osteokalcin

Osteokalcin, or osteocalcin, is a non-collagenous protein produced primarily by osteoblasts and, to a lesser extent, osteocytes in bone. It is encoded by the BGLAP gene and is synthesized as a precursor that undergoes vitamin K–dependent gamma-carboxylation, producing carboxylated osteocalcin. The carboxylated form binds tightly to hydroxyapatite in the bone matrix, contributing to mineralization and bone strength.

Two main forms circulate in blood: carboxylated osteocalcin, which is largely bone-bound, and undercarboxylated osteocalcin, which is released into the circulation. The circulating undercarboxylated form has been proposed to act as a hormone, influencing energy metabolism and reproductive function in animal models. In particular, studies in rodents have suggested roles in regulating insulin secretion and sensitivity, adipose tissue metabolism, and testosterone production. In humans, associations between osteocalcin levels and metabolic markers have been observed, but causal relationships remain under investigation, and the endocrine significance is not yet fully established.

Clinical relevance of osteocalcin includes its use as a bone turnover marker. Serum osteocalcin reflects osteoblast activity and is sometimes measured to monitor bone formation, especially in osteoporosis management. However, levels can be influenced by vitamin K status, bone turnover rate, age, and kidney function, so osteocalcin is interpreted alongside other markers of bone health.

Osteocalcin participates in the complex regulation of bone formation and, potentially, systemic metabolism. Ongoing research aims to clarify its hormonal roles in humans and its potential implications for metabolic and skeletal diseases.