Histological features of knee osteoarthritis treated with triamcinolone acetonide and hyaluronic acid

Charnwichai,Pattaranatcha; Tammachote,Rachaneekorn; Tammachote,Nattapol; Chaichana,Thiamjit; Kitkumthorn,Nakarin

doi:10.3892/br.2023.1623

Histological features of knee osteoarthritis treated with triamcinolone acetonide and hyaluronic acid

Authors:
- Pattaranatcha Charnwichai
- Rachaneekorn Tammachote
- Nattapol Tammachote
- Thiamjit Chaichana
- Nakarin Kitkumthorn
View Affiliations

Affiliations: Program in Biotechnology, Faculty of Science, Chulalongkorn University, Pathumwan 10330, Thailand, Department of Botany, Faculty of Science, Chulalongkorn University, Pathumwan 10330, Thailand, Department of Orthopedics, Faculty of Medicine, Thammasat University Hospital, Khlong Nueng, Pathumthani 10120, Thailand, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand, Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand
Published online on: May 8, 2023 https://doi.org/10.3892/br.2023.1623
Article Number: 40
Copyright: © Charnwichai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoarthritis (OA) is one of the most common degenerative joint diseases leading to disability in the end stage. Although intra‑articular triamcinolone acetonide (TA) is one of the OA treatments that have been widely used, the side effects of such corticosteroids are still controversial. Intra‑articular hyaluronic acid (HA) injection is another therapeutic option for patients with OA who do not want to use corticosteroids because of their side effects. However, the difference between the histological features associated with TA and HA in the treatment of OA remains unclear. Thus, the present study aimed to compare the histological effects of TA and HA on the cartilage of patients with knee OA. In the current study, 31 patients diagnosed with grade 3‑4 knee OA on the Kellgren‑Lawrence radiographic grading scale were separated into three groups: TA (n=12); HA (n=7) and untreated group (n=12). Histological examination of the whole articular cartilages of the patients was performed with hematoxylin and eosin and Alcian staining, as well as using a TUNEL assay. Clinical data such as cartilage thickness, structural and component deterioration, proteoglycan levels, apoptosis and empty lacunae were compared between the three groups. The results showed a high level of deterioration in both TA and HA groups but not in the untreated group, although the thickness of cartilage in the HA group was lower compared with that in the TA and untreated groups. The proteoglycan levels in the TA group were lower compared with those in the HA group. Moreover, the number of empty lacunae in the HA group was higher compared with that in the TA group, while no difference in apoptosis was found between TA and HA groups. A significant difference was not found in the histological staining between TA and HA groups. On the other hand, a significant difference was found in cartilage deterioration between the medial and lateral sides in these groups. TA and HA groups showed comparable histological results. TA injection is cheaper and easier but has more adverse effects for patients with knee OA than HA injection. Therefore, orthopaedists should select TA or HA based on the economic and specific needs of patients.

View Figures

View References

1	Plotnikoff R, Karunamuni N, Lytvyak E, Penfold C, Schopflocher D, Imayama I, Johnson ST and Raine K: Osteoarthritis prevalence and modifiable factors: A population study. BMC Public Health. 15(1195)2015.PubMed/NCBI View Article : Google Scholar
2	Braun HJ and Gold GE: Diagnosis of Osteoarthritis: Imaging. Bone. 51:278–288. 2012.PubMed/NCBI View Article : Google Scholar
3	Sinusas K: Osteoarthritis: Diagnosis and treatment. Am Fam Physician. 85:49–56. 2012.PubMed/NCBI
4	Sulzbacher I: Osteoarthritis: Histology and pathogenesis. Wien Med Wochenschr. 163:212–219. 2013.PubMed/NCBI View Article : Google Scholar
5	Das SK and Farooqi A: Osteoarthritis. Best Pract Res Clin Rheumatol. 22:657–675. 2008.PubMed/NCBI View Article : Google Scholar
6	Arya RK and Jain V: Osteoarthritis of the knee joint: An overview. Indian Acad Clin Med. 14:154–162. 2013.
7	Ringdahl E and Pandit S: Treatment of knee osteoarthritis. Am Fam Physician. 83:1287–1292. 2011.PubMed/NCBI
8	Neustadt DH: Intra-articular injections for osteoarthritis of the knee. Cleve Clin J Med. 73:897–898. 901–904. 906–911. 2006.PubMed/NCBI View Article : Google Scholar
9	Nguyen C and Rannou F: The safety of intra articular injections for the treatment of knee osteoarthritis: A critical narrative review. Expert Opin Drug Saf. 16:897–902. 2017.PubMed/NCBI View Article : Google Scholar
10	Raynauld JP, Buckland-Wright C, Ward R, Choquette D, Haraoui B, Martel-Pelletier J, Uthman I, Khy V, Tremblay JL, Bertrand C and Pelletier JP: Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee A randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 48:370–377. 2003.PubMed/NCBI View Article : Google Scholar
11	Takagi S and Blaha JD: The suitable use of intra-articular corticosteroid injection in knee osteoarthritis. Osteoarthritis and Cartilage. 26 (Suppl 1)(S291)2018.
12	Creamer P: Intra-articular corticosteroid injections in osteoarthritis: Do they work and if so, how? Ann Rheum Dis. 56:634–636. 1997.PubMed/NCBI View Article : Google Scholar
13	Gibson T, Burry HC, Poswillo D and Glass J: Effect of intra-articular corticosteroid injections on primate cartilage. Ann Rheum Dis. 36:74–79. 1976.PubMed/NCBI View Article : Google Scholar
14	Syed HM, Green L, Bianski B, Jobe CM and Wongworawat MD: Bupivacaine and triamcinolone may be toxic to human chondrocytes: A pilot study. Clin Orthop Relat Res. 469:2941–2947. 2011.PubMed/NCBI View Article : Google Scholar
15	Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM and Pringle EK: In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg Am. 92:599–608. 2010.PubMed/NCBI View Article : Google Scholar
16	Nakazawa F, Matsuno H, Yudoh K, Watanabe Y, Katayama R and Kimura T: Corticosteroid treatment induces chondrocyte apoptosis in an experimental arthritis model and in chondrocyte cultures. Clin Exp Rheumatol. 20:773–781. 2002.PubMed/NCBI
17	Farkas B, Kvell K, Czompoly T, Illes T and Bardos T: Increased chondrocyte death after steroid and local anesthetic combination. Clin Orthop Relat Res. 468:3112–3120. 2010.PubMed/NCBI View Article : Google Scholar
18	Suntiparpluacha M, Tammachote N and Tammachote R: Triamcinolone acetonide reduces viability, induces oxidative stress, and alters gene expressions of human chondrocytes. Eur Rev Med Pharmacol Sci. 20:4985–4992. 2016.PubMed/NCBI
19	Stove J, Schöniger R, Huch K, Brenner R, Günther KP, Puhl W and Scharf HP: Effects of dexamethasone on proteoglycan content and gene expression of IL-1beta-stimulated osteoarthrotic chondrocytes in vitro. Acta Orthop Scand. 73:562–567. 2002.PubMed/NCBI View Article : Google Scholar
20	Pelletier JP, Raynauld JP, Abram F, Dorais M, Paiement P and Martel-Pelletier J: Intra-articular corticosteroid knee injection induces a reduction in meniscal thickness with no treatment effect on cartilage volume: A case-control study. Sci Rep. 10(13789)2020.PubMed/NCBI View Article : Google Scholar
21	Uthman I, Raynauld JP and Haraoui B: Intra-articular therapy in osteoarthritis. Postgrad Med J. 79:449–453. 2003.PubMed/NCBI View Article : Google Scholar
22	Siebelt M, Korthagen N, Wei W, Groen H, Bastiaansen-Jenniskens Y, Müller C, Waarsing JH, de Jong M and Weinans H: Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo. Arthritis Res Ther. 17(352)2015.PubMed/NCBI View Article : Google Scholar
23	Euppayo T, Siengdee P, Buddhachat K, Pradit W, Chomdej S, Ongchai S and Nganvongpanit K: In vitro effects of triamcinolone acetonide and in combination with hyaluronan on canine normal and spontaneous osteoarthritis articular cartilage. In Vitro Cell Dev Biol Anim. 52:723–735. 2016.PubMed/NCBI View Article : Google Scholar
24	Suntiparpluacha M, Tammachote N and Tammachote R: Triamcinolone acetonide alters expressions of matrix metalloproteinase-3 gene in primary human chondrocytes. Genomics and Genetics. 9:66–71. 2016.
25	Altman RD, Manjoo A, Fierlinger A, Niazi F and Nicholls M: The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: A systematic review. BMC Musculoskelet Disord. 16(321)2015.PubMed/NCBI View Article : Google Scholar
26	Necas J, Bartosikova L, Brauner P and Kolar J: Hyaluronic acid (hyaluronan): A review. Veterinarni Medicina. 53:397–411. 2008.
27	Moreland LW: Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: Mechanisms of action. Arthritis Res Ther. 5:54–67. 2003.PubMed/NCBI View Article : Google Scholar
28	Neustadt D, Caldwell J, Bell M, Wade J and Gimbel J: Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: A randomized, controlled, multicenter trial. J Rheumatol. 32:1928–1936. 2005.PubMed/NCBI
29	Diracoglu D, Vural M, Baskent A, Dikici F and Aksoy C: The effect of viscosupplementation on neuromuscular control of the knee in patients with osteoarthritis. J Back Musculoskelet Rehabil. 22:1–9. 2009.PubMed/NCBI View Article : Google Scholar
30	Day R, Brooks P, Conaghan PG and Petersen M: Multicenter Trial Group. A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee. J Rheumatol. 31:775–782. 2004.PubMed/NCBI
31	Trigkilidas D and Anand A: The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain. Ann R Coll Surg Engl. 95:545–551. 2013.PubMed/NCBI View Article : Google Scholar
32	Leopold SS, Redd BB, Warme WJ, Wehrle PA, Pettis PD and Shott S: Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. A prospective, randomized trial. J Bone Joint Surg Am. 85:1197–1203. 2003.PubMed/NCBI View Article : Google Scholar
33	Jones AC, Pattrick M, Doherty S and Doherty M: Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis. Osteoarthritis Cartilage. 3:269–273. 1995.PubMed/NCBI View Article : Google Scholar
34	Abedi M, Kamkar P, Afshari M and Mirkazemi M: Comparison of the effectiveness of intra-articular injections of hyaluronic acid and corticosteroid in the treatment of patients with knee osteoarthritis symptomse. Ortho & Rheum Open Access J. 7(555704)2017.
35	Kohn MD, Sassoon AA and Fernando ND: Classifications in Brief: Kellgren-Lawrence classification of osteoarthritis. Clin Orthop Relat Res. 474:1886–1893. 2016.PubMed/NCBI View Article : Google Scholar
36	Charnwichai P, Kitkumthorn N, Ruangvejvorachai P, Wongphoom J, Meesakul T, Tammachote N and Tammachote R: Rapid decalcification of articular cartilage and subchondral bone using an ultrasonic cleaner with EDTA. Acta Histochem. 125(152009)2023.PubMed/NCBI View Article : Google Scholar
37	Al-Sabaawy HB, Rahawi AM and Al-Mahmood SS: Standard techniques for formalin-fixed paraffin-embedded tissue: A Pathologist's perspective. Iraqi J Veter Sci. 35:127–135. 2021.
38	Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D and van den Berg WB: Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. 14:13–29. 2006.PubMed/NCBI View Article : Google Scholar
39	Ayhan E, Kesmezacar H and Akgun I: Intraarticular injections (corticosteroid,hyaluronic acid,platelet rich plasma) for the knee osteoarthritis. World J Orthop. 5:351–361. 2014.PubMed/NCBI View Article : Google Scholar
40	Brooks EM, Hu CH, Kingston KA and Matzkin EG: Corticosteroid Injections: A review of sex-related side effects. Orthopedics. 40:e211–e215. 2017.PubMed/NCBI View Article : Google Scholar
41	Vaishya R, Pandit R, Agarwal AK and Vijay V: Intra-articular hyaluronic acid is superior to steroids in knee osteoarthritis: A comparative, randomized study. J Clin Orthop Trauma. 8:85–88. 2017.PubMed/NCBI View Article : Google Scholar
42	Migliore A and Granata M: Intra-articular use of hyaluronic acid in the treatment of osteoarthitis. Clin Interv Aging. 3:365–369. 2008.PubMed/NCBI View Article : Google Scholar
43	Barreto RB, Sadigursky D, Rezende MU and Hernandez AJ: Effect of hyaluronic acid on chondrocyte apoptosis. Acta Ortop Bras. 23:90–93. 2015.PubMed/NCBI View Article : Google Scholar
44	Rudnik-Jansen I, Schrijver K, Woike N, Tellegen A, Versteeg S, Emans P, Mihov G, Thies J, Eijkelkamp N, Tryfonidou M and Creemers L: Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model. Drug Deliv. 26:226–236. 2019.PubMed/NCBI View Article : Google Scholar
45	Temple-Wong MM, Ren S, Quach P, Hansen BC, Chen AC, Hasegawa A, D'Lima DD, Koziol J, Masuda KL, Lotz MK and Sah RL: Hyaluronan concentration and size distribution in human knee synovial fluid: Variations with age and cartilage degeneration. Arthritis Res Ther. 18(18)2016.PubMed/NCBI View Article : Google Scholar
46	Ke Y, Jiang W, Xu Y, Chen Y, Zhang Q, Xue Q, Lin J, Ngai W, Nian G, Fazeli MS, et al: Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis. C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China. BMC Musculoskelet Disord. 22(428)2021.PubMed/NCBI View Article : Google Scholar
47	Chevalier X, Jerosch J, Goupille P, van Dijk N, Luyten FP, Scott DL, Bailleul F and Pavelka K: Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthitis of the knee: A randomised, multicentre, double-blind, placebo controlled trail. Ann Rheum Dis. 69:113–119. 2010.PubMed/NCBI View Article : Google Scholar
48	Chou CW, Lue KH, Lee HS, Lin RC and Lu KH: Hylan G-F 20 has better pain Relief and cost-effectiveness than sodium hyaluronate in treating early osteoarthritic knee in Taiwan. J Formos Med Assoc. 108:663–672. 2009.PubMed/NCBI View Article : Google Scholar
49	Tammachote N, Kanitnate S, Yakumpor T and Panichkul P: Intra-Articular, Single-Shot Hylan G-F 20 hyaluronic acid injection compared with corticosteroid in knee osteoarthritis. A Double-Blind, Randomized Controlled Trial. J Bone Joint Surg Am. 98:885–892. 2016.PubMed/NCBI View Article : Google Scholar
50	Penning LI, de Bie RA and Walenkamp GH: Subacromial triamcinolone acetonide, hyaluronic acid and saline injections for shoulder pain an RCT investigating the effectiveness in the first days. BMC Musculoskelet Disord. 15(352)2014.PubMed/NCBI View Article : Google Scholar
51	Jones RK, Chapman GJ, Findlow AH, Forsythe L, Parkes MJ, Sultan J and Felson DT: A new approach to prevention of knee osteoarthritis: Reducing medial load in the contralateral knee. J Rheumatol. 40:309–315. 2013.PubMed/NCBI View Article : Google Scholar
52	Felson DT, Nevitt MC, Zhang Y, Aliabadi P, Baumer B, Gale D, Li W, Yu W and Xu L: High prevalence of lateral knee osteoarthritis in Beijing Chinese compared with framingham caucasian subjects. Arthritis Rheum. 46:1217–1222. 2002.PubMed/NCBI View Article : Google Scholar
53	Prodromos CC, Andriacchi TP and Galante JO: A relationship between gait and clinical changes following high tibial osteotomyit. J Bone Joint Surg Am. 67:1188–1194. 1985.PubMed/NCBI