PT  - JOURNAL ARTICLE
AU  - Kelly E Mercer
AU  - Rebecca A Wynne
AU  - Oxana P Lazarenko
AU  - Charles K. Lumpkin
AU  - William R Hogue
AU  - Larry J. Suva
AU  - Jin-Ran Chen
AU  - Andrew Z Mason
AU  - Thomas M Badger
AU  - Martin J.J. Ronis
TI  - Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice
AID  - 10.1124/jpet.112.197038
DP  - 2012 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.112.197038
4099  - http://jpet.aspetjournals.org/content/early/2012/08/14/jpet.112.197038.short
4100  - http://jpet.aspetjournals.org/content/early/2012/08/14/jpet.112.197038.full
AB  - Chronic alcohol abuse results in decreased bone mineral density (BMD) which can lead to increased fracture risk. In contrast, low levels of alcohol have been associated with increased BMD in epidemiological studies. Alcohol's toxic effects on the skeleton have been suggested to involve impaired vitamin D/calcium homeostasis. Therefore, dietary vitamin D supplementation may be beneficial in reducing bone loss associated with chronic alcohol consumption. Six week old, female C57BL/6J mice were pair-fed ethanol (EtOH)-containing liquid diets (10% or 36% total calories) for 78 days. EtOH exposure at 10% calories had no effects on any measured bone or serum parameter. EtOH consumption at 36% of calories reduced BMD and bone strength (p<0.05), decreased osteoblastogenesis, increased osteoclastogenesis, suppressed 1, 25 hydroxyvitamin D3 (1,25(OH)2D3) serum concentrations (p<0.05), and increased apoptosis in bone cells when compared to pair-fed controls. In a second study, female mice were pair-fed 30% EtOH diets with or without dietary supplementation with cholecalciferol (VitD) for 40 days. VitD supplementation in the EtOH diet protected against cortical bone loss, normalized alcohol-induced hypocalcemia, and suppressed EtOH-induced expression of Receptor of NFκB ligand (RANKL) mRNA in bone. In vitro, pre-treatment of 1,25(OH)2D3 in osteoblastic cells inhibited EtOH-induced apoptosis. In EtOH/VitD mice, circulating 1,25(OH)2D3 was lower compared to mice receiving EtOH alone (P<0.05), suggesting increased sensitivity to feedback control of VitD metabolism in the kidney. These findings suggest dietary VitD supplementation may prevent skeletal toxicity in chronic drinkers by normalizing calcium homeostasis, by preventing apoptosis and by suppressing EtOH-induced increases in bone resorption.