Elevated Fracture Risk in Iron Overload: Large UK Cohort Study

Overview

This population-based matched cohort study found a 55% increased risk of fractures in patients with iron overload disorders compared to controls. The highest fracture risk was observed for vertebral fractures, particularly among patients with serum ferritin levels exceeding 1000 µg/L.

Background

Iron overload disorders such as hereditary hemochromatosis and iron-loading anemias are associated with decreased bone mineral density (BMD) and impaired bone microarchitecture. While low BMD is a known risk factor for osteoporosis, evidence linking iron overload to fracture risk has been limited and inconsistent. Previous studies have suggested increased fracture risk in patients with severe iron overload, but large population-based data have been lacking. This study aimed to clarify the association between iron overload and osteoporotic fractures using a large UK general practice database.

Data Highlights

Key Findings

• Iron overload patients had a 55% increased risk of any fracture compared to matched controls (HR 1.55 [1.42–1.68]).
• Vertebral fractures showed the highest increased risk among fracture sites (HR 1.97 [1.63–2.10]).
• Patients with serum ferritin >1000 µg/L had a 91% increased risk of any fracture and a 2.5-fold increased risk of vertebral fractures.
• No increased fracture risk was observed in iron overload patients without elevated serum ferritin levels.
• Fracture risk was similar between males and females with iron overload.

Clinical Implications

Clinicians should recognize that patients with iron overload, especially those with serum ferritin levels above 1000 µg/L, are at significantly increased risk for osteoporotic fractures. Consideration should be given to early osteoporosis screening and initiation of bone-protective therapies in this high-risk population to reduce fracture incidence. Monitoring ferritin levels may help stratify fracture risk and guide management.

Conclusion

This large UK cohort study demonstrates a clear association between iron overload and increased fracture risk, particularly vertebral fractures, with the highest risk among patients with confirmed elevated serum ferritin. These findings underscore the importance of fracture risk assessment and preventive strategies in patients with iron overload disorders.

References

1. Healthcare Improvement Network/UK IMRD/2023 -- Elevated Fracture Risk in Individuals with Iron Overload: A Matched Cohort Analysis