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Utilize polygenic risk score to enhance fracture risk estimation and improve the performance of FRAX in patients with osteoporosis

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Abstract

Summary

This study examined the use of polygenic risk scores (PGS) in combination with the Fracture Risk Assessment Tool (FRAX) to enhance fragility fractures risk estimation in osteoporosis patients. Analyzing data from over 57,000 participants, PGS improved fracture risk estimation, especially for individuals with intermediate to low risks, allowing personalized preventive strategies.

Introduction

Osteoporosis and fragility fractures are multifactorial, with contributions from both clinical and genetic determinants. However, whether using polygenic risk scores (PGS) may enhance the risk estimation of osteoporotic fracture in addition to Fracture Risk Assessment Tool (FRAX) remains unknown. This study investigated the collective association of PGS and FRAX with fragility fracture.

Methods

We conducted a cohort study from the Taiwan Precision Medicine Initiative (TPMI) at Taichung Veterans General Hospital, Taiwan. Genotyping was performed to compute PGS associated with bone mineral density (BMD). Phenome-wide association studies were executed to pinpoint phenotypes correlated with the PGS. Logistic regression analysis was conducted to ascertain factors associated with osteoporotic fractures.

Results

Among all 57,257 TPMI participants, 3744 (904 men and 2840 women, with a mean age of 66.7) individuals had BMD testing, with 540 (14.42%) presenting with fractures. The 3744 individuals who underwent BMD testing were categorized into four quartiles (Q1-Q4) based on PGS; 540 (14.42%) presented with fractures. Individuals with PGS-Q1 exhibited lower BMD, a higher prevalence of major fractures, and elevated FRAX-major and FRAX-hip than those with PGS-Q4. PGS was associated with major fractures after adjusting age, sex, and FRAX scores. Notably, the risk of major fractures (PGS-Q1 vs. Q4) was significantly higher in the subgroups of FRAX-major scores < 10% and 10–20%, but not in participants with a FRAX-major score ≧ 20%.

Conclusions

Our study highlights the potential of PGS to augment fracture risk estimation in conjunction with FRAX, particularly in individuals with middle to low risks. Incorporating genetic testing could empower physicians to tailor personalized preventive strategies for osteoporosis.

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Data availability

Data used in this article will be shared on reasonable request to the corresponding author.

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Acknowledgements

We thank all participants and investigators from the Taiwan Precision Medicine Initiative.

Funding

This study was funded by Academia Sinica 40-05-GMM and AS-GC-110-MD02, National Science and Technology Council, Taiwan [NSTC -111-2634-F-A49-014, NSTC-111-2218-E-039-001, and NSTC-111-2314-B-075A-003-MY3], and Taichung Veterans General Hospital, Taiwan [TCVGH-1127301C, TCVGH-1127302D, TCVGH-YM1120110, and TCVGH-1127304B].

Author information

Authors and Affiliations

  1. Department of Orthopedics, Taipei Veterans General Hospital, Taipei, Taiwan

    Jian-Jiun Chen

  2. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

    I-Chieh Chen, Chia-Yi Wei & Yi-Ming Chen

  3. Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan

    Shih-Yi Lin

  4. Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung, Taiwan

    Shih-Yi Lin & Yi-Ming Chen

  5. School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

    Shih-Yi Lin & Yi-Ming Chen

  6. Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan

    Yi-Ming Chen

  7. Institute of Biomedical Science and Rong-Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, Taiwan

    Yi-Ming Chen

  8. Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan

    Yi-Ming Chen

Authors
  1. Jian-Jiun Chen
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  2. I-Chieh Chen
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  3. Chia-Yi Wei
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Contributions

J-J C conceived the study and drafted and revised the manuscript. J-J C, I-CC, Chia-Yi Wei, S-Y L, and Y-MC verified the analytical methods. S-Y L and Y-MC helped supervise the project. Y-MC formed the original hypothesis, designed the study, and drafted and revised the manuscript. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Shih-Yi Lin or Yi-Ming Chen.

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Ethics approval and consent to participate

This study was reviewed and approved by the Institutional Review Board of Taichung Veterans General Hospital (CE23140B). All participants provided written informed consent according to the Helsinki Declaration.

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Not applicable.

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None.

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Chen, JJ., Chen, IC., Wei, CY. et al. Utilize polygenic risk score to enhance fracture risk estimation and improve the performance of FRAX in patients with osteoporosis. Arch Osteoporos 18, 147 (2023). https://doi.org/10.1007/s11657-023-01357-0

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