11: Osteoarthritis Flashcards
What is osteoarthritis?
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.
Describe the epidemiology of osteoarthritis
- 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
What are the demographics of OA?
- F>M
- Age>50
NB: Dx via radiographic OA (may precede sx) or symptomatic OA (will also have radiographic OA)
What are the common sx of OA?
- Pain
- Related to use
- Worse over course of day
- Transient stiffness in AM (5-30min)
- Transient stiffness after inactivity (“gel” feeling)
- Swelling occasionally
What are the common exam findings of OA?
- +/- swelling (usually cool)
- Tenderness at joint line
- Bony enlargement
- Crepitus
- ↓ROM in late stage
- Deformity of joint (e.g., varus = bow-legged)
Heberden’s vs. Bouchard’s nodes
Heberden’s = DIP
**Bouchard’s **= PIP
With Heberden’s nodes, what is the ddx?
Gout, psoriatic arthritis, OA
What does lab testing reveal for OA?
- No specific tests; dx via H&P, imaging
- ↑CRP, but this is obesity-related
- Synovial fluid:
- Highly viscous
- Non-inflammatory (WBC <1.5K)
What are the radiographic features of OA?
- Joint space narrowing (non-specific)
- Marginal osteophytes (specific)
- Bony sclerosis (subchondral bone)
- Subchondral cysts
- Malalignment (end stage)
True or false: MCPs are affected in OA
False
What is the ddx for join erosions on x-ray?
HLA-B27 associated diseases, gout, erosive OA
What are common MRI findings in OA?
- Bone marrow lesions (“edema”)
- Synovitis
- Cartilage loss
- Effusion
What is the distribution of primary OA?
- DIP, PIP, 1st CMC, hip, knee, 1st MTP, spine
- Exceptions suggest secondary OA
What are the causes of secondary OA?
- 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
What does the presence of chondrocalcinosis with OA suggest?
Secondary OA (consider metabolic problems and endocrinopathies)
- Hemochromatosis
- Hyperparathyroidism
- Hypothyroidism
- Hypophasphatasia
- Hypomagnesemia
- Neuropathic joints
- Trauma
- Aging/hereditary
What are risk factors for primary OA?
- Age
- Sex
- Obesity
- genetics
- bone mass/density
- joint injury
- joint deformity
- muscle weakness
- joint inflammation
- occupation
NB: 3 F’s: fifty, female, fat
What is the general pathogenesis of OA?
- Mechanically driven
- Chemically mediated
- Attempted (aberrant) repair
What is the function and structure of articular cartilage?
FUNCTION
- Bear and distribute load applied to joint
- Provide low friction movement
STRUCTURE
- Matrix
- Chondrocytes
True or false: One pound of weight gain transmits one pound of load on the knee
False; it transmits FOUR pounds of load on the knee
What is the anaboloic function of chondrocytes in cartilage?
- Synthesize and secrete matrix components:
- Collagens
- Aggrecan
- Leucine rich repeat (LRR) proteins
- Other macromolecules
What is the function of proteoglycans?
Water retention to provide cushioning effect in joints
What is the catabolic function of chondrocytes?
- Synthesize and secrete substances which degrade matrix:
- MMPs (collagenases, stromelysins, gelatinases)
- Aggrecanases (ADAMTS-4,5)
- Cytokines (especially IL-1) and other inflammatory mediators
Describe chondrocyte activation in OA
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
What are the pathologic changes to cartilage in OA?
- Degradation of collagen fibrils
- Loss of sulfated proteoglycans
- –> loss of water
- –> decreased compressibility/distensability
- Cartilage fibrillation
- Joint space narrowing = cartilage loss
Describe the imbalance seen in cartilage of progressive OA
INJURY PREDOMINATES
- ↑MMP
- COX-2 –> PGE2
- iNOS –> NO
- Chondrocyte apoptosis
- Proteoglycan degradation
- Collagen degradation
REPAIR INSUFFICIENT
- ↓proteoglycan synthesis
- ↓collagen synthesis
- ↓water content
- ↓elasticity
Describe peri-articular bone changes in OA
- ↑thickness subchondral bone plate –> sclerosis
- Remodeling of subchondral trabecular bone –> cysts and bone lesions on MRI
- Osteophytes (formation of new bone at joint margins)
Which occurs first: cartilage degradation or bone changes?
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
How do changes in subchondral bone precipitate changes in cartilage?
- ↑bone volume
- ↑turnover –> ↓mineralization –> ↓bone stiffness –> microfractures (this causes the pain seen in OA)
- originally called “bone marrow edema”
What are osteocytes?
- 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
Describe synovitis in OA
- 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)
