5 - Bone structure, growth and repair

Question 1

What do I need to know?

Answer 1

• features of bone, types, structure
• how primary and secondary osteons are formed
• how bones undergo remodelling
• how the epiphyseal plate increases the length of the bones
• how fractures heal

Question 2

What are the 4 essential features of bone?

Answer 2

It resists tension, pressure and torsion
Light (fresh bone feels heavy due to bone marrow)
Strong
Dynamic and can and does remodel consistently

Question 3

How does it differ from other CTs?

Answer 3

Differs due to hydroxyapatite in the ECM that resists pressure and torsion. It is a calcium phosphate mineral that is deposited ON collagen fibrils with a crystalline structure. It is a very dense mineral so when it covers the fibrils you can’t see them

Question 4

What are the three types of bone?

Answer 4

1. Fine cancellous
   In fetuses and young children where the collagen fibres are arranged in a half hazard fashion in all 3 directions (woven bone)
2. Coarse Cancellous
3. Compact

In adults the fibrils are layed down in layers (lamellar bone)

Question 5

Describe membrane bone?

Answer 5

Membrane bone where the bone has formed out of mesenchymal tissue (CT) and the cells take on osteogenic properties and the bone forms from NO precursor for example the flat bones of the skull

Question 6

How are most of the bones in the body preceded with the exception of membrane bones?

Answer 6

By cartilage - this is cartilage bone. Bones are not made of cartilage and the cartilage does not turn into bone, the bone replaces the cartilage

Question 7

How do the trabeculae in cancellous bone arrange themselves?

Answer 7

The trabeculae align themselves perpendicular to the compressive forces that arise at the compact bone at the epiphysis of the bones. The trabeculae then transmit the forces from the head of the bone to the shaft/diaphysis and distributes the forces from a wide platform in the joint onto the outside of the shaft
- they are aligned to the lines of compression in the bone

Question 8

Describe a histological section of a slice of vertebral bone

Answer 8

• the volume of actual cancellous bone is small relative to the volume of tissue as it is very strong and don’t need much. Increases as you go down column but not much
• On the surface of compact bone is a fibrous layer 1/2 a dozen cell layers thick that are spaced far apart due to collagen called the periosteum
• thinner fibrous layer with flattened cells is endosteum that lines inside of compact bone and lines
• in COMPACT bone the larger holes are blood vessels not osteocyte lacunae

Question 9

Mature bone cell? Primitive bone cells and where are they found?

Answer 9

Osteocytes. Osteoblasts - found mostly on the surfaces of bone in the osteogenic layers (peri/endosteum)

Question 10

How does bone grow?

Answer 10

By appositional growth at the periosteal and endosteal surfaces

• osteoblasts divide and the progeny closest to the bone secrete and surround themselves with new bone matrix (collagen and hydroxyapatite) adding it to the existing surface of bone
• the cells then become osteocytes
• those away from the bone surface remain the peri/endosteum and will divide again

Question 11

How are osteocytes linked?

Answer 11

By cell processes passing through canaliculi which join lacunae

Question 12

How do deeper osteocytes get their nutrients?

Answer 12

Capillary at endosteal/periosteal surface
They receive their nutrients by the cell processes as they can’t diffuse through the dense hydroxyapatite mineral
Means the deeper cells will be most deprived

Question 13

How far can nutrients pass before the last cell becomes deprived?

Answer 13

• 0.2mm. This means a trabeculum can be 0.4mm with a BV/endosteum on either side
• compact bone can be several mm meaning a blood supply must be enclosed WITHIN the bone
• bones are full of blood so when you fracture them you get a blood clot around the fractured surface

Question 14

How do blood vessels get inside compact bone?

Answer 14

Two ways

1. At the periosteal and endosteal(less) surface there are capillaries. As the bone grows by appositional growth the blood vessel doesn’t move and the bone grows around it (primary osteon)
2. The blood vessels invade the channels in bone bored out by osteoclasts (secondary osteon)

Question 15

Describe primary osteon formation

Answer 15

1. Surface of the bone/shaft is not smooth but has ridges and grooves
2. The periosteum over the ridges forms bone by appositional growth to make the ridges higher - then ridges then meet and fuse and the groove becomes a tunnel
3. The periosteum of the groove now becomes the endosteum of the tunnel
4. The endosteum is still active and the osteoblasts continue putting down bone matrix in a lamellar fashion until the tunnel closes just big enough for the blood vessel forming a Haversian System/Osteon

Question 16

How can you see lamellae in osteons?

Answer 16

Under polarised light (light in one direction)

Question 17

What is outer circumferential lamellae?

Answer 17

The outer and outer lamella of compact bone aren’t circular or in osteons because they are within 0.2mm of the BVs in the periosteum or endosteum

Question 18

How do osteons get a blood supply?

Answer 18

Via BVs in the periosteum. These infiltrate through holes in the bone, through perpendicular Volkmann’s Canals and parallel Haversian Canals to the osteon.

Question 19

How does bone remodel and repair?

Answer 19

By a combination of removing the bone from the inside (usually not always) and add it to the outside of the bone via appositional. Means the shape and proportions stay the same

Question 20

How is bone removed?

Answer 20

• By Osteoclasts - large multinucleated cells that eat/digest at bone all the time slowly
• The osteoclast sits in a Howships Lacunae which is a concave area that has had the bone removed
• the osteoclast takes out mineral, canniliculi, cell processes and osteocytes
• They release enzymes and acids with a low pH which you don’t want seeping out into tissues so you create a collar around the edge to attach to the bone that keeps these in a concentrated pool
• this keeps the secretions at high concentration and efficiency by increasing its absorption and secretion surface area by a ruffled border (foldings)

Question 21

What is the sequence of the degradation of bone?

Answer 21

1. Decalcification of the soluble hydroxyapatite by organic acids (carbonic, citric, lactic)
2. Digestion of extracellular materials (collagen) by acid hydrolases (enzymes) such as cathepsins that digest EXPOSED collagen fibrils

Question 22

How to osteoblasts contribute to bone removal?

Answer 22

They prepare the surface of bone for osteoclasts by digesting the OSTEOID they put down. There is co-operation as the osteoblast is usually on the surface so has to move

Question 23

What are the two main hormones involved in the hormonal control of bone removal?

Answer 23

PTH (parathyroid hormone)

Calcitonin

Question 24

Give an example of how mechanical forces influence bone removal and repair

Answer 24

Braces - move the root of the tooth by digesting and rebuilding bone slowly.

Question 25

What does parathyroid hormone do (PTH)?

Answer 25

Increases both osteoblast and osteoclast activity resulting in decreases bone mass

Question 26

What does Calcitonin do?

Answer 26

Only decreases osteoclast activity. Reduces membrane ruffling, number of osteoclasts, movement of osteoclasts

Question 27

What are the 3 things that PTH and calcitonin act on to control osteoclast activity?

Answer 27

1. RANK receptor on primitive osteoclasts 2. RANKL - RANK Ligand on osteoblasts 3. OPG (Osteoprotegerin) - this is a decoy molecule that fits over and caps the RANKL on osteoblasts. It is also released by osteoblasts so these control the whole process of remodelling RANK + RANKL leads to differentiation of primitive osteoclast to mature osteoclast

Question 28

Why is OPG clinically significant?

Answer 28

OPG prevents bone removal so is important with the ageing population as everyone starts to lose bone (osteoporosis)

Question 29

How can you decrease PTH and so decrease bone loss?

Answer 29

Ca supplements and vitamin D can increase Serum Calcium and this will decrease Parathyroid Hormone

Question 30

What pharmacotherapy will decrease osteoclast activity?

Answer 30

Biphosphonates Hormone Replacement Therapy (increases estrogen) Cathepsin K inhibitors (affects the enzyme production)

Question 31

What pharmacotherapy will decrease RANKL

Answer 31

Denosumab (binds/acts like OPG)

Question 32

What does sclerostin normally do?

Answer 32

Stops osteoblasts producing bone

Question 33

What pharmacotherapy will decrease sclerostin?

Answer 33

Anti-sclerostin antibodies | Exercise

Question 34

Where can osteoclasts remove bone?

Answer 34

On flat surfaces and they can remove bone inside compact bone by drilling holes and this allows bone to remodel

Question 35

Briefly describe secondary osteon formation

Answer 35

- osteoclasts dig down from the surface and a blood vessel follows into the cavity - periosteal cells (osteoblasts) also follow the invading BV and osteoclasts and become the endosteum - in a cross section of a secondary osteon you will normally see 2 blood vessels as it loops into the cavity and only 1 in a primary osteon

Question 36

What type of osteon is most adult bone composed of?

Answer 36

Secondary osteons as the original primary osteons have been replaced. Bone is replaced at 2% per year

Question 37

Where does growth in length occur in long bones?

Answer 37

Near the ends of the bones at the cartilaginous plates called the epiphyseal plates which stains blue - during puberty the appositional growth like at width ins't fast enough

Question 38

How does growth at the length of long bones occur?

Answer 38

The cells in the cartilaginous plates divide and one slips under the other forming columns. This means the cartilage plate grows upwards (and at other end of the bone) and you grow in height

Question 39

Why doesn't the epiphyseal plate thicken as you grow?

Answer 39

- At the other side of the plate towards the bone, the cartilage cells die after hypertrophy - The matrix around these cells breaks down and allows small blood vessels to invade from the bone into the dead cartilage - the BVs bring with them osteoblasts which start to lay down bone over the fragments of collagen left behind

Question 40

When and why do you get closure of the epiphyseal plates?

Answer 40

Until 18 the rate of growth of epiphyseal plate EQUALS the loss of cartilage Later the rate of growth slows and rate of loss stays the same so plates get thinner until it disappears and you get closure Leaves an epiphyseal line that is prone to fracture in youth until it remodels and strengthens

Question 41

What are the zones of the epiphyseal plate?

Answer 41

``` Resting Proliferation Maturation Hypertrophy Calcification New Bone ```

Question 42

Where do the cells come from for healing of bone fractures?

Answer 42

Peri/endosteum are a source of new bone cells/osteogenic cells for healing

Question 43

How do fractures heal?

Answer 43

1. the peri/endosteum will proliferate and act as a source of new bone cells for healing which migrate to the fracture site 2. often bleeding/haematoma which forms a blood clot that is soft so we need support/casts 3. at the osteoblasts move FASTER than the blood vessels they initially produce CARTILAGE this is because a osteoblast in low oxygen will act as a chondrocyte 4. later when the BV infiltrates and oxygen increases new bone is laid down, replacing the cartilage, in a COLLAR around the fracture site called a BONE CALLUS 5. this lumpiness around the fracture site will be remodelled as osteoclasts dig out channels and form secondary osteons to knit the bone ends together 6. Post fracture sites are actually very strong

Question 44

When is assisted healing/external support needed in the healing of bone fractures?

Answer 44

- metal plates and screws can help with the ALIGNMENT of the broken bone and prevents CALLUS formation as the metal rod will take its place for extra support during healing

Question 45

What is a downside to assisted healing of bone fractures?

Answer 45

The fractures are weaker when the plates and screws are removed and take longer to heal

Question 46

What is a callus?

Answer 46

A callus is bony and cartilaginous material forming a connecting bridge across a bone during fracture