Investigation of bone disease using isomerized and racemized fragments of type I collagen.
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.
Cloos
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Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. PC@nordicbioscience.com
Fledelius
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Christgau
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Christiansen
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C
Engsig
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Delmas
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Body
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JJ
Garnero
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D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D001847:Bone Diseases / Q000652:urine*; D001859:Bone Neoplasms / Q000556:secondary / Q000652:urine; D001862:Bone Resorption / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000652:urine*; D024042:Collagen Type I; D004164:Diphosphonates / Q000494:pharmacology; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000652:urine; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000652:urine; D000077268:Pamidronate; D010446:Peptide Fragments; D010455:Peptides / Q000187:drug effects / Q000652:urine*; D017698:Postmenopause; D017697:Premenopause; D011471:Prostatic Neoplasms / Q000473:pathology / Q000652:urine
D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D010446:Peptide Fragments; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000077268:Pamidronate