6.5 Osteoarthritis

1. Osteoarthritis (OA)

Pathophysiology & Risk Factors

Osteoarthritis is not merely "wear and tear," but an active, progressive biomechanical and biochemical failure of the entire diarthrodial joint organ, involving the articular cartilage, subchondral bone, synovium, menisci, ligaments, and periarticular musculature.

• Pathobiology: Chondrocytes undergo phenotypic alteration, downregulating type II collagen and aggrecan while upregulating matrix metalloproteinases (MMP-13) and aggrecanases (ADAMTS-4/5). This drives articular cartilage fibrillation, clefting, and full-thickness erosion. The underlying subchondral bone responds with increased remodeling, resulting in subchondral sclerosis, microfractures with fluid intrusion forming subchondral cysts (geodes), and new fibrocartilaginous outgrowth at joint margins forming osteophytes (bone spurs).
• Major Risk Factors: Advanced age (>50 years), female sex, obesity (mechanical load + pro-inflammatory adipokines like leptin), prior intra-articular trauma (ACL rupture, meniscectomy), repetitive occupational loading, joint malalignment (genu varum/valgum), and genetic predisposition.

Clinical Presentation & Joint Distribution

• Symptom Profile: Deep, dull, aching joint pain that is insidious in onset, aggravated by weight-bearing and activity, and relieved by rest. In advanced OA, pain occurs at rest and disrupts sleep.
• Morning Gel Phenomenon: Morning stiffness is characteristically brief, lasting <30 minutes (differentiating OA from the >60 min stiffness of RA).
• Physical Examination: Joint line tenderness, coarse crepitus with range of motion, bony enlargement, joint effusion (cool, non-inflammatory), decreased active and passive range of motion, and angular deformities.
• Characteristic Joint Distribution:
  • Hands: Distal Interphalangeal (DIP) joints (Heberden nodes), Proximal Interphalangeal (PIP) joints (Bouchard nodes), and the 1st Carpometacarpal (CMC) joint of the thumb (causes "squaring" of the hand base).
  • Lower Extremities: Knees (medial tibiofemoral compartment most common), Hips (groin pain radiating to anterior thigh/knee), and 1st Metatarsophalangeal (MTP) joint (hallux valgus / bunion).
  • Spine: Cervical (C5-C7) and Lumbar (L3-S1) facet joints and uncovertebral joints.
  • Sparing Rule: OA characteristically spares the MCP joints, wrists, elbows, and ankles (involvement of these joints suggests secondary OA from hemochromatosis, CPPD, or prior trauma).

Diagnostic Radiographic Features

Plain weight-bearing radiographs demonstrate the 4 cardinal radiographic signs of OA:

1. Asymmetric Joint Space Narrowing (loss of articular cartilage).
2. Subchondral Sclerosis (increased bone density beneath cartilage loss).
3. Marginal Osteophyte Formation (new bone spurs at joint peripheries).
4. Subchondral Cysts (Geodes) (radiolucent cystic lesions in subchondral bone).

Comprehensive Management of Osteoarthritis

                                  OSTEOARTHRITIS STEPWISE MANAGEMENT PYRAMID
                             
                                     [ Total Joint Arthroplasty ]
                                     (Refractory, End-Stage OA)
                                                 ▲
                                [ Intra-Articular Injections ]
                               (Steroids for Acute Exacerbations)
                                                 ▲
                           [ Systemic Pharmacotherapy: Duloxetine / Oral NSAIDs ]
                             (Shortest duration, lowest dose + PPI if high GI risk)
                                                 ▲
                            [ Topical Pharmacotherapy: Topical Diclofenac Gel ]
                               (First-line for knee OA; minimal systemic toxicity)
                                                 ▲
                 [ Non-Pharmacological Foundation (MANDATORY FOR ALL) ]
           Weight Loss (>=5-10% body weight), Low-Impact Exercise (Swimming/Cycling), 
                   Physical Therapy (Quadriceps Strengthening), Contralateral Cane

1. Non-Pharmacological Interventions (Foundational for All Patients)

• Weight Loss: Every 1 pound of weight lost eliminates 4 pounds of compressive force across the knee joint during walking. Achieving >=5–10% body weight loss significantly reduces pain and improves physical function.
• Low-Impact Aerobic & Resistance Exercise: Aquatic therapy, stationary cycling, walking, and targeted quadriceps strengthening.
• Biomechanics: Contralateral single-point cane (reduces joint reaction forces by up to 50%), medial/lateral wedge insoles, and patellar taping.

2. Pharmacological Interventions

• Topical NSAIDs (Topical Diclofenac 1% Gel / Patch): Preferred first-line pharmacologic therapy for Knee Osteoarthritis in older adults and patients with comorbidities. Provides pain relief equivalent to oral NSAIDs with <5% systemic absorption, drastically reducing the risk of gastrointestinal bleeding, acute kidney injury, and cardiovascular events.
• Oral NSAIDs (Ibuprofen, Naproxen, Meloxicam, Celecoxib): Indicated when topical agents are ineffective, particularly for Hip Osteoarthritis (where topical agents cannot penetrate). Use the lowest effective dose for the shortest duration. In patients aged >=65 years or with elevated GI risk, co-prescribe a Proton Pump Inhibitor (PPI) or select a COX-2 selective inhibitor (Celecoxib).
• Duloxetine (Cymbalta): Serotonin-norepinephrine reuptake inhibitor (SNRI, 30–60 mg daily). Highly effective as monotherapy or adjunct for chronic OA pain, especially in patients with neuropathic features, central sensitization, multi-joint OA, or contraindications to NSAIDs.
• Intra-Articular Glucocorticoid Injections: Provides short-term moderate pain relief (2 to 4 weeks) for acute flare-ups with joint effusion. Limit frequency (maximum 3–4 injections per year) to avoid potential acceleration of cartilage loss.
• Avoided / Not Recommended Therapies: Non-tramadol opioids are conditionally recommended against (limited efficacy with substantial harm, especially falls and cognitive impairment in older adults), and tramadol is only a conditional last-line option when other therapies have failed or are contraindicated. Intra-articular hyaluronic acid is conditionally recommended against for the knee and strongly recommended against for the hip. Glucosamine is strongly recommended against at all three sites, as is chondroitin for the knee and hip.

2. Separating Osteoarthritis from Inflammatory Arthritis, Grading & Referral

Synovial Fluid: the Non-Inflammatory Threshold

Osteoarthritis produces an effusion, but a non-inflammatory one. Aspiration is the fastest way to settle the differential when a single joint is warm, swollen, or disproportionately painful.

The exam application is direct: a knee effusion with 30,000 leukocytes is not osteoarthritis, no matter how convincing the radiograph. Crystal analysis under polarized light distinguishes the negatively birefringent needle-shaped monosodium urate crystals of gout from the positively birefringent rhomboid crystals of calcium pyrophosphate. Remember that crystals and infection can coexist, so a positive crystal result never excludes septic arthritis when the count is high.

Laboratory Discriminators

Osteoarthritis has a normal erythrocyte sedimentation rate and C-reactive protein, a normal complete blood count, and no autoantibodies. Ordering an antinuclear antibody or rheumatoid factor in a patient with a classic osteoarthritis picture actively causes harm: rheumatoid factor is positive in roughly 5% of healthy adults and rises with age, and an antinuclear antibody at a 1:80 titer is present in a quarter or more of healthy people. Each false positive generates referrals, repeat serologies, and patient anxiety. Order inflammatory markers and serologies only when there is genuinely prolonged morning stiffness, constitutional symptoms, or true synovitis on examination.

Kellgren-Lawrence Radiographic Grading

• Grade 0: no radiographic features of osteoarthritis.
• Grade 1: doubtful joint space narrowing with possible osteophytic lipping.
• Grade 2: definite osteophytes with possible joint space narrowing — conventionally the threshold for "radiographic osteoarthritis."
• Grade 3: multiple osteophytes, definite joint space narrowing, some sclerosis, possible bone contour deformity.
• Grade 4: large osteophytes, marked joint space narrowing, severe subchondral sclerosis, and definite bone contour deformity.

Radiographic-symptom discordance is the rule, not the exception. Roughly half of people with Grade 2 or higher radiographic knee osteoarthritis have no knee pain, and many symptomatic patients have nearly normal films. Treat the patient's pain and function, not the grade. Routine MRI is not indicated in suspected osteoarthritis: it detects incidental degenerative meniscal tears in the majority of adults over 50, and those incidental findings drive inappropriate arthroscopy.

Erosive (Inflammatory) Hand Osteoarthritis

A distinct subset presents with abrupt, painful inflammatory flares of the distal and proximal interphalangeal joints, with soft-tissue swelling and erythema that can convincingly imitate an inflammatory arthritis. The radiographic signature is central subchondral erosion producing a "gull-wing" or saw-tooth deformity — anatomically distinct from the marginal erosions of rheumatoid arthritis, which also spares the distal interphalangeal joints. Inflammatory markers are normal or only minimally elevated, and rheumatoid factor and anti-cyclic citrullinated peptide antibodies are negative. Management remains topical and oral non-steroidal anti-inflammatory drugs plus hand therapy and splinting; conventional disease-modifying antirheumatic drugs, hydroxychloroquine, and anti-tumor necrosis factor agents have not demonstrated benefit in trials.

When to Suspect Secondary Osteoarthritis

Suspect an underlying cause when osteoarthritis appears at an atypical joint or an atypically young age:

• Hereditary hemochromatosis — the second and third metacarpophalangeal joints with characteristic hook-like osteophytes; check ferritin and transferrin saturation.
• Calcium pyrophosphate deposition disease — chondrocalcinosis with radiocarpal and patellofemoral involvement.
• Prior trauma, meniscectomy, or anterior cruciate ligament rupture — the most common secondary cause overall.
• Osteonecrosis, acromegaly, ochronosis (alkaptonuria), and Charcot neuroarthropathy in long-standing diabetes or neuropathy.

Surgical Referral and What Not to Do

• Total joint arthroplasty is indicated for severe, radiographically advanced disease with pain that limits daily function and disturbs sleep despite an adequate trial of non-surgical management. Outcomes are excellent and durable. Deferring referral until the patient is markedly deconditioned or much older worsens results; optimize weight, glycemic control, and smoking status preoperatively rather than using them as indefinite barriers.
• Arthroscopic lavage and debridement for knee osteoarthritis is strongly recommended against. Multiple randomized trials, including sham-controlled trials, showed no benefit over placebo or structured physical therapy — including for degenerative meniscal tears occurring in the presence of osteoarthritis, which are best managed with physical therapy first.
• The 2019 ACR/Arthritis Foundation guideline strongly recommends against platelet-rich plasma and stem cell injections for knee and hip osteoarthritis, largely because of heterogeneous, unstandardized preparations and absent evidence of benefit.
• Frequently forgotten but conditionally recommended: self-efficacy and self-management programs, tai chi, acetaminophen as a limited-efficacy adjunct, topical capsaicin for the knee, radiofrequency ablation for the knee, and cognitive behavioral therapy for patients with central sensitization.