Ossification And Bone Disease

Question 1

What is the process of endochondral ossification?

Answer 1

Initially whole bone is cartilage. As embryo, collar of periosteal bone appears in shaft (around the edge). As foetus, the central cartilage calcifies and becomes primary centre (in diaphysis). nutrient artery penetrates supplying osteogenic cells. primary ossification. Post natal, Medulla becomes cancellous bone, cartilage forms epiphysial growth plates. Epiphyses develop secondary centres of ossification. Prepubertal, Epiphyses ossify and grow plates move apart, lengthening bone. Mature adult, epiphyseal growth plates replaced by bone (mineralised to become bone). Hyaline cartilage only at articulating surfaces.

Question 2

What are the different zones that form from the growth plate in endochondal ossification?

Answer 2

Zone of reserve cartilage- no cellular proliferation or active matrix production.
Zone of proliferation- chondrocytes actively dividing it form columns, cells enlarge and secrete matrix.
Zone of hypertrophy- cells enlarge greatly. Matrix compressed into linear bands between cell columns.
Zone of calcified cartilage- enlarged cells begin to degenerate and matrix calcifies.
Zone of resorption- calcium matrix in direct contact with marrow cavity. Small blood vessels and connective tissue invade region occupied by dying chondrocytes leaving the calcified cartilage as spicules between them. Bone is laid down on the cartilage spicules.

Question 3

What is an osteoid?

Answer 3

Non calcified (mineralised) bone

Question 4

Why do osteoclasts have lots of nuclei?

Answer 4

They are phagocytic and were formed from merging of a few macrophages.

Question 5

In what way too bones grow by endochondral ossification?

Answer 5

Increase in lengths he to the epiphyseal growth plates. Grow in diameter by deposition of bone at periphery of shaft (intramembranous)

Question 6

What bones develop by endochondral ossification?

Answer 6

Long bones

Question 7

What happens to the cartilage in the growth plate prior to endochondral ossification?

Answer 7

Columns of cartilage extend from the growth plate

Question 8

What happens in intramembranous ossification?

Answer 8

Development starts in highly vascularised connective tissue. This focus of activity is primary centre. Mesenchymal cells differentiate into osteoblasts which are surrounded by collagen fibres and ground substance. The osteoblasts secrete uncalcified matrix (osteoid) which layer becomes calcified and forms rudimentary spicules. Osteoblasts become osteocytes (entombed in osteoid). Spicules joint to form trabeculae which merge to form woven bone. Finally replaced by lamellae of mature compact bone.

Question 9

What is formed initially in intramembranous ossification and what does this become?

Answer 9

Spongy bone which is then transformed to compact bone.

Question 10

How does the structure of bone constantly change?

Answer 10

By bone resorption and bone remodelling.

Question 11

What types of bones have intramembranous ossification?

Answer 11

Flat bones eg skull

Also thicken long bones

Question 12

What causes osteogenesis imperfecta?

Answer 12

Autosomal dominant group of disorders of connective tissue caused by mutation in gene for type 1 collagen. Therefore abnormal collagen synthesis by osteoblasts and fibroblasts.

Question 13

What is osteogenesis imperfecta characterised by?

Answer 13

Bone fragility (predisposes sufferer to fractures and deformity), abnormalities of eyes, ears, teeth, joints, skin, skeleton.

Question 14

What can multiple fractures due to osteogenesis imperfecta be confused with?

Answer 14

Deliberate injury

Question 15

what happens in osteoperosis?

Answer 15

Bone density is reduced due to osteoclast activity being higher than osteoblast activity, produces holes that can’t be filled by the osteoblasts so there are large gaps between the trabeculae.

Question 16

What does loss of mass of the trabeculae in osteoperosis mean?

Answer 16

Susceptible to fracture as bone no longer provides adequate mechanical support.

Question 17

What is type 1 osteoperosis, who does it affect and what happens?

Answer 17

Rapidly falling levels of oestrogen after the menopause therefore affects postmenopausal women. Oestrogen usually regulated osteoclast activity by increasing osteoblast activity to keep the ratio balanced. Less oestrogen means that the ratio of activity changes and so the osteoclasts activity increases compared to osteoblast. This means more bone is broken down than is made so there are more gaps between the trabeculae and so the bones become weaker.

Question 18

What is type 2 osteoperosis and who does it affect?

Answer 18

Reduction in osteoblast function, affects elderly of both sexes.

Question 19

What are risk factors for osteoperosis?

Answer 19

Age- older, bones start to become thinner and more porous
Gender- women mor likely post menopause
Poor diet- not enough calcium or vit d
Insufficient exercise- immobilisation leads to accelerated bone loss
Smoking

Question 20

What are some treatments for osteoperosis?

Answer 20

Hormone replacement therapy (for women)
Change in diet/ calcium and vit d supplements
Exercise
Stopping smoking

Question 21

What can cause osteomalacia?

Answer 21

Inadequate intake of calcium/vit d/phosphate or a combination.

Question 22

Why is vit d important in bone development?

Answer 22

Involved in absorption of calcium an phosphate by SI. In its absence poorly mineralised matrix known as osteoid is formed and prevents osteoblasts to osteoclasts. bones are unable to support the body weight so bend.

Question 23

Where is vit d hydrolysed?

Answer 23

First in the liver then again in the kidney, could be deficient if these aren’t working due to liver/kidney disease.

Question 24

When does osteomalacia occur?

Answer 24

During bone remodelling

Question 25

What does decrease in calcification of recently formed bones cause and result in?

Answer 25

Decreases calcium levels per unit of bone. Results in softening of bone due to weakened trabeculae.

Question 26

What happens to the trabeculae in osteomalacia?

Answer 26

Their surface is covered in a thicker than normal layer of osteoid, trabeculae are the same size but not fully mineralised.

Question 27

When does rickets occur?

Answer 27

When children whose bones are growing don’t get enough vit d so insufficient calcium depositation for adequate bone rigidity.

Question 28

What are some symptoms of osteomalacia?

Answer 28

Bone pain
Bach ache
Muscle weakness

Question 29

What happens in rickets?

Answer 29

Lots of osteoid as matrix is not properly calcified. The epiphyseal plates become distorted by body weight as bones aren’t strong enough. Bones grow slowly and become deformed and are prone to fractures.

Question 30

What is a rickety rosary?

Answer 30

In rickets where there is enlargement of costochondral junctions of ribs which bulge.

Question 31

What is achondroplasia and what causes it?

Answer 31

Autosomal dominant skeletal disorder caused by failure of proliferation and column formation of epiphyseal cartilage cells.

Question 32

What does achondroplasia affect and what does it cause?

Answer 32

Affects endochondral bone formation which impairs the longitudinal growth of the tubular bones.

Question 33

What is not affected by achondroplasia?

Answer 33

The skull, made by intramembranous ossification.

Question 34

What happens in achondroplasia?

Answer 34

Epiphyseal plates are thin and reduced in action. Few cells in the proliferating zone. There is decreased cellular hypertrophy. Hypertrophic cartilage cells form irregular columns. The zone of provisionally calcified cartilage is small and doesn’t provide adequate scaffolding for bone matrix deposition by osteoblasts.

Question 35

What happens if you are homozygous for the achondroplasia gene?

Answer 35

It would be fatal

Question 36

How can children be born with achondroplasia if neither of their parents have it?

Answer 36

Result of a new mutation

Question 37

How does levels of growth hormone affect bone development?

Answer 37

Pre puberty
Lack affects the epiphyseal cartilage causing pituitary dwarfism
Excess causes excessive growth of long bones causing gigantism.(promotion of epiphyseal plate activity)
Adult
Bones cannot increase in length as no growth plate cartilage.
Excess causes increase in width of bones by periosteal growth- acromegaly.

Question 38

How do sex hormones affect bone development?

Answer 38

Influence time of appearance and development of ossification centres.
Precocious sexual maturity (caused by sex hormone producing tumours) retard body growth due to premature closure of epiphyses.
Deficiencies cause growth plates to remain for longer leading to tall stature.

Question 39

How does thryoid hormone deficiency affect bone development?

Answer 39

Not enough T3/4 causes cretinism, stunted physical and mental development. In newborn can be readily reversed by prompt admin of thyroxine.

Question 40

What are the two types of ossification? What is the starting material for the two?

Answer 40

Endochondral (hyaline cartilage) and intramembranous (sheet of mesenchyme or loose connective tissue)