Bone Alkaline Phosphatase Isoforms in Hemodialysis Patients With Low Versus Non-Low Bone Turnover: A Diagnostic Test Study

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.

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The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease

Nutrients ◽

10.3390/nu13124402 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4402

Author(s):

Mathias Haarhaus ◽

Anders Fernström ◽

Abdul Rashid Qureshi ◽

Per Magnusson

Keyword(s):

Chronic Kidney Disease ◽

Alkaline Phosphatase ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Bone Turnover ◽

Aortic Pulse Wave Velocity ◽

Bone Alkaline Phosphatase ◽

Protein Energy Wasting ◽

Wasting Syndrome ◽

Low Bone Turnover

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

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Parathormone and bone-specific alkaline phosphatase for the follow-up of bone turnover in hemodialysis patients: Is it so simple?

Clinica Chimica Acta ◽

10.1016/j.cca.2012.12.009 ◽

2013 ◽

Vol 417 ◽

pp. 35-38 ◽

Cited By ~ 6

Author(s):

Pierre Delanaye ◽

Bernard E. Dubois ◽

François Jouret ◽

Jean-Marie Krzesinski ◽

Olivier Moranne ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Bone Turnover ◽

Hemodialysis Patients ◽

Specific Alkaline Phosphatase ◽

Bone Specific Alkaline Phosphatase

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A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone

Head & Face Medicine ◽

10.1186/s13005-020-00249-9 ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Henning Staedt ◽

Michael Dau ◽

Eik Schiegnitz ◽

Daniel G. E. Thiem ◽

Olga Tagadiuc ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Acid Phosphatase ◽

Bone Turnover ◽

Bone Substitute ◽

Bone Alkaline Phosphatase ◽

Collagen Membrane ◽

Bovine Bone ◽

Total Acid ◽

Turnover Markers

Abstract Background The aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo. Methods Eight weeks after formation of a lateral full-thickness perforating bone defect in the mandible of 40 rabbits, bovine bone substitute with (“+”;n = 20) and without (“-”;n = 20) collagen membrane was applied. Blood and bone was collected 24, 72 h, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points. Results Twenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in “+” group when compared to “-” (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in “+” (all p < 0.05). Fourteen days after surgery, the significant highest values for all bone turnover markers were detected in “-” (all p < 0.05). A significant difference in favor of group “-” could also be detected after 3 weeks in terms of both acid phosphatases (p < 0.05). In histology, no significant differences could be detected. Conclusion Bone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.

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Differential Patterns of Bone Turnover in Relation to Bone Pain and Disease Extent in Bone in Cancer Patients with Skeletal Metastases

Clinical Chemistry ◽

10.1093/clinchem/45.8.1240 ◽

1999 ◽

Vol 45 (8) ◽

pp. 1240-1247 ◽

Cited By ~ 80

Author(s):

Alfredo Berruti ◽

Luigi Dogliotti ◽

Gabriella Gorzegno ◽

Mirella Torta ◽

Marco Tampellini ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Bone Turnover ◽

Urinary Excretion ◽

Bone Metastases ◽

Primary Tumor ◽

Bone Pain ◽

Bone Alkaline Phosphatase ◽

Skeletal Metastases ◽

Disease Extent ◽

Tumor Types

Abstract Background: The alteration of the bone microenvironment as a consequence of skeletal metastases is poorly understood. The aim of this study was to search for patterns of bone markers in relation to primary tumor type, bone pain, and number of sites involved in patients with bone metastases. Methods: We studied 323 patients with bone metastases from various primary malignancies. We sequentially measured the serum concentrations of bone alkaline phosphatase [by an electrophoretic technique (BALP)], carboxy-terminal telopeptide of type I collagen (ICTP), calcium (CaS), intact parathyroid hormone (PTH), and the fasting urinary excretion of calcium (Ca:Cr). Immunoradiometric serum bone alkaline phosphatase (I-BALP) and urinary excretion of deoxypyridinoline (DPYD) were also assessed in the 175 cases. Data were analyzed as a function of bone pain (assessed by a validated pain questionnaire), the number of radiographically confirmed sites of bone involvement, and the most frequent primary tumor types: breast cancer (BC; 124 patients), prostate cancer (PC; 90 patients), and non-small cell lung cancer (LC; 49 patients). Results: Serum BALP and I-BALP correlated with the number of radiologically identified blastic bone lesions. BALP and I-BALP were more frequently increased in PC (72% for both measurements) than in BC (50% and 60%, respectively) or LC (3% and 5%, respectively; P <0.001 for BALP and P = 0.001 for I-BALP). ICTP and DPYD values did not differ among PC, BC, and LC, but they did show a direct relationship with the disease extent in bone (P <0.001). CaS and Ca:Cr did not vary significantly according to the bone tumor burden. Bone pain directly correlated with ICTP (P <0.001), DPYD (P = 0.002), CaS (P <0.002), and Ca:Cr (P = 0.001), whereas the relationship was inverse for serum PTH (P = 0.002). When patients were stratified according to the primary tumor, ICTP correlated with the bone pain in all subsets (P <0.005, <0.005, and <0.001 for BC, PC, and LC, respectively), as did CaS and Ca:Cr in LC patients (P = 0.01 and 0.02, respectively) but not in PC and BC patients. Conclusions: The patterns of bone turnover markers differ among the primary tumor types. Both resorption and formation markers reflect the number of radiographically identified sites of bone metastases, whereas resorption markers and serum calcium but not formation markers correlate with bone pain.

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Effect of chronic renal failure on bone turnover and bone alkaline phosphatase isoforms

Kidney International ◽

10.1046/j.1523-1755.2001.00794.x ◽

2001 ◽

Vol 60 (1) ◽

pp. 257-265 ◽

Cited By ~ 60

Author(s):

Per Magnusson ◽

Christopher A. Sharp ◽

Martin Magnusson ◽

Juha Risteli ◽

Michael W.J. Davie ◽

...

Keyword(s):

Renal Failure ◽

Alkaline Phosphatase ◽

Chronic Renal Failure ◽

Bone Turnover ◽

Bone Alkaline Phosphatase

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Is it possible to predict a risk of osteoporosis in patients with juvenile idiopathic arthritis? A study of serum levels of markers of bone turnover

Acta Biochimica Polonica ◽

10.18388/abp.2017_2561 ◽

2018 ◽

Vol 65 (2) ◽

pp. 297-302 ◽

Cited By ~ 1

Author(s):

Marta Janicka-Szczepaniak ◽

Krzysztof Orczyk ◽

Katarzyna Szymbor ◽

Danuta Chlebna-Sokół ◽

Elzbieta Smolewska

Keyword(s):

Alkaline Phosphatase ◽

Juvenile Idiopathic Arthritis ◽

Bone Turnover ◽

Fracture Risk ◽

Serum Levels ◽

Bone Alkaline Phosphatase ◽

Common Finding ◽

Treatment Needs ◽

Mineral Density ◽

Markers Of Bone Turnover

Background: Low bone mineral density is a common finding in children with systemic connective tissue diseases, including juvenile idiopathic arthritis (JIA). The influence of the ongoing process of bone remodeling on the disease course merits further investigation. The aim of the study was to assess the clinical relevance of markers of bone turnover and their potential role as predictors of higher fracture risk and, by extension, risk of osteoporosis.Materials and methods: Blood samples were collected from 59 patients diagnosed with JIA in order to determine serum levels of the following markers of bone turnover: Beta-Crosslaps, osteocalcin, bone alkaline phosphatase, osteoprotegerin and receptor activator for nuclear factor kappa-B ligand. The values were analyzed with laboratory parameters and results of dual X-ray absorptiometry (DXA).Results: Osteoprotegerin and bone alkaline phosphatase levels were age-dependent. Beta‑Crosslaps values were significantly higher in patients with positive JADAS27 score (p=0.0410). Osteoprotegerin levels were higher in patients treated with biological agentsthan only withdisease-modifying anti-rheumatic drugs (p=0.0273). There was no relation between markers of bone turnover and sex, DXA results, dosage of glucocorticosteroids and disease duration.Conclusions:Authors postulate performing DXA measurements every 6 months in patients with higher disease activity. The potential lower fracture risk in children with JIA within biological treatment needs future assessment. Age- and sex-adjusted reference rates of markers of bone turnover for Central Europe need to be developed in order to assess individual values properly.

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A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone

10.21203/rs.3.rs-48773/v3 ◽

2020 ◽

Author(s):

Henning Staedt ◽

Michael Dau ◽

Eik Schiegnitz ◽

Daniel G.E. Thiem ◽

Olga Tagadiuc ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Acid Phosphatase ◽

Bone Turnover ◽

Bone Substitute ◽

Bone Alkaline Phosphatase ◽

Collagen Membrane ◽

Bovine Bone ◽

Total Acid ◽

Turnover Markers

Abstract Background: The aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo. Methods: Eight weeks after formation of a lateral full-thickness perforating bone defect in the mandible of 40 rabbits, bovine bone substitute with (“+”;n=20) and without (“-“;n=20) collagen membrane was applied. Blood and bone was collected 24, 72 hours, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points.Results: Twenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in “+” group when compared to “-“ (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in “+” (all p<0.05). 14 days after surgery, the significant highest values for all bone turnover markers were detected in “-“ (all p<0.05). A significant difference in favor of group “-“ could also be detected after 3 weeks in terms of both acid phosphatases (p<0.05). In histology, no significant differences could be detected.Conclusion: Bone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.

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Comparison between bone alkaline phosphatase immunoassay and electrophoresis technique in hemodialysis patients

Journal of Medical Biochemistry ◽

10.2478/jomb-2019-0048 ◽

2019 ◽

Vol 0 (0) ◽

Author(s):

Neda Milinković ◽

Marija Sarić Matutinović ◽

Svetlana Pejanović ◽

Svetlana Ignjatović

Keyword(s):

Alkaline Phosphatase ◽

Bone Alkaline Phosphatase ◽

Hemodialysis Patients ◽

Cusum Test ◽

Agar Gel ◽

Agar Gel Electrophoresis ◽

Automated Methods ◽

Electrophoresis Technique ◽

Total Alkaline ◽

Good Agreement

Summary Background Problem of the variability between the different methods using for bone alkaline phosphatase (bALP) determination greately influences the clinical significance of bALP as direct marker of bone metabolism. The aim of this study was to compare immunoassay with electrophoresis technique for bALP determination. Methods We measured bALP in 71 patients on hemodialysis with agar gel electrophoresis (ISO-PAL, SEBIA) and immunoassay (OSTASE, Beckman Coulter). Results The analyzed methods showed significant correlation (Spearman’s rho: 0.776, P < 0.01), but we found statistically significant (P < 0.01) positive bias (27%) for the results measured by immunoassay. In support of this, using electrophoresis technique we have detected presence of the intestinal isoenzymes of alkaline phosphatase in 55% of patients with median value of 30% of the total alkaline phoshatase and presence of liver-2 alkaline phosphatase isoform in 42% of patients with median value of 16.6%. The Kendall’s W of 0.787 (P<0.0001) revealed significant concordance between two analysed methods. Cusum test showed no significant deviation from linearity (P=0.850). Conclusions Despite good agreement between immunoassay methods and electrophoresis technique for bALP determination, interchangeability between these two methods is questionable. Although immunoassays are increasingly used, as fully automated methods, in a large number of laboratories and become routine methods for bALP determination, it should be beared in mind, besides various interferences, also the heterogeneity of the bALP itself, especially in patients on hemodialysis.

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