March 2 - Osteoarthritis

Question 1

What is osteoarthritis (OA)?

Answer 1

Aka “wear-and-tear” arthritis
A progressive joint disease
Occurs when damaged joint tissues are unable to normally repair themselves resulting in a breakdown of cartilage and bone

Question 2

Describe the epidemiology of OA

Answer 2

1 in 10 Canadians
Most prevalent kind of arthritis (more common than RA)
Prevalence rates vary depending on joint involved, ethnicity, age, and gender
Leading cause of disability in Canada and the USA

Question 3

What are the etiology (risk factors) associated with OA?

Answer 3

Obesity
Occupation, sports, trauma
Non-modifiable risk factors: genetics, age, gender

Question 4

Describe obesity as a risk factor for OA

Answer 4

It is the most preventable risk factor for OA of knee/hip/hand
In obesity, weight loss of 5 kg = 50% risk reduction for OA
Predictor for prosthetic joint replacement
If obesity climb continues, approx 70% of all adults will be overweight/obese by 2040

Question 5

Describe overuse/trauma as a risk factor for OA

Answer 5

Overuse: increased OA in occupations with repetitive motions (kneeling, squatting, etc.) and/or those including heavy lifting (farming, construction, sports, etc.)
Injury to joint cartilage due to trauma = improper load bearing and stability = OA risk
Disease: malalignment disorders

Question 6

What type of occupations are associated with OA in the ankles?

Answer 6

Ballet dancers

Soccer players

Question 7

What type of occupations are associated with OA in the knees?

Answer 7

Miners, dockers, physical education teachers, male athletes, concrete workers, shipyard workers, carpenters

Question 8

Describe age as a non-modifiable risk factor for OA

Answer 8

The older you get the more prone to get OA

• 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 9

What is the most common form of OA? Describe it

Answer 9

Primary OA (idiopathic OA)
There is no identifiable cause
It is considered localized when it affects 1-2 joints
It is considered generalized when it affects 3 or more joints

Question 10

Describe secondary OA?

Answer 10

There is a known cause or trigger, such as RA, trauma, disease, obesity, etc.

Question 11

What is the role of chondrocytes?

Answer 11

Chondrocytes produce two major macromolecules that make up cartilage: type II collagen and aggrecan. Chondrocytes also produce enzymes that break down cartilage matrix: matrix metalloproteinases (MMP-3) and ADAMTS-4 and ADAMTS-5

Question 12

What is the role of type II collagen?

Answer 12

Provides cartilage with its tensile strength

Question 13

What is aggrecan?

Answer 13

It is a proteoglycan linked with hyaluronic acid

It is a highly negative charged glycosaminoglycans

Question 14

How do type II collagen and aggrecan work together?

Answer 14

Tightly woven type II collagen constrains aggrecan forcing molecules together. Electrostatic repulsion gives cartilage its compressive stiffness

Question 15

What is the role of MMP-13?

Answer 15

It breaks down type II collagen

Question 16

What i the role of ADAMTS-4 and ADAMTS-5?

Answer 16

Breaks down aggrecan

Question 17

What is required of chondrocytes to maintain healthy cartilage?

Answer 17

Homeostatic balance of synthesis and degradation is required to maintain and restore cartilage quality and volume

Question 18

Describe the pathophysiology of OA

Answer 18

Previously thought that all cartilage damage was due to loss of support structures and subsequent mechanical damage. Now we know that:

1. Mechanical wear/trauma acts as a catalyst starting disease process
2. Actual cartilage damage is a chemically-mediated disease process
3. Complex cellular mechanisms involving increased catabolic (breaking down) responses and blunted anabolic (building up) mechanisms

Question 19

What is the result of cartilage damage?

Answer 19

Cartilage damage leads to increases in chondrocyte activity. The balance of breakdown vs. re-synthesis is lost. It is a vicious cycle of increasing breakdown leading to further cartilage loss

Question 20

Describe the cycle of cartilage breakdown

Answer 20

Present risk factors (age, gender, injury, occupation, sports, etc.) activate chondrocyte activity. Increases in ADAMTS-5 causes the destruction of aggrecans. The loss of aggrecans exposes a collagen receptor, known as DDR-2, which is inactive in healthy cartilage because of the aggrecan masking. Active DDR-2 increases MMP-13. These enzymes are overexpressed, shifting the balance towards degradation. This results in the loss of collagen and proteoglycans

Question 21

Describe the role of pro-inflammatory cytokines in OA

Answer 21

Pro-inflammatory cytokines (TNF-alpha, IF-gamma, IL-1, IL6) drive the breakdown of cartilage and amplifies MMP by:

1. Modulating chondrocyte metabolism to increase MMP synthesis
2. Inhibiting synthesis of MMP inhibitor molecules
3. Inhibiting synthesis of collagen and proteoglycans (structural cells of cartilage)
4. Inducing chondrocyte to increase prostglandin E2, NO, and bone morphogenic protein 2 (BMP-2) synthesis, all which effect matrix synthesis and degradation

Question 22

What are the results of cartilage breakdown?

Answer 22

Changes in sub-chondral bone (osteoclasts and osteoblasts become activated (by cytokines, GFs); thickening of sub-chondral plate)
At the joint margin, near areas of cartilage loss, osteophytes form (initially: outgrowths of new cartilage; eventually become ossified; osteophytes are classic radiographic finding of OA)
The synovium can become edematous and inflamed aka synovitis (capsule stretches and can become fibrotic)

Question 23

What are common sites for OA?

Answer 23

OA primarily affects joints of frequent repetitive movements and/or large load bear; may be non-symmetrical
Neck (very common)
Lumbar spine (very common)
Hip (very common)
Fingers (very common)
Knee (very common)

Question 24

What are physical findings in the clinical presentation of OA?

Answer 24

Tenderness
Crepitus (cracking) with joint motion
Bony enlargement of joint (e.g., Heberden or Bouchard modes at the DIP and PIP joints, respectively)
Restricted range of motion
Pain on passive range of motion
Deformity (e.g., varus deformity of the knees)
Joint instability

Question 25

What will be found in the clinical history of someone presenting with OA?

Answer 25

Joint stiffness upon waking usually lasting less than 30 minutes
Pain often worse with exercise
Pain improvement with rest (but increased stiffness with prolonged rest, over 1 hour)
Chronic, progressively worsening symptoms

Question 26

What is the definition of OA?

Answer 26

Joint pain that occurs for most days of the prior month plus radiographic changes in the symptomatic joint

Question 27

How OA diagnosed?

Answer 27

There is no reliable tests specific to OA
Any lab tests are primarily to:
-exclude other types of arthritis (ESR/CRP - for RA)
-monitor disease
In clinical practise, diagnosis is generally based on history and physical examination
Radiography and joint aspiration used in atypical cases or to exclude other conditons (e.g., red, hot and swollen joint required immediate joint aspiration)

Question 28

Can laboratory test, such as ESR, ANA, CRP, help with the diagnosis of OA?

Answer 28

Yes, but they are used to rule out other forms of arthritis such as RA

Question 29

What are the goals of therapy in OA?

Answer 29

Reduce joint pain
Improve joint function and mobility
Maintain normal articular and peri-articular structures (OT,PT)
Prevent (and possibly reverse) joint cartilage damage

Question 30

What causes pain in OA?

Answer 30

Pain is not related to cartilage loss (since cartilage is aneural - no nerves to transmit pain). However, nerves innervate structures within the joint (synovium, ligaments, joint capsule, muscles, and sub-chondral bone). Osteophytes (bone spurs) can also cause pain

Question 31

What are mediators of pain in OA?

Answer 31

Mediators of pain in OA are a highly active area of research. There’s: vasoactive intestinal peptide (VIP), Transient receptor potential cation channel subfamily V member 1 (TRPV1; aka vanilloid receptor 1 or the capsaicin receptor), nitric oxide (NO), nerve growth factor (NGF), prostanoids (example: prostaglandins). Also substance P

Question 32

What are non-pharmacological treatment options?

Answer 32

Patient education
Weight loss (reduce load on affected joint
Exercise
Physical therapy
Braces
Physical modalities (TENS, acupuncture)

Question 33

Explain patient education as a non-pharmacological treatment option

Answer 33

Educate the patient regarding the chronic nature of the disease (reasonable outcome expectations), referral to patient groups

Question 34

How does exercise treat OA?

Answer 34

Strengthens supportive muscles around the joint (aquatic exercise is great because it reduces the load during movement)

Question 35

How does physical therapy treat OA?

Answer 35

It targets range-of-motion, walking/compensatory assessment

Question 36

How do braces help treat OA?

Answer 36

They help reduce load and provide structural support for joint space and surrounding ligament/muscles

Question 37

What are pharmacological treatment options?

Answer 37

Acetaminophen, NSAIDs, COX-2 inhibitors, Capsaicin cream, Intra-articular glucocorticoids, Intra-articular sodium hyaluronate