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Signifcant Items in House, Senate, and Conference Appropriations Committee Reports
FY 2002 Budget

February 2001 (historical)

FY 2001 House Appropriations Committee Report Language (H. Rpt. 106-645)

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Childhood skeletal malignancies - There is a need to conduct clinical outcome assessments of children with skeletal cancers. While mortality rates have improved among children with these tumors, little is known of the long-term effects and risks associated with various treatment options. The Committee encourages NIAMS to enhance research into the effects of treatment protocols on the health of persons treated as adolescents for skeletal cancers. (p. 85)

Action taken or to be taken

The NIAMS is committed to strengthening our pediatric research portfolio both intramurally and extramurally. The Institute is currently participating in a request for applications for clinical trial planning grants for pediatric rehabilitation with a focus on pediatric musculoskeletal conditions, burn wounds, and genetic skin disorders. This new solicitation is built on an understanding that, although disorders in adults and children may be similar in causality, diagnosis and treatment, a wide range of developmental phenomena distinguishes the rehabilitation of infants, children and adolescents from that of adults. The establishment of appropriate interventions and rehabilitation goals for children, therefore, must take account of the developmental process.

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Duchenne muscular dystrophy - Duchenne muscular dystrophy remains the most common childhood form of muscular dystrophy. The Committee is encouraged by the recent scientific workshop to explore promising research efforts in this field. The Committee encourages NIAMS to build on this promising research and collaborate with other Institutes to develop an enhanced focus on muscle disease research and finding a cure for this tragic disease through all available mechanisms, as appropriate, including establishing a muscle study section whose members would have both knowledge of muscle tissue structure and function, and technical expertise on pathophysiology, biochemistry, and genetics. (p. 85)

Action taken or to be taken

The NIAMS has a strong interest in stimulating and supporting research to enhance our understanding of the causes of, and potential treatments for, the various muscular dystrophies, including Duchenne muscular dystrophy (DMD). DMD is a genetic, muscle-wasting disease that is caused by mutations in the gene for the protein dystrophin. NIAMS-funded scientists recently reported a number of exciting advances in mouse models of DMD. These include the successful application of the common antibiotic gentamicin to restore the function of the dystrophin protein, and the successful use of gene replacement to restore the missing protein and thereby reduce muscle disease. Such animal studies hold promise for potential future therapies for human patients affected by DMD.

Last spring, NIAMS staff partnered with colleagues from the National Institute of Neurological Disorders and Stroke (NINDS) and other NIH components, as well as research and patient advocacy organizations, to sponsor a scientific workshop on therapeutic approaches for DMD. The meeting provided an opportunity for DMD investigators to share new findings, identify gaps in current research, and recommend future directions for promising studies of this disease. The insights from this conference will shape new research solicitations in DMD and other muscular dystrophies being developed by the NIH. These initiatives will build on projects funded through the currently active program announcement on the pathogenesis and therapy of the muscular dystrophies. Furthermore, the NIH intramural research program is building expertise in muscle diseases, with the recent addition of several renowned scientists.

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Heritable disorders of connective tissue - The Committee acknowledges NIAMS for its support of research on heritable disorders of connective tissue, for its sponsorship of two conferences held on this body of disorders in 1990 and 1995, and for the upcoming Scientific Conference. These disorders are rare; they involve a variety of organs in the body, are genetic in origin, and affect the connective tissue. Because of their multi-organ character, the Committee believes a coordinated research approach will more quickly lead to development of effective therapies and perhaps ultimately a cure for these disorders. NIAMS is encouraged to use all available mechanisms, as appropriate, to enhance efforts in this area, including establishing scientific research centers. (p. 85)

Action taken or to be taken

Heritable connective tissue disorders, while mostly rare, are often highly disabling and are potentially fatal for patients who have them. Further advances in the basic understanding of these diseases will allow more targeted and effective therapeutic interventions. For example, researchers supported by the NIAMS are working to identify the specific mutations that cause a heritable disorder of connective tissue known as Marfan syndrome, a condition characterized by manifestations in the skeletal, ocular, and cardiovascular systems. Results to date suggest that mutations in the gene for fibrillin 1 may ultimately lead to tissue failure in patients with this disorder. A better grasp of which mutations lead to disease could point researchers toward new therapeutic targets and treatment modalities. Promising work has also been funded on another connective tissue disorder known as pseudoxanthoma elasticum, or PXE, an inherited condition characterized by progressive calcification of elastic fibers in the skin, eye, and cardiovascular system. Scientists studying PXE have identified the gene that causes this disease, a discovery that could lead to the design of therapeutic interventions to treat the disorder.

This fall, the NIAMS joined with the Coalition for Heritable Disorders of Connective Tissue to sponsor the Third Research Symposium on the Pathogenesis of Connective Tissue Disorders. The meeting was designed to bring together investigators with an interest in connective tissue disorders to share recent advances and novel approaches to the treatment of these diseases. Insights gained at this meeting will inform the development of future research initiatives in this area. The NIAMS is also committed to disseminating science-based health information for patients and families affected by connective tissue disorders. To this end, the Institute recently developed a fact sheet on heritable disorders of connective tissue, including information on conditions such as Ehlers-Danlos syndrome, epidermolysis bullosa, Marfan syndrome, and osteogenesis imperfecta.

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Lupus - Lupus is an autoimmune disease that mainly affects women of child-bearing age, can lead to severe organ injury, and the treatment is often as devastating as the disease. African-American women are three times more likely to have lupus than Caucasian women. The Committee is encouraged by recent NIAMS research success in identifying genes and mechanisms which lead to the onset of lupus and urges enhanced research to continue this work. Gaining understanding of the factors associated with the high prevalence of lupus in women and minorities and developing new and innovative treatments while protecting the poor and the uninsured from financial devastation are important priorities for the Committee. The Committee encourages NIAMS, in collaboration with other Institutes, to enhance research efforts at developing safer and more effective treatments, and ultimately, a cure. (p. 86)

Action taken or to be taken

The NIAMS is committed to enhancing basic, clinical, and translational research to improve our understanding of autoimmune diseases such as systemic lupus erythematosus (SLE), which predominantly affect women. The Institute is currently supporting two specialized centers of research in SLE. The first, at the University of Alabama in Birmingham, represents a unique consortium of research organizations and is studying the disease's genetic aspects. The second, at the University of Virginia in Charlottesville, is addressing genetic and immune mechanisms that underlie SLE flare-ups and organ damage. In addition, the Institute continues to fund the Lupus in Minorities, or LUMINA, study, an effort designed to examine the relationship of cultural, socioeconomic, demographic, immunogenetic, and clinical variables to presentation and early outcome in Hispanic, African American and Caucasian SLE patients. The NIAMS also supports two lupus research registries, one at the Oklahoma Medical Research Foundation that collects data on families with lupus, and a second at the Hospital for Joint Diseases in New York that focuses on cases of neonatal lupus. Such registries facilitate studies that could ultimately lead to improved diagnosis, treatment, and prevention strategies.

To stimulate further work on lupus, the Institute recently issued a solicitation for rheumatic diseases core centers that will provide support for a number of established, currently funded investigators to adopt multidisciplinary approaches to common research problems in rheumatic diseases, such as lupus. The Institute is also participating in major research conferences that include a focus on lupus, such as the annual meeting of the National Medical Association in the summer of 2001. In the NIAMS intramural research program, we have recently established an autoimmunity branch to assess the cellular and molecular basis of autoimmune diseases such as lupus, and we have begun novel therapeutic trials involving targeted biologic agents. In addition, the NIAMS Health Partnership Program is working to establish a local Community Health Center in Washington, DC, to explore the reasons that lupus affects members of the African American and Hispanic/Latino communities more often and more severely.

Finally, the NIAMS is committed to disseminating science-based health information on lupus for affected patients and their caregivers. To this end, the Institute continues to make available copies of the popular publication "Lupus: A Patient Care Guide for Nurses and Other Health Professionals." This resource guide represents a collaboration between Federal health agencies and SLE voluntary organizations, and provides a strong model for future dissemination efforts. We are currently partnering with a local health voluntary to develop easy-to-read and bilingual booklets on SLE.

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National occupational research agenda - The Committee encourages NIAMS to work with the National Institute for Occupational Safety and Health to enhance research in relevant National Occupational Research Agenda priority areas such as Allergic and Irritant Dermatitis, Low Back Disorders, Traumatic Injuries, Musculoskeletal Disorders of the Upper Extremities, and Special Populations at Risk. (p. 86)

Action taken or to be taken

Since the unveiling of the National Occupational Research Agenda (NORA) in 1996, the NIAMS has participated in a number of productive partnerships with the NIOSH on research initiatives related to NORA priority areas in allergic and irritant dermatitis and musculoskeletal disorders. In FY 1999, the Institute funded a major, multicenter clinical trial on low back pain, in conjunction with the NIOSH and the NIH Office of Research on Women's Health. The trial is the largest federally funded study to date on low back disorders and is expected to provide scientific evidence on the efficacy of nonoperative and operative treatments for three of the most common, costly, and potentially debilitating spinal disorders. We are also supporting a study on the impact of knee osteoarthritis on work loss and related disability, as well as an investigation of the impact of psychosocial and physical risk factors on the job-related health status of hospital workers. The NIAMS continues to work with the NIOSH and other Federal partners to identify and promote opportunities to further enhance research related to NORA areas by participating, for example, in the recently released program announcement on occupational safety and health research. The new solicitation is designed to develop knowledge that can be used in preventing occupational diseases and injuries, and to better understand their underlying pathophysiology.

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Osteoporosis - The Committee encourages NIAMS to enhance research in the area of osteoporosis with a particular emphasis on studying OP in the non-white population. The Institute is encouraged to focus on interventions to improve quality of life and the relationship between hypertension and OP. (p. 86)

Action taken or to be taken

Osteoporosis is a metabolic bone disease characterized by low bone mass, which makes bones fragile and susceptible to fracture. Osteoporosis is often called a "silent disease" because there are no symptoms or pain until a fracture occurs. While African American women tend to have higher bone mineral density than Caucasian women throughout life, they are still at significant risk of developing osteoporosis. Furthermore, as African American women age, their risk of developing osteoporosis more closely resembles the risk among Caucasian women. At present, approximately 300,000 African American women have osteoporosis, and between 80 and 95 percent of fractures in African American women over 64 years of age are due to the disease. As these women age, their risk of hip fracture doubles approximately every 7 years, and African American women are more likely than Caucasian women to die following a hip fracture. We know that adequate intake of calcium plays a crucial role in building peak bone mass, as well as preventing bone loss. Studies indicate that African American women consume, on average, 50 percent less calcium than the recommended dietary allowance. This finding points to opportunities for behavioral interventions that could reduce disease risk in this population.

NIAMS presently supports a study of the effects of calcium supplementation on both bone mineral density and blood pressure in a 7 year, randomized clinical trial in adolescent girls. In addition, the Institute has recently issued a request for applications on bone formation and calcification in cardiovascular disease, in conjunction with the National Heart, Lung, and Blood Institute. The solicitation is designed to address the possible mechanistic links between vascular calcification and bone formation, and between osteoporosis and heart disease. In particular, interdisciplinary studies are being encouraged to look at the effects of common therapeutic agents on the skeleton and cardiovascular system. The request builds on a scientific workshop held in the fall of 1999 and reflects the recognition that recent research developments suggest significant parallels between bone remodeling and vascular calcification, with implications for the epidemiology and treatment of both osteoporosis and heart disease. Furthermore, last spring, the Institute sponsored a major consensus development conference on osteoporosis at which national and international experts presented the latest research findings on this disorder, and developed recommendations to enhance future diagnosis, prevention, and treatment approaches.

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Paget's disease - The Committee is aware of the importance of research on the viral and genetic factors that may cause Paget's disease and encourages NIAMS to enhance efforts in this area. (p. 86)

Action taken or to be taken

Paget's disease is a chronic disorder that typically results in enlarged and deformed bones. The excessive breakdown and formation of bone tissue that occurs in Paget's disease can cause bone to weaken, resulting in bone pain, arthritis, deformities, and fractures. Paget's disease may be caused by a chronic viral infection, present for many years before symptoms appear. Hereditary factors are also involved as the disease may appear in more than one family member. NIAMS-supported scientists are currently working to identify the gene or genes that trigger this disease, an important step towards the development of effective treatments. Other researchers have been exploring the role of the measles virus in Paget's disease, in an effort to clarify how the presence of the virus causes abnormalities in the cells that break down bone. These studies could lead to the development of animal models of Paget's disease, which would allow detailed investigations of the influence of viral factors on the breakdown of bone cells and, ultimately, may be used to test new therapeutic strategies. Furthermore, the NIAMS is committed to disseminating science-based health information on Paget's disease and related bone disorders. To this end, the Institute has partnered with the Paget Foundation, the National Osteoporosis Foundation, and the Osteogenesis Imperfecta Foundation to support a national resource center on a wide range of metabolic bone diseases for patients, health professionals, and the public.

Congressional Justifications

FY 2001 Senate Appropriations Committee Report Language (S. Rpt. 106-293)

Item

Arthritis - Forty-three million Americans have some form of arthritis. These painful and disabling degenerative diseases wear away protective joint cartilage and are the leading cause of disability in the U.S. The economic cost to the U.S. for musculoskeletal and skin diseases and arthritis is staggering. Between 1988 and 1995, the total cost rose by 70 percent. (p. 153)

Action taken or to be taken

Rheumatic diseases such as rheumatoid arthritis and osteoarthritis affect people of all races and ages, and are the leading cause of disability among adults age 65 and older in the United States. It is estimated that by the year 2020, nearly 60 million Americans will be affected by arthritis and other rheumatic conditions. These diseases may cause pain, stiffness, and swelling in joints and other supporting structures of the body such as muscles, tendons, ligaments, and bones. Some rheumatic diseases, such as lupus and scleroderma, can also affect other parts of the body, including various internal organs. The NIAMS funds a broad array of research studies across the spectrum from basic to clinical to translational, in an effort to better understand what causes these conditions and how best to treat and prevent them. Such investments include support for studies of target organ damage in rheumatoid arthritis (RA), an inflammatory disease of the lining of the joint, and of new imaging technologies in animal models of RA. Other scientists funded by the NIAMS have launched a multicenter clinical trial to test the oral administration of a small peptide for RA treatment.

The Institute is also building the research infrastructure needed to stimulate additional innovative studies of arthritis and other rheumatic conditions. Such efforts include support for a consortium that is searching for genes that predispose individuals to RA, with the overall scientific goal of developing better diagnostic and treatment methods; funding of a new research registry on RA in the African American population; and support for specialized centers of research in both RA and osteoarthritis, which is also known as degenerative joint disease. In addition, the Institute has recently issued a solicitation for rheumatic diseases core centers that will provide support for a number of established, currently funded investigators to adopt multidisciplinary approaches to common research problems in rheumatic diseases. In the NIAMS intramural research program, we continue to support studies designed to understand the genetic and cellular bases of arthritis, as well as novel therapeutic trials involving targeted biologic agents. Moreover, we have recently launched a cartilage biology branch to examine the causes of osteoarthritis. Finally, the NIAMS is committed to disseminating science-based health information on arthritis and related conditions. For that purpose, the Institute recently published a bilingual brochure, in Spanish and English, entitled "Do I Have Arthritis?" and developed a primer for patients on new medications for RA and OA.

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Behavioral and social science research - The Committee notes that the portion of the NIAMS research portfolio devoted to behavioral and social sciences research is significantly lower than the NIH average. Therefore, the Committee urges NIAMS to fund promising behavioral [and] social sciences research. Additionally, the Committee urges favorable consideration of research in the area of behavioral and social science factors relating to the adherence to medical recovery regimes, exercise, and weight reduction programs. (p. 153)

Action taken or to be taken

The diseases within the mandate of the NIAMS are among the most chronic and costly affecting our Nation, and the Institute remains committed to bettering the quality of life for people affected by these diseases. NIAMS-funded researchers are studying novel approaches to self-efficacy, including the use of on-line chat rooms for patients with chronic back pain. Other studies have revealed that arthritis educators can provide a meaningful boost to traditional care for patients with rheumatic diseases. Teaching and support by trained educators have been proven to have a positive impact on the knowledge and satisfaction with services for patients with arthritis who visit rheumatology clinics. Further projects are looking at differences between individuals who remain active participants in research studies and patients who drop out, as a way of assessing whether attrition by certain subgroups could bias research results. Data thus far suggest that psychosocial and socioeconomic factors are more important determinants of continued participation in long-term research studies than are most clinical disease characteristics.

The NIAMS will continue to support promising research in the areas of health services and professional and patient education. The Institute is currently participating, along with a number of other NIH components, in a program announcement to stimulate research exploring self-management strategies across chronic diseases, such as arthritis. We have also initiated a program for multipurpose clinical research centers that includes behavioral and social sciences as areas of emphasis. Furthermore, we have recently enhanced our extramural expertise in behavioral and social sciences, and hosted a major scientific conference on health disparities in December 2000 that featured sessions on social and behavioral factors that influence the frequency and impact of disease.

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Duchenne/Becker muscular dystrophy - ...Therefore, the Committee urges the NIH to consider establishing a Muscle Study Section Review. Furthermore, the Committee feels that efforts should be made by NIAMS and NINDS to increase the amount of research devoted to skeletal muscle, especially DMD/BMD. The Committee strongly recommends NIH, in conjunction with all appropriate institutes, evaluate the current state of research so as to identify the critical path for DMD/BMD research, filling in the "gaps" in basic muscle science. In this regard, the Committee urges NIH to conduct a research conference to evaluate the status of research and assist in properly directing the critical science investment areas [in] muscle research. The Committee requests that NIH prepare a report on the progress of research related to D/BMD and indicate proposed investment strategies to ensure that technical progress is sustained. The Committee requests the report by January, 2001. The Committee also urges that NIH develop trans-institute initiatives for D/BMD to ensure appropriate coordination across relevant institutes and further recommends that additional research be reviewed at the consensus conference. (p. 154)

Action taken or to be taken

Please refer to page NIAMS-29 of this document for NIAMS' response to this significant item regarding Duchenne muscular dystrophy.

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Ehlers-Danlos syndrome - Ehlers-Danlos Syndrome (EDS) is a family of genetic disorders whose manifestations include but are not limited to the skin, joints and other components of the connective tissue. The prevalence of each type and of EDS overall is not well defined, although the figure of 1:5-10,000 individuals for the syndrome is generally accepted. EDS is potentially a model for a number of more common medical and biological problems stemming from genetic acquired connective tissue defect. The Institute is encouraged to provide the highest possible funding for continued research of this disease. (p. 154)

Action taken or to be taken

The NIAMS has a long-standing commitment to research on heritable disorders of connective tissue, including Ehlers-Danlos syndrome (EDS). EDS is a set of conditions characterized by hyperextensibility of the skin, easy bruisability, increased joint mobility, and abnormal tissue fragility. This fall, the NIAMS joined with the Coalition for Heritable Disorders of Connective Tissue to sponsor the Third Research Symposium on the Pathogenesis of Connective Tissue Disorders. The meeting was designed to bring together investigators with an interest in connective tissue disorders such as EDS to share recent advances and novel approaches to the treatment of these diseases. Insights gained at this meeting will inform the development of future research initiatives in this area. The NIAMS is also committed to disseminating science-based health information for patients and families affected by connective tissue disorders. To this end, the Institute recently developed a fact sheet on heritable disorders of connective tissue, including information on conditions such as EDS, epidermolysis bullosa, Marfan syndrome, and osteogenesis imperfecta.

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Facioscapulohumeral muscular dystrophy and facioscapulohumeral disease (FSHD) - The Committee is extremely concerned that funding for FSHD has decreased and that no new projects have been funded over the past year. The Committee requests that the NIH report after the research planning conference on steps it will take to create a comprehensive research portfolio in FSHD. The Committee further urges that NIH make research in FSHD a high priority. (p. 154)

Action taken or to be taken

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common genetic disease of skeletal muscle. FSHD is heritable, and the inheritance of the disease inevitably leads to the expression of symptoms, which include progressive weakening of the muscles of the face, shoulders, and upper arms. A number of projects with potential implications for FSHD have been funded as a result of a currently active program announcement on the pathogenesis and therapy of the muscular dystrophies. These include NIAMS-supported grants focused on developing safe and effective methods to perform gene therapy on skeletal muscle, and a project funded by the National Institute of Neurological Disorders and Stroke (NINDS) that builds on the identification of a new protein, found only in muscle, whose genetic locus is very close to the locus for FSHD and that may play a role in the development of the disorder.

Last spring, the NIAMS, together with the NINDS and other NIH components, as well as FSHD research and patient advocacy organizations, cosponsored a scientific conference on the cause and treatment of the disorder. Researchers from the United States, Canada, Europe, South America, and Asia met to share their latest findings and identify exciting directions for future studies on this disease. The recommendations that emerged from the conference fall into several categories, including efforts to enhance our understanding of the molecular processes and tissue changes associated with FSHD; ways to explore possible therapies to treat the disorder; and strategies to promote the establishment of population-based studies of the disease, as well as needed research resources. These recommendations are being considered as the NIH develops new program initiatives in this area, such as the recently released solicitations for exploratory research applications on FSHD, and for projects on therapeutic and pathogenic approaches for the muscular dystrophies, including FSHD.

In an effort to further develop research resources for FSHD, the NIAMS recently joined with the NINDS to fund a registry on FSHD and another form of muscular dystrophy known as myotonic dystrophy (MD). The long-term goal of the registry is to facilitate research in FSHD and MD by serving as a liaison between families affected by these diseases who are eager to participate in specific research projects, and investigators interested in studying these disorders. The registry will recruit and classify patients, and store medical and family history data for individuals with clinically diagnosed FSHD and MD. Scientists will be provided with statistical analyses of the registry data, as well as access to registry members who have agreed to assist with particular research studies. Finally, the NIH intramural research program is building expertise in muscle diseases, with the recent addition of several renowned scientists.

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Fibromyalgia - Fibromyalgia syndrome (FMS) is a clinically diagnosed disorder which is poorly understood and difficult to treat. It is a syndrome of chronic, debilitating, widespread pain, fatigue, sleep disturbance, and other associated disorders. Research in the eight years following the ACR's case definition of FMS and four years since the first NIH awards on FMS has created a solid body of knowledge. The Committee urges the Institute to support two centers for research into FMS. These centers would conduct multi-disciplinary studies which have the potential to add significantly to science's understanding of this complex and disabling disease. (p. 155)

Action taken or to be taken

In FY 1999, the NIAMS funded a number of new research projects, along with other NIH components, on the basic and clinical aspects of fibromyalgia syndrome (FMS) as a result of a special solicitation for applications. The 13 projects - from basic research on the mechanisms of chronic pain, to clinical studies of cognitive behavioral therapies, to outcomes research on the health status of young women with FMS - represent an important opportunity to strengthen our understanding of a disease that causes much pain, suffering, and lost productivity in many people. One of these new studies seeks to identify genes that contribute to FMS so that, in the long run, the underlying causes and biological mechanisms of this illness will be better understood. These novel efforts complement ongoing studies funded by the Institute that are aimed at developing better ways to diagnose, treat, and prevent this disorder. Furthermore, the NIAMS is committed to disseminating science-based health information for patients and families affected by FMS. To this end, the Institute has a question and answer fact sheet on the disorder, as well as a summary of FMS research challenges and future opportunities.

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Lupus - ... Gaining an understanding of the factors associated with the high prevalence of lupus in women and minorities and the development of new and innovative treatments should be a high priority. The Committee urges NIAMS to explore all available scientific opportunities that presently exist in lupus research and treatment. (p. 155)

Action taken or to be taken

Please refer to page NIAMS-31 of this document for NIAMS' response to this significant item regarding lupus.

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Minority Populations and Osteoporosis - The Committee encourages NIAMS to devote additional resources to studying osteoporosis in the non-white population and is urged to increase its work in this area. Moreover, given the large number of individuals affected by this disease, including a disproportionate number of women, the Institute should focus on interventions to improve quality of life. Another area of research which deserves attention is the investigation of the relationship between hypertension and OP. (p. 155)

Action taken or to be taken

Please refer to page NIAMS-33 of this document for NIAMS' response to this significant item regarding osteoporosis.

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Nutrition therapy and osteoporosis - Enhanced intake of calcium and vitamin D for both the prevention and treatment of osteoporosis in the at-risk Medicare population is strongly supported by a considerable body of data, including multiple randomized controlled trials. However, current data is lacking on whether counseling by a nutrition professional improves the probability of meeting adequate calcium, vitamin D, protein and other micronutrient intake, with or without the use of supplements. With the elderly, who take multiple medications and supplements, many of these medications and supplements interact and work against each other. In addition, many older women have a strong intolerance for milk. The Committee recommends that research be conducted to determine the effectiveness of nutrition counseling in insuring against the intake of excess levels of calcium and on the interactions of supplements and hormone replacement therapies. The role of calcium, vitamin D, protein and other micronutrients in preventing OP and associated problems, such as hip fractures, should also be considered. (p. 155)

Action taken or to be taken

The NIAMS has a long-standing interest in the implications of nutritional approaches for the onset and progression of osteoporosis, a skeletal disorder characterized by compromised bone strength, predisposing individuals to an increased risk of fracture. For example, scientists at the Institute's specialized center for research on osteoporosis at Creighton University have reported that giving lower doses of estrogen and progesterone during hormone replacement therapy (HRT), in combination with calcium and vitamin D, spares older women significant bone mass loss while limiting HRT's more negative side effects. In other studies, researchers confirmed that elderly women who have decreased calcium absorption have an increased risk of osteoporosis-related hip fractures, especially if those women already have low dietary calcium intake. Further investigations point to the importance of nutritional factors other than calcium, such as dietary potassium, magnesium, and fruit and vegetable intake, for long-term bone health.

These and other insights will be built upon as the Institute continues to stimulate studies on risk factors, such as diet, that may be modified in populations at risk for osteoporosis. In addition, last spring, the Institute sponsored a major consensus development conference on osteoporosis at which national and international experts presented the latest research findings on this disorder, and developed recommendations to enhance future diagnosis, prevention, and treatment approaches. Finally, the NIAMS is committed to providing science-based health information on osteoporosis to affected patients, their caregivers, and the public. To this end, the Institute supports a national resource center on osteoporosis and related bone diseases, in collaboration with the National Osteoporosis Foundation, the Paget Foundation, and the Osteogenesis Imperfecta Foundation.

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Osteoarthritis - Early diagnosis of a disease is important to prevent or reduce long-term disability. For musculoskeletal conditions such as osteoarthritis, early diagnosis is hampered because of insufficient knowledge of the early stages of the disease. OA, which can completely destroy the joints of the hips and knees, affects over 20 million Americans, most often the elderly. With the aging of the population expected to double by the year 2020, a significant investment must be made now to reduce the burden of OA later. If not, the dynamics of this condition in the aging population alone will generate an avalanche of costs, disability and suffering to the American people in the future. The Committee therefore encourages the Institute to assign OA research a high priority. (p. 156)

Action taken or to be taken

The NIAMS is pursuing a multipronged approach to the challenge that osteoarthritis (OA), a degenerative joint disease, poses as the U.S. population ages. This approach includes efforts to create a public-private partnership to identify biomarkers and surrogate endpoints that can facilitate clinical trials and enhance drug development for OA; the awarding of a major research contract, in collaboration with the National Center for Complementary and Alternative Medicine, to study the efficacy of the dietary supplements glucosamine and chondroitin sulfate for the treatment of knee OA; and the recent publication of a handout on health on OA for affected patients, family members, health care providers, and health educators. Scientists supported by the Institute have made a number of important contributions in the field of OA in the last year, including investigations to develop specific chemical compounds that prevent the expression of enzymes that cause cartilage degradation, and studies to determine the genetic predisposition of daughters whose mothers have knee OA in the hopes of identifying susceptible individuals as early as possible.

These projects complement other efforts supported by the Institute that range from basic studies to examine biomechanical signaling mechanisms in cartilage, to tissue engineering work that includes the use of animal models to develop joint scaffolds and test surgical approaches for engineered joints, to novel imaging studies designed to better identify joint disorders and assess their progression. We are also supporting several pilot projects to test the feasibility of new methodologies to understand the causes of, and develop novel treatments for, OA. Furthermore, we recently funded a number of new grants to identify and evaluate chondroprotective agents that prevent cartilage destruction, or facilitate its repair. In addition, the NIAMS is building on the insights gained at a scientific conference on OA held in the summer of 1999 to issue a solicitation for research on the onset, progression, and disability associated with OA, in conjunction with other interested Institutes.

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Osteoporosis - The Committee urges NIAMS to consider funding additional specialized Centers for Research for osteoporosis. The Committee notes that these centers have made significant contributions to the progress of osteoporosis research and patient care, and can help in reducing bone fractures and other complications from the disease. (p. 156)

Action taken or to be taken

The NIAMS leads the Federal research effort on osteoporosis and related bone diseases, and supports research ranging from very basic studies to clinical and translational projects, as well as early intervention and prevention efforts. Significant advances in the prevention and treatment of osteoporosis are available today as the direct result of research focused on determining the causes and consequences of bone loss at cellular and tissue levels, assessing risk factors, developing strategies to maintain and even enhance bone density, and exploring the roles of such factors as hormones, calcium, vitamin D, drugs, and exercise on bone mass. For example, scientists at the NIAMS-funded specialized center for research on osteoporosis at Creighton University recently reported that giving lower doses of estrogen and progesterone during hormone replacement therapy (HRT), in combination with calcium and vitamin D, spares older women significant osteoporotic bone mass loss while limiting HRT's more negative side effects.

In FY 1999, the Institute funded two new core centers for research on musculoskeletal disorders. The first, at the Hospital for Special Surgery in New York City, is concentrating on studies of skeletal integrity, which encompasses biological, chemical, and mechanical influences on bone. The second core center, at Yale University in New Haven, focuses on basic bone biology and bone diseases. The work at these core centers will boost the critical mass of talented scientists working on problems of bone growth and disease. In addition, in FY 2000, the NIAMS issued a request for applications for specialized centers for research in osteoporosis. Such centers work with the NIAMS to further the translation of basic research findings to clinical applications that will help affected patients. Furthermore, last spring, the Institute sponsored a major consensus development conference on osteoporosis at which national and international experts presented the latest research findings on this disorder, and developed recommendations to enhance future diagnosis, prevention, and treatment approaches.

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Paget's disease - The Committee is aware of the importance of research on the viral and genetic factors that may cause Paget's disease, and encourages the Institute to expand its work in this area. (p. 156)

Action taken or to be taken

Please refer to page NIAMS-33 of this document for NIAMS' response to this significant item regarding Paget's disease.

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Psoriasis - Psoriasis is a genetically-acquired immune-mediated disease of the skin and joints that affects over 7 million American men, women and children. Over 1 million Americans suffer from severe psoriasis and psoriatic arthritis, which causes cracked, red skin lesions and swollen joints, extreme physical and emotional pain, and limited quality of life. The Committee encourages NIAMS to continue to support additional genetic research to determine which genes are the causative genes for psoriasis and psoriatic arthritis, as well as to pursue research on the immunological mechanisms of the disease. The Committee has been informed that through continued support for this research, new knowledge will be gained to develop improved therapeutic approaches for the treatment of this chronic immune disease. (p. 156)

Action taken or to be taken

Psoriasis is a chronic immune disease of the skin characterized by scaling and inflammation. Scaling occurs when cells in the outer layer of the skin reproduce faster than normal and pile up on the skin's surface. Although the disease occurs in all age groups and about equally in men and women, it primarily affects adults. People with psoriasis may suffer discomfort, including pain and itching, restricted motion in their joints, and emotional distress. Scientists are working to improve our understanding of what happens in the body to trigger this disease. In addition, much research is focused on developing new and better treatments. Some of these experimental treatments, such as agents directed at specific types of white blood cells, known as T cells, involved in the disease, aim to improve symptoms with less overall suppression of the immune system.

Researchers also continue to search for genes that contribute to the inherited and other causes of psoriasis. In a large-scale collaborative study supported by the NIAMS, patients with familial psoriasis were examined in an effort to localize the disease's susceptibility genes. This project indicated that psoriasis susceptibility genes lie very near to, but are not part of, a known group of immune system genes. Work to identify the specific disease-causing genes is ongoing, with the hope that this discovery will aid in our understanding of the pathophysiology of the disease and allow for more targeted interventions. Furthermore, the NIAMS is committed to disseminating science-based health information to patients and families affected by psoriasis. For that purpose, the Institute has developed a question and answer fact sheet on this disorder, in collaboration with the National Psoriasis Foundation.

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Scleroderma - Scleroderma is a chronic, degenerative disease which causes the overproduction of collagen in the body's connective tissue. It affects between 300,000 and 500,000 Americans and is often life-threatening, yet it remains relatively unknown and under-funded. The Committee urges the Institute to provide additional resources to expand the research in this area and to work collaboratively with private research foundations to coordinate research findings. (p. 156)

Action taken or to be taken

Scleroderma is an autoimmune disorder of the body's connective tissue that occurs more often in women than in men, usually between the ages of 45 and 55. The hallmark of this condition is widespread thickening of the skin and internal organs. Although the cause of the disease is unknown, researchers believe that both environmental and genetic factors may play a role in scleroderma. In an effort to build the research resources necessary to better understand the causes of, and develop possible treatments for, this disease, the NIAMS has recently expanded support for a national registry to facilitate investigations of the genetic causes of scleroderma. The Institute also continues to fund a specialized center of research on scleroderma at the University of Texas Health Science Center. Researchers at this center have identified a gene site associated with scleroderma in Oklahoma Choctaw Native Americans.

At a more basic level, scientists supported by the Institute are exploring the molecules that control collagen production in scleroderma, as it is the overproduction of collagen that defines the disease. The hope is that new therapeutics could be developed to restore a balanced collagen synthesis in affected patients. New studies of the disease, which were supported as part of the NIH's autoimmunity initiative, include a multicenter clinical trial that is testing the efficacy of oral collagen in the treatment of scleroderma, and projects focused on target organ damage. To stimulate further research in this area, the NIAMS recently requested applications for specialized centers of research in scleroderma, and has issued a special solicitation for projects on molecular pathogenesis and new interventions for this disorder. In addition, the NIAMS is committed to making science-based health information available to patients with scleroderma and their families. To this end, the Institute has recently developed a handout on health on this disease.

Congressional Justifications

FY 2001 Conference Committee Report Language (H. Rpt. 106-1033)

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Osteogenesis imperfecta - Osteogenesis Imperfecta (OI), more commonly known as Children's Brittle Bone Disease, is a rare genetic disorder for which there is presently no cure. The conferees strongly encourage NIH to expand its support for research into the causes, diagnosis, treatment, prevention, and eventual cure for OI and to coordinate public research efforts with those supported by the private sector. The Director of NIAMS should be prepared to testify on this issue at the fiscal year 2002 appropriations hearing. (p. 138)

Action taken or to be taken

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has a long-standing interest in conditions such as osteogenesis imperfecta (OI), a genetic disorder characterized by bones that break easily, often for little or no apparent cause. In the fall of 1999, the Institute sponsored a scientific workshop on new research strategies in OI, in partnership with the NIH Office of Rare Diseases, the Osteogenesis Imperfecta Foundation, and the Children's Brittle Bone Foundation. Recommendations from that meeting influenced the development of a new research initiative on OI that is being sponsored by the NIAMS and other interested Institutes, including the National Institute on Aging and the National Institute of Child Health and Human Development. Novel projects which may emerge from this solicitation will complement recently funded studies in OI, which seek, among other goals, to develop cutting-edge gene and cell therapies and to test new drug treatments in mouse models of the disease. Furthermore, the NIAMS is participating in a request for applications for clinical trial planning grants for pediatric rehabilitation with a focus on pediatric musculoskeletal disorders and genetic skin disorders. Finally, the NIAMS supports the NIH Osteoporosis and Related Bone Diseases~National Resource Center, a collaborative effort with several health voluntary organizations, including the Osteogenesis Imperfecta Foundation. The resource center develops and disseminates health information for the public, patients, and health providers.

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Osteoporosis resource center - Important strides have been made with the establishment of the Osteoporosis and Related Bone Diseases National Resource Center. The conferees urge NIAMS to expand support for the resource center's current activities, including developing and disseminating information based on current research findings that improve knowledge and understanding of the prevention, diagnosis, and treatment of osteoporosis and related bone diseases, implementing and evaluating model education programs to enhance bone health and reduce future risk of osteoporosis, and supporting public and private efforts to broaden the base of knowledge about osteoporosis and related bone diseases. (p. 138)

Action taken or to be taken

The NIH Osteoporosis and Related Bone Diseases~National Resource Center was established in 1994 with funding from the NIAMS and is presently also supported by a number of other NIH components, as well as the Department of Health and Human Services' Office of Women's Health. Its mission is to provide patients, health professionals, and the public with resources and information on metabolic bone diseases, including osteoporosis, Paget's disease of the bone, osteogenesis imperfecta, and hyperparathyroidism. The Center is currently operated by the National Osteoporosis Foundation, in collaboration with the Paget Foundation and the Osteogenesis Imperfecta Foundation. In recent years, the Resource Center has expanded its efforts to increase the awareness, knowledge, and understanding of physicians, health professionals, patients, underserved and at-risk populations, and the general public about the prevention, early detection, and treatment of osteoporosis and related bone diseases.

Recent projects undertaken by the Resource Center include the development and dissemination of publications on falls and fracture prevention, fitness and bone health for female athletes, skeletal effects of eating disorders, and prostate cancer that has spread to bone. The Center has also pioneered a pilot program in partnership with the National Alliance for Hispanic Health to work with Hispanic girls in Phoenix, Arizona, to deliver bone health messages through peer theater performances. Other current activities include the development of new osteoporosis education projects aimed at both Asian and Hispanic women, as well as efforts to educate physicians and patients on the importance of assessing risk for osteoporosis once a fracture has occurred. The NIAMS is committed to enhancing efforts in this area and will continue to support an active information dissemination program on osteoporosis and related bone diseases.

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Pediatric rheumatology - The conferees commend NIAMS for its growing support of research on rheumatic diseases of childhood, including the recent opening of a new Pediatric Rheumatology Clinic on the NIH campus. However, the conferees are concerned about the cadre of pediatric rheumatologists who are trained to treat and study these diseases. NIAMS is therefore encouraged to work with the Secretary of HHS and other PHS components, as appropriate, to assist in evaluating the status of the pediatric rheumatology workforce. In particular, the Institute is encouraged to take advantage of opportunities to support loan repayment for researchers working in the area of childhood rheumatic diseases. (p. 138)

Action taken or to be taken

A number of the rheumatic diseases within the mandate of the NIAMS affect children and adolescents, including juvenile rheumatoid arthritis (JRA), neonatal lupus, and juvenile dermatomyositis (JDMS). These conditions can be particularly devastating because of their chronic and costly nature. The NIAMS supports a wide range of research and training activities to better understand these pediatric diseases and how to treat them effectively. Such support includes a major investment in research and training on pediatric rheumatic diseases through one of the Institute's Multipurpose Arthritis and Musculoskeletal Diseases Center, where scientists recently reported that the drug Enbrel, a medication used to treat adults with rheumatoid arthritis, is also safe and effective for children and teenagers with JRA. Furthermore, the Institute funds research registries for JRA, neonatal lupus, and JDMS which serve as national research resources for scientists studying these pediatric rheumatic diseases. The Institute recently expanded the JRA registry to include a major emphasis on a genome-wide search for JRA susceptibility genes. The NIAMS has also supported career awards for scientists studying pediatric rheumatic diseases, and placed a greater focus on these conditions in recent research solicitations, highlighting the Institute's interest in receiving applications in this area. Finally, the NIAMS intramural research program has recently opened a pediatric rheumatology clinic on the NIH campus to treat and study children with JRA and related conditions. The clinic is building on insights gained through the intramural program's laboratory work, and is facilitating the translation of research advances to improve patient care.

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Facioscapulohumeral disease - The conferees are aware of concerns raised regarding the progress of NIH research into facioscapulohumeral muscular dystrophy and facioscapulohumeral disease and encourage NIH to expand research in this area. (p. 142)

Action taken or to be taken

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common genetic disease of skeletal muscle. FSHD is heritable, and the inheritance of the disease inevitably leads to the expression of symptoms, which include progressive weakening of the muscles of the face, shoulders, and upper arms. A number of projects with potential implications for FSHD have been funded as a result of a currently active program announcement on the pathogenesis and therapy of the muscular dystrophies. These include NIAMS-supported grants focused on developing safe and effective methods to perform gene therapy on skeletal muscle, and a project funded by the National Institute of Neurological Disorders and Stroke (NINDS) that builds on the identification of a new protein, found only in muscle, whose genetic locus is very close to the locus for FSHD and that may play a role in the development of the disorder.

Last spring, the NIAMS, together with the NINDS and other NIH components, as well as FSHD research and patient advocacy organizations, cosponsored a scientific conference on the cause and treatment of the disorder. Researchers from the United States, Canada, Europe, South America, and Asia met to share their latest findings and identify exciting directions for future studies on this disease. The recommendations that emerged from the conference fall into several categories, including efforts to enhance our understanding of the molecular processes and tissue changes associated with FSHD; ways to explore possible therapies to treat the disorder; and strategies to promote the establishment of population-based studies of the disease, as well as needed research resources. These recommendations are being considered as the NIH develops new program initiatives in this area, such as the recently released solicitations for exploratory research applications on FSHD, and for projects on therapeutic and pathogenic approaches for the muscular dystrophies, including FSHD.

In an effort to further develop research resources for FSHD, the NIAMS recently joined with the NINDS to fund a registry on FSHD and another form of muscular dystrophy known as myotonic dystrophy (MD). The long-term goal of the registry is to facilitate research in FSHD and MD by serving as a liaison between families affected by these diseases who are eager to participate in specific research projects, and investigators interested in studying these disorders. The registry will recruit and classify patients, and store medical and family history data for individuals with clinically diagnosed FSHD and MD. Scientists will be provided with statistical analyses of the registry data, as well as access to registry members who have agreed to assist with particular research studies. Finally, the NIH intramural research program is building expertise in muscle diseases, with the recent addition of several renowned scientists.