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

Summary. 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 (β-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-β-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.