The relationship between serum fetuin-a levels and the clinical severity of generalized osteoarthritis

Abstract

Osteoarthritis (OA) is increasingly recognized as a disease in which inflammatory mechanisms contribute to its pathogenesis, particularly in generalized osteoarthritis (GOA). Fetuin-A, a glycoprotein with context-dependent inflammatory properties, has recently gained attention as a potential biomarker in chronic inflammatory conditions. This study aimed to investigate serum fetuin-A levels in patients with generalized osteoarthritis and to evaluate their relationship with inflammatory markers and clinical disease severity. This cross-sectional study included patients with generalized osteoarthritis and age- and sex-matched healthy controls. Serum fetuin-A, C-reactive protein (CRP), and interleukin-1 beta (IL-1β) levels were measured. Pain severity was assessed using the Visual Analog Scale (VAS), and clinical severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Group comparisons and correlation analyses were performed using appropriate statistical methods, with p < 0.05 considered statistically significant. Serum fetuin-A levels were significantly higher in patients with generalized osteoarthritis compared to controls (p = 0.017). Within the GOA group, fetuin-A levels showed a weak but significant positive correlation with IL-1β concentrations (p = 0.005). No significant associations were observed between fetuin-A levels and VAS or WOMAC scores (p = 0.726 and p = 0.681, respectively). Elevated serum fetuin-A levels in patients with generalized osteoarthritis suggest a potential association with underlying inflammatory or pathological processes in the disease. However, the lack of correlation with clinical severity measures indicates that fetuin-A may not reflect symptom burden. Further longitudinal studies are required to clarify the biological role and clinical relevance of fetuin-A in generalized osteoarthritis.

Keywords

• Alfa2HS-Glikoprotein
• Biomarker
• Fetuin-A
• Generalized Osteoarthritis
• Inflammation

Supporting Institution

Zonguldak Bülent Ecevit University Scientific Research Projects

Project Number

2020-93733444-01

References

1. Aaron RK, Racine JR, Voisinet A, Evangelista P, Dyke JP. Subchondral bone circulation in osteoarthritis of the human knee. Osteoarthritis Cartilage. 2018;26(7):940–4.
2. De Santis M, Di Matteo B, Chisari E, Cincinelli G, Angele P, Lattermann C, et al. The role of Wnt pathway in the pathogenesis of osteoarthritis and its potential therapeutic implications in regenerative medicine. Biomed Res Int. 2018;2018:7402947.
3. Kalunian K, Tugwell P, Greene J. Pathogenesis of osteoarthritis. In: Osteoarthritis. 2010.
4. Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011;23(5):471–8.
5. Sharma L, Berenbaum F. Epidemiology of osteoarthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. Osteoarthritis: A Companion to Rheumatology. 1st ed. Elsevier Health Sciences; 2007.
6. Li W, Zhu S, Li J, Huang Y, Zhou R, Fan X, et al. A hepatic protein, fetuin-A, occupies a protective role in lethal systemic inflammation. PLoS One. 2011;6(2):e16945.
7. Vashist SK, Schneider EM, Venkatesh AG, Luong JH. Emerging human fetuin-A assays for biomedical diagnostics. Trends Biotechnol. 2017;35(5):407–21.
8. Dabrowska AM, Tarach JS, Wojtysiak-Duma B, Duma D. Fetuin-A (AHSG) and its usefulness in clinical practice: review of the literature. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159(3):352–9.

9. Xiao J, Wang XR, Hu KZ, Li MQ, Chen JW, Ma T, et al. Serum fetuin-A levels are inversely associated with clinical severity in patients with primary knee osteoarthritis. Biomarkers. 2013;18(1):51–4.
10. Favero M, Belluzzi E, Frallonardo P, Peruzzo L, Tauro L, Oliviero F, et al. Synovial fluid fetuin-A levels in patients affected by osteoarthritis with or without evidence of calcium crystals. Rheumatology (Oxford). 2019;58(4):729–30.
11. Dougados M, Nakache JP, Gueguen A. Criteria for generalized and focal osteoarthritis. Rev Rhum Engl Ed. 1996;63(9):569–75.
12. Kellgren JH, Moore R. Generalized osteoarthritis and Heberden’s nodes. Br Med J. 1952;1(4751):181–7.
13. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum. 1986;29(8):1039–49.
14. Guzeldemir M. Pain assessment methods. Sendrom. 1995;7:11–21.
15. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. 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;15(12):1833–40.
16. Tuzun EH, Eker L, Aytar A, Daskapan A, Bayramoglu M. Acceptability, reliability, validity and responsiveness of the Turkish version of WOMAC osteoarthritis index. Osteoarthritis Cartilage. 2005;13(1):28–33.
17. Orlowsky EW, Kraus VB. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol. 2015;42(3):363–71.
18. Scanzello CR. Role of low-grade inflammation in osteoarthritis. Curr Opin Rheumatol. 2017;29(1):79–85.
19. Lebreton JP, Joisel F, Raoult JP, Lannuzel B, Rogez JP, Humbert G. Serum concentration of human alpha 2-HS glycoprotein during the inflammatory process: evidence that alpha 2-HS glycoprotein is a negative acute-phase reactant. J Clin Invest. 1979;64(4):1118–29.
20. Harman H, Tekeoğlu İ, Gürol G, Sağ MS, Karakeçe E, Çiftçi IE, et al. Comparison of fetuin-A and transforming growth factor beta 1 levels in patients with spondyloarthropathies and rheumatoid arthritis. Int J Rheum Dis. 2017;20(12):2020–7.
21. Tuylu T, Sari I. Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case-control study. Clinics (Sao Paulo). 2014;69(10):688–93.
22. Yamasandhi PG, Dharmalingam M, Balekuduru A. Fetuin-A in newly detected type 2 diabetes mellitus as a marker of non-alcoholic fatty liver disease. Indian J Gastroenterol. 2021;40(6):556-62.
23. Almarashda O, Abdi S, Yakout S, Khattak MNK, Al-Daghri NM. Hepatokines Fetuin-A and Fetuin-B status in obese Saudi patient with diabetes mellitus type 2. Am J Transl Res. 2022;14(5):3292-302.