Differential Mortality and the Excess Rates of Hip Fracture Associated With Type 2 Diabetes: Accounting for Competing Risks in Fracture Prediction Matters.
Tebé C., Martinez-Laguna D., Moreno V., Cooper C., Diez-Perez A., Collins GS., Prieto-Alhambra D.
Type 2 diabetes (T2DM) is associated with a reduced life expectancy. The latest published evidence suggests an increased risk of fractures among T2DM patients. We conducted a population-based cohort study to determine the impact of mortality as a competing risk in the study of the association between T2DM and hip fracture rates. Participants were all diagnosed T2DM patients registered in the Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) database aged 65 years and older; up to two non-T2DM were matched by age, sex, and primary care facility. We used Cox regression models to estimate cause-specific hazard ratio (HR) of death or hip fracture according to T2DM status. Fine and Gray models were then fitted to estimate the subhazard ratio (SHR) of hip fracture while accounting for competing risk with death and to estimate the probability of hip fracture within 5 years. A total of 55,891 T2DM and 103,093 matched non-T2DM patients were observed for a median of 8 years. Mortality was 48.8 per 1000 person years (py) in T2DM, and 33.8 per 1000 py in non-T2DM; hip fracture rates were 6.0 per 1000 py and 4.9 per 1000 py, respectively. Cox models confirmed a significant association for death and hip fracture: HR 1.51 (95% CI, 1.48 to 1.55), and HR 1.32 (95% CI, 1.24 to 1.40), respectively. Accounting for death as a competing event (Fine-Gray models), the association between T2DM and hip fracture risk remained statistically significant (SHR 1.15; 95% CI, 1.09 to 1.21) and the probability of a hip fracture within 5 years was 2.3% for TD2M and 1.9% for non-TD2M patients compared to 2.6% and 2.1% respectively using Kaplan-Meier (KM) estimates. T2DM patients have a 50% increased mortality and, after adjusting for differential survival at 5 years, a 21% increased incidence of hip fracture when compared to matched non-T2DM. Failing to account for differential mortality leads to an overestimation of fracture risk. © 2018 American Society for Bone and Mineral Research.