|MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)|
|WYNNE, REBECCA - University Arkansas For Medical Sciences (UAMS)|
|LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)|
|LUMPKIN, CHARLES - University Arkansas For Medical Sciences (UAMS)|
|HOGUE, WILLIAM - University Arkansas For Medical Sciences (UAMS)|
|SUVA, LARRY - University Arkansas For Medical Sciences (UAMS)|
|CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)|
|RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Journal of Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: 7/1/2012
Publication Date: 1/10/2013
Citation: Mercer, K., Wynne, R., Lazarenko, O., Lumpkin, C., Hogue, W., Suva, L., Chen, J., Badger, T.M., Ronis, M.J. 2013. Vitamin D supplementation prevents hypocalcemia and cortical bone loss associated with chronic feeding in female mice [abstract]. Journal of Bone and Mineral Research. 27(Issue Supplement 1):http://www.asbmr.org/Meetings/PastAnnualMeetings.aspx.
Technical Abstract: Dietary cholecalciferol supplementation alone or combined with calcium has shown great promise in improving bone health, which has been attributed to endocrine actions involved in calcium regulation and/or paracrine/autocrine actions within bone. Indeed, we and others have suggested that dietary supplementation may also be an effective strategy to protect against EtOH-mediated bone loss in young females. Previously, we reported bone loss in cycling females receiving EtOH diets through intragastric infusion. EtOH-mediated bone loss was associated with excessive reactive oxygen species (ROS) production in osteoblastic populations resulting in the inhibition of bone formation and increased bone resorption. In addition, EtOH-generated ROS in the kidney increased CYP24A1 mRNA expression, which resulted in a reduction of circulating 1,25 hydroxyvitamin D3 (1,25 (OH2)D3) concentrations to below normal baseline levels, thus contributing to the disruption of normal vitamin D and calcium homeostasis. In the current study, 6-wk-old female C57BL/6J mice were pair-fed (PF) LieberDeCarli liquid diets containing 0% or 30% EtOH supplemented with 400 IU (EtOH/400) or 2000 IU (EtOH/2000) of cholecalciferol for 40 d. In the EtOH/400 group, chronic EtOH feeding resulted in decreased bone strength and stiffness (p<0.05), reductions in trabecular BV/TV and cortical volumetric BMD (p<0.05), and increased biochemical markers of bone resorption. The levels of circulating 1,25(OH)2D3 and ionized calcium were significantly decreased in the serum (p<0.05), and apoptosis was increased in the bone marrow cells when compared to PF controls. In contrast, increasing daily cholecalciferol intake from 400 to 2000 IU/kg completely prevented the cortical bone loss by reducing EtOH-mediated increases in bone resorption and protected against EtOH-mediated hypocalcaemia. In cultured cells, pre-treatment of 1,25 (OH)2D3 in EtOH-treated ST2 cells protected against increased caspase-3 activity. In the EtOH/2000 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 data suggest that daily dietary intake of cholecalciferol of 2000 IU may protect against bone toxicity associated with chronic alcohol abuse in younger women, thus reducing the increased risk of osteoporosis and fracture that comes with age.