WASHINGTON -- 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 older 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, called 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 Health Care System, and the senior author of the study.

Experts on osteoporosis, the brittle bone disease, said if estren is found to work as well in humans it could substitute for the 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 like hot flashes and the thinning of the 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 percent to 40 percent since then.

At the conclusion on 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," said Zerhouni.

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," said Carrington. "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 percent of those over 50 years of age -- 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 that there are about 1.5 million fractures annually among osteoporosis patients, leading to medical costs of about $17 billion in 2001.

In the new 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 six percent in bone density and 23 percent of strength in the leg bones after six weeks. The mice receiving estren, however, had a four percent increase in bone density and a 12 percent increase in bone strength.

He said bone strength and density improved for both the male and female test animals.

Manolagas said an examination of breast cells from the female animals detected no abnormality, and there was no change in the other sex organs.

The researchers now plan to expand the experiments to rats and to additional mice to search more closely for side effects. Manolagas said it will take two to three years of additional work before the compound would be ready for human testing.

Carrington said the experimental compound "has a ways to go" before it's ready for humans but she added: "The approach is very promising. The fact that he was able to demonstrate in live animals an increase in bone strength and density is very exciting."

Manolagas said he stands to financially benefit if estren becomes a successful therapy. He founded a privately held company, Anabonix Inc. in Little Rock, Ark., that holds the license to develop and commercialize the drug. The University of Arkansas holds a use patent on the compound, he said.

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