home Calculators COPD and osteoporosis study design 14.01 04. Osteoporosis in patients with COPD: comorbidity or systemic manifestation? Early diagnosis and treatment of osteoporosis

COPD and osteoporosis study design 14.01 04. Osteoporosis in patients with COPD: comorbidity or systemic manifestation? Early diagnosis and treatment of osteoporosis

As a manuscript

Volkorezov Igor Alekseevich

EARLY DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS

IN PATIENTS WITH CHRONIC OBSTRUCTIVE DISEASE

LUNG

Dissertations for a degree

Candidate of Medical Sciences

Voronezh - 2010

The work was performed at the State Educational Institution of Higher Professional Education “Voronezh State Medical Academy named after I.I. N.N. Burdenko” of the Ministry of Health and Social Development (GOU VPO VSMA named after N.N. Burdenko of the Ministry of Health and Social Development of Russia)

^ Scientific adviser: Doctor of Medical Sciences

Prozorova Galina Garaldovna

Official opponents: doctor of medical sciences, professor

Nikitin Anatoly Vladimirovich

Candidate of Medical Sciences

Symbolokov Sergey Ivanovich

^ Lead organization : SEI HPE "Kursk State Medical University" of the Ministry of Health and Social Development

The defense will take place on December 1, 2010 at 1300 at a meeting of the dissertation council D.208.009.02 at the State Educational Institution of Higher Professional Education VSMA. N.N. Burdenko Ministry of Health and Social Development of Russia at the address: 394036, Voronezh, st. Student, 10

The dissertation can be found in the library of the State Educational Institution of Higher Professional Education of the Voronezh State Medical Academy. N.N. Burdenko Ministry of Health and Social Development of Russia

Scientific Secretary

dissertation council

A.V. Budnevsky

^ GENERAL DESCRIPTION OF WORK

Relevance of the topic. Chronic obstructive pulmonary disease (COPD) is defined as a disease characterized by partially irreversible airflow limitation, which is usually steadily progressive and is associated with an inflammatory response of lung tissue to irritation by various pathogenic agents and gases (Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, 2007).

This definition focuses on the bronchopulmonary manifestations of COPD. At the same time, in recent years, extrapulmonary manifestations of COPD have been increasingly discussed, the most famous of which are metabolic and musculoskeletal disorders: skeletal muscle dysfunction, weight loss, osteoporosis, etc. (Avdeev S.N., 2007; Bachinsky O. N. et al., 2009; Andreassen H., Vestbo J., 2003). The mediator of some of these systemic effects may be an increase in the concentrations of inflammatory mediators, including tumor necrosis factor alpha (TNF-α), interleukin-6, C-reactive protein (CRP) and free oxygen radicals (Kochetkova E.A. et al. , 2004; Yang Y. M. et al., 2006).

In recent years, in the development of the topic of COPD and systemic manifestations of this disease, attention has been paid to the study of the nature of osteoporosis, the role of the endocrine system and metabolic syndrome in this category of patients. The fact of a significant effect of glucocorticosteroid (GCS) therapy on bone tissue metabolism is indisputable; a racial and genetic predisposition to the osteoporotic effects of corticosteroids has been established (Dvoretsky L.I., Chistyakova E.M., 2007; Bolton C.E. et al., 2008). Therapeutic programs for osteoporosis, including the appointment of vitamin D, calcitonin, drugs containing calcium, of course, also apply to patients with COPD, the course of which was complicated by a violation of bone tissue metabolism.

However, at present there are no algorithms for early diagnosis and treatment of osteoporosis in patients with COPD and data on the need for treatment of osteoporosis in the early stages, depending on the therapy of pulmonary pathology, which determines the relevance of the study.

^ The purpose of the dissertation work is based on the analysis of risk factors, the clinical course of the disease and the level of biomarkers of systemic inflammation, to improve the effectiveness of therapeutic and preventive measures and the quality of life (QoL) in COPD patients with osteoporosis.

^ Research objectives

To study the features of the clinical course of COPD in patients with impaired bone mineral density (osteopenia, osteoporosis) depending on the level of biomarkers of systemic inflammation (TNF-α, CRP) in the blood serum;
To identify the main factors affecting the quality of life in COPD patients with impaired bone mineral density (osteopenia, osteoporosis);
Based on the analysis of the dynamics of systemic inflammation markers, to substantiate the possibility of therapy in the early stages of osteoporosis in patients with moderate and severe COPD using alfacalcidol and alendronic acid.
To study the clinical efficacy of complex therapy of osteoporosis in patients with COPD with alfacalcidol and alendronic acid and to evaluate its effect on the quality of life of patients.

^ Scientific novelty

the features of the clinical course of COPD in combination with bone mineral density disorders were studied depending on the level of biomarkers of systemic inflammation (TNF-α, CRP) in the blood serum;
substantiated the therapy of osteoporosis in patients with moderate and severe COPD using alfacalcidol and alendronic acid based on the analysis of the dynamics of systemic inflammation markers;
The effect of osteoporosis therapy with alfacalcidol and alendronic acid on the quality of life of patients with moderate and severe COPD was studied.

^ Practical significance. The study of the features of the clinical course of COPD in patients with impaired bone mineral density, depending on the level of markers of systemic inflammation, makes it possible to optimize complex programs for the treatment of comorbidities (COPD + osteoporosis) and improve the quality of life of patients. It has been shown that one of the optimal options for the complex therapy of osteoporosis in patients with stage II-III COPD may be the use of alfacalcidol (Alpha D3 TEVA) at a dose of 1 μg/day. and alendronic acid (Tevanat) at a dose of 70 mg once a week, the use of which for 12 months. allows to reduce the severity of systemic inflammation, the frequency of COPD exacerbations and the frequency of hospitalizations of patients, increase bone mineral density (BMD), exercise tolerance and QoL of patients with COPD.

^ Reliability and validity of the results The research is ensured by the representativeness of the sample, the vastness of the primary material, the thoroughness of its qualitative and quantitative analysis, the systematic nature of the research procedures, and the use of modern methods of statistical information processing.

^ The following provisions are put forward for defense:

The main factors affecting the quality of life of COPD patients with BMD disorders are the level of the systemic inflammation biomarker TNF-α, the frequency of exacerbations and hospitalizations in COPD patients, exercise tolerance, the concentration of acute phase protein - CRP, T-criterion and FEV1 values.
Therapy of osteoporosis in patients with moderate and severe COPD with alfacalcidol and alendronic acid helps to reduce the frequency of exacerbations of COPD and hospitalizations of patients, increase the T-criterion and exercise tolerance of patients with COPD, improve the quality of life of patients.
The study of the level of TNF-α in COPD patients with osteoporosis in dynamics allows monitoring the effectiveness of maintenance therapy for comorbidity, predicting the number of exacerbations and hospitalizations of patients.

^ Implementation of research results

The results of the study were tested in the pulmonology departments of the Central City Clinical Hospital of Lipetsk, the Voronezh Regional Clinical Hospital No. 1, the Voronezh State Clinical Hospital No. 1, in educational and clinical practice at the Department of General Medical Practice (Family Medicine) of the IPMO GOU VPO "Voronezh State medical academy. N.N. Burdenko” of the Ministry of Health and Social Development.

The implementation of the results allows to obtain a medical and socio-economic effect by improving the effectiveness of osteoporosis therapy in the early stages and the quality of life of COPD patients with impaired bone mineral density.

^ Approbation of work. The main results were reported and discussed at the XVI Russian National Congress "Man and Medicine" (Moscow, 2009), XXII Interregional Scientific and Practical Conference "Actual Issues of Medical Prevention and Formation of a Healthy Lifestyle" (Lipetsk, 2009), scientific and methodological seminars of the Department of General medical practice (family medicine) IPMO (2008-2010), Voronezh Regional Society of Therapists (2009-2010).

^ Structure and scope of work. The dissertation consists of an introduction, 4 chapters, conclusions and practical recommendations, contains a list of references from 221 sources, is presented on 145 pages of typewritten text, which contains 45 tables and 58 figures.

^ MAIN RESULTS OF THE WORK

The clinical part of the dissertation work was carried out on the basis of the pulmonological and rheumatological departments of the Lipetsk Central Clinical Hospital in 2008-2009.

A total of 130 COPD patients aged 52 to 84 years were examined, the mean age was 61.75±0.71 years (92 men (mean age 61.49±0.85 years) and 38 women (mean age 62.37 years). ±1.32 years).

The diagnosis of chronic obstructive pulmonary disease was established on the basis of complaints (cough, sputum production, shortness of breath), anamnestic data on exposure to risk factors, instrumental data (measurement of airflow limitation (spirometry) - the ratio of FEV 1 / VC
The study of the function of external respiration with a bronchodilator test was carried out using a Schiller spiroanalyzer (Switzerland). An ECG was recorded, the clinical symptoms of COPD were assessed using a visual analogue scale (VAS), the content of TNF-α in the blood serum was determined using reagents from Biosource Europe S.A. and C-reactive protein with reagents from Hoffman La Roche. The daily requirement for short-acting bronchodilators was analyzed. Exercise tolerance was assessed using the 6-minute walk test (WST). The SF-36 questionnaire was used to assess QoL. The state of bone mineral density was assessed by dual-energy X-ray densitometry (DEXA) using the DTX-200 device (USA) in accordance with the recommendations of the International Society for Osteoporosis.

TO a comprehensive clinical and instrumental examination of 130 patients made it possible to diagnose COPD stage II in 79 people (60.77%), stage III - in 51 people (39.23%) (Fig. 1).

Rice. 1. Distribution of patients according to the severity of COPD

The study consisted of 3 stages.

Stage 1 - clinical and instrumental examination of patients with COPD to identify osteopenia and osteoporosis.

Stage 2 - analysis of the severity of systemic inflammation activity and the clinical course of osteoporosis, depending on the severity of the disease.

Stage 3 - study of the possibility of treating osteoporosis in patients with COPD using alfacalcidol (Alpha D3 TEVA) 1 mcg / day. and alendronic acid (Tevanat) at a dose of 70 mg once a week.

The average value of the duration of the disease (from the moment of registration in the official medical documentation of a chronic disease of the lower respiratory tract) in patients with COPD stage III. was - 9.49±0.49 years, in patients with COPD stage II. – 7.42±0.39 years (F=10.08, p=0.0013).

1 group amounted to

2 group, which consisted of 23 patients with COPD stage II and III (19 men and 4 women aged 42 to 80 years, mean age 61.43±1.96 years) was considered as a comparison group. Patients in this group received only COPD therapy in accordance with the recommendations of the Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2007).

In patients with COPD and osteoporosis in the comparison groups, a comprehensive clinical and instrumental examination was performed (study of respiratory function, clinical symptoms of COPD using a visual analogue scale, determination of exercise tolerance, X-ray densitometry), the level of biomarkers of systemic inflammation (TNF-α, CRP) was assessed, assessed the quality of life using the SF-36 questionnaire. These studies were performed before the start of therapy and after 12 months. observations. Stage II COPD was diagnosed in the first comparison group in 11 people (27.50%), stage III - in 13 people (32.50%), in the second group - 6 (15.00%) and 10 (25.00%) ) patients, respectively.

^ Statistical processing digital data was carried out using an IBM PC Celeron 2100 using the STATGRAPHICS 5.1 for WINDOWS software package. When choosing a data comparison method, the normality of the distribution of the trait in subgroups was taken into account, taking into account the Shapiro-Wilks test. The null hypothesis when comparing groups was rejected at the significance level
^ Analysis of the state of bone mineral density in patients with COPD

On fig. 2 shows a frequency diagram of the distribution of patients with COPD depending on the BMD. The T-score value in patients with COPD ranged from -3.7 SD to 3.0 SD, the mean value was -1.40±0.09 SD.

H
On the basis of densitometry, the diagnosis of osteoporosis (OP) was established in 40 patients with COPD (30.77%), osteopenia - in 77 (59.23%), BMD disorders were not detected in 13 patients (10.0%) (Fig. 3).

Rice. 2. Frequency diagram of COPD patients depending on T-criterion

Rice. 3. Distribution of patients with COPD depending on the severity

violations of the IPC

At the same time, there were no significant differences between COPD patients with moderate and severe course of the disease (χ 2 =0.81, p=0.6656). Among patients with stage II COPD, OP was diagnosed in 24 people (18.46%), osteopenia - in 45 (34.62%), with stage III - in 16 (12.31%) and 32 (24.62%). Analysis of the effect of COPD severity on BMD did not reveal significant differences between patients with moderate and severe course of the disease - the average value of the T-criterion in patients with stage II of the disease was -1.40 ± 0.12 SD, with stage III -

1.39±0.15 SD (F=0.01, p=0.9211).

The assessment of the dependence of BMD on sex, carried out using analysis of variance, did not reveal significant differences between men and women - the average value of the T-test for men was -1.79±0.17 SD, for women - -1.55±0.11 SD (F=1.32, p=0.2530).

Fractures as an indicator of severe AP were identified in history in 27 patients (20.77%), including 17 patients with moderate COPD (13.08%) and 10 with severe disease (7.69%). There were no significant differences in the severity of AP in patients with COPD II and III stages of the disease (χ 2 =0.07, p=0.7931). The presence of a history of fractures was associated with significantly lower T-score values, which amounted to -2.20±0.19 SD, while the absence of fractures corresponded to a significantly higher T-score value of 1.19±0.09 SD. (F=23.74, p=0.0000).

P
Patients diagnosed with OP walked a significantly shorter distance than patients with normal BMD and osteopenia. The average value of TNT in persons with OP was 340.25±9.94 m, with osteopenia - 379.74±5.07 m, with normal BMD - 382.73±7.74 m (F=7.04, p= 0.0013).

^ Rice. Fig. 4. Mean BMI values and their 95% confidence intervals in COPD patients depending on BMD disorders (0 - normal BMD, 1 - osteopenia, 2 - osteoporosis)

The relationship between body mass index and the presence of osteoporotic changes in patients with COPD is illustrated in Fig. 4. As can be seen from fig. 4, in patients with OP, the average BMI was 21.55±0.76 kg/m 2 , with osteopenia - 24.60±0.51 kg/m 2 , in patients without BMD disorders - 30.21±0.62 kg/m 2 (F=38.97; p=0.0000).

Correlation analysis of the relationships between BMD disorders, AP severity, the presence of amyotrophies and socio-demographic indicators revealed the following patterns. A significant direct moderate correlation was found between the age of patients and BMD disorders (OP, osteopenia), a weak direct correlation between age and the severity of OP, direct average correlations between age and T-criterion, age and the presence of amyotrophies.

Table 1

The results of the correlation analysis of the relationship between violations of the BMD and socio-demographic indicators of patients with COPD

Indicators	IPC Violations		Severity of OP		T-test		Amyotrophy
Indicators	Rx	R	Rx	p	Rx	p	Rx	p
TNF-α	0,4742	0,0000	0,1339	0,1381	-0,5230	0,0000	0,0503	0,5769
SRP	-0,0278	0,7581	-0,0790	0,3808	0,0054	0,9525	0,0425	0,6376

Rice. 5. Dependence of the T-criterion on the level of TNF-α

As follows from the data in Table. 1, a significant direct medium-strength relationship between BMD disorders (OP, osteopenia) and the level of TNF-α and an inverse medium-strength relationship between the T-criterion and the level of TNF-α were revealed.

As follows from the data in Table. 2, violations of the BMD had a significant moderate direct correlation with the duration of COPD, exercise tolerance, smoking, the number of hospitalizations for exacerbations of COPD; a weak direct correlation with self-reported dyspnea and smoking, a strong direct correlation with the duration of COPD. The severity of AP (history of fractures) was significantly associated (medium-strength correlation) with the duration of COPD, an inverse weak correlation was obtained with TST data, and a direct weak correlation with the number of hospitalizations for exacerbation of COPD.

The values of the T-criterion had a direct weak correlation with the data of TSH, the number of exacerbations of COPD and the average severity - with the duration of COPD. The presence of amyotrophies was associated with a correlation dependence of the average strength with TSH and the duration of COPD, a weak correlation with the scoring of dyspnea.

table 2

The results of the correlation analysis of the relationship between BMD disorders, clinical and behavioral parameters of patients with COPD

Indicators	IPC Violations		Severity of OP		T-test		Amyotrophy
Indicators	Rx	R	Rx	p	Rx	p	Rx	p
COPD stage	0,0525	0,5533	-0,0230	0,3950	0,0088	0,9211	0,0680	0,4823
Cough	0,0854	0,2765	0,0321	0,7621	-0,0076	0,9281	0,0065	0,9143
Sputum	0,0844	0,4320	0,0652	0,5432	0,0912	0,2115	-0,07654	0,2449
Dyspnea	0,1885	0,0054	0,1007	0,1652	-0,1943	0,0072	0,2151	0,0006
TSHH	0,3922	0,0000	-0,1818	0,0384	-0,1762	0,0011	0,3421	0,0000
Number of COPD exacerbations	0,1642	0,1007	0,1054	0,1219	-0,0954	0,2105	0,2876	0,0054
Total number of hospitalizations in the last year	-0,0202	0,8130	-0,0039	0,9746	0,0177	0,7832	-0,0665	0,6511
Number of hospitalizations for exacerbations of COPD	0,3218	0,0000	0,2761	0,0216	0,1651	0,0932	0,1292	0,1120
Disease duration	0,6119	0,0000	0,3647	0,0000	-0,4122	0,0000	0,3724	0,0000
Smoking	0,1954	0,0076	0,0605	0,4939	-0,2177	0,0003	-0,0773	0,3821

Table 3

Results of correlation analysis of relationships between BMD disorders and comorbidities in COPD patients

Indicators	IPC Violations		Severity of OP		T-test		Amyotrophy
Indicators	Rx	R	Rx	p	Rx	p	Rx	p
coronary artery disease, CV	0,4897	0,0000	0,3302	0,0001	-0,3586	0,0000	0,3488	0,0000
THEM	0,5321	0,0000	0,1498	0,1271	-0,3177	0,0000	0,4117	0,0000
SD	0,0908	0,2630	0,0144	0,8712	-0,0530	0,5430	0,0376	0,6761
BMI	-0,3211	0,0000	-0,5433	0,0000	0,3992	0,000	-0,6112	0,0000

As follows from the data in Table. 3, BMD disorders had a significant moderate direct correlation with the presence of coronary heart disease, stable exertional angina (SHF), a history of myocardial infarction (MI), type 2 diabetes mellitus (DM) and an inverse medium strength relationship with the index body weight (BMI).

The severity of OP (history of fractures) had a significant medium-strength direct correlation with the presence of coronary artery disease, CVD as a concomitant pathology and an inverse medium-strength relationship with BMI. The values of the T-criterion had a significant medium-strength inverse correlation with the presence of concomitant pathology - coronary heart disease, heart failure, a history of myocardial infarction and a direct moderate-strength relationship with BMI. The presence of amyotrophy was associated with a direct correlation dependence of the average strength with the presence as a concomitant pathology - coronary artery disease, heart failure, MI in history and an inverse medium-strength relationship with BMI. The level of TNF-α was negatively correlated with the stage of the disease and TSH data, positive correlations were found with the frequency of exacerbations of COPD, the total number of hospitalizations and the number of hospitalizations for exacerbations of COPD, the duration of the disease, the presence of concomitant pathology of coronary artery disease, CHF, a history of MI, BMI . All correlations, with the exception of the total number of hospitalizations and the presence of coronary artery disease, CSI were of medium strength.

Table 4

Results of the correlation analysis of the relationship between BMD disorders and spirometry parameters in patients with COPD

Indicators	IPC Violations		Severity of osteoporosis		T-test		Amyotrophy
Indicators	Rx	R	Rx	p	Rx	p	Rx	p
VC	-0,1151	0,1872	-0,3187	0,0011	0,0872	0,4143	-0,4321	0,0000
FZhEL	-0,2321	0,1007	-0,1321	0,1992	-0,0177	0,5423	-0,4117	0,0000
FEV 1	-0,1908	0,0630	-0,2144	0,0531	0,0923	0,5875	-0,3266	0,0000
FEV 1 / FVC	-0,3752	0,0000	-0,5433	0,0000	-0,3992	0,000	-0,6112	0,0000
POS vyd.	-0,0972	0,3498	-0,0665	0,4221	-0,0652	0,4875	-0,1851	0,1165
MOS 25	-0,1088	0,2865	-0,0822	0,3359	-0,0154	0,5872	-0,1872	0,1407
MOS 50	-0,0762	0,4766	-0,0388	0,6772	-0,1123	0,1671	-0,1708	0,0930
MOS 75	-0,0522	0,6112	-0,0963	0,2664	0,0092	0,8842	-0,3251	0,0000

In table. 4 presents the main results of the correlation analysis of the data of the study of the function of external respiration (EP) and violations of the BMD. As follows from Table. 4, significant correlations were found between the parameters of respiratory function: the Tiffno index and BMD disorders, the severity of osteoporosis, T-test values and the presence of amyotrophies (moderate feedback), FVC, FEV 1, VC and the presence of amyotrophies (moderate feedback), Tiffno index and the presence of amyotrophies (strong inverse correlation). The relationship between FEV 1 and indicators characterizing the state of bone tissue in patients with COPD was close to statistically significant and weak in strength.

Thus, the use of correlation analysis made it possible to identify the main relationships between the level of serum biomarkers of systemic inflammation (TNF-α and CRP), clinical, instrumental and laboratory parameters, which must be taken into account when assessing the effectiveness of COPD therapy with impaired BMD.

^ Clinical course of COPD in patients with impaired BMD and the level of systemic biomarkers in blood serum

The mean value of the TNF-α level in the general group of COPD patients was 24.48±0.63 pg/ml, the minimum value was 8.0 pg/ml, the maximum value was 46 pg/ml, CRP was 4.26±0.17 mg/ml. l; minimum - 0.5, maximum - 9.1 mg / l. The average values of the concentration in the blood serum of the cytokine TNF-α and CRP in patients with COPD, depending on the stage of the disease, are presented in Table. 5. As follows from the table. 5, patients with COPD II and III stages of the disease did not significantly differ from each other in the average values of CRP and TNF-α (p>0.05).

Table 5

Concentration of systemic biomarkers in serum in patients with COPD depending on the stage of the disease

Rice. Fig. 6. Mean values of TNF-α levels and their 95% confidence intervals in patients with COPD depending on BMD disorders (0 - without BMD disorders, 1 - osteopenia, 2 - osteoporosis)

Rice. 6 illustrates mean TNF-α values as a function of BMD disturbances. As can be seen from fig. 6, in patients with osteoporosis, the average value of TNF-α was statistically significantly higher than in patients with osteopenia and without BMD disorders and amounted to 26.80±1.06, respectively; 24.45±0.78 and 17.56±1.57 pg/ml (F=9.20; p=0.0002).

There were no significant differences in the level of CRP between patients with osteoporosis, osteopenia and without BMD disorders (F=0.23, p=0.7976). The level of CRP in COPD patients with osteoporosis was 4.01±0.31, with osteopenia - 4.30±0.22, and without BMD disorders - 4.46±0.54 mg/l.

^ Quality of life in COPD patients with impaired bone mineral density

The quality of life of COPD patients of stage II-III, included in our study, was characterized as rather low, especially on the following scales: physical activity (FA), the role of physical problems in disability (RF), the role of emotional problems in disability (RE), general health (OH).

**
^ Rice. 7. QoL of patients with COPD II- IIIstages with osteoporosis (1), osteopenia (2) and without BMD disorders (3) (* -p p

The quality of life of COPD patients with osteoporosis and osteopenia was statistically significantly lower on all scales of the SF-36 questionnaire compared to the quality of life of patients without BMD disorders. Significant differences were found between COPD patients with osteoporosis and osteopenia on the following scales: physical activity (PA), the role of physical problems in disability (RF), pain (B), the role of emotional problems in disability (RE), general health (OH ), viability (LS) (Fig. 7). Next, we conducted a dispersion analysis of the influence of the main clinical, instrumental, laboratory, and socio-demographic factors on the quality of life of COPD patients, depending on the severity of BMD disorders.

Rice. Fig. 8. Dependence of the indicator of the role of physical problems in disability (RF) of COPD patients on the values of the T-criterion (abscissa - T-criterion, ordinate - RF index)

According to most scales of the SF-36 questionnaire, the quality of life of COPD patients statistically significantly depended on the number of exacerbations and hospitalizations of the disease. To a greater extent, these changes were characteristic of the following scales: physical activity (PA), the role of physical problems in disability (RF), the role of emotional problems in disability (RE), general health (OH), mental health (PH), social activity (SA).

Table 6

Analysis of variance of the influence of TST parameters in COPD patients on QoL parameters

The T-criterion values were significantly associated with QoL indicators on the FA, RF, B, OZ, RE, ZhS, PZ, and SA scales, which indicates the effect of BMD on the perception of the main limitations of QoL by COPD patients. Rice. 8 illustrates the relationship between the average values of the T-criterion, reflecting the state of the BMD and the values of the scale "the role of physical problems in disability (RF)". As can be seen from fig. 8, the QoL of patients with COPD on the RF scale was significantly associated with the average values of the T-test.

The level of TNF-α significantly affected the values of the FA, RF, B, OZ, ZhS scales, the concentration of C-reactive protein - on the average values of the FZ, OZ, and PZ scales. The data of the analysis of the relationship between exercise tolerance (according to the results of TST) and QoL in patients with COPD are presented in Table. 6, from which it follows that the TSHH indicator significantly influenced the values of the following scales of the SF-36 method: FA, RF, B, OZ and SA.

The spirometry indicator FEV 1 (% predicted) significantly influenced the scores of the SF-36 methodology scales: FA, RF, B, OZ, ZhS, PZ, and SA. Thus, as the analysis of QoL indicators in patients with moderate and severe COPD showed, the main factors determining QoL were the frequency of exacerbations and hospitalizations of COPD, exercise tolerance, the level of the biomarker of systemic inflammation TNF-α, the concentration of the acute phase protein - CRP, the values of T- criteria and FEV 1 .

^ Analysis of the effectiveness of complex therapy for severe chronic obstructive pulmonary disease in combination with osteoporosis

Analysis of the effectiveness of complex therapy in patients with stage II-III COPD and osteoporosis was performed in 2 groups of patients.

1 group consisted of 17 patients (11 men and 6 women aged 43 to 83 years, mean age 58.72 ± 1.99 years) with stage II and III COPD, who, in addition to correcting the complex therapy of COPD, were prescribed osteoporosis therapy using alfacalcidol ( Alpha D3 TEVA) 1 mcg/day. and alendronic acid (Tevanat) at a dose of 70 mg once a week.

Table 7

Clinical symptoms in COPD patients of the first and second comparison groups before and after therapy (points, M±m)

Clinical symptoms of COPD according to VAS, mm	Before therapy		After 12 months observations
Clinical symptoms of COPD according to VAS, mm	First group, n=17	Second group, n=23	First group, n=17	Second group, n=23
cough	5.11±0.22	5.24±0.18	4.32±0.18 *	4.19±0.18 *
dyspnea	6.14±0.18	6.33±0.16	4.88±0.19*	5.41±0.17 ,*
sputum	4.49±0.19	4.27±0.18	3.22±0.12 *	3.57±0.18 *
wheezing	5.12±0.21	5.24±0.17	4.26±0.18 *	4.41±0.15 *
general weakness, fatigue	6.08±0.24	5.94±0.20	4.04±0.20 *	5.01±0.17, *

Tab. 7 illustrates the severity of clinical symptoms in patients of the first and second comparison groups before treatment and after 12 months. observations. As follows from the data in Table. 7, in patients of the first and second comparison groups, there was a comparable significant positive dynamics of symptoms of self-reported symptoms of cough, shortness of breath, sputum, wheezing in the lungs and general weakness. However, the average values of self-assessment of dyspnea and general weakness by patients in the first group were significantly lower than in the second group.

At
patients suffering from COPD in combination with osteoporosis in the first and second comparison groups, there was an unreliable positive dynamics of respiratory function after 12 months. observations.

Rice. Fig. 9. Mean values of the frequency of exacerbations and their 95% confidence intervals in patients with COPD and osteoporosis of the first (A) and second (B) groups before (0) and after 12 months. (1) therapy

The dynamics of the frequency of exacerbations in the first and second comparison groups is shown in Fig. 9. In the first group, the number of exacerbations significantly decreased from 2.56±0.21 to 1.81±0.20 per year (F=6.63; p=0.0152), the number of hospitalizations decreased from 1.94±0 .19 to 1.06±0.20 (F=11.14, p=0.0023), no significant dynamics of the analyzed parameters was revealed in the second group.

After 12 months therapy significantly decreased the concentration of TNF-α from 29.48±2.35 pg/ml to 19.58±2.16 pg/ml (F=9.57; p=0.0041). No significant changes in the level of CRP were revealed; before therapy, this indicator was 3.92±0.42 mg/l, after 12 months. therapy − 3.54±0.38 mg/l (F=0.42; p=0.5193). In the second group after 12 months. decrease in TNF-α concentration from 26.85 ± 1.85 pg/ml to 23.66 ± 1.68 pg/ml was not significant (F=1.62; p=0.2091).

Also, no significant changes in the level of CRP were found; before therapy, this figure was 4.20 ± 0.30 mg/l, after 12 months. therapy - 3.90 ± 0.29 mg/l (F=0.39; p=0.5346).

Next, we analyzed the dynamics of exercise tolerance in patients of the first group who received alfacalcidol (Alpha D3 TEVA) 1 µg/day against the background of corrected basic therapy for COPD. and alendronic acid (Tevanat) at a dose of 70 mg once a week.

Rice. Fig. 10. Mean values of TNR (m) and their 95% confidence intervals in patients with COPD and osteoporosis of the first (A) and second (B) groups before (0) and after 12 months. therapy (1)

Analyzing the TSH data before and after therapy, we revealed a significant positive dynamics of exercise tolerance in the first comparison group (Fig. 10). Patients suffering from COPD and osteoporosis underwent 350.0 ± 7.61 m before treatment, after 12 months. therapy with alfacalcidol at a dose of 1 mcg / day. and alendronic acid at a dose of 70 mg once a week - 372.9±6.44 m (F=5.29, p=0.0281). In the second group, the TSH data before therapy amounted to 361.5±8.3 m, after 12 months. observations − 348.3±6.8 m (F=1.59, p=0.2133).

Table 8

Dynamics of T-criterion in patients with COPD and osteoporosis before therapy and after 12 months. observations

Evaluation of BMD in patients with COPD and osteoporosis in dynamics revealed the following patterns (Table 8). Patients with COPD and osteoporosis had a mean T-score before treatment of -2.86 ± 0.05 SD, after 12 months. therapy with alfacalcidol at a dose of 1 mcg / day. and alendronic acid at a dose of 70 mg once a week - -2.68±0.04 SD (F=5.64, p=0.0237). In the second group, the mean T-score before therapy was -2.72±0.06 SD, after 12 months. observations - -2.82±0.06 (F=1.44, p=0.2362).

We analyzed the dynamics of QoL in COPD patients with osteoporosis. The main limitations that reduce the quality of life of patients before therapy were the limitations described by the following scales of the SF-36 questionnaire: physical activity (PA), the role of physical problems in disability (RF), general health (OH) and the role of emotional problems in disability (RE). ). In the first group after 12 months. therapy with alfacalcidol at a dose of 1 mcg / day. and alendronic acid at a dose of 70 mg once a week, there was a significant increase in the average values of QoL on the scales of FA, RF, B and OZ, in the second group, the dynamics of indicators was not statistically significant (Fig. 11).

Rice. 11. Indicators of QoL of patients with COPD and osteoporosis of the first and second comparison groups (1 - QoL of patients of the first group before treatment, 2 - QoL of patients of the second group before treatment, 3 - QoL of patients of the first group after 12 months of therapy, 4 - QoL of patients of the second group after 12 months of therapy); * - R

Thus, one of the optimal options for the complex therapy of osteoporosis in patients with COPD in real clinical practice may be the use of a combination of alfacalcidol (Alpha D3 TEVA) at a dose of 1 μg/day. and alendronic acid (Tevanat) at a dose of 70 mg once a week, the use of which for 12 months. allows to reduce the severity of systemic inflammation, the frequency of exacerbations of COPD and the frequency of hospitalizations of patients, improve BMD, increase exercise tolerance and quality of life of patients.

CONCLUSIONS

The main relationships between the level of serum biomarkers of systemic inflammation (TNF-α and CRP), clinical, instrumental and laboratory parameters have been identified, which must be taken into account when assessing the effectiveness of therapy for COPD with a stable course in patients with impaired BMD.
The quality of life of COPD patients with osteoporosis was significantly lower than in patients with osteopenia and without BMD disorders. The main factors determining QoL in individuals with BMD disorders were the frequency of exacerbations and hospitalizations of COPD, exercise tolerance, the level of the biomarker of systemic inflammation TNF-α, the concentration of acute phase protein - CRP, the values of T-criterion and FEV 1 .
Treatment of osteoporosis in patients with stage II-III COPD with alfacalcidol at a dose of 1 mcg/day. and alendronic acid at a dose of 70 mg once a week for 12 months. allows to reduce the severity of systemic inflammation, which is manifested by a significant decrease in the level of TNF-α.
The best option for the treatment of osteoporosis in patients with moderate and severe COPD is the use of alfacalcidol and alendronic acid, which help reduce the frequency of exacerbations of COPD and hospitalizations of patients, increase the T-score and exercise tolerance, and improve the quality of life of patients with COPD.

^ PRACTICAL RECOMMENDATIONS

One of the options for the treatment of osteoporosis in the early stages in patients with moderate to severe COPD may be the use of alfacalcidol at a dose of 1 µg/day. and alendronic acid at a dose of 70 mg once a week.
In COPD patients with osteoporosis, it is advisable to conduct a study of the level of TNF-α, which allows monitoring the effectiveness of maintenance therapy for comorbidity, predicting the number of exacerbations and hospitalizations of patients.

^ LIST OF WORKS PUBLISHED ON THE THEME OF THE THEsis

Prozorova G.G., Budnevsky A.V., Pashkova O.V., Volkorezov I.A. Features of the treatment of chronic obstructive pulmonary disease: emphasis on safety // Collection of materials of the XVI Russian National Congress "Man and Medicine". - M., 2009. - P. 228.
Prozorova G.G., Pashkova O.V., Volkorezov I.A., Nogavitsina A.S., Bunina T.I., Plotnikova N.F. Systemic effects and comorbidity in patients with chronic obstructive pulmonary disease. scientific and practical works "Actual issues of health protection of metallurgists" - Magnitogorsk, 2009. - P. 136-137.
Prozorova G.G., Pashkova O.V., Volkorezov I.A., Simonaites S.V., Nogavitsina A.S. New possibilities for predicting the course of COPD // Journal of Theoretical and Practical Medicine. - 2009. - no. 2. - S. 65-67.
Prozorova G.G., Pashkova O.V., Volkorezov I.A. Systemic manifestations of chronic obstructive pulmonary disease // Collection of materials of the XVI Russian National Congress "Man and Medicine". - M., 2009. - P. 61.
Pashkova O.V., Volkorezov I.A. Features of the clinical course of COPD: the role of systemic inflammation // Applied Information Aspects of Medicine 2009. - V. 12, No. 1. - P. 81-85.
Prozorova G.G., Budnevsky A.V., Volkorezov I.A., Pashkova O.V. A systematic approach to assessing the features of the clinical course of chronic obstructive pulmonary disease in patients with osteoporosis // System analysis and management in bimedical systems. - 2010. - V. 9, No. 2. - S. 321-326.

^ LIST OF ABBREVIATIONS

VAS - visual analogue scale

GCS - glucocorticosteroids

IHD - ischemic heart disease

BMI - body mass index

MI - myocardial infarction

QOL - quality of life

BMD - bone mineral density

OP - osteoporosis

OPN - osteopenia

FEV 1 - forced expiratory volume in 1 second

POS - peak expiratory flow rate

CRP - C-reactive protein

CCH - stable exertional angina

TShK - 6-minute walk test

COPD - chronic obstructive pulmonary disease

FVD - function of external respiration

TNF-α - tumor necrosis factor α

NAUMOV

ANTON VYACHESLAVOVYCH

Prevalence and course of osteoporosis in patients with somatic diseases

Moscow - 2010

The work was performed at the State Educational Institution of Higher Professional Education "Moscow State University of Medicine and Dentistry"

Scientific consultant:

Honored Worker of Science of the Russian Federation,

doctor of medical sciences, professor Vertkin Arkady Lvovich;
Official opponents:

Academician of the Russian Academy of Medical Sciences, Professor Martynov Anatoly Ivanovich

Doctor of Medical Sciences, Professor Stryuk Raisa Ivanovna

Doctor of Medical Sciences, Professor Alekseeva Lyudmila Ivanovna

Lead organization:Russian State Medical University. N.I. Pirogov
The defense will take place on "___" ______________ 2010 at ___ o'clock at a meeting of the dissertation council D.208.041.01. at the Moscow State Medical and Dental University of Roszdrav (127473, Moscow, Delegatskaya st., 20/1)
The dissertation can be found in the library of the State Educational Institution of Higher Professional Education of the MGMSU of Roszdrav (127206, Moscow, Vuchetich St., 10a)
The abstract was sent on "____"______________ 2010

Scientific Secretary of the Dissertation Council

doctor of medical sciences, professor Yushchuk E.N.

RELEVANCE OF THE PROBLEM.

According to official statistics, annually in the Russian Federation, people over 50 years of age are diagnosed with an average of 105.9 cases of fractures of the proximal femur per 100,000 population (78.8 and 122.5 in men and women, respectively). The leading cause of such fractures is osteoporosis, a progressive systemic skeletal disease characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue, leading to increased bone fragility and the risk of fractures (WHO, 1999).

According to the report of the International Osteoporosis Foundation (IOF, 2006), in the world after 50 years, complications of this disease are diagnosed in every 3rd woman and every 5th man, and a third of them die within the first year after an osteoporotic fracture of the femoral neck. It is for this reason that osteoporosis ranks 4th in the structure of global mortality after cardiovascular pathology, diabetes mellitus (DM) and oncological diseases, which indicates a high medical and social significance of the problem (Johnell O. et all, 2004).

However, in the current literature, when discussing osteoporosis, more attention is paid to postmenopausal women, during which excessive activation of bone resorption induced by estrogen deficiency leads to a significant loss of bone mineral density (BMD). However, according to Nasonov E.L. (2005) in 20% of cases the disease occurs in men. Moreover, one third of all cases of osteoporotic hip fractures in the world occur in males, and their immediate and long-term consequences are much more severe than in women. Thus, inpatient and outpatient (within a year) mortality after hip fractures in men is 2 times higher than in women (Terrence H. et al., 1997), averaging 40% and 20%, respectively. In addition, about half of men with osteoporosis who have suffered hip fractures are more disabled and need the daily help of medical and social workers. This position is of paramount importance for Russia, where the incidence and premature mortality of men is much higher than in other countries.

According to official data of the Ministry of Health and Social Development of the Russian Federation, published in 2009, the highest mortality in the country is mainly determined by cardiovascular diseases (CVD), which account for 56.6%. At the same time, according to autopsy data, inpatient mortality from heart and vascular diseases in Moscow is 48.8%, including more than half of acute vascular accidents (Vertkin A.L., 2009). The situation is further complicated by the fact that patients older than 50 who died of cardiovascular disease have more than three background or concomitant diseases. Not without interest in this regard are the data of Dashdamirov A.Kh., (2005) and Goruleva E.I. (2008) showed that more than 60% of patients with CVD have risk factors for osteoporosis, which is consistent with the results of the Farhat G study. N., et al. (2007), showing lower BMD in the vertebral bodies, femoral neck and distal forearm in this category of patients. Moreover, according to U. Sennerby et al. (2007) in cardiovascular pathology, there is a multiple increase in the risk of fracture of the proximal femur, and according to Vasan R.S., et al. (2003) among similar patients, the majority have a high level of pro-inflammatory cytokines in combination with osteoporosis. The given data allowed Marcovitz P.A. et all (2005) consider that the loss of BMD is one of the predictors of the development of CVD.

It is well known that type 2 diabetes is one of the main background diseases in cardiovascular pathology. According to Vertkin A.L. (2009) among 3239 autopsies of patients who died in a multidisciplinary hospital, 19% had DM, including 97, 1% had type 2. About 50 years ago, Albrigt and Reifehstein suggested that DM could cause bone loss. This condition is now called diabetic osteopenia. It is especially pronounced in men with cardiovascular pathology (Ermachek E.A., 2006). Diabetes mellitus of the second type develops, as a rule, after 30 years, when men begin an age-related decrease in the secretion of total testosterone, which leads to the appearance of an androgen-deficient state, which, according to Amin S. et all, (2000) and Khaibulina E.T. (2007) is the main cause of osteoporosis. In the study of Dedov I.I. (2005) and Khalvashi R.Z., (2008) showed that approximately 2/3 of men with hypogonadism are diagnosed with reduced bone density, including a third with osteoporosis.

Oncological diseases occupy the second place in the country in terms of mortality (Ministry of Health and Social Development, 2009). At the same time, according to autopsies of deceased patients in general somatic departments, malignant neoplasms are diagnosed in 6–8% of cases (Vertkin A.L., 2009). Cancer patients (including those already conditionally cured) are also at risk of developing osteoporosis and its complications. There are a number of explanations for this, including the forced intake of cytostatics, the hormonal background changed after surgical benefits, etc. (N.P. Makarenko, 2000). It is important to emphasize that the earlier the influence of unfavorable factors on the bone is observed, the higher the risk of developing osteoporosis and fractures already at a young age (Mahon S., 1998).

Another reason contributing to the high incidence of osteoporosis and associated fractures is chronic obstructive pulmonary disease (COPD). This pathology is the cause of death in 13% of cases in patients in a general somatic hospital (Vertkin A.L., 2009).

According to epidemiological studies by Van Staa T.P. et al. (2001) carried out for 5 years in patients with COPD, approximately half of the cases are diagnosed with either osteopenia or osteoporosis. The authors explain the results obtained, first of all, by common risk factors for COPD and osteoporosis (smoking, vitamin D deficiency and body weight), long-term use of glucocorticosteroids, activation of bone resorption under the influence of systemic inflammatory mediators: TNF-α and interleukin-6 (Eid A.A., et al. 2005).

Thus, these data provide convincing evidence of the role of somatic pathology in patients with osteoporosis. This is of particular relevance in connection with the growing number of people over the age of 65 with a high comorbid background. For these people, according to experts, the cost of treating osteoporotic fractures and, above all, the femoral neck will increase progressively, and by 2025 will amount to 31.8 billion euros (IOF, 2006).

To prevent such an unfavorable situation for any society, a global strategy is the timely diagnosis and prevention of the disease among the general population (IOF, 2001 - 2007), as well as the identification of patients who have a high risk of developing fractures (Michigan Quality Improvement Consortium; 2008).

In this regard, it is of interest to determine early markers of osteoporosis using simple clinical manipulations (IOF, 2005). Among them are the studies of Mohammad A.R. et al., (2003) showing that edentulous patients have low BMD. This led the authors to suggest that tooth loss due to periodontal disease can be considered a marker of systemic BMD loss. This can be confirmed by the still few clinical studies indicating that in women with chronic generalized periodontitis, the risk of developing osteoporosis is more than 3 times higher than in patients without significant damage to the oral mucosa (Gomes-Filho S. et al. , 2007). Similar data were obtained in studies by Wactawski-Wende J. et al., (2005), according to which women during menopause had a significantly higher risk of chronic generalized periodontitis with reduced BMD.

It has traditionally developed that the diagnosis, prevention and treatment of osteoporosis are a priority, first of all, rheumatologists, less often endocrinologists and gynecologists. This is due to the fact that most studies on the effectiveness of the treatment of osteoporosis with antiresorptive drugs were carried out mainly in the population of postmenopausal women, and severe somatic diseases were exclusion criteria (Povoroznyuk V.V., 2003).

At the same time, the Russian health care system provides primary health care with ample opportunities to implement a set of measures for primary and secondary prevention of diseases in most patients (L.I. Benevolenskaya, 2007; I.V. Galkin et al., 2009). Therefore, the transfer of the center of gravity for the early detection of osteoporosis to district clinics will significantly improve the provision of medical care for this and highly common pathology. This study is devoted to the development of effective screening programs, clinical features, prevention and treatment of osteoporosis in somatic patients.

PURPOSE OF THE STUDY

Determination of the prevalence, clinical and prognostic significance of osteoporosis and methods for its optimal drug correction in patients with somatic pathology.

OBJECTIVES OF THE RESEARCH

Develop a program for the detection, prevention and treatment of osteoporosis on the basis of multidisciplinary medical institutions
To carry out a retrospective analysis of the features of the comorbid background in patients with an atraumatic fracture of the proximal femur.
Conduct a comparative histomorphological analysis of the state of bone tissue in patients with somatic pathology.
To assess the prevalence of osteopenia and osteoporosis in patients with comorbid conditions
To clarify the gender characteristics of bone mineral density loss in patients with somatic diseases.
To study the role of screening for osteoporosis in patients with periodontal disease as an early marker of BMD loss.
To determine the effectiveness of programs for the prevention and treatment of osteoporosis in patients with somatic diseases.

SCIENTIFIC NOVELTY.

For the first time, a large sample of patients with somatic pathology was screened for osteoporosis. It was shown that osteoporosis was diagnosed in 34.3% of 8600 patients with various diseases of internal organs, while out of 1200 patients without chronic somatic diseases, it was detected only in 18.6% of cases. At the same time, the loss of BMD is observed in 77.5% of patients with somatic pathology.

It was found that OP is more often detected in patients with cardiovascular pathology, COPD, and oncological diseases. Patients with type 2 diabetes are more likely to be diagnosed with osteopenia. The severity of BMD loss in any somatic diseases significantly exceeds that in the control group.

It was stated that the most significant risk factors for osteoporosis, both in men and women, is hypogonadism in combination with somatic pathology (significance of the factor p=0.013 and p=0.014, respectively).

It has been shown that almost all patients with an atraumatic fracture of the proximal femur have chronic somatic diseases, at different times before the fracture occurred, all of them repeatedly consulted a therapist. Atraumatic fracture of the proximal femur occurs more often in women (the ratio of men and women is 1:3), mainly in old age (77.3±7.5), but in men, almost 7 years earlier. In the overwhelming majority of cases, these patients undergo surgical benefits depending on the type of traumatic injuries.

A histomorphometric study in the bone tissue of patients who died not from somatic diseases revealed the predominance of the matrix over the number of resorption cavities, while in patients who died from somatic diseases, an inverse ratio is observed, while there is also a significant decrease in newly formed bone units (Haversian systems). These ratios remain relevant even when adjusted for age. This is evidence of a significant loss of bone mass and density in patients with somatic pathology, in contrast to patients whose death was not due to somatic diseases.

For the first time, as an early clinical marker of OP, it was proposed to consider the pathology of the periodontal complex. It has been determined that in the presence of osteoporosis, periodontal damage is practically independent of the degree of BMD loss, while in patients with osteopenia, and to a greater extent in patients without BMD loss, the severity of periodontal damage is proportional to the level of BMD.

The study found that the prevention of osteoporosis in patients with somatic pathology (patient education, lifestyle changes, the appointment of combined calcium and vitamin D3 preparations) leads to an increase in BMD by more than 7% in the first two years. While only education and lifestyle changes are accompanied by an additional loss of BMD and the development of OP in almost 15% of patients in the next two years.

The most effective antiresorptive drugs for the treatment of OP in patients with somatic pathology are ibandronic acid, semi-synthetic salmon calcitonin, and alendronic acid. Patients with somatic pathology and OP who do not receive antiresorptive drugs additionally lose 5.6% of BMD in the next two years (p
PRACTICAL SIGNIFICANCE.

For the first time, on the basis of a multidisciplinary hospital, a city osteoporosis office was created for screening, diagnosing and treating osteoporosis in patients with somatic pathology, equipped with a bone densitometer, which allows performing X-ray, two-photon absorptiometry of the distal forearm.

For the first time in the work, "additional" risk factors for OP in patients with somatic diseases were identified. Thus, inadequate control of blood pressure, hypercholesterolemia and organ damage in CVD (LVH, impaired myocardial contractility) is less prognostically favorable for the loss of BMD. In patients with COPD, the presence of chronic obstructive bronchitis, the use of systemic steroids, are also unfavorable for the course of AP, however, the use of inhaled corticosteroids contributes to some preservation of the BMD. In patients with type 2 DM, age, as well as inadequate control of carbohydrate metabolism, contribute to an additional loss of BMD. In oncological pathology, patients who have undergone radical surgery on the thyroid gland, mastectomy, as well as localization of a malignant tumor in the kidney or prostate gland require special attention of doctors in terms of identifying and correcting osteoporotic changes in bone tissue.

In the structure of the somatic pathology of patients who underwent an atraumatic fracture of the proximal femur, cardiovascular pathology, type 2 diabetes and COPD predominate, more often (86.3%) their combination is noted. This is reflected in the prognosis of the disease, both in the early stationary and in the long-term periods. Thus, hospital mortality is 6.2%, and one in four dies within the first year after suffering a fracture as a result of the development of acute coronary events, pulmonary embolism and erosive and ulcerative bleeding from the upper digestive tract.

The study found that, despite a slightly higher prevalence of osteoporosis and osteopenia in menopausal women, in the presence of androgen deficiency in men, the loss of BMD is more significant than in women with hypogonadism.

It was found that in patients with osteoporosis, the state of the periodontal complex is characterized by a significantly greater lesion than in patients with osteopenia and without loss of BMD. Computed radiovisiography can serve as a screening tool for detecting low BMD. Between the index of optical density of the alveolar bone and BMD of the peripheral skeleton, measured by bone densitometry, a moderate, significant correlation was revealed (r=0.4, p=0.002).

The relevance of research.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent and progressive airflow limitation associated with chronic inflammation in the airways and lungs by harmful particles or gases, especially from inhaled cigarette smoke. COPD is now recognized as a systemic disease with various comorbidities including lung cancer, atherosclerosis, osteoporosis, diabetes, anxiety/depression. Management of these comorbidities is clinically important as they are associated with hospitalization, mortality, and reduced quality of life in patients with COPD. Osteoporosis is one of the main comorbid pathologies in COPD. Although the pathophysiological relationship between COPD and osteoporosis has not yet been established, recent epidemiological studies have clearly shown that osteoporosis is very common in patients with COPD.

Purpose of the study

To assess the prevalence and course of osteoporosis in patients with COPD. Research methods

75 patients with COPD were studied. Research results

Osteoporosis is a skeletal disorder characterized by impaired bone strength, predisposing a person to an increased risk of fractures. The most important outcome is fracture and the risk of fracture depends on the strength of the bone, which is determined by bone mineral density (BMD) and its quality. Based on a systematic review, analyzing a total of 75 patients with COPD, the prevalence of osteoporosis is determined by low BMD and was 35.1%. The prevalence of fractures on radiographs in patients with COPD is 24% to 79%, but the values may vary, depending on features such as age , sex and severity of COPD. Data on the quality of bone tissue in COPD is limited: there are almost no data on the material properties of bones, such as degeneration of the bone matrix, the degree of calcification. A bone biopsy is the best way to directly assess bone microarchitecture at the tissue level. There is only one report in which histomorphometric analysis was performed on bone biopsies from postmenopausal women with COPD who were not taking systemic glucocorticoids. Women with COPD showed significantly lower trabecular bone volume and junction density, and decreased cortical width and increased cortical porosity, compared with age-matched controls postmortem. Joint density was negatively correlated with smoking (pack-years). This suggests that structural damage affects bone strength in COPD patients. With respect to bone metabolism in COPD, it should be noted that bone undergoes continuous remodeling and the balance between resorption and formation is critical to maintaining bone mass and quality. Biochemical bone markers are useful for non-invasive evaluation of bone metabolism. It should be noted that there are several factors that can either enhance or suppress bone metabolism to varying degrees in patients with COPD, including vitamin D deficiency, glucocorticoid deficiency, immobilization, hypoxia, and so on. Little is known about the mechanisms that lead to osteoporosis in COPD patients. However, clinical studies have shown that osteoporosis and other systemic COPD comorbidities are associated with various general and disease-specific risk factors, such as systemic inflammation, pulmonary dysfunction, glucocorticoid use, and vitamin D deficiency/insufficiency. Older age and smoking are common risk factors for osteoporosis and COPD. Smoking is an established risk factor for osteoporotic fractures. Weight loss is common in COPD, especially in advanced stages, and is associated with poor prognosis. Overall, Body Mass Index (BMI) is a factor in BMD and fracture risk in the general population, weight loss and cachexia in severe COPD has been attributed to systemic inflammation with increased levels of cytokines such as tumor necrosis factor alpha (TNF-α) and oxidative stress. which can cause metabolic disorders in bone tissue directly or indirectly through sarcopenia, the extent to which they contribute to the correlation between BMD and BMI in patients with COPD requires further study.

Disease-specific risk factors for osteoporosis in COPD:

Systemic inflammation. The pathophysiological process of COPD is characterized by infiltration of the mucosal, submucosal, and glandular tissue of inflammatory cells into the airways, leading to increased mucus content, epithelial hyperplasia, and resulting thickening of the airway wall.

Chronic inflammation and imbalance between proteases and their inhibitors leads to narrowing, obliteration and destruction of the terminal bronchioles. Smoke-induced damage to epithelial cells stimulates the release of early cytokines such as IL-1, interleukin-2 and TNF-α. "Systemic inflammation is reflected by elevated levels of c-reactive protein (CRP), which has been associated with osteoporosis and increased bone resorption, as well as a role for inflammation in COPD-associated osteoporosis. COPD patients with lower BMD showed high levels of CRP and pro-inflammatory cytokines such as as TNF-α, IL-1 and IL-6. However, a simple mechanism for the increase in bone resorptive cytokines was not confirmed because increased bone resorption was not seen except in COPD-associated osteoporosis.Our preliminary results indicate that systemic inflammation in COPD is associated with impaired bone microarchitecture. The precise roles of systemic inflammation in COPD associated with osteoporosis and its contribution to fracture risk remain to be determined.

Pulmonary dysfunction. The association between lung function and fractures must be interpreted with caution as they may mutually influence each other. The visual effects can cause back pain, chest deformities, kyphosis and reduced height, all leading to impaired lung function. A systematic review of the relationship between lung function and visual effects in COPD demonstrated that each impairment was associated with a 9% decrease in lung capacity (VC). This study confirmed the presence of a fracture with a decrease in VC and a fracture in the number with a decrease in FEV1.

Glucocorticoid drugs are a secondary cause of osteoporosis. Glucocorticoid-induced osteoporosis (GIO) is dose-dependent but occurs even at low doses. Most recent studies of COPD-associated osteoporosis, however, have included only a small number of subjects taking systemic glucocorticoids, or have demonstrated an increased incidence of fractures in subjects without systemic glucocorticoid use.

Vitamin D insufficiency/deficiency leads to decreased calcium absorption from the intestine, impaired skeletal calcification, and secondary hyperparathyroidism with high bone turnover, leading to bone loss and an increased risk of fracture. Several studies have shown that vitamin D status does indeed correlate with BMD in COPD subjects, and one study found that in 100 stable COPD patients, vitamin D deficiency at baseline increased the risk of developing osteoporosis by 7.5-fold over a 3-year follow-up period. These results support a role for vitamin D deficiency/insufficiency in COPD-associated osteoporosis, and its contribution to fracture risk in COPD patients should be more accurately assessed in a large prospective study in the future.

Conclusion. There is ample evidence that osteoporosis and osteoporotic fractures are very common in COPD patients. Although the mechanisms by which COPD leads to osteoporosis are still unclear, patients with COPD have many common and more specific risk factors for osteoporosis. It is important for pulmonologists as well as general practitioners to be aware of the high prevalence of osteoporosis in COPD patients and assess their risk of fracture. Osteoporosis screening will allow physicians to diagnose COPD patients with comorbid conditions early and provide appropriate treatment to prevent damage that can lead to improved quality of life as well as a better long-term prognosis for these patients.

Bibliography

1. Sudakov O.V. Analysis of the incidence of fractures of various localization in patients with chronic obstructive pulmonary disease during complex treatment / O.V. Sudakov, E.A. Fursova, E.V. Minakov // System analysis and management in biomedical systems. 2011. V. 10. No. 1. S. 139-142.

2. Sudakov O.V. A comprehensive approach to the treatment of chronic obstructive pulmonary disease / O.V. Sudakov, E.V. Minakov, E.A. Fursova // GOUVPO "Voronezh State Technical University". Voronezh, 2010. -195 p.

3. Sudakov O.V. A comprehensive approach to the evaluation of individual pharmacotherapy in patients with chronic obstructive pulmonary disease and arterial hypertension / O.V. Sudakov, A.V. Sviridov. - Voronezh: VgTU, 2007. - 188 p.

4. Sudakov O.V. The problem of osteoporosis in patients with bronchial asthma and chronic obstructive pulmonary disease during treatment with glucocorticosteroids / O.V. Sudakov // System analysis and management in biomedical systems. 2007. V. 6. No. 4. S. 996-1000.

NAUMOV

ANTON VYACHESLAVOVYCH

Prevalence and course of osteoporosis in patients with somatic diseases

Moscow - 2010

The work was performed at the State Educational Institution of Higher Professional Education "Moscow State University of Medicine and Dentistry"

Scientific consultant:

Honored Worker of Science of the Russian Federation,

Doctor of Medical Sciences, Professor Vertkin Arkady Lvovich;

^ Official opponents:

Academician of the Russian Academy of Medical Sciences, Professor Martynov Anatoly Ivanovich

Doctor of Medical Sciences, Professor Stryuk Raisa Ivanovna

Doctor of Medical Sciences, Professor Alekseeva Lyudmila Ivanovna

Lead organization:Russian State Medical University. N.I. Pirogov

The defense will take place on "___" ______________ 2010 at ___ o'clock at a meeting of the dissertation council D.208.041.01. at the Moscow State Medical and Dental University of Roszdrav (127473, Moscow, Delegatskaya st., 20/1)

The dissertation can be found in the library of the State Educational Institution of Higher Professional Education of the MGMSU of Roszdrav (127206, Moscow, Vuchetich St., 10a)
The abstract was sent on "____"______________ 2010

Scientific Secretary of the Dissertation Council

Doctor of Medical Sciences, Professor Yushchuk E.N.

^ RELEVANCE OF THE PROBLEM.

According to official data of the Ministry of Health and Social Development of the Russian Federation, published in 2009, the highest mortality in the country is mainly determined by cardiovascular diseases (CVD), which account for 56.6%. At the same time, according to autopsy data, inpatient mortality from heart and vascular diseases in Moscow is 48.8%, including more than half of acute vascular accidents (Vertkin A.L., 2009). The situation is further complicated by the fact that patients older than 50 who died of cardiovascular disease have more than three background or concomitant diseases. Not without interest in this regard are the data of Dashdamirov A.Kh., (2005) and Goruleva E.I. (2008) showed that more than 60% of patients with CVD have risk factors for osteoporosis, which is consistent with the results of the study by Farhat G. N., et al. (2007), showing lower BMD in the vertebral bodies, femoral neck and distal forearm in this category of patients. Moreover, according to U. Sennerby et al. (2007) in cardiovascular pathology, there is a multiple increase in the risk of fracture of the proximal femur, and according to Vasan R.S., et al. (2003) among similar patients, the majority have a high level of pro-inflammatory cytokines in combination with osteoporosis. The given data allowed Marcovitz P.A. et all (2005) consider that the loss of BMD is one of the predictors of the development of CVD.

^ PURPOSE OF THE STUDY

Determination of the prevalence, clinical and prognostic significance of osteoporosis and methods for its optimal drug correction in patients with somatic pathology.

^ OBJECTIVES OF THE RESEARCH

Develop a program for the detection, prevention and treatment of osteoporosis on the basis of multidisciplinary medical institutions
To carry out a retrospective analysis of the features of the comorbid background in patients with an atraumatic fracture of the proximal femur.
Conduct a comparative histomorphological analysis of the state of bone tissue in patients with somatic pathology.
To assess the prevalence of osteopenia and osteoporosis in patients with comorbid conditions
To clarify the gender characteristics of bone mineral density loss in patients with somatic diseases.
To study the role of screening for osteoporosis in patients with periodontal disease as an early marker of BMD loss.
To determine the effectiveness of programs for the prevention and treatment of osteoporosis in patients with somatic diseases.

^ SCIENTIFIC NOVELTY.

It has been shown that almost all patients with an atraumatic fracture of the proximal femur have chronic somatic diseases, at different times before the fracture occurred, all of them repeatedly consulted a therapist. Atraumatic fracture of the proximal femur occurs more often in women (the ratio of men and women is 1:3), predominantly in old age (77.3±7.5), but in men, almost 7 years earlier. In the overwhelming majority of cases, these patients undergo surgical benefits depending on the type of traumatic injuries.

The study did not reveal a statistically significant difference in the effectiveness of drugs with a combination of calcium and vitamin D3 and with a combination of calcium, vitamin D3 and magnesium for the prevention of OP in patients with somatic pathology. All modern antiresorptive drugs for the treatment of osteoporosis are effective in patients with somatic diseases. At the same time, their appointment in complex therapy also leads to better control of the main symptoms of somatic pathology.

^ PERSONAL PARTICIPATION OF THE DISSERTANT IN THE DEVELOPMENT OF THE PROBLEM.

The dissertation student independently recruited patients, conducted their clinical, instrumental and laboratory examination, filled in the appropriate and specially designed for this study registration forms and clinical cards. The author was directly involved in the creation of the city office of the Moscow Department of Health for the diagnosis and treatment of osteoporosis. The author personally carried out statistical processing of the generalized material, made scientific conclusions and presented practical recommendations.

^ MAIN PROVISIONS FOR DEFENSE.

There is a high prevalence and low detection of osteoporosis in patients with somatic pathology.
Somatic pathology is a factor that exacerbates the loss of bone mineral density.
Periodontal disease can serve as early markers of osteoporosis.
The inclusion of anti-osteoporotic therapy in the complex therapy of somatic diseases leads to an increase in bone mineral density and increases the effectiveness of the treatment of the underlying disease.

^ IMPLEMENTATION OF RESEARCH RESULTS

The results of the work are implemented and used in the practice of the city office for the diagnosis and treatment of osteoporosis of the Department of Health (DZ) of the city of Moscow on the basis of the polyclinic department of the City Clinical Hospital No. 81, polyclinics No. 81 and No. Clinical Hospital (CCH) of the Moscow City Clinical Hospital, cardiology, therapeutic and endocrinological departments of the City Clinical Hospital No. 20, No. 50 and No. 81 of the Moscow City Clinical Hospital, and in educational and methodological work with students and cadets of the Faculty of Postgraduate Education at the Department of Clinical Pharmacology, Pharmacotherapy and Emergency Medicine MGMSU.

^ DISSERT APPROVAL

The dissertation materials were presented at the Siberian National Congress "Human Health as the Basis of National Security" (Krasnoyarsk, 2006), the International Scientific and Practical Conference "Osteoporosis: Epidemiology, Clinic, Diagnostics, Prevention and Treatment" (Evpatoria, Ukraine, 2006), the All-Russian Congress on andrology (Sochi, 2007), 1st European Congress of the Aging Male (Warsaw, Poland, 2007), II Congress of Cardiologists of the Siberian Federal District (Tomsk, 2007), Joint Russian National Congress of Cardiology and Congress of Cardiologists of the CIS countries (Moscow, 2007) , XI Congress of the Russian Society of Urology (Moscow, 2007), I and II National Congress of Therapists (Moscow, 2006, 2007), Round table "Men's health as a demographic factor" of the committee on social policy of the Federal Assembly of the Russian Federation (Moscow, 2007) and at the inter-institutional interdepartmental clinical conference of employees of the Research Institute of Rheumatology of the Russian Academy of Medical Sciences, departments of clinical pharmacology, pharmacotherapy and emergency medical care and general dentistry and training of dental technicians of the FPDO MSMSU.

PUBLICATIONS

^ STRUCTURE AND VOLUME OF THE THESIS

The dissertation work is presented on 250 pages of typewritten text and consists of an introduction, a literature review, research materials and methods, a chapter with research results, a conclusion, conclusions, practical recommendations and a list of references. The dissertation is illustrated with figures, table. The list of references includes sources (domestic and foreign).

^ MATERIALS AND METHODS.

The possibility of screening for osteoporosis in patients with somatic pathology was realized on the basis of the Moscow City Department of Osteoporosis Department, established in 2004, on the basis of the polyclinic department of the City Clinical Hospital No. 81. The office is located on the territory of the X-ray department and is equipped with a DTX 200 bone densitometer (Osteometr, Denmark) and Lunar DPX BRAVO for x-ray two-photon absorptiometry, medical scales, a height meter, a computer system, audio and video equipment.

A total of 12985 clinical cases were studied in the study. The study consisted of 6 stages, the design is shown in Scheme 1. The criterion for inclusion in the screening for OP was: age over 30 years. Exclusion criteria: age less than 30 years, acute respiratory viral infections, the presence of cancerous diseases of the gastrointestinal tract, hematological diseases, fever.

Screening was carried out for 5 years, the total number of included patients was 10,200, divided into 2 groups: A and B.

^ SCHEME №1. DESIGN RESEARCH
Evaluation of the prevalence of BMD loss in somatic patients			n= 10 200, Based on the created (2004) city cabinet for the prevention and treatment of osteoporosis
^ Evidence of the relationship between therapeutic pathology and OP	Retrospective study		ABSOLUTELY PROVEN OSTEOPOROSIS - BROKEN HIP, n= 227
	Morphological study		^ ABSOLUTELY PROVEN SOMATIC PATHOLOGY,
	prospective study	Features of the course of osteoporosis and somatic diseases in their combination			CVD, n=396
					COPD, n=151
					Type 2 DM, n=134
					Oncology, n=300
^ Early clinical markers	Sexual characteristics			Men, n=721
				Women, n=1111
	Dental diseases			Study, n=158
				Screening, n=2400
^ AWARENESS OF DOCTORS OF THERAPEUTIC SPECIALTIES ABOUT THE PROBLEM OF OP
EFFECTIVENESS OF OSTEOPOROSIS PREVENTION IN THERAPEUTIC PATIENTS
^ EFFICACY OF TREATMENT OF OSTEOPOROSIS IN THERAPEUTIC PATIENTS

Group A included 8,600 patients with various therapeutic (somatic) pathologies, the average age of patients was 57.3 ± 6.4 years, among them 6255 (72.7%) women and 2345 (27.3%) men . The structure of somatic pathology is presented in Table. 1. It should be noted that these diagnoses were stated from the form - referral for densitometry and patients were not subjected to clarification of the diagnosis.

Group B included 1600 patients conditionally without somatic pathology. In this group, the average age of patients was 54.3±9.3 years, among them - 1134 (70.9%) - women and 466 (29.1%) - men. In most cases, these were women in the perimenopausal period who underwent a routine examination, a number of patients with community-acquired pneumonia, colds, and patients undergoing medical examination.

^ Table 1. Structure of somatic pathology in group A.

PATHOLOGIES	% of patients	^ Mean age	Floor
Cardiovascular diseases (including ischemic heart disease, hypertension and their combinations)	69	57.3±6.4 years	6255 (72.7%) women 2345 (27.3%) men
^ Cardiovascular disease and type 2 diabetes	19,8
Type 2 LED	2,2
COPD	1,5
^ COPD in combination with CVD	2,7
Oncological diseases	2,9
^ Alcoholic polyvisceropathy	1,5
Rheumatic diseases (RA, SLE)	0,3

We divided the study of evidence of the relationship between therapeutic pathology and osteoporosis into three stages: in the presence of absolute evidence of OP (specific OP complications - a fracture of the proximal femur), study the therapeutic history; in the presence of absolute evidence of therapeutic pathology (data from pathoanatomical studies), to study the state of the bone tissue; within the framework of the study, to clarify the therapeutic diagnosis of the patient and to identify the relationship between the clinical picture of OP and the therapeutic disease.

We studied the case histories of 227 patients with a femoral fracture at the age of 76.8±7.4 years, including 54 (23.8%) men and 173 (76.2%) women hospitalized in the traumatology department. In all patients, the traumatic force did not exceed the fall from the height of one's own height, and the fracture can be classified as domestic. All patients were delivered to the hospital on average 1–3 hours after the injury, and the duration of inpatient observation was 23.5±13.8 days. Surgical interventions were performed in 197 (86.8%) patients: skeletal traction, osteosynthesis, hip replacement. 17 (7.5%) patients underwent conservative therapy. 58 out of 227 patients died, including 14 in the hospital, 44 within a year after discharge. In discharged patients, in addition to studying the archival medical history, a telephone survey was conducted. In all cases, it was specified whether osteoporosis was diagnosed before the fracture, and if so, what therapy was received, which specialists were observed before the fracture (therapist, gynecologist, endocrinologist, rheumatologist, urologist). In addition, risk factors for osteoporosis were identified according to the international minute test (WHO, 1999).

In the first part of the morphological study, we performed bone densitometry in the corpses of patients who died from somatic pathology. 53 studies were performed, among which 17 were in male cadavers. The mean age at death was 72.2±14.5 years. In the structure of pathoanatomical conclusions, as the main diagnosis, there were: CHD (IHD. Acute myocardial infarction - 17 (32.1%), IHD. Postinfarction cardiosclerosis - 19 (35.8%); Acute cerebrovascular accident of ischemic type - 8 (15.1%) COPD - 9 (16.98%)

In 36 (67.9%) cases, the presence of arterial hypertension was clinically and morphologically stated, in 14 (26.4%) cases - diabetes mellitus type 2. No rheumatological diseases were detected on the basis of morphological examination, and in clinical and pharmacological a history of taking systemic steroids.

For histomorphological analysis of the state of bone tissue in patients with therapeutic pathology, bone tissue samples from 14 young people (7 men and 7 women) aged 36.6 ± 2.1 years were previously studied ( morphological control group), who died from a car traumatic brain injury. In the medical documents (accompanying coupons and emergency call cards, case histories and protocols of forensic medical examination) of all 10 deceased there was no mention of any somatic pathology, risk factors for osteoporosis (age over 65 years, deficiency of sex hormones, previous atraumatic fractures, steroid use, smoking, alcohol abuse) and clinical and radiological signs of osteoporosis.

IN studied morphological group 30 corpses were selected (14 men and 16 women) aged 69.3±14.3 years who died from severe somatic pathology, including 12 from ischemic stroke, 13 from myocardial infarction and 5 from alcoholic polyvisceropathy. In all cases, there were risk factors and pathomorphological signs of osteoporosis (thinning and disappearance of trabeculae, enlargement of intertrabecular spaces, with the latter filled with connective tissue). A comprehensive morphological study was carried out at the Moscow City Center for Pathological Anatomical Research. Bone preparations made from the epiphysis of the femur and the iliac crest on the right were studied.

For a prospective analysis of the relationship between AP and therapeutic pathology, we decided to clarify whether the degree of BMD loss depends on the type of pathology and the presence of standardized organ lesions.

Group I included 396 patients, including 342 with AH and 54 with IHD. Among them were 346 women (87.4%) and 50 men (12.6%) aged 61.6±9.4 years. The study did not include patients with acute forms of coronary artery disease and cerebrovascular accidents, as well as patients with paroxysmal arrhythmias and chronic heart failure III-IV FC (according to NYHA). The average duration of cardiovascular pathology in this group was 8.6±4.3 years. Patients with hypertension underwent 24-hour blood pressure monitoring (ABPM) according to the standard method before and after 12 months of treatment. Patients with coronary artery disease underwent Holter ECG monitoring according to the standard method with continuous recording of three leads for 24 hours. Of the 54 patients, 20 (37.1%) had transient ischemic changes, including 17 (85.0%) accompanied by angina pectoris.

^ Table number 2. Characteristics of patients with somatic pathology and risk factors for osteoporosis

Groups/ Characteristics		Group I (CVD)	Group II (COPD and BA)	Group III (DM type 2)	IV group (oncologist. pathology)	Group V (control)
n=		396	151	134	300	194
Age		61.6±9.4	60.3±11.2	62.3±7.8	52.6±12.3	58.6±4.3
Floor	M	50 (12,6%)	21 (13,9%)	32 (23,9%)	151 (50,3%)	40 (20,6%)
Floor	AND	346 (87,4%)	130 (86,1%)	102 (76,1%)	149 (49,7%)	154 (79,4%)
BMI, kg/m²		29.2±6.8	29.7±5.8	30.4±4.6	24.3±3.8	30.2± 4.8