Purpose Osteocalcin (OC), an osteoblast-derived regulator of metabolic processes, and circulating early endothelial progenitor cells (EPC, CD34 − /CD133 + /KDR +) expressing OC (OC +) are potential candidates linking bone metabolism and the vasculature and might be involved in vascular atherosclerotic calcification. This study aimed at assessing the association of circulating levels of different OC forms and of EPCs count with disease severity in patients with documented coronary atherosclerosis (CAD). Methods Patients (n = 59) undergoing coronary angiography were divided, according to stenosis severity, into (1) early coronary atherosclerosis (ECA) (n = 22), and (2) late coronary atherosclerosis (LCA) (n = 37). Total OC (TOC), carboxylated OC (cOC), undercarboxylated OC (unOC) were quantified by ELISA. EPC OC + count was assessed by flow cytometry. Results EPC OC + counts showed significant differences between ECA and LCA groups. unOC and unOC/TOC ratio were inversely correlated with EPC OC + count. A significant decrease in TOC and unOC plasma levels was associated with higher cardiovascular risk factors (CVRFs) number. EPC OC + count was correlated with LDL-C, total cholesterol, and triglycerides, with a greater significance in the LCA group. No association between the different forms of circulating OC (TOC, ucOC, cOC) and severity of CAD was found. Conclusion This study showed a significant association between EPCs (CD34 − /CD133 + /KDR + /OC +), CAD severity and CVRFs, suggesting an active role for EPC OC + in the development of CAD. An inverse correlation between TOC, ucOC, and number of CVRFs was observed, suggesting that OC, regardless of its carboxylation status, may be developed as a further cardiovascular risk biomarker.

Background: New assumption concerning association of osteocalcin and Vascular calcification has emerged in reaction to observations that the mechanism of vascular calcification resembles that of bone mineralization, thus linking bone and the vasculature. However, studies reported contrasting results about the association between osteocalcin and atherosclerosis. This study was designed to evaluate capacity relationships among different forms of circulating osteocalcin and cardiovascular risk markers in male with coronary atherosclerosis. Methods: A cross-sectional study was conducted on 58 male patients, divided into two groups according to the severity of coronary artery disease (CAD), as determined by coronary angiography assessment: Early coronary atherosclerosis (ECA), n=20, patients with mild CAD (<50% stenosis in any major epicardial arteries), and late coronary atherosclerosis (LCA), n=38, patients with severe, multivessel CAD (>50% stenosis in at least one or more major epicardial arteries). The healthy control (HC) group included 26 healthy male subjects. Carboxylated (cOC) and ucOC were measured using ELISA technique. Results: We observed significantly lower ucOC levels in both stages of cardiovascular disease (CVD) (ECA and LCA) compared to the HC group (2.34±2.23 and 2.48±1.60 vs 6.65±1.78ng/mL, P<0.01). ucOC was inversely correlated with an increasing number of cardiovascular risk factors (CVRFs). Moreover, ucOC levels were markedly reduced in high-fasting plasma glucose (FPG) groups (IFG and T2DM-threshold level), compared to the normal FPG group (NG). cOC levels were higher in the IFG group, compared to the normal FPG group (8.50±4.76 vs 7.13±3.13ng/mL, p=0.008) possibly predicting such condition. Conclusions: In the present study, patients with coronary atherosclerosis, regardless of the onset of stenosis, showed lower ucOC levels which were inversely correlated with an increasing number of CVRFs. Moreover, ucOC levels were markedly reduced in high-FPG groups. Serum ucOC may be considered as a potential biomarker for coronary atherosclerosis disease and therefore its measurement may help to establish preventive and therapeutic approaches. Moreover, cOC may be associated with a high alert for diabetes at the IFG stage, but not when the disease progresses to diabetes.

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