The relationship of biochemical markers of bone metabolism, osteopenic syndrome and coronary atherosclerosis in men with stable coronary heart disease

   Aim: To assess the levels of bone metabolism markers in patients with stable coronary artery disease according to the severity of osteoporosis, coronary atherosclerosis and coronary artery calcification.

   Material and Methods: 112 males with angiographically verified stable coronary artery disease with an average age of 59.8 (55; 70) years were included in the study. All the patients underwent coronary angiography, multislice computed tomography (MSCT) and densitometry. The levels of mineral metabolism markers were measured by enzyme-linked immunosorbent assay. The allocation of comparison groupswas based on the severity of coronary atherosclerosis (the Syntax Score), the degree of coronary artery calcification (the Agatston score), the presence and absence of osteopenic syndrome defined by the femoral neck T-score in accordance with the guidelines of the International Society for Clinical Densitometry (ISCD, 2007).

   Results: Osteopenic syndrome has been reported in 90 (80.4 %) patients: 34 (30.4 %) patients with signs of osteoporosis, and 56 (50 %) with osteopenia. A significant decrease in cathepsin K and an increase inosteocalcinhave been found in the group with radiographically verified osteopenic syndrome compared to the group with normal bone mineral density (BMD). The assessment of coronary artery disease severity reported that multivessel coronary artery disease and severe lesions were more commonly found in patients with osteopenic syndrome. Moreover, this group of patients had more pronounced calcification compared with patients with normal BMD. Patients with severe coronary atherosclerosis had the lowest cathepsin K levels. Severe coronary artery calcification was significantly associated with lower levels of cathepsin K and osteoprotegerin, elevated alkaline phosphatase and parathyroid hormone levels.

   Conclusion: A significant association between osteopenic syndrome and severe coronary atherosclerosis and calcification has been found in males with stable coronary artery disease. Biochemical markers of bone metabolism were more likely associated with the calcification of the existing vascular lesions than with the development of coronary atherosclerosis. The findings of the study suggest that the most significant markers are cathepsin K whichsignificantly reduced in all cases, i. e. in patients with osteopenic syndrome, severe atherosclerosis and severe coronary calcification, and osteocalcin which elevated levels are associated with decreased BMD.

1. Оганов Р. Г. Факторы риска и профилактика сердечно-сосудистых заболеваний. Качество жизни / Р. Г. Оганов. – М.: Медицина, 2003. – С. 2–5.

2. Шишкова В. Н. Клиническая взаимосвязь остеопороза и атеросклероза / В. Н. Шишкова // Фарматека. – 2012. – С. 17–21.

3. Marcovitz P. A., Tran H. H., Franklin B. A. et al. Userfulness of bone mineral density to predict significant coronary artery disease // Am. J. Cardiol. 2005. Vol. 96, N 8. P. 1059–1063.

4. Fujita T. Osteoporosis: past, present and future // Osteoporosis Int. 1997. Vol. 7, N 3. P. 6–9.

5. Tanko L. B. Relationship between osteoporosis and cardiovascular disease in postmenopausal women // J. Bone. Miner. Res. 2005. Vol. 20, N 11. P. 1912–1920.

6. Banks L. M., Lees B., MacSweeney J. E., Stevenson J. C. Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? // Eur. J. Clin. Invest. 1994. Vol. 24. P. 813–817.

7. Hjortnaes J., Butcher J., Figueiredo J. L., Riccio M. et al. Arterial and aortic valve calcification inversely correlates with osteoporotic bone remodelling: a role for inflammation // Eur. Heart J. 2010. Vol. 31. P. 1975–1984.

8. Dhore C. R., Cleujens J. P. M., Lutgens E. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques // Atheroscler. Thromb. Vasc. Biol. 2001. Vol. 21. P. 1998–2003.

9. Demer L. L., Tintut Y. Mechanisms linking osteoporosis with cardiovascular calcification // Curr. Osteoporos. Rep. 2009. Vol. 7. P. 42–46.

10. Farhat G. N., Strotmeyer E. S., Newman A. B., Sutton-Tyrrell K. et al. Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the Health, Aging, and Body Composition Study // Calcif. Tissue Int. 2006. Vol. 79. P. 102–111.

11. Tekin G. O., Kekilli E., Yagmur J., Uckan A. et al. Evaluation of cardiovascular risk factors and bone mineral density in post menopausal women undergoing coronary angiography// Int. J. Cardiol. 2008. Vol. 131. P. 66–69.

12. Boskey A. L., Gelb D. E., Pourmand E., Kudrashov V. et al. Ablation of cathepsin K activity in the young mouse causes hypermineralization of long bone and growth plates // Calcif. Tissue Int. 2009. Vol. 84. P. 229–239.

13. Doherty T. M., Fitzpatrick L. A., Inoue F. Molecular, endocrine and genetic mechanisms of arterial calcification // Endocr. Rev. 2004. Vol. 24. P. 1161–1170.

14. Tintut Y., Morony S., Demer L. L. Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo // Arterioscler. Thromb. Vasc. Biol. 2004. Vol. 24. P. 6–10.

15. Vatticuti R., Towler D. A. Osteogenic regulation of vascular calcification: an early perspective // Am. J. Phisiol. Endocrinol. Metab. 2004. Vol. 286. P. 686–696.

16. Sophie E. P., Aikawa E. Molecular Imaging insights into EeInflammatory tasges of arterial and aortic valve calcification // Circ. Res. 2011. Vol. 108. P. 1381–1391.

17. Simionescu A., Simionescu D. T., Vyavahare N. R. Osteogenic responses in fibroblasts activated by elastin degradation products and transforming growth factor-beta1: role of myofibroblasts in vascular calcification // Am. J. Pathol. 2007. Vol. 171. P. 116–123.

18. Barascuk N., Skjot-Arkil H., Register T. C. Hesuea-march artnicl macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes // Cardiovascular. Disorders. 2010. Vol. 10. P. 19–24.

19. Frost M. L., Grella R., Millasseau S. C., Jiang B. Y. et al. Relationship of calcification of atherosclerotic plaque and arterial stiffness to bone mineral density and osteoprotegerin in postmenopausal women referred for osteoporosis screening // Calcif. Tissue Int. 2008. Vol. 83. P. 112–120.