Pathophysiology of Osteoarthritis
Understanding the Disease Mechanism
Osteoarthritis develops through a multifactorial process involving both mechanical stress and systemic inflammation, with risk factors categorized as modifiable (obesity, muscle weakness, inactivity), potentially modifiable (trauma, reduced proprioception, poor joint biomechanics), and immutable (age, gender, inheritance, congenital malformations). 1
Mechanical and Biomechanical Factors
The pathophysiology begins with quadriceps muscle weakness, which serves as both a risk factor and consequence of OA. 1 Muscle weakness reduces joint stability and shock-absorbing capacity, creating a cycle where:
- Isolated quadriceps weakness is strongly associated with radiographic knee OA, even in patients without prior knee pain history 1
- Decreased muscle strength leads to reduced joint stability and diminished shock absorption, accelerating cartilage degradation 1
- Reduced proprioception (diminished position sense) contributes significantly to OA development, though whether this is cause or consequence remains unclear 1
The Obesity-Inflammation Connection
Obesity drives OA pathogenesis through two distinct mechanisms: direct mechanical overload and systemic inflammatory processes. 2, 3
The inflammatory pathway operates as follows:
- Adipose tissue produces pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, which are found in elevated levels in synovial fluid, synovial membrane, subchondral bone, and cartilage of OA patients 3
- These cytokines induce production of matrix metalloproteinases (MMP-1, MMP-3, MMP-13) and aggrecanases (ADAMTS-4, ADAMTS-5), leading to cartilage matrix degradation 3
- Adipokines (adiponectin and leptin) regulate inflammatory immune responses in cartilage, with leptin at high levels assuming inflammatory characteristics that trigger articular cartilage degeneration 3, 4
- This creates a systemic low-grade inflammation condition that affects both weight-bearing and non-weight-bearing joints, explaining why obesity increases OA prevalence even in hands 3, 4
Joint Distribution and Progression
Age is the most consistent risk factor for both radiographic and symptomatic OA at all articular sites, with prevalence increasing after age 40 in women and age 50 in men. 1 The disease affects approximately:
- 27% of people aged 63-70 years have radiographic knee OA 1
- 44% of those 80 years or older show radiographic evidence 1
- 50% of persons age 65 and older are affected, increasing to 85% in those 75 and older 1
The Inactivity Paradox
Inactivity compounds OA pathophysiology by contributing to muscle weakness, which then perpetuates joint instability. 1 This creates additional morbidity through:
- Increased risk of diabetes mellitus, cerebrovascular disease, coronary artery disease, congestive heart failure, osteoporosis, and depression 1
- Disuse muscle atrophy that was previously thought to develop only because patients avoid loading painful joints, but is now recognized as a primary risk factor 1
Clinical Implications for Management
Understanding this pathophysiology directly informs treatment strategy:
Comprehensive management must address both mechanical and inflammatory components through non-pharmacological interventions combined with medications. 1 The rationale is clear:
- Weight loss reduces both mechanical stress and systemic inflammation by lowering adipose-derived cytokines 2, 5, 3
- Exercise programs targeting muscle strengthening improve joint stability and proprioception, breaking the cycle of weakness and instability 1
- Medications should never be used as primary monotherapy but rather as adjuncts to address the underlying mechanical and inflammatory drivers 1
Critical Pitfall to Avoid
Never conceptualize OA as purely mechanical wear-and-tear. The inflammatory component driven by obesity explains why non-weight-bearing joints are affected and why systemic interventions (weight loss, exercise) produce benefits beyond simple load reduction. 3, 4 This understanding prevents the common error of focusing solely on pharmacological pain management while ignoring the modifiable risk factors that drive disease progression.