New vitamin D analogs.
BACKGROUND
1,25-(OH)2D3 (calcitriol) controls parathyroid gland growth and suppresses the synthesis and secretion of parathyroid hormone. Because of this, 1,25-(OH)2D3 has been used successfully for the treatment of secondary hyperparathyroidism, which almost always accompanies renal failure. However, the potent effect of 1,25-(OH)2D3 on intestinal calcium and phosphorus absorption and bone mineral mobilization often leads to the development of hypercalcemia and hyperphosphatemia precluding 1,25-(OH)2D3 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)2D2 and 1,alpha(OH)D2, 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 D3.


RESULTS
All four analogs suppressed PTH, but had less calcemic and phosphatemic activity than 1,25-(OH)2D3. In rats, 19-nor-1,25-(OH)2D2 has been shown to be less calcemic and phosphatemic compared to 1,alpha(OH)D2.


CONCLUSIONS
Therapeutic doses of 19-nor-1,25-(OH)2D2 could produce a lower Ca x P product compared to 1,alpha(OH)D2, 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.
Slatopolsky
Eduardo
E
Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. Eslatopo@im.wustl.edu
Finch
Jane
J
Brown
Alex
A
D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications; D010280:Parathyroid Glands / Q000187:drug effects / Q000473:pathology; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
D010281:Parathyroid Hormone; D014807:Vitamin D