MINERAL'NAYa PLOTNOST' KOSTI I SOSTOYaNIE SOSUDISTOY STENKI V ZAVISIMOSTI OT STATUSA REPLIKATIVNOGO KLETOChNOGO STARENIYa U ZhENShchIN V POSTMENOPAUZAL'NOM PERIODE

Objective: to examine the relationship between bone mineral density (BMD), the parameters of vascular stiffness and biomarkers of cellular aging in postmenopausal women. Materials and Methods: In a cross-sectional study107 patients were included: women at the age range of 45 to 82 years who were observed outpatient and signed a written informed consent. Assessment of BMD was performed using DXA (Delphi W, Hologic, USA). The intima-media thickness (IMT), the presence and quantity of atherosclerotic plaques (AP), and the degree of carotid stenosis were examined by duplex scanning. The pulse wave velocity (PWV), augmentation index (Aix) were measured by applanation tonometry (SphygmoCor).To determine telomere length (DT) in leukocytes the method of real-time PCR was used. This was done by measuring the relative telomere length in the genomic DNA. Determination of telomerase activity (Aix) was carried out on pure monocyte fraction of isolated blood cells on the basis of telomerase polymerase reaction.Statistical analysis was performed using the software application Statistical Analysis System (USA). Results: With the increase in duration of menopause a gradual increase in the stiffness rate (PWV, AI), IMT and decrease of BMD was noticed in all examined parts of the skeleton. The maximal values of vascular stiffness, minimal values of BMD and the shortest telomeres were found in patients with 10+ years of menopause. The risk of bone mass loss and osteoporosis increased by 3 times in patients with high values of PWV ≥10 m/sec[OP-3,1, 95%CI, 1,13-9,89 (p<0,05)], by more than 4 times in patients with AI≥ 20% [OP-4,35, 95%CI, 1,02-11,0 (p<0,05)]and the IMT >0,9 mm by 2,45 times in patients with presence of AP in the carotid arteries and with the shortest telomeres [OP-2,45, 95%CI, 1,05-6,08 (p<0,05)]. During multivariate regression analysis after adjusting for age and menopause duration the negative relationship between IA, IMT and BMD remained highly significant, while in relation to PWV, AP presence and telomere length, such a correlation was not confirmed. Conclusion: In postmenopausal women low BMD is associated with high rates of Aix and the thickness of the IMT. The independent relationship of BMD with Aix, rather than with PWV, apparently could be explained by the involvement of small vessels -arterioles. Short telomeres are 2.45 times more frequent in patients with low bone mass, but the relationship has not been confirmed in the regression analysis, which excludes the independent nature of this aging marker with BMD.

bone mineral density, pulse wave velocity, augmentation index, intima-media complex, telomere length, telomerase activity, postmenopausal women

1. Оганов Р.Г., Масленникова Г.Я. Смертность от сердечно-сосудистых и других неинфекционных заболеваний среди трудоспособного населения России. Кардиоваскулярная терапия и профилактика. 2002;3:4-8.

2. Скрипникова И.А., Оганов Р.Г. Остеопороз и сердечнососудистые заболевания, обусловленные атеросклерозом, у женщин постменопаузального периода: общность поведенческих и социальных факторов риска. Остеопорозиостеопатии. 2009;2:5-9.

3. LimY.H., Shin J, Lee J.U., Lim H.K., Hong S., Kim M.K., Choi B.Y., KimY.M.Bone Mineral Density is an Independent Determinant of Left Ventricular Mass Index in the General Female Population. Korean Cicc J. 2010; 406; 573-80.

4. Adler Y., Fink N., Spector D., Wiser I., Sagie A. Mitral annulus calcification a window to diffuse atherosclerosis of the vascular system. Atherosclerosis. 2001; 155; 1-8.

5. Mangiafico R.A., Alagona C., Pennisi P. Increased augmentation index and central aortic blood pressure in osteoporotic postmenopausal women. Osteoporos Int. 2008; 19:49-56.

6. Laurent S., Cockcroft J., van Bortel L.,Boutouyrie P., Giannattasio C., Hayoz D., Pannier B., Vlachopoulos C., Wilkinson I., Struijker-Boudier H. European Network for Non-invasive Investigation of Large Arteries Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J., 2006; 27(21): 2588-2605.

7. Toth P.P. Subclinical atherosclerosis: what it is, what itmeans and w hat we can do about it. Int J Clin Pract.2008; 62(8):1246-54.

8. Sumino H., Ichikawa S., Kasama S., Takahashi T., Kumakura H., Takayama Y., Kanda T., Sakamaki T., Kurabayashi M.Elevated arterial stiffness in postmenopausal women with ostoporosis. Maturitas. 2006; 55: 212-218.

9. Sabit R., Bolton C.E., Edwards P.H.,Pettit R.J., Evans W.D., McEniery C.M., Wilkinson I.B., Cockcroft J.R., Shale D.J.Arterial stiffness and osteoporosis in chronic obstructive pulmonary desease. Am. J. Respir Crit Care Med. 2007; 175:1259-1265.

10. Benetos A., Okuda K., Lajemi M., Kimura M., Thomas F., Skurnick J., Labat C., Bean K., Aviv A. Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 2001; 37: 381-385.

11. Yudoh K., Matsuno H., Nakazawa F.,Katayama R., Kimura T. Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts. J Bone Miner Res 2001; 16(8):1453-1464.

12. Valdes A.M., Richards J.B. Gardner J.P,Swaminathan R., Kimura M., Xiaobin L., Aviv A., Spector T.D. Telomere lenght in leucocytes correlates with bone mineral density and is shorter in women with ostеoporosis. Osteoporos Int 2007: 18:1203-1210.

13. Saeed H., Abdallah B.M., Ditzel N.,Catala-Lehnen P., Qiu W., Amling M., Kassem M. Telomerase-deficient mice exhibit bone loss owing to detects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment. J Bone Miner Res.2011:26(7); 1494-505.

14. Fitzpatrick A.L., Kronmal R.A., Kimura M. Leukocyte telomere length and mortality in the cardiovascular health study. J. Gerontol. Biol. Sci. Med. 2011; 66: 421-429.

15. Bauer D.C., Browner W.S., Cauley J.A., Orwoll E.S., Scott J.C., Black D.M., Tao J.L., Cummings S.R. Factors associated with appendicular bone mass in older women: the Study of Osteoporotic Fractures Research Group. Ann Intern Med 1993;118: 657-65.

16. Kawecka-Jaszcz K., Czarnecka D., Olszanecka A., Rajzer M., Jankowski P. The effect of hormone replacement therapy on arterial blood pressure and vascular compliance in postmenopausal women with arterial hypertension. J Hum Hypertens 2002;16: 509-16.

17. Hirose K., Tomiyama H., Okazaki R., Arai T., Koji Y., Zaydun G., Hori S., Yamashina A. Increased pulse wave velocity associated with reduced calcaneal quantitative osteo-sono index: possible relationship between atherosclerosis and osteopenia. J Clin Endocrinol Metab 2003; 88: 2573-2578.

18. London G.M., Blacher J., Pannier B, Guérin A.P, Marchais S.J., Safar M.E.Arterial wave Reflections and Survival in End-Stage Renal Failure.Hypertension. 2001;38:434-438.

19. Van Guldener C., Janssen M.F, Lambert J.,Steyn M., Donker A.J., Stehouwer C.D. Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients. Nephrol Dial Transplant. 1998;13:1782-1786

20. Griffith J.F., Wang Y.X., Zhou H.A., Kwong W.H., Wong W.T., Sun Y.L., Huang Y., Yeung D.K., Qin L., Ahuja A.T. Redused bone perfusion in osteoporosis: likely causes in an ovariectomy rat model. RSNA, 2010; 3: 739-746

21. McEniery C.M., Wallace S., Mackenzie I.S., McDonnell B., Yasmin, Newby D.E., Cockcroft J.R., Wilkinson I.B. Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans. Hypertension 2006; 48: 602-608

22. Sanada M., Taguchi A., Higashi Y., Tsuda M., Kodama I., Yoshizumi M., Ohama K. Forearm endothelial function and bone mineral loss in postmenopausal women. Atherosclerosis 2004; 176:387-392

23. den Ruijter H.M., Vaartjes I., Sutton-Tyrrell K.,Bots M.L., Koffijberg H. Long-term health benefits and costs of measurement of carotid intima-media thickness in prevention of coronary heart disease. J Hypertens 2013; 31: 782-90

24. Mohammadi А., Shateri К., Behzadi F.,Maleki-Miandoab T., Lesha E., Ghasemi-Rad M., Rosta Y.Relationship between intima-media thickness and bone mineral density in postmenopausal women: a crosssectional study. Int J Clin Exp Med 2014;7(12):5535-5540

25. Varri M., Tuomainen T.P., Honkanen R., Rikkonen T., Niskanen L., Kröger H., Tuppurainen M.T. Carotid intima-media thickness and calcification in relation to bone mineral density in postmenopausal women-the ostpre-bba study. Maturitas 2014; 78 (4): 304-9.

26. Tauchi H., Sato T., Watanabe T. Japanese Centenarians: Medical Research for the Final Stages of Human Aging. Aichi, Japan: Aichi Medical University, 1999. 200р.

27. Fitzpatrick A.L., Kronmal R.A., Gardner J.P., Psaty B.M., Jenny N.S., Tracy R.P., Walston J., Kimura M., Aviv A. Leukocyte telomere length and cardiovascular disease in the Cardiovascular Health Study. Am J Epidemiol.2007;165(1):14- 21.

28. von Zglinicki T., Serra V., Lorenz M., Saretzki G., Lenzen-Grossimlighaus R., Gessner R., Risch A., Steinhagen-Thiessen E.Short telomeres in patients with vascular dementia: an indicator of low antioxidative capacity and a possible risk factor? Lab. Invest. 2000; 80: 1739-47.