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

A Randomized Trial

  1. Herbert Marini, MD;
  2. Letteria Minutoli, MD;
  3. Francesca Polito, PhD;
  4. Alessandra Bitto, MD;
  5. Domenica Altavilla, PhD;
  6. Marco Atteritano, MD;
  7. Agostino Gaudio, MD;
  8. Susanna Mazzaferro, MD;
  9. Alessia Frisina, MD;
  10. Nicola Frisina, MD;
  11. Carla Lubrano, MD;
  12. Michele Bonaiuto, MD;
  13. Rosario D'Anna, MD;
  14. Maria Letizia Cannata, MD;
  15. Francesco Corrado, MD;
  16. Elena Bianca Adamo, MD;
  17. Steven Wilson, PhD; and
  18. Francesco Squadrito, MD
  1. From Azienda Ospedaliera Universitaria Policlinico “G. Martino,” University of Messina, Messina, Italy.

    Abstract

    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.

    Article and Author Information

    • 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.

    Responses to this article

    • Geographic Differences in Dietary Influences May Play a Bigger Issue in Postmenopausal Women
      • An T. Tran and
      • Daniel D. Arkfeld, M.D., Jeffrey B. Canceko MD, David Patterson
      Ann Intern Med published online October 26, 2009

    Summary for Patients

    • Summaries for Patients:Effects of the Phytoestrogen Genistein on Bone Health in Postmenopausal Women Ann Intern Med June 19, 2007 146:I-34
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