The detrimental effects of iron to the joint; aggravation by inflammation

Authors: van Vulpen, Lize F D; van Bergen, Eline D P; Pulles, AE; Mastbergen, SC

Affiliations: Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Centre (UMC) Utrecht, Utrecht University, Utrecht, the Netherlands. Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, the Netherlands. Department of Hematology, Cancer Center, University Medical Center (UMC) Utrecht, Utrecht University, Utrecht, the Netherlands.

Publication: Haemophilia; 2022

Abstract: With great interest, we read the article ‘Which part of the blood in the knee joint is responsible for its detrimental effects? (An experimental study on the knee joint in rabbits)’ which was recently published in Haemophilia.1 Colak et al. investigated the influence of different blood components on joint damage by injecting them separately into a rabbit knee. They found the most profound joint changes upon iron injections compared to plasma or the cellular components of autologous blood. The iron and iron & chelator groups showed more articular cartilage changes, although cartilage damage in general was modest (median score in these groups was 8 out of a maximum score of 21). Also, the synovial changes were scored highest in the iron and iron & chelator group. In the cellular component group and chelator only group prominent synovial proliferation and hyperplasia was seen too. This indicates that iron injected as ferric iron (Fe3+), as well as the cellular components containing ferrous iron (Fe2+) and additional proinflammatory leukocytes, but also a chelator only can cause significant synovial alterations. Therewith this study confirms the well-known harmful effects of iron on the joint, especially in an inflammatory environment. It also raises questions about the small, if at all, therapeutic window of iron chelating therapy.