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Background <p>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).</p> Methods <p>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.</p> Results <p>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&#xa0;years for high-risk women and 69&#xa0;years for low-risk women. Compared to medium-risk participants, high-risk participants developed osteoporosis 4.99&#xa0;years earlier (<i>RAP</i>, 4.99; 95% <i>CI</i>, 4.94, 6.28), whereas low-risk participants developed it 4.89 years later (<i>RAP</i>, − 4.89; 95% <i>CI</i>, − 6.54, − 4.69).</p> Conclusions <p>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>

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Polygenic risk score-guided personalized osteoporosis screening: a population-based study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Dongxue Wang,
  • Wen Sun,
  • Di Liu,
  • Huan Yi,
  • Xiao Wang,
  • Xiaodan Li,
  • Jianguang Ji

摘要

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.