Bone Physiology

Question 1

What’re the constituents of connective tissue?

What’s the importance of ECM?

Answer 1

Made of cells and extracellular matrix

ECM made of fibrous proteins and ground substance

Ground substance = proteoglycans, glycoproteins and water

ECM composition determines the tissues physical properties

Question 2

What are two features of bone and what substances form them?

Answer 2

Rigidity - mineralised ECM with hydroxyapatite

Resilience - type 1 collagen fibres

Question 3

What are the functions of bone?

Answer 3

Movement
Protection
Site of haematopoiesis
Mineral homeostasis
Support

Question 4

Where does the growth plate on a bone sit? How can you tell on imaging?

Answer 4

Between epiphysis and metaphysics

Children still have growth plates present so on imaging will see gaps in the ends of the bones (don’t confuse with a fracture)

Question 5

What’s the difference between woven and lamellar bone?

Answer 5

Woven bone = immature/primary bone; first bone formed at any sites, collagen fibres arranged randomly

Lamellar bone = mature bone, collagen fibres are remodelled into an orderly arrangement to provide strength

Woven bone is the first type of bone to occur at fracture healing sites

Question 6

Where do trabecular and cortical bone sit?

Answer 6

Trabecular provides the scaffolding in the centre of the bone
Cortical is the outside

Question 7

Outline the microstructure of cortical (compact) bone

Answer 7

Lamellae = bony plates made of collagen fibres in parallel
There’s inner circumferential and outer circumferential lamellae

Interstitial lamellae is the result of bone remodelling and formation of new Haversian systems

Haversian systems are found within concentric lamellae (encircled by)

Question 8

What are Haversian systems? (Osteons)

What do Haversian canals contain and how are they different to Volkmann’s canals?

Answer 8

Haversian systems are the functional unit of compact/cortical bone

Haversian canals contain blood vessels, lymphatic vessels and nerves

Volkmann’s canals run transversely, allowing communication between Haversian canals, the periosteum (outer bone layer) and the bone marrow cavity

Question 9

Outline the microscopic structure of Trabecular bone (cancellous/spongy)

Answer 9

3D network of beams and struts of lamellar bone oriented along lines of stress

Large areas of intercommunicating spaces (marrow spaces) for haematopoiesis

Question 10

What’s the blood supply along a bone? How does this relate to fractures?

Answer 10

Epiphyseal artery
Metaphyseal artery
Periosteal arteries
Nutrient artery

Bone fractures may cause bleeding and lead to compartment syndrome = pain as pressure rises from formation of haematoma around the bone

Question 11

What’s the differentiation of bone cells from mesenchymal stem cells?
What are periosteal cells?

Answer 11

Mesenchymal stem cells -> osteoprogenitor cells -> osteoblasts -> osteocyte

Periosteal cells are bone lining cells that are just resting osteoblasts - they have an important role in fracture healing

Question 12

What’s the role of osteocytes?

Answer 12

Mechanotransduction and matrix maintenance/calcium homeostasis

Question 13

Outline the structure of osteocytes

Answer 13

They’re mature bone cells that don’t undergo cell division

Occupy lacunae surrounded by bone matrix; dendritic processes of osteocytes pass through canaliculus to radiate from lacunae and anastomose with those from other lacunae

Gap junctions between dendritic processes allow transfer of ions and nutrients

Question 14

Outline the structure and role of osteoclasts

Answer 14

Haematopoitic origin

Large multinucleated cells with rugged border to resorb bone matrix by synthesising and secreting enzymes and acid

Involved in remodelling, growth and repair

Form Howship’s lacunae (resorption craters)

Question 15

What do osteoblasts secrete?

Answer 15

Osteoid - the unmineralised organic component of bone

Question 16

What’s the normal bone remodelling cycle?

Answer 16

Continual process throughout life in response to changing mechanical stress or micro fractures of bone

Relies on balance between bone resorption and formation by osteoclasts and osteoblasts

Formation (matrix synthesis) -> Quiescence (osteoclasts recruitment, differentiation and activation)-> Resorption (by osteoclasts) -> Reversal (osteoblast recruitment, differentiation and activation)

Question 17

How is bone remodelling regulated?

Answer 17

By signalling molecules: ratio of OPG:RANKL determines degree of resorption (cytokines, hormones and drugs can alter the balance)

Osteoblasts secrete RANKL which binds to RANK on osteoclasts to active them for bone resorption

Osteoblasts also secrete OPG which prevents binding of RANKL to RANK

Question 18

What drugs can affect RANKL and OPG activity - so alter bone remodelling?

Answer 18

Bisphosphonates reduce osteoclast activity to inhibit bone resorption and therefore increase bone mass in cortical and trabecular bone

Question 19

How does bone develop by intramembranous ossification? What bones does this happen in?

Answer 19

Mesenchymal -> bone (direct replacement by bone tissue, without a cartilage precursor)

Ossification centre (lots of osteoblasts + osteoid) -> secretion of osteoid to form newly calcified bone matrix -> formation of woven bone and periosteum (blood vessels invade, mesenchymal condenses to form periosteum) -> formation of bone collar and appearance of red marrow (plate of compact bone with marrow cavities + osteoblasts and fibrous periosteum)

Occurs in flat bones of skull, clavicle and mandible

Question 20

Outline bone development by endochondral ossification?

What type of bones does it typically occur in?

Answer 20

Mesenchymal -> Cartilage -> Bone
Miniature hyaline cartilage model is formed, which continues to grow providing a scaffold for bone development and is eventually resorted and replaced by bone

Primary ossification centre (osteoblasts secrete bone matrix onto calcified cartilage) -> secondary ossification centre (OPG invade cartilage and differentiate into osteoblasts, laying down bone on cartilage scaffold)

Occurs in weight bearing bones eg long bones, vertebrae, pelvis

Question 21

What’s the difference between primary and secondary ossification centres?

Answer 21

Primary ossification in diaphysis, develops in foetal life

Secondary ossification centres in epiphysis and develops after birth

Question 22

Outline the two types of bone growth?

Answer 22

Longitudinal growth: at the epiphyseal growth plate of weight bearing long bones: proliferation of cartilage cells followed by endochondral ossification

Apposition growth: growth in width, new bone formed under periosteum

Question 23

What are the different zones are the epiphyseal growth plate?
After bone growth what happens to the zones?

Answer 23

Resting/quiescent zone (EPIPHYSIS)
Growth/proliferation zone
Hypertrophic zone
Calcification zone
Ossification zone (DIAPHYSIS)

Eventually ossification zone takes over the rest zones and the epiphyseal growth plate closes

Question 24

What’s the clinical significance of the epiphyseal growth plate?

Answer 24

Relative weak point to shearing forces
Fractures involving growth plate (Salter-Harris fractures) = deformities in developing bone (shortened/angulation)
Disorders affecting bone mineralisation (Rickets) can affect size and shape of growth plate

Question 25

What is a fracture?

What are the different types of fracture?

Answer 25

= a breach in the integrity of part, or whole of a bone
Transverse fracture
Oblique fracture
Spiral fracture
Grossly comminuted fracture
Greenstick fracture
Crush fracture (in vertebrae)

Compound/open fracture = direct communication between broken bone and skin surface
Simple/closed fracture = clean break with intact overlying tissues

Question 26

What are the 6 stages of fracture healing?

Answer 26

Haematoma
Granulation tissue
Callus
Woven bone
Lamellar bone
Remodelling

Question 27

Outline the haematoma and granulation tissue stages of fracture healing

Answer 27

Haematoma: rupture of vessels in region of fracture form haematoma = necrosis of bone fragments = inflammatory reaction so phagocytes migrate to area to remove necrotic tissue

Granulation tissue forms: blood clot invaded by small capillaries and fibroblasts -> cytokines and growth factors induce cellular proliferation

Question 28

Outline callus and woven bone formation stages in fracture healing

Answer 28

Callus: forms from fibrous tissue + inflammatory cells + cartilage, forming a bridge between bone ends

Woven bone: OPG cells proliferate and differentiate into osteoblasts to form woven bone -> strengthens callus and rigidity -> no more movement means fracture site is clinically united

Question 29

Outline lamellar bone formation and remodelling stages of fracture healing

Answer 29

Lamellar bone gradually replaces woven bone (around reformed marrow cavity)

Remodelling: osteoclasts and osteoblasts remodel lamellar bone in response to stresses -> excessive callus is reabsorbed and medulla cavity reestablished

Question 30

What factors affect fracture healing? (Aid and delay it)

Answer 30

Aid healing: stability of the fracture, apposition of bone ends, adequate blood supply

Delay healing: excessive movement of bone ends, poor blood supply, infection, foreign bodies

Question 31

Define malunion, delayed union and non-union

Answer 31

Malunion = healing in unsatisfactory positions
Delayed union = takes longer than expected to unite
Non-union = leads to fibrous union or pseudoarthritis