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

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.