This proposal attempts to elucidate certain aspects of pathogenetic mechanisms for various bone diesease, by a careful examination of the interrelationships between vitamin D, parathyroid status, and calcium metabolism. In diabetes mellitus, a search will be made for the occurrence of renal hypercalciuria and secondary hyperparathyroidism (associated with glycosuria) and reduced intestinal calcium absorption (associated with low 1,25-dihydroxycholecalciferol synthesis). In postmenopausal osteoporosis, the subgroup with renal hypercalciuria will be identified, and the response to thiazide and 25-hydroxycholecalciferol assessed. The abnormal vitamin D metabolism, characterizing various vitamin D-resistant states, will be examined. The hypothesis that an impaired synthesis of 1,25-dihydroxycholecalciferol plays an essential pathogenetic role in pseudohypoparathyroidism will be tested by a careful examination of PTH responsiveness with respect to the production of various vitamin D metabolites, and changes in serum calcium and in intestinal calcium absorption. The possibility that 25-hydroxycholecalciferol is itself capable of increasing the circulating concentration of 24,25-dihydroxycholecalciferol and 1,25-dihydroxycholecalciferol will be tested. Finally, the effect of growth hormone, estrogen, and prolactin on vitamin D metabolism will be evaluated.