New vitamin D analogs

Background. 1,25-(OH)(2)D-3 (calcitriol) controls parathyroid gland growth and suppresses the synthesis and secretion of parathyroid hormone. Because of this, 1,25-(OH)(2)D-3 has been used successfully for the treatment of secondary hyperparathyroidism, which almost always accompanies renal failure. However, the potent effect of 1,25-(OH)(2)D-3 on intestinal calcium and phosphorus absorption and bone mineral mobilization often leads to the development of hypercalcemia and hyperphosphatemia precluding 1,25-(OH)(2)D-3 therapy. Methods. This has led to the development of vitamin D analogs that retain the suppressive action on PTH and parathyroid gland growth, but that have less calcemic and phosphatemic activity. Currently, two analogs, 19-nor-1,25-(OH)(2)D-2 and 1,alpha(OH)D-2, are being used for the treatment of secondary hyperparathyroidism in the United States, and two are being used in Japan, 22-oxa-calcitriol and 1,25-(OH)(2)-26,27F6 D-3. Results. All four analogs suppressed PTH, but had less calcemic and phosphatemic activity than 1,25-(OH)(2)D-3. In rats, 19-nor-1,25-(OH)(2)D-2 has been shown to be less calcemic and phosphatemic compared to 1,alpha(OH)D-2. Conclusion. Therapeutic doses of 19-nor-1,25-(OH)(2)D-2 could produce a lower Ca x P product compared to 1,alpha(OH)D-2, which could be an important consideration in patient treatment. Further studies are necessary to define these differences and to understand the mechanisms behind the differential actions of vitamin D analogs.