title: Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice.
abstract: Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy protein-associated phytoestrogens such as genistein (GEN). In this study, male mice were pair-fed (PF), a control diet, an ethanol (EtOH) diet, or EtOH diet supplemented with 250 mg/kg of GEN for 8 weeks to test if GEN protects against bone loss associated with chronic drinking. Interestingly, alcohol consumption reduced cortical area and thickness and trabecular bone volume in both EtOH and EtOH/GEN groups when compared to the corresponding PF and PF/GEN controls, P < 0.05. However, in the trabecular bone compartment, we observed a significant increase in overall trabecular bone density in the PF/GEN group compared to the PF controls. Bone loss in the EtOH-treated mice was associated with the inhibition of osteoblastogenesis as indicated by decreased alkaline phosphatase staining in ex vivo bone marrow cultures, P < 0.05. GEN supplementation improved osteoblastogenesis in the EtOH/GEN cultures compared to the EtOH group, P < 0.05. Vertebral expression of bone-formation markers, osteocalcin, and runt-related transcription factor 2 (Runx2) was also significantly up-regulated in the PF/GEN and EtOH/GEN groups compared to the PF and EtOH-treated groups. GEN supplementation also increased the expression of receptor activator of nuclear factor κ-B ligand (RANKL) in the PF/GEN, an increase that persisted in the EtOH/GEN-treated animals (P < 0.05), and increased basal hydrogen peroxide production and RANKL mRNA expression in primary bone marrow cultures in vitro, P < 0.05. These findings suggest that GEN supplementation increases the overall bone remodeling and, in the context of chronic alcohol consumption, does not protect against the oxidative stress-associated EtOH-mediated bone resorption.
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
authors.forename: Carrie S
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Mercer
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Alund
authors.affiliation: Orthopaedic Surgery, Center for Orthopedic Research, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Suva
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA RonisMartinJ@uams.edu.
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced* / Q000517:prevention & control*; D001842:Bone and Bones / Q000473:pathology; D004032:Diet / Q000379:methods; D019587:Dietary Supplements; D000431:Ethanol / Q000009:adverse effects*; D019833:Genistein / Q000008:administration & dosage*; D008297:Male; D008810:Mice, Inbred C57BL; D048789:Phytoestrogens / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D048789:Phytoestrogens; D000431:Ethanol; D019833:Genistein
keywords: Alcohol; RANKL; bone loss; genistein