OA

Question 1

Types of arthritis

Answer 1

Inflammatory Arthritis conditions

Degenerative athritis

Question 2

Define inflammatory arthritis

Answer 2

Characterised by inflammation of joints often other tissues, e.g RA, Ankylosing spondylitis, Juvenile Idiopathic Arthritis

Question 3

Define Osteoarthritis (OA)

Answer 3

Degenerative joint disease that may cause progressive damage to articular cartilage and surrounding structures

Question 4

Pathology of OA

Answer 4

Caused by subchondral bone remodelling, neovascularization of the synovium, calcified cartilage and non-calcified cartilage and calcification of cartilage:

1. Loss of joint space
2. Osteophyte formation
3. Subchondral sclerosis - ‘white’ appearance on joint margin
4. Subchondral cyst ‘dark’ appearance on X-rays
5. Deformity

Question 5

Prevalence of OA

Answer 5

• Most prevalent MSK disorder and one of the most oldest diseases in the world
• Pathophysiological changes associated with OA start to show on radiograph but often are not evident in early stages progression
• OA is a well conserved active, reparative process, i.e. when the repair process is sub-optimal
• Most OA is clinically occult: Small patches of OA at knee not likely to progress, Hip OA very likely to progress
• Bone Marrow Lesions (BMLs) are strongly associated w/ pain in OA
• Multifactorial disease: Risk factors for onset and/or progression of OA, Attributable risk varies between joints, Risk factors may interact, Biomechanical risk factors appear dominant
• Hip joint = 2nd most commonly affected joint by OA; (11% England pop)
• Knee OA = most commonly affected joint; 8.5 million UK; 4th largest cause of disability

Question 6

Risk factors for onset of knee OA

Answer 6

1. Older age
2. Female sex
3. Heberden’s (finger) nodes/hand OA
4. Intensive physical activity
5. Occupational risk, i.e. prolonged kneeling, squatting
6. Obesity

Question 7

Clinical symptoms of Knee OA

Answer 7

1. (Persistent) Pain on most days of the last month.
2. Inactivity stiffness lasting no longer than 30 minutes (>30 mins = inflammatory arthritis)
3. Crepitus on moving the joint. 4. Bony tenderness.
4. Limitation of movement.
5. No palpable warmth - Mainly observed in inflammatory arthritis; although may observe in late stages of OA
6. Bony enlargement with osteophytic lipping or osseous protrusions.
7. Symptomatic individuals are usually greater than 50 years of age (But can be younger)

Question 8

Normal articular cartilage

Answer 8

Cartilage tissue is composed of extracellular matrix that is produced by chondrocytes (cells in articular cartilage - making >5% of tissue volume).
• Extracellular matrix consists of 80% water, collagen fibres, proteoglycans, glycosaminoglycans and some non-collagenous proteins
• No blood vessels, nerves or lymphatics in normal articular cartilage - chondrocytes receive nutrition by diffusion of molecules from synovial fluid within joint capsule via extracellular matrix

Question 9

Articular cartilage in OA

Answer 9

Increase in H2O content
Progressive breakdown in collagen network due to demineralisation of type II collagen
Enzymes normally involved in homeostasis play an important role in OA:
1. Stimulation of chondrocytes cause IL-1 to produce plasminogen activators
2. Plasminogen activators increase levels of plasmin
3. Increased levels of plasmin directly results in cartilage degradation by activation of MMPs
4. Collagenase (MMP-3) = breakdown of triple helicase structure of type II collagen

Question 10

Knee Cartilage Homeostasis

Answer 10

Homeostasis of the cartilage within the knee joint is maintained by delicate balance between synthesis and degradation components of the extracellular matrix by chondrocytes and by the actions of soluble meditators that are derives from the chondrocytes and synovium

Question 11

Degradation components of Cartilage homeostasis

Answer 11

Matrix Metalloproteinases (MMP) = key in degradation of type II collagen and aggrecan
Cytokines - IL-1, TNF-α LIF = increase activity of MMPs

Question 12

Synthesis components in cartilage homeostasis

Answer 12

Proteinase inhibitor - naturally occurring tissue induced metalloproteinases (TIMP) = inhibit degradation of type II collagen fibres by MMPs therefore maintain homeostasis

Question 13

Structure of normal articular cartilage

Answer 13

1. Zone I = most superficial; fewest chondrocytes and collagen fibres
   ○ Chondrocytes are quite flat in shape
   ○ At this level there are fewer proteoglycans and higher numbers of organized collagen fibres
   ○ This layer protects the deeper layers from sheer stresses, but is very thin
   ○ It is also in direct contact with the synovial fluid of the joint capsule.
2. Zone II (intermediate)
   ○ Chondrocytes are rounder in this second layer.
   ○ Here, proteoglycans are more prevalent than in any of the other layers, while collagen fibres are relatively disorganized in comparison to the layer above.
   ○ This layer acts as a bridge between the superficial and deep zones, and is the thickest layer.
   ○ It can absorb compressive forces, but not to the same degree as the underlying zone 3
3. Zone 3 (deep)
   ○ Chondrocytes begin to form columns along an axis of vertical collagen fibres.
   ○ This structure is at right angles to the underlying bone – an arrangement that provides the most resistance to compressive forces
4. Zone IV (calcified layer) - superficial to subchondral bone
   ○ Distinguished by the ‘tidemark’ between deep and calcified layers
   ○ This layer provides the connection between bone and cartilage through partial mineralization.
   ○ It acts as a transition between cartilage and the underlying subchondral bone, allowing strong adhesion of the two different tissue types.
   ○ Very few chondrocytes are found in this layer.

Question 14

Normal subchondral bone

Answer 14

Primary cells:
Osteoblasts - produce collagen and bone matrix
Osteoclasts - recruited from circulation; initiate bone matrix reabsorption, ossification of bone matrix and release of enzymes in breakdown of bone matrix
Bone remodelling maintained through coupling of these cells

Question 15

Subchondral bone changes in knee OA

Answer 15

1. Tidemark is breached - articular cartilage in zones 1-3 extend into subchondral plate and blood vessels from subchondral bone breach tidemark into CC and NCC; Causes articular cartilage to lose its avascular nature
2. Vascularisation accompanied by unmyelinated sensory nerve growth into synovium, NCC and osteophytes; aneural property of articular cartilage lost; Causing pain
3. Pain may originate from neural tissue in ligament, muscle, joint capsule, articular cartilage, synovium and osteophytes

Question 16

What scale can be used for knee OA classification on X-ray

Answer 16

The Kellgren-Lawrence OA Classification

Question 17

What is Grade 0 on Kellgren-Lawrence OA Classification

Answer 17

Normal

Question 18

What is Grade 1 on Kellgren-Lawrence OA Classification

Answer 18

Doubtful narrowing of joint space, possible osteophyte development

Question 19

What is Grade 2 on Kellgren-Lawrence OA Classification

Answer 19

Definite osteophytes, absent or questionable narrowing of joint space

Question 20

What is Grade 3 on Kellgren-Lawrence OA Classification

Answer 20

Moderate osteophytes, definite narrowing, some scelerosis and possible joint deformity

Question 21

What is Grade 4 on Kellgren-Lawrence OA Classification

Answer 21

Large osteophytes, marked narrowing, severe sclerosis and joint deformity

Question 22

Key Pathophysiological features observed in knee OA

Answer 22

1. Subchondral sclerosis = subchondral bone remodelling leads to increased bone reabsorption causing the appearance of sclerosis
2. Osteophyte formation = bony outgrowths capped by fibrocartilage; Induced by: mechanical instability in an attempt to stabilise joint or abnormal repair of subchondral bone stress #
3. Progressive cartilage degradation (loss of joint space)

Question 23

Pathogenesis of Bone Marrow Lesions (BMLs) in OA

Answer 23

BMLs strongly associated w/ pain, cartilage attrition (wearing down), meniscal pathology, bone attrition in OA
Cause is uncertain one of the theories:
BMLs are a result of synovial fluid penetrating through defects within the articular cartilage and entering the subchondral bone leading to microfracture and oedema
Frequently identified in patients w/ progressive OA
Can be seen in healthy population - if seen it increases risk of developing OA in the future
Seen in MRI scans

Question 24

Clinical features of LL OA

Answer 24

1. high levels of activity (early OA)
2. hip pain on movement/walking +/- diurnal variations
3. Pain around joint
4. loss of motion (on PROM with R>P)
5. Antalgic or Trendelenburg gait
6. Leg length discrepancy
7. Age - 15% of >55years