Measurement Of Serum Alkaline Phosphatase Research Articles

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis.

To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

Multiple Forms of Human Serum Alkaline Phosphatase: Detection and Quantitation

The measurement of serum alkaline phosphatase (EC 3.1.3.1 ALP) has been popular in clinical practice for over 50 years despite a limited knowledge of the structure, function and pathophysiology of this enzyme family. The existence of multiple forms of the enzyme has provided a great deal of opportunity for research and this has helped to refine ideas on the clinical utility of measurement of the enzymes in serum as well as to elucidate their structure and function. 1,2

Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy

It is known that many patients with osteosarcoma have high serum alkaline phosphatase (SAP) levels. The prognostic significance of this finding, however, is still controversial. The pretreatment SAP levels of 656 patients with osteosarcoma of the extremities (107 metastatic and 549 localized at presentation) were examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients with increased SAP levels was significantly higher in the metastatic group than in the group of patients with localized disease (91.5% versus 61.3%; P < 0.001). In the latter group, treated with adjuvant and neoadjuvant chemotherapy, the relapse rate was significantly higher in patients with elevated pretreatment SAP levels than in those with normal levels (55.1% versus 26.4%; P < 0.001). Among patients with elevated SAP levels, the percentage of relapses was higher in patients with high levels of the enzyme in comparison with patients with moderately elevated values (66.4% versus 47%; P < 0.05). After treatment, SAP levels almost always return to normal values, and a correlation between postoperative levels of the enzyme and prognosis could not be made. These data demonstrate that in osteosarcoma of the extremities, pretreatment SAP levels have a prognostic value and they should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.

Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study.

Bisphosphonates have been shown to be effective agents in the treatment of postmenopausal osteoporosis. Because corticosteroid associated osteoporosis is often associated with increased bone turnover, the effect of intermittent intravenous infusions of pamidronate on this condition has been investigated. Seventeen patients (five male) with chronic corticosteroid dependent lung disease (15 asthma, two sarcoidosis) were treated with infusions of 30 mg pamidronate once every three months for one year. These patients had been taking an average of 14 (range 7.5-40) mg prednisolone a day for an average of 14 (range 3-30) years. Bone density measurements, by dual energy x ray absorptiometry, and radiography of the dorsolumbar spine were carried out before and one year after treatment. Bone formation was assessed by measurement of serum alkaline phosphatase and bone resorption by measurement of the fasting urinary hydroxyproline: creatinine ratio at the same time as densitometry and radiography were performed. Pretreatment density of L2-4 and the neck of the femur was significantly lower in these patients compared with a cohort of 100 age and sex matched controls (L2-4 (mean (SEM)): 0.906 (0.050) g/cm2 v 1.142 (0.016) g/cm2; neck of femur: 0.793 (0.030) g/cm2 v 0.936 (0.013)) g/cm2. After treatment there was a significant fall in serum alkaline phosphatase activity from (mean (SEM)) 220 (16) U/1 to 174 (9) U/1 (normal 80-280 U/1) and in the fasting urinary hydroxyproline:creatinine ratio from (mean (SEM) 0.040 (0.006) to 0.024 (0.003) (normal < 0.033). A significant rise was noted in L2-4 density to 0.927 (0.047) g/cm2; mean rise of 3.4%). No change was noted in density of the neck of the femur. Intermittent infusions of intravenous pamidronate would seem to be effective in both reducing turnover of bone and increasing bone density in corticosteroid induced osteoporosis associated with chronic lung disease. Longer term controlled studies are indicated.

Simplified measurement of serum alkaline phosphatase utilizing electrochemical detection of 4-aminophenol

Alkaline phosphatase is determined amperometrically using a simple two-electrode system; results are presented as a kinetic increase in electroactive product. Of the substrates investigated, 4-aminophenyl phosphate gives rise to the optimum signal against background interference in serum. The results are correlated with a routine spectrophotometric assay. The final method is unaffected by interfernce or fouling problems, with electrodes covered by either a non-selective dialysis membrane or a selective cellulose acetate membrane. Diffusion through both membranes is sufficiently fast for following the kinetic response.

Liver Function Tests Abnormalities in Patients with Inflammatory Bowel Disease Receiving Artificial Nutrition: A Prospective Randomized Study of Total Enteral Nutrition vs Total Parenteral Nutrition

Liver and biliary abnormalities are well-known complications of inflammatory bowel disease (IBD). It has been suggested that using total parenteral nutrition (TPN) may further impair liver function in these patients; this seems not to be so with total enteral nutrition (TEN). However, prospective trials comparing the incidence of liver function test (LFT) abnormalities with either TPN or TEN have not been carried out. Twenty-nine IBD inpatients with normal LFT, randomized to receive either TEN with a polymeric diet or isocaloric, isonitrogenous "all-in-one" TPN because of protein-energy malnutrition and/or severe disease, were included in the study. Sixteen patients (five with ulcerative colitis and 11 with Crohn's disease) received TEN, and 13 patients (eight ulcerative colitis and five Crohn's disease) were on TPN. All patients were on systemic steroids, and nine of them were on oral metronidazole. Both groups were homogeneous regarding age, sex, diagnosis, disease activity, nutritional status, daily nutrient supply, and days on artificial nutrition. Serum albumin levels significantly increased with TEN (32 +/- 1 to 38.2 +/- 1.6 g/liter, p less than 0.01), but not with TPN (32.1 +/- 2.2 to 33.9 +/- 1.4 g/liter, NS). Clinical improvement occurred in both groups of patients as shown by the change in the disease activity indexes. In all cases, measurements of serum alkaline phosphatase, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase were performed weekly. There were no significant differences in the initial LFT between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in Liver Function Tests in Patients with Inflammatory Bowel Disease on Enteral Nutrition

Morphologic and functional hepatic changes occur in inflammatory bowel disease (IBD). Patients with this disease often require the administration of artificial nutritional support. Liver function tests (LFT) derangement is a widely recognized side-effect of total parenteral nutrition (TPN). Therefore, the use of this modality of nutritional support may be an additional factor to cause hepatic damage in IBD patients. However whether or not the same occurs in patients receiving total enteral nutrition (TEN) is not well-established. The aim of the present study was to evaluate the effect of TEN upon LFT in patients with moderate to severe acute attacks of IBD, by means of a prospective, controlled, and nonrandomized design. Forty-nine patients were included; 29 (11 patients with ulcerative colitis and 18 with Crohn's disease) received TEN, and 20 (11 with ulcerative colitis and 9 with Crohn's disease) did not. Both groups were homogeneous regarding age, sex, disease activity index, nutritional status, and length of the study (24.8 +/- 1.3 vs 23.9 +/- 16.8 days). In all cases, weekly measurements of serum alkaline phosphatase, GOT, and GPT were performed. There were no significant differences in LFT at the beginning of the study between groups. The percentage of patients showing derangement of some LFT during the study did not differ between both groups: six of 29 (20.6%) in TEN group vs three of 20 (15%) in control group. Six out of the nine patients (in both groups) who developed LFT derangement had one or more causes, other than TEN for explaining hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

51Cr-EDTA/99Tcm-MDP ratio: a simple non-invasive method for assessing renal osteodystrophy

We have used 99Tcm-MDP to develop a measure of overall skeletal activity for use in renal disease. The method utilizes the relative clearances of 99Tcm-MDP and 51Cr-EDTA from the blood after simultaneous injection. This is expressed as a ratio and the upper limit in normals is 1.4. This ratio has been evaluated in 42 patients with chronic renal failure and compared with appearances of left-hand radiographs. The ratio was elevated in these patients and the level corresponded to the degree of severity of the subperiosteal resorption. Similarly, there was a close correlation between the ratio values and the serum alkaline phosphatase measurements and parathyroid hormone values. Thirty-three patients had sequential studies performed at intervals of up to 2 years. Twenty-one patients showed no change on clinical, biochemical or bone scan evaluation. Of these, only one patient showed a change in ratio value of greater than 20%. Twelve patients showed evidence of change based either on clinical, biochemical or bone scan alteration and all 12 patients showed changes in ratio values greater than 20%. The 51Cr-EDTA/99Tcm-MDP ratio appears to offer not only a single plasma sample method for the detection and evaluation of renal bone disease, but our results also suggest that it may be valuable in the follow-up of these patients.

Non-invasive evaluation of bone formation: Measurements of serum alkaline phosphatase, whole body retention of diphosphonate and serum osteocalcin in metabolic bone disorders and thyroid disease

Non-invasive evaluation of bone formation: Measurements of serum alkaline phosphatase, whole body retention of diphosphonate and serum osteocalcin in metabolic bone disorders and thyroid disease

Non-invasive evaluation of bone formation: Measurements of serum alkaline phosphatase, whole body retention of diphosphonate and serum osteocalcin in metabolic bone disorders and thyroid disease

Three noninvasive indices of bone formation, serum alkaline phosphatase (s-AP), 24-h whole body retention of diphosphonate (WBR), and serum osteocalcin (s-OC), the two lastnamed clearance-corrected, were compared in 121 patients with various bone disorders and in 50 patients with thyroid disease. In conditions with qualitatively normal matrix formation and mineralization, i.e. thyrotoxicosis, primary hyperparathyroidism, myxoedema and osteoporosis, the three indices deviated from average normal by about the same extent: 134%/128%/200%, 120%/113%/133%, 105%/100%/79% and 89%/86%/69%, respectively. A disproportionately marked deviation of s-AP was observed in states of abnormal matrix formation or mineralization, i.e. osteomalacia and Paget's disease: 430%/145%/282% and 348%/145%/202%, respectively. Furthermore, the formation indices correlate differently with s-calcium in hyper- and hypocalcaemic conditions. In primary hyperparathyroidism the respective r-values were 0.32/0.62/0.68, while an inverse pattern was observed in osteomalacia: -0.60/-0.51/-0.47. As very little is known about the secretion of AP and OC and their role in bone formation and mineralization, the cause(s) for the observed differences remain(s) uncertain.

Calcium intake and bone density of lactating women in their late childbearing years

Researchers have shown through epidemiological surveys that osteoporosis results in hip, vertebra, or long bone fractures in at least 10% of women over 50 years of age. The primary objective of this study was to determine calcium intake and bone mineral content in lactating women in their later childbearing years. Eight lactating women over 37 years of age were compared with eight nulliparous women to determine differences in dietary intake of energy, protein, vitamin D, calcium, and phosphorus. Anthropometric measurements, bone density measurements, serum calcium, serum phosphate, and serum alkaline phosphatase measurements were made at 2 weeks and 6 weeks postpartum. Intakes of protein, vitamin D, and calcium were significantly lower in the diets of control women. No significant differences were found in biochemical analysis (except for a significantly lower serum phosphorus in the control group of women), bone density, nutrition assessment, or physical assessment between lactating and control groups. Thus, when dietary calcium intake is greater than the RDA for lactating women, bone mineral content is not affected during the first 6 weeks of lactation.

Seasonal variations in indices of bone formation precede appropriate bone mineral changes in normal men

In 10 normal males aged 23–50 years measurements of serum alkaline phosphatase (s-AP) and the 24-h whole body retention of 99mTc-diphosphonate (WBR), as indices of bone formation, and the fasting urinary hydroxyproline: creatinine ratio (OHPr:Cr), as an index of bone resorption, were performed monthly from January 1983 to May 1984. Bone mineral content of the distal forearm (BMC) was measured in the middle of each quarter. From January to May BMC exhibited a reproducible, significant average increase of 2.5%, returning to baseline level between May and August. During the first quarter of both 1983 and 1984 a significant increase in s-AP and WBR was seen. Subsequently, during the second quarter of 1983, these variables fell below the mean of the year. Confirming their interrelationship, the deviations of s-AP and WBR were positively correlated throughout the study period ( r = 0.51, P < 0.05). Since the urinary OHPr:Cr ratio remained constant, the reported seasonal changes in bone mass of normal, adult males appear to result from primary changes in bone formation.

Changes in plasma bone GLA protein during treatment of bone disease.

Bone Gla protein (BGP) was measured in the plasma by radioimmunoassay (RIA) during treatment of 59 patients with bone diseases including Paget's disease (N = 9), primary hyperparathyroidism (N = 25), chronic renal failure (N = 20), and cancer involving bone (N = 5). Plasma BGP was increased above normal in all patients. BGP decreased in the patients with Paget's disease following the acute and chronic administration of salmon calcitonin. Plasma BGP was higher in women then in men with primary hyperparathyroidism. Following parathyroidectomy, BGP decreased in both sexes but the decrease was significant in women only. Plasma BGP was increased in patients with renal osteodystrophy and did not change after hemodialysis. In the patients with bone cancer, plasma BGP decreased during treatment of the attendant hypercalcemia with salmon calcitonin. Although plasma BGP and serum alkaline phosphatase (AP) levels were generally correlated in these studies, there were examples of dissociation between the two. The measurement of plasma BGP appears to provide a specific index of bone metabolism that may in some circumstances be more sensitive than serum alkaline phosphatase measurement. However, further studies are necessary to establish the clinical value of plasma BGP measurement by RIA in the management of patients with bone diseases.

The Measurement of Serum Alkaline Phosphatase in Clinical Medicine

Publisher Summary The measurement of alkaline phosphatase in serum or plasma constitutes one of the most widely employed tests in the clinical chemistry laboratory. Serum alkaline phosphatase measurements continue to be widely used in clinical medicine. The test is relatively easy to perform, its cost is low, and a high degree of precision is readily achievable. As long as the results (especially normal results) are not overinterpreted, serum alkaline phosphatase can continue to have a place in the diagnostic work-up of many clinical problems. A delay of 1–2 hours between venepuncture and blood centrifugation does not influence serum alkaline phosphatase values. Prolonged standing “on the clot” causes minor rises. The effect of freezing and thawing must be distinguished from the effect of storage at freezing temperatures. Serum alkaline phosphatase seems stable for long periods when frozen. There are now many studies that demonstrate sex- and age-related differences in serum alkaline phosphatase activities in adults, although the age-related changes are much less marked than those observed in children. An age-related increase in serum alkaline phosphatase values has been demonstrated in both sexes. The chapter discusses several disorders such as familial hperphosphatasemia, familial hpophosphatasia, benign bony tumors, eosinophilic granuloma, islet cell tumors, and endocrine disorders in context to serum alkaline phosphatase activities in the body.

Monitoring of murine osteosarcoma by serial alkaline phosphatase determinations.

To establish that alkaline phosphatase (AP) was released by osteosarcoma cells, we measured this enzyme in C3H/HeJ mice with im-implanted osteosarcoma and in in vitro cultures of neoplastic cells subjected to short-term incubation. We found that 10(5) osteosarcoma cells synthesized a significant amount of AP in vitro in 30 minutes at 37 degrees C. A good correlation existed between pulmonary metastatic tumors and the AP values. Serum AP measurements indicated approximate sizes of disseminated and localized tumors, but could not monitor early localized tumors.

Evaluation of a New System For the Kinetic Measurement of Serum Alkaline Phosphatase

Abstract Data are presented from the study of a new systematized, kinetic method for the determination of alkaline phosphatase* which was run concurrently in three geographically separated laboratories. The data include estimates of within-day and day-to-day precision, and laboratory-to-laboratory reproducibility. Comparisons are made with three other alkaline phosphatase procedures. An estimated range of normal values is given for adult males and females.

Rapid Method for the Quantitative Determination of Serum Alkaline Phosphatase

Abstract A new procedure is described for the simple, rapid, quantitative measurement of serum alkaline phosphatase. The procedure is based on the direct photometric measurement of phenolphthalein released from sodium phenolphthalein phosphate. The substrate is available in a convenient, stabilized form as a tablet containing buffer and substrate in optimum amounts for a single analysis. As many as 30 analyses can be performed in an hour.