Physiology of bone repair Flashcards
Describe the balance in healthy bone physiology
Balance between one resorption and bone formation
What does an imbalance in bone resorption lead to?
Osteoporosis
Osteopenia
Rickets
What does imbalance in bone formation lead to?
Osteopetrosis
Describe the classifications of bone structure
Long bone
Flat bone
Macroscopic - cortical bone, cancellous sponge
Microscopic - Lamellar (osteons) and woven (immature and disorganised)
Name the 3 types of cells in bone
Osteoclasts
Osteoblasts
Osteocytes
What is between the cells in bone?
Extracellular matrix
Where are osteoblasts found?
On surface bone
What do osteoblasts do?
produce protein component acellular matrix – regulate bone growth and degradation
Where are osteocytes found?
Embedded in bone matrix
What do osteocytes do?
Maintain bone.
What are osteoclasts responsible for?
Responsible for bone degradation and remodelling
What is meant by organic?
Cells and proteins
What is meant by inorganic?
Minerals, eg Ca2+ & PO4- (hydroxyapatite)
What is bone dominated by?
Extracellular matrix
What is the Harversian system in lamellar bone?
Osteons - structural unit which allows for cells of the bone to receive nutrients from central canal
Communication system between cells immobilised in bone matrix
HS runs Parallel to bone and along long axis of bone
Canaliculi allows communication
Haversian canal - allows main flow of nutrients
Where do osteocytes arise?
From osteoblasts from mesenchyme
From precursor cells in bone marrow stroma
Describe osteoblasts
Osteoblasts are post-mitotic
Most osteoblasts will undergo apoptosis
Number of osteoblasts decrease with age
What will happen to a small percentage of osteoblasts
A low % of osteoblasts will become osteocytes locked in lacuna
What is the function of osteoclasts?
Resorption
Describe the structure of osteoclasts
Multinucleate
40 micrometer in diameter.
15-20 closely packed oval-shaped nuclei.
Can proliferate
Give the function of osteoclasts
Phagocytose (bone matrix & crystals)
Secrete Acids - easier to manipulate the bone as acid causes re-solubilization of calcium
Secrete proteolytic enzymes from lysosomes
Where does bone resorption occur?
Ruffled border
What percentage of extracellular matrix is minerals
70%
Describe compressive and tensile strength of bone
High
List the acellular components of bone
collagen fibres – protein, flexible but strong
hydroxyapatite – mineral, provides rigidity
calcium/phosphate crystals > 50 %
What are Glycosaminoglycans?
long polysaccharides Highly negative Attract Water Repel each other Resists compression
Abundant in Cartilage
Where are growth factors found in bone?
In the ECM
What is the function of growth factors in bone?
They are revealed by osteoclast action
Which leads to proliferation & mineralisation
bone remodelling = bone turnover = the activation-resorption-formation sequence
How does bone form?
bone forms either as compact or cancellous and by either intramembranous or endochondral bone formation
What 2 factors remodel bone?
Recurrent mechanical stress
calcium homeostasis
Plasma calcium is essential in maintaining structural integrity of skeleton
Describe the effect of mechanical stress on bone
inhibits bone resorption promotes deposition
Surface osteoblasts & osteocyte network detect stresses
skeleton reflects forces acting on it
What happens to bone when there is not any mechanical stress?
Bone weakens
Give two examples of where there is no mechanical stress to bone
Bed rest
Lack of gravity
What are bisphosphonates used for?
For osteoporosis
Name a drug used for osteoporosis
Alendronate
Describe the function of bisphosphonates
inhibit osteoclast-mediated bone-resorption
related to inorganic pyrophosphate
the endogenous regulator of bone turnover
Accumulate on bone & ingested by osteoclasts
Interfere with osteoclasts metabolism
What other drugs are used for osteoporosis
Encourage osteoblast formation of bone
Teriparatide
portion of human parathyroid hormone (PTH)
Intermittent application activates osteoblasts more than osteoclasts
Prevent osteoclast maturation
Denosumab
Monoclonal Antibody that targets RANKL
What is bone composed of?
Living cells and acellular matrix
Describe the mechanism o osteopetrosis
Osteoclasts cannot remodel bone
Defective Vacuolar proton pump or
Defective Chloride channel
What does osteopetrosis lead to?
Excess bone growth
Bone growths at foramina press on nerves
Brittle (dense) bones
Blindness
Deafness
Severe anaemia
How long do fractures to bones in the upper body take to heal?
2-3 weeks
How long do fractures to bones in the lower body take to heal?
> 4 weeks
How does parathyroid hormone regulate calcium?
Parathyroid chief cells
Increases plasma Ca2+
How does vitamin D regulate calcium?
1,25-di-OH cholecalciferol (calcitriol)
Made in stages: Skin - Liver - Kidney
Increases plasma Ca2+
How does calcitonin regulate calcium?
Made by thyroid C cells
“tones down” blood calcium
Calcium goes into bone
Used as a treatment for osteoporosis
How does PTH stimulate resorption via osteoblasts?
When PTH is high, Binds on osteoblast cell which presents RANK ligand
Precursor on osteoclast binds and differentiates to fuse and form an activated osteoclast - leads to bone resorption
List some causes of low plasma concentration
Loss - Pregnancy, Lactation, Kidney dysfunction
Low Intake - Insufficient ingestion of Calcium, Rickets (low vit D)
Parathyroid dysfunction
How is vitamin D produced and activated?
Cholecalciferol (Vitamin D3) - 25OH cholecalciferol - 1,25 OH cholecalciferol (calcitriol) - calbindin in gut enterocytes - increase intestinal absorption of calcium and increase calcium resoption by kidney - increase plasma calcium
What does chronic hypocalcemia result in?
Skeletal deformities
Increased tendency toward bone fractures
Impaired growth
Short stature (adults less than 5 feet tall)
Dental deformities
What does acute hypocalcemia cause?
C - Convulsions
A – Arrhythmias
T – Tetany
List some signs of acute hypocalcemia
Chvostek’s sign
Trousseau’s sign
Name a syndrome where there is hypocalcemia?
DiGeorge syndrome
Describe how low calcium leads to excitability
Effect seems paradoxical
i.e. counter-intuitive
Hypocalcaemia makes membranes “more excitable” and “less stable”
Sodium is more able to leak through it
Explains latent tetany and its signs
Hypercalcaemia paradoxically reduces excitability
By making membranes more stable
List some signs and symptoms of hypercalcemia
Can be asymptomatic
Reduced excitability
- Esp. Constipation
- Depression + other psychiatric
Abnormal heart rhythms
Severe hypercalcemia
- Coma
- Cardiac arrest
How does hypercalcemia do to excitability?
Less excitability
Describe intramembranous ossification
Direct mineralisation of connective tissue (mesenchyme)
Cells divide and condense around capillary network
Starting point is called primary ossification center
Grows radially, finally fusing together replacing the connective tissue
Connective tissue that remains penetrated by blood cells and undifferentiated mesenchyme gives rise to bone marrow.
Examples include the skull, mandible and clavicle
Describe endochondral ossification
Cartilaginous template made from the mesenchyme
Template is replace by bone- osteogenesis
Different ossification centres emerge, a primary one in the diaphysis and secondary ones in the epiphysis
Initially a bone collar is produced and from here the primary centre develops
The epiphyseal plate (Growth Plate) exists between the diaphysis and the epiphysis
