Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Typical features of hereditary vitamin D-dependent (pseudovitamin D-deficient) rickets were observed beginning at ages 20 and 5 months in a brother and sister. Both had calcium malabsorption correctable with high doses of 25-hydroxyvitamin D. During periods of hypocalcemia they both manifested secondary hyperparathyroidism with hypophosphatemia and high serum concentrations of endogenously produced 1,25-dihydroxyvitamin D. In each, normalization of serum calcium concentration and resolution of osteomalacia were obtained with continuous administration of high doses of ergocalciferol or high doses of 1,25-dihydroxycholecalciferol. Chemical features of vitamin D deficiency were corrected in the presence of high circulating concentrations of 1,25-dihydroxyvitamin D2, produced endogenously, or of 1,25-dihydroxyvitamin D3, administered by mouth. Serum concentrations of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal in five first degree relatives. We conclude that in these five first degree relatives. We conclude that in these siblings, rickets and osteomalacia resulted from a hereditary decreased sensitivity to 1,25-dihydroxyvitamin D at the intestine and perhaps other vitamin D target tissues.
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PMID:A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. 23 95

Intestinal malabsorption of calcium and the development of osteomalacia in conservatively treated renal failure is explained by a quantitative deficiency of 1,25-dihydroxycholecalciferol, which also contributes to the development of hypocalcaemia. Excess of 25-hydroxycholecalciferol can substitute for this deficiency. The presence and healing of azotaemic osteomalacia is unrelated to the prevailing plasma [Ca] x [P] product. The data suggest that "vitamin D" acts directly on bone mineralisation, but the claim that this apparent effect is normally due to 25-hydroxycholecalciferol is considered unproven. Most of the phenomena of azotaemic osteodystrophy are encountered in simple vitamin D deficiency; as in that condition, deficiency of 1,25-dihydroxycholecalciferol may be of primary significance in causing secondary hyperparathyroidism in renal failure.
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PMID:Vitamin D and the syndromes of azotaemic osteodystrophy. 36 40

Oncogenic osteomalacia is a syndrome in which unexplained osteomalacia remits after resection of a coexisting mesenchymal tumor. We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 42-yr-old woman. The biochemical abnormalities were: hypophosphatemia; decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate; negative calcium and phosphorus balance; hyperaminoaciduria; and subnormal calcemic response to exogenously administered parathyroid hormone. Malabsorption, hypophosphatasia, fluorosis, and acidosis were excluded as causes of the osteomalacia. Serum 25-hydroxycholecalciferol was normal (27+/-1 ng/ml). However, the serum concentration of 1alpha,25-dihydroxycholecalciferol was low (1.6+/-0.1 ng/100 ml). Oral administration of physiological amounts of 1alpha,25-dihydroxycholecalciferol resulted in resolution of the biochemical abnormalities of the syndrome and healing of the bone pathology. We suggest that tumor-induced inhibition of 1alpha,25-dihydroxycholecalciferol synthesis caused the osteomalacia. The causal role of the tumor was proved by demonstrating that resection was accompanied by roentgenographic evidence of bone healing and maintenance of normal serum phosphorus; renal tubular maximum for the reabsorption of phosphate; calcium and phosphorus balance; aminoaciduria; and calcemic response to exogenous parathyroid hormone.
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PMID:Osteomalacia due to 1alpha,25-dihydroxycholecalciferol deficiency. Association with a giant cell tumor of bone. 90 49

Intestinal Ca2+ malabsorption has been described in spontaneously hypertensive rats (SHRs), but the molecular basis for this defect is unknown. In this study, we measured intestinal alkaline phosphatase and vitamin D-dependent Ca(2+)-binding protein (calbindin-D9k), two proteins implicated in the active pathway of intestinal Ca2+ absorption. Both proteins were measured in the small intestines of SHRs and their normotensive controls, Wistar-Kyoto rats, before, during, and after development of hypertension (4, 9, 14, 18, and 28 wk of age). At all ages, alkaline phosphatase activity in duodenum (0-6 cm) was decreased by 30-57% (P less than 0.001) and by 47-75% in the 2nd intestinal segment (6-12 cm) (P less than 0.001-0.05). Calbindin-D9k was decreased similarly. The decreases of calbindin were statistically significant (P less than 0.001-0.05) in the duodena at 4, 14, 18, and 28 wk (9-30% decreases) and in the 2nd segment at 4, 14, and 18 wk (38-69% decreases; P less than 0.001-0.005). Decreased calbindin in SHRs was documented in animals from two suppliers. The deficiencies of calbindin-D9k and alkaline phosphatase could not be attributed to malnutrition or to a generalized brush-border defect as indicated by body weights and the intestinal marker enzyme sucrase. Although calbindin-D9k was decreased in young SHRs, the serum 1,25-dihydroxycholecalciferol [1,25(OH)2D3] was increased by 59 and 129% in 4- and 9-wk-old SHRs (P less than 0.001), respectively; by contrast, serum 1,25(OH)2D3 was unchanged or decreased in older SHRs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal vitamin D-dependent calbindin-D9k and alkaline phosphatase in spontaneously hypertensive rats. 203 38

An 82-year-old woman, with clinically and histologically documented osteomalacia associated with a history of several gastrointestinal operations and malabsorption, was successfully treated with low dose calcitriol. Osteomalacia, with particular reference to the gastrointestinal type, and the role of vitamin D and its metabolites are discussed. Therapy with calcitriol is compared with conventional vitamin D treatment. Calcitriol should be considered in the treatment of osteomalacia induced by gastrointestinal disorders.
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PMID:[Osteomalacia after intestinal operations--therapeutic effect of calcitriol. Report of a case]. 375 50

Elucidation of the vitamin D endocrine system and the availability of potent metabolites have led to new approaches to vitamin D therapy. The traditional management of exogenous (sunlight) or endogenous (malabsorption) vitamin D deficiency without evidence of disordered vitamin D metabolism has not changed, since it consists of treatment with vitamin D itself--a therapy which preserves the normal intrinsic mechanisms for regulating the rate of production of 1,25-dihydroxycholecalciferol. 1,25-DHCC and the analogue compound 1 alpha-CC should be reserved for treatment of hypocalcemia consequent on chronic renal failure or hypoparathyroidism, where 1-hydroxylation is lacking or impaired. Hypophosphatemic rickets has been treated with 1-hydroxylated compounds, with promising results; this use of the latter metabolites warrants further investigation. The use of vitamin D metabolites and of pharmacological doses of vitamin D itself must be regarded as substitution of a hormone or hormone precursors. Therefore, careful monitoring of serum and urine calcium is required in every patient receiving these compounds, in order to avoid excessive dosage. Special attention must be paid to patients with sarcoidosis since they often develop hypercalcemia after vitamin D or UV-light exposure, as a result of an intrinsic regulation defect in 1,25-DHCC synthesis.
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PMID:[Therapy with vitamin D and D-metabolites]. 626 26

A 38-year-old woman, who 5 years earlier had undergone a jejunoileal bypass for gross obesity, fractured the distal forearm by a minor trauma. Circulating 25-hydroxycholecalciferol was undetectable without vitamin D3 supplement but increased to the lower normal range on a daily dose of 1200 units of vitamin D3. Serum 1,25-dihydroxycholecalciferol was, however, in the upper normal range, both without and with vitamin D supplement. After intestinal reanastomosis the fracture healed and the biochemical changes normalized. Malabsorption due to reduced amount of functioning intestine may cause severe metabolic bone disease, which may not always be reverted by a high-calcium diet and vitamin D supplementation.
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PMID:Delayed fracture healing following jejunoileal bypass surgery for obesity. 680 54

Familial hypophosphoremic rickets, although exceptional, is a frequent form of presentation in communities where nutritional rachitism has been eradicated. Hypophosphoremia is the biochemical defect which led to an insuffieient osseous mineralization. The real pathogenic mechanism of the disease is still unknown. Two patients, mother and son, who presented anamnesic, biochemical and roentgenographic characteristics suggesting a familial hypophosphoremic rachitism are reported. Clinical, biochemical and roentgenologic data of a secondary reactive hyperparathyroidism were absent in both cases. The present knowledge on the metabolic pathway of vitamin D and its metabolites led us to consider that the basic pathogenic defect appears as a consequence of an intestinal malabsorption of phosphates due to an altered synthesis of 1,25-dihydroxycholecalciferol or its precursor 25-hydroxycholecalciferol.
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PMID:[Familial hypophosphoremic rickets: pathogenic considerations based on two cases (author's transl)]. 738 20

Increased cytokine release and increased activity of osteoclasts (reduced osteoclast apoptosis) due to a fall in estrogen is of causal significance in postmenopausal bone loss as well as malfunction of the vitamin D activation and concomitant calcium (Ca) malabsorption. Alfacalcidol prevents rapid postmenopausal bone loss by elimination of Ca malabsorption and by blocking resorbing cytokines. Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodeling induced by sex hormone deficits and by a so-called somatopause (insulin-like growth factor [IGF]-deficit), but also by lack of vitamin D and, very importantly, by reduced synthesis of D-hormone (Calcitriol) in kidneys and bone as well as by a lack of receptors or receptor affinity for D-hormone in the target organs. As a consequence of these facts, a rise in parathormone (PTH) frequently occurs. The lack of D-hormone and IGF-1 evidently causes a reduction in muscle strength as well and reinforces the risk of falling and, thus, the risk of a fracture. Alfacalcidol, a prodrug of D-hormone, is a specific antiosteoporotic therapy. In alfacalcidol therapy, D-hormone is provided to the body in circumvention of its own regulation, by means of which much higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. Chances have been significantly improved of reducing and frequently preventing the real osteoporosis complication for older male and female patients, i. e., bone fractures, by alfacalcidol. A clear distinction should be made between supplementation with low-dosed plain vitamin D and calcium as base supply in elderly housebound subjects or as adjuvant to antiosteoporotic drugs and the specific antiosteoporotic therapy with alfacalcidol in patients with osteoporosis. The expanded understanding of the pathogenesis of corticosteroid-induced osteoporosis with its disturbed Ca homeostasis and the pharmacological effects of alfacalcidol, counteracting such iatrogenic bone loss, explain the particularly good clinical efficacy in this most frequent form of secondary osteoporosis. Normalizing de-coupled bone remodeling due to cytokine modulation and the potential influence on deteriorated bone quality in patients with rheumatoid arthritis and Crohn's disease predestine this form of therapy for prevention and treatment of osteoporosis as a result of chronic inflammatory diseases as well as of transplantation osteoporosis cases in particular.
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PMID:Rationale for treatment of involutional osteoporosis in women and for prevention and treatment of corticosteroid-induced osteoporosis with alfacalcidol. 1048 85

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the (45)Ca single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937 mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0. 25 microg twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease [0.74 (+/- 0.35 SD) to 0.58 (+/- 0. 22), Dalpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Dalpha = +0.16 (+/- 0. 30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha >/=0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. Increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.
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PMID:Calcium absorption in postmenopausal osteoporosis: benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers. 1066 58


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