On the effectiveness and safety of parafarmaceuticals products with chondroprotective effects in patients with II-III stage knee osteoarthritis: results of non-interventional observational program

Background. The current focus of scientific research is to find treatment methods and auxiliary support for patients with OA with an improved safety and tolerability profile, including parafarmaceuticals with chondroprotective effects.

Objective. The purpose of the study was to evaluate the efficacy and safety of the parafarmaceutical Chondroguard Quadro in patients with stage II-III (K-L) OA of the knee and grade 1-2 joint functional insufficiency (FI).

Materials and methods. The non–interventional follow-up program included 47 patients (14 men and 33 women aged 59-74 years) with stage II-III (K-L) and grade 1-2 FI. The control group (CG) included 15, and the main group (MG) included 32 patients who received standard therapy for OA (NSAIDs) for courses of up to 10 days. The MG patients parafarmaceutical with chondroprotective effects Chondroguard Quadro take 2 tablets 2 times per day with meals in the morning and afternoon for 1 month after taking NSAIDs. The dynamics of pain were assessed using the VAS, the severity of OA using the Leken index, the quality of life (QL) using the SF-36 questionnaire before and after treatment, the global assessment of therapy effectiveness by the doctor and the patient using the 5-point Likert scale. A radiological examination of the knee was performed. The dynamics of CRP, TNF-α, interleukin-6, PIIANP, N-osteocalcin, COMP, 25(OH)D₃, vitamin K₂, as well as uCTX-1, deoxypyridinoline, uCTX-II in urine by ELISA, CLIA and HPLC/MS. The safety of parafarmaceutical with chondroprotective effects was evaluated using the WHO and Naranjo scales.

Results. In MG after taking parafarmaceutical with chondroprotective effects, the difference from the initial indicators of pain severity was more significant compared to CG: the dynamics of pain intensity according to VAS during movement (-85.1% vs. -73.8% in CG) and at rest (-86% vs. -58.1% in CG), according to the Leken index (-83.5% vs. -61.8% in CG). In MG the most pronounced improvement of the QL of patients was noted using the SF-36. On the 40th day of the program, a significant increase in the patient's and doctor's assessment of the overall effectiveness and tolerability of the therapy was observed using the Likert scale compared to the CG. In patients with OA, there was a significant decrease in all biomarkers in the blood, an increase in the levels of 25(OH)D₃ and vitamin K₂ in the blood, and there were intergroup differences in all laboratory tests by the 40th day of the program. No adverse events were reported during the use of parafarmaceutical with chondroprotective effects.

Conclusion. Parafarmaceutical with chondroprotective effects Chondroguard Quadro can be recommended as an adjuvant support for patients with OA of the knee with moderate to mild pain syndrome when markers of cartilage degradation and calcification are detected.

1. Peat G., Thomas M. Osteoarthritis Year in Review 2020: Epidemiology & Therapy. Osteoarthr. Cartil. 2021; 29: 180-189. DOI: 10.1016/j.joca.2020.10.007.

2. Deshpande B., et al. Number of persons with symptomatic knee osteoarthritis in the us: Impact of race and ethnicity, age, sex, and obesity. Arthritis Care. Res. (Hobok.). 2016; 68 (12): 1743-1750. DOI: 10.1002/acr.22897.

3. Driban J., Harkey M., Liu S.-H., Salzler M., McAlindon T. Osteoarthritis and aging: Young adults with osteoarthritis. Curr. Epidemiol. Rep. 2020; 7 (1): 9-15. DOI: 10.1007/s40471-02000224-7.

4. Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013; 21 (9): 1145-1153. DOI: 10.1016/j.joca.2013.03.018.

5. Malemud C. Biologic basis of osteoarthritis: State of the evidence. Curr. Opin. Rheumatol. 2015; 27: 289-294. PMID: 25784380; PMCID: PMC4492522.

6. Maldonado M., Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed. Res. Int. 2013; 2013: 284873. DOI: 10.1155/2013/284873.

7. Hawellek T., Hubert J., Hischke S., Krause M., Bertrand J., Pap T., Püschel K., Rüther W., Niemeier A. Articular cartilage calcification of the hip and knee is highly prevalent, independent of age but associated with histological osteoarthritis: Evidence for a systemic disorder. Osteoarthr. Cartil. 2016; 24: 2092-2099. PMID: 27390030.

8. McCarthy G., Westfall P., Masuda I., Christopherson P., Cheung H., Mitchell P. Basic calcium phosphate crystals activate human osteoarthritic synovial fibroblasts and induce matrix metalloproteinase-13 (collagenase-3) in adult porcine articular chondrocytes. Ann. Rheum. Dis. 2001; 60: 399-406. DOI: 10.1136/ard.60.4.399.

9. Xue W., Wallin R., Olmsted-Davis E., Borrás T. Matrix GLA protein function in human trabecular meshwork cells: Inhibition of BMP2-induced calcification process. Investig. Ophthalmol. Vis. Sci. 2006; 47: 997-1007. DOI: 10.1167/iovs.05-1106.

10. Theuwissen E., Smit E., Vermeer C. The role of vitamin K in soft-tissue calcification. Adv. Nutr. 2012; 3: 166-173. DOI: 10.3945/an.111.001628.

11. Stewart M., Cibere J., Sayre E., Kopec J. Efficacy of commonly prescribed analgesics in the management of osteoarthritis: a systematic review and meta-analysis. Rheumatol. Int. 2018; 38 (11): 1985-1997. DOI: 10.1007/s00296-018-4132-z.

12. Minasov T. B., Lila A. M., Nazarenko A. G., et al. Morphological manifestations of the action of highly purified chondroitin sulfate in patients with decompensated knee osteoarthritis. Sovremennaya Revmatologiya. 2022; 16 (6): 55-63. DOI: 10.14412/1996-7012-2022-6-55-63. (In Russ.)

13. El-Brashy A., El-Tanawy R., Hassan W., Shaban H., Bhnasawy M. Potential role of vitamin K in radiological progression of early knee osteoarthritis patients. Egypt. Rheumatol. 2016; 38: 217-223. DOI: 10.1016/j.ejr.2016.03.001.

14. Shea M., Kritchevsky S., Loeser R., Booth S. Vitamin K status and mobility limitation and disability in older adults: The Health, Aging, and Body Composition Study. J. Gerontol. A Biol. Sci. Med. Sci. 2019; 75: 792-797. DOI: 10.1093/gerona/glz108.

15. https://www.rlsnet.ru/baa/xondrogard-kvadro91096?ysclid=miefkjn8r6130942656.

16. Association of Professional Members of Hospice Care, Association for Interdisciplinary Medicine. Clinical guidelines. Chronic pain syndrome (CPS) in adult patients requiring palliative care. 2018.

17. Haefeli M., Elfering A. Pain assessment. Eur Spine J. 2006; 15 Suppl 1 (Suppl 1): S17-24. DOI: 10.1007/s00586-005-1044-x.

18. Lequesne M. The algofunctional indices for hip and knee osteoarthritis. J. Rheumatol. 1997; 24 (4): 779-781. PMID: 9101517.

19. Ware J., Kosinski M., Keller S. SF-36 Physical and Mental Health Summary Scales: A User`s Manual. The Health Institute, New England Medical Center. Boston,: Mass., 1994. https://therapy.irkutsk.ru/doc/sf36.pdf.

20. Kosolapov M. S. Likert Scale. Sotsiologicheskii slovar. otv. red. G. V. Osipov, L. N. Moskvichev; uch. sekr. O. E. Chernoshchek. M.: Akademicheskii uchebno-nauchnyi tsentr RAN-MGU im. M.V. Lomonosova, NORMA, NITs INFRA M., 2015. S. 372-373 (In Russ.)

21. Luyten F. P., Bierma-Zeinstra S., Dell’Accio F. Toward classification criteria for early osteoarthritis of the knee. SeminArthritisRheum 2018; 47 (4): 457-63. DOI: 10.1016/j.semarthrit.2017.08.006.

22. Minasov T. B., Lila A. M., Nazarenko A. G., Sarvilina I. V., Zagorodnii N. V. Stratification of decompensated osteoarthritis and modern opportunities for preoperative therapy with the drug Chondroguard® based on pheno- and endotyping. RMZh. Meditsinskoe Obozrenie. 2023;7 (3): 124-136. DOI: 10.32364/2587-6821-2023-7-3-124-136 (In Russ.)

23. Pravdyuk N. G. Early osteoarthritis – current state of the problem. Klinitsist 2025; 19 (1): 54-61. DOI: 10.17650/1818-8338-2025-19-1-K738. (In Russ.)

24. Van Spil W., Welsing P., Bierma-Zeinstra S., 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. OsteoarthritisCartilage 2015; 23 (8): 1388-1397. DOI: 10.1016/j.joca.2015.03.023.

25. Kadler K. Matrix loading: assembly of extracellular matrix collagen fibrils during embryogenesis. Birth Defects Res C Embryo Today. 2004; 72 (1): 1-11. DOI: 10.1002/bdrc.20002.

26. Brody L. Knee osteoarthritis: Clinical connections to articular cartilage structure and function. Phys Ther Sport. 2015; 16 (4): 301-316. DOI: 10.1016/j.ptsp.2014.12.001.

27. Melrose J., Fuller E., Roughley P., et al. Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues. Arthritis Res Ther. 2008; 10 (4): R79. DOI: 10.1186/ar2453.

28. Monfort J., Pelletier J. P., Garcia-Giralt N., Martel-Pelletier J. Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues. Ann Rheum Dis. 2008; 67 (6): 735-740. DOI: 10.1136/ard.2006.068882.

29. Arwenfeld M. New data about glucosamin sulphate. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2005; 43 (4): 76-80. DOI: 10.14412/1995-4484-2005-622. (In Russ.)

30. Tetlow L., Woolley D. Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic cartilage and human articular chondrocytes in vitro. Osteoarthr. Cartil. 2001; 9 (5): 423-431. DOI: 10.1053/joca.2000.0408.

31. Adams J., Hewison M. Update in vitamin D. J. Clin. Endocrinol. Metab. 2010; 95 (2): 471-478. DOI: 10.1210/jc.2009-1773.

32. Lips P. Vitamin D physiology. Prog. Biophys. Mol. Biol. 2006; 92 (1): 4-8. DOI: 10.1016/j.pbiomolbio.2006.02.016.

33. Kim H.-J., Lee J.-Y., Kim T.-J., Lee J.-W. Association between serum vitamin D status and health-related quality of life (HRQOL) in an older Korean population with radiographic knee osteoarthritis: data from the Korean national health and nutrition examination survey (20102011). Health Qual Life Outcomes. 2015; 13 (1): 1. DOI: 10.1186/s12955-015-0245-1.

34. Atkins G., Welldon K., Wijenayaka A., Bonewald L., Findlay D. Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by {gamma}-carboxylation-dependent and -independent mechanisms. Am. J. Physiol. Cell Physiol. 2009; 297: C1358-1367. DOI: 10.1152/ajpcell.00216.2009.

35. Nakao M., Nishiuchi Y., Nakata M., Kimura T., Sakakibara S. Synthesis of human osteocalcins: gamma-carboxyglutamic acid at position 17 is essential for a calcium-dependent conformational transition. Pept. Res. 1994; 7: 171-417. PMID: 7696837.

36. S theneur C., Dumontier M.-F., Guedes C., Fulchignoni-Lataud M.-C., Tahiri K., Karsenty G., et al. Basic fibroblast growth factor as a selective inducer of matrix Gla protein gene expression in proliferative chondrocytes. Biochem. 2003; 369 (1): 63-70. DOI: 10.1042/BJ20020549.

37. Askari A., Naghizadeh M., Homayounfar R., Shahi A., Afsarian M., Paknahad A., et al. Increased Serum Levels of IL-17A and IL-23 Are Associated with Decreased Vitamin D3 and Increased Pain in Osteoarthritis. PloS One. 2016; 11 (11): e0164757. DOI: 10.1371/journal.pone.0164757.