March 2 - Osteoarthritis Flashcards
What is osteoarthritis (OA)?
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
Describe the epidemiology of OA
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
What are the etiology (risk factors) associated with OA?
Obesity
Occupation, sports, trauma
Non-modifiable risk factors: genetics, age, gender
Describe obesity as a risk factor for OA
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
Describe overuse/trauma as a risk factor for OA
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
What type of occupations are associated with OA in the ankles?
Ballet dancers
Soccer players
What type of occupations are associated with OA in the knees?
Miners, dockers, physical education teachers, male athletes, concrete workers, shipyard workers, carpenters
Describe age as a non-modifiable risk factor for OA
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
What is the most common form of OA? Describe it
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
Describe secondary OA?
There is a known cause or trigger, such as RA, trauma, disease, obesity, etc.
What is the role of chondrocytes?
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
What is the role of type II collagen?
Provides cartilage with its tensile strength
What is aggrecan?
It is a proteoglycan linked with hyaluronic acid
It is a highly negative charged glycosaminoglycans
How do type II collagen and aggrecan work together?
Tightly woven type II collagen constrains aggrecan forcing molecules together. Electrostatic repulsion gives cartilage its compressive stiffness
What is the role of MMP-13?
It breaks down type II collagen
What i the role of ADAMTS-4 and ADAMTS-5?
Breaks down aggrecan
What is required of chondrocytes to maintain healthy cartilage?
Homeostatic balance of synthesis and degradation is required to maintain and restore cartilage quality and volume
Describe the pathophysiology of OA
Previously thought that all cartilage damage was due to loss of support structures and subsequent mechanical damage. Now we know that:
- Mechanical wear/trauma acts as a catalyst starting disease process
- Actual cartilage damage is a chemically-mediated disease process
- Complex cellular mechanisms involving increased catabolic (breaking down) responses and blunted anabolic (building up) mechanisms
What is the result of cartilage damage?
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
Describe the cycle of cartilage breakdown
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
Describe the role of pro-inflammatory cytokines in OA
Pro-inflammatory cytokines (TNF-alpha, IF-gamma, IL-1, IL6) drive the breakdown of cartilage and amplifies MMP by:
- Modulating chondrocyte metabolism to increase MMP synthesis
- Inhibiting synthesis of MMP inhibitor molecules
- Inhibiting synthesis of collagen and proteoglycans (structural cells of cartilage)
- Inducing chondrocyte to increase prostglandin E2, NO, and bone morphogenic protein 2 (BMP-2) synthesis, all which effect matrix synthesis and degradation
What are the results of cartilage breakdown?
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)
What are common sites for OA?
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)
What are physical findings in the clinical presentation of OA?
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
