Skeletal Biology Laboratory

BACKGROUND: Estrogen signaling is essential for the sexual dimorphism of the skeleton, is required for normal bone remodeling balance in adults, and may influence the skeletal response to alcohol. High levels of alcohol consumption lower bone mass in ovary-intact but not ovariectomized (ovx) rats. However, the extremely rapid rate of bone loss immediately following ovx may obscure the effects of alcohol. We therefore determined (1) whether heavy alcohol consumption (35% caloric intake) influences bone in sexually mature ovx rats with established cancellous osteopenia, and (2) whether ICI 182,780 (ICI), a potent estrogen receptor-signaling antagonist, alters the skeletal response to alcohol.

METHODS: Three weeks following ovx, rats were randomized into five groups: (1) baseline, (2) control+vehicle, (3) control+ICI, (4) ethanol+vehicle, or (5) ethanol+ICI and treated accordingly for four weeks. Dual energy X-ray absorptiometry, micro-computed tomography, blood measurements of markers of bone turnover, and gene expression in femur and uterus were used to evaluate response to alcohol and ICI.

RESULTS: Rats consuming alcohol had lower bone mass and increased fat mass. Bone microarchitecture of the tibia and gene expression in femur were altered; specifically, there was reduced accrual of cortical bone, net loss of cancellous bone, and differential expression of 19/84 genes related to bone turnover. Furthermore, osteocalcin, a marker of bone turnover, was lower in alcohol-fed rats. ICI had no effect on weight gain, body composition, or cortical bone. ICI reduced cancellous bone loss and serum CTX-1, a biochemical marker of bone resorption; alcohol antagonized the latter two responses. Neither alcohol nor ICI affected uterine weight or gene expression.

CONCLUSION: Alcohol exaggerated bone loss in ovx rats in the presence or absence of estrogen receptor blockade with ICI. The negligible effect of alcohol on uterus and limited effects of ICI on bone in alcohol-fed ovx rats suggests that estrogen receptor signaling plays a limited role in the action of alcohol on bone in a rat model for chronic alcohol abuse. This article is protected by copyright. All rights reserved.