Clinical utility of serum sclerostin measurements

Sclerostin is an osteocyte-secreted soluble antagonist of the Wnt/β-catenin signaling pathway requisite for osteoblast development and activity. Efforts over the past several years have focused on unraveling the role of sclerostin in both normal physiological and pathological conditions. Sclerostin levels are undetectable in the serum of patients with sclerosteosis. In normal individuals, serum sclerostin levels are higher in males and increase in both sexes across the adult lifespan. Some, but not other, studies have demonstrated that higher serum sclerostin levels are associated with increased fracture risk, particularly when paired with lower bone mineral density. Levels of circulating sclerostin are highly correlated with bone marrow sclerostin levels. Sclerostin levels are inversely related to parathyroid hormone levels. Clinical conditions in which serum sclerostin levels have been measured include ankylosing spondylitis, chronic kidney disease, diabetes, fractures, hypercortisolism, multiple myeloma and spinal cord injury. Even within clearly defined clinical conditions, however, consistent changes in serum sclerostin levels have not always been seen. This may reflect differences in currently available commercial assays or sample sources (serum versus plasma), and suggests further study is needed before sclerostin measurements are introduced into routine clinical practice. Until such issues are resolved, measurement of sclerostin levels appears to be most useful for understanding the mechanisms by which osteocytes regulate bone turnover through the integration of hormonal, physical and pharmacological stimuli, rather than to guide clinical-care decisions.