Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.
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.
Marini
Herbert
H
Azienda Ospedaliera Universitaria Policlinico G. Martino, University of Messina, Messina, Italy.
Minutoli
Letteria
L
Polito
Francesca
F
Bitto
Alessandra
A
Altavilla
Domenica
D
Atteritano
Marco
M
Gaudio
Agostino
A
Mazzaferro
Susanna
S
Frisina
Alessia
A
Frisina
Nicola
N
Lubrano
Carla
C
Bonaiuto
Michele
M
D'Anna
Rosario
R
Cannata
Maria Letizia
ML
Corrado
Francesco
F
Adamo
Elena Bianca
EB
Wilson
Steven
S
Squadrito
Francesco
F
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*
D019833:Genistein