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Effects of Repeated Co-Injections of Corticosteroids and Hyaluronic Acid on Knee Osteoarthritis: A Prospective, Double-Blind Randomized Controlled Trial

  • Chun-Ping Wang
    Affiliations
    Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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  • Wen-Chung Lee
    Affiliations
    College of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
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  • Ru-Lan Hsieh
    Correspondence
    Requests for reprints should be addressed to Ru-Lan Hsieh, MD, Department of Physical Therapy and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shi-Lin Dist., Taipei City 11101, Taiwan.
    Affiliations
    Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Published:December 23, 2021DOI:https://doi.org/10.1016/j.amjmed.2021.11.016

      Abstract

      Background

      We compared the effects of repeated co-injections of corticosteroids plus hyaluronic acid (HA) with the effects of HA injections alone in patients with knee osteoarthritis.

      Methods

      A double-blind randomized controlled trial was conducted between October 2016 and July 2017 at a medical center. Patients (n = 57) who fulfilled the clinical and radiographic criteria for knee osteoarthritis established by the American College of Rheumatology with a Kellgren-Lawrence score of 2 or 3 were included. They were assigned to either the HA group (n = 29) or corticosteroids plus HA group (n = 28), and injections were administered under ultrasound guidance once a week for 3 consecutive weeks. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were the primary outcomes. Physical functional performance (10-m fast walking and chair-rising time) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were secondary outcomes. The assessment was performed prior to injections, 1 week, and 1, 3, and 6 months after injections. Data were analyzed through repeated-measures analysis of covariance.

      Results

      Both groups experienced decreased pain and improved physical function and physical functional performance over time. We found significant group × time interaction effects favoring the corticosteroids plus HA group in WOMAC-pain (P = .005) and physical function (P = .005), chair-rising time (P = .032), and KOOS-pain (P = .001).

      Conclusions

      Repeated co-injections of corticosteroids plus HA more effectively decreased pain and improved physical function and physical functional performance than injections of HA alone from 1 week through 6 months posttreatment.

      Keywords

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      References

        • Hsieh RL
        • Lee WC
        Clinical effects of lateral wedge arch support insoles in knee osteoarthritis: a prospective double-blind randomized study.
        Medicine (Baltimore). 2016; 95: e3952
        • Lespasio MJ
        • Piuzzi NS
        • Husni ME
        • Muschler GF
        • Guarino A
        • Mont MA
        Knee osteoarthritis: a primer.
        Perm J. 2017; 21: 16-183
        • Allen KD
        • Golightly YM
        State of the evidence.
        Curr Opin Rheumatol. 2015; 27: 276-283
        • Somers TJ
        • Keefe FJ
        • Godiwala N
        • Hoyler GH
        Psychosocial factors and the pain experience of osteoarthritis patients: new findings and new directions.
        Curr Opin Rheumatol. 2009; 21: 501-506
        • Quicke JG
        • Foster NE
        • Thomas MJ
        • Holden MA
        Is long-term physical activity safe for older adults with knee pain? A systematic review.
        Osteoarthritis Cartilage. 2015; 23: 1445-1456
        • Hochberg MC
        • Altman RD
        • April KT
        • et al.
        American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.
        Arthritis Care Res (Hoboken). 2012; 64: 465-474
        • Georgiev T
        • Angelov AK
        Modifiable risk factors in knee osteoarthritis: treatment implications.
        Rheumatol Int. 2019; 39: 1145-1157
        • Healey EL
        • Afolabi EK
        • Lewis M
        • et al.
        Uptake of the NICE osteoarthritis guidelines in primary care: a survey of older adults with joint pain.
        BMC Musculoskelet Disord. 2018; 19: 295
        • Riddle DL
        • Makowski M
        • Kong X
        Knee osteoarthritis worsening across the disease spectrum and future knee pain, symptoms, and functioning: a multisite prospective cohort study.
        Arthritis Care Res (Hoboken). 2015; 67: 1722-1729
      1. 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(11):1578-1589.

        • Altman R
        • Hackel J
        • Niazi F
        • Shaw P
        • Nicholls M
        Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: a systematic review.
        Semin Arthritis Rheum. 2018; 48: 168-175
        • Maricar N
        • Parkes MJ
        • Callaghan MJ
        • Felson DT
        • O'Neill TW
        Where and how to inject the knee–a systematic review [published correction appears in Semin Arthritis Rheum. 2015 Apr;44(5):e18].
        Semin Arthritis Rheum. 2013; 43: 195-203
        • Bauer C
        • Niculescu-Morzsa E
        • Jeyakumar V
        • Kern D
        • Späth SS
        • Nehrer S
        Chondroprotective effect of high-molecular-weight hyaluronic acid on osteoarthritic chondrocytes in a co-cultivation inflammation model with M1 macrophages.
        J Inflamm (Lond). 2016; 13: 31
        • Leighton R
        • Akermark C
        • Therrien R
        • et al.
        NASHA hyaluronic acid vs. methylprednisolone for knee osteoarthritis: a prospective, multi-center, randomized, non-inferiority trial.
        Osteoarthritis Cartilage. 2014; 22: 17-25
        • He WW
        • Kuang MJ
        • Zhao J
        • et al.
        Efficacy and safety of intraarticular hyaluronic acid and corticosteroid for knee osteoarthritis: a meta-analysis.
        Int J Surg. 2017; 39: 95-103
        • Bannuru RR
        • Natov NS
        • Obadan IE
        • Price LL
        • Schmid CH
        • McAlindon TE
        Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis.
        Arthritis Rheum. 2009; 61: 1704-1711
        • Wang SZ
        • Wu DY
        • Chang Q
        • Guo YD
        • Wang C
        • Fan WM
        Intra-articular, single-shot co-injection of hyaluronic acid and corticosteroids in knee osteoarthritis: A randomized controlled trial.
        Exp Ther Med. 2018; 16: 1928-1934
        • Petrella RJ
        • Emans PJ
        • Alleyne J
        • Dellaert F
        • Gill DP
        • Maroney M
        Safety and performance of Hydros and Hydros-TA for knee osteoarthritis: a prospective, multicenter, randomized, double-blind feasibility trial.
        BMC Musculoskelet Disord. 2015; 16: 57
        • Altman R
        • Asch E
        • Bloch D
        • et al.
        Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.
        Arthritis Rheum. 1986; 29: 1039-1049
        • Ozgonenel L
        • Aytekin E
        • Durmusoglu G
        A double-blind trial of clinical effects of therapeutic ultrasound in knee osteoarthritis.
        Ultrasound Med Biol. 2009; 35: 44-49
        • Bellamy N
        • Bucyhanan WW
        • Goldsmith CH
        • Campbell J
        • Stitt LW
        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 or knee.
        J Rheumatol. 1988; 15: 1833-1840
        • Roos EM
        • Lohmander LS
        The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis.
        Health Qual Life Outcomes. 2003; 1: 64
        • Marubini E
        • Valsecchi MG
        Analyzing Survival Data from Clinical Trials and Observational Studies.
        John Wiley, Chichester, UK1995
        • Trombini-Souza F
        • Matias AB
        • Yokota M
        • et al.
        Long-term use of minimal footwear on pain, self-reported function, analgesic intake, and joint loading in elderly women with knee osteoarthritis: a randomized controlled trial.
        Clin Biomech (Bristol, Avon). 2015; 30: 1194-1201
        • Jevsevar D
        • Donnelly P
        • Brown GA
        • Cummins DS
        Viscosupplementation for osteoarthritis of the knee: a systematic review of the evidence.
        J Bone Joint Surg Am. 2015; 97: 2047-2060
        • Vannabouathong C
        • Bhandari M
        • Bedi A
        • et al.
        Nonoperative treatments for knee osteoarthritis: an evaluation of treatment characteristics and the intra-articular placebo effect: a systematic review.
        JBJS Rev. 2018; 6: e5
        • Shewale AR
        • Barnes CL
        • Fischbach LA
        • Ounpraseuth ST
        • Painter JT
        • Martin BC
        Comparison of low-, moderate-, and high-molecular-weight hyaluronic acid injections in delaying time to knee surgery.
        J Arthroplasty. 2017; 32: 2952-2957.e21
        • Altman R
        • Hackel J
        • Niazi F
        • Shaw P
        • Nicholls M
        Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: a systematic review.
        Semin Arthritis Rheum. 2018; 48: 168-175
        • Navarro-Sarabia F
        • Coronel P
        • Collantes E
        • et al.
        A 40-month multicenter, randomized placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.
        Ann Rheum Dis. 2011; 70: 1957-1962
        • O'Hanlon CE
        • Newberry SJ
        • Booth M
        • et al.
        Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews.
        Syst Rev. 2016; 5: 186
        • Zhang Y
        • Chen X
        • Tong Y
        • Luo J
        • Bi Q
        Development and prospect of intra-articular injection in the treatment of osteoarthritis: a review.
        J Pain Res. 2020; 13: 1941-1955
        • de Campos GC
        • Rezende MU
        • Pailo AF
        • Frucchi R
        • Camargo OP
        Adding triamcinolone improves viscosupplementation: a randomized clinical trial.
        Clin Orthop Relat Res. 2013; 471: 613-620
        • Hangody L
        • Szody R
        • Lukasik P
        • et al.
        Intraarticular injection of a cross-linked sodium hyaluronate combined with triamcinolone hexacetonide (Cingal) to provide symptomatic relief of osteoarthritis of the knee: a randomized, double-blind, placebo-controlled multicenter clinical trial.
        Cartilage. 2018; 9: 276-283
        • Bellamy N
        • Campbell J
        • Robinson V
        • Gee T
        • Bourne R
        • Wells G
        Intraarticular corticosteroid for treatment of osteoarthritis of the knee.
        Cochrane Database Syst Rev. 2006; CD005328
        • Smith C
        • Patel R
        • Vannabouathong C
        • et al.
        Combined intra-articular injection of corticosteroid and hyaluronic acid reduces pain compared to hyaluronic acid alone in the treatment of knee osteoarthritis.
        Knee Surg Sports Traumatol Arthrosc. 2019; 27: 1974-1983
        • Parisi S
        • Ditto MC
        • Priora M
        • et al.
        Ultrasound-guided intra-articular injection: efficacy of hyaluronic acid compared to glucocorticoid in the treatment of knee osteoarthritis.
        Minerva Med. 2019; 110: 515-523
        • Ong KL
        • Anderson AF
        • Niazi F
        • Fierlinger AL
        • Kurtz SM
        • Altman RD
        Hyaluronic acid iinjections in Medicare knee osteoarthritis patients are associated with longer time to knee arthroplasty.
        J Arthroplasty. 2016; 31: 1667-1673
        • Spitzer AI
        • Richmond JC
        • Kraus VB
        • et al.
        Safety and efficacy of repeat administration of triamcinolone acetonide extended-release in osteoarthritis of the knee: a Phase 3b, open-label study.
        Rheumatol Ther. 2019; 6: 109-124
        • Jüni P
        • Hari R
        • Rutjes AW
        • et al.
        Intra-articular corticosteroid for knee osteoarthritis.
        Cochrane Database Syst Rev. 2015; CD005328
        • McAlindon TE
        • LaValley MP
        • Harvey WF
        • et al.
        Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial.
        JAMA. 2017; 317: 1967-1975
        • Wehling P
        • Evans C
        • Wehling J
        • Maixner W
        Effectiveness of intra-articular therapies in osteoarthritis: a literature review.
        Ther Adv Musculoskelet Dis. 2017; 9: 183-196
        • Ozturk C
        • Atamaz F
        • Hepguler S
        • Argin M
        • Arkun R
        The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1-year, single-blind, randomized study.
        Rheumatol Int. 2006; 26: 314-319
        • Raynauld JP
        • Buckland-Wright C
        • Ward R
        • et al.
        Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial.
        Arthritis Rheum. 2003; 48: 370-377
        • Lundstrom ZT
        • Sytsma TT
        • Greenlund LS
        Rethinking viscosupplementation: ultrasound- versus landmark-guided injection for knee osteoarthritis.
        J Ultrasound Med. 2020; 39: 113-117