About Us

Hearing on Chronic Diseases
FY 2002

Witness appearing before the House Subcommittee on Labor-HHS-Education Appropriations

Statement by

Stephen I. Katz, M.D., Ph.D., Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases

Mr. Chairman and Members of the Committee:

Diseases of bones, joints, muscles, and skin are common, chronic, very costly, and often disabling, and they often result in significantly reduced quality of life. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports research in this broad array of diseases, including osteoporosis and other bone diseases; osteoarthritis, rheumatoid arthritis, fibromyalgia, and other rheumatic diseases; psoriasis, lupus, and other autoimmune diseases; and skin diseases such as blistering diseases and eczema. In addition, we support research on the many forms of muscular dystrophy which may be chronic or deadly. I am privileged to report our highlights of progress and opportunities in selected areas.

Osteoporosis

We know that bone is by no means a static part of the body, but that it is continually remodeled and built up and broken down by a balanced interplay between cells with different functions. Too little bone build up or too rapid bone breakdown can result in osteoporosis, with fragile bones and increased susceptibility to bone fractures. Osteoporosis is a major health risk for 28 million Americans today: 10 million individuals have osteoporosis and 18 million more have low bone mass. American women are four times more likely to develop osteoporosis than men. The use of bisphosphonate drugs, that affect the balance between bone build up and breakdown, has improved the management of diseases that involve bone loss. Great progress has come in understanding the roles of genetics, the environment, nutrition, exercise, hormones, behavior, and other factors in the maintenance of bone health.

The NIAMS invests in many types of research to better identify methods for the diagnosis, treatment, and prevention of osteoporosis. Although genetic influences are believed to account for up to three-quarters of the variation in bone mass, there is still room for the modifiable factors (including nutrition) to play an important role. Major attention has been focused on calcium and its importance to bone health, but the role of other nutritional factors has been under-emphasized. Dietary potassium and magnesium, as well as fruits and vegetables, have been hypothesized to preserve bone mass and prevent bone loss through their effects on the body's metabolism.

Other advances are coming from more fundamental basic and animal studies. In the past year, investigators have found that the statins, drugs that lower serum cholesterol, increase the production of a bone-enhancing molecule. This is leading to clinical studies of the effects of these drugs on bone density and to the development of drugs that can be directly delivered to the bone to exert their maximal effect. Other studies have shown that a protein called leptin, which acts to control food intake as well as other aspects of behavior and physiology, also seems to inhibit bone formation in mice. This unexpected effect of leptin may help to explain some conditions of bone loss. Thus, if drugs can be designed to specifically block leptin's action on bone, they may be useful as therapies to restore lost bone.

Osteoarthritis and Total Joint Replacements

As our population ages, the cartilage that protects many of our joints degenerates, causing the pain and dysfunction of osteoarthritis. You will hear about some of the new approaches to the treatment of osteoarthritis from my colleague in NCCAM. When medical approaches fail, joint replacement is used to alleviate the pain and suffering from osteoarthritis. Considerable research on the biomaterials used for total joint replacements has taught us that particles may be released from these replacement parts and cause loosening and ultimate failure of the artificial joint. The mechanism of loosening is under intensive study and may help identify methods to circumvent this cause of joint replacement failure. In addition, new and modified implant materials and designs are under study to determine if they are less likely to be affected by implant loosening caused by wear particles.

Rheumatoid Arthritis, Psoriasis, Lupus, and Other Autoimmune Diseases

There are more than 100 rheumatic diseases, and an estimated 2.1 million Americans have rheumatoid arthritis - a chronic disease that is much more common in women than men, affects the entire body, is characterized by progressive destruction of the joints, and is widely considered to be the prototype of an autoimmune joint disease (in autoimmune diseases, the body literally turns against itself and destroys its own tissues as it would a foreign substance). In rheumatoid arthritis, the patient's own immune and inflammatory cells mistakenly attack and destroy the joints. Research on the role of inflammation in rheumatoid arthritis determined that tumor necrosis factor, a naturally occurring protein that was studied for its tumor-destroying effects, also causes inflammation in the joints. In a clear example of translational research, these findings from basic science were applied to improved clinical treatment. A new class of drug treatments called "biologic agents" was designed to interfere with the specific biological process of diseases like rheumatoid arthritis. The drug etanercept acts as a "sponge" to absorb tumor necrosis factor, and the drug infliximab is an antibody to tumor necrosis factor - thereby blocking the role of tumor necrosis factor in inflammation. Etanercept has recently been shown to be a safe and effective drug in the treatment of children and teenagers with juvenile rheumatoid arthritis (JRA), according to recent clinical trial results organized by one of the NIAMS research centers and investigators in the Pediatric Rheumatology Collaborative Study Group.

The NIAMS also supports research in a number of other chronic and disabling autoimmune diseases, including psoriasis, lupus, scleroderma, alopecia areata, and blistering skin diseases. Psoriasis is a common and chronic skin disease characterized by scaling and inflammation, and it affects an estimated 5.5 million Americans, including people of all ages. In addition, some people with psoriasis have joint inflammation, called psoriatic arthritis. Research has now established that psoriasis is probably a disorder of the immune system, and that cells involved in immune function start reacting against the skin and joints, triggering inflammation and excessive skin cell reproduction. Therapies to reverse this immune response are being developed. As well, since psoriasis is often inherited, researchers continue to search for susceptibility genes, studying large families affected by psoriasis to identify a susceptibility gene or genes.

Lupus is an autoimmune disease that can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain, and it mainly affects young women. Nine times more women than men have the disease; it is also three times more common in African American women than in Caucasian women; and it is more common in women of Hispanic, Asian, and Native American descent. African American women tend to develop the disease at a younger age than Caucasian women and to develop more serious complications. Research areas include socioeconomic and demographic characteristics, clinical features, behavioral-psychosocial factors, and genetic factors, as well as identifying those factors that are modifiable.

Muscular Dystrophies

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy, and affected children often die during their third decade of life. The NIAMS has continued to work collaboratively with the NINDS, the NIH Office of Rare Diseases, and outside muscular dystrophy organizations to stimulate and support further research on DMD and other forms of the disease. Last year, we sponsored major conferences on both facioscapulohumeral muscular dystrophy (FSHD) and DMD, bringing together experts from around the world to discuss the current state of research and promising directions for future studies. In follow-up to these meetings, the NIAMS and NINDS have issued research solicitations for exploratory studies of FSHD, as well as for projects aimed at therapeutic and pathogenic approaches for the muscular dystrophies. In addition, the NIAMS and the NINDS have recently funded a research registry for FSHD and myotonic dystrophy (another form of muscular dystrophy). This registry will facilitate research by serving as a liaison between families affected by these diseases, and investigators who are interested in studying these disorders.

Since many muscle diseases have a genetic basis, there has been a strong emphasis on trying to modify or replace the altered gene in various animal models of muscle diseases. As well, various studies of muscles have suggested other methods for altering gene function when the gene is faulty or can not be produced. Recent studies have demonstrated that intramuscular injection of a gene that codes for a certain type of growth factor can restore muscle mass in aging mice. Although these results are promising, considerable research is needed to pursue genetic transfer technology in people.

Conclusion

Almost every household in America is affected in some way by chronic diseases of bones, joints, muscles, and skin. These diseases can occur in people of all ages, racial and ethnic populations, and economic strata. Many of the diseases within our mandate disproportionately affect women and minorities, who, in many cases, also suffer worse outcomes. We are committed to uncovering the bases of these gender, racial, and ethnic disparities and to devising effective strategies to treat or prevent them. NIAMS research has ramifications for this generation and generations to come. We are investing in the future health of our nation, and American people of all ages and population groups will benefit from these investments.