A completely new type of therapy, using a unique class of synthetic compounds, may someday protect both men and women from the bone-weakening disease osteoporosis. Researchers reported in the October 25 issue of Science that early studies of one of these compounds called estren successfully preserved and even restored bone mass in an animal model without the side effects associated with sex hormone therapies.
The group found that estren protected bone mass in both female and male mice as well as estrogen or testosterone did, but without the changes in reproductive organs associated with sex hormone therapy. They call this new class of compounds, ANGELS (Activators of Non-Genomic Estrogen-Like Signalling).
"The sex hormones estrogen and testosterone play a role in building bone throughout life as well as protecting the reproductive health of both sexes. To safeguard the bone mass often lost as women age, doctors may give estrogen. This is quite effective at preserving bone, but can have serious side effects," explained Jill Carrington, Ph.D., from the Biology of Aging Program at the National Institute on Aging (NIA). "This study suggests a new direction in research toward treating the disabling disease osteoporosis in both men and women." The NIA and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supported the study by Stavros Manolagas, M.D., Ph.D., and colleagues at the University of Arkansas for Medical Sciences (UAMS) and the Central Arkansas Veterans Health Care System (CAVHCS), Little Rock, AR.
This new therapy evolved out of our knowledge of the role that sex hormones play in bone remodeling. Based on earlier work by Dr. Manolagas, he and his associates hypothesized that thebone building actions of sex hormones could be separated from their effects on the reproductive system; a different process seemed to be involved. If so, they proposed that it should be possible to trigger the bone building activities of cells without creating side effects in reproductive tissue.
For example, estrogen influences many organs in the body besides the breasts, ovaries, and uterus. These include the brain, cardiovascular system, and the skeleton. All of these organs contain estrogen receptors that link up with estrogen molecules and then turn on genes in the cells to perform various cellular functions. The investigators set out to identify whether it would be possible to use a substance that would attach to the estrogen receptors but only initiate the bone building activity and possibly beneficial activities in other non-reproductive tissues that use this process.
Estren appears to do that. The scientists looked at four groups of female mice and four of male mice: a group with ovaries or testes removed but no treatment, one with ovaries or testes removed that received estren, one with ovaries or testes removed that received a sex hormone, and a control group that kept their ovaries or testes, the natural source of sex hormones. In female mice the estren and estradiol (the type of estrogen used) were equally effective at preserving overall and spinal bone mineral density (BMD). In the hind limb of the estren-treated female mice the BMD appeared to be greater than that in either the estradiol-treated or control group, suggesting that estren treatment actually led to the addition of new bone. In male mice the estren was as effective as the sex hormone testosterone, and BMD in the spine was greater in the estren-treated group than in the control group. Lastly, estren did not cause any abnormal growth of cells in the uteri in the female mice or the seminal vesicles in the male mice, and in the laboratory estren did not stimulate breast cancer cells to grow.
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