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

Matrix

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 is the role of osteoprogenitor cells?

Answer 7

These differentiate into the other types of bone cell

Question 8

What is the role of osteocytes?

Answer 8

They are involved in bone homeostasis (they are found in the lacunae and have projections into the canaliculi)

Question 9

How often does bone normally turnover?

Answer 9

120 days

Question 10

Describe normal bone turnover.

Answer 10

The osteoclast will dissolve away the bone
Preosteoblasts will move in and differentiate into osteoblasts
In a healthy person, the osteoblasts will lay down more bone than the osteoclasts dissolved (so you don’t get any bone loss)

Question 11

How is bone turnover different in an elderly person?

Answer 11

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 12

What effect do bisphosphonates have on osteoblasts and osteoclasts?

Answer 12

Bisphosphonates encourage cell death in osteoclasts

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

Question 13

What is a major problem with bisphosphonate use?

Answer 13

Atypical fractures

Question 14

What causes atypical fractures from bisphosphonate use?

Answer 14

Bisphosphonates also have an effect on osteoblasts
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 15

What is the half-life of alendronate?

Answer 15

Around 10 years

Question 16

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

Answer 16

Denusomab (half-life = 6 months)- RANKL antibody

Question 17

Describe the action of RANKL.

Answer 17

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

Question 18

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

Answer 18

Osteoprotegrin

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

Question 19

State Wolff’s Law.

Answer 19

Bone remodels according to the stresses applied to it

Question 20

At what age is peak bone mass reached?

Answer 20

30-40 years- most bone is layed down in pre-pubescent years

Question 21

State some other factors that contribute to bone mass

Answer 21

Genetics
Nutrition
Vitamin D
Exercise

Question 22

What are the five stages of fracture healing?

Answer 22

Haematoma  
Inflammation  
Soft Callous  
Hard Callous  
Remodelling

Question 23

Which type of collagen is deposited in the soft callous?

Answer 23

Type 2 collagen

Question 24

What prevents mineralisation in the soft callous?

Answer 24

Proteoglycans

Question 25

What happens in stage 3 of fracture healing?

Answer 25

The soft callous (like cartilage) 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 26

What happens in stage 4 of fracture healing?

Answer 26

Woven bone remodels to lamellar bone
It is shaped relative to the load (Wolff’s law)
Medullar canal reforms

Question 27

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

Answer 27

Greenstick fractures

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