S3: Bone - Biological Properties and Remodelling

Question 1

Function of bone

Answer 1

• Calcium regulation: there are various hormones involved particularly calcitonin, parathyroid, 1,23 diOH vitamin D and oestrogen.
• Mechanical support and locomotion as bones are the ultimate biomaterial. They are strong yet light and able to adapt to the functional demands because they are live tissue. Bones are also able to self repair.
• Protection of vital organs. For example the brain is encased within the skull.

Question 2

What are the three compositions that make up bone?

Answer 2

1. Protein called osteoid which is organic material (25%)
2. Mineral as the protein has to be mineralised with calcium and phosphate (75%)
3. Bone cells

Question 3

Describe the Osteoid Protein Matrix composition in bone and given an example of associated disease

Answer 3

The protein matrix is largely composed of type I collagen which accounts for over 90% of the protein. The remainder consists of glycoproteins, proteoglycans and others. The function of this is that collagen is flexible but it also has high tensile strength.
- There are diseases that can occur in bone if there’s an abnormality in a person’s type I collagen due to genetic reasons e.g. osteogenesis imperfecta/brittle bone disease.

Question 4

Describe the Mineral composition in bone and given an example of associated disease

Answer 4

The protein structure in bone has to be mineralised with calcium and phosphate. This combination of calcium and phosphate is called hydroxyapatite (hydrated calcium and phosphate). This makes the bone more rigid with high compressional strength. We usually have about 20% of unmineralised bone because when we make new bone with protein matrix it needs to be mineralised which is a slow process.
- Abnormalities in bone mineral can cause diseases such as osteomalacia and rickets where only about 50% of bone is mineralised at one time (compared to 80%). This makes the bone more flexible in rickets can lead to bowing of bones (vitamin D deficiency).

Question 5

What is the two types of bone?

Answer 5

Cortical bone and Trabecular bone (fine, lighter with holes).

Question 6

Composition of cortical and trabecular bone in the femur

Answer 6

The shaft of long bones contain mostly cortical (compact) bone while the ends of bone contains mostly trabecular bone (also called cancellous or spongy bone).

Question 7

Describe trabecular bone

Answer 7

Tabecular bone has lower density and has a high surface area compared to cortical bone. It has a high remodelling rate and it is in different directions to withstand the force when walking - these patterns change throughout life. Trabecular bone is the part of the bone where most cells sit (at the edge of struts and plates) so it is very metabolically active with osteoblasts and osteoclasts. Thus a lot of the remodelling of bone that occurs during life will occur in the trabecular bone. In the spaces of the trabecular bone is red bone marrow (at the ends of the bone and only in certain bones).

Question 8

Describe cortical bone

Answer 8

Cortical bone has some remodelling, but not as much as trabecular. It also has a higher density and lower surface area and made up of concentric rings of bone with vascular channels running through. The whole thing is called a Haversian system (lots of collagen with a central blood vessel which is mineralised).
Within the bone are the osteocytes and cortical bone has less cells than trabecular bone.

Question 9

Why is bone light?

Answer 9

The shaft of the bone is hollow in the middle and trabeular bone has many holes in it.

Question 10

Describe bone remodelling cycle

Answer 10

1. Osteoclasts come in and resorb bone leaving resorption pits.
2. Osteoblasts come in and produce a new layer of bone, filling in the pits with the protein matrix (osteoid) and some of the osteoblasts will get stuck and become osteocytes.
3. The osteoid is then mineralised with the calcium and phosphate.
4. Quiescent period.

Question 11

Describe osteoblasts

Answer 11

• They synthesis the new bone matrix: the collagen and other matrix proteins.
• They also synthesis the bone mineral (calcium and phosphate) to then mineralise the bone matrix.
• Osteoblasts are derived from mesenchymal stem cells.

Question 12

Describe osteoclasts

Answer 12

• Similar lineage to monocytes
• Function is to digest and reabsorb the bone matrix aswell as the transceullular removal of calcium and mineral component
• Osteoclasts work by producing acid to remove/dissolve the mineral and producing proteolytic enzymes to digest the matrix

Question 13

Describe the changes in bone mass with age and why this happens

Answer 13

Changes in bone mass is due to the bone cells activity which change with age.
When younger, osteoblasts are more active than osteoclasts so there is a net gain in bone mass up to about 30. From age 30-40 there is a steady state where osteoblast and osteoclast activity are even.
However, after 40 years of age, osteoclasts are more active than osteoblasts and there is a net loss of bone so bone mass decreases.

Question 14

Why are women at risk of osteoporosis?

Answer 14

When women are older, they experience menopause and there is a large loss of bone mass with reduction in oestrogen (which inhibit osteoclasts). Bone is therefore more fragile and at risk of osteoporosis.

Question 15

Relationship between bone mass and fractures

Answer 15

There is a fracture threshold for bone mass. Lower bone mass means weaker bones and higher chance of fractures.

Question 16

What does generalised overactivity of osteoclasts lead to?

Answer 16

Generalised overactivity of osteoclasts leads to osteoporosis which is the most common imbalance of bone formation and resorption. There are then microfractures in osteoporotic bone and less bone in general so it will be unable to withstand as much force hence osteoporosis is the commonest cause of fractures.

Question 17

What is localised imbalances that result in increased bone turnover?

Answer 17

Paget’s disease which causes pain at joints. For example, the femur is thickened because osteoblasts are producing too much bone and there are areas where osteoclasts are too active causing disordered bone turnover. This one is also weak,

Question 18

What are the two main types of regulators of bone remodelling?

Answer 18

1. Hormones and Local Factors
2. Mechanical Forces
   They both usually regulate bone remodelling by affecting bone cells.

Question 19

What hormones increase bone density?

Answer 19

• Oestrogen/androgens (suppress osteoclasts)
• GH/IGF-1
• Calcitonin

Question 20

What hormones decrease bone density?

Answer 20

• Thyroxine
• Glucocorticoids
• PTH

Question 21

Give example of local factor affecting bone remodelling

Answer 21

Local regulators, like RANK ligand, which is how osteoblasts activate osteoclasts.

Question 22

Give example of how mechanical forces can affect bone remodelling

Answer 22

e.g. Andy Murray would have greater bone density in his tennis playing arm due to mechanical reasons, with increased force being put on that arm.

Question 23

When do fractures occur?

Answer 23

Fractures occur when there is a force exceeding the bones strength.

Question 24

What are the types of forces bone is strong and weak to?

Answer 24

Bone has good compressional strength and tensile strength but not that strong against twisting (torsional) forces i.e. bones torsional strength is weaker.

Question 25

Describe the stages of fracture healing

Answer 25

1. Bleeding, bruising. Inflammatory cells turn up and macrophages remove debris and granulation tissue is laid down (similar to soft tissue injury). Then fibrous tissue is made which needs to be vascularised.
2. Osteoblasts produce a soft callus which is then mineralised to form woven bone (hard callus). This is not that strong.
3. Woven bone is remodelled into lamellar bone. This is the cortical bone that is very strong.