title: Skeletal toxicity associated with chronic ethanol exposure in a rat model using total enteral nutrition.
abstract: Chronic alcohol abuse decreases bone mass, inhibits osteoblast differentiation and function, increases fracture incidence, and delays fracture healing. Four studies were designed to use intragastric ethanol delivery as part of a total enteral nutrition (TEN) system to determine the negative systemic effects of chronic ethanol on 1) the rat skeleton and 2) local rapid bone formation during limb lengthening (distraction osteogenesis, DO). In study 1, three-point bending tests demonstrated that after 75 days of ethanol exposure, the tibiae had significantly lower load to failure versus control diet (p = 0.0006) or ad libitum chow-fed rats (p = 0.0029). Study 2 examined alcohol's effects on the density and cross-sectional area of the proximal tibial metaphysis using peripheral quantitative computed tomography and found that after 25 days of ethanol exposure the trabecular volumetric bone mineral density (p = 0.011) and cortical cross-sectional area (p = 0.011) were lower compared with controls. In study 3, a comparison of distracted tibial radiographs and histological sections demonstrated ethanol-related decreases in both gap mineralization (p = 0.03) and bone column formation (p = 0.01). Histological comparisons in study 4 reproduced the ethanol-related deficits in new bone formation during DO (p = 0.001). These results indicate that the TEN system is a viable model to study ethanol's effects on the skeleton and that chronic ethanol delivery via TEN decreases trabecular bone density, cortical area, and mature bone strength. Also, the DO studies demonstrate, for the first time, that chronic ethanol inhibits rapid bone formation during limb lengthening.
authors.affiliation: Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Little Rock, AR 72202, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Brown
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Perrien
authors.forename: Terry W
authors.initials: TW
authors.lastname: Fletcher
authors.forename: David J
authors.initials: DJ
authors.lastname: Irby
authors.forename: James
authors.initials: J
authors.lastname: Aronson
authors.forename: Guan G
authors.initials: GG
authors.lastname: Gao
authors.forename: William J
authors.initials: WJ
authors.lastname: Hogue
authors.forename: Robert A
authors.initials: RA
authors.lastname: Skinner
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Suva
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: Reza
authors.initials: R
authors.lastname: Hakkak
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.forename: Charles K
authors.initials: CK
authors.lastname: Lumpkin
mesh_terms: D000437:Alcoholism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001846:Bone Development / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage*; D007441:Intubation, Gastrointestinal / Q000379:methods; D008297:Male; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010289:Parenteral Nutrition, Total / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol