Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of alkaline agents to a 16-year-old girl with severe renal tubular acidosis and osteomalacia caused an almost immediate rise of the urinary excretion of total hydroxyproline. The increment of the dyalizable fraction predominated over the nondyalizable component. Gradually serum phosphate and serum alkaline phosphatase increased whereas urinary calcium and magnesium and phosphate clearance declined. Serum PTH remained elevated throughout. We suggest that the correction of the metabolic acidosis might increase the transport of phosphate and calcium across the functional bone membrane leading to a rapid deposition of lime salts in the uncalcified matrix with a concomitant increase in bone collagen turnover.
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PMID:Early skeletal effect of alkali therapy upon the osteomalacia of renal tubular acidosis. 127 May 79

Material has been obtained by biopsy from the right iliac crest of 60 adult epileptic out-patients receiving chronic anticonvulsant therapy with diphenylhydantoin (DPH), either in single-drug or combined-drug regime, and of 16 controls with the same distribution by sex and age. Four (7%) of the epileptics were hypocalcemic and 25 (42%) had elevated serum alkaline phosphatase values. A quantitative analysis of the morphological bone changes was performed on decalcified and undecalcified bone, using integrating filters and the point count principle. An increased amount of unmineralized bone was found in 32 (53%) of the epileptics. The trabecular osteoclastic resorption surfaces and the mean volume of periosteocytic lacunae were increased in 36 (69%) and 45 (75%) patients, respectively. The calcification rate was decreased in relation to what is referred to elsewhere as normal. The bone changes suggest a mineralization defect analogous to osetomalacia with secondary hyperparathyroidism. An increased osteoid volume or thickness and decreased calcification rate were correlated to low dietary vitamin D intake, low exposure to sunlight, high hepatic clearance rate of DPH, combined-drug treatment and the male sex. These parameters should be considered risk factors of anticonvulsant osteomalacia.
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PMID:Anticonvulsant osteomalacia determined by quantitative analysis of bone changes. Population study and possible risk factors. 127 72

Four patients had symptomless osteomalacia at the time of starting regular haemodialysis. After 21-40 months they became hypophosphataemic and developed disabling skeletal symptoms. In each case an exacerbation of histological osteomalacia was shown. Symptoms improved after measures designed to raise serum inorganic phosphate concentrations or vitamin D administration, or both. Patients undergoing maintenance haemodialysis should have their serum phosphate and alkaline phosphatase levels monitored every month. Predialysis phosphate levels below 1 mmol/1 (3 mg/100 ml) and rising serum alkaline phosphatase concentrations are danger signals. If the diagnosis is confirmed early aggressive treatment should be started.
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PMID:Hypophosphataemic osteomalacia in patients receiving haemodialysis. 127 33

26 years after a partial gastric resection (Billroth II) for recurrent gastric ulcer a 62-year-old man developed severe intestinal osteopathy. For three years he had increasing pain in the lower back and hip with a noticeable waddling gait. Serum concentration of calcium (2.0 mmol/l) and 25-hydroxy-vitamin D3 (38 mmol/l) were reduced, those of alkaline phosphatase (572 U/l) and parathormone (532 pg/ml) increased. Radiology demonstrated Looser's zones in the ribs and iliac crest. Osteodensitometry showed obviously diminished bone density. Iliac crest biopsy revealed signs of osteomalacia and secondary hyperparathyroidism. Within three months of starting oral vitamin D3 and calcium the symptoms had definitely receded and serum concentrations of calcium and alkaline phosphatase had become normal (2.4 mmol/l and 156 U/l, respectively). Osteopathic symptoms are often the expression of an abnormal calcium/phosphate metabolism. The cause often lies in the gastrointestinal tract; not rarely it is a late complication of a gastrojejunostomy.
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PMID:[Intestinal osteopathy following partial gastric resection]. 131 Apr 61

Hypophosphatasia is a heritable form of rickets/osteomalacia with extremely variable clinical expression. Severe forms are inherited in an autosomal recessive fashion; the mode of transmission of mild forms is uncertain. The biochemical hallmark of hypophosphatasia is deficient activity of the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Previously, we demonstrated in one inbred infant that an identical missense mutation in both alleles of the gene encoding TNSALP caused lethal disease. We have now examined TNSALP cDNAs from four unrelated patients with the severe perinatal or infantile forms of hypophosphatasia. Each of the eight TNSALP alleles from these four individuals contains a different point mutation that causes an amino acid substitution. These base changes were not detected in at least 63 normal individuals and, thus, appear to be causes of hypophosphatasia in the four patients. (Two additional base substitutions, found in one allele from each of the four patients, are linked polymorphisms.) Twenty-three unrelated patients (of 50 screened), who reflect the entire clinical spectrum of hypophosphatasia, possess one of our of the above eight mutations. In two of these additional patients, mild forms of the disease are also inherited in an autosomal recessive fashion. Our findings indicate that hypophosphatasia can be caused by a number of different missense mutations and that the specific interactions of different TNSALP mutant alleles are probably important for determining clinical expression. Severe forms, perinatal and infantile disease, are largely the result of compound heterozygosity for different hypophosphatasia alleles. At least some cases of childhood and adult hypophosphatasia are inherited as autosomal recessive traits.
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PMID:Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. 140 20

A case of adult onset hypophosphatemic vitamin D resistant osteomalacia is described. A 40-year-old female who complained of thorax and lumbar pain and gait disturbance was admitted to our hospital on 7 November, 1988. The patient had hypophosphatemia with normal plasma calcium, parathyroid hormone and 25-hydroxy vitamin D3 concentrations, but had decreased tubular reabsorption of phosphate and decreased plasma 1, 25-dihydroxy vitamin D3 concentrations. The iliac crest bone biopsy showed osteomalacic changes. The 99mTc-MDP bone scintigram showed evidence of increased bone turnover with raised plasma alkaline phosphatase concentrations. After treatment with oral 1 alpha-hydroxy vitamin D3 (3-6 micrograms/day) and intravenous or oral phosphate supplement (0.47-1.74g/day), the subjective and clinical findings improved.
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PMID:[A case of adult onset hypophosphatemic vitamin D resistant osteomalacia]. 144 82

Postgastrectomy bone disease was a term devised to describe the metabolic disorders of bone which may follow a gastrectomy operation. Although the use of this operation has declined drastically in recent years, this metabolic bone disorder is still with us and may escape and confuse the unwary. These disorders may take the form of osteomalacia, osteoporosis in excess of normal ageing, or a combination of both. For screening purposes, regular estimations of plasma alkaline phosphatase levels identify patients who may be developing osteomalacia which can then be treated with calcium and vitamin D supplements. Numerically, osteoporosis in excess of ageing is a bigger problem and its prevention and treatment is at present unsatisfactory. Screening procedures for osteoporosis are reviewed, including the more recent methods of bone mineral density assessment. Osteopenia or demineralization occurs in both osteomalacia and osteoporosis therefore osteomalacia must be excluded before attributing any loss to osteoporosis. The present situation with regards to the prevention and treatment of osteoporosis is also reviewed.
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PMID:A review of postgastrectomy bone disease. 148 91

The synthesis of osteocalcin or bone gla protein by osteoblasts is markedly stimulated by 1,25-(OH)2D, a key hormone in the regulation of bone mineralization. The circulating levels of osteocalcin have been shown to reflect both the osteoid matrix production and the formation rate of mineralized bone in several metabolic bone diseases (osteoporosis, thyrotoxicosis, primary hyperparathyroidism) in which both mechanisms are tightly coupled because of the absence of mineralization defect. In this study, we measured in 12 patients (7 women, 5 men, 56 +/- 15 yr old) with untreated osteomalacia serum osteocalcin and vitamin D metabolites (25OHD and 1,25-(OH)2D). The results were correlated with biochemical and histomorphometric assessment of bone remodeling. Osteomalacia was due to vitamin D deficiency (5 cases), to vitamin D malabsorption (6 cases), and to hypophosphataemia in 1 case. When compared to control values, serum osteocalcin was increased in patients with osteomalacia (7.4 +/- 4 vs. 3.7 +/- 1.3 ng/mL; P less than 0.001) and was positively correlated with serum alkaline phosphatase (r = 0.65; P = 0.03) and negatively with 25 OHD (r = -0.61; P = 0.04). Serum osteocalcin was not correlated with 1,25-(OH)2D [r = -0.45; not significant (NS)] even after exclusion of the patient with hypophosphataemia. Serum osteocalcin was positively correlated with the osteoid volume and osteoid perimeter (r = 0.71 and 0.69 respectively; P less than 0.01) but not with any of the tetracycline-based parameter of bone mineralization at the tissue level (r ranging from -0.41 to +0.42, NS). Serum 25 OHD, but not 1,25-(OH)2D, was positively correlated with the mineralization rate (r = 0.59; P less than 0.05 and r = 0.54; NS). We conclude that in patients with osteomalacia, a condition which is characterized by an increased osteoid accumulation due to a decreased mineralization rate, the increased level of serum osteocalcin reflects the increased osteoid synthesis but not the mineralization defect. In this disease, serum osteocalcin is inversely correlated to the severity of vitamin D deficiency reflected by serum 25 OHD, but not to the serum levels of 1,25-(OH)2D.
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PMID:Serum osteocalcin is increased in patients with osteomalacia: correlations with biochemical and histomorphometric findings. 156 62

In a group of 88 patients, immobile for various reasons a markedly reduced bone mineralization was found, significantly more in patients with denervation of the muscles. As to laboratory indicators, the author recorded a significantly reduced serum calcium level which correlated positively with the mineralization level; there was an insignificantly elevated alkaline phosphatase activity and calciuria. After comprehensive calcium treatment with small doses of vitamin D, and in patients without signs of osteomalacia also with sodium fluoride raised also significantly the serum calcium level, while there was a decline of the alkaline phosphatase activity and a slight increase of calciuria. The fundamental requirement of therapy is burdening of the bones by graded mobilization of the patients. The following series proved useful: isometric contraction of muscles in a recumbent position--standing up, assisted next to the bed--moving round the bed--active rehabilitation.
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PMID:[The effect of inactivity on bone mineralization]. 163 93

Osteomalacia is characterized by large osteoid seams and a preserved volume of bone trabeculae. The mineralization of newly formed bone requires adequate concentrations of calcium and phosphate: the Ca.P product has been regarded as a useful, empirical diagnostic test of osteomalacia. It decreases in patients with osteomalacia mainly because they have very low plasma phosphate levels. At present total body bone mineral and total body bone density can be directly measured by whole body absorptiometry, which indicates the lowest total mineral content of the skeleton which can increase quickly after adequate treatment. The main symptoms of osteomalacia are: bone pain; muscular weakness (commonly as pelvic girdle myopathy); Looser-Milkman pseudofractures or more often a pattern of generalized demineralization at X-ray. The main biochemical parameters in osteomalacia include: defective calcium absorption with hypocalcemia and hypocalciuria; defective intestinal phosphate absorption with hypophosphatemia; there is often increased renal phosphate clearance due to hypocalcemia and secondary hyperparathyroidism; elevated alkaline phosphatase and osteocalcin levels; high bone turnover confirmed by kinetic studies carried out with radiocalcium or 99mTc-MDP. An etiological classification of the osteomalacias includes: 1) nutritional osteomalacia: a) inadequate exposure to sunlight and/or insufficient vitamin D intake; b) defective intestinal absorption of vitamin D because of malabsorption syndromes (e.g. jejuno-ileal bypass for obesity).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The osteomalacias. 166 41


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