BackgroundThe increasing life expectancy of individuals with Down syndrome has led to a growing awareness of mid‐ and late‐life conditions.MethodsBased on the Disease Analyser database (IQVIA), this retrospective cohort study compared adults ≥18 years of age with Down syndrome (ICD‐10: Q90) in general practices in Germany with a propensity score‐matched cohort without Down syndrome. The outcome was the first diagnosis of a fracture within 5 years of the index date. The cumulative incidence of fractures over a 5‐year period was presented using Kaplan–Meier curves. Univariable Cox regression analyses by age group and sex were performed to assess the association between Down syndrome and fractures.ResultsA total of 2547 individuals with Down syndrome and 12 735 individuals without Down syndrome were included in the study. A significantly higher cumulative fracture incidence within 5 years was observed in the age group 51–60 years (9.3% Down syndrome vs. 4.8% without Down syndrome, P = 0.003) as well as in the age group >60 years (20.3% Down syndrome vs. 8.6% without Down syndrome, P < 0.001) compared with the cohort without Down syndrome. Regression analysis showed a significant association between Down syndrome and fracture risk in women with Down syndrome aged 51–60 years (hazard ratio [HR] = 1.60; 95% confidence interval [CI]: 1.13–2.26), and in those aged 51–60 years (HR = 2.08; 95% CI: 1.27–3.41) and >60 years (HR = 2.98; 95% CI: 1.87–4.73)), but not in men. When comparing fractures in individuals with and without Down syndrome, shoulder and arm fractures were most common in the Down syndrome cohort.ConclusionThe results of our study indicate a positive association between individuals with Down syndrome and subsequent fractures in women and those aged >50 years. Prevention of falls appears to be particularly important in these populations. However, future studies should clarify the extent to which socio‐economic factors, such as housing, play a role in this context.