Investigation of Bone Disease Using Isomerized and Racemized Fragments of Type I Collagen

Calcif Tissue Int. 2003 Jan;72(1):8-17. doi: 10.1007/s00223-002-2034-1. Epub 2002 Oct 21.

Abstract

In the collagen type I C-telopeptide an aspartyl-glycine site within the sequence AHDGGR is susceptible to molecular rearrangement. In newly synthesized collagen this site is in the native form, denoted alpha L. During aging a spontaneous reaction occurs resulting in three age-modified forms: an isomerized form (beta L) a racemized form (alpha D), and an isomerized/racemized form (beta D). In this study, we measured the urinary excretion of the four forms of C-telopeptides (CTX) in healthy adults and in patients with bone diseases. Levels of all CTX forms were higher in healthy postmenopausal women (P<0.001) compared with premenopausal controls. Levels decreased within 3 days of bisphosphonate treatment indicating that all CTX forms reflect bone resorption. In hyperthyroidism, characterized by a generalized increased bone turnover, native (alpha L) and age-modified (beta L, alpha D and beta D) forms increased to a similar extent compared to controls, resulting in normal ratios between the alpha L and age-modified forms of CTX. Conversely, in Paget's disease and prostate cancer-induced bone metastases, conditions characterized by focal increased bone turnover, alpha L CTX levels were more elevated than those of age-related CTX forms, resulting in increased ratios between native and age-modified CTX. For example, the ratio alpha L/alpha D was increased 7-fold in Paget's disease (P<0.001) and 2-fold in prostate cancer-induced bone metastases (P<0.002). In conclusion, the study suggests that in conditions with a localized alteration in bone turnover the ratio between alpha L CTX and the age-modified forms is significantly elevated. This may provide a new diagnostic and monitoring tool for diseases such as metastatic bone cancer and Paget's disease.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / urine
  • Bone Diseases / urine*
  • Bone Neoplasms / secondary
  • Bone Neoplasms / urine
  • Bone Resorption / metabolism
  • Cells, Cultured
  • Collagen / drug effects
  • Collagen / urine*
  • Collagen Type I
  • Diphosphonates / pharmacology
  • Female
  • Humans
  • Hyperthyroidism / urine
  • Isomerism
  • Male
  • Middle Aged
  • Osteitis Deformans / urine
  • Pamidronate
  • Peptide Fragments
  • Peptides / drug effects
  • Peptides / urine*
  • Postmenopause
  • Premenopause
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / urine

Substances

  • Biomarkers
  • Collagen Type I
  • Diphosphonates
  • Peptide Fragments
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Collagen
  • Pamidronate