Vitamin D Deficiency-Rickets and Osteomalacia

Rickets is a disease of young children and adolescents, resulting from a failure of the mineralization of newly formed bone. In infants, epiphyseal cartilage continues to grow, but is not replaced by bone matrix and mineral. The earliest 

Rickets was more or less eradicated as a nutritional deficiency disease dur-ingthe 1950s, as aresultofwidespread enrichment ofinfantfoods with vitamin D. The level of supplementation was reduced as a result of the development of hypercalcemia caused by vitamin D intoxication (Section 3.6.1) in a small number of especially susceptible infants. As a result, rickets has reemerged, especially in northern cities in temperate countries. 

Osteomalacia is the defective remineralization of bone during normal bone turnover in adults, so that there is a progressive demineralization, but with adequate bone matrix, leading to bone pain and skeletal deformities, with muscle weakness. Women with inadequate vitamin D status are especially at risk of osteomalacia after repeated pregnancies, as a result of the considerable drain on calcium reserves for fetal bone mineralization and lactation. 

Elderly people are at risk of osteomalacia, because of both decreased synthesis of 7-dehydrocholesterol in the skin with increasing age and low exposure to sunlight. Plasma concentrations of calcidiol below 10 nmol per L are commonly seen in people over 75 years of age, not rising above 20 nmol per L at any time of the year. Histologically proven osteomalacia is observed in 2% to 5% of elderly people presenting to the hospital in Britain. 

Rickets was more or less eradicated as a nutritional deficiency disease during the 1950s, as a result of widespread enrichment of infant foods with vitamin 

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Vitamin D deficiency rickets, and osteomalacia tend to arise in several conditions or environments, as listed hereunder. Generally the combined lack of sunlight and dietary deficiency must exist before any sign of the deficiency arises. 

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... 

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. 

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 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. 

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. 

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. 

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 is derived via cholesterol in a series of reactions, one of which requires the action of UV light to break the bond between two carbon atoms. Deficiency of vitamin D causes rickets in children and osteomalacia in adults. 

Vitamin D deficiency remains the most common cause of rickets and osteomalacia in the world, with the exception of the United States and the Scandinavian countries where most dairy products are supplemented with this vitamin. This deficiency can be caused either by dietary habits or by insufficient exposure to ultraviolet light. The same type of symptoms can be observed when there is interruption of the normal vitamin D metabolic pathways due to a number of liver and/or kidney diseases. In addition, a number of inherited factors can lead to different types of vitamin D resistance which require massive supplements of vitamin D and/or minerals. Extensive reviews have been published depicting both the clinical features and their most likely causes, as well as the possible treatments of the different types of clinical disorders resulting from vitamin D deficiencies [113-117], The newly defined role for l,25(OH)2D3 upon the hematopoietic system could also have clinical relevance in bone disorders such as osteoporosis where patients have been shown to possess abnormal T-cell subsets [118]. 

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. Metabolically active vitamin D hormone results from two successive hydroxylations in the liver at position 25 (- calcifediol) and in the kidney at position 1 (- calcitriol = vitamin D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca2+ and phosphate. Vitamin D hormone promotes enteral absorption and renal reabsorption of Ca2+ and phosphate. As a result of the increased Ca2+ 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 vitamin D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic use aims at replacement. Mostly, vitamin D is given in liver disease, calcifediol may be indi-... 

Cystic fibrosis patients are usually advised to take more than the recommended daily amounts of these vitamins in order to prevent deficiency. A common problem associated with poor absorption of fat-soluble vitamins is deficiency of vitamin K. Vitamin K is required by the liver to produce many blood coagulation factors. Part of the problem for cystic fibrosis patients is their chronic antibiotic therapy, which decreases the bacterial population of the colon colonic bacteria synthesize vitamin K. Vitamin K deficiency leads to prolonged blood-clotting time. Vitamin D deficiency could cause rickets in a child or osteomalacia in adults. Vitamin A deficiency leads to night blindness, skin and other ocular defects. 

The main symptom of vitamin D deficiency in children is rickets and in adults is osteomalacia. 

The definition of vitamin D deficiency is a condition where the concentration of 25-hydroxyvitamin D3 in the blood serum occurs at 12 ng/ml or less. Prolonged deficiency can result in two diseases, namely rickets (in children) and osteomalacia (in adults). Mtamin D deficiency tends to occur in those who do not get enough exposure to srmlight and who also fail to eat foods that are rich in vitamin D. In an ideal world, where everyone was regularly exposed to sunshine, vitamin D would never be classified as a vitamin. 

Vitamin D deficiency results in rickets in infants and children as a result of inadequate calcification of bones. In adults, osteomalacia most often occurs during pregnancy and lactation. Rickets is rare in the United States because of fortification of foods. Deficiencies in the elderly, however, result from underexposure to. sunlight. 

Acute symptomatic hypocalcemia may be seen in hospitalized patients for various reasons. Rapid remineralization of bone after surgery for primary hyperparathyroidism (hungry bone syndrome), treatment for hyperthyroidism, or treatment for hematological malignancy may result in hypocalcemia. Acute hemorrhagic or edematous pancreatitis is frequently complicated by hypocalcemia. Vitamin D deficiency may also be associated with hypocalcemia because of impaired intestinal absorption of calcium and skeletal resistance to PTH. Osteomalacia and rickets are discussed in a later section of this chapter. 

Osteomalacia and rickets are caused by a mineralization defect during bone formation, resulting in an increase in osteoid, the unmineralized organic matrix of bone. Defective mineralization produces rickets in children and osteomalacia in adults. Osteomalacia or rickets is usually due to either vitamin D deficiency or phosphate depletion. 

Laboratory findings in rickets and osteomalacia include an increased serum ALP, with other alterations in bone and mineral metabolism dependent on the cause and severity of the disorder. ALP is usually increased because of the increased osteoblastic activity associated with producing unmineralized osteoid. Calcium may be low-normal or low in vitamin D deficiency depending on the severity of the disease. Phosphate may be normal or low, but falls with the development of secondary hyperparathyroidism. The serum calcium and PTH concentrations are usually normal in renal tubular defects of phosphate transport. Vitamin D nutrition may be assessed by the determination of serum 25(OH)D. Renal phosphate defects can be best assessed by determination of the renal phosphate threshold. 

Low-turnover bone diseases include osteomalacia and adynamic (also known as aplastic) bone diseases. Osteomalacia and adynamic bone disease are distinguished by the extent of unmineralized bone matrix or osteoid osteoid is increased in osteomalacia and normal or low in adynamic bone disease. Osteomalacia in chronic renal failure may reflect vitamin D deficiency because of the decreased renal synthesis of l,25(OH)2D (see Osteomalacia and Rickets) or aluminum-related disease. In the 1970s and 1980s, aluminum intoxication was a significant contributing factor to the development of osteomalacia and adynamic bone... 

Osteomalacia—the adult form of rickets—is another calcium deficiency disease. Instead of making bones more brittle and porous as osteoporosis does, osteomalacia makes bones more flexible, resulting in deformities and pain. The cause is usually vitamin D deficiency, and the most effective reversal is short-term use of high dosages of vitamin D, gradually reducing dosages to 400 lU (International Units) daily. This should always be done under the supervision of a doctor since vitamin D is a very potent hormone and can become toxic if improperly used. 

Vitamin D and its metabolites play an important role in the maintenance of extracellular calcium concentrations and in normal skeletal structure and mineralization. Vitamin D is necessary for the optimal absorption of calcium and phosphorus. On a worldwide basis, the most common cause of hypocalcemia is nutritional vitamin D deficiency. In malnourished populations, manifestations include rickets and osteomalacia. Nutritional vitamin D deficiency is uncommon in Western societies because of the fortification of miUc with ergocalciferol. " The most common cause of vitamin D deficiency in Western societies is gastrointestinal disease. Gastric surgery, chronic pancreatitis, small-bowel disease, intestinal resection, and bypass surgery are associated with decreased concentrations of vitamin D and its metabolites. Vitamin D replacement therapy may need to be administered by the intravenous route if poor oral bioavailability is noted. Decreased production of 1,25-dihydroxyvitamin D3 may occur as a result of a hereditary defect resulting in vitamin D-dependent rickets. It also can occur secondary to chronic renal insufficiency if there is insufficient production of the 1 -a -hydroxylase enzyme for the... 

Vitamin D deficiency may give rise to rickets and osteomalacia, with marked hyperphosphatasemia (B30, S48, S76). This problem is further discussed in Section 6.3.1. 

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