By manipulating how sex steroids are processed in bone-building cells, it may be possible to increase the survival of these cells without causing many of the complications associated with hormone replacement therapy. The finding, published in the March 9, 2001 issue of Cell, could have important implications for the development of new drugs to prevent or treat osteoporosis in both women and men.
In cell culture experiments, a research team led by Stavros Manolagas, M.D. Ph.D., of the University of Arkansas for Medical Sciences in Little Rock successfully used synthetic molecules that mimic some effects of estrogen to selectively activate the anti-apoptosis, or “cell rescue” pathway of estrogen and androgen receptors in mouse bone cells. By activating this pathway alone, the scientists were able to promote the longevity of osteoblasts, the cells that lay down new bone, without sparking other sex steroid activities within the cell. Preserving osteoblasts could help prevent osteoporosis, a bone-thinning disease, which is a major health risk for 28 million Americans, the majority of them over age 50.
“This work, for the first time, delineates the way sex steroids might protect bone-forming cells and bone-maintaining cells from cell death in both women and men,” said Jill Carrington, Ph.D., director of the musculoskeletal biology program at the National Institute on Aging (NIA). “With further work to understand this mechanism, it may be possible to design new treatments for osteoporosis without some of the detrimental effects of estrogen, such as an increased risk of endometrial cancer.” The National Institute on Aging and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), two components of the National Institutes of Health in Bethesda, Maryland, supported the research.
In the United States today, 10 million individuals already have osteoporosis and 18 million more have low bone mass, placing them at increased risk for this disease. One out of every two women and one in eight men over 50 will have an osteoporosis-related fracture in her or his lifetime. Osteoporosis is responsible for more than 1.5 million fractures annually, including 300,000 hip fractures, approximately 700,000 vertebral (spinal) fractures, 250,000 wrist fractures, and more than 300,000 fractures at other sites. In addition to hormone replacement therapy, exercise and adequate intake of calcium and vitamin D can help preserve bone mass and prevent or slow osteoporosis in older women and men.
S. Kousteni, T. Bellido, D.L. Bodenner, K. Han., J.A. Katzenellenbogen, B.S., Katzenllenbogen, P.K. Roberson, R.S. Weinstein, R.L. Jilka, and S.C. Manolagas, “Non-Genotropic, Sex Non-Specific Signaling Through The Classical Estrogen ( α or β ) or Androgen Receptors: Dissociation From Transcriptional Activity,” Cell, 104:5, pp 719-730.