title: 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.
abstract: 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.
authors.affiliation: Department of Haematology, Aarhus University Hospital, Denmark. niels.abild@dadlnet.dk
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.forename: Jens E
authors.initials: JE
authors.lastname: Kristensen
authors.forename: Erik F
authors.initials: EF
authors.lastname: Eriksen
authors.forename: Johan L
authors.initials: JL
authors.lastname: Nielsen
authors.forename: Lene
authors.initials: L
authors.lastname: Heickendorff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001862:Bone Resorption; D003094:Collagen / Q000652:urine*; D024042:Collagen Type I; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000652:urine*; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen