Osteoarthritis vs. Rheumatoid Arthritis

Osteoarthritis (OA) vs. Rheumatoid Arthritis (RA) Comparison

Osteoarthritis (OA)

• Wear-and-tear, aging, and biomechanical stress are causes
• Cartilage degrades, with an imbalance between synthesis and degradation
• Chondrocytes secrete MMPs, degrading type II collagen
• Inflammation is secondary, pain is nociceptive, stemming from structural joint damage
• Sensitization occurs peripherally and centrally
• Pain is deep and achy, worsening with use
• Morning stiffness lasts less than 1 hour; joint crepitus may occur
• Bouchard's and Heberden's nodes (bony outgrowths) are present
• Weight-bearing joints (knees, hips, spine) are often affected
• Onset is gradual, developing over years
• Joint pattern is asymmetrical and localized to affected joints
• Synovial fluid is non-inflammatory with mild WBCs
• Biomarkers are not prominent
• Cytokines involved are TNF and IL-1, but play a less dominant role
• No systemic features are present
• The disease is initiated by cartilage matrix damage from mechanical injury
• Chondrocytes release MMPs, TNF, and nitric oxide
• Synovial inflammation (synovitis) is secondary
• Cartilage degradation leads to bone-on-bone contact & osteophyte formation
• Joint damage is degeneration of articular cartilage and remodeling of subchondral bone
• Typical finger joint deformities include Bouchard's and Heberden's nodes
• Synovial fluid is non-inflammatory
• Extra-articular features are rare
• Pain worsens with activity and improves at the end of the day

Rheumatoid Arthritis (RA)

• An autoimmune disease with genetic, environmental, and epigenetic factors as causes
• Autoimmune attack occurs on the synovial membrane
• CD4+ T cells activate a cytokine cascade
• Synovial hyperplasia (pannus formation) occurs
• RANKL release stimulates osteoclasts, leading to bone erosion
• Pain is inflammatory, caused by joint destruction due to chronic inflammation
• Symmetrical joint swelling (hands, wrists, feet) occurs
• Morning stiffness lasts more than 1 hour
• Fatigue, malaise, rheumatoid nodules, and systemic involvement (e.g., skin, heart, lungs) are present
• Onset is relatively rapid, occurring over weeks to months
• Joint involvement is symmetrical, affecting small and large joints
• Synovial fluid is inflammatory with exudate and a high WBC count
• Biomarkers include Rheumatoid Factor (RF), anti-citrullinated protein antibodies (ACPA), and elevated CRP and ESR
• Cytokines involved are TNF-α, IL-1, IL-6, IL-17, and IFN-γ
• They promote synovial inflammation and cartilage degradation
• RANKL increases bone erosion via osteoclast activation
• Systemic features present include fatigue, weight loss, fever, and systemic organ involvement
• CD4+ T cells initiate an immune response, cytokines activating macrophages and synovial cells leading to inflammation
• B cells produce rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)
• Synovial hyperplasia leads to pannus formation and joint destruction
• Joint damage is inflammatory destruction of synovial membrane, cartilage, bone, and ligaments
• Typical deformities include ulnar deviation, swan neck, and boutonniere deformities
• Synovial fluid is inflammatory with immune markers (RF, ACPA)
• Common extra-articular features include rheumatoid nodules, lung involvement, vasculitis, and pericarditis
• Pain improves with use and lasts more than 1 hour

Cytokines and Biomarkers in Rheumatoid Arthritis (RA)

• CD4+ T-helper cells are central to initiating RA by recognizing modified self-proteins and promoting cytokine cascades
• Treg and Th17 subsets contribute to disease progression via inflammatory signaling

Key Cytokines Involved:

• TNF-α stimulates synovial cells to produce proteases, leading to cartilage damage
• IL-1 works with TNF-α to enhance synovial inflammation and bone erosion
• IL-17 stimulates neutrophils and monocytes, contributing to joint destruction
• IFN-γ activates macrophages and synovial fibroblasts
• RANKL promotes osteoclast differentiation and activation, leading to bone resorption

Key Biomarkers:

• Rheumatoid Factor (RF): Autoantibodies (IgG/IgM) against the Fc portion of IgG
• Not specific, but present in many RA patients
• Anti-Citrullinated Protein Antibodies (ACPA): Highly specific, present in ~70% of RA cases
• Often detected before clinical symptoms
• C-Reactive Protein (CRP) & ESR: General markers of systemic inflammation
• Used to monitor disease activity
• RANKL/OPG Pathway: Imbalance contributes to bone erosion, increased RANKL and decreased OPG promote osteoclastogenesis