New vitamin D analogs. 2003

Eduardo Slatopolsky, and Jane Finch, and Alex Brown
Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. Eslatopo@im.wustl.edu

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.

UI MeSH Term Description Entries
D006962 Hyperparathyroidism, Secondary Abnormally elevated PARATHYROID HORMONE secretion as a response to HYPOCALCEMIA. It is caused by chronic KIDNEY FAILURE or other abnormalities in the controls of bone and mineral metabolism, leading to various BONE DISEASES, such as RENAL OSTEODYSTROPHY. Secondary Hyperparathyroidism,Hyperparathyroidisms, Secondary,Secondary Hyperparathyroidisms
D007676 Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION. ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D010280 Parathyroid Glands Two pairs of small oval-shaped glands located in the front and the base of the NECK and adjacent to the two lobes of THYROID GLAND. They secrete PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body. Gland, Parathyroid,Glands, Parathyroid,Parathyroid Gland
D010281 Parathyroid Hormone A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates. Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014807 Vitamin D A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.

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