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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #177543
Title: MECHANISMS OF ETHANOL-INDUCED BONE LOSS DIFFER WITH PHYSIOLOGICAL STATE

Author
item RONIS, MARTIN - UAMS/ACNC
item BADGER, THOMAS - UAMS/ACNC
item LUMPLIN, CHARLES - UAMS
item ARNSON, JAMES - UAMS
item HIDESTRAND, MATS - UAMS/ACNC
item SHANKAR, KARTIK - UAMS/ACNC
item HALEY, RANI - UAMS STUDENT

Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: 7/20/2004
Publication Date: 3/15/2005
Citation: Ronis, M.J., Badger, T.M., Lumplin, C.K., Arnson, J., Hidestrand, M., Shankar, K., Haley, R. 2005. Mechanisms of ethanol-induced bone loss differ with physiological state. The Toxicologist. 84(S-1):211.

Interpretive Summary: This abstract describes a presentation made as part of a symposium and it summarized a wealth of information on the effects of alcohol consumption on bone loss.

Technical Abstract: Clinical surveys indicate that heavy drinking is a risk factor for the development of osteoporosis. However, the molecular mechanisms underlying ethanol-induced bone loss remain the subject of dispute with some studies showing ethanol effects on bone formation and others on bone breakdown. In these series of investigations, we have demonstrated dose-dependent ethanol-induced bone loss in both pregnant and non-pregnant female Sprague-Dawley rats. However, the severity of skeletal toxicity was substantially greater in non-pregnant rats at the same urine ethanol concentration and the molecular mechanism of bone loss was shown to differ. Peripheral computerized tomography, histomorphometry and molecular markers of bone turnover demonstrated that in pregnant rats bone formation was inhibited with no effects on osteoclasts (bone degrading cells) while in cycling females bone breakdown was stimulated by ethanol accompanied by increased expression of osteoclast specific genes including tartarate resistant acid phosphatase (TRAP) and a 70 kD vacuolar ATPase. Estradiol treatment of non-pregnant rats to produce plasma concentrations comparable to those found in pregnancy significantly protected against ethanol-induced bone loss. In addition, in physiological conditions where bone formation is increased such as in female rats following weaning and in rats undergoing distraction osteogenesis (a surgical procedure where bone is broken and forced apart mechanically to stimulate the making of new bone), ethanol was found to selectively block bone formation. Ethanol-induced bone loss was accompanied by reduced blood vitamin D as the result of increased breakdown of the hormone. In addition, effects on bone formation were blocked by inhibitors of the peptide growth factor TNF alpha. These studies illustrate that alternative pathways of ethanol-induced bone loss exist and that there are multiple effects of ethanol on the skeleton are and these are dependent on physiological and endocrine status.