ARS | Publication request: Inhibited osteoblastogenesis, enhanced bone resorption and disrupted vitamin d3 homeostasis in female c57bl/6 mice fed alcohol

Submitted to: Alcoholism: Clinical and Experimental
Publication Type: Abstract Only
Publication Acceptance Date: March 15, 2009
Publication Date: June 15, 2009
Citation: Ronis, M.J., Chen, J., Lazarenko, O., Badger, T.M., Shankar, K. 2009. Inhibited osteoblastogenesis, enhanced bone resorption and disrupted vitamin d3 homeostasis in female c57bl/6 mice fed alcohol [abstract]. Alcoholism: Clinical and Experimental Research. 33(S1):32A. Program No. P087.

Technical Abstract: Alcohol abuse is a well-known factor for increased risk of osteoporosis. Previous studies have shown that molecular mechanisms underlying alcohol-induced bone loss are complex, involving direct effects on both bone formation and resorption and additional indirect actions via endocrine disruption. Which mechanism predominates is dependent on variables such as species, age, sex, reproductive stage, and dose of ethanol. In the current study we examined the skeletal effects of chronic ethanol exposure in cycling female C57BL/6 mice between ages 6 and 22 wk of age using Lieber DeCarli liquid diets. Slowly increasing EtOH content of the diet over 30 d to a final concentration of 36% total calories resulted in final blood ethanol concentrations of 200 + 10 mg/dl, and although body weight was reduced in the EtOH-fed group (P<0.05), equivalent body weights were observed in pair-fed controls and ad libitum chow-fed control mice. EtOH treatment reduced both cancellous and cortical bone mineral density of the tibia (P<0.05) relative to pair-fed or chow-fed groups. In addition while the bone formation marker osteocalcin was reduced (P<0.05), serum pro-collagen cross-links, a marker of bone resorption was increased (P<0.05). Ex-vivo bone marrow cultures from EtOH-treated mice demonstrated reduced levels of osteoblastogenesis and increased levels of osteoclastogenesis (P<0.05) relative to cultures from pair-fed animals. Serum 1,25 dihydroxycholecalciferol values were also significantly reduced after EtOH treatment (P<0.05). These data replicate those of previous studies in female rats fed by total enteral nutrition and suggest that this mouse model can be utilized to study molecular mechanisms underlying EtOH-effects on both bone and vitamin D3 homeostasis.