Bone Formation and Metabolism

Question 1

What is meant by ‘lamellar’ bone?

Answer 1

Mature bone with a highly ordered collagen structure

Question 2

What is meant by ‘woven’ bone?

Answer 2

Immature bone with a randomised collagen structure

Question 3

What are the different types of lamellar bone?

Answer 3

Cortical(compact) bone and spongy (cancellous/trabecular) bone

Question 4

Describe the composition of the extracellular matrix of bone

Answer 4

35% is organic element (osteoid) with type I collagen for tensile strength, proteoglycans for compressive strength and growth factors. 60% is inorganic and largely calcium hydroxyapatite. 5% is water

Question 5

Name the cells present in bone.

Answer 5

Osteoclasts, osteoblasts, osteocytes and osteoprogenitor cells

Question 6

Describe the role of osteoblasts

Answer 6

Form new bone

Question 7

Describe the role of osteoclasts

Answer 7

Degrade bone (desorption)

Question 8

Describe the role of osteocytes

Answer 8

Maintain bone integrity

Question 9

Describe the role of osteoprogenitor cells

Answer 9

Are stem cells derived from mesenchymal cells which can differentiate into osteoblasts to form new bone

Question 10

Define ‘ossification’

Answer 10

Laying down new bone material by osteoblasts

Question 11

Name the two different types of bone ossification

Answer 11

Intramembranous ossification and endochondral ossification

Question 12

Define ‘intramembranous ossification’

Answer 12

Formation of bone from within a condensed layer of membrane (primitive mesenchymal tissue) which occurs in the development of flat bones such as the skull

Question 13

Define ‘ endochondral ossification’

Answer 13

Formation of bone from cartilage model as in long bone development

Question 14

Describe the process of intramembranous ossification

Answer 14

1) In mesenchyme tissue, cells differentiate into osteoblasts -> many centres of ossification (COO) formed
2) Osteoblasts secrete osteoid at these centres which mineralise to form spicules of bone
3) COO size increases as more osteoblasts formed from differentiation, COO grow around foetal blood vessels until centres meet & fuse to form trabecular bone and mesenchyme condenses on outer surface to form vascularised periosteum
4) More fusion, until outer layer continuous with woven bone. Then remodelling so outer woven -> compact, and inner -> lamellar spongy bone and red bone marrow develops in space in spongy bone.

Question 15

What is a ‘primary ossification centre’?

Answer 15

First part of bone to start ossifying (in diaphysis/centre of bone)

Question 16

What is a ‘secondary ossification centre’?

Answer 16

Site where bone formation continues (epiphysis.bone ends)

Question 17

Describe the formation of the primary ossification centre in endochondral ossification.

Answer 17

1) Perichondrium around shaft of cartilage model converted to periosteum (with osteogenic potential) and mesenchymal cells differentiate into osteoblasts here to form collar of bone.
2) Chondrocytes in centre of diaphysis hypertrophy leaving thin intervening matrix which calcifies and cartilage cells die
3) Nutrient artery perforates bony collar, enters diaphysis to carry osteoprogenitor cells and primitive mesenchymal cells which form osteoblasts and secrete osteoid to form bone on remnants of calcified cartilage - forming trabecular bone which is the primary ossification centre

Question 18

Describe the formation of the secondary ossification centre in endochondral ossification - completion of bone formation.

Answer 18

At epiphyseal ends the chondrocytes hypertrophy and die, the intervening matrix calcifies, and the epiphyseal arteries carry osteoprogenitor cells into the area where they differentiate into osteoblasts to form trabecular bone (secondary ossification sites). The bone continues to replace the cartilage in the epiphyses until articulating cartilage and epiphyseal growth plate (between epiphysis and diaphysis) are only cartilage that remains.

Question 19

Name the 5 zones present in the histology of endochondral ossification

Answer 19

zone of reserve cartilage, zone of cartilage proliferation, zone of maturation and hypertrophy of chondrocytes, zone of degeneration and calcification of chondrocytes, zone of osteogenesis

Question 20

At what age do bones stop growing?

Answer 20

18-25

Question 21

Which is the last bone to fully ossify?

Answer 21

Clavicle

Question 22

What is ‘appositional growth’

Answer 22

The widening of the bones (growing out sideways instead of upwards)

Question 23

Describe the process of appositional growth.

Answer 23

Periosteum cells differentiate into osteoblasts and secrete new bone matrix which forms ridges on either side of periosteum blood vessels until ridges fuse and enclose blood vessels to form tunnel of bone moving out sideways.

Question 24

Name two reasons for bone remodelling.

Answer 24

It renews bone prior to deterioration, and redistributes the bone matrix along the lines of mechanical stress.

Question 25

Describe the process of bone remodelling

Answer 25

Osteoclasts secrete HCl and protein-digesting enzymes beneath bone surface to break down collagen fibres and dissolve minerals. These proteins and minerals then enter the osteoclasts to exit into the interstitial fluid (and then blood) to increase serum calcium levels (bone desorption). Osteoblasts then fill the lacuna with osteoid which then mineralises to create new bone formation (takes 7-10 days)

Question 26

Describe the role of calcium in bone metabolism.

Answer 26

Low serum calcium levels stimulates the secretion of parathyroid hormone from the parathyroid glands. Conversely, high serum calcium levels stimulate secretion of calcitonin from the thyroid glands (C-cells).

Question 27

What is the normal serum level of calcium?

Answer 27

2.2-2.6mmol/L

Question 28

Describe the role of parathyroid hormone in bone metabolism.

Answer 28

PTH promotes: calcium reabsorption in kidney (and phosphate excretion), bone resorption by increasing activity and number of osteoclasts (osteoblasts have PTH receptor and express RANKL, osteoclast precursors have RANK receptor leading to differentiation), also stimulate synthesis of 1,25-dihydroxyvitamin D which increase calcium reabsorption from the gut

Question 29

Describe the role of oestrogen in bone metabolism

Answer 29

Decreases calcium absorption in the gut, and also inhibits osteoclasts (bone resorption)

Question 30

Describe the role of glucocorticoids in bone metabolism

Answer 30

Decrease calcium absorption in the gut and increase bone degradation (bone desorption)

Question 31

Describe the role of calcitonin in bone metabolism

Answer 31

Rising serum calcium levels stimulate the thyroid gland to release calcitonin which stimulate bone deposition and inhibits osteoclasts, and also reduce the calcium uptake in the kidneys