What is the stepwise (graded) management approach for knee osteoarthritis?

Gradewise Treatment of Osteoarthritis Knee

All patients with knee osteoarthritis should begin with combined non-pharmacological interventions (education, exercise, weight loss if overweight) plus acetaminophen/paracetamol as first-line pharmacological therapy, escalating through topical NSAIDs, then oral NSAIDs, then intra-articular injections, and finally surgical options when conservative management fails after 3-6 months. 1, 2

Grade 1: Initial Management (All Patients)

Non-Pharmacological Foundation

• Patient education about the disease, prognosis, and self-management strategies should be initiated immediately, as this reduces pain, improves coping skills, and decreases healthcare visits 1, 2
• Exercise programs must start immediately with quadriceps strengthening and progressive resistance training (effect size 0.57-1.0), including both land-based cardiovascular/resistance exercises and aquatic exercises 1, 2
• Weight reduction is mandatory for overweight/obese patients, as weight loss directly reduces knee OA risk and progression 1, 2
• Walking aids (canes, sticks) should be prescribed as needed to reduce joint loading 1
• Knee bracing or patellar taping can be considered for mechanical support 1

First-Line Pharmacological Treatment

• Acetaminophen/Paracetamol 3,000-4,000 mg daily is the preferred initial and long-term oral analgesic due to its favorable safety profile 1, 3, 2
• Re-evaluate at 2 weeks after initiating treatment 2

Grade 2: Inadequate Response to Acetaminophen

Add Topical Agents Before Oral NSAIDs

• Topical NSAIDs should be the next step before oral NSAIDs, with superior safety profile and clinical efficacy (effect size 0.16-1.03) 1, 3, 2
• Topical capsaicin can be added as an alternative topical agent (effect size 0.41-0.56) 1

Physical Modalities

• TENS (transcutaneous electrical nerve stimulation) for pain management (effect size 0.76) 1, 3
• Manual therapy combined with supervised exercise (not manual therapy alone) 1
• Thermal agents (heat/cold therapy) 1

Grade 3: Persistent Symptoms Despite Topical Therapy

Oral NSAIDs with Risk Stratification

• Oral NSAIDs at the lowest effective dose for the shortest duration should be considered only after topical agents fail 1, 3, 2
• Critical contraindications to avoid:
  • Heart failure patients: NSAIDs cause fluid retention and cardiovascular risks 2
  • Impaired renal function: All NSAIDs are contraindicated; use acetaminophen, tramadol, or opioids instead 2
  • Gastrointestinal problems: Start with acetaminophen or topical NSAIDs first 2
• COX-2 selective inhibitors (coxibs) have lower gastrointestinal toxicity (effect size 0.50) compared to non-selective NSAIDs 1
• For patients with increased GI risk on non-selective NSAIDs, add gastroprotection 1

Alternative Oral Agents

• Tramadol can be considered, though evidence shows only 2 of 3 studies positive versus placebo 1
• Duloxetine may be considered in select cases 1

Grade 4: Acute Flares or Effusion Present

Intra-Articular Corticosteroids

• Intra-articular corticosteroid injections are particularly effective for acute pain flares with effusion (effect size 1.27) 1, 3
• Evidence is mixed on whether effusion predicts better response, so do not reserve injections only for patients with effusion 1

Intra-Articular Hyaluronic Acid

• Intra-articular hyaluronate has mixed evidence (effect size 0.0-0.9 across studies), with 18 of 20 studies showing benefit over placebo 1
• The American College of Rheumatology provides no strong recommendation for or against this modality 1

Grade 5: Refractory to Maximum Conservative Management (3-6 Months)

Opioid Analgesics

• Opioid analgesics are strongly recommended only for patients who have failed both non-pharmacological and pharmacological modalities AND are either unwilling to undergo or not candidates for surgery 1
• Patients must be carefully selected and monitored due to inherent adverse effects 4

Surgical Referral Criteria

• Refer for orthopedic consultation when symptoms persist despite 3-6 months of maximum conservative management 2
• Total knee arthroplasty should be considered when there is radiographic evidence of OA, refractory pain and disability, and significant impact on quality of life 2, 5, 4
• Unicompartmental knee arthroplasty or osteotomy can be considered in young, active patients with single-compartment disease 5
• Arthroscopic lavage and débridement does not alter disease progression and has been shown to have no benefit in knee OA 5, 4

Agents NOT Recommended

• Glucosamine: Conditionally recommended against by the American College of Rheumatology 1
• Chondroitin sulfate: Conditionally recommended against by the American College of Rheumatology 1
• Arthroscopic surgery: No benefit demonstrated 4

Monitoring Schedule

• Initial re-evaluation: 2 weeks after starting exercise and acetaminophen 2
• Ongoing monitoring: Every 3-6 months to assess treatment response 2
• Weight-bearing radiographs (Kellgren-Lawrence grading) should be used to assess joint space narrowing and disease severity, as they demonstrate functional narrowing under physiological load 3, 2

Common Pitfalls to Avoid

• Do not skip non-pharmacological interventions—they provide additional benefit even when analgesics/NSAIDs are used 1
• Do not use oral NSAIDs before trying topical NSAIDs 2
• Do not prescribe NSAIDs to patients with heart failure, renal impairment, or significant GI disease without appropriate risk mitigation 2
• Do not refer for arthroscopic surgery as it provides no benefit 5, 4
• Do not delay surgical referral beyond 3-6 months of failed conservative management in appropriate candidates 2