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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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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DOI: https://doi.org/10.1038/leu.2010.173
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