Calciferols vitamin rickets

The term vitamin D is used for a range of compounds which possess the property of preventing or curing rickets. They include ergocalciferol (calciferol, vitamin D ), chole-calciferol (vitamin Dg), dihydrotachysterol, alfacalcidol (la-hydroxycholecalciferol) and calcitriol (1,25-dihydroxycholecalciferol). 

The effects of the steroid hormone calcitriol (see p. 330) in bone are complex. On the one hand, it promotes bone formation by stimulating osteoblast differentiation (top). This is particularly important in small children, in whom calcitriol deficiency can lead to mineralization disturbances (rickets see p.364). On the other hand, calcitriol increases blood Ca "" levels through increased Ca "" mobilization from bone. An overdose of vitamin D (chole-calciferol), the precursor of calcitriol, can therefore have unfavorable effects on the skeleton similar to those of vitamin deficiency (hypervitaminosis see p.364). 

Vitamin D (cholecalciferol ergocalciferol) has its active form as 1,25-dihydroxylchole-calciferol. It is responsible for calcium uptake, and a deficiency of the vitamin results in rickets (in children) and osteomalacia (in adults). The symptoms of both syndromes are soft, pliable bones. High levels of vitamin D are toxic. 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

In 1918, Mellanby produced experimental rickets in dogs. In 1919, Huldschinsky ameliorated rachitic symptoms in children with ultraviolet radiation. Hess, in 1922, showed that liver oils contain the same antirachitic factor as sunlight In that same year, McCollum increased calcium deposition in rachitic rats with cod liver oil factor. In 1924. Steenbook and Hess demonstrated irradiated foods have antirachitic properties, It was in 1925 that McCollum named antirachitic factor as vitamin D. In 1931, Angus isolated crystalline vitamin D (calciferol). In 1936, Windaus isolated vitamin D3 (activated 7-dehydrocholesterol). 

Vitamin D analogs Calcifediol (Calderol) Calcitriol (Rocaltrol) Dihydrotachysterol (DHT, Hytakerol) Ergocalciferol (Calciferol, Drisdol) Generally enhance bone formation by increasing the absorption and retention of calcium and phosphate in the body useful in treating disorders caused by vitamin D deficiency, including hypocalcemia, hypophosphatemia, rickets, and osteomalacia... 

Vitamin D [calciferol) Men women 5-15 pg/d Maintain serum calcium and phosphorus concentrations prevents rickets Hypercalcemia secondary to elevated vitamin D metabolites in plasma... 

Calcidiol la-hydroxylase is not restricted to the kidney, but is also found in placenta, bone cells (in culture), mammary glands, and keratinocytes. The placental enzyme makes a significant contribution to fetal calcitriol, but it is not clear whether the calcidiol 1-hydroxylase activity of other tissues is physiologically significant or not. Acutely nephrectomized animals given a single dose of calcidiol do not form any detectable calcitriol, but there is some formation of calcitriol in anephric patients, which increases on the administration of cholecalciferol or calcidiol. However, thus extrarenal synthesis is not adequate to meet requirements, so that osteomalacia develops in renal failure (Section 3.4.1). The enzyme is inhibited, or possibly repressed, by strontium ions this is the basis of strontium-induced vitamin D-resistant rickets, which responds to the administration of calcitriol or la-hydroxycalciol, but not calciferol or calcidiol (Omdahl and DeLuca, 1971). 

Chemistry of Vitamin D 341 Formula of Calciferol 341 Metabolism and Mode of Action 343 Rickets 345... 

A fat-soluble factor that counteracts the disturbance in bone development called rickets was separated from fat-soluble A by McCollum in 1922. Ultraviolet irradiation was soon found to produce antirachitic activity. Several substances are now known to have vitamin D activity, and structures have been ascertained for the more important ones. Calciferol or vitamin Ds is the principal one obtained by irradiation, while vitamin Da is the naturally occurring activated 7-dehydro-cholesterol. 

Vitamin D Standard and Begnirements.— The international standard adopted by the I eague of Nations (1931) is the biological activity of 1 mg. of a standard solution of calciferol in oil. This quantity given daily to a young rat rendered rachitic by a diet free from vitamin D will produce in eight days a characteristic band of calcium deposits in the metaphyses of the long bones. One gm. of crystalline calciferol is equivalent to more than 40,000 international units. The daily requirements of vitamin D needed to prevent or cure mild rickets in children is about 3,000 units, in the form of calciferol, or 1,000 units in the form of liver oil (vitamin Dj). 

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