Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment:​ a need for international reference standards

Vasikaran, S.<sup>1,2</sup>; Eastell, R.<sup>3</sup>; Bruyère, O.<sup>4</sup>; Foldes, A. J.<sup>5</sup>; Garnero, P.<sup>6</sup>; Griesmacher, A.<sup>7</sup>; McClung, M.<sup>8</sup>; Morris, H. A.<sup>9</sup>; Silverman, S.<sup>10</sup>; Trenti, T.<sup>11</sup>; Wahl, D. A.<sup>12</sup>; Cooper, C.<sup>13,14</sup>; Kanis, J. A.<sup>15</sup>

Affiliations

¹Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, WA, Australia

²School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia

³Centre for Biomedical Research, Northern General Hospital, Herries Road, Sheffield, South Yorkshire, England S5 7AU, UK

⁴Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium

⁵Osteoporosis Center, Hadassah University Hospital, Mount Scopus, Jerusalem 91240, Israel

⁶INSERM Unit 664, Lyon, France

⁷Central Institute of Medical and Chemical Laboratory Diagnostics, University Hospital of Innsbruck, 6080, Innsbruck, Austria

⁸Oregon Osteoporosis Center, 5050 NE Hoyt Street, Suite 651, Portland, OR 97213, USA

⁹School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia

¹⁰Cedars-Sinai/University of California, Los Angeles, CA, USA

¹¹Patologia Clinica, Tossicologia e Diagnostica Avanzata, Dipartimento di Patologia Clinica, Ospedale Nuovo Sant’Agostino Estense, via Giardini 1355, 4110, Modena, Italy

¹²International Osteoporosis Foundation, Nyon, Switzerland

¹³MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK

¹⁴NIHR Musculoskeletal Biomedical Research Unit, Institute of Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK

¹⁵Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK

Abstract and keywords

The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies. Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda. Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001. High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine. BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.

Keywords: Bone makers; Bone turnover; Fracture risk; IOF; Monitoring treatment; Reference standards

Links

DOI: 10.1007/s00198-010-1501-1

PubMed: 21184054

WoS: 000286207800002

History

Received: 2010-11-08

Accepted: 2010-11-09

Online: 2010-12-24

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