Osteoarthritis

Osteoarthritis is a degenerative joint disorder characterized by the progressive loss of articular cartilage, changes in subchondral bone, synovitis, and osteophyte formation. The pathogenesis involves a complex interplay between mechanical, biochemical, and genetic factors:

1. Cartilage Degradation
   • In healthy joints, articular cartilage is maintained by a balance between anabolic and catabolic activities of chondrocytes.
   • In OA, increased production of matrix-degrading enzymes such as matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS) leads to the breakdown of collagen type II and aggrecan, resulting in cartilage loss.
   • Cartilage fragments release into the synovial fluid, promoting synovial inflammation.
2. Subchondral Bone Changes
   • Increased mechanical loading stimulates bone remodeling, causing subchondral sclerosis and formation of subchondral cysts.
   • The resultant bone marrow lesions are associated with pain and joint dysfunction.
3. Synovial Inflammation
   • Synovitis is present in many OA cases and contributes to symptom severity.
   • Inflammatory cytokines (e.g., IL-1β, TNF-α) promote chondrocyte catabolism and synovial inflammation, leading to further cartilage degradation.
4. Osteophyte Formation
   • Growth of new bone at joint margins (osteophytes) occurs in response to mechanical stress and biochemical signaling, leading to joint deformity.

Risk Factors

4. Age: Risk increases with advancing age.
5. Gender: More common in women, especially after menopause, suggesting hormonal influence.
6. Genetics: Family history increases risk, indicating genetic susceptibility.
7. Obesity: Excess weight increases joint loading and adipose tissue-derived cytokines contribute to inflammation.
8. Joint Injury: Previous joint injuries (e.g., ACL tear, meniscus injury) predispose to OA development.
9. Occupation and Physical Activity: Repetitive stress from certain jobs or sports can increase risk.

Clinical Presentation

1. Symptoms
   • Joint Pain: Worsens with activity and improves with rest; early morning stiffness lasts <30 minutes.
   • Joint Stiffness: Particularly after periods of inactivity (gelling phenomenon).
   • Limited Range of Motion: Due to pain and structural changes.
   • Crepitus: Sensation of grating within the joint.
2. Commonly Affected Joints
   • Knees: Most commonly affected; weight-bearing stress leads to pain, instability, and deformity (varus or valgus).
   • Hips: Causes groin pain radiating to the thigh or buttocks.
   • Hands: Involvement of the distal interphalangeal joints (Heberden’s nodes), proximal interphalangeal joints (Bouchard’s nodes), and first carpometacarpal joint.
   • Spine: Involvement of the cervical and lumbar spine may cause radiculopathy.

Diagnosis

1. Clinical Evaluation
   • Based on history and physical examination findings, including joint pain, stiffness, crepitus, and reduced range of motion.
   • American College of Rheumatology (ACR) Criteria for Knee OA Diagnosis:
     • Age ≥ 50 years, morning stiffness < 30 minutes, and crepitus on active motion of the knee.
2. Radiographic Findings
   • Joint Space Narrowing (JSN): Due to cartilage loss.
   • Osteophytes: Bony projections at joint margins.
   • Subchondral Sclerosis and Cysts: Increased bone density and fluid-filled cysts beneath the cartilage.
3. Advanced Imaging
   • MRI: Useful for evaluating early cartilage changes, bone marrow lesions, and meniscal tears.
   • Ultrasound: Detects synovitis, effusions, and osteophytes.
4. Laboratory Tests
   • Usually unremarkable; normal ESR and CRP help distinguish OA from inflammatory arthritis (e.g., rheumatoid arthritis).
   • Synovial fluid analysis typically shows non-inflammatory characteristics (WBC < 2,000 cells/µL).

Management

1. Non-Pharmacological Management

• Patient Education and Self-Management
  • Involves teaching patients about the disease, lifestyle modifications, and coping strategies.
• Weight Loss
  • For overweight or obese patients, even a 5% reduction in body weight can significantly alleviate symptoms.
• Exercise
  • Low-impact aerobic activities (e.g., swimming, cycling) and strengthening exercises for quadriceps and hamstrings improve joint stability and function.
• Physical Therapy
  • Focus on range of motion, muscle strengthening, and joint stabilization.
• Assistive Devices
  • Use of braces, orthotics, or canes to reduce joint loading.

2. Pharmacological Management

• Analgesics and NSAIDs
  • Acetaminophen: Initial choice for mild pain; up to 3-4 g/day, with caution in liver disease.
  • NSAIDs: More effective for moderate to severe pain.
    • Ibuprofen: 400-800 mg TID-QID.
    • Naproxen: 500 mg BID.
    • Celecoxib (COX-2 inhibitor): 100-200 mg once or twice daily; preferred in patients at risk for gastrointestinal complications.
  • Topical NSAIDs: Diclofenac gel can be applied to joints (e.g., 4 g QID for knees, hands).
• Intra-Articular Injections
  • Corticosteroids: Triamcinolone acetonide (40 mg for large joints) every 3-4 months for acute exacerbations.
  • Hyaluronic Acid: Viscosupplementation to improve joint lubrication, although evidence of efficacy is variable.
• Other Medications
  • Duloxetine: Approved for chronic musculoskeletal pain, 30-60 mg daily.
  • Tramadol: For patients with inadequate response to NSAIDs; start at 25 mg and titrate to 50-100 mg every 4-6 hours.

3. Surgical Management

• Arthroscopy: Indicated for mechanical symptoms (locking, catching) due to loose bodies.
• Osteotomy: Realignment procedures for unicompartmental knee OA.
• Joint Replacement (Arthroplasty)
  • Total Knee Arthroplasty (TKA) or Total Hip Arthroplasty (THA): For patients with severe pain and functional limitations refractory to conservative measures.
  • Unicompartmental Knee Arthroplasty: Suitable for isolated medial or lateral compartment knee OA.

Complications

• Progressive Joint Damage: May lead to significant disability.
• Spinal OA: Can cause nerve impingement, spinal stenosis, and radiculopathy.
• Secondary Infections: Following intra-articular injections or surgical interventions.
• Comorbidities: Obesity, cardiovascular disease, and depression are commonly associated.

Monitoring and Follow-Up

• Regular Assessment: Evaluate pain, joint function, and side effects of ongoing treatment.
• Radiographic Monitoring: To assess joint deterioration and guide the need for surgical intervention.
• Adjust Management Based on Disease Progression: Escalate treatment for worsening symptoms.

Emerging Treatments and Future Directions

• Disease-Modifying Osteoarthritis Drugs (DMOADs): Potential agents targeting cartilage regeneration, including anti-NGF antibodies, matrix metalloproteinase inhibitors, and intra-articular gene therapy.
• Platelet-Rich Plasma (PRP): Intra-articular injections for symptom relief, though more research is needed.
• Stem Cell Therapy: Being explored for regenerative potential in damaged cartilage.