Osteocalcin, the most important non - collagen protein in bone matrix, is a bone - specific, calcium - binding protein which is dependent on vitamin K. It contains 49 amino acids and has a molecular weight of approx. 5800 daltons. It contains up to three γ‑carboxyglutamic acid residues (bone - GLA - protein, BGP).
During bone synthesis osteocalcin is produced by the osteoblasts. Its production is dependent upon vitamin K (formation of γ‑carboxyglutamic acid residues) and is stimulated by vitamin D3. After release from the osteoblasts, osteocalcin is not only assimilated into the bone matrix but also secreted into the blood stream. Accordingly, the serum (plasma) osteocalcin level is related to the rate of bone turnover in various disorders of bone metabolism, e.g. osteoporosis in particular, but also in primary and secondary hyperparathyroidism or Paget's disease.
Osteocalcin is therefore termed a bone turnover marker and is used for this purpose. By means of osteocalcin measurements it is possible to monitor therapy with antiresorptive agents (bisphosphonates or hormone replacement therapy, HRT) in, for example, patients with osteoporosis or hypercalcemia.
Both intact osteocalcin (amino acids 1‑49) and the large N‑MID fragment (amino acids 1‑43) occur in blood. Intact osteocalcin is unstable due to protease cleavage between amino acids 43 and 44. The N‑MID‑fragment resulting from cleavage is considerably more stable