Physiology Of Bone

Question 1

What are the main physiological functions of bone tissue?

Answer 1

Support, movement, protection, mineral storage, blood cell formation, energy storage and energy metabolism

Question 2

What do the organic components and especially collagen contribute to bone tissue?

Answer 2

The flexibility and tensile strength that allow bone to resist stretching and twisting

Question 3

What are the organic components of bone ECM?

Answer 3

Osteonectin, osteocalcin, proteoglycans, sialoproteins, osteopontin and thrombospondin

Question 4

What is the function of osteonectin and osteocalcin in organic bone ECM?

Answer 4

Aid in hydroxyapatite crystallization and bind Ca

Question 5

What is the function of proteoglycans in organic bone ECM?

Answer 5

Bind growth factors (ex. TGF-beta)

Question 6

What is the function of sialoproteins, osteopontin and thrombospondin in organic bone ECM?

Answer 6

Mediate osteoclast adhesion to bone surface (bind osteoclast integrins)

Question 7

What are the inorganic components of bone ECM?

Answer 7

Hydroxyapatite or mineral salts primarily Ca phosphate (some Ca carbonate, K and Mg)

Question 8

What is the function of the inorganic component of bone ECM?

Answer 8

Present as tiny crystals to line and around collagen fibrils in ECM
Pack tightly contributing to hardness and ability to resist compression

Question 9

What are osteogenic cells?

Answer 9

Stem cells that differentiate into bone forming osteoblasts

Question 10

Where are osteogenic cells located?

Answer 10

Within the deep/inner layer of periosteum and the marrow

Question 11

What are osteoblasts?

Answer 11

Cuboidal shaped cells derived from mesenchymal stem cells

Question 12

What do osteoblasts directly regulate?

Answer 12

Bone matrix synthesis and mineralization

Question 13

What do osteoblasts indirectly control?

Answer 13

Bone resorption through release of paracrine factors that regulate osteoclasts (RANKL/OPG)

Question 14

What can osteoblasts become?

Answer 14

Osteocytes embedded in the matrix
Bone lining cells which protect inactive bone surfaces
Or will die by apoptosis

Question 15

What are osteocytes?

Answer 15

Terminally differentiated osteoblasts but smaller in size and contain projections that branch into the matrix

Question 16

Where as osteoblasts located?

Answer 16

Growing portions of bone including periosteum and endosteum

Question 17

Where are osteocytes located?

Answer 17

Trapped within newly deposed bone matrix

Question 18

What is the function of osteocytes?

Answer 18

Respond to mechanical loading by releasing paracrine factors
Stimulate and coordinate bone remodeling and Ca release from the matrix

Question 19

What are osteoclasts?

Answer 19

Specialized multinucleated cells derived from mononuclear cells in the bone marrow
Resorb mineralized bone matrix by secreting acid and lytic enzymes

Question 20

What is osteoclast differentiation controlled by?

Answer 20

Receptor activation of nuclear factor kB (RANKL) from osteoblasts
Can be inhibited by OPG which sequesters RANKL

Question 21

Where are osteoclasts located?

Answer 21

Bone surfaces and site of old or injured bone matrix

Question 22

What does Wolff’s law state?

Answer 22

That your bones will adapt based on the stress or demands placed on them
When you work your muscles, they put stress on your bones and in response your bone tissue remodels and becomes stronger

Question 23

What is the purpose of bone remodeling?

Answer 23

Repairs micro damage, maintains bone strength and maintains serum Ca levels within normal physiological ranges

Question 24

Regulation of bone remodeling and modeling is through a number of what?

Answer 24

Local and systemic regulators including TGF-beta, BMPs, OPG, FGFs, IGFs, PDGF, interleukins and PTH

Question 25

What function does TGF-beta play during bone remodeling?

Answer 25

Stimulates the proliferation and differentiation of osteoblasts and bone formation Increases OPG production

Question 26

What function do BMPs play during bone remodeling?

Answer 26

Potent inducers of osteoblasts and bone formation | Regulate matrix production

Question 27

How are BMPs used clinically?

Answer 27

rhBMP-2 is used in fracture healing/spinal fusion

Question 28

What function does osteoprotegerin (OPG) play during bone remodeling?

Answer 28

Secreted from osteoblasts and bind to RANKL to prevent osteoclast activation (aka prevents bone resorption)

Question 29

What function do FGFs play during bone remodeling?

Answer 29

Increase proliferation of osteoblasts | Enhance callus formation during fracture repair

Question 30

What does FGF-2 stimulate during bone remodeling?

Answer 30

Angiogenesis during fracture repair

Question 31

What function do insulin like growth factors (IGFs) play during bone remodeling?

Answer 31

Stimulated by growth hormone and increase bone collagen matrix synthesis Also inhibits degradation

Question 32

What function does platelet derived growth factor (PDGF) play during bone remodeling?

Answer 32

Increase collagen synthesis

Question 33

What function does RANKL play during bone remodeling?

Answer 33

Secreted from osteoblasts | Activates osteoclasts for bone resorption

Question 34

What is RANKL regulated by?

Answer 34

OPG

Question 35

What function do interleukins play during bone remodeling?

Answer 35

Stimulate bone resorption | IL-1 is the most potent

Question 36

IL-1 expression is decreased by what?

Answer 36

Estrogen which is a possible mechanism for post-menopausal bone resorption increases

Question 37

What function does PTH play during bone remodeling?**

Answer 37

Falling blood Ca (Hypocalcemia) signals parathyroid glands to release PTH which signals osteoclasts to degrade bone matrix and release Ca into the blood

Question 38

Fracture healing is what?

Answer 38

A specialized type of wound healing involving inflammation, repair and remodeling

Question 39

The healing sequence of fracture repair depends on what?

Answer 39

Movement between fragments Limited movement = indirect bone healing No movement = direct bone healing

Question 40

What are the 5 stages of indirect (secondary) fracture healing?

Answer 40

1. Tissue destruction and hematoma formation 2. Inflammatory phase which stimulates blood vessel formation and recruitment of mesenchymal cells 3. Soft callus formation (made up of fibrous CT and helps restrict fragment movement) 4. Hard callus formation (woven -> lamellar bone) 5. Remodeling of bone

Question 41

Inflammatory phase of indirect fracture healing occurs when?

Answer 41

Week 1

Question 42

Soft callus formation phase of indirect fracture healing occurs when?

Answer 42

Weeks 2-3

Question 43

Hard callus formation phase of indirect fracture healing occurs when?

Answer 43

Weeks 4-12

Question 44

Bone remodeling phase of indirect fracture healing occurs when?

Answer 44

For years

Question 45

Describe direct (primary) fracture healing

Answer 45

Contact healing between bones No callus is formed Requires absolute stability between fracture fragments (no motion)

Question 46

What is contact healing in direct fracture healing?

Answer 46

Direct contact between bone fragments ends (lamellar bone)

Question 47

When there is a gap between bone fragments that is 200-500nm wide what will occur with direct fracture healing?

Answer 47

Woven —> lamellar bone

Question 48

When there is a gap between bone fragments that is 500nm wide what will occur with fracture healing?

Answer 48

Indirect healing will occur

Question 49

What are examples of anti-resorption treatments?

Answer 49

Bishophophonates, hormone replacement (estrogen, selective estrogen receptor modulators or denosumab

Question 50

How are bisphosphonates used as an anti-resorption agent?

Answer 50

They inhibit osteoclast activity and induce osteoclast apoptosis

Question 51

What is denosumab and how is it used as an anti-resorption agent?

Answer 51

It is a monoclonal Ab against RANKL

Question 52

What are examples of anabolic therapeutic agents?

Answer 52

BMP2 and PTH

Question 53

How does BMP2 function as an anabolic therapeutic agent?

Answer 53

Induces osteoblast proliferation and activity for increased bone matrix production

Question 54

How is PTH used as an anabolic therapeutic agent?

Answer 54

Intermittent (daily) administration is anabolic with reductions in vertebral fractures of up to 70% being reported over untreated pts Mechanism is unclear

Question 55

Continual administration of PTH is what?

Answer 55

Catabolic for bone with increased osteoclast formation due to changes in expression of OPG and RANKL by osteoblasts

Question 56

What are examples of endocrine regulation of bone metabolism?

Answer 56

Estrogen, thyroid hormones, glucocorticoids, PTH and growth hormone

Question 57

Explain how estrogen is an example of an endocrine regulator of bone metabolism

Answer 57

Stimulates fracture healing through receptor mediated mechanisms Decrease RANKL production from osteoblasts Modulates release of specific inhibitor of IL-1

Question 58

Explain how thyroid hormones are an example of an endocrine regulator of bone metabolism

Answer 58

Thyroxine and T3 stimulate osteoclastic bone resorption

Question 59

Explain how glucocorticoids are an example of an endocrine regulator of bone metabolism

Answer 59

Inhibit Ca absorption from the gut causing increased PTH and therefore increased orthroclastic bone restoration

Question 60

Explain how PTH is an example of an endocrine regulator of bone metabolism*

Answer 60

Intermittent exposure stimulates osteoblasts and increases bone formation More chronic exposure or pathological levels (hyperparathryoid) stimulates osteoclasts to release Ca and can lead to hypercalcemia

Question 61

Explain how growth hormone is an example of an endocrine regulator of bone metabolism

Answer 61

Mediated through IGF-1 | Increases callus formation and fracture strength by stimulating osteoblasts