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OSTEOPOROSIS
PROGRESS AND PROMISE
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About
Osteoporosis
Osteoporosis is a
disease characterized by low bone mass and structural deterioration
of bone tissue, leading to bone fragility and an increased susceptibility
to fractures–especially of the hip, spine, and wrist. It is
the most prevalent of the bone diseases that affect Americans.
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.
Osteoporosis is a
major threat for 28 million Americans. In the U.S. today, 10
million individuals already have osteoporosis and 18 million
more have low bone mass, placing them at increased risk for
this disease. American women are four times as likely to develop
osteoporosis as men. One out of every two women and one in eight
men over 50 will have an osteoporosis-related fracture in his
or her lifetime.
Osteoporosis is
responsible for more than 1.5 million fractures annually, including
300,000 hip fractures, and approximately 700,000 vertebral fractures,
250,000 wrist fractures, and more than 300,000 fractures at
other sites.
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 six 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. The burden of health
care costs due to osteoporotic fractures is estimated to be
$13.8 billion per year.
Osteoporosis does
not need to be a consequence of aging, however. It is largely
a preventable disease, and many research opportunities exist
to enhance our knowledge about how to maintain a healthy skeleton
throughout life.
Remarkable progress
has been made in our understanding of the causes, diagnosis,
treatment and prevention of osteoporosis. However, many avenues
of scientific opportunity remain. Every increment of research
progress brings us closer to eliminating the pain and suffering
caused by this disease.
Addressing
Osteoporosis: A Collaborative Approach
Significant efforts
are underway at the Federal level aimed at addressing this serious
public health threat. In particular, several components of the
National Institutes of Health (NIH) are currently supporting
basic and/or clinical research on osteoporosis and related bone
diseases. The National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS) has taken the lead in initiating the
Federal Working Group on Bone Diseases. This group provides
a forum for the sharing of information between NIH institutes
and other Federal agencies to enhance communication and to coordinate
research efforts.
The Basic Osteoporosis
New Experimental Strategies (BONES) initiative (created by NIAMS,
the National Institute on Aging (NIA), and the National Institute
of Diabetes and Digestive and Kidney Diseases), is an example
of a collaborative effort to capitalize on opportunities in
osteoporosis research. The initiative has served to encourage
established investigators to address osteoporosis-related problems,
as well as to increase the pool of investigators working in
osteoporosis-related basic science areas.
The Study of Osteoporotic
Fractures (SOF), supported by NIAMS and NIA, and involving more
than 9000 women 65 years or older, described risk factors for
hip, wrist and spine fractures. The study demonstrated that
bone mineral density predicts hip and other types of fractures,
and also provided evidence that women with low bone density
have an increased risk of stroke, as well as evidence of a relationship
between bone mineral density and breast cancer incidence. The
NIH Women's Health Initiative currently supports the largest
study of osteoporosis and fractures ever conducted. This study
will determine the usefulness of 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.
Addressing
Osteoporosis: NIAMS' Research Agenda
NIAMS leads the Federal
research effort on osteoporosis and related bone diseases, and
is responsible for nearly half of the funding for research in
this area, NIH-wide (which totals over $110 million in FY 1997).
NIAMS-supported research ranges from very basic studies to clinical
and translational research and early intervention and
prevention
projects, such as "Camp Calcium", a novel program for adolescent
girls, which has as its goal the determination of how much calcium
growing girls need in their diets so that they can develop the
strongest possible bones, and thus help reduce their chance
of getting osteoporosis later in life.
Overall, significant
advances in 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.
Selected
Scientific Advances
- The
identification of a gene essential for the formation of bone
-- Through
a convergence of efforts by investigators around the world,
research has shown that normal skeletal development--in both
mice and humans–apparently requires two active copies of the
gene Cbfa1. This discovery is expected to open a number of
exciting new research areas.
- The
finding that estrogen induces "programmed cell death" in the
cells that are responsible for the degradation of bone (osteoclasts)
-- By paving the way for future assessment of whether other
drugs can also affect the programmed cell death of osteoclasts
(thereby making them potentially useful as bone-protecting
treatments) this discovery represents an exciting link between
basic research and tangible patient benefit.
-
The finding that one of a collection of molecules fabricated
by researchers (called peptidomimetics) successfully blocks
part of the bone resorption process
-- This is the first clear indication that a particular synthetic
antagonist may be effective in the prevention of osteoporosis,
and the finding may hold promise for combating bone loss in
women who cannot tolerate estrogen.
-
Patient-based research showing that
the elderly women who already had several spine fractures
at the start of a study experienced the greatest health benefit
from calcium supplementation (both in terms of reduction in
the rate of new spine fractures and cessation of bone loss)
-- This finding has clear implications for developing and
targeting new preventive strategies.
Current
and Planned Initiatives
In the past decade,
there has been an explosion of basic and clinical research in
osteoporosis. However, many fundamental advances in molecular
and cellular biology, immunology, genetics, and bioengineering
have not yet been applied to skeletal biology. In addition,
research on a new class of drugs called Selective Estrogen Receptor
Modulators (SERMs) also holds promise in terms of reducing bone
loss in postmenopausal women without adverse effects on other
organs. Vast opportunities exist to expand the current knowledge
base, continuing in a diversified approach to osteoporosis.
Initiatives which may serve as a springboard for further research
include:
- Multi-center
clinical intervention studies on combination therapies for
osteoporosis --
Because pharmaceutical companies tend to focus resources on
bringing individual drugs to market, federal support is needed
to test combinations of drugs, as well as possible exercise
and nutritional modifications to various drug combination
regimes. Lower doses and combinations of effective agents
may serve to reduce side effects and risks associated with
current individual drug treatments, and may improve overall
responsiveness. These studies will also generate information
on osteoporosis in men, and in children, adolescents, and
others who have diseases and conditions that put them at high
risk of osteoporosis--not just on postmenopausal women--the
group on whom most private sector research has been concentrated.
-
Development of new technologies to measure
bone quality as well as bone mineral density
-- The need to evaluate the contribution of bone architecture--in
addition to bone mass--in determining resistance of bone to
fracture in vivo is spurring interest in new methods, which
may include variations of micro-computed tomography or magnetic
resonance imaging (MRI) techniques. Ultrasound technology
is emerging as an alternative to bone densitometry for some
clinical applications and studies are also underway to develop
blood and urine tests that may one day be used to screen for
osteoporosis.
-
The Bone Density, Biomarkers and Physical
Activity component of the National Health and Nutrition Examination
Survey (NHANES) IV
-- National
Health and Nutrition Examination Surveys have been conducted
periodically since the 1960s, via household interviews and
physical examinations provided in specially designed mobile
examination centers, and with data collections periods ranging
from 3 to 6 years. NHANES IV is planned as a continuous survey
with data collection beginning in 1999. NIAMS is specifically
interested in information from three tests to be included
in the exam–dual energy x-ray absorptiometry (DXA), measurements
of markers of bone resorption in urine and blood samples,
and assessment of musculoskeletal strength in participants
aged 50 and over (one of two levels of physical fitness included
for the first time in the Survey).
-
Research on bone and hematopoiesis (a
process in which blood cells are produced, including the many
different cells of the immune system)
-- Following an August 1997 workshop, a program announcement
has been developed which focus on the interactions between
two cellular systems which develop in close proximity in the
bone marrow--the cells of the skeletal system (the cells that
form and break down bone) and the cellular components of the
immune system. The initiative will encourage collaboration
between investigators with expertise in one area, such as
bone biology or immunology, with other investigators having
complementary expertise.
- Research
on risk factors for bone fragility fractures in children and
adolescents
-- Current research is underway which will examine bone mineral
density and measure dietary calcium intake in children and
adolescents with distal forearm fractures and in normal controls.
It is expected that this research will provide significant
evidence that calcium may immediately reduce the number of
fractures in children, and that it may serve to provide an
incentive to families and their adolescent children to increase
calcium intakes.
-
A Consensus Development Conference on
Osteoporosis Prevention, Diagnosis and Therapy
-- The last Consensus Development Conference on Osteoporosis
(1984) marked a turning point in the view of the public and
the research community about osteoporosis. Because there has
been an explosion of information about diagnosis, treatment
and prevention since that time, an assessment of recent developments
and research directions is warranted, aimed at ensuring that
all physicians who see people at risk of osteoporosis-- not
just expert bone endocrinologists--have the up-to-date information.
Information
Dissemination and Education Efforts
The
NIH Osteoporosis and Related Bone Diseases~National Resource
Center was created by NIAMS in 1994 in response to
a groundswell of interest by several voluntary and professional
groups and key congressional leaders. Other Federal partners
now support the Resource Center in addition to NIAMS, including
NIA, as well as the National Institute of Child Health and Human
Development, National Institute of Dental Research, National
Institute of Environmental Health Sciences, the NIH Office of
Research on Women's Health and the HHS Office of Women's Health--in
cooperation with the National Osteoporosis Foundation, The Paget
Foundation and the Osteogenesis Imperfecta Foundation. This
Center provides an important link to resources and information
on metabolic bone diseases, and its mission is to expand awareness
and enhance knowledge and understanding of the prevention, early
detection, and treatment of these diseases as well as strategies
for coping with them.
Through the Resource
Center, collaborative efforts to enhance the strategies to promote
bone health for women are being instigated through the National
Osteoporosis Education Campaign. The initial focus
of the campaign will be to encourage teenage women to develop
positive health behaviors (for example, diet, exercise, calcium
intake) that can have effects on bone strength that last a lifetime.
For
information on osteoporosis and other bone diseases, contact:
NIH Osteoporosis and Related Bone Diseases ~ National Resource
Center
1150 17th St., NW, Suite 500
Washington, DC 20036-4603
Phone: (202) 223-0344 or (800) 624-BONE (2663), TTY: (202) 466-4315
Fax: (202) 223-2237
World Wide Web: http://www.osteo.org
For
general information on NIAMS and its research programs, contact:
Office of Communications and Public Liaison
National Institute of Arthritis and Musculoskeletal and Skin
Diseases/NIH
Building 31/Room 4C05
31 Center Drive, MSC 2350
Bethesda, MD 20892-2350
Phone: (301) 496-8188, TTY: (301) 565-2966
Fax: (301) 480-2814 World
Wide Web: http://www.nih.gov/niams
National
Institute of Arthritis and
Musculoskeletal and Skin Diseases
10/98
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