Hoble and osteoporosis study design 14.01 04. Chronic obstructive pulmonary disease and osteoporosis. Clinical significance of op in patients with COPD

Intestinal enteropathy is a common name for non-inflammatory chronic intestinal diseases that develop as a result of fermentopathy (enzymopathy) or congenital anomalies in the structure of the intestinal wall.

Fermentopathy, or enzymopathy (fermentopathia; enzyme + Greek.

Pathos suffering, disease) is the general name of diseases or pathological conditions that develop due to the absence or violation of the activity of any enzymes (enzymes).

Allocate:

Congenital (primary):

they are predominantly genetically monogenic, that is, they are caused by a mutation in one gene, however, there are also combinations of mutations in different genes; such diseases are called "polygenic".

Acquired (secondary):

develop against the background of inflammatory or degenerative changes in the mucous membrane of the small intestine.

Classification of congenital enteropathies

1. Diseases associated with congenital absence or deficiency of enzymes.

o Congenital deficiency of disaccharidases. Disaccharidase

insufficiency is a violation of the digestion and absorption of disaccharides (lactose, sucrose, trehalose, maltose and isomaltose), due to a deficiency of the corresponding intestinal enzymes (lactase, sucrase, trehalase, maltase and isomaltase). The main clinical symptom of all fermentopathies is diarrhea. Clinical manifestations of different types of disaccharidase deficiency practically do not differ.

o Congenital deficiency of enterokinase (enteropeptidase).

o Congenital deficiency of peptidases - celiac disease (celiac disease).

2. Diseases associated with congenital absence or deficiency of transport carriers.

They are extremely rare. Usually seen in

childhood:

o Monosaccharide malabsorption syndrome. Insufficiency of absorption of monosaccharides (glucose, galactose and fructose) is due to defects in transport systems - carrier proteins of the brush border of epithelial cells of the small intestine. The process of absorption of glucose and galactose occurs with the participation of the same carrier proteins, therefore, in the presence of their defect, malabsorption of both monosaccharides occurs. In severe lesions of the small intestine (chronic enteritis, celiac enteropathy), secondary (acquired) insufficiency of absorption of monosaccharides may develop. o Amino acid malabsorption syndrome - congenital malabsorption (tryptophan malabsorption - Hartnup's disease, methionine malabsorption, Low's syndrome, cystinuria, lysinuria, immunoglycinuria, etc.). o Lipid malabsorption syndrome (abetalipoproteinemia, bile acid malabsorption). o Vitamin malabsorption syndrome (impaired absorption of vitamin B2 and folic acid). o Mineral malabsorption syndrome (enteropathic acrodermatitis, primary hypomagnesemia, Menkes syndrome, primary hemochromatosis, familial hypophosphatemic rickets).

o Electrolyte malabsorption syndrome (congenital chlororrhoea, lethal familial diarrhea).

Classification of secondary malabsorption:

1. Absorption disorders against the background of inflammatory diseases (acute and chronic enteritis, Crohn's disease, diverticulitis, intestinal tuberculosis).

2. Malabsorption due to degenerative processes in the small intestine (amyloidosis of the small intestine, Whipple's disease - intestinal lipodystrophy, systemic scleroderma).

3. Malabsorption due to a decrease in the absorptive surface of the small intestine (resection

small intestine, surgical anastomoses of the small intestine/

4. Malabsorption due to ischemic disease of the digestive system.

5. Absorption disorders due to diseases of the hematopoietic system (lymphogranulomatosis, lymphosarcomatosis, chronic lymphocytic leukemia).

6. Malabsorption due to the development of intestinal dysbiosis.

7. Malabsorption due to allergic and autoimmune lesions of the small intestine.

8. Absorption disorders due to psychogenic disorders (due to anorexia nervosa).

9. Malabsorption due to endocrine diseases (intestinal endometriosis).

10. Malabsorption due to radiation sickness.

11. Malabsorption due to abuse of laxatives.

Digestive insufficiency syndrome - maldigestion

These are manifestations of disorders of the digestion of nutrients due to a deficiency of digestive enzymes. There are several forms of malnutrition syndrome:

Violation of predominantly abdominal digestion;

Violation of the predominantly parietal

(membrane) digestion;

Violation of predominantly intracellular digestion;

mixed forms.

Violation of predominantly abdominal digestion (dyspepsia) occurs as a result of an uncompensated decrease in the secretory function of the stomach, intestines, pancreas, bile secretion and impaired motor function of the gastrointestinal tract.

Causes of indigestion:

1. Insufficiency of digestion of alimentary genesis (deficiency in the synthesis of digestive enzymes due to a deficiency in the diet of protein, trace elements, vitamins).

2. Gastrogen insufficiency of digestion

(atrophic gastritis, decompensated stenosis

pylorus, resection of the stomach, gastric cancer, vagotomy and other operations).

3. Pancreatic insufficiency of digestion

(chronic pancreatitis with exocrine

insufficiency, subtotal or total pancreatectomy, cystic fibrosis, kwashiorkor, pancreatic cancer).

4. Insufficiency of digestion due to

pathology of the liver and biliary tract, insufficient synthesis of bile acids and impaired excretion of bile (cirrhosis of the liver and chronic active hepatitis of any etiology, obstructive jaundice of any etiology, congenital bile acid deficiency, hepatocarcinoma, PBC and primary sclerosing cholangitis).

5. Insufficiency of digestion due to

pathology of the endocrine glands (diabetes mellitus, thyroid pathology, hypoparathyroidism, hypothalamic-pituitary and adrenal insufficiency).

6. Insufficiency of digestion of medicinal genesis (treatment with cholestyramine, calcium carbonate, cytostatics).

7. Insufficiency of digestion due to

overgrowth of microflora in the distal colon.

8. Digestive insufficiency due to reduced contact time with food and bile acids (short bowel syndrome, small bowel resection and dysmotility).

Insufficiency of parietal digestion develops in chronic diseases of the small intestine, the morphological substrate of which is inflammatory, degenerative and sclerotic changes in the mucous membrane, changes in the structure of villi and microvilli and a decrease in their number per unit surface.

The occurrence of insufficiency of parietal digestion is facilitated by:

1. Changes in the enzyme layer of the intestinal surface and disorders of intestinal motility, in which the transfer of nutrients from the intestinal cavity to the surface of enterocytes is disrupted. Insufficient adsorption of pancreatic enzymes.

2. Exocrine pancreatic insufficiency.

3. Enteropathy of various origins with a violation of the intestinal ultrastructure.

4. Deficiency of intestinal enzymes (congenital or acquired).

5. Disaccharidase deficiency.

6. Peptidase deficiency.

Insufficiency of intracellular digestion is associated with primary or secondary fermentopathy, which is based on genetically determined or acquired intolerance to disaccharides and some proteins.

In the pathogenesis of the syndrome, the intensification of fermentation processes due to the entry of unsplit disaccharides into the large intestine and the activation of the microbial flora, the toxic effect of fractions of certain proteins (gliadin) is essential.

Malabsorption syndrome (malabsorption)

characterized by a disorder of absorption in the small intestine of one or more nutrients and the occurrence of metabolic disorders. Distinguish between hereditary and acquired malabsorption syndrome. Intestinal manifestations of malabsorption are diarrhea, polyfecal matter, steatorrhea, creatorrhea, and amylorrhea. Malabsorption syndrome is manifested by violations of protein, carbohydrate, fat, vitamin, mineral and water-salt metabolism.

The term "exudative enteropathy" refers to a pathological condition characterized by the loss of blood plasma proteins through the gastrointestinal tract. Usually, exudative enteropathy is accompanied by a violation of intestinal absorption (which results in a pronounced decrease in the content of blood proteins), the appearance of edema, undigested fat in the feces. Unlike other syndromes of malabsorption in exudative enteropathy, there may be no pronounced symptoms of damage to the small intestine. In rare cases, the child may lag behind in physical development.

Allocate primary and secondary forms of exudative enteropathy.

Primary forms are due to the phenomenon of loss of lymph through the small intestine, which may be caused by pathological expansion of the lymphatic vessels or a generalized lesion of the lymphatic system. Lymph loss can also be observed as a result of a violation of the outflow of lymph with a blockade of initially unchanged lymphatic vessels or obstructed venous outflow (for example, with heart disease).

Secondary causes of the development of exudative enteropathy, leading to a violation of the integrity of the intestinal mucosa, include a number of diseases from the gastrointestinal tract, from the kidneys, liver, and lungs. In addition, disorders of the immune system, the presence of allergic reactions, and many other diseases can play a role in the development of exudative enteropathy.

Clinical manifestations of the disease are determined by the loss of plasma proteins, the severity of subsequent disorders, as well as age-related features. The allocation of a certain amount of protein through the intestines is a physiological norm. A decrease in plasma protein content occurs when the loss of protein exceeds the rate of its synthesis in the body. Due to differences in the rate of synthesis of various protein fractions, the violation of their ratio is as follows: the amount of albumin decreases and ¡ globulins in blood serum. The fibrinogen level almost always remains within the normal range. The constant loss of lymphocytes leads to a persistent absolute or relative decrease in their number, which is an important criterion for making a diagnosis. Along with protein, fats, trace elements and some vitamins are lost. Deficiency of these substances can change the clinical picture in the direction of greater or lesser severity, and in some cases may be leading (for example, convulsions against the background of a pronounced decrease in the amount of calcium in the blood).

Primary intestinal lymphangiectasia (dilation of the lymphatic vessels of the small intestine) is a special form of the syndrome that occurs with the loss of blood plasma protein. This pathology was first described in 1966. It is assumed that it is inherited in an autosomal recessive manner. However, the possibility of dominant inheritance with a high frequency of manifestation and varying degrees of expression of the pathological gene is not excluded.

The clinical picture is dominated by massive asymmetric edema that persists for a long time, located mainly on the lower extremities, as well as in body cavities (abdominal, pericardial, pleural cavities), a decrease in the amount of plasma proteins, a violation of the ratio of their fractions, symptoms of dysfunction gastrointestinal tract, secondary immunodeficiency. In some children, the disease begins to manifest itself at birth. The expansion of the lymphatic vessels in Noonan syndrome is accompanied by a severe form of constantly appearing edema of the hands and feet, the toenails turn yellow, become convex, and their transverse striation appears. There are cases of a combination of expansion of the lymphatic vessels of the intestine with Di George's syndrome, underdevelopment of tooth enamel.

Diagnosis for this disease is based on the detection of a reduced number of lymphocytes in the blood, changes in the biochemical parameters of the blood. Diagnosis is possible by determining serum proteins in feces. Quantitative loss of protein in the intestine can be determined by special technically complex research methods carried out in large hospitals. The study of the state of the lymphatic system by introducing a contrast agent often reveals the underdevelopment of its peripheral parts and a visible slowdown in the movement of the lymph (up to its complete absence in some vessels). In some cases, there may be no lymph nodes near the aorta, as well as blockage of the thoracic lymphatic duct with the flow of a contrast agent into the intestinal lumen. Great diagnostic value is attached to clarifying the condition of the intestinal mucosa. An endoscopic examination of the intestine reveals the following picture: the folds of the mucosa of the jejunum are preserved, pale pink or pink in color with a pronounced vascular pattern, sometimes pinpoint hemorrhages, an increase in lymph nodes are determined, and a peculiar growth of the mucous membrane is also observed in the form of numerous bulges. Characteristic of the disease under consideration is the detection during histological examination of pieces of the intestinal mucosa, taken during endoscopic examination, dilated lymphatic vessels.

Therapeutic measures for exudative enteropathy are reduced to intravenous administration of protein preparations, a sharp restriction of animal fats in the diet with their replacement with vegetable oil. They use preparations containing fats, which are easily broken down by pancreatic enzymes without the participation of bile acids and absorbed into the venous system, helping to reduce the formation of lymph and facilitate its movement. Signs of the inflammatory process in the form of accelerated ESR, an increase in the level of circulating immune complexes dictate the need for the use of hormonal drugs, the treatment of which can lead to the elimination of clinical manifestations of exudative enteropathy. With severe edematous syndrome, diuretics (diuretics) are needed. In addition, it is necessary to use preparations of potassium, calcium, iron and vitamins.

Dissertation abstractin medicine on the topic Early diagnosis and treatment of osteoporosis in patients with chronic obstructive pulmonary disease

As a manuscript

Volkorezov Igor Alekseevich

EARLY DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS IN PATIENTS WITH CHRONIC OBSTRUCTIVE DISEASE

dissertations for the degree of 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. H.H. 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: MD, professor

Nikitin Anatoly Vladimirovich Candidate of Medical Sciences Sergey Ivanovich Symbolokov

Lead organization: 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. H.H. 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. H.H. Burdenko Ministry of Health and Social Development of Russia

Scientific Secretary of the Dissertation Council

A.B. 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 N., 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-a), 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. There is no doubt about the significant effect of glucocorticosteroid (GCS) therapy on bone tissue metabolism; 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, apply to patients with COPD, the course of which was complicated by impaired bone 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 to improve the effectiveness of therapeutic and preventive measures and quality of life (QoL) in patients with COPD with osteoporosis based on the analysis of risk factors, the clinical course of the disease and the level of biomarkers of systemic inflammation.

Research objectives

1. 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-a, CRP) in the blood serum;

2. To identify the main factors affecting the quality of life in COPD patients with impaired bone mineral density (osteopenia, osteoporosis);

3. 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.

4. To study the clinical efficacy of complex therapy of osteoporosis in COPD patients with alfacalcidol and alendronic acid and evaluate its effect on patients' QoL.

Scientific novelty

1. the features of the clinical course of COPD in combination with impaired bone mineral density depending on the level of biomarkers of systemic inflammation (TNF-a, CRP) in the blood serum were studied;

2. 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 is justified;

3. 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 treatment of osteoporosis in patients with stage II COPD can be the use of alfacalcidol (Alpha DZ TEVA) at a dose of 1 μg/day. and alendronova

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.

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

The following provisions are put forward for defense:

1. The main factors affecting the quality of life of COPD patients with BMD disorders are the level of the systemic inflammation biomarker TNF-a, the frequency of exacerbations and hospitalizations in COPD patients, exercise tolerance, the concentration of acute phase protein - CRP, T-test and FEV values].

2. 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.

3. The study of the level of TNF-a 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. H.H. 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) - ratio of FEV] / VC<70%; по-стбронходилатационное значение ОФВ1 менее 80% от должного) (Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, 2007).

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-a 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.

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

□ COPD P ■ COPD S 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 the activity of systemic inflammation 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 DZ 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).

use of alfacalcidol (Alpha DZ TEVA) 1 mcg / day. and alendronic acid (Tevanat) at a dose of 70 mg once a week.

Group 2, which consisted of 23 patients with COPD II and III stages (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-a, 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 of 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<0,05. Проверка гипотез о различиях между группами проводилась с использованием критерия %2 для категориальных переменных и Краскелла-Уоллиса для количественных и порядковых, с последующим применением точного критерия Фишера. Проверка гипотез о различиях в динамике проверялась с использованием точного критерия Фишера для категориальных переменных и Вилкоксона - для количественных и порядковых. Использовали корреляционный анализ (по Пирсону, Спирмену, Кендаллу) и однофакторный дисперсионный анализ.

Analysis of the state of bone mineral density in patients with COPD 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.

Based on densitometry, the diagnosis of osteoporosis (OP) was established in 40 patients with COPD (30.77%), osteopenia - in 11 (59.23%), BMD disorders were not detected in 13 patients (10.0%) (Fig. 3).

60 50 40 30 20 10 o

4,2 -2,2 -0,2 1,8 3,8 5,8

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

□ normal n osteopenia ¡8 osteoporosis

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 (%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 BO, with stage III - 1.39 ±0.15 EB (B=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 dB, for women -1.55±0.11 8B (7=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 (%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 vE, while the absence of fractures corresponded to a significantly higher T-score value of -1.19±0.09 vB. (P=23.74, p=0.0000).

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 (B=7.04, p= 0.0013).

32 30 28 26 24 22 20

Rice. Fig. 4. Mean BMI values and their 95% confidence intervals in patients with COPD 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/m2, with osteopenia - 24.60±0.51 kg/m2, in patients without BMD disorders - 30.21±0.62 kg/m2 m2 (B=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 medium-strength correlation was found between the age of patients and BMD disorders (OP, osteope-

ing), a weak direct relationship between age and the severity of AP, direct medium-strength 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_

Yah R I, R Yah R Their R

TNF-a 0.4742 0.0000 0.1339 0.1381 -0.5230 0.0000 0.0503 0.5769

SRV -0.0278 0.7581 -0.0790 0.3808 0.0054 0.9525 0.0425 0.6376

3.7......................--: I

O 10 20 30 40 50

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

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

It is correlated with TSH data, and there is a direct weak relationship with the number of hospitalizations for exacerbations 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 a scoring of dyspnea.

table 2

Results of correlation analysis of relationships between BMD disorders, clinical and behavioral parameters of patients with COPD

Indicators Violations of BMD Severity of OP T-criterion Amyotrophy

I. R R k * R R

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

Shortness of breath 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

The results of the correlation analysis of the relationship between BMD disorders and _ comorbidities in patients with COPD _

Indicators Violations of BMD Severity of OP T-criterion Amyotrophy

ix R R I, R Yax R

IHD, CSI 0.4897 0.0000 0.3302 0.0001 -0.3586 0.0000 0.3488 0.0000

MI 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 moderate direct correlation with the presence of coronary artery disease as a concomitant pathology,

SSN and inverse mean 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, myocardial infarction in anamnesis and an inverse medium-strength relationship with BMI. The level of TNF-a 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 IHD, 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 correlation analysis of relationships between BMD disorders and _spirometry parameters in patients with COPD_

Indicators Impaired BMD Severity of osteoporosis T-criterion Amyotrophy

R Yah R Yah R Yah R

VC -0.1151 0.1872 -0.3187 0.0011 0.0872 0.4143 -0.4321 0.0000

FVC -0.2321 0.1007 -0.1321 0.1992 -0.0177 0.5423 -0.4117 0.0000

FEV, -0.1908 0.0630 -0.2144 0.0531 0.0923 0.5875 -0.3266 0.0000

FEV/FVC -0.3752 0.0000 -0.5433 0.0000 -0.3992 0.000 -0.6112 0.0000

pos, „i -0.0972 0.3498 -0.0665 0.4221 -0.0652 0.4875 -0.1851 0.1165

MOS25 -0.1088 0.2865 -0.0822 0.3359 -0.0154 0.5872 -0.1872 0.1407

MOS50 -0.0762 0.4766 -0.0388 0.6772 -0.1123 0.1671 -0.1708 0.0930

MOS75 -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-criterion values and the presence of amyotrophies (moderate feedback), FVC, FEVC and the presence of amyotrophies (moderate feedback), Tiffno index and the presence of amyotrophy (strong inverse correlation). The relationship between FEV1 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 warfare.

burning (TNF-a and CRP), clinical, instrumental and laboratory parameters, which must be taken into account when evaluating 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-a level in the general group of patients with COPD 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; the minimum is 0.5, the maximum is 9.1 mg/l. The average values of the concentration in the blood serum of the cytokine TNF-a 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-a (p>0.05).

Table 5

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

Indicator Groups of patients Р р

COPD stage II COPD III stage.

TNF-a, pg/ml 24.91±0.83 23.89±0.97 0.63 0.4281

CRP, mg/l 4.31±0.22 4.19±0.26 0.13 0.7235

29 26 23 20 17 14

Rice. Fig. 6. Mean values of the FIO-a level and their 95% confidence intervals in COPD patients depending on BMD disorders (0 - without BMD disorders, 1 - osteopenia, 2 - osteoporosis) 6 illustrates the mean TNF-a values depending on the disturbances.

IPC. As can be seen from fig. 6, in patients with osteoporosis, the average value of TNF-a 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 (P=9.20; p=0.0002).

There were no significant differences in the level of CRP between patients with osteoporosis, osteopenia and without BMD disorders (P=0.23, p=0.7976). .CRP level 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 patients with stage 11-III COPD included in the 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 (03).

Rice. Fig. 7. QoL of patients with COPD-III stage with osteoporosis (1), osteopenia (2) and without BMD disorders (3) (* - р<0,05 - различия достоверны между больными без нарушений МПК и остеопорозом; ** - р<0,05 - различия достоверны между больными с остеопорозом и остеопенией) КЖ больных ХОБЛ с остеопорозом и остеопенией было статистически значимо ниже по всем шкалам опросника 8Б-36 по сравнению с КЖ пациентов без нарушений МПК. Между больными с ХОБЛ с остеопорозом и остеопенией выявлены достоверные различия по следующим шкалам: физическая активность (ФА), роль физических проблем в ограничении жизнедеятельности (РФ), боли (Б), роль эмоциональных проблем в ограничении жизнедеятельности (РЭ), общее здоровье (03), жизнеспособности (ЖС) (рис. 7). Далее мы провели дисперсионный анализ влияния основных клинических, инструментальных, лабораторных и социально-демографических факторов на показатели КЖ больных ХОБЛ в зависимости от степени выраженности нарушений МПК.

2,4 -2,6 -2,8 -3 -3,2

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) QoL of COPD patients was statistically significantly dependent on most scales

questionnaire EB-Zb 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 (03), mental health (Ph), social activity (SA).

Table 6

Analysis of variance of the influence of indicators of TSH in patients with COPD on indicators

Analyzed parameters

QOL scales B-ratio Significance level

FA 12.94 0.0000

RF 12.11 0.0000

TShH B 4.67 0.0473

RE 1.56 0.2355

ZhS 4.01 0.0577

PZ 3.96 0.1271

SA 4.76 0.0498

The T-criterion values were significantly associated with QoL indicators on the FA, RF, B, 03, RE, ZhS, PZ, and SA scales, which indicates the effect of BMD on the perception by COPD patients of the main limitations of QoL. 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-a significantly influenced the values of the FA, RF, B, 03, ZhS scales, the concentration of C-reactive protein - on the average values of the FZ, 03 and PZ scales. Data

analysis of the relationship between exercise tolerance (according to the results of TSHH) 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, 03 and SA.

The spirometry indicator FEV] (% of the predicted value) significantly influenced the scores of the SF-36 methodology: FA, RF, B, 03, 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-a, the concentration of acute phase protein - CRP, the values of T- criteria and FEV).

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.

Group 1 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 with using alfacalcidol (Alpha DZ TEVA) 1 µg/day. and alendronic acid (Tevanat) at a dose of 70 mg once a week.

Group 2, 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 GOLD 2007 guidelines.

Table 7

Clinical symptoms in COPD patients of the first and second comparison groups before and after

after therapy (points, M±m)

Clinical symptoms of COPD according to VAS, mm Before therapy After 12 months observations

First group, n=17 Second group, n=23 First group, n=17 Second group, n=23

1. cough 5.11±0.22 5.24±0.18 4.32±0.18" 4.19±0.18*

2. shortness of breath 6.14±0.18 6.33±0.16 4.88±0.19" 5.41±0.17""

3. sputum 4.49±0.19 4.27±0.18 3.22±0.12" 3.57±0.18"

4. wheezing 5.12±0.21 5.24±0.17 4.26±0.18* 4.41±0.15*

5. 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.

In 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 (P=6.63; p=0.0152), the number of hospitalizations - from 1.94±0 .19 to 1.06±0.20 (T=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-a from 29.48±2.35 pg/ml to 19.58±2.16 pg/ml (P=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 (P=0.42; p=0.5193). In the second group after 12 months. the decrease in TNF-a concentration from 26.85±1.85 pg/ml to 23.66±1.68 pg/ml was not significant (P=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 (P=0.39; p=0.5346).

Next, we analyzed the dynamics of exercise tolerance in patients of the first group who received alfacalcidol (Alpha DZ 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 (P=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 (P=1.59, p=0.2133).

Table 8

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

observations

Parameters T-test before therapy T-test after 12 months therapy B R

The first group -2.86±0.05 -2.68±0.04 5.64 0.0237

Second group -2.72±0.06 -2.82±0.06 1.44 0.2362

Evaluation of BMD in patients with COPD and osteoporosis in dynamics revealed the following patterns (Table 8). Patients suffering from COPD and osteoporosis had a mean T-score before treatment of -2.86±0.05 EB, 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 vB (P=5.64, p=0.0237). In the second group, the average value of the T-criterion before therapy was -2.72 ± 0.06 EC, after 12 months. observations -2.82±0.06 ^=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 BR-3b questionnaire: physical activity (FA), the role of physical problems in disability (RF), general health (03) and the role of emotional problems in disability (EC ). 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 indicators on the FA, RF, B and 03 scales, 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<0,05 - различия достоверны до и после терапии в первой группе

Thus, one of the optimal options for the complex therapy of osteoporosis in patients with COPD in real clinical practice can be the use of a combination of alfacapcidol (Alpha DZ 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.

1. The main relationships between the level of serum biomarkers of systemic inflammation (TNF-a and CRP), clinical, instrumental and laboratory parameters have been identified, which must be taken into account when evaluating the effectiveness of therapy for COPD with a stable course in patients with impaired BMD.

2. The quality of life of COPD patients with osteoporosis is 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-a, the concentration of acute phase protein - CRP, T-criger and FEV1 values.

3. Treatment of osteoporosis in patients with stage II-III COPD with alfacalcidol at a dose of 1 μg/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-a.

4. 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 T-criterion and exercise tolerance, improve the quality of life of patients with COPD.

1. 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.

2. In patients with COPD with osteoporosis, it is advisable to conduct a study of the level of TNF-a, which allows monitoring the effectiveness of maintenance therapy for comorbidity, predicting the number of exacerbations and hospitalizations of patients.

1. Features of the treatment of chronic obstructive pulmonary disease: emphasis on safety / G.G. Prozorova, A.B. Budnevsky, O.V. Pashkova, I.A. Volkorezov // Collection of materials of the 16th Russian National Congress "Man and Medicine", - M., 2009. - P. 228.

2. Systemic effects and comorbidity in patients with chronic obstructive pulmonary disease / G.G. Prozorova, O.V. Pashkova, I.A. Volkorezov, A.S. Nogavitsin, T.I. Bunin, N.F. Plotnikova // Topical issues of health protection of metallurgists: a collection of scientific and practical works. - Magnitogorsk, 2009. - S. 136-137.

3. New possibilities for predicting the course of COPD / G.G. Prozorova, O.V. Pashkova, I.A. Volkorezov, C.B. Simonites, A.C. Nogavitsin // Journal of Theoretical and Practical Medicine. - 2009. - no. 2. - S. 65-67.

4. Prozorova G.G. Systemic manifestations of chronic obstructive pulmonary disease / G.G. Prozorova, O.V. Pashkova, I.A. Volkorezov // Collection of materials of the 16th Russian National Congress "Man and Medicine". - M., 2009. - P. 61.

5. Pashkova O.V. Features of the clinical course of COPD: the role of systemic inflammation / O.V. Pashkova, I.A. Volkorezov // Applied Information Aspects of Medicine 2009. - V. 12, No. 1. - P. 81-85.

6. A systematic approach to assessing the features of the clinical course of chronic obstructive pulmonary disease in patients with osteoporosis / G.G. Prozorova, A.B. Budnevsky, I.A. Volkorezov, O.V. Pashkova // System analysis and management in biomedical systems. - 2010. - V. 9, No. 2. - S. 321-326.

LIST OF ABBREVIATIONS

VAS - visual analogue scale GCS - glucocorticosteroids CHD - coronary heart disease BMI - body mass index MI - myocardial infarction QoL - quality of life

BMD - bone mineral density OP - osteoporosis OPN - osteopenia

FEV, - forced expiratory volume in 1 second

POS - peak expiratory flow rate

CRP - C-reactive protein

CCH - stable exertional angina

TSHH - 6-minute walk test

COPD - chronic obstructive pulmonary disease

FVD - function of external respiration

TNF-a - tumor necrosis factor a

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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.

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