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

Haruka Kaneko,Muneaki Ishijima,Takayuki Kawasaki,Kazuo Kaneko,Yoshitomo Saita,Ryo Sadatsuki,Tokuhide Doi,Yuji Takazawa,Hiroshi Ikeda,Anwarjan Yusup,Mitsuaki Kubota,Lizu Liu,Hisashi Kurosawa,Shinnosuke Hada,Ippei Futami

doi:10.1186/1471-2474-14-34

Haruka Kaneko, Muneaki Ishijima + Show 13 more

Open Access

https://doi.org/10.1186/1471-2474-14-34

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Abstract

BackgroudWhile 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.Methods372 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.ResultsThe 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.ConclusionsThese 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).

Highlights

Osteoarthritis (OA) Biomarkers Network, which was funded by National Institute of Health (NIH) and developed as a partnership with Osteoarthritis Research Society International (OARSI) and the Arthritis Foundation, proposed the BIPEDS biomarker classification (Burden of disease, Investigative, Prognostic, Efficacy of intervention, Diagnosis of the Disease and Safety of interventions) which suggests the optimal study design and analytic methods forThe serum level of hyaluronic acid is a potential biomarker for the establishment of a proper management system in knee OA
The ln-serum level of hyaluronic acid (sHA) levels of the subjects with Kellgren & Lawrence grade (K/L) grade 4 were significantly increased in comparison to those with K/L grade 1, 2 and 3, respectively (Table 1)
No significant difference of the Logarithmically transformed sHA (ln-sHA) levels were observed between the subjects with K/L grade 3 and those with K/L grade 1 and 2 (Table 1)

Summary

Introduction

SHA has been reported to be a useful burden of disease marker in OA [4-7], it is still far from being practical. The reference intervals for a biomarker must be established before the marker can be adequate and useful for clinical interpretation. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and Clinical and Laboratory Standards Institute (CLSI) have defined reference intervals as the interval between two reference limits. Reference intervals are designated as the interval between and including two numbers, an upper and lower reference limit, which are estimated to enclose a specified percentage (usually 95%) of the values for a population from which the reference subjects are drawn [8].

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