title: The detrimental effects of iron on the joint: a comparison between haemochromatosis and haemophilia.
abstract: Joint damage due to (recurrent) joint bleeding in haemophilia causes major morbidity. Although the exact pathogenesis has not been fully elucidated, a central role for iron is hypothesised. Likewise, in hereditary haemochromatosis joint destruction is caused by iron overload. A comparison between these types of arthropathy could provide more insight in the influence of iron in inducing joint damage. A literature review was performed to compare both disorders with respect to their clinical and histological characteristics, and preclinical studies on the influence of iron on different joint components were reviewed. Similarities in the features of arthropathy in haemochromatosis and haemophilia are cartilage degeneration, subchondral bone changes with osteophyte and cyst formation, and osteoporosis. In both disorders synovial inflammation and proliferation are seen, although this is much more explicit in haemophilia. Other substantial differences are the age at onset, the occurrence of chondrocalcinosis radiographically and calcium pyrophosphate dihydrate deposition disease in haemochromatosis, and a rapid progression with joint deformity and neovascularisation in haemophilia. Preclinical studies demonstrate detrimental effects of iron to all components of the joint, resulting in synovial inflammation and hyperplasia, chondrocyte death, and impaired osteoblast function. These effects, particularly the synovial changes, are aggravated in the presence of a pro-inflammatory signal, which is prominent in haemophilic arthropathy and minimal in haemochromatosis. Additional research is needed to further specify the role of iron as a specific target in treating these types of arthropathy.
authors.affiliation: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Lize F D
authors.initials: LF
authors.lastname: van Vulpen
authors.affiliation: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Goris
authors.initials: G
authors.lastname: Roosendaal
authors.affiliation: Department of Internal Medicine & Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: B Sweder
authors.initials: BS
authors.lastname: van Asbeck
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Mastbergen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
authors.affiliation: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Roger E G
authors.initials: RE
authors.lastname: Schutgens
mesh_terms: D000818:Animals; D018450:Disease Progression; D006395:Hemarthrosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D006432:Hemochromatosis / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D006467:Hemophilia A / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors
chemical_list: D007501:Iron
keywords: HAEMOPHILIA; IRON; IRON METABOLISM; JOINT PATHOLOGY