Osteomalacia deficiency

Common but usually transient side effects are lethargy, incoordination, blurred vision, higher cortical dysfunction, and drowsiness. At concentrations greater than 50 mcg/mL, phenytoin can exacerbate seizures. Chronic side effects include gingival hyperplasia, impaired cognition, hirsutism, vitamin D deficiency, osteomalacia, folic acid deficiency, carbohydrate intolerance, hypothyroidism, and peripheral neuropathy. 

Rickets, which is diagnosed by X-rays of leg bones, heals promptly with 4000 lU of oral vitamin D per day, with treatment for a month. In performing this treatment, the physician needs to monitor plasma 25 hydroxyvitamm D to make certain that they are raised to the normai range. The bone abnormalities (visible by X-ray) disappear gradually over the course of 3-9 months. Parents are instructed to take their infants outdoors for about 20 minutes per day with their faces exposed in order to prevent deficiency. Osteomalacia is treated by eating 2500 ID/day for about three months. Measurements of 25-hydroxyvitamin D, calcium, and parathyroid hormone are also part of the treatment process. 

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. 

Clinical stresses which interfere with vitamin metabohsm, can result in calcium deficiency leading to osteomalacia and osteoporosis (secondary vitamin D deficiency). These stresses include intestinal malabsorption (lack of bile salts) stomach bypass surgery obstmctive jaundice alcoholism Hver or kidney failure decreasing hydroxylation of vitamin to active forms inborn error of metabohsm and use of anticonverdiants that may lead to increased requirement. 

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. 

The nutritional experiments with carotene and fish oils led to the conclusion that a second fat-soluble compound was essential for normal rat growth. Rickets, the condition caused by vitamin D deficiency, is a disease afflicting children where, because of impaired calcification, bone formation is disturbed and the bones become bowed and otherwise deformed. In adults, especially multiparous women, vitamin D deficiency produced osteomalacia—demineralization of bone, leading to tenderness over the bones, pain, and muscle weakness. Rickets was particularly prevalent in slum areas. Glasgow, Vienna, and Lahore were notorious for the high incidence of the disease. 

The two hydroxylase enzymes can also utilize the plant-derived steroid, ergocalci-ferol, (vitamin D2) as a substrate. The final product is biologically active and so food manufacturers often fortify their products with ergocalciferol to prevent the occurrence of vitamin D deficiency and consequent rickets in childhood or osteomalacia in adults. 

Vitamin D deficiency after epiphyseal fusion causes osteomalacia, which produces less deformity than rickets. Osteomalacia may present as bone pain and muscle weakness. 

A clear lack of adequate vitamin D in childhood results in the disease rickets, characterized by deformed bones and stunted growth. Extracellular calcium levels are too low to permit normal bone mineralization. A related disease, osteomalacia, occurs in adults deficient in vitamin D. Osteomalacia is characterized by weakened bones and bone pain as a result of insufficient mineralization. 

The small family of molecules known as vitamin D is essential for bone health and other aspects of human well-being. Rickets and osteomalacia are vitamin D deficiency diseases. 

Light increases the concentration of a specific Ca " ion transport protein in the enterocytes of small intestine to increase ion uptake. This increases the Ca " ion concentration in the plasma which is required for mineralisation of bone. A deficiency of the vitamin/hormone results in osteomalacia (i.e. a deficiency of mineral in the bone), also known as rickets in children. The growth of the skeleton and the role of vitamin D is discussed in Appendix 15.2. 

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

Abuse/Dependency Chronic use of laxatives, particularly stimulants, may lead to laxative dependency, which in turn may result in fluid and electrolyte imbalances, steatorrhea, osteomalacia, vitamin and mineral deficiencies, and a poorly functioning colon. Also known as laxative abuse syndrome (LAS), it is difficult to diagnose. Cathartic colon Cathartic colon, a poorly functioning colon, results from the chronic abuse of stimulant cathartics. 

The pharmacotherapeutic uses of vitamin D include vitamin D deficiencies, rickets in children and osteomalacia in adults, and renal osteodystrophy in patients with chronic renal failure. For metabolic rickets in patients with a deficiency of... 

Cholecalciferol (D3) and its active form 1,25-di-hydroxycholecalciferol are only to a certain extend vitamins because they can be synthesized by the human body. However deficiencies resulting in rickets in children and osteomalacia in adults do exist. Cholecalciferol can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. Plants synthesize ergosterol, which is converted to vitamin D2 (ergocalciferol) by ultraviolet light. Vitamin D2 may be less active in humans. Vitamin D promotes uptake of calcium and phosphate in the intestine and it stimulates osteoclasts to break down hydroxyapatite and release calcium into blood. Vitamin D is discussed in more detail in Chapter 24, Section V.a. 

Osteomalacia is the condition in which bone becomes demineralised due to deficiency of vitamin D. In this condition parathyroid hormone (PTH) acts on the bone to maintain serum calcium, resulting in demineralisation. Serum calcium is usually normal or slightly low alkaline phosphatase levels are high, reflecting excessive osteoblast activity, and serum phosphate falls as an effect of PTH on the kidney. The same condition in children results in defects in long bone formation, and is termed rickets. 

Calcium Multiple physiologic actions through regulation of multiple enzymatic pathways Strontium suppresses bone resorption and increases bone formation, calcium and phosphate required for bone mineralization Osteoporosis, osteomalacia, deficiencies in calcium or phosphate Ectopic calcification... 

Bowed legs of middle-aged man with osteomalacia, a nutritional vitamin D deficiency which results in malformation of the skeleton. 

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). 

Vitamin D deficiency (also calcium deficiency) produces a condition known in children as rickets and in adults as osteomalacia. The bones and teeth of children with rickets are poorly formed and soft. A child with rickets frequently has malformed limbs, especially bowlegs. Blood dotting may be impaired, and. in extreme cases, there may be disturbances of the nervous system. An improvement in the level of calcium in the diet, along with vitamin D or parathyroid extract when required, brings about a hardening of the bones, but leaves them misshapen if deformity has already occurred. 

Certain human populations depend on dietary sources of vitamin D because of insufficient biosynthesis of the vitamin due to inadequate skin exposure to sunlight. The classic symptoms of vitamin D deficiency are rickets in children and osteomalacia in adults. 25-Hydroxyvitamin D3 is the major circulating metabolite in the blood, but the hormonally active form of the vitamin is 1,25-dihydroxyvitamin D3. The latter metabolite stimulates the intestine to absorb calcium and phosphate by two independent mechanisms and acts with parathyroid hormone to mobilize calcium, accompanied by phosphate, from the bone fluid compartment into the bloodstream. 1,25-dihydroxyvitamin D 3 is also involved in the formation of osteoclasts—giant cells that are solely responsible for the resorption of bone matrix (33). Resorption is an essential process for the development, growth, maintenance, and repair of bone. 

Calcium deficiency in blood plasma causes muscle cramps, twitching and eventually convulsions. If the blood calcium level falls, calcium is leached from the bones, causing osteomalacia. A group of cardioactive drugs known as the Ca antagonists block influx of Ca2+ into infarcted, dying heart muscle cells following myocardial infarction.55,80... 

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... 

Symptoms of deficiency include weak bones, leading to rickets in children and osteomalacia in adults. 

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