Osteomalacia calcium

In an attempt to compensate for the acidosis, bone salts are mobilized. Unless the patient is treated with alkalies, bone salt mobilization results in osteomalacia. Calcium is excreted in the urine, and the combination of high calcium levels, high pH, and low citrate concentration in the tubular fluid facilitates precipitation of calcium salts, thus leading to nephrocalcinosis. Secondary hyperparathyroidism develops as a consequence of the negative calcium balance. The inability to concentrate urine and the accompanying polyuria result in part from the hypokalemia and in part from the hypercalciuria. 

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. 

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. 

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. 

Aluminium toxicity is the likely cause of three human disorders arising from long-term haemodialysis vitamin D-resistant osteomalacia, iron adequate microcytic anaemia, and dialysis dementia (Martin, 1994). The first of these conditions is consistent with interference with calcium deposition into bone, and the accumulation of aluminium in the bone matrix. 

The GP made a provisional diagnosis of osteomalacia and prescribed vitamin D supplements. Vitamin D measurements are not performed routinely, but the assumption is that a low result would have been obtained on the blood sample. Most of the vitamin D necessary to maintain normal calcium homeostasis is derived from endogenous synthesis by reactions in the skin (which require UV radiation from sunlight), liver and kidney. The cultural habits of Mrs Al-Ameri required her to dress in a burqah and niqab whenever she left the home, meaning that very little of her skin was exposed to daylight. 

There are numerous metabolic diseases, infantile and other tetanies, steatorrhea, osteomalacia, arthritis of old age, epilepsy, etc., in which calcium either is or may be implicated. Each of these diseases needs to be studied against a background of wide variability in calcium needs, probably genetically determined, and involving "normal" individuals as well as those having overt disease. 

Vitamin D is really a small family of closely related molecnles that prevent the bone disease rickets in children and osteomalacia in adnlts. In both cases, inadeqnate mineralization of bone results in bone deformation and weakness. Calcinm, Ca +, homeostasis is one goal of vitamin D activity, a goal it shares with parathyroid hormone and calcitonin. Calcium is intimately involved in bone mineralization and distnrbances of calcium levels in the blood can resnlt in inadeqnate bone mineralization or excessive calcification of other tissues. 

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. 

Osteoporosis, a condition in which bone becomes porous and weak (potentially leading to fractures), is a far more prevalent disease than osteomalacia. While modest levels of serum 25-hydroxyvitamin D will prevent osteomalacia, these levels may not be sufficient to minimize the risk of osteoporosis. Clinical studies have demonstrated that bone mineral density is directly related to serum 25-hydroxyvitamin D levels up to 40 ng/ml. It has also been demonstrated that in elderly women given unusually high doses of calcium and vitamin D3 the risk of both hip and vertebral fractures is substantially reduced. Optimizing bone health in both young and old may require higher levels of vitamin D activity than are typically achieved at recommended doses. This story will play out over time. 

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... 

Oral calcium may also be used in the treatment of osteoporosis, osteomalacia, rickets, and latent tetany. 

Calcium chloride and gluconate - A6 unct /e therapy in the treatment of insect bites or stings, such as Black Widow spider bites to relieve muscle cramping sensitivity reactions, particularly when characterized by urticaria depression due to overdosage of magnesium sulfate acute symptoms of lead colic rickets osteomalacia. 

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. 

Clinical trials have demonstrated that the use of the bisphosphonates, nasal calcitonin, or human rPTH combined with calcium and vitamin D supplementation is effective in preventing drug-induced osteoporosis. Thus, individuals receiving over the long term any medication that can induce osteomalacia should also take one of these compounds and have periodic bone density determinations. 

Contraindications Primary or secondary hyperparathyroidism, including hypercalci-uria (renal calcium leak), hypomagnesemic states (serum magnesium less than 1.5 mg/dl), bone disease (osteoporosis, osteomalacia, osteitis), hypocalcemic states (e.g., hypoparathyroidism, intestinal malabsorption), normal or low intestinal absorption and renal excretion of calcium, enteric hyperoxaluria, and patients with high fasting urinary calcium or hypophosphatemia. 

Hypoparathyroidism PO 625 mcg-5 mg/day (with calcium supplements). Nutritional rickets, osteomalacia PO 25-125 meg/day for 8-12 wk. Those with malabsorption syndrome. 250-7,500 meg/day. 

Calcium play vital role in excitation - contraction coupling in myocardium. Calcium mediates contraction in vascular and other smooth muscles. Calcium is required for exocytosis and also involved in neurotransmitters release. Calcium also help in maintaining integrity of mucosal membranes and mediating cell adhesions. Hypercalcemia may occur in hyperthyroidism, vitamin D intoxication and renal insufficiency, which can be treated by administration of calcitonin, edetate sodium, oral phosphate etc. Hypocalcemia may occur in hypothyroidism, malabsorption, osteomalacia secondary to leak of vitamin D or vitamin D resistance, pancreatitis and renal failure. Hypocalcemia can be treated by chloride, gluconate, gluceptate, lactate and carbonate salts of calcium. 

A number of gastrointestinal and hepatic diseases result in disordered calcium and phosphate homeostasis, which ultimately leads to bone disease. The bones in such patients show a combination of osteoporosis and osteomalacia. 

Cholecalciferol Regulate gene transcription via the vitamin D receptor Stimulate intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption decrease parathyroid hormone (PTH) promote innate immunity inhibit adaptive immunity Osteoporosis, osteomalacia, renal failure, malabsorption Hypercalcemia, hypercalciuria the vitamin D preparations have much longer half-life than the metabolites and analogs... 

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... 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

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). 

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