title: Bone alkaline phosphatase isoforms in hemodialysis patients with low versus non-low bone turnover: a diagnostic test study.
abstract: BACKGROUND
  Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (bALP) isoform B1x is exclusively found in serum of some patients with CKD.
  
  
  METHODS
  The aim of this cross-sectional diagnostic test study was to examine the relationship between serum bALP isoform activity and histomorphometric parameters of bone in patients with CKD receiving maintenance hemodialysis.
  
  
  METHODS
  Anterior iliac crest bone biopsy samples from 40 patients with CKD were selected on the basis of bone turnover for histomorphometric analysis. There were samples from 20 patients with low and 20 with non-low bone turnover.
  
  
  METHODS
  In serum, bALP, bALP isoforms (B/I, B1x, B1, and B2), and parathyroid hormone (PTH) were measured.
  
  
  METHODS
  Low bone turnover was defined by mineral apposition rate < 0.36μm/d. Non-low bone turnover was defined by mineral apposition rate ≥ 0.36μm/d.
  
  
  METHODS
  PTH.
  
  
  RESULTS
  B1x was found in 21 patients (53%) who had lower median levels of bALP, 18.6 versus 46.9U/L; B/I, 0.10 versus 0.22 μkat/L; B1, 0.40 versus 0.88 μkat/L; B2, 1.21 versus 2.66 μkat/L; and PTH, 49 versus 287pg/mL, compared with patients without B1x (P<0.001). 13 patients (65%) with low bone turnover and 8 patients (40%) with non-low bone turnover (P<0.2) had detectable B1x. B1x correlated inversely with histomorphometric parameters of bone turnover. Receiver operating characteristic curves showed that B1x can be used for the diagnosis of low bone turnover (area under the curve [AUC], 0.83), whereas bALP (AUC, 0.89) and PTH (AUC, 0.85) are useful for the diagnosis of non-low bone turnover.
  
  
  CONCLUSIONS
  Small number of study participants. Requirement of high-performance liquid chromatography methods for measurement of B1x.
  
  
  CONCLUSIONS
  B1x, PTH, and bALP have similar diagnostic accuracy in distinguishing low from non-low bone turnover. The presence of B1x is diagnostic of low bone turnover, whereas elevated bALP and PTH levels are useful for the diagnosis of non-low bone turnover.
authors.affiliation: Department of Clinical Chemistry, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: mathias.loberg-haarhaus@karolinska.se.
authors.forename: Mathias
authors.initials: M
authors.lastname: Haarhaus
authors.affiliation: Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Albert B. Chandler Medical Center, Lexington, KY.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Monier-Faugere
authors.affiliation: Department of Clinical Chemistry, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Magnusson
authors.affiliation: Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Albert B. Chandler Medical Center, Lexington, KY. Electronic address: hhmall@uky.edu.
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers; D001706:Biopsy; D001862:Bone Resorption / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007085:Ilium / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D020033:Protein Isoforms / Q000097:blood; D012372:ROC Curve; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D020033:Protein Isoforms; D000469:Alkaline Phosphatase
keywords: B/I, B1x, B1, B2; Bone-specific alkaline phosphatase (bALP); bALP isoforms; bone histology; diagnostic test study; end-stage renal disease (ESRD); hemodialysis; low bone turnover; mineral apposition rate; parathyroid hormone (PTH); renal osteodystrophy
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