Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women

A Randomized Trial

19 June 2007 | Volume 146 Issue 12 | Pages 839-847

Background: Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive.

Objective: To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: 3 university medical centers in Italy.

Patients: 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm² at the femoral neck and no significant comorbid conditions.

Intervention: After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D.

Measurements: The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected.

Results: At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm² [95% CI, 0.035 to 0.059] vs. –0.053 g/cm² [CI, –0.058 to –0.035]; difference, 0.10 g/cm² [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm² [CI, 0.025 to 0.042] vs. –0.037 g/cm² [CI, –0.044 to –0.027]; difference, 0.062 g/cm² [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study.

Limitations: The study did not measure fractures and had limited power to evaluate adverse effects.

Conclusion: Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women.

ClinicalTrials.gov registration number: NCT00355953.

Editors' Notes Context Women seeking alternative treatments to preserve bone often use phytoestrogens, but evidence of their effectiveness is lacking. Phytoestrogens are found in soy products. Genistein is a phytoestrogen with a structure similar to that of 17ß-estradiol. Contribution This randomized trial compared genistein, 54 mg/d, with placebo for 24 months in 389 osteopenic postmenopausal women. Increases in bone mineral density were greater with genistein than with placebo. Genistein also had favorable effects on markers of bone metabolism. Genistein did not increase endometrial thickness, but it did cause gastrointestinal side effects. Implications Genistein appears to have a favorable effect on markers of bone health in osteopenic postmenopausal women. Studies of its effect on fractures are needed. —The Editors

 

Author and Article Information

From Azienda Ospedaliera Universitaria Policlinico "G. Martino," University of Messina, Messina, Italy.

Grant Support: By the Italian Ministry of Education, University, and Research and the University of Messina.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Francesco Squadrito, MD, Department of Experimental and Clinical Medicine and Pharmacology, Section of Pharmacology, Torre Biologica, 5th Floor, Azienda Ospedaliera Universitaria Policlinico "G. Martino," Via C. Valeria, 98125 Messina, Italy; e-mail, Francesco.Squadrito{at}unime.it.

Current Author Addresses: Drs. Marini and Adamo: Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, Azienda Ospedaliera Universitaria Policlinico "G. Martino," Via C. Valeria, 98125 Messina, Italy.

Drs. Minutoli, Polito, Bitto, Altavilla, and Squadrito: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Azienda Ospedaliera Universitaria Policlinico "G. Martino," Via C. Valeria, 98125 Messina, Italy.

Drs. Atteritano, Gaudio, Mazzaferro, A. Frisina, N. Frisina, and Bonaiuto: Department of Internal Medicine, Azienda Ospedaliera Universitaria Policlinico "G. Martino," Via C. Valeria, 98125 Messina, Italy.

Dr. Lubrano: Department of Medical Physiopathology, "La Sapienza" University, Rome, Italy.

Drs. D'Anna, Cannata, and Corrado: Department of Obstetrical and Gynecological Sciences, Azienda Ospedaliera Universitaria Policlinico "G. Martino," Via C. Valeria, 98125 Messina, Italy.

Dr. Wilson: Department of Health Initiatives, National Jewish Medical and Research Center, Denver, CO 80206.

Author Contributions: Conception and design: H. Marini, R. D'Anna, F. Squadrito.

Analysis and interpretation of the data: H. Marini, L. Minutoli, F. Polito, R. D'Anna, S. Wilson, F. Squadrito.

Drafting of the article: H. Marini, A. Bitto, D. Altavilla, R. D'Anna, F. Squadrito.

Critical revision of the article for important intellectual content: H. Marini, R. D'Anna, F. Squadrito.

Provision of study materials or patients: M. Atteritano, A. Gaudio, S. Mazzaferro, A. Frisina, N. Frisina, C. Lubrano, M. Bonaiuto, R. D'Anna, M.L. Cannata, F. Corrado, E.B. Adamo.

Obtaining of funding: N. Frisina, C. Lubrano, R. D'Anna.

Administrative, technical or logistic support: N. Frisina, R. D'Anna, F. Squadrito.

Collection and assembly of data: H. Marini, L. Minutoli, F. Polito.

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