NATIONAL COALITION FOR OSTEOPOROSIS …

               NATIONAL COALITION FOR OSTEOPOROSIS
                    AND RELATED BONE DISEASES
                                        Fact Sheet ­ FY 2007



What is the Mission of the Bone Coalition?
The National Coalition for Osteoporosis and Related Bone Diseases is dedicated to increasing federal
research funding for bone diseases through advocacy and education.

Who are the Coalition Participants?
The participants are leading national bone disease organizations:

American Society for Bone and Mineral Research ­ a non-profit medical and scientific society of 4,000
members established to bring together clinical and basic scientists who study bone and mineral
metabolism. The ASBMR mission is to promote excellence in bone and mineral research, foster
integration of clinical and basic research, and facilitate the translation of that science to health care and
clinical practice. ASBMR hosts the premier annual scientific meeting, and publishes the field's highest
impact journal and textbook.

National Osteoporosis Foundation (NOF) is the nation's leading voluntary health organization solely
dedicated to osteoporosis and bone health. NOF's mission is to prevent osteoporosis, to promote lifelong
bone health, to help improve the lives of those affected by osteoporosis and related fractures and to find a
cure. NOF achieves its mission through programs of awareness, advocacy, public and health professional
education and research.

Osteogenesis Imperfecta Foundation ­ the only national voluntary health organization dedicated to
improving the quality of life for people with osteogenesis imperfecta (OI), through research to find
treatments and a cure, education, awareness, and mutual support. To accomplish the Foundation's
mission, staff and volunteers balance the dual demands of funding biomedical research and providing
support to help people with OI and their families cope with daily life.

The Paget Foundation for Paget's Disease of Bone and Related Disorders, a voluntary health agency
founded in 1978, addresses several disorders including Paget's disease of bone, primary
hyperparathyroidism, the rare disorders fibrous dysplasia and osteopetrosis and the complications of
certain cancers of the skeleton. Foundation programs include educational publications and programs for
patients and health professionals and research grants.

Description of Osteoporosis, Paget's Disease of Bone and Osteogenesis Imperfecta
OSTEOPOROSIS, or porous bone, is a disease characterized by low bone mass and structural
deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the
hip, spine, and wrist.
PAGET'S DISEASE OF BONE is a chronic skeletal disorder that may result in enlarged or deformed
bones in one or more regions of the skeleton. Excessive bone breakdown and formation can result in
bone that is dense, but fragile. Complications may include arthritis, fractures, bowing of limbs, and
hearing loss if the disease affects the skull.

OSTEOGENESIS IMPERFECTA (OI) causes brittle bones that break easily due to a problem with
collagen production. For example, a cough or sneeze can break a rib, rolling over can break a leg. There
are four recognized types of OI, representing extreme variations in severity and affecting 20,000 to
50,000 people in the United States. Besides fragile bones, people with OI may have hearing loss, brittle
teeth, short stature, skeletal deformities, and respiratory difficulties.

Social and Economic Impact of Bone Diseases
·   Osteoporosis is a major public health threat for 44 million Americans. Of the 10 million who have
    osteoporosis, 80 percent are women.

·   A woman's risk of hip fracture is equal to her combined risk of breast, uterine and ovarian cancer.
    Therefore a woman is more likely to experience hip fracture than these three forms of cancer.

·   Today, 2 million men have osteoporosis and almost 12 million more are at risk for the disease. Men
    with low levels of testosterone are especially at risk. This includes men being treated with certain
    medications for prostate cancer.

·   Men suffer one-third of all hip fractures that occur and approximately one-third of these men will not
    survive more than one year after the fracture.

·   Women of all ethnic groups are at risk for osteoporosis. The percentages of women age 50 and older
    by selected ethnic groups with osteoporosis are:

        ·   20% of non-Hispanic white and Asian women
        ·   10% of Hispanic women
        ·   5% of non-Hispanic black women

In addition, 49% of Hispanic women and 35% of black women have low bone mass.

·   Studies show that the estimated national direct expenditures (hospitals and nursing homes) for
    osteoporotic fractures annually are up to $18 billion dollars (in 2002 dollars) and the cost is rising.
    Indirect costs likely add billion of dollars to this figure.

·   Osteoporosis is responsible for more than 1.5 million fractures annually, including

        ·   Over 300,000 hip fractures
        ·   700,000 vertebral fractures
        ·   250,000 wrist fractures
        ·   300,000 fractures at other sites

·   Osteogenesis Imperfecta (OI) affects between 20,000 and 50,000 Americans. In severe cases
    fractures occur before and during birth. In some cases, an affected child can suffer repeated fractures
    before a diagnosis can be made. Undiagnosed OI may result in accusations of child abuse.



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·   Paget's disease of bone, the second most prevalent bone disease after osteoporosis, is associated with
    bone pain, deformity, neurological complications, and arthritic conditions. Prevalence in the
    population ranges from 1.5 percent to 8 percent depending on the person's age and geographical
    location. Paget's disease primarily affects people over 50.

·   A frequent complication of cancer is its spread to bone (bone metastasis) that occurs in up to 80
    percent of patients with myeloma, 70 percent of patients with either breast or prostate cancer, and 15
    to 30 percent of patients with lung, colon, stomach, bladder, uterine, rectal, and renal cancer causing
    severe bone pain and pathologic fractures. Only 20% of breast cancer patients and 5% of lung cancer
    patients survive more than 5 years after discovery of bone metastasis.

How has Bone Research Helped People?
·   Research has taught us how many Americans have low bone mass and therefore are at risk for
    osteoporosis (44 million either have the disease or are at risk). These individuals can then address
    their risk with exercise, diet, other behavioral and lifestyle changes, and medication, as appropriate.

·   Research has found that without intervention one in two women and one in four men age 50 and
    above will experience a fracture due to osteoporosis. Intervention reduces the incidence of future
    fracture thereby improving quality of life.

·   Research has led us to develop simple, non-invasive and accurate tests that can determine bone mass
    and help predict future fracture risk. These tests also allow us to monitor the impact of treatment.

·   Research has identified and demonstrated a variety of drugs that can reduce bone loss and fractures,
    and even build new bone. Thirty years ago, there was no treatment for osteoporosis.

·   Research has led to a better understanding of calcium metabolism and, as a result, manufacturers of a
    variety of food products have fortified their products with this vital nutrient.

·   Research has shown the necessity of vitamin D, protein, iron, and other nutrients, in building and
    maintaining strong bones, while also emphasizing a major public health problem of vitamin D
    deficiency.

·   Research has helped us to understand the need for weight-bearing exercise to build and maintain bone
    in order to reduce fracture risk. Falling can be reduced by strength-building exercise that increases
    balance and flexibility.

·   Research has also identified genetic components responsible for many bone diseases, paving the way
    for the development of genetic approaches for diagnosis and treatment.

·   Research has decreased fracture risk and extended the lifespan for people with OI to normal.

·   Research has identified drugs which improve the quality of life of people whose cancer has
    metastasized to bone.




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What are the Future Opportunities for Bone Research?
Diagnostics/Imaging

·   DXA is an imaging test that measures bone mineral density (BMD). It is the gold standard for
    predicting fracture risk, yet it can either under-diagnose or over-diagnose patients at risk. Moreover,
    DXA uses databases that are largely based on BMD scores of white women. Relating BMD scores to
    fracture risk for women of other racial groups and ethnicities ­ and doing the same for men ­ is even
    more imprecise.

·   New diagnostic measures are required to predict fragility and fracture risk better through three
    dimensional imaging of both the entire and the internal micro-structure of bone.

·   Current approaches under development may lead to "virtual biopsies" ­ using computer modeling to
    avoid invasive procedures and provide critical information about bone strength and fracture risk.

Treatment/Pharmacotherapy

·   Much attention has been focused on the Women's Health Initiative study results and the risks
    involved in estrogen treatment. However, more information is needed about low-dose estrogen and
    its bone-protective benefits and risks.




                           J Bone Miner Res 1986 1:15:21. Reprinted with permission
                           of the American Society for Bone and Mineral Research


·   Most current drug treatments for osteoporosis work by slowing down the natural process of bone
    breakdown. Parathyroid hormone (PTH) actually builds bone (see above). However, we need more
    studies to learn how best to use the drugs currently available, for what populations, with or after what
    drug regimens, for how long, and how best to assess response and interaction with exercise and diet.

·   The discovery of new molecules with unexpected roles in modulating bone mass points the way to
    development of other new therapies. One example is leptin, a molecule made by fat cells.




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·   A five-year observational study suggested that regular intravenous doses of pamidronate (a
    bisphosphonate) helped increase bone mineral density, reduce fractures, increase mobility, and
    decrease bone pain in children with osteogenesis imperfecta. Controlled clinical drug therapy trials
    will enable assessment of the potential use of bisphosphonate drugs to improve quality of life for
    children and adults.

·   The discovery that tumor cells increase the number of bone resorbing cells called osteoclasts has led
    to the use of drugs called bisphosphonates that improve the treatment and quality of life for cancer
    patients with bone metastasis. However, further research is needed to study the pathology of bone
    disease in breast cancer, prostate cancer and multiple myeloma.

·   Research is needed to improve survival and quality of life and to prevent metastatic osteosarcoma for
    the approximately 600 children and teenagers in the U.S. who develop this cancer. Specifically,
    research is needed to:

        ·   Identify new intervention targets for therapy;
        ·   Develop better predictors of response to osteosarcoma treatment;
        ·   Develop in vivo and in vitro preclinical assays to improve treatment;
        ·   Study metastatic osteosarcoma biology compared to biology of normal bone cells and that of
            other cancer cells.

Novel Approaches

·   Investigations into genetic approaches for bone disease are critical and stem from recent findings that
    bone doesn't form when a protein called Cbfa-1 or one called Osterix is missing. Understanding how
    these proteins are activated or turned on may lead to new therapies for bone disease.

·   The identification and study of families with very high bone mass who never fracture have led to the
    discovery of the involvement of the "Wnt pathway" in regulating bone mass. This pathway has not
    only become a potential therapeutic target for controlling skeletal mass, but has recently been
    implicated in the bone loss experienced in multiple myeloma (a bone- and blood-related cancer).

·   Understanding the role of genes and the underlying abnormal functioning of cells involved in bone
    breakdown in patients with Paget's disease is critical to developing new treatments. We need
    additional investigation to understand the role the bone microenvironment plays in the development
    of Paget's disease and to identify the molecular processes involved.

·   Bone marrow transplantation is being tested in the laboratory for the treatment of osteogenesis
    imperfecta. One technique requiring further development focuses on genetically engineering bone
    precursor cells, which reside in the bone marrow, so that the faulty osteogenesis imperfecta gene
    which causes frequent fractures would be blocked or turned off. Then these engineered cells could be
    transplanted back into the bone marrow to form healthy bone.

·   The potential for genetic therapy to cure osteogenesis imperfecta has been demonstrated in the test
    tube. Suppressing the gene that causes the mutant collagen must now be demonstrated in animal
    models.

·   Genetic profiling may help to identify individuals susceptible to bone diseases such as osteoporosis so
    that preventative treatment can be initiated before the individual develops the disease.


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For additional information contact:

Ann Elderkin, P.A.
American Society for Bone and Mineral Research
2025 M St., NW, Suite 800
Washington, DC 20036, USA
(202) 367-1161
Email: aelderkin@asbmr.org
Website: http://www.asbmr.org

Roberta Biegel
National Osteoporosis Foundation
1232 22nd Street, N.W.
Washington, DC 20037
(202) 223-2226
Email: roberta@nof.org
Website: http://www.nof.org

Heller An Shapiro
Osteogenesis Imperfecta Foundation
804 WestDiamond Avenue, Suite 210
Gaithersburg, MD 20878
(301) 947-0083
Email: hshapiro@oif.org
Website: http://www.oif.org

Charlene Waldman
The Paget Foundation for Paget's Disease of Bone
and Related Disorders
120 Wall Street, Suite 1602
New York, NY 10005
(212) 509-5335
Email: CharleneWaldman@aol.com
Website: http://www.paget.org




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