Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma.

BACKGROUND AND OBJECTIVES Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate these methods in predicting bone events in MM patients. DESIGN AND METHODS Thirty newly diagnosed MM patients were enrolled. Serum C-terminal telopeptide (ICTP) and urinary N-terminal telopeptide (NTx) of collagen I were measured for assessment of bone resorption, and serum C-terminal (PICP) and N-terminal (PINP) propeptides of procollagen I, bone-specific alkaline phosphatase, and osteocalcin were measured to estimate bone formation. Dual energy X-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD) of the lumbar spine, hip, and whole body. Serum and urine samples were collected every 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were less informative. In Cox analysis, ICTP showed the highest predictive value, but should be replaced with NTx in patients with nephropathy. Pretreatment low lumbar BMD was predictive of early vertebral fractures. INTERPRETATION AND CONCLUSIONS Sequential DEXA-scans showed heterogeneous local BMD changes, and our data do not support routine use of sequential DEXA-scans. However, lumbar DEXA-scans at diagnosis can identify patients with increased risk of early vertebral collapses. Sequential analyses of serum ICTP and urinary NTx are useful for monitoring bone damage.

[1]  S. Ljunghall,et al.  Acute effects of high-dose chemotherapy followed by bone marrow transplantation on serum markers of bone metabolism , 1994, Calcified Tissue International.

[2]  M. Karsdal,et al.  The Type I Collagen Fragments ICTP and CTX Reveal Distinct Enzymatic Pathways of Bone Collagen Degradation , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  N. Abildgaard,et al.  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 , 2003, British journal of haematology.

[4]  B. Barlogie,et al.  Myeloma interacts with the bone marrow microenvironment 
to induce osteoclastogenesis and is dependent on osteoclast activity , 2002, British journal of haematology.

[5]  J. Michaeli,et al.  Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[6]  C. Pascutto,et al.  Biochemical markers of bone disease in asymptomatic early stage multiple myeloma. A study on their role in identifying high risk patients. , 2001, Haematologica.

[7]  E. Terpos,et al.  Effect of pamidronate administration on markers of bone turnover and disease activity in multiple myeloma , 2000, European journal of haematology.

[8]  R. Clark,et al.  Biochemical markers of bone turnover following high-dose chemotherapy and autografting in multiple myeloma. , 2000, Blood.

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

[10]  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.

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

[12]  Y. Shima,et al.  in patients with multiple myeloma Elevated soluble MUC 1 levels and decreased anti-MUC 1 antibody levels , 2000 .

[13]  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.

[14]  B. Barlogie,et al.  Biologic and therapeutic determinants of bone mineral density in multiple myeloma. , 1998, Leukemia & lymphoma.

[15]  S. Jagannath,et al.  CRITERIA FOR EVALUATING DISEASE RESPONSE AND PROGRESSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED BY HIGH‐DOSE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION , 1998, British journal of haematology.

[16]  M. Arning,et al.  Monitoring of multiple myeloma patients by simultaneously measuring marker substances of bone resorption and formation. , 1998, Clinica chimica acta; international journal of clinical chemistry.

[17]  P. L. Bergsagel,et al.  Multiple myeloma: increasing evidence for a multistep transformation process. , 1998, Blood.

[18]  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.

[19]  S. Barbagallo,et al.  Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity , 1997, British journal of haematology.

[20]  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.

[21]  N. Abildgaard,et al.  Assessment of bone involvement in patients with multiple myeloma using bone densitometry , 1996, European journal of haematology.

[22]  H. Deicher,et al.  Pyridinium cross-links in multiple myeloma: correlation with clinical parameters and use for monitoring of intravenous clodronate therapy--a pilot study of the German Myeloma Treatment Group (GMTG). , 1996, European journal of cancer.

[23]  M. Laakso,et al.  Monitoring the action of clodronate with type I collagen metabolites in multiple myeloma. , 1996, European journal of cancer.

[24]  J. Risteli,et al.  Immunoassay for intact amino-terminal propeptide of human type I procollagen. , 1996, Clinical chemistry.

[25]  M. Laval-jeantet,et al.  Evolution of bone densitometry in patients with myeloma treated with conventional or intensive therapy , 1995, Cancer.

[26]  R. Bataille,et al.  Excessive bone resorption in human plasmacytomas: direct induction by tumour cells in vivo , 1995, British journal of haematology.

[27]  M. Dougados,et al.  Biologic, histologic and densitometric effects of oral risedronate on bone in patients with multiple myeloma. , 1994, Bone.

[28]  J. Risteli,et al.  Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. , 1993, Clinical chemistry.

[29]  P. Ravaud,et al.  Bone densitometry in patients with multiple myeloma. , 1992, The American journal of medicine.

[30]  D. Eyre,et al.  A specific immunoassay for monitoring human bone resorption: Quantitation of type I collagen cross‐linked N‐telopeptides in urine , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  J. Kanis,et al.  Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption , 1992, European journal of haematology.

[32]  P. Virkkunen,et al.  Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma. , 1992, British Journal of Cancer.

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

[34]  J. Risteli,et al.  Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. , 1990, Clinical chemistry.

[35]  R. Bataille,et al.  Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  W. Behr,et al.  Quantification of bone alkaline phosphatase in serum by precipitation with wheat-germ lectin: a simplified method and its clinical plausibility. , 1986, Clinical chemistry.

[37]  P. Price,et al.  Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[38]  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.