Lower uncarboxylated osteocalcin and higher sclerostin levels are significantly associated with coronary artery disease.

Systemic roles for bone-derived proteins have emerged from recent studies. In particular, the serum concentration of osteocalcin (OCN) or sclerostin was found to be associated with altered glucose metabolism or atherosclerosis. The aims of this study were to evaluate OCN and sclerostin levels in subjects who underwent coronary artery bypass graft (CABG) surgery compared with those in normal controls and to analyze their relationships with atherosclerosis. This was an age- and sex-matched case-control study that included 61 male subjects who underwent CABG and 61 controls. Forty-six subjects (37.7%) with diabetes and 62 hypertensive subjects (50.8%) were included. Serum sclerostin, uncarboxylated OCN (ucOCN) and carboxylated OCN (cOCN) were measured. Coronary artery calcium (CAC) score was calculated according to Agatston's method, using a 64-slice multi-detector computed tomography scanner. The levels of serum ucOCN were significantly lower and sclerostin concentrations were higher in the CABG group than in the controls (p<0.05 for both), and these significances were maintained after adjusting for atherosclerotic risk factors in both diabetic and nondiabetic patients (p<0.05 in both groups). However, there was no difference in cOCN levels between CABG patients and controls. The group with abnormal CAC scores (CAC scores ≥100) had significantly higher levels of serum sclerostin (p<0.05). In multiple logistic regression analysis, both lower ucOCN and higher sclerostin levels were independently associated with CABG (odds ratio [OR] 0.43, 95% CI 0.22-0.84, p<0.05 for log(ucOCN); and OR 2.09, 95% CI 1.08-4.05, p<0.05 for log(sclerostin)). In subjects with CAD who underwent CABG, the serum ucOCN level was decreased and the sclerostin level was increased compared with those in the controls, regardless of diabetic status. Longitudinal studies are warranted to establish the precise roles of ucOCN and sclerostin in the pathogenesis of atherosclerosis.