Bone: Function, Structure and Development Flashcards
What are the functions of bone
- Resistance of compression and tension (locomotion)
- Calcium homeostasis
- Houses the bone marrow.
Which element of bone aids resistance of compression
The inorganic content (hydroxyapatite)
Which element of bone aids resistance of tension
The organic matrix (collagen)
What are the three types of bone cells
- Osteoblasts
- Osteoclasts
- Osteocytes
What are the two types of ossification of bone
- Intramembranous ossification
- Endochondral ossification
What are the three parts of long bones from the ends to the centre
Epiphysis, metaphysis and diaphysis.
Where is the growth plate of long bones situated
Between the epiphysis and the diaphysis.
What determines when the growth plate closes
Genetics - this is why people have different heights.
What are the two types of bone
- Cortical/compact bone
- Trabecular/ cancellous/ spongy bone.
What is there more of in the body, compact or cancellous bone
Compact bone.
Where is the compact/cortical bone in long bones
The diaphysis of the bone is mostly cortical bone. There is very little trabecular bone here.
Where is the cancellous bone in long bones
The epiphysis is mostly made up of cancellous bone.
What is the role of compact/cortical bone
It provides most of the structural support and resists bending stresses which is why it is thicker in the mid part of the bone.
What are osteons/haversian canals in cortical bone
These are bone cylinders with an axis parallel to the long axis of the long bone. They have a central cavity with blood vessels and a nerve.
What are Volkmann’s canals in cortical bone
These carry blood vessels from the periosteum to the .haversian system
What is the role of the haversian canals
To provide strength and nutrients to the bone.
What is the function of trabecular bone
Trabecular bone provides a large surface area for the metabolic function of bone. Most metabolic activities occur here.
How are the trabeculae in cancellous bone organised
Along lines of maximum mechanical stress. This allows the transmission of weight to the thicker cortical bone.
What can change the organisation of the trabeculae in cancellous bone
Alteration in the stress on the bone can change the organisation of trabeculae.
What is the main component of bone - organic or inorganic
Organic (osteoid)
What are the two elements of the osteoid (the organic part of the bone)
Type I collagen and non-collagenous proteins
What makes up the inorganic part of the bone
Calcium hydroxyapatite.
What is the osteoid
The unmineralised bone matrix.
What is the main component of osteoid
Type I collagen
What are the non-collagenous proteins that are also part of the osteoid
Osteocalcin, osteonectin and osteopontin
What are the two descriptions of bone matrix dependent on how the collagen fibres are laid down
Lamellar bone or woven bone.
How is collagen laid down in lamellar bone
Type I collagen fibres are laid down in parallel sheets called lamellae. This is a very organised structure and is very strong.
How is collagen laid down in woven bone
In woven bone, collagen is randomly arranged. Woven bone is the structure that tends to arise when bone is bring produced very rapidly such as in the foetus. It tends to be pathological if found in adults.
What is the role of osteoblasts
These are bone forming cells. They secrete osteoid.
What is the role of osteocytes
Osteocytes are mature osteoblasts which are laid down and become surrounded by bone matrix.
What is the role of osteoclasts
Osteoclasts function in resorption and degradation of existing bone.
What are osteoprogenitor cells
Osteoprogenitor cells are osteoblast precursors. Osteoblasts are derived from osteoprogenitor cells.
Which signalling pathway is required for the formation and proliferation of preosteoblast cells
The Wnt-frizzled-Lrp5-beta-catenin signalling pathway pathway
Which two transcription factors control osteoblast differentiation
Runx2 and osterix. if these are not present, no osteoblasts are formed.
What interaction between osteoclasts and osteoblasts regulates osteoclast differentiation and function
RANK ligand (on osteoblasts) and RANK (on osteoclasts) interactions.
What happens to osteoblasts after they secrete and deposit osteoid
Some become part of the bone matrix as osteocytes while some die by apoptosis or differentiate into bone lining cells.
What are the most common cells in the bone
Osteocytes
How do osteocytes connect to other osteocytes, osteoblasts and osteoclasts
By long cytoplasmic processes.
What is the function of osteocytes
They regulate bone remodelling
How do osteocytes regulate bone remodelling
They respond to local (biomechanical) or systemic (PTH) signals
What does signalling from RANKL do
RANKL is expressed on osteoblasts while RANK is expressed on osteoclasts. RANKL increases osteoclast formation.
What does signalling from sclerostin do
It inhibits osteoblast formation.
What is the production of sclerostin inhibited by
Sclerostin production is inhibited by PTH and mechanical loading.
What is PTH
Parathyroid hormone
What is the role of PTH
It causes rapid calcium release.
Which cells are osteoclasts derived from
Monocytes/macrophages.
What is the formation of osteoclasts regulated by
RANK-RANKL interactions and growth factors.
How do RANK and RANKL interactions increase osteoclast activity
RANK-RANKL interactions induce precursor cell fusion and this increases osteoclast activity.
What is the function of osteoprotegerin
Osteoprotegerin is a decoy receptor that binds RANKL and inhibits osteoclast formation. This means osteoprotegerin regulates RANK-RANKL interactions.
What is the name of the molecule which regulated RANK-RANKL interactions
Osteoprotegerin (OPG)
What two substances do osteoclasts produce
Acid and proteases
What does the acid released by osteoclasts do
Releases calcium from bone
What do proteases released by osteoclasts do
Breakdown organic matrix.
What is the main method of calcium regulation
The breakdown of bone by osteoclasts.
What are the two major routes by which bone is formed in utero
Intramembranous and endochondral ossification
What happens in intramembranous ossification
Osteoid is laid down within loose fibroconnective tissue of a fibrous membrane.
What happens in endochondral ossification
Osteoid is deposited on cartilage scaffolds.
Which bones are formed by intramembranous ossification
The skull, the maxilla, parts of the clavicle, parts of the mandible, subperiosteal bone growth, fracture repair
Which type of ossification forms the skull
Intramembranous ossification
Which type of ossification is seen in fracture repair
Intramembranous ossification or endochondral ossification
In intramembranous ossification what is bone trabeculae formed from
Mesenchyme
What happens in the process of intramembranous ossification
Mesenchymal stem cells proliferate. These differentiate into osteoblasts to form the ossification centre. Osteoid is produced and laid down as woven bone. The matrix is mineralised and the osteoblasts become embedded in the matrix as osteocytes. Blood vessels grow in and the bone is remodelled into lamellar trabecular bone.
By which method is most of the skeleton produced
Endochondral ossification
By which method are the growth plates produced
Endochondral ossification
What happens in endochondral ossification
Osteoid is deposited on preformed cartilage.
Where does endochondral ossification in long bones start
Endochondral ossification starts from the diaphysis and extends out towards the metaphyses. The ephiphyses remain as cartilage in the foetus.
What is formed by endochondral ossification
- Most of the skeleton
- Growth plates
- Fracture repair.
What is required in terms of the chondrocytes in order for endochondral ossification to occur
Programmed changes in the chondrocyte. The chondrocytes first proliferate and become hypertrophic. they then form type X collagen before dying.
What is the stages of the process of endochondral ossification
- The perichondrium transforms to the periosteum.
- There is formation of a bony collar
- Chondrocyte hypertrophy
- Matric calcification
- Osteoprogenitor and blood vessel in growth.
When does ossification of the epiphysis occur
After birth.
Where are the secondary ossification centres
The epiphyses
Where are the primary ossification centres
The diaphysis
What is the line of cartilage between the primary and secondary ossification centres known as
The epiphyseal/growth plate.
When does growth stop
When the growth plates close.
What determines the cessation of growth
Genetics
Which gland control growth of bones
The pituitary gland which produces growth hormones.
What is achondroplasia
Achondroplasia is a growth plate abnormality which causes short stature.
What causes achondroplasia
Achondroplasia is caused by a mutation in fibroblast growth factor receptor 3 - FGFR3. It causes decreased chondrocyte proliferation and hypertrophy so while bones like the skull are of normal size (since they are reliant on intramembranous ossification), bones dependent on growth plates are short.
Which is gigantism
Tall stature.
What is gigantism caused by
Excess growth hormone production before puberty.
What is acromegaly
This is increased growth hormone production after puberty (growth plates of long bones will have closed) and it results in large bones of the face (not dependent on growth plates).
What happens with remodelling in normal bone
The amount of new bone laid down is the same as the amount of bone that was removed.
When is bone remodelling normal
Bone remodelling happens all the time to repair micro-damaged bone and to reinforce bone in areas subject to increased stress to strengthen the bone depending on load.
How much of the skeleton is replaced each year
18%
What is quicker - removal of bone or formation of bone
Removal of bone is a lot quicker than formation of new bone.
What factors are involved in regulation of bone remodelling
- Mechanical load
- Systemic hormones - PTH, Vitamin D, endocrine hormones
- Local cytokines.
What is the first stage of bone remodelling
Activation.
What happens in activation
Osteoclasts are activated due to RANK-RANKL interactions between the osteoclast and osteoblasts/osteocytes.
What happens if the resorption stage of bone remodelling
Osteoclasts adhere to the bone via integrins. They form a ruffled border and secrete acid and proteases into the space between the bone and the ruffled border.
How do osteoclasts die
Apoptosis
What are osteoclasts replaced by
Mononuclear cells which lay down the cement line
What is the cement line laid down by the mononuclear cells which replace the osteoclasts
The cement line is the glue which allows new osteoid to be deposited.
What happens in the reversal stage of bone remodelling
Osteoblasts differentiate from bone marrow stromal cells.
What happens in the formation stage of bone remodelling
Osteoblasts lay down osteoid and the osteoid is mineralised. Osteoblasts become entrapped in the matric and become osteocytes.
What is the name of a molecule which inhibits bone formation
Sclerostin.
What Pi/PPi ratio promotes mineralisation
A high Pi/PPi ratio promotes mineralisation.
What Pi/PPi ratio inhibits mineralisation
A low Pi/PPi ratio inhibits mineralisation
What does osteopontin - the non-organic protein - do
Osteopontin inhibits mineralisation.
When is peak bone mass achieved
Peak bone mass is achieved in young adulthood - in a persons 20s-30s.
What is peak bone mass determined by
- Genetic factors
- Physical activity
- Muscle strength
- Diet - calcium intake
- Hormonal state
What are three bone remodelling disorders
- Osteoporosis
- Paget’s disease of the bone
- Osteopetrosis
What happens in osteoporosis
Resorption happens at a faster rate than formation so bone density decreases (resorption > formation)
What happens in Paget’s disease of the bone
Bone resorption and formation are both increased.
What happens in osteopetrosis
Resorption is decreased - there is too much formation.
What are three examples of metabolic bone diseases
- Vitamin D deficiency (rickets, osteomalacia)
- Hyperparathyroidism
- renal osteodystrophy
What are the three stages of Pagets Disease
- Lytic - bone is removed
- Mixed - there is bone absorption and formation
- Sclerotic - there is lots of active bone remodelling
What are the consequences of Pagets disease
Weak deformed bone and nerve compression. Bone is thickened but is still weak.
How could deafness result from Pagets disease
Due to nerve compression as a result of thickened bone.
What is the presentation of osteopetrosis (marble bone disease)
Hard dense bone.
What causes osteopetrosis
A decrease in the number or activity of osteoclasts.
What is a primary cause of hyperparathyroidism
Parathyroid adenoma
What are secondary causes of hyperparathyroidism
Chronic renal disease (leading to low calcium), low serum calcium and phosphate induce parathyroid hyperplasia.
What does hyperparathyroidism bring about in bones
Increased bone turnover due to increased osteoclastic activity and increased osteoblastic activity.
What are the sources of vitamin D
The skin, however this requires sunlight to be activated, as well as dietary intake.
What is the role of vitamin D
It helps the body to absorb calcium.
What are the 5 causes of vitamin D deficiency
- Lack of sunlight
- Dietary
- GI disease leading to malabsorption (such as is crohns disease)
- Liver disease
- Kidney disease.
What is the result of vitamin D deficiency in the blood
Decreased serum calcium levels as calcium cannot be absorbed as well.
What is the name given vitamin D deficiency
In children - rickets
In adults - osteomalacia.
What happens in osteomalacia
There is decreased mineralisation of the bone.
What happens in rickets
Children have soft bones that deform easily - bow legs (varus)
