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The Effect of Three Weekly Intra-Articular Injections of Hyaluronate on Pain, Function, and Balance in Patients with Unilateral Ankle Arthritis
Shu-Fen Sun, MD1; Chien-Wei Hsu, MD1; Hsien-Pin Sun, MD2; Yi-Jiun Chou, MD1; Hung-Ju Li, MS3; Jue-Long Wang, MD1
1 Departments of Physical Medicine and Rehabilitation (S.-F.S., J.-L.W.), Internal Medicine (C.-W.H.), and Orthopedic Surgery (Y.-J.C.), Kaohsiung Veterans General Hospital, Number 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan. E-mail address for S.-F. Sun: sfsun.tw@yahoo.com.tw
2 Department of General Surgery, Cheng Ching Hospital, 118 Sec. 3, Chung Kang Road, Taichung 407, Taiwan
3 Institute of Statistics, National University of Kaohsiung, 700, Kaohsiung University Road, Nanzih District 811, Kaohsiung, Taiwan
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Investigation performed at Kaohsiung Veterans General Hospital and National Yang-Ming University School of Medicine, Taiwan

Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Sep 21;93(18):1720-1726. doi: 10.2106/JBJS.J.00315
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Ankle arthritis can cause substantial pain and functional limitation. Previous studies have indicated that five weekly intra-articular injections of hyaluronate were safe and effective in the treatment of ankle osteoarthritis. The purpose of this study was to evaluate the effect and safety of three weekly injections of hyaluronate in patients with unilateral ankle arthritis.


Fifty patients who had had unilateral ankle pain for at least six months and were classified radiographically as having Kellgren-Lawrence grade-2 or 3 ankle arthritis were recruited for a prospective study. Patients received three weekly intra-articular injections of hyaluronate. The primary outcome was the change in the Ankle Osteoarthritis Scale score at six months after the third injection. Secondary outcomes included the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Score, four clinical tests of balance, consumption of rescue analgesics, and global patient satisfaction.


Forty-six participants completed the study. A significant reduction in the mean Ankle Osteoarthritis Scale score was noted at one, three, and six months after the third injection (p < 0.05 for each follow-up visit compared with baseline). The mean AOFAS Ankle-Hindfoot Score improved from 60.5 points at baseline to 73.5, 75.5, and 76.7 points at one, three, and six months of follow-up, respectively (p < 0.05). The patients demonstrated significant improvement on all four balance tests at each follow-up visit (p < 0.05 for each test compared with baseline). Acetaminophen consumption dropped significantly following treatment (p < 0.05). The patients’ satisfaction rate was high, and no serious adverse events were reported.


This study suggests that three weekly injections of hyaluronate are well-tolerated and can provide pain relief and improve function and balance in patients with unilateral ankle arthritis. Larger controlled trials with longer follow-up are necessary to verify the effects of hyaluronate in the treatment of ankle arthritis.

Level of Evidence: 

Therapeutic Level IV. 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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