Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications

Abstract

Hereditary hemochromatosis (HHC) is characterized by excessive intestinal iron absorption resulting in a pathological increase of iron levels. Parenchyma damage may be a consequence of iron deposition in affected organs (e.g., liver, pancreas, gonads) as well as bones and joints, leading to osteoporosis with increased fracture risk and arthropathy. Up to date, it is not known whether HHC can also be considered as a risk factor for osteonecrosis. Likewise, the underlying skeletal changes are unknown regarding, e.g., microstructural properties of bone. We aimed to study the spectrum of skeletal complications in HHC and the possible underlying microarchitectural changes. Therefore, we retrospectively analyzed all patients with HHC (n = 10) presenting in our outpatient clinic for bone diseases. In addition to dual-energy X-ray absorptiometry (DXA), highresolution peripheral quantitative computed tomography (HR-pQCT) was performed and bone turnover markers, 25-OH-D3, ferritin and transferrin saturation were measured. Cortical volumetric bone mineral density (Ct.BMD) and cortical thickness (Ct.Th) were reduced, whereas trabecular microstructure (Tb.Th) and volumetric bone mineral density (Tb.BMD) were preserved compared to age-and gender-adjusted reference values from the literature. Interestingly, the occurrence of bone complications was age dependent; while younger patients presented with osteonecroses or transient bone marrow edema, patients older than 65 years presented with fractures. Our study provides first insights into altered bone microarchitecture in HHC and sheds new light on the occurrence of osteonecrosis. If available, HR-pQCT is a useful complement to fracture risk assessment and to determine microstructural deterioration and volumetric bone mineralization deficits.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Effect of Naringin Treatment on Postmenopausal Osteoporosis in Ovariectomized Rats: A Meta-Analysis and Systematic Review

“…Therefore, the microstructural analysis of trabecular bone is very important in bone analysis. Micro-CT can perform nondestructive 3D imaging of trabecular bone microstructure and display the microstructure of trabecular bone, making it possible to analyze the topology of trabecular bone microstructure [ 36 ]. Tb.Th is one of the main indexes to evaluate the spatial structure of trabeculae [ 37 ].…”

Differential Iron Requirements for Osteoblast and Adipocyte Differentiation

“…( 57 ) Indeed, iron‐overload disorders studied in mice, including hereditary hemochromatosis, have been shown to have reduced bone compared with WT mice. ( 58 ) In this way, holo‐transferrin directly delivers iron through the transferrin‐receptor–mediated pathway reducing the accumulation of free iron. Cells, differentiated toward osteoblasts but not exposed to DFO, showed little effect of holo‐transferring either at the low or high concentrations showing the iron‐bound delivery did not result in toxicity of the cells.…”

“…In vitro, when osteoblasts are treated with free iron in the form of ferric ammonium citrate, this has shown to induce cell death as free iron can be toxic to cells (57). Indeed, iron overload disorders studied in mice, including hereditary hemochromatosis, have been shown to have reduced bone compared to wild type mice (58). In this way, holo-transferrin directly delivers iron through the transferrin receptor mediated pathway reducing the accumulation of free iron.…”

Bone and joint complications in patients with hereditary hemochromatosis: a cross-sectional study of 93 patients

“…Cortical volumetric BMD and cortical thickness were lower compared with age- and gender-adjusted reference values from the literature, whereas trabecular microstructure and volumetric BMD were preserved. 32 …”