The overall goal of this project is to identify mechanisms by which ethanol produces bone changes in rats with physical dependence on ethanol. We will study the toxic effects of ethanol on rats consuming an ethanol-containing liquid diet as the only source of water and food intake. With this rat model we have previous shown some bone abnormalities. Similarities and differences of the changes in bone in the ethanol-treated rats to the well known bone changes seen in alcoholic humans will be identified. The investigation will then focus on major nutritional and hormonal factors that may be involved either directly or indirectly in the development of the bone change and their beneficial effects in the recovery of the bone defects. These nutritional and hormonal factors include calcium, phosphorus, vitamin D, parathyroid hormone, calcitonin, and sex hormones. Removal of specific endocrine organs and selective replacement therapy will identify factors that enhance, restrict, or prevent the development of alcohol-induced bone changes. In other experiments dietary restriction and supplementation of the intake of calcium, phosphorus, and vitamin D will provide information as to the usefullness of these factors in restricting the development of the bone changes and in enhancing the recovery of bone after ceasing alcohol consumption. The methods to be employed include analysis of calcium, phosphorus, and magnesium in serum and bone ash, determining concentrations of blood ethanol, immunoassays of calcitonin, parathyroid hormone, vitamin D metabolites, and sex hormones. Bone mineral content, mechanical strength, and morphology will also be assessed by accepted procedures. The results of these experiments should provide information that will be useful in future studies on humans, especially in developing rational approaches to the prevention and treatment of bone disorders that occur in alcoholics.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006872-02
Application #
3110285
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Peng, T C; Lian, J B; Hirsch, P F et al. (1991) Lower serum osteocalcin in ethanol-fed rats. J Bone Miner Res 6:107-15
Kusy, R P; Hirsch, P F; Peng, T C (1989) Influence of ethanol on stiffness, toughness, and ductility of femurs of rats. Alcohol Clin Exp Res 13:185-9
Peng, T C; Kusy, R P; Hirsch, P F et al. (1988) Ethanol-induced changes in morphology and strength of femurs of rats. Alcohol Clin Exp Res 12:655-9
Peng, T C; Garner, S C; Kusy, R P et al. (1988) Effect of number of suckling pups and dietary calcium on bone mineral content and mechanical properties of femurs of lactating rats. Bone Miner 3:293-304