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High levels of alcohol consumption lower bone mass in ovary\u2010intact 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 (i) whether heavy alcohol consumption (35% caloric intake) influences bone in sexually mature ovx rats with established cancellous osteopenia and (ii) whether <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content> 182,780 (<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>), a potent estrogen receptor signaling antagonist, alters the skeletal response to alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three weeks following ovx, rats were randomized into 5 groups, (i) baseline, (ii) control\u00a0+\u00a0vehicle, (iii) control\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>, (iv) ethanol (EtOH)\u00a0+\u00a0vehicle, or (v) EtOH\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>, and treated accordingly for 4\u00a0weeks. Dual\u2010energy X\u2010ray absorptiometry, microcomputed tomography, blood measurements of markers of bone turnover, and gene expression in femur and uterus were used to evaluate response to alcohol and <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010fed rats. <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content> had no effect on weight gain, body composition, or cortical bone. <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content> reduced cancellous bone loss and serum <jats:styled-content style=\"fixed-case\">CTX<\/jats:styled-content>\u20101, a biochemical marker of bone resorption; alcohol antagonized the latter 2 responses. Neither alcohol nor <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content> affected uterine weight or gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alcohol exaggerated bone loss in ovx rats in the presence or absence of estrogen receptor blockade with <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>. The negligible effect of alcohol on uterus and limited effects of <jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content> on bone in alcohol\u2010fed ovx rats suggest that estrogen receptor signaling plays a limited role in the action of alcohol on bone in a rat model for chronic alcohol abuse.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14185","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T19:40:47Z","timestamp":1567539647000},"page":"2301-2311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Alcohol and Estrogen Receptor Blockade Using <scp>ICI<\/scp> 182,780 on Bone in Ovariectomized Rats"],"prefix":"10.1111","volume":"43","author":[{"given":"Lindsay","family":"Wagner","sequence":"first","affiliation":[{"name":"Skeletal Biology Laboratory School of Biological and Population Health Sciences Oregon State University Corvallis 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