Fracture through the Ages

Question 1

Define bone strength.

Answer 1

The ability of bone to resist fracture

Question 2

What factors contribute to bone strength?

Answer 2

Density

Structure

Question 3

What method has been used for diagnosing osteoporosis and what are the limitations of this method?

Answer 3

DEXA scans

This gives a reading of bone mineral density (BMD) but it doesn’t tell you anything about the bone structure

Question 4

Describe the effects of oestrogen on osteoclasts.

Answer 4

Oestrogen stimulates apoptosis in osteoclasts

Question 5

What are the two main divisions of bone composition?

Answer 5

Cell (10% of volume)

Matrix (90%)

Question 6

What are the two subsets of bone matrix and what falls undereach?

Answer 6

Organic – collagen, non-collagenous proteins, mucopolysaccharides

Inorganic – hydroxyapatite crystals (calcium and phosphorus)

Question 7

What are the four types of bone cells?

Answer 7

Osteoprogenitor cells
Osteocytes
Osteoblasts
Osteoclasts

Question 8

What is the role of osteoprogenitor cells?

Answer 8

These differentiate into the other types of bone cell

Question 9

What is the role of osteocytes?

Answer 9

They are involved in bone homeostasis

Stimulate the activity of osteoblasts and clasts depending on the bone load

Question 10

How often does bone normally turnover?

Answer 10

120 days

Question 11

Describe normal bone turnover.

Answer 11

The osteoclast will dissolve away the bone

Preosteoblasts will move in and differentiate into osteoblasts

Osteoblasts lay down matrix

Matrix gets ossifed by hydroxyapetite

In a healthy person, the osteoblasts will lay down more bone than the osteoclasts dissolved (so you don’t get any bone loss)

Question 12

How is bone turnover different in an elderly person?

Answer 12

There is less apoptosis of osteoclasts and the resorption pits are very big and don’t get filled in by osteoblasts so you get loss of bone

Question 13

How do bisphosphonates work?

Answer 13

Bisphosphonates are absorbed into the bone during remodelling.

When osteoclats dissolve the bone they release the bisphosphonates

This is absorbed by osteoclasts

They damage their cytoskeleton so that the osteoblasts lose their RUFFLED BORDER, and without this they can’t function

Question 14

What is a major problem with bisphosphonate use?

Answer 14

Atypical fatigue fractures

Question 15

What causes the major problem with bisphosphonates?

Answer 15

They reduce bone remodelling (which replaces old and damaged bone) so you get premature ageing of the bone

Furthermore, microcracks form in the bones due to day-to-day use and if these microcracks are not filled in by bone remodelling they will eventually join up and cause stress fractures

Question 16

What is the half-life of alendronate?

Answer 16

Around 10 years

Question 17

What new drug has come onto the market that has a similar action to bisphosphonates but with a shorter half-life?

Answer 17

Denusomab (half-life = 6 months)

An antibody to RANK-L

Question 18

Describe the action of RANKL.

Answer 18

RANKL binds to RANK receptors on macrophages and promotes their maturation to osteoclasts

Question 19

In a healthy person, what protein is responsible for regulating the bone remodelling process and how does it do this?

Answer 19

Osteoprotegrin

It prevents the binding to RANKL to the RANK receptor (this is what denusomab also does)

Question 20

State Wolff’s Law.

Answer 20

Bone remodels according to the stresses applied to it

Question 21

At what age is peak bone mass reached?

Answer 21

30-40 years

Question 22

State some other factors that contribute to bone mass

Answer 22

Genetics
Nutrition
Vitamin D
Exercise

Question 23

What are the five stages of fracture healing?

Answer 23

Haematoma  
Inflammation  
Soft Callous  
Hard Callous  
Remodelling

Question 24

Which type of collagen is deposited in the soft callous?

Answer 24

Type 2 collagen

Question 25

What prevents mineralisation in the soft callous?

Answer 25

Proteoglycans

Question 26

What happens in stage 3 of fracture healing?

Answer 26

The soft callous is invaded by blood vessels

Chondroblasts break down the calcified callous

It is replaced by osteoid (type I collagen) produced by osteoblasts

Osteoid calcifies to form woven bone

Question 27

What happens in stage 4 of fracture healing?

Answer 27

Woven bone remodels to lamellar bone

It is shaped relative to the load (Wolff’s law)

Medullar canal reforms

Question 28

Name four types of fracture and how they’re caused

Answer 28

Spiral - twisting
Oblique - direct compression
Butterfly fragment - bending
Transverse - pulling

Question 29

What type of fracture can occur in the bones of children due to their plasticity?

Answer 29

Greenstick fractures

One cortex could break but the other cortex could bend but stay intact

Question 30

What are osteocytes?

Answer 30

Osteoblasts that become stuck in the bone when it is being remodelled

Question 31

Where are osteocytes found?

Answer 31

In the lacuna of bone

These are connected by Canaliculi

Question 32

How do osteoclasts sense bone load?

Answer 32

Have projections into fluid filled canaliculi

Load is applied to the bone:

If the bone structure is too dense for the load then there will be low pressure in the fluid and the cytes signal for osteoclasts to thin the bone

If the bone strucutre is too weak for the load then the pressure in the liquid will be higher and the cytes will signal to blasts to strengthen the bone

Question 33

What are the results from a DEXA scan?

Answer 33

Compares your BMD to that of the average healthy adult

If more than 2.5 SD from mean - osteopeosis

Question 34

Why might denusomab be favoured over bisphosphonates?

Answer 34

Bisphosphonates last for over a decade in the bone

denusomab has a half life of 6 months