School of Medicine Publications and Presentations
Document Type
Article
Publication Date
2-2025
Abstract
Screening for and prevention of osteoporosis and osteoporotic fractures is imperative, given the high burden on individuals and society. This study constructed and validated an aging-related biomarker derived from the urinary proteomic profile (UPP) indicative of osteoporosis (UPPost-age). In a prospective population study done in northern Belgium (1985-2019), participants were invited for a follow-up examination in 2005-2010 and participants in the 2005-2010 examination again invited in 2009-2013. Participants in both the 2005-2010 and 2009-2013 examinations (n = 519) constituted the derivation (2005-2016 data) and time-shifted validation (2009-2013 data) datasets; 187 participants with only 2005-2010 data formed the synchronous validation dataset. The UPP was assessed by capillary electrophoresis coupled with mass spectrometry. Analyses focused on 2372 sequenced urinary peptides (101 proteins) with key roles in maintaining the integrity of bone tissue. In multivariable analyses with correction for multiple testing, chronological age was associated with 99 urinary peptides (16 proteins). Peptides derived from IGF2 and MGP were upregulated in women compared to men, whereas COL1A2, COL3A1, COL5A2, COL10A1 and COL18A1 were downregulated. Via application of a 1000-fold bootstrapped elastic regression procedure, finally, 29 peptides (10 proteins) constituted the UPPost-age biomarker, replicated across datasets. In cross-sectional analyses of 2009-2013 data (n = 706), the body-height-to-arm-span ratio, an osteoporosis marker, was negatively associated with UPPost-age (p&;lt0.0001). Over 4.89 years (median), the 10-year risk of osteoporosis associated with chronological age and UPPost-age (53 cases including 37 fractures in 706 individuals) increased by 21% and 36% (p ≤ 0.044). Among 357 women, the corresponding estimates were 55% and 60% for incident osteoporosis (37 cases; p ≤ 0.0003) and 42% and 44% for osteoporotic fractures (25 cases; p ≤ 0.017). In conclusion, an aging-related UPP signature with focus on peptide fragments derived from bone-related proteins is associated with osteoporosis risk and available for clinical and trial research.
Recommended Citation
Yu, Y. L., Martens, D. S., An, D. W., Chori, B., Latosinska, A., Siwy, J., Odili, A. N., Stolarz-Skrzypek, K., Maestre, G. E., Asayama, K., Li, Y., Verhamme, P., Allegaert, K., Mischak, H., Nawrot, T. S., & Staessen, J. A. (2024). Osteoporosis in Relation to a Bone-Related Aging Biomarker Derived from the Urinary Proteomic Profile: A Population Study. Aging and disease, 16(1), 633–644. Advance online publication. https://doi.org/10.14336/AD.2024.0303
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Aging and Disease
DOI
10.14336/AD.2024.0303
Academic Level
faculty
Mentor/PI Department
Neuroscience
Comments
Copyright: © 2025 Yu et al.
this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.