, Volume 72, Issue 1, pp 8-17

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

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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 aL. During aging a spontaneous reaction occurs resulting in three age-modified forms: an isomerized form (bL) a racemized form (aD), and an isomerized/racemized form (bD). 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 (aL) and age-modified (bL, aD and bD) forms increased to a similar extent compared to controls, resulting in normal ratios between the aL and age-modified forms of CTX. Conversely, in Paget's disease and prostate cancer-induced bone metastases, conditions characterized by focal increased bone turnover, aL 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 aL/aD 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 aL 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.