Overview

Knee osteoarthritis is a chronic, whole-joint disorder characterized by pain, stiffness, functional limitation and progressive structural change affecting cartilage, subchondral bone, synovium, menisci, ligaments and peri-articular muscles. Prevalence rises with age and obesity and contributes substantially to global disability; recent GBD analyses and reviews highlight knee OA as a leading cause of pain and years lived with disability worldwide. Clinically, diagnosis is often made without imaging using validated rules, and core first-line care is education + exercise + weight management; pharmacologic options (topical/oral NSAIDs, short-term intra-articular corticosteroid) and device/surgical options are layered according to severity and phenotype. Important risk factors include age, female sex, obesity/metabolic factors, prior knee injury, malalignment and high occupational load; major complications are chronic pain, falls risk, deconditioning, adverse medication effects, and eventual need for arthroplasty. ILLUStration: Population funnel (general population → risk factors → symptomatic KOA) with side bars: Risk factors (age, obesity, prior injury, malalignment, high occupational kneeling/squatting) and Complications (functional decline, falls, analgesic harms, arthroplasty). (The Lancet, NICE, AAFP)

Anatomy & Physiology

• Joint surfaces: femorotibial (medial/lateral) and patellofemoral compartments lined by hyaline cartilage; menisci distribute load and enhance stability; collateral and cruciate ligaments constrain translation/rotation.
  
• Synovium: regulates nutrient exchange and produces hyaluronan-rich fluid for lubrication; can mount inflammatory responses.
  
• Subchondral bone: shock absorption and load transfer; communicates with cartilage via osteochondral channels.
  
• Neuromuscular control: quadriceps, hip abductors and calf musculature modulate joint loading; alignment and gait mechanics determine compartmental stresses.

Aetiology and Risk Factors

Aetiology (multifactorial, interacting “whole-joint” mechanisms)

• Mechanical: abnormal joint loading (varus/valgus malalignment, meniscal loss) drives focal degeneration.
  
• Biological: low-grade synovitis, subchondral remodeling and BMLs; nociceptive and nociplastic pain contributions.
  
• Metabolic: obesity/adipokines and insulin resistance increase risk and symptom burden. (The Lancet, ScienceDirect)

Risk Factors

• Non-modifiable: age; female sex; genetics/family history.
  
• Modifiable: overweight/obesity; prior knee injury (e.g., ACL/meniscus); high occupational kneeling/squatting/lifting; malalignment; low muscle strength; physical inactivity. Highest-yield modifiables for incident KOA: obesity, previous knee injury, high occupational load.

Pathophysiology

• Joint load mismatch (demand > capacity) → focal cartilage matrix damage + meniscal stress.
  
• Synovial activation (cytokines, neuropeptides) → pain and effusion; central sensitization in some.
  
• Subchondral bone remodeling and BMLs → nociceptor ingrowth/angiogenesis → pain and structural progression.
  
• Malalignment/deconditioning perpetuate compartmental overload → osteophytes, joint-space loss, functional decline.

Clinical Manifestations

• Symptoms: activity-related knee pain (walking, stairs, squatting), short morning stiffness (<30 min), “giving way”, crepitus, swelling, reduced function and confidence; flares after load spikes; nocturnal pain in advanced disease.
  
• Signs: crepitus on motion, bony enlargement, varus/valgus malalignment, effusion/warmth (mild), reduced ROM (flexion loss), quadriceps weakness, antalgic gait; patellofemoral tenderness and pain with squat/stair descent if PFJ predominant.
  
• Function: slower timed-up-and-go, difficulty rising from chair, reduced walking endurance; reduced balance.

Diagnosis

• Primary-care diagnostic rule (NICE NG226): diagnose clinically without imaging when all present—age ≥45, activity-related pain, no morning stiffness or stiffness ≤30 minutes; image if atypical features or red flags.

• EULAR exam features (useful triad): symptoms—persistent pain, short-lived morning stiffness, reduced function; signs—crepitus, restricted movement, bony enlargement; imaging not required for a confident diagnosis when these are present. (EULAR)
  
• Imaging (when needed): weight-bearing AP/lateral and skyline views to classify and plan; radiograph severity by K-L grade; MRI not routinely required—consider if alternative pathology suspected; US can detect effusion/synovitis and guide injections. (Radiopaedia, eprints.whiterose.ac.uk)
  
• Key differentials (with discriminators): inflammatory arthritis (prolonged morning stiffness, synovitis, ↑CRP/ESR), crystal arthritis (acute flares, crystals on aspiration), septic arthritis (fever, ↑inflammatory markers, urgent aspirate), avascular necrosis (risk factors, MRI changes), meniscal tear (mechanical symptoms, provocative tests), patellofemoral pain syndrome (younger, load-related anterior pain, normal x-ray), referred pain from hip/spine. (The Lancet)
  

Table 1. Diagnostic frameworks at a glance

Classification

• By compartment: medial/lateral tibiofemoral; patellofemoral; mixed. (The Lancet)
  
• By radiograph: Kellgren–Lawrence 0–4 (0 normal → 4 severe with marked joint-space loss and deformity). (Radiopaedia)
  
• By phenotype (useful clinically): biomechanical–malalignment/instability; inflammatory/synovitis-dominant; metabolic–obesity; bone-driven (BML-dominant); pain-sensitization predominant. (The Lancet)

Treatment

• Core (all patients)
  
  • Education, reassurance and shared decision-making; structured exercise (strength—esp. quadriceps/hip; aerobic; neuromuscular/balance; tai chi); weight loss if overweight/obese (goal ≥5–10%); pacing and flare plans; consider supervised programmes. Remember: No single exercise is superior—the best plan is the one they’ll do consistently. (AAFP, NICE)
    
• Devices/adjuncts
  
  • Cane in contralateral hand, knee taping, tibiofemoral unloader bracing for unicompartmental OA (selected), patellofemoral brace for PFJ OA (conditional). Footwear/insoles: lateral wedges generally not recommended. (RheumGuide.ca, rheumatologyadvisor.com)
    
• Pharmacologic (use lowest effective dose, shortest duration, alongside exercise)
  
  • Topical NSAIDs (first-line); oral NSAIDs + PPI if needed; acetaminophen limited benefit; duloxetine conditional for persistent pain; topical capsaicin optional; avoid routine opioids. (AAFP, evawebsiteprod.azurewebsites.net)
    
• Intra-articular therapies
  
  • Corticosteroid: short-term relief for flares; avoid frequent repeat courses (signals of cartilage loss with repeated triamcinolone).
    
  • Hyaluronic acid: ACR conditionally against routine use (shared decision if others fail); OARSI conditionally for in selected knee OA.
    
  • PRP/stem cells: evidence inconsistent; many guidelines advise against outside research/specialist settings. (JAMA Network, Deep Blue, oarsijournal.com, rheumnow.com)
    
• Interventional pain
  
  • Radiofrequency ablation (genicular nerves): conditional option in refractory knee OA (specialist). (escholarship.org)
    
• Surgery
  
  • Do not perform arthroscopy for primary degenerative knee disease (no meaningful long-term benefit).
    
• Consider realignment osteotomy (younger, unicompartmental malalignment) or unicompartmental/total knee arthroplasty for severe, function-limiting disease after optimal non-surgical care. (BMJ, Guideline Central)

Table 2. Pharmacologic & injection quick guide

Complications and Prognosis

Complications

• Functional decline, falls/deconditioning; analgesic adverse effects (GI/CV with NSAIDs; dependence with opioids); post-injection flare; accelerated progression in some with repeated IA steroids; surgical risks after arthroplasty. (JAMA Network)
  Prognosis
  
• Variable course; many stabilize/improve with sustained exercise and weight loss; poor prognostic factors include obesity, varus/valgus malalignment, prior major knee injury, severe baseline radiographic/structural damage, and depression/low self-efficacy.

Acronym

• KNEE-OA = Kilos down (weight loss) + NSAIDs (topical → oral) + Exercise (strength/aerobic/balance) + Education/self-management + Offload (brace/tape/cane) + Adjuvants (IA steroid short-term; duloxetine) — escalate to surgery if refractory. (NICE, Arthritis Foundation)
  

References

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2. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of OA of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149-162. (Arthritis Foundation)
   
3. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular OA. Osteoarthritis Cartilage. 2019;27:1578-1589. (ScienceDirect)
   
4. American Academy of Orthopaedic Surgeons (AAOS). Management of Osteoarthritis of the Knee (Non-Arthroplasty). 3rd ed. 2021. (aaos.org)
   
5. EULAR. Evidence-based recommendations for the diagnosis of knee OA. Ann Rheum Dis. 2024. (EULAR)
   
6. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393:1745-1759. (acpacprogram.ca)
   
7. Oo WM, Hunter DJ, et al. Bone marrow lesions in osteoarthritis: recent advances. Skeletal Radiol. 2024;53:—. (SpringerLink)
   
8. Hall M, et al. Risk factors for incident knee OA: systematic review. Osteoarthritis Cartilage. 2025;—. (oarsijournal.com)
   
9. Filbay SR, et al. Risk of knee OA after knee injury in youth. Br J Sports Med. 2020;54(12):725-—. (bjsm.bmj.com)
   
10. Siemieniuk RAC, et al. Arthroscopic surgery for degenerative knee arthritis and meniscal tears: guideline. BMJ. 2017;357:j1982. (BMJ)
    
11. EULAR 2024 update—non-pharmacological core management of hip/knee OA. Ann Rheum Dis. 2024;—. (ard.bmj.com)
    
12. AAFP. Osteoarthritis Management: Updated ACR Guidelines. Am Fam Physician. 2021;103(2):120-122. (AAFP)
    
13. Radiopaedia. Kellgren and Lawrence system for classification of OA. 2025. (Radiopaedia)
    
14. EULAR recommendations for imaging in OA clinical management. Ann Rheum Dis. 2017;76:1484-1494. (eprints.whiterose.ac.uk)
    
15. The Knee Journal. K-L grade and morphological parameters. 2019. (thekneejournal.com)
    
16. Kolasinski SL, et al. ACR/AF guideline—hyaluronic acid conditional against. Arthritis Care Res (Hoboken). 2020;72:149-162. (acrjournals.onlinelibrary.wiley.com)
    
17. NICE NG226 Visual Summary. 2022. (NICE)
    
18. McAlindon TE, et al. Intra-articular triamcinolone vs saline and cartilage volume. JAMA. 2017;317:1967-1975. (JAMA Network)
    
19. GuidelineCentral summary of AAOS: lavage/debridement not recommended. 2021. (Guideline Central)