Osteoarthritis¶

Chapter 383 | Harrison's 22e · Part 11 – Rheumatology & Immunology · Chapter 383

Key Clinical Points¶

Osteoarthritis (OA) is the most common type of arthritis and a leading cause of disability in the elderly.
Pathophysiology involves joint failure characterized by hyaline articular cartilage loss, subchondral bone changes, and synovial inflammation.
Joint protection relies on the capsule, ligaments, muscles, sensory nerves, and synovial fluid (hyaluronic acid and lubricin).
OA is a complex inflammatory process involving DAMPs, cytokines, and mechanoinflammation, not just simple 'wear and tear'.
Commonly affected joints include the hip, knee, first metatarsal phalangeal (MTP) joint, and the cervical/lumbosacral spine.
Hand OA specifically affects the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints.
Symptomatic OA is less common than structural OA; many individuals with radiographic evidence of OA are asymptomatic.
Risk factors include a combination of joint susceptibility (age, genetics) and mechanical loading (obesity, injury).
Malalignment (varus/valgus) significantly contributes to localized joint stress and progression.
Pharmacologic management includes NSAIDs, COX-2 inhibitors, opiates, and topical capsaicin.

DEFINITION & CLASSIFICATION¶

• Definition: OA is joint failure, a disease in which all structures of the joint have undergone pathologic change, often in concert. • Pathologic Sine Qua Non: Hyaline articular cartilage loss, present in a focal and, initially, nonuniform manner. • Associated Structural Changes: ◦ Increased thickness and sclerosis of the subchondral bony plate ◦ Outgrowth of osteophytes at the joint margin ◦ Stretching of the articular capsule ◦ Variable degrees of synovitis ◦ Weakness of muscles bridging the joint ◦ Meniscal degeneration (specifically in knees)

EPIDEMIOLOGY¶

• Prevalence: Most common type of arthritis; prevalence increases significantly with age. • Demographics: More common in women than in men. • Global Trends: Prevalence and disability related to OA are increasing globally, especially in developed countries due to aging populations. • Regional Variations: ◦ Hip OA: Roughly one-third as common as disease in the knee; rare in China and among immigrants from China to the United States (likely due to anatomical differences). ◦ Knee OA: At least as common, if not more so, in Chinese populations; a major cause of disability in China, especially in rural areas. • Symptomatic vs. Structural: ◦ Many individuals with X-ray evidence of OA have no joint symptoms. ◦ Symptomatic knee OA (defined as pain on most days of a recent month + x-ray evidence of OA) occurs in ~12% of persons age ≥60 in the US and 6% of all adults age ≥30. ◦ X-ray evidence of OA in the lower back and neck is not typically tied to clinical pain; these are treated separately.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Joint Protective Mechanisms: ◦ Capsule and Ligaments: Provide limits to excursion and structural integrity. ◦ Synovial Fluid: Reduces friction; contains hyaluronic acid and lubricin (lubricin concentration diminishes after joint injury and in the face of synovial inflammation). ◦ Sensory Nerves: Provide feedback via the spinal cord to muscles/tendons to ensure proper tension. ◦ Muscles and Tendons: Distribute force across joint surfaces; prevent focal stress. • Mechanisms of Failure: ◦ Loss of sensory nerves → rapid OA development (e.g., Charcot's arthropathy). ◦ Rupture of ligaments → early development of OA. • Inflammatory & Molecular Drivers: ◦ DAMPs (Damage-Associated Molecular Patterns): Released from cartilage; stimulate synovium. ◦ Cytokines: Released by synovium to induce chondrocytes to produce pro-inflammatory molecules. ◦ Enzymes: Matrix metalloproteinases (MMPs, especially collagenases) and ADAMTS-5 are critical for cartilage matrix breakdown. ◦ Growth Factors: BMP-2 and TGF-β promote osteophyte development; VEGF leads to vascular invasion of cartilage → nociceptive innervation. ◦ Mechanoinflammation: Local inflammation induced by mechanical stimuli.

CLINICAL FEATURES¶

• Commonly Affected Joints: ◦ Hip ◦ Knee ◦ First metatarsal phalangeal (MTP) joint ◦ Cervical and lumbosacral spine • Hand Involvement: ◦ Distal interphalangeal (DIP) joints (Heberden's nodes) ◦ Proximal interphalangeal (PIP) joints (Bouchard's nodes) ◦ Base of the thumb • Typically Spared Joints: ◦ Wrist ◦ Elbow ◦ Ankle (due to articular cartilage resistance to loading stresses) • Clinical Presentation: ◦ Symptoms vary; many patients with structural changes are asymptomatic. ◦ Pain, disability, and clinical visits are driven by symptomatic OA.

DIAGNOSTIC APPROACH¶

Clinical Assessment: Identify joint pain, determine degree of disability, and identify specific sites (e.g., Heberden's/Bouchard's nodes in hands).
Radiographic Imaging (X-ray): ◦ Used to identify structural abnormalities. ◦ Key findings: Joint space loss (cartilage loss) and osteophytes.
Advanced Imaging (MRI): ◦ Used to identify 'soft' tissue damage (e.g., meniscal tears, synovitis) and bone marrow lesions (evidence of bone injury).

MANAGEMENT & TREATMENT¶

Pharmacologic Treatment (Table 383-1): • Oral NSAIDs and COX-2 inhibitors: ◦ Naproxen: 375–500 mg bid ◦ Salsalate: 1500 mg bid (up to 2 g/d) ◦ Ibuprofen: 600–800 mg qid/tid ◦ Celecoxib: 100–200 mg qd → Notes: Take with food; risk of GI side effects (ulcers, bleeding) and cardiovascular risks. Use proton pump inhibitor or misoprostol for patients at high risk for gastrointestinal side effects. • Opiates: ◦ Dosage: 4 g qid → Notes: Less efficacious than oral NSAIDs; common side effects include dizziness, sedation, nausea, vomiting, dry mouth, constipation, urinary retention, and pruritus. Addiction risk. • Capsaicin: ◦ Dosage: 0.025–0.075% cream tid/qid → Notes: Can irritate mucous membranes. • Injections: ◦ Frequency: Varies from 3 to 5 weekly injections.

KEY PEARLS & HIGH-YIELD POINTS¶

• Not just wear and tear: OA is a complex inflammatory disease involving DAMPs, cytokines, and bone remodeling. • Heberden's vs. Bouchard's: Heberden's nodes (DIP) and Bouchard's nodes (PIP) are classic markers of hand OA. • Risk Factor Synergy: OA progression typically requires a combination of joint susceptibility (age/genetics) and mechanical loading (obesity, injury). • Malalignment Impact: Varus → medial compartment stress; Valgus → lateral compartment stress.

Reference Tables¶

TABLE 383-1 Pharmacologic Treatment for Osteoarthritis TREATMENT Oral NSAIDs and COX-2 inhibitors¶

Harrison's 22e, p.2955

TREATMENT	MAXIMAL DOSAGE	COMMENTS
Oral NSAIDs and COX-2 inhibitors Naproxen Salsalate Ibuprofen Celecoxib	375–500 mg bid 1500 mg bid 600–800 mg qid/tid 100–200 mg qd	Take with food. Increased risk of myocardial infarction and stroke for some NSAIDs. High rates of gastrointestinal side effects, including ulcers and bleeding. Patients at high risk for gastrointestinal side effects should also take either a proton pump inhibitor or misoprostol.a There is an increase in gastrointestinal side effects or bleeding when taken with acetylsalicylic acid. Can also cause edema and renal insufficiency.
	Up to 2 g/d
Opiates		Common side effects include dizziness, sedation, nausea, vomiting, dry mouth, constipation, urinary retention, and pruritus. Addiction risk. Less efficacious than oral NSAIDs.
	4 g qid
Capsaicin	0.025–0.075% cream tid/qid	Can irritate mucous membranes.
	Various
	Varies from 3 to 5 weekly injections