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Na-Cl Co-transporter (NCC) gene inactivation is associated with improved bone microstructure

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Abstract

Summary

Gitelman syndrome (GS) is the disease model of the inactivation of thiazide‐sensitive sodium chloride cotransporter (NCC), which is believed to benefit bone mass and reduce fracture risk. In this study, we found that GS patients have superior bone microarchitecture, which is associated with the disease status. Several decreased bone parameters with aging in healthy controls were reversed in GS patients to a certain extent.

Purpose

To evaluate the impact of the inactivation of NCC on bone turnover and microarchitecture in Gitelman syndrome patients.

Methods

A cross-sectional study was conducted in 45 GS patients (25 males and 20 females). Serum procollagen type 1 N-terminal propeptide (P1NP), β-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX), and osteocalcin were measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in GS patients and age- and sex-matched healthy controls. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously.

Results

GS patients had a relatively lower level of β-CTX. aBMD at several skeletal sites was improved in GS patients. HR-pQCT assessment revealed that GS patients had slightly thinner but significantly more compact trabecular bone (increased trabecular number and decreased thickness), notably decreased cortical porosity, and increased volume BMD (vBMD) at both the radius and tibia compared with controls. The disease severity, represented as the relationship with the minimum level of magnesium during the course and standard base excess, was associated with bone microarchitecture parameters after adjusting for age, sex, and BMI. The decreased vBMD and Tb.BV/TV, and increased Tb.Sp and Ct.Po with aging, were reversed in GS patients to a certain extent.

Conclusion

GS patients have superior bone microarchitecture, which suggests that the inactivation of NCC might be beneficial for avoiding osteoporosis.

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Data availability

Dr. Xia and Dr. Tong had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.

The data that support the findings of this study are available on request from the corresponding authors. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

The authors express heartfelt thanks to all the patients and the healthy controls for their participation in the study.

Funding

This work was financially supported by the National Natural Science Foundation of China (81970757), The Chinese National Key Technology R&D Program, Ministry of Science and Technology (2021YFC2501700), and CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1–002).

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Author notes

  1. Wenting Qi and Zinan Yin contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No.1, Wangfujing Street, Dongcheng District, Beijing, 100730, China

    Wenting Qi, Zinan Yin, Hanting Liang, Yue Chi, Wei Liu, Ruizhi Jiajue, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Anli Tong & Weibo Xia

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  1. Wenting Qi
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  11. Anli Tong
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Corresponding authors

Correspondence to Anli Tong or Weibo Xia.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of PUMCH and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Supplementary file2

Supplementary Figure 1. Correlation analysis between bone turnover markers and clinical characteristics in Gitelman syndrome (GS) patients. P-value was adjusted for age, sex, and BMI. Abbreviations: GS, gitelman syndrome; K min, minimum level of potassium; SBE, standard base excess. (PNG 341 kb)

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Qi, W., Yin, Z., Liang, H. et al. Na-Cl Co-transporter (NCC) gene inactivation is associated with improved bone microstructure. Osteoporos Int 33, 2193–2204 (2022). https://doi.org/10.1007/s00198-022-06471-2

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  • DOI: https://doi.org/10.1007/s00198-022-06471-2

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