T3 L1: Bone physiology and homeostasis

Question 1

What is osteopetrosis?

Answer 1

A rare disorder that causes bones to grow abnormally and become overly dense because there is increased bone formation

Question 2

What is osteopenia?

Answer 2

The stage before osteoporosis where the bone density decreases

Question 3

What do osteoclasts do?

Answer 3

They’re phagocytes that create bone by degradation and remodelling
-They phagocytose, secrete acids, and secrete proteolytic enzymes from lysosomes

They originate from haematopoietic stem cells like monocytes

Question 4

What do osteocytes do?

Answer 4

They are quiescent mature cells embedded in bone that maintain bone

Question 5

What do osteoblasts do?

Answer 5

Found on the surface of bone. they regulate bone growth and degradation

Question 6

What does organic and inorganic mean in bone?

Answer 6

Organic: cells and proteins
Inorganic: minerals like Ca2+, PO4-

Question 7

What is the function of a Haversian canal?

Answer 7

Found in the centre of an osteon and contains maintenance nutrients

Question 8

What is woven bone?

Answer 8

Produced when osteoblasts produce osteoid rapidly, which occurs initially in all foetal bones, but is later replaced by more resilient lamellar bone

Question 9

Which cell do osteocytes arise from?

Answer 9

From osteoblasts

Osteoblasts are post-mitotic and most undergo apoptosis. A small % become osteocytes locked in lacuna

Question 10

What is the ruffled border of bone for?

Answer 10

It’s where bone resorption occurs

Question 11

What are the components of bone?

Answer 11

Collagen fibres: strong, flexible protein
Hydroxyapatite: rigid mineral
Calcium/phosphate crystals (50%)

Just like reinforced cement: collagen is the rods and crystals are the cement

Question 12

What are glycosaminoglycans?

Answer 12

Long polysaccharides abundant in the extracellular matrix of bone. They are highly negative so attract lots of water

It helps the bone resist compression

Question 13

What is the function of growth factors in the extracellular matrix of bone?

Answer 13

They allow for proliferation and mineralisation

Question 14

What is Howship’s lacuna?

Answer 14

Any of the tiny depressions, pits, or irregular grooves in bone that is being resorbed by osteoclasts

Question 15

What is the difference between cancellous and compact bone?

Answer 15

Compact: harder outer shell of the bone
Eg. long bones

Cancellous: porous, less dense layers of the bone
Eg. Cancellous bone is the meshwork of spongy tissue (trabeculae) of mature adult bone typically found at the core of vertebral bones in the spine and the ends of the long bones

Question 16

What is the difference between intramembranous and endochondral ossification?

Answer 16

In intramembranous ossification, bone develops directly from sheets of mesenchymal connective tissue. In endochondral ossification, bone develops by replacing hyaline cartilage

Question 17

How does mechanical stress promote bone growth?

Answer 17

Surface osteoblasts and osteocytes detect stresses and inhibit bone resorption to promote deposition instead

Without weight bearing, bone rapidly weakens

The skeleton reflects the forces acting on it

Question 18

How do the drugs Bisphosphonates work?

Answer 18

Eg. Alendronate

They inhibit osteoclast-mediated bone resorption

Question 19

What is the function of inorganic pyrophosphate in bones?

Answer 19

It’s the endogenous regulator of bone turnover

It accumulates in bone and is ingested by osteoclasts and interferes with their metabolism

Question 20

How does the drug Teriparatide work?

Answer 20

It’s a portion of human parathyroid hormone (PTH) and it encourages osteoclast formation of bone

Intermittent application activates osteoblasts more than osteoclasts so more bone is laid down

Question 21

How does the drug Denosumab work?

Answer 21

It’s a monoclonal antibody that targets RANKL

It prevents osteoclast maturation so less bone is degraded and remodelled

Question 22

What is the mechanism behind osteopetrosis?

Answer 22

• Osteoclasts cannot remodel bone because they can’t secrete the acid to break down the bone so it continues to grow
• Defective vacuole proton pump
• Defective chloride channel

Question 23

What are the consequences of osteopetrosis?

Answer 23

Excessive bone growth causing:

• Brittle bones (not enough collagen)
• Blindness
• Deafness
• Severe anaemia

Question 24

What are the 4 stages of fracture healing?

Answer 24

Reactive phase: haematoma and inflammation
-Blood and inflammatory cells enter wound and
granulation tissue forms

Soft callus formation: woven bone formation

Hard callous formation: Lamellar bone replaces woven bone

Remodelling: trabecular bone replaces lamellar bone. original shape forms and bone becomes more compact

Question 25

Which hormones help regulate calcium?

Answer 25

Parathyroid hormone
Vitamin D (calcitriol)
Calcitonin

Question 26

How does Vitamin D help calcium absorption?

Answer 26

• It increases interstitial Ca2+ absorption by increasing calbindin
• It stimulates kidneys to absorb calcium
• Indirectly stimulates osteoclasts via osteoblasts
• It facilitates bone remodelling thus increases serum Ca2+

Question 27

What can cause low plasma calcium?

Answer 27

• Loss through pregnancy, lactation, or kidney dysfunction
• Low intake of calcium or vitamin D
• Parathyroid dysfunction

Question 28

What does chronic hypocalcaemia result in?

Answer 28

• Skeletal deformities (rickets)
• Increased bone fractures
• Impaired growth (short stature)
• Dental deformities

Question 29

What are the effects of acute hypocalcaemia?

Answer 29

It causes excitability because it makes membranes less stable:
Convulsions
Arrhythmias
Tetany

Chvostek’s sign and Trousseaus sign caused by latent tetany

Question 30

What are the effects of acute hyperexcitability?

Answer 30

Reduced excitability because it makes membranes more stable as less Na+ will be going through

Causes:

• Constipation
• Depression
• Abnormal heart rhythms

Coma and cardiac arrest is severe hypercalcaemia