Sclerostin measurement in human disease: Validity and current limitations

Sclerostin a potent regulator of bone formation, is an antagonist of the Wnt-signaling pathway. The advent of assays to measure circulating sclerostin has enabled research to be performed with the aim to understand the potential role of circulating sclerostin as a pathophysiological marker in a variety of clinical settings. At this time, however, assays to measure circulating sclerostin are still relatively new and have not demonstrated consistent internal agreement in addition to which there are differences between serum and plasma levels. Nevertheless, measurement of sclerostin in the circulation has the potential to reflect the dynamics of bone formation with particular reference to situations in which osteocytes, the major source of circulating sclerostin, may be perturbed. Because of technical uncertainties regarding sclerostin assays that are currently available, circulating sclerostin measurements should be interpreted cautiously with attention to reference ranges for each assay and whether or not the measurement is made in serum or plasma.