Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
BALP; Bone status indices; Bone turnover markers; PINP; TRACP5b; β-CTX-I; Biomarkers; Peptide Fragments; Procollagen; procollagen Type I N-terminal peptide; Collagen Type I; Bone Density Conservation Agents; Peptides; collagen type I trimeric cross-linked peptide; Humans; Biomarkers/blood; Osteoporotic Fractures/prevention & control; Osteoporotic Fractures/etiology; Peptide Fragments/blood; Procollagen/blood; Risk Assessment/methods; Collagen Type I/blood; Bone Density Conservation Agents/therapeutic use; Peptides/blood; Consensus; Bone Remodeling/physiology; Osteoporosis/diagnosis; Osteoporosis/physiopathology; Osteoporosis/drug therapy; Osteoporosis/blood; Osteoporosis/therapy; Bone Remodeling; Osteoporosis; Osteoporotic Fractures; Risk Assessment; Endocrinology, Diabetes and Metabolism
Abstract :
[en] [en] PURPOSE: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.
METHODS: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined.
RESULTS: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications.
CONCLUSION: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Bhattoa, Harjit Pal ; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei Blvd. 98, 4032, Debrecen, Hungary. harjit@med.unideb.hu
Vasikaran, Samuel ; PathWest Laboratory Medicine WA, Murdoch, WA6150, Australia
Trifonidi, Ioulia ; Clinical Biochemistry Department-KAT General Hospital, Kifissia, Athens, Greece ; Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, University of Athens, Athens, Greece
Kapoula, Georgia ; Clinical Biochemistry Department, General Hospital of Lamia, 35100, Lamia, Greece
Lombardi, Giovanni ; Laboratory of Experimental Biochemistry, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy ; Department of Athletics, Strength and Conditioning, Poznań University of Physical Education, Poznań, Poland
Jørgensen, Niklas Rye ; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark ; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark ; Translational Research Centre, Rigshospitalet, Copenhagen, Denmark
Pikner, Richard ; Department of Clinical Biochemistry and Bone Metabolism, Klatovska Hospital, Klatovy, Czech Republic ; Department of Clinical Biochemistry and Haematology, Faculty of Medicine Pilsen, Charles University Prague, Pilsen, Czech Republic ; Faculty of Health Care Studies, University of West Bohemia, Pilsen, Czech Republic
Miura, Masakazu ; Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
Chapurlat, Roland ; INSERM UMR 1033, Université Claude Bernard-Lyon1, Hôpital E Herriot, 69437, Lyon, France
Hiligsmann, Mickael ; Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands
Haarhaus, Mathias ; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, 141 86, Stockholm, Sweden ; Diaverum AB, Hyllie Boulevard 53, 215 37, Malmö, Sweden
Evenepoel, Pieter ; University Hospitals Leuven and Laboratory of Nephrology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Louvain, Belgium
Jørgensen, Hanne Skou ; Department of Clinical Medicine - Department of Medicine and Nephrology, Aarhus University, Aarhus, Denmark ; Department of Clinical Medicine and Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark ; Department of Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KatholiekeUniversitet Leuven (KU Leuven), Louvain, Belgium
Herrmann, Markus ; Clinical Institute of Medical and Chemical Diagnostics, Medical University of Graz, Auenbruggerplatz 15 /1, 8036, Graz, Austria
Kaufman, Jean-Marc ; Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
Clark, Patricia ; Clinical Epidemiology Unit, Faculty of Medicina UNAM, Hospital Infantil Federico Gómez, Mexico City, Mexico
Tuzun, Şansın ; Department of Physical Medicine and Rehabilitation, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey
Al-Daghri, Nasser ; Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia
Silverman, Stuart ; Cedars-Sinai Medical Center, OMC Clinical Research Center, Beverly Hills, CA, 90211, USA
Alokail, Majed S; Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia
Yerro, María Concepción Prieto; Spanish Agency for Medicines and Medical Devices, Madrid, Spain
Matijevic, Radmila ; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Laslop, Andrea ; Scientific Office, Austrian Medicines and Medical Devices Agency, Vienna, Austria
da Silva Rosa, Mario Miguel Coelho ; Centro de Estudos Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal
Zakraoui, Leith ; University of Tunis El Manar, Tunis, Tunisia
Burlet, Nansa ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
McCloskey, Eugene ; Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Sheffield, UK
Harvey, Nicholas C ; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK ; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
Radermecker, Régis ; Université de Liège - ULiège > Département des sciences cliniques > Pharmacologie clinique
Fusaro, Maria ; Institute of Clinical Physiology, 56124, Pisa and Department of Medicine, National Research Council, University of Padova, Padua, Italy
Torre, Carla ; Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal ; Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon (iMed.ULisboa), Lisbon, Portugal
Kanis, John A ; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK
Rizzoli, René ; Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique ; Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia
Makris, Konstantinos ; Clinical Biochemistry Department-KAT General Hospital, Kifissia, Athens, Greece ; Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, University of Athens, Athens, Greece
Cavalier, Etienne ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
Publication date :
April 2025
Journal title :
Osteoporosis International
ISSN :
0937-941X
eISSN :
1433-2965
Publisher :
Springer Science and Business Media Deutschland GmbH, England
Open access funding provided by University of Debrecen.The ESCEO Working Group was funded by the ESCEO. The ESCEO receives unrestricted educational grants to support its educational and scientific activities from non-governmental organizations, not-for-profit organizations, and non-commercial or corporate partners. The choice of topics, participants, content, and agenda of the Working Groups as well as the writing, editing, submission, and reviewing of the manuscript are the sole responsibility of the ESCEO, without any influence from third parties.This work was supported by the Distinguished Scientist Fellowship Program (DSFP) of the King Saud University, Riyadh, Kingdom of Saudi Arabia. The expert opinion of Jotheeswaran Amuthavalli Thiyagarajan is acknowledged.
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