Change in estimated glomerular filtration rate and fracture risk in the Action to Control Cardiovascular Risk in Diabetes Trial

Objective: Patients with type 2 diabetes (T2DM) are at increased risk of fracture. High prevalence of chronic kidney disease (CKD) in T2DM may contribute to bone fragility, but whether dynamic change in kidney function is associated with fracture risk is unclear. Research design and methods: To evaluate the association of pre-randomization baseline estimated glomerular filtration (eGFR) and its change over time with subsequent fracture risk in the Bone substudy of Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial, we conducted an observational study of 2262 women and 4737 men with T2DM and with at least 2 eGFR values. Results: During a mean follow-up of 4.40. ±. 1.54. years, 235 women and 223 men sustained a new non-vertebral fracture. In multivariable adjusted sex-specific models, pre-randomization baseline eGFR was not a significant predictor of fracture risk in either men or women. However, a steeper decline in eGFR was associated with greater risk of fracture in women (hazard ratio [HR] per standard deviation [SD] decrement in eGFR slope, 1.30; 95%CI 1.17-1.44) but not men (HR per SD decrement in eGFR slope, 0.97; 95%CI 0.82-1.13). Accounting for competing risk of death modestly attenuated the association in women (HR per SD decrement in eGFR slope, 1.19; 95%CI 1.04-1.37), with the relationship in men remaining non-significant (HR per SD decrement in eGFR slope, 0.96; 95%CI 0.77-1.18). Conclusions: Declining kidney function predicts fracture risk in women but not in men with T2DM. Future studies should investigate the mechanisms for these associations.