Vitamin D Supplementation Protects against Bone Loss Associated with Chronic Alcohol Administration in Female Mice

作者：Mercer Kelly E; Wynne Rebecca A; Lazarenko Oxana P; Lumpkin Charles K; Hogue William R; Suva Larry J; Chen Jin Ran; Mason Andrew Z; Badger Thomas M; Ronis Martin J J^*

来源：Journal of Pharmacology and Experimental Therapeutics, 2012, 343(2): 401-412.

DOI：10.1124/jpet.112.197038

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%26apos;s toxic skeletal effects 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 %26lt; 0.05), decreased osteoblastogenesis, increased osteoclastogenesis, suppressed 1,25-hydroxyvitamin D-3 [1,25(OH)(2)D-3] serum concentrations (P %26lt; 0.05), and increased apoptosis in bone cells compared with pair-fed controls. In a second study, female mice were pair-fed 30% EtOH diets with or without dietary supplementation with vitamin D-3 (cholecalciferol; VitD) for 40 days. VitD supplementation in the EtOH diet protected against cortical bone loss, normalized alcohol-induced hypocalcaemia, and suppressed EtOH-induced expression of receptor of nuclear factor-kappa B ligand mRNA in bone. In vitro, pretreatment of 1,25(OH)(2)D-3 in osteoblastic cells inhibited EtOH-induced apoptosis. In EtOH/VitD mice circulating 1,25(OH)(2)D-3 was lower compared with mice receiving EtOH alone (P %26lt; 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, preventing apoptosis, and suppressing EtOH-induced increases in bone resorption.

• 出版日期2012-11