Increased risk of fracture among patients with iron overload: a population-based matched cohort study

Abstract

Abstract Introduction Iron overloading disorders are associated with decreased bone mineral density. However, evidence on fracture risk is scarce. Therefore, we evaluated the risk of fracture associated with iron overload disorders, compared to matched controls. Methods Using THIN, a Cegedim database of UK general practice data, we identified patients >18 years with elevated iron (ferritin value >1000 µg/L) or an eligible diagnosis code for iron overloading disorders between 2010-2022. The first date of elevated iron or a diagnosis code defined the index date for iron overload patients, who were matched with to up to 10 controls. Time-varying confounder adjusted Cox proportional hazard models estimated the hazard ratios (HRs) and 95% confidence intervals. Analyses were stratified by osteoporotic fracture site (hip, vertebral, humerus, forearm), evidence of elevated serum ferritin at baseline (ferritin >1000 µg/L), and sex. Results We identified 20,264 eligible patients and 192,956 controls. Overall, there was a 55% increased risk of any fracture among iron overload patients (HR 1.55 [1.42-1.68]). Fracture risk was increased at all sites, with the highest risk observed for vertebral fractures (HR 1.97 [1.63-2.10]). Patients with ferritin >1000µg/L had a 91% increased risk of any fracture (HR 1.91 [1.73-2.16]) and a 2.5-fold increased risk of vertebral fractures (HR 2.51 [2.01-3.12]). There was no increased risk among patients without elevated serum ferritin at any site. Fracture risk was similar between sexes. Discussion This large population-based cohort study found a 55% increased risk of fracture associated with iron overload. The risk was highest among patients with laboratory confirmed iron overload, highlighting the importance for clinicians to consider initiating osteoporosis therapy in patients with serum ferritin >1000 µg/L to minimize fracture risk.