What is the recommended treatment for osteoarthritis (OA) of the knee?

Treatment Prescription for Knee Osteoarthritis

Start with oral acetaminophen up to 4,000 mg daily as first-line therapy, and if inadequate response after 2 weeks, escalate to oral NSAIDs (such as ibuprofen 1,200-2,400 mg/day or naproxen) or topical NSAIDs (diclofenac sodium topical solution 2%, 40 mg twice daily to each knee), combined with a structured exercise program including quadriceps strengthening and aerobic conditioning. 1

Initial Pharmacologic Management

First-Line: Acetaminophen

• Begin with acetaminophen 1,000 mg four times daily (maximum 4,000 mg/day) for mild to moderate pain 1
• Counsel patients to avoid all other acetaminophen-containing products including over-the-counter cold remedies and combination opioid products 1
• Acetaminophen provides statistically significant pain relief compared to placebo, though the clinical importance is modest 1
• This recommendation prioritizes safety over maximal efficacy, as acetaminophen has significantly fewer gastrointestinal complications than NSAIDs 1

Important caveat: Recent evidence suggests acetaminophen may be less effective than traditionally believed. One high-quality RCT found acetaminophen no better than placebo at 2 and 12 weeks, while diclofenac showed significant improvement 2. However, guidelines still recommend acetaminophen first due to superior safety profile 1.

Second-Line: NSAIDs (If Acetaminophen Fails)

For patients without GI risk factors:

• Oral NSAIDs: Ibuprofen 1,200-2,400 mg/day or naproxen 500-1,000 mg/day 1
• Topical NSAIDs: Diclofenac sodium topical solution 2%, apply 40 mg (2 pump actuations) to each painful knee twice daily 1, 3
• NSAIDs demonstrate superior efficacy to acetaminophen with effect sizes of 0.20 for pain reduction 4
• Patient preference studies show 2.46 times more patients prefer NSAIDs over acetaminophen 4

For patients with increased GI risk (age ≥60 years, history of peptic ulcer disease, GI bleeding, concurrent corticosteroids, or anticoagulants):

• Topical NSAIDs (preferred due to lower systemic absorption) 1
• OR oral NSAIDs plus gastroprotective agent (PPI or misoprostol) 1
• OR COX-2 selective inhibitors (celecoxib 200 mg daily) 1
• All three options show reduced GI adverse events compared to non-selective NSAIDs alone, with no clear advantage among them 1

Topical NSAID Application Instructions

• Apply to clean, dry skin without cuts, infections, or rashes 3
• Prime pump by pressing 4 times before first use (discard this portion) 3
• Dispense 2 pump actuations into palm, apply evenly around front, back, and sides of knee without massaging 3
• Wash hands immediately after application 3
• Avoid showering/bathing for 30 minutes after application 3
• Do not cover with clothing until completely dry 3
• Avoid heat, occlusive dressings, and sun exposure to treated area 3

Non-Pharmacologic Management (Essential Component)

Strongly Recommended Interventions

• Cardiovascular/resistance land-based exercise programs targeting quadriceps strengthening and range of motion 1
• Aquatic exercise as alternative for aerobically deconditioned patients 1
• Weight loss counseling for all overweight patients (reduces OA risk and symptoms) 1
• Patient education and self-management programs 1

These non-pharmacologic interventions show effect sizes of 0.57-1.0 for pain reduction and provide sustained benefits for 6-18 months 1.

Adjunctive Therapies for Inadequate Response

Intra-articular Corticosteroids

• Use for acute pain flares, especially with effusion 1
• Provides clinically important short-term pain relief at 1 week post-injection 1
• Benefits diminish after 2-3 weeks with little evidence for longer-term efficacy 1
• Reserve for episodic exacerbations rather than routine use 1

Conditionally Recommended Options

• Manual therapy combined with supervised exercise (not manual therapy alone) 1
• Medially wedged insoles for lateral compartment OA 1
• Laterally wedged subtalar strapped insoles for medial compartment OA 1
• Walking aids as needed for functional support 1

Treatments NOT Recommended

Strong Recommendations Against

• Glucosamine and chondroitin sulfate: Best evidence shows no benefit over placebo 1
• Oral narcotics including tramadol: Notable increase in adverse events without effective pain or function improvement 1
• Topical capsaicin: Conditionally recommended against 1

Inconclusive Evidence (No Recommendation)

• Intra-articular hyaluronic acid: Evidence quality concerns regarding publication bias and trial quality; not recommended for routine use 1
• Duloxetine and opioid analgesics: Insufficient evidence 1

Clinical Algorithm Summary

1. Initiate acetaminophen 4,000 mg/day + exercise program + weight loss if indicated 1
2. If inadequate response after 2 weeks: Add or switch to NSAIDs (topical preferred if GI risk factors present) 1
3. For acute flares with effusion: Add intra-articular corticosteroid injection 1
4. If persistent inadequate response: Consider referral for surgical evaluation (high tibial osteotomy for unicompartmental disease or arthroplasty for advanced disease) 1

Critical Safety Considerations

• Avoid combining oral and topical NSAIDs unless benefit clearly outweighs risk, with periodic laboratory monitoring 3
• Monitor for NSAID cardiovascular and renal complications, especially in elderly patients 1
• Use lowest effective NSAID dose for shortest duration to minimize adverse events 3
• Reassess treatment response every 2-4 weeks and adjust therapy accordingly rather than continuing ineffective treatments 1