INTRODUCTION: Increased biochemical bone turnover markers (BTMs) measured in serum are associated with bone loss, increased fracture risk and poor treatment adherence, but their role in clinical practice is presently unclear. The aim of this consensus group report is to provide guidance to clinicians on how to use BTMs in patient evaluation in postmenopausal osteoporosis, in fracture risk prediction and in the monitoring of treatment efficacy and adherence to osteoporosis medication. METHODS: A working group with clinical scientists and osteoporosis specialists was invited by the Scientific Advisory Board of European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). RESULTS: Serum bone formation marker PINP and resorption marker βCTX-I are the preferred markers for evaluating bone turnover in the clinical setting due to their specificity to bone, performance in clinical studies, wide use and relatively low analytical variability. BTMs cannot be used to diagnose osteoporosis because of low sensitivity and specificity, but can be of value in patient evaluation where high values may indicate the need to investigate some causes of secondary osteoporosis. Assessing serum levels of βCTX-I and PINP can improve fracture prediction slightly, with a gradient of risk of about 1.2 per SD increase in the bone marker in addition to clinical risk factors and bone mineral density. For an individual patient, BTMs are not useful in projecting bone loss or treatment efficacy, but it is recommended that serum PINP and βCTX-I be used to monitor adherence to oral bisphosphonate treatment. Suppression of the BTMs greater than the least significant change or to levels in the lower half of the reference interval in young and healthy premenopausal women is closely related to treatment adherence. CONCLUSION: In conclusion, the currently available evidence indicates that the principal clinical utility of BTMs is for monitoring oral bisphosphonate therapy.

Belgium WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Ageing Liège Belgium

CEDOC NOVA Medical School Medical Sciencies Faculty NOVA University of Lisbon Lisbon Portugal

Centre for Metabolic Bone Diseases University of Sheffield Medical School Sheffield UK

Chair for Biomarkers of Chronic Diseases Biochemistry Department College of Science King Saud University Riyadh Kingdom of Saudi Arabia

Clinical Center of Vojvodina Clinic for Orthopedic Surgery Novi Sad Serbia

Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University of Graz Graz Austria

Department of Clinical Biochemistry and Bone Metabolism Klatovska Hospital Klatovy Czech Republic

Department of Clinical Biochemistry and Heamathology Faculty of Medicine Pilsen Charles University Prague Pilsen Czech Republic

Department of Clinical Biochemistry Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Endocrinology Ghent University Hospital 9000 Ghent Belgium

Department of Internal Medicine and Medical Disciplines Rome University Sapienza Italy

Department of Oncology and Metabolism Centre for Integrated Research in Musculoskeletal Ageing University of Sheffield Sheffield UK

Department of Pharmacology Medical Faculty Medical University Sofia 2 Zdrave Str 1431 Sofia Bulgaria

Department of Public Health and Health Management University of Medicine Pharmacy Science and Technology of Targu Mures Targu Mures Romania

Department of Public Health Epidemiology and Health Economics University of Liège Liège Belgium

Department of Rheumatology and EA 44090 CHU Lille and University of Lille 59000 Lille France

Faculty of Health Care Studies University of West Bohemia Pilsen Czech Republic

FirmoLab Fondazione F 1 R M O University of Florence Florence Italy

Geriatric Medicine Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Hospital del Mar Institue of Medical Investigation Autonomous University of Barcelona and Biomedical Research Network on Frailty and Healthy Aging Madrid Spain

INSERM UMR 1033 Université de Lyon Hôpital E Herriot 69437 Lyon Cedex 03 France

Mary MacKillop Institute for Health Research Australian Catholic University Melbourne Australia

MRC Lifecourse Epidemiology Unit University of Southampton Southampton UK

NHS Foundation Trust Southampton UK

NIHR Oxford Biomedical Research Centre University of Oxford Oxford UK

NIHR Southampton Biomedical Research Centre University of Southampton and University Hospital Southampton Southampton UK

OPEN Odense Patient Data Explorative Network Odense University Hospital Institute of Clinical Research University of Southern Denmark Odense Denmark

Region Västra Götaland Geriatric Medicine Clinic Sahlgrenska University Hospital Gothenburg Sweden

Rheumatology Department Egas Moniz Hospital CHLO Lisbon Portugal

Scientific Office Federal Office for Safety in Health Care Austrian Agency for Health and Food Safety Vienna Austria

Service of Bone Diseases Geneva University Hospital and Faculty of Medicine 1211 Geneva 14 Switzerland

University of Liège CHU de Liège Liège Belgium

University of Novi Sad Faculty of Medicine Novi Sad Serbia

WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging University of Liège Liège Belgium

WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging Department of Public Health Epidemiology and Health Economics University of Liège Liège Belgium

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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)

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