Healthnotes Newswire (March 22, 2001)—According to a clinical trial published in this week’s Journal of the American Medical Association (JAMA), ipriflavone supplementation failed to prevent bone loss in postmenopausal women with osteoporosis who took the product for three years.¹ Ipriflavone is a synthetic isoflavone, derived from the soy compound daidzien.

The trial enrolled 474 women from Belgium, Denmark, and Italy, who were diagnosed with osteoporosis. Their ages ranged from 45 to 75 years. Once enrolled, each participant was randomly given either 200 mg of ipriflavone or a placebo three times per day. All participants also took 500 mg of calcium per day during the trial.

At the end of the three-year trial, the researchers determined that bone loss, measured in the lumbar spine, was the same in both groups. Not only did ipriflavone fail to slow bone loss, but it also did not produce a decrease in chemical markers used to measure bone loss.

To compound matters, the researchers report that 29 of the 132 women (22%) in the ipriflavone group completing the three-year clinical trial developed a clinically significant drop in lymphocytes. These cells, which make up approximately nearly one-third of the white blood cells in the normal adult, are critical components of the immune system and its ability to respond to viral infections. In some of these women, a return to normal levels took almost two years after they had stopped supplementing the ipriflavone.

The researchers conclude that, “… the relative benefit-risk ratio of ipriflavone appears low when compared with the alternative antiosteoporotic drugs available. Its use in treatment is not supported by these data.”

Ipriflavone was first synthesized in the 1930s and has been primarily researched in Japan and Europe. The product is sold in the United States as a dietary supplement, with a typical recommendation of 200 mg three times per day.

The results of this new clinical trial veer dramatically from the promising results seen in several earlier clinical trials with either osteoporotic women^{2 3 4 5} or those at risk for osteoporosis.⁶ These trials have found that 200 mg of ipriflavone three times per day paired with 800–1,000 mg of calcium per day prevented bone loss and, in some cases, actually increased bone density and reduced vertebral fractures.

However, none of these trials was greater than two years in length. As noted by the researchers of the new trial, the women enrolled in their study were somewhat older than women in earlier trials, suggesting that ipriflavone may be more likely to work in younger postmenopausal women with early signs of bone loss.

The red flag in the current trial is the significant drop in lymphocyte levels measured in almost 22% of the women taking ipriflavone. Although this finding has been reported in one other smaller clinical trial,⁷ it suggests that women choosing to take ipriflavone should have their lymphocytes measured regularly by their doctor.

While the results of the current trial do not bode well for the future of ipriflavone in the treatment of osteoporosis, there continues to be a need for safe and effective approaches to the prevention and treatment of osteoporosis. Despite the endorsement of the authors of this study for drugs to treat and prevent osteoporosis, the fact remains that most of these have very unpleasant side effects that negatively affect the quality of life of the many women taking them.^{8 9 10 11}