26024 Osteocalcin, Serum (OSCAL)

Monitoring and assessing effectiveness of antiresorptive therapy in patients treated for osteopenia, osteoporosis, Paget disease, or other disorders in which osteocalcin levels are elevated.

As an adjunct in the diagnosis of medical conditions associated with increased bone turnover, including Paget disease, cancer accompanied by bone metastases, primary hyperparathyroidism, and renal osteodystrophy.

This test is not useful for the diagnosis of osteoporosis. 

​​Measurements of bone turnover markers are not useful for the diagnosis of osteoporosis, which should be made on the basis of bone density or clinical history of low-trauma fracture.​

Osteocalcin is cleared by the kidneys; therefore, elevations may be observed in patients with impaired kidney function without increased bone turnover.

Serum osteocalcin may not reflect bone formation in patients treated with the hormone 1,25-dihydroxy vitamin D or those with abnormalities in that hormone since osteocalcin is regulated by 1,25-dihydroxy vitamin D.

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may also interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.

In rare cases, interference due to extremely high titers of antibodies to ruthenium or streptavidin can occur.

​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 daltons. 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 [HRT]) in, for example, patients with osteoporosis or hypercalcemia. 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 renal 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.

Elevated levels of osteocalcin indicate increased bone turnover.

In patients taking antiresorptive agents (bisphosphonates or hormone replacement therapy), a decrease of 20% or less from baseline osteocalcin level (ie, prior to the start of therapy) after 3 to 6 months of therapy, suggests effective response to treatment.

Patients with diseases such as hyperparathyroidism, which can be cured, should have a return of osteocalcin levels to the reference range within 3 to 6 months after complete cure.