Prospective study of urinary and serum cross-linked N-telopeptide of type I collagen (NTx) for diagnosis of bone metastasis in patients with lung cancer

Clin Lung Cancer. 2013 Jul;14(4):364-9. doi: 10.1016/j.cllc.2012.11.006. Epub 2012 Dec 29.

Abstract

Background: Many cancers metastasize to bone, which may cause an increase in bone resorption because of the direct effects of the tumor itself or osteoclastic activation.

Patients and methods: Levels of urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum cross-linked N-telopeptide of type I collagen (sNTx) were measured in 100 patients with lung cancer and 50 patients with benign respiratory disease using the Osteomark NTx urine and serum assays (Osteomark, Princeton, NJ). Bone metastasis was diagnosed by bone scintigraphy. Receiver operating characteristic (ROC) analysis was used to evaluate the detection of bone metastasis. Sensitivity and specificity to detect bone metastasis were calculated when cutoff points were set to 64 nmol bone collagen equivalents (BCE)/mmol Cr for uNTx and 22 nmol BCE/L for sNTx.

Results: Patients with lung cancer and bone metastasis had significantly higher levels of both uNTx and sNTx (uNTx median [range], 61.3 [22.7-593.1] nmol BCE/mmol creatinine [Cr]; sNTx median [range], 19.7 [10.7-97.1] nmol BCE/L) than did patients with lung cancer without bone metastasis (uNTx median [range], 45.2 [19.8-153.0] nmol BCE/mmol Cr; sNTx median [range], 16.7 [11.0-28.4] nmol BCE/L), or patients with benign respiratory diseases (uNTx median [range], 40.6 [15.2-155.9] nmol BCE/mmol Cr; sNTx median [range], 14.8 [9.5-55.5] nmol BCE/L.). There was good correlation between uNTx and sNTx (R = 0.807). Area under the curve (AUC) for ROC was 0.743 for uNTx and 0.712 for sNTx. The sensitivity and specificity for the diagnosis of bone metastasis were 48.0% and 86.0%, respectively, using uNTx, and 40.0% and 87.0%, respectively, using sNTx.

Conclusion: This prospective study indicates equivalency between sNTx and uNTx in sensitivity and specificity to detect bone metastasis, and both uNTx and sNTx may have value as aids in the diagnosis of bone metastasis in patients with lung cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / pathology
  • Adenocarcinoma / urine
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / urine*
  • Bone Neoplasms / blood
  • Bone Neoplasms / secondary*
  • Bone Neoplasms / urine
  • Carcinoma, Large Cell / blood
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Large Cell / urine
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / urine
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / urine
  • Case-Control Studies
  • Collagen Type I / blood*
  • Collagen Type I / urine*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / urine
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Peptides / blood*
  • Peptides / urine*
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity
  • Small Cell Lung Carcinoma / blood
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / urine

Substances

  • Biomarkers, Tumor
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide