Bone structure, formation, growth and repair Flashcards
Give 5 roles of bone as a connective tissue
Structural support
Metabolic support
Cell adhesion
Medium of exchange
Defence, protection and repair
What are the two components of connective tissue? Give examples of each
Cells
Fibroblasts, Adipocytes and osteocytes
Extracellular matrix
Fibrous protiens - collagen/elastin
Ground substance - proteoglycans and glycoprotiens
What are the two main features of bone?
What gives these properties?
Rigidity - Mineralised ECM
Resilience - Type 1 collagen fibres
What are the main functions of bone?
Movement
Mineral Homeostasis
Support
Protection
Site of haematopoiesis
What is the Periosteum?
A non-calcified dense irregular connective tissue layer covering bone where tendons and ligaments insert.
Absent on surfaces covered by articular cartilage and around sesamoid bones (e.g. patella).
What does the periosteum consist of?
Consists of two layers: outer fibrous layer and inner cellular layer (contains osteoprogenitor cells and osteoblasts).
What is the role of the periosteum?
Helps bones grow in thickness (as it contains osteoprogenitor cells and osteoblasts)
Helps protect the bone
Assists in fracture repair
Helps nourish bone tissue
Is an attachment point for tendons and ligaments.
What is woven bone?
Immature/primary bone
First bone formed at any site. Occurs at sites of fracture healing
Collagen fibres arranged randomly.
What is Lamellar bone?
Mature bone
Collagen fibres remodelling into an orderly arrangment
Results in strong bone
What is cortical bone (compact) made up of?
Lamellae =
Bony plates made up of collagen fibres arranged in parallel
Outer circumferential lamellae
Haverian Systems (osteons)
Interstitial lamellae =
A result of bone remodelling and formation of new Havarsian systems
Inter-circumferntial lamellae
What is a Havarsain system (osteons)?
How does the Havarsian system work?
Concentric lamellae form around a Haversian Canal
Haversian Canals contain blood vessels, lymphatic vessels and nerves
Volkmans Canals run transversly or obliquely to the Haversian canals, allowing communication between Haversian canals, the periosteum, the marrow cavity and itself
What is Trabecular bone?
Cancellous/Spongey bone
A three dimensional network of beams and struts of lamellar bone - orientated along the lines of stress
Contain large areas of intercommunicating marrow spaces for haematopoesis
What are the 4 main arteries that supply the bone? State which part of the bone each artery supplies
Epiphyseal artery
Epiphysis region
Metaphyseal artery
Metaphysis region
Periosteal artery
Diaphysis region
Nutrient artery
Diaphysis region
Describe how bone cells are formed
Derived from mesenchymal stem cells
Differentiate into osteoproginator cells
Differentiate into osteoblasts
Osteoblasts line the bone and secrete organic bone matrix (osteoid) which is subsequently mineralised
Osteoid contains type 1 collagen, proteoglycans and glycoprotiens along with other protiens secreted by osteoblasts that aid in the mineralisation of the ECM
Differentiate into osteocytes
As osteoblasts are surrounded by matrix they become trapped and become osteocytes.
What are periosteal cells important in?
They are bone lining cells (resting osteoblasts)
Play an important role in fracture healing
What are osteocytes?
Mature bone cells that do not divide
They occupy the lacunae surrounded by bone matrix
Has roles in mechanotransduction and matrix maintenance
How do osteocytes carry out their role of mechanotransduction?
Dendritic processes of osteocytes pass through canaliculi which radiate from lacunae
The dendritic processes then anastomose with those from other lacunae allowing signals to be passed
How do osteocytes carry out their role of matrix homeostasis?
Gap junctions between dendritic processes of osteocytes allow transfer of ions and nutrients
What are osteoclasts?
Large multinucleated cells with a ruffled border (aids with bone reabsorption)
Derived from the monocyte-macrophage system
What role do osteoclast play?
Involved in bone remodelling, growth and repair
Main role is reabsorption of the bone matrix - sysnthesise and secrete enzymes and acid
Form Howship’s lacunae (reabsoption craters)
Nutrients is reabsorbed back into the blood
Describe the normal bone remodelling cycle
Continual process throughout life in response to mechanical stress or microfractures of the bone
Coupling of bone resorption and formation
Resorption
Osteoclast apoptosis and removal
Reversal
Osteoblast recruitment, differentiation and activation
Results in matrix synthesis
Formation
Mineralisation
Quiescence
Osteoclast recruitment, differentiation and activation
RETURNS TO RESORPTION
Describe how in normal cortical bone remodelling, new Haversian systems are replaced and remodelled
Osteoclasts form cone shaped tunnels into the compact bone (resorption cavities).
The tunnels then become invaded by blood vessels, osteoblasts and osteoprogenitor cells.
Osteoblasts lay down new bone in concentric lamellae around blood vessels forming new Haversian systems (closing cone).
How is normal bone remodelling regulated?
What can alter this system
Differentiation of osteoclasts is regulated by signalling molecules secreted by osteoblasts
RANKL
Binds to RANK on osteoclasts and causes activation
Osteoprotegerin (OPG)
Non-signalling decoy receptor of RANKL
Results in less osteoclast activation as less RANKL binding to RANK
This system can be altered by cytokines, hormones, and drugs. Balance of RANKL to OPG is important in determining the degree of resorption
Name the two processes that bone develops by
How do these processes differ?
Intramembronous ossification
Mesenchyme –> Bone
Endochondral ossification
Mesenchyme –> Cartilage –> Bone
Describe the process of intramembranous ossification.
Where would this process occur?
Direct replacement of mesenchyme by bone tissue without a cartilage precursor
Membrane of mesenchyme which differentiates directly into osteoprogenitor cells –> osteoblasts –> secrete osteoid which is then calcified.
This region is known as the primary ossification centre.
Blood vessels invade. A sponge-like trabeculae is established and vascular connective tissue is transformed into bone marrow.
Occurs in flat bones of the skull, clavicle and mandible
What are the two main steps in endochondrial ossification?
Where is this process likely to occur?
Miniature hyaline cartilage model is formed
Cartilage model continues to grow, providing scaffolding bone developement. It is eventually resorbed and replaced by bone
Occurs mainly in weight bearing bones eg. long bones, vertebrae, pelvis etc.
How is the primary ossification centre formed in endochondral ossification?
- Mesenchyme develops into chondroblasts which form a cartilage model
- Cartilage cells in the centre of the diaphysis hypertrophy, die and become calcified –> leaves large open spaces in cartilage (future 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 differentiate into osteoblasts
- Osteoblasts secrete bone matrix on surface of calcified cartilage
What are the differences in formation of the secondary ossification centres compared to the primary ossification centres in endochondral ossification?
Occurs in the Epiphyses
Similar process to primary ossification centre formation
Osteoprogenitor cells invade the cartilage and differentiate into osteoblasts which lay down bone on cartilige scaffold
Except at articular surface and epiphyseal plate
No bony collar
Compare the primary and secondary ossification centres
Primary :
Reside in diaphyses
Develop in foetal life
Secondary :
Reside in Epiphyses
Develop in after birth
What is longitudinal bone growth?
Occurs at the epiphyseal growth plate of weightbearing long bones
Is the proliferation of cartilage cells followed by endochondrial ossification
Replacement by bone occurs at the diaphyseal aspect
Eventually the ossification zone overtakes proliferation and rest zones causing the epiphyseal growth plate to close
What is appositional growth?
Growth in width of the bone
New bone is formed under the periosteum
Name the zones and zone functions on the epiphyseal growth plate
Resting zone (quiescent zone/zone of reserve cartilage)
Cartilage cells found
Proliferation zone (zone of proliferation) Cartilage cells proliferation under influence of insulin-like growth factor which is produced by hepatocytes in response to growth hormone. Chondrocytes are stacked in columns like coins.
Hypertrophic zone (zone of maturation and hypertrophy)
Chondrocytes mature and hypertrophy
Calcification zone
Hypertrophied chondrocytes die and cartilage matrix is calcified. Osteoclasts remove calcified matrix.
Ossification zone
Osteoprogenitor cells invade and differentiate into osteoblasts which lay down bone on cartilage scaffold
What is a fracture?
Give 3 examples of fractures
A breach in the integrety of part or whole of the bone
Transverse (straight across)
Crush (compression of bone)
Oblique (diagonally up)
What are the 6 stages of fracture healing?
- Haematoma
- Granulation tissue
- Callus
- Woven bone
- Lamellar bone
- Remodelling
Regarding fracture healing, describe what happens in the following stage:
Haematoma
- Rupture of vessels in region of fracture site causing haematoma to form
- Necrosis of bone fragments
- Initiates inflammatory reaction
- Phagocytes migrate to area to remove necrotic tissue
Regarding fracture healing, describe what happens in the following stage:
Granulation tissue
- Blood clot is invaded by small capillaries and fibroblasts from surrounding connective tissue
- Granulation tissue forms
- Cytokines and growth factors induce cellular proliferation
Regarding fracture healing, describe what happens in the following stage:
Callus
- Fibrous tissue, inflammatory cells and cartilage form a soft callus
- Forms a bridge between bone ends
Regarding fracture healing, describe what happens in the following stage:
Woven bone
Osteoprogenitor cells proliferate and differentiate into osteoblasts to form woven bone
Strengthens the callus and gives rigidity (bony callus)
When callus is hard enough that no movement takes place, the fracture site is clinically united
Regarding fracture healing, describe what happens in the following stage:
Lamellar bone
Gradually replaces woven bone
Regarding fracture healing, describe what happens in the following stage:
Remodelling
- Osteoclasts and osteoblasts remodel lamellar bone in response to stresses
- Excessive callus is reabsorbed and medullar cavity re-established
Give 3 factors that aid fracture healing
Stability of the fracture
Apposition of bone ends
Adequate blood supply
Factors that delay fracture healing
Excessive movement of bone ends
Poor blood supply
Infection
Foreign bodies
Define the following terms in regards to fracture healing:
- Malunion
- Delayed union
- Non-union
- Healing in unsatifactory positions
- Takes longer than expected to unite
- Can lead to fibrous union or pseudoarthritis
