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 fundamentally 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 respectively. 1, 2, 3

Cartilage Pathology

• 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 4, 5
• The cartilage matrix—normally composed of water, collagen fibers, and proteoglycan macromolecules cross-linked with hyaluronic acid—undergoes progressive erosion as catabolic processes overwhelm repair mechanisms 5
• This degradation involves a complex interplay of pro-inflammatory cytokines, growth factors, matrix metalloproteinases, aggrecanases, and chondrodegradative enzymes that break down the cartilage structure 5, 3

Bone and Synovial Changes

• Subchondral bone undergoes reactive changes including marginal and central new bone formation (osteophytes), which are key structural features of knee OA 4, 6
• The synovial membrane develops underlying inflammation early in the disease process, contributing to joint degeneration through release of inflammatory mediators 5, 6
• Synovial fluid demonstrates decreased concentration and viscosity in osteoarthritic joints, reducing the lubricating and cushioning properties critical for joint protection 5

Obesity-Specific Mechanisms

In obesity-related knee OA, the pathogenesis extends beyond simple mechanical overload to include systemic metabolic inflammation. 2

• Obesity induces higher levels of pro-inflammatory cytokines and increased production of adipokines with both protective and destructive effects on articular cartilage 2
• Metabolic syndrome contributes through up-regulation of proteolytic enzymes (matrix metalloproteinases and aggrecanases) and increased free fatty acids and reactive oxygen species induced by dyslipidemia 2
• The risk of knee OA increases progressively with BMI, from a relative risk of 0.1 for BMI <20 kg/m² to 13.6 for BMI ≥36 kg/m² compared to normal weight 7
• If all overweight and obese individuals reduced their weight by 5 kg or achieved normal BMI, 24% of surgical knee OA cases could be prevented 7

Post-Traumatic Mechanisms

• Previous knee trauma significantly increases OA risk, with various single and multistructure injuries (cruciate ligament tears, meniscal injuries, chondral injuries, fractures) increasing odds of symptomatic OA 4
• Post-traumatic OA accounts for approximately 12% of all OA cases globally, affecting about 36 million people 4
• Obesity and previous knee injury interact more than additively—individuals with both obesity, Heberden's nodes, and previous knee injury have a relative risk of 78 compared to normal-weight individuals without these factors 7

Age and Constitutional Factors

• Age represents a significant risk factor, with nearly 50% of people developing symptomatic knee OA by age 85 4
• Genetics play a substantial role, with heritability estimates from twin studies ranging from 0.39 to 0.65 4
• Women demonstrate higher prevalence following the fourth decade, potentially related to hormonal factors 4, 5

Clinical Implications for Management

The whole-joint disease concept necessitates addressing not only symptoms but underlying pathophysiology through weight optimization and mobility programs. 1, 2

• Core treatments must include patient education, structured exercise (local muscle strengthening and general aerobic fitness), and weight loss interventions for those with BMI ≥25 kg/m² targeting minimum 5-7.5% body weight reduction 1, 8
• Prevention efforts should focus on implementing injury prevention programs and addressing modifiable risk factors such as obesity and quadriceps muscle weakness 4
• Future therapeutic strategies may include pharmacological agents targeting specific molecules involved in obesity-related OA pathogenesis, including personalized treatment approaches 2