Low dose estrogen improves bone health

December 03, 2000

A low dose of estrogen was as effective in reducing bone turnover -- with fewer side effects -- as higher doses when given to a group of healthy women 65 years and older, according to a study published in the December issue of the Journal of Clinical Endocrinology and Metabolism. This is the first controlled clinical trial to directly compare the effects of different doses of estrogen on bone turnover in older women.

Bone turnover refers to the bone remodeling cycle in which new bone is formed as older bone is dissolved (resorption). Osteoporosis develops when more bone is dissolved than is formed, weakening the bones and making them prone to fracture. The risk for developing osteoporosis increases with age. Decreases in bone turnover among the women who took 0.25 mg of estradiol, a form of estrogen, was quite similar to the decrease among the women who took 1.0 mg of estradiol, according to lead author Karen Prestwood, M.D., of the University of Connecticut (UCONN). The 1.0 mg estrogen dose that women conventionally are prescribed as part of estrogen replacement therapy (ERT) to treat symptoms of menopause, reduce bone turnover, and treat osteoporosis, sometimes results in side effects such as breast tenderness, fluid retention, headaches, and bloating. The group taking 0.25 mg estradiol had no more side effects than the placebo group, according to the study, conducted at UCONN's Claude D. Pepper Older Americans Independence Center.

A group of 107 white, African American, and Hispanic women over 65 were recruited over an 18-month period, beginning in July 1997. At the beginning of the study, African American women were found to have the highest bone mineral density while Hispanic women had the highest bone turnover and were most at risk for osteoporosis, according to the authors who will write a second report on the ethnic differences. Each of the three racial or ethnic groups was represented in the four dose groups: a placebo group, those taking the conventional dose of 1.0 mg 17-beta estradiol, a group taking 0.5 mg estradiol, and a group taking 0.25 mg estradiol. The women, whose mean age was 75, received 1300 mg of elemental calcium with 1000 IUs of vitamin D per day throughout the three-month study. Researchers have no ties to Bristol-Myers-Squibb, which provided the estradiol and placebos, or to Mission Pharmaceuticals, which provided the calcium citrate and vitamin D.

The women tracked their estimated dietary calcium intake with food diaries and their physical activity by the Physical Activity Scale for the Elderly every 12 weeks. Side effects were recorded at each visit by a questionnaire. Women kept track of vaginal bleeding with diaries and endometrial thickness was measured to the closest 1mm by transvaginal ultrasound. Bone mineral density of the hip, lumbar spine and total body was measured by dual energy x-ray absorptiometry (DEXA scan) at the first visit.

Researchers examined biochemical bone markers that detect bone turnover at baseline, 6 weeks, and 12 weeks on treatment and 6 and 12 weeks off treatment. All markers of bone resorption significantly decreased at 12 weeks on treatment compared to the placebo and returned towards baseline 12 weeks after treatment, regardless of race or ethnicity. Bone turnover in response to 0.25 mg estradiol was similar to that seen with 1.0 mg estradiol.

"Dr. Prestwood's findings advance the UCONN Pepper Center's mission of studying interventions that improve bone strength and reduce fractures," said Stanley L. Slater, M.D., Deputy Associate Director for Geriatrics at the National Institute on Aging (NIA), which supported the research. "Longer term studies are needed to determine whether the effects on bone turnover seen with 0.25 mg estradiol will translate into increases in bone density and decreases in fractures."

Such studies are needed to help the more than 10 million Americans who have osteoporosis, a disease that thins and weakens bones with the most common fractures occurring to the spine, wrist and hip. Some 18 million more have lost enough bone to make them more likely to develop osteoporosis. More than 80 percent of these 28 million people are women. Osteoporosis is costly both in dollars and in human suffering. Hip fractures alone amount to $10 to $14 billion in health care expenditures each year.

The study was conducted by Prestwood and Anne M. Kenny, M.D., assistant professors of medicine at UCONN Health Center's Center on Aging, Christine Unson, Ph.D., research associate at the Center on Aging, and Martin Kulldorff, Ph.D., in the UCONN Health Center's Department of Community Medicine. One of 10 such research centers funded by the NIA, the UCONN Pepper Center conducts research on muscle and bone problems, especially osteoporosis.
The NIA, which leads the federal effort supporting basic, clinical, epidemiological and social research on aging and the special needs of older people, recently updated its Age Page, Osteoporosis: The Bone Thief, with practical information on the prevention and treatment of osteoporosis for the general public. For a free copy, contact the NIA Information Center at 1-800-222-2225. For other information, visit NIA's website at http://www.nih.gov/nia/.

NIH/National Institute on Aging

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