Osteoarthritis (OA)

Definition

Osteoarthritis is characterized by failed repair of synovial joint tissues after intra-articular stress. The resulting breakdown of cartilage and bone leads to pain, stiffness, and functional disability. Structural changes on imaging often correlate poorly with patient-reported symptoms. - Goldman-Cecil Medicine

Although the term implies inflammation, OA is primarily a degenerative disorder of articular cartilage, with inflammation acting as a secondary contributor. - Robbins & Kumar Basic Pathology

Epidemiology

The most common disease of joints worldwide, affecting >50 million people
Women are disproportionately affected
Prevalence increases exponentially after age 50; ~40% of people older than 70 are affected
Primary (idiopathic) OA: appears without apparent cause as an aging phenomenon; typically oligoarticular, affecting weight-bearing joints
Secondary OA (~5% of cases): younger individuals with a predisposing condition - joint deformity, prior injury, obesity, or diabetes

Pathogenesis

FIG. 19.31 - Schematic progression of OA from chondrocyte injury through early and late disease (Robbins Pathology)

Biomechanical stress is the principal pathogenic mechanism, but genetic polymorphisms in matrix and signaling molecules predispose to chondrocyte injury. The sequence proceeds:

Chondrocyte injury (genetic + biomechanical triggers) → early matrix changes
Early OA: Chondrocytes proliferate and secrete matrix metalloproteinases (MMPs) that degrade type II collagen. Water content of matrix increases; proteoglycan concentration decreases. Collagen fibers are cleaved, creating surface fissures (fibrillation)
Cytokines (TGF-β, IL-1, IL-6), prostaglandins (PGE2), and nitric oxide (NO) from chondrocytes, synovial cells, and macrophages amplify damage
BMPs and TGF-β drive osteophyte formation at articular margins
Late OA: Chondrocyte loss, full-thickness sloughing, loose bodies ("joint mice"), subchondral bone exposure and eburnation

Morphology (Pathological Changes)

FIG. 19.32 - (A) Fibrillation of articular cartilage on histology. (B) Eburnated articular surface (1), subchondral cyst (2), residual cartilage (3)

Feature	Description
Cartilage fibrillation	Surface cracking and clefting; earliest histologic sign
Cartilage loss	Full-thickness sloughing in advanced disease
Loose bodies ("joint mice")	Dislodged fragments of cartilage and subchondral bone
Bone eburnation	Exposed subchondral bone polished to ivory-like appearance by friction
Subchondral cysts	Formed by synovial fluid forced into fracture gaps (ball-valve mechanism)
Osteophytes	Bony outgrowths at articular margins capped by fibrocartilage, then ossify
Synovium	Mildly congested and fibrotic; only scattered chronic inflammatory cells (unlike RA)

OA vs. Rheumatoid Arthritis - Key Differences

FIG. 19.33 - Comparison of joint morphology in RA (left) vs. OA (right)

Feature	Osteoarthritis	Rheumatoid Arthritis
Primary mechanism	Mechanical injury to cartilage	Autoimmunity
Inflammation	Secondary; low-grade	Primary driver
Joints involved	Weight-bearing (knees, hips, spine)	Small joints of fingers first; then multiple joints
Pathology	Cartilage degeneration, osteophytes, subchondral cysts	Inflammatory pannus, joint erosion, ankylosis
Serum antibodies	None	ACPA, rheumatoid factor
Other organs	No	Yes (lungs, heart, etc.)
Joint fusion	Does NOT occur	Occurs (ankylosis)

Clinical Features

Primary OA typically presents after age 50
Joint pain that worsens with use (activity-related pain)
Morning stiffness (typically brief, <30 minutes - unlike RA where it lasts >1 hour)
Crepitus on movement
Limited range of motion
Joint deformity over time, but no fusion

Commonly involved joints:

Knees and hips (weight-bearing)
Lower lumbar and cervical vertebrae
Proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints of fingers
First carpometacarpal joints
First tarsometatarsal joints

Heberden nodes - osteophytes at the DIP joints; more common in women Bouchard nodes - osteophytes at the PIP joints

Spinal OA: Osteophytes impinge on spinal foramina causing nerve root compression, radicular pain, muscle spasms, atrophy, and neurologic deficits.

Important: Radiographic severity does not correlate well with pain and disability.

Management

There are no treatments to prevent or halt OA progression. Therapy is directed at symptom control and functional restoration. - Robbins Pathology; Goldman-Cecil Medicine

Non-pharmacologic:

Physical and occupational therapy to restore functional status (a critical component of care)
Weight loss (particularly for knee/hip OA)
Activity modification
Assistive devices

Pharmacologic:

NSAIDs - reduce inflammation and pain; first-line pharmacologic agents
Intra-articular corticosteroids - for acute flares
Analgesics (acetaminophen, topical agents)
Pain management strategies

Surgical:

Joint replacement is indicated when functional status interferes with activities of daily living and supportive care has failed; highly effective for end-stage hip and knee OA

Genetics (Key Points)

The largest OA GWAS (>800,000 samples from 9 populations) identified >52 OA risk loci, demonstrating different genetic risk variants for different joint sites. Key genes include:

GDF5 (chromosome 20) - codes for growth factor protein important in chondrogenesis
RUNX2, SMAD3, PTHLH - important in skeletal/bone development
BMI has a causative effect on OA risk (demonstrated via Mendelian randomization)
Firestein & Kelley's Textbook of Rheumatology

Sources: Robbins & Kumar Basic Pathology; Goldman-Cecil Medicine International Edition; Firestein & Kelley's Textbook of Rheumatology

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