title: Intraperitoneal injection of ethanol results in drastic changes in bone metabolism not observed when ethanol is administered by oral gavage.
abstract: BACKGROUND
  Chronic alcohol abuse is associated with increased risk of osteoporosis while light-to-moderate alcohol intake correlates with reduced osteoporosis risk. Addition of alcohol to a liquid diet is often used to model chronic alcohol abuse. Methods to model intermittent drinking (including binge drinking and light-to-moderate consumption) include (i) intragastric administration of alcohol by oral gavage or (ii) intraperitoneal (ip) administration of alcohol by injection. However, it is unclear whether the latter 2 methods produce comparable results. The purpose of this investigation was to determine the skeletal response to alcohol delivered daily by oral gavage or ip injection.
  
  
  METHODS
  Ethanol (EtOH) or vehicle was administered to 4-month-old female Sprague-Dawley rats once daily at 1.2 g/kg body weight for 7 days. Following necropsy, bone formation and bone architecture were evaluated in tibial diaphysis (cortical bone) and proximal tibial metaphysis (cancellous bone) by histomorphometry. mRNA was measured for bone matrix proteins in distal femur metaphysis.
  
  
  RESULTS
  Administration of alcohol by gavage had no significant effect on body weight gain or bone measurements. In contrast, administration of the same dose of alcohol by ip injection resulted in reduced body weight, total suppression of periosteal bone formation in tibial diaphysis, decreased cancellous bone formation in proximal tibial metaphysis, and decreased mRNA levels for bone matrix proteins in distal femur.
  
  
  CONCLUSIONS
  Our findings raise concerns regarding the use of ip injection of EtOH in rodents as a method for modeling the skeletal effects of intermittent exposure to alcohol in humans. This concern is based on a failure of the ip route to replicate the oral route of alcohol administration.
authors.affiliation: Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA. urszula.iwaniec@oregonstate.edu
authors.forename: Urszula T
authors.initials: UT
authors.lastname: Iwaniec
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
mesh_terms: D000284:Administration, Oral; D000437:Alcoholism; D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007274:Injections, Intraperitoneal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D000431:Ethanol
keywords: Gene Expression; Histomorphometry; Rat Model; Tibia
references.citation: Alcohol. 2008 Dec;42(8):649-56
references.pmid: 19038696
references.citation: J Endocrinol Invest. 2008 Apr;31(4):321-6
references.pmid: 18475050
references.citation: Alcohol Clin Exp Res. 1999 Jul;23(7):1228-31
references.pmid: 10443990
references.citation: Alcohol Clin Exp Res. 2001 Nov;25(11):1662-72
references.pmid: 11707641
references.citation: Alcohol Clin Exp Res. 1998 Oct;22(7):1591-9
references.pmid: 9802546
references.citation: J Bone Miner Res. 1987 Dec;2(6):595-610
references.pmid: 3455637
references.citation: Osteoporos Int. 2009 Sep;20(9):1529-38
references.pmid: 19238309
references.citation: J Bone Miner Res. 2010 Sep;25(9):2078-88
references.pmid: 20229598
references.citation: Alcohol Clin Exp Res. 1998 Nov;22(8):1746-53
references.pmid: 9835290
references.citation: Public Health Nutr. 2013 Apr;16(4):704-12
references.pmid: 22800300
references.citation: Alcohol Clin Exp Res. 2003 Sep;27(9):1463-70
references.pmid: 14506408
references.citation: Skeletal Radiol. 1992;21(7):431-6
references.pmid: 1439893
references.citation: Alcohol Clin Exp Res. 2000 Nov;24(11):1693-701
references.pmid: 11104117
references.citation: Osteoporos Int. 2011 Apr;22(4):1175-81
references.pmid: 20549487
references.citation: Pharmacol Biochem Behav. 2009 Feb;91(4):560-5
references.pmid: 18940195
references.citation: Alcohol Clin Exp Res. 2012 May;36(5):748-58
references.pmid: 22141380
references.citation: Alcohol Clin Exp Res. 1997 Aug;21(5):809-16
references.pmid: 9267530
references.citation: Alcohol Clin Exp Res. 2010 Oct;34(10):1723-32
references.pmid: 20608904
references.citation: Am J Clin Nutr. 2009 Apr;89(4):1188-96
references.pmid: 19244365
references.citation: Pharmacol Biochem Behav. 1999 Nov;64(3):563-6
references.pmid: 10548272
references.citation: J Bone Miner Res. 1993 May;8(5):625-34
references.pmid: 8511990
references.citation: Alcohol Res Health. 2001;25(4):276-81
references.pmid: 11910705
references.citation: Alcohol Clin Exp Res. 2002 Aug;26(8):1269-74
references.pmid: 12198404
references.citation: J Am Geriatr Soc. 2006 Nov;54(11):1649-57
references.pmid: 17087690
references.citation: Osteoporos Int. 1999;9(1):45-54
references.pmid: 10367029
references.citation: Am J Public Health. 2001 Jul;91(7):1089-93
references.pmid: 11441736
references.citation: Am J Med. 2008 May;121(5):406-18
references.pmid: 18456037
references.citation: Alcohol. 2011 May;45(3):227-38
references.pmid: 21051177
references.citation: Alcohol Clin Exp Res. 1998 Dec;22(9):2159-64
references.pmid: 9884164
references.citation: J Bone Miner Res. 2009 Aug;24(8):1380-8
references.pmid: 19257829
references.citation: Am J Physiol. 1991 Sep;261(3 Pt 1):E348-53
references.pmid: 1887882
references.citation: Menopause. 2012 Sep;19(9):974-9
references.pmid: 22922514
references.citation: Dig Dis Sci. 1999 Oct;44(10):1963-74
references.pmid: 10548344
references.citation: Alcohol Clin Exp Res. 1997 May;21(3):467-76
references.pmid: 9161607
references.citation: Am J Clin Nutr. 2012 May;95(5):1261-9
references.pmid: 22456655
references.citation: Hepatology. 1989 Oct;10(4):501-10
references.pmid: 2673971
references.citation: Alcohol. 1996 Nov-Dec;13(6):575-80
references.pmid: 8949952
references.citation: Alcohol Clin Exp Res. 1997 Apr;21(2):352-9
references.pmid: 9113275
references.citation: Cytokine. 2005 May 7;30(3):109-15
references.pmid: 15826817
references.citation: J Bone Miner Res. 1987 Feb;2(1):61-6
references.pmid: 3455157
references.citation: Methods Mol Biol. 2008;447:325-41
references.pmid: 18369927
references.citation: Am J Physiol. 1992 Oct;263(4 Pt 1):E724-9
references.pmid: 1415691