title: Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis.
abstract: BACKGROUND
  The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial.
  
  
  METHODS
  Cross-sectional retrospective diagnostic test study.
  
  
  METHODS
  492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20 °C) serum.
  
  
  METHODS
  Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP).
  
  
  METHODS
  Bone histomorphometric assessment of turnover (bone formation rate/bone surface [BFR/BS]) and receiver operating characteristic curves for discriminating diagnostic ability.
  
  
  RESULTS
  The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve > 0.70 but < 0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was <103.8 pg/mL, and to discriminate high from nonhigh BFR/BS was >323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was <33.1 U/L, and for high from nonhigh BFR/BS, 42.1U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively.
  
  
  CONCLUSIONS
  Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries.
  
  
  CONCLUSIONS
  The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions.
authors: NorthShore University HealthSystem, University of Chicago, Evanston, IL. Electronic address: stuartmsprague@gmail.com.
authors: Stuart M
authors: SM
authors: Sprague
authors: University Hospital of Caracas, Caracas, Venezuela.
authors: Ezequiel
authors: E
authors: Bellorin-Font
authors: University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Vanda
authors: V
authors: Jorgetti
authors: Federal University of São Paulo, São Paulo, Brazil.
authors: Aluizio B
authors: AB
authors: Carvalho
authors: University of Kentucky Medical Center, Lexington, KY.
authors: Hartmut H
authors: HH
authors: Malluche
authors: Hospital Curry Cabral, Faculdade de Ciências Médicas-Universidade Nova de Lisboa, Lisbon, Portugal.
authors: Aníbal
authors: A
authors: Ferreira
authors: University of Antwerp, Antwerp, Belgium.
authors: Patrick C
authors: PC
authors: D'Haese
authors: Inserm U 1088, UFR Médecine/Pharmacie, UPJV, Amiens, France.
authors: Tilman B
authors: TB
authors: Drüeke
authors: NorthShore University HealthSystem, University of Chicago, Evanston, IL.
authors: Hongyan
authors: H
authors: Du
authors: National Kidney Foundation, New York, NY.
authors: Thomas
authors: T
authors: Manley
authors: University Hospital of Caracas, Caracas, Venezuela.
authors: Eudocia
authors: E
authors: Rojas
authors: Indiana University School of Medicine and Roudebush Veterans Administration Hospital, Indianapolis, IN.
authors: Sharon M
authors: SM
authors: Moe
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000473:pathology*; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D000469:Alkaline Phosphatase
keywords: BSAP); Sensitivity and specificity; alkaline phosphatases; bone histomorphometry; bone-specific alkaline phosphatase (bALP; chronic kidney disease–mineral bone disorder (CKD-MBD); parathyroid hormone (PTH); procollagen type 1 N propeptide (P1NP); renal osteodystrophy