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Background  Impaired orthostatic blood pressure response and syncope confer a high risk of falls and trauma. The relationship between a history of unexplained syncope and orthostatic hypotension (OH) with subsequent fractures, however, has not been thoroughly examined. In this study, we aimed to investigate the relationship between previous hospital admissions due to unexplained syncope and OH and incident fractures in a middle-aged population.    Methods  We analysed a large population-based prospective cohort of 30,399 middle-aged individuals (age, 57.5 ± 7.6; women, 60.2%). We included individuals hospitalised due to unexplained syncope or OH as the main diagnosis. Multivariable-adjusted Cox regression analysis was applied to assess the impact of unexplained syncope and OH hospitalisations on subsequent incident fractures.    Results  During a follow-up period of 17.8 + 6.5 years, 8201 (27%) subjects suffered incident fractures. The mean time from baseline and first admission for syncope ( n  = 493) or OH ( n  = 406) was 12.6 ± 4.2 years, and the mean age of the first hospitalisation was 74.6 ± 7.4 years. Individuals with incident fractures were older, more likely to be women, and had lower BMI, higher prevalence of prevalent fractures, and family history of fractures. Multivariable-adjusted Cox regression showed an increased risk of incident fractures following hospitalisations due to unexplained syncope (HR 1.20; 95% CI 1.02–1.40;  p  = 0.025) and OH (HR 1.42; 95% CI 1.21–1.66;  p  < 0.001) compared with unaffected individuals.    Conclusions  Individuals hospitalised due to unexplained syncope and orthostatic hypotension have an increased risk of subsequent fractures. Our findings suggest that such individuals should be clinically assessed for their syncope aetiology, with preventative measures aimed at fall and fracture risk assessment and management.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12916-021-02065-7.

Risk of incident fractures in individuals hospitalised due to unexplained syncope and orthostatic hypotension