FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology

Advanced search

Modern achievements in pharmacotherapy of osteoarthritis based on endo- and phenotyping

Full Text:


The review of medical literature is devoted to modern data in the field of diagnosis and treatment of osteoarthritis using endo- and phenotyping. It includes the latest data on the epidemiology of osteoarthritis of different localizations, modern definitions and classifications of osteoarthritis endotypes and phenotypes, pathobiochemical patterns and pathomorphological parallels of disease phenotypes, new methodological approaches to the phenotyping of osteoarthritis (prognostic, prescriptive phenotyping, alternative methods), as well as modern advances in pharmacotherapy of the disease based on data from selected randomized controlled trials and meta-analyzes.

About the Authors

I. V. Sarvilina
Medical Centre “Novomeditsina”
Russian Federation

Irina V. Sarvilina – Dr. Med. Sc., Clinical Pharmacologist, Chief Physician

RSCI SPIN-code: 7308-6756

74 Sotsialisticheskaya, Rostov-on-Don 344002, Russia

O. A. Shavlovskaya
International University of Restorative Medicine
Russian Federation

Olga А. Shavlovskaya – Dr. Med. Sc., Professor, Chair of Organization of Medical Rehabilitation and Sanatorium-Resort Treatment

WoS ResearcherID: V-4470-2018; Scopus Author ID: 15124744300; RSCI SPIN-code: 5300-4282 

8/2 Furmannyy Al., Moscow 105062, Russia

O. A. Gromova
Institute of Pharmacoinformatics, Federal Research Center “Informatics and Management”, Russian Academy of Sciences; Big Data Storage and Analysis Center, Lomonosov Moscow State University
Russian Federation

Olga A. Gromova – Dr. Med. Sc., Professor, Research Supervisor; Leading Researcher

Scopus Author ID: 7003589812; WoS ResearcherID: J-4946-2017; RSCI SPIN-code: 6317-9833 

4 Vavilov Str., Moscow 2119333, Russia 

1 Leninskie Gory, Moscow 119991, Russia

A. V. Naumov
Pirogov Russian National Research Medical University
Russian Federation

Anton V. Naumov – Dr. Med. Sc., Professor, Chair of Diseases of Aging

16 Pervaya Leonov Str., Moscow 129226, Russia

M. N. Sharov
Yevdokimov Moscow State University of Medicine and Dentistry; Spasokukotskiy City Clinical Hospital
Russian Federation

Mikhail N. Sharov – Dr. Med. Sc., Professor, Chair of Nervous Diseases, Faculty of Dentistry; Head

Scopus Author ID: 57212167091; RSCI SPIN-code: 8506-6900 

10 bld. 2 Delegatskaya Str., Moscow 127473, Russia

21 Vuchetich Str., Moscow 127206, Russia

Yu. S. Prokofyeva
Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Yulia S. Prokofyeva – Postgraduate, Chair of Nervous Diseases, Faculty of Dentistry

Scopus Author ID: 57216579623; RSCI SPIN-code: 8789-3644

10 bld. 2 Delegatskaya Str., Moscow 127473, Russia


1. Balabanova R.M., Erdes S.F. Trends in the prevalence of rheumatic diseases in ICD-10 in the adult population of the Russian Federation over 2000–2010. Rheumatology Science and Practice. 2012; 50 (3): 10–2 (in Russ.).

2. Lawrence R.C., Felson D.T., Helmick C.G., et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008; 58 (1): 26–35.

3. Murphy L., Schwartz T.A., Helmick C.G., et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008; 59 (9): 1207–13.

4. Erdes Sh.F., Folomeeva O.M. Disability of the adult population of Russia due to rheumatic diseases. Russian Medical Journal. 2007; 15 (26): 1946–50 (in Russ.).

5. Litwic A., Edwards M.H., Dennison E.M., Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013; 105 (1): 185–99.

6. Neogi T., Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin N Am. 2013; 39 (1): 1–19.

7. Ishijima M., Watari T., Naito K., et al. Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis. Arthritis Res Ther. 2011; 13 (1): R22.

8. Zaitseva E.M., Alekseeva L.I., Nasonov E.L. Pathogenesis of osteoarthritis and substantiation of the use of strontium ranelate. Rheumatology Science and Practice. 2013; 51 (6): 696–702 (in Russ.).

9. Bartlett S.J., Ling S.M., Mayo N.E., et al. Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis. Arthritis Care Res (Hoboken). 2011; 63 (12): 1722–8.

10. Collins J.E., Katz J.N., Dervan E.E., Losina E. Trajectories and risk profiles of pain in persons with radiographic, symptomatic knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthritis Cartilage. 2014; 22 (5): 622–30.

11. Karsdal M.A., Bihlet A., Byrjalsen I., et al. OA phenotypes, rather than disease stage, drive structural progression – identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA. Osteoarthritis Cartilage. 2015; 23 (4): 550–8.

12. Bruyere O., Cooper C., Arden N., et al. Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis. Drugs Aging. 2015; 32 (3): 179–87.

13. Bannuru R.R., Osani M.C., Vaysbrot E.E., et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019; 27 (11): 1578–89.

14. Weinstein A.M., Rome B.N., Reichmann W.M., et al. Estimating the burden of total knee replacement in the United States. J Bone Joint Surg Am. 2013; 95 (5): 385–92.

15. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 389 (10053): 1545–602.

16. Losina E., Weinstein A., Reichmann W., et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res (Hoboken). 2013; 65 (5): 703–11.

17. 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): 1323–30.

18. WHO. Priority diseases and reasons for inclusion. Osteoarthritis. Available at: (accessed 16.08.2021).

19. Tang X., Wang S., Zhan S., et al. The prevalence of symptomatic knee osteoarthritis in China: results from the China Health and Retirement Longitudinal Study. Arthritis Rheumatol. 2016; 68 (3): 648–53.

20. Kodama R., Muraki S., Oka H., et al. Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: the third survey of the ROAD study. Mod Rheumatol. 2016; 26 (5): 767–73.

21. Park J.H., Hong J.Y., Han K., et al. Prevalence of symptomatic hip, knee, and spine osteoarthritis nationwide health survey analysis of an elderly Korean population. Medicine (Baltimore). 2017; 96 (12): e6372.

22. Holt H.L., Katz J.N., Reichmann W.M., et al. Forecasting the burden of advanced knee osteoarthritis over a 10-year period in a cohort of 60–64 year-old US adults. Osteoarthrritis Cartilage. 2011; 19 (1): 44–50.

23. Deshpande B.R., Katz J.N., Solomon D.H., et al. Number of persons with symptomatic knee osteoarthritis in the US: impact of race and ethnicity, age, sex, and obesity. Arthritis Care Res (Hoboken). 2016; 68 (12): 1743–50.

24. Moss A.S., Murphy L.B., Helmick C.G., et al. Annual incidence rates of hip symptoms and three hip OA outcomes from a U.S. population based cohort study: the Johnston County Osteoarthritis Project. Osteoarthrritis Cartilage. 2016; 24 (9): 1518–27.

25. Reyes C., Leyland K.M., Peat G., et al. Association between overweight and obesity and risk of clinically diagnosed knee, hip, and hand osteoarthritis: a population-based cohort study. Arthritis Rheumatol. 2016; 68 (8): 1869–75.

26. Leyland K.M., Judge A., Javaid M.K., et al. Obesity and the relative risk of knee replacement surgery in patients with knee osteoarthritis: a prospective cohort study. Arthritis Rheumatol. 2016; 68 (4): 817–25.

27. Suh D.H., Han K.D., Hong J.Y., et al. Body composition is more closely related to the development of knee osteoarthritis in women than men: a cross-sectional study using the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1, 2). Osteoarthritis Cartilage. 2016; 24 (4): 605–11.

28. Dubé C.E., Liu S.H., Driban J.B., et al. The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016; 24 (3): 465–72.

29. Bevis M., Marshall M., Rathod T., Roddy E. The association between gout and radiographic hand, knee and foot osteoarthritis: a cross sectional study. BMC Musculoskelet Disord. 2016; 17: 169.

30. Ding X., Zeng C., Wei J., et al. The associations of serum uric acid level and hyperuricemia with knee osteoarthritis. Rheumatol Int. 2016; 36 (4): 567–73.

31. Veronese N., Trevisan C., De Rui M., et al. Association of osteoarthritis with increased risk of cardiovascular diseases in the elderly: findings from the Progetto Veneto Anziano study cohort. Arthritis Rheumatol. 2016; 68 (5): 1136–44.

32. Chung W.S., Lin H.H., Ho F.M., et al. Risks of acute coronary syndrome in patients with osteoarthritis: a nationwide population-based cohort study. Clin Rheumatol. 2016; 35 (11): 2807–13.

33. Kluzek S., Sanchez-Santos M.T., Leyland K.M., et al. Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women. Ann Rheum Dis. 2016; 75 (10): 1749–56.

34. Felson D.T. Identifying different osteoarthritis phenotypes through epidemiology. Osteoarthritis Cartilage. 2010; 18 (5): 601–4.

35. Van Spil W.E., Kubassovab О., Boesenb М., et al. Osteoarthritis phenotypes and novel therapeutic targets. Biochem Pharmacol. 2019; 165: 41–8.

36. Castañeda S., Roman-Blas J.A., Largo R., Herrero-Beaumont G. Osteoarthritis: a progressive disease with changing phenotypes. Rheumatology (Oxford). 2014; 53 (1): 1–3.

37. Waarsing J.H., Bierma-Zeinstra S.M., Weinans H. Distinct subtypes of knee osteoarthritis: data from the Osteoarthritis Initiative. Rheumatology (Oxford). 2015; 54 (9): 1650–8.

38. Karsdal M.A., Christiansen C., Ladel C., et al. Osteoarthritis – a case for personalized health care? Osteoarthritis Cartilage. 2014; 22 (1): 7–16.

39. Lieberthal J., Sambamurthy N., Scanzello C.R. Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2015; 23 (11): 1825–34.

40. Li G., Yin J., Gao J., et al. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther. 2013; 15 (6): 223.

41. Vlychou M., Koutroumpas A., Malizos K., Sakkas L.I. Ultrasonographic evidence of inflammation is frequent in hands of patients with erosive osteoarthritis. Osteoarthritis Cartilage. 2009; 17 (10): 1283–7.

42. Mancarella L., Addimanda O., Pelotti P., et al. Ultrasound detected inflammation is associated with the development of new bone erosions in hand osteoarthritis: a longitudinal study over 3.9 years. Osteoarthritis Cartilage. 2015; 23 (11): 1925–32.

43. Kortekaas M.C., Kwok W.Y., Reijnierse M., Kloppenburg M. Inflammatory ultrasound features show independent associations with progression of structural damage after over 2 years of follow-up in patients with hand osteoarthritis. Ann Rheum Dis. 2015; 74 (9): 1720–4.

44. Baker K., Grainger A., Niu J., et al. Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann Rheum Dis. 2010; 69 (10): 1779–83.

45. Felson D., Niu J., Neogi T., et al. Synovitis and the risk of knee osteoarthritis: the MOST Study. Osteoarthritis Cartilage. 2016; 24 (3): 458–64.

46. Dell’Isola A., Steultjens M. Classification of patients with knee osteoarthritis in clinical phenotypes: data from the osteoarthritis initiative. PLoS One. 2018; 13 (1): e0191045.

47. Herrero-Beaumont G., Roman-Blas J., Bruyère O., et al. Clinical settings in knee osteoarthritis: pathophysiology guides treatment. Maturitas. 2017; 96: 54–7.

48. Jameson J.L., Longo D.L. Precision medicine – personalized, problematic, and promising. N Engl J Med. 2015; 372 (23): 2229–34.

49. Hunter D.J., Altman R.D., Cicuttini F., et al. OARSI Clinical Trials Recommendations: knee imaging in clinical trials in osteoarthritis. Osteoarthritis Cartilage. 2015; 23 (5): 698–715.

50. Okano T., Filippucci E., Di Carlo M., et al. Ultrasonographic evaluation of joint damage in knee osteoarthritis: feature-specific comparisons with conventional radiography. Rheumatology (Oxford). 2016; 55 (11): 2040–9.

51. Mobasheri A., Henrotin Y. Biomarkers of (osteo)arthritis. Biomarkers. 2015; 20 (8): 513–8.

52. Kraus V.B., Burnett B., Coindreau J., et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis Cartilage. 2011; 19 (5): 515–42.

53. Kraus V.B., Blanco F.J., Englund M., et al. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthritis Cartilage. 2015; 23 (8): 1233–41.

54. Orlowsky E.W., Kraus V.B. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol. 2015; 42 (3): 363–71.

55. Steinberg J., Ritchie G.R., Roumeliotis T.I., et al. Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis. Sci Rep. 2017; 7 (1): 8935.

56. Sanchez C., Bay-Jensen A.C., Pap T., et al. Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis. Osteoarthritis Cartilage. 2017; 25 (8): 1199–209.

57. Collins J.A., Diekman B.O., Loeser R.F. Targeting aging for disease modification in osteoarthritis. Curr Opin Rheumatol. 2018; 30 (1): 101–7.

58. Jeon O.H., Kim C., Laberge R.M., et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med. 2017; 23 (6): 775–81.

59. Mobasheri A., Matta C., Zákány R., Musumeci G. Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas. 2015; 80 (3): 237–44.

60. van der Kraan P., Matta C., Mobasheri A. Age-related alterations in signaling pathways in articular chondrocytes: implications for the pathogenesis and progression of osteoarthritis – a mini-review. Gerontology. 2017; 63 (1): 29–35.

61. Rahmati M., Mobasheri A., Mozafari M. Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, current prospects, and future challenges. Bone. 2016; 85: 81–90.

62. Sakkas L.I., Platsoucas C.D. The role of T cells in the pathogenesis of osteoarthritis. Arthritis Rheum. 2007; 56 (2): 409–24.

63. Sellam J., Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010; 6 (11): 625–35.

64. Kaukinen P., Podlipská J., Guermazi A., et al. Associations between MRI-defined structural pathology and generalized and localized knee pain – the Oulu Knee Osteoarthritis study. Osteoarthritis Cartilage. 2016; 24 (9): 1565–76.

65. Koski J.M., Saarakkala S., Helle M., et al. Power Doppler ultrasonography and synovitis: correlating ultrasound imaging with histopathological findings and evaluating the performance of ultrasound equipments. Ann Rheum Dis. 2006; 65 (12): 1590–5.

66. Attur M., Belitskaya-Lévy I., Oh C., et al. Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011; 63 (7): 1908–17.

67. Mobasheri A., Rayman M., Gualillo O., et al. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2017; 13 (5): 302–11.

68. Roze R.H., Bierma-Zeinstra S.M., Agricola R., et al. Differences in MRI features between two different osteoarthritis subpopulations: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016; 24 (5): 822–6.

69. Sniekers Y.H., Weinans H., Bierma-Zeinstra S.M., et al. Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment – a systematic approach. Osteoarthritis Cartilage. 2008; 16 (5): 533–41.

70. Tanamas S.K., Wijethilake P., Wluka A.E., et al. Sex hormones and structural changes in osteoarthritis: a systematic review. Maturitas. 2011; 69 (2): 141–56.

71. Cardoso J.S., Riley J.L. 3rd, Glover T., et al. Experimental pain phenotyping in community-dwelling individuals with knee osteoarthritis. Pain. 2016; 157 (9): 2104–14.

72. Frey-Law L.A., Bohr N.L., Sluka K.A., et al. Pain sensitivity profiles in patients with advanced knee osteoarthritis. Pain. 2016; 157 (9): 1988–99.

73. Osgood E., Trudeau J.J., Eaton T.A., et al. Development of a bedside pain assessment kit for the classification of patients with osteoarthritis. Rheumatol Int. 2015; 35 (6): 1005–13.

74. Carlesso L.C., Neogi T. Identifying pain susceptibility phenotypes in knee osteoarthritis. Clin Exp Rheumatol. 2019; 37 Suppl. 120 (5): 96–9.

75. Carlesso L.C., Segal N.A., Frey-Law L., et al. Pain susceptibility phenotypes in those free of knee pain with or at risk of knee osteoarthritis: the multicenter osteoarthritis study. Arthritis Rheumatol. 2019; 71 (4): 542–9.

76. Egsgaard L.L., Eskehave T.N., Bay-Jensen A.C., et al. Identifying specific profiles in patients with different degrees of painful knee osteoarthritis based on serological biochemical and mechanistic pain biomarkers: a diagnostic approach based on cluster analysis. Pain. 2015; 156 (1): 96–107.

77. Goldring M., Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011; 23 (5): 471–8.

78. Bijlsma J.W., Berenbaum F., Lafeber F.P. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011; 377 (9783): 2115–26.

79. Guermazi A., Roemer F.W., Hayashi D. Imaging of osteoarthritis: update from a radiological perspective. Curr Opin Rheumatol. 2011; 23 (5): 484–91.

80. Sellam J., Berenbaum F. Clinical features of osteoarthritis. In: Firestein G.S., Budd R.C., Harris E.D. Jr., et al. (Eds.) Kelley’s textbook of rheumatology. Philadelphia: Elsevier Inc.; 2008: 1547–61.

81. Ayral X., Pickering E.H., Woodworth T.G., et al. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis – results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage. 2005; 13 (5): 361–7.

82. Roemer F.W., Guermazi A., Felson D.T., et al. Presence of MRI detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study. Ann Rheum Dis. 2011; 70 (10): 1804–9.

83. Pearle A.D., Scanzello C.R., George S., et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage. 2007; 15 (5): 516–23.

84. Stürmer T., Brenner H., Koenig W., Günther K.P. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis. 2004; 63 (2): 200–5.

85. Blom A.B., van Lent P.L., Holthuysen A.E., et al. Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis. Osteoarthritis Cartilage. 2004; 12 (8): 627–35.

86. Blom A.B., van Lent P.L., Libregts S., et al. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2007; 56 (1): 147–57.

87. Hussein M.R., Fathi N.A., El-Din A.M., et al. Alterations of the CD4(+), CD8 (+) T cell subsets, interleukins-1beta, IL-10, IL-17, tumor necrosis factoralpha and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: preliminary observations. Pathol Oncol Res. 2008; 14 (3): 321–8.

88. Haywood L., McWilliams D.F., Pearson C.I., et al. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 2003; 48 (8): 2173–7.

89. Mapp P.I., Walsh D.A. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol. 2012; 8 (7): 390–8.

90. E X., Cao Y., Meng H., et al. Dendritic cells of synovium in experimental model of osteoarthritis of rabbits. Cell Physiol Biochem. 2012; 30 (1): 23–32.

91. Suurmond J., Dorjée A., Boon M.R., et al. Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther. 2011; 13 (5): R150.

92. Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002; 111 (7): 927–30.

93. Kim H.A., Cho M.L., Choi H.Y., et al. The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis Rheum. 2006; 54 (7): 2152–63.

94. García-Arnandis I., Guillén M.I., Gomar F., et al. High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes. Arthritis Res Ther. 2010; 12 (4): R165.

95. Scanzello C.R., Plaas A., Crow M.K. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol. 2008; 20 (5): 565–72.

96. van Lent P.L., Blom A.B., Schelbergen R.F., et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheum. 2012; 64 (5): 1466–76.

97. Sohn D.H., Sokolove J., Sharpe O., et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll like receptor 4. Arthritis Res Ther. 2012; 14 (1): R7.

98. Nair A., Kanda V., Bush-Joseph C., et al. Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to toll-like receptor 4 and toll-like receptor 2 ligands via soluble CD14. Arthritis Rheum. 2012; 64 (7): 2268–77.

99. Scanzello C.R., Umoh E., Pessler F., et al. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis Cartilage. 2009; 17 (8): 1040–8.

100. Wang Q., Rozelle A.L., Lepus C.M., et al. Identification of a central role for complement in osteoarthritis. Nat Med. 2011; 17 (12): 1674–9.

101. MacMullan P., McMahon G., McCarthy G. Detection of basic calcium phosphate crystals in osteoarthritis. Joint Bone Spine. 2011; 78 (4): 358–63.

102. Rosenthal A.K. Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol. 2011; 23 (2): 170–3.

103. Bougault C., Gosset M., Houard X., et al. Stress-induced cartilage degradation does not depend on NLRP3 inflammasome in osteoarthritis. Arthritis Rheum. 2012; 64 (12): 3972–81.

104. Denoble A.E., Huffman K.M., Stabler T.V., et al. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci USA. 2011; 108 (5): 2088–93.

105. Martinon F., Pétrilli V., Mayor A., et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440 (7081): 237–41.

106. Attur M., Statnikov A., Aliferis C., et al. Inflammatory genomic and plasma biomarkers predict progression of symptomatic knee OA (SKOA). Osteoarthritis Cartilage. 2012; 20 (Suppl. 1): S34–5.

107. Fernández-Puente P., Mateos J., Fernández-Costa C., et al. Identification of a panel of novel serum osteoarthritis biomarkers. J Proteome Res. 2011; 10 (11): 5095–101.

108. Bowes M.A., Vincent G.R., Wolstenholme C.B., Conaghan P.G. A novel method for bone area measurement provides new insights into osteoarthritis and its progression. Ann Rheum Dis. 2015; 74 (3): 519–25.

109. Pottie P., Presle N., Terlain B., et al. Obesity and osteoarthritis: more complex than predicted! Ann Rheum Dis. 2006; 65 (11): 1403–5.

110. Yusuf E., Nelissen R.G., Ioan-Facsinay A., et al. Association between weight or body mass index and hand osteoarthritis: a systematic review. Ann Rheum Dis. 2010; 69 (4): 761–5.

111. Gabay O., Berenbaum F. Adipokines in arthritis: new kids on the block. Curr Rheumatol Rev. 2009; 5 (4): 226–32.

112. Gómez R., Conde J., Scotece M., et al. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol. 2011; 7 (9): 528–36.

113. Gosset M., Berenbaum F., Salvat C., et al. Crucial role of visfatin/ pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum. 2008; 58 (5): 1399–409.

114. Puenpatom R.A., Victor T.W. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med. 2009; 121 (6): 9–20.

115. Sowers M., Karvonen-Gutierrez C.A., Palmieri-Smith R., et al. Knee osteoarthritis in obese women with cardiometabolic clustering. Arthritis Rheum. 2009; 61 (10): 1328–36.

116. Hoeven T.A., Kavousi M., Clockaerts S., et al. Association of atherosclerosis with presence and progression of osteoarthritis: the Rotterdam Study. Ann Rheum Dis. 2012; 72 (5): 646–51.

117. Tedgui A., Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006; 86 (2): 515–81.

118. Filková M., Lisková M., Hulejová H., et al. Increased serum adiponectin levels in female patients with erosive compared with non erosive osteoarthritis. Ann Rheum Dis. 2009; 68 (2): 295–6.

119. de Boer T.N., van Spil W.E., Huisman A.M., et al. Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis Cartilage. 2012; 20 (8): 846–53.

120. Clockaerts S., Bastiaansen-Jenniskens Y.M., Runhaar J., et al. The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthritis Cartilage. 2010; 18 (7): 876–82.

121. Distel E., Cadoudal T., Durant S., et al. The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. Arthritis Rheum. 2009; 60 (11): 3374–7.

122. Kyrkanides S., Tallents R.H., Miller J.N., et al. Osteoarthritis accelerates and exacerbates Alzheimer’s disease pathology in mice. J Neuroinflammation. 2011; 8: 112.

123. Licastro F., Candore G., Lio D., et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing. 2005; 2 (1): 8.

124. Loeser R.F. Aging and osteoarthritis. Curr Opin Rheumatol. 2011; 23 (5): 492–6.

125. Coppé J.P., Desprez P.Y., Krtolica A., Campisi J. The senescence associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5: 99–118.

126. Campisi J., Andersen J.K., Kapahi P., Melov S. Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol. 2011; 21 (6): 354–9.

127. Forsyth C.B., Cole A., Murphy G., et al. Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli. J Gerontol A Biol Sci Med Sci. 2005; 60 (9): 1118–24.

128. Lotz M., Loeser R.F. Effects of aging on articular cartilage homeostasis. Bone. 2012; 51 (2): 241–8.

129. Rasheed Z., Akhtar N., Haqqi T.M. Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end productmediated activation of mitogen-activated protein kinases and nuclear factor-κB in human osteoarthritis chondrocytes. Rheumatology. 2011; 50 (5): 838–51.

130. Tankó L., Søndergaard B.C., Oestergaard S., et al. An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage. Climacteric. 2008; 11 (1): 4–16.

131. Richette P., Dumontier M.F., Tahiri K., et al. Oestrogens inhibit interleukin 1beta-mediated nitric oxide synthase expression in articular chondrocytes through nuclear factor-kappa B impairment. Ann Rheum Dis. 2007; 66 (3): 345–50.

132. Pfeilschifter J., Köditz R., Pfohl M., Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr Rev. 2002; 23 (1): 90–119.

133. Guilak F. Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 2011; 25 (6): 815–23.

134. Chauffier K., Laiguillon M.C., Bougault C., et al. Induction of the chemokine IL-8/Kc by the articular cartilage: possible influence on osteoarthritis. Joint Bone Spine. 2012; 79 (6): 604–9.

135. Gosset M., Berenbaum F., Levy A., et al. Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is a mechanosensitive gene. Arthritis Res Ther. 2006; 8 (4): R135.

136. Issa R.I., Griffin T.M. Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation. Pathobiol Aging Age Relat Dis. 2012; 2 (2012).

137. Sanchez C., Pesesse L., Gabay O., et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression. Arthritis Rheum. 2012; 64 (4): 1193–203.

138. Stevens A.L., Wishnok J.S., White F.M., et al. Mechanical injury and cytokines cause loss of cartilage integrity and upregulate proteins associated with catabolism, immunity, inflammation, and repair. Mol Cell Proteomics. 2009; 8 (7): 1475–89.

139. Berenbaum F. Signaling transduction: target in osteoarthritis. Curr Opin Rheumatol. 2004; 16 (5): 616–22.

140. Bierma-Zeinstra S.M., Verhagen A.P. Osteoarthritis subpopulations and implications for clinical trial design. Arthritis Res Ther. 2011; 13 (2): 213.

141. van Meurs J.B., Uitterlinden A.G. Osteoarthritis year 2012 in review: genetics and genomics. Osteoarthritis Cartilage. 2012; 20 (12): 1470–6.

142. van der Esch M., Knoop J., van der Leeden M., et al. Clinical phenotypes in patients with knee osteoarthritis: a study in the Amsterdam osteoarthritis cohort. Osteoarthritis Cartilage. 2015; 23 (4): 544–9.

143. Petersen K.K., Olesen A.E., Simonsen O., Arendt-Nielsen L. Mechanistic pain profiling as a tool to predict the efficacy of 3-week nonsteroidal anti-inflammatory drugs plus paracetamol in patients with painful knee osteoarthritis. Pain. 2019; 160 (2): 486–92.

144. Cai P., Jiang T., Li B., et al. Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profiles of human joint fibroblast-like synoviocytes. Cell Biochem Funct. 2019; 37 (1): 31–41.

145. Haraden C.A., Huebner J.L., Hsueh M.F., Byers Kraus V. Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation. Arthritis Res Ther. 2019; 21 (1): 146.

146. Conaghan P.G., Tennant A., Peterfy C.G., et al. Examining a whole organ magnetic resonance imaging scoring system for osteoarthritis of the knee using Rasch analysis. Osteoarthritis Cartilage. 2006; 14 (Suppl. A): A116–21.

147. Beavers K.M., Beavers D.P., Newman J.J., et al. Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis Cartilage. 2015; 23 (2): 249–56.

148. Daghestani H.N., Pieper C.F., Kraus V.B. Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis. Arthritis Rheumatol. 2015; 67 (4): 956–65.

149. Huebner J.L., Bay-Jensen A.C., Huffman K.M., et al. Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis. Arthritis Rheumatol. 2014; 66 (9): 2440–9.

150. Van Spil W.E., Nair S.C., Kinds M.B., et al. Systemic biochemical markers of joint metabolism and inflammation in relation to radiographic parameters and pain of the knee: data from CHECK, a cohort of early osteoarthritis subjects. Osteoarthritis Cartilage. 2015; 23 (1): 48–56.

151. Deveza L.A., Downie A., Tamez-Pena J.G., et al. Trajectories of femorotibial cartilage thickness among persons with or at risk of knee osteoarthritis: development of a prediction model to identify progressors. Osteoarthritis Cartilage. 2019; 27 (2): 257–65.

152. Collins J.E., Katz J.N., Losina E. Identifying rapid structural disease progression in knee osteoarthritis. American College of Reumatology. Meeting abstracts. Available at: (accessed 16.08.2021).

153. LaValley M.P., Lo G.H., Price L.L., et al. Development of a clinical prediction algorithm for knee osteoarthritis structural progression in a cohort study: value of adding measurement of subchondral bone density. Arthritis Res Ther. 2017; 19 (1): 95.

154. Liukkonen M.K., Mononen M.E., Klets O., et al. Simulation of subject-specific progression of knee osteoarthritis and comparison to experimental follow-up data: data from the Osteoarthritis Initiative. Sci Rep. 2017; 7: 9177.

155. Zhang W., McWilliams D.F., Ingham S.L., et al. Nottingham knee osteoarthritis risk prediction models. Ann Rheumatic Dis. 2011; 70 (9): 1599–604.

156. Riddle D.L., Stratford P.W., Perera R.A. The incident tibiofemoral osteoarthritis with rapid progression phenotype: development and validation of a prognostic prediction rule. Osteoarthritis Cartilage. 2016; 24 (12): 2100–7.

157. Deveza L.A., Melo L., Yamato T.P., et al. Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. Osteoarthritis Cartilage. 2017; 25 (12): 1926–41.

158. Niu J., Felson D.T., Neogi T., et al. Patterns of coexisting lesions detected on magnetic resonance imaging and relationship to incident knee osteoarthritis: the multicenter osteoarthritis study. Arthritis Rheumatol. 2015; 67 (12): 3158–65.

159. Ornetti P., Brandt K., Hellio-Le Graverand M.P., et al. OARSI OMERACT definition of relevant radiological progression in hip/knee osteoarthritis. Osteoarthritis Cartilage. 2009; 17 (7): 856–63.

160. Loeser R.F., Pathmasiri W., Sumner S.J., et al. Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study. Osteoarthritis Cartilage. 2016; 24 (8): 1479–86.

161. Kraus V.B., Collins J.E., Hargrove D., et al. Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium. Ann Rheum Dis. 2017; 76 (1): 186–95.

162. Paterson K.L., Kasza J., Bennell K.L., et al. Moderators and mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis: an exploratory analysis of the SHARK randomised controlled trial. Osteoarthritis Cartilage. 2018; 26 (2): 227–35.

163. van Middelkoop M., Arden N.K., Atchia I., et al. The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids. Osteoarthritis Cartilage. 2016; 24 (7): 1143–52.

164. Laslett L.L., Doré D.A., Quinn S.J., et al. Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012; 71 (8): 1322–8.

165. Hochberg M.C. Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies. Osteoarthritis Cartilage. 2015; 23 (Suppl. 1): S18–21.

166. Hu T., Oksanen K., Zhang W., et al. An evolutionary learning and network approach to identifying key metabolites for osteoarthritis. PLoS Comput Biol. 2018; 14 (3): e1005986.

167. Lazzarini N., Runhaar J., Bay-Jensen A.C., et al. A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women. Osteoarthritis Cartilage. 2017; 25 (12): 2014–21.

168. Mobasheri A., van Spil W.E., Budd E., et al. Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes. Curr Opin Rheumatol. 2019; 31 (1): 80–9.

169. Nelson A.E., Fang F., Arbeeva L., et al. A machine learning approach to knee osteoarthritis phenotyping: data from the FNIH Biomarkers Consortium. Osteoarthritis Cartilage. 2019; 27 (7): 994–1001.

170. Hastie T., Tibshirani R., Friedman J. The elements of statistical learning: data mining, inference, and prediction. 2nd ed. Springer; 2009.

171. Bastick A.N., Wesseling J., Damen J., et al. Defining knee pain trajectories in early symptomatic knee osteoarthritis in primary care: 5-year results from a nationwide prospective cohort study (CHECK). Br J Gen Pract. 2016; 66 (642): e32–9.

172. Wang H., Marron J.S. Object oriented data analysis: sets of trees. Ann Stat. 2007; 35 (5): 1849–73.

173. An H., Marron J.S., Schwartz T.A., et al. Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women. Osteoarthritis Cartilage. 2016; 24 (4): 640–6.

174. Marron J.S., Todd M.J., Ahn J. Distance-weighted discrimination. J Am Stat Assoc. 2007; 102 (480): 1267–71.

175. Wei S., Lee C., Wichers L., Marron J.S. Direction-projection permutation for high-dimensional hypothesis tests. J Comput Graph Stat. 2016; 25 (2): 549–69.

176. Chevalier X., Goupille P., Beaulieu A.D., et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, doubleblind, placebo-controlled study. Arthritis Rheum. 2009; 61 (3): 344–52.

177. Bennell K.L., Ahamed Y., Bryant C., et al. A physiotherapist-delivered integrated exercise and pain coping skills training intervention for individuals with knee osteoarthritis: a randomised controlled trial protocol. BMC Musculoskelet Disord. 2012; 13: 129.

178. Kroon F.B., van der Burg L.R., Buchbinder R., et al. Self-management education programmes for osteoarthritis. Cochrane Database Syst Rev. 2014; 15 (1): CD008963.

179. Coleman S., Briffa N.K., Carroll G., et al. A randomised controlled trial of a selfmanagement education program for osteoarthritis of the knee delivered by health care professionals. Arthritis Res Ther. 2012; 14 (1): R21.

180. Driban J.B., Boehret S.A., Balasubramanian E., et al. Medication and supplement use for managing joint symptoms among patients with knee and hip osteoarthritis: a cross-sectional study. BMC Musculoskelet Disord. 2012; 13: 47.

181. Snijders G.F., van den Ende C.H., van den Bemt B.J., et al. Treatment outcomes of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis in daily clinical practice. Clin Exp Rheumatol. 2012; 30 (2): 164–70.

182. Maillefert J.F., Roy C., Cadet C., et al. Factors influencing surgeons' decisions in the indication for total joint replacement in hip osteoarthritis in real life. Arthritis Rheum. 2008; 59 (2): 255–62.

183. Jenkinson C.M., Doherty M., Avery A.J., et al. Effects of dietary intervention and quadriceps strengthening exercises on pain and function in overweight people with knee pain: randomized controlled trial. BMJ. 2009; 18 (339): b3170.

184. Gleicher Y., Croxford R., Hochman J., Hawker G. A prospective study of mental health care for comorbid depressed mood in older adults with painful osteoarthritis. BMC Psychiatry. 2011; 11: 147.

185. Iyengar R.L., Gandhi S., Aneja A., et al. NSAIDs are associated with lower depression scores in patients with osteoarthritis. Am J Med. 2013; 126 (11): 1017.e11–18.

186. Atukorala I., Makovey J., Lawler L., et al. Is there a dose-response relationship between weight loss and symptom improvement in persons with knee osteoarthritis? Arthritis Care Res (Hoboken). 2016; 68 (8): 1106–14.

187. King W.C., Chen J.Y., Belle S.H., et al. Change in pain and physical function following bariatric surgery for severe obesity. JAMA. 2016; 315 (13): 1362–71.

188. Bartels E.M., Juhl C.B., Christensen R., et al. Aquatic exercise for the treatment of knee and hip osteoarthritis. Cochrane Database Syst Rev. 2016; 3: Cd005523.

189. Verbruggen G., Wittoek R., Vander Cruyssen B., Elewaut D. Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification. Ann Rheum Dis. 2012; 71 (6): 891–8

190. Maksymowych W.P., Russell A.S., Chiu P., et al. Targeting tumor necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee. Arthritis Res Ther. 2012; 14 (5): R206.

191. Vaysbrot E.E., Osani M.C., Musetti M.C., et al. Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2018; 26 (2): 154–64.

192. Aitken D., Laslett L.L., Cai G., et al. A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients – ZAP2. BMC Musculoskelet Disord. 2018; 19 (1): 217.

193. Pelletier J.P., Roubille C., Raynauld J.P., et al. Disease-modifying effect of strontium ranelate in a subset of patients from the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions protects against cartilage loss. Ann Rheum Dis. 2015; 74 (2): 422–9.

194. Kloppenburg M., Ramonda R., Bobacz K., et al. Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2018; 77 (12): 1757–64.

195. Fleischmann R.M., Bliddal H., Blanco F.J., et al. SAT0575 Safety and efficacy of lutikizumab (ABT-981), an anti-interleukin-1 alpha/beta dual variable domain (DVD) immunoglobulin, in subjects with knee osteoarthritis: results from the randomised, double-blind, placebo controlled, parallel-group phase 2 trial. Ann Rheumat Dis. 2018; 77 (Suppl. 2): 1141–2.

196. Bhala N., Emberson J., Merhi A., et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta analyses of individual participant data from randomised trials. Lancet. 2013; 382 (9894): 769–79.

197. da Costa B.R., Reichenbach S., Keller N., et al. Effectiveness of non steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017; 390 (10090): e21–33.

198. Moore N., Salvo F., Duong M., Gulmez S.E. Does paracetamol still have a future in osteoarthritis? Lancet. 2016; 387 (10033): 2065–6.

199. Essex M.N., O’Connell M.A., Behar R., Bao W. Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebocontrolled study. Int J Rheum Dis. 2016; 19 (3): 262–70.

200. Vanderstraeten G., Lejeune T.M., Piessevaux H., et al. Gastrointestinal risk assessment in patients requiring non-steroidal anti-inflammatory drugs for osteoarthritis: the GIRANO study. J Rehabil Med. 2016; 48 (8): 705–10.

201. Derry S., Conaghan P., Da Silva J.A., et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2016; 4 (4): CD007400.

202. Yataba I., Otsuka N., Matsushita I., et al. Efficacy of S-flurbiprofen plaster in knee osteoarthritis treatment: results from a phase III, randomized, active-controlled, adequate, and well-controlled trial. Mod Rheumatol. 2017; 27 (1): 130–6.

203. Arden N.K., Cro S., Sheard S., et al. The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial. Osteoarthritis Cartilage. 2016; 24 (11): 1858–66.

204. McCabe P.S., Maricar N., Parkes M.J., et al. The efficacy of intra articular steroids in hip osteoarthritis: a systematic review. Osteoarthritis Cartilage. 2016; 24 (9): 1509–17.

205. Zhang Q., Zhang T. Effect on pain and symptoms of aspiration before hyaluronan injection for knee osteoarthritis: a prospective, randomized, single-blind study. Am J Phys Med Rehabil. 2016; 95 (5): 366–71.

206. Altman R., Fredericson M., Bhattacharyya S.K., et al. Association between hyaluronic acid injections and tie-to-total knee replacement surgery. J Knee Surg. 2016; 29 (7): 564–70.

207. Tammachote N., Kanitnate S., Yakumpor T., Panichkul P. Intraarticular, single-shot Hylan G-F 20 hyaluronic acid injection compared with corticosteroid in knee osteoarthritis: a doubleblind, randomized controlled trial. J Bone Jt Surg Am. 2016; 98 (11): 885–92.

208. Bisicchia S., Bernardi G., Tudisco C. HYADD 4 versus methylprednisolone acetate in symptomatic knee osteoarthritis: a single-centre single blind prospective randomised controlled clinical study with 1-year follow-up. Clin Exp Rheumatol. 2016; 34(5): 857–63.

209. Dahlberg L.E., Aydemir A., Muurahainen N., et al. A first-in human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis. Clin Exp Rheumatol. 2016; 34 (3):445–50.

210. Pers Y.M., Rackwitz L., Ferreira R., et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med. 2016; 5 (7): 847–56.

211. Forogh B., Mianehsaz E., Shoaee S., et al. Effect of single injection of platelet-rich plasma in comparison with corticosteroid on knee osteoarthritis: a double-blind randomized clinical trial. J Sports Med Phys Fitness. 2016; 56 (7–8): 901–8.

212. Simental-Mendía M., Vilchez-Cavazos J.F., Peña-Martínez V.M., et al. Leukocyte-poor platelet-rich plasma is more effective than the conventional therapy with acetaminophen for the treatment of early knee osteoarthritis. Arch Orthop Trauma Surg. 2016; 136 (12): 1723–32.

213. Smith P.A. Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med. 2016; 44 (4): 884–91.

214. Dallari D., Stagni C., Rani N., et al. Ultrasound-guided injection of platelet-rich plasma and hyaluronic acid, separately and in combination, for hip osteoarthritis: a randomized controlled study. Am J Sports Med.2016; 44 (3): 664–71.

215. Lane N.E., Schnitzer T.J., Birbara C.A., et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010; 363 (16): 1521–31.

216. Schnitzer T.J., Easton R., Pang S., et al. Effect of tanezumab on joint pain, physical function, and patient global assessment of osteoarthritis among patients with osteoarthritis of the hip or knee: a randomized clinical trial. JAMA. 2019; 322 (1): 37–48.

217. Lila A.M., Gromova O.A., Torshin I.Yu., et al. Molecular effects of chondroguard in osteoarthritis and herniated discs. Neurology, Neuropsychiatry, Psychosomatics. 2017; 9 (3): 88–97 (in Russ.).

218. Lila A.M., Torshin I.Yu., Gromova O.A. Is it worthwhile rethinking the positive experience of the last 50 years of using chondroitin sulfates against atherosclerosis? FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (2): 184–91 (in Russ.).

219. Volpi N. Anti-inflammatory activity of chondroitin sulphate: new functions from an old natural macromolecule. Inflammopharmacology. 2011; 19 (6): 299–306.

220. Reginster J.Y. In people with hand osteoarthritis, chondroitin sulphate therapy for 6 months improves pain and function compared with placebo. Evid Based Med. 2012; 17 (5): 152–3.

221. Torshin I.Yu., Lila A.M., Naumov A.V., et al. Meta-analysis of clinical trials of osteoarthritis treatment effectiveness with Chondroguard. FARMAKOEKONOMIKA. Sovremennaya farmako ekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (4): 388–99 (in Russ.).

222. Gromova O.A., Torshin I.Yu., Lila A.M., et al. Standardised forms of chondroitin sulfate as a pathogenetic treatment of osteoarthritis in the context of post-genomic studies. Modern Rheumatology Journal. 2021; 15 (1): 136–43 (in Russ.).

223. Bay-Jensen A.C., Thudium C.S., Mobasheri A. Development and use of biochemical markers in osteoarthritis: current update. Curr Opin Rheumatol. 2018; 30 (1): 121–8.

224. Gullo T.R., Golightly Y.M., Cleveland R.J., et al. Defining multiple joint osteoarthritis, its frequency and impact in a community-based cohort. Semin Arthritis Rheum. 2019; 48 (6): 950–7.

For citation:

Sarvilina I.V., Shavlovskaya O.A., Gromova O.A., Naumov A.V., Sharov M.N., Prokofyeva Yu.S. Modern achievements in pharmacotherapy of osteoarthritis based on endo- and phenotyping. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2021;14(3):379-406. (In Russ.)

Views: 50

ISSN 2070-4909 (Print)
ISSN 2070-4933 (Online)