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Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study

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Abstract

Background

A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia.

Objectives

To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia.

Design

Prospective cohort study.

Setting

UK Biobank.

Participants

496,331 participants (54.6% women) free of dementia at baseline.

Measurements

History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia.

Results

Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14–1.43; adjusted HR: 1.48; 95% CI: 1.18–1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95–1.15; adjusted HR: 1.01; 95% CI: 0.87–1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia.

Conclusions

This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.

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Data sharing: Data used in the present study were obtained from the UK Biobank under Application Number 90492. Further details can be found at https://www.ukbiobank.ac.uk.

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Acknowledgements

We appreciate efforts made by the original data creators, depositors, copyright holders, the funders of the data collections, and their contributions to the access of data from the UK Biobank team (project no. 90492). We are also grateful to the participants for generously dedicating their time to take part in the UK Biobank study.

Funding

Role of the funding sources: This study was supported by grants from the National Natural Science Foundation of China (project number 82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2019 Irma and Paul Milstein Program for Senior Health Research Project Award. The funders had no role in the study design; the collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the article for publication.

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Authors and Affiliations

  1. Heart and Vascular Health Research, Center Peking University Clinical Research Institute, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, 100034, Beijing, China

    D. Gao, C. Li, Y. Wang & Wuxiang Xie

  2. Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China

    D. Gao, C. Li, Y. Wang & Wuxiang Xie

  3. Department of Orthopedics, Beijing Tsinghua Changgung Hospital Medical Center, Tsinghua University, Beijing, China

    W. Rong

  4. School of Nursing, Peking Union Medical College, Chinese Academy of Medical Sciences, 33 Ba Da Chu Road, Shijingshan District, 100144, Beijing, China

    J. Liang, Y. Pan, W. Zhang & Fanfan Zheng

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  1. D. Gao
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  3. C. Li
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  9. Wuxiang Xie
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Contributions

Author contributions: Fanfan Zheng and Wuxiang Xie conceived the study. Darui Gao and Chenglong Li did the data analysis and data interpretation. Darui Gao drafted the initial manuscript. All authors critically revised the manuscript. Fanfan Zheng and Wuxiang Xie are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Corresponding authors

Correspondence to Fanfan Zheng or Wuxiang Xie.

Ethics declarations

Ethical statement: Ethics Committee approval for UK Biobank was obtained from the North West Multi-Centre Research Ethics Committee (Research Ethics Committee reference: 16/NW/0274). As part of the UK Biobank recruitment process, informed consent was obtained from all individual participants included in this study.

Declaration of interests: All other authors declare that there are no competing interests.

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Gao, D., Rong, W., Li, C. et al. Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study. J Prev Alzheimers Dis (2024). https://doi.org/10.14283/jpad.2024.56

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