Potential of diacerein in combination with aerobic exercise in comprehensive treatment of knee osteoarthritis

Abstract

BACKGROUND: Knee osteoarthritis is a common degenerative disease characterized by cartilage destruction and inflammatory changes in the synovial membrane. Obesity and metabolic syndrome are significant risk factors that exacerbate inflammatory processes and contribute to the progression of osteoarthritis. Modern treatment methods include both pharmacological agents and non-pharmacological approaches such as aerobic exercise.

AIM: To evaluate and compare the effectiveness of diacerein combined with aerobic physical activity (Nordic walking) in the comprehensive treatment of knee osteoarthritis.

MATERIALS AND METHODS: The study involved 65 patients aged 45 to 70 years with knee osteoarthritis and metabolic syndrome. The participants were divided into three groups. The first group received diacerein (Artrocare); the second group was engaged in Nordic walking; the third group – a combination of these methods. The visual analog scale of pain, Western Ontario and McMaster University Osteoarthritis (WOMAC) index, quality of life (Short Form-36), glycated hemoglobin levels, and other biochemical parameters were assessed over 16 weeks of observation.

RESULTS: The study demonstrated statistically significant reductions in pain levels and improvements in functional parameters in all the groups. The greatest improvements were observed in the group receiving combined therapy. The method showed a significantly positive impact on quality of life and reduced the need for analgesics in comorbid patients. Additionally, the patients with metabolic syndrome showed improved biochemical parameters with the combination of diacerein and Nordic walking.

CONCLUSIONS: The combined use of diacerein and Nordic walking is an effective and safe method for treating knee osteoarthritis, particularly in patients with metabolic syndrome. This approach significantly reduces pain, improves joint function, and enhances overall quality patient’s life.

Keywords

diacerein / osteoarthritis / SYSADOA / Nordic walking

References

[1] Mazurov VI, Gaidukova IZ, Belyaeva IB. Clinical Rheumatology. A Guide for Doctors. Ed. by V.I. Mazurov. 3rd ed. Moscow: E-noto; 2021. 696 p. (In Russ.)

[2] Мазуров В.И., Гайдукова И.З., Беляева И.Б. Клиническая ревматология. Руководство для врачей / под ред. В.И. Мазурова. 3-е изд., перераб. и доп. Москва: Е-ното, 2021. 696 с.

[3] Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–1330. doi: 10.1136/annrheumdis-2013-204763

[4] Cross M., Smith E., Hoy D., et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study // Ann Rheum Dis. 2014. Vol. 73, N 7. P. 1323–1330. doi: 10.1136/annrheumdis-2013-204763

[5] Turkiewicz A, Kiadaliri AA, Englund M. Cause-specific mortality in osteoarthritis of peripheral joints. Osteoarthritis Cartilage. 2019;27(6):848–854. doi: 10.1016/j.joca.2019.02.793

[6] Turkiewicz A., Kiadaliri A.A., Englund M. Cause-specific mortality in osteoarthritis of peripheral joints // Osteoarthritis Cartilage. 2019. Vol. 27, N 6. P. 848–854. doi: 10.1016/j.joca.2019.02.793

[7] Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001;44(6):1237–1247. doi: 10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F

[8] Pelletier J.P., Martel-Pelletier J., Abramson S.B. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets // Arthritis Rheum. 2001. Vol. 44, N 6. P. 1237–1247. doi: 10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F

[9] Martel-Pelletier J, Lajeunesse D, Pelletier JP. Etiopathogenesis of osteoarthritis. In: Koopman WJ, Moreland LW, editors. Arthritis and Allied Conditions: A Textbook of Rheumatology. Baltimore: Lippincott, Williams and Wilkins; 2005. P. 2199–2296.

[10] Martel-Pelletier J., Lajeunesse D., Pelletier J.P. Etiopathogenesis of osteoarthritis. In: Koopman W.J., Moreland L.W., editors. Arthritis and Allied Conditions: A Textbook of Rheumatology. Baltimore: Lippincott, Williams and Wilkins, 2005. P. 2199–2296.

[11] Trofimova AS, Mazurov VI, Shokhin AA, Trofimov EA. The use of symptomatic slow-acting drugs for osteoarthritis of the joints of the hands: accent on microcirculation parameters. Scientific and Practical Rheumatology. 2024;62(1):104–108. EDN: KOMTFW doi: 10.47360/1995-4484-2024-104-108

[12] Трофимова А.С., Мазуров В.И., Шохин А.А., Трофимов Е.А. Применение симптоматических средств замедленного действия при остеоартрите суставов кистей: акцент на параметры микроциркуляции // Научно-практическая ревматология. 2024. Т. 62, № 1. С. 104–108. EDN: KOMTFW doi: 10.47360/1995-4484-2024-104-108

[13] Lee CH, Chiang CF, Kuo FC, et al. High-molecular-weight hyaluronic acid inhibits IL-1β-induced synovial inflammation and macrophage polarization through the GRP78-NF-κB signaling pathway. Int J Mol Sci. 2021;22(21):11917. doi: 10.3390/ijms222111917.

[14] Lee C.H., Chiang C.F., Kuo F.C., et al. High-molecular-weight hyaluronic acid inhibits IL-1β-induced synovial inflammation and macrophage polarization through the GRP78-NF-κB signaling pathway // Int J Mol Sci. 2021. Vol. 22, N 21. P. 11917. doi: 10.3390/ijms222111917

[15] Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175–184. doi: 10.1172/JCI29881

[16] Lumeng C.N., Bodzin J.L., Saltiel A.R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization // J Clin Invest. 2007. Vol. 117. P. 175–184. doi: 10.1172/JCI29881

[17] McNulty AL, Miller MR, O’Connor SK, Guilak F. The effects of adipokines on cartilage and meniscus catabolism. Connect Tissue Res. 2011;52(6):523–533. doi: 10.3109/03008207.2011.597902

[18] McNulty A.L., Miller M.R., O’Connor S.K., Guilak F. The effects of adipocytes on cartilage and meniscus catabolism // Connect Tissue Res. 2011. Vol. 52, N 6. P. 523–533. doi: 10.3109/03008207.2011.597902

[19] Mazurov VI, Trofimov EA, Trofimova AS. The effect of various multi-drug regimens on clinical manifestations of osteoarthritis of the knee and parameters of t2 mapping of the knee cartilage. Doctor.Ru. 2017;(10):53–56. EDN: ZXWOKP

[20] Мазуров В.И., Трофимов Е.А., Трофимова А.С. Влияние различных комбинированных медикаментозных методов лечения на клинические проявления гонартроза и показатели Т2-картирования хряща // Доктор. Ру. 2017. № 10(139). С. 53–56. EDN: ZXWOKP

[21] Mazurov VI, Trofimova AS, Trofimov EA. Risk factors and some aspects of osteoarthritis pathogenesis. Bulletin of the Northwest State Medical University named after I.I. Mechnikov. 2016;8(2):116–125. EDN: WLSQZR

[22] Мазуров В.И., Трофимова А.С., Трофимов Е.А. Факторы риска и некоторые аспекты патогенеза остеоартрита // Вестник Северо-Западного государственного медицинского университета им. И.И. Мечникова. 2016. Т. 8, № 2. С. 116–125. EDN: WLSQZR

[23] Kashevarova NG, Alekseeva LI, Taskina EA, Smirnov AV. Leading factors for progression of osteoarthritis of the knee. effects of symptomatic slow release preparations on the course of the disease (5-year prospective study). Pharmateca. 2017;7(340):40–45. EDN: YPJQZF

[24] Кашеварова Н.Г., Алексеева Л.И., Таскина Е.А., Смирнов А.В. Ведущие факторы прогрессирования остеоартрита коленных суставов. Влияние симптоматических препаратов замедленного действия на течение заболевания (5-летнее проспективное исследование) // Фарматека. 2017. № 7(340). С. 40–45. EDN: YPJQZF

[25] Wang Y, Simpson JA, Wluka AE, et al. Relationship between body adiposity measures and risk of primary knee and hip replacement for osteoarthritis: a prospective cohort study. Arthritis Res Ther. 2009;11(2):R31. doi: 10.1186/ar2636

[26] Wang Y., Simpson J.A., Wluka A.E., et al. Relationship between body adiposity measures and risk of primary knee and hip replacement for osteoarthritis: a prospective cohort study // Arthritis Res Ther. 2009. Vol. 11, N 2. P. R31. doi: 10.1186/ar2636

[27] Bruyere O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337–350. doi: 10.1016/j.semarthrit.2019.04.008

[28] Bruyere O., Honvo G., Veronese N., et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) // Semin Arthritis Rheum. 2019. Vol. 49, N 3. P. 337–350. doi: 10.1016/j.semarthrit.2019.04.008

[29] Bruyere O, Cooper C, Al-Daghri NM, et al. Inappropriate claims from non-equivalent medications in osteoarthritis: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Aging Clin Exp Res. 2018;30(2):111–117. doi: 10.1007/s40520-017-0861-1

[30] Bruyere O., Cooper C., Al-Daghri N.M., et al. Inappropriate claims from non-equivalent medications in osteoarthritis: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) // Aging Clin Exp Res. 2018. Vol. 30, N 2. P. 111–117. doi: 10.1007/s40520-017-0861-1

[31] Mazurov VI, Lesnyak OM, Trofimov EA, et al. Rheumatology. Error-free pharmacotherapy. Moscow: E-noto; 2017. 528 p. (In Russ.)

[32] Мазуров В.И., Лесняк О.М., Трофимов Е.А., и др. Ревматология. Фармакотерапия без ошибок. Москва: Е-ното, 2017. 528 с.

[33] The tactics of a rheumatologist: a practical guide Ed. by V.I. Mazurov. Moscow: GEOTAR-Media; 2022. 320 p. EDN: RFJSLM doi: 10.33029/9704-6824-1-ТOR-2022-1-320. (In Russ.)

[34] Тактика врача-ревматолога: практическое руководство / под ред. В.И. Мазурова. Москва: ГЭОТАР-Медиа, 2022. 320 с. EDN: RFJSLM doi: 10.33029/9704-6824-1-ТOR-2022-1-320

[35] Denisov LN, Alekseeva LI, Zotkin EG, et al. Evidence-based therapy for knee osteoarthritis: expected short-, medium-, and long-term outcomes of prescription crystalline glucosamine sulfate administration. Modern Rheumatology. 2022;16(4):80–87. EDN: BAEIIW doi: 10.14412/1996-7012-2022-4-80-87

[36] Денисов Л.Н., Алексеева Л.И., Зоткин Е.Г., и др. Терапия остеоартрита коленных суставов с точки зрения доказательной медицины: ожидаемые краткосрочные, среднесрочные и долгосрочные результаты применения рецептурного кристаллического глюкозамина сульфата // Современная ревматология. 2022. Т. 16, № 4. С. 80–87. EDN: BAEIIW doi: 10.14412/1996-7012-2022-4-80-87

[37] Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–162. doi: 10.1016/j.joca.2007.12.013

[38] Zhang W., Moskowitz R.W., Nuki G., et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines // Osteoarthritis Cartilage. 2008. Vol. 16, N 2. P. 137–162. doi: 10.1016/j.joca.2007.12.013

[39] Denisov LN, Tsvetkova ES, Golubev GS, et al. The European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis is applicable in Russian clinical practice: a joint opinion of leading Russian specialists and ESCEO experts on osteoarthritis. Scientific and Practical Rheumatology. 2016;54(6):641–653. EDN: YSTSBJ

[40] Денисов Л.Н., Цветкова Е.С., Голубев Г.Ш., и др. Алгоритм лечения остеоартрита коленного сустава Европейского общества по клиническим и экономическим аспектам остеопороза и остеоартрита (ESCEO) применим в российской клинической практике: совместное заключение ведущих российских специалистов и экспертов ESCEO по остеоартриту // Научно-практическая ревматология. 2016. Т. 54, № 6. С. 641–653. EDN: YSTSBJ

[41] Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum. 2005;52(7):2026–2032. doi: 10.1002/art.21139

[42] Messier S.P., Gutekunst D.J., Davis C., DeVita P. Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis // Arthritis Rheum. 2005. Vol. 52, N 7. P. 2026–2032. doi: 10.1002/art.21139

[43] Roddy E, Zhang W, Doherty M, et al. Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee — the MOVE consensus. Rheumatology. 2005;44(1):67–73. doi: 10.1093/rheumatology/keh399

[44] Roddy E., Zhang W., Doherty M., et al. Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee — the MOVE consensus // Rheumatology. 2005. Vol. 44, N 1. P. 67–73. doi: 10.1093/rheumatology/keh399

[45] Dougados M, Nguyen M, Berdah L, et al. Evaluation of the structure — modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip. Arthritis Rheum. 2001;44(11):2539–2547. doi: 10.1002/1529-0131(200111)44:11<2539::aid-art434>3.0.co;2-t

[46] Dougados M., Nguyen M., Berdah L., et al. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the chondromodulating effect of diacerein in OA of the Hip // Arthritis Rheum. 2001. Vol. 44, N 11. P. 2539–2547. doi: 10.1002/1529-0131(200111)44:11<2539::aid-art434>3.0.co;2-t

[47] Luchikhina LV, Karateev DE. Diacerein for osteoarthritis: an open-label comparative trial. Modern Rheumatology. 2016;10(1):21–25. EDN: WXJMZD doi: 10.14412/1996-7012-2016-1-21-25

[48] Лучихина Л.В., Каратеев Д.Е. Диацереин при остеоартрозе: открытое сравнительное исследование // Современная ревматология. 2016. Т. 10, № 1. С. 21–25. EDN: WXJMZD doi: 10.14412/1996-7012-2016-1-21-25

[49] Kongtharvonskul J, Anothaisintawee T, McEvoy M, et al. Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis. Eur J Med Res. 2015;20:24. doi: 10.1186/s40001-015-0115-7

[50] Kongtharvonskul J., Anothaisintawee T., McEvoy M., et al. Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis // Eur J Med Res. 2015. Vol. 20. P. 24. doi: 10.1186/s40001-015-0115-7

[51] Tschentscher M, Niederseer D, Niebauer J. Health benefits of Nordic walking: a systematic review. Am J Prev Med. 2013;44(1):76–84. doi: 10.1016/j.amepre.2012.09.043

[52] Tschentscher M., Niederseer D., Niebauer J. Health benefits of Nordic walking: a systematic review // Am J Prev Med. 2013. Vol. 44, N 1. P. 76–84. doi: 10.1016/j.amepre.2012.09.043

[53] Gram B, Christensen R, Christiansen C, Gram J. Effects of Nordic walking and exercise in type 2 diabetes mellitus: a randomized controlled trial. Clin J Sport Med. 2010;20(5):355–361. doi: 10.1227/NEU.0b013e3181e56e0a

[54] Gram B., Christensen R., Christiansen C., Gram J. Effects of Nordic walking and exercise in type 2 diabetes mellitus: a randomized controlled trial // Clin J Sport Med. 2010. Vol. 20, N 5. P. 355–361. doi: 10.1227/NEU.0b013e3181e56e0a

[55] Mannerkorpi K, Gard G. Physiotherapy group treatment for patients with fibromyalgia — an embodied learning process. Disabil Rehabil. 2003;25(24):1372–1380. doi: 10.1080/09638280310001616367

[56] Mannerkorpi K., Gard G. Physiotherapy group treatment for patients with fibromyalgia — an embodied learning process // Disabil Rehabil. 2003. Vol. 25, N 24. P. 1372–1380. doi: 10.1080/09638280310001616367

[57] Fritz T, Caidahl K, Osler M, et al. Effects of Nordic walking on health-related quality of life in overweight individuals with type 2 diabetes mellitus, impaired or normal glucose tolerance. Diabet Med. 2011;28(11):1362–1372. doi: 10.1111/j.1464-5491.2011.03348.x

[58] Fritz T., Caidahl K., Osler M., et al. Effects of Nordic walking on health-related quality of life in overweight individuals with type 2 diabetes mellitus, impaired or normal glucose tolerance // Diabet Med. 2011. Vol. 28, N 1. P. 1362–1372. doi: 10.1111/j.1464-5491.2011.03348.x

[59] Eliseeva LN, Kartashova SV. The role of diacereins in the treatment of osteoarthritis from the perspective of the new paradigm of pathogenesis. South Russian Journal of Therapeutic Practice. 2021;2(4):79–84. EDN: JROLAN doi: 10.21886/2712-8156-2021-2-4-79-84

[60] Елисеева Л.Н., Карташова С.В. Роль диацереинов в лечении остеоартрита с позиции новой парадигмы патогенеза // Южно-Российский журнал терапевтической практики. 2021. Т. 2, № 4. С. 79–84. EDN: JROLAN doi: 10.21886/2712-8156-2021-2-4-79-84

[61] Balabanova RM, Kaptaeva AK. Arthrodarin – a new drug for osteoarthritis pathogenetic therapy. Scientific and Practical Rheumatology. 2009;47(2):49–53. EDN: RCXJMB doi: 10.14412/1995-4484-2009-459

[62] Балабанова Р.М., Каптаева А.К. Артродарин новый препарат для патогенетической терапии остеоартроза // Научно-практическая ревматология. 2009. Т. 47, № 2. С. 49–53. EDN: RCXJMB doi: 10.14412/1995-4484-2009-459

[63] Karateev AE, Alekseeva LI. Estimation of diacerein tolerability in real clinical practice: results of the racada (retrospective assessment of clinical aspects of using diaflex in osteoarthritis). Scientific and Practical Rheumatology. 2015;53(2):169–174. EDN: TXMRDP doi: 10.14412/1995-4484-2015-169-174

[64] Каратеев А.Е., Алексеева Л.И. Оценка переносимости диацереина в реальной клинической практике. Результаты исследования РОКАДА (Ретроспективная Оценка Клинических Аспектов применения Диафлекса при остеоартрозе) // Научно-практическая ревматология. 2015. Т. 53, № 2. С. 169–174. EDN: TXMRDP doi: 10.14412/1995-4484-2015-169-174

[65] Mendes AF, Caramona MM, de Carvalho AP, et al. Diacerhein and Rhein reduce the ICE-induced IL-1b-induced nuclear factor-kappa B activation by inhibiting the degradation of inhibitor kappa B-alfa. Pharmacol Toxicol. 2002;91:22–28. doi: 10.1034/j.1600-0773.2002.910104.x

[66] Mendes A.F., Caramona M.M., de Carvalho A.P., Lopes MC. Diacerhein and Rhein reduce the ICE-induced IL-1b -induced nuclear factor-kappa B activation by inhibiting the degradation of inhibitor kappa B–alfa // Pharmacol Toxicol. 2002. Vol. 91. P. 22–28. doi: 10.1034/j.1600-0773.2002.910104.x

[67] Felisaz N, Boumediene K, Ghayor C, et al. Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1. Osteoarthritis Cartilage. 1999;7(3):255–264. doi: 10.1053/joca.1998.0199

[68] Felisaz N., Boumediene K., Ghayor C., et al. Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1 // Osteoarthritis Cartilage. 1999. Vol. 7, N 3. P. 255–264. doi: 10.1053/joca.1998.0199

[69] Moldovan F, Pelletier JP, Jolicoeur FC, et al. Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthritis Cartilage. 2000;8(3):186–196. doi: 10.1053/joca.1999.0289

[70] Moldovan F., Pelletier J.P., Jolicoeur F.C., et al. Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage // Osteoarthritis Cartilage. 2000. Vol. 8, N 3. P. 186–196. doi: 10.1053/joca.1999.0289

[71] Pelletier JP, Mineau F, Boileau C, Martel-Pelletier J. Diacerein reduces the level of cartilage chondrocyte DNA fragmentation and death in experimental dog osteoarthritic cartilage at the Same time that it inhibits caspase-3 and inducible nitric oxide synthase. Clin Exp Rheumatol. 2003;21(2):171–177.

[72] Pelletier J.P., Mineau F., Boileau C., Martel-Pelletier J. Diacerein reduces the level of cartilage chondrocyte DNA fragmentation and death in experimental dog osteoarthritic cartilage at the Same time that it inhibits caspase-3 and inducible nitric oxide synthase // Clin Exp Rheumatol. 2003. Vol. 21, N 2. P. 171–177.

[73] Misra D, Fielding RA, Felson DT, et al. Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia. Arthritis Rheumatol. 2019;71(2):232–237. doi: 10.1002/art.40692

[74] Misra D., Fielding R.A., Felson D.T., et al. Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia // Arthritis Rheumatol. 2019. Vol. 71, N 2. P. 232–237. doi: 10.1002/art.40692

[75] Alekseeva LI, Kashevarova NG, Taskina EA, et al. Efficacy and safety of diacerein in patients with knee osteoarthritis. Modern Rheumatology. 2017;11(3):50–57. EDN: ZHNWTN doi: 10.14412/1996-7012-2017-3-50-57

[76] Алексеева Л.И., Кашеварова Н.Г., Таскина Е.А., и др. Эффективность и безопасность диацереина у пациентов с остеоартритом коленных суставов // Современная ревматология. 2017. Т. 11, № 3. С. 50–57. EDN: ZHNWTN doi: 10.14412/1996-7012-2017-3-50-57

[77] Mazurov VI, Gaidukova IZ, Bashkinov RA, et al. Asymptomatic hyperuricemia impact on the comorbid pathology course in patients with osteoarthritis and the possibility of its correction. RMJ. 2021;(6):56–62. EDN: GDWNGZ

[78] Мазуров В.И., Гайдукова И.З., Башкинов Р.А., и др. Влияние бессимптомной гиперурикемии на течение коморбидной патологии у пациентов с остеоартритом и возможности ее коррекции // РМЖ. 2021. Т. 29, № 6. С. 56–62. EDN: GDWNGZ

[79] Martynov AI, Naumov AV, Vertkin AL, et al. Management of patients with osteoarthritis with comorbidity in general medical practice: experts’ opinion based on evidence-based medicine. Lechaschi Vrach. 2015;(4):39–45. EDN: TPLKIL (In Russ.)

[80] Мартынов А.И., Наумов А.В., Верткин А.Л., и др. Ведение больных остеоартритом с коморбидностью в общей врачебной практике: мнение экспертов, основанное на доказательной медицине // Лечащий врач. 2015. № 4. С. 39–45. EDN: TPLKIL

[81] American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. Pain Med. 2009;10(6):1062–1083. doi: 10.1111/j.1526-4637.2009.00699.x

[82] American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons // Pain Med. 2009. Vol. 10, N 6. P. 1062–1083. doi: 10.1111/j.1526-4637.2009.00699.x

RIGHTS & PERMISSIONS

Eco-Vector