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Associations Between Surrogates of Skeletal Muscle Mass and History of Bone Fracture in Patients with Chronic Kidney Disease: The Fukuoka Kidney disease Registry (FKR) Study

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Abstract

Patients with chronic kidney disease (CKD) are at increased risks of both sarcopenia and fragility fractures. However, information on the association between skeletal muscle mass (SMM) and the risk of bone fractures in patients with CKD is lacking. We performed a cross-sectional analysis of 4146 patients with CKD using the baseline dataset of the Fukuoka Kidney disease Registry Study, as a multicenter, prospective cohort study of pre-dialysis CKD patients. The main measure was estimated SMM (eSMM) calculated using an equation validated by bioelectrical impedance analysis with two independent datasets of 100 and 81 CKD patients. The main outcome was historical bone fractures. The associations between sex-specific quartiles (Q1–Q4) of eSMM and fracture history were assessed by logistic regression analyses. The prevalence of a history of fractures increased and eSMM decreased with progressive CKD stages. Among the 4146 patients, 249 had prior bone fractures, including 111 patients in Q1 (lowest quartile), 65 in Q2, 46 in Q3, and 27 in Q4 (highest quartile). A multivariable-adjusted model revealed that patients in Q1 had a significantly higher odds ratio (95% confidence interval) for bone fracture history than those in Q4 (reference): Q1, 2.77 (1.32–5.80); Q2, 1.95 (1.05–3.65); and Q3, 1.57 (0.90–2.75) (P-value for trend < 0.001). Similar associations were obtained when other skeletal muscle surrogates were applied: serum creatinine to serum cystatin C and daily urinary creatinine excretion. These results suggest that a lower eSMM is associated with an increased prevalence of historical bone fractures in pre-dialysis CKD patients.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Code used for the statistical analysis during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank all the doctors and medical staff who participated in the FKR Study.

Steering Committee and Principal Collaborators of the FKR Study Group: Satoru Fujimi (Fukuoka Renal Clinic), Hideki Hirakata (Fukuoka Renal Clinic), Tadashi Hirano (Hakujyuji Hospital), Tetsuhiko Yoshida (Hamanomachi Hospital), Takashi Deguchi (Hamanomachi Hospital), Hideki Yotsueda (Harasanshin Hospital), Kiichiro Fujisaki (Iizuka Hospital), Keita Takae (Japanese Red Cross Fukuoka Hospital), Koji Mitsuiki (Japanese Red Cross Fukuoka Hospital), Akinori Nagashima (Japanese Red Cross Karatsu Hospital), Ritsuko Katafuchi (Kano Hospital), Hidetoshi Kanai (Kokura Memorial Hospital), Kenji Harada (Kokura Memorial Hospital), Tohru Mizumasa (Kyushu Central Hospital), Takanari Kitazono (Kyushu University), Toshiaki Nakano (Kyushu University), Toshiharu Ninomiya (Kyushu University), Kumiko Torisu (Kyushu University), Akihiro Tsuchimoto (Kyushu University), Shunsuke Yamada (Kyushu University), Hiroto Hiyamuta (Kyushu University), Shigeru Tanaka (Kyushu University), Dai Matsuo (Munakata Medical Association Hospital), Yusuke Kuroki (National Fukuoka-Higashi Medical Center), Hiroshi Nagae (National Fukuoka-Higashi Medical Center), Masaru Nakayama (National Kyushu Medical Center), Kazuhiko Tsuruya (Nara Medical University), Masaharu Nagata (Shin-eikai Hospital), Taihei Yanagida (Steel Memorial Yawata Hospital), Shotaro Ohnaka (Tagawa Municipal Hospital). We also thank Susan Furness, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shunsuke Yamada, Shigeru Tanaka, Hokuto Arase, Hiroto Hiyamuta, Eriko Yoshizumi, Toshiaki Nakano & Takanari Kitazono

  2. Division of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan

    Masanori Tokumoto

  3. Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Kazuhiko Tsuruya

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  1. Shunsuke Yamada
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Contributions

Conception and study design: SY, ST; data acquisition: ST, HH, HA, and KT; data analysis interpretation: SY, ST, HA, HH, MT; statistical analysis: SY and ST; supervision or mentorship: TN, KT, and TK. Each author contributed important intellectual content during manuscript drafting and accepts accountability for the overall work by ensuring that questions related to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. KT takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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Correspondence to Kazuhiko Tsuruya.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Yamada, S., Tanaka, S., Arase, H. et al. Associations Between Surrogates of Skeletal Muscle Mass and History of Bone Fracture in Patients with Chronic Kidney Disease: The Fukuoka Kidney disease Registry (FKR) Study. Calcif Tissue Int 109, 393–404 (2021). https://doi.org/10.1007/s00223-021-00851-2

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