Bone Structure, Formation, Growth

Question 1

What are the constituents of connective tissue?

Answer 1

• Cells:
  
  • Fibroblasts
  • Adipocytes
  • Specialised cells
    
    • Osteocytes and osteoblasts= bone
    • Chondrocytes and chondroblasts= cartilage
  • Immune cells:
    
    • Macrophages
    • Mast cells
    • Plasma cells
• Extracellular matrix:
  
  • Fibrous proteins (collagen, elastin),
  • Ground substance (proteoglycans, glycoproteins, water)

Question 2

Which cells secrete ECM?

Answer 2

Fibroblasts

Question 3

What are the features of bone?

Answer 3

Rigidity (from mineralised component of ECM- hydroxyapatite)

Resilience (from type 1 collagen fibres)

Question 4

What is responsible for the rigidity of bone?

Answer 4

Hydroxyapatite: mineralised component of ECM

Question 5

What is responsible for the resilience of bone?

Answer 5

Type 1 collagen fibres

Question 6

What are the functions of bone?

Answer 6

• Movement
• Mineral homeostasis
• Structural support
• Protection
• Haematopoiesis

Question 7

What does the periosteum consist of?

Answer 7

Non-calcified, dense, irregular connective tissue:

• Outer fibrous layer
• Cellular layer (contains osteoprogenitor cells and osteoblasts- absent on surfaces covered by articular cartilage and around sesamoid bones)

Question 8

What is the function of the periosteum?

Answer 8

• Helps bone grow in thickness
• Protects bone
• Assists in fracture repair
• Helps to nourish bone tissue
• Attachment point for tendons and ligaments

Question 9

Where is the periosteum absent?

Answer 9

On surfaces covered by articular cartilage and around sesamoid bones

Question 10

What is woven bone?

Answer 10

• Collagen fibres randomly arranged.
• First bone formed at any site- occurs at sites of fracture healing.

Question 11

Describe the microscopic appearance of lamellar bone

Answer 11

Collagen fibres remodelling into orderly arrangement which increases the bone strength

Question 12

Name the two types of lamellar bone

Answer 12

• Cortical
• Trabecular

Question 13

What does cortical bone consist of?

Answer 13

Lamellae: bony plates made up of collagen fibres arranged in parallel:

• Outer circumferential lamellae
• Haversian systems (osteons, concentrically arranged lamellae, arranged in parallel to the long axis of the bone)
• Interstitial lamellae (result of bone remodelling and formation of new osteons)
• Inner circumferential lamellae

Question 14

Describe the arrangement of haversian systems (osteons)

Answer 14

Concentric lamellae surrounding central canal (Haversian canal)

Canal contains blood vessels, lymph and nerves

Volkmann’s canals run transversely or obliquely to allow communication between Haversian canals, periosteum, marrow cavity and each other.

Question 15

What is trabecular bone?

Answer 15

Three dimensional network of beams and struts of lamellar bone, orientated along lines of stress.

Contains large areas of intercommunicating spaces which serves as a space for bone marrow (haematopoiesis)

Question 16

Describe the blood supply of bones

Answer 16

• Epiphyseal artery supplies epiphysis
• Metaphyseal artery supplies metaphysis- also supports nutrient and epiphyseal arteries.
• Nutrient artery spans length of bone (may be more than 1)
• Periosteal arteries supply periosteum (branch off nutrient artery)

Question 17

What are the different types of bone cell?

Answer 17

Osteoprogenitor cells

Osteoblasts

Osteocytes

Osteoclasts

Question 18

What are osteoblasts and what is their role?

Answer 18

• Line bone surface
• Synthesise and secrete osteoid:
  
  • Bone matrix: type 1 collagen, proteoglycans, glycoproteins, alkaline phosphatase, osteocalcin, osteopontin
• As they secrete osteoid they become trapped and become osteocytes.
• Secrete RANKL which binds to RANK on osteoclasts to activate them.
  
  • Also secrete osteoprotegerin (OPG): non-signalling molecule which binds to excess RANKL preventing excess bone resorption

Question 19

What are osteocytes and what is their role?

Answer 19

• Mature bone cells
• Not capable of cell division
• Occupy lacunae surrounded by bone matrix
• Dendritic processes extend through canaliculi which radiate from lacunae and anastomose with those from other lacunae- gap junctions between dendritic processes of different osteocytes allow ion transfer and nourishment of deep bone cells.

Mechanotransduction: detection of stresses on bone triggers the action of surrounding bone cells to lay down new bone in response.

Matrix maintenance/calcium homeostasis

Question 20

What are osteoclasts? What is their function?

Answer 20

Multinucleated, large cells

Derived from monocyte-macrophage system

Have ruffled border which is in contact with bone, through which enzymes and acid are secreted onto bone surface to metabolise it (resorption)

Create Howship’s lacunae (resorption sites)

Have RANK receptors which activate osteoclast activity (activated by RANKL)

Question 21

Which two cells are needed for bone remodelling?

Answer 21

The balance between osteoclasts and osteoblasts is needed for bone resorption and remodelling.

Question 22

Describe the cycle of bone remodelling

Answer 22

Continual cycle throughout life in response to changing mechanical stress or microfractures of bone.

Coupling of bone resorption and formation.

Question 23

Describe the process of bone remodelling in cortical bone

Answer 23

Haversian systems are replaced and remodelled- osteoclasts form cone shaped tunnels called resorption cavities.

Resorption cavities become invaded by blood vessels, osteoblasts and progenitor cells.

Osteoblasts lay down new bone around the blood vessels forming new haversian systems (closing cone)

Question 24

What regulates bone remodelling?

Answer 24

Osteoblasts secrete RANKL which binds to RANK on osteoclasts, activating them thus resorption.

Osteoblasts also secrete osteoprotegerin which binds to excess RANKL, preventing it binding to RANK and therefore preventing excess resorption.

The OPG:RANKL ratio is important in controlling degree of resorption- can be altered by various drugs (e.g oesotrogen= increased OPG)

Question 25

What do the different bone cells stem from?

Answer 25

Osteoprogenitor cells → osteoblasts → osteocytes Monocyte-macrophage system → osteoclasts

Question 26

What are the two types of bone development?

Answer 26

Intramembranous ossification Endochondral ossification

Question 27

Describe Intra-membranous Ossification

Answer 27

Direct replacement of mesenchyme by bone tissue (no cartilage precursor) * Occurs in flat bones of the skull, clavicles, mandible * Stages: * Mesenchyme membrane differentiates directly into osteoprogenitor cells * Osteoprogenitor cells differentiate into osteoblasts * Osteoblasts secrete osteoid which becomes calcified * Blood vessels invade and sponge-like trabeculae form, blood vessels become bone marrow. * Mesenchyme on outside differentiates into fibrous periosteum and bone cells form cellular layer of periosteum. * Compact bone forms deep to the periosteum with trabecular bone in between.

Question 28

Describe Endochondral Ossification

Answer 28

Bone develops from cartilage model. Occurs mainly in weight bearing bones; 2 main stages: * Miniature hyaline cartilage is formed * Cartilage model grows to form scaffolding for bone development (eventually resorbed and replaced by bone) * Stages: * Mesenchyme forms chondroblasts which form cartilage model * Cartilage cells in the centre of the diaphysis hypertrophy and die, then become calcified which leaves large spaces in the cartilage (future bone marrow cavity) * Osteoblasts secrete matrix and form a subperiosteal bony collar * Vascularisation of the perichondrium transforms it into periosteum * Blood vessels invade cartilage model with osteoprogenitor cells * Osteoprogenitor cells become osteoblasts * Osteoblasts secrete bone matrix on surface of calcified cartilage. This is called the primary (or diaphyseal) ossification centre

Question 29

What are the primary and secondary ossification centres?

Answer 29

**Primary:** in diaphysis, develops in foetal life **Secondary:** in epiphysis, develops after birth. Endochondral ossification occurs in similar way as in primary ossification centre: * No bony collar * Osteoprogenitor cells invade, become osteoblasts and secrete bone matrix on cartilage except at articular surface and epiphyseal plate.

Question 30

What are the two types of bone growth?

Answer 30

Longitudinal growth Appositional growth

Question 31

Describe longitudinal growth

Answer 31

Occurs at the epiphyseal growth plate of weight bearing long bones: * Cartilage proliferation occurs at epiphyseal aspect * Replacement by bone occurs at the diaphyseal aspect * Eventually ossification zone overtakes proliferation and rest zones, epiphyseal growth plate closes (18-25 years of age)

Question 32

Describe the structure of the epiphyseal growth plate

Answer 32

* EPIPHYSEAL ASPECT * **Zone1:** Quiescent (resting) zone, cartilage cells * **Zone 2:** Growth (proliferation) zone, cartilage cells undergo mitosis * **Zone 3:** Hypertrophic, older cartilage cells enlarge * **Zone 4:** Calcification; matrix becomes calcified, cartilage cells die, matrix begins deteriorating * **Zone 5:** Ossification, formation of new bone (endochondral) * DIAPHYSEAL ASPECT

Question 33

Describe the phases of fracture healing

Answer 33

* **Phase 1:** Haematoma: ruptured vessels at # site, necrosis of bone fragments, inflammatory reaction initiated→ phagocytes migrate to area. * **Phase 2:** Granulation: Blood clot invaded by small capillaries and fibroblasts from surrounding connective tissue forms granulation tissue. * Cytokines and growth factors induce cellular proliferation. * **Phase 3:** Callus: Fibrous tissue, inflammatory cells and cartilage form a soft callus which forms a bridge between bone ends. * **Phase 4:** Woven bone: Osteoprogenitor cells proliferate and differentiate into osteblasts to form woven bone which strengthens the callus and gives it ridigity --\> bony callus. When callus is sufficiently firm and movement no longer takes place, the # site is clinically united. * **Phase 5:** Lamellar bone gradually replaces woven bone * **Phase 6:** Remodelling: osteoblasts and osteoclasts remodel lamellar bone in response to stress. Excess callus is reabsorbed and medullary cavity re-established.

Question 34

What factors aid fracture healing?

Answer 34

Stability of # Apposition of bone ends Adequate blood supply

Question 35

What factors delay/impair fracture healing?

Answer 35

Excessive movement of bone ends Poor blood supply Infection Foreign bodies