Short-term efficacy and safety of hyaluronic acid injection for plantar fasciopathy
Plantar fasciopathy is the most common cause of plantar heel pain and is considered to be a type of enthesopathy. The short-term efficacy, safety, and dose-response relationship of high-molecular-weight hyaluronic acid (HA) was investigated in patients with plantar fasciopathy.
In this multicenter, prospective, randomized, double-blind, placebo-controlled trial, 168 patients with persistent pain from plantar fasciopathy for more than 12 weeks were randomly assigned to receive 2.5 mL of 1% HA (H-HA), 0.8 mL of 1% HA (L-HA), or 2.5 mL of 0.01% HA (control group) once a week for 5 weeks. The primary endpoint was improvement in visual analogue scale (VAS) score for pain from baseline to week 5.
The VAS scores (least squares mean ± standard error) in each group decreased gradually after the start of treatment, a change of −3.3 ± 0.3 cm for the H-HA group, −2.6 ± 0.3 cm for the L-HA group, and −2.4 ± 0.3 cm for the control group, with the H-HA group improving significantly more than the control group (P = 0.029). No serious adverse events were reported. There was no difference between the groups in the incidence rates of adverse drug reactions.
The administration of five injections of high-molecular-weight HA is an effective treatment with no serious adverse drug reactions and is a conservative treatment option for plantar fasciopathy. This treatment contributed to alleviation of pain in patients with plantar fasciopathy and improvement in their activities of daily living.
Level of evidence
KeywordsPlantar fascia Heel pain Enthesopathy Hyaluronic acid Double-blind Randomized controlled trial
We thank the study investigators, their staff, and their patients for participating in this clinical study. The following investigators participated in the study: Jun Tsujino, Keijinkai Teine Keijinkai Hospital; Satoru Nakajo, Nakajo Orthopaedic Clinic; Atsushi Kita, Japanese Red Cross Sendai Hospital; Masahito Hatori, Tohoku University School of Medicine; Kazuo Ohuchi, Fukushima Medical University; Satoru Ozeki, Koshigaya Hospital, Dokkyo University School of Medicine; Akihiro Tsuchiya, Funabashi Orthopaedic Sports Medicine Center; Masato Takao, Teikyo University School of Medicine; Michiyasu Kayaoka, Tokyo Rosai Hospital; Yasunori Tsukimura, Kitasato Institute Hospital; Hisateru Niki, St. Marianna University School of Medicine; Atsushi Kato, Ando Orthopaedics Hospital; Ikuo Wada, Nagoya City University Hospital; Tatsuya Koike, Osaka City University Graduate School of Medicine; Hiroshi Nakajima, Otemae Hospital; Mitsuo Kinoshita, Osaka Medical College; Yoshitaka Ishizaki, Higashiosaka City General Hospital; Ichiro Higashiyama, Matsukura Hospital; Masatoshi Naito, Fukuoka University Faculty of Medicine; Toshio Inoue, Hakujyuji Hospital; Hiroshi Tsurukami, Tsurukami Orthopaedic Clinic; Shunji Oba, Oba Orthopaedics. This study was funded by Chugai Pharmaceutical Co., Ltd. (Chugai). Investigational drugs were provided at no cost by Chugai. Publication of this article was not contingent upon approval by Chugai.
Compliance with ethical standards
Conflict of interest
Yoshinori Takakura has received consulting fees from Chugai. Tsukasa Kumai, Norihiro Samoto, Atsushi Hasegawa, Hideo Noguchi, Atsushi Shiranita, Masaharu Shiraishi, Satoshi Ikeda, and Kazuya Sugimoto received grants from Chugai as study investigators. Yasuhito Tanaka declares no conflict of interest.
This study was funded by Chugai Pharmaceutical Co., Ltd. (Chugai). Investigational drugs were provided at no cost by Chugai. Publication of this article was not contingent upon approval by Chugai.
The study was performed in accordance with the ethics principles of the Declaration of Helsinki and was conducted with the approval of the institutional review boards at each of the centers where the study was performed.
Informed consent was obtained from all individual participants included in this study.
- 8.Crawford F, Thomson C (2003) Interventions for treating plantar heel pain (Review). Cochrane Database Syst Rev. 3: CD000416. Review. (2010) Update. Cochrane Database Syst Rev 1:CD000416Google Scholar
- 11.Higashiyama I, Kumai T, Hayashi K, Shinohara Y, Matsuda T, Tanaka Y, Takakura Y (2007) Effect of hyaluronic acid for plantar fasciitis. J Jpn Soc Surg Foot (Edinb) 28:25–28 (Japanese)Google Scholar
- 15.Kikuchi T, Shimmei M (1994) Effects of hyaluronan on proteoglycan metabolism of rabbit articular chondrocytes in culture. Jpn J Rheumatol 5:207–215Google Scholar
- 17.Kumai T, Muneta T, Tsuchiya A, Shiraishi M, Ishizaki Y, Sugimoto K, Samoto N, Isomoto S, Tanaka Y, Takakura Y (2014) The short-term effect after a single injection of high-molecular-weight hyaluronic acid in patients with enthesopathies (lateral epicondylitis, patellar tendinopathy, insertional Achilles tendinopathy, and plantar fasciitis): a preliminary study. J Orthop Sci 19(4):603–611CrossRefPubMedGoogle Scholar
- 18.Leach RE, DiIorio E, Harney RA (1983) Pathologic hindfoot conditions in the athlete. Clin Orthop Relat Res 177:116–121Google Scholar
- 29.Rathleff MS, Mølgaard CM, Fredberg U, Kaalund S, Andersen KB, Jensen TT, Aaskov S, Olesen JL (2015) High-load strength training improves outcome in patients with plantar fasciitis: a randomized controlled trial with 12-month follow-up. Scand J Med Sci Sports 25(3):e292–e300CrossRefPubMedGoogle Scholar
- 34.Schepsis AA, Leach RE, Gorzyca J (1991) Plantar fasciitis. Etiology, treatment, surgical results, and review of the literature. Clin Orthop Relat Res 266:185–196Google Scholar
- 36.Tamoto K, Nochi H, Tokumitsu Y (1994) High molecular weight hyaluronic acids inhibit interleukin-1-induced prostaglandin E2 generation and prostaglandin E2-elicited cyclic AMP accumulation in human rheumatoid arthritis synovial cells. Jpn J Rheumatol 5:227–236Google Scholar