTH on bone metabolism

Answer 28

Low serum calcium stimulates PTH production which then promotes calcium reabsorption from kidney (and phosphate excretion), calcium resorption (osteoblasts PTH receptor --> RANKL --> RANK receptor on osteoclasts) and increased 1,25 dihydroxyvitamin D production (increases calcium absorption from gut)

Question 29

Outline the effect of calcitonin on bone metabolism

Answer 29

Released when serum calcium is just within the normal range. Causes inhibition of osteoclasts, increases calcium excretion from kidney and inhibits calcium absorption in the gut.

Question 30

Outline the effect of vitamin D on bone metabolism

Answer 30

Increases calcium absorption in the gut, and increases bone resorption (activates RANKL --> more osteoclast differentiation)

Question 31

What is the active form of vitamin D?

Answer 31

1,25 dihydroxyvitamin D

Question 32

Outline the effect of oestrogen on bone metabolism?

Answer 32

Increases calcium absorption from the gut (increases production of 1,25 dihydroxyvitamin D) and inhibits osteoclasts

Question 33

Outline the effect of glucocorticoids on bone metabolism

Answer 33

Decreases calcium absorption in the gut and increases bone resorption and decreases bone formation (prolonged steroid use can therefore lead to osteoporosis)

Question 34

Outline the effect of progesterone on bone metabolism

Answer 34

Adding progesterone cream in osteoporosis therapy has shown to increase bone density (mechanism unknown)

Question 35

What is the role of calcitonin on bone metabolism?

Answer 35

Prevents bone formation by osteoblasts; it up regulates the production of sclerostin by osteocytes

Question 36

What stimulates the release of PTH?

Answer 36

Low serum calcium levels

Question 37

What stimulates the secretion of calcitonin?

Answer 37

Serum calcium levels just within the normal range (2.25mmol/L)

Question 38

What is the normal daily requirement of vitamin D?

Answer 38

400IU/day

Question 39

Where is 1,25 dihydroxyvitamin D formed?

Answer 39

Kidney, and it's the active form of vitamin D.

Question 40

How may vitamin D aid in the production of mineralised bone matrix?

Answer 40

By producing pro-collagen type 1 anad alkaline phosphatase vesicles