Osteocalcin

Description
Osteocalcin (OC) or bone Gla protein is the most abundant non-collagenous protein found in bone and is produced by osteoblasts. It is a small 5.8kD protein with 49 amino acids, and has three *-carboxyglutamic acid residues at positions 17, 21, and 24. These residues serve to bind calcium ions which are required to stabilize the alpha helical region of the molecule, and also enable binding of the molecule to hydroxyapatite in bone. OC biosynthesis is stimulated by 1,25 (OH)2vitamin D. Vitamin K is required for the *-carboxylation of glutamic acid residues in OC, and reports indicate that Vitamin K could be important as a modulator of osteoblast function. A proportion of the OC that is synthesized is incorporated into the bone matrix (60 to 90%), and the rest is released into the circulation where it is rapidly degraded in the kidneys and liver. Intact OC is probably not released into the circulation during bone resorption.

Clinical Use:
During bone synthesis, osteocalcin is produced by the osteoblasts. Its production is dependent upon vitamin K and is stimulated by vitamin D3.After release from osteoblasts, osteocalcin is not only assimilated into bone matrix but also secreted into the bloodstream. Accordingly, the level in serum is related osteoblast function and can be altered in various disorders of bone metabolism. Osteocalcin can be increased Paget’s disease of bone, thyrotoxicosis and some patients with primary hyperparathyroidism. Osteocalcin can also be decreased in patients with low bone turnover such as some patients with osteoporosis in renal failure and patients with adynamic bone. OC is a particularly sensitive marker of corticosteroid effects on osteoblasts and is markedly decreased in patients receiving acute high dose steroids

Patient preparation:
None. A baseline pre-treatment measurement is required if assessing response to antiresorption therapy.

Comments and interpretation:
Osteocalcin (OC) is a relatively small protein (5.8Kda) produced by bone osteoblasts and is regulated at transcription level by 1,25 dihyroxy-vitamin D3. Other calcified tissues, including dentin and calcified cartilage also contain OC.Most of the circulating OC is a product of osteoblast activity and therefore considered an index of bone formation. In the process of matrix synthesis, some OC is released and circulates in blood with short half-life determined mainly by renal clearance. OC is increased in diseases resulting in coupled high bone turnover with increased osteoblast activity such as Paget’s disease, thyrotoxicosis and some patients with primary hyperparathyroidism.
OC is decreased in patients with low bone turnover such as some types of osteoporosis in renal failure and adynamic bone.
OC is a particularly sensitive marker of corticosteroid effects on osteoblasts and is markedly decreased in patients receiving acute high dose steroids. In patients with low vitamin K and vitamin D intake osteocalcin can be decreased.

SAS Centre providing osteocalcin and sample requirements:

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