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)

Hypophosphatasia, a rare heritable form of rickets/osteomalacia, is characterized by deficient activity of the tissue nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequence of either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213-234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality. We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5 1/2 years and has had a much milder clinical course. Although consanguinity is absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are consistent with heterozygosity in each parent. Fibroblast ALP activity is less than 1% normal in all 3 patients with no complementation observed in heterokaryon analysis. Accordingly, the genetic defects appear to be identical in all 3 patients. Our findings show that infantile hypophosphatasia may be inherited as an AR condition where there is variable expressivity and that homozygosity or compound heterozygosity, as may be the case in this family, is not necessarily lethal.
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PMID:Infantile hypophosphatasia: autosomal recessive transmission to two related sibships. 233 3

We report clinical and bone morphometric findings in 18 osteoporotic patients who experienced stress fractures during fluoride therapy. Patients were treated with either sodium fluoride (n = 15), or sodium monofluorophosphate (n = 3). Oral calcium supplementation was given in 11 patients, and vitamin D in 13. Stress fractures occurred after 17.1 +/- 10.3 months of therapy (range: 5-41 months). Atraumatic sudden pain in a lower limb bone extremity, normal initial roentgenogram, high 99technetium uptake on early bone scan, and a 3 to 4 week delay in linear bone condensation area at the same site were characteristics of stress fracture. The most frequent sites were the tibial metaphysis (n = 13), femoral neck (n = 10), and calcaneus (n = 4). Biochemical data showed increased plasma alkaline phosphatase levels in 11 patients, and mild renal failure in 2. Bone histomorphometry was performed on an iliac crest specimen in 10 patients at the time of the stress fracture. Trabecular bone volume was normal, and formation parameters were increased. Features of osteomalacia were encountered in only 2 patients with decreased renal function. Trabecular resorption was increased, as assessed by the osteoclastic surface (1.01 +/- 1.15% bone surface), and the number of osteoclasts (0.44 +/- 0.49 per mm2 bone section). The clinical course was favorable in all patients who stopped fluoride, although 5 patients who continued the treatment had either completion of femoral neck stress fractures to hip fractures (n = 2), or recurrent stress fractures (n = 2), or both (n = 1). Fluoride appears to be a key factor in the pathogenesis of stress fractures, and may be associated with increased trabecular resorption in some treated patients.
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PMID:Stress fractures of the lower limbs in osteoporotic patients treated with fluoride. 233 28

Alkaline phosphatase, osteocalcin and hydroxyproline levels were evaluated in patients with the following conditions: primary hyperparathyroidism, renal dialysis, hyperthyroidism, Cushing's syndrome, long term corticosteroid therapy, Paget's disease, osteoblastic metastases, osteolytic or mixed metastases, and nutritional osteomalacia. In all cases the levels of the three substances were increased, with the following exceptions: a) in endogenous or exogenous hypercortisolism states osteocalcin level was reduced and those of alkaline phosphatase and hydroxyproline were unchanged; and b) in blastic or lytic metastases osteocalcin level was unchanged. In general, alkaline phosphatase and hydroxyproline levels had a higher sensitivity than those of osteocalcin in structural bone disease (Paget's disease, blastic or lytic metastases), whereas the converse was true for endocrine bone disease (the remaining conditions except osteomalacia, which is mixed, both structural and endocrine; in this syndrome, the three substances showed the same sensitivity.
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PMID:[Different behavior of bone turnover markers in endocrine (extrinsic) and structural (intrinsic) osteopathies]. 234 91

The authors investigated in a group of 38 subjects with type I diabetes and 222 subjects with type II diabetes laboratory values indicating the level of bone metabolism: calcium, phosphorus, alkaline phosphatase activity in serum, urinary calcium excretion, and they compared the values mutually and with the level of bone mineralization. The authors found significantly lower serum calcium values in all investigated groups, the lowest ones in women with type II diabetes. To these values corresponded always reduced values of bone mineralization which were also lowest in women with type II diabetes. The very lowest bone mineralization was found in groups of subjects treated with oral antidiabetics, the values in women being lower than in men. The authors found also a higher alkaline serum phosphatase activity, in particular of its bone isoenzyme. The significant correlation between the reduced serum calcium value and bone mineralization indicates that this laboratory value has a decisive influence and importance in the development of osteoporosis. The high alkaline phosphatase activity suggests that there is also prescut osteomalacia.
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PMID:[Diabetic osteopathy. 4. Laboratory findings]. 237 77

We analyzed transiliac bone biopsy specimens obtained after tetracycline double labeling from 24 patients with aluminum-related bone disease who had undergone long-term hemodialysis. The specimens were selected by the following criteria: Al deposits at the mineralization fronts, a dramatic reduction in double-labeled surfaces, reflecting a low mineralization rate, and a significant increase in osteoid volume and osteoid surfaces. The bone formation rate at the tissue level and at the basic multicellular unit level was decreased in all patients. Seventeen biopsy specimens (group 1) showed morphologic and dynamic evidence of osteomalacia, as defined by an increase in the osteoid seam thickness and a decreased mineralization rate. In one specimen from group 1, thickened osteoid seams were present only in a small part of the specimen. In seven specimens (group 2), the osteoid seam thickness index was normal, indicating "aplastic bone." Two specimens from group 2, however, showed morphologic and dynamic evidence of focal osteomalacia either in trabecular or in cortical bone. Specimens from group 2 patients differed from those in group 1 in their significantly lower values of osteoid volume and lower levels of serum alkaline phosphatase and parathyroid hormone. These data show that the absence of significant increase in osteoid seam thickness and the focal distribution of thickened osteoid seams in patients with Al overload and low rate of bone formation reflect the marked reduction of bone matrix formation at the cellular level. It is suggested that low parathyroid activity might play a role in the reduction of bone matrix formation.
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PMID:Low rate of bone formation with or without histologic appearance of osteomalacia in patients with aluminum intoxication. 241 May 22

Skeletal uptake of diphosphonate was measured by emission tomography in 30 patients on chronic dialysis treatment. In 19 patients mean plasma aluminium concentrations, measured over the preceding 12 months, were 'high' (greater than 1.0 mumol/l, and in the other 11 were 'low' (less than 1.0 mumol/l). There was a strong correlation between serum alkaline phosphatase and skeletal uptake of diphosphonate in each group, but no difference in diphosphonate uptake between the groups. Additionally, when six patients with positive desferrioxamine tests were matched for serum alkaline phosphatase with six patients from the 'low' aluminium group there was no significant difference in uptake of diphosphonate (median and range 7.2; 5.2-16.5 and 5.9; 2.7-10.8 respectively). We conclude that skeletal uptake of diphosphonate is not suppressed in patients with moderate aluminium loading, but reflects bone turnover as indicated by serum alkaline phosphatase. Quantitative bone scintigraphy is not a useful discriminator for early aluminium osteomalacia.
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PMID:Quantitative bone scanning in the diagnosis of aluminium osteomalacia. 251 81

A patient is described with neurofibromatosis, increasing walking problems and low back pain. Initially, osteoporosis or pressure caused by a neurofibroma was suspected. However, the progressively increasing alkaline phosphatase activity and hypophosphataemia found during laboratory investigations led to metabolic studies which revealed proximal tubular dysfunction. A bone biopsy showed severe osteomalacia. A diagnosis of hypophosphataemic osteomalacia was made based on the Fanconi-syndrome. The association between hypophosphataemic osteomalacia and neurofibromatosis may be akin to the relationship between this type of osteomalacia and mesenchymal tumours, which has been noticed several times in the literature. The underlying mechanism is unknown.
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PMID:Adult hypophosphataemic osteomalacia with Fanconi syndrome presenting in a patient with neurofibromatosis. 251 47

Tumor-induced osteomalacia is a clinicopathological entity in which vitamin D-resistant osteomalacia or rickets occurs in association with a tumor. A total of 72 cases (three current, 69 from review of literature) has been reported to date. Men and women are equally affected. The majority are adults over 30 years old who exhibit progressive lower leg and back pain. Forty bone and 31 soft-tissue tumors were responsible for this syndrome; two-thirds occurred in the extremities. Chemical findings are typical: low serum phosphorus, normal serum calcium, and elevated alkaline phosphatase. Serum levels of 1,25-dihydroxyvitamin D were low or undetectable. Histologically, more than a third were classified as vascular tumors, and half of these cases were hemangiopericytomas that were distributed equally between bone and soft tissues. Other common diagnoses included nonossifying fibromas, "mesenchymal" and giant-cell tumor variants. Features common to all tumors were prominent vascularity, and giant and primitive stromal cells. Only 10 were histologically malignant. Ultrastructural studies have not shown any secretory granules suggestive of a hormone-secreting tumor. It is clear, however, that the tumor is responsible for the osteomalacia because the complete removal generally results in a dramatic reversal of all symptoms and signs.
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PMID:Tumor-induced osteomalacia and rickets. 254 16

The serum concentration of 25-hydroxyvitamin D level and plasma albumin-adjusted calcium, phosphate, and alkaline phosphatase levels were studied in 200 patients with hip fracture (age range 49-93 years) and 427 elderly subjects living in the community (age range 60-90 years). The mean serum 25-hydroxyvitamin D levels in controls were higher than in temperate countries, but the 25-hydroxyvitamin D concentration was significantly lower in the patients than the controls for all sex and age groups. There was little difference in albumin-adjusted calcium and alkaline phosphatase levels, but the phosphate level was higher in the patients than in the controls. None of the patients with a low 25-hydroxyvitamin D level had a blood picture suggestive of osteopathy resulting from vitamin D deficiency or frank osteomalacia. Hip fracture patients with a low 25-hydroxyvitamin D level were much less ambulant and went outdoors much less frequently than hip fracture patients with a normal vitamin D level. A low vitamin D level was a risk factor for hip fracture in Hong Kong Chinese, and may be prevented by frequent outdoor exposure.
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PMID:Plasma 25-hydroxyvitamin D concentration in patients with hip fracture in Hong Kong. 258 33

The author examined a group of 143 patients with osteomalacia of different origin before treatment and after adequate treatment with vitamin D, using laboratory tests, assessment of body weight and muscular strength (grip of the dominant hand). After treatment there was a significant rise of calcaemia, phosphataemia and calciuria and a drop of alkaline phosphatase activity. The body weight increased within the first month of treatment on average by 1.27 kg, during the second month by another 1.15 kg. The patients gained a total of 2.42 kg. The muscular strength increased during the first month on average by 3.23 kg and during the second month by another 2.16 kg, i.e. a total of 5.39 kg. From these results it may be concluded that vitamin D may have a certain anabolic effect if used in pharmacological does either due to an increased nutrient absorption from the gut because of hypertrophy of the intestinal wall or indirectly via hypercalcaemia which increases the hydrochloric acid secretion in the stomach as well as pepsin secretion, and promotes activation of trypsin and lipase in the duodenum and moreover causes retardation of the intestinal transit. The increased muscular strength in due to a rise of calcaemia, improved muscle contraction and probably also due to the mentioned nutritional factors. There may be also the factor of an improved lifestyle due to the immunomodulating action of vitamin D and disappearance of bone pain.
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PMID:[Anabolic effects of vitamin D in patients with osteomalacia]. 263 59


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