Osteocalcin: Beyond Bones

Apart from basic roles such as supporting the body, protecting internal organs, and storing calcium, the skeletal system also performs hormonal functions. In recent years, several reports have been published on proteins secreted by bones and their impact on the homeostasis of the entire body. These proteins include fibroblast growth factor 23, sclerostin, lipocalin 2, and osteocalcin. Osteocalcin, the most abundant non-collagenous protein in bone tissue, is routinely measured as a clinical marker for diagnosing bone metabolism disorders. Its molecule undergoes numerous transformations, with decarboxylation being the critical process. Decarboxylation occurs in the acidic environment typical of bone resorption, facilitating the release of the molecule into the bloodstream and enabling its hormonal action. Decarboxylated osteocalcin promotes insulin secretion and stimulates the proliferation of pancreatic islet β-cells. It also plays a role in reducing the accumulation of visceral fat and decreasing fat storage in the liver. Furthermore, decarboxylated osteocalcin levels are inversely correlated with fasting serum glucose levels, total body fat, visceral fat area, and body mass index. Apart from its role in energy metabolism, osteocalcin affects testosterone production and the synthesis of glucagon-like peptide-1. It is also actively involved in muscle-bone crosstalk and influences cognitive function.