Flashcards in ToB 13 Ossification and Bone Disease Deck (116)
Name the 2 possible processes of bone growth:
1) Endochondral ossification
2) Intramembraneous ossification
What is endochondral ossification?
The formation of bone, using a pre-existing hyaline cartilage template.
The templates of most bones in the body are made from what material?
What happens to the epiphyseal growth plate of a long bone after cessation of growth?
The epiphyseal growth plate disappears
When does the epiphyseal growth plate disappear?
After cessation of growth, ~18yrs old
During endochondral ossification, where does compact bone first appear?
In the shaft of the diaphysis, forming a collar around the cartilage
During long bone development, at what age does compact bone first appear?
Around 6-8 week old embryo
What type of bone growth occurs during long bone development?
Where does the primary ossification center appear during long bone development?
In the center of the shaft/diaphysis
At which area do blood vessels first penetrate during long bone growth?
In the shaft/diaphysis of the bone, creating the primary ossification center
How is the primary ossification center formed during long bone development?
Blood vessels penetrate the center of the hyaline cartilage template, at the shaft/diaphysis. These supply bone-depositing osteogenic cells, creating the primary ossification center.
At what age does the primary ossification center first appear during lone bone growth?
Around 8-12 week old foetus
Why are secondary ossification centers required in long bone growth?
The primary ossification center cannot ossify past the epiphyseal growth plates, so secondary centers are required for ossification of the epiphysis.
Where do secondary ossification centers develop during long bone growth?
At the epiphysis
What is always between the primary and secondary ossification centers?
Epiphyseal growth plate
When do epiphyseal growth plates develop?
The number of secondary ossifications centers needed for long bone development is dependent on what?
The number of epiphyseal growth plates present
Why is hyaline cartilage still present in mature long bone, after endochondral ossification is complete?
It persists at the articular surfaces of long bones, to reduce friction and absorb shock
What are epiphyseal growth plates made of?
Calcified hyaline cartilage
By what process do long bones grow in length?
By what process do long bones grow in width?
Why do long bones increase in length at the epiphyseal growth plates?
Hyaline cartilage can grow at the epiphyseal growth plates, and can then be replaced by bone, extending the shaft
Why is the articular surface of a long bone sometimes referred to as a 'superficial growth plate'?
Because hyaline cartilage is present at the articular surface, however it does not grow or calcify, so cannot contribute to bone growth.
Why are there often columns of calcified cartilage in the metaphysis of a long bone?
During bone growth, the cartilage from the epiphyseal growth plate proliferates, matures and calcifies, which can then be used as a structural framework by osteoblasts for new bone.
What are the 5 processes hyaline cartilage goes through, from the epiphyseal growth plate to becoming a framework for new bone?
What supplies osteoprogenitor cells to the degraded cartilage framework during bone growth?
Blood vessels from the periosteum
What is the 'periosteum'?
A dense layer of vascular connective tissue enveloping the bones except at the articulating surfaces of the joints.
Why is it necessary for blood vessels to invade an area of calcified hyaline cartilage, in order for that area to be replaced by bone?
Blood vessels supply osteoprogenitor cells, which can differentiate into osteoblasts, which can lay down new bone matrix.
What name is given to the calcified framework left behind after cartilage degradation during endochondral ossification?
What happens within the zone of hypertrophy during endochondral ossification?
Hyaline chondrocytes grow/enlarge greatly, and form columns of cells.
In what zone of the epiphyseal growth plate are hyaline chondrocytes actively dividing and secreting matrix?
Zone of proliferation
What is the name of the zone, in which the calcified matrix (left after cartilage has degenerated) is in direct contact with the bone marrow cavity?
Zone of resorption
The thin vascular connective tissue lining the medullary cavity of a bone.
What is 'intramembraneous ossification'?
The formation of bone from condensations of mesenchymal tissue (not a pre-existing hyaline cartilage template)
Name 5 bones which develop via intramembraneous ossification:
1) Skull bones - Parietal, occipital, temporal, frontal
Which skull bones form via intramembraneous ossification?
Temporal, parietal, frontal, occipital, mandible, maxilla
How do condensations of mesenchymal tissue become bone during intramembraneous ossification?
The condensations of mesenchymal cells differentiate into osteoprogenitor cells. These differentiate into osteoblasts, which lay down new bone.
What must happen in osteoprogenitor cells for them to differentiate into osteoblasts?
They must develop lots of golgi and rER
What is the name given to the growth of bone such that the diameter of the bone increases?
What process contributes to the appositional growth of long bones?
How can you tell the difference between bone that has developed via intramembraneous vs endochondral ossification, via histology slides?
The bone created by both methods is identical, and indistinguishable.
What type of inheritance does Osteogenesis imperfecta follow?
Osteogenesis imperfecta is caused by a mutation in the gene for what?
Type I collagen
What does Osteogenesis imperfecta affect?
What is the initial presented complaint which may lead to a diagnosis of Osteogenesis imperfecta?
Multiple fractures due to thin, delicate bones
Why is Osteogenesis imperfecta of medicolegal importance?
There is possible confusion over whether the multiple fractures are caused by deliberate injury or not.
Where is Growth Hormone synthesised and stored?
Excessive Growth Hormone before puberty may cause...?
Insufficient Growth Hormone before puberty may cause...?
What is Gigantism usually caused by?
Excessive Growth Hormone before puberty
What is pituitary dwarfism usually caused by?
Insufficient Growth Hormone before puberty
Excessive Growth Hormone after puberty may cause...?
What is Acromegaly usually caused by?
Excessive Growth Hormone after puberty
What is the most common reason that someone may have excessive Growth Hormone being synthesised and released?
Benign tumour in the anterior pituitary
How does Growth Hormone affect bone development?
It promotes growth at the epiphyseal growth plates of long bones.
What are the 5 types of bone?
How do sex hormones affect bone growth?
They promote the pubertal growth spurt. If in excess, cause premature epiphyseal plate closure leading to short stature, or if deficient, epiphyseal plate will close later leading to a tall stature.
How can the presence of excess sex hormone cause short stature?
Will cause premature closure of the epiphyseal growth plate.
Neonatal hypothyroidism must be treated quickly to avoid cretinism and short stature. What must it be treated with?
If untreated, what does neonatal hypothyroidism cause?
Cretinism (neurological and intellectual damage)
Why are Osteoporosis sufferers more susceptible to fractures?
Their trabecular bone becomes thin and weak, due to increased bone resoption:formation
What is Osteoporosis?
A metabolic bone disease in which mineralised bone is decreased in mass, such that it no longer provides adequate mechanical support.
Why is Osteoporosis more common in the elderly?
Bones are constantly remodelled throughout life, broken down by osteoclasts, and laid down by osteoblasts. Gradually osteoblasts stop laying down as much bone as the osteoclasts break down, leading to thinner bones.
During which period of life does bone mass peak?
Generally by gender, age and ethnicity, who are most at risk of developing Osteoporosis?
Old, white females
What is the most common type of Osteoporosis?
Primary (as opposed to secondary which is caused by another disease)
What causes Type 1 primary osteoporosis?
Oestrogen withdrawal in postmenopausal women, causes an increase in osteoclast number.
What causes Type 2 primary osteoporosis?
Attenuated osteoblast function, which happens with age.
What group(s) of people are at risk of developing type 2 primary osteoporosis?
Elderly people (male/female)
What type of osteoporosis are all elderly people at risk of developing?
Type 2 primary osteoporosis
What type of osteoporosis are postmenopausal women at risk of developing?
Type 1 primary osteoporosis
What are the 5 main risk factors of osteoporosis?
1) Genetics - white/Asian are more at risk than black population
2) Insufficient calcium/vit D intake
3) Poor absorption of calcium/vit D
4) Low levels of exercise
5) Cigarette smoking (particularly in women)
Why is lack of exercise a risk factor of osteoporosis?
Immobilisation of bone leads to accelerated bone loss
Why do the elderly population have an increased risk of poor calcium absorption?
There is decreased renal activation of vitamin D with age
How does Achondroplasia affect the mental capacity and lifespan of a sufferer?
Doesn't affect mental capacity or lifespan.
Name one of the most common forms of short-limbed dwarfism:
What type of inheritance pattern does Achondroplasia follow?
Where does the mutation occur which gives rise to Achondroplasia?
Fibroblast Growth Factor Receptor-3 gene (FGFR3)
What condition is caused by a mutation in the FGFR3 gene? (Fibroblast Growth Factor Receptor-3)
Achondroplasia - short-limbed dwarfism
How does the Achondroplasia-causing mutation affect the FGFR3 gene in which it occurs?
It causes a gain of function
What 4 factors are affected by a gain of function of the FGFR3 gene? (Fibroblast Growth Factor Receptor-3)
1) Decreased endochondral ossification
2) Inhibited proliferation of chondrocytes in epiphyseal growth plate
3) Decreased cellular hypertrophy
4) Decreased cartilage matrix production
What type of bone formation is disrupted by the Achondroplasia-causing mutation?
How does the Achondroplasia-causing mutation affect endochondral ossification?
- Inhibits proliferation of chondrocytes in the epiphyseal growth plates
- Decreases cellular hypertrophy of chondrocytes
- Decreases cartilage matrix production
What type of bones does the Achondroplasia-mutation affect?
Long bones (as mutation affects endochondral ossification)
Why does the Achondroplasia-causing mutation only affect long bone formation?
The mutation in the FGFR3 gene disrupts endochondral ossification, which only occurs in long bones
What are the main symptoms of Achondroplasia?
- Short stature
- Short arms and legs in comparison to body height
- Disproportionately large head
- Wide forehead
Is Achondroplasia an inherited disorder?
Yes it can be inherited (autosomal dominant), but can also occur due to random mutation
If 2 parents with Achondroplasia have a child, what is the probability of their child not being affected?
1/4 chance (Autosomal dominant)
If 2 parents with Achondroplasia have a child, what is the probability that their child will also have Achondroplasia?
1/2 chance (Autosomal dominant, homozygous dominant is fatal)
What is the genotype of someone with Achondroplasia?
Heterozygote (1 normal gene, 1 mutated FGFR3 gene)
homozygote faulty is fatal
What is the incident rate of Achondroplasia (per live births)?
What are the mean adult heights of a man and woman with Achondroplasia? (in cm)
Man - 131cm
Woman - 125cm
A man presents with:
- height of 130cm
- short stature
- short limbs
- no family history of any genetic disorders
What is the most likely diagnosis?
How would the histology slide of an epiphyseal plate differ between someone with Achondroplasia, and someone without?
The epiphyseal plate would not be present in the person with Achondroplasia, the bones will be sealed off.
How do humans get vitamin D(3)?
Sunlight - Vit D3 is synthesised in skin when exposed to sunlight
Dietary - Some foods ie fish, milk, eggs contain vit D3
Which organs are necessary for vitamin D activation?
What is the active form of vitamin D?
What is the first reaction during activation of vitamin D3, and where does it occur?
Vit D ---> 25-Hydroxyvitamin D (25-(OH)D)
What is the 2nd reaction during activation of vitamin D3, and where does it occur?
25-Hydroxyvitamin D ----> 1,25-Dihydroxyvitamin D
What is the major circulating form of vitamin D?
25-Hydroxyvitamin D (25-(OH)-D)
What stimulates the activation of 25-Hydroxyvitamin D into 1,25-(OH)2-D?
Parathyroid glands sense low serum calcium levels, and increase secretion of PTH. PTH stimulates activity of 1-alpha hydroxylase in kidneys, which produces activated vitamin D.
What are both the names given to activated vitamin D?
How does Calcitriol affect the serum calcium concentration?
Increases calcium absorption in the small intestine
Causes calcium to be released from bone
Therefore serum calcium concentration is increased by presence of Calcitriol
What is Rickets?
Childhood disease in which the bones either do not harden, or become soft/weak due to vitamin D or calcium deficiency.
What are the possible causes for vitamin D deficiency?
Lack of sunshine
What disease(s) does vitamin D deficiency lead to?
Rickets in children,
Osteomalacia in adults
What is Osteomalacia?
Adult form of rickets, in which bones become soft/weak due to vitamin D or calcium deficiency.
What are the common symptoms of osteomalacia?
What are the common signs of rickets?
Long bones become soft and malformed
Bossing of skull bone
Enlargement of costochondral junctions of the ribs
How are the trabeculae of cancellous bone different between a healthy adult, and an adult with osteomalacia?
The adult with osteomalacia will have an abnormal amount of non-mineralised osteoid covering the trabeculae surface.
Why do bones begin to bend with rickets and osteomalacia?
Due to insufficient presence of calcium or vitamin D, the osteoid in bone cannot mineralise, so cannot harden.
What are the 4 most common fracture sites in an individual with osteomalacia?
1) Femoral neck
2) Pubic ramus
Name 2 bone diseases which follow autosomal dominant inheritance:
1) Osteogenesis imperfecta
Name 2 metabolic bone diseases:
What is the difference between osteoporosis and osteomalacia?
Osteoporosis is the weakening of bones due to the increased breakdown of mineralised bone, making them brittle.
Osteomalacia is the weakening of bones due to the inability to mineralise osteoid, causing them to bend.