title: Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.
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.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  3 university medical centers in Italy.
  
  
  METHODS
  389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The study did not measure fractures and had limited power to evaluate adverse effects.
  
  
  CONCLUSIONS
  Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.
authors.affiliation: Azienda Ospedaliera Universitaria Policlinico G. Martino, University of Messina, Messina, Italy.
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Marco
authors.initials: M
authors.lastname: Atteritano
authors.forename: Agostino
authors.initials: A
authors.lastname: Gaudio
authors.forename: Susanna
authors.initials: S
authors.lastname: Mazzaferro
authors.forename: Alessia
authors.initials: A
authors.lastname: Frisina
authors.forename: Nicola
authors.initials: N
authors.lastname: Frisina
authors.forename: Carla
authors.initials: C
authors.lastname: Lubrano
authors.forename: Michele
authors.initials: M
authors.lastname: Bonaiuto
authors.forename: Rosario
authors.initials: R
authors.lastname: D'Anna
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Cannata
authors.forename: Francesco
authors.initials: F
authors.lastname: Corrado
authors.forename: Elena Bianca
authors.initials: EB
authors.lastname: Adamo
authors.forename: Steven
authors.initials: S
authors.lastname: Wilson
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D004311:Double-Blind Method; D004717:Endometrium / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*
chemical_list: D019833:Genistein