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Key to Preventing Osteoporosis May Be A Beta Blocker
Feb. 20, 2005 – Research released today says the
answer to preventing osteoporosis may be the use of a beta blocker, a
drug commonly used to lower blood pressure and ward off repeat heart
attacks. Over 10 million American seniors over the age of 50 suffer from
osteoporosis, according to most estimates.
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In a report that appears online today in the
journal Nature, Dr. Gerard Karsenty, Baylor College of Medicine,
professor of molecular and human genetics, and his colleagues
demonstrate in mice that the sympathetic nervous system mediates the
resorption or destruction of bone through a special receptor on bone
cells, and that this effect is required for the development of
osteoporosis after menopause in mice. Preventing the sympathetic nervous
systems from activating this receptor could prevent osteoporosis.
It is estimated that 30 million people worldwide
have osteoporosis, a disease in which there is less bone mass and a high
risk of fracture. Each year, 1.5 million Americans suffer a fracture
because of the disease.
In a report last October, the U.S. Surgeon General
estimated that the cost of caring for people with osteoporosis-related
fractures totals $18 billion per year, a figure that will increase
unless prevention efforts improve.
Karsenty's work started five years ago when his
group demonstrated that one of the main functions of leptin, a hormone
initially thought only to regulate appetite, is to regulate bone
formation. Later, they showed that the sympathetic nervous system
mediates only this action of leptin.
In the most recent study, they showed that leptin
also affects bone destruction or resorption through a receptor for the
sympathetic nervous system present on bone cells.
Mice lacking this receptor have "what every woman
at time of menopause would like to experience," said Karsenty. "They
make more bone, they destroy less bone and do not lose bone when their
ovaries are removed. This is the first demonstration that nerve cells
are involved in osteoporosis development. This has tremendous clinical
implications especially since these mice are not obese."
Drugs that inhibit the sympathetic nervous system
are already commonly in use. They are called beta blockers and a study
in the Journal of the American Medical Association (JAMA. 2004 Sep 15)
buttresses Karsenty's hypothesis, by demonstrating that older patients
with osteoporosis who took beta blockers had fewer fractures than those
who did not.
"The task now is to develop beta blockers that are
specific to bone and do not affect cells in the heart muscle. Then you
would have the prevention of osteoporosis with a safe drug and no heart
effect. There is a lot of reason to believe it can be done," said
Karsenty.
He is also studying the effect of beta blockers on
men who have undergone surgical castration as treatment for prostate
cancer. This study is being carried out in collaboration with The
University of Texas M.D. Anderson Cancer Center in Houston.
Others who participated in the research include:
Drs. Florent Elefteriou, Jong Deok Ahn, Shu Takeda, Michael Starbuck,
Xiangli Yang, and Xiuyun Liu, all of BCM; Hisataka Kondo and Masaki Noda
of Tokyo Medical and Dental University in Japan; William G. Richards and
Tony W. Bannon of Amgen Inc., in Thousand Oaks, California; Karine
Clement of INSERM Avenir team; University Paris, and Christian Vaisse of
the University of California, San Francisco.
This work was supported by grants from the
National Institutes of Health, the National Space Biomedical Research
Institute, the Children's Nutrition Research Center, the Arthritis
Foundation and the Children's Brittle Bone Foundation.
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