title: OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration.
abstract: 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.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, A.O.U. Policlinico G. Martino, 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: Francesco
authors.initials: F
authors.lastname: Cancellieri
authors.forename: Marianna
authors.initials: M
authors.lastname: Faraci
authors.forename: Rolando
authors.initials: R
authors.lastname: Marini
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: 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*
chemical_list: D053244:Osteoprotegerin; D010919:Placebos; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D019833:Genistein