ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1624505
The Association Between Bone Turnover Biomarkers and the Severity of White Matter Hyperintensities
Provisionally accepted
- Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
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Background: Bone health may be associated with cerebral small vessel disease. This study aims to explore the correlation between bone turnover biomarkers (BTMs) and parathyroid hormone (PTH) with the severity of white matter hyperintensities (WMH). Materials and Methods: We retrospectively analyzed 213 inpatients from the Neurology Department of Beijing Jishuitan Hospital between June 2021 and May 2022. The WMH burden was assessed semi-quantitatively using the age-related white matter changes scale and the Fazekas scale, with the latter separately evaluating periventricular WMH (PWMH) and deep WMH (DWMH). Participants were categorized into two groups based on WMH severity. Binary logistic regression was performed to investigate the relationship, and subgroup analyses were conducted across subgroups stratified by sex, hypertension, and diabetes. Results: Patients with severe WMH, PWMH, and DWMH had significantly higher β-carboxy-terminal cross-linked telopeptide of type 1 collagen (β-CTX) and PTH levels compared to those in the mild groups. After adjusting for confounding factors, elevated β-CTX levels remained associated with severe WMH (OR: 4.44, 95% CI: 1.33-14.81) and severe PWMH (OR: 6.37, 95% CI: 1.80-22.47), while increased PTH levels were associated with severe DWMH (OR: 1.02, 95% CI: 1.01-1.05). Subgroup analysis showed a significant relationship between PTH and the severity of WMH and PWMH in patients with diabetes (p for interaction < 0.05). Conclusions: β-CTX was independently linked to WMH/PWMH severity, and PTH to DWMH severity, pointing to a possible bone-cerebrovascular axis. Larger prospective and interventional studies should confirm these markers as potential CSVD biomarkers and treatment targets.
Keywords: bone turnover biomarkers1, white matter hyperintensities2, parathyroid hormone3, carboxy-terminal cross-linked telopeptide of type 1 collagen4, cerebral small vessel disease5
Received: 07 May 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 You, Li, Ge, You, Chen, Lei and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hongtao Hu, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
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