CHICAGO (AP) - A supplement marketed as a bone-building alternative to estrogen didn't prevent bone loss in women with osteoporosis and caused changes in their disease-fighting immune systems, a Danish study has found.

The research involved ipriflavone, a synthetic form of an estrogen-like substance found in plants such as soybeans. It is sold as dietary supplement pills under various brand names on the Internet and in health food stores in the United States and several other countries.

The study followed research suggesting such products could benefit bones and was published in Wednesday's Journal of the American Medical Association.

In the four-year study of 292 women aged 63 on average and already diagnosed with bone-thinning osteoporosis, ipriflavone supplements had no effect on preserving bone density. But women who took the supplements, in standard doses of 600 milligrams daily, were more likely than those on dummy pills to develop a reduction in disease-fighting white blood cells called lymphocytes.

The women remained otherwise healthy, but low lymphocyte counts are a symptom of an immune system that is potentially more vulnerable to infection. In most of the women, the white cell counts returned to normal within two years after they stopped taking ipriflavone.

The authors, led by Dr. Peter Alexandersen of the Center for Clinical and Basic Research in Ballerup, Denmark, said the significance of the lymphocyte problems was unknown.

``The relative benefit-risk ratio of ipriflavone appears low when compared with the alternative anti-osteoporotic drugs available. Its use in treatment is not supported by these data,'' the authors said.

Osteoporosis affects more than 80 million people worldwide, 80 percent of them women. Women are most susceptible because at menopause they lose naturally occurring estrogen, which helps keep bones strong.

The Food and Drug Administration has approved five medications to treat or prevent osteoporosis: estrogen replacement therapy, alendronate (Fosamax), raloxifene (Evista), risedronate (Actonel) and calcitonin (Calcimar), which have varying results.

To avoid osteoporosis, women also are advised to get adequate calcium, a mineral that helps build strong bones. Study participants all received calcium supplements.

Ipriflavone is not FDA approved, but has been marketed as a natural alternative without the side effects of estrogen supplements.

``This whole idea about natural being better has an emotional component'' which isn't always scientifically proven, said Dr. Murray Favus, a University of Chicago osteoporosis expert who was not involved in the study.

The results suggest ipriflavone ``isn't the lock on getting the job done if you want to use it to preserve bone mass,'' he said.

Still, he noted that the study started with 474 women and said the findings are weakened by the high number of dropouts - 182 - including almost half the ipriflavone takers. The results, Favus said, also don't indicate whether ipriflavone would be beneficial for women who don't already have low bone density.

The study was funded by Chiesi Pharmaceuticals Inc., an Italian maker of ipriflavone. The company's Paolo Chiesi did not return telephoned and faxed requests for comment Monday.

On the Net:

JAMA: http://jama.ama-assn.org

National Osteoporosis Foundation: http://www.nof.org

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