Clinical and immunological features of metabolic phenotype of osteoarthritis

Forty women with gonarthrosis were included in this study. The main group consisted of 19 patients having osteoarthritis (OA) with metabolic syndrome (MS), the control group consisted of 21 patients with OA but without MS. It was found that metabolic phenotype of gonarthrosis, i.e. OA with concomitant MS, was different from OA without MS in terms of pain measured with visual analogue scale (VAS) (65 mm in the main group vs 47 mm in control group, р = 0.001) and other OA symptoms in accordance with Knee Osteoarthritis Outcome Scale (KOOS) (43.2 points in the main group vs 76.1 points in the control group, р = 0.001). These main distinguishing features were associated with low quality of life measured with non-specific questionnaire Short Form -36 (SF-36) (30 points in the main group and 40 points in the control) and clinically significant signs of depression, detected with Patient Health Questionnaire-9 (PHQ-9) (12 points in the main group and 7 points in the control group). The metabolic phenotype of gonarthrosis was characterized with laboratory features of low-grade systemic inflammation as evidenced by increased CRP (11.4 mg/ml in the main group vs 3.2 mg/ml in the control group, р = 0.03), IL-6 (2.6 pg/ml in the main group vs 0.7 pg/ml in the control group, р = 0.001), IL-18 (196.6 pg/ml in the main group vs 61.4 pg/ml in the control group, р = 0.001) in the peripheral blood serum, as well as increase in antibodies against Col2 (27.1 ng/ml in the main vs 5.5 ng/ml in the control group, р = 0.01) , and dyslipidaemia — increase in LDL-cholesterol (5.5 mmol/l in the main group vs 5.9 mmol/l in the control group, р = 0.032) and triglycerides (2.026 mmol/l in the main group and 1.36 mmol/l in the control gropu, р = 0.02). In conclusion, MS-associated OA phenotype occurs due to pathogenetic similarities between OA and MS (syntropy) based on systemic low grade inflammation. This OA phenotype is not well studied and needs further research to develop new treatments targeting these two comorbid disorders as a single disease.

1. Alekseeva L.I., Taskina E.A., Kashevarova N.G., Sharapova E.P., Anikin S.G., Strebkova E.A., Korotkova T.A., Raskina T.A., Zonova E.V., Otteva E.N. Knee osteoarthritis and metabolic syndrome: new approachesto therapy. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2018, Vol. 56, no. 2, pp. 157-163. (In Russ.)

2. Alekseeva LI. New ideas about the pathogenesis of osteoarthritis, the role of metabolic disorders. Ozhirenie i metabolizm = Obesity and Metabolism, 2019, Vol. 16, no. 2, pp. 75-82. (In Russ.)

3. Balabanova R.M., Dubinina T.V., Erdes S.F. Trends in the incidence of rheumatic diseases in the adult population of Russia over 2010-2014. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2016, Vol. 54, no. 3, pp. 266-270. (In Russ.)

4. Golovach I.Yu. Metabolic phenotype of osteoarthritis. modern views on pathogenesis, mechanisms of progression and approaches to treatment [Electronic resource]. Ukrainskiy revmatologicheskiy zhurnal = Ukrainian Journal of Rheumatology, 2018, no. 71 (1). (In Russ.) Access mode: http://www.rheumatology.kiev.ua/article/10652/metabolicheskij-fenotip-osteoartrita-sovremennye-vzglyady-na-patogenez-mexanizmy-progressirovaniya-i-podxody-k-lecheniyu.

5. Diagnosis and treatment ofmetabolic syndrome. In: Collection of national clinical recommendations. Moscow: Silitseya-Poligraf, 2009, pp. 106-143.

6. Kazygasheva E.V., Shirinsky V.S., Shirinsky I.V. Diabetes-associated osteoarthritis: a syntropy? Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, Vol. 18, no. 4, pp. 317-330. (In Russ.) doi: 10.15789/1563-0625-2016-4-317-330.

7. Karateev A.E., Lila A.M. Osteoarthritis: current clinical concept and some promising therapeutic approaches. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2018, Vol. 56, no. 1, pp. 70-81. (In Russ.)

8. Korshunov N.I., Rechkina E.V., Filatova Yu.S., Yaltseva N.V. Osteoarthritis and depression. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2018, Vol. 56, no. 1, pp. 93-98. (In Russ.)

9. Pogosova N.V., Dovzhenko T.V., Babin A.G., Kursakov A.A., Vygodin V.A. Russian version of PHQ-2 and 9 questionnaires: sensitivity and specificity in detection of depression in outpatient general medical practice. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention, 2014, Vol. 13, no. 3, pp. 18-24. (In Russ.)

10. Puzyrev V.P. Genetic view on the phenomenon of combined pathology in human. Meditsinskaya genetika = Medical Genetics, 2008, no. 9, pp. 3-9. (In Russ.)

11. Rudoy A.S., Chernysh O.V. Metabolic syndrome: a modern view on the problem. Voennaya meditsina = Military Medicine, 2016, no. 1, pp. 107-114. (In Russ.)

12. Strebkova E.A., Alekseeva L.I. Osteoarthrosis and metabolic syndrome. Farmateka = Farmateka, 2015, Vol. 17, pp. 15-19. (In Russ.)

13. Shirinsky V.S., Kazygasheva E.V., Shirinsky I.V. Inflammation and immunity: a role of pathogenesis of osteoarthritis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2019, Vol. 21, no. 1, pp. 39-48. (In Russ.) doi: 10.15789/1563-0625-2019-1-39-48.

14. Barabasi A.L. Network Medicine - from obesity to the “diseasome”. N. Engl. J. Med., 2007, no. 357,pp. 404-407.

15. Bellamy N., Buchanan W.W., Goldsmith C.H., Campbell J., Stitt L.W. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J. Rheumatol., 1988, no. 15, pp. 1833-1840.

16. Berenbaum F., Griffin T.M., Liu-Bryan R. Metabolic regulation of inflammation in osteoarthritis. Arthritis Rheum., 2017, Vol. 69, no. 1, pp. 9-21.

17. Bliddal H., Leeds A.R., Christensen R. Osteoarthritis, obesity and weight loss: evidence, hypotheses and horizons - a scoping review. Obes Rev., 2014, Vol. 15, no. 7, pp. 578-586.

18. Calay E.S., Hotamisligil G.S. Turning off the inflammatory, but not the metabolic, flames. Nat. Med., 2013, Vol. 19, no. 3, pp. 265-267.

19. Capettini L.S., Montecucco F., Mach F., Stergiopulos N., Santos R.A., da Silva R.F. Role of renin-angiotensin system in inflammation, immunity and aging. Curr. Pharm. Des., 2012, Vol. 18, no. 7, pp. 963-970.

20. Farnaghi S., Crawford R., Xiao Y., Prasadam I. Cholesterol metabo-lism in pathogenesis of osteoarthritis disease. Int. J. Rheum. Dis., 2017, Vol. 20, no. 2, pp. 131-140.

21. Han C.D., Yang I.H., Lee W.S. Correlation between metabolic syndrome and knee osteoarthritis: data from the Korean National Health and Nutrition Examination Survey (KNHANES). BMC Public Health, 2013, Vol. 13, 603. doi: 10.1186/1471-2458-13-603.

22. Li H., George D.M., Jaarsma R.L., Mao X. Metabolic syndrome and components exacerbate osteoarthritis symptoms of pain, depressionand reduced knee function. Ann. Transl. Med., 2016, Vol. 4, no. 7, 133. doi: 10.21037/atm.2016.03.48.

23. Miller M.D., Paradis C.F., Honck P.R., Mazumdar S., Stack J.A., Rifai A.H. Rating chronic medical illness burden in geropsychiatric practice and research application of the Cummulative illness Rating Scale. Psychiatry Res., 1992, Vol. 41, no. 3, pp. 237-242.

24. Puenpatom R.A., Victor T.W. Increased prevalenceof metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad. Med., 2009, Vol. 121, no. 6, pp. 9-20.

25. Roos E.M., Roos H.P., Lohmander L.S., Ekdahl C., Beynnon B.D. Knee Injury and Osteoarthritis Outcome Score (KOOS) - development of a self-administered outcome measure. J. Orthop. Sports Phys. Ther., 1998, no. 28, pp. 88-96.

26. Ware J.E., Sherbourne C.D. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med. Care, 1992, Vol. 30, no. 6, pp. 473-483.

27. Yoshimura N., Muraki S., Oka H. Association of kneeosteoarthritis with the accumulation of metabolic risk factors such as overweight, hypertension, dyslipidemia, and impaired glucose tolerance in japanese men and women: the ROAD study. J. Rheumatol., 2011, Vol. 38, no. 5, pp. 921-930.

28. Yoshimura N., Muraki S., Oka H. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, andimpaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis Cartilage, 2012, Vol. 20, no. 11, pp. 1217-1226.