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Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis

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Abstract

Background

Hyponatremia is implicated in pathological bone resorption and has been identified as a risk factor for bone fracture in the general population. However, there are limited data on the association between serum sodium levels and fracture risk in patients undergoing hemodialysis (HD).

Methods

We analyzed a historical cohort of 2220 maintenance HD patients to examine the association between serum sodium levels and the risk of fracture and mortality. We also examined the association between serum sodium levels and osteoporosis, based on metacarpal bone mineral density, in a subcohort of 455 patients with available data. In addition, we examined the association between serum sodium levels and bone turnover markers in a separate cross-sectional cohort of 654 maintenance HD patients.

Results

During a median follow-up of 5.4 years, 712 patients died, 113 experienced clinical fractures, and 64 experienced asymptomatic vertebral fractures. Lower serum sodium levels were associated with an increased risk of mortality (HR 1.06 per 1 mEq/L decrease; 95% CI 1.03–1.09) but not with the risk of clinical fracture (HR 1.04 per 1 mEq/L decrease; 95% CI 0.97–1.11). A similar lack of association was observed for asymptomatic vertebral fracture and any fracture. Serum sodium levels were also not associated with osteoporosis in a subcohort with available data (n = 455) or with bone alkaline phosphatase or tartrate-resistant acid phosphatase-5b in a separate cross-sectional cohort.

Conclusion

Serum sodium levels were associated with mortality but not with fracture risk, osteoporosis, or bone turnover markers in maintenance HD patients.

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Data availability

The data that support the findings of this study are not publicly available due to ongoing analyses for further publications but are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the following investigators who participated in the study: Hajime Suzuki (Bousei Hiratsuka Clinic), Mitsunori Yagame (Bousei Oone Clinic), Kayoko Watanabe (Bousei Fujisawa Clinic), Nobuyoshi Takagi (Bousei Kannai Clinic), Hiroshi Kida (Bousei Akabane Clinic), Mitsumine Fukui (Bousei Tanashi Clinic), Ken-ichi Oguchi (Bousei Hospital), Tetsuo Shirai (Bousei Clinic), Mikako Nagaoka (Honatsugi Medical Clinic), Tsuneyoshi Oh (Tsurumi Nishiguchi Hospital), Eiji Nakano (Motomachi Medical Clinic), Takayuki Hashiguchi (Fujisawa Medical Clinic), Hirofumi Ishii (Shonan Seiwa Clinic), Yoshihide Tanaka (Higasiyamato Nangai Clinic), Yasuji Sugano (Kitahachioji Clinic), Toru Furuya (Higashikurume Clinic), Naoto Ishida (Seichi Clinic), Hiroyuki Ogura (Hadano Minamiguchi Clinic), Yoko Omori (Kitasenju Higashiguchi Jin Clinic), Miho Enomoto (Ayase Ekimae Jin Clinic) and Yuichiro Yamaguchi (Adachi Iriya Toneri Clinic), and Juichi Abe (Chigasaki Central Clinic).

Funding

This study was supported by grants from the Salt Science Research Foundation, No. 2128 (to HK) and JSPS KAKENHI Grant Numbers JP23790958 (to HK) and JP25461257 (to MF). This study was also supported by Roche Diagnostics K.K. (Tokyo, Japan), which provided assay reagents for measuring intact PTH free of charge in the Tokai Dialysis Prospective Cohort Study.

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Authors and Affiliations

  1. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, 259-1193, Japan

    Keisuke Soeda, Hirotaka Komaba, Yosuke Nakagawa, Chiaki Kawabata, Takehiko Wada & Masafumi Fukagawa

  2. The Institute of Medical Sciences, Tokai University, Isehara, Japan

    Hirotaka Komaba

  3. Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

    Chiaki Kawabata

  4. Department of Nephrology, Toranomon Hospital, Tokyo, Japan

    Takehiko Wada

  5. Division of Nephrology and Diabetes, Tokai University Oiso Hospital, Oiso, Japan

    Hiroo Takahashi

  6. Jinken Clinic, Ebina, Japan

    Hiroo Takahashi & Yuichiro Takahashi

  7. Medical Corporation Kuratakai, Hiratsuka, Japan

    Toru Hyodo & Miho Hida

  8. Medical Corporation Showakai, Tokyo, Japan

    Takao Suga

  9. Division of Nephrology, Endocrinology and Metabolism, Tokai University Hachioji Hospital, Hachioji, Japan

    Takatoshi Kakuta

Authors
  1. Keisuke Soeda
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  2. Hirotaka Komaba
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  3. Yosuke Nakagawa
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Contributions

KS, HK, YN, and CK designed the study with contributions from TW, HT, YT, TH, MH, TS, TK, and MF. KS and HK analyzed data and wrote the draft of the manuscript. All authors contributed to interpretation of the data and critically revised the final draft of the manuscript.

Corresponding author

Correspondence to Hirotaka Komaba.

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Conflict of interest

HK has received honoraria, consulting fees, and/or grant support from Chugai Pharmaceutical, Kissei Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho, and Torii Pharmaceutical. YN has received grant support from Bayer Yakuhin. TW has received honoraria, consulting fees, and/or grant support from Astellas Pharma, AstraZeneca, Daiichi Sankyo, Fuso Pharmaceutical, Kissei Pharmaceutical, Kyowa Kirin, Mitsubishi Tanabe Pharma, Novartis, Ono Pharmaceutical, and Otsuka Pharmaceutical. TK has received honoraria and/or consulting fees from Chugai Pharmaceutical, Kissei Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho, and Toray Medical. MF has received honoraria, consulting fees, and/or grant support from Bayer Yakuhin, Chugai Pharmaceutical, Kissei Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, and Sanwa Kagaku Kenkyusho. The remaining authors have nothing to disclose.

Ethical approval

This study was approved by the Institutional Review Board of Tokai University School of Medicine (No. 11R-061 and No. 15R-220).

Human and animal rights

The present study complies with the guidelines for human studies. This study does not contain any studies with animals.

Informed consent

The institutional review board waived the requirement for written informed consent from participants in the historical cohort study, whereas all participants in the Tokai Dialysis Prospective Cohort Study provided written informed consent.

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Soeda, K., Komaba, H., Nakagawa, Y. et al. Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis. J Nephrol (2024). https://doi.org/10.1007/s40620-024-01904-z

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