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Osteocalcin, also known as Bone-γ-carboxyglutamic Acid-Containing protein (BGP), is composed of 49 amino acids with a relative low molecular weight of about 5.8 kDa. BGP is a kind of non-collagenous bone protein widely exists in bone tissue of vertebrates, which accounting for 25% of non-collagenous protein in bone tissue and 1-2% of total bone protein. BGP is specifically synthesized and secreted by osteoblasts and a large amount of BGP is deposited in the bone matrix, while small partial of it enters into the blood circulatory system, and is finally cleared by the kidneys.

Biological functions of Osteocalcin (BGP)

1）Maintaining the normal rate of bone mineralization

One of the important functions of BGP is maintaining the normal rate of bone mineralization. After osteocalcin is synthesized, glutamic carboxylation modifications are only carried out at three sites: 17, 21 and 24. When the affinity between carboxylated BGP, free calcium ions and hydroxyapatite (HA) increases, BGP inhibits the abnormal formation of crystal HA and the mineralization rate of cartilages by tightly binding to hydroxyapatite, thus maintaining the normal mineralization rate.

2）Inhibiting the activity of osteoblasts

BGP can also inhibit the activity of osteoblasts by binding to the G-protein coupled BGP receptors expressed on osteoblasts.

3）Regulating bone resorption

BGP regulates bone resorption by recruiting, chemotaxis and activating bone resorbing cells.

Clinical significance of osteocalcin (BGP)

Serum BGP concentration can reflect the activity of osteoblasts, bone formation and transformation, and can be used as an indicator of bone metabolism.
Detection of serum BGP has good sensitivity and specificity for the diagnosis, monitoring and efficacy evaluation of osteoporosis, diabetic bone diseases, renal osteodystrophy and other osteal diseases.

A. Osteocalcin (BGP) and primary osteoporosis

The balance of bone formation and bone resorption is broken in patients with osteoporosis, and their serum BGP level has specific changes. The serum BGP level increases despite of the differences in bone formation, resorption and bone turnover rates among postmenopausal women and elderly patients with primary osteoporosis. Higher BGP levels of postmenopausal women indicate the faster loss of bone density and the greater risk of fractures. The BGP level of the elderly decreases gradually with increasing age. However, the BGP level of elderly osteoporosis patients is higher than that of normal elderly people.

Table 1. Clinical reference range of osteocalcin level for osteoporosis

Data Source	Clinical laboratory of Zhongshan hospital affiliated to Fudan University, Shanghai			Clinical laboratory of Shanghai Donghua hospital
Group	Male	Premenopausal female	Postmenopausal female	Male	Premenopausal female	Postmenopause female
N-MID BGP Concentration (μg/L)	6.00~24.66	4.11~21.87	8.87~29.05	13.4±3.6	14.8±4.8	21.6±4.6
Detection Assay	Electrochemiluminescence (ECL)

Note: The data comes from "WS/T 375-2011 guidelines for clinical application of bone metabolism indicators" Appendix B. Reference range of bone metabolic indicators; N-MID BGP is the N-terminal fragment of osteocalcin, and the BGP molecules are not homogeneous in blood. Intact BGP is unstable in the blood, and is easily cleaved into stable N-MID macromolecular fragments. Intact BGP accounts for 36% of the total BGP, N-MID accounts for 30%, and the rest are other small fragments.

B. Osteocalcin (BGP) and secondary bone diseases

Secondary bone diseases are mostly caused by other diseases such as diabetes, renal diseases, hyperthyreosis, etc. or the use of drugs. The bone metabolism is disordered in such kinds of patients and there are specific changes in their BGP levels. The insulin level decreases in diabetic patients, leading to less interactions between the insulin and the insulin receptors in osteoblasts, thus reducing the promotional effect of insulin-like growth factor 2 (IGF2) on the activity of osteoblasts. The lower activity of osteoblasts, the lower BGP level in serum. Renal function changes in patients with renal osteodystrophy (such as renal insufficiency, renal failure, etc.). The ability of the kidney to clear BGP decreases causing the content of BGP in the blood to increase.

References

[1] Bouillon R, Vanderschueren D, Van HE, et al. Homologous radioimmunoassay of human osteocalcin[J].Clin Chem, 1992, 38(10): 2055-. 2060.