Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients

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Abstract

Background

To compare intra-articular (IA) knee injections of a cross-linked high-molecular-weight hyaluronic acid (HMW-HA) with a linear low-molecular weight HA (LMW-HA) in terms of pain and functional improvement among knee osteoarthritis (OA) patients.

Methods

In this single-blinded RCT, the patients were randomly divided into two groups for HA injections. The first group received an HMW-HA (Arthromac) injection, while the other received three weekly LMW-HA (Hyalgan) injections. Pain and function were assessed using the outcome measures including WOMAC, Lequesne and VAS indices, once prior to injection, as well as 2 and 6 months after injections.

Results

A total of 90 patients were included. There was no significant difference in baseline characteristics including age and sex between the two groups. Our analysis showed that total WOMAC, Lequesne and VAS mean scores remarkably improved at both follow-up time-points compared to the baseline measurements ( p < 0.001). There was no significant superiority between the two therapeutic protocols according to our outcome measures at any time-point of follow-up. The only except was about the improvement in WOMAC stiffness subscale that was significantly higher in LMW-HA group compared to HMW-HA ( p = 0.021). Moreover, no significant difference was observed in minor complications and injection-induced pain scores between the two groups.

Conclusion

This study proved that a single HMW-HA injection is as effective as multiple injections of LMW-HA counterparts in periods of 2 and 6 months follow-up.

This study protocol was registered in Iranian database of RCTs (IRCT; www.irct.ir) with the trial registration number IRCT20130523013442N24 and registration date 2018-07-13.

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Most cited references 27

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Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis.

Egemen Ayhan, Hayrettin Kesmezacar, Isik Akgun (2014)

Osteoarthritis (OA) is a complex "whole joint" disease pursued by inflammatory mediators, rather than purely a process of "wear and tear". Besides cartilage degradation, synovitis, subchondral bone remodeling, degeneration of ligaments and menisci, and hypertrophy of the joint capsule take parts in the pathogenesis. Pain is the hallmark symptom of OA, but the extent to which structural pathology in OA contributes to the pain experience is still not well known. For the knee OA, intraarticular (IA) injection (corticosteroids, viscosupplements, blood-derived products) is preferred as the last nonoperative modality, if the other conservative treatment modalities are ineffective. IA corticosteroid injections provide short term reduction in OA pain and can be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with OA. IA hyaluronic acid (HA) injections might have efficacy and might provide pain reduction in mild OA of knee up to 24 wk. But for HA injections, the cost-effectiveness is an important concern that patients must be informed about the efficacy of these preparations. Although more high-quality evidence is needed, recent studies indicate that IA platelet rich plasma injections are promising for relieving pain, improving knee function and quality of life, especially in younger patients, and in mild OA cases. The current literature and our experience indicate that IA injections are safe and have positive effects for patient satisfaction. But, there is no data that any of the IA injections will cause osteophytes to regress or cartilage and meniscus to regenerate in patients with substantial and irreversible bone and cartilage damage.

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A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

Mikel Sánchez, Nicolás Fiz, Juan Azofra … (2012)

This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level I, randomized controlled multicenter trial. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial)

Seyed Ahmad Raeissadat, Seyed Mansoor Rayegani, Hossein Hassanabadi … (2015)

INTRODUCTION Knee osteoarthritis (OA) is the most common articular disease. Different methods are used to alleviate the symptoms of patients with knee OA, including analgesics, physical therapy, exercise prescription, and intra-articular injections (glucocorticoids, hyaluronic acid [HA], etc). New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage, including the use of platelet-rich plasma (PRP) as a complex of growth factors. Due to the high incidence of OA and its consequences, we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA. METHOD This non-placebo-controlled randomized clinical trial involved 160 patients affected by knee OA, grade 1–4 of Kellgren–Lawrence scale. In the PRP group (n = 87), two intra-articular injections at 4-week interval were applied, and in the HA group (n = 73), three doses of intra-articular injection at 1-week interval were applied. All patients were prospectively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index (WOMAC) and SF-36 questionnaires. The results were analyzed using SPSS 16.1 software (RCT code: IRCT2014012113442N5). RESULTS At the 12-month follow-up, WOMAC pain score and bodily pain significantly improved in both groups; however, better results were determined in the PRP group compared to the HA group (P < 0.001). Other WOMAC and SF-36 parameters improved only in the PRP group. More improvement (but not statistically significant) was achieved in patients with grade 2 OA in both the groups. CONCLUSION This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment.

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Author and article information

Contributors

Adel Ebrahimpour: a.ebrahimpour@sbmu.ac.ir

Journal

Journal ID (nlm-ta): BMC Musculoskelet Disord

Journal ID (iso-abbrev): BMC Musculoskelet Disord

Title: BMC Musculoskeletal Disorders

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2474

Publication date (Electronic): 15 August 2020

Publication date PMC-release: 15 August 2020

Publication date Collection: 2020

Volume: 21

Electronic Location Identifier: 550

Affiliations

[1 ]GRID grid.411600.2, Physical Medicine and Rehabilitation Department and Research Center, Shohada-e-Tajrish Hospital, , Shahid Beheshti University of Medical Sciences, School of Medicine, ; Tehran, Iran

[2 ]GRID grid.411600.2, Clinical Development Research Center of Shahid Modarres Hospital, Physical Medicine and Rehabilitation Department and Research Center, , Shahid Beheshti University of Medical Sciences, School of Medicine, ; Tehran, Iran

[3 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Physical Medicine and Rehabilitation Department, , Tehran University of Medical Sciences (TUMS), School of Medicine, ; Tehran, Iran

[4 ]GRID grid.411600.2, Orthopedic surgery Department, Taleghani Hospital, , Shahid Beheshti University of Medical Sciences, School of Medicine, ; No. 1998734383, Velenjak, Tehran, Iran

Article

Publisher ID: 3577

DOI: 10.1186/s12891-020-03577-8

PMC ID: 7429877

PubMed ID: 32799851

SO-VID: 01ea3366-4fea-4ba7-a3ee-c0e7b04fbc27

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 27 September 2019

Date accepted : 6 August 2020

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ScienceOpen disciplines: Orthopedics

Keywords: intra-articular injections,cross-linked,hyaluronic acid,knee osteoarthritis

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ScienceOpen disciplines: Orthopedics

Keywords: intra-articular injections, cross-linked, hyaluronic acid, knee osteoarthritis

Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients

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Abstract

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Orthopedics

Most cited references 27

Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis.

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial)

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