title: Chronic ethanol consumption inhibits postlactational anabolic bone rebuilding in female rats.
abstract: EtOH consumption significantly impaired anabolic rebuilding of bone after lactation. Lower BMD and BMC in EtOH-fed rats were associated with decreased bone formation in the proximal tibia, increased proportion of adipocytes, and increased expression of TNF-alpha. EtOH-induced skeletal deficits were prevented by treatment with either NAC or sTNFR1. These data suggest that postlactational anabolic rebuilding is influenced by EtOH consumption and may affect the long-term risk of osteopenia.
  
  
  BACKGROUND
  Despite significant loss of bone during lactation, BMD is restored by a powerful anabolic rebuilding process after weaning. A significant number of women resume alcohol consumption after weaning their offspring from breast feeding. The objectives of this study were to examine the consequences of chronic ethanol (EtOH) consumption on the postlactational rebuilding process and to investigate the underlying mechanisms by which EtOH mediates its detrimental effects.
  
  
  METHODS
  Female Sprague-Dawley rats (n = 7-9 per group) were fed EtOH-containing diets (13 g/kg/d) for 1, 2, or 4 wk after weaning of their offspring. Skeletal parameters in the proximal tibia were examined using pQCT, microCT, and histomorphometric techniques, and interventional studies were performed on the mechanistic roles of EtOH-induced oxidative stress and TNF-alpha.
  
  
  CONCLUSIONS
  EtOH consumption completely abolished the anabolic bone rebuilding that occurred after lactation. Decreased BMD and BMC were associated with decreased bone formation and not with increased osteoclast activity. Furthermore, EtOH-fed rats showed greater proportion of fat volume/bone volume and expression of adipocyte-specific genes. EtOH-induced skeletal effects were mitigated by the dietary antioxidant, N-acetyl cysteine or by blocking TNF-alpha signaling. These data suggest EtOH consumption in the period immediately postweaning may significantly impair the mother's skeletal health and lead to long-term osteopenia.
authors.affiliation: Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Kartik
authors.initials: K
authors.lastname: Shankar
authors.forename: Mats
authors.initials: M
authors.lastname: Hidestrand
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Jin Ran
authors.initials: JR
authors.lastname: Chen
authors.forename: Rani
authors.initials: R
authors.lastname: Haley
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Perrien
authors.forename: Robert A
authors.initials: RA
authors.lastname: Skinner
authors.forename: Charles K
authors.initials: CK
authors.lastname: Lumpkin
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D007774:Lactation / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D000111:Acetylcysteine