Rickets

Spectroscopic analysis of the lipids and sterols yielding vitamin D activity under the influence of ultraviolet irradiation provided useful clues for detecting the active sterols. A preparation acquiring vitamin D activity manifests characteristic absorption spectra not observed in sterols (such as pure cholesterol) that can- 

Animal and plant tissues contain several provitamin D s (see Fig. 5-3). They all are composed of a steroid ring substituted by a hydroxyl on carbon 3, a methyl on carbons 18 and 19, and a side chain on carbon 17. All provitamin D s have the same steroid derivative 3(j8)-hydroxy-zl-5,7-steroid. Ergosterol was the first provitamin the structure of which was elucidated. It carries an extended side chain on carbon 17 as indicated by the formula, and the configuration of the side chain of ergosterol has been established by studies with the aid of X-ray crystallography. All other provitamins have a different side chain. There is no vitamin Di because the compound originally referred to as vitamin was found to be vitamin D2. 

Irradiation of the provitamin with moderate doses of ultraviolet light yields a mixture of compounds from which pure active vitamins can be isolated. In the active product, the jS-ring has been opened between carbons 

10 and 19 positions. The other compounds formed during irradiation— luminosterol, tachysterol, precalciferol— were at first thought to be intermediates between the provitamin with its intact steroid ring and the active vitamin with the open ring (see Fig. 5-4). 

However, it is now accepted that luminosterol and tachysterol arise from a side reaction. Excessive irradiation of the provitamin leads to the formation of toxic compounds, which in the case of ergosterol are toxisterol 2, supersterol 2-1, and suprasterol 2-2. The exact structure of these compounds is not known. 

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Vitamin Dj has m.p. 115-117°C and D, m.p. 82 83 "C. Both vitamins, which have almost identical actions, are used for the prevention and cure of infantile rickets they are essential for the normal development of teeth, and are used for treating osteomalacia and dental caries. They are necessary for the absorption of Ca and P from the gut. 

Our word vitamin was coined m 1912 m the belief that the substances present m the diet that prevented scurvy pellagra beriberi rickets and other diseases were vital amines In many cases that belief was confirmed certain vitamins did prove to be amines In many other cases however vitamins were not amines Nevertheless the name vitamin entered our language and stands as a reminder that early chemists recognized the crucial place occupied by amines m biological processes... 

Vitamin D3 is a key compound m the process by which Ca " is absorbed from the mtes tine Low levels of vitamin D3 lead to Ca " concentrations m the body that are msuffi cient to support proper bone growth resulting m the bone disease called rickets... 

Other Calcium Disorders. In addition to hypocalcemia, tremors, osteoporosis, and muscle spasms (tetary), calcium deficiency can lead to rickets, osteomalacia, and possibly heart disease. These, as well as Paget s disease, can also result from faulty utilization of calcium. Calcium excess can lead to excess secretion of calcitonin, possible calcification of soft tissues, and kidney stones when combined with magnesium deficiency. 

Phosphorus Disorders. Phosphoms nutrient deficiency can lead to rickets, osteomalacia, and osteoporosis, whereas an excess can produce hypocalcemia. Faulty utilisation of phosphoms results in rickets, osteomalacia, osteoporosis, and Paget s disease, and renal or vitamin D-resistant rickets. 

Vitamin D [1406-12-2] is a material that is formed ia the skin of animals upon kradiation by sunlight and serves as a precursor for metaboUtes that control the animal s calcium homeostasis and act ki other hormonal functions. A deficiency of vitamin D can cause rickets, as weU as other disease states. This tendency can be a problem wherever animals, including humans, especially kifants and children, receive an kiadequate amount of sunshine. The latter phenomenon became prevalent with the advent of the kidustrial revolution, and efforts to cute rickets resulted ki the development of commercial sources of vitamin D for supplementation of the diet of Hvestock, pets, and humans. 

In 1919, Huldschinski (8) realized that uv light cured rickets and impacted on its etiology. The uv light and codHver oil were found to be usehil in the treatment of the disease, and irradiation of food produced the same effect as irradiation of the animal. The link between irradiation and plant materials led to the conclusion that ergosterol was an antirachitic substance, and an extensive effort was made to characterize the chemistry of irradiated ergosterol. 

Chronic renal disease Hypophosphatemic vitamin D-resistant rickets Vitamin D-dependent rickets... 

Historically, rickets prevention or cure was used to evaluate adequate vitamin nutrient levels. More recendy, in the absence of uv light, Edwards (216) found different vitamin levels were required for the optimisa tion of the various effects of vitamin in poultry, ie, 275 lU/kg for growth, 503... 

Disease States. Rickets is the most common disease associated with vitamin D deficiency. Many other disease states have been shown to be related to vitamin D. These can iavolve a lack of the vitamin, deficient synthesis of the metaboUtes from the vitamin, deficient control mechanisms, or defective organ receptors. The control of calcium and phosphoms is essential ia the maintenance of normal cellular biochemistry, eg, muscle contraction, nerve conduction, and enzyme function. The vitamin D metaboUtes also have a function ia cell proliferation. They iateract with other factors and receptors to regulate gene transcription. 

Vitamin D is a family of closely related molecules that prevent rickets, a childhood disease characterized by inadequate intestinal absorption and kidney reabsorption of calcium and phosphate. These inadequacies eventually lead to the demineralization of bones. The symptoms of rickets include bowlegs,... 

One of the triumphs of the science of nutrition is the careful investigation that linked childhood rickets with vitamin D deficiency. This work, which led to methods for treating the disease, is too familiar to need repetition. A direct consequence of these efforts was the elucidation of the pivotal role played by vitamin D in calcium metabolism, as well as the structural studies that revealed that this compound (102) is in fact a steroid derivative. The past... 

D Calciferol Maintenance of calcium balance enhances intestinal absorption of Ca and mobilizes bone mineral Rickets = poor mineralization of bone osteomalacia = bone demineralization... 

Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source. Only when sunlight is inadequate is a dietary source required. The main function of vitamin D is in the regulation of calcium absorption and homeostasis most of its actions are mediated by way of nuclear receptors that regulate gene expression. Deficiency—leading to rickets in children and osteomalacia in adults—continues to be a problem in northern latitudes, where sunlight exposure is poor. 

In the vitamin D deficiency disease rickets, the bones of children are undermineralized as a result of poor absorption of calcium. Similar problems occur in adolescents who are deficient during their growth spurt. Osteomalacia in adults results from demineralization of bone in women who have little exposure to sunlight, often after several pregnancies. Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is little evidence that it is beneficial in treating osteoporosis. 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

The basic clinical tool used at the present time Is the competitive ligand binding assay for 25-OH-D. Although concentrations are low In the serum of patients with osteomalacia and v . tamln D deficiency rickets, we have recently noted the Interesting paradox that levels can be only 1/2 normal In the face of oyert bone disease (32). This had led us to propose that substrate levels of 25-OH-D3 available to the hydroxylase In kidney which Is responsible for the conversion of 25-OH-D3 to the tissue active metabolite, l,25(OH)2D3, may be rate limiting for this enzyme. 

Chisolm JJ Jr, Harrison HC, Eberlein WR, et al. 1955. Aminoaciduria, hypophosphatemia, and rickets in lead poisoning Study of a case. Am J Dis Child 89 159-168. 

Vitamin D receptor (VDR) 1,25 dihydroxyvitamin-D3 Vitamin D response in patients affected with rickets (96) Susceptibility to osteoporosis (97) and autosomal dominant rickets disease (96)... 

Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest 1997 99[2] 297-304. 

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