Osteoporosis Drug May Be Safe Alternative to Estrogen
A compound that works like estrogen, but with none of the side effects, has been found to prevent brittle bone disease in mice. The discovery may offer an alternative for women who stopped hormone replacement therapy because of the risks of cancer and heart disease.
In a study appearing today in the journal Science, researchers say experiments with the compound estren increased bone density and strength in mice that had been surgically altered to mimic menopause. The scientists said they found none of the dangerous side effects linked to estrogen.
“This seems to be superior to estrogen in its effect on the bone, but it has no effect on the sex organs,” said Dr. Stavros C. Manolagas, a researcher at the University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, and the senior author of the study.
Experts on osteoporosis, or brittle bone disease, said that if estren is found to work as well in humans it could substitute for hormone replacement therapy, or HRT, that has been used to maintain bone health in women after menopause.
An estimated 20 million American women were regularly taking hormone supplements to treat post-menopausal symptoms such as hot flashes and thinning bones. But in July, federal scientists abruptly ended a study of the combination of estrogen and progestin after finding evidence that long-term use increased the risk of breast cancer, strokes and heart attacks. Sales of various formulations of HRT have dropped 15% to 40% since then.
At the conclusion Thursday of a two-day meeting at the National Institutes of Health, officials urged that women not use HRT on a long-term basis.
NIH director Dr. Elias Zerhouni said the therapy should not be used to prevent chronic diseases because it has more risks than benefits, but HRT may still be used by some women for relief of menopausal symptoms such as hot flashes.
“There is not a simple, single answer for all women,” Zerhouni said.
Jill L. Carrington of the National Institute on Aging, part of the NIH, said in an interview that Manolagas’ research is important because he has demonstrated that there are compounds that can safely replace estrogen hormone therapy for treating the loss of bone density.
“This opens up a new direction for how to treat osteoporosis with drugs that can be designed to take advantage of the best effect of estrogen without adding some of the harmful effects,” Carrington said. “It also opens up the possibility of finding new avenues of treatment of men with osteoporosis.”
Federal health officials estimate that 10 million people have been diagnosed with osteoporosis and another 34 million -- 55% of those older than 50 -- are at high risk of the disorder. Eighty percent of osteoporosis patients are women.
As people age and the sex hormones estrogen and testosterone decline, bones can become porous and brittle. Eventually, an ordinary bump or strain can cause bone fractures, particularly in the spine and hip. Officials estimate there are about 1.5 million fractures annually among osteoporosis patients, leading to medical costs of about $17 billion in 2001.
In the study, Manolagas and his colleagues screened a number of compounds to find one, which they called estren, that activated the bone-building action of estrogen without affecting cells in the sex organs or breasts.
They then tested the compound in an experiment using mice whose ovaries and testicles had been removed. This surgery mimics menopause in the females and prevents the male animals from making sex hormones that maintain bone density.
Manolagas said surgically altered mice that got no drugs lost 6% bone density and 23% of the strength in the leg bones after six weeks. The mice receiving estren, however, had a 4% increase in bone density and a 12% increase in bone strength.
