Osteoarthritis associated with metabolic syndrome: epidemiology, pathogenesis, treatment

Cover Page

Cite item

Full Text

Abstract

   Metabolic syndrome (MS) is a complex of metabolic disorders, including insulin resistance, abdominal obesity, diabetes mellitus, hyperuricemia and arterial hypertension. According to the World Health Organization, the number of people with obesity worldwide is steadily increasing, taking on the characteristics of a “pandemic”. Against this backdrop, diseases pathogenetically linked to MS, such as osteoarthritis (OA), are gaining particular significance. Modern biochemical and molecular-genetic research has provided new data on the etiology and pathogenesis of OA, allowing the identification of phenotypes of the condition. One such phenotype is OA associated with MS, or metabolic OA. The development of this form of the disease is influenced by numerous factors, including hypersecretion of pro-inflammatory adipokines, transformation of synovial macrophages, direct effects of free fatty acids, biomechanical overload of joints, and others. Treatment of metabolic OA, in addition to standard approaches outlined in numerous clinical guidelines, has its own specific features. Particular emphasis is placed on weight reduction through lifestyle modification, strengthening of musculo-tendinous complexes, and concomitant therapy for metabolic disorders. These measures have demonstrated significant therapeutic effects, including pain reduction, decreased inflammation, and slowing of disease progression. One of the modern comprehensive remedies with phytonutritional components is Revocca capsules (“BIOTECHNOS”, Russia). Their composition in daily dosage includes phytosterols (calculated as β-sitosterol) at 100 mg, unsaponifiable compounds from avocado and soybean oils (in a 1:2 ratio) at 300 mg, rosehip extract at 300 mg, resveratrol at 70 mg, and zinc (as zinc citrate) at 12 mg. Given the increasing number of patients with the metabolic phenotype of OA, comprehensive hypolipidemic and anti-inflammatory therapy provided by multi-component drugs is becoming increasingly significant.

About the authors

A. A. Klimenko

N. I. Pirogov Russian National Research Medical
University, Ministry of Health of Russia; N.I. Pirogov City Clinical Hospital No. 1, Moscow Healthcare Department

ORCID iD: 0000-0002-7410-9784

Faculty Therapy of Institute of Clinical Medicine; Аcad. A. I. Nesterov Department

117997;  1 Ostrovitianov St.; 119049; 8 Leninskiy Avenue; Moscow

Russian Federation

N. A. Shostak

N. I. Pirogov Russian National Research Medical
University, Ministry of Health of Russia

ORCID iD: 0000-0003-4669-1006

Faculty Therapy of Institute of Clinical Medicine; Аcad. A. I. Nesterov Department

117997;  1 Ostrovitianov St.; Moscow

Russian Federation

Yu. M. Saakyan

N. I. Pirogov Russian National Research Medical
University, Ministry of Health of Russia

Author for correspondence.
Email: saakyan.yuriy@yandex.ru
ORCID iD: 0000-0002-0457-8921

Yuri Mikhailovich Saakyan

Faculty Therapy of Institute of Clinical Medicine; Аcad. A. I. Nesterov Department

117997;  1 Ostrovitianov St.; Moscow

Russian Federation

References

  1. Hunter D.J., Bierma-Zeinstra S. Osteoarthritis. Lancet 2019;393(10182):1745–59. doi: 10.1016/S0140-6736(19)30417-9
  2. Allen K.D., Choong P.F., Davis A.M. et al. Osteoarthritis: Models for appropriate care across the disease continuum. Best Pract Res Clin Rheumatol 2016;30(3):503–35. doi: 10.1016/j.berh.2016.09.003
  3. World Health Organization: Obesity and overweight. Fact Sheet No. 311. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/
  4. Kabalyk M.A. Prevalence of osteoarthritis in Russia: regional aspects of trends in statistical parameters over 2011–2016. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice 2018;56(4):416–22. (In Russ.). doi: 10.14412/1995-4484-2018-416-422
  5. Lila A.M., Alekseeva L.I., Telyshev K.A. Current approaches to osteoarthritis phenotyping. Sovremennaya revmatologiya = Modern Rheumatology Journal 2019;13(2):4–8. (In Russ.). doi: 10.14412/1996-7012-2019-2-4-8
  6. Osteoarthritis disorders. Edited by K.E. Kuettner and V.M. Goldberg. Illinois: American Academy of Orthopaedic Surgeons, 1995.
  7. Blom A.B., van der Kraan P.M., van den Berg W.B. Cytokine targeting in osteoarthritis. Curr Drug Targets 2007;8(2):283–92. doi: 10.2174/138945007779940179
  8. 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. doi: 10.1074/mcp.M800181-MCP200
  9. Valdes A.M., Spector T.D. The contribution of genes to osteoarthritis. Rheum Dis Clin North Am 2008;34(3):581–603. doi: 10.1016/j.rdc.2008.04.008
  10. Nelson F.R.T. The Value of phenotypes in knee osteoarthritis research. Open Orthop J 2018;12:105–14. doi: 10.2174/1874325001812010105
  11. Dell’Isola A., Allan R., Smith S.L. et al. Identification of clinical phenotypes in knee osteoarthritis : a systematic review of the literature. BMC Musculoskelet Disord 2016;17(1):425. doi: 10.1186/s12891-016-1286-2
  12. 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. doi: 10.1371/journal.pone.0191045
  13. Han C.D., Yang I.H., Lee W.S. et al. Correlation between metabolic syndrome and knee osteoarthritis: data from the Korean National Health and Nutrition Examination Survey (KNHANES). BMC Public Health 2013;13:603. doi: 10.1186/1471-2458-13-603
  14. Shirinsky V.S., Kalinovskaya N.Yu., Filatova K.Yu. et al. Clinical and immunological features of metabolic phenotype of osteoarthritis. Meditsinskaya immunologiya = Medical Immunology 2020;22(2):327–34. (In Russ.). doi: 10.15789/1563-0625-CAI-1881
  15. Sosnova E.A. Metabolic syndrome. Arxiv akusherstva i ginekologii imeni V.F. Snegireva = V.F. Snegirev Archives of Obstetrics and Gynecology 2016;3(4):172–80. (In Russ.). DOI: http://dx.doi.org/10.18821/2313-8726-2016-3-4-172-180
  16. Alferova V.I., Mustafina S.V. The prevalence of obesity in the adult population of the Russian Federation (literature review). Ozhirenie i metabolism = Obesity and Metabolism 2022;19(1):96–105. (In Russ.). doi: 10.14341/omet12809
  17. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 2016;387(10026):1377–96. doi: 10.1016/S0140-6736(16)30054-X
  18. Balanova Yu.A., Shalnova S.A., Deev A.D. et al. Obesity in russian population – prevalence and association with the non-communicable diseases risk factors. Rossijskij kardiologicheskij zhurnal = Russian Journal of Cardiology 2018;23(6):123–30. (In Russ.). doi: 10.15829/1560-4071-2018-6-123-130
  19. Alekseeva L.I., Taskina E.A., Kashevarova N.G. et al. Knee osteoarthritis and metabolic syndrome: new approaches to therapy. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice 2018;56(2):157–63. (In Russ.). doi: 10.14412/1995-4484-2018-157-163
  20. Neeland I.J., Ross R., Després J.P. et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol 2019;7(9):715–25. doi: 10.1016/S2213-8587(19)30084-1
  21. Kolosnitsyna M.G., Kulikova O.A. Overweight: socioeconomic factors and consequences. Demograficheskoe obozrenie = Demographic overview 2018;5(4):92–124. (In Russ.). doi: 10.17323/demreview.v5i4.8664
  22. Felson D.T. The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. Semin Arthritis Rheum 1990;20(1):42–50. doi: 10.1016/0049-0172(90)90046-i
  23. Nelson A.E., Hu D., Arbeeva L. et al. The prevalence of knee symptoms, radiographic, and symptomatic osteoarthritis at four time points: the Johnston County Osteoarthritis Project, 1999–2018. ACR Open Rheumatol 2021;3(8):558–65. doi: 10.1002/acr2.11295
  24. Lo K., Au M., Ni J. et al. Association between hypertension and osteoarthritis : A systematic review and meta-analysis of observational studies. J Orthop Translat 2021;32:12–20. doi: 10.1016/j.jot.2021.05.003
  25. Visser A.W., de Mutsert R., le Cessie S. et al. The relative contribution of mechanical stress and systemic processes in different types of osteoarthritis: the NEO study. Ann Rheum Dis 2015;74(10):1842–7. doi: 10.1136/annrheumdis-2013-205012
  26. Tomi A.L., Sellam J., Lacombe K. et al. Increased prevalence and severity of radiographic hand osteoarthritis in patients with HIV-1 infection associated with metabolic syndrome: data from the cross-sectional METAFIB-OA study. Ann Rheum Dis 2016;75(12):2101–7. doi: 10.1136/annrheumdis-2016-209262
  27. McLaughlin T., Ackerman S.E., Shen L. et al. Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest 2017;127(1):5–13. doi: 10.1172/JCI88876
  28. Hotamisligil G.S., Shargill N.S., Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259(5091):87–91. doi: 10.1126/science.7678183
  29. Romantsova T.I., Sych Yu.P. Immunometabolism and metainflammation in obesity. Ozhirenie i metabolizm = Obesity and Metabolism 2019;16(4):3–17. (In Russ.). doi: 10.14341/omet12218
  30. Mocanu V., Timofte D.V., Zară-Dănceanu C.M. et al. Obesity, metabolic syndrome, and osteoarthritis require integrative understanding and management. Biomedicines 2024;12(6):1262. doi: 10.3390/biomedicines12061262
  31. Azamar-Llamas D., Hernández-Molina G., Ramos-Ávalos B. et al. Adipokine contribution to the pathogenesis of osteoarthritis. Mediators Inflamm 2017;2017:5468023. doi: 10.1155/2017/5468023
  32. Sobieh B.H., El-Mesallamy H.O., Kassem D.H. Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets. Heliyon 2023;9(5):e15700. doi: 10.1016/j.heliyon.2023.e15700
  33. Cinti S., Mitchell G., Barbatelli G. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005;46(11):2347–55. doi: 10.1194/jlr.M500294-JLR200
  34. Gancheva S., Jelenik T., Álvarez-Hernández E. et al. Interorgan metabolic crosstalk in human insulin resistance. Physiol Rev 2018;98(3):1371–415. doi: 10.1152/physrev.00015.2017
  35. Hotamisligil G.S. Inflammation, metaflammation and immunometabolic disorders. Nature 2017;542(7640):177–85. doi: 10.1038/nature21363
  36. Hamada D., Maynard R., Schott E. et al. Suppressive effects of insulin on tumor necrosis factor-dependent early osteoarthritic changes associated with obesity and type 2 diabetes mellitus. Arthritis Rheumatol 2016;68(6):1392–402. doi: 10.1002/art.39561
  37. Hashimoto K., Akagi M. The role of oxidation of low-density lipids in pathogenesis of osteoarthritis : a narrative review. J Int Med Res 2020;48(6):300060520931609. doi: 10.1177/0300060520931609
  38. Belenska-Todorova L., Lambova S.N., Stoyanova S. et al. Disease-modifying potential of metformin and alendronate in an experimental mouse model of osteoarthritis. Biomedicines 2021;9(8):1017. doi: 10.3390/biomedicines9081017
  39. Krasnokutsky S., Oshinsky C., Attur M. et al. Serum urate levels predict joint space narrowing in non-gout patients with medial knee osteoarthritis. Arthritis Rheumatol 2017;69(6):1213–20. doi: 10.1002/art.40069
  40. Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011;29:415–45. doi: 10.1146/annurev-immunol-031210-101322
  41. McNulty A.L., Miller M.R., O’Connor S.K. et al. The effects of adipokines on cartilage and meniscus catabolism. Connect Tissue Res 2011;52(6):523–33. doi: 10.3109/03008207.2011.597902
  42. Culemann S., Grüneboom A., Krönke G. Origin and function of synovial macrophage subsets during inflammatory joint disease. Adv Immunol 2019;143:75–98. doi: 10.1016/bs.ai.2019.08.006
  43. Liu B., Zhang M., Zhao J. et al. Imbalance of M1/M2 macrophages is linked to severity level of knee osteoarthritis. Exp Ther Med 2018;16(6):5009–14. doi: 10.3892/etm.2018.6852
  44. Mengie Ayele T., Tilahun Muche Z., Behaile Teklemariam A. et al. Role of JAK2/STAT3 signaling pathway in the tumorigenesis, chemotherapy resistance, and treatment of solid tumors : a systemic review. J Inflamm Res 2022;15:1349–64. doi: 10.2147/JIR.S353489
  45. Chen L., Zheng J.J.Y., Li G. et al. Pathogenesis and clinical management of obesity-related knee osteoarthritis: Impact of mechanical loading. J Orthop Translat 2020;24:66–75. doi: 10.1016/j.jot.2020.05.001
  46. Reijman M., Pols H.A., Bergink A.P. et al. Body mass index associated with onset and progression of osteoarthritis of the knee but not of the hip: the Rotterdam Study. Ann Rheum Dis 2007;66(2):158–62. doi: 10.1136/ard.2006.053538
  47. Jiang L., Tian W., Wang Y. et al. Body mass index and susceptibility to knee osteoarthritis : a systematic review and meta-analysis. Joint Bone Spine 2012;79(3):291–7. doi: 10.1016/j.jbspin.2011.05.015
  48. Shostak N.A., Pravdyuk N.G., Anishchenko M.O., Dzhauari M.S. Osteoarthritis: management strategies depending on the location of lesions. Klinitsist = The Clinician 2022;16(1):К657. (In Russ.). doi: 10.17650/1818-8338-2022-16-1-К657
  49. Messier S.P., Resnik A.E., Beavers D.P. et al. Intentional weight loss in overweight and obese patients with knee osteoarthritis: Is more better? Arthritis Care Res (Hoboken) 2018;70(11):1569–75. doi: 10.1002/acr.23608
  50. Kolasinski S.L., Neogi T., Hochberg M.C. et al. 2019 American College of Rheumatology / Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol 2020;72(2):220–33. doi: 10.1002/art.41142
  51. Messier S.P., Mihalko S.L., Legault C. et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA 2013;310(12):1263–73. doi: 10.1001/jama.2013.277669
  52. Richette P., Poitou C., Garnero P. et al. Benefits of massive weight loss on symptoms, systemic inflammation and cartilage turnover in obese patients with knee osteoarthritis. Ann Rheum Dis 2011;70(1):139–44. doi: 10.1136/ard.2010.134015
  53. Salis Z., Sainsbury A., Keen H.I. et al. Weight loss is associated with reduced risk of knee and hip replacement: a survival analysis using Osteoarthritis Initiative data. Int J Obes (Lond) 2022;46(4):874–84. doi: 10.1038/s41366-021-01046-3
  54. Singh J.A., Noorbaloochi S., MacDonald R. et al. Chondroitin for osteoarthritis. Cochrane Database Syst Rev 2015;1(1):CD005614. doi: 10.1002/14651858.CD005614.pub2
  55. Colletti A., Cicero A.F.G. Nutraceutical approach to chronic osteoarthritis: from molecular research to clinical evidence. Int J Mol Sci 2021;22(23):12920. doi: 10.3390/ijms222312920
  56. Castrogiovanni P., Trovato F.M., Loreto C. et al. Nutraceutical supplements in the management and prevention of osteoarthritis. Int J Mol Sci 2016;17(12):2042. doi: 10.3390/ijms17122042
  57. Micallef M.A., Garg M.L. Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals. Atherosclerosis 2009;204(2):476–82. doi: 10.1016/j.atherosclerosis.2008.09.020
  58. Pollak O.J. Reduction of blood cholesterol in man. Circulation 1953;7(5):702–6. doi: 10.1161/01.cir.7.5.702
  59. Law M. Plant sterol and stanol margarines and health. BMJ 2000;320(7238):861–4. doi: 10.1136/bmj.320.7238.861
  60. O’Neill F.H., Brynes A., Mandeno R. et al. Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism. Nutr Metab Cardiovasc Dis 2004;14(3):133–42. doi: 10.1016/s0939-4753(04)80033-4
  61. Calpe-Berdiel L., Escolà-Gil J.C., Blanco-Vaca F. New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis 2009;203(1):18–31. doi: 10.1016/j.atherosclerosis.2008.06.026
  62. Cater N.B., Garcia-Garcia A.B., Vega G.L. et al. Responsiveness of plasma lipids and lipoproteins to plant stanol esters. Am J Cardiol 2005;96(1A):23D–28D. doi: 10.1016/j.amjcard.2005.03.016
  63. Appelboom T., Schuermans J., Verbruggen G. et al. Symptoms modifying effect of avocado / soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study. Scand J Rheumatol 2001;30(4):242–7. doi: 10.1080/030097401316909602
  64. Pourentezari M., Sharifian Z., Mardani M. et al. Comparison of TGF-β3 and avocado / soybean unsaponifiable on chondrogenesis of human adipose-derived stem cells on poly (lactic-co-glycolic) acid/hyaluronic acid hybrid scaffold. Iran J Basic Med Sci 2021;24(1):24–9. doi: 10.22038/ijbms.2020.44409.10391
  65. Pervaiz S. Resveratrol: from grapevines to mammalian biology. FASEB J 2003;17(14):1975–85. doi: 10.1096/fj.03-0168rev
  66. Karomatov I.D., Bajmuradov R.R., Shodieva M.S. Biologically active substance of plant origin resveratrol – medicinal properties (literature review). Biologiya i integrativnaya medicina = Biology and integrative medicine 2018;20(3):178–98. (In Russ.).
  67. Sokolova L.K., Pushkarev V.M. Prospects of using resveratrol for the treatment of diabetes mellitus and its complications. Mezhdunarodnyj endokrinologicheskij zhurnal = International Journal of Endocrinology 2018;14(8):761–8. (In Russ.). doi: 10.22141/2224-0721.14.8.2018.154857
  68. Jimenez-Gomez Y., Mattison J.A., Pearson K.J. et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell Metab 2013;18(4):533–45. doi: 10.1016/j.cmet.2013.09.004
  69. Baur J.A., Pearson K.J., Price N.L. et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444(7117):337–42. doi: 10.1038/nature05354
  70. Colotti G., Ilari A., Boffi A. et al. Metals and metal derivatives in medicine. Mini Rev Med Chem 2013;13(2):211–21. PMID: 23438056
  71. Bonaventura P., Benedetti G., Albarède F. et al. Zinc and its role in immunity and inflammation. Autoimmun Rev 2015;14(4):277–85. doi: 10.1016/j.autrev.2014.11.008

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Klimenko A.A., Shostak N.A., Saakyan Y.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-36931 от  21.07.2009.