Skeletal Physiology and Adaptation Flashcards
Functions of bones
Protection
Movement
Support
Metabolic
Mineral storage
Hearing
3 factors of the metabolic role of bone
Haematopoiesis, blood production
Homeostasis of Ca2+
Defence against acidosis
What is bone the main mineral reserve for
Calcium
Phosphorus
5 classifications of bones
Long
Flat (sternum, cranium)
Irregular (vertebrae)
Sessamoid (patella)
Short (talus, carpal etc)
5 features of long bones
Highly vascularised
Enclosed by fibrocartilagenous periosteum
Articular cartilage at joint surfaces
Red bone marrow (metaphysis)
Yellow bone marrow (diaphysis)
What does red bone marrow contain
RBCs
What does yellow bone marrow contain
Fat cells
Two types of bone material
Cortical - hard outside (80%)
Trabecular - marrow site (20%)
How does intramembranous ossification form
A fibrous plate then bone cells differentiation from fibroblasts and haemopoietic precursors
NO cartilaginous phase
Example of a bone type that undergoes intramembranous ossification
Flat bone
How does endochrondral ossification form
Bone cartilage forms at 13 months
Bone vessels invade the cartilage
Cartilage remains at the growth plates but bone forms elsewhere by osteogenic cells.
Growth plates fuse at the end of puberty.
Composition of bone
Water (20%) - heat to get dry weight
Mineral (hydroxyapatite) (50%) - burn to get ash weight
Organic (proteins e.g. collagen) (30%) - dry - ash
What is the bone mineral name and its role
Hydroxyapatite forms rigidity
Features of older bone
More mineralised
Further from the surface
What happens to bone when only mineral present when weight is dropped on it
Disintegrates completely
Collagen type 1 features
Triple helix protien
Combine to make fibrils
Fibrils combine to make fibers and then the gaps are filled with mineral bone.
If the bone is only organic what would happen if a weight is dropped on it
Would be extremely elastic as no mineral content to give it its rigidity.
Types of bone water
Pore water - in haversian canals
Bound water - works with collagen to give elasticity
What happens to water with age
Pore increases and bound water decreases
What machine is used for bone composition
Spectroscopy
What is the function of osteoclasts
Multinucleated cells formed by the fusion of mononuclear precursors - responsible bone degradation
What is the function of osteoblasts
Synthesis of new bones
What is the function of osteocytes
Osteoblasts who have become embedded within the bone - function as sensors of mechanical load.
Which cells does osteoblasts and osteocytes come from
Mesenchymal stem cells
Where do osteoclasts come from
haemopoietic stem cells
What is osteoid
Uncalcified bone matrix - formed by osteoblasts
How do osteoclasts degrade bone
Form an F-actin ring to secret acid and cathepsin K (enzyme) to break down bone.
How long does the bone remodelling cycle take
3 months
The 4 stages of bone remodelling cycle
Quiescence - bone linning cells (at rest)
Resorption - osteoclasts working to remove one
Reversal - synthesis of new bone matrix formation as osteoblasts are recruited
Formation - synthesis of new non-mineralised bone and is then mineralised overtime
When is bone formation more than resorption in humans
Younger
Opposite for older
Factors that influence bone mass
Genes
Exercise
Nutrition
Smoking
How does osteoporosis affect the bone
Decrease in bone mass
Normal mineral and organic content
How does osteoarthritis affect bone
Increase in bone mass
Decrease in mineral content
Increase in organic content
Drugs that inhibit bone resorption
Bisphosphonates
SERM
HRT
How do bisphosphonates work
Induce osteoclast death
How do SERM work
Acts as oestrogen in bone to reduce osteoclast activity
How does PTH stimulate bone formation
Activated Vit D
Increases Ca uptake in the gut
Increases bone formation
How are osteocytes mechanosensitive
Number of cycles
Strain magnitute
Load distribution
Dynamic stimulus is better for bone formation than static load
What is released by osteocytes with increased loading
Sclerostin (Decrease of connectivity with age)
How to optimise the bone formation
Increase dynamic strain magnitude
Increase number of strain cycles/rate
Have rest/refractory periods
Define Wolffs law
Bone is a dynamic tissue that will adapt to the loads placed on it.
Put wolffs law into exam answer
What does a DXA scan do
Measure bone density
What imaging technique to see trabeculae in vivo
HRpQCT
What imaging technique to see trabeculae ex-vivo
Microscopy
Why are larger bones less likely to break when bending
The further the bend is from the centre of the bone the greater the strength
Why do bones grow more anteriorly-posteriorly and not mediolaterally
Bones grow wider via periosteal formation - this is not symmetrical and there is usually more present anteriorly and posteriorly due to this is where the most forces are present - this keeps them strong but also light
As X4 amount of bone would be needed if it grew anteriorly-posteriorly AND mediolaterally.
What is disuse osteoporosis
Lack of loading leads to bone loss -
Bed rest
Space flight
Spinal cord injury
What is just as important as bone density to its strength
Bone shape
What are the two stages of osteoblast formation
EXTRA READING - DIRCKX and MAES
Stage 1 - matrix producing osteoblasts - secrete collagen type 1
Stage 2 - mineralizing osteoblasts - secrete osteocalcin (OCN)
3 fates of osteoblasts
EXTRA READING - DIRCKX and MAES
1 - Apoptosis
2 - matrix-embedded osteocytes
3 - bone lining cells
2 markers that form osteoprogenitor cells
EXTRA READING - DIRCKX and MAES
RUNx2
Osterix
How do stable fractures heal
EXTRA READING - DIRCKX and MAES
Intramembranous ossification - osteoprogenitor cells are recruited and differentiate into osteoblasts.
How do unstable fractures heal
EXTRA READING - DIRCKX and MAES
Endochondral ossification - haematoma releases cytokines which recruit progenitor cells.
What controls the formation of collagen and mineralisation
EXTRA READING - BRADLEY
ALK Phosphate
Osteocalcin
etc
Other than strength what is another role of hydroxyapitite
EXTRA READING - BRADLEY
Can hold on to toxins e.g lead before forming in bone
What is the chemical that affects osteocyte connection via its cytoskeleton
EXTRA READING - bonewald
Fimbrin - commonly found in high conc at the edges of osteocytes
What do osteoblasts do to activate osteoclasts
EXTRA READING - bonewald
RANKL expression when feel areas of microfractures –> recruits monocytes to form osteoclasts
Where are progenitor stem cells found
EXTRA READING
Periosteum inner layer
What enzyme do osteoclasts secrete
EXTRA READING
Collagenase and hydrochloric acid
What does hydrochloric acid form
EXTRA READING
Dissolves hydroxyapatite -
Calcium and phosphate
How do osteoclasts get controlled to prevent excess bone breakdown
Osteoprotegerin binds to RANKL to slow down osteoclasts
How does parathyroid hormone affect bone remodelling
PTH released when low Ca so causes bone resorption so decrease bone mass
When does bone shape change
Menopause and age to combat the effects of bone loss - to keep bone strength for as long as possible.
How does long term bisphosphonates affect bone strength
Decreases fibril and mineral strain therefore –> followings wolffs law –> decreases bone strength
How do corticosteroids affect bones
EXTRA READING - BRIOT AND ROUX
Impairement of bone formation as they significantly decrease P1NP and ostecalcin (markers for bone formation)
How do corticosteroids affect osteoblasts
EXTRA READING - BRIOT AND ROUX
Decrease growth hormone and IGF1 so decreases osteoblast function
How do corticosteroids affect osteoclasts
EXTRA READING - BRIOT AND ROUX
Increase RANK-ligand and decrease osteoprotegerin (inhibitor for osteoclasts) –> longer time for osteoclasts to be active so more bone degradation
How does glucocorticoids cause an increase in falls
EXTRA READING - BRIOT AND ROUX
Causes GC-induced myopathy which makes muscles weaker
Define osteoporosis
EXTRA READING
osteoclastic bone resorption not compensated by osteoblastic bone formation
3 causes of osteoporosis
EXTRA READING
Oestrogen, vitamin D defciency and hyperparathryoidism
How does gut biome and age increase the risk of osteoporosis
EXTRA READING
With age, disease anf fraility - the gut microbiome changes rapidly. This can cause a a distruption in short chain fatty acids which are used to regulate osteoclast differentiation causing a dysregulation in the abundance of osteoclasts
How does the menopause affect bone remodelling
EXTRA READING - MENG XIA JI
Menopause causes decrease in oestrogen which affects bone by -
1 - lowering bone sensitivty to PTH
2 - Increasing calcitonin thus inhibiting bone resorption
3 - accelerating calcium resorption from intestine
4 - reducing calcium excretion from kidney
5 - direct affects on bone as there is oestrogen receptors there
A loss of oestrogen means a loss of these protective functions
What endocrine conditions can cause oseoporosis
EXTRA READING - MENG XIA JI
Cushings
Menopause
Hyperparathyroidism
How does oestrogen directly affect bone
EXTRA READING - MENG XIA JI
Ostreogen receptors found on osteoclasts and their progenitor cells.
When ostrogen decreases this inhibition is lost.
