Bone Function and Repair

Question 1

What are the functions of bone?

Answer 1

Mechanical such as protection of organs and tissue.
Involved in movement.
Synthesis of cells in haemopoeisis.
Metabolic such as mineral storage of calcium and phosphorus.
Fat storage/energy storage in yellow marrow.
Acid-base homeostasis.

Question 2

What are the two ossification types?

Answer 2

Endochondral ossification

Intra-membranous ossification

Question 3

Briefly explain endochondral ossification.

Answer 3

Formation of long bones from cartilage template.

Continued lengthening is by ossification at epiphyseal plates (appositional growth)

Question 4

Briefly explain intramembranous ossification.

Answer 4

The formation of bone from clusters of mesenchymal stem cells in the centre of the bone. For example how spicules for trabeculae. This is interstitial growth and does not involve cartilage!

Question 5

What do flat bones develop by?

Answer 5

Intramembranous ossification directly from mesenchymal stem cells.

Question 6

When can appositional growth occur in intramembranous ossification?

Answer 6

When thickening of long bones occur. This is at the periosteal surfaces.

Question 7

Are long bones only made from endochondral ossification?

Answer 7

No intramembranous ossification occur as to thicken the long bones. Lengthening however is done by endochondral ossification.

Question 8

How do blood vessels end up in spongy bone from intramembranous ossification?

Answer 8

As spicules are built and eventually come together they trap blood vessels in between.

Question 9

Look at page 9.

Answer 9

Yup

Question 10

What are the stages of intramembranous ossification?

Answer 10

MSCs form a tight cluster.
MSCs become osteoprogenitor cells and then osteoblasts.
Osteoblasts lay down osteoid (ECM containing collagen type 1)
The osteoid mineralises and form bone spicules. Osteocytes are found within the spicules and osteoblasts are found on the outside of the spicules.
The spicules join together to form trabeculae and trap blood vessels.
Trabeculae are then replaced by the lamellae of mature compact bone.

Question 11

Why are there no Haversian and volksmann canals in cancellous bone?

Answer 11

Because it has red marrow surrounding it.

Question 12

Why are the lamellae important regarding bone strength?

Answer 12

Because they are thought to be able to slip relative to each other to resists fracture. Works a little bit like a spring then.

Question 13

What are the factors affecting bone stability/strength?

Answer 13

Activity of osteocytes which can both act as osteoblasts and osteoclasts.
Activity of osteoblasts
Activity of osteoclasts

Question 14

What are some nutritional factors that affect bone stability?

Answer 14

Vitamin D
Vitamin C (synthesis of collagen, hydroxylation of lysine and proline)
Vitamin K and B12

Question 15

How does calcitonin work?

Answer 15

Released by thyroid gland to inhibit the action of osteoclasts.

Question 16

How does PTH work?

Answer 16

Indirectly increases the activity of osteoclasts. (Makes more osteoclasts.)

Question 17

Mention what steps are involved in fracture repair.

Answer 17

Haematoma formation
Fibrocartilaginous callus formation
Bony callus formation
Bone remodelling

Question 18

What happens in step 1 of fracture repair?

Answer 18

A haematoma is formed. As the haematoma forms now blood supply reaches the site and tissue dies because of this. Swelling and inflammation occurs as granulocytes enter the site. Phagocytic cells and osteoclasts begin to remove dead and damaged tissue. Macrophages will eventually remove the haematoma.

Question 19

What happens in step 2 of fracture repair?

Answer 19

A fibrocartilaginous callus is formed. New blood vessels infiltrate the fracture haematoma. The soft callus formed here is rich in capillaries and fibroblasts.
Fibroblasts lay down collagen fibres. Other fibroblasts turn into chondroblasts that will lay down hyaline cartilage.
Osteoblasts near the periosteum and endosteum invade the fracture site and begin bone reconstruction by forming spongy/trabecular bone.

Question 20

What happens in step 3 of fracture repair?

Answer 20

A bony callus is formed. New bone trabeculae start to appear in the soft callus.
Endochondral ossification replaces cartilage with cancellous bone.
Intramembranous ossification produces new cancellous bone in any gaps.

Question 21

What happens in step 4 of fracture repair?

Answer 21

Bone remodelling. The cancellous bone is remodelled into compact bone. This is by continuous osteoblastic and osteoclastic activity.
The material bulging from the outside of the bone will eventually be removed by osteoclasts.

Question 22

What are the two steps of bone remodelling?

Answer 22

Osteoclasts make a wide tunnel in the bone called cutting cone.
Osteoblasts make a smaller tunnel of cortical bone called closing cone.

Question 23

Look at page 31.

Answer 23

Yup

Question 24

What are some clinical conditions relating to bone formation?

Answer 24

Osteogenesis imperfecta
Rickets and osteomalacia
Osteoporosis
Achondroplasia

Question 25

Briefly explain Osteogenesis Imperfecta.

Answer 25

Mutation in COL1A

An incorrect production or close to no production of collagen 1 fibres.

Question 26

What are symptoms of Osteogenesis Imperfecta?

Answer 26

Weak bones and increased fracture risk
Shortened height and stature
Blue sclera
Poor teeth development
Hearing loss

Question 27

Briefly explain Rickets.

Answer 27

Mainly affects children
Result from a vitamin D deficiency
Poor calcium mobilisation
Ineffective mineralisation

Question 28

What are symptoms of Rickets?

Answer 28

Weakened bone development
Soft bones
Shortened height and stature
Painful to walk and classic bowed legs.

Question 29

Briefly explain Osteomalacia.

Answer 29

The same as Rickets but in adults
Vitamin D deficiency
Lower mineralisation

Question 30

Osteomalacia can be caused by other things than vitamin D deficiency, or indirectly vitamin D deficiency. What?

Answer 30

Increased calcium resorption from:
Kidney disease (Kidneys activate vitamin D)
Protection from sunlight (produces vitamin D)
Surgery (stomach and intestine)
Drugs that prevent vitamin D absorption

Question 31

What are the main groups of Osteoporosis?

Answer 31

Primary and secondary osteoporosis.

Question 32

Explain primary osteoporosis type 1.

Answer 32

Occurs mostly in postmenopausal women
This is due to an increase in osteoclast number which means more bones broken down.
The increase in osteoclastic activity is from loss of oestrogen after the menopause.

Question 33

Explain primary osteoporosis type 2.

Answer 33

Occurs in both older men and women.
This is due to a loss of osteoblast function
This comes from a loss of oestrogen and androgen

Question 34

What is secondary osteoporosis?

Answer 34

Weak or hollow bone formed ‘external’ factors:
Result of drug therapy
processes after bone remodelling like malnutrition, prolonged immobilisation or weightlessness like space travel.
Metabolic bone diseases like hyperparathyroidism. This causes an increase in PTH which indirectly causes an increase in osteoclast activity.

Question 35

How can primary osteoporosis be managed?

Answer 35

By increasing the calcium intake of elderly men and women.

Question 36

How can secondary osteoporosis be treated?

Answer 36

By exercise. Immobilisation leads to weaker bone, then exercise instead.

Question 37

Explain Achondroplasia.

Answer 37

Inherited mutation in FGF3 receptor gene.
FGF promotes collagen formation from cartilage.
This means that endochondral ossification does not work properly and this results in shorter long bones.
However intramembranous ossification still works properly.
This results in shorted long bones but normally sized short bones, flat bones, irregular bones and sesamoid bones.