Bone Ossification

Question 1

9 stages of intramembranous ossification

Answer 1

1.Mesenchymal stem cells differentiate into osteoblasts
2.osteoblasts aggregate to ossification centre
3.here osteoblasts produce and secrete osteoid
4.matrix becomes calcified and hardens and traps osteoblasts
5.osteoblasts become osteocytes
6.osteogenic cells differentiate into new osteoblasts at edge of newly formed bone
7.as osteoblasts secrete osteoid it surrounds blood vessels and forms trabecular bone and vessels eventually form red bone marrow
8.mesenchymal cells on outer of surface of newly formed bone form periosteum
9.mesenchymal cells on inner surface of periosteum differentiate into osteoblasts and secrete osteoid to form layers of compact bone

Question 2

Stage 1 of endochondral ossification -9 steps

Answer 2

1.mesenchymal cells differentiate into chondroblasts that secrete extracellular matrix
2.chondroblasts become encased in matrix and become chondrocytes
3.perichondrium forms around cartilage model
4.chondrocytes become hypertrophic and burst to release alkaline phosphotase and they stop releasing collagen and proteoglycans
5.chondrocyte cell death within calcifying matrix forms small cavities for osteoblasts to move into
6.presence of growth factors promotes vascularisation (blood vessels invade perichondrium)
7.osteoprogenitor cells within perichondrium become osteoblasts
8.perichondrium becomes periosteum when osteoblasts start producing osteoid
9.osteoblasts produce compact bone around diaphysis (bone collar)

Question 3

Difference between perichondrium and periosteum

Answer 3

-perichondrium - contains chondrocytes for cartilage formation, covers cartilage, provides cell nutrients for growth and repair

-periosteum - contains osteoblasts for bone formation, cover outer surface of bone to provide blood, nerves and cells for bone growth, healing and attachment of muscles

Question 4

What does formation of the bone collar do in endochondral ossification?

Answer 4

Prevents nutrients from diffusing into hyaline cartilage and leads to chondrocytes death at centre to bring in osteocytes to form medullary cavity

Question 5

4 stages of primary ossification in endochondral ossification

Answer 5

1.lack of diffusion of nutrients to hyaline cartilage precursor - chondrocytes die and cavities form
2.blood vessels penetrate cavities and connective tissue around them brings in osteoblasts and osteoclasts from periosteum
3.osteoblasts start producing bone in center which becomes primary ossification center
4.osteoclasts then break down bone in middle to form the medullary cavity

Question 6

Secondary ossification in endochondral ossification

Answer 6

1.blood supply moves to epiphysis
2.cartilage and chondrocytes continue to grow at ends of bones to form spongy bone - secondary oss centers formed

Question 7

5 zones of epiphyseal growth plate

Answer 7

1.zone of resting cartilage
2.zone of proliferation
3.zone of hypertrophy
4.zone of calcification
5.bone diaphysis

Question 9

Zone of resting cartilage in epiphyseal growth plate

Answer 9

-Resting chondrocytes
-layer of hyaline cartilage anchoring growth plate to epiphysis

Question 10

Zone of proliferation in epiphyseal growth plate

Answer 10

-contains chondrocytes undergoing rapid mitosis to produce new cartilage cells
-proliferation and increasing number of cells pushes rest of cartilage outwards and pushes diaphysis away from epiphysis

Question 11

Zone of hypertrophy (zone of maturation) in epiphyseal growth plate

Answer 11

-chondrocytes become increasingly hypertrophic
-as chondrocytes enter zone they secrete alkaline phosphotase and calcify

Question 12

Zone of hypertrophy (zone of degeneration) in epiphyseal growth plate

Answer 12

-chondrocytes degrade and die and leave empty lacunae
-lacunae infiltrated by osteoprogenitor cells

Question 13

Why do chondrocytes die in zone of hypertrophy?

Answer 13

Due to calcification as it restricts nutrient diffusion

Question 14

Zone of calcification in epiphyseal growth plate

Answer 14

-osteoblasts lay down new bony matrix in lacunae infiltrated by osteoprogenitor cells

Question 15

Bone of diaphysis in epiphyseal growth plate

Answer 15

Newly formed bone that adds to length of bone

Question 16

Difference between bone modelling and remodelling in arrangement of osteoblasts and osteoclasts

Answer 16

Modelling - arranged on different surfaces

Remodelling - arranged in the same surface

Question 17

Difference between bone modelling and remodelling - activity

Answer 17

Modelling - continuous

Remodelling - cyclical

Question 18

Difference between bone modelling and remodelling - direct coupling (action of osteblasts and clasts)

Answer 18

Modelling - no

Remodelling - yes

Question 19

Difference between bone modelling and remodelling - effect on bone mass

Answer 19

Modelling - fast

Remodelling - slow

Question 20

Wolff’s law

Answer 20

Bone in a healthy animal will adapt to the loads under which it is placed

Question 21

Bone remodelling cycle - when strain detected

Answer 21

1.osteoclasts recruited to the site
2.secrete acid which degrades matrix and as a result calcium is released
3.macrophages recruited to site to clean up site and initiate osteoblasts to start differentiating
4.osteoblasts line up along surface and secrete osteoid
5.osteoblasts also in communication with osteocytes below and once new bone deposited osteoblasts on top become new bone lining cells and return to starting point (resting phase - quinessence)

Question 22

Function of osteoid in bone remodelling

Answer 22

Calcifies and produces new bone on top of existing old bone

Question 23

Types of bone healing

Answer 23

-primary (direct) healing
- secondary (indirect) healing

Question 24

What does secondary healing involve?

Answer 24

-most common
-involves endochondral and intramembranous ossification

Question 25

Requirements for primary bone healing

Answer 25

-relies on immobilisation of fracture site to reduce strain between fragments -edges must touch exactly -usually requires internal flexion

Question 26

Two types of primary bone healing

Answer 26

-contact healing -gap healing

Question 27

Primary healing - contact healing

Answer 27

-at site of fracture, osteoclasts congregate and tunnel across the fracture site -osteoblasts move to site and deposit bone material - bony material laid down in lamellar along length of bone -blood vessels penetrate lamellae, creating Haversian system, blood vessels run through the middle

Question 28

Primary healing - gap healing

Answer 28

- if small gap (<150-300micrometers) -similar to contact healing but osteoblasts lay down new lamellar bone perpendicular to longitudinal axis of bone, which is weaker -needs remodelling and takes longer to heal

Question 29

5 stages of secondary bone healing

Answer 29

1.haematoma 2.inflammation 3.fibrovascular phase 4.bone formation 5.remodelling

Question 30

Secondary bone healing - haematoma

Answer 30

-bleeding -activation of coagulation cascade -clot formation -haemostasis

Question 31

Secondary bone healing - inflammation

Answer 31

-clot releases cytokines -recruitment of inflammatory cells (lymphocytes, macrophages, eosinophils and neutrophils) -fibroblasts and Mesenchymal stem cells migrate to fracture site and granulation tissue forms around fracture ends

Question 32

Secondary bone healing - fibrovascular phase

Answer 32

-angiogenesis and neovascularisation -TNF-a drives Mesenchymal stem cell differentiation into chondrocytes and osteoblasts -primary soft callus formed

Question 33

Secondary bone healing - bone formation

Answer 33

-intramembranous ossification - osteoblasts (stable environment) -endochondral ossification - chondrocytes (unstable environment) -endochondral ossification converts soft callus to hard callus

Question 34

Secondary bone healing - remodelling

Answer 34

-resorption of remaining cartilage -woven bone replaced with mature lamellar bone (aligns with strain)