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A groundbreaking study has identified iron overload as a significant risk factor for fractures, revealing that patients with elevated serum ferritin levels (>1000 μg/L) are at a 91% higher risk of any fracture compared to individuals without iron overload. The findings, published in The Journal of Clinical Endocrinology & Metabolism, highlight the silent yet severe impact of iron overload on bone health, particularly increasing the risk of vertebral and humerus fractures.
Study Highlights
Researchers from ETH Zürich, led by Andrea Michelle Burden, PhD, conducted a comprehensive population-based cohort study using a UK general practice database. The study involved 20,264 patients with iron overload and 192,956 matched controls, with a mean age of 57 years and an even gender distribution.
Patients were categorized based on laboratory-confirmed iron overload (serum ferritin levels >1000 μg/L) or a diagnosis of an iron overloading disorder, such as hemochromatosis, sickle cell disease, or thalassemia major. The primary outcome was the incidence of osteoporotic fractures post-diagnosis.
Key Findings
- Patients with iron overload exhibited a 55% higher risk for any osteoporotic fracture (adjusted hazard ratio [aHR], 1.55).
- Those with laboratory-confirmed iron overload faced a 91% increased fracture risk (aHR, 1.91), with risks highest for vertebral fractures (aHR, 2.51) and humerus fractures (aHR, 2.41).
- Elevated fracture risks were not observed in patients with diagnosed iron-overloading disorders but without laboratory-confirmed high ferritin levels.
- The study found no significant differences in fracture risk between men and women.
Clinical Implications
The study underscores the importance of recognizing iron overload as a potential driver of osteoporosis and fractures. The authors recommended proactive screening and treatment strategies for high-risk patients with serum ferritin levels exceeding 1000 μg/L, aligning with osteoporosis management guidelines for individuals with hepatic disease.
“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture,” the authors stated.
Limitations and Future Directions
While the study is robust, the authors acknowledged limitations, including the inability to assess the long-term impact of iron overload and potential misclassification of controls. Additionally, inflammation—a potential confounder—could not be fully accounted for due to a lack of comprehensive biomarker data.
Future research is needed to explore the effects of chronic iron overload on fracture risk and to refine strategies for identifying and managing at-risk patients.
Conclusion
Iron overload, often overlooked in clinical practice, may silently compromise bone health and significantly elevate fracture risk. These findings advocate for increased vigilance and targeted osteoporosis interventions in patients with high serum ferritin levels.
The study was supported by the German Research Foundation, with no reported conflicts of interest.
