Causes of Osteoarthritis
Osteoarthritis is caused by a complex interplay of mechanical, cellular, and biochemical factors involving both constitutional risk factors (age, sex, obesity, genetics) and local adverse mechanical factors (trauma, occupational stress, joint alignment), with emerging evidence suggesting gut microbiota may serve as a missing link between metabolic conditions and OA development. 1
Constitutional Risk Factors
Age
- Age is one of the strongest risk factors for OA development 1
- Age-related changes in cartilage matrix composition and structure reduce tissue resilience 2
- Age-related alterations in gut microbiota composition (increased pro-inflammatory bacteria, decreased anti-inflammatory species) contribute to systemic inflammation that may accelerate OA 1
Genetic Factors
- Significant genetic component with heritability estimates of 39-65% independent of environmental factors 1
- Genetic predisposition affects quality and resistance of articular cartilage 3
- Twin studies confirm substantial genetic contribution to OA prevalence 1
Obesity and Metabolic Factors
- Obesity contributes to OA through:
Sex and Reproductive Variables
- OA is more prevalent in women (70%) than men (60%) after age 65 5
- Hormonal and reproductive factors influence disease susceptibility 1
Local Mechanical Factors
Trauma and Joint Injury
- Joint trauma significantly increases risk of post-traumatic OA (PTOA) 6
- Even with optimal treatment of joint injuries (anatomic reduction, rigid fixation, ligament reconstruction), PTOA risk ranges from 20% to over 50% 6
- Mechanical damage triggers changes in gene expression and cartilage metabolism, initiating a cascade of degenerative events 6
- The American Academy of Orthopaedic Surgeons confirms that previous injuries accelerate the degenerative process 3
Occupational and Recreational Stressors
- Repetitive joint use in certain occupations increases OA risk 1
- High-impact recreational activities may contribute to joint degeneration 1
Joint Alignment and Biomechanics
- Abnormal loading of joints increases OA risk 1
- Joint malalignment contributes to uneven stress distribution and accelerated cartilage wear 1
Pathophysiological Mechanisms
Cartilage Degeneration
- OA is characterized by focal loss of articular cartilage and new bone formation at joint margins 1
- Limited capacity of adult chondrocytes to regenerate original cartilage matrix architecture 2
- Chondrocytes attempt to recapitulate early cartilage development but cannot replicate precise zonal variations 2
Inflammation
- OA is now recognized as a low-grade inflammatory condition 1
- Systemic inflammation contributes to OA development and enhances symptomatic expression 1
- Chondrocytes produce inflammatory mediators, proteinases, and cytokines in early OA 2
Gut Microbiota Connection
- Emerging evidence suggests gut microbiota (GMB) may be the missing link between metabolic conditions and OA 1
- GMB dysbiosis is associated with metabolic syndrome and low-grade inflammation 1
- Interventional studies show probiotics and prebiotics may reduce OA symptoms and protect against cartilage damage 1
Clinical Implications
- OA management should target modifiable risk factors (weight management, joint protection, activity modification) 7
- Treatment should be based on pain severity, disability, and distress rather than radiographic changes 7
- Understanding early pathophysiological mechanisms may open opportunities for preventive interventions 6
Pitfalls and Caveats
- Radiographic evidence of OA correlates poorly with symptoms 3
- OA is not simply "wear and tear" but involves active cellular processes 2
- Multiple joint tissues contribute to pathogenesis, not just cartilage 2
- No proven structure-modifying therapy is currently available 2
- The time course for PTOA progression is highly variable, suggesting biological factors beyond mechanical damage 6