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.