Serum Osteocalcin

Osteocalcin is a noncollagenous, 49 amino acid glutamate-rich polypeptide bone matrix protein with a molecular weight of about 5800 kDa. Osteoblasts produce osteocalcin and incorporate it into the bone matrix. Osteocalcin is released into the circulation from the matrix during bone resorption and, therefore, is considered a marker of bone turnover rather than a specific marker of bone formation. ^[1]

The reference ranges for osteocalcin are as follows: ^{[2, 3]}

• Younger than 18 years - Not established

• Adult males (>22 y) - 5.8-14 ng/mL

• Adult females (>22 y) - 3.1-14.4 ng/mL

The image below depicts osteocalcin.

Osteocalcin levels are related to increased bone turnover. Osteocalcin decreases in patients taking antiresorptive agents (bisphosphonates or hormone-replacement therapy [HRT]); this usually occurs within 3-6 months after therapy begins. Decreasing osteocalcin levels indicate effective response to treatment. Within 3-6 months after surgical cure, osteocalcin levels in patients with primary hyperparathyroidism should return to the reference range. ^[4] See Bone Markers in Osteoporosis for more information.

Collection details are as follows:

• Specimen type - Serum

• Collection container - Red-top tube, serum gel tube is acceptable

• Submission container - Plastic vial

• Specimen volume - 1 mL, minimum volume 0.5 mL

• Collection instructions - 12-hour fast

• Reject due to gross hemolysis, mild hemolysis is acceptable

• Stability - 14 days frozen (preferred) or 72 hours refrigerated

Description

Osteocalcin is a noncollagenous, 49 amino acid glutamate-rich polypeptide bone matrix protein with a molecular weight of about 5800 kDa. Osteoblasts produce osteocalcin and incorporate it into the bone matrix. Osteocalcin is released into the circulation from the matrix during bone resorption and, therefore, is considered a marker of bone turnover rather than a specific marker of bone formation. ^[1]

The production of osteocalcin is stimulated by 1,25 dihydroxy vitamin D and depends on vitamin K. Vitamin K increases the carboxylation of osteocalcin, but it does not increase its overall rate of synthesis. Although its function is not completely understood, osteocalcin may exist as a deposition site for hydroxyapatite crystals; it may also affect energy metabolism via the production and action of insulin.

Indications/Applications

Because different antibodies recognize different fragments, no standard currently exists for osteocalcin assays. Antibodies that recognize both the large amino-terminal mid-molecule fragment and the intact molecule appear to provide superior clinical information. Osteocalcin levels vary widely among healthy individuals and those patients with osteoporosis, Paget disease, and chronic renal failure. Both the large N-terminal/midregion (N-MID) fragment (amino acids 1-43) and intact osteocalcin (amino acids 1-49) and are found in blood. ^[5] Because of protease cleavage between amino acids 43 and 44, intact osteocalcin is unstable. The N-MID-fragment, which results from cleavage, is considerably more stable, some assays are able to detect both intact osteocalcin and the stable N-MID-fragment. ^[6]

One predictor of fracture is undercarboxylated osteocalcin. Osteocalcin is rapidly cleared by the kidneys and, to a lesser extent, the liver; in circulation, the half-life of osteocalcin is about 5 minutes. Osteocalcin increases during high bone turnover (such as with hyperparathyroidism, acromegaly, and Paget disease). It decreases with hypoparathyroidism and hypothyroidism and in patients on glucocorticoid therapy. Measurement of osteocalcin can be used to monitor therapy with antiresorptive agents. The reference intervals for osteocalcin are about 1.1–11 ng/mL (adult male) and 0.7–6.5 ng/mL (adultfemale). ^[7]

Considerations

The diagnosis of osteoporosis should be based on bone density or a clinical history that includes low-trauma fracture. Osteocalcin levels should not be used to diagnose osteoporosis. Osteocalcin is cleared by the kidneys; impaired renal function causes osteocalcin levels to increase.

Serum osteocalcin may not reflect bone formation in patients treated with 1,25 dihydroxy vitamin D. This is because osteocalcin is regulated by 1,25 dihydroxy vitamin D.

Biotin may also interfere with osteocalcin testing. Do not obtain a specimen until at least 8 hours after the last biotin administration.

Patients treated with mouse antibodies or patients who have been exposed to monoclonal mouse antibody–containing products may produce erroneous findings.

Similar to the inverse correlation found in adults between serum osteocalcin levels and body mass index (BMI), a study of overweight children by Oh et al reported serum osteocalcin levels to be negatively correlated with BMI, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) index. A causal relationship, however, was not established. ^[8]