Osteoarthritis (OA)

01Pathophysiology

Osteoarthritis is fundamentally a disease of progressive articular cartilage degradation combined with a failure of the chondrocyte repair response. It is the most common form of arthritis worldwide and the leading cause of chronic disability in older adults. Understanding its mechanism is essential because every symptom and exam finding tested on vignettes maps directly to the underlying cartilage and bone pathology.

Normal articular cartilage is composed of type II collagen and proteoglycans (primarily aggrecan), which trap water and provide a smooth, compressible surface for load-bearing. In osteoarthritis, the balance between cartilage synthesis and degradation shifts toward destruction. Matrix metalloproteinases (MMPs) and aggrecanases produced by chondrocytes and synovial cells break down the collagen-proteoglycan framework faster than it can be rebuilt. The cartilage loses its water content, becomes thin and fibrillated, and eventually erodes down to the subchondral bone.

Once the cartilage is lost, the subchondral bone is exposed to direct mechanical stress. The bone responds in two ways. First, it undergoes sclerosis (thickening and hardening) directly beneath the eroded cartilage surface, which accounts for the subchondral sclerosis seen on X-ray. Second, microfractures in the sclerotic bone allow synovial fluid to be forced into the marrow space, forming subchondral cysts. At the joint margins, new bone growth occurs as the body attempts to stabilize the joint and redistribute load. These bony outgrowths are called osteophytes and are the hallmark radiographic finding.

The clinical correlation is direct. Pain occurs because subchondral bone, periosteum, and the joint capsule are richly innervated, while cartilage itself has no nerve supply. This explains why pain worsens with activity (mechanical loading on exposed bone) and improves with rest. The brief morning stiffness (less than 30 minutes) reflects mild gelling of the joint during inactivity, as opposed to the prolonged stiffness of inflammatory arthritis caused by overnight accumulation of inflammatory cytokines. Crepitus on exam is the sound and sensation of roughened cartilage and bone surfaces grinding against each other. Heberden nodes (DIP) and Bouchard nodes (PIP) are palpable osteophytes at the joint margins of the hands.

A critical point for exam purposes: osteoarthritis is not primarily an inflammatory process. While low-grade synovial inflammation can occur as cartilage debris triggers innate immune responses, the disease is driven by mechanical wear and failed repair. This distinction separates it from rheumatoid arthritis and other inflammatory arthropathies both clinically and on laboratory testing.

02Classification and Clinical Manifestation

Common causes of secondary osteoarthritis:

Joint distribution and clinical features by location:

03Diagnostic Workup

Best Initial Test: Plain Radiograph (X-ray)

The diagnosis of osteoarthritis is fundamentally clinical and radiographic. When a patient older than 50 presents with gradual onset of use-related joint pain, brief morning stiffness, and bony enlargement on exam, the first step is to obtain a weight-bearing X-ray of the symptomatic joint. The four classic radiographic findings can be remembered as the mnemonic "LOSS": Loss of joint space (narrowing), Osteophytes, Subchondral sclerosis, and Subchondral cysts.

Joint space narrowing in osteoarthritis is characteristically asymmetric, affecting the portion of the joint under the greatest mechanical load. In the knee, medial compartment narrowing is most common. This contrasts with inflammatory arthritis (such as rheumatoid arthritis), where joint space narrowing tends to be symmetric and uniform.

Laboratory Tests: The Role of Ruling Out

There is no laboratory test that confirms osteoarthritis. Instead, labs are ordered to exclude other diagnoses. ESR, CRP, rheumatoid factor, anti-CCP antibodies, and ANA should all be normal. If any of these are abnormal, the examiner is redirecting you toward an inflammatory or autoimmune arthritis. This is a common testing strategy: the vignette describes what sounds like osteoarthritis, but an elevated ESR or positive rheumatoid factor should make you reconsider the diagnosis.

Synovial Fluid Analysis

When a joint effusion is present and the diagnosis is uncertain, arthrocentesis with synovial fluid analysis is the next step. Osteoarthritis produces a non-inflammatory fluid: clear or straw-colored, highly viscous (high hyaluronic acid content), and a WBC count below 2,000 cells per mm³. This distinguishes it from inflammatory arthritis (2,000 to 50,000 WBC), and septic arthritis (over 50,000 WBC, often over 100,000). Polarized light microscopy should show no crystals, ruling out gout and pseudogout.

When to Order MRI

MRI is not needed for routine diagnosis. It is indicated when the clinical picture is atypical, when you suspect an internal derangement (such as a meniscal tear) as a contributing factor, or for preoperative planning. For board purposes, if a vignette gives you a classic presentation and asks for the "best next step," the answer is X-ray, not MRI.

04Management and Treatment

Non-pharmacologic Management

Every exam question about osteoarthritis management begins here. Exercise and weight loss are the foundation of treatment and should be recommended to all patients regardless of disease severity. Weight reduction is particularly high yield for knee OA: even modest weight loss (5% of body weight) meaningfully reduces joint loading and pain. Physical therapy improves quadriceps strength and joint stability. These interventions are always the correct "first step" in a vignette asking about initial management.

Pharmacologic Therapy

For hand and knee osteoarthritis, topical NSAIDs (diclofenac gel) are preferred as the initial pharmacologic agent because they provide local relief with minimal systemic absorption and fewer gastrointestinal and cardiovascular side effects than oral formulations. For hip osteoarthritis, topical agents are impractical due to the depth of the joint, so oral NSAIDs are the first-line pharmacologic choice.

When prescribing oral NSAIDs, always consider the patient's comorbidities. In patients with cardiovascular disease, naproxen is the preferred NSAID due to its relatively lower cardiovascular risk. In patients with chronic kidney disease (GFR below 30), NSAIDs are contraindicated, and acetaminophen (up to 2 to 3 g per day) becomes the safer alternative despite its modest efficacy. In patients at risk for GI bleeding, co-prescribe a proton pump inhibitor or use a COX-2 selective inhibitor (celecoxib 200 mg daily).

Intra-articular Corticosteroid Injections

These are appropriate for patients who have an acute flare with a joint effusion or who have not responded adequately to oral therapy. The effect is temporary, typically lasting 4 to 8 weeks. Repeated injections (more than 3 to 4 per year in the same joint) may accelerate cartilage loss and are generally avoided.

Duloxetine

This serotonin-norepinephrine reuptake inhibitor (SNRI) is conditionally recommended as an adjunctive agent for chronic knee OA pain, particularly in patients who cannot tolerate NSAIDs or who have concomitant depression or neuropathic pain.

Surgical Management

Total joint arthroplasty (knee or hip replacement) is reserved for patients with end-stage disease: persistent pain despite maximal medical therapy, significant functional limitation, and radiographic evidence of advanced joint destruction. This is the definitive treatment and reliably improves quality of life. On the exam, the indication for surgery is a patient who has "failed all conservative measures" and has severe functional impairment.

Therapies to Avoid or Deprioritize

Intra-articular hyaluronic acid (viscosupplementation) is not recommended by current guidelines due to inconsistent evidence of benefit. Glucosamine and chondroitin sulfate have not demonstrated efficacy in rigorous trials and are not endorsed. Long-term opioid therapy is strongly discouraged due to the risks of dependence, tolerance, and lack of disease modification.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common trap with osteoarthritis questions is confusing it with rheumatoid arthritis based on hand involvement. Both diseases affect the hands, but they affect different joints. Osteoarthritis targets the DIP joints (Heberden nodes), PIP joints (Bouchard nodes), and the first CMC joint. Rheumatoid arthritis targets the MCP and PIP joints while characteristically sparing the DIP joints. If a vignette describes DIP involvement with bony enlargement and brief morning stiffness, the answer is osteoarthritis, even if the hand involvement seems "arthritic." Conversely, if the vignette mentions MCP swelling with prolonged morning stiffness and elevated inflammatory markers, the answer is rheumatoid arthritis regardless of the patient's age.

A second common error is ordering the wrong test. When a vignette describes a classic presentation in a patient over 50 with use-related pain and crepitus, the next step is a plain X-ray, not MRI, not labs, and not synovial fluid analysis. MRI is more sensitive, but it is not the best initial test and is reserved for atypical presentations. Synovial fluid analysis is only indicated when there is an effusion and the differential includes infection or crystal disease.

A third trap involves management sequencing. Exam questions will test whether you know that non-pharmacologic therapy is always the first step before any medication. A vignette that asks for the "best initial management" in a newly diagnosed patient with mild knee OA is looking for "exercise and weight loss," not NSAIDs. Additionally, students frequently forget that topical NSAIDs are preferred over oral NSAIDs for hand and knee OA as the initial pharmacologic agent, due to their safer side effect profile.

Finally, watch for the patient with osteoarthritis of the second and third MCP joints. This is an unusual distribution for primary OA and should trigger consideration of hemochromatosis as the underlying cause. The vignette may include clues such as elevated liver enzymes, skin hyperpigmentation, or diabetes. Missing this pattern is a classic board trap that tests your ability to distinguish primary from secondary osteoarthritis.

The core competency being tested across all osteoarthritis questions is pattern recognition: identifying the non-inflammatory, degenerative joint pattern (DIP, first CMC, knees, hips, spine), distinguishing it from inflammatory arthritis through the history, exam, and labs, and applying a stepwise management approach that prioritizes non-pharmacologic therapy before medications and reserves surgery for end-stage disease.