OBJECTIVES: Patients with hereditary hemochromatosis, beta-thalassemia, and sickle-cell disease have an elevated risk of fracture. However, the extent that this is due to iron overload remains unclear. We aimed to assess the risk of fractures among patients with iron overload (i.e., serum ferritin values >1000ug/L) and among those with a diagnosis of hemochromatosis, beta-thalassemia, or sickle-cell disease without iron overload, compared to matched controls.

METHODS: We used primary care data from the UK from the IQVIA Medical Research Database that incorporates data from THIN, a Cegedim Database of anonymized electronic health records. Patients aged >18 years with an incident diagnosis of hemochromatosis, beta-thalassemia, or sickle-cell disease or with an incident record of elevated serum ferritin values (>1000ug/L) were identified between 2010-2022. Each case was matched with up to 10 controls. We used time-varying Cox proportional hazard models adjusted for confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of major osteoporotic fracture associated stratified by incident diagnosis vs evidenced iron overload.

RESULTS: We identified 6754 patients with incident diagnosis and 13,510 with iron overload, who were matched to 79,256 and 113,700 controls, respectively. Incident diagnosis patients had an average age of 63.2 and 34.3% were female, while high ferritin value patients had an average age of 47 and 48.7% were female. We observed that patients with an incident diagnosis had no elevated risk of fractures (HR 0.99, 95% CI 0.84 – 1.16), but patients with high ferritin value had a statistically significant increased risk for fractures (HR 1.91, 95% CI 1.73 – 2.10).

CONCLUSIONS: In this population-based cohort study we found that patients with high ferritin value had a 91% increased risk of suffering a fracture. Our findings highlight the importance of considering ferritin levels in the assessment of fracture risk in hemochromatosis patients.