Osteoarthritis

Osteoarthritis is the most common form of arthritis in the United States. The incidence increases with advancing age. Many patients can achieve significant relief of their symptoms with appropriate care. Current therapies are being investigated to see if they improve the long-term outcomes of this disease. Ongoing research is aiming to identify patients who have a more rapidly progressive illness, and it is evaluating disease-specific molecular pathways as potential new targets for intervention. Advances in joint replacement surgery have made this an excellent treatment for many patients with more severe disease.

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 either 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.

Pathophysiology

Understanding the metabolic pathways at the molecular level has greatly enhanced our understanding of the tissue factors involved.

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. 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. Previous trauma or other prior joint insults like inflammation, infection, or avascular necrosis increase the risk of developing osteoarthritis at that anatomic site.

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. Several cytokines, such as interleukin-1-β 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. Increased production of bone and cartilage degradation products has been shown to herald more rapid disease progression.

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 usefulness 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.

Radiographic studies are reserved for patients with symptoms. Again, they are useful in excluding other causes of the patient's symptoms and to evaluate 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.

Ultrasound, computed tomography, and magnetic resonance imaging (MRI) may show more extensive joint detail. Although changes in soft tissue and cartilage are better visualized by MRI than by radiographs, and MRI is more sensitive for picking up early bone changes, this is generally unhelpful to the practicing physician. Felson and colleagues have shown that men with osteoarthritis of the knee who have MRI evidence of subchondral bone bruising or marrow edema experience a more rapid progression of their disease than men who have none. Joint malalignment correlates strongly with the presence of the bone marrow lesions. In addition, asymptomatic patients with osteoarthritis might have significant abnormalities on MR imaging, making abnormal findings even harder to interpret. These more-expensive imaging modalities are usually reserved for evaluating other possible causes of symptoms, such as meniscal tears and tumors. Until it can be shown that a therapeutic intervention can significantly prevent or retard the progression of this disease, the role of these imaging modalities in osteoarthritis is of limited value.

Treatment

Treatments have not been shown to reverse this disease, although some treatments can halt its progression. The goal of treatment is adequate pain relief and preservation of function. The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have published guidelines for managing hip and knee osteoarthritis.

Weight loss, even small amounts, can significantly benefit overweight arthritis patients. Relaxation programs and moderate exercise, good nutrition, and education can all help relieve suffering in arthritis patients. Caring health care professionals can alleviate worry and help a patient to achieve realistic goals. Devices such as canes, supports, and braces can take some stress off the affected joint. Avoiding aggravating factors such as trauma, excessive weight gain, or overly strenuous exercise is essential. Other analgesic therapies, such as heating pads or ice packs, also alleviate suffering. Care should be taken, as in all pain-related illnesses, to treat concomitant aggravating factors such as psychosocial stress or other painful maladies, such as secondary bursitis.

Analgesics and Anti-Inflammatories

Acetaminophen (paracetamol in Europe) is generally recommended as first-line pharmacologic therapy. Acetaminophen is a relatively safe treatment with significantly lower gastrointestinal (GI), renal, and cardiovascular toxicities than other medications. When taken on a regular basis, doses of 500 to 750 mg three to four times daily can provide substantial relief. Care should be taken not to exceed 4 g/day. 2,3

Nonsteroidal anti-inflammatory drugs (NSAIDs) can provide significant acute relief in patients with osteoarthritis. However, because osteoarthritis occurs more commonly in older patients who often have other comorbidities, the use of NSAIDs is limited by their potential for or actual side effects. Notably, they can cause or worsen GI hemorrhage, renal insufficiency, congestive heart failure, and hypertension.

Several agents (e.g., rofecoxib, celecoxib) that specifically inhibit cyclooxygenase-2 (COX-2) are approved by the U.S. Food and Drug Administration in the United States and in Europe for use in arthritis patients. Although they are more expensive than over-the-counter generic drugs, they have a better GI safety profile. The concern with these newer agents, as for the older NSAIDs, is that there may be an increased risk of cardiovascular events for patients taking these medications. Indeed, one of these agents (rofecoxib [Vioxx]) was withdrawn from the market because of evidence documenting such side effects. Whether these findings are specific to rofecoxib or represent a class effect remains to be determined. They should be used with extreme caution or not at all in patients with renal or cardiovascular disease.

Topical aspirin or NSAID preparations, which are more widely available in Europe, are an alternative to oral medications. However, the incidence of side effects from NSAIDs is often dose related, and thus they should probably be reserved for acute flares or more recalcitrant disease.

Alternative Treatments

Viscosupplements, although approved by the FDA, appear to provide little more relief than sham injections. Despite the promise for these drugs, well-performed placebo-controlled trials have had disappointing results. Thus, we do not recommend routine use of intra-articular hyaluronate or its derivatives until there is stronger evidence that they are clearly beneficial.

Many patients with osteoarthritis use alternative therapies in an attempt to relieve their suffering. Natraceuticals have shown some promise in this regard. Glucosamine and chondroitin sulfate are by far the most studied agents in this category and have been shown in several studies to be as effective as acetaminophen and NSAIDs, with significantly fewer adverse effects. These agents appear to significantly alleviate pain and suffering by an unknown mechanism. They have a slow onset of action (placebo-controlled trials show that it takes several weeks to see an effect in the treated groups), and they appear to have a more sustained post-treatment effect than NSAIDs or analgesics. A 3-year placebo-controlled trial showed that glucosamine might retard radiographic progression. We recommend trying glucosamine and chondroitin sulfate at a dose of 1200 to 1500 mg daily in most patients with osteoarthritis, given that the safety profile and efficacy are similar to those of NSAIDs and acetaminophen.

Acupuncture, although used by many patients, appears to be no better than sham needling in controlled trials, and it is not without its own risks, which include reports of hepatitis transmission and pneumothoraces.