11. Bone Function And Repair Flashcards
What is the mechanical function of Bone?
- Protect important and delicate tissues and organs
- Provide a framework for the overall shape of the human body
- Form the basis of levers involved in movement
What is the synthetic function of bone?
• Haemopoiesis (holds and protects red bone marrow)
What is the metabolic function of bone
Mineral storage (calcium and phosphorus)
• Fat storage (yellow bone marrow)
• Acid-base homeostasis (absorbs or releases alkaline salts to help regulate blood pH
What are the two types of ossification
Endochondral ossification
Intra-membranous ossification
Summarise endochondral ossification
- the formation of long bones from a cartilage template
- continued lengthening is by ossification at epiphyseal plates, e.g. appositional growth (growth at edges)
Summarise Intra-membranous ossification
- the formation of bone from clusters of MSC in the centre of bone – trabecular bone e.g. interstitial growth (growth in the middle)
• The process also contributes to the thickening (not the lengthening) of long bones, at their periosteal surfaces (appositional growth).
• This produces immature bone that undergoes remodelling into mature bone
• The bones of the skull are formed by intramembranous ossification
Describe the 9 stages of Intra-membranous ossification ossification
- Mesenchymal stem cells (MSCs) form a tight cluster
- The MSCs transform into osteoprogenitor cells and then transform into osteoblasts
- Osteoblasts lay down a osteoid (extracellular matrix containing Type I collagen)
- The osteoid mineralises (crystals of calcium form in and around it) to form rudimentary bone tissue spicules [surrounded by osteoblasts and containing osteocytes]
- The spicules join to form trabeculae, which merge to form woven bone
- Trabeculae replaced by the lamellae of mature compact bone
- Internal spongy bone remains
- Vascular tissue within trabecular spaces forms red marrow
- Osteoblasts remain on bone surface to remodel when needed
What is the main difference between endochondral and intra-membranous ossification?
Intramembranous ossification takes place within condensations of mesenchymal tissue and not by replacement of a pre-existing hyaline cartilage template
The process also contributes to the thickening (not the lengthening) of long bones, at their periosteal surfaces (appositional growth).
How can you tell the difference between immature and mature bone?
• Immature bone has osteocytes in random
arrangements
• Mature bone has osteocytes arranged in concentric lamellae of osteons
In which bone is the Haversian and Volkmann’s canals which carry blood vessels, lymph vessels and nerves found?
Compact bone
Why does bone resist fracture?
it has great tensile and compressive strength, a degree of flexibility
Where are the main force lines of bone?
Main force lines are through the cortical bone
(small cancellous bone component) • Why?
• lamellae are thought to be able to slip, relative to each other to resist fracture - excessive load causes fracture
What happens to thicken bone?
The osteon is remodelled
What is a key determinant of bone strength?
Exercise - increased exercise leads to increased osteon. Inactivity increases bone resorption (1/3 of mass lost when immobile)
What are the factors affection bone stability
- Activity of osteocytes (osteoid recycling)
- Activity of osteoblasts (bone deposition)
- Activity of osteoclasts (bone resorption)
How does Activity of osteocytes (osteoid recycling) affect bone stability?
- Can act like osteoblasts and lay down ‘scavenged’ osteoid into their lacunae (increased by oestrogen/thyroid hormone)
- Can act like osteoclasts and degrade bone (a little) – known as osteocyctic ostoelysis (increased by PTH)
What stimulates Activity of osteoblasts (bone deposition)?
Stimulated by calcitonin, GH (via IGF-1), oestrogen and testosterone (also by PTH), thyroid hormones, vitamin A
What affect activity of osteoclasts?
- Increased by PTH – releases calcium ions into the blood
* Calcitonin blocks the action of PTH at the PTH receptor
What are the nutritions affecting bone stability?
Vitamin D3 (either absorbed from gut or synthesised in the skin) – produces calcitriol (calcium absorption)
Vitamin C – synthesis of collagen
Vitamins K and B12 – synthesis of bone proteins
Describe an overview of fracture repair
- A blood clot (haematoma) is formed in which granulation tissue arises
- The procallus of granulation tissue is replaced by a fibrocartilaginous callus in which bony trabeculae are developing
- Endochondral and intramembranous ossification give rise to a bony callus of spongy/ cancellous bone
- Cancellous bone is replaced by compact cortical bone until remodelling is complete
Describe what happens in stage 1 of fracture repair, haemotoma formation
> Blood vessels in bone and periosteum break.
A mass of clotted blood (haematoma) forms
Bone cells at the fracture edge die (no blood supply)
Swelling and inflammation occurs (granulocytes enter the site)
Phagocytic cells and osteoclasts begin to remove dead and damaged tissue
Macrophages will eventually remove the blood clot
Describe what happens in stage 2 of fracture repair,fibrocartilaginous callus formation
> New blood vessels infiltrate the fracture haematoma
A procallus (soft callus) of granulation tissue (i.e. tissue rich in capillaries and fibroblasts) develops
Fibroblasts produce collagen fibres that span the break. Others differentiate into chondroblasts that give rise to a sleeve of hyaline cartilage
[An externally bulging, fibrocartilaginous matrix thus splints the broken bone]
Simultaneously:
osteoblasts from the nearby periosteum and endosteum, (and multipotent cells from the bone marrow) invade the fracture site and begin bone Fibrocartilaginous callus
reconstruction by forming spongy/ trabecular bone
Describe what happens in stage 3 of the fracture repair, bony callus formation
> Within a week, new bone trabeculae begin to appear in the fibrocartilaginous (soft) callus.
The trabeculae develop as the former fibrocartilaginous callus is converted to a hard (bony) callus of cancellous bone
Endochondral ossification replaces all cartilage with cancellous bone
Intramembranous ossification produces new cancellous bone in any gaps
Bony callus formation continues for about two months until a very firm union across the fracture site is formed
Describe what happens in stage 4 of fracture repair, bone remodelling/
> Cancellous bone begins to be re-modelled into compact bone, especially in the prior cortical region (i.e. in the region of the former bone shaft walls)
This process continues for several months (or even
years)
The material bulging from the outside of the bone, and inwards, into the medullary cavity, is removed by osteoclasts
The final shape of the re-modelled area is the same as that of the original unbroken bone because it responds to the same set of mechanical stressors
Summarise Bone repair
Haematoma formation - Clot forms
Tissue death - No blood supply
Inflammation / cellular proliferation - Neutrophils and macrophages/osteoclasts
Formation of granulation tissue (fibrin mesh with ingrowth of capillaries) - New blood vessels develop in fibrin mesh
Fibrocartilagenous (soft callus) formation - Fibroblasts lays down collagen, chondroblasts lay down hyaline cartilage, cancellous bone starts
Consolidation (hard) callus formation - Endochondral and intra-membranous ossification Lays down compact and cancellous bone
Bone Remodelling - Cancellous bone converted to compact bone
What are the two steps in Bone remodelling?
- Osteoclasts make a wide tunnel in the
bone (cutting cone), resorbing the old cancellous bone. - Osteoblasts make a smaller tunnel of
cortical bone (closing cone)by laying down matrix to make trabecular bone
Which is larger, the cutting or closing cone?
The cutting cone is larger than the closing cone
Which diseases are a result of deletion of bone mass and thus have increases susceptibility to fracture?
Osteogenesis imperfecta
Rickets
Osteomalacia
Osteoporosis
What causes osteogenesis imperfecta?
- Mutation in COL1A gene
- Incorrect production of collagen 1 fibres
- Weak bones and increased fracture risk
What does osteogenesis imperfecta result in?
- Weakened bones (fractures are common)
- Short height andstature (depends on type)
- Presence of blue sclera
- Hearing loss
- Hypermobility (loose joints) and flat or arched feet
- Poor teeth development
Who are mainly effected by osteogenesis imperfecta?
Mainly affects neonates and children
What causes rickets?
- Vitamin D deficiency
- Poor calcium mobilisation
- Ineffective mineralisation of collagen in bones
- Weakened bone development
What does rickets result in?
- Soft bones
- Shortened height and stature
- Painful to walk
- Characteristic bowed legs
Who are mainly affected by rickets?
Children
What is osteomalacia and what causes it?
• ‘Rickets’ in the adult Rickets’ in the adult
• Vitamin D deficiency
• Lower mineralisation
• Increased osteoid - trabecular bone not as strong as it should be - shafts of long bones particularly susceptible to fracture
• Increased calcium resorption
Due to
• Kidney disease - activates Vit D
• Protection from sunlight - produces vit D
• Surgery – Stomach and intestine
• Drugs – phenytoin prevents vit D absorption
What are the two types of osteoporosis?
Primary and secondary
What cause primary type 2 osteoporosis?
- occurs in (older) men and women
- due to loss of osteoblast function (senile osteoporosis)
- loss of both oestrogen and androgen
What causes secondary osteoporosis?
• result of drug therapy (i.e., corticosteroids)
• processes affect bone remodelling
malnutrition, prolonged immobilisation weightlessness (i.e., with space travel)
• metabolic bone diseases (i.e., hyperparathyroidism, metastatic cancers)
What are the modifiable risk factors for osteoporosis?
- Insufficient calcium intake: recommended value for postmenopausal women is 700 mg/day
- Exercise: immobilisation of bone (prolonged bed rest or application of a cast) leads to accelerated bone loss. Physical activity is needed to maintain bone mass. The weightlessness experienced by astronauts can result in osteoporosis
- Cigarette smoking: in women smoking is correlated with increased incidence of osteoporosis
What could osteoporosis result in?
> Back pain, caused by a fractured or collapsed vertebra
Loss of height over time
A stooped posture
A bone that breaks much more easily than expected
What causes achondroplasia?
- Inherited mutation in the FGF3 receptor gene
- FGF promotes collagen formation from cartilage (endochondrial ossification affected; intra-membranous ossification unaffected)
What does achondroplasia result in?
- Results in short stature, but normal sized head and torso
* Long bones cannot lengthen properly
What causes primary type 1 osteoporosis?
- occurs in postmenopausal women
- due to an increase in osteoclast number
- loss of oestrogen after the menopause
