https://doi.org/10.4081/ejtm.2024.12413
Intra-articular injections with Carboxymethyl-Chitosan in patients affected by knee osteoarthritis non-responders to hyaluronic acid: a pilot study
Submitted: 21 February 2024
Accepted: 2 May 2024
Published: 22 August 2024
Accepted: 2 May 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Osteoarthritis (OA) is a disabling disease that causes pain and functional limitation. OA symptoms can be treated with intra-articular injections of anti-inflammatory, viscosupplementary, or viscoinductive products. Non-responders to these approaches have limited options, often surgical (e.g. knee replacement). This retrospective study aims to evaluate the efficacy of a single injection of Carboxymethyl-Chitosan for advanced (Kellgren-Lawrence ≥3) and symptomatic knee OA in non-responders to hyaluronic acid. We enrolled 10 patients (5 female, 5 male). Treatment efficacy was assessed through the Visual Analogue Scale (VAS, pain) and the Knee Injury and Osteoarthritis Outcome Score (KOOS, knee function). Data are acquired from rating scales were administered at the time of injection (T0), one month (T1), three months (T2), and six months (T3) after treatment as for clinical practice. Results showed a significant improvement in pain and function at T1, with a subsequent gradual resumption of symptoms. In conclusion, the treatment showed a better outcome in the short term (i.e. up to 1 month after treatment); however, raw values of VAS and KOOS did not return to baseline levels showing a maintenance of improvement albeit not statistically significant.
Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthr Cartilage 2022;30:184–95.
DOI: https://doi.org/10.1016/j.joca.2021.04.020
Jang S, Lee K, Ju JH. Recent updates of diagnosis, pathophysiology, and treatment on osteoarthritis of the knee. IJMS 2021;22:2619.
DOI: https://doi.org/10.3390/ijms22052619
Dantas LO, Salvini TDF, McAlindon TE. Knee osteoarthritis: key treatments and implications for physical therapy. Brazilian J Physical Ther 2021;25:135–46.
DOI: https://doi.org/10.1016/j.bjpt.2020.08.004
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: A disease of the joint as an organ. Arthritis Rheumatism 2012;64:1697–707.
DOI: https://doi.org/10.1002/art.34453
Guilak F, Nims RJ, Dicks A, et al. Osteoarthritis as a disease of the cartilage pericellular matrix. Matrix Biol 2018;71–72:40–50.
DOI: https://doi.org/10.1016/j.matbio.2018.05.008
Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthr Cartilage 2009;17:971–9.
DOI: https://doi.org/10.1016/j.joca.2009.03.002
Lee YC, Lu B, Bathon JM, et al. Pain sensitivity and pain reactivity in osteoarthritis. Arthritis Care Res 2011;63:320–7.
DOI: https://doi.org/10.1002/acr.20373
Abramoff B, Caldera FE. Osteoarthritis. Med Clin North Am 2020;104:293–311.
DOI: https://doi.org/10.1016/j.mcna.2019.10.007
Panayotov K. Pain Treatment. In: Papathanasiou J, Panayotov K, eds. Essentials of Physical and Rehabilitation Medicine for undergraduate medical students. 2nd ed. Ruse, BG: Avangard; 2023. p. 229–40.
Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA 2021;325:568.
DOI: https://doi.org/10.1001/jama.2020.22171
Nelson AE, Allen KD, Golightly YM, et al. A systematic review of recommendations and guidelines for the management of osteoarthritis: The Chronic Osteoarthritis Management Initiative of the U.S. Bone and Joint Initiative. Semin Arthritis Rheum 2014;43:701–12.
DOI: https://doi.org/10.1016/j.semarthrit.2013.11.012
He Z, Wang B, Hu C, Zhao J. An overview of hydrogel-based intra-articular drug delivery for the treatment of osteoarthritis. Colloids and Surfaces B: Biointerfaces 2017;154:33–9.
DOI: https://doi.org/10.1016/j.colsurfb.2017.03.003
Sancesario A, Foti C. Intra-articular and periarticular injection therapy. In: Papathanasiou J, Panayotov K, eds. Essentials of Physical and Rehabilitation Medicine for undergraduate medical students. 2nd ed. Ruse, BG: Avangard; 2023. p. 203–18.
Zhao D, Yu S, Sun B, et al. Biomedical applications of chitosan and its derivative nanoparticles. Polymers 2018;10:462.
DOI: https://doi.org/10.3390/polym10040462
Oprenyeszk F, Sanchez C, Dubuc JE, et al. Chitosan enriched three-dimensional matrix reduces inflammatory and catabolic mediators production by human chondrocytes. PLoS ONE 2015;10:e0128362.
DOI: https://doi.org/10.1371/journal.pone.0128362
Chien RC, Yen MT, Mau JL. Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells. Carbohydrate Polymers 2016;138:259–64.
DOI: https://doi.org/10.1016/j.carbpol.2015.11.061
Busilacchi A, Gigante A, Mattioli-Belmonte M, Manzotti S, Muzzarelli RAA. Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration. Carbohydrate Polymers 2013;98:665–76.
DOI: https://doi.org/10.1016/j.carbpol.2013.06.044
Ngo DH, Kim SK. Antioxidant effects of chitin, chitosan, and their derivatives. Adv Food Nutrition Res 2014:73:15–31.
DOI: https://doi.org/10.1016/B978-0-12-800268-1.00002-0
Cheung R, Ng T, Wong J, Chan W. Chitosan: an update on potential biomedical and pharmaceutical applications. Marine Drugs 2015;13:5156–86.
DOI: https://doi.org/10.3390/md13085156
Kaderli S, Viguier E, Watrelot-Virieux D, et al. Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model. Eu J Pharmaceut Biopharmaceut 2015;96:388–95.
DOI: https://doi.org/10.1016/j.ejpb.2015.09.005
Kaderli S, Boulocher C, Pillet E, et al. A novel biocompatible hyaluronic acid–chitosan hybrid hydrogel for osteoarthrosis therapy. Int J Pharmaceut 2015;483:158–68.
DOI: https://doi.org/10.1016/j.ijpharm.2015.01.052
Patchornik S, Ram E, Ben Shalom N, et al. Chitosan-hyaluronate hybrid gel intraarticular injection delays osteoarthritis progression and reduces pain in a rat meniscectomy model as compared to saline and hyaluronate treatment. Adv Orthoped 2012;2012:1–5.
DOI: https://doi.org/10.1155/2012/979152
Douette P, Chausson M, Theatre E, et al. Biological safety evaluation of KiOmedine® CM-chitosan, an innovative non-animal carboxymethyl-chitosan biomaterial intended for injectable biomedical applications. JB 2020;4:39.
DOI: https://doi.org/10.11648/j.jb.20200402.12
Li H, Xu Q, Chen Y, Wan A. Effect of concentration and molecular weight of chitosan and its derivative on the free radical scavenging ability. J Biomed Materials Res 2014;102:911–6.
DOI: https://doi.org/10.1002/jbm.a.34749
Vandeweerd JM, Innocenti B, Rocasalbas G, et al. Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study. PLoS ONE 2021;16:e0256770.
DOI: https://doi.org/10.1371/journal.pone.0256770
Emans PJ, Skaliczki G, Haverkamp D, et al. First-in-human study to evaluate a single injection of KiOmedine®CM-Chitosan for treating symptomatic knee osteoarthritis. TORJ 2022;16:e187431292206100.
DOI: https://doi.org/10.2174/18743129-v16-e2206100
Mavrov M. The law institute of patient’s informed consent. Publishing house Stovi Group Bulgaria. 2018;17–8.
Kohn MD, Sassoon AA, Fernando ND. Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. Clin Orthopaed Related Res 2016;474:1886–93.
DOI: https://doi.org/10.1007/s11999-016-4732-4
Scott J, Huskisson EC. Graphic representation of pain. Pain 1976;2:175–84.
DOI: https://doi.org/10.1016/0304-3959(76)90113-5
Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short‐Form McGill Pain Questionnaire (SF‐MPQ), Chronic Pain Grade Scale (CPGS), Short Form‐36 Bodily Pain Scale (SF‐36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res 2011;63:20543
DOI: https://doi.org/10.1002/acr.20543
Monticone M, Ferrante S, Salvaderi S, et al. Development of the Italian version of the knee injury and osteoarthritis outcome score for patients with knee injuries: cross-cultural adaptation, dimensionality, reliability, and validity. Osteoarthritis Cartilage 2012;20:330–5.
DOI: https://doi.org/10.1016/j.joca.2012.01.001
Kolmogorov–Smirnov Test. In: The Concise Encyclopedia of Statistics [Internet]. New York, NY: Springer New York; 2008 [cited 2024 Feb 16]. p. 283–7. Available from: http://link.springer.com/10.1007/978-0-387-32833-1_214
Haynes W. Bonferroni correction. In: Dubitzky W, Wolkenhauer O, Cho KH, Yokota H, editors. Encyclopedia of Systems Biology [Internet]. New York, NY: Springer New York; 2013 [cited 2024 Feb 16]. p. 154–154. Available from: http://link.springer.com/10.1007/978-1-4419-9863-7_1213
DOI: https://doi.org/10.1007/978-1-4419-9863-7_1213
Muhammad LN. Guidelines for repeated measures statistical analysis approaches with basic science research considerations. Journal of Clinical Investigation 2023;133:e171058.
DOI: https://doi.org/10.1172/JCI171058
Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019;27:1578–89.
DOI: https://doi.org/10.1016/j.joca.2019.06.011
Aljehani MS, Christensen JC, Snyder-Mackler L, et al. Knee biomechanics and contralateral knee osteoarthritis progression after total knee arthroplasty. Gait Posture 2022;91:266–75.
DOI: https://doi.org/10.1016/j.gaitpost.2021.10.020
Sharma L. Osteoarthritis of the Knee. Solomon CG, editor. N Engl J Med 2021;384:51–9.
DOI: https://doi.org/10.1056/NEJMcp1903768
Saviola G, Da Campo G, Bianchini MC, et al. Intra-articular clodronate in patients with knee osteoarthritis non-responder to intra-articular hyaluronic acid - a case report series of 9 patients with 8-month follow-up. Clin Ter 2023;174:245-8.
International classification of functioning, disability and health. Geneva: World Health Organization; 2001.
Emans PJ, Skaliczki G, Haverkamp D, et al. KiOmedine® CM-Chitosan is effective for treating advanced symptomatic knee osteoarthritis up to six months following a single intra-articular injection: a post hoc analysis of aproove clinical study. TORJ 2023;17:e187431292302010.
DOI: https://doi.org/10.2174/18743129-v16-e220206-2022-19
How to Cite
Manocchio, N., Ljoka, C., Piacentini, N., Sorge, R., Vita, G., & Foti, C. (2024). Intra-articular injections with Carboxymethyl-Chitosan in patients affected by knee osteoarthritis non-responders to hyaluronic acid: a pilot study. European Journal of Translational Myology, 34(3). https://doi.org/10.4081/ejtm.2024.12413
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