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Extracellular-to-intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis: results from the Nagahama Study

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Abstract

Introduction/objectives

To test the hypothesis that greater extracellular-to-intracellular water (ECW/ICW) ratios in lower-limb muscles are associated with worsened functional abilities in patients with knee osteoarthritis (OA).

Methods

We analyzed data from 787 participants (82.2% female; mean age, 69.6 ± 5.3 years) from the Nagahama Prospective Cohort who were ≥60 years old and had radiographically confirmed bilateral knee OA. The Knee Scoring System (KSS) was used to assess functional abilities. Lower-limb ECW/ICW ratios and skeletal mass index values were determined with multi-frequency bioelectrical impedance analysis (BIA). Multiple linear regression analysis was used to test for associations between ECW/ICW ratios and functional abilities. Subgroup analyses based on OA severities and symptomaticity were also conducted.

Results

Increased ECW/ICW ratios were associated with a 4.38-point decrease in the KSS function scores (95% confidence interval [CI], 3.15–5.62 points) after adjusting for covariates. This association varied according to the degree of knee symptoms, especially in individuals with radiologically mild OA. ECW/ICW ratios in individuals with asymptomatic mild OA were associated with a 2.14-point decrease in the KSS function score (95% CI, 0.32–3.96 points), whereas those in individuals with severe symptomatic mild OA were associated with a 6.16-point decrease (95% CI, 2.13–10.19 points).

Conclusions

Our findings indicate that higher ECW/ICW ratios are associated with greater functional disability in patients with knee OA. Therefore, ECW/ICW ratio measurements with multi-frequency BIA can serve as valuable indicators for functional disability in patients with knee OA.

Key Points

• Higher extracellular-to-intracellular water (ECW/ICW) ratios are associated with greater functional disability levels in patients with knee osteoarthritis (OA).

• ECW/ICW ratios are useful clinical signs as a biomarker for poor functional abilities in patients with knee OA.

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Acknowledgements

We are extremely grateful to the Nagahama City Office and a non-profit organization called the Zeroji Club for their help in conducting the Nagahama Study. We would like to thank Editage (www.editage.cn) for English language editing.

Funding

The work was supported by a university grant, the Center of Innovation Program, the Global University Project, and a Grant-in-Aid for Scientific Research (25293141, 26670313, 26293198, 17H04182, 17H04126, 17H04123, 18K18450, and 19K17634) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Practical Research Project for Rare/Intractable Diseases (ek0109070, ek0109070, ek0109196, and ek0109348), the Comprehensive Research on Aging and Health Science Research Grants for Dementia R&D (dk0207006, dk0207027), the Program for an Integrated Database of Clinical and Genomic Information (kk0205008), the Practical Research Project for Lifestyle-related Diseases including Cardiovascular Diseases and Diabetes Mellitus (17ek0210066, 18ek0210096, and 19ek0210116), and the Research Program for Health Behavior Modification by Utilizing IoT (le0110005, le0110013) from the Japan Agency for Medical Research and Development (AMED); the Takeda Medical Research Foundation, the Mitsubishi Foundation, the Daiwa Securities Health Foundation, and the Sumitomo Foundation; the Comprehensive Research on Aging and Health Science Research Grants for Dementia R&D from Japan Agency for Medical Research and Development (H26-Choju-Ippan-001, 15dk0107007h0003, 16dk0110007h0003); and the JSPS KAKENHI Grant-in-Aid for Research Activity Start-up (19K21493).

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Authors and Affiliations

  1. Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, 53-Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Masashi Taniguchi, Tome Ikezoe, Tadao Tsuboyama & Noriaki Ichihashi

  2. Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Tsukasa Kamitani

  3. Department of Physical Therapy, School of Health Sciences, Bukkyo University, Kyoto, Japan

    Tadao Tsuboyama

  4. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Hiromu Ito & Shuichi Matsuda

  5. Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yasuharu Tabara & Fumihiko Matsuda

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  1. Masashi Taniguchi
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  2. Tome Ikezoe
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on behalf of the Nagahama Study Group

Contributions

All authors have made substantial contributions to (1) the conception and design of the study, (2) revising it critically for important intellectual content, and (3) final approval of the version to be submitted. The specific contributions of each author are as follows:

1. Analysis and interpretation of the data: MT, TI, TK, and NI.

2. Drafting of the article: MT, TI, TK, and NI.

3. Statistical expertise: MT and TK.

Corresponding author

Correspondence to Masashi Taniguchi.

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All study procedures were approved by the Ethics Committee of the Kyoto University Graduate School of Medicine and the Nagahama Municipal Review Board (G278) and were conducted in accordance with the principles of the Declaration of Helsinki.Written informed consent for the use of data was obtained from all participants in the Nagahama Study.

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Taniguchi, M., Ikezoe, T., Kamitani, T. et al. Extracellular-to-intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis: results from the Nagahama Study. Clin Rheumatol 40, 2889–2896 (2021). https://doi.org/10.1007/s10067-021-05591-0

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