Fracture through the Ages Flashcards
Define bone strength.
The ability of bone to resist fracture
What factors contribute to bone strength?
Density
Structure
What method has been used for diagnosing osteoporosis and what are the limitations of this method?
DEXA scans
This gives a reading of bone mineral density (BMD) but it doesn’t tell you anything about the bone structure
Describe the effects of oestrogen on osteoclasts.
Oestrogen stimulates apoptosis in osteoclasts
What are the two main divisions of bone composition?
Cell (10% of volume)
Matrix (90%)
What are the two subsets of bone matrix and what falls undereach?
Organic – collagen, non-collagenous proteins, mucopolysaccharides
Inorganic – hydroxyapatite crystals (calcium and phosphorus)
What are the four types of bone cells?
- Osteoprogenitor cells
- Osteocytes - mature osteoblasts, act as mechanoreceptors
- Osteoblasts- lay down new bone
- Osteoclasts- break down bone, have a RUFFLED border
What is the role of osteoprogenitor cells?
These differentiate into the other types of bone cell
What is the role of osteocytes?
They are involved in bone homeostasis (they are found in the lacunae and have projections into the canaliculi)
How often does bone normally turnover?
120 days
Describe normal bone turnover.
- is continuous, 5% at any time
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)
How is bone turnover different in an elderly person?
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
What effect do bisphosphonates have on osteoblasts and osteoclasts?
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
What is a major problem with bisphosphonate use?
Atypical fractures
What causes these atypical fractures associated w bisphosphonate use?
Bisphosphonates also have an effect on osteoblasts
They reduce bone remodelling (which replaces old and damaged bone) but this can leas to a build up of micro-fractures which can then spontaneity break over time and use
(supressed activity can make the bone more brittle- the act thing bisphosphonates try to stop)
Give an example of a bisphosphonate drug. What is its half life?
alendronate
Around 10 years
What new drug has come onto the market that has a similar action to bisphosphonates but with a shorter half-life? What type of drug is it?
Denosumab (half-life = 6 months)
- a human monoclonal antibody
Describe the action of RANKL.
RANKL binds to RANK receptors on precursors to osteoclasts and promotes their maturation to osteoclasts
In a healthy person, what protein is responsible for regulating the bone remodelling process and how does it do this?
Osteoprotegrin
It prevents the binding to RANKL to the RANK receptor (this is what denusomab also does)
State Wolff’s Law.
Bone remodels according to the stresses applied to it
At what age is peak bone mass reached?
early 20s in females and late 20s in males.
State some other factors that contribute to bone mass
Genetics
Nutrition
Vitamin D
Exercise
What are the five stages of fracture healing?
- Haematoma
- Soft Callous
- Hard Callous
- Remodelling
Which type of collagen is deposited in the soft callous?
Type 2 collagen
What prevents mineralisation in the soft callous?
Proteoglycans
What happens in stage 3 of fracture healing?
hard callus formation
1. The soft callous is invaded by blood vessels
2. Chondroblasts break down the calcified callous
It is replaced by osteoid (type I collagen) produced by osteoblasts
3. Osteoid calcified to form woven bone
What happens in stage 4 of fracture healing?
remodelling
- Woven bone remodels to lamellar bone
- It is shaped relative to the load (Wolff’s law)
- Medullar canal reforms- central cavity of bone shafts where red bone marrow and/or yellow bone marrow is stored;
Name and describe four types of general fracture
- Spiral
- Oblique
- Comminuted (break or splinter of the bone into more than two fragments.)
- Transverse (compressive forces)
What type of fracture can occur in the bones of children due to their plasticity?
Greenstick fractures
One side of bone could break but the other side could bend but stay intact
What do oesteoclasts exhibit?
RANK
What do oesteoblasts exhibit?
RANKL
What is the mechanism of Denosumab?
inhibits osteoclast activation by binding to RANKL and blocking its interaction with RANK so osteoclasts cant be activated hence less bone resorption
What happens in stage 1 of fracture healing?
haematoma (or inflmmation)
- macrophages, leucocytes, IL1-6, BMPs
- granulation tissue forms
- progenitor cell invasion
What are BMPs (bone morphogenetic proteins)
BMPs are a group of growth factors also known as cytokines and as metabologens-(molecule) that can initiate, promote and maintain metabolism and homeostasis. .)
What happens in stage 2 of fracture healing?
soft callus forms
- chondrocytes and fibroblasts differentiate and from collagen (II) and fibrous tissue
- proteoglycan produced (prevent mineralisation)
- chondrocytes release calcium and enzymes to break gown proteoglycans (allows mineralisation)
How long doe each of the stages of fracture healing approximately take? How does this change in children?
haematoma- up to 1 week
soft callus- 1-4 weeks
hard callus- 1-4 months
remodelling- up to several years
-sped up in kids they heal faster than adults
In a DEXA scan, whats the difference between a T score and Z score? What the range of score you can get?
t score- based off score of white premenopausal woman
z score - age and gender matched
range is -4 to +1
osteoporosis is below than -2.5
(above -1 is normal)
