Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis

Stuart M. Sprague, Ezequiel Bellorin-Font, Vanda Jorgetti, Aluizio B. Carvalho, Hartmut H. Malluche, Aníbal Ferreira, Patrick C. D'Haese, Tilman B. Drüeke, Hongyan Du, Thomas Manley, Eudocia Rojas, Sharon Moe

Research output: Contribution to journalArticle

75 Citations (Scopus)

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. Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20°C) serum. Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test: 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, 42.1. U/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. Limitations: 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.

Original languageEnglish
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jun 6 2014

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Bone Remodeling
Dialysis
Histology
Bone and Bones
Osteogenesis
Parathyroid Hormone
Alkaline Phosphatase
Biomarkers
ROC Curve
Chronic Kidney Disease-Mineral and Bone Disorder
Venezuela
Portugal
Bone Diseases
Collagen Type I
Turkey
Serum
Practice Guidelines
Routine Diagnostic Tests
Brazil
Cross-Sectional Studies

Keywords

  • Alkaline phosphatases
  • Bone histomorphometry
  • Bone-specific alkaline phosphatase (bALP
  • BSAP)
  • Chronic kidney disease-mineral bone disorder (CKD-MBD)
  • Parathyroid hormone (PTH)
  • Procollagen type 1 N propeptide (P1NP)
  • Renal osteodystrophy
  • Sensitivity and specificity

ASJC Scopus subject areas

  • Nephrology

Cite this

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis. / Sprague, Stuart M.; Bellorin-Font, Ezequiel; Jorgetti, Vanda; Carvalho, Aluizio B.; Malluche, Hartmut H.; Ferreira, Aníbal; D'Haese, Patrick C.; Drüeke, Tilman B.; Du, Hongyan; Manley, Thomas; Rojas, Eudocia; Moe, Sharon.

In: American Journal of Kidney Diseases, 06.06.2014.

Research output: Contribution to journalArticle

Sprague, SM, Bellorin-Font, E, Jorgetti, V, Carvalho, AB, Malluche, HH, Ferreira, A, D'Haese, PC, Drüeke, TB, Du, H, Manley, T, Rojas, E & Moe, S 2014, 'Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis', American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2015.06.023
Sprague, Stuart M. ; Bellorin-Font, Ezequiel ; Jorgetti, Vanda ; Carvalho, Aluizio B. ; Malluche, Hartmut H. ; Ferreira, Aníbal ; D'Haese, Patrick C. ; Drüeke, Tilman B. ; Du, Hongyan ; Manley, Thomas ; Rojas, Eudocia ; Moe, Sharon. / Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis. In: American Journal of Kidney Diseases. 2014.
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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. Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20°C) serum. Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test: 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, 42.1. U/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. Limitations: 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.",
keywords = "Alkaline phosphatases, Bone histomorphometry, Bone-specific alkaline phosphatase (bALP, BSAP), Chronic kidney disease-mineral bone disorder (CKD-MBD), Parathyroid hormone (PTH), Procollagen type 1 N propeptide (P1NP), Renal osteodystrophy, Sensitivity and specificity",
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T1 - Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis

AU - Sprague, Stuart M.

AU - Bellorin-Font, Ezequiel

AU - Jorgetti, Vanda

AU - Carvalho, Aluizio B.

AU - Malluche, Hartmut H.

AU - Ferreira, Aníbal

AU - D'Haese, Patrick C.

AU - Drüeke, Tilman B.

AU - Du, Hongyan

AU - Manley, Thomas

AU - Rojas, Eudocia

AU - Moe, Sharon

PY - 2014/6/6

Y1 - 2014/6/6

N2 - 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. Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20°C) serum. Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test: 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, 42.1. U/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. Limitations: 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.

AB - 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. Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20°C) serum. Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test: 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, 42.1. U/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. Limitations: 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.

KW - Alkaline phosphatases

KW - Bone histomorphometry

KW - Bone-specific alkaline phosphatase (bALP

KW - BSAP)

KW - Chronic kidney disease-mineral bone disorder (CKD-MBD)

KW - Parathyroid hormone (PTH)

KW - Procollagen type 1 N propeptide (P1NP)

KW - Renal osteodystrophy

KW - Sensitivity and specificity

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