Top

Osteoporosis International

Published in:

01-04-2013 | Original Article

Association of bone turnover markers with mortality in men referred to coronary angiography

Authors: E. Lerchbaum, V. Schwetz, S. Pilz, T. B. Grammer, M. Look, B. O. Boehm, B. Obermayer-Pietsch, W. März

Published in: Osteoporosis International | Issue 4/2013

Abstract

Summary

We aimed to examine the association of fatal events with osteocalcin (OC) and beta-crosslaps (β-CTX) levels in men. We observed a U-shaped association of OC and β-CTX levels with fatal events in a large cohort of men at high cardiovascular risk.

Introduction

Accumulating evidence suggests an association of low OC levels with metabolic disturbances. Whether OC levels are related to fatal events is, however, less clear. Further, high β-CTX levels are linked to increased mortality. We aimed to examine the association of fatal events with both OC and β-CTX in men.

Methods

We measured OC and β-CTX in 2,271 men referred to coronary angiography (1997–2000).

Results

We observed a U-shaped association of OC and β-CTX with fatal events. Crude hazard ratios (HRs) for all-cause and non-cardiovascular mortality in the highest OC quintile were 1.38 (1.04–1.83) and 1.47 (0.89–2.40), respectively, and 2.11 (1.61–2.75) and 2.06 (1.29–3.29) for men in the lowest compared to the third OC quintile. In multivariate-adjusted models, HRs for all-cause, and non-cardiovascular mortality in the lowest OC quintile were 1.63 (1.23–2.16) and 1.79 (1.10–2.92), respectively, compared to the third OC quintile, whereas the association of high OC with mortality lost its significance. Crude and multivariate-adjusted HRs for cardiovascular mortality in the lowest OC quintile compared to the third OC quintile were 2.08 (1.49–2.90) and 1.74 (1.24–2.46), respectively. Moreover, high as well as low β-CTX levels were independently associated with all-cause (quintile 1 vs. quintile 3: HR 1.42 (1.05–1.92); quintile 5 vs. quintile 3: HR 1.79 (1.31–2.45)) and cardiovascular mortality (quintile 1 vs. quintile 3: HR 1.55 (1.05–2.28); quintile 5 vs. quintile 3: HR 1.85 (1.23–2.77)).

Conclusions

We observed a U-shaped association of OC and β-CTX with fatal events in a large cohort of men at high cardiovascular risk.

Sambrook PN, Chen CJ, March L, Cameron ID, Cumming RG, Lord SR, Simpson JM, Seibel MJ (2006) High bone turnover is an independent predictor of mortality in the frail elderly. J Bone Miner Res 21(4):549–555PubMedCrossRef

Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ 3rd (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137(9):1001–1005PubMed

Trivedi DP, Khaw KT (2001) Bone mineral density at the hip predicts mortality in elderly men. Osteoporos Int 12(4):259–265PubMedCrossRef

Reyes-Garcia R, Rozas-Moreno P, Jimenez-Moleon JJ, Villoslada MJ, Garcia-Salcedo JA, Santana-Morales S, Muñoz-Torres M (2011) Relationship between serum levels of osteocalcin and atherosclerotic disease in type 2 diabetes. Diabetes Metab in press

Vogt MT, San Valentin R, Forrest KY, Nevitt MC, Cauley JA (1997) Bone mineral density and aortic calcification: the Study of Osteoporotic Fractures. J Am Geriatr Soc 45(2):140–145PubMed

Watson KE, Boström K, Ravindranath R, Lam T, Norton B, Demer LL (1994) TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify. J Clin Invest 93(5):2106–2113PubMedCrossRef

Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, Spronk HM, Vermeer C, Daemen MJ (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21(12):1998–2003PubMedCrossRef

Im JA, Yu BP, Jeon JY, Kim SH (2008) Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chem Acta 396(1–2):66–69CrossRef

Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94(3):827–832PubMedCrossRef

10.

Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, Sugimoto T (2009) Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 94(1):45–49PubMedCrossRef

11.

Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Hankey GJ, Beilby JP, Norman PE (2012) Associations of total osteocalcin with all-cause and cardiovascular mortality in older men. The Health In Men Study. Osteoporos Int 23(2):599–606PubMedCrossRef

12.

Peichl P, Griesmacherb A, Marteau R, Hejc S, Kumpan W, Müller MM, Bröll H (2001) Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers. Clin Biochem 34(2):131–139PubMedCrossRef

13.

Winkelmann BR, März W, Boehm BO, Zotz R, Hager J, Hellstern P, Senges J, LURIC Study Group (LUdwigshafen RIsk and Cardiovascular Health) (2001) Rationale and design of the LURIC study—a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics 2(1 Suppl 1):S1–S73PubMedCrossRef

14.

National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) (2002) National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation 106(25):3143–3421

15.

Hamann C, Kirschner S, Günther KP, Hofbauer LC (2012) Bone, sweet bone-osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 8(5):297–305PubMedCrossRef

16.

Hagström E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundström J, Melhus H, Held C, Lind L, Michaëlsson K, Arnlöv J (2009) Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation 119(21):2765–2771PubMedCrossRef

17.

Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130(3):456–469PubMedCrossRef

18.

Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G (2011) Endocrine regulation of male fertility by the skeleton. Cell 144(5):796–809PubMedCrossRef

19.

Kirmani S, Atkinson EJ, Melton LJ 3rd, Riggs BL, Amin S, Khosla S (2011) Relationship of testosterone and osteocalcin levels during growth. J Bone Miner Res 26(9):2212–2216PubMedCrossRef

20.

Wehr E, Pilz S, Boehm BO, März W, Grammer TB, Obermayer-Pietsch B (2010) Sex steroids and mortality in men referred for coronary angiography. Clin Endocrinol 73(5):613–621CrossRef

21.

Wehr E, Pilz S, Boehm BO, März W, Grammer T, Obermayer-Pietsch B (2011) Low free testosterone is associated with heart failure mortality in older men referred for coronary angiography. Eur J Heart Fail 13(5):482–488PubMedCrossRef

22.

Pal SN, Rush C, Parr A, Van Campenhout A, Golledge J (2010) Osteocalcin positive mononuclear cells are associated with the severity of aortic calcification. Atherosclerosis 210(1):88–93PubMedCrossRef

23.

Montalcini T, Emanuele V, Ceravolo R, Gorgone G, Sesti G, Perticone F, Pujia A (2004) Relation of low bone mineral density and carotid atherosclerosis in postmenopausal women. Am J Cardiol 94(2):266–269PubMedCrossRef

24.

Pennisi P, Signorelli SS, Riccobene S, Celotta G, Di Pino L, La Malfa T, Fiore CE (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15(5):389–395PubMedCrossRef

25.

Meier C, Nguyen TV, Center JR, Seibel MJ, Eisman JA (2005) Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study. J Bone Miner Res 20(4):579–587PubMedCrossRef

26.

Szulc P, Garnero P, Claustrat B, Marchand F, Duboeuf F, Delmas PD (2002) Increased bone resorption in moderate smokers with low body weight: the Minos study. J Clin Endocrinol Metab 87(2):666–674PubMedCrossRef

27.

Szulc P, Samelson EJ, Kiel DP, Delmas PD (2009) Increased bone resorption is associated with increased risk of cardiovascular events in men: the MINOS study. J Bone Miner Res 24(12):2023–2031PubMedCrossRef

28.

Sambrook PN, Chen JS, March LM, Cameron ID, Cumming RG, Lord SR, Schwarz J, Seibel MJ (2004) Serum parathyroid hormone is associated with increased mortality independent of 25-hydroxy vitamin d status, bone mass, and renal function in the frail and very old: a cohort study. J Clin Endocrinol Metab 89(11):5477–5481PubMedCrossRef

29.

Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281PubMedCrossRef

30.

Lerchbaum E, Pilz S, Grammer TB, Boehm BO, März W, Obermayer-Pietsch B (2011) High estradiol levels are associated with increased mortality in older men referred to coronary angiography. Exp Clin Endocrinol Diabetes 119(8):490–496PubMedCrossRef

31.

Røysland R, Bonaca MP, Omland T, Sabatine M, Murphy SA, Scirica BM, Bjerre M, Flyvbjerg A, Braunwald E, Morrow DA (2012) Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes. Heart 98(10):786–791PubMedCrossRef

32.

Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142(2):296–308PubMedCrossRef

33.

Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105(13):5266–5270PubMedCrossRef

34.

Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22(1):187–194PubMedCrossRef

35.

Shea MK, Gundberg CM, Meigs JB, Dallal GE, Saltzman E, Yoshida M, Jacques PF, Booth SL (2009) Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr 90(5):1230–1235PubMedCrossRef

36.

Gundberg CM (2009) Vitamin K and bone: past, present, and future. J Bone Miner Res 24(6):980–982PubMedCrossRef

37.

Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, Bilezikian JP, Shoback DM, Black DM (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96(12):E1982–E1989PubMedCrossRef

Title: Association of bone turnover markers with mortality in men referred to coronary angiography
Authors: E. Lerchbaum
V. Schwetz
S. Pilz
T. B. Grammer
M. Look
B. O. Boehm
B. Obermayer-Pietsch
W. März
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 4/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-012-2076-9

At a glance: The STEP trials

Springer Medicine

Association of bone turnover markers with mortality in men referred to coronary angiography

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2013

A comparison of DXA and CT based methods for estimating the strength of the femoral neck in post-menopausal women

Bilateral ulna fractures associated with bisphosphonate therapy

Performance of FRAX in a cohort of community-dwelling, ambulatory older men: the Osteoporotic Fractures in Men (MrOS) study

Prognostic value of cardiac troponins in elderly patients with hip fracture—a systematic review

The contributions of First Nations ethnicity, income, and delays in surgery on mortality post-fracture: a population-based analysis

Increased risk of osteoporosis-related fractures in patients with irritable bowel syndrome