Relationship Of Serum Osteocalcin Levels With Body Fat And Cardiovascular Risk Factors

Objective: Changes in body composition including excess body fat and/or skeletal muscle loss,and the related QT interval prolongation and atherosclerosis are closely associated with cardiovascular disease.Bone has been newly recognized as an endocrine organ.Osteocalcin(OCN),a major bone-derived factor,plays a role in glycolipid metabolism,which may reduce the risk for metabolic diseases and cardiovascular adverse outcomes.The aim of this study was to explore the correlation of serum OCN levels with body fat distribution and skeletal muscle loss and prolonged QT interval,as well as to evaluate the value of serum OCN levels in identifying subclinical atherosclerosis.Methods: All subjects were recruited in the communities in Shanghai.The abdominal fat accumulation,including visceral fat area(VFA)and subcutaneous fat area(SFA),was assessed by magnetic resonance imaging.Body composition was measured using an automatic bioelectric impedance analyser.Relative skeletal muscle index was calculated using the related equation to evaluate skeletal muscle mass.Carotid intima-media thickness(C-IMT)was measured using ultrasonography.Corrected QT interval(QTc)was measured using a 12-lead electrocardiogram and calculated based on the Bazett formula.Serum OCN levels were determined using an electrochemiluminescence immunoassay.Serum fibroblast growth factor 23(FGF23)and lipocalin-2(LCN-2)were determined using a sandwich enzyme-linked immunosorbent assay.Results:(1)In 1742 subjects(775 men and 967 postmenopausal women),OCN was negatively correlated with body fat especially accunmulation of abdorminal fat.In men with hyperglycemia,especially those with impaired glucose tolerance,OCN was positively correlated with skeletal muscle index;however,the relationship was not detected in postmenopausal women.(2)In 1210 subjects(488 men and 722 women),decreasing serum OCN levels acompanied the prolongation of QTc interval.Serum OCN levels were independently correlated with QTc interval,and thus VFA partially mediates the negative correlation.(3)In 618 middle-aged and elderly men,serum OCN levels were independently and inversely associated with elevated C-IMT.Furthermore,combining the atherosclerotic cardiovascular disease risk score and low serum OCN levels could improve the recognition rate of elevated C-IMT.(4)In 1179 subjects(465 men and 714 women),bone-derived fibroblast growth factor 23(FGF23)and lipocalin-2(LCN-2)were positively correlated with body fat parameters,whereas OCN levels were inversely correlated.In addition,serum OCN,FGF23,and LCN-2 levels were independently associated with body fat distribution(no interaction observed).Conclusions: Serum OCN levels were inversely associated with body fat and visceral adiposity.The positive relationship between serum OCN levels and skeletal muscle index in men is affected by hyperglycemia,but was not detected in postmenopausal women.VFA partially mediates the independent and inverse correlation between serum OCN levels and QTc interval.Serum OCN levels strengthen identifying subclinical atherosclerosis over the atherosclerotic cardiovascular disease risk score.There was no interaction among the relationship of bone-derived factors(serum OCN,FGF23 and LCN-2 levels)with body fat distribution.