Expression and circulating levels of sclerostin are influenced by multiple factors

Sclerostin plays a central role in regulating bone homeostasis by simultaneously mediating the functions of osteoblasts and osteoclasts. Expression and circulating levels of sclerostin are influenced by multiple physiological and pathological factors including age, gender, mechanical loading, renal functions, hormonal changes, and metabolic disorders. Sclerostin also mediates the anabolic effects of parathyroid hormone, showing negative correlation with circulating parathyroid hormone levels. The influence of vitamin D on sclerostin levels remains controversial. Although serum sclerostin levels are associated with bone mineral density and may reflect bone metabolism status to some extent, the clinical significance of changes in serum sclerostin levels should be interpreted carefully due to the diverse influencing factors and the lack of assay standardization. This review summarizes the current knowledge on factors influencing sclerostin expression and circulating levels, analytical methods for sclerostin measurement, and the clinical significance of sclerostin as a potential biomarker for bone metabolism.