Skeletal toxicity associated with chronic ethanol exposure in a rat model using total enteral nutrition

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...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of pharmacology and experimental therapeutics Vol. 301; no. 3; p. 1132
Main Authors:	Brown, Elizabeth C, Perrien, Daniel S, Fletcher, Terry W, Irby, David J, Aronson, James, Gao, Guan G, Hogue, William J, Skinner, Robert A, Suva, Larry J, Ronis, Martin J J, Hakkak, Reza, Badger, Thomas M, Lumpkin, Jr, Charles K
Format:	Journal Article
Language:	English
Published:	United States 01-06-2002
Subjects:	Alcoholism - pathology Alcoholism - physiopathology Animals Bone and Bones - drug effects Bone and Bones - pathology Bone and Bones - physiopathology Bone Density - drug effects Bone Density - physiology Bone Development - drug effects Bone Development - physiology Central Nervous System Depressants - administration & dosage Disease Models, Animal Drug Administration Schedule Ethanol - administration & dosage Intubation, Gastrointestinal - methods Male Osteogenesis - drug effects Osteogenesis - physiology Parenteral Nutrition, Total - methods Rats Rats, Sprague-Dawley
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	0022-3565
DOI:	10.1124/jpet.301.3.1132