Polygenic risk score-guided personalized osteoporosis screening : a population-based study
(2026) In BMC Medicine 24(1).- Abstract
Background: Despite robust evidence that genetic factors substantially influence both osteoporosis development and fracture risk, current screening guidelines fail to incorporate genetic factors into risk-assessment protocols. This study aims to determine personalized screening ages for osteoporosis based on polygenic risk score (PRS). Methods: This prospective cohort study utilized data from 223,818 women in the UK Biobank, and only participants who were osteoporosis-free at baseline were included in the study. Participants were categorized into three subgroups (low, medium, and high groups) based on their PRS. Ten-year cumulative risk of osteoporosis, risk-adapted starting age of osteoporosis screening, and risk advancement periods... (More)
Background: Despite robust evidence that genetic factors substantially influence both osteoporosis development and fracture risk, current screening guidelines fail to incorporate genetic factors into risk-assessment protocols. This study aims to determine personalized screening ages for osteoporosis based on polygenic risk score (PRS). Methods: This prospective cohort study utilized data from 223,818 women in the UK Biobank, and only participants who were osteoporosis-free at baseline were included in the study. Participants were categorized into three subgroups (low, medium, and high groups) based on their PRS. Ten-year cumulative risk of osteoporosis, risk-adapted starting age of osteoporosis screening, and risk advancement periods (RAP) of women across different stratifications based on PRS were calculated as the main outcomes. Results: In the general female population at age 65 (current US Preventive Services Task Force recommended screening age), the 10-year cumulative osteoporosis risk was 5.95%. Women reached this risk threshold depending on their PRS, which was 60 years for high-risk women and 69 years for low-risk women. Compared to medium-risk participants, high-risk participants developed osteoporosis 4.99 years earlier (RAP, 4.99; 95% CI, 4.94, 6.28), whereas low-risk participants developed it 4.89 years later (RAP, − 4.89; 95% CI, − 6.54, − 4.69). Conclusions: The integration of PRS could revolutionize osteoporosis prevention by enabling early detection in genetically high-risk women, potentially years before the current screening guidelines. Our findings advance the field of precision prevention for osteoporosis and may significantly reduce the population burden of osteoporotic fractures.
(Less)
- author
- Wang, Dongxue ; Sun, Wen ; Liu, Di ; Yi, Huan ; Wang, Xiao LU ; Li, Xiaodan and Ji, Jianguang
- organization
- publishing date
- 2026-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Osteoporosis, Polygenic risk score, Screening age, Women health
- in
- BMC Medicine
- volume
- 24
- issue
- 1
- article number
- 56
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:41530839
- scopus:105028667821
- ISSN
- 1741-7015
- DOI
- 10.1186/s12916-025-04601-1
- language
- English
- LU publication?
- yes
- id
- 556c7aec-dc4a-4976-8052-7963d1e3cee9
- date added to LUP
- 2026-02-17 13:50:38
- date last changed
- 2026-02-18 03:00:02
@article{556c7aec-dc4a-4976-8052-7963d1e3cee9,
abstract = {{<p>Background: Despite robust evidence that genetic factors substantially influence both osteoporosis development and fracture risk, current screening guidelines fail to incorporate genetic factors into risk-assessment protocols. This study aims to determine personalized screening ages for osteoporosis based on polygenic risk score (PRS). Methods: This prospective cohort study utilized data from 223,818 women in the UK Biobank, and only participants who were osteoporosis-free at baseline were included in the study. Participants were categorized into three subgroups (low, medium, and high groups) based on their PRS. Ten-year cumulative risk of osteoporosis, risk-adapted starting age of osteoporosis screening, and risk advancement periods (RAP) of women across different stratifications based on PRS were calculated as the main outcomes. Results: In the general female population at age 65 (current US Preventive Services Task Force recommended screening age), the 10-year cumulative osteoporosis risk was 5.95%. Women reached this risk threshold depending on their PRS, which was 60 years for high-risk women and 69 years for low-risk women. Compared to medium-risk participants, high-risk participants developed osteoporosis 4.99 years earlier (RAP, 4.99; 95% CI, 4.94, 6.28), whereas low-risk participants developed it 4.89 years later (RAP, − 4.89; 95% CI, − 6.54, − 4.69). Conclusions: The integration of PRS could revolutionize osteoporosis prevention by enabling early detection in genetically high-risk women, potentially years before the current screening guidelines. Our findings advance the field of precision prevention for osteoporosis and may significantly reduce the population burden of osteoporotic fractures.</p>}},
author = {{Wang, Dongxue and Sun, Wen and Liu, Di and Yi, Huan and Wang, Xiao and Li, Xiaodan and Ji, Jianguang}},
issn = {{1741-7015}},
keywords = {{Osteoporosis; Polygenic risk score; Screening age; Women health}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Medicine}},
title = {{Polygenic risk score-guided personalized osteoporosis screening : a population-based study}},
url = {{http://dx.doi.org/10.1186/s12916-025-04601-1}},
doi = {{10.1186/s12916-025-04601-1}},
volume = {{24}},
year = {{2026}},
}