Physiology of Bone

Question 1

What are the physiological functions of bone tissue?

Answer 1

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

Question 2

What are the main bone cell types?

Answer 2

Osteoclasts, osteoblasts, osteocytes, osteogenic cells

Question 3

What do osteoclasts do?

Answer 3

Secrete acid and lytic enzymes to resorb bone (break down and releases minerals)

Question 4

Where will you find osteoclasts?

Answer 4

Bone surfaces and sites of old/injured bone

Question 5

What do osteogenic cells do?

Answer 5

Stem cells that will differentiate into osteoblasts

Question 6

Where will you find osteogenic cells?

Answer 6

Inner layer of periosteum

Question 7

What do osteoblasts do?

Answer 7

Build bone by directly regulating bone matrix synthesis and mineralization
Indirectly control bone resorption via controlling osteoclasts

Question 8

Where will you find osteoblasts?

Answer 8

Growing portions of bone including periosteum and endosteum

Question 9

Describe the differentiation process for osteoblasts

Answer 9

Mesenchymal stem cells
Preosteoblasts
Osteoblasts
Osteocytes

Question 10

What do osteocytes do?

Answer 10

Maintain bone tissue by being a terminally differentiated osteoblast AND
Respond to mechanical loading by releasing paracrine factors that stimulate bone remodeling and Ca++ release

Question 11

Where will you find osteocytes?

Answer 11

Trapped within newly deposited bone matrix

Question 12

What 2 divisions is the ECM of bone divided into?

Answer 12

Organic and inorganic

Question 13

What is the job of the organic ECM?

Answer 13

(35%) - mostly collagen, contributes to tensile strength and flexibility of bone

Question 14

What is the job of the inorganic ECM?

Answer 14

(65%) - mostly inorganic hydroxyapatites or mineral salts (calcium phosphate), contribute to the hardness and compressive strength of bone

Question 15

What is Wolff’s law?

Answer 15

If loading on a particular bone increases, the bone will remodel itself over a period of time to withstand greatest strength with the least amount of material by changing its architecture

Question 16

Why is bone remodeling an ongoing process?

Answer 16

In order to repair microdamage, maintain strength, maintain calcium serum levels

Question 17

Describe the bone remodeling process

Answer 17

Osteoclasts progenitors bind to RANKL on osteoblasts using a RANK receptor and then differentiate into osteoclasts to degrade bone (resorption)
OPG then is secreted by osteoblasts and binds RANKL to prevent further osteoclast activation
Osteoblasts then differentiate from mesenchymal cells to build and remodel the bone

Question 18

Transforming growth factor beta (TGFbeta)

Answer 18

Stimulate proliferation of osteoblasts, OPG and bone formation

Question 19

Bone morphogenic proteins (BMPs)

Answer 19

Stimulates proliferation of osteoblasts and bone formation, regulates matrix production, used clinically for fracture healing and spinal fusion

Question 20

OPG

Answer 20

Prevents osteoclast activation

Question 21

Fibroblast growth factors (FGF)

Answer 21

Increase proliferation of osteoblasts and enhance callus formation during fracture repair

Question 22

Insulin-like growth factors (IGFs)

Answer 22

Increase bone collagen matrix synthesis and inhibits degradation

Question 23

Platelet derived growth factor (PDGF)

Answer 23

Increase collagen synthesis

Question 24

RankL

Answer 24

Secreted from osteoblasts, activates osteoclasts to resorb bone and is inhibited by OPG

Question 25

Interleukins (IL-1 = most potent)

Answer 25

Stimulate bone resorption IL-1 is decreased by estrogen... may be a cause of bone resorption increase in post-menopausal women because IL-1 is increased when their estrogen is decreased

Question 26

Parathyroid hormone (PTH)

Answer 26

Low blood calcium levels signals to parathyroid gland to release PTH which then tells osteoclasts to degrade bone to increase calcium levels

Question 27

What does fracture healing depend on?

Answer 27

Amount of movement and space between bone fragments

Question 28

What constitutes indirect bone healing?

Answer 28

Limited movement of bones, gaps greater than 500 nm

Question 29

What constitutes direct bone healing?

Answer 29

NO MOVEMENT, rigid internal fixation, no gaps or gaps between 200 and 500 nm

Question 30

What are the steps of indirect fracture healing?

Answer 30

``` Tissue injury and hematoma Inflammatory phase (1 week) Soft callus formation (2-3 weeks) - unmineralized cartilage Hard callus formation (4-12 weeks) Remodeling of bone (years) ```

Question 31

Is a callus formed in direct fracture healing?

Answer 31

NOOOOOOOO

Question 32

What are some Anti-resorption treatments for bone?

Answer 32

Bisphosphonates (inhibit osteoclasts by inducing their apoptosis), hormone replacement (estrogen), selective estrogen receptor modulators, denosumab (Ab against RANKL)

Question 33

What are some Anabolic Agents (build bone)?

Answer 33

BMP-2 (induces osteoblast formation) PTH: continual admin = catabolic for bone PTH: intermittent admin (daily) = anabolic for bone... weird

Question 34

How do glucocorticoids increase bone resorption?

Answer 34

They inhibit calcium absorption in the gut, which signals for PTH which then increases osteoclastic bone resorption