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Different molecular mechanisms underlie ethanol-induced bone loss in cycling and pregnant rats. Endocrinology 2006 Jan;147(1):166-78

Date

10/22/2005

Pubmed ID

16239303

DOI

10.1210/en.2005-0529

Scopus ID

2-s2.0-29344462225   28 Citations

Abstract

Chronic ethanol (EtOH) consumption can result in osteopenia. In the current study, we examined the modulation of EtOH-induced bone loss during pregnancy. Nonpregnant and pregnant dams were intragastrically infused either control or EtOH-containing diets throughout gestation (gestation d 5 through 20 or an equivalent period of 15 d) by total enteral nutrition. The effects of EtOH (8.5 to 14 g/kg/d) on tibial bone mineral density (BMD), mineral content (BMC), and bone mineral area were assessed at gestation d 20 via peripheral quantitative computerized tomography. EtOH caused a dose-dependent decrease in BMD and BMC without affecting bone mineral area. Trabecular BMD and BMC were significantly lower in EtOH-treated, nonpregnant dams, compared with pregnant cohorts at the same infused dose of EtOH and urinary ethanol concentrations. Static histomorphometric analysis of tibiae from pregnant rats after EtOH treatment showed decreased osteoblast and osteoid surface, indicating inhibited bone formation, whereas EtOH-treated cycling rats showed higher osteoclast and eroded surface, indicative of increased bone resorption. Circulating osteocalcin and 1,25-dihydroxyvitamin D3 were lower in both EtOH-fed nonpregnant and pregnant rats. Gene expression of osteoclast markers, 70 kDa v-ATPase, and tartrate-resistant acid phosphatase were increased selectively in nonpregnant EtOH-treated rats but not pregnant rats. Moreover, only nonpregnant EtOH-fed rats showed induction in bone marrow receptor activator of nuclear factor-kappaB ligand mRNA and decreased circulating 17beta-estradiol levels. Our data suggest that EtOH-induced bone loss in pregnant rats is mainly due to inhibited bone formation, whereas in nonpregnant rats, the data are consistent with increased osteoclast activation and bone resorption concomitant with decreased estradiol levels.

Author List

Shankar K, Hidestrand M, Haley R, Skinner RA, Hogue W, Jo CH, Simpson P, Lumpkin CK Jr, Aronson J, Badger TM, Ronis MJ

Author

Mats Hidestrand PhD Adjunct Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Density
Bone Resorption
Cell Division
Chondrocytes
Dose-Response Relationship, Drug
Estrus
Ethanol
Female
Pregnancy
Pregnancy Complications
Pregnancy, Animal
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc