Bones

Question 1

What is the mechanical role of bone?

Answer 1

Structural support and muscle attachment

Question 2

What is the protective role of bone?

Answer 2

Protects vital organs

Bone marrow

Question 3

What is the metabolic role of bone?

Answer 3

Ion homeostasis

Calcium and phosphate

Question 4

What is bone?

Answer 4

Specialised connective tissues
Extracellular matrix calcifies
30% organic: collagen and non-collagenous protein
70% inorganic: calcification, formation of hydroxyapatite

Question 5

What are the cells within bone?

Answer 5

Osteoclasts
Osteoblasts
Bone lining cells
Osteocyte

Question 6

What is an osteoclast?

Answer 6

Bone resorption

Question 7

What is an osteoblast?

Answer 7

Bone forming

Question 8

What are bone lining cells?

Answer 8

Specialist inactive osteoblastlast

Initiate bone forming

Question 9

What are osteocytes?

Answer 9

Mechanosensing cells

Question 10

What is the basic structure of bone?

Answer 10

Cortical, compact bone
Spongy, trabecular bone
Surrounded by periosteum

Question 11

What do osteoblasts do?

Answer 11

Formation of bone matrix
Regulation of mineralisation
Regulation of osteoclast differentiation
Precursors of bone living cells and osteocytes

Question 12

What do osteoblasts differentiate from?

Answer 12

Stromal precursor cells

Question 13

What do osteoblasts express?

Answer 13

RUNX2 and Osx

Question 14

How do osteoblasts differentiate?

Answer 14

Unknown
HOX genes
Bone morphogenic proteins
Wnt
PTH

Question 15

What can protect against osteoblast apoptosis?

Answer 15

Intermittent PTH

Question 16

What do osteoclasts do?

Answer 16

Bone resorption

Calcium homeostasis

Question 17

What do osteoclasts develop from?

Answer 17

Arise from mononuclear cells

Either from the marrow or circulating monocytes

Question 18

What signals are necessary for osteocyte differentiation?

Answer 18

Macrophage colony stimulating factor

RANKL

Question 19

What is the order of osteoclast differentiation?

Answer 19

Bone marrow precursor
Pre-osteoclast
Proliferate
Fused prokaryon
Active osteoclast

Question 20

What does an active osteoclast express?

Answer 20

F4/80 -ve
Trap +ve
CTR +ve
Beta3 +ve

Question 21

How do osteoclasts function?

Answer 21

Move by chemotaxis
Cell is highly polarised
Creates a sealed environment
Secretes acids and enzymes
Bone is resorbed by combination of enzymes
Forms a Howships lacuna

Question 22

What is the RANKL/OPG system?

Answer 22

Signalling between osteoblasts and osteoclasts
Receptor activator of Nf-kappabeta (RANK) is a receptor on osteoclasts
RANKL produced by osteoblasts and stromal cells and some lymphocytes
RANK+RANKL causes osteoclast differentiation and activation

Question 23

What is osteoprogerin?

Answer 23

Osteoprogerin is a dummy receptor for RANKL

Question 24

What happens if over express osteoprogerin?

Answer 24

Too much inhibition of bone resorption

Osteopetrosis

Question 25

What can cause osteoporosis?

Answer 25

Loss of osteoprogerin | RANKL overexpression

Question 26

What can cause osteopetrosis?

Answer 26

Overexpression of osteoprogerin Absence of RANKL Absence of RANK

Question 27

Factors increasing RANKL expression?

Answer 27

Parathyroid hormone Oestrogen deficiency Inflammatory cytokines Glucocorticoids

Question 28

How do osteocytes form?

Answer 28

Osteoblasts are incorporated into the bone matrix During bone ossification and mineralisation Integrated into osteocyte network

Question 29

What is the function of osteocytes?

Answer 29

Regulation of local mineralisation Mechanosensing Initiation of bone remodelling cycle Sclerostin and BMPs

Question 30

What regulates osteocytes?

Answer 30

Shear stress Damage Canalicular fluid flow

Question 31

How does bone remodel in trabecular bone?

Answer 31

Bone resorption Formation of osteoid Osteoid mineralisation New bone

Question 32

How is cortical bone remodelled?

Answer 32

Via the Haversian system

Question 33

What are bone remodelling units?

Answer 33

Cutting zone Reversal zone Closing cone

Question 34

Where does bone grow?

Answer 34

Periosteal surfaces

Question 35

What is the definition of osteoporosis?

Answer 35

A progressive systemic skeletal disease Characterised by low bone mass Micro-architectural deterioration Increase in fragility and susceptibility

Question 36

What fractures are common of osteoporosis?

Answer 36

Head of ulna wrist fracture (Colles') Spinal collapse Vertebral fractures Fratured neck of femur

Question 37

What are the causes of osteoporosis?

Answer 37

Oestrogen deficiency Glucocorticoids Vitamin D/ calcium deficiency Ageing

Question 38

What does oestrogen do to the skeleton?

Answer 38

Maintain skeletal health Oestrogen deficiency results in increased bone resorption Oestrogen receptors are expressed in osteoblasts not osteoclasts Oestrogen deficiency leads to increased expression of RANKL

Question 39

Can oestrogen be used as a therapy?

Answer 39

``` Oestrogen treatment as HRT Given by mouth, patch or implant Reduces bone resorption Increase bone density Reduces fracture risk Complications of DVT, breast cancer, uterine cancer, heart disease and dementia ```

Question 40

How do SERMs work?

Answer 40

Selective oestrogen receptor modulators Tamoxifen Increases bone mineral density

Question 41

What is Raloxifene?

Answer 41

Increases bone mineral density at all sites Decreases risk of breast cancer Cardiovascular risk is uncertain Partial agonist on bone, decreases BMD in pre-menopausal

Question 42

What are bisphosphonates?

Answer 42

Alendronate Potent inhibitor of bone resorption Inhibits intracellular signalling pathway Increases osteoclast apoptosis

Question 43

What are advantages of bisphonates?

Answer 43

``` Bone selective Relatively few side effects Improve cortical and trabecular bone Once daily/weekly tablet Equal effect in men and women ```

Question 44

What are the disadvantages of bisphonates?

Answer 44

Incorporated into the skeleton Unknown long-term effect Risk of blocking repair of microfractures Uncommon fractures: diaphyseal of femur

Question 45

Why is vitamin D important?

Answer 45

Vitamin D is essential for calcium absorption and osteoblast differentiation

Question 46

What happens if vitamin D is absent?

Answer 46

Osteomalacia | Mild deficiency impairs osteoblast function

Question 47

What happens to the parathyroid if calcium is deficient?

Answer 47

Secondary hyperparathyroidism Stimulates osteoclastic activity Increases resorption PTH receptors on osteoblasts increase RANKL

Question 48

How can we treat calcium and vitamin D deficiency?

Answer 48

Supplementation

Question 49

Whats the effect of hyperparathyroidism?

Answer 49

Bone loss due to bone resorption

Question 50

What is the effect of PTH injection?

Answer 50

Increased bone formation | Essential in differentiation of osteoblasts

Question 51

What effect do glucocorticoids have on bone?

Answer 51

Fracture risk increases with the use of steroids Decrease activity of osteoblasts Mitigate osteoclasts Treated with bisphosphonates or intermittent PTH injection