IJPR.2022.192

Type of Article:  Original Research

Volume 11; Issue 1 (February 2023)

Page No.: 4453-4460

DOI: https://dx.doi.org/10.16965/ijpr.2022.192

Hyaluronic acid alone versus hyaluronic acid associated with adelmidrol for Intra-articular treatment of knee osteoarthritis: A long-term follow-up

Maria Chiara Vulpiani ¹, Mario Vetrano ¹, Sveva Maria Nusca ¹, Eleonora Latini ¹, Flavia Santoboni ¹, Francesca Musa ¹, Donatella Trischitta ¹, Flaminia Coluzzi ^2,3, Davide Lardo ⁴, Ernesto Ippolito ⁴.

¹ Physical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, “Sapienza” University of Rome, Rome, Italy.

² Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, Rome, Italy.

³ Department of Medical and Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Latina, Italy.

⁴ Department of Orthopaedic Surgery, University of “Tor Vergata”, Rome, Italy.

Corresponding Author: Prof. Ernesto Ippolito, Department of Orthopaedic Surgery, University of “Tor Vergata”, Rome, Italy. E-Mail: ernesto.ippolito@uniroma2.it

ORCiD

Maria Chiara Vulpiani: 0000-0002-9943-492X

Mario Vetrano: 0000-0002-8680-4004

Sveva Maria Nusca: 0000-0003-1746-7398

Eleonora Latini: 0000-0003-0032-215X

Flavia Santoboni: 0000-0001-9864-6333

Francesca Musa: 0000-0002-6774-3023

Donatella Trischitta: 0000-0002-1280-5143

Flaminia Coluzzi: 0000-0001-7184-5519

Davide Lardo: 0000-0002-3111-695X

Ernesto lppolito: 0000-0002-3706-7693

ABSTRACT

Background: Hyaluronic acid (HA) has been used for many years for intra-articular treatment of knee osteoarthritis with satisfactory results. HA associated with Adelmidrol – an anti-neuroinflammatory compound – have been only recently introduced in orthopedic clinical practice with good preliminary results.

Objective: To investigate whether HA associated with Adelmidrol provides better results than HA alone.

Methods: Two cohorts of patients with moderate knee osteoarthritis were treated. Cohort 1 received 5 weekly intra-articular injections of HA during 2017 while Cohort 2, 4 weekly intra-articular injections of HA associated with Adelmidrol during 2018. The patients of the two Cohorts were assessed by WOMAC scale, SF-12 questionnaire and PGIC scale at 1 week (T0), 6 months (T1), 1 year (T2), and 2 years (T3) after the end of treatment. All the data were statistically analyzed. A p-value of <0.05 was considered statistically significant.

Results: According to the WOMAC Scale Cohort 1 had higher mean scores than Cohort 2 at each follow-up time, with a statistically significant difference between the two cohorts at T3 (p<0.03) for all the WOMAC components, except for Stiffness. WOMAC Total mean score worsened statistically significantly only in Cohort 1, from T1 to T3 (T2 vs T1: p=0.0033; T3 vs T2: p=0.0007). The same happened for WOMAC Physical Function (T2 vs T1: p=0.0146; T3 vs T2: p=0.0046) and WOMAC Pain (T2 vs T1: p=0.0004; T3 vs T2: p=0.0002).  WOMAC Stiffness worsened statistically significantly in Cohort 1 from T2 to T3 (T3 vs T2: p=0.0041), while in Cohort 2 no change on WOMAC scale was statistically significant at any time-point, for any components. The mean scores of the SF-12 questionnaire were better in Cohort 2 than in Cohort 1 at each follow-up time for both the Physical and the Mental components, with a statistically significant difference between the two groups for the latter, at T0 (p=0.0001). In both cohorts the mean score of the Physical component decreased from T0 to T3, but the difference was not statistically significant between the two groups (p=0.25). The mean score of the Mental component slightly increased in Cohort 1 and decreased in Cohort 2, without statistically significant differences between the two groups at any time-point. PGIC showed that Cohort 2 scored significantly better than Cohort 1 at T3 (p=0.0336).

Conclusions: Overall, HA associated with Adelmidrol gave better long-term results than HA alone.

KEY WORDS: Hyaluronic acid, Adelmidrol, Palmitoylethanolamide, Knee, Osteoarthritis, Synovitis, Mastocytes, Intra-articular injections, Visco-induction.

 REFERENCES

[1]. Rydell NW, Balasz EA. Effect of intra-articular injection of hyaluronic acid on the clinical symptoms of osteoarthritis and on granulation tissue formation. Clin Orthop Relat Res 1971;80:25-32. https://doi.org/10.1097/00003086-197110000-00006
[2]. Honvo G, Reginster JY, Ramon F, et al. Safety of intra-articular hyaluronic acid injections in osteoarthritis. Outcomes of a systematic review and meta-analysis. Drugs Aging 2019;36:101-127. https://doi.org/10.1007/s40266-019-00657-w
[3]. Miller LE, Fredericson M, Altman RD. Hyaluronic acid injections or oral non steroid anti-inflammatory drugs for knee osteoarthritis: systematic review and meta-analysis of randomized trials. Orthop J Sports Med 2020;8:2325967119897909. https://doi.org/10.1177/2325967119897909
[4]. Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther.2008;10(2):R43.
[5]. Azim S, Nicholson J, Rebecchi MJ, Galbavy W, Feng T, Reinsel R, et al. Endocannabinoids and acute pain after total knee arthroplasty. Pain. February 2015;156(2):341-7.
[6]. Skaper SD, Facci L, Barbierato M, et al. N-Palmitoylethanolamine and neuroinflammation: a novel therapeutic strategy of resolution. Mol Neurobiol 2015; 52: 1034-1042.
[7]. Petrosino S, Puidgemont A, Della Valle MF, et al. Adelmidrol increases the endogenous concentration of palmitoylethanolamide in canine keratinocytes and down-regulates an inflammatory reaction in an in vitro model of contact allergic dermatitis. Vet J 2016;207:85-91.
[8]. Buckley, M. G., et al. (1998). “Mast cell subpopulations in the synovial tissue of patients with osteoarthritis: selective increase in numbers of tryptase-positive, chymase-negative mast cells.” J Pathol 186(1): 67-74.
[9]. Nigrovic PA, Binstadt BA, Monach PA, et al. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci USA 2007;104:2325-2230.https://doi. org/10.1073/pnas.0610852103
[10]. Wang Q, Lepus CM, Raghu H, et al. IgE-mediated mast cells activation promotes inflammation and cartilage destruction in osteoarthritis. Elife 2019;8:e39905.https://doi.org/10.7554/ eLife.39905
[11]. de Lange-Brokaar BJ, Klappenburg M, Andersen SN, et al. Characterization of synovial mast cells in knee oste-oarthritis: association with clinical parameters. Osteoarthr Cartilage 2016;24:664-671.https://doi.org/10.1016/j. joca.2015.11.011
[12]. Gigante A, Farinelli L, Manzotti S, et al. Synovial mast cells in Osteoarthritis. 2018; eBook: Osteoarthritis-online edition:http//meddocsonline.org/.
[13]. Di Paola R,Fusco R,Impellizzeri D, et al. Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats. Arthritis Res Ther 2016;18:291.https://doi.org/10.1186/s13075-016-1189-5
[14]. Sousa-Valente J, Calvo L, Vacca V, et al. Role of TrkA signaling and mast cells in the initiation of osteoarthritis pain in the monoiodoacetate model. Osteoarthritis Cartilage 2018;26;84-94.https://doi.org/10.1016/j.joca.2017.08.006
[15]. Vulpiani M, Tucciarone A, Vetrano M, Trischitta D, Santoboni F, Nusca S, et al. Il trattamento della gonartrosi mediante infiltrazioni intra-articolari con un’associazione di acido ialuronico e Adelmidrol (Hyadrol®).Giorn Ital Ortop Traumatol.2021;47:166-79.
[16]. Vulpiani MC, V. M., Trischitta D, et al. (2022). “Risultati a lungo termine del trattamento della gonartrosi mediante infiltrazioni intra-articolari di Hyadrol®.” Giornale Italiano di Ortopedia e Traumatologia(48): 100-106.
[17]. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957;16:494-502.https://doi. org/10.1136/ard.16.4.494
[18]. Bellamy N, Buchanan WW, Goldsmith CH, et al. 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 and knee.J Rheumatol 1988;15:1833-1840.
[19]. Ware JE Jr, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220-233.https:// doi.org/10.1097/00005650-199603000-00003
[20]. Guy W.ECDEU assessment manual for psychopharmacology. Rockville, MD:U.S.Dept of Health Education and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extra-mural Research Programs. 1976.
[21]. Akmal M, Singh A, Anand A, et al. The effects of hyaluronic acid on articular chondrocytes. J Bone Joint Surg Br 2005;87:1143-1149. https://dol.org/10.1302/0301-620X.87B8.15083
[22]. Brun P, Zavan B, Vindigni V, Schiavinato A, Pozzuoli A, Iacobellis C, Abatangelo G. In vitro response of osteoarthritic chondrocytes and fibroblast-like synoviocytes to a 500-730 kDa hyaluronan amide derivative. J Biomed Mater Res Part B 2012 Nov;100(8):2073-81.
[23]. Mora JC,Przkora R,Cruz-Almeida Y.Knee osteoarthritis: pathophysiology and current treatment modalities.J Pain Res 2018;11:2189-2196. https://doi.org/10.2147/JPR. S154002
[24]. Primorac D, Molnar V, Rod E, et al. Knee osteoarthritis:a review of pathogenesis and state-of-the-art non-operative therapeutic considerations. Genes (Basel) 2020;11:854. https://doi.org/10.3390/genes11080854
[25]. Ghosh P,Guidolin D. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin Arthritis Rheum 2002; 32: 10-37.
[26]. Tannin A. Schmidt, Nicholas S. Gastelum, Quynhhoa T. Nguyen, Barbara L Schumacher, Robert L. Sah. Boundary lubrication of articular cartilage: Role of synovial fluid constituents. Arthr. Rheum 2007; 56(3):882-891
[27]. De Filippis D, D’Amico A, Cinelli MP, Esposito G, Di Marzo V, luvone T. Adelmidrol, a palmitoylethanolamide analogue, reduces chronic inflammation in a carrageenin-granuloma model in rats. J Cell Mol Med. giugno 2009;13(6):1086-95.
[28]. Bischoff SC, Sellge G, Lorentz A, Sebald W, Raab R, Manns MP. IL-4 enhances proliferation and mediator release in mature human mast cells.Proc Natl Acad Sci U S A. 6 luglio 1999;96(14):8080-5.
[29]. Royer B, Varadaradjalou S, Saas P, Guillosson JJ, Kantelip JP, Arock M.Inhibition of IgE-induced activation of human mast cells by IL-10. Clin Exp Allergy. maggio 2001;31(5):694-704.
[30]. Gebhardt T, Lorentz A, Detmer F, Trautwein C, Bektas H, Manns MP, et al. Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1. Gut.luglio 2005;54(7):928-34.
[31]. Noble PW. Hyaluronan and its catabolic products in tissue injury and repair.Matrix Biol. gennaio 2002;21(1):25-9.
[32]. Fukuishi N, Metcalfe D, Kulka M. Sounding the alarm in infection. Allergy Clin Immunol Int. 2004;16:70-4.
[33]. Pásztói M, Nagy G, Géher P, Lakatos T, Tóth K, Wellinger K, et al. Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts. Arthritis Res Ther.2009;11(3):R68.
[34]. Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol.febbraio 2010;125(2 Suppl 2):S73-80.
[35]. Hummer CD, Angst F, Ngai W. High molecular weight intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network metanalysis. BMC Musculoskelet Disord 2020;21:702.
[36]. Kolarz G, Kotz R, Hochmayer I. Long-term benefits and repeated treatment cycles of intra-articular sodium hyaluronate (Hyalgan®) in patients with osteoarthritis of the knee. Semin Arthritis Rheum 2003;32:310-319.
[37]. Birchall D,Ismail AM,Peat G.Clinical outcomes from a physiotherapist-led intra-articular Hyaluronic acid injection clinic. Musculoskelet Care 2008;6:135-143.
[38]. Benazzo F, Perticarini L, Padolino A et al. A multi-centre, open label, long-term follow-up study to evaluate the benefits of a new viscoelastic hydrogel (Hymovis®) in the treatment of knee osteoarthritis. Eur Rev Med Pharma Sci 2016;20:959-968.

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