Vitamin D: the discovery of its metabolites and their therapeutic applications. 1976

M G Beale, and J C Chan, and S B Oldham, and H F Deluca

Our understanding of the role of vitamin D in calcium-phosphorus metabolism has changed considerably in the last decade. Studies performed in tissue culture, animal, and man have firmly established that the natural compound requires hydroxylation in the liver at the C-25 position and in the kidney at the C-1 position to form the biologically active derivative 1,25-(OH)2D3. These hydroxylation reactions are finely regulated to maintain normal calcium-phosphorus homeostasis: We now regard 1,25-(OH)2D3 as a hormone which is released by the kidney during periods of hypocalcemia. This hormone acts on the intestinal mucosa to facilitate calcium absorption and on bone to increase calcium mobilization. Its function in other tissues is still being evaluated. The active metabolites of vitamin D and several closely related analogs have been synthesized. It has been clearly demonstrated that 1,25-(OH)2D3 and 1alpha-OH-D3 promote healing in uremic bone disease. Administration of small amounts of these compounds has corrected the biochemical disturbances in vitamin D-dependency and hypoparathyroidism. Limited clinical experience with 25-OH-D3 and 1,25-(OH)2D3 in children with familial hypophosphatemia has failed to show convincing evidence of a therapeutic effect. Further clinical studies are needed to fully evaluate the therapeutic potential of this new family of compounds.

UI MeSH Term Description Entries
D007011 Hypoparathyroidism A condition caused by a deficiency of PARATHYROID HORMONE (or PTH). It is characterized by HYPOCALCEMIA and hyperphosphatemia. Hypocalcemia leads to TETANY. The acquired form is due to removal or injuries to the PARATHYROID GLANDS. The congenital form is due to mutations of genes, such as TBX1; (see DIGEORGE SYNDROME); CASR encoding CALCIUM-SENSING RECEPTOR; or PTH encoding parathyroid hormone. Idiopathic Hypoparathyroidism,Hypoparathyroidism, Idiopathic
D007015 Hypophosphatemia, Familial An inherited condition of abnormally low serum levels of PHOSPHATES (below 1 mg/liter) which can occur in a number of genetic diseases with defective reabsorption of inorganic phosphorus by the PROXIMAL RENAL TUBULES. This leads to phosphaturia, HYPOPHOSPHATEMIA, and disturbances of cellular and organ functions such as those in X-LINKED HYPOPHOSPHATEMIC RICKETS; OSTEOMALACIA; and FANCONI SYNDROME. Diabetes, Phosphate,Familial Hypophosphatemia,Hyperphosphaturia,Phosphate Diabetes,Phosphaturia,Familial Hypophosphatemias,Hypophosphatemias, Familial
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
D010758 Phosphorus A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions. Black Phosphorus,Phosphorus-31,Red Phosphorus,White Phosphorus,Yellow Phosphorus,Phosphorus 31,Phosphorus, Black,Phosphorus, Red,Phosphorus, White,Phosphorus, Yellow
D011547 Pseudohypoparathyroidism A hereditary syndrome clinically similar to HYPOPARATHYROIDISM. It is characterized by HYPOCALCEMIA; HYPERPHOSPHATEMIA; and associated skeletal development impairment and caused by failure of response to PARATHYROID HORMONE rather than deficiencies. A severe form with resistance to multiple hormones is referred to as Type 1a and is associated with maternal mutant allele of the ALPHA CHAIN OF STIMULATORY G PROTEIN. Albright Hereditary Osteodystrophy,PHPIa,Albright Hereditary Osteodystrophy with Multiple Hormone Resistance,PHD Ib,PHD1b,PHP Ia,Pseudohypoparathyroidism Type 1B,Pseudohypoparathyroidism, Type Ia,Pseudohypoparathyroidism, Type Ib,Hereditary Osteodystrophy, Albright,Osteodystrophy, Albright Hereditary,Pseudohypoparathyroidism Type 1Bs,Pseudohypoparathyroidisms,Pseudohypoparathyroidisms, Type Ia,Pseudohypoparathyroidisms, Type Ib,Type Ia Pseudohypoparathyroidism,Type Ia Pseudohypoparathyroidisms,Type Ib Pseudohypoparathyroidism,Type Ib Pseudohypoparathyroidisms
D012080 Chronic Kidney Disease-Mineral and Bone Disorder Decalcification of bone or abnormal bone development due to chronic KIDNEY DISEASES, in which 1,25-DIHYDROXYVITAMIN D3 synthesis by the kidneys is impaired, leading to reduced negative feedback on PARATHYROID HORMONE. The resulting SECONDARY HYPERPARATHYROIDISM eventually leads to bone disorders. Renal Osteodystrophy,Renal Rickets,Rickets, Renal,CKD-MBD,Osteodystrophy, Renal,Chronic Kidney Disease Mineral and Bone Disorder,Osteodystrophies, Renal,Renal Osteodystrophies
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D004100 Dihydroxycholecalciferols Cholecalciferols substituted with two hydroxy groups in any position. Dihydroxyvitamins D
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders

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