Эффективность, безопасность и перспективы применения комбинации нативного коллагена II типа, метилсульфонилметана, босвеллиевых кислот, витаминов С и D3 при остеоартрите коленных суставов: резолюция Совета экспертов

1. Резолюция консенсуса экспертов Российской Федерации по диагностике и лечению остеоартрита для врачей первичного звена. Терапия. 2022;8(5):119-28 [Resolution of the consensus of Russian Federation experts on the diagnosis and treatment of osteoarthritis for primary care physicians. Therapy. 2022;8(5):119-28 (in Russian)]. DOI:10.18565/therapy.2022.5.119-128
2. Алексеева Л.И., Наумов А.В. Ведение остеоартрита с коморбидностью в общей врачебной практике (клинические рекомендации). Доктор.Ру. 2017;5(134):51-69 [Alekseyeva LI, Naumov AV. Management of Comorbid Osteoarthritis: Clinical Recommendations for General Practitioners. Doctor.Ru. 2017;5(134):51-69 (in Russian)].
3. Veronese N, Cereda E, Maggi S, et al. Osteoarthritis and mortality: A prospective cohort study and systematic review with meta-analysis. Semin Arthritis Rheum. 2016;46(2):160-7. DOI:10.1016/j.semarthrit.2016.04.002
4. Taskina E, Kashevarova N, Telyshev K, et al. POS1129 Main predictors of structural progression in patients with metabolic phenotype of osteoarthritis. Annals of the Rheumatic Diseases. 2022;81(Suppl. 1):893.2-893. DOI:10.1136/annrheumdis-2022-eular.4358
5. Лила А.М., Алексеева Л.И., Таскина Е.А., и др. Клинические рекомендации (проект) по диагностике и лечению первичного остеоартрита для специалистов первичного звена (врачей-терапевтов, врачей общей практики). Терапия. 2023;9(1):7-22 [Lila AM, Alekseeva LI, Taskina EA, et al. Clinical guidelines (project) for the diagnostics and treatment of primary osteoarthritis for primary care specialists (general practitioners, therapists). Therapy. 2023;9(1):7-22 (in Russian)]. DOI:10.18565/therapy.2023.1.7-22
6. Мазуров В.И., Трофимова А.С., Трофимов Е.А. Факторы риска и некоторые аспекты патогенеза остеоартрита. Вестник СЗГМУ им. И.И. Мечникова. 2016;8(2):116-24 [Mazurov VI, Trofimova AS, Trofimov EA. Risk factors and some aspects of the pathogenesis of osteoarthritis. Bulletin of NWSMU named after. I.I. Mechnikov. 2016;8(2):116-24 (in Russian)].
7. Griffin TM, Scanzello CR. Innate inflammation and synovial macrophages in osteoarthritis pathophysiology. Clin Exp Rheumatol. 2019;37Suppl.120(5):57-63. PMID: 31621560
8. Беляева И.Б., Мазуров В.И., Трофимов Е.А. Анализ терапевтических преимуществ медленнодействующих симптоматических средств при остеоартрите: акцент на структурно-модифицирующее действие. Современная ревматология. 2021;15(6):117-23 [Belyaeva 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):117-23 (in Russian)]. DOI:10.14412/1996-7012-2021-6-117-123
9. Насонов Е.Л. Современная концепция аутоиммунитета в ревматологии. Научно-практическая ревматология. 2023;61(4):397-420 [Nasonov EL. Modern concept of autoimmunity in rheumatology. Rheumatology Science and Practice. 2023;61(4):397-420 (in Russian)]. DOI:10.47360/1995-4484-2023-397-420
10. Xie X, van Delft MAM, Shuweihdi F, et al. Auto-antibodies to post-translationally modified proteins in osteoarthritis. Osteoarthritis Cartilage. 2021;29(6):924-33. DOI:10.1016/j.joca.2021.03.008
11. Eyre D. Collagen of articular cartilage. Arthritis Res. 2002;4(1):30-5. DOI:10.1186/ar380
12. Ikeda T, Nakamura K, Kida T, Oku H. Possible roles of anti-type II collagen antibody and innate immunity in the development and progression of diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2022;260(2):387-403. DOI:10.1007/s00417-021-05342-6
13. Sohn HS, Choi JW, Jhun J, et al. Tolerogenic nanoparticles induce type II collagen-specific regulatory T cells and ameliorate osteoarthritis. Sci Adv. 2022;8(47):eabo5284. DOI:10.1126/sciadv.abo5284
14. Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage. 2020;28(5):555-61. DOI:10.1016/j.joca.2020.01.007
15. Faria AM, Weiner HL. Oral tolerance: therapeutic implications for autoimmune diseases. Clin Dev Immunol. 2006;13(2-4):143-57. DOI:10.1080/17402520600876804
16. Tong T, Zhao W, Wu YQ, et al. Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis. Inflamm Res. 2010;59(5):369-77. DOI:10.1007/s00011-009-0109-4
17. Martínez-Puig D, Costa-Larrión E, Rubio-Rodríguez N, Gálvez-Martín P. Collagen Supplementation for Joint Health: The Link between Composition and Scientific Knowledge. Nutrients. 2023;15(6):1332. DOI:10.3390/nu15061332
18. Nagler-Anderson C, Bober LA, Robinson ME, et al. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci USA. 1986;83(19):7443-6. DOI:10.1073/pnas.83.19.7443
19. Bagi CM, Berryman ER, Teo S, Lane NE. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA). Osteoarthritis Cartilage. 2017;25(12):2080-90. DOI:10.1016/j.joca.2017.08.013
20. Sahin E, Orhan C, Erten F, et al. The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats. Sci Rep. 2023;13(1):6499. DOI:10.1038/s41598-023-33763-2
21. Crowley DC, Lau FC, Sharma P, et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009;6(6):312-21. DOI:10.7150/ijms.6.312
22. Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14. DOI:10.1186/s12937-016-0130-8
23. Collagenase and rheumatoid arthritis. N Engl J Med. 1968;279(17):942-3. DOI:10.1056/NEJM196810242791710
24. Harris RB, Fonseca FLA, Sharp MH, Ottinger CR. Functional Characterization of Undenatured Type II Collagen Supplements: Are They Interchangeable? J Diet Suppl.
2022;19(6):717-32. DOI:10.1080/19390211.2021.1931621
25. Dai M, Liu X, Wang N, Sun J. Squid type II collagen as a novel biomaterial: Isolation, characterization, immunogenicity and relieving effect on degenerative osteoarthritis via inhibiting STAT1 signaling in pro-inflammatory macrophages. Mater Sci Eng C Mater Biol Appl. 2018;89:283-94. DOI:10.1016/j.msec.2018.04.021
26. Barnett ML, Kremer JM, St Clair EW, et al. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 1998;41(2):290-7. DOI:10.1002/1529-0131(199802)41:2<290::AID-ART13>3.0.CO;2-R
27. Barnett ML, Combitchi D, Trentham DE. A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum. 1996;39(4):623-8. DOI:10.1002/art.1780390413
28. Liu X, Machado GC, Eyles JP, et al. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167-75.
DOI:10.1136/bjsports-2016-097333
29. Sadigursky D, Sanches MM, Garcia NM, et al. Effectiveness of the use of non-hydrolysed type II collagen in the treatment of osteoarthritis: a systematic review and meta-analysis. Brazilian Journal of Health Review. 2023;6(1):1649-60. DOI:10.34119/bjhrv6n1-131
30. Gupta RC, Canerdy TD, Lindley J, et al. Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate. J Anim Physiol Anim Nutr (Berl). 2012;96(5):770-7. DOI:10.1111/j.1439-0396.2011.01166.x
31. Yu G, Xiang W, Zhang T, et al. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20(1):225. DOI:10.1186/s12906-020-02985-6
32. Cameron M, Chrubasik S. Oral herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2014;2014(5):CD002947. DOI: 10.1002/14651858.CD002947.pub2.
33. Ernst E. Frankincense: systematic review. BMJ. 2008;337:a2813. DOI:10.1136/bmj.a2813
34. Sengupta K, Alluri KV, Satish AR, et al. A double blind, randomized, placebo-controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther. 2008;10(4):R85. DOI:10.1186/ar2461
35. Дыдыкина И.С., Коваленко П.С., Коваленко А.А., Аболешина А.В. Значение неденатурированного коллагена для нормализации функции хрящевой ткани суставов. Медицинский совет. 2022;16(14):145-53 [Dydykina IS, Kovalenko PS, Kovalenko AA, Aboleshina AV. The importance of undenatured collagen for normalizing the function of joint cartilage tissue. Medical Council. 2022;16 (14):145-53 (in Russian)]. DOI:10.21518/2079-701X-2022-16-14-145-153
36. Мазуров В.И., Беляева И.Б., Трофимов Е.А., и др. Сравнение эффективности комбинации неденатурированного коллагена II типа, босвеллиевых кислот, метилсульфонилметана, витаминов С и D₃ и комбинации хондроитина сульфата и глюкозамина гидрохлорида в терапии первичного остеоартрита коленного сустава. Терапевтический архив. 2023;95(12):1141-50 [Mazurov VI, Belyaeva IB, Trofimov EA, et al. Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D₃ and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee joint. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(12):1141-50 (in Russian)]. DOI:10.26442/00403660.2023.12.202540
37. MacKay JW, Low SBL, Smith TO et al. Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis. Osteoarthritis Cartilage. 2018;26(9):1140-52. DOI:10.1016/j.joca.2017.11.018
38. Emanuel KS, Kellner LJ, Peters MJM, et al. The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2022;30(5):650-62. DOI:10.1016/j.joca.2021.10.016

________________________________________________

1. Resolution of the consensus of Russian Federation experts on the diagnosis and treatment of osteoarthritis for primary care physicians. Therapy. 2022;8(5):119-28 (in Russian). DOI:10.18565/therapy.2022.5.119-128
2. Alekseyeva LI, Naumov AV. Management of Comorbid Osteoarthritis: Clinical Recommendations for General Practitioners. Doctor.Ru. 2017;5(134):51-69 (in Russian).
3. Veronese N, Cereda E, Maggi S, et al. Osteoarthritis and mortality: A prospective cohort study and systematic review with meta-analysis. Semin Arthritis Rheum. 2016;46(2):160-7. DOI:10.1016/j.semarthrit.2016.04.002
4. Taskina E, Kashevarova N, Telyshev K, et al. POS1129 Main predictors of structural progression in patients with metabolic phenotype of osteoarthritis. Annals of the Rheumatic Diseases. 2022;81(Suppl. 1):893.2-893. DOI:10.1136/annrheumdis-2022-eular.4358
5. Lila AM, Alekseeva LI, Taskina EA, et al. Clinical guidelines (project) for the diagnostics and treatment of primary osteoarthritis for primary care specialists (general practitioners, therapists). Therapy. 2023;9(1):7-22 (in Russian). DOI:10.18565/therapy.2023.1.7-22
6. Mazurov VI, Trofimova AS, Trofimov EA. Risk factors and some aspects of the pathogenesis of osteoarthritis. Bulletin of NWSMU named after. I.I. Mechnikov. 2016;8(2):116-24 (in Russian).
7. Griffin TM, Scanzello CR. Innate inflammation and synovial macrophages in osteoarthritis pathophysiology. Clin Exp Rheumatol. 2019;37Suppl.120(5):57-63. PMID: 31621560
8. Belyaeva 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):117-23 (in Russian). DOI:10.14412/1996-7012-2021-6-117-123
9. Nasonov EL. Modern concept of autoimmunity in rheumatology. Rheumatology Science and Practice. 2023;61(4):397-420 (in Russian). DOI:10.47360/1995-4484-2023-397-420
10. Xie X, van Delft MAM, Shuweihdi F, et al. Auto-antibodies to post-translationally modified proteins in osteoarthritis. Osteoarthritis Cartilage. 2021;29(6):924-33. DOI:10.1016/j.joca.2021.03.008
11. Eyre D. Collagen of articular cartilage. Arthritis Res. 2002;4(1):30-5. DOI:10.1186/ar380
12. Ikeda T, Nakamura K, Kida T, Oku H. Possible roles of anti-type II collagen antibody and innate immunity in the development and progression of diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2022;260(2):387-403. DOI:10.1007/s00417-021-05342-6
13. Sohn HS, Choi JW, Jhun J, et al. Tolerogenic nanoparticles induce type II collagen-specific regulatory T cells and ameliorate osteoarthritis. Sci Adv. 2022;8(47):eabo5284. DOI:10.1126/sciadv.abo5284
14. Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage. 2020;28(5):555-61. DOI:10.1016/j.joca.2020.01.007
15. Faria AM, Weiner HL. Oral tolerance: therapeutic implications for autoimmune diseases. Clin Dev Immunol. 2006;13(2-4):143-57. DOI:10.1080/17402520600876804
16. Tong T, Zhao W, Wu YQ, et al. Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis. Inflamm Res. 2010;59(5):369-77. DOI:10.1007/s00011-009-0109-4
17. Martínez-Puig D, Costa-Larrión E, Rubio-Rodríguez N, Gálvez-Martín P. Collagen Supplementation for Joint Health: The Link between Composition and Scientific Knowledge. Nutrients. 2023;15(6):1332. DOI:10.3390/nu15061332
18. Nagler-Anderson C, Bober LA, Robinson ME, et al. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci USA. 1986;83(19):7443-6. DOI:10.1073/pnas.83.19.7443
19. Bagi CM, Berryman ER, Teo S, Lane NE. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA). Osteoarthritis Cartilage. 2017;25(12):2080-90. DOI:10.1016/j.joca.2017.08.013
20. Sahin E, Orhan C, Erten F, et al. The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats. Sci Rep. 2023;13(1):6499. DOI:10.1038/s41598-023-33763-2
21. Crowley DC, Lau FC, Sharma P, et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009;6(6):312-21. DOI:10.7150/ijms.6.312
22. Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14. DOI:10.1186/s12937-016-0130-8
23. Collagenase and rheumatoid arthritis. N Engl J Med. 1968;279(17):942-3. DOI:10.1056/NEJM196810242791710
24. Harris RB, Fonseca FLA, Sharp MH, Ottinger CR. Functional Characterization of Undenatured Type II Collagen Supplements: Are They Interchangeable? J Diet Suppl.
2022;19(6):717-32. DOI:10.1080/19390211.2021.1931621
25. Dai M, Liu X, Wang N, Sun J. Squid type II collagen as a novel biomaterial: Isolation, characterization, immunogenicity and relieving effect on degenerative osteoarthritis via inhibiting STAT1 signaling in pro-inflammatory macrophages. Mater Sci Eng C Mater Biol Appl. 2018;89:283-94. DOI:10.1016/j.msec.2018.04.021
26. Barnett ML, Kremer JM, St Clair EW, et al. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 1998;41(2):290-7. DOI:10.1002/1529-0131(199802)41:2<290::AID-ART13>3.0.CO;2-R
27. Barnett ML, Combitchi D, Trentham DE. A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum. 1996;39(4):623-8. DOI:10.1002/art.1780390413
28. Liu X, Machado GC, Eyles JP, et al. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167-75.
DOI:10.1136/bjsports-2016-097333
29. Sadigursky D, Sanches MM, Garcia NM, et al. Effectiveness of the use of non-hydrolysed type II collagen in the treatment of osteoarthritis: a systematic review and meta-analysis. Brazilian Journal of Health Review. 2023;6(1):1649-60. DOI:10.34119/bjhrv6n1-131
30. Gupta RC, Canerdy TD, Lindley J, et al. Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate. J Anim Physiol Anim Nutr (Berl). 2012;96(5):770-7. DOI:10.1111/j.1439-0396.2011.01166.x
31. Yu G, Xiang W, Zhang T, et al. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20(1):225. DOI:10.1186/s12906-020-02985-6
32. Cameron M, Chrubasik S. Oral herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2014;2014(5):CD002947. DOI: 10.1002/14651858.CD002947.pub2.
33. Ernst E. Frankincense: systematic review. BMJ. 2008;337:a2813. DOI:10.1136/bmj.a2813
34. Sengupta K, Alluri KV, Satish AR, et al. A double blind, randomized, placebo-controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther. 2008;10(4):R85. DOI:10.1186/ar2461
35. Dydykina IS, Kovalenko PS, Kovalenko AA, Aboleshina AV. The importance of undenatured collagen for normalizing the function of joint cartilage tissue. Medical Council. 2022;16 (14):145-53 (in Russian). DOI:10.21518/2079-701X-2022-16-14-145-153
36. Mazurov VI, Belyaeva IB, Trofimov EA, et al. Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D₃ and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee joint. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(12):1141-50 (in Russian). DOI:10.26442/00403660.2023.12.202540
37. MacKay JW, Low SBL, Smith TO et al. Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis. Osteoarthritis Cartilage. 2018;26(9):1140-52. DOI:10.1016/j.joca.2017.11.018
38. Emanuel KS, Kellner LJ, Peters MJM, et al. The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2022;30(5):650-62. DOI:10.1016/j.joca.2021.10.016

В.И. Мазуров*¹, Л.И. Алексеева^2,3, И.Б. Беляева¹, И.Г. Беленький^4,5, А.Л. Бурулев¹, И.З. Гайдукова¹, Е.В. Зонова⁶, О.В. Калюжин⁷, О.Б. Несмеянова⁸, Э.Н. Оттева⁹, Е.А. Трофимов<sup>1

1</sup>ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Россия;
²ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
³ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
⁴ГБУ «Санкт-Петербургский научно-исследовательский институт скорой помощи им. И.И. Джанелидзе», Санкт-Петербург, Россия;
⁵ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия;
⁶ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава России, Новосибирск, Россия;
⁷ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
⁸ГБУЗ «Челябинская областная клиническая больница», Челябинск, Россия;
⁹КГБОУ ДПО «Институт повышения квалификации специалистов здравоохранения» Минздрава Хабаровского края, Хабаровск, Россия
*maz.nwgmu@yandex.ru

________________________________________________

Vadim I. Mazurov*¹, Liudmila I. Alekseeva^2,3, Irina B. Belyaeva¹, Igor G. Belenkiy^4,5, Artem L. Burulev¹, Inna Z. Gaydukova¹, Elena V. Zonova⁶, Oleg V. Kalyuzhin⁷, Olga B. Nesmeyanova⁸, Elvira N. Otteva⁹, Evgeniy A. Trofimov<sup>1

1</sup>Mechnikov North-Western State Medical University, Saint Petersburg, Russia;
²Nasonova Research Institute of Rheumatology, Moscow, Russia;
³Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
⁴Janelidze Saint Petersburg Research Institute of Emergency Aid, Saint Petersburg, Russia;
⁵Saint Petersburg University, Saint Petersburg, Russia;
⁶Novosibirsk State Medical University, Novosibirsk, Russia;
⁷Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
⁸Chelyabinsk Regional Clinical Hospital, Chelyabinsk, Russia;
⁹Institute for Advanced Training of Health Care Professionals, Khabarovsk, Russia
*maz.nwgmu@yandex.ru