Method for predicting osteopenic syndrome in postmenopausal women

Abstract

FIELD: therapy; cardiology; rheumatology.SUBSTANCE: used to predict osteopenic syndrome in postmenopausal women. Vascular stiffness is determined using the augmentation index, the presence of atherosclerotic plaques in the carotid arteries and the body mass index are assessed. The predicted probability of developing osteopenic syndrome (Y) is calculated using a special formula. For a probability value of Y ≥ 0.5 predicts osteopenic syndrome.EFFECT: increasing the accuracy and accessibility of predicting the risk of developing osteopenic syndrome in postmenopausal women at the preclinical stage by taking into account complex markers of vascular changes and metabolic risk factors.1 cl, 3 tbl, 3 ex

Description

[0001] Scope and purpose.

[0002] The invention relates to the field of medicine, in particular to therapy, cardiology, rheumatology and can be used to predict osteopenic syndrome (osteopenia / osteoporosis) in postmenopausal women.

[0003] Technique level.

[0004] Atherosclerosis-associated cardiovascular diseases (AAS) and osteoporosis, which continue to lead the structure of disability and mortality in the population, were previously considered as independent processes associated with age, but later epidemiological and clinical studies demonstrated links between bone loss and changes in the condition of the vascular wall, as well as clinical manifestations of atherosclerosis (AS) and osteoporosis [1-4].

[0005] Currently, common risk factors for CVD-AS and osteoporotic fractures have been identified, which have proven their influence on the development and progression of both diseases [5, 6], some of which are included in prognostic models for assessing the risks of complications of AS and osteoporosis. In epidemiological [7] and clinical [8, 9] studies using the SCORE (Systematic Coronary Risk Evaluation, a scale for assessing the 10-year risk of fatal cardiovascular events) and FRAX (Fracture risk assessment tool, a scale for assessing the 10-year probability of osteoporotic fractures) scales, it was shown that the relationship between these diseases is already traced at the level of risk formation.

[0006] To date, common mechanisms in the pathogenesis of osteoporosis and AS have been discovered that are independent of age and show that coupled metabolic processes occur in bone tissue and the vascular wall, leading to bone loss, on the one hand, and atherosclerotic lesions and calcification of the vascular wall, on the other hand [10-12]. Moreover, associations between osteoporosis and CVD-AS are determined and proven more often using preclinical or "surrogate" markers of diseases - arterial calcification, vascular stiffness parameters, subclinical AS and bone mineral density (BMD) [13, 14]. The main markers characterizing the elastic properties of arteries are pulse wave velocity (PWV) and augmentation index (AI). IA differs from PWV in that it reflects not only the stiffness of large arteries, but also the state of small arterioles and the microcirculatory bed, which predominate in the periosteum and bone tissue

[15] .

[0007] These processes are more clearly observed in postmenopausal women, since estrogen deficiency contributes to the development of a cascade of disorders leading to both pathologies. It has been established that postmenopausal women with a high risk of cardiovascular events are more likely to have a decrease in bone mass, and the risk is directly proportional to the severity of osteoporosis

[16] . It has also been shown that in relatively healthy women, i.e., without diseases that contribute to the development of secondary osteoporosis, changes in the vascular wall develop earlier than in bone tissue and are often determined already in perimenopause

[17] . Therefore, parameters of vascular stiffness and subclinical AS may have prognostic significance and claim to be predictors of the development of osteoporosis and, accordingly, an increased risk of fractures.Furthermore, the identification of a link between changes in the vascular wall and bone mass in a prospective, long-term study suggests a two-way prognostic effect. Measuring BMD in women without clinical manifestations of CVD-AS may provide information on cardiovascular risk, allowing for the tailoring of preventive measures to comorbid pathology. Since BMD, arterial stiffness, and atherosclerotic plaques (AP) are modifiable factors and are amenable to therapy, and given that AS and osteoporosis are asymptomatic at onset and often diagnosed only after serious complications have developed, early detection of cardiovascular and bone pathology and timely preventive measures at the preclinical stage will help reduce the incidence of cardiac and skeletal complications, as well as the risk of fatal events.

[0008] Currently, several methods for predicting the presence of osteoporosis have been registered, however, data on the association of vascular wall parameters and bone mass were obtained from cross-sectional studies, which do not allow us to judge the presence of a relationship between them.

[0009] A known method for predicting the presence of osteoporosis based on the level of arterial stiffness in patients at high risk of cardiovascular complications [Patent RU 2746837, IPC A61B 5 / 00, A61B 5 / 0285, published 04 / 21 / 2021 Bulletin No. 12] is within the framework of which the pulse wave velocity along the brachial-ankle segment (PWV) was measured in patients aged 50-75 years with a high risk of CVD-AS complications (n=86) by recording sphygmograms on four limbs using occlusion cuffs. When selecting patients for the study, patients with hypertension who had achieved the target blood pressure level while receiving regular antihypertensive therapy, which is known to affect the condition of the vascular wall and bone mass, were also included. With a PWV value of ≥14.2 m / sec, the presence of osteoporosis in patients with high cardiovascular risk was predicted, which allows for the identification of patients for timely additional examination at the primary health care level.

[0010] The disadvantage of this method is the prediction of osteoporosis using only one labile parameter of arterial stiffness, SVp, within the framework of a one-time study against the background of regular antihypertensive therapy, which is known to affect the condition of the vascular wall and bone mass, which reduces the informativeness of the results obtained.

[0011] In recent years, much attention has been paid to clinical risk factors for osteoporosis, some of which are included in prognostic models for assessing the risk of fracture complications. For the Russian population, the FRAX calculator (Russian Model) has been recognized as such a tool. It is a mathematical model for calculating the individual 10-year fracture probability based on age, clinical risk factors, and femoral neck BMD data when dual-energy X-ray absorptiometry (DXA) is available

[18] . The calculation results in two percentage fracture probability indicators (the risk of major osteoporotic fractures and the risk of hip fracture), which are used to stratify the fracture risk according to the national intervention threshold (developed for the country).The FRAX calculator is a simple and accessible method for assessing the risk of osteoporosis complications and identifying high-risk groups for fractures. However, like any mathematical model, it has limitations and disadvantages: it does not consider the levels (severity) of risk factors (for example, two previous fractures have twice the weight in assessing the total risk than one, but this is not taken into account in the model); the model takes into account only clinically evident vertebral fractures, and this may reduce the risk indicator in the presence of asymptomatic vertebral fractures diagnosed morphometrically in a patient; only the BMD (T-score) of the femoral neck can be used, and the results of measurements of other locations cannot be used; the tendency to falls, which are an important cause of peripheral fractures, is not taken into account; in the absence of BMD data, the model does not assess the main determinant of osteoporosis and fracture.In addition, the data on the level of the local (Russian) intervention threshold remain ambiguous.

[0012] The closest to the claimed method is the method for determining the probability of developing osteopenic syndrome in patients with multifocal AS [Patent RU 2624816, MPKA61B 10 / 00, published 06.07.2017 Bulletin No. 19], which analyzed the data of 186 patients with coronary heart disease (CHD) in combination with verified atherosclerotic lesions of the coronary and carotid arteries, who underwent a comprehensive study of calcium deposits of the ASP of the coronary and carotid arteries with a quantitative assessment of calcification according to multispiral computed tomography using the Agatston method. The factors influencing the probability of osteopenia in a patient were assessed as follows: the presence of carotid artery stenosis of more than 30% (X1), the values ​​of the calcium index of the coronary (X2) and brachiocephalic (X3) arteries, as well as the value of the equivalent mass of calcium deposits of the brachiocephalic arteries (X4).Based on the obtained data, the probability of osteopenia (P) was calculated using the original formula. A probability (P) value greater than 0.688 indicates that the patient likely has osteopenia.

[0013] A disadvantage of this method is the late detection of osteopenia or osteoporosis in individuals with already verified AS and coronary artery disease, i.e., with developed clinical manifestations. This delays the timely detection of bone metabolism disorders and early treatment and preventive measures. The prototype method also requires multislice computed tomography of both the carotid and coronary arteries, which is considered a drawback given the high radiation exposure.

[0014] Disclosure of the essence of the invention.

[0015] The objective of the invention is to create an alternative accessible method for predicting osteopenic syndrome in postmenopausal women based on the assessment of preclinical markers of AS (IA and ASP).

[0016] The technical result of the invention consists in increasing the accuracy and accessibility of predicting the risk of developing osteopenic syndrome in asymptomatic postmenopausal women at the preclinical stage, which, as a consequence, makes it possible to objectify the prognosis and promptly initiate treatment and preventive measures.

[0017] The technical result is achieved due to the fact that in order to determine the predicted probability of developing osteopenic syndrome, vascular stiffness is determined using IA, the presence of atherosclerotic plaques in the carotid arteries and the body mass index (BMI) are assessed, and the predicted probability of developing osteopenic syndrome is calculated using the formula:

[0018] Y=0.929 + 0.011 *X1- 0.030*Х2+ 0.435*Х3, where

[0019] Y predictive individual probability of osteopenic syndrome in postmenopausal women,

[0020] X1 - IA value in %,

[0021] X2- BMI in kg / m 2 ,

[0022] X3 - the presence of an ASB, which is equal to 0 in the absence of an ASB, and is equal to 1 in the presence of at least one ASB,

[0023] and with a value of Y≥0.5, osteopenic syndrome is predicted.

[0024] Implementation of the invention.

[0025] The proposed method is based on the results of a study conducted at the Federal State Budgetary Scientific Institution “NMITs TPM” of the Ministry of Health of the Russian Federation (Moscow) and includes a comprehensive analysis of data from 93 patients.

[0026] This retrospective-prospective study included an analysis of data from two visits, 9.4±0.9 years apart. At the first (baseline) visit in 2012–2014, 107 women aged 45 to 82 years without clinical manifestations of AS were examined. Of this cohort, 93 were examined at the second (repeat) visit (response rate was 87%).

[0027] The study showed the relationship between markers of subclinical AS and vascular stiffness with osteopenic syndrome and determined the prognostic significance of IA and ASP in reducing bone mass using mathematical analysis.

[0028] The inclusion criterion was the presence of menopause for ≥1 year. The study did not include patients with coronary heart disease, a history of cerebrovascular accidents, transient ischemic attack, established peripheral arterial disease, with hemodynamically significant lesions of the valvular heart apparatus; with an established diagnosis of arterial hypertension (AH) grade 2-3 (constant use of antihypertensive therapy); with diseases causing secondary osteoporosis, with chronic renal failure; receiving therapy affecting bone metabolism and vascular stiffness indicators: drugs for the treatment of osteoporosis, menopausal hormone therapy, glucocorticosteroids, lipid-lowering agents, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics; surgical interventions on the spine and hip joints, accompanied by the installation of metal structures.

[0029] All women underwent clinical and instrumental examinations at both visits, including:

[0030] - questionnaire survey using the same questionnaire specially developed for this study, including questions on cardiovascular risk factors and fracture risk;

[0031] - BMD study was performed using DXA on a Hologic (Delphi W) device in the lumbar vertebrae (L1-L4) and proximal femur (PF). BMD values ​​were assessed in absolute values ​​(g / cm 2 ), and in SD values ​​from the peak bone mass (T-score). According to the WHO criteria, osteopenia was considered to be a T-score level below -1.0 and up to -2.4 SD, osteoporosis - -2.5 SD and below;

[0032] - PWV and AI were determined using applanation tonometry. The study was performed using a Sphygmocor device (Australia). The mean PWV level, calculated from two consecutively recorded values ​​with a maximum difference of no more than 0.4 m / s, was used for analysis. AI was calculated automatically. Vascular stiffness criteria: PWV of 10 m / s or more was considered pathological. AI was considered normal with a negative value; a positive AI indicated increased stiffness. A median threshold of 25% was chosen in the study group.

[0033] - An ultrasound examination of both carotid arteries to determine the intima-media thickness (IMT) was performed using a Philips system with a high-resolution transducer. Measurements were taken at three levels of the vascular bed and bilaterally: at the proximal, medial, and distal points along a 1 cm path from the bifurcation along the posterior wall of the common carotid artery. The distance between the first and second echogenic lines of the located vessel determined the IMT thickness. The first line is the boundary between the vessel wall and its lumen, and the second line represents the collagen layer along the adventitial edge. The average IMT thickness is calculated as the mean of all 12 measurements. The highest IMT value was selected for analysis. Criteria for subclinical AS: values ​​greater than 0.9 mm were considered to be increased IMT thickness. An IMT thickness greater than 1.5 mm or a local thickening of 0.5 mm compared to the IMT values ​​in adjacent areas of the carotid artery indicated the presence of atherosclerotic plaque.

[0034] Statistical analysis of the data was performed using the SAS (Statistical Analysis System, SAS Institute Inc., USA). Intergroup comparisons of interval parameters with non-normal distributions, including simultaneous comparisons of several groups formed depending on the state of BMD, duration of menopause, and age of the patients, were performed using the NPAR1WAY SAS procedure, which automatically calculated all the following non-parametric tests: ANOVA-1-WAY analysis of variance, Wilcoxon test, Kruskal-Wallis test, van der Waerden test, and Savage test. To assess the contribution of a number of clinical and instrumental factors to bone mass loss and to evaluate their predictive probability in the development of osteopenic syndrome (osteopenia / osteoporosis), both linear and logistic regression modeling with the calculation of multivariate stepwise regressions were used.

[0035] The age-adjusted odds ratio (OR) for detecting osteopenic syndrome at visit 1 was 4.3 (95% CI 1.73-10.95, p=0.005) in the presence of atherosclerotic plaques in the carotid arteries, OR=7.17 (95% CI 2.63-19.58, p=0.001) - with AI ≥ 25%, OR=6.14 (95% CI 1.68-22.48, p=0.01) - with IMT thickness values ​​>0.9 mm. No association with elevated PWV values ​​was noted.

[0036] In the studied cohort of women, during the observation period, with increasing age and duration of menopause, a reliable increase in all the studied parameters of the vascular wall condition, with the exception of PWV, was noted. By the 2nd visit, the frequency of increased IMT (> 0.9 mm) increased by 50% (p < 0.001), the frequency of detection of ASP - by 22.5% (p < 0.001), the total number of ASP increased by 45% (p < 0.001), the frequency of increased AI by 14% (p < 0.01), the frequency of increased PWV statistically insignificantly decreased by 5% (p = 0.23). A significant decrease in BMD was also noted in all measured areas of the skeleton: in the femoral neck by 5.3%, in the entire PB by 3.2% (p < 0.001), and in the spine - by 0.8% and did not reach statistical significance. In patients with low bone mass, the AI, IMT thickness, and ASP rates were significantly higher than in patients with normal BMD (Table 1).

[0037]

[0038]

[0039] Since Visit 1, anti-osteoporosis therapy has been initiated in 17 women. Since osteoporosis medications increase bone mass and affect bone turnover, an analysis of the relationship between BMD and vascular wall condition was conducted separately in the group of patients who did not receive antiresorptive drugs (n=76). Similar results were obtained with the overall cohort of patients, indicating no effect of anti-osteoporosis drugs on the relationship between BMD and vascular stiffness and subclinical AS. While at Visit 1, 23.6% of patients with mild stage 1-2 hypertension received antihypertensive drugs irregularly, and their effect on the relationship between BMD and vascular stiffness and subclinical AS was not taken into account, at Visit 2, 55.9% of patients received antihypertensive therapy on a regular basis.At the baseline visit, women were not taking lipid-lowering therapy, but by the 2nd visit, 24 (26%) had started taking statins and had been receiving them for more than 1 year.

[0040] To construct predictive models for the development of osteopenic syndrome, risk factors identified at Visit 1 were used. Multivariate linear regression analysis, adjusted for factors identified at Visit 1 (age, postmenopausal duration, BMI, and hypertension), showed that at Visit 2, AI independently contributed to the reduction in BMD in the POP, while IMT was an independent factor in the reduction in BMD in the spine and femoral neck. No association was found between PWV and the number of ASPs with BMD in different skeletal regions (Table 2).

[0041]

[0042] Of the vascular stiffness indicators, only AI showed a significant association with low bone mass, so this indicator was selected to assess its prognostic significance in the development of osteopenic syndrome in postmenopausal women.

[0043] While the number of ASPs showed no association with bone mass in the linear regression model, the association of having at least one ASP with low bone mass along with elevated AI (≥25%) at Visit 2 was demonstrated in multivariate logistic regression analysis models with the inclusion of the following explanatory variables obtained at Visit 1: age ≥55 years, low body weight (BMI≤20 kg / m 2 ), hypertension, taking statins, AIF inhibitors, β-blockers and thiazide diuretics (Table 3).

[0044]

[0045] It was revealed that carotid artery plaque, elevated AI (≥25%), along with age ≥55 years, are independent factors for decreased bone mass, and antihypertensive drugs and statins taken do not affect this relationship.

[0046] In logistic regression analysis models, where low bone mass served as the dependent variable, and increased IMT thickness and increased PWV were the explanatory variables, along with age ≥55 years, low body weight, hypertension, use of statins, ACE inhibitors, β-blockers and thiazide diuretics, it was found that only age was a significant predictor of decreased bone mass, increasing the likelihood of decreased bone mass by almost 2 times (OR = 1.95; 95% CI [1.15-3.30], p = 0.012).

[0047] Since the presence of at least one ASP showed a stable association with low bone mass, independent of clinical risk factors and cardiovascular therapy, this indicator seemed appropriate to use as a predictor for predicting the development of osteopenic syndrome in postmenopausal women.

[0048] The individual risk function for developing osteopenic syndrome can be calculated using the following final linear regression equation:

[0049] Y=0.929 + 0.011 *X1- 0.030*X2+ 0.435*X3,

[0050] where Y is the predicted individual probability of osteopenic syndrome in postmenopausal women,

[0051] X1- value of AI (%),

[0052] Х2- BMI (kg / m 2 ),

[0053] X3 - presence of ASB,

[0054] in this case, X3 takes a value equal to 0 if the patient does not have ASB, 1 if at least one ASB is present.

[0055] If Y is ≥0.5 (50%), the patient is likely to develop osteopenic syndrome; based on this, it is recommended to assess the 10-year fracture probability using FRAX and perform DXA to diagnose low bone mass and verify a high fracture risk.

[0056] The method is carried out as follows.

[0057] In asymptomatic postmenopausal women aged 45 years and older who are referred for carotid artery ultrasound and applanation tonometry to determine cardiovascular risk, vascular stiffness is measured using an AI, the presence of atherosclerotic plaques in the carotid arteries, and BMI is assessed. Based on the data obtained, the predicted probability of developing osteopenic syndrome is determined using the following formula:

[0058] Y=0.929 + 0.011 *X1- 0.030*X2+ 0.435*X3,

[0059] where Y is the predicted individual probability of osteopenic syndrome in postmenopausal women,

[0060] X1- value of AI (%),

[0061] Х2- BMI (kg / m 2 ),

[0062] X3 - presence of ASB,

[0063] where X3 is 0 in the absence of atherosclerotic plaques and 1 in the presence of at least one atherosclerotic plaque. A Y value of ≥0.5 (50%) predicts osteopenic syndrome.

[0064] A conclusion is made about the individual risk of decreased bone mass and it is recommended that the patient undergo further examination to diagnose low bone mass using a more expensive and less accessible DXA method, as well as an assessment of the 10-year probability of fractures using FRAX, followed by timely implementation of preventive measures to prevent fractures.

[0065] Examples of the invention.

[0066] Example No. 1.

[0067] Patient B., born in 1967, presented to the National Medical Research Center for Traumatology and Malignancy (NMRC TPM) for a routine examination in 2013 at the age of 46. She considers herself healthy and has not previously seen a doctor. She has no active complaints. She denies any chronic illnesses. She has no fractures. She does not receive ongoing therapy. She has never received medications that affect the skeletal system. She has no burdened family history of CVD-AS and osteoporosis. She does not smoke and does not abuse alcohol. Gynecological history: B-2, P-2. Menopause since age 45. She does not receive menopausal hormone therapy.

[0068] Examination data: body build is normal, normosthenic type. Height is 162.0 cm (no decrease in height was noted during life). Weight is 67.4 kg. BMI is 25.68 kg / m 2 The skin is normal in color and moisture content. Vesicular breathing is present in the lungs. Cardiovascular system: heart rate 76 beats / min. Blood pressure 110 / 64 mmHg. The patient denies any gastrointestinal or urinary tract pathology.

[0069] According to laboratory tests: total cholesterol 5.49 mmol / L, total alkaline phosphatase 170 U / L, total calcium 2.37 mmol / L.

[0070] Duplex scanning of the carotid arteries: the largest value of the IMC (right or left) is 1 mm. ASP (right or left) is not detected.

[0071] Applanation tonometry revealed an increase in AI of 37%. PWV 10.4 m / sec.

[0072] The predicted probability of asthenopenic syndrome was calculated using the original formula:

[0073] Y=0.929 + 0.011*37 - 0.030*25.68 + 0.435*0 = 0.56

[0074] Since the predictive probability value (Y) is greater than 0.5, the risk of developing osteopenic syndrome is increased.

[0075] DXA data revealed decreased BMD in the spine, consistent with osteopenia (T-score -1.3 SD). In the femoral neck, the T-score was within the normal range of -0.6 SD.

[0076] Repeat examination conducted in 2022 at age 56. No active complaints. No medical attention since the previous visit and no ongoing therapy. No fractures since the previous visit. Height 162.0 cm, weight 68 kg. BMI 25.91 kg / m². 2 Cardiovascular system: blood pressure 111 / 72 mm Hg. heart rate 76 beats / min.

[0077] Laboratory tests: total cholesterol 5.8 mmol / L, total alkaline phosphatase 103 U / L, total calcium 2.30 mmol / L.

[0078] Duplex scanning of the carotid arteries: an increase in the value of the IMC (maximum value 1.5 mm) was noted; an atherosclerotic plaque was detected on the right side of the posterior wall of the bifurcation of the common carotid artery, stenotic the lumen by up to 15-20%.

[0079] Applanation tonometry: AI - 40%. PWV - 6.9 m / sec.

[0080] DXA data on the same device showed a decrease in BMD in the spine, corresponding to osteoporosis (T-score -2.9 SD), and in the femoral neck - osteopenia (T-score -1.1 SD).

[0081] Thus, a patient initially examined at age 46, with a low risk of cardiovascular complications and a low risk of osteoporotic fractures, was found to have elevated AI and decreased BMD to the level of osteopenia. Ten years later, progression of atherosclerotic vascular lesions and the development of atherosclerotic plaques were noted, accompanied by further loss of BMD and the development of osteoporosis.

[0082] Example #2.

[0083] Patient A., born in 1957, presented to the National Medical Research Center for Traumatology and Malignancy (NMIC TPM) for a routine examination in 2013 at the age of 56. She has no active complaints and denies any chronic illnesses. She has no history of fractures and is not receiving ongoing therapy. She has no family history of cardiovascular disease (CVD) or osteoporosis. She has no bad habits. She has never taken any medications that affect bone health. Gynecological history: B-2, p-1. Natural menopause since age 50. She does not receive menopausal hormone therapy.

[0084] Examination data: body build is normal, of the hypersthenic type. Height is 170.0 cm (no decrease in height was noted during life). Weight is 93 kg. BMI is 32.18 kg / m 2 The skin is normal in color and moisture content. Vesicular breathing is present in the lungs. Cardiovascular system: heart rate 84 beats / min. Blood pressure 127 / 76 mmHg. The patient denies any pathology of the endocrine system, gastrointestinal tract, or genitourinary system.

[0085] According to laboratory tests: total cholesterol 6.9 mmol / L (first detected), total alkaline phosphatase 181 U / L, total calcium 2.52 mmol / L.

[0086] Duplex scanning of the carotid arteries: the IMC value is 0.78 mm, an atherosclerotic plaque was detected in the common carotid artery on the left, stenotic the lumen of the artery by 20%.

[0087] Applanation tonometry: AI - 12%. PWV - 10.6 m / sec.

[0088] The predicted probability of asthenopenic syndrome was calculated using the original formula:

[0089] Y=0.929 + 0.011*12 - 0.030*32.18 + 0.435*1 = 0.53

[0090] Since the predictive probability value (Y) is greater than 0.5, the risk of developing osteopenic syndrome is increased.

[0091] DXA data: T-score in the lumbar spine -0.8 SD, T-score in the femoral neck -1.0 SD (which corresponds to normal BMD values).

[0092] A follow-up examination was conducted in 2023 (age 66). No active complaints. Since 2016 (age 58), frequent episodes of elevated blood pressure to 150-160 / 90-100 mmHg have appeared, which were relieved by taking capoten. Since 2018 (age 60), the patient has been taking antihypertensive medications (ACE inhibitors, β-blockers) and statins on a regular basis. In 2020, a low-grade ankle fracture occurred (she twisted her foot).

[0093] Examination data: Height 169.0 cm. Weight 105 kg. BMI 37.11 kg / m 2 Cardiovascular system: heart rate 54 beats / min. blood pressure 152 / 89 mm Hg.

[0094] Laboratory tests: total cholesterol 4.40 mmol / L, total alkaline phosphatase 181 U / L, total calcium 2.46 mmol / L.

[0095] Duplex scanning of the carotid arteries: an increase in the thickness of the IMC of 1.60 mm, in the common carotid artery on the left there is an atherosclerotic plaque, stenotic the lumen up to 35%, on the right along the posterior wall of the bifurcation of the common carotid artery there is an atherosclerotic plaque, stenotic the lumen up to 15-20%.

[0096] Applanation tonometry: AI-22%. PWV - 10.6 m / sec.

[0097] Data from DXA performed on the same device: T-score in the lumbar spine -1.4 SD, T-score in the femoral neck -1.2 SD (which corresponds to osteopenia).

[0098] Thus, in a postmenopausal patient with carotid atherosclerosis (AAP) in the carotid arteries and normal BMD, with a low fracture risk, after 10 years, in addition to increasing stenosis in the area of ​​the previously detected AAP and an increasing number of AAP, a loss of BMD in the osteopenic range was observed, which led to a low-trauma fracture. A parallel increase in cardiovascular risk and fracture risk was noted.

[0099] Example #3.

[0100] Patient B., born in 1953, presented to the Federal State Budgetary Institution National Medical Research Center for Traumatology and Microbiology for a routine examination in 2013 at the age of 60. She complained of intermittent increases in blood pressure, up to a maximum of 140 / 90 mmHg, which were relieved by taking 1 tablet of Capoten. She is not receiving regular antihypertensive therapy. She denies any chronic illnesses. She had no fractures. She has a significant family history of cardiovascular disease: her mother has hypertension, and her father has coronary heart disease. There were no hip fractures in any of her blood relatives. She has no bad habits. She has never taken any medications that affect the skeletal system. Gynecological history: natural menopause at the age of 49. She did not receive menopausal hormone therapy.

[0101] Examination data: body build is normal, normosthenic type. Height is 165.0 cm (no decrease in height was noted during life). Weight is 67 kg. BMI is 24.61 kg / m 2The skin is normal in color and moisture content. Vesicular breathing is present in the lungs. Cardiovascular system: heart rate 70 beats / min. Blood pressure 120 / 74 mmHg. The patient denies any pathology of the endocrine system, gastrointestinal tract, or genitourinary system.

[0102] According to laboratory tests: total cholesterol 5.8 mmol / L, total alkaline phosphatase 220 U / L, total calcium 2.17 mmol / L.

[0103] Duplex scanning of the carotid arteries: atherosclerosis of the carotid arteries with maximum stenosis of up to 20% on the right and up to 30% on the left.

[0104] Applanation tonometry: AI - 30%. PWV - 9 m / sec.

[0105] The predicted probability of asthenopenic syndrome was calculated using the original formula:

[0106] Y=0.929 + 0.011*30 - 0.030*24.61 + 0.435*1 = 0.95

[0107] Since the predictive probability value (Y) is greater than 0.5, the risk of developing osteopenic syndrome is increased.

[0108] According to DXA data: T-score in the lumbar spine is -1.8 SD (which corresponds to osteopenia), T-score in the femoral neck is -0.4 SD (which corresponds to normal values).

[0109] A follow-up examination was conducted in 2023 (age 70). History: in 2018, she consulted a cardiologist complaining of frequent pain in the occipital region associated with elevated blood pressure. Following examination, she was diagnosed with hypertension and prescribed antihypertensive therapy (losartan, metoprolol, indapamide) and statins (rosuvastin). There were no fractures over the 10-year period.

[0110] Examination data: Height 162 cm (height loss 3 cm). Weight 72 kg. BMI 27.43 kg / m 2 Cardiovascular system: heart rate 58 beats / min. blood pressure 147 / 85 mm Hg.

[0111] Laboratory tests: total cholesterol 3.2 mmol / L, total alkaline phosphatase 69 U / L, total calcium 2.34 mmol / L.

[0112] Duplex scanning of the carotid arteries: increased stenosis up to 30% on the right and up to 40% on the left.

[0113] Applanation tonometry: AI 32%. PWV 8.7 m / sec

[0114] DEXA study revealed a decrease in BMD in the lumbar spine, characteristic of osteoporosis (T-score -2.6 SD), in the femoral neck - characteristic of osteopenia (T-score -1.3 SD).

[0115] Thus, in a postmenopausal patient with initial manifestations of decreased BMD (osteopenia in the spine) and normal BMD values ​​in the hip, with high IA and atherosclerotic changes in the carotid arteries, after 10 years, a pronounced loss of BMD in the range of osteoporosis in the spine and osteopenia in the femoral neck was detected.

[0116] Thus, an accessible and easy-to-use method provides data on the individual probability of bone loss in asymptomatic postmenopausal women by assessing vascular stiffness and the presence of atherosclerotic plaques and identifies patients for further examination, contributes to improving the diagnostic capabilities of existing methods for the early detection of cardiovascular and bone pathology in order to implement timely and comprehensive treatment and preventive measures, as well as the rational use of non-invasive instrumental resources.

[0117] List of used literature

[0118] 1. Debby den Uyl, Nurmohamed MT, van Tuyl Lilian HD, et al. (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis / / Arthritis Research & Therapy. 2011. Vol.13. No. 1. R5. doi:10.1186 ar3224.

[0119] 2. Zengin A., Jarjou LM, Janha RE, et al. Sex-Specific Associations Between Cardiac Workload, Peripheral Vascular Calcification, and Bone Mineral Density: The Gambian Bone and Muscle Aging Study / / Journal of Bone and Mineral Research. 2021. Vol.36. No. 2. P. 227-235. doi: 10.1002 / jhmr.4196.

[0120] 3. Xu X., Zhang M., Fei Z., et al. Calcification of lower extremity arteries is related to the presence of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a cross-sectional observational study / / Osteoporosis International. 2021. Vol.32. No. 6. P. 1185 1193. doi:0198-020-05775-5.

[0121] 4. Kokov AH, Masenko VL, Barbarash OL Prognostic significance of the equivalent density of coronary artery calcium deposits in men with osteopenic syndrome who underwent coronary artery bypass grafting: a prospective study / / Therapeutic archive. 2022. Vol. 94. No. 4. P. 467-472. https: / / doi.org / 10.26442 / 00403660.2022.04.201463.

[0122] 5. Muniyappa R., Telia S. Osteoporosis and cardiovascular disease in the elderly / / Elsevier Inc. 2018. Second Ed.: P. 721-733.

[0123] 6. Lello S., Capozzi A., Scambia G. Osteoporosis and cardiovascular disease: an update / / Gynecol. Endocrinol. 2015. Vol.31. No. 8. P. 590-594. https: / / doi.org / 10.3109 / 09513590.2015.1041908.

[0124] 7. Myagkova MA, Skripnikova IA, Shalnova SA, et al. Associations of 10-year probability of osteoporotic fractures with total cardiovascular risk and cardiovascular diseases caused by atherosclerosis among urban and rural populations / / Preventive Medicine. 2021. Vol. 24. No. 6. P. 18-27. https: / / doi.org / 10.17116 / profmed20212406118.

[0125] 8. Alikhanova N.A., Skripnikova I.A., Tkacheva O.N. et al. Association of vascular stiffness parameters and subclinical atherosclerosis with bone mass in postmenopausal women / / Cardiovascular Therapy and Prevention. 2016. Vol. 15. No. 2. P. 51-56. https: / / doi.org / 10.15829 / 1728-8800-2016-2-51-56.

[0126] 9. Skripnikova I.A., Kolchina M.A., Kosmatova O.V., et al. Association of cardiovascular risk and fracture risk in women without clinical manifestations of atherosclerosis / / Cardiovascular Therapy and Prevention. 2020. Vol. 19. No. 6. P. 2724. https: / / doi.org / 10.15829 / 1728-8800-2020-2724.

[0127] 10. Lampropoulos S.E., Papaioannou I., D'Cruz DP. Osteoporosis A risk factor for cardiovascular disease? / / Nat. Rev. Rheumatol. 2012. Vol.8. No. 10. P. 587-98. doi: 10.1038 / nrrheum.2012.120.

[0128] 11. Skripnikova IA, Alikhanova NA, Kolchina MA, et al. Atherosclerosis and osteoporosis. Common targets for the influence of cardiovascular and antiosteoporosis drugs (Part I). The effect of cardiovascular drugs on bone strength / / Rational Pharmacotherapy in Cardiology. 2019. Vol. 15. No. 1. P. 69-76. https: / / doi.org / 10.20996 / 1819-6446-2019-15-l-69-76.

[0129] 12. Park J., Yoon YE, Kim KM, et al. Prognostic value of lower bone mineral density in predicting adverse cardiovascular disease in Asian women / / Heart. 2021. 107, P: 1040-6. https: / / doi. org / 10.1136 / heartinl-2020-318764.

[0130] 13. Mangiafico RA, Alagona C, Pennisi P, et al. Increased augmentation index and central aortic blood pressure in osteoporotic postmenopausal women / / Osteoporos Int. 2008. Vol.19. No. 1. P.49-56. doi: 10.1007 / s00198-007-0438-5.

[0131] 14. Rodriguez A.J., Scott D., Hodge A., et al. Associations between hip bone mineral density, aortic calcification and cardiac workload in community-dwelling older Australians. Osteoporos Int / / 2017. Vol.28. №7. P. 2239-2245. doi: 10.1007 / s00198-017-4024-1.

[0132] 15. van Guldener С., Janssen M. J.F., Lambert J., et al. Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients / / Nephrol. Dial. Transplant. 1998. Vol.13. №7. P. 1782-6. doi: 10.1093 / ndt I i.7.1782.

[0133] 16. Tanko L.B., Christiansen C., Cox D.A., et al. Relationship between osteoporosis and cardiovascular disease in postmenopausal women / / Journal of Bone and Mineral Research. 2005. Vol.20. №11. P. 1912-1920. doi: 10.1359 / JBMR.050711.

[0134] 17. Skripnikova IA, Kolchina MA, Kosmatova OB, et al. Assessment of preclinical manifestations of atherosclerosis of coronary and peripheral arteries and bone strength parameters in women / / Rational pharmacotherapy in cardiology. 2020. Vol. 16. No. 6. P. 868-875. https: / / doi.org / 10.20996 / 1819-6446-2020-ll-02.

[0135] 18. Lesnyak O.M., Ershova O.V., Belova K.Yu. et al. Epidemiology of fracture in the Russian Federation and the development of a FRAX model / / Arch. Osteoporos. 2012. Vol.7. No. 1-2. P. 67-73. https: / / doi.org / 10.1007 / sll657-012-0082-3.

Claims

A method for predicting osteopenic syndrome in postmenopausal women, including an analysis of the clinical and instrumental results of a patient's examination and the calculation of the risk of bone mass loss using a formula, characterized in that vascular stiffness is determined using the augmentation index (AI), the presence of atherosclerotic plaques in the carotid arteries (CAP) and the body mass index (BMI) are assessed, and the predicted probability of developing osteopenic syndrome is calculated using the formula: Y = 0.929 + 0.011⋅Х1– 0.030⋅Х2+ 0.435⋅Х3, where Y is the predicted individual probability of osteopenic syndrome in postmenopausal women, X1 – IA value, %, X2 – BMI, kg / m 2 , X3 – the presence of an ASB, which is equal to 0 in the absence of an ASB, and is equal to 1 in the presence of at least one ASB, and with a value of Y≥0.5, osteopenic syndrome is predicted.

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