rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2022-306-313rsp-3178Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESМультиморбидность при остеоартритеMultimorbidity in osteoarthritishttps://orcid.org/0000-0001-8218-3223ТаскинаЕ. А.TaskinaE. A.

115522, Москва, Каширское шоссе, 34а 

115522, Moscow, Kashirskoye Highway, 34A

braell@mail.ruhttps://orcid.org/0000-0001-7017-0898АлексееваЛ. И.AlekseevaL. I.

115522, Москва, Каширское шоссе, 34а;

125993, Москва, ул. Баррикадная, 2/1, стр. 1

115522, Moscow, Kashirskoye Highway, 34A;

125993, Moscow, Barrikadnaya str., 2/1, building 1

https://orcid.org/0000-0001-8732-2720КашевароваН. Г.KashevarovaN. G.

115522, Москва, Каширское шоссе, 34а 

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-6068-3080ЛилаА. М.LilaA. M.

115522, Москва, Каширское шоссе, 34а;

125993, Москва, ул. Баррикадная, 2/1, стр. 1

115522, Moscow, Kashirskoye Highway, 34A;

125993, Moscow, Barrikadnaya str., 2/1, building 1

https://orcid.org/0000-0002-1598-8360НасоновЕ. Л.NasonovE. L.

115522, Москва, Каширское шоссе, 34а;

119991, Москва, ул. Трубецкая, 8, стр. 2 

115522, Moscow, Kashirskoye Highway, 34A;

119991, Moscow, Trubetskaya str., 8, building 2

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian FederationRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)Russian Federation202209072022603306313Copyright © Таскина Е.А., Алексеева Л.И., Кашеварова Н.Г., Лила А.М., Насонов Е.Л., 20222022Таскина Е.А., Алексеева Л.И., Кашеварова Н.Г., Лила А.М., Насонов Е.Л.Taskina E.A., Alekseeva L.I., Kashevarova N.G., Lila A.M., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/3178

В настоящем обзоре рассматривается вопрос о терминологии сочетанной патологии в современной клинической практике. Продемонстрировано, что мультиморбидность представляет собой одну из главных проблем здравоохранения, и ведение таких больных требует интегрального подхода, ориентированного на сочетанный характер патологии. Показано негативное влияние полиморбидности на течение остеоартрита (ОА) и сопутствующей патологии, приводящей к увеличению риска полипрагмазии и смертности. Большое внимание уделено симптоматическим препаратам замедленного действия, которые обладают позитивными плейотропными эффектами и оказывают влияние не только на ОА, но и на сопутствующие заболевания. В частности, в литературе накапливается все больше информации, свидетельствующей о том, что назначение хондроитина сульфата способствует повышению эффективности терапии ОА, улучшению кардиометаболического прогноза, снижению риска прогрессирования нарушений углеводного обмена и смертности. 

This review is focused on the issue of terminology in patients with multiple coexisting diseases in modern clinical practice. We articulate that multimorbidity is one of the leading problems in the field of public healthcare and that the treatment of these patients demands an integral approach derived from the combined nature of the pathology . It was shown that multiple coexisting diseases have a negative effect both on the course of osteoarthritis (OA) and its concomitant ailments, including higher risk of polypharmacy and death. Extra attention is paid to slow-acting symptomatic drugs, which often have positive pleiotropic effects towards both the OA and the concomitant diseases. In particular, there is more and more research showing evidence of the beneficial effects of chondroitin sulfate both on the OA treatment effectiveness as well as on the terms of cardiometabolic prognosis, mitigation of glucose metabolism deficiency and mortality. 

мультиморбидностьостеоартритплейотропные эффектыSYSADOAАлфлутопmultimorbidityosteoarthritispleiotropic effectsSYSADOAAlflutopСтатья подготовлена в рамках научно-исследовательской работы ФГБНУ «Научно-исследовательский институт ревматологии им. В. . Насоновой», № государственного задания 1021051503111-9.ReferencesФедеральная служба государственной статистики. Старшее поколение. URL: https://rosstat.gov.ru/folder/13877/ (Accessed: 20th March 2022).Federal State Statistics Service. The older generation. (In Russ). URL: https://rosstat.gov.ru/folder/13877/ (Accessed: 20th March 2022).Parekh AK, Barton MB. The challenge of multiple comorbidity for the US health care system. JAMA. 2010;303(13):1303-1304. doi: 10.1001/jama.2010.381Parekh AK, Barton MB. The challenge of multiple comorbidity for the US health care system. JAMA. 2010;303(13):1303-1304. doi: 10.1001/jama.2010.381Garin N, Koyanagi A, Chatterji S, Tyrovolas S, Olaya B, Leo - nardi M, et al. Global multimorbidity patterns: A cross-sectional, population-based, multi-country study. J Gerontol A Biol Sci Med Sci. 2016;71(2):205-214. doi: 10.1093/gerona/glv128Garin N, Koyanagi A, Chatterji S, Tyrovolas S, Olaya B, Leo - nardi M, et al. Global multimorbidity patterns: A cross-sectional, population-based, multi-country study. J Gerontol A Biol Sci Med Sci. 2016;71(2):205-214. doi: 10.1093/gerona/glv128Вёрткин АЛ, Румянцев МА, Скотников АС, Ларюшкина ЕД, Соколова ИН, Фельдман МА, и др. Коморбидность: от истоков развития до современного понятия. Как оценить и прогнозировать? Врач скорой помощи. 2011;(7):4-14.Vyortkin AL, Rumyantsev MA, Skotnikov AS, Laryushkina ED, Sokolova IV, Feldman MA, et al. Comorbidity: From the start of development up to modern conception. How to estimate and prognosticate? Emergency Doctor. 2011;(7):4-14 (In Russ).Souza DLB, Oliveras-Fabregas A, Minobes-Molina E, de Camargo Cancela M, Galbany-Estragués P, Jerez-Roig J. Trends of multimorbidity in 15 European countries: A populationbased study in community-dwelling adults aged 50 and over. BMC Public Health. 2021;21(1):76. doi: 10.1186/s12889-020-10084-xSouza DLB, Oliveras-Fabregas A, Minobes-Molina E, de Camargo Cancela M, Galbany-Estragués P, Jerez-Roig J. Trends of multimorbidity in 15 European countries: A populationbased study in community-dwelling adults aged 50 and over. BMC Public Health. 2021;21(1):76. doi: 10.1186/s12889-020-10084-xWang X, Yao S, Wang M, Cao G, Chen Z, Huang Z, et al. Multimorbidity among two million adults in China. Int J Environ Res Public Health. 2020;17(10):3395. doi: 10.3390/ijerph17103395Wang X, Yao S, Wang M, Cao G, Chen Z, Huang Z, et al. Multimorbidity among two million adults in China. Int J Environ Res Public Health. 2020;17(10):3395. doi: 10.3390/ijerph17103395Almirall J, Fortin M. The coexistence of terms to describe the presence of multiple concurrent diseases. J Comorb. 2013;3:4- 9. doi: 10.15256/joc.2013.3.22Almirall J, Fortin M. The coexistence of terms to describe the presence of multiple concurrent diseases. J Comorb. 2013;3:4- 9. doi: 10.15256/joc.2013.3.22Оганов РГ, Драпкина ОМ. Полиморбидность: закономерности формирования и принципы сочетания нескольких заболеваний у одного пациента. Кардиоваскулярная терапия и профилактика. 2016;15(4):4-9. doi: 10.15829/1728-8800-2016-4-4-9Oganov RG, Drapkina OM. Polymorbidity: Specifics of co-development and concomitance of several diseases in one patient. Cardiovascular Therapy and Prevention. 2016; 15(4):4-9 (In Russ.). doi: 10.15829/1728-8800-2016-4-4-9Feinstein AR. The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis. 1970;23(7):455-468. doi: 10.1016/0021-9681(70)90054-8Feinstein AR. The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis. 1970;23(7):455-468. doi: 10.1016/0021-9681(70)90054-8Лазебник ЛБ, Конев ЮВ. Исторические особенности и семантические трудности использования терминов, обозначающих множественность заболеваний у одного больного. Экспериментальная и клиническая гастроэнтерология. 2018;154(6):4-9.Lazebnik LB, Konev YuV. Historical features and semantic difficulties of using terms denoting the multiplicity of diseases in one patient. Experimental and Clinical Gastroenterology. 2018;154(6):4-9 (In Russ.).Вёрткин АЛ, Скотников АС. Коморбидность. Лечащий врач. 2013;6:66-68.Vertkin AL, Skotnikov AS. Сomorbidity. Lechaschi vrach. 2013;6:66-68 (In Russ.).Le Reste JY, Nabbe P, Manceau B, Lygidakis C, Doerr C, Lingner H, et al. The European General Practice Research Network presents a comprehensive definition of multimorbidity in family medicine and long term care, following a systematic review of relevant literature. J Am Med Dir Assoc. 2013;14(5):319- 325. doi: 10.1016/j.jamda.2013.01.001Le Reste JY, Nabbe P, Manceau B, Lygidakis C, Doerr C, Lingner H, et al. The European General Practice Research Network presents a comprehensive definition of multimorbidity in family medicine and long term care, following a systematic review of relevant literature. J Am Med Dir Assoc. 2013;14(5):319- 325. doi: 10.1016/j.jamda.2013.01.001Kernick D, Chew-Graham CA, O’Flynn N. Clinical assessment and management of multimorbidity: NICE guideline. Br J Gen Pract. 2017;67(658):235-236. doi: 10.3399/bjgp17X690857Kernick D, Chew-Graham CA, O’Flynn N. Clinical assessment and management of multimorbidity: NICE guideline. Br J Gen Pract. 2017;67(658):235-236. doi: 10.3399/bjgp17X690857Gomes F, Schuetz P, Bounoure L, Austin P, BallesterosPomar M, Cederholm T, et al. ESPEN guidelines on nutritional support for polymorbid internal medicine patients. Clin Nutr. 2018;37(1):336-353. doi: 10.1016/j.clnu.2017.06.025Gomes F, Schuetz P, Bounoure L, Austin P, BallesterosPomar M, Cederholm T, et al. ESPEN guidelines on nutritional support for polymorbid internal medicine patients. Clin Nutr. 2018;37(1):336-353. doi: 10.1016/j.clnu.2017.06.025Оганов РГ, Симаненков ВИ, Бакулин ИГ, Бакулина НВ, Барбараш ОЛ, Бойцов СА, и др. Коморбидная патология в клинической практике. Алгоритмы диагностики и лечения Кардиоваскулярная терапия и профилактика. 2019;18(1):5-66. doi: 10.15829/1728-8800-2019-1-5-66Oganov RG, Simanenkov VI, Bakulin IG, Bakulina NV, Barbarash OL, Boytsov SA, et al. Comorbid pathology in clinical practice. Algorithms for diagnosis and treatment. Cardiovascular Therapy and Prevention. 2019;18(1):5-66 (In Russ). doi: 10.15829/1728-8800-2019-1-5-66Swain S, Sarmanova A, Coupland C, Doherty M, Zhang W. Comorbidities in osteoarthritis: A systematic review and metaanalysis of observational studies. Arthritis Care Res (Hoboken). 2020;72(7):991-1000. doi: 10.1002/acr.24008Swain S, Sarmanova A, Coupland C, Doherty M, Zhang W. Comorbidities in osteoarthritis: A systematic review and metaanalysis of observational studies. Arthritis Care Res (Hoboken). 2020;72(7):991-1000. doi: 10.1002/acr.24008Dell’Isola A, Pihl K, Turkiewicz A, Hughes V, Zhang W, BiermaZeinstra S, et al. Risk of comorbidities following physician-diagnosed knee or hip osteoarthritis: A register-based cohort study. Arthritis Care Res (Hoboken). 2021 Jun 4. doi: 10.1002/acr.24717Dell’Isola A, Pihl K, Turkiewicz A, Hughes V, Zhang W, BiermaZeinstra S, et al. Risk of comorbidities following physician-diagnosed knee or hip osteoarthritis: A register-based cohort study. Arthritis Care Res (Hoboken). 2021 Jun 4. doi: 10.1002/acr.24717Marshall DA, Liu X, Barnabe C, Yee K, Faris PD, Barber C, et al. Existing comorbidities in people with osteoarthritis: A retrospective analysis of a population-based cohort in Alberta, Canada. BMJ Open. 2019;9(11):e033334. doi: 10.1136/bmjopen-2019-033334Marshall DA, Liu X, Barnabe C, Yee K, Faris PD, Barber C, et al. Existing comorbidities in people with osteoarthritis: A retrospective analysis of a population-based cohort in Alberta, Canada. BMJ Open. 2019;9(11):e033334. doi: 10.1136/bmjopen-2019-033334Swain S, Coupland C, Mallen C, Kuo CF, Sarmanova A, BiermaZeinstra SMA, et al. Temporal relationship between osteoarthritis and comorbidities: A combined case control and cohort study in the UK primary care setting. Rheumatology (Oxford). 2021;60(9):4327-4339. doi: 10.1093/rheumatology/keab067Swain S, Coupland C, Mallen C, Kuo CF, Sarmanova A, BiermaZeinstra SMA, et al. Temporal relationship between osteoarthritis and comorbidities: A combined case control and cohort study in the UK primary care setting. Rheumatology (Oxford). 2021;60(9):4327-4339. doi: 10.1093/rheumatology/keab067Calders P, Van Ginckel A. Presence of comorbidities and prognosis of clinical symptoms in knee and/or hip osteoarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 2018;47(6):805-813. doi: 10.1016/j.semarthrit.2017.10.016Calders P, Van Ginckel A. Presence of comorbidities and prognosis of clinical symptoms in knee and/or hip osteoarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 2018;47(6):805-813. doi: 10.1016/j.semarthrit.2017.10.016de Rooij M, van der Leeden M, Heymans MW, Holla JF, Häkkinen A, Lems WF, et al. Prognosis of pain and physical functioning in patients with knee osteoarthritis: A systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2016;68(4):481- 492. doi: 10.1002/acr.22693de Rooij M, van der Leeden M, Heymans MW, Holla JF, Häkkinen A, Lems WF, et al. Prognosis of pain and physical functioning in patients with knee osteoarthritis: A systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2016;68(4):481- 492. doi: 10.1002/acr.22693Muckelt PE, Roos EM, Stokes M, McDonough S, Grønne DT, Ewings S, et al. Comorbidities and their link with individual health status: A cross-sectional analysis of 23,892 people with knee and hip osteoarthritis from primary care. J Comorb. 2020;10:2235042X20920456. doi: 10.1177/2235042X20920456Muckelt PE, Roos EM, Stokes M, McDonough S, Grønne DT, Ewings S, et al. Comorbidities and their link with individual health status: A cross-sectional analysis of 23,892 people with knee and hip osteoarthritis from primary care. J Comorb. 2020;10:2235042X20920456. doi: 10.1177/2235042X20920456Kiadaliri A, Englund M. Osteoarthritis and risk of hospitalization for ambulatory care-sensitive conditions: A general populationbased cohort study. Rheumatology (Oxford). 2021;60(9):4340-4347. doi: 10.1093/rheumatology/keab161Kiadaliri A, Englund M. Osteoarthritis and risk of hospitalization for ambulatory care-sensitive conditions: A general populationbased cohort study. Rheumatology (Oxford). 2021;60(9):4340-4347. doi: 10.1093/rheumatology/keab161Constantino de Campos G, Mundi R, Whittington C, Toutounji MJ, Ngai W, Sheehan B. Osteoarthritis, mobility-related comorbidities and mortality: An overview of meta-analyses. Ther Adv Musculoskelet Dis. 2020;12:1759720X20981219. doi: 10.1177/1759720X20981219Constantino de Campos G, Mundi R, Whittington C, Toutounji MJ, Ngai W, Sheehan B. Osteoarthritis, mobility-related comorbidities and mortality: An overview of meta-analyses. Ther Adv Musculoskelet Dis. 2020;12:1759720X20981219. doi: 10.1177/1759720X20981219Mazzucchelli R, Rodríguez-Martín S, García-Vadillo A, Gil M, Rodríguez-Miguel A, Barreira-Hernández D, et al. Risk of acute myocardial infarction among new users of chondroitin sulfate: A nested case-control study. PLoS One. 2021;16(7):e0253932. doi: 10.1371/journal.pone.0253932Mazzucchelli R, Rodríguez-Martín S, García-Vadillo A, Gil M, Rodríguez-Miguel A, Barreira-Hernández D, et al. Risk of acute myocardial infarction among new users of chondroitin sulfate: A nested case-control study. PLoS One. 2021;16(7):e0253932. doi: 10.1371/journal.pone.0253932Melgar-Lesmes P, Sánchez-Herrero A, Lozano-Juan F, de la Torre Hernández JM, Montell E, Jiménez W, et al. Chondroitin sulphate attenuates atherosclerosis in ApoE knockout mice involving cellular regulation of the inflammatory response. Thromb Haemost. 2018;118(7):1329-1339. doi: 10.1055/s-0038-1657753Melgar-Lesmes P, Sánchez-Herrero A, Lozano-Juan F, de la Torre Hernández JM, Montell E, Jiménez W, et al. Chondroitin sulphate attenuates atherosclerosis in ApoE knockout mice involving cellular regulation of the inflammatory response. Thromb Haemost. 2018;118(7):1329-1339. doi: 10.1055/s-0038-1657753Park YM, Febbraio M, Silverstein RL. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima. J Clin Invest. 2009;119(1):136-145. doi: 10.1172/JCI35535Park YM, Febbraio M, Silverstein RL. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima. J Clin Invest. 2009;119(1):136-145. doi: 10.1172/JCI35535Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP, et al. CD146 and its soluble form regulate monocyte transendothelial migration. Arterioscler Thromb Vasc Biol. 2009;29(5):746-753. doi: 10.1161/ATVBAHA.108.183251Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP, et al. CD146 and its soluble form regulate monocyte transendothelial migration. Arterioscler Thromb Vasc Biol. 2009;29(5):746-753. doi: 10.1161/ATVBAHA.108.183251Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(11):2292-2301. doi: 10.1161/ATVBAHA.107.149179Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(11):2292-2301. doi: 10.1161/ATVBAHA.107.149179Braun J, Hoffmann SC, Feldner A, Ludwig T, Henning R, Hecker M, et al. Endothelial cell ephrinB2-dependent activation of monocytes in arteriosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(2):297-305. doi: 10.1161/ATVBAHA.110.217646Braun J, Hoffmann SC, Feldner A, Ludwig T, Henning R, Hecker M, et al. Endothelial cell ephrinB2-dependent activation of monocytes in arteriosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(2):297-305. doi: 10.1161/ATVBAHA.110.217646Melgar-Lesmes P, Garcia-Polite F, Del-Rey-Puech P, Rosas E, Dreyfuss JL, Montell E, et al. Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity. Atherosclerosis. 2016;245:82-87. doi: 10.1016/j.atherosclerosis.2015.12.016Melgar-Lesmes P, Garcia-Polite F, Del-Rey-Puech P, Rosas E, Dreyfuss JL, Montell E, et al. Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity. Atherosclerosis. 2016;245:82-87. doi: 10.1016/j.atherosclerosis.2015.12.016Pang H, Li J, Miao Z, Li SJ. Inhibitory effects of chondroitin sulfate on alpha-amylase activity: A potential hypoglycemic agent. Int J Biol Macromol. 2021;184:289-296. doi: 10.1016/j.ijbiomac.2021.06.062Pang H, Li J, Miao Z, Li SJ. Inhibitory effects of chondroitin sulfate on alpha-amylase activity: A potential hypoglycemic agent. Int J Biol Macromol. 2021;184:289-296. doi: 10.1016/j.ijbiomac.2021.06.062Bell GA, Kantor ED, Lampe JW, Shen DD, White E. Use of glucosamine and chondroitin in relation to mortality. Eur J Epidemiol. 2012;27(8):593-603. doi: 10.1007/s10654-012-9714-6Bell GA, Kantor ED, Lampe JW, Shen DD, White E. Use of glucosamine and chondroitin in relation to mortality. Eur J Epidemiol. 2012;27(8):593-603. doi: 10.1007/s10654-012-9714-6King DE, Xiang J. Glucosamine/chondroitin and mortality in a US NHANES cohort. J Am Board Fam Med. 2020;33(6): 842-847. doi: 10.3122/jabfm.2020.06.200110King DE, Xiang J. Glucosamine/chondroitin and mortality in a US NHANES cohort. J Am Board Fam Med. 2020;33(6): 842-847. doi: 10.3122/jabfm.2020.06.200110Masola V, Zaza G, Onisto M, Lupo A, Gambaro G. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: Biological roles and pharmacological effects. Int Angiol. 2014;33(3):243-254.Masola V, Zaza G, Onisto M, Lupo A, Gambaro G. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: Biological roles and pharmacological effects. Int Angiol. 2014;33(3):243-254.Herrero-Beaumont G, Marcos ME, Sánchez-Pernaute O, Granados R, Ortega L, Montell E, et al. Effect of chondroitin sulphate in a rabbit model of atherosclerosis aggravated by chronic arthritis. Br J Pharmacol. 2008;154(4):843-851. doi: 10.1038/bjp.2008.113Herrero-Beaumont G, Marcos ME, Sánchez-Pernaute O, Granados R, Ortega L, Montell E, et al. Effect of chondroitin sulphate in a rabbit model of atherosclerosis aggravated by chronic arthritis. Br J Pharmacol. 2008;154(4):843-851. doi: 10.1038/bjp.2008.113Xu CX, Jin H, Chung YS, Shin JY, Woo MA, Lee KH, et al. Chondroitin sulfate extracted from the Styela clava tunic suppresses TNF-alpha-induced expression of inflammatory factors, VCAM1 and iNOS by blocking Akt/NF-kappaB signal in JB6 cells. Cancer Lett. 2008;264(1):93-100. doi: 10.1016/j.canlet.2008.01.022Xu CX, Jin H, Chung YS, Shin JY, Woo MA, Lee KH, et al. Chondroitin sulfate extracted from the Styela clava tunic suppresses TNF-alpha-induced expression of inflammatory factors, VCAM1 and iNOS by blocking Akt/NF-kappaB signal in JB6 cells. Cancer Lett. 2008;264(1):93-100. doi: 10.1016/j.canlet.2008.01.022Chou MM, Vergnolle N, McDougall JJ, Wallace JL, Marty S, Teskey V, et al. Effects of chondroitin and glucosamine sulfate in a dietary bar formulation on inflammation, interleukin-1beta, matrix metalloprotease-9, and cartilage damage in arthritis. Exp Biol Med (Maywood). 2005;230(4):255-262. doi: 10.1177/153537020523000405Chou MM, Vergnolle N, McDougall JJ, Wallace JL, Marty S, Teskey V, et al. Effects of chondroitin and glucosamine sulfate in a dietary bar formulation on inflammation, interleukin-1beta, matrix metalloprotease-9, and cartilage damage in arthritis. Exp Biol Med (Maywood). 2005;230(4):255-262. doi: 10.1177/153537020523000405Лила АМ, Алексеева ЛИ, Таскина ЕА. Современные подходы к терапии остеоартрита с учетом обновленных международных рекомендаций. РМЖ. Медицинское обозрение. 2019;3(11-2): 48-52.Lila AM, Alekseeva LI, Taskina EA. Modern approaches to osteoarthritis therapy taking into account updated international guidelines. RMJ. Medical Review. 2019;3(11-2):48-52 (In Russ.).Лила АМ, Таскина ЕА, Алексеева ЛИ, Кашеварова НГ. Симптоматические препараты замедленного действия (SYSADOA): новые возможности применения. Современная ревматология. 2022;16(2):99-106. doi: 10.14412/1996-7012-2022-2-99-106Lila AM, Taskina EA, Alekseeva LI, Kashevarova NG. Symptomatic delayed-acting drugs (SYSADOA): New applications. Modern Rheumatology Journal. 2022;16(2):99-106 (In Russ). doi: 10.14412/1996-7012-2022-2-99-106Yang W, Sun C, He SQ, Chen JY, Wang Y, Zhuo Q. The efficacy and safety of disease-modifying osteoarthritis drugs for knee and hip osteoarthritis – A systematic review and network metaanalysis. J Gen Intern Med. 2021;36(7):2085-2093. doi: 10.1007/s11606-021-06755-zYang W, Sun C, He SQ, Chen JY, Wang Y, Zhuo Q. The efficacy and safety of disease-modifying osteoarthritis drugs for knee and hip osteoarthritis – A systematic review and network metaanalysis. J Gen Intern Med. 2021;36(7):2085-2093. doi: 10.1007/s11606-021-06755-zReginster JY, Veronese N. Highly purified chondroitin sulfate: A literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment. Aging Clin Exp Res. 2021;33(1):37-47. doi: 10.1007/s40520-020-01643-8Reginster JY, Veronese N. Highly purified chondroitin sulfate: A literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment. Aging Clin Exp Res. 2021;33(1):37-47. doi: 10.1007/s40520-020-01643-8Rubio-Terrés C; Grupo del estudio VECTRA. Evaluación económica del uso de condroitín sulfato y antiinflamatorios no esteroideos en el tratamiento de la artrosis. Datos del estudio VECTRA [An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study]. Reumatol Clin. 2010;6(4):187-195. (In Spanish). doi: 10.1016/j.reuma.2009.12.009Rubio-Terrés C; Grupo del estudio VECTRA. Evaluación económica del uso de condroitín sulfato y antiinflamatorios no esteroideos en el tratamiento de la artrosis. Datos del estudio VECTRA [An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study]. Reumatol Clin. 2010;6(4):187-195. (In Spanish). doi: 10.1016/j.reuma.2009.12.009Rubio-Terrés C, Bernad Pineda M, Herrero M, Nieto C, RubioRodríguez D. Analysis of the health and budgetary impact of chondroitin sulfate prescription in the treatment of knee osteoarthritis compared to NSAIDs and COXIBs. Clinicoecon Outcomes Res. 2020;12:505-514. doi: 10.2147/CEOR.S265994Rubio-Terrés C, Bernad Pineda M, Herrero M, Nieto C, RubioRodríguez D. Analysis of the health and budgetary impact of chondroitin sulfate prescription in the treatment of knee osteoarthritis compared to NSAIDs and COXIBs. Clinicoecon Outcomes Res. 2020;12:505-514. doi: 10.2147/CEOR.S265994Olariu L, Dumitriu B, Buse E, Rosoiu N. The “in vitro” effect of Alflutop® product on some extracellular signaling factors involved in the osteoarthicular pathology inflammation. Acad Rom Sci Ann Ser Biol Sci. 2015;(4):7-17.Olariu L, Dumitriu B, Buse E, Rosoiu N. The “in vitro” effect of Alflutop® product on some extracellular signaling factors involved in the osteoarthicular pathology inflammation. Acad Rom Sci Ann Ser Biol Sci. 2015;(4):7-17.Olariu L, Pyatigorskaya N, Dumitriu B, Pavlov A, Vacaru AM, Vacaru A. “In vitro” chondro-restitutive capacity of Alflutop® proved on chondrocytes cultures. Rom Biotechnol Lett. 2016;(22):12047-12053.Olariu L, Pyatigorskaya N, Dumitriu B, Pavlov A, Vacaru AM, Vacaru A. “In vitro” chondro-restitutive capacity of Alflutop® proved on chondrocytes cultures. Rom Biotechnol Lett. 2016;(22):12047-12053.Каратеев АЕ. Биоактивный концентрат мелкой морской рыбы: оценка эффективности и безопасности препарата на основании анализа 37 клинических исследований. Современная ревматология. 2020;14(4);111-124. doi: 10.14412/1996-7012-2020-4-111-124Karateev AE. Bioactive concentrate from small sea fish: Evaluation of the efficacy and safety of the drug on the basis of the analysis of 37 clinical trials. Modern Rheumatology Journal. 2020;14(4):111- 124 (In Russ.). doi: 10.14412/1996-7012-2020-4-111-124Алексеева ЛИ, Шарапова ЕП, Таскина ЕА, Чичасова НВ, Имаметдинова ГР, Шостак НА, и др. Многоцентровое слепое рандомизированное плацебо-контролируемое исследование симптом- и структурно-модифицирующего действия препарата Алфлутоп у больных остеоартрозом коленных суставов. Сообщение 1 – оценка симптом-модифицирующего действия препарата. Научно-практическая ревматология. 2013;51(5);532- 538. doi: 10.14412/1995-4484-2013-1545Alekseeva LI, Sharapova EP, Taskina EA, Chichasova NV, Imametdinova GR, Shostak NA, et al. Multicenter double-blind randomized placebo-controlled trial of the symptom- and structuremodifying effect of Alflutop in patients with knee osteoarthrosis. Communication 1. Evaluation of the symptom-modifying effect of the drug. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2013;51(5):532-538 (In Russ.). doi: 10.14412/1995-4484-2013-1545Алексеева ЛИ, Шарапова ЕП, Таскина ЕА, Чичасова НВ, Имаметдинова ГР, Шостак НА, и др. Многоцентровое слепое рандомизированное плацебоконтролируемое исследование симптом- и структурно-модифицирующего действия препарата Алфлутоп у больных остеоартрозом коленных суставов. Сообщение 2 – оценка структурно- модифицирующего действия препарата. Научно-практическая ревматология. 2014;52(2); 174-177. doi: 10.14412/1995-4484-2014-174-177Alekseeva LI, Sharapova EP, Taskina EA, Chichasova NV, Imametdinova GR, Shostak NA, et al. A multicenter, blind, randomized, placebo-controlled study of the symptom- and structuremodifying effect of Alflutop in patients with knee osteoarthritis. Report 2: The assessment of the struc ture-modifying effect of the drug. Nauchno-Prakticheskaya Revmatologia = Rheumato - logy Science and Practice. 2014;52(2): 174-177 (In Russ.). doi: 10.14412/1995-4484-2014-174-177Беляева ИБ, Мазуров ВИ, Трофимов ЕА. Анализ терапевтических преимуществ медленнодействующих симптоматических средств при остеоартрите: акцент на структурномодифицирующее действие. Современная ревматология. 2021;15(6);117-123. doi: 10.14412/1996-7012-2021-6-117-123Belyaeva IB, Mazurov VI, Trofimov EA. Analysis of the therapeutic benefits of symptomatic slow acting drugs in osteoarthritis: Emphasis on structural-modifying action. Modern Rheumatology Journal. 2021;15(6):117-123 (In Russ.). doi: 10.14412/1996-7012-2021-6-117-123Алексеева ЛИ, Таскина ЕА, Лила АМ, Мазуров ВИ, Шостак НА, Шмидт ЕИ, и др. Многоцентровое проспективное рандомизированное исследование эффективности и безопасности препарата Алфлутоп® в альтернирующем режиме по сравнению со стандартным режимом. Сообщение 1: оценка эффективности препарата при различных схемах применения. Современная ревматология. 2019;13(3);51-59. doi: 10.14412/1996-7012-2019-3-51-59Alekseeva LI, Taskina EA, Lila AM, Mazurov VI, Shostak NA, Shmidt EI, et al. A multicenter, prospective, randomized trial of the efficacy and safety of Alflutop® in an alternating dosing regimen versus the standard one. Communication 1: Evaluation of the efficacy of the drug in different treatment regimens. Modern Rheumatology Journal. 2019;13(3):51-59 (In Russ.). doi: 10.14412/1996-7012-2019-3-51-59Шарапова ЕП, Алексеева ЛИ, Таскина ЕА, Кашеварова НГ, Аникин СГ, Стребкова ЕА, и др. Многоцентровое проспективное рандомизированное исследование эффективности и безопасности препарата Алфлутоп® в альтернирующем режиме по сравнению со стандартным режимом. Сообщение 2: оценка безопасности препарата при различных схемах применения. Современная ревматология. 2020;14(1):67-73. doi: 10.14412/1996-7012-2020-1-67-73Sharapova EP, Alekseeva LI, Taskina EA, Kashevarova NG, Anikin SG, Strebkova EA, et al. A multicenter, prospective, randomized trial of the efficacy and safety of Alflutop® in an alternating dosing regimen versus the standard one. Communication 2: Evaluation of the efficacy of the drug in different use regimens. Modern Rheumatology Journal. 2020;14(1):67-73 (In Russ.). doi: 10.14412/1996-7012-2020-1-67-73Куксгауз ИА, Шекунова ЕВ, Кашкин ВА, Фаустова НМ, Гущин ЯА, Макарова МН, и др. Изучение гастропротективного эффекта препарата Алфлутоп на модели индуцированной диклофенаком гастропатии у крыс. Экспериментальная и клиническая гастроэнтерология. 2019;166(5):15-21. doi: 10.31146/1682-8658-ecg-166-5-15-21Kuksgauz IA, Shekunova EV, Kashkin VA, Faustova NM, Guschin YA, Makarova MN, et al. Gastroprotective effect of Alflutop on diclofenac-induced gastropathy in rats. Experimental and Clinical Gastroenterology. 2019;166(5):15-21 (In Russ.). doi: 10.31146/1682-8658-ecg-166-5-15-21Дроздов ВН, Коломиец ЕВ. Применение Алфлутопа у больных с остеартрозом с НПВС-гастропатией. Фарматека. 2005;20:21.Drozdov VN, Kolomiets EV. The use of Alflutop in patients with ostearthrosis with NSAID gastropathy. Farmateka. 2015;20:21 (In Russ.).

The authors declare that there are no conflicts of interest present.