Osteoarthritis, which is the most common form of arthritis in the United States and other Western countries, is increasing in incidence as the population ages, and it is likely to rise further with the obesity epidemic. Significant disability and loss of function are associated with this disease, and its management is an enormous cost to the health care system. Progress in prevention and treatment has been slow, related in part to the insidious onset and generally slow progression of the disease.1-3 As a result, clinical trials can take many years to show a significant disease benefit. Therefore, despite its being the most prevalent form of arthritis, few long-term clinical trials have studied the therapeutic outcomes.
Definition
Osteoarthritis (also known as degenerative arthritis, hypertrophic arthritis, or age-related arthritis) implies an inflamed joint by its very name, but for a long time the role of inflammation in osteoarthritis has been somewhat controversial. The pathology reflects the result of joint disease, with loss and erosion of articular cartilage, subchondral sclerosis, and bone overgrowth (osteophytes).
Rather than one uniform disease, osteoarthritis may be a primary or an idiopathic phenomenon, or it may be secondary to some other disorder. Osteoarthritis is also commonly seen as a secondary form of arthritis in patients with other inflammatory arthritides, such as rheumatoid arthritis. Mechanical and genetic factors play roles in the development of this disease as well. Histologic evidence clearly shows ongoing inflammation and cartilage destruction in osteoarthritis, although not to the same degree as in other arthritides, such as rheumatoid arthritis.1,4,5
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Prevalence and Incidence
Osteoarthritis is the most prevalent form of arthritis in the United States, affecting more than 70% of adults between 55 and 78 years of age.5 Women are affected more than men.5,6 Hip osteoarthritis is more common in Western populations, suggesting that race and environmental factors might also be important.5 The incidence of symptomatic knee osteoarthritis is 1% per year, with a radiographic incidence of 2% per year. The rate of radiographic progression has been estimated at about 4% per year.6
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Pathophysiology
Understanding the metabolic pathways at the molecular level has greatly enhanced our understanding of the tissue factors involved.7
Although the role of inflammation in osteoarthritis has been unclear for a long time, significant progress has been made in more recent years. The molecular pathways involved are being more clearly defined, and this is an area of intense ongoing research. Studies also show that there are ongoing inflammation and synovitis that result in permanent joint damage.1,5,8 At times, this may be more striking, with flares of symptoms or joint effusions. Effusions can be very large at times, and we have aspirated more than 100 mL of fluid from an acutely swollen knee on more than one occasion. Biopsies of synovium from patients with osteoarthritis show more inflammatory infiltrates than normal controls do.
Some patients appear to have a more hereditary form of this disease. The striking features are usually seen in women who, shortly after menopause, develop distal (Heberden’s nodes) and proximal (Bouchard’s nodes) interphalangeal joint involvement in their hands, which eventually leads to the characteristic bony swelling and correlates with the presence of radiographic knee involvement.8 Previous trauma or other prior joint insults, such as inflammation, infection, or avascular necrosis, increase the risk of developing osteoarthritis at that anatomic site.1,8
Histologically, articular cartilage comprises chondrocytes and their extracellular matrices. Three distinct zones are recognizable: superficial, middle, and deep. Mechanical or inflammatory injury that disrupts these zones can lead to irreparable damage and to further inflammation and cartilage degradation as the body attempts to heal itself. In essence, there is a defective repair mechanism, resulting in scarring, thinning, and erosion of the articular cartilage in the joints of subjects with osteoarthritis.9 Several cytokines, such as interleukin-1β and transforming growth factor β, proteases (the most important of which is matrix metalloprotease), and nitric oxide synthetase all appear to be essential for cartilage degradation in the pathogenesis of osteoarthritis. It was previously believed that bone changes occur later in this disease, but newer evidence suggests that subchondral bone changes might take place earlier than previously suspected.10 Increased production of bone and cartilage degradation products has been shown to herald more rapid disease progression.4
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Symptoms, Signs, and Diagnosis
Stiffness, joint pain, and swelling are the earliest symptoms of osteoarthritis. In contrast to inflammatory arthritis, the pain of osteoarthritis is often exacerbated by activity or weight bearing and relieved by rest. Early symptoms are usually of an insidious nature and often do not correlate well with radiographic abnormalities. Later, extensive bone changes, muscle weakness, and loss of joint integrity can lead to more-dramatic joint deformity and disability. Physical findings include painful limitation of movement, bony crepitus, and, occasionally, joint effusions and joint line or bone tenderness. As the disease progresses, more permanent joint deformities can occur in the forms of contractures, osteophytes, and loss of joint function.
Synovial fluid analyses and laboratory investigations are generally not diagnostic. Their utility lies mainly in excluding other causes for the patient’s symptoms or other common forms of arthritis such as crystal deposition diseases. Newer studies using markers of bone, cartilage, and synovium turnover might help identify patients who have a more rapidly progressive form of joint disease, but they are not recommended in routine clinical practice. Data on high-sensitivity C-reactive protein have been reported, with somewhat conflicting findings. Elevated levels of C-reactive protein appear to correlate best with symptoms of pain and stiffness rather than extent or progression of disease.11
Radiographic studies are reserved for patients with symptoms. They are useful in excluding other causes of the patient’s symptoms and in evaluating the extent of joint pathology. However, although radiographs might show osteoid changes such as joint-space narrowing, effusions, bone cysts, and osteophytes, radiographs are limited in sensitivity and in their ability to show nonosseous structures.