11: Osteoarthritis

Question 1

What is osteoarthritis?

Answer 1

A disease in which all structures of the joint have undergone pathologic change, often in concert. The pathologic sine qua non of disease is hyaline articular cartilage loss, present in a focal and, initially, nonuniform manner. This is accompanied by increasing thickness and sclerosis of the subchondral bony plate, by outgrowth ofosteophytes at the joint margin, by stretching of the articular capsule, by mild synovitis in many affected joints, and by weakness of muscles bridging the joint.

Question 2

Describe the epidemiology of osteoarthritis

Answer 2

• Most common form of arthritis
• At least 20 million (>10%) of US
• More functional limitation, work loss and physical disability than any other chronic dz
• Most common indication for total joint arthroplasty

Question 3

What are the demographics of OA?

Answer 3

• F>M
• Age>50

NB: Dx via radiographic OA (may precede sx) or symptomatic OA (will also have radiographic OA)

Question 4

What are the common sx of OA?

Answer 4

• Pain
  
  • Related to use
  • Worse over course of day
• Transient stiffness in AM (5-30min)
• Transient stiffness after inactivity (“gel” feeling)
• Swelling occasionally

Question 5

What are the common exam findings of OA?

Answer 5

• +/- swelling (usually cool)
• Tenderness at joint line
• Bony enlargement
• Crepitus
• ↓ROM in late stage
• Deformity of joint (e.g., varus = bow-legged)

Question 6

Heberden’s vs. Bouchard’s nodes

Answer 6

Heberden’s = DIP

**Bouchard’s **= PIP

Question 7

With Heberden’s nodes, what is the ddx?

Answer 7

Gout, psoriatic arthritis, OA

Question 8

What does lab testing reveal for OA?

Answer 8

• No specific tests; dx via H&P, imaging
• ↑CRP, but this is obesity-related
• Synovial fluid:
  
  • Highly viscous
  • Non-inflammatory (WBC <1.5K)

Question 9

What are the radiographic features of OA?

Answer 9

• Joint space narrowing (non-specific)
• Marginal osteophytes (specific)
• Bony sclerosis (subchondral bone)
• Subchondral cysts
• Malalignment (end stage)

Question 10

True or false: MCPs are affected in OA

Answer 10

False

Question 11

What is the ddx for join erosions on x-ray?

Answer 11

HLA-B27 associated diseases, gout, erosive OA

Question 12

What are common MRI findings in OA?

Answer 12

• Bone marrow lesions (“edema”)
• Synovitis
• Cartilage loss
• Effusion

Question 13

What is the distribution of primary OA?

Answer 13

• DIP, PIP, 1st CMC, hip, knee, 1st MTP, spine
• Exceptions suggest secondary OA

Question 14

What are the causes of secondary OA?

Answer 14

• Dysplastic
  
  • Chondrodysplasia
  • Epiphyseal dysplasia
  • Contenital hip dislocation
• Post-traumatic
  
  • Acute
  • Repetetive
  • Postoperative
• Post-inflammatory
  
  • Infection
  • Inflammatory arthropathy (e.g., RA)
• Neuropathic (Charcot joint: loss of joint sensation/proprioception)
  
  • DM –> diabetic neuropathy (midfoot, MTPs 1-5 b/l, destruction secondary OA > primary OA)
  • Tabes dorsalis (slow degeneration of nerves primarily in the dorsal columns of the spinal cord)
  • EtOH
• Endocrine/metabolic
  
  • Acromegaly
  • Hyperparathyroidism
  • Ochronosis
  • Hemochromatosis
• Connective tissue
  
  • Hypermobility syndromes
  • Mucopolysaccharidoses
• Endemic
  
  • Kashin-Beck dz
  • Mseleni dz
• Skeletal failure
  
  • Osteonecrosis
  • Osteochondritis
  • Paget’s dz

Question 15

What does the presence of chondrocalcinosis with OA suggest?

Answer 15

Secondary OA (consider metabolic problems and endocrinopathies)

• Hemochromatosis
• Hyperparathyroidism
• Hypothyroidism
• Hypophasphatasia
• Hypomagnesemia
• Neuropathic joints
• Trauma
• Aging/hereditary

Question 16

What are risk factors for primary OA?

Answer 16

• Age
• Sex
• Obesity
• genetics
• bone mass/density
• joint injury
• joint deformity
• muscle weakness
• joint inflammation
• occupation

NB: 3 F’s: fifty, female, fat

Question 17

What is the general pathogenesis of OA?

Answer 17

• Mechanically driven
• Chemically mediated
• Attempted (aberrant) repair

Question 18

What is the function and structure of articular cartilage?

Answer 18

FUNCTION

• Bear and distribute load applied to joint
• Provide low friction movement

STRUCTURE

• Matrix
• Chondrocytes

Question 19

True or false: One pound of weight gain transmits one pound of load on the knee

Answer 19

False; it transmits FOUR pounds of load on the knee

Question 20

What is the anaboloic function of chondrocytes in cartilage?

Answer 20

• Synthesize and secrete matrix components:
  
  • Collagens
  • Aggrecan
  • Leucine rich repeat (LRR) proteins
  • Other macromolecules

Question 21

What is the function of proteoglycans?

Answer 21

Water retention to provide cushioning effect in joints

Question 22

What is the catabolic function of chondrocytes?

Answer 22

• Synthesize and secrete substances which degrade matrix:
  
  • MMPs (collagenases, stromelysins, gelatinases)
  • Aggrecanases (ADAMTS-4,5)
  • Cytokines (especially IL-1) and other inflammatory mediators

Question 23

Describe chondrocyte activation in OA

Answer 23

ACTIVATION

• Mechanical stress
• Inflammatory cytokines (inflammation is minor; not to same extent as in RA or gout)
• Collagen and fibronectin fragments (aggravators; bind chondrocytes and activate them)

RESPONSE

• Chondrocytes release: IL-1, TNF-a, NO, PGE2
  
  • ​Suppress matrix synthesis
  • Promote matrix degradation
  • Chondrocyte apoptosis

Question 24

What are the pathologic changes to cartilage in OA?

Answer 24

• Degradation of collagen fibrils
• Loss of sulfated proteoglycans
  
  • –> loss of water
  • –> decreased compressibility/distensability
• Cartilage fibrillation
• Joint space narrowing = cartilage loss

Question 25

Describe the imbalance seen in cartilage of progressive OA

Answer 25

INJURY PREDOMINATES

• ↑MMP
• COX-2 –> PGE2
• iNOS –> NO
• Chondrocyte apoptosis
• Proteoglycan degradation
• Collagen degradation

REPAIR INSUFFICIENT

• ↓proteoglycan synthesis
• ↓collagen synthesis
• ↓water content
• ↓elasticity

Question 26

Describe peri-articular bone changes in OA

Answer 26

• ↑thickness subchondral bone plate –> sclerosis
• Remodeling of subchondral trabecular bone –> cysts and bone lesions on MRI
• Osteophytes (formation of new bone at joint margins)

Question 27

Which occurs first: cartilage degradation or bone changes?

Answer 27

Evidence favors bone as initial site of changes in OA

• Early increase in bone turnover
• Development of osteophytes, changes in subchondral cortical/trabecular bone organizatin precede decreased thickness of articular cartilage

Question 28

How do changes in subchondral bone precipitate changes in cartilage?

Answer 28

• ↑bone volume
• ↑turnover –> ↓mineralization –> ↓bone stiffness –> microfractures (this causes the pain seen in OA)
• originally called “bone marrow edema”

Question 29

What are osteocytes?

Answer 29

• Proliferation of periosteal cells at joint margins –> differentiation into chondrocytes
• Endochondral ossification stimulated by **TGF-B **and **BMP-2 **as a reparative attempt to increase joint surface area for joint stability
• Leads to limitation of mobility

Question 30

Describe synovitis in OA

Answer 30

• Synovial lining layer hyperplasia
• ↑angiogenesis
• ↑expression IL-1, TNF, COX2, MMPs
• Predictive of OA progression
• ↑proinflammatory genes in cartilage and peripheral blood mononuclear cells (PBMCs)