Aim. To assess the body composition and functional activity (FA) parameters in men with heart failure (HF) of various nature depending on the stage, class and echocardiographic characteristics of the disease.Material and methods. The study included 100 men aged 23-70 years. The main group consisted of 60 men with HF, the control group — 40 men without HF. Quantitative body composition assessment (fat, lean and bone body mass) was carried out using dual-energy X-ray absorptiometry (DXA). Physical activity was assessed using handgrip test, short physical performance battery (SPPB) test, 6-minute walk test (6MWT), and Timed Up and Go (TUG) test.Results. In the HF group, there were a significant decrease in total bone mass, trunk and limb bone mass, total muscle mass, trunk and limbs’ muscle mass, appendicular skeletal muscle index (ASMI), and FA as HF class increased. Fat mass did not differ in individuals with different HF class and stage. HF class was an independent factor in the reduction of total bone mass (b=-301,9, p=0,015), total muscle mass (b=-1903, p=0,03), limb bone mass (b=-147,6, p=0,013) and appendicular muscle mass (AMM) (b=-1903, p=0,001). Total bone mass (b=-2,637, p=0,02) and AMM (b=-3,512, p=0,01) were independently associated with the Vasilenko-Strazhesko HF stage. AMM also had an independent association with left ventricular ejection fraction (LVEF) (b=0,274, p=0,03). The average body composition scores did not differ between the study and control groups, while the scores of handgrip test, 6MWT, SPPB and TUG test were significantly worse in the HF group. NYHA HF class, stage of HF, LVEF, left ventricular end-diastolic volume (LVEDV) and pulmonary artery systolic pressure (PASP) made an independent contribution to FA decrease in men with HF.Conclusion. In patients with HF, there was deterioration in musculoskeletal parameters depending on HF class, stage and LVEF, without significant differences compared to the control group. There was no association of fat mass with the disease, clinical and echocardiographic characteristics. The average parameters of muscle strength and tests of FA were reduced in men with HF compared with the control group and depended on the NYHA class and stage of HF, LVEF, LVEDV, and PASP.

Aim. To study associations between arterial stiffness and bone mineral density in postmenopausal women.Material and methods. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation. The Bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry.Results. A significant correlation of PWV with age, duration of menopause was revealed, a more pronounced correlation was noted with blood pressure (BP), maximum IMT thickness. There was no significant correlation between PWV and BMD. AI showed a statistically significant but weak negative correlation with the HN (rs=0.12, p<0.05); a more pronounced negative correlation was obtained for BMD (rs=0.16, p<0.01). For indicators characterizing the degree of bone mass increased, there is a significant correlation with age (rs=-0.4, p<0.01), weight (rs=0.4, p<0.01), Quetelet index (rs=0.3, p<0.01) and the presence of AP (rs=-0.12, p<0.05). According to the results of multivariate regression analysis, the most significant predictors of arterial stiffness were indicators reflecting obesity and diastolic BP. The relationship between BMD and age-adjusted vascular stiffness was not statistically significant.Conclusion. In our study, postmenopausal women have increased arterial stiffness, suggesting a higher risk of cardiovascular disease. The relationship between bone mineral density and vascular wall stiffness was insignificant. To a greater extent, arterial stiffness depended on age, increased blood pressure, and the presence of atherosclerotic changes.

Aim. To evaluate bone mineral density (BMD) and parameters of bone metabolism in men with heart failure (HF) of various origins.Material and methods. The study included 100 men aged 20-70 years. The main group consisted of 60 men with HF, while the control group — 40 men without HF. BMD was measured using dual energy X-ray absorptiometry. The levels of C-terminal telopeptide type I collagen (CTx) and N-terminal propeptide type 1 procollagen (P1NP) were determined in blood serum by electrochemiluminescence immunoassay.Results. Analysis in the group with HF showed a significant inverse correlation for the BMD of the spine, femoral neck and proximal femur with HF class, the independent nature of which was confirmed by multivariate regression analysis: BMD L1-L4 (β=-0,135, p=0,001), femoral neck (β=-0,122, p=0,001), proximal femur (β=-0,127, p=0,001). However, the average values of BMD in all measured areas did not differ in the main and control groups. The mean P1NP level was significantly lower in the HF group compared to the control group — 42,5±15,0 vs 52,6±19,8 ng/ml (p=0,007). The bone resorption marker CTx was independently associated with HF stage (β=0,137, p=0,001) and N-terminal pro-brain natriuretic peptide level (β=0,128, p=0,001), and also negatively correlated with the left ventricular ejection fraction (r=-0,36, p<0,01) and positively — with left ventricular end-diastolic volume (r=0,34, p<0,01).Conclusion. In men with HF, BMD is inversely related to HF class, which acts as an independent factor in reducing bone mass. There were no differences in the frequency of low bone mass in men with HF and in the control group. A significant decrease in bone formation marker in patients with HF compared with the control group and an association of bone resorption marker with HF severity were noted.

Background: The identification of genetic factors that are simultaneously responsible for the predisposition to the development of cardiovascular diseases (CVD) and osteoporosis (OP) is important for the prevention of both conditions.Aim: The aim of this study is to evaluate three genetic risk scales (GRS) that previously showed an association with bone mineral density (BMD) and fracture risk, as well as to study the associations of these GRS with vascular wall pathology.Materials and methods: 250 female outpatients (aged 45 to 69) were enrolled into a cross-sectional study. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. Coronary vessels calcium deposits were registered by multispiral computed tomography (MSCT) using the Agatston calcium index (CI). The BMD of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. Bone resorption marker type-1 collagen C-terminal telopeptide (CTx) was assessed solid-phase enzyme immunoassay. The genetic study included DNA extraction from whole blood samples. Targeted sequencing was performed on the Nextseq550 sequencer (Illumina, USA). Statistical analysis was carried out using the SAS software package for Windows, version 9.0 (SAS Institute Inc., USA).Results: The chance of detecting low bone mass increased more than 4 times at values of IMT ≥0.9 mm (OR=4.17; 95%CI [1.2–14.4], p<0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p><0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p><0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p><0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p><0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI. Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.>< 0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p< 0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p< 0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p< 0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p<0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.>< 0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.

Background: Possible differences in the results of planned RCTs and real clinical practice were the reason for the analysis of long-term therapy with denosumab in patients with osteoporosis (OP) of various origins on an outpatient basis.Aim: To assess the effectiveness of long-term administration of denosumab in terms of the effect on BMD and markers of bone metabolism, tolerance and consequences of drug withdrawal in patients with OP of various etiologies.Materials And Methods: A retrospective analysis of the outpatient records of women with OP of various etiology, who were observed at the FSBI «NMRC TPM» from 1 to 10 years and regularly received denosumab 60 mg once every 6 months subcutaneously (at least 2 injections), was carried out. All completed examination and anthropometric research; DXA of the lumbar spine and proximal femur (PF); laboratory tests: marker of bone resorption CTx (β-crosslaps) in blood serum; survey on the presence of adverse events.Results: The study included 148 patients who were divided into 2 groups: 1 (N=98) - did not take anti-osteoporotic therapy (AT), 2 (N=50) - who took AT before the appointment of denosumab. Long-term therapy with denosumab was associated with a steady and reliable increase in BMD in the spine and PF, as well as a decrease in the concentration of CTx of both those who didn’t take and who previously took AT. In 54% of patients BMD in the spine reached values of osteopenia, in 43.4% of women target BMD values in the femoral neck were determined. During the first year of therapy, there was a decrease in the concentration of CTx by 67% in those who didn’t take AT and by 58% in those who had previously taken AT. Discontinuation of denosumab therapy without subsequent administration of AT was associated with a significant decrease in BMD in the spine (by 4.4-8.2%) during the first year after discontinuation of the drug.Conclusion: Denosumab therapy effectively increases BMD in the spine and PF and decreases CTx levels both in untreated patients and in those who previously received AT. It is necessary to discontinue therapy, further management of the patient should be discussed to prevent «withdrawal syndrome».

The aim to demonstrate that subclinical atherosclerosis and vascular rigidity in a postmenopausal patient without clinical sings of cardiovascular disease and osteoporosis are connected with a decreased bone mass.Materials and methods. Patient O., 64 years old, was examined at the National Medical Research Center for Preventive Medicine within the program “Comprehensive assessment of total risks and early preclinical markers of osteoporosis and atherosclerosis complications”. No complaints during the examination were revealed. Laboratory tests were performed to evaluate blood lipids level, calcium-phosphorus metabolism, determine marker of bone resorption – CTX (β-crosslaps), measure levels of vitamin D and parathyroid hormone. Instrumental examinations included dual-energy x-ray absorptiometry of the spine and femoral neck, carotid ultrasound, applanation tonometry, multispiral computed tomography of coronary arteries with calcium score determination.Results. During outpatient examination, densitometry revealed decreased bone mineral density in the lumbar spine and in the femoral neck, corresponding to osteoporosis, carotid ultrasound identified atherosclerotic plaques, multispiral computed tomography of coronary arteries – coronary calcification, applanation tonometry – increased aortic stiffness.Conclusion. The clinical case is an example of early-detected preclinical signs of atherosclerosis and osteoporosis, as well as an increased risk of cardiovascular complications. Due to the high frequency of subclinical atherosclerosis, vessel wall state should be examined in women at the beginning of postmenopause. Signs of vascular stiffness and subclinical atherosclerosis give occasion to assess risk of fractures using the FRAX ® calculator and, if necessary, to diagnose bone mass loss using X-ray densitometry. Proposed algorithm can contribute to the early detection of cardiovascular diseases and at the same time improve fracture risk assessment.

Aim. To assess the relationship of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with vascular wall condition and bone mineral density (BMD) in postmenopausal women.Material and methods. The cross-sectional study included 107 outpatients aged 45-82 years who signed informed consent. The inclusion criterion was a menopause during ≥1 year. The level of serum NT-proBNP was determined by electrochemiluminescence. BMD was assessed by dual energy x-ray absorptiometry. Intima-media thickness (IMT), the presence and number of atherosclerotic plaques were evaluated using carotid duplex scanning. Pulse wave velocity (PWV) and augmentation index were estimated by applanation tonometry. To assess 10-year cardiovascular risk, the SCORE high-risk charts were used. Using the Russian model of FRAX® score, 10-year fracture risk was assessed.Results. NT-proBNP level in women with postmenopause >10 years was significantly higher than in those with postmenopause <5 years — 98,7 vs 56,3 pg/ml (p<0,001), but there was no independent relationship according to the regression analysis. According to multivariate regression analysis adjusted for age, menopause duration, systolic blood pressure, hypercholesterolemia, smoking, elevated C-reactive protein and interleukin-6 levels, there were independent relationship between the following parameters: NT-proBNP and IMT (β=2,38, p<0,03), NT-proBNP and PWV (β=1,76, p<0,001). NT-proBNP level in patients with osteoporosis was significantly higher than in women with normal bone mass (p<0,01). A negative correlation was observed between NT-proBNP and BMD of the proximal femur (r=-0,26, p<0,05), while the relationship between BMD of the lumbar vertebrae (L1-L4) and NT-proBNP did not reach significance. In multivariate regression analysis, this relationship has not been confirmed. A positive correlation was obtained between cardiovascular risk (SCORE) and NT-proBNP levels (r=0,28, p<0,001). NT-proBNP levels did not differ in women with a high and low 10-year risk of both major osteoporotic fractures and femoral fractures.Conclusion. An independent relationship of NT-proBNP with vascular stiffness and preclinical atherosclerosis was demonstrated: IMT and PWV. This indicates the participation of NT-proBNP in the atherosclerosis development. The association of elevated NT-proBNP levels with osteoporosis is significant, but not independent, and is apparently related to other factors.

Objective: to investigate the correlation of bone mass, the parameters of vascular stiffness and subclinical atherosclerosis with biochemical markers of inflammation in postmenopausal women. Subjects and methods. The cross-sectional investigation included 98 patients aged 45–82 years who were followed up in the outpatient setting and signed an informed consent. The investigation did not include patients with any clinical manifestations of atherosclerosis, malignant neoplasms, with diseases causing secondary osteoporosis, as well as with the presence of symptoms of acute bacterial or viral infections and an exacerbation of chronic diseases, who took drugs affecting bone metabolism and vascular stiffness. C-reactive protein (CRP) level was determined by a high-sensitive immunoturbidimetric assay using carboxylated polystyrene particles. interleukin (IL)-6 concentration was measured by an enzyme immunoassay. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (ASP) were studied with duplex scanning. Pulse wave velocity (PWV) and augmentation index (AI) were measured by applanation tonometry using a SphygmoCor device (AtCor Medical Pty. Ltd., Sydney, Australia). Lumbar spine and hip bone mineral density (BMD) was determined using dual energy X-ray absorptiometry. Results and discussion. There was an increase in the parameters of vascular stiffness, subclinical atherosclerosis, and CRP level and a decrease in bone mass with a longer length of menopause. The vascular stiffness parameters, including IMT (r=0.26; p<0.05), AI (r=0.25; p<0.05), the presence of ASP (r=0.24; p<0.05), and PWV (r=0.23; p<0.05), directly correlated with CRP level. A negative correlation was found between LI–IV BMD and CRP (r=-0.31; p<0.05). The probability of detecting increased IMT with a high CRP level was increased by 2.64 times, ASP by 3.18 times, and low BMD by 2.4 times. There was no association of bone mass, and the parameters of subclinical atherosclerosis and vascular stiffness with IL-6. Conclusion. Lower bone mass and the development of osteoporosis in postmenopausal women were associated with increased vascular stiffness and the presence of signs of subclinical atherosclerosis, and with a high level of CRP, which allows one to discuss the common mechanisms for development of osteoporosis and atherosclerosis, as well as the involvement of chronic inflammation in them.

Objective: to analyze the clinical and organizational feasibility of using different intervention thresholds for the Russian population.Subjects and methods. The probability of fractures using the Russian FRAX model was calculated on a sample of 3,866 postmenopausal female residents from 6 cities of the Russian Federation. Different intervention thresholds, including fixed (20% for major fractures and 3% for hip fractures), age-dependent (European and Russian) ones, as well as alternative models, were analyzed. The proportion of women to be treated was estimated using different intervention thresholds.Results and discussion. The analysis of the effectiveness of the thresholds showed that the European threshold was the least appropriate one for the formed sample, since more than half (53.6%) of the women to be treated using the threshold, while the vast majority (90%) of the patients were in the younger age groups (50—54 years). There were very similar results of the effectiveness analysis of the fixed threshold (according to the USA National Osteoporosis Foundation — NOF) recommendations and that of the age-dependent threshold for Russia (in the context of the national clinical recommendations). Using the NOF approach in our sample could identify 47.8% of the postmenopausal women to be treated for osteoporosis. Their proportion rose from 29.6% of the patients aged 50—54 years to 80.6% of those aged 85 years and older. The alternative analyses of age-dependent thresholds showed great effectiveness when the fracture was considered not as a risk factor for future fractures, but as a clinical disease manifestation that was sufficient to recommend that the patient should be treated without FRAX counting. However, with their use, the proportion of older people to be treated remains not high enough. In this connection, there remains a need to search for the more adequate application of the existing intervention threshold or to develop a new, for example, hybrid variant of the age-dependent threshold.

AIM:To evaluate the efficiency and safety of long-term Prolia therapy in patients with postmenopausal osteoporosis (OP).SUBJECTS AND METHODS:The open prospective study enrolled 98 women (mean age, 68±9 years; mean menopause duration, 17±4 years) with postmenopausal OP, who were followed up in an outpatient setting at the National Medical Research Center for Preventive Medicine and who had been treated with denosumab 60 mg subcutaneously every 6 months for 12 months or more. The maximum follow-up period was 4 years: 48, 29, 11, and 10 patients were treated for 12, 24, 36, and 48 months, respectively. The patients were allocated into 2 groups: those who received and those who had not previously received antiosteoporotic therapy. Bone mineral density (BMD) was measured using dual-energy X-ray densitometry of the lumbar spine (LI-LIV) and proximal femur (PF). The ten-year probability of major osteoporotic fractures was estimated once in 72 patients not previously receiving antiosteoporotic therapy before the prescription of denosumab.RESULTS:In the patients not previously receiving therapy, the median 10-year probability of major fractures using the FRAX algorithm was 14.9%; that of femoral neck (FN) fractures was 3.7%. During denosumab treatment, the BMD increase in the lumbar spine was 4.2% at 12 months, 7.5% at 24 months, was 8.8% at 36 months; that in FN was 3.1, 3.9, and 5.3%, that in PF was 2.8, 4.1, and 5%; and that in the 1/3 forearm was 0.9, 1.4, and 2.6%, respectively (p < 0.001). In the persons receiving and not previously receiving the therapy, the BMD increase was similar, i.e. there was an additional positive effect when switching to denosumab. The decrease in the serum concentration of C-terminal telopeptide of type I collagen (CTX-I) was 54% at 6 months after initiation of denosumab therapy (p < 0.001) and 72% at 12 months (p<0.001); and the achieved marker level remained unchanged at 48 months. Transition from the OP zone to osteopenia one was noted in 23 patients with low BMD (T-score -2.5 SD) in LI-LII and in 12 patients with that in FN at 12 months of denosumab therapy and this was in 25 patients at 24 months. Nine-eight patients receiving the first Prolia injection refused to continue treatment on their own; adverse events were not the reason for drug discontinuation.CONCLUSION:Therapy with denosumab was effective in increasing BMD in routine outpatient practice and in allowing 25% of patients to achieve target values of this indicator. The marked decrease in the level of the bone resorption marker STX suggested that the drug had antiresorptive potency. The frequency of adverse reactions was low, confirming the good tolerability and safety profile of the drug. The convenience of the scheme and route of drug administration contributed to strict compliance with the doctor's recommendations. Denosumab was effective in increasing BMD not only in untreated patients, but also in those who had previously received antiosteoporotic therapy. The pharmacokinetic characteristics of denosumab, which contribute to its uniform distribution in trabecular and cortical bone tissue, regardless of active bone remodeling, and the fact that the clearance of the drug is independent of kidney function offer an advantage of administering the drug to patients with significant loss of FN and radius BMD and of reducing kidney function.

Цель: изучить взаимосвязь параметров сосудистой жесткости, МПК и биомаркеров клеточного старения у женщин в постменопаузальном периоде. Материал и методы. В одномоментное исследование включено 107 пациенток от 45 до 82 лет (ср. возраст -58 ± 0,86 лет), наблюдавшихся амбулаторно и подписавших информированное согласие. В исследование не включались пациентки с любыми клиническими проявлениями атеросклероза, злокачественными заболеваниями, с заболеваниями вызывающие вторичный остеопороз, принимающие препараты, влияющие на костный обмен и на показатели сосудистой жесткости. Толщина комплекса интима-медиа (ТКИМ), наличие и количество атеросклеротических бляшек (АБ), степень стеноза сонных артерий исследовались с помощью дуплексного сканирования. Оценка скорости распространения пульсовой волны (СРПВ), индекса аугментации (ИА) проводилось методом аппланационной тонометрии (SphygmoCor). СРПВ 10 м/с и более считали патологической. ИА считался нормальным при отрицательном его значении, положительный ИА свидетельствовал о повышенной жесткости. Был выбран медианный порог ИА- >20%. Значения более 0,9 мм принимались за повышение толщины КИМ. Толщина КИМ более 1,5 мм или локальное утолщение на 0,5 мм по сравнению со значениями КИМ в прилежащих участках сонной артерии свидетельствовали о наличии АБ. Для определения длины теломер (ДТ) в лейкоцитах использовался метод ПЦР в реальном времени. При этом проводилось измерение относительной длины теломер на геномной ДНК. Теломеры с диной >10,0 у.е. принимались за «длинные», а с длиной < 9,5 у.е. за «короткие». Определение активности теломеразы (АТ) (проводилась на чисто выделенной моноцитарной фракции клеток крови на основании теломеразной полимеразной реакции. МПК позвоночника и бедра измерялась с помощью двухэнергетической рентгеновской абсорбциометрии (Delphi W, Hologic, USA). Статистический анализ осуществлялся с помощью пакета прикладных программ Statistical Analysis System (USA). Результаты. Риск наличия низкой костной массы и остеопороза достоверно возрастал в 3 раза при высоких значениях СРПВ(>10 м/с), более чем в 4 раза при ИА > 20%, толщины КИМ >0,9мм, в 2,45 раза при наличии АБ в сонных артериях и при наличии «коротких» теломер. Показатель АТ не ассоциировался с костной массой. С увеличением продолжительности менопаузы отмечалось постепенное увеличение показателей жесткости (СРПВ, ИА), толщины КИМ и снижение МПК во всех измеренных отделах скелета. Максимальные показатели сосудистой жесткости, наиболее низкая МПК и «самые короткие» теломеры были выявлены после 10 лет менопаузы. В многомерном регрессионном анализе отрицательная связь между ИА, толщиной КИМ и МПК осталась высокодостоверной, в то время как в отношении СРПВ, наличия АБ и ДТ эта ассоциация не подтвердилась. Заключение. Снижение МПК у женщин в постменопаузе ассоциируется с высокими показателями ИА и толщины КИМ. Короткие теломеры в 2,45 раза чаще встречались у пациентов с низкой костной массой, но связь не была подтверждена в регрессионном анализе, что исключает независимый характер связи этого маркера с МПК и свидетельствует в пользу того, что остеопороз является возраст-ассоциированным заболеванием, а не процессом естественного старения.

Aim. To assess influence of nebivolol on microcirculation (MC) and mineral density of bones (MDB) in postmenopausal women with mild arterial hypertension (AH) and osteopenia.Material and methods. To randomized controlled study were included 56 women of postmenopausal period at the age 50-65 y.o. with osteopenia and mild AH. During 12 months the main group (n=28) were taking nebivolol 2,5-5 mg, and controls (n=28) — atenolol 25-50 mg. At baseline and in 12 months clinical investigation was done, with anthropometry, blood pressure measurement, electrocardiogram registration, and qualitative MDB assessment via double energetic x-ray absorptiometry and assessment of MC with the application of computerized monochannel laser analyzer of capillary flow. In addition, we measured the levels of ionized calcium (Ca2+), total alkaline phosphatase (TAP), C-telopeptide of collagen I type (CTP).Results. At the background of mild AH therapy with nebivolol during 12 months there was increase of MDB in the spine by T-criterium from -1,7±0,4SD to -1,4±0,53 (р<0,001), in femoral cervix (FC) from -1,4±0,44SD to -1,27±0,5SD (р=0,015), in proximal part of femur (PPF) from -0,58±0,4SD to -0,49±0,4SD (р=0,003), however in control group on atenolol there was decrease of MDB of the spine by T-criteria from -1,5±0,7SD to -1,6±0,64SD (p<0,001), in FC from -1,3±0,64SD to -1,5±0,65 (р=0,0005), MDB of PPF was stable (р=0,3). In the main group there was difference of MC value by 107,4±11,2% (р<0,001) and MC effectiveness index by 318±53% (р<0,001), in control group MC value decreased by 15,7±8,5% (р=0,07), decrease of MC effectiveness index was not significant. During therapy, there was decrease of CTP in serum by 17,7±2,6% (р<0,001), though in control group this parameter increased by 44,7±11,2% (р<0,001). Dynamics of MDB in all studied regions, of MC parameters, of CTP level on therapy during 12 months significantly differed between main and control groups.Conclusion. In the study, we showed positive effect of nebivolol on MDB and MC.

Цель: изучить взаимосвязь параметров сосудистой жесткости, МПК и биомаркеров клеточного старения у женщин в постменопаузальном периоде. Материал и методы. В одномоментное исследование включено 107 пациенток от 45 до 82 лет (ср. возраст -58 ± 0,86 лет), наблюдавшихся амбулаторно и подписавших информированное согласие. В исследование не включались пациентки с любыми клиническими проявлениями атеросклероза, злокачественными заболеваниями, с заболеваниями вызывающие вторичный остеопороз, принимающие препараты, влияющие на костный обмен и на показатели сосудистой жесткости. Толщина комплекса интима-медиа (ТКИМ), наличие и количество атеросклеротических бляшек (АБ), степень стеноза сонных артерий исследовались с помощью дуплексного сканирования. Оценка скорости распространения пульсовой волны (СРПВ), индекса аугментации (ИА) проводилось методом аппланационной тонометрии (SphygmoCor). СРПВ 10 м/с и более считали патологической. ИА считался нормальным при отрицательном его значении, положительный ИА свидетельствовал о повышенной жесткости. Был выбран медианный порог ИА- >20%. Значения более 0,9 мм принимались за повышение толщины КИМ. Толщина КИМ более 1,5 мм или локальное утолщение на 0,5 мм по сравнению со значениями КИМ в прилежащих участках сонной артерии свидетельствовали о наличии АБ. Для определения длины теломер (ДТ) в лейкоцитах использовался метод ПЦР в реальном времени. При этом проводилось измерение относительной длины теломер на геномной ДНК. Теломеры с диной >10,0 у.е. принимались за «длинные», а с длиной 10 м/с), более чем в 4 раза при ИА > 20%, толщины КИМ >0,9мм, в 2,45 раза при наличии АБ в сонных артериях и при наличии «коротких» теломер. Показатель АТ не ассоциировался с костной массой. С увеличением продолжительности менопаузы отмечалось постепенное увеличение показателей жесткости (СРПВ, ИА), толщины КИМ и снижение МПК во всех измеренных отделах скелета. Максимальные показатели сосудистой жесткости, наиболее низкая МПК и «самые короткие» теломеры были выявлены после 10 лет менопаузы. В многомерном регрессионном анализе отрицательная связь между ИА, толщиной КИМ и МПК осталась высокодостоверной, в то время как в отношении СРПВ, наличия АБ и ДТ эта ассоциация не подтвердилась. Заключение. Снижение МПК у женщин в постменопаузе ассоциируется с высокими показателями ИА и толщины КИМ. Короткие теломеры в 2,45 раза чаще встречались у пациентов с низкой костной массой, но связь не была подтверждена в регрессионном анализе, что исключает независимый характер связи этого маркера с МПК и свидетельствует в пользу того, что остеопороз является возраст-ассоциированным заболеванием, а не процессом естественного старения.

Aim. To study the effects of nebivolol on bone mineral density (BMD) in postmenopausal women with mild hypertension (HT) and osteopenia. Material and methods. Postmenopausal women (n=56) aged 50-65 years with mild HT фтв osteopenia were included into the randomized controlled study and divided in two groups (28 patients in each). During 12 months patients of the main group received treatment with nebivolol (5-7.5 mg/day) and patients of the control group received treatment with atenolol (12.5-25 mg/day). Clinical and anthropometric examinations, blood pressure measurements, ECG registrations were performed in all patients initially and after 12 months of treatment. Quantitative estimation of BMD was performed by dual energy X-ray absorptiometry with osteodensitometry DELPHI W manufactured by HOLOGIC company (USA) in the lumbar spine (L1-L4), femoral neck and proximal femur in the anterior-posterior projection. In addition, calcium and bone metabolism indices were determined: ionized calcium, total alkaline phosphatase, C-telopeptide of type I collagen (CTX). Results. Therapy of mild HT with nebivolol during 12 months showed increase in BMD in the spine according to the T-test from -1.7±0.4 SD to -1.4±0.53 SD (p<0.001), while in atenolol group this index decreased from -1.5±0.7 SD to -1.6±0.64 SD (p<0.001). When evaluating T-test of the femoral neck the index changed in the main group from - 1.4±0.44 SD to -1.27±0.5 SD (p=0.015), in the control group - from -1.3±0.64 SD to -1.5±0.65 SD (p=0.0005). In the study group T-test of proximal femur changed from -0.58±0.4 SD to -0.49±0.4 SD (p=0.003), and in the control group - from -0.8±0.84 SD to -0.83±0.93 SD (p=0.3). The dynamics of the BMD due to 12 month therapy in all investigated bone segments distinguished significantly between study and control groups. Nebivolol therapy group showed reduction in CTX level from 0.367±0.16 to 0.294±0.12 ng/ml (p<0.001), whereas the control group showed increase in this parameter from 0.369±0.15 to 0.499±0.18 ng/ml (p<0.001). The dynamics of the CTX levels distinguished significantly between groups (p<0.001). Conclusion. The study demonstrated the positive effect of nebivolol on BMD, whereas atenolol had no effect on bone mass.

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.