Clinical Information

Osteocalcin, the most important noncollagen protein in bone matrix, accounts for approximately 1% of the total protein in human bone. It is a 49-amino acid protein with a molecular weight of approximately 5800 Da. Osteocalcin contains up to 3 gamma-carboxyglutamic acid residues as a result of posttranslational, vitamin K-dependent enzymatic carboxylation. Its production is dependent upon vitamin K and is stimulated by 1,25 dihydroxy vitamin D.

Osteocalcin is produced by osteoblasts and is widely accepted as a marker of bone osteoblastic activity. Osteocalcin, incorporated into the bone matrix, is released into the circulation from the matrix during bone resorption and, hence, is considered a marker of bone turnover rather than a specific marker of bone formation. Osteocalcin levels are increased in metabolic bone diseases with increased bone or osteoid formation, including osteoporosis, osteomalacia, rickets, hyperparathyroidism, renal osteodystrophy, thyrotoxicosis, and in individuals with fractures, acromegaly, and bone metastasis. By means of osteocalcin measurements, it is possible to monitor therapy with antiresorptive agents (bisphosphonates or hormone replacement therapy) in, for example, patients with osteoporosis or hypercalcemia.(1) Decrease in osteocalcin is also observed in some disorders (eg, hypoparathyroidism, hypothyroidism, and growth hormone deficiency).

Immunochemical and chromatographic studies have demonstrated considerable heterogeneity for concentrations of circulating osteocalcin in normal individuals and in patients with osteoporosis, chronic kidney failure, and Paget disease. Both intact osteocalcin (amino acids 1-49) and the large N-terminal/midregion (N-MID) fragment (amino acids 1-43) are present 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. This assay detects both the stable N-MID fragment and intact osteocalcin.