Major Review Reveals That Osteoarthritis is a Complex Disease with New Solutions

A multidisciplinary group of scientists has declared that osteoarthritis (OA), the most common form of arthritis, is "surprisingly complex," but has outlined a number of new approaches to its understanding, prevention and treatment. Their report, a review by 28 researchers at 17 academic and government institutions, cites over 250 published articles and is presented in two parts in the Annals of Internal Medicine.

The effort was led by David T. Felson, M.D., M.P.H., of Boston University, and Reva C. Lawrence, M.P.H., of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH).

The disease, says the review, can result from an inherited predisposition to OA combined with a joint injury. Regular runners have almost no additional risk of OA, but football and soccer players and baseball pitchers are at increased risk. A healthy lifestyle helps �� exercise can lessen disability if OA has developed. Strengthening the thigh muscles reduces risk of OA of the knee, as can losing weight. For people who have the disease, a combination of treatment approaches, including new medications and patient education, is effective.

"I am delighted that we have been able to publish this comprehensive, two-part review arising from our 1999 conference 'Stepping Away from OA,' " says Stephen I. Katz, M.D., Ph.D., director of the NIAMS. "OA is a major public health problem, affecting some 20 million people in this country."

The review points out that in the United States about 6 percent of adults over 30 have OA of the knee and about 3 percent have OA of the hip. The disease is responsible for more trouble walking and stair climbing than any other disease, and it is the most common indication for total joint replacement of the hip and knee. Before age 50 the prevalence of OA in most joints is higher in men than women. After this age, more women are affected by OA of the hand, foot and knee. The occurrence of the disease increases with age, rising 2- to 10-fold in people from 30 to 65 years of age.

In osteoarthritis, there is focused, progressive loss of cartilage, the slippery material that cushions the ends of bones, along with changes in the bone below the cartilage leading to bony overgrowth. The tissue lining of the joint can become inflamed, the ligaments looser, and associated muscles weak, with resulting pain when the joint is used.

The review covers risk factors, such as being overweight and joint injury from specific sports, and treatments ranging from established and new medications, exercise, and patient education to surgery when other treatments do not work. It also discusses new areas of research, such as easily measured disease indicators known as biomarkers, as well as engineering of new cartilage. Specific findings are given on the attached backgrounder.

"This review shows that arthritis research is a vibrant area, yielding new means of preventing the disease and slowing its progression, as well as new and effective combinations of drug and behavioral treatments," says Dr. Katz, NIAMS director. "People with osteoarthritis and those at risk for the disease should be encouraged that there is much that they and their doctors can do about it."

The mission of the NIAMS is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research and the dissemination of information on research progress in these diseases. For more information about NIAMS, call our information clearinghouse at 1-877-22-NIAMS or visit the NIAMS Web site at http://www.nih.gov/niams. References:

The two-part review appears as: Felson DT, Lawrence RC, Dieppe PA, et al. Osteoarthritis: New Insights. Part 1: The Disease and Its Risk Factors. Ann Internal Med 2000;133(8):635-646 Felson DT, Lawrence RC, Hochberg MC, et al. Osteoarthritis: New Insights. Part 2: Treatment Approaches. Ann Internal Med 2000;133(9):726-737

The development of the review was coordinated and funded by the NIAMS and was based on a July 1999 conference at NIH initiated, organized and funded by the Institute. Conference cosponsors were the NIH Office of Disease Prevention, NIH National Center for Complementary and Alternative Medicine, NIH Office of Research on Women's Health, NIH Office of Behavioral and Social Sciences Research, NIH National Center for Medical Rehabilitation Research, National Institute of Child Health and Human Development, Centers for Disease Control and Prevention, Arthritis Foundation and American Academy of Orthopaedic Surgeons.

To interview Dr. Felson, contact Rebecca Sullivan, Boston University, at (617) 638-8491. For Ms. Lawrence, contact Connie Raab, NIAMS, at (301) 496-8190 or RaabC@mail.nih.gov. Backgrounder

Findings from the two-part NIAMS Annals of Internal Medicine article: "Osteoarthritis: New Insights"

Risk factors and disease prevention:

Serious joint injury can lead to osteoarthritis (OA), but more often the disease results from a combination of systemic and joint-related factors. OA is strongly genetically determined, with genetic factors accounting for about half of OA in the hands and hips and a smaller percentage of OA of the knees. However, several steps can be taken to prevent or delay onset of OA.

Weight loss can reduce the risk of OA. In one major study cited by the review, people who lost 11 pounds cut their risk in half.

Weakness of the quadriceps muscle (in front of the thigh) is common in patients with OA. It is clear that strengthening the quadriceps can help: a relatively small increase in strength (20 percent for men and 25 percent for women) can lead to a 20-30 percent decrease in risk of OA.

There is low or no additional risk of OA from regular, moderate running. However, sports that involve high-intensity, acute, direct joint impact from contact with other players, playing surfaces or equipment do have an increased risk of OA; football is an example. Sports that involve both repetitive joint impact and twisting also have an increase risk of OA; examples are soccer and baseball pitching. The authors suggest that individual counseling, rule changes, changes in equipment and playing surfaces, and training can help reduce injuries. Early diagnosis and treatment of and complete rehabilitation from joint injuries can decrease risk of subsequent OA.

High intakes of vitamin C are associated with lower rates of OA on X-ray and less knee pain from OA. High levels of vitamin D protect against new and progressive OA.

Much of the OA in men is attributable to occupational activities, particularly jobs requiring kneeling or squatting, along with heavy lifting.

In the future, research may enable doctors to use biomarkers to help identify people at risk for OA and people with OA at risk for disease progression. These biomarkers could also help doctors assess the effectiveness of treatments. OA biomarkers are substances in joint fluid, blood or urine that indicate changes in bone or cartilage.

Treatment:

Once OA develops, certain factors put a patient at risk for disability. These include pain, depression, muscle weakness and poor aerobic capacity. Although the expert group said that OA cannot be cured, there are new medications available, and recent studies have shown the potential of treatments that range from new medications to complementary medicine, patient education approaches, exercise and surgery. These approaches are often combined.

Medications

Acetaminophen can help mild or moderate joint pain in OA.

The next drugs of choice are tramadol and nonsteroidal anti-inflammatory drugs (NSAIDs).

The use of NSAIDs is often associated with problems in the gastrointestinal (GI) tract and kidney problems. For people who experience these problems, the review suggests use of either a combination of an NSAID and a drug that protects the GI system or newer agents known as COX-2 inhibitors. These new agents act against inflammation but with much less effect on the GI system. The federal Food and Drug Administration recently approved two such drugs, celecoxib and rofecoxib.

Opioid painkillers can also be used in patients with OA, as can creams containing painkillers applied to the skin (for example, capsaicin cream).

Nondrug approaches, including exercise and patient education

Glucosamine and chondroitin sulfate have received tremendous popular attention, and a recent meta-analysis of 15 studies cited by the review shows they may have some positive effects on OA. However, the review authors call for high-quality independent studies to evaluate the efficacy of these compounds. They cite an NIH study underway that is expected to yield results in 2004.

Exercise is important in people with OA. The review says that deconditioned muscle, inadequate motion, and joint stiffness make the signs and symptoms of OA worse. It recommends well-designed exercise programs that include training for strength and endurance. Exercise can help patients regain or maintain motion and flexibility through low-intensity, controlled movements that don't increase pain.

Shock-absorbing footwear and other devices can help OA of the knee. Two papers cited suggest that heel wedges in the shoes are an alternative to knee replacements in certain cases of OA of the knee.

Research on the efficacy of acupuncture in OA thus far is inconclusive but promising. A large NIH study of this approach is underway that should be completed in June 2001.

Behavioral interventions are safe and effective in the treatment of OA. Interventions include telephone, mail-delivered and group self-management programs, which are more effective than just providing information. In fact, the review called patient education "the cornerstone" of osteoarthritis treatment. One group patient education program developed with NIAMS support at Stanford University and now taught nationwide by the Arthritis Foundation as the Arthritis Self-Management Program has been shown to reduce pain, doctor's visits, and depression in patients with arthritis as long as 4 years later.

Surgery (after nonsurgical treatments fail)

Removal of bone or joint tissue can relieve symptoms.

Joint fusion can also relieve pain, and is most often done in the spine and in the small joints of the hands and feet.

Total joint replacement, according to the review, is the greatest advance in OA treatment in the past century. It can reduce pain and disability and restore patients to near-normal function. To help replacements last longer, intense research is focusing on more wear- and corrosion-resistant materials as well as how the tissue around the replacements responds.

Replacement of damaged cartilage shows promise, with three types available: use of one's own cartilage, use of donor cartilage, and tissue engineering of cartilage progenitor cells. Development of the latter is still in its infancy.