WEEK 3: Bone Physiology

Question 1

What is ossification or osteogenesis?

Answer 1

= process of bone formation

• begins 6 weeks after fertilisation
• before 6 wks, embryonic skeleton is fibrous membranes and hyaline cartilage
• bone growth continues for roughly 25 years; after this the epiphyseal bone plate fuses

Question 2

What are the 2 processes of embryological bone formation?

Answer 2

1) INTRAMEMBRANOUS = mesenchyme to bone (occurs in-utero and flat bones; skull, sterum, ribs)

2) ENDOCHONDRAL = replacement of hyaline cartilage with bone

Question 3

Explain the process of INTRAMEMBRANOUS ossification

Answer 3

1) Mesenchyme differentiates into osteoblasts (build bone).

2) Osteoblasts group into clusters and form ossification centres.

3) Osteoblasts begin secreting osteoid until they are surrounded.

4) Binding of calcium hydroxyapatite (calcium and phosphorus) hardens extracellular matrix (they are deposited into the extracellular matrix which signals calcification).

5) Extracellular matrix surrounds blood vessels and forms spongy bone. Trabeculae are formed. Blood cells around these will eventually become red bone marrow.

6) Mesenchymal cells on the surface of bone differentiate to form periosteum (the fibrous membrane that surrounds bone).

7) Osteoblasts inside the periosteum secrete osteoid forming compact bone (not around blood vessels but in parallel lines to form osteons).

Question 4

Explain the process of ENDOCHONDRAL ossification

Answer 4

1) Mesenchyme differentiates into chondroblasts (immature cartilage cells).

2) Chondroblasts secrete extracellular matrix to form a cartilage model for bone.

3) Chondrocytes undergo hypertrophy and alter the matrix by adding collagen and other proteins, which allows for calcification.

4) Calcification prevents nutrients from reaching chondrocytes causing apoptosis (death).

5) Apoptosis allows blood vessels to invade, bringing with it osteoblasts and osteoclasts.

6) Osteoblasts trigger the transformation of perichondrium to the periosteum.

7) Osteoclasts breakdown the extracellular matrix to form medullary cavity.

8) Osteoblasts form a periosteal collar of compact bone around the diaphysis.

9) Chondrocytes continue to proliferate at epiphyses increasing bone length.

Question 5

Difference between intramembranous and endochondral ossification

Answer 5

PROCESS:
Intramembranous ossification = bone > mesenchymal connective tissue.

Endochondral ossification = bone > hyaline cartilage.

TYPES OF BONES:
Intramembranous ossification = flat bones.

Endochondral ossification = all other bones.

Question 6

What are the two ways that bones can grow?

Answer 6

1) Appositional – in thickness
2) Interstitial – in length

Question 7

What is appositional growth?

Answer 7

• can occur throuhgout lifetime
• osteoblasts deposit bone (secrete osteiod) of the outside and osteoclasts resorb bone (breakdown bone) on the inside

Question 8

What is interstitial growth?

Answer 8

1) Growth of cartilage on the epiphyseal side of the epiphyseal plate (end of the bone increases).

2) Replacement of cartilage with bone on the diaphyseal side of the epiphyseal plate by endochondral ossification. (cartilage replaced on the other side).

Question 9

What is the epiphyseal plate?

Answer 9

• Plate of hyaline cartilage found in children and adolescents.
• Located at metaphysis at each end of a lone bone.
• Site of lengthwise growth (interstitial growth)
• In adults, the plate becomes a line (completely ossified)

Question 10

What are the four layers of the epiphyseal plate?

Answer 10

1) ZONE of resting cartilage

2) ZONE of proliferating cartilage

3) ZONE of hypertrophic cartilage

4) ZONE of calcified cartilage

Question 11

What is the zone of resting cartilage?

Answer 11

Small, scattered chondrocytes.
Anchors epiphyseal plate to epiphysis of bone.
No growth.

Question 12

What is the zone of proliferating cartilage?

Answer 12

Slightly larger chondrocytes, stacked like coins.
Divide and secrete extracellular matrix.

Question 13

What is the zone of hypertrophic cartilage>

Answer 13

Large, maturing chondrocytes arranged in columns.

Question 14

What is the zone of the calcified cartilage?

Answer 14

Only a few cells thick.
Mostly dead chondrocytes surrounded by calcified extracellular matrix.
Osteoclasts dissolve calcified cartilage.
Osteoblasts secrete extracellular matrix, replacing cartilage via endochondral ossification.

Question 15

What are the two processes of bone remodelling?

Answer 15

= the ongoing replacement of old bone tissue with new bone tissue

1) bone resorption
2) bone deposition

Question 16

What is bone resorption?

Answer 16

= the removal of minerals and collagen fibers from bone by osteoclasts (break down of bone)

• osteoclasts release enzymes that breakdown bone extracellular matrix
• calcium and phosphorus are released from the matrix and into the blood

Question 17

What is bone deposition?

Answer 17

= the addition of minerals and collagen fibres to bone by osteoblast (building bone)

• occurs via osteoblasts

Deposition = formation and mineralisation

Question 18

What four factors affect bone growth and remodelling?

Answer 18

1) Minerals - calcium, phosphorus

2) Vitamins - A, C, D

3) Hormones - growth, thyroid, sex

4) Mechanical stress - Wolff’s Law

Question 19

Discuss minerals:

Answer 19

• Calcium and phosphorus needed for bone growth
• Also need magnesium, fluoride, and manganese

Question 20

Discuss vitamins:

Answer 20

A: inhibits load-induced osteoblast activity.

C: essential in the production of collagen.

D: essential for absorption of calcium.

Question 21

Discuss homrones:

Answer 21

Growth: stimulates bone growth and remodelling. Proliferates number of chondrocytes at epiphyseal plate.

Thyroid: influence chondrocytes, osteoblasts, and osteoclasts.

Sex hormones: growth (osteoblast activity), bone density (production of extracellular matrix), closure of epiphyseal plate. Contribute to bone remodelling in adult hood.

Parathyroid and calcitonin: regulate blood calcium concentration.

• Parathyroid = inhibits osteoblast activity, leaving calcium in the blood
• Calcitonin = reduces blood calcium levels by inhibiting the osteoclast activity.

Question 22

Discuss Wolff’s law:

Answer 22

-Bone will adapt to the loads under which it is placed (Wolff’s law)

• Increased load = increased bone remodelling
• Decreased load = decreased bone remodelling

Question 23

How do the bones adapt to tensions?

Answer 23

• Mechano receptors in the osteocytes of the trabeculae detect mechanical load and stimulate osetblast activity. They secrete osteoid to produce new bone trabeculae.
• They also produce secondary change in the osteons of the cortical bone to increase thickness/strength of the cortial bone.

Question 24

Stages of fracture repair

Answer 24

1) Reactive phase

2) Reparative phase

3) Bone remondelling phase

Question 25

STEPS OF INTRA

Answer 25

1. ossification center forms in mesenchyme
2. a soft matrix is depositied
3. matrix is mineralised/ calcified
4. spongy bone forms
5. the periosteum forms from mesenchyme
6. compact bone forms

Question 26

STEPS OF ENDO

Answer 26

1. osteoblasts differentiate
2. bony collar forms
3. cartilage hypertrophy and calcification forming the primary ossification center
4. cavity formation and model elongation
5. periosteal bud invades cavity
6. secondary ossification centers form

Question 27

Fracture Repair - step 1

Answer 27

1. Blood vessels tear which results in clotted blood or hematoma. The blood vessels are sealed by this clotting process and so bone cells die.

Question 28

Fracture Repair - step 2

Answer 28

2. Capillaries grow into the hematoma and phagocytic cells clear the dead cells. Fibroblasts and osteoblasts enter the region to repair tissue. Soft bone callus is formed which turns into a bony callus.

Question 29

Fracture Repair - step 3

Answer 29

Bony callus of spongy bone forms

Question 30

Fracture Repair - step 4

Answer 30

Bony callus remodeled via osteoclasts and osteoblasts.