Herbert Marini, MD; Letteria Minutoli, MD; Francesca Polito, PhD; Alessandra Bitto, MD; Domenica Altavilla, PhD; Marco Atteritano, MD; Agostino Gaudio, MD; Susanna Mazzaferro, MD; Alessia Frisina, MD; Nicola Frisina, MD; Carla Lubrano, MD; Michele Bonaiuto, MD; Rosario D'Anna, MD; Maria Letizia Cannata, MD; Francesco Corrado, MD; Elena Bianca Adamo, MD; Steven Wilson, PhD; Francesco Squadrito, MD
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@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.
Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive.
To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women.
Randomized, double-blind, placebo-controlled trial.
3 university medical centers in Italy.
389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions.
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.
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.
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.
The study did not measure fractures and had limited power to evaluate adverse effects.
Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women.
ClinicalTrials.gov registration number: NCT00355953.
Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, et al. Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women: A Randomized Trial. Ann Intern Med. 2007;146:839–847. doi: 10.7326/0003-4819-146-12-200706190-00005
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Published: Ann Intern Med. 2007;146(12):839-847.
Endocrine and Metabolism, Metabolic Bone Disorders.
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