Gastrointestinal and hepatic disorders constitute a substantial proportion of the patient population with vitamin D deficiency-related metabolic bone disease in this country. Despite major advances in our understanding of vitamin D metabolism, the diagnosis and treatment of vitamin D deficiency and osteomalacia in patients with gastrointestinal and liver disease has received small attention. To arrive at appropriate decisions regarding prevention and treatment, a detailed understanding of the pathogenesis of vitamin D deficiency in these conditions is required. We will use bile fistula rats in vitamin D deficient and vitamin D replete states to further delineate events in the hepatic metabolism, enterohepatic circulation and conservation of the vitamin D pool. Detailed studies of the efficiency and mechanism of intestinal absorption of 25-hydroxyvitamin D, and 1, 25-dihydroxy D as candidate therapeutic agents will be performed in bile fistula and lymph fistula rats. In turn, clinical studies of the pathogenesis of vitamin D deficiency in primary biliary cirrhosis and in Crohn's disease, as models of cholestatic and malabsorptive diseases, will assess hepatic 25-hydroxylation, enterohepatic circulation and turnover of vitamin D. Assays of serum 25-OH and 1,25(OH)2 vitamin D, quantitative histomorphometric analyses of iliac cress bone biospies, calcium absorption tests and clinical parameters will be employed to characterize vitamin D deficiency and to monitor the therapeutic doses of vitamin D or metabolites in patients with osteomalacia complicating intestinal or hepatic disease.