Different molecular mechanisms underlie ethanol-induced bone loss in cycling and pregnant rats.
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.
Shankar
Kartik
K
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, and Arkansas Children's Nutrition Center, Little Rock, Arkansas 72202, USA.
Hidestrand
Mats
M
Haley
Rani
R
Skinner
Robert A
RA
Hogue
William
W
Jo
Chan-Hee
CH
Simpson
Pippa
P
Lumpkin
Charles K
CK
Aronson
James
J
Badger
Thomas M
TM
Ronis
Martin J J
MJ
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced*; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004971:Estrus / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol