What is the pathophysiology and management of knee osteoarthritis in older adults, particularly those with a history of obesity or previous joint injuries?

Pathophysiology of Knee Osteoarthritis

Knee osteoarthritis is a "whole joint disease" involving progressive cartilage degradation, subchondral bone remodeling, synovial inflammation, and soft tissue changes driven by mechanical stress and inflammatory mediators, with obesity and previous joint trauma serving as the most significant modifiable and historical risk factors. 1

Primary Pathological Mechanisms

Cartilage Degeneration

• Articular cartilage degeneration represents the primary pathological feature, characterized by focal loss of cartilage through an imbalance between destructive and synthetic processes in the extracellular matrix 1, 2
• The cartilage matrix normally contains water, collagen fibers, and proteoglycan macromolecules cross-linked with hyaluronic acid, but in OA this integrated network breaks down through complex interactions of cells and soluble mediators 3
• Proteolytic enzymes including matrix metalloproteinases and aggrecanases become up-regulated, accelerating cartilage destruction 4

Subchondral Bone Changes

• Subchondral bone undergoes reactive changes including marginal and central new bone formation (osteophytes), which are key structural features of knee OA 1, 2
• These bone changes occur early in the disease process and contribute to joint degeneration through altered biomechanical loading 5

Synovial Inflammation

• Underlying inflammation of the synovium occurs alongside decreased concentration and viscosity of synovial fluid, reducing the lubricating and cushioning properties of the joint 3
• The synovial membrane becomes involved early in the disease process, not as a secondary phenomenon 5

Risk Factors and Their Mechanisms

Age and Genetics

• Age represents a significant risk factor, with nearly 50% of people developing symptomatic knee OA by age 85 1, 2
• Genetics play a substantial role, with heritability estimates from twin studies ranging from 0.39 to 0.65 1, 2

Previous Joint Trauma

• Previous knee trauma significantly increases OA risk, with various single and multistructure injuries increasing odds of symptomatic OA 1, 2
• Specific high-risk injuries include cruciate ligament injuries, collateral ligament injuries, meniscal injuries, chondral injuries, patellar/tibiofemoral dislocations, knee fractures, and multistructure injuries 2
• Post-traumatic OA accounts for approximately 12% of all OA cases globally, affecting about 36 million people 2
• The combination of obesity, Heberden's nodes, and previous knee injury increases relative risk 78-fold compared to normal-weight individuals without these factors 6

Obesity and Metabolic Factors

• Obesity contributes to knee OA not simply through increased mechanical loading but through systemic effects of obesity-induced inflammation 4
• Higher levels of pro-inflammatory cytokines, increased production of adipokines with both protective and destructive effects on articular cartilage, and increased free fatty acids and reactive oxygen species induced by dyslipidemia all contribute to disease progression 4
• The risk of knee OA increases progressively from a relative risk of 0.1 for BMI <20 kg/m² to 13.6 for BMI ≥36 kg/m², with obesity interacting more than additively with Heberden's nodes, earlier knee injury, and meniscectomy 6

Joint Malalignment

• Abnormal mechanical loading due to malalignment contributes to cartilage degeneration through altered biomechanical forces 2

Molecular and Biochemical Pathways

• The entire pathological process involves complex interactions of cells and soluble mediators including cytokines, growth factors, inflammatory mediators, metalloproteinases, and chondrodegradative enzymes 3
• Pro-inflammatory and anti-inflammatory cytokines, chemokines, growth factors, and adipokines can be measured in serum, synovium, and histological samples, potentially serving as biomarkers of disease stage and progression 7
• The epigenome regulates genetic expression through DNA methylation, histone modifications, and mRNA interference, representing another key aspect of disease progression 7

Clinical Implications for Management

Weight Optimization

• The American College of Rheumatology recommends weight loss interventions for those with BMI ≥25 kg/m² targeting minimum 5-7.5% body weight reduction 1, 8
• If all overweight and obese people reduced their weight by 5 kg or until their BMI was within the recommended normal range, 24% of surgical cases of knee OA might be avoided 6

Exercise and Mobility

• Land-based cardiovascular and resistance exercise programs are recommended to address the whole-joint disease concept 8
• Strengthening quadriceps muscles represents a modifiable risk factor that should be addressed 2

Injury Prevention

• Prevention efforts should focus on implementing evidence-based injury prevention programs, particularly for those at high risk of knee trauma 2
• People undergoing meniscectomy or with a history of knee injury should receive targeted advice about weight management and joint protection 6