Comparison of five biochemical markers of bone resorption in multiple myeloma: elevated pre-treatment levels of S-ICTP and U-Ntx are predictive for early progression of the bone disease during standard chemotherapy

Increased osteoclastic bone resorption is the major causal factor of bone disease in multiple myeloma. Recently, non-invasive methods have been developed for the estimation of bone resorptive activity. To evaluate the biological sensitivity and clinical usefulness of five biochemical assays for measuring the C-terminal telopeptide of collagen I (ICTP) in serum (beta-Crosslaps ELISA and ICTP radioimmunoassay) and urinary creatinine-adjusted excretions of pyridinoline (PYR), deoxypyridinoline (DPD) and N-terminal telopeptide of collagen I (Ntx), we performed a study of 34 consecutive newly diagnosed myeloma patients. Serum and morning-fasting, second-void urine samples were taken before the start of treatment. In total, 40 age- and sex-adjusted healthy individuals served as controls. Results were expressed as Z-scores. All test variables were highly significantly elevated in the patients (P < 0.001). Serum (S)-ICTP was elevated (Z-score > 2) in most patients (85%) and showed significantly higher Z-score values than the other markers. S-ICTP remained more sensitive than the urinary assays when patients with impaired renal function were excluded from analysis. S-ICTP and the urinary metabolites correlated significantly with skeletal morbidity. S-beta-Crosslaps correlated with the bone morbidity only when patients with renal insufficiency were excluded from the analysis. High levels of S-ICTP and urinary (U)-Ntx correlated with an increased risk for early progression of bone lesions during standard melphalan-prednisolone treatment. U-Ntx and S-ICTP are sensitive tools for estimating the increased bone resorption in multiple myeloma and are clinically useful for identifying patients with increased risk of early progression of bone disease.