Osteoarthritis of the Knee (ข้อเข่าเสื่อม)

• ICD-10:
  • M17.0 Bilateral primary osteoarthritis of knee
  • M17.1 Unilateral primary osteoarthritis of knee
  • M17.2 Bilateral post-traumatic osteoarthritis of knee
  • M17.3 Unilateral post-traumatic osteoarthritis of knee
  • M17.4 Other bilateral secondary osteoarthritis of knee
  • M17.5 Other unilateral secondary osteoarthritis of knee
  • M17.9 Osteoarthritis of knee, unspecified
• ICD-11:
  • FA01.0 Primary osteoarthritis of knee
  • FA01.1 Post traumatic osteoarthritis of knee
  • FA01.2 Other secondary osteoarthritis of knee
  • FA01.Z Osteoarthritis of knee, unspecified

Overview

Osteoarthritis (OA) of the knee is a degenerative joint disease characterised by progressive loss of articular cartilage, subchondral bone changes, synovial inflammation, and osteophyte formation. It represents the leading cause of disability among musculoskeletal disorders, with significant socioeconomic burden due to reduced mobility, work disability, and increased healthcare costs. Clinically, patients present with pain, stiffness, swelling, reduced range of motion, and functional limitations. The disease course is chronic and progressive, with periods of exacerbation.

Unlike inflammatory arthritides such as rheumatoid arthritis, knee OA is primarily a disease of “wear and repair imbalance,” where mechanical loading, biochemical factors, and genetic predisposition interact to damage joint structures. The condition is most common in elderly populations but increasingly affects younger adults due to obesity and sedentary lifestyle.

Epidemiology

Osteoarthritis is the most common joint disorder worldwide. According to the Global Burden of Disease study (2019), over 528 million people are affected globally, with knee OA accounting for more than 80% of cases. Prevalence increases with age: approximately 10% of men and 20% of women aged over 60 years have symptomatic knee OA. Female sex is associated with higher prevalence, particularly post-menopause, suggesting hormonal influence. Obesity is a major modifiable risk factor, with each 5 kg of excess weight increasing the risk of knee OA by 30–40%. Occupational risk (e.g., farmers, miners, construction workers) and high-impact sports (e.g., football, wrestling) also contribute. In Asia, knee OA tends to develop earlier and progress faster, possibly due to lifestyle factors such as squatting and sitting cross-legged.

Pathology and Biomechanics

Pathophysiology

The hallmark of OA pathogenesis is the imbalance between matrix degradation and synthesis. Chondrocytes, under biomechanical and biochemical stress, release degradative enzymes such as matrix metalloproteinases (MMP-13) and aggrecanases, leading to breakdown of type II collagen and aggrecan. Loss of cartilage results in decreased shock absorption. Subchondral bone undergoes sclerosis and formation of bone marrow lesions, visible on MRI. Osteophytes represent a repair attempt but contribute to joint deformity. Inflammatory mediators (IL-1β, TNF-α, prostaglandins) from synovium contribute to pain sensitisation and effusion. Chronic nociceptive input may induce central pain sensitisation, explaining discordance between radiographic severity and symptoms.

Clinical Features

Sign & Symptom	Pathogenesis	Frequency	Specificity
Knee pain (activity-related)	Cartilage loss, subchondral bone stress	++++	++
Morning stiffness <30 min	Synovial inflammation	+++	+++
Crepitus	Irregular cartilage surface	++	++
Reduced range of motion	Capsular thickening, osteophytes	+++	++
Bony enlargement	Osteophyte formation	++	+++

Investigations

The diagnosis of knee OA is primarily clinical but confirmed with imaging:

• Plain radiograph (gold standard): Joint space narrowing, osteophyte formation, subchondral sclerosis, cysts.
• Kellgren–Lawrence grading: Widely used severity scale (Grade 0–4).
• MRI: Sensitive for cartilage, meniscus, and bone marrow lesions; not routinely required.
• Laboratory tests: Usually normal; used to exclude inflammatory arthritis (ESR, CRP, RF, anti-CCP).

Diagnosis

The American College of Rheumatology (ACR) clinical criteria for knee OA include:

• Knee pain plus ≥3 of: age ≥50, morning stiffness <30 min, crepitus, bony tenderness, bony enlargement, no palpable warmth.
• Sensitivity ~95%, specificity ~69%.

In clinical practice, the KL system remains the standard for radiographic diagnosis and is endorsed by ACR and OARSI. Early OA (KL 1–2) may not correlate with symptoms, highlighting the importance of clinical-radiographic correlation. Advanced OA (KL 3–4 or Ahlbäck III–V) strongly correlates with functional impairment and surgical indications. Ultimately, diagnosis of knee OA requires integration of history (pain, stiffness, functional loss), examination (crepitus, deformity, reduced ROM), and imaging evidence, with grading systems serving as tools to standardise disease severity and guide management.

Differential Diagnosis

Disease	Signs & Symptoms	Lab findings	Specific test	Other
Rheumatoid arthritis	Polyarthritis, prolonged morning stiffness	↑ ESR, CRP; RF, anti-CCP positive	Serology	Symmetrical, erosive
Gout	Acute monoarthritis, severe pain	↑ Serum uric acid	Synovial fluid crystals	Tophi in chronic disease
Meniscal tear	Joint line pain, locking, instability	Normal labs	MRI	History of trauma
Septic arthritis	Acute pain, swelling, fever	↑ ESR, CRP, leucocytosis	Joint aspiration	Emergency condition

Treatment Overview

Management of knee OA is multidisciplinary, aiming to relieve pain, improve function, and slow progression. Approaches include:

• Non-pharmacological: Patient education, weight reduction, physical therapy, muscle strengthening, walking aids.
• Pharmacological: Paracetamol, topical/oral NSAIDs, intra-articular corticosteroids or hyaluronic acid, duloxetine.
• Surgical: Arthroscopy (limited role), high tibial osteotomy, unicompartmental or total knee arthroplasty.

Pharmacology / Dosage

Drug	Indication	Dosage
Paracetamol	Mild pain	500–1000 mg PO q6h (max 4 g/day)
Topical NSAIDs (diclofenac gel)	Localised pain	2–4 g applied qid to affected knee
Oral NSAIDs (ibuprofen, naproxen)	Moderate-severe pain	Ibuprofen 400 mg q8h; Naproxen 250–500 mg bid (lowest effective dose)
Duloxetine	Chronic OA pain (central sensitisation)	30–60 mg PO daily
Intra-articular corticosteroid	Flare, severe pain, effusion	Triamcinolone 40 mg IA, up to 3–4/year
Hyaluronic acid injection	Symptom relief in selected patients	2–4 mL IA weekly × 3–5 doses

Pharmacology: Hyaluronic Acid and Platelet-Rich Plasma (PRP)

Intra-articular therapies play an adjunctive role in managing symptomatic knee osteoarthritis (OA), particularly for patients who do not achieve adequate relief from oral or topical pharmacological interventions. Among these, hyaluronic acid (HA) and platelet-rich plasma (PRP) have been widely studied. Both aim to reduce pain, improve joint function, and delay the need for surgery, although evidence and guideline recommendations differ.

Agent	Mechanism	Dosage / Protocol	Efficacy	Guideline stance
Hyaluronic Acid (HA)	• Viscosupplementation: restores viscoelastic properties of synovial fluid • Anti-inflammatory and chondroprotective effects • Improves lubrication and shock absorption	• 2–4 mL intra-articular injection • Weekly × 3–5 doses (depending on preparation) • Some high-molecular weight HA given as single injection	• Provides modest pain relief (peak at 8–12 weeks) • Benefit may last up to 6 months • Effect greater in mild-to-moderate OA	• OARSI: “Conditional” recommendation in selected patients • ACR: Not routinely recommended due to inconsistent efficacy • NICE: Not recommended in routine clinical practice
Platelet-Rich Plasma (PRP)	• Autologous concentrate of platelets, growth factors, cytokines • Promotes cartilage repair, reduces synovial inflammation • Enhances local tissue regeneration	• 3–5 mL intra-articular injection • Single or repeated (commonly 2–3 injections at 2–4 week intervals) • Preparation methods vary (leukocyte-rich vs leukocyte-poor)	• Increasing evidence for pain reduction and function improvement • May have longer-lasting effect than HA (up to 12 months) • More effective in younger patients with mild-to-moderate OA	• OARSI: Insufficient evidence for strong recommendation • ACR: Not routinely recommended outside research • Growing use in clinical practice despite guideline variability

Summary: Both HA and PRP provide intra-articular treatment options for knee OA. HA is established but offers modest and short-term benefits, while PRP is promising with potentially greater and longer-lasting efficacy, especially in early disease. However, variability in preparation techniques and lack of standardisation limit its universal adoption. Current guidelines recommend cautious, individualised use of these agents, preferably in patients not suitable for surgery and after failure of conservative therapy.

Treatment Guideline by Kellgren–Lawrence (KL) Grading

The management of knee osteoarthritis (OA) should follow a stepwise strategy, guided by disease severity on the Kellgren–Lawrence (KL) grading system. The table below summarises recommended interventions at each stage:

KL Grade	Severity	Core Management	Pharmacological	Procedural / Surgical
Grade 1	Doubtful OA	• Patient education • Weight management • Exercise therapy (quadriceps strengthening, low-impact aerobic) • Joint protection strategies	• Usually not required • Paracetamol if symptomatic	• None
Grade 2	Mild OA	• Continue lifestyle and exercise • Bracing / orthotics if malalignment	• Topical NSAIDs (first-line) • Paracetamol as alternative • Oral NSAIDs if inadequate relief	• None routinely
Grade 3	Moderate OA	• Physiotherapy + activity modification • Walking aids if needed	• Oral NSAIDs (lowest effective dose) • Intra-articular corticosteroids for flares • Duloxetine for chronic pain • Consider hyaluronic acid injection	• Arthroscopy not routinely recommended • Surgical evaluation if refractory
Grade 4	Severe OA	• Symptomatic care only • Prehabilitation for surgery	• Limited benefit from conservative drugs • Short-term injections for symptom control	• Total knee arthroplasty (gold standard) • High tibial osteotomy / unicompartmental replacement (selected younger patients)

Summary: Early KL grades (1–2) focus on lifestyle and non-pharmacological interventions, KL 3 adds pharmacologic and injectable therapies, and KL 4 is best managed with surgery. This structured approach ensures patients receive optimal care appropriate to disease stage.

Example Doctor’s Orders

Prognosis

Knee OA is chronic and progressive. Early disease can be managed effectively with lifestyle and pharmacological measures, often delaying need for surgery. Prognosis depends on age, severity at diagnosis, comorbidities, and adherence to weight management. Total knee arthroplasty provides excellent pain relief and functional restoration, with prosthesis survival of 85–90% at 15–20 years. Poor prognostic factors include obesity, severe malalignment, advanced radiographic grade, and persistent pain despite minimal structural changes (suggesting central sensitisation).

Prevention

Preventive strategies include maintenance of healthy body weight, regular low-impact exercise (walking, swimming, cycling), injury prevention in sports, correction of malalignment (orthotics, braces), and early management of meniscal/ligament injuries. Public health interventions targeting obesity and sedentary lifestyle are crucial for reducing global burden of knee OA.

Conclusion

Quiz (USMLE/OSCE)

FAQ

Q: Is knee OA an inevitable part of ageing?

A: No. Age is a strong risk factor, but not all elderly individuals develop OA. Modifiable factors such as obesity, occupational strain, and trauma strongly influence risk. Preventive measures such as maintaining healthy weight and engaging in regular low-impact exercise can reduce risk.

Q: How effective are hyaluronic acid and PRP injections?

A: Hyaluronic acid provides modest short-term pain relief, especially in mild-to-moderate OA. PRP shows promising longer-lasting results but evidence is heterogeneous. Guidelines remain cautious, recommending their use on a case-by-case basis.

Q: When should surgical intervention be considered?

A: Surgery is indicated in advanced OA (KL 3–4) with severe pain and functional limitation despite optimal conservative management. Total knee arthroplasty is the gold standard.