Mr. Chairman and Members of the Subcommittee, I am Dr. Stephen Katz, Director of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the lead institute
at the National Institutes of Health (NIH) for research on osteoporosis and related bone disorders.
I am pleased to have this opportunity to testify before you today to highlight recent research
advances and opportunities that relate to osteoporosis and related bone diseases and to the
enhancement of bone health in general. I would like to leave you today with knowledge of how
far research has brought us in understanding this disease and in providing us with critical clues
about how to prevent this disease from impacting our lives and the lives of our families and
friends. Osteoporosis does not need to be a consequence of aging. It is largely a preventable
disease, and many research opportunities exist to enhance our knowledge about how to maintain
a healthy skeleton throughout our lives.
Osteoporosis is the most prevalent of the bone diseases that affect Americans. It results in low
bone mass and architectural abnormalities that contribute to bone fragility and increased fracture
risk. Although it is the underlying cause of most fractures in older people, the condition is silent
and undetected in most cases until a fracture occurs. A fracture is not a benign event,
particularly in older people. The major fracture sites associated with osteoporosis are the hip, the
spine, and the wrist. Of all the injury sites, hip fractures have the greatest morbidity and
socioeconomic impact. Following a hip fracture, there is a 10-20 percent mortality rate during
the next 6 months. This means people can and do die as a result of hip fractures. Fifty percent
of those people experiencing a hip fracture will be unable to walk without assistance, and 25
percent will require long-term care.
Recently we gained insight into how many Americans are affected by osteoporosis through the
National Health and Nutrition Examination Survey (NHANES). Conducted from 1988 to 1994,
this survey measured the bone mineral density of a sample population across the United States
and indicates that osteoporosis and low bone mass are common. For women, estimates indicate
that 13 to 18 percent over the age of 50 have osteoporosis of the hip, and another 37 to 50
percent have low bone mass placing them at increased risk for developing osteoporosis as they
age. Conservatively, this means that osteoporosis is a threat to more than 28 million Americans.
The percentage of men affected is lower but still adds up to millions of men at risk of fractures.
Although white women account for 75 percent of the approximately $14 billion cost of fractures
in the United States, men and minority women are substantially vulnerable. The development of
prevention and therapeutic strategies is critical given the impact of this problem in the United
States.
Women are particularly vulnerable to getting osteoporosis. In the United States, women are four
times as likely to develop osteoporosis as men. This is attributable to two factors: women have
approximately a 10 percent lower peak bone mass by maturity, and they experience an
accelerated bone loss after menopause. Although African American women have a considerably
lower rate of osteoporosis and fractures, the NHANES data indicate that 10 percent of African
American women over 50 have osteoporosis and 29 percent have low bone mass. While men are
at a lower risk for osteoporosis than women, they are not exempt from this disease.
A great many research studies in osteoporosis and related bone diseases are underway at the
NIH. In addition to the NIAMS, 13 other institutes, centers, and offices at the NIH are involved
in research on osteoporosis and related bone diseases ranging from very basic studies to early
intervention and prevention projects to clinical and translational research. Studies being
conducted range from investigations of the causes and consequences of bone loss at cellular and
tissue levels to clinical trials testing strategies to maintain and even enhance bone density.
Evaluation of skeletal status is of major concern as scientists explore the roles of such factors as
hormones, calcium, vitamin D, drugs, and exercise on bone mass. The influence of
environmental factors (e.g., cadmium, lead, and boron) is also being examined.
Each NIH institute, center and office comes to the study of osteoporosis and related bone
diseases from the vantage point of its individual and different mission. These efforts are both
collaborative and complementary. For example, the NIAMS supports research across the
spectrum from basic studies that are attempting to understand the normal functions of cells that
build up and break down bone to clinical studies of the diagnosis, treatment, prevention, and
epidemiology of osteoporosis and related bone diseases. The NIAMS bone biology and bone
diseases programs not only provide improved understanding of osteoporosis, but also of other
bone diseases such as Paget's disease, osteogenesis imperfecta, cancer metastasis to bone, and
multiple myeloma. The National Institute on Aging (NIA) has unique lines of research that are
derived from its mission to understand the aging processes and pathological changes that cause
disability and compromise the quality of life in older people. The NIA supports a strong
program of clinical studies of age-related bone loss and fracture epidemiology, intervention
trials to prevent or reverse bone loss, and basic research studies on bone cell biology and the role
of sex steroids, cytokines, and growth factors on bone cell function. NIA, in conjunction with
the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's
Health (ORWH) supports a large multi-ethnic longitudinal study of women, aged 42-52 years, at
five clinical field sites to evaluate mid-life changes on bone loss and the risk of osteoporosis as
women approach and traverse the menopause. The National Institute of Dental Research (NIDR)
supports a strong basic bone biology program with a focus on the connection between oral bone
loss and osteoporosis. The NIDR also has an intramural program that researches normal bone
growth and turnover as well as the pathophysiological mechanisms of brittle bone diseases,
including the hereditary disease osteogenesis imperfecta. The National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) provides support for research on nutrition and
endocrinology, including the hormones regulating bone metabolism. The National Institute of
Child Health and Human Development (NICHD) supports research to enhance understanding of
how to prevent this disease by influencing the behaviors of children in such areas as diet and
exercise, and supports studies in reproductive endocrinology and the possible impact of
hormones and reproductive history on the etiology of osteoporosis. In addition, through the
NICHD intramural program, studies are conducted on the genetics, growth, and rehabilitation of
children with heritable disorders of connective tissue such as osteogenesis imperfecta. The
National Institute of Environmental Health Sciences (NIEHS) research focuses on metals such as
cadmium, lead, and boron found in the environment as risk factors in development of the disease.
The NIH Office of Research on Women's Health has made a vital contribution to osteoporosis
research through supplemental grants and the Director's leadership role in the Women's Health
Initiative (WHI). The WHI project is led by the National Heart, Lung, and Blood Institute and
coordinated with the NIAMS, the NIA, and the National Cancer Institute. This project contains
the largest test of the effect of hormone replacement therapy and calcium and vitamin D
supplementation on osteoporosis.
Osteoporosis and related bone diseases are complex, and their study reflects a multiplicity of
interests. To provide coordination and to enhance cooperative research and education activities
across agencies, the NIAMS launched the Federal Working Group on Bone Diseases (FWGBD)
in 1993. As Director of the NIAMS, I chair the FWGBD, whose membership includes not only
representation from the NIH institutes, centers and offices, but also other Federal agencies
including the Agency for Health Care Policy and Research, the Department of Defense (DOD),
the National Aeronautics and Space Administration (NASA), and the Public Health Service
(PHS) Office on Women's Health. I have attached to my statement a list of all NIH components
and Federal agencies represented on the FWGBD. The FWGBD meets regularly throughout the
year and provides a structure for information sharing, formulation of collaborative research
efforts, and coordination of osteoporosis research across all Federal agencies with an interest in
bone diseases and bone health.
Outside of the DHHS, the NASA and the DOD have supported osteoporosis and related bone
diseases research over the past several years. The NASA's interests relate to what happens to
bone in a reduced-gravity environment. The depletion of bone and muscle while in space is a
significant risk to astronauts. Exposure to reduced gravity during space travel profoundly alters
the load placed on bone and muscle, and thereby has direct effects on the tissues. The DOD
initiated an osteoporosis program in 1995, and this expanded in 1997 with grants solicited in the
area of mechanical stimulation of bone growth, focussing on military preparedness in a
physically active population. The NIAMS program and review staff helped with the planning of
the solicitation of application and with their review.
With this as background on the importance of a broad multipronged approach to targeting
osteoporosis and related bone diseases, I would like to focus my remaining testimony on research
highlights, advances, and opportunities. Specifically I will address (1) the importance of
identifying prevention, early intervention, and assessment/diagnostic tools to reduce the
prevalence of osteoporosis; (2) recent breakthroughs in basic research leading to improved
understanding of bone formation and the role genetics in predisposing one to osteoporosis, (3)
the status of treatments for this disease; and (4) a summary of exciting research opportunities.
IMPORTANCE OF PREVENTION, EARLY INTERVENTION, AND ASSESSMENT
TOOLS
Prevention of Osteoporosis Through Diet and Physical Exercise
This is an exciting time for research related to osteoporosis and bone health. There has been a
revolution in thinking about osteoporosis over the last decade. The most significant insight
comes from the recognition that osteoporosis and fractures are not a natural consequence of
aging. NIH support for clinical studies of nutrition and physical activity interventions has
provided strong evidence that fractures can be prevented and bone loss reduced even in older
individuals. We have learned a great deal about the need to build bone across the life span,
beginning at a very young age. Most significantly, we have learned that rapid bone acquisition
occurs before, but also at and after puberty, and this period is crucial in skeletal development and
critical for the prevention of osteoporosis later in life.
This past August, the Institute of Medicine (IOM) completed a study of calcium and related
nutrients. The goal was to provide an update of the dietary information published in 1989 as the
Recommended Dietary Allowances (RDAs). This IOM study follows and in many ways
parallels the successful 1994 NIH Consensus Development Conference on Optimal Calcium
Intake. Key calcium metabolic studies supported by the NIH made it possible for the Consensus
Conference and the IOM to approach the issue of optimizing calcium intakes, not only to prevent
deficiency diseases, but to build a better skeleton and to preserve it throughout life.
The primary data used for setting adequate intakes for children 9 through 18 years of age are
derived from careful and innovative metabolic studies estimating the intakes necessary to achieve
maximal calcium retention in the body. The NIH has supported several studies of calcium in
young girls. In one such study, young girls have attended "Camp Calcium" where careful
calcium balance studies that require several weeks to be completed are carried out on the Purdue
University Campus in a sorority house where the girls have fun and see how scientists work.
Understanding the role of calcium absorption and vitamin D intake in pre- and postmenopausal
women is also extremely important to maximizing bone health later in life. Critical long-term
studies with a major impact on the field of calcium nutritional physiology have been conducted
with NIH support that began in the late 1960's. Investigators have followed a cohort of Catholic
nuns for more than 30 years from early premenopause up through their early seventies, thus far.
Results emanating from the "Nuns' Study" have described the changes in calcium balance with
age, hormone status, and vitamin D intake and have also contributed to our understanding of
calcium absorption from different food sources (milk vs. vegetables) and from different types of
supplements. This study and others indicate that adequate calcium intake may prevent bone loss,
decrease the prevalence of osteoporosis, and prevent fractures in the elderly.
While the progress to date has clearly been impressive, the story is not complete. The largest
study of osteoporosis and fractures ever conducted is now underway as part of the NIH Women's
Health Initiative. Hip fractures are the most devastating consequence of osteoporosis, but testing
the effectiveness of calcium and vitamin D in preventing hip fractures requires a large number of
women over a long period of time (8 years). This study will determine what can be achieved
with calcium and vitamin D supplements and may lead to new public health initiatives to
optimize the intake of these nutrients in the U.S. population.
Identification of Risk Factors for Hip Fractures in Women
The NIAMS and the NIA cooperatively support the Study of Osteoporotic Fractures (SOF), a
study that followed more than 9,000 women for over 10 years in order to determine what risk
factors are associated with hip fractures and especially which ones are preventable. Results of
this study have shown that one in every six white woman will have a hip fracture in her lifetime;
thus identifying preventable risks can make an enormous impact on preventing disability in older
women. Some prominent and modifiable risk factors identified in this study that increase the
chance of hip fracture are poor visual acuity, especially poor depth perception and contrast
sensitivity; weight loss after age 25; more than two cups of coffee a day; no walking for exercise;
being on one's feet less than 4 hours a day; and the use of some medications such as long-acting
benzodiazepines and anticonvulsant drugs. Clearly an increase in physical activity, an eye
checkup and a review of medications can do a lot to prevent hip fractures.
Identification of Risk Factors for Hip Fractures in Men
Although 50-year-old white men have about a 13 percent lifetime risk of fractures of the hip,
spine, or wrist, the causes of and mechanisms involved in osteoporosis in men have received
little research attention to date. Men develop osteoporosis and osteoporotic fractures about a
decade later than women do. This has been attributed to a higher peak bone mass at maturity and
a more gradual diminution in sex steroid influence in aging men. At each age, the rate of hip
fracture in men is about 50 percent that in women. With the decline in premature cardiovascular
mortality in men, fractures later in life are becoming an increasingly important cause of
morbidity and mortality in older men. In a recent study, risk factors thought to affect bone
density (weight, smoking, physical activity, some drugs) as well as factors identified as risk
factors for falls (lower limb dysfunction, psychotropic drugs) appear to be important
determinants of the risk of hip fracture in men. Physical activity may be a particularly promising
preventive measure for men and can favorably influence other chronic diseases such as heart
disease.
Assessment and Diagnostic Tools
As new treatment strategies become available, it becomes critical to be able to assess skeletal
health to identify those in need of intervention as well as to determine the effectiveness of
particular treatments. The development of new technology to measure bone mineral density as
well as bone quality is an active focus of research. Ultrasound technology is emerging as an
alternative to bone densitometry for some clinical applications. It is faster, cheaper, and without
the radiation exposure of conventional bone densitometry devices. Studies are also underway to
develop blood and urine tests that may one day be used to screen for osteoporosis.
Prevention Through Public Education Campaigns
As stated many times throughout this testimony, prevention of osteoporosis is the key to
reducing the risk of this disease for men and women in later life. Because the window of
opportunity to add bone to the skeleton is limited, educational strategies are extremely important,
for example, encouraging calcium intake by children and adolescents at the recommended levels
and encouraging regular exercise. Likewise, strategies to encourage regular exercise, especially
weight-bearing activities, discourage smoking and limit alcohol consumption across the life span
are important to maintaining optimal bone health. Equally important are educational strategies
designed to inform those most at risk of developing osteoporosis of the modifiable risk factors
and available diagnostic tools so that early intervention is possible.
The NIAMS supports the Osteoporosis and Related Bone Diseases--National Resource Center
(ORBD~NRC). The Center is currently operated by the National Osteoporosis Foundation
(NOF) in partnership with The Paget Foundation and the Osteogenesis Imperfecta Foundation
under a grant from the NIAMS. The Center provides patients, health professionals, and the
public with resources and information on osteoporosis and related bone disorders. Information
on prevention, early detection, treatments, and coping strategies is disseminated widely through
publications, online services, professional and patient meetings, and general media outreach.
The NIAMS, along with several other NIH institutes including the NIA, the NICHD, the NIDR,
the NIEHS, and the Office of Research on Women's Health, has issued a Request for
Applications (RFA) inviting applications to continue support for such a center.
The NIAMS has collaborated with the PHS Office on Women's Health, the NOF through the
Osteoporosis Resource Center and the Centers for Disease Control and Prevention (CDC) to
enhance the strategies to promote bone health for women. The National Osteoporosis Education
Campaign will first focus on 9-12 year old girls, just approaching their peak bone building years,
but as the campaign develops, it will expand to cover 13-18 year old girls. The goal is to develop
strategies for effectively reaching this age range so as to influence life-long healthy bone
behaviors.
"Milk Matters" is another public health campaign led by the NICHD. It is designed to increase
calcium consumption among children and teens. Studies show that most kids are not getting
adequate levels of calcium during this critical period when bones grow and incorporate calcium
most rapidly. The "Milk Matters" campaign works to reach children and teens, as well as parents
and health care professionals, with the message that increased calcium and weight-bearing
exercise during the first two decades of life can be critical to good health as an adult.
BASIC RESEARCH ADVANCES
Bone Formation and Breakdown
Treatments for osteoporosis and further information on preventive strategies for osteoporosis and
related bone diseases will come from basic studies on understanding the genetics of bone
formation and the process of bone loss and remodeling. Bone is constantly being built up and
broken down. As evidenced by what has been learned about the role of calcium, we try to build
bone up as much as possible with calcium in the early years because this serves as a storage bank
for later years. Enhancement of cells that build bone (osteoblasts) and interference with cells that
break down bone (osteoclasts) tend to result in sturdier bones. All of our achievements and future
progress in osteoporosis and other bone diseases, such as Paget's disease and osteogenesis
imperfecta, are based on understanding the normal functions of bone cells and investigating
strategies to manipulate the normal physiology of bone for therapeutic advantage. Likewise, new
insights into the control of bone remodeling by bisphosphonates (chemicals that block resorption
of bone) have led to approaches to controlling the skeletal complications of malignancy.
Genetics of Bone Formation
In an exciting convergence of efforts by investigators around the world, a gene essential for the
formation of bone has been identified. Researchers made two key observations: First, mice in
which both copies of the Cbfa1 gene have been inactivated exhibit a complete lack of bone and
bone-forming cells and die at an early age. Thus, the Cbfa1 protein appears to function as a
"master switch" for bone formation. Second, mice in which one of the two Cbfa1 genes was
inactivated exhibited a combination of specific skeletal defects that closely resembled those seen
in a heritable human disorder called cleidocranial dysplasia, which is characterized by defective
bone formation. Consistent with this evidence from mice, genetic studies in families with
cleidocranial dysplasia showed that the disorder is associated with mutations in the human Cbfa1
gene. Thus, in order for normal skeletal development to occur in both mice and humans, the
Cbfa1 protein must be present in amounts that can be provided only by two active copies of the
gene. The discovery of the critical role of Cbfa1 in bone formation opens a number of exciting
new research areas.
Understanding the role of genetics in predisposing one to osteoporosis is a very important area of
research. Bone mass at any point in life represents a balance between the amount of bone
accumulated during growth and development and the amount of bone lost with aging. Studies
using families, particularly twins, indicate that bone mass and osteoporosis may be due to an
inherited trait in some families. Resolving the genetic underpinnings of a complex trait in
humans is difficult, because human populations are genetically diverse. Thus, current efforts
include studies of the genetics of bone mass in animals such as mice, in which selective breeding
can reduce the complexity of the problem. Because both bone metabolism and genetic
organization exhibit parallels across mammalian species, it is expected that the results of the
animal studies will provide important guidance to further efforts in human populations.
Several human candidate genes have been examined for their regulatory effect on bone mass
including those for collagen type I, estrogen and vitamin D. A great deal of work has focused on
the vitamin D receptor (VDR) gene, and experience with this locus will probably act as a model
for many future studies. There is increasing evidence of a complex interaction between this gene
and environmental factors in the regulation of bone mass. Moreover, it is clear that bone mass
and density are influenced by many genes (mostly unknown) and a complex interaction with
environmental factors such as nutrition and physical activity.
Interactions of Bone and the Hematopoietic and Immune Systems as Consequences for
Skeletal Health
Bones are not only a crucial mechanical support for our bodies, they also enclose the bone
marrow, the site of the process called hematopoiesis, in which blood cells are produced,
including the many different cells of the immune system. Interactions among bone cells,
hematopoietic cells, immune cells, and other cells of the marrow environment can have
important consequences for skeletal health. In August of 1997, the NIAMS and several other
NIH components sponsored a scientific workshop entitled "Bone and the Hematopoietic and
Immune Systems" that brought together over 200 bone biologists, hematologists, immunologists,
and physicians for 2 days of scientific presentations and discussions. As a result, a number of
areas have been identified in which further research seems especially important. Future efforts
seem likely to be particularly rewarding if they can either clarify the importance of specific cell
types and effector molecules or identify previously unrecognized cellular and molecular agents
that influence bone physiology.
Examples of important areas of pursuit include (1) the determination of mechanisms that regulate
the differentiation of different bone cell types, including the nature of stem cells and factors that
govern their development, and (2) the identification of other bone marrow cell types, such as
hematopoietic cells and stages of lymphoid and myeloid differentiation, that may influence bone
cells. The development and application of treatments for conditions of bone loss, such as
osteoporosis and for rarer conditions of bone formation, depend upon a thorough understanding
of the factors that control the breakdown and formation of bone. It is likely that bone cells do not
function in isolation, but instead respond to a complex mixture of influences arising in part from
immune, hematopoietic, and stromal cells. Understanding these influences may identify targets
for new bone-active agents, and may help to explain the complex effects of agents already in use.
TREATMENTS FOR OSTEOPOROSIS
Although there is no cure for osteoporosis, there are now several effective therapies to help stop
further bone loss and potentially prevent future fractures. Studies have shown that estrogen can
prevent the loss of bone in postmenopausal women; however, many questions remain about the
effect of estrogen on other tissues in the body. The questions about estrogen have led to the
development of a new class of drugs called Selective Estrogen Receptor Modulators (SERM's).
The hope is to produce a drug with all the positive effects of estrogen on bone and lipids and not
to stimulate the activity of the breast or the uterus. Tamoxifen is a SERM that has recently been
shown to reduce the risk of breast cancer in women at high risk. Another SERM, raloxifene has
recently been approved by the Food and Drug Administration (FDA) for the prevention of
osteoporosis.
Alendronate, a bisphosphonate, has recently been approved by the FDA for treatment of
postmenopausal osteoporosis. This class of drug targets bone specifically, reducing bone
breakdown and decreasing fractures in older women. These are very promising avenues of
development and will undoubtedly lead to even more choices for postmenopausal women.
NIH-supported studies of the underlying pathophysiologic mechanisms of bone loss and
remodeling as well as the development of animal and cellular models, have made new drug
approaches possible. These approaches are crucial to determine the underlying mechanisms of
action of drugs and to devise alternative therapies. In recent research results investigators have
shown that estrogen induces programmed cell death in osteoclasts which are responsible for the
degradation of bone. This discovery opens up an exciting new avenue of research opportunities
for investigators to explore whether other drugs can also affect the programmed cell death of
osteoclasts, making them potentially useful as bone-protecting treatments.
RESEARCH OPPORTUNITIES
Numerous research opportunities exist to alter the increasing occurrence of osteoporosis. In the
past decade, there has been an explosion of fundamental and clinical research in osteoporosis.
Large epidemiological studies have identified risk factors for low bone mass and fractures.
Clinical studies have pointed to the efficacy of calcium and vitamin D supplementation in a
subset of elderly women, and physical activity has been associated with decreased bone loss and
improved musculoskeletal stature and balance. There are many fundamental advances in
molecular and cellular biology, immunology, genetics, and bioengineering that have not yet been
applied to skeletal biology. Many opportunities exist to build on and expand the current
knowledge base.
Basic Research
Details are beginning to emerge about the complex network of signaling mechanisms that control
bone growth and maintain skeletal integrity. Specific probes have made it possible to identify
new molecules responsible for the local and systemic regulation of bone cell function, as well as
the cell surface molecules and linked signal transduction pathways that mediate their effect.
Research opportunities exist to better understand osteoclasts and osteoblasts, cells that are
essential for bone remodeling. Furthermore, the complex relationship between the bone
microenvironment and the immune system demands attention. Evidence is accumulating to
indicate that regulation of the immune system operates on common principles and employs
common effectors.
The identification, mapping, and structural analysis of genes with crucial functions in the
regulation of bone are increasingly feasible research goals. The use of genetically manipulated
animals allows investigators to test the effects of specific gene inactivation or overexpression.
The identification of genetic variations in the human population that underlie different
vulnerabilities to bone loss is made possible by the increasing knowledge of the human genome
and advancing molecular screening technology. While several candidate genes have been
identified in osteoporosis, the complete picture will require both human and population genetics
and further animal studies. The study of the genetics of osteoporosis is likely to yield insights
into the pathophysiology of the disease and clues for targeting interventions.
Behavior Modification and Education Research
Translating knowledge to behavior change is extremely difficult. While current evidence
indicates that there are effective dietary, exercise, and lifestyle guidelines that one can follow to
increase peak bone mass and promote long-term bone health, translating this message into
changed behavior is a challenge. Research targeted at identifying promising health education
approaches that enhance awareness and knowledge for young and adolescent females is needed.
Similarly, education messages targeted to postmenopausal women that identify risk factors,
promote regular exercise and physical activity, and discuss intervention and treatment strategies
are critical as well.
Imp
roved Diagnostic and Assessment Tools
The establishment of new diagnostic procedures that provide insight into the structural defects in
diseased bone and allow a means to assess bone strength is an important area of research.
Currently, the approaches to the assessment of osteoporosis are largely limited to measurement
of bone density, for example, dual energy x-ray absorptiometry (DXA). While these methods are
good predictors of future fractures, they do have their limitations in accuracy and precision. One
significant limitation is that they do not provide insight to the underlying abnormalities in
osteoporotic bone. Bone mass and architecture together determine the resistance of bone to
fracture. New technologies are being developed to evaluate the contribution of architecture in
vivo. These new methods may include variations of micro-computed tomography or magnetic
resonance imaging (MRI) techniques.
One alternative diagnostic technique recently approved by the FDA is ultrasound. With
ultrasound, different properties of bone can be measured, reflecting mechanical quality, an
important determinant of bone strength. Biochemical markers of bone turnover offer yet another
technique for assessment of osteoporosis. These measurements may add to the ability to assess
the pathophysiological basis for the disorder and the effects of therapy. However, biological
variability limits the utility of these measures to population screening, and they are not yet
applicable to detailed evaluation of an individual patient.
New Improved Treatments
Bisphosphonates that target bone and reduce bone loss and fractures have been approved for
osteoporosis treatment and prevention. These new agents may also have promise in reducing the
skeletal complications of malignancy. Estrogen replacement therapy has been clearly shown to
effectively retard bone loss in postmenopausal women. However, it has effects on multiple
organ systems and is not without risk. The new selective estrogen receptor modulators that have
been developed appear to lessen bone loss in postmenopausal women without the adverse effects
on other organs. Fundamental research on estrogen receptors and their target organs fuel the
development of these new agents.
In closing, I hope that I have increased the Committee's awareness of the tremendous progress
we have made through research in understanding the fundamentals of bone biology and how to
prevent and treat osteoporosis. Our objectives over the next decade are to stimulate new
fundamental research, to translate advances in other fields to bone biology, to move
basic/fundamental research to clinical application, to enhance the uptake of research knowledge
by the public, especially the population most at risk of osteoporosis, and to apply this knowledge
to develop effective preventive strategies. Our goal in osteoporosis and other musculoskeletal
diseases that are our research focus is to reduce the burden of disability and enhance the lives and
contributions of the populations who suffer from these chronic musculoskeletal disorders.
I would be happy to answer any questions that you may have regarding osteoporosis research.
FEDERAL WORKING GROUP ON BONE DISEASES
Federal Member Organizations
- National Institutes of Health:
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Child Health and Human Development
- National Institute of Environmental Health Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Cancer Institute
- National Institute of Dental Research
- National Institute on Aging
- National Institute of Nursing Research
- National Institute on Alcohol Abuse and Alcoholism
- National Center for Research Resources
- Office of Research on Women's Health
- Other Federal Agencies:
- Agency for Health Care Policy and Research/Forum for Quality and Effectiveness of
Health Care
- Health Care Financing Administration/Office of Research and Demonstration
- Department of Agriculture/Human Nutrition Research Center
- Department of Defense/Army Operational Research Program
- Centers for Disease Control and Prevention
- National Center for Chronic Disease Prevention and Health Promotion
- National Center for Health Statistics
- Food and Drug Administration/Division of Metabolism and Endocrine Drug Products
- Department of Education/National Institute on Disability and Rehabilitation Research
- National Aeronautics and Space Administration/Life and Biomedical Sciences
Applications Division
Liaison Organizations/Federal and Non-Federal:
- NIH Office of Disease Prevention
- NIH Clinical Center Nursing Department
- NIH Nutrition Coordinating Committee
- U.S. Department of Health and Human Services
-
Office on Women's Health
- Administration on Aging
- Osteoporosis and Related Bone Diseases National Resource Center
- National Osteoporosis Foundation
- The Paget Foundation
- American Society for Bone and Mineral Research
