Total Serum Alkaline Phosphatase Activity Research Articles

Clinical value of the measurement of bone remodelling markers in primary hyperparathyroidism.

This study was performed in order to evaluate the clinical usefulness of the measurement of total serum alkaline phosphatase activity (AP), serum osteocalcin (BGP) and urinary hydroxyproline (OHPr) in assessing bone remodelling in primary hyperparathyroidism. Thirty-two patients with primary hyperparathyroidism were included in the study. No statistically significant differences were observed between the mean values of Z-scores obtained for each marker. Furthermore, an inverse correlation was found between percentage of bone mineral content at the distal radius and both BGP (r = -0.57; p less than 0.05) and AP (r = -0.49; p less than 0.05). The results obtained demonstrate that, contrary to other metabolic bone diseases (e.g. Paget's disease of bone), all three markers examined may be used in clinical practice to evaluate the entity of skeletal turnover in primary hyperparathyroidism.

Benign Familial Hyperphosphatasemia

Elevated alkaline phosphatase activity in serum suggests bone or liver disease or a neoplasm but can also indicate pregnancy or another benign condition. A family with benign hyperphosphatasemia was studied to elucidate the genetics and enzyme defect. Serum total alkaline phosphatase activity was greater than the population mean in all six family members, and more than 7 SDs above the mean in two of four offspring. Monoclonal antibodies to three alkaline phosphatase isoenzymes, intestinal, placental, and tissue nonspecific (liver/bone/kidney), demonstrated markedly increased intestinal alkaline phosphatase levels (29% to 44% of total) in all family members and significantly elevated liver/bone/kidney activity in the two offspring. Guanidine hydrochloride denaturation of the liver/bone/kidney component showed high alkaline phosphatase activity from liver in both siblings and from bone in one. The mode of inheritance in this family is obscure, but a complex regulation of the products of two different alkaline phosphatase genes seems likely. Steps toward diagnosis are suggested. Early recognition of this benign biochemical abnormality should help to avoid unnecessary diagnostic tests.

Serum osteocalcin and total alkaline phosphatase levels as prognostic indicators in tibial shaft fractures

Serum samples were obtained periodically from 50 adult patients with closed tibial shaft fractures. Total alkaline phosphatase activity was measured in all cases and osteocalcin activity was measured in 14 patients. Fractures produced by high-energy violence generally had lower values of osteocalcin activity. This could be due to depressed circulating vitamin K levels throughout the healing period in the former fractures. In addition, normally uniting fractures had generally higher values of osteocalcin activity compared with fractures exhibiting delayed union. This indicates depressed osteoblastic activity in slowly healing fractures. The results suggest that measurement of osteocalcin activity after fracture could provide a useful prognostic indicator. By contrast, total serum alkaline phosphatase activity was not significantly different between the injury groups and between the healing groups.

The prevalence of variant alkaline phosphatase in hepatocellular carcinoma in southern African blacks.

The prevalence of variant alkaline phosphatase in the serum of 335 southern African blacks with hepatocellular carcinoma was determined using polyacrylamide gel electrophoresis. The isoenzyme was detected in 2% (seven of 335) of the patients: it could not be found in the serum of 300 matched, healthy individuals or in 56 patients with various benign hepatic diseases. Variant alkaline phosphatase is thus of little use as a diagnostic marker of hepatocellular carcinoma in southern African blacks. The reported prevalence of this isoenzyme in hepatocellular carcinoma ranges between 3% and 31%. Higher frequencies usually are recorded in populations with a low incidence of the tumor, and the lowest frequencies have been found in Chinese patients. Our finding of variant alkaline phosphatase in only 2% of another high incidence population fits this trend. Patients with tumors that secreted the variant isoenzyme had a significantly higher serum total alkaline phosphatase activity than those with tumors lacking this property.

Toxicity studies of VP 16-213 (IV)--Intravenous one-month subacute toxicity in rats

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 0.15, 0.50, 1.5 and 4.5 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. For the purpose of comparison, vincristine (abbr. to VCR) was administered in the same manner at dose levels of 0.04 and 0.08 mg/kg/day. The summarized results obtained are as follows: VP 0.50 mg/kg and higher suppressed body weight increase and food intake dose-responsively. VP 4.5 mg/kg brought depilation and anemia, and some of male animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 0.50 mg/kg and higher decreased white blood cell count accompanied with lowered lymphocyte fraction, and 1.5 and 4.5 mg/kg predominantly decreased red blood cell count. VP 1.5 and 4.5 mg/kg lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 0.50 mg/kg and higher predominantly decreased testicular weight, and 1.5 and 4.5 mg/kg predominantly brought thymic atrophy, hypoplasia of bone marrow and testicular atrophy with suppression of spermatogenesis and tubular atrophy. VP 4.5 mg/kg induced atrophy of germinal centers and hemosiderosis in spleen, and epididymal atrophy with decrease of sperms in number and appearance of giant cells. Above-described changes excluding the findings on testis and epididymis were generally reversible. Most of the findings for a reference drug, VCR, were similar to those for VP, and their severities brought by VP 1.5 and 4.5 mg/kg were comparable to those by VCR 0.04 and 0.08 mg/kg, respectively. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 0.15 mg/kg/day against rats of both sexes.

Toxicity studies of VP 16-213 (II)--Oral one-month subacute toxicity in rats

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 3, 10, 30 and 100 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought soft stool. VP 100 mg/kg decreased body weight and feed intake, and induced diarrhea, depilation and so forth. Furthermore, half of the animals at this dose level died showing systemic debility and emaciation. VP 30 and 100 mg/kg predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 10 mg/kg and higher lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 10 mg/kg and higher caused thymic atrophy and a decrease in testicular weight; 30 and 100 mg/kg brought suppression of spermatogenesis; and 100 mg/kg predominantly induced appearance of giant cells in epididymis, hypoplasia of bone marrow, ileocecitis, and atrophy of prostate, seminal vesicle and splenic germinal centers. Above-described changes excluding exacerbation of the findings on testis and epididymis were shown to be generally reversible. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against rats of both sexes.

Effect of cimetidine on serum carboxyl and aminoterminal fragments of parathyroid hormone in chronic uraemic patients.

The effect of cimetidine on abnormally elevated serum levels of parathyroid hormone was studied in 21 patients with secondary hyperparathyroidism due to chronic renal failure, receiving regular dialysis treatment. The concentrations of carboxyl (-COOH) and aminoterminal (-NH2) fragments of circulating immunoreactive parathyroid hormone (iPTH) were determined before and after 2 months af treatment with cimetidine 400 mg/day. All patients had, on admission, raised levels of either hormonal fragment. The mean pre-treatment value was 17.2 mU/ml for -COOH terminus (upper normal limit 6.5 mU/ml) and 5.7 mU/ml for -NH2 terminus (upper normal limit 1.9 mU/ml). At the end of cimetidine treatment the mean values were 19.9 and 5.7 mU/ml respectively for the two forms of circulating iPTH. No changes in total serum calcium, phosphate or alkaline phosphatase activity were recorded during the study. These results do not indicate any lowering effect of cimetidine on serum iPTH in chronic uraemic patients with secondary hyperparathyroidism.

Alterations in human serum alkaline phosphatase and its isoenzymes by hypolipidemic agents: Colestipol and clofibrate

Total serum alkaline phosphatase (TSAP) determinations were done as part of the biochemical screening in comparative studies of lipid lowering agents in type lla hyperlipoproteinemic patients. TSAP determinations were made by using a modification of the Bessey-Lowry method and the Statland method. Increases in TSAP following colestipol treatment of 20% ( P < 0.05) and 32% ( P < 0.005) were seen by using the respective methods. Isoenzymatic determinations were done by employing the Statland method and all fractions were increased from baseline levels during colestipol therapy. Clofibrate was associated with 34% ( P < 0.005) and 28% ( P < 0.005) reductions in TSAP activity by using the respective methods; significant reductions in both “bone” and “other” isoenzymatic components occurred. Gamma-glutamyltransferase (γGT) results did not consistently reflect TSAP or “liver” isoenzyme results.

Monofluorophosphate Physiology: The Effects of Fluoride on Bone

Fluoride is an effective agent in the treatment of osteoporosis and is the only available agent that is capable of producing a large increment in bone mass. Fluoride stimulates bone formation largely through its action to increase osteoblast number. In vitro work suggests that the effect of fluoride to increase osteoblast number is due to a direct action of fluoride to stimulate the proliferation of osteoblast precursors. In fluoride-treated patients the increase in bone formation leads to an increase in bone mass as manifested by an increase in X-ray density, which in turn leads to a decrease in bone pain and a decrease in fracture rate. These positive effects are limited to the axial skeleton and are not observed in the appendicular skeleton in the dose used. The increase in bone formation is reflected by an increase in serum total alkaline phoshatase activity, which is due to an increase in the bone isoenzyme and which can be used to assess serially the action of fluoride on bone. Serum total alkaline phosphatase activity measurements indicate that, during 2 years of fluoride treatment, about 80% of patients respond and that the magnitude of the response is quite variable. The major disadvantages of fluoride in the treatment of osteoporosis include: (1) All patients do not exhibit a response. (2) Fluoride treatment causes gastric and joint side effects in a significant proportion of patients.

Urinary excretion of hydroxyproline in parathyroid disorders, with special reference to its changes before and after parathyroidectomy in primary hyperparathyroidism

It is possible to assess bone resorption from a determination of urinary excretion of hydroxyproline, which is the specific amino-acid of collagen. As dietary collagen affects 24-hour urinary excretion of hydroxyproline, it has been stated that the urine should be collected under a gelatin-free diet. A new sampling method was described in the present paper for the determination of hydroxyproline in urine, which could eliminate the affection of dietary collagen by simple fasting. The method was useful for the evaluation of bone metabolism in patients with parathyroid disorders. 10 patients with primary hyperparathyroidism (3 skeletal types and 7 non-skeletal types), 3 patients with idiopathic hypoparathyroidism and 5 normal subjects were studied. It was found that the urinary excretion of hydroxyproline increased at night and diminished during the day in patients with primary hyperparathyroidism as well as in normal subjects, but this diurnal rhythm was not clear in a patient with idiopathic hypoparathyroidism. A pilot study revealed that 10 g gelatin administered orally did not affect the urinary excretion of hydroxyproline after a 12-hour fast. Therefore, 2-hour urine samples (700 h-900 h) were collected, and blood samples were drawn at 800 h after a 13-hour fasting from 1800 h on the previous day to 700 h in the morning studied. The urinary excretion of hydroxyproline was expressed as follows: HOP (microgram/ml)/Cr(mg/dl). The 2-hour urinary excretion of hydroxyproline thus determined was highly correlated with that determined in 24-hour urine collected under a gelatin-free diet (r = 0.995, p less than 0.001) and with the total serum alkaline phosphatase activity (r = 0.987, p less than 0.001). The levels of 2-hour urinary excretion of hydroxyproline in normal subjects were 0.18-0.28 in range, and those in patients with the skeletal type of primary hyperparathyroidism were high. However, the levels were not always higher than those in the patients with the non-skeletal type, in which cases the 2-hour excretion of hydroxyproline was higher than 0.50 except in one patient. The 9 patients with primary hyperparathyroidism who had elevated levels of the 2-hour urinary excretion of hydroxyproline showed tetany after parathyroidectomy.(ABSTRACT TRUNCATED AT 400 WORDS)

Improved method for quantitative determination in serum of alkaline phosphatase of skeletal origin.

In this quantitative method for detection of skeletal alkaline phosphatase (EC 3.1.3.1) activity in human serum, intestinal and placental alkaline phosphatase activities are recognized by their susceptibility to inhibition by L-phenylalanine, and skeletal and hepatic alkaline phosphatases are distinguished by their different sensitivities to inactivation by heat. Alkaline phosphatase isoenzymes prepared from organ sources may behave differently from the corresponding isoenzymes in serum. Our procedure allows us to include organ-derived internal standards of skeletal, intestinal, and biliary alkaline phosphatase to minimize between-assay variation. In preliminary applications, we have found that (a) total serum alkaline phosphatase activity is extremely variable in post-menopausal osteoporotic subjects and is not a reliable index of skeletal alkaline phosphatase activity; (b) seven osteoporotic patients responding to therapy with sodium fluoride with increased bone formation showed increased skeletal alkaline phosphatase activity in their serum as compared with age-matched controls (p less than 0.005); and (c) 10 post-menopausal osteoporotic patients responding to therapy with stanozolol with increased total body calcium showed an increase in circulating skeletal alkaline phosphatase activity (p less than 0.001).

Tissue sources of elevated serum alkaline phosphatase activity in hyperthyroid patients.

Total alkaline phosphatase (ALP) and its isoenzymes were studied in the sera of 72 hyperthyroid patients and 24 age- and sex-matched controls. Eighty-nine per cent of thyrotoxic patients had elevated total serum ALP activity. Both liver (LALP) and bone (BALP) isoenzymes were present in the sera of 75% of patients. Women (43%) most frequently had elevated levels of LALP and BALP. Men (41%) most often had elevated levels of BALP and normal levels of LALP. The units of BALP present, but not of LALP, were related to measures of thyroid function. Levels of the activity of the aminotransferases and lactic dehydrogenase were usually normal. Gammaglutamyl transferase activity was elevated in nearly 40% of both sexes. The data presented, when correlated with previously reported information, suggest that elevations of serum LALP activity may be due to hepatocellular necrosis with leakage of preformed enzyme into the serum.

Properties and clinical significance of an alkaline phosphatase-lipoprotein-X complex.

The existence of an alkaline phosphatase-lipoprotein-X complex was demonstrated as an abnormally moving band in the agar-agarose gel alkaline phosphatase pattern of sera from 58 patients in a group of 72 patients whose sera contained lipoprotein-X. The position of the abnormally moving band in the agar-agarose gel alkaline phosphatase pattern and the percentage of alkaline phosphatase activity in the complex in relation to the total serum alkaline phosphatase activity depend on the serum lipoprotein-X concentration. The presence of the complex is a reliable indicator for cholestasis and of limited value in the differentiation between intrahepatic and extrahepatic cholestasis.

Properties and clinical significance of an alkaline phosphatase-lipoprotein-X complex.

Abstract The existence of an alkaline phosphatase-lipoprotein-X complex was demonstrated as an abnormally moving band in the agar-agarose gel alkaline phosphatase pattern of sera from 58 patients in a group of 72 patients whose sera contained lipoprotein-X. The position of the abnormally moving band in the agar-agarose gel alkaline phosphatase pattern and the percentage of alkaline phosphatase activity in the complex in relation to the total serum alkaline phosphatase activity depend on the serum lipoprotein-X concentration. The presence of the complex is a reliable indicator for cholestasis and of limited value in the differentiation between intrahepatic and extrahepatic cholestasis.

Serum alkaline phosphatase isoenzyme patterns in patients with chronic renal failure

1. 1. Using acrylamide gel electrophoresis the serum alkaline phosphatase (ALP) isoenzyme patterns of 204 patients with chronic renal failure have been examined for periods up to 18 months in length. 2. 2. Of those with elevated serum ALP activity the bone isoenzyme was largely responsible. The presence of increasing amounts of the bone isoenzyme even if the total serum ALP activity remains within the normal reference range should also indicate bone pathology. 3. 3. Intestinal alkaline phosphatase was the major serum alkaline phosphatase in 15% of patients on regular haemodialysis and 10% of uraemic patients not on dialysis. The overall incidence of detectable intestinal alkaline phosphatase in those with normal serum ALP activity was 36%. 4. 4. With those patients whose serum ALP activity changed significantly during the investigation this usually reflected changes in the amount of the bone isoenzyme. Patients with abnormal amounts of the intestinal isoenzymes in their serum usually showed little variation in serum ALP activity over the period of the study.

Serum alkaline phosphatase isoenzymes in epileptic children receving anticonvulsant drugs.

In 40 epileptic children on long-term anticonvulsant treatment, serum alkaline phosphatase (AP) isoenzymes were separated semiquantitatively using a combination of L-phenylalanine inhibition and heat inactivation. Though mean total serum AP activity was significantly increased compared to age matched controls, only 4 individual values exceeded the upper limit (mean + 2SD) of the reference sample. In epileptics the mean activity of the heat-sensitive non L-phenylalanine sensitive AP fraction (non-LPSAP) was significantly increased (P less than 0.01) and the mean Q-value (i.e. percentage ratio of heat-stable non-LPSAP/non-LPSAP) was significantly decreased (P less than 0.05), thus indicating an enhancement of the bone isoenzymes during anticonvulsant treatment. In 4 patients the isoenzyme pattern was abnormal although total serum AP activity was normal and in 3 of them the deviation indicated enhanced bone isoenzyme. The data provide evidence that in anticonvulsant treated children the bone isoenzyme, rather than hepatobiliary isoenzyme fraction, may be increased even when total serum AP activity is normal. Thus, semiquantitative separation of serum AP isoenzymes may be a helpful guide as to whether or not an eplieptic child should be given vitamin D.

Serum alkaline phosphatase isoenzymes in childhood.

Using a combination of L-phenylalanine inhibition and heat inactivation, the serum alkaline phosphatase (AP) in 2 to 13 year old children without evidence of hepatobiliary, osseous, or intestinal disease was separated in three fractions; i.e. L-phenylalanine sensitive AP (LPSAP), heat-stable non-L-phenylalanine sensitive AP (heat-stable non-LPSAP) and heat sensitive non-L-phenylalanine sensitive AP (heat-sensitive non-LPSAP). The activities of total AP and the different fractions were measured using optimized test conditions. LPSAP, (mainly intestinal AP), accounts for approximately 12% of the total serum AP activity, heat-stable non-LPSAP (mainly hepatobiliary AP) for approximately 9%, and heat-sensitive non-LPSAP (mainly bone AP) for approximately 77%. To give a better differentiation between bone and liver AP, the percentage ratios of heat-stable non-LPSAP/non-LPSAP (Q value), and heat-stable non-LPSAP/total AP, were determined. Both quotients showed a significant negative correlation with total AP, which has to be taken into account in the interpretation of the results of isoenzyme determinations of serum AP activity. The above semiquantitative separation of AP isoenzymes can be readily done in a routine clinical laboratory.

Serum gamma glutamyl transferase and alkaline phosphatase activities in epileptics receiving anticonvulsant therapy

1. 1. Serum gamma glutamyl transferase (γGT) and alkaline phosphatase (ALP) activities have been estimated in 49 epileptic patients taking anticonvulsant drugs. 2. 2. Serum γGT activity was clearly elevated in 12 of the patients and borderline in 8, giving a 40% frequency of abnormal values. 3. 3. Total serum ALP activity was elevated in 7 out of 33 adult patients and 2 of 16 juveniles. 4. 4. Electrophoresis on polyacrylamide gel showed that the bone isoenzyme was responsible for most of the increased serum ALP activity and that even when the total was not elevated, the contribution of the bone isoenzyme was greater than normal. 5. 5. There was no correlation between total serum ALP and γGT activities but elevations of serum γGT were often accompanied by an increase in the proportion of the bone enzyme in the total serum ALP activity.

Radioimmunoassay of procollagen in serum of patients with Paget's disease of bone.

A new radioimmunoassay for human procollagen showed that the sera of 46 of 50 untreated patients with Paget's disease of bone contained increased concentrations of procollagen protein as compared to normal adults. After therapy with disodium etidronate, all the elevated serum procollagen concentrations decreased significantly, falling to normal levels in 33 of 40 patients. The procollagen levels before and after treatment were coordinate with the values for urinary total hydroxyproline and serum alkaline phosphatase activity. The data show that the radioimmunoassay for procollagen is a dependable and useful adjunct to the study of Paget's disease of bone.

Variations in total serum alkaline phosphatase activity with age and sex in adult and adolescent ghanaians

Variations in the mean serum alkaline phosphatase activity with age and sex in 500 healthy Ghanaians aged 16 to 80 years have been studied. The values are on the whole higher in males than females. The highest levels in both sexes are found in adolescence. After the age of 20 years in both sexes, there is a fall in the mean serum alkaline phosphatase level which tends to rise again after the age of 40 years in females and 50 years in males.