Open Access Open Badges Research article

Reference intervals of serum hyaluronic acid corresponding to the radiographic severity of knee osteoarthritis in women

Haruka Kaneko12, Muneaki Ishijima123*, Tokuhide Doi4, Ippei Futami12, Lizu Liu23, Ryo Sadatsuki12, Anwarjan Yusup1, Shinnosuke Hada12, Mitsuaki Kubota2, Takayuki Kawasaki2, Yoshitomo Saita2, Yuji Takazawa2, Hiroshi Ikeda2, Hisashi Kurosawa5 and Kazuo Kaneko123

Author affiliations

1 Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan

2 Department of Orthopaedics, Faculty of Medicine, Juntendo University, Tokyo, Japan

3 Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan

4 Fukuoka Clinic, Tokyo, Japan

5 Department of Orthopaedic Surgery, Juntendo Tokyo Metropolitan Koto Geriatric Medical Center, Tokyo, Japan

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Citation and License

BMC Musculoskeletal Disorders 2013, 14:34  doi:10.1186/1471-2474-14-34

Published: 18 January 2013



While serum levels of hyarulonic acid (sHA) is known to be useful for a burden of disease biomarker in knee OA, it is far from practical. The reference intervals must be established for biomarkers to be useful for clinical interpretation. The aim of this study was to establish the reference intervals of sHA corresponding to the radiographic severity of knee OA for elucidating whether sHA can be useful as a burden of disease marker for individual patient with knee OA.


372 women with Kellgren & Lawrence grade (K/L) 1 through 4 painful knee OA were enrolled in this study. The patients included 54 with K/L 1, 96 with K/L 2, 97 with K/L 3, and 118 with K/L 4. Serum samples were obtained from all subjects on the day that radiographs taken. A HA binding protein based latex agglutination assay that employed an ELISA format was used to measure sHA. Age and BMI adjusted one way ANOVA was used to set the reference intervals of sHA.


The reference intervals for sHA corresponding to the patients with K/L 4 (49.6 – 66.5 ng/ml) was established without any overlap against to those with K/L 1, 2 and 3, while those with K/L 1, 2 and 3 showed considerable overlap.


These results indicate that sHA can be available as a burden of disease marker for the individuals with severe knee OA (K/L 4), while it is not for those with primary to moderate knee OA (K/L 1–3).

Osteoarthritis (OA); Hyarulonic Acid (HA); Reference intervals; Biomarker; Radiography