Session 7

Question 0

Describe the development of long bones by endochrondral ossification

Answer 0

• Embryo 5-6 weeks: Cartilage models develops
• Embryo 6-8 weeks: Collar of periosteal bone forms around the diaphysis (shaft) (intramembranous ossification)
• Fetus 8-12 weeks: Central cartilage calcifies; nutrient artery penetrates which supplies bone-depositing osteogenic cells; primary ossification centre forms
• Postnatal: Medulla becomes cancellous bone; cartilage forms the epiphyseal growth plates; secondary centres of ossification develop in the epiphyses
• Prepubertal: Epiphyses ossify and growth plates continue to move apart which lengthens the bone
• Mature adult: Epiphyseal growth plates replaced by bone; hyaline cartilage persists at edge of epiphyses

Question 1

What is endochondral ossification?

Answer 1

• Replacement of a pre-existing hyaline cartilage template by bone
• Most bones of the body develop in the this way

Question 2

What are the zones of the epiphyseal growth plate?

Answer 2

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

Question 3

What is the zone of reserve cartilage?

Answer 3

• No cellular proliferation or active matrix production

Question 4

What is the zone of proliferation?

Answer 4

• Cartilage cells divide and organise into distinct columns

- Cells enlarge and secrete matrix (collagen-mainly type II and XI, and other cartilage matrix proteins)

Question 5

What is the zone of hypertrophy?

Answer 5

• Cells enlarge greatly

- Matrix is compressed into linear bands between cell columns

Question 6

What is the zone of calcified cartilage?

Answer 6

• Enlarged cells begins to degenerate

- Matrix calcifies (initial scaffold for new bone)

Question 7

What is the zone of resorption?

Answer 7

• Calcified cartilage is in direct contact with the connective tissue of the
  marrow cavity
• Small blood vessels and connective tissue invade the region previously occupied by dying chondrocytes
• This leaves the calcified cartilage as spicules, onto which bone is laid down

Question 8

What is intramembranous ossification?

Answer 8

• Condensations of mesenchymal tissue, not the replacement of a pre-existing hyaline cartilage template

Question 9

What bones develop by intramembranous ossification?

Answer 9

• Flat bones:
  ~ Skull bones (eg parietal, occipital, temporal, frontal)
  ~ Maxilla
  ~ Mandible
  ~ Pelvis
  ~ Clavicle
• Also contributes to thickening if long bones

Question 10

How does intramembranous ossification occur?

Answer 10

• Mineral deposits within trabeculae radiate from a central point (primary ossification centre)

Question 11

What is osteogenesis imperfecta?

Answer 11

• Autosomal dominant group of heritable disorders of connective tissue
• Caused by mutations in the gene for type I collagen - abnormal collagen synthesis by osteoblasts and fibroblasts
• Affects the skeleton, joints, ears, ligaments, teeth, sclerae and skin
• Leads to ‘brittle bones’ - bone fragility which causes predisposition to fractures and deformity
• Multiple fractures are usually present at/before birth and are often fatal

Question 12

Where is growth hormone synthesised and stored?

Answer 12

• Anterior pituitary gland

Question 13

What are the effects of growth hormone on bones before puberty?

Answer 13

• Excessive: Gigantism (promotion of epiphyseal growth plate)
• Insufficient: Pituitary dwarfism (affects epiphyseal cartilage)

Question 14

What are the effects of growth hormone on bone as an adult?

Answer 14

• Excessive: cannot cause gigantism as there are no longer epiphyseal growth plates
• Insufficient: Acromegaly (promotion of periosteal growth by increase in bone width)

Question 15

What is the effect of sex hormones on bone?

Answer 15

• Influence the development of ossification centres
• Induce secondary sexual characteristics and pubertal growth spurt
• Bone growth is retarded because of premature closure (fusion) of epiphyses as a result of precocious sexual maturity (can be caused by tumours producing sex hormone)
• Prolonged bone growth and tall stature can result if epiphyseal growth plates persist later into life that normal because of sex hormone deficiency

Question 16

What is the effect of thyroid hormone on bone?

Answer 16

• Thyroid hormone deficiency can lead to an infant with cretinism (permanent neurological/intellectual damage) and other abnormalities eg short stature
• Effects of neonatal hypothyroidism can be reversed with prompt administration of thyroxine

Question 17

What is osteoporosis?

Answer 17

• Metabolic bone disease where bone mass decreases so that it cannot provide adequate mechanical support
• Incomplete filling of osteoclasts resorption bays
• Osteoclasts activity is more than osteoblast activity

Question 18

What is the most common type of osteoporosis?

Answer 18

• Primary osteoporosis
  ~ Type 1: occurs in postmenopausal women; caused by an increase in osteoclasts number (result of oestrogen withdrawal)
  ~ Type 2: occurs in the elderly of both sexes (senile osteoporosis) generally occurs after age 70; reflects attenuated osteoblasts function

Question 19

What are some osteoporosis risk factors?

Answer 19

• Genetic: peak bone mass is higher in blacks that whites or Asians
• Insufficient calcium intake: 800 mg/day is recommended for postmenopausal women
• Insufficient calcium absorption and vitamin D: decreased renal activation of vitamin D with age (occurs in populations without vitamin D supplementation or elderly confined indoors)
• Exercise: immobilisation of bone (eg prolonged bed rest/cast) leads to accelerated bone loss as physical activity is needed to maintain bone mass
• Cigarette smoking: has been correlated with increased incidence of osteoporosis in women

Question 20

What is achondroplasia caused by?

Answer 20

• Autosomal dominant point mutation in the fibroblast growth receptor-3 gene

Question 21

What does the mutation in the gene that causes achondroplasia do?

Answer 21

• Decreased endochondral ossification
• Inhibited proliferation of chondrocytes in growth plate cartilage
• Decreased cellular hypertrophy
• Decreased cartilage matrix production

Question 22

What is achondroplasia?

Answer 22

• Short limb dwarfism
• Have a normal intelligence and an average lifespan
• Is heritable

Question 23

Where do we get Vitamin D from?

Answer 23

• Dietary eg fish

- Synthesised by skin using UV ligh

Question 24

What happens to Vitamin D in the body and where?

Answer 24

- Is hydroxylated in the liver | - Undergoes more hydroxylation in the kidney to form active 1,25-dihydroxyvitamion D3

Question 25

What does the hydroxylated, active form of vitamin D do?

Answer 25

- Increase calcium absorption by the small bowel | - Promotes mineralisation of bone

Question 26

What is rickets?

Answer 26

- A childhood disease where bones do not harden due to a deficiency of vitamin D

Question 27

What causes rickets?

Answer 27

- Insufficient calcium deposition for adequate bone rigidity - Bones (especially long bones) become soft and malformed - Distortion of skull bone (leading to 'bossing') - Enlargement of costochondral junctions of ribs (rickety rosary)

Question 28

What osteomalacia?

Answer 28

- Adult counterpart of rickets - Caused by significant calcium deficiency or a lack of vitamin D (eg because of poor diet, lack of sunshine, intestinal malabsorption, liver/kidney disease

Question 29

What are common symptoms of osteomalacia?

Answer 29

- Bone pain - Back ache - Muscle weakness

Question 30

What happens to the bone in osteomalacia?

Answer 30

- Trabeculae of cancellous bone have an abnormally large amount of non-mineralised bone (osteoid-uncalcified matrix secreted by osteoblasts) covering the trabecular surface - The trabeculae are weakened by insufficient mineralisation