"Lack of estrogen in postmenopausal women leads to decreased bone
formation and more bone resorption, resulting in a net loss of bone," says
NIA scientist, Dr. Liang, who conducted the study. "Our results in animals
suggest that an inexpensive antibiotic, minocycline, may not only prevent
bone loss, but may increase bone mineral density beyond that of
premenopausal bone mineral density. The next step would be to test the drug
Dr. Liang and his colleagues studied five groups of old female rats.
They removed the ovaries to induce a postmenopausal state in four groups.
The control group retained their ovaries and received no medication or
hormone therapy. Of the 4 "menopausal" groups, 1 received 10 mg of
minocycline daily, 1 group received 24 µg of estrogen daily, 1 group
received 10 mg of minocycline and 24 µg of estrogen daily, and the control
group did not receive medication or hormone. The treatment phase of the
study lasted for 8 weeks.
After the treatment was completed, researchers measured bone mineral
density of the femur, or thigh bone, using dual energy X-ray
absorptiometry, a sophisticated bone scan. The femur is made of a hard
cortical bone on the outside, spongy trabecular bone inside, with an inner
cavity of bone marrow. The trabecular bone (the name means "little beam")
gives the bone its strength. There is more trabecular bone toward both ends
of the femur, near the knee and hip joints. By measuring both total bone
mineral density in the femur and specifically in the knee and hip joint
regions, scientists can determine if the bone is weak or strong, thereby
predicting fracture risk.
The control group of rats without ovaries lost 14 percent of their total
femoral bone mineral density, 10 percent close to the hip joint, and 19
percent close to knee joint compared to the control group with ovaries.
Rats treated with minocycline maintained bone mineral density levels
similar to the group of rats with ovaries and significantly above levels
observed in the control group without ovaries. Previous rat studies looking
at the effects of estrogen also have shown an increase in bone mineral
Earlier studies have confirmed the benefits of taking estrogen to
prevent bone loss in menopausal women. The studies also have linked
estrogen to the development of endometrial cancer in some people.
Minocycline has several potential advantages over estrogen in terms of its
influence on bone. Not only does minocycline prevent bone resorption
similar to estrogen, but also and unlike estrogen, minocycline increases
bone formation and connectivity between bony trabeculae. Thus, minocycline
has an additional mechanism of action and because it is not a hormone, it
should not exert adverse effects on the uterine lining.
"The action of minocycline on bone formation and resorption is unique
compared to estrogen and bisphosphonate, a commonly prescribed medication
to treat osteoporosis," Liang said. "Estrogen and bisphosphonate prevent
the resorption of bone. Minocycline is very inexpensive, it accumulates in the
bone, and it causes the synthesis of strong, hard bone." According to
Liang, scientists do not understand fully how minocycline works, and he is
beginning studies to find the answers.
Meanwhile, researchers at Johns Hopkins University and the NIA are
launching a 1-year clinical trial at the General Clinical Research Center
at the Johns Hopkins Bayview Medical Center in Baltimore to study the
effects of minocycline in postmenopausal women with osteoporosis. Those
interested in participating in the study may call (410) 550-1882 for
Osteoporosis is a major public health threat for 25 million
Americans, 80 percent of whom are women. In the United States, 7 to 8
million individuals already have the disease and 17 million more have low
bone mass, placing them at increased risk for osteoporosis.
Osteoporosis is responsible for 1.5 million fractures annually,
including more than 300,000 hip fractures, 500,000 vertebral fractures,
200,000 wrist fractures, and more than 300,000 fractures at other sites.
Moreover, individuals suffering hip fractures have a 5 to 20 percent
greater risk of dying within the first year following that injury than
others in their age group.
The estimated national direct costs for osteoporosis and associated
fractures is $10 billion-$27 million each day -- and the cost is rising.
Prevention is the best hope for diminishing the personal and financial
losses associated with osteoporosis.
A free fact sheet on osteoporosis, "Osteoporosis: The Bone Thinner,"
is available by calling the NIA Information Center's toll-free number,
The National Institute on Aging, a component of the National
Institutes of Health, conducts and supports biomedical, social, and
behavioral research related to the aging process, age-associated diseases,
and other special needs of older people.