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.
Footnotes
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This study was supported by National Institutes of Health Grants AA-12223 and AA-08645.
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E.C.B. and D.S.P. are co-first authors.
- Abbreviations:
- TEN
- total enteral nutrition
- DO
- distraction osteogenesis
- EtOH
- ethanol
- UEC
- urinary ethanol content
- NBF
- neutral buffered formalin
- BMD
- volumetric bone mineral density
- pQCT
- peripheral quantitative computed tomography
- Received January 17, 2002.
- Accepted February 26, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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