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Monitoring and assessing effectiveness of antiresorptive therapy in patients treated for osteopenia, osteoporosis, Paget's 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's disease, cancer accompanied by bone metastases, primary hyperparathyroidism, and renal osteodystrophy
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 hyper-calcemia.(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 renal failure, and Pagetâ€™s 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.
<18 years: not established
> or =18 years: 9-42 ng/mL
Elevated levels of osteocalcin indicate increased bone turnover.
In patients taking antiresorptive agents (bisphosphonates or hormone replacement therapy), a decrease of > or =20% from baseline osteocalcin level (ie, prior to the start of therapy) after 3 to 6 months of therapy, suggests effective response to treatment.(2)
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.(3)
Measurements of bone turnover markers are not useful for the diagnosis of osteoporosis; diagnosis of osteoporosis should be made on the basis of bone density or clinical history of low-trauma fracture.
Osteocalcin is cleared by the kidneys, hence, elevations may be observed in patients with impaired renal 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 patients receiving therapy with high doses of biotin (ie, >5 mg/day), wait at least 8 hours after the last biotin administration before drawing a specimen, to avoid assay interference from biotin.
As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from specimens taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes.
In rare cases, interference due to extremely high titers of antibodies to ruthenium or streptavidin can occur.
1. Chen JT, Hosoda K, Hasumi K, et al: Serum N-terminal osteocalcin is a good indicator for estimating responders to hormone replacement therapy in postmenopausal women. J Bone Miner Res 1996 Nov;11(11):1784-1792
2. Delmas PD, Eastell R, Garnero P, et al: The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 2000;11(6):S2-S17
3. Harris SS, Soteriades E, Dawson-Hughes B, et al: Secondary hyperparathyroidism and bone turnover in elderly blacks and whites. J Clin Endocrinol Metab 2001 Aug;86(8):3801-3804