Breast cancer patients with bone metastases are characterised by increased levels of nonisomerised type I collagen fragments

BACKGROUND: Fragments of collagen type I containing the epitope AHDGGR (CTX) are generated during bone resorption. The aspartyl-glycine (DG) site within CTX is synthesised in the L-aspartyl peptide (αL) form, but converts to the age-modified forms L-isoaspartyl peptide (βL) and D-aspartyl peptide (αD) over time. The purpose of the present study was to test the ability of the various CTX forms to identify breast cancer patients with bone metastases and to investigate whether such patients had an altered CTX excretion pattern. METHODS: In this cross-sectional study we compared CTX excretion in healthy premenopausal and postmenopausal women with CTX levels in patients with breast cancer. The breast cancer cohort comprised eight hypercalcemic patients with bone metastases (HC+), 100 normocalcemic patients with bone metastases (NC+) and 15 normocalcemic patients without bone metastases (NC-). RESULTS: In HC+ patients and NC+ patients, the excretion of αL CTX was highly increased compared with NC- patients (P < 0.01), with Z scores of 3.4 and 2.0, respectively. The excretion of the age-modified forms (βL and αD CTX) was less increased in HC+ patients and in NC+ patients as compared with NC- patients, with Z scores of 2.2 and 1.0, respectively, for βL CTX, and of 1.6 and 0.8, respectively, for αD CTX. CONCLUSION: Assays for the various isoforms of CTX have different sensitivities to identify patients affected by bone metastases. The αL CTX isoform reflecting resorption of young bone appeared to provide the best differentiation of patients affected by breast cancer-induced bone metastases. In conclusion, patients affected by metastatic bone disease present an altered excretion pattern of CTX isoforms.