Osteoarthritis affects more than 50 million U.S. adults, making it the most common form of arthritis.¹ It is the second leading cause of disability and one of the most common chronic diseases in older adults.² In addition to these medical consequences, osteoarthritis has economic effects: $15 billion annually in lost work productivity and direct medical costs.^1-3

Etiology
Osteoarthritis has traditionally been viewed as an age-related degenerative disease, and it is true that the incidence of arthritis increases with age. But osteoarthritis is not a result of normal wear and tear alone.^1-5 In fact, research shows osteoarthritis begins sometime in the second or third decade of life. By age 40, most people have some pathologic changes in articular cartilage that are indicative of osteoarthritis, but the majority won't experience symptoms until after age 50.^3,6

 Gender Differences
Osteoarthritis demonstrates some interesting sex distinctions. At age 45, men have a higher incidence of osteoarthritis than age-matched women. Between ages 45 and 55, the incidence of osteoarthritis equalizes. After age 55, osteoarthritis is more common in women - possibly due to diminished estrogen levels.^3,4,7,8

Women are more likely to develop osteoarthritis at the proximal interphalangeal (PIP) joints and the base of the thumb at the carpometacarpal joint, while men are more likely to develop it in the hips.

Race Differences
Race appears to influence the development of osteoarthritis as well. People of Japanese descent have a greater incidence of hip osteoarthritis compared with whites, and the incidence in Chinese, Jamaican blacks, South African blacks and Asian Indians is significantly lower as well. Black American women have a lower incidence of osteoarthritis in the PIP joints compared with other ethnic groups, but they have a higher incidence of knee osteoarthritis compared with white American women.²

Risk Factors
The development of osteoarthritis can be idiopathic, surfacing in patients with no history of joint injury or compromise. Other patients develop secondary osteoarthritis as a result of injury or certain conditions (Table). Particular culprits are conditions that lead to joint instability; situations that exert extreme, protracted and atypical stresses on a joint; and activities that directly injure joint cartilage.³

Several risk factors for osteoarthritis are modifiable. Obesity is closely associated with osteoarthritis and is clearly modifiable. Repetitive occupational and recreational stress on joints and lack of moderate exercise and muscle strengthening are additional modifiable risk factors.^3,4

Pathophysiology
Articular cartilage contains chondrocytes, extracellular matrix (ECM) and up to 70 percent water. ECM contains elastin, fibronectin, type II cartilage and proteoglycan molecules such as hyaluronic acid and glycosaminoglycans. Smooth white articular cartilage allows for low-friction articulation at a joint. The compressibility and elasticity of cartilage creates an ability to withstand a load while weight bearing. In normal articular cartilage, chondrocytes facilitate balance between degradation and regeneration of ECM. A major component of osteoarthritis is imbalance in cartilage remodeling.⁷

Osteoarthritis is a degenerative cartilage process stemming from multiple factors including metabolic, mechanical and genetic factors. Patients with osteoarthritis develop cartilage irregularities called fibrillations. Ulcerations and loss of articular cartilage lead to areas of unprotected bone and the development of cysts in subchondral bone. If these cysts rupture, their contents empty into the joint and disrupt the overlying articular cartilage. Osteophytes form at the joint margins, and the cartilage continues to degrade and erode. Small pieces of osteophyte and cartilage may break off, causing joint "mice" that can irritate the synovial lining, leading to synovitis and effusion.^2,7

Enzymatic degradation of cartilage may occur as a major component of osteoarthritis development. Evidence suggests normal chondrocyte metabolism is changed by mechanical stress. Chondrocytes release interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha) and growth factors. These cytokines enzymatically degrade collagen and proteoglycans, blocking the production of collagen matrix protein. Cytokines also fuel prostaglandin release, causing pain and stiffness. Enzymes, including gelatinases, stromolysins, collagenases and matrix metalloproteinases, are released as a result of the mechanical stress that degrades the ECM of the affected joint.^1,2,4,7

The enzymatic breakdown of proteoglycans leads to a disturbance of water and synovial fluid movement in and out of the cartilage. Excess fluid accumulates in the cartilage as a result of proteoglycan disruption, altering cartilage ability to endure mechanical stress. The breakdown of type II collagen leads to decreased tensile strength in the cartilage.^2,7