Factors associated with fragility fractures in type 2 diabetes: An analysis of the randomised controlled Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Aims: Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes-related characteristics are independently associated with fracture risk. In this post-hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility.Materials and Methods: The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50-75 years) to receive oral co-micronised fenofibrate 200 mg (n = 4895) or placebo (n = 4900) daily for a median of 5 years. We used Coxproportional hazards models to identify baseline sex-specific diabetes-related parameters independently associated with incident fractures.Results: Over 49,470 person-years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures; incidence rates for the first fracture of 4.4 (95% CI 3.8-5.2) and 7.7 per 1000 person-years (95% CI 6.5-9.1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1.52, 95% CI 1.05-2.21, p = 0.03), insulin use (HR 1.62, HR 1.03-2.55, p = 0.03), and HDL-cholesterol (HR 2.20, 95% CI 1.11-4.36, p = 0.02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2.04, 95% CI 1.16-3.59, p = 0.01) and insulin use (HR 1.55, 95% CI 1.02-2.33, p = 0.04).Conclusions: Insulin use and sex-specific complications (in men, macrovascular disease; in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.