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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #306121
Title: Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice

Author
item YANG, CARRIE - University Arkansas For Medical Sciences (UAMS)
item MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)
item ALUND, ALEX - Arkansas Children'S Nutrition Research Center (ACNC)
item SUVA, LARRY - University Arkansas For Medical Sciences (UAMS)
item Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/2014
Publication Date: 10/1/2014
Citation: Yang, C.S., Mercer, K.E., Alund, A.W., Suva, L.J., Badger, T.M., Ronis, M.J. 2014. Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice. Experimental Biology and Medicine. 239(10):1380-1389.

Interpretive Summary: In this study we fed mice an 8-week liquid diet with or without alcohol and also with or without Genistein, a phytoestrogen in soy, to see if Genistein has a protective effect against alcohol-induced osteoporosis. MicroCT analysis of the tibias did not show a protective effect from Genistein supplementation. Staining analysis of mice femurs showed an increase in osteoblastogenesis; however, RNA analysis showed increases in markers of both osteoblastogenesis and osteoclastogenesis. Our findings show that Genistein increases overall bone turnover, osteoblastogenesis, and osteoclastogenesis, and therefore does not exhibit a protective effect on alcohol-induced osteoporosis.

Technical 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 '-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.