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The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

Leukemia volume 24, pages 1700–1712 (2010)Cite this article

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Abstract

Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

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Author notes

  1. E Terpos, M A Dimopoulos, O Sezer, D Roodman, N Abildgaard, R Vescio, P Tosi, R Garcia-Sanz, F Davies, A Chanan-Khan, A Palumbo, P Sonneveld, M T Drake, J-L Harousseau, K C Anderson and B G M Durie: See appendix

Authors and Affiliations

  1. Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece

    E Terpos & M A Dimopoulos

  2. Department of Hematology, Oncology and Stem cell Transplantation, University Medical Center Hamburg, Hamburg, Germany

    O Sezer

  3. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    D Roodman

  4. Department of Hematology, Odense University, Odense, Denmark

    N Abildgaard

  5. Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA

    R Vescio & B G M Durie

  6. Institute of Hematology and Oncology, University of Bologna, Bologna, Italy

    P Tosi

  7. Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain

    R Garcia-Sanz

  8. Institute of Cancer Research and Royal Marsden Hospital, Section of Haemato-oncology, Sutton, Surrey, UK

    F Davies

  9. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    A Chanan-Khan

  10. Divisione di Ematologia, University of Torino, Torino, Italy

    A Palumbo

  11. Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands

    P Sonneveld

  12. Division of Endocrinology, Mayo Clinic, Rochester, MN, USA

    M T Drake

  13. Institut de Biologie, Laboratoire d’Hematologie, Nantes, France

    J-L Harousseau

  14. Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    K C Anderson

Authors
  1. E Terpos
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  2. M A Dimopoulos
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  3. O Sezer
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  4. D Roodman
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  5. N Abildgaard
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  6. R Vescio
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  7. P Tosi
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  8. R Garcia-Sanz
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  9. F Davies
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  10. A Chanan-Khan
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  11. A Palumbo
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  12. P Sonneveld
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  13. M T Drake
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  14. J-L Harousseau
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  15. K C Anderson
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  16. B G M Durie
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Consortia

on behalf of the International Myeloma Working Group

Corresponding author

Correspondence to E Terpos.

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Competing interests

The authors declare no conflict of interest.

Additional information

Authors’ Contributions

ET collected data and wrote paper; MAD collected data and wrote paper; OS contributed comments and edited paper; DR contributed comments and edited paper; RV contributed comments and edited paper; NA contributed comments and edited paper; PT contributed comments and edited paper; RG-S contributed comments and edited paper; FD contributed comments and edited paper; AC-K contributed comments and edited paper; AP contributed comments and edited paper; PS contributed comments and edited paper; MTD contributed comments and edited paper; J-LH contributed comments and edited paper; KCA contributed comments and edited paper; BGMD contributed comments and edited paper

Appendix

Appendix

International myeloma working group

Rafat Abonour, Indiana University School of Medicine, Indianapolis, Indiana, USA

Ray Alexanian, MD Anderson, Houston, Texas, USA

Kenneth C. Anderson, DFCI, Boston, Massachusetts, USA

Michael Attal, Purpan Hospital, Toulouse, France

Herve Avet-Loiseau, Institute de Biologie, Nantes, France

Ashraf Badros, University of Maryland, Baltimore, Maryland, USA

Bart Barlogie, M.I.R.T. UAMS Little Rock, Arkanas, USA

Regis Batille, Institute de Biologie, Nantes, France

Meral Beksac, Ankara University, Ankara, Turkey

Andrew Belch, Cross Cancer Institute, Alberta, Canada

Bill Bensinger, Fred Hutchinson Cancer Center, Seattle, Washington, USA

P. Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA

Jenny Bird, Bristol Haematology and Oncology Center, Bristol, UK

Joan Bladé, Hospital Clinica, Barcelona, Spain

Mario Boccadoro, University of Torino, Torino, Italy

Michele Cavo, Universita di Bologna, Bologna, Italy

Wen Ming Chen, MM Research Center of Beijing, Beijing, China

Tony Child, Leeds General Hospital, Leeds, United Kingdom

James Chim, Department of Medicine, Queen Mary Hospital, Hong Kong

Wee-Joo Chng, National University Health System, Singapore

Ray Comenzo, Tufts Medical School, Boston, Massachusetts, USA

John Crowley, Cancer Research and Biostatistics, Seattle, Washington, USA

William Dalton, H. Lee Moffitt, Tampa, Florida, USA

Faith Davies, Royal Marsden Hospital, London, England

Cármino de Souza, Univeridade de Campinas, Caminas, Brazil

Michel Delforge, University Hospital Gasthuisberg, Leuven, Belgium

Meletios Dimopoulos, University of Athens School of Medicine, Athens, Greece

Angela Dispenzieri, Mayo Clinic, Rochester, Minnesota, USA

Matthew Drake, Mayo Clinic, Rochester, Minnesota, USA

Brian G.M. Durie, Cedars-Sinai Outpatient Cancer Center, Los Angeles, California, USA

Johannes Drach, University of Vienna, First Dept. of Internal Medicine, Vienna, Austria

Hermann Einsele, Universitätsklinik Würzburg, Würzburg, Germany

Theirry Facon, Centre Hospitalier Regional Universitaire de Lille, Lille, France

Dorotea Fantl, Socieded Argentinade Hematolgia, Buenos Aires, Argentina

Jean-Paul Fermand, Hopitaux de Paris, Paris, France

Rafael Fonseca, Mayo Clinic Arizona, Scottsdale, Arizona, USA

Gosta Gahrton, Karolinska Institute for Medicine, Huddinge, Sweden

Christina Gasparetto, Duke University Medical Center, Durham, North Carolina, USA

Morie Gertz, Mayo Clinic, Rochester, Minnesota, USA

John Gibson, Royal Prince Alfred Hospital, Sydney, Australia

Sergio Giralt, MD Anderson Cancer Center, Houston, Texas, USA

Hartmut Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany

Philip Greipp, Mayo Clinic, Rochester, Minnesota, USA

Roman Hajek, Brno University, Brno, Czech Republic

Izhar Hardan, Tel Aviv University, Tel Aviv, Israel

Jean-Luc Harousseau, Institute de Biologie, Nantes, France

Hiroyuki Hata, Kumamoto University Hospital, Kumamoto, Japan

Yutaka Hattori, Keio University School of Medicine, Tokyo, Japan

Tom Heffner, Emory University, Atlanta, Georgia, USA

Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia

Vania Hungria, Clinica San Germano, Sao Paolo, Brazil

Shinsuke Ida, Nagoya City University Medical School, Nagoya, Japan

Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa

Sundar Jagannath, St. Vincent's Comprehensive Cancer Center, New York, New York, USA

Hou Jian, Shanghai Chang Zheng Hospital, Shanghai, China

Douglas Joshua, Royal Prince Alfred Hospital, Sydney, Australia

Artur Jurczyszyn, The Myeloma Treatment Foundation, Poland

Asher Chanan Kahn, Roswell Park Cancer Institute, Buffalo, New York, USA

Michio Kawano, Yamaguchi University, Ube, Japan

Nicolaus Kröger, University Hospital Hamburg, Hamburg, Germany

Shaji Kumar, Department of Hematology, Mayo Clinic, Minnesota, USA

Robert Kyle, Department of Laboratory Med. and Pathology, Mayo Clinic, Minnesota, USA

Juan Lahuerta, Grupo Espanol di Mieloma, Hospital Universitario, Madrid, Spain

Ola Landgren, National Cancer Institute, Bethesda, Maryland, USA

Jacob Laubach, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Jae Hoon Lee, Gachon University Gil Hospital, Incheon, Korea

Xavier LeLeu, Hospital Huriez, CHRU Lille, France

Suzanne Lentzsch, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Henk Lokhorst, University Medical CenterUtrecht, Utrecht, The Netherlands

Sagar Lonial, Emory University Medical School, Atlanta, Georgia, USA

Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria

Angelo Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil

Maria Mateos, University of Salamanca, Salamanca, Spain

Jayesh Mehta, Northwestern University, Chicago, Illinois, USA

GiamPaolo Merlini, University of Pavia, Pavia, Italy

Joseph Mikhael, Mayo Clinic Arizona, Scottsdale, Arizona, USA

Angelina Rodriquez Morales, Bonco Metro Politano de Sangre, Caracas, Venezuela

Philippe Moreau, University Hospital, Nantes, France

Gareth Morgan, Royal Marsden Hospital, London, England

Nikhil Munshi, Diane Farber Cancer Institute, Boston, Massachusetts, USA

Ruben Niesvizky, Weill Medical College of Cornell University, New York, New York, USA

Amara Nouel, Hospital Rutz y Paez, Bolivar, Venezuela

Yana Novis, Hospital SírioLibanês, Bela Vista, Brazil

Robert Orlowski, MD Anderson Cancer Center, Houston, Texas, USA

Antonio Palumbo, Cathedra Ematologia, Torino, Italy

Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina

Linda Pilarski, University of Alberta, Alberta, Canada

Raymond Powles, Leukemia & Myeloma, Wimbledon, England

S. Vincent Rajkumar, Mayo Clinic, Rochester, Minnesota, USA

Donna Reece, Princess Margaret Hospital, Toronto, Canada

Tony Reiman, Cross Cancer Institute, Alberta, Canada

Paul G. Richardson, Dana Farber Cancer Institute, Boston, Massachusetts, USA

David Roodman, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Laura Rosinol, Hospital Clinic, Barcelona, Spain

Jesus San Miguel, University of Salamanca, Salamanca, Spain

Orhan Sezer, Universität Hamburg, Hamburg, Germany

Jatin Shah, MD Anderson Cancer Institute, Houston, Texas, USA

John Shaughnessy, M.I.R.T. UAMS, Little Rock, Arkansas, USA

Kazuyuki Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan

Chaim Shustik, McGill University, Montreal, Canada

David Siegel, Hackensack, Cancer Center, Hackensack, New Jersey, USA

Seema Singhal, Northwestern University, Chicago, Illinois, USA

Pieter Sonneveld, Erasmus MC, Rotterdam, The Netherlands

Andrew Spencer, The Alfred Hospital, Melbourne, Australia

Edward Stadtmauer, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Keith Stewart, Mayo Clinic Arizona, Scottsdale, Arizona, USA

Evangelos Terpos, University of Athens School of Medicine, Athens, Greece

Patrizia Tosi, Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy

Guido Tricot, Huntsman Cancer Institute, Salt Lake City, Utah, USA

Ingemar Turesson, Department of Hematology, Malmo University, Malmo, Sweden

Karin Vanderkerken, Vrije University Brussels VUB, Brussels, Belgium

Brian Van Ness, University of Minnesota, Minneapolis, Minnesota, USA

Ivan Van Riet, Brussels Vrija University, Brussels, Belgium

Robert Vescio, Cedars-Sinai Cancer Center, Los Angeles, California, USA

David Vesole, Hackensack Cancer Center, Hackensack, New Jersey, USA

Anders Waage, University Hospital, Trondheim, Norway NSMG

Michael Wang, M.D. Anderson, Houston, Texas, USA

Donna Weber, MD Anderson, Houston, Texas, USA

Jan Westin, Sahlgrenska University Hospital, Gothenburg, Sweden

Keith Wheatley, University of Birmingham, Birmingham, United Kingdom

Dina B. Yehuda, Department of Hematology, Hadassah University Hospital, Hadassah, Israel

Jeffrey Zonder, Karmanos Cancer Institute, Detroit, Michigan, USA

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Terpos, E., Dimopoulos, M., Sezer, O. et al. The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group. Leukemia 24, 1700–1712 (2010). https://doi.org/10.1038/leu.2010.173

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