2) Osteoarthritis

Question 1

What is osteoarthritis?

Answer 1

The most prevalent of the arthritis’ occurring when damaged joint tissues are unable to
normally repair themselves resulting in a
breakdown of cartilage and bone

Question 2

The ratio of people who have osteoarthritis?

Answer 2

1 in 10 (3 million Canadians)

Question 3

Modifiable and Non-Modifiable Risk Factors for Osteoarthritis.

Answer 3

Modifiable: obesity, occupation, sports, and trauma

Non-modifiable: genetics, age, and gender

Question 4

How does obesity affect osteoarthritis?

Answer 4

Most important preventable risk factor.

It’s is predictor of prosthetic joint replacement. With the loss of 5kg results in 50% risk reduction.

Question 5

How does overuse and trauma affect osteoarthritis?

Answer 5

Repetitive motion causing wear and trauma to joint, similar to the results of injury

Question 6

What gender is more commonly affected by osteoarthritis?

Answer 6

Females

Question 7

Why does age affect the risk of getting osteoarthritis?

Answer 7

• Blunted chondrocyte repair potential
• Weakened muscles (joint protection)
• Slower sensory nerve input: less effective muscle and tendon response
• Ligaments stretch with increasing age: less effective absorption of force

Question 8

Primary vs Secondary causesOsteoarthritis

Answer 8

Primary: idopathic, with no identifiable causes
Secondary: rheumatoid arthritis, trauma, obesity and disease

Question 9

Name 4 joint protective mechanisms

Answer 9

Joint capsule and ligament (fixes range of motion)
Synovial fluid (fills joint space to reduce friction btwn cartilage)
Mechanoreceptor sensory afferent nerve (provide feedback for muscles and tendons for positioning) 
Muscles and tendons (minimize focal stress across the joint)

Question 10

Osteoarthritis is what kind of disease?

Answer 10

Progressive, “wear and tear”, large joint disease

Question 11

What is cartilage and what is its function?

Answer 11

Thin rim of tissue on either end of two bones lubricated by synovial fluid with no vascular supply or nerve innervation.
It is to absorb shock.

Question 12

What are Chrondrocytes?

Answer 12

They produce the two major macromolecules that make up cartilage and also the enzymes that break down cartilage.

Question 13

What are the two major macromolecules that make up cartilage?

Answer 13

Type II Collagen: provides strength
Aggrecan: proteoglycan linked with hyaluronic acid. Negatively charged.
Work together to give compressive stiffness through electrostatic repulsion.

Question 14

What are the enzymes involved in cartilage breakdown?

Answer 14

• Matrix metalloproteinases (MMP-13) : breaks down Type II Collagen
• ADAMTS-4 and ADAMTS-5: breaks down Aggrecan

Question 15

True or Flase: Actual cartilage damage is a chemically-mediated disease process?

Answer 15

True

Question 16

Describe the basic steps of osteoarthritis in cartilage.

Answer 16

1) Damage to Cartilage
2) Chondrocyte activity increases
3) Balance of breakdown vs re-synthesis lost
4) Vicious cycle of increasing breakdown leading to further cartilage loss

Question 17

Describe the cycle of cartilage breakdown.

Answer 17

Cartilage damage occurs which activates ADAMTS-5. ADAMTS-5 triggers aggrecan destruction exposing the DDR-2 receptor to collagen, activating it. DDR-2 then increases MMP-13 which destroys collagen.

Question 18

The enzymes are overexpressed when injury occurs to cartilage, shifting balance towards degradation resulting in loss of collagen and proteoglycans

Answer 18

Cartilage matrix degrading enzymes also known as Matrix Metalloproteases

Question 19

Where is proteoglycan protein found and what is it a major component of?

Answer 19

Found in connective tissue and cartilage; Major component of extracellular matrix and has lubricating functions which is inhibited in cartilage breakdown.

Question 20

Name 4 pro-inflammatory cytokines.

Answer 20

TNF-α, IF gamma, IL-1 and IL-6

Question 21

How do pro inflammatory cytokines drive the breakdown of cartilage and amplify MMP?

Answer 21

1. Modulate chondrocyte metabolism to ↑ MMP
   synthesis
2. Inhibit synthesis of MMP inhibitor molecules
3. Inhibit synthesis of collagen & proteoglycans
4. Induce chondrocyte to ↑ prostaglandin which effect matrix synthesis and degradation

Question 22

Does the sub chondral plate thicken or thin during cartilage breakdown?

Answer 22

Thicken, due to the activation of osteoclasts and osteoblasts by cytokines and GFs

Question 23

What do osteophytes form at the joint margin after cartilage damage?

Answer 23

Causes outgrowths of new cartilage which become ossified.

Question 24

What can occur to the synovium upon cartilage breakdown?

Answer 24

Can develop synovitis (becomes edematous and inflamed), which stretches the capsule possibly causing it to become fibrotic.

Question 25

Is osteoarthritis symmetrical or non-symmetrical

Answer 25

Can be non-symmetrical.

Question 26

Where are the most common sites of osteoarthritis?

Answer 26

Neck, Lumbar Spine, Hips, Fingers and Knees

Question 27

Common signs of OA

Answer 27

Large joints that have cracking and stiffness that is relieved with movement.

Question 28

7 physical presentation of OA

Answer 28

``` • Tenderness • Crepitus with joint motion • Bony enlargement of joint Ex) Heberden (DIP) or Bouchard (PIP) • Restricted range on motion • Pain on passive range of motion • Deformity Ex)bowed legs • Joint instability and stiffness that decreases with movement ```

Question 29

Are osteoarthritis symptoms chronic or acute?

Answer 29

Chronic with progressively worsening symptoms

Question 30

What are bone spurs?

Answer 30

Osteophytes that have a parrot beak appearances that fill in the space between the joints where cartilage used to be.

Question 31

What are the lab tests that can be done to diagnose for OA

Answer 31

There are no lab tests specific to OA, just tests that exclude other types of athritis. These tests are: ANA,ESR/C Reactive Protein: identifies general non-specific inflammation if +ve. Followed by RF and anti-CCP to confirm RA with anti-CCP (more specific than RF)

Question 32

Because cartilage has no nerves to transmit pain, the nerves of their structures associates with the joint send pain signals in the form of these 5 pain mediators:

Answer 32

* VIP= vasoactive intestinal peptide * TRPV1= Transient receptor potential cation channel subfamily V member 1 (AKA, vanilloid receptor 1 or, the capsaicin receptor) * NO = Nitric oxide * NGF = nerve growth factor * Prostanoids- example: prostaglandins

Question 33

What are the 5 non-pharrmalogical methods of management for osteoarthritis?

Answer 33

``` Weight loss Exercise Physical therapy Braces Physical modalities (TENS, Acupuncture) ```

Question 34

Name the three main pharmacological treatments of OA.

Answer 34

Acetaminophen (Block pain-impulse from PNS and inhibit CNS PG synthesis) Capsaicin cream (depletes substance P from neurons) Intra-articular sodium hyaluronate (May restore viscoelasticity of synovial fluid and normalize HA synthesis and/or inhibit degradation)