Skeletal System

Question 1

What do skeletal problems arise from?

Answer 1

• disease/genetics (osteoperosis)
• hormone ablative therapy
• spinal cord or nerve injury
• surgery and rehabilitation
• aging (type 2 osteroporsis)
• Bedrest
• microgravity

Question 2

What are the two main bone types?

Answer 2

• Long (e.g., femur)
• Flat (e.g., skull)

Question 3

What is the haversain system?

Answer 3

• Blood supply to the entire bone

Question 4

What is cancellous/trabecular bone?

Answer 4

• Spongy bone with many connections to make it strong but also flexible.

Question 5

How do long bones form?

Answer 5

• Endochondral Ossification (six steps)
  1. Cartilage: stem cells (chondrocytes) make cartilage
  2. Growth or cartilage: cells in centre burst causing a pH shift, triggering calcification
  3. Primary Ossificaion Centre: nutrient artery penetrates centre of the cartilage. Bone mineral matrix covers the calcified cartilage froming spongy bone.
  4. Medullary cavity: bone mineral is reshaped and remodelled to from the medullary cavity.
  5. Secondary ossification centre: blood vessels enter the epiphyses (around birth). Cancellous bone is formed but no medullary cavity.
  6. Formation of cartilage on the joints: cartilage on ends of bone remain as articular cartilage.

Question 6

How do long bones get longer?

Answer 6

• occurs at the epiphyseal plate, or cartilage growth plate
• cartilage cells are produced by mitosis (proliferation) on epiphyseal side of the plate
• cartilage cells are destroyed and replaced by bone on diaphseal side of plate
• between ages 18 to 25, epiphseal plates close and cartilage cells stop dividing and bone replaces the cartilage (epiphyseal line).

Question 7

How do flat bones grow?

Answer 7

• intramembranous ossification
• flat bones form directly from bone forming cells (osteoblasts) and DO NOT have a growth plate.
• Mesenchymal cells differentiate into osteogenic cells
• osteogenic cells differentiate into the osteoblasts and mineralise.
• This forms osteoids (skull plates) which grow towards each other, ultimatley growing the flat bone.

Question 8

What are the 4 components that bone is made up of?

Answer 8

• collagen matrix
• mineral - calcium and phosphorus salts
• water
• magnesium, sodium, and bicarbonate.

Question 9

What forms the organic collagen matrix in bones and what properties does it give bone?

Answer 9

• gives bone strength and flexibility.
• collagen is formed in three different stages: chains, triple helices, and fibrils.
• The fibrils then are arranged in layers, and mineral crystals are deposited between the layers (like concrete)
• This organised structure gives strength to bones.

Question 10

List the bone cell types and their function in bone remodelling.

Answer 10

• osteoblasts: Matrix formation, secretes fibrils, regulates mineralization, positioned above the osteoid matrix, matrix is usually polarazied but can surround cells, differentiates to become osteocytes.
• osteoclasts: digests bone, large multi-nucleated, exhibits ruffled border and clear zone, exhibits polarity with nuclei away from the bone surface, high density of golgi stacks, mitochondria and lysozomal vesicles, secrete enzymes and proteoases.
• osteocytes: born from osetoblasts, maintains bone matrix, occupies lucunae, extends filopodia through canaliculi and communicates from this filopodia, forms gap junctions with neighbouring cells.
• bone lining cells: flat, elongated cells, generally inactive, cover surfaces of inactive bone, thought to be precursor cells to osteoblasts.

Question 11

How do bone cells make and remodel bone?

Answer 11

osteoblasts -> osteoclasts -> osteocytes

1. osteogenic STEM cells differentiate into osteoblats
2. osteoblasts are bone forming cells on the bones surface. They make collagen chains that form mature organic collagen matrix. They control the deposition of calcium and phsophate on the surface (calcify the bone).
3. Once the osteoblast creates the new bone matrix, the osteoblasts results in four diferent ways; become surrounded by the matrix, some differentiate into lining cells on the surface, others will differentiate into osteocytes, and the rest will undergo apoptosis.
4. Then a cluster of osteoclasts form sealed compartments next to the bone surface and secrete acids and enzymes to degrade the bone. Once finished they undergo apoptosis.
5. osteocytes reside in lacunae and extend long branches of cannuliculi to communicate with other osteocytes and the bone surface (neural nework). They sense any mechanical strain and microfractures and respond and secrete hormonal factors which regulate osteoblasts and osteoclasts to remodel bone.

Question 12

Why is it necessary to remodel bone?

Answer 12

• to repair microfractures
• to heal major fractures
• to adapt the skeleton to the demands of the struture
• to supply mineral (calcium and phosphate) as required for maintaining homeostasis.

Question 13

How are microfractures repaired?

Answer 13

1. microfracture occurs
2. osteclasts come to the site to ‘chew’ and create a pit to remove the fracture, triggering osteoblasts to attend to the site.
3. osteoblasts come to the site and form collagen which minerliseses overtime until the microfracture is healed.

Question 14

How does the skeleton adapt to the demands of the structure?

Answer 14

• The sturcture of spongy bone is a bunch of interwoven fibres which are strong, but flexible and allow for the molding when other unsual forces are acting on it.

Question 15

What are the three methods of the endocrine system puts in place to mainatin calcium and phosphate homeostasis?

Answer 15

• bone turnover
• renal system (re-absorption and filtration in the kidney)
• gastrointestinal system (food -> feaces)

Question 16

What are the two hormones involved in controlling bone metabolism?

Answer 16

• Parathyroid Hormone (PTH)
• Active vitamin D (calcitriol)

Question 17

How does PTH work to restore calcium homeostasis?

Answer 17

• Secreted by the parathyroid glands
• Released in response to low blood calcium levels
• increase bone resorption.

Question 18

How does calcitriol work to maintain calcium homeostasis?

Answer 18

• Produced from cholesterol-derived precursors and enzymatic steps in the liver and kidney.
• Synthesised in response to high PTH levels
• Increase bone resorption.

Question 19

How do PTH and calcitriol work to maintain calcium homeostasis?

Answer 19

• Will stimulate calcium in the gut first before they turn to bone as a last resort.
• If there is not a substantial amount in the gut, they will trigger osteoclasts to come to the site and chew away at the mineral phase (containing calcium) and release more calcium into the extracellular environmnet by doing so, increasing the blood calcium levels.

Question 20

What factors regulate and balance the rate of bone remodelling?

Answer 20

• nutrition: adequate levels of minerals and vitamins
• vitamin D (hormone): promotes calcium and phosphorus absorption at the intestine to supply the growing skeleton. Regulates osteoblast and osteoclast function
• sex steroids: at pubery eostrogen and testosterone stimulate growth, at menopause a lack of estrogen accelerates bone resorption.
• Other hormone such as parathyroid hormone.

Question 21

What is the difference in structure of trabecular bone between a young adult and an osteoperoic adult?

Answer 21

• elderly adult with osteoperosis is a lot less structuralised, and has a lower bone density, larger spaces for increased amounts of bone marrow.

Question 22

Describe the process of bone health as we age.

Answer 22

• Our bone mass increases untul the age of about 30, where is flattens, and then starts to decrease.
• for women, menopause produces a lack of estrogen and then, this lack of hormone leads to accelerated bone resorption.
• After this ‘peak’ there are a greater number of osteclasts than osteoblasts, resulting in bone loss.

Question 23

What is osteoperosis?

Answer 23

• a condition which the holes in spongy bone become larger
• there is an imbalance of bone resorption and bone formation
• Bone is typically minerlised
• instead of bone, the spaces are filled with bone marrow cells and the bone density is decreased
• can impact bone as well.

Question 24

What are the causes of osteoperosis?

Answer 24

• genetic
• hormonal factors
• nutritional abnormailities
• women are more likely to develop the condition over men due to meopause
• bone mineral denisty is determined by a combination of heredity and lifestyle factors (e.g., diet, exercise, smoking, and various medications).

Question 25

How do you find out if you have osteoperosis and what are the treatments?

Answer 25

- when fractures occur throughout the skeleton, osteoperosis is not painful until the bone breaks Treatment: - surgery fro fractures - to reduce further bone loss: increased vitamin D and calcium, estrogen replacement, andti-resorptive drugs

Question 26

It is estimated that space-flight journey to Mars and back will take 18 months and cause 30% loss in bone mass. How and why does the bone sense micro-gravity and change its mass? [4 marks]

Answer 26

Osteocytes are the mechano-sensing cells that reside within lacunae and the major cell which detects changes in strain on the skeleton. During space flight, the reduced force on the skeleton results in reduced compression on the skeleton, i.e. increased tension. According to Wolfs Law, compressive forces on the skeleton results in increased bone formation. Whereas tension on the skeleton results in bone resorption. Osteocytes sense compression and tension through their arrangement in the skeleton. Each osteocyte, residing in a lacunae, sends or cellular processes, called filipodia, which extend along canaliculi and makes connections with other filipodia from other osteocytes. The osteocytes within their lacunae and canaliculi network are surrounded by fluid and the compressive or tension causes changes in fluid shear stress on the cells resulting in osteocytes sending signals which results ion osteoclast formation, bone resorption and bone loss.