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EPIDEMIOLOGY AND PATHOPHYSIOLOGY OF OSTEOARTHRITIS OF THE KNEE

Osteoarthritis (OA) is the most prevalent type of arthritis in the United States (U.S.).^1,2 OA most frequently affects the knee joint, and knee and hip OA are the most common causes of walking-related disability in the U.S.^1,3 The disability associated with OA impacts all areas of an individual’s life; instability, loss of mobility, pain, stiffness, and weakness lead to declines in overall health and quality of life.⁴ Treatment of knee OA requires addressing all affected areas and includes promoting mobility and strength while decreasing pain and discomfort.

Bone remodeling, cartilage loss, muscle weakness, and joint swelling are all characteristics of knee OA. Unfortunately, the pathophysiology of this condition is much more complex than previously understood. What was once considered to be a non-inflammatory, “wear and tear” condition is now recognized to have an inflammatory component in which the deleterious effects reach beyond simple cartilage breakdown and involve the release of inflammatory mediators. Knee OA affects the entire joint: cartilage, periarticular bone, synovium, ligaments, and supporting musculature, such as the meniscus.² Normal synovium refers to relatively acellular soft tissue lining the space of the knee joint, tendon sheaths, and bursae: it is comprised of the intima and subintima—surface cell layers and underlying tissue, respectively.⁵ The synovium has a progressive role in the pathogenesis of knee OA, and changes seen with this disease include synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis, and fibrosis.² Inflammatory mediators produced by synovial cells can lead to the synthesis of more inflammatory mediators, which promotes cartilage degradation.⁶ In addition to propagating cartilage degeneration, synovial inflammation is also associated with a greater degree of OA pain and joint dysfunction.^2,6 Emerging therapies aim to target some of these inflammatory mediators and will be discussed later in this module.

As stated, knee OA affects the entire joint, and inflammation is not initiated solely by the synovium. Subchondral inflammation is also considered to contribute to increased bone turnover and joint damage.⁷ Additionally, obesity, a strong risk factor for OA, adds to the complexity of the disease and influences its inflammatory component. Adipose tissue is a contributor to inflammation and releases many inflammatory mediators including, but not limited to, tumor necrosis factor, interleukin 1 (IL-1), and leptin.⁸ Studies support that OA is not simply a degenerative joint disorder but a systemic disorder in which pathophysiological mechanisms leading to OA may be tied to lipid homeostasis dysregulation.⁸ Research evaluating the impact of leptin in cartilage homeostasis has shown that the level of leptin expression is directly proportional to the grade of cartilage destruction.⁸ Furthermore, studies also show that inflammation occurring in the joint is revealed systemically such that levels of inflammatory mediators are higher in OA patients than in healthy non-OA patients.⁶

Risk factors for knee OA

Risk factors for knee OA include older age, previous injury to the knee, and excess body weight. Importantly, the risk of hand OA is increased 2-fold in obese patients.⁶ This continuing education module focuses on knee OA, but the fact that hand OA occurs more frequently in obese patients underscores the deleterious role obesity may have in OA, in addition to the negative impact it has on weight-bearing joints such as the knee.