OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration.
BACKGROUND
RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1-5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood.


METHODS
We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49-67 yr) with a femoral neck BMD <0.795 g/cm(2) and no significant comorbid conditions after 24-mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D(3). All patients received dietary instruction in an isocaloric fat-reduced diet.


RESULTS
In comparison with placebo, sRANKL level was lower (p < 0.001 versus placebo) and OPG higher in genistein recipients (p < 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = -0.021, 95% CI, -0.020 to -0.022; placebo = +0.004, 95% CI, 0.003-0.005; difference = -0.020, 95% CI, -0.015 to -0.025, p < 0.001).


CONCLUSIONS
Our findings suggest that genistein plus calcium and vitamin D(3) as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL-OPG balance after 24 mo of treatment.
Marini
Herbert
H
Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, A.O.U. Policlinico G. Martino, 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
Cancellieri
Francesco
F
Faraci
Marianna
M
Marini
Rolando
R
Adamo
Elena Bianca
EB
Wilson
Steven
S
Squadrito
Francesco
F
D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D010919:Placebos; D017698:Postmenopause; D053245:RANK Ligand / Q000097:blood*
D053244:Osteoprotegerin; D010919:Placebos; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D019833:Genistein