IFCC committee on markers for bone turnover and bone disease--project presentation

In 1995 a proposal to establish a Committee on Bone Markers was presented to the Scientific Division of the International Federation of Clinical Chemistry. Following the Terms of Reference that were adopted by the Committee two tasks were selected as the first focus. To establish sources for reference materials for two of the many potential analytes of bone metabolism, namely pyridinoline/desoxypyridinoline and osteocalcin. Details on the first of these analytes were presented in a previous paper [1]. In this presentation, the steps to establish a reference material for osteocalcin are outlined. Due to the immunoheterogeneity of circulating osteocalcin the epitope specificity of antibodies used in immunoassays determines the values measured. Different degrees of carboxylation at the three gamma-carboxy-glutamic acid residues not only influence crossreactivity in assay systems but also represent biological functionality. Stability of osteocalcin and the effect of preanalytical steps has been described as problematic and depending on assay characteristics. After the characterisation and selection of reference preparations for osteocalcin, their performance in immunoassays, but also the clinical value in terms of clinical usefulness should be evaluated. Eventually, the standardization should further the comparability of measurements and promote the appropriate and rational use of biochemical markers of bone turnover.