Increased excretion of collagen crosslinks in irradiated patients indicates destruction of collagen

Abstract

Purpose: In a recent study we showed an instant radiogenic destruction of collagen in dental tissues. The hypothesis of this analysis was that there is a destruction of collagen directly in bone during irradiation. Our intention was to prove this assumption by the analysis of the intraindividual progression of urinary excretion of bone specific collagen crosslinks before, during and after radiotherapy (RT) of secondary malignant bone tumors.

Material and methods: Forty-six patients were irradiated with a mean dose of 32 Gy (range 30 – 46 Gy). Four urine probes were collected from each patient before, during, at the end and 6 – 8 weeks after RT. Measurement of the mature collagen crosslinks hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) was performed by high performance liquid chromatography (HPLC).

Results: In 43 patients we found increasing HP and LP concentrations by comparing the different chosen time-points. As regards to HP the urine excretion was significantly increased at the end (p = 0.02) and six weeks after RT (p = 0.01) and for LP six weeks after RT (p = 0.01). We observed significantly higher urinary HP levels in patients treated with doses of 35 – 46 Gy as compared to patients treated with 30 Gy (p = 0.05).

Conclusions: The urinary excretion of HP and LP was increased directly after a course of RT. This finding may reflect either destruction of collagen or increased bone remodeling/resorption after radiotherapy. Either way these findings suggest a relation to the mechanical instability of bone directly after radiotherapy. Future investigations of irradiated patients without osseous metastases will further clarify this matter.

Keywords:

• Radiotherapy
• collagen damage
• pyridinoline
• bone metastases
• bone remodelling