Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy

J Am Soc Nephrol. 2018 May;29(5):1557-1565. doi: 10.1681/ASN.2017050584. Epub 2018 Mar 19.

Abstract

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.

Keywords: chronic kidney disease; chronic renal failure; hyperparathyroidism; mineral metabolism; parathyroid hormone; renal osteodystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Area Under Curve
  • Biomarkers / blood
  • Bone Remodeling*
  • Chronic Kidney Disease-Mineral and Bone Disorder / blood*
  • Chronic Kidney Disease-Mineral and Bone Disorder / diagnostic imaging*
  • Chronic Kidney Disease-Mineral and Bone Disorder / etiology
  • Collagen Type I / blood
  • Cross-Sectional Studies
  • Female
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Peptide Fragments / blood
  • Peptides / blood
  • Procollagen / blood
  • ROC Curve
  • Radius / diagnostic imaging
  • Tartrate-Resistant Acid Phosphatase / blood
  • Tibia / diagnostic imaging
  • Tomography, X-Ray Computed / methods*

Substances

  • Biomarkers
  • Collagen Type I
  • Parathyroid Hormone
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Alkaline Phosphatase
  • ACP5 protein, human
  • Tartrate-Resistant Acid Phosphatase