Biomarkers of hand osteoarthritis: the key to a personalized algorithm of treatment and diagnostic tactics

Introduction. Hand osteoarthritis (HOA) is a poorly studied form of the disease, and biomarkers with diagnostic and prognostic value have not been identified yet.

The objective was to study the role of some biomarkers in patients with НОА.

Materials and methods. 52 women with НОА were included into the study. The degree of pain, morning stiffness and functional impairment in hand joints was determined in all patients. The laboratory examination included determination of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1 beta (IL-1β), osteocalcin, cartilage oligomeric matrix protein (COMP) and C-terminal telopeptides of type II collagen in urine (uCTX-II). All women underwent hand joint radiography and densitometry.

Results. COMP increase was detected in the «50-65 years» age subgroup, while the values of ESR, CRP, IL-1β, uCTX-II, COMP and osteocalcin in the study group were within the reference range. The use of IL-1β in the diagnosis of НOA is limited by its extremely low concentration in the blood, but the biomarker may be a predictor of a more severe course of the disease in obese patients. No significant correlations were found between the studied biomarkers and functional parameters. In contrast to the body mass index (BMI) and bone mineral density (BMD), age and menopause did not have significant effect on the studied parameters.

Conclusions. The determination of uCTX-II and COMP is potentially useful in the diagnosis of not only НOA in general, but also the osteoporotic phenotype of НOA in particular.

1. O’Neill T. W., McCabe P. S., McBeth J. Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Practice Research Clinical Rheumatology. 2018;32(2):312–326. http://dx.doi.org/10.1016/j.berh.2018.10.007.

2. Alekseeva L. I., Anoshenkova O. N., Dolganova N. G. et al. Resolution of the Council of Experts of May 20, 2023 “Issues of safety in the treatment of a rheumatological patient”. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2023;17(4):115-119. (In Russ.) https://doi.org/10.14412/1996-7012-2023-4-115-119.

3. Puig-Junoy J., Ruiz Zamora A. Socio-economic costs of osteoarthritis: A systematic review of cost-of-illness studies. Seminars in Arthritis and Rheumatism. 2015;44(5):531–541. http://dx.doi.org/10.1016/j.semarthrit.2014.10.012.

4. Lila A. M., Mazurov V. I., Martynov A. I. et al. Resolution of the consensus of the Russian Federation experts on the diagnosis and treatment of osteoarthritis, 2022. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2022;16(6):106-116. (In Russ.) https://doi.org/10.14412/1996-7012-2022-6-106-116.

5. Steinmetz J. D., Culbreth G. T., Haile L. M. et al. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Rheumatology. 2023;5(9):e508–522. http://dx.doi.org/10.1016/s2665-9913(23)00163-7.

6. Alekseeva L. I., Sharapova E. P., Lila A. M. Osteoarthritis of hand joints: prevalence, risk factors, phenotypes, diagnosis, treatment. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2022;16(6):98-105. (In Russ.) https://doi.org/10.14412/1996-7012-2022-6-98-105.

7. Filatova Y. S., Ilyin M. V. Osteoarthritis of the joints of the hands. Review of clinical recommendations. Meditsinskiy sovet = Medical Council. 2022;(21):146-154. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-21-146-154.

8. Altman R., Alarcon G., Appelrouth D. et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheumatism. 1990;33(11):1601–1610. http://dx.doi.org/10.1002/art.1780331101.

9. Haugen I. K., Felson D. T., Abhishek A. et al. 2023 EULAR classification criteria for hand osteoarthritis. Annals of the Rheumatic Diseases. 2024;83(11):1428–1435. http://dx.doi.org/10.1136/ard-2023-225073.

10. Lennerová T., Pavelka K., Šenolt L. Biomarkers of hand osteoarthritis. Rheumatology International. 2017;38(5):725– 735. http://dx.doi.org/10.1007/s00296-017-3864-5.

11. Kraus V. B., Karsdal M. A. Clinical monitoring in osteoarthritis: Biomarkers. Osteoarthritis and Cartilage. 2022;30(9):1159–1173. http://dx.doi.org/10.1016/j.joca.2021.04.019.

12. Saberi Hosnijeh F., Runhaar J., van Meurs J. B. J. et al. Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic review. Maturitas. 2015;82(1):36–49. http://dx.doi.org/10.1016/j.maturitas.2015.04.004.

13. Van Spil W. E., Welsing P. M. J., Bierma-Zeinstra S. M. A. et al. The ability of systemic biochemical markers to reflect presence, incidence, and progression of early-stage radiographic knee and hip osteoarthritis: data from CHECK. Osteoarthritis and Cartilage. 2015;23(8):1388–1397. http://dx.doi.org/10.1016/j.joca.2015.03.023.

14. Udomsinprasert W., Mookkhan N., Tabtimnark T. et al. Cartilage oligomeric matrix protein as a potential biomarker for knee osteoarthritis. Bone Joint Research. 2024;13(6):261–271. http://dx.doi.org/10.1302/2046-3758.136.bjr-2023-0180.r1.

15. Akinmade A., Oginni L. M., Adegbehingbe O. O. et al. Serum cartilage oligomeric matrix protein as a biomarker for predicting development and progression of knee osteoarthritis. International Orthopaedics. 2021;45(3):551–557. http://dx.doi.org/10.1007/s00264-021-04943-4.

16. Mazurov V. I., Lila A. M., Alekseeva L. I. et al. Multimorbidity in osteoarthritis and pleiotropic effects of slow-acting symptomatic drugs. Resolution of the multidisciplinary International Expert Council. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2023;17(5):123-131. (In Russ.) https://doi.org/10.14412/1996-7012-2023-5-123-131.

17. Alekseeva L. I. Are osteoarthritis and osteoporosis – two opposites or one whole? Opinion Leader. 2018;(1):32-36. (In Russ.)

18. Nagy E., Nagy-Finna C., Popoviciu H. V. et al. Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update. Clinical Interventions in Aging. 2020;15:501–518. http://dx.doi.org/10.2147/cia.s242288.

19. Kosinskaya N. S., Rohlin D. G. Rabochaya klassifikaciya i obshchaya harakteristika porazhenij kostno–sustavnogo apparata. L.: Medgiz, 1961. (In Russ.)

20. Kanis J. A. Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK, 2007.

21. 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 and Cartilage. 2007;15(5):516–523. http://dx.doi.org/10.1016/j.joca.2006.10.010.

22. Choi J., Joseph L., Pilote L. Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obesity Reviews. 2013;14(3):232–244. http://dx.doi.org/10.1111/obr.12003.

23. Firdous S. Correlation of CRP, fasting serum triglycerides and obesity as cardiovascular risk factors. Journal of the College of Physicians and Surgeons Pakistan. 2014;24(5):308-313.

24. Courties A., Kouki I., Soliman N. et al. Osteoarthritis year in review 2024: Epidemiology and therapy. Osteoarthritis and Cartilage. 2024;32(11):1397–1404. http://dx.doi.org/10.1016/j.joca.2024.07.014.

25. Gersing A. S., Schwaiger B. J., Nevitt M. C. et al. Is Weight Loss Associated with Less Progression of Changes in Knee Articular Cartilage among Obese and Overweight Patients as Assessed with MR Imaging over 48 Months? Data from the Osteoarthritis Initiative. Radiology. 2017;284(2):508–520. http://dx.doi.org/10.1148/radiol.2017161005.

26. Jiang L., Xie X., Wang Y. et al. Body mass index and hand osteoarthritis susceptibility: an updated meta-analysis. International Journal of Rheumatic Diseases. 2016;19(12):1244–1254. http://dx.doi.org/10.1111/1756-185x.12895.

27. Alekseeva L. I., Taskina E. A., Kashevarova N. G. Osteoarthritis: epidemiology, classification, risk factors, and progression, clinical presentation, diagnosis, and treatment. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2019;13(2):9-21. (In Russ.) https://doi.org/10.14412/1996-7012-2019-2-9-21.

28. Funck-Brentano T., Nethander M., Movérare-Skrtic S. et al. Causal Factors for Knee, Hip, and Hand Osteoarthritis: A Mendelian Randomization Study in the Biobank. Arthritis Rheumatology. 2019;71(10):1634–1641. http://dx.doi.org/10.1002/art.40928.

29. Salis Z., Driban J. B., McAlindon T. E. et al. Association of Weight Loss and Weight Gain With Structural Defects and Pain in Hand Osteoarthritis: Data From the Osteoarthritis Initiative. Arthritis Care Research. 2024;76(5):652–663. http://dx.doi.org/10.1002/acr.25284.

30. Punzi L., Ramonda R., Oliviero F. et al. Value of C reactive protein in the assessment of erosive osteoarthritis of the hand. Annals of the Rheumatic Diseases. 2005;64(6):955– 957. http://dx.doi.org/10.1136/ard.2004.029892.

31. Chen H. C., Shah S., Stabler T. V. et al. Biomarkers associated with clinical phenotypes of hand osteoarthritis in a large multigenerational family: the CARRIAGE family study. Osteoarthritis and Cartilage. 2008;16(9):1054–1059. http://dx.doi.org/10.1016/j.joca.2007.12.010.

32. Wen L., Shin M. H., Kang J. H. et al. The value of high-sensitivity C-reactive protein in hand and knee radiographic osteoarthritis: data from the Dong-gu Study. Clinical Rheumatology. 2018;37(4):1099–1106. http://dx.doi.org/10.1007/s10067-017-3921-1.

33. Dolzani P., Assirelli E., Pulsatelli L. et al. Systemic inflammation and antibodies to citrullinated peptides in hand osteoarthritis. Clinical and Experimental Rheumatology. 2011;29(6):1006-1009.

34. Liu H., Luo T., Tan J. et al. ‘Osteoimmunology’ offers new perspectives for the treatment of pathological bone loss. Current Pharmaceutical Design. 2017;23(41):6272–6278. http://dx.doi.org/10.2174/1381612823666170511124459.

35. Koh J. M., Khang Y. H., Jung C. H. et al. Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporosis International. 2005;16(10):1263–1271. http://dx.doi.org/10.1007/s00198-005-1840-5.

36. Schett G., Kiechl S., Weger S. et al. High-Sensitivity C-Reactive Protein and Risk of Nontraumatic Fractures in the Bruneck Study. Archives of Internal Medicine. 2006;166(22):2495-2501. http://dx.doi.org/10.1001/archinte.166.22.2495.

37. Pasco J. A., Kotowicz M. A., Henry M. J. et al. High-Sensitivity C-Reactive Protein and Fracture Risk in Elderly Women. JAMA. 2006;296(11):1349-1355. http://dx.doi.org/10.1001/jama.296.11.1353.

38. Balabanova R. M. Osteoarthrosis or osteoarthritis? A current view of the disease and its treatment. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2013;7(3):67-70. (In Russ.) https://doi.org/10.14412/1996-7012-2013-276.

39. Ma C. A., Rajandran S. N., Liu J. et al. The association of plasma IL-1Ra and related cytokines with radiographic severity of early knee osteoarthritis. Osteoarthritis and Cartilage Open. 2020;2(2):100046. http://dx.doi.org/10.1016/j.ocarto.2020.100046.

40. Azizieh F. Y., Shehab D., Al Jarallah K. et al. Circulatory pattern of cytokines, adipokines and bone markers in postmenopausal women with low BMD. Journal of Inflammation Research. 2019;12:99–108. http://dx.doi.org/10.2147/jir.s203590.

41. Scherbakov V. I., Skosyreva G. A., Ryabichenko T. I. et al. Cytokines and regulation of glucose and lipid metabolism in the obesity. Obesity and metabolism. 2022;19(3):317- 323. (In Russ.) https://doi.org/10.14341/omet12863.

42. Gløersen M., Steen Pettersen P., Neogi T. et al. Associations of Body Mass Index With Pain and the Mediating Role of Inflammatory Biomarkers in People With Hand Osteoarthritis. Arthritis Rheumatology. 2022;74(5):810–817. http://dx.doi.org/10.1002/art.42056.

43. Svintsitskaya I. S., Aganov D. S., Raimuev K. V. et al. Osteoarthritis: modern aspects of pathogenesis, focus on low-intensity inflammation. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2025;19(2):119-126. (In Russ.) https://doi.org/10.14412/1996-7012-2025-2-119-126.

44. Roux C. H., Foltz V., Maheu E. et al. MRI and serum biomarkers correlate with radiographic features in painful hand osteoarthritis. Clinical and Experimental Rheumatology. 2016;34(6):991-998.

45. Jung M., Christgau S., Lukoschek M. et al. Increased Urinary Concentration of Collagen Type II C-Telopeptide Fragments in Patients with Osteoarthritis. Pathobiology. 2004;71(2):70–76. http://dx.doi.org/10.1159/000074419.

46. Aslam I., Perjar I., Shi X. A. et al. Associations Between Biomarkers of Joint Metabolism, Hand Osteoarthritis, and Hand Pain and Function: The Johnston County Osteoarthritis Project. The Journal of Rheumatology. 2014;41(5):938–944. http://dx.doi.org/10.3899/jrheum.130904.

47. Verma P., Dalal K. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: A novel diagnostic and prognostic biomarker. Journal of Orthopaedic Research. 2013;31(7):999–1006. http://dx.doi.org/10.1002/jor.22324.

48. Mouritzen U., Christgau S., Lehmann H. J. et al. Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index. Annals of the Rheumatic Diseases. 2003;62(4):332–336. http://dx.doi.org/10.1136/ard.62.4.332.

49. Kord-Varkaneh H., Djafarian K., Khorshidi M. et al. Association between serum osteocalcin and body mass index: a systematic review and meta-analysis. Endocrine. 2017;58(1):24–32. http://dx.doi.org/10.1007/s12020-017-1384-4.

50. Jia L., Cheng M. Correlation analysis between risk factors, BMD and serum osteocalcin, CatheK, PINP, β-crosslaps, TRAP, lipid metabolism and BMI in 128 patients with postmenopausal osteoporotic fractures. European Review for Medical and Pharmacological Sciences. 2022;26(21):7955- 7959. http://dx.doi.org/10.26355/eurrev_202211_30147.