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Low serum osteocalcin levels are correlated with left ventricular systolic dysfunction and cardiac death in Chinese men


Osteocalcin is a newly identified type of cytokine secreted by osteoblasts, which has an endocrine function, mediates energy and glycol-lipid metabolism, and is closely related to cardiovascular diseases. In this study, we investigated the value of serum osteocalcin levels in predicting left ventricular systolic dysfunction and cardiac death. A total of 258 patients in the Department of Cardiology were included. Two-dimensional echocardiography was performed in all the subjects. The cardiac death of subjects occurring with a median follow-up of 4.6 years was informed via phone calls or the electronic medical records. The serum osteocalcin levels were measured using electrochemiluminescent immunoassay. We found that the median left ventricular ejection fractions (LVEFs) were 62% in men and 63% in women. In the men with a LVEF > 62%, the serum osteocalcin levels were significantly higher than in those with LVEF ≤ 62% (P= 0.042), whereas this difference was absent in the women. Both the serum osteocalcin (β = 0.095, P= 0.028) and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP; β = −0.003, P< 0.01) levels remained independently significantly correlated with LVEF in the men but not in the women. Receiver operating characteristic (ROC) analyses of the men revealed that the serum osteocalcin (P = 0.007), serum NT-pro-BNP (P = 0.018) and serum osteocalcin + NT-pro-BNP (P < 0.01) levels were all significant in identifying left ventricular systolic dysfunction at baseline, but the pairwise comparisons of the three areas under the curves (AUCs) were all non-significant. The men in the lower osteocalcin level group at baseline suffered a greater risk of future cardiac death than those in the higher osteocalcin level group, whereas the result for NT-pro-BNP exhibited the opposite pattern. In conclusion, lower serum osteocalcin levels in the men could identify left ventricular systolic dysfunction and cardiac death in a manner that was not inferior to high serum NT-pro-BNP levels.

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  1. 1.

    Sennerby U, Melhus H, Gedeborg R, Byberg L, Garmo H, Ahlbom A, et al. Cardiovascular diseases and risk of hip fracture. JAMA. 2009;302:1666–73.

  2. 2.

    Lai SW, Liao KF, Lai HC, Tsai PY, Lin CL, Chen PC, et al. Risk of major osteoporotic fracture after cardiovascular disease: a population-based cohort study in Taiwan. J Epidemiol. 2013;23:109–14.

  3. 3.

    Reyes-Garcia R, Rozas-Moreno P, Jimenez-Moleon JJ, Villoslada MJ, Garcia-Salcedo JA, Santana-Morales S, et al. Relationship between serum levels of osteocalcin and atherosclerotic disease in type 2 diabetes. Diabetes Metab. 2012;38:76–81.

  4. 4.

    Szulc P, Garnero P, Claustrat B, Marchand F, Duboeuf F, Delmas PD. Increased bone resorption in moderate smokers with low body weight: the Minos study. J Clin Endocrinol Metab. 2002;87:666–74.

  5. 5.

    Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456–69.

  6. 6.

    Bao YQ, Zhou M, Lu ZG, Li HT, Wang Y, Sun LQ, et al. Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin Endocrinol (Oxf). 2011;75:196–201.

  7. 7.

    Schleithoff SS, Zittermann A, Stüttgen B, Tenderich G, Berthold HK, Körfer R, et al. Low serum levels of intact osteocalcin in patients with congestive heart failure. J Bone Miner Metab. 2003;21:247–52.

  8. 8.

    Dou JX, Li HT, Ma XJ, Zhang ML, Fang QC, Nie MY, et al. Osteocalcin attenuates high fat diet-induced impairment of endothelium-dependent relaxation through Akt/eNOS-dependent pathway. Cardiovasc Diabetol. 2014;13:74.

  9. 9.

    Judkins MP. Percutaneous transfemoral selective coronary arteriography. Radiol Clin North Am. 1968;6:467–92.

  10. 10.

    World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. WHO, Geneva, Switzerland 1999.

  11. 11.

    Whitworth JA, World Health Organization. International Society of Hypertension Writing Group. World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983–92.

  12. 12.

    Yang GH, Fan LX, Tan J, Qi GM, Zhang YF, Samet JM, et al. Smoking in China: findings of the 1996 National Prevalence Survey. JAMA. 1999;282:1247–53.

  13. 13.

    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233–70.

  14. 14.

    Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anat Valid Method Circ. 1977;55:613–8.

  15. 15.

    Zou KH, O’Malley AJ, Mauri L. Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation. 2007;115:654–7.

  16. 16.

    Verheyen N, Fahrleitner-Pammer A, Belyavskiy E, Gruebler MR, Dimai HP, Amrein K, et al. Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial. PLoS ONE. 2017;12:e0173799.

  17. 17.

    Bozic B, Loncar G, Prodanovic N, Radojicic Z, Cvorovic V, Dimkovic S, et al. Relationship between high circulating adiponectin with bone mineral density and bone metabolism in elderly males with chronic heart failure. J Card Fail. 2010;16:301–7.

  18. 18.

    Wu C, Kato TS, Pronschinske K, Qiu S, Naka Y, Takayama H, et al. Dynamics of bone turnover markers in patients with heart failure and following haemodynamic improvement through ventricular assist device implantation. Eur J Heart Fail. 2012;14:1356–65.

  19. 19.

    Yeap BB, Chubb SAP, Flicker L, McCaul KA, Ebeling PR, Hankey GJ, et al. Associations of total osteocalcin with all-cause and cardiovascular mortality in older men. The Health In Men Study. Osteoporos Int. 2012;23:599–606.

  20. 20.

    Yamashita T, Okano K, Tsuruta Y, Akiba T, Nitta K. Serum osteocalcin levels are useful as a predictor of cardiovascular events in maintenance hemodialysis patients. Int Urol Nephrol. 2013;45:207–14.

  21. 21.

    Hwang YC, Kang M, Cho IJ, Jeong IK, Ahn KJ, Chung HY, et al. Association between the circulating total osteocalcin levels and the development of cardiovascular disease in middle-aged men: a mean 8.7-year longitudinal follow-up study. J Atheroscler Thromb. 2015;22:136–43.

  22. 22.

    Bao YQ, Ma XJ, Yang R, Wang FF, Hao YP, Dou JX, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab. 2013;98:345–51.

  23. 23.

    Luo YQ, Ma XJ, Hao YP, Pan XP, Xu YT, Xiong Q, et al. Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels. Acta Pharmacol Sin. 2015;36:1497–502.

  24. 24.

    Kareinen A, Viitanen L, Halonen P, Lehto S, Laakso M. Cardiovascular risk factors associated with insulin resistance cluster in families with early-onset coronary heart disease. Arterioscler Thromb Vasc Biol. 2001;21:1346–52.

  25. 25.

    Pi M, Quarles LD. Multiligand specificity and wide tissue expression of GPRC6A reveals new endocrine networks. Endocrinology. 2012;153:2062–9.

  26. 26.

    Wellendorph P, Bräuner-Osborne H. Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene. 2004;335:37–46.

  27. 27.

    Gamal SM, Sadek NB, Rashed LA, Shawky HM, Gamal EM. Effect of gamma-carboxylase inhibition on serum osteocalcin may be partially protective against developing diabetic cardiomyopathy in type 2 diabetic rats. Diab Vasc Dis Res. 2016;13:405–17.

  28. 28.

    Jung CH, Lee WJ, Hwang JY, Lee MJ, Seol SM, Kim YM, et al. The preventive effect of uncarboxylated osteocalcin against free fatty acid-induced endothelial apoptosis through the activation of phosphatidylinositol 3-kinase/Akt signaling pathway. Metabolism. 2013;62:1250–7.

  29. 29.

    Luo YQ, Ma XJ, Hao YP, Xiong Q, Xu YT, Pan XP, et al. Relationship between serum osteocalcin levels and carotid intima-media thickness in a metabolically healthy Chinese population. Cardiovasc Diabetol. 2015;14:82.

  30. 30.

    Jung KY, Kim KM, Ku EJ, Kim YJ, Lee DH, Choi SH, et al. Age- and sex-specific association of circulating osteocalcin with dynamic measures of glucose homeostasis. Osteoporos Int. 2016;27:1021–29.

  31. 31.

    Jagtap VR, Ganu JV, Nagane NS. BMD and serum intact osteocalcin in postmenopausal osteoporosis women. Indian J Clin Biochem. 2011;26:70–3.

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The authors thank all the staff of the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for their efforts in this study. This study was supported by the Translational Medicine Innovation Foundation of Shanghai Jiao Tong University School of Medicine (15ZH4006), and National Natural Science Foundation of China (31571212).

Author contribution:

X-JM and Y-QB designed the study and revised the manuscript; Y-TX, QX, X-LZ and YS performed the data collection; X-LZ and YS performed the analyses and drafted the manuscript; Z-GL performed the angiography at baseline. All authors have revised the paper critically for intellectual content and approved the final version.

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Correspondence to Yu-qian Bao.

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The authors declare no competing interests.

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  • cardiac death
  • coronary artery disease
  • left ventricular systolic dysfunction
  • osteocalcin
  • N-terminal pro-brain natriuretic peptide
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