Scientific Article   |    
Corticosteroid Compared with Hyaluronic Acid Injections for the Treatment of Osteoarthritis of the Knee A Prospective, Randomized Trial
Seth S Leopold, MD; Brigham B Redd, MD; Winston J Warme, MD; Paul A Wehrle, MD; Patrick D Pettis, LVN; Susan Shott, PhD
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Investigation performed at the Orthopaedic Surgery Service, William Beaumont Army Medical Center, El Paso, Texas, and the Department of Orthopaedics and Sports Medicine, University of Washington Medical Center, Seattle, Washington

Seth S. Leopold, MD
Department of Orthopaedics and Sports Medicine, University of Washington Medical Center, 1959 N.E. Pacific Street, Box 356500, Seattle, WA 98195. E-mail address: leopold@u.washington.edu

Brigham B. Redd, MD
Winston J. Warme, MD
Patrick D. Pettis, LVN
Orthopaedic Surgery Service (B.B.R., W.J.W., and P.D.P.) and Rheumatology Service (P.A.W.), William Beaumont Army Medical Center, 5005 North Piedras Street, El Paso, TX 79920

Paul A. Wehrle, MD
Rheumatology Service, Walter Reed Army Medical Center, 6900 Georgia Avenue N.W., Washington CD 20307

Susan Shott, PhD
Biostatistics Unit (OB-GYN), Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from William Beaumont Army Medical Center, Department of Clinical Investigation (WBAMC Grant 00/22). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Defense or the United States Government.

J Bone Joint Surg Am, 2003 Jul 01;85(7):1197-1203
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Background: Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments.

Methods: One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale.

Results: Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system).

Conclusions: No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation.

Level of Evidence: Therapeutic study, Level I-1b (randomized controlled trial [no significant difference but narrow confidence intervals]). See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Seth S. Leopold
    Posted on October 16, 2003
    Dr. Leopold responds to Dr. Charalambous
    University of Washington Medical Center

    Thank you for your letter. You are correct in noting that in our Hylan G-F 20 (Synvisc) group we aspirated any detectable effusions prior to injecting the product, while in the corticosteroid group, aspirations were not performed prior to injection.

    As you point out, and as the reference you indicated suggests (1), the aspiration of joint effusions may produce some relief of symptoms, and this may indeed have had some impact on our results.

    Our goal was to perform each study intervention as it is commonly used in practice, and as the manufactuer of the drug/device directs. The manufacturer's directions (on the package insert) for Synvisc call for joint aspiration prior to injection, and we felt it was important to follow this directive carefully. The package insert for the corticosteroid used in the study does not mandate joint aspiration, and there is inconsistent performance of joint aspiration before injection of corticosteroids in the literature, including in the article you referenced, which apparently aspirated only very large effusions (ones in which the "bulge sign" or positive patellar tap was present) (1).

    In any case, we used corticosteroid injection as the "control" group, against which the newer, more expensive product was tested. There were no consequential differences in efficacy observed between corticosteroid and Synvisc in our study. Since this appears to be the case, despite what you -- perhaps correctly -- perceive to be a bias favoring the Synvisc group, this would tend to support our conclusion: "we do not consider Hylan G-F 20 a first-line treatment for patients with osteoarthritis who are considering intra-articular knee injections for palliation of symptoms."

    Thank you again for your interest in our work.

    1. Gaffney K, Ledingham J, Perry JD Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response. Ann Rheum Dis 1995; 54: 379-381

    Charalambos P Charalambous
    Posted on October 13, 2003
    Corticosteroid Compared with Hyaluronic Acid Injections of the Knee

    To the Editor:

    I read with interest the article by Leopold et al. I am writing regarding the methodology of this study.

    The aim of the study was to compare Hylan with steroid injections. However, the group that received Hyalan also underwent aspiration of effusions while the group that had steroid injections did not. Aspiration of effusions alone may influence symptomatology(1). It is thus possible that part of the response attributed to Hylan may have been due to aspiration of the effusion.

    In the article, no justification was given for not performing aspirations in the steroid group.


    1. Gaffney K, Ledingham J, Perry JD Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response. Ann Rheum Dis 1995; 54: 379-381

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