Minocycline, an antibiotic related to tetracycline, has been shown to increase bone mineral density, improve bone strength and formation, and slow bone resorption in old laboratory animals with surgically-induced menopause. As a result of these promising effects, the National Institutes of Health (NIH) is funding a clinical trial of the drug in women to begin in January. The laboratory results underlying the clinical trial were obtained by Dr. C. Tony Liang et al. of the National Institute on Aging (NIA) and are published in the December 1996 journal, Bone.
"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 in humans."
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 ug of estrogen daily, 1 group received 10 mg of minocycline and 24 ug 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 density.
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 medicationto treat osteoporosis," Liang said. "Estrogen and bisphosphonate preventthe 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 information.
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, 800-222-2225.
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.
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