Ossification And Bone Disease

Question 0

Describe the process of endochondral ossification:

Answer 0

The fetal skeleton is made of hyaline cartilage.
Initially, a collar of periosteal bone forms around the shaft of the bone.
The central cartilage calcifies, and a nutrient artery penetrates, which supplies osteogenic cells. This forms the primary ossification centre.
The medulla becomes cancellous bone, and cartilage forms the epiphyseal growth plates. This occurs after birth. Secondary ossification centres appear in the epiphyses.
The epiphyses ossify, leaving hyaline cartilage on the articulating surfaces. The epiphyseal growth plates continue to move apart, lengthening bone.
After puberty, the epiphyseal growth plates are replaced by bone.

Question 1

What are the two methods of ossification?

Answer 1

Endochondral and intramembranous.

Question 2

What are the five zones found at an epiphyseal growth plate?

Answer 2

Zone of reserve cartilage
Zone of proliferation
Zone of hypertrophy
Zone of calcified cartilage
Zone of resorption

Question 3

Where is the epiphyseal growth plate is there no active matrix production or cell proliferation?

Answer 3

Zone of reserve cartilage

Question 4

What happens in the zone of proliferation?

Answer 4

Chondrocytes divide, form columns, enlarge and secrete matrix.

Question 5

What occurs in the zone of hypertrophy?

Answer 5

Cells enlarge, and matrix is compressed into linear bands between columns of cells.

Question 6

What happens in the zone of calcified cartilage?

Answer 6

Cells begin to degenerate, matrix calcifies.

Question 7

What occurs in the zone of resorption?

Answer 7

Blood vessels and connective tissue invade spaces left by chondrocytes, bone is laid down on spicules of calcified cartilage.

Question 8

What is the role of intramembranous ossification?

Answer 8

Increasing the girth of long bones.

Ossification of bones of the skull (parietal, occipital, temporal, frontal), clavicle, etc.

Question 9

How does intramembranous ossification occur?

Answer 9

Occurs within mesenchymal tissue - mesenchymal stem cells differentiate into osteoprogenitor cells, then into osteoblasts and osteocytes. Bone forms in spicules then connects to form trabeculae.

Question 10

What is the inheritance pattern for osteogenesis imperfecta?

Answer 10

Autosomal dominant

Question 11

What gene is affected in osteogenesis imperfecta?

Answer 11

The gene for type one collagen.

Question 12

What is the frequency of osteogenesis imperfecta in the population?

Answer 12

1 in 10,000

Question 13

What are the characteristics of osteogenesis imperfecta type 1?

Answer 13

Blue sclerae
Multiple fractures as child learns to sit and walk.
Condition improves with age.
Bones are thin, delicate and curved.
Progressive hearing loss - auditory ossicles fuse.

Question 14

What characterises osteogenesis imperfecta type two?

Answer 14

It is a lethal perinatal disease, as almost all bones are broken during labour due to contractions of the uterus, or during delivery.

Question 15

What characterises osteogenesis imperfecta type three?

Answer 15

It is progressive, many fractures, skeletal deformities and growth retardation.

Question 16

What characterises osteogenesis imperfecta type four?

Answer 16

Like type one, but normal sclerae. Patients are aggressively treated with rods in the medulla of bones and other orthopaedic devices to prevent dwarfing consequences of multiple fractures.

Question 17

Why is osteogenesis imperfecta of medicolegal importance?

Answer 17

Possible to confuse multiple fractures from deliberate injury with osteogenesis imperfecta.

Question 18

What is the consequence of excessive growth hormone before puberty?

Answer 18

Gigantism - promotion of epiphyseal growth plate activity.

Question 19

What is the consequence of insufficient growth hormone before puberty?

Answer 19

Pituitary dwarfism - affects epiphyseal cartilage.

Question 20

What is the consequence of excessive growth hormone in adults?

Answer 20

Acromegaly - promotes periosteal growth. Cannot promote gigantism as there are no longer any epiphyseal growth plates.

Question 21

What are the effects of sex hormones (androgens and oestrogens) on bone?

Answer 21

Sex hormones give rise to pubertal growth spurt.
Precocious sexual maturity can lead to premature fusion of epiphyses, short stature.
Sex hormone deficiency can mean epiphyseal growth plates persist for longer than they usually would - prolonged bone growth and tall stature.

Question 22

What are the consequences of hypothyroidism in a newborn, and how can this be rectified?

Answer 22

Can lead to cretinism - neurological and intellectual damage, and short stature, characteristic facial features.
Prompt administration of thyroxine.

Question 23

What is osteoporosis?

Answer 23

Decreased bone mass (more than 2.5 standard deviations below the bone mass of a 30yr old white woman, as measured by a dexa scan)
Due to enhanced osteoclast activity compared to osteoblast activity - incomplete filling of osteoclast absorption bays.

Question 24

What are three characteristic fractures in osteoporosis?

Answer 24

Colles fracture
Compression fracture of vertebrae
Fractured neck of femur.

Question 25

When does bone mass peak?

Answer 25

Age 25-35

Question 26

When does bone mass start to decline?

Answer 26

5th or 6th decade

Question 27

What are the two types of osteoporosis?

Answer 27

Type one - occurs in post menopausal women - osteoclast number increases in the absence of oestrogen
Type two - senile osteoporosis - occurs in both sexes after the age of 70, reflects attenuated osteoblast function.

Question 28

What are the risk factors for osteoporosis?

Answer 28

Genetics including ethnicity (black people have higher bone density)
Smoking
Reduced calcium intake
Reduced calcium absorption/vitamin D/sunlight.
Lack of exercise/bed rest/application of cast.

Question 29

What causes achondroplasia?

Answer 29

Autosomal dominant mutation causes increase in function of FGFR3 gene.
Leads to decreased endochondral ossification, inhibited proliferation of chondrocytes at epiphyseal growth plates, decreased cellular hypertrophy and decreased cartilage matrix production.

Question 30

What is the result of being homozygous for the allele of the FGFR3 gene that causes achondroplasia?

Answer 30

Child dies soon after birth.

Question 31

What is the physical appearance of someone with achondroplasia?

Answer 31

Short stature - enlarged vault of the skull, normal trunk length, short limbs. Small face, flat bridge of nose.

Question 32

What percentage of cases of achondroplasia arise from a random mutation, rather than being inherited?

Answer 32

80%

Question 33

What is the mean adult height of someone with achondroplasia?

Answer 33

131cm for males

125cm for females

Question 34

What is rickets?

Answer 34

Vitamin D deficiency, poor absorption of calcium, leads to decreased mineralisation of bone.
Bones become soft and malformed, bossing of skull, enlargement of chostochondral junctions of ribs.

Question 35

What is osteomalacia?

Answer 35

The counterpart of rickets in adults - leads to back ache, bone pain and muscle weakness.

Question 36

What causes osteomalacia?

Answer 36

Calcium deficiency or vitamin d deficiency.

Insufficient sunlight, malabsorption, insufficient dietary intake, liver or kidney disease.

Question 37

What is the appearance of trabeculae in cancellous bone in osteomalacia?

Answer 37

Large amount of osteoid (nonmineralised bone) covering the surface of trabeculae.

Question 38

What are the commonest fracture sites in osteomalacia?

Answer 38

Neck of femur
Spine
Pubic ramus
Ribs