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Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma

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Abstract

Purpose

Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL).

Methods

A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and β-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously.

Results

PPGL patients had a higher level of β-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent.

Conclusions

PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

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Data availability

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 (No. 82270938); the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2021YFC2501700); and the Chinese Academy of Medical Sciences-CAMS Innovation Fund for Medical Sciences (CIFMS-2021-I2M-1–002).

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Authors and Affiliations

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

    W. Qi, L. Cui, R. Jiajue, Q. Pang, Y. Chi, W. Liu, Y. Jiang, O. Wang, M. Li, X. Xing, A. Tong & W. Xia

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  1. W. Qi
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Contributions

AT and WX designed the study and revised the manuscript. WQ analyzed the data and drafted the manuscript. LC, RJ, QP, YC, YJ, OW, Ml, and XX collected clinical information of patients. WQ, AT, and WX are responsible for the integrity of the data analysis. All authors read and approved the final manuscript.

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Correspondence to A. Tong or W. Xia.

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All authors declare that they have no conflict of interest.

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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. The study was approved by the Department of Scientific Research, PUMCH (ZS-1689).

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Qi, W., Cui, L., Jiajue, R. et al. Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma. J Endocrinol Invest 47, 843–856 (2024). https://doi.org/10.1007/s40618-023-02198-x

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