Bone resorption parameters [carboxy‐terminal telopeptide of type‐I collagen (ICTP), amino‐terminal collagen type‐I telopeptide (NTx), and deoxypyridinoline (Dpd)] in MGUS and multiple myeloma

Abstract: Skeletal morbidity is a major problem in multiple myeloma. Histomorphometric studies have demonstrated that increased bone resorption can be present even in the absence of radiographic abnormalities. To overcome diagnostic problems in estimating the activity of bone resorption, new laboratory parameters that reflect bone metabolism accurately are urgently needed. We analyzed three parameters of osteoclastic bone destruction, i.e. deoxypyridinoline (Dpd) and amino‐terminal collagen type‐I telopeptide (NTx) in urine and carboxy‐terminal telopeptide of type‐I collagen (ICTP) in serum, of 75 patients with multiple myeloma (n = 57) or monoclonal gammopathy of undetermined significance (MGUS, n = 18) by ELISA/RIA techniques. Serum ICTP and urinary Dpd levels increased parallel to the stage of the disease and differed significantly (P < 0.001 for ICTP and P = 0.03 for Dpd) between MGUS, myeloma stage I, and myeloma in stages II and III according to Salmon and Durie. ICTP and Dpd were significantly elevated in patients with multiple myeloma in stage I compared to individuals with MGUS, while no significant difference was found for NTx. In this first study comparing the prognostic relevance of ICTP, NTx, and Dpd in multiple myeloma patients, ICTP was found to be a prognostic factor for overall survival in the Kaplan–Meier analysis (log‐rank test: P < 0.03). Urinary NTx showed borderline significance (P = 0.05), and Dpd had no prognostic value in the survival analysis. Our data show that serum ICTP and urinary Dpd levels increase in parallel to advanced disease stages, and gives the first report on a significant difference in the bone resorption parameters ICTP and Dpd between individuals with MGUS and patients with myeloma in stage I. Among the bone resorption parameters studied serum ICTP was found to be the best prognostic factor for survival in multiple myeloma.

[1]  O. Sezer,et al.  Human bone marrow myeloma cells express RANKL. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  G. Martinelli,et al.  Molecular therapy for multiple myeloma. , 2001, Haematologica.

[3]  O. Sezer,et al.  Differentiation of monoclonal gammopathy of undetermined significance and multiple myeloma using flow cytometric characteristics of plasma cells. , 2001, Haematologica.

[4]  R. Fonseca,et al.  Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients , 2000, British journal of haematology.

[5]  J. Risteli,et al.  Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K. , 2000, Bone.

[6]  J. Rungby,et al.  Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma , 2000, European journal of haematology.

[7]  L. L. Lewis,et al.  Bone Resorption Levels by Age and Menopausal Status in 5,157 Women , 2000, Menopause.

[8]  S. Ljunghall,et al.  Evaluation of bone disease in multiple myeloma: a comparison between the resorption markers urinary deoxypyridinoline/creatinine (DPD) and serum ICTP, and an evaluation of the DPD/osteocalcin and ICTP/osteocalcin ratios , 1999, European journal of haematology.

[9]  F. Carrera,et al.  Effects of Age, Menopause and Osteoporosis on Free, Peptide-Bound and Total Pyridinium Crosslink Excretion , 1999, Osteoporosis International.

[10]  T. Miki,et al.  [Biochemical markers of bone metabolism]. , 1998, Nihon rinsho. Japanese journal of clinical medicine.

[11]  J. Lappe,et al.  Influence of Activity Level on Patellar Ultrasound Transmission Velocity in Children , 1998, Osteoporosis International.

[12]  M. Seibel,et al.  Bone resorption in multiple myeloma and in monoclonal gammopathy of undetermined significance: quantification by urinary pyridinium cross-links of collagen. , 1997, Blood.

[13]  N. Abildgaard,et al.  Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy‐terminal telopeptide of type I collagen (ICTP) , 1997, British journal of haematology.

[14]  R. Bataille,et al.  Quantifiable excess of bone resorption in monoclonal gammopathy is an early symptom of malignancy: a prospective study of 87 bone biopsies. , 1996, Blood.

[15]  T. Sone,et al.  Urinary excretion of type I collagen crosslinked N-telopeptides in healthy Japanese adults: age- and sex-related changes and reference limits. , 1995, Bone.

[16]  L. Mosekilde,et al.  Serum markers of type I collagen formation and degradation in metabolic bone disease: Correlation with bone histomorphometry , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  F. Singer,et al.  Bone-resorption markers galactosyl hydroxylysine, pyridinium crosslinks, and hydroxyproline compared. , 1992, Clinical chemistry.

[18]  B. Klein,et al.  C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. , 1992, Blood.

[19]  R. Bataille,et al.  Osteoblast stimulation in multiple myeloma lacking lytic bone lesions , 1990, British journal of haematology.

[20]  M. Gobbi,et al.  [Allogeneic bone marrow transplantation in multiple myeloma]. , 1991, Haematologica.

[21]  S. Salmon,et al.  A clinical staging system for multiple myeloma correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival , 1975, Cancer.

[22]  R. Kyle Multiple myeloma: review of 869 cases. , 1975, Mayo Clinic proceedings.

[23]  A I Pick,et al.  THE TREATMENT OF MULTIPLE MYELOMA , 1948, Harefuah.