|Mercer, Kelly -|
|Wynne, Rebecca -|
|Lazarenko, Oxana -|
|Lumpkin, Charles -|
|Hogue, William -|
|Suva, Larry -|
|Chen, Jinran -|
|Ronis, Martin -|
Submitted to: Journal of Pharmacology and Experimental Therapeutics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 13, 2012
Publication Date: November 15, 2012
Citation: Mercer, K.E., Wynne, R., Lazarenko, O., Lumpkin, C.K., Hogue, W.R., Suva, L.J., Chen, J., Badger, T.M., Ronis, M.J. 2012. Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice. Journal of Pharmacology and Experimental Therapeutics. 343(2):401-412. Interpretive Summary: Female alcoholics (approx. 7 drinks/day) are likely to have poor bone quality, which increases their chances for bone breaks after falling. However, female social drinkers (1-2 drinks/day) have improved bone mass and quality and are not at risk for bone breaks. Alcohol's toxic effects have been linked to changes in vitamin D and calcium levels in the body; therefore, adding vitamin D back to the body through the diet may protect against poor bone quality seen in alcoholics. In this study, female mice received alcohol liquid diets similar to what an alcoholic or a social drinker would consume on a daily basis for 78 days. Alcohol consumed by the "social drinking" mice did not improve bone quality. Alcohol consumed by the "alcoholic" mice had severe defects in bone quality. Vitamin D and calcium levels in the body were very low. The population of cells which make bone decreased, while the population of cells which remove bone increased, which maked the bones more likely to break. Adding back vitamin D to the diets of the alcoholic mice increased vitamin D and calcium levels, prevented the increase in the size of bone-removing cell population, all of which made the bone less likely to break after falling. These findings suggest that dietary supplementation of vitamin D may prevent alcohol's bad effects on bone quality in alcoholics.
Technical Abstract: Chronic alcohol consumption is detrimental to bone by decreasing bone mineral density (BMD) resulting in increased risk of osteoporosis risk and fracture, particularly in women. In moderation, alcohol is positively associated with increased BMD and reduced fracture risk. Alcohol's toxic effects have been suggested to involve impaired vitamin D and calcium homeostasis. Dietary vitamin D supplementation may be potentially beneficial in reducing bone loss associated with chronic alcohol consumption. Six-week-old wild type C57BL/6J mice were pair fed liquid diets at 10% or 36% ethanol for 78 days. Ethanol (EtOH) exposure at 10% calories had no effect 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, reduced calcium and 1,25 hydroxyvitamin D3 (1,25(OH)2D3)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 of cholecalciferol (VitD) for 40 days. VitD supplementation in the EtOH diet protected against bone loss, normalized serum calcium homeostasis, and suppressed EtOH-induced RANKL expression 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 significantly lower compared to mice receiving EtOH alone, suggesting increased sensitivity to feedback control of vitamin D metabolism in the kidney. These findings suggest a role for dietary vitamin D supplementation in preventing bone toxicity in chronic drinkers by normalizing calcium homeostasis, and the prevention of apoptosis and increased resorption in bone.