Bone modelling, remodelling and RANKL/RANK/OPG pathway

Question 1

What are the 2 methods of bone modelling/growth, and what do they increase?

Answer 1

Longitudinal growth causes increase in length

Appositional growth causes increase in width/diameter

Question 2

Where is the main site of longitudinal growth of bone?

Answer 2

Growth plate

Question 3

What are the 3 zones of the growth plate, and where is each zone located in the growth plate?

Answer 3

Proliferation zone is closest to epiphyseal side

Hypertrophic zone is in the middle of the other 2 zones

Ossification zone is closest to the diaphyseal side

Question 4

What occurs in the proliferating zone of the growth plate during longitudinal growth of a bone?

Answer 4

Proliferating chondrocytes undergo interstitial growth by forming new cartilage inside the existing cartilage (growth plate)

Question 5

What is interstitial growth of cartilage?

Answer 5

New cartilage produced inside existing cartilage

Question 6

What occurs in the hypertrophic zone of the growth plate during longitudinal growth of bone?

Answer 6

Mature chondrocytes enlarge and degenerate

Question 7

What occurs in the ossification zone of the growth plate during longitudinal growth of bone?

Answer 7

Dead/dying chondrocytes are calcified, so this layer becomes fragile and disintegrates and is replaced by new bone

Question 8

In longitudinal growth, what part of the bone structure is elongated?

Answer 8

Diaphysis

Question 9

When does the growth plate become the epiphyseal line?

Answer 9

After puberty

Question 10

What is epiphyseal fusion?

Answer 10

Replacement of growth plate by epiphyseal line after sexual maturation and bone has grown to full length

Question 11

After epiphyseal fusion, does the bone still grow?

Answer 11

Bone can only grow by appositional growth

Question 12

How does epiphyseal fusion occur after bone has grown to full length?

Answer 12

Chondrocytes stop proliferating and growth plate is ossified

Question 13

What is bone modelling?

Answer 13

Processes of bone growth that change individual shape of bone, that involves osteoclasts and osteoblasts

Question 14

Why is appositional growth balanced by osteoblastic and osteoclastic activity?

Answer 14

Prevents bone from becoming too bulky/weak

Question 15

What osteoclastic activity occurs during appositional growth of the bone?

Answer 15

Lining of medullary cavity resorbed

Question 16

Why do osteoclasts resorb the medullary cavity lining in appositional growth of bone?

Answer 16

So that medullary cavity diameter increases as the bone grows

Question 17

What osteoblastic activity occurs in appositional growth of bone?

Answer 17

Osteoblasts produce tissue under periosteum

Question 18

By which process does the tissue under periosteum change into bone in appositional growth?

Answer 18

Intramembranous ossification, where bone is formed from connective tissue

Question 19

What is the rate of longitudinal growth compared to rate of appositional growth of bone?

Answer 19

Longitudinal at faster rate than appositional

Question 20

What is bone remodelling?

Answer 20

Cell turnover of bone that occurs after longitudinal growth arrest at epiphyseal fusion

Question 21

What 2 processes cause bone remodelling?

Answer 21

Bone resorption by osteoclasts

Bone formation by osteoblasts

Question 22

What are the 4 phases of bone remodelling?

Answer 22

Activation, Resorption, Reversal, Formation

Question 23

What happens in the activation phase of bone remodelling?

Answer 23

Resting bone surface is converted to remodelling surface which attracts osteoclast precursors that now fuse into large, multinucleated osteoclasts

Question 24

What 2 processes do osteoclasts use in the resorption phase of bone remodelling?

Answer 24

Osteoclasts resorb bone matrix by acidification and proteolytic digestion

Question 25

In which specific structure does resorption occur in the resorption phase of bone remodelling?

Answer 25

Howship's lacunae (scallop-shaped depression)

Question 26

After bone resorption has occurred in the resorption phase of bone remodelling, what 2 things happen?

Answer 26

Calcium released into bloodstream Osteoclasts leave resorption site or undergo apoptosis

Question 27

What happens in the reversal phase of bone remodelling?

Answer 27

Osteoblasts recruited to remodelling surface

Question 28

What happens in the formation phase of bone remodelling?

Answer 28

Osteoblasts secrete osteoid, which is the basis for mineralisation, then matrix hardens to form bone

Question 29

What pathway is used to regulate bone remodelling?

Answer 29

RANK/RANKL/OPG pathway

Question 30

What is RANK?

Answer 30

Receptor on osteoclast precursor that binds to RANKL to stimulate osteoclast proliferation and bone resorption

Question 31

What is RANKL?

Answer 31

Cytokine that binds to RANK receptor to promote osteoclastic activity, so is a key mediator of bone resorption

Question 32

What is Osteoprotegerin (OPG)?

Answer 32

Glycoprotein produced by osteoblasts, that inhibits bone resorption by inhibiting osteoclast formation, and promotes bone formation

Question 33

How do RANKL and OPG work antagonistically in bone remodelling?

Answer 33

OPG can bind to RANK and block RANKL from binding, which inhibits osteoclastic activity If RANKL binds to RANK then osteoblastic activity is inhibited

Question 34

How can alterations of the RANKL/OPG ratio be harmful?

Answer 34

Increased bone resorption is cause of some bone diseases