From clinical evidence to mechanism: Blood cover study on intravenous iron and fracture risk

A translational study involving Dr. Michel V. Hadjihannas and Prof. Andre Franke from the Institute of Clinical Molecular Biology (IKMB) at Kiel University and University Hospital Schleswig-Holstein has identified clinically relevant differences between intravenous iron formulations. The study has been published as a Plenary Paper and featured on the cover of Blood, Volume 148, Issue 1.

Iron deficiency anaemia is frequently treated with intravenous iron, particularly when oral treatment is ineffective or when rapid iron replacement is required. Although different formulations are used for the same therapeutic purpose, their effects beyond iron replacement may not be identical.

The international research team examined ferric carboxymaltose, a widely used intravenous iron formulation, and compared its skeletal effects with ferric derisomaltose. By combining patient-level clinical evidence with experimental studies in iron-deficient mice, the researchers found that ferric carboxymaltose was associated with a higher fracture risk while the experimental studies showed reduced bone formation. The experimental work also provided biological evidence linking the clinical signal to effects within bone tissue. 

“The precision-medicine question is not simply whether iron deficiency should be treated, but which formulation is most appropriate for a particular patient, especially when repeated treatment may be required,” said co-corresponding author Dr. Michel V. Hadjihannas, who played a central role in shaping the clinical-translational analysis and bringing together the patient-level and mechanistic evidence.

Connecting the patient observations with experimental biology was central to the study. This approach allowed the researchers to move beyond identifying an association and investigate a plausible biological explanation for the difference between formulations.

The findings may have implications for clinical decision-making, particularly when selecting intravenous iron treatments for patients likely to receive repeated infusions. They also illustrate an important principle of precision medicine: treatments within the same therapeutic class may differ in clinically meaningful ways, and treatment choice should take both efficacy and individual risk of complications into account.

This translational perspective aligns closely with the aims of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI), which include predicting complications and individual responses to treatment and translating interdisciplinary research into improved patient care. 

The paper is accompanied by an editorial commentary and coverage in ASH Clinical News, reflecting the wider scientific and clinical interest in the findings. 

Links:

ashpublications.org/blood/article/148/1/15/567279/Ferric-carboxymaltose-increases-fracture-risk-in

https://ashpublications.org/blood/article/148/1/1/569398/A-bone-to-pick-with-ferric-carboxymaltose

ashpublications.org/blood/issue/148/1

https://ashpublications.org/ashclinicalnews/news/9239/IV-Iron-Formulation-Increases-Risk-of-Fracture

Original publication

Wagner SA, Panzer M, Pertler E, et al.
Ferric carboxymaltose increases fracture risk in patients and reduces bone formation in mice with iron deficiency anemia.
Blood. 2026;148(1):15–30.
doi: 10.1182/blood.2025031806