What causes knee swelling in patients with knee osteoarthritis?

Pathophysiology of Knee Swelling in Osteoarthritis

Knee swelling in osteoarthritis results from synovial inflammation and joint effusion, which are direct consequences of the inflammatory cascade triggered by cartilage degradation and the release of catabolic mediators from the inflamed synovium. 1

Primary Mechanism: Synovial Inflammation

The inflamed synovial membrane is the primary source of knee swelling in OA patients. 2 The pathophysiological sequence unfolds as follows:

• Cartilage breakdown releases degradation products into the joint space, which activate the synovial membrane and trigger an inflammatory response 3, 2
• The activated synovium produces catabolic and proinflammatory mediators including cytokines, nitric oxide, prostaglandin E2, and neuropeptides that perpetuate joint inflammation 2
• This inflammatory synovium produces excess synovial fluid (effusion), leading to clinically detectable knee swelling 1

The Vicious Cycle of Inflammation

A self-perpetuating inflammatory loop develops between cartilage and synovium. 2 Understanding this cycle is critical:

• The inflamed synovium produces proteolytic enzymes that accelerate cartilage matrix degradation 2
• Further cartilage breakdown releases more inflammatory mediators, which amplify synovial inflammation and create a vicious circle 2
• This bidirectional relationship explains why synovitis is present in both early and late phases of OA 2

Changes in Synovial Fluid Composition

Beyond increased volume, the synovial fluid itself becomes pathologically altered in OA. 3

• Decreased concentration and viscosity of synovial fluid impairs the lubricating and cushioning properties of the joint 3
• These changes contribute to both mechanical symptoms and ongoing inflammation 3

Whole-Joint Pathology

OA is characterized by pathology involving the entire joint structure, not just cartilage. 1

• Cartilage degradation, bone remodeling, osteophyte formation, and synovial inflammation occur simultaneously and lead to pain, stiffness, swelling, and loss of normal joint function 1
• Subchondral bone undergoes reactive changes that contribute to the overall inflammatory milieu 3

Clinical Significance of Effusions

Effusions indicate active disease and have important treatment implications. 4

• Physical examination routinely reveals knee effusions in OA patients, as documented in clinical practice guideline case examples 4
• Changes in synovitis/effusion severity are significantly related to the risk of frequent knee pain (p=0.045 for improving effusions) 4
• Both bone marrow lesions and synovitis/effusion may indicate the origin of knee pain in OA patients 4
• Intra-articular corticosteroid injections are more effective when effusion is present, making assessment for effusion clinically important for guiding treatment 4

Important Clinical Caveats

Not all OA patients have clinically detectable effusions, but when present, they indicate active disease and potential for symptomatic benefit from aspiration or injection 4

MRI is more sensitive than clinical examination for detecting effusions and should be considered when initial radiographs reveal a joint effusion but pain persists, as it can accurately depict the extent of effusion and presence of synovitis 4