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Osteoporosis is a metabolic bone disease characterized by a decrease in the amount of bone tissue per unit volume and changes in bone microstructure, often resulting in bone fragility and increased susceptibility to fracture. Iron plays an important role in the normal physiological activities of human body, and its abnormal metabolism is one of the risk factors of osteoporosis. Iron overload, as an abnormality of iron metabolism, has been reported to be associated with osteoporosis in recent years. However, the mechanism of iron overload involved in the process of osteoporosis is not fully understood. In this review, we summarize what we have learned about iron overload-associated bone loss from clinical studies and animal models. Starting from the three signaling pathways of Wnt/β-catenin, BMP/SMADs, PI3K/AKT/mTOR, the mechanism of iron overload affecting the process of osteoporosis was explored, we got the conclusion that iron overload accelerates the process of osteoporosis by inhibiting normal wnt signaling, suppressing the BMP-2/SMADs pathway, down-regulating the PI3K/AKT/mTOR pathway to inhibit bone formation, and destroying the bone strength and load-bearing capacity, which providing a new direction for clinical treatment.
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http://dx.doi.org/10.1186/s13018-025-05588-4 | DOI Listing |
Cell Signal
September 2025
Department of Orthopedics, Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China. Electronic address:
Bone morphogenetic proteins (BMPs) are effective for treating various orthopedic conditions and are widely used clinically. However, their therapeutic efficacy is limited in osteoporosis patients. Iron overload represents a key risk factor for osteoporosis, inducing ferroptosis and suppressing the osteogenic differentiation of bone marrow stromal cells (BMSCs).
View Article and Find Full Text PDFMol Cell Biol
September 2025
Department of Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Erythropoiesis, i.e., process of red blood cell (RBC) production, is highly dependent on iron, with 60-70% of the total body iron incorporated into hemoglobin.
View Article and Find Full Text PDFCongenital dyserythropoietic anemia type III (CDA III) is an extremely rare inherited disorder characterized by ineffective erythropoiesis, multinucleated erythroblasts in the bone marrow, and variable clinical gravity. We report the case of a 6-year-old boy, presenting with abdominal distension, failure to thrive, dark urine, intermittent itching, and recurrent infections. Physical examination revealed pallor, hepatomegaly, and splenomegaly.
View Article and Find Full Text PDFBlood
September 2025
Université Paris cité, INSERM, Institut Cochin, CNRS, Paris, France.
Hepcidin is the key hyposideremic hormone produced primarily by the liver. However, recent reports reveal extra-hepatic functional sources of hepcidin, including the intestine, the site of dietary iron absorption. To determine whether intestinal hepcidin may play a role in plasma iron lowering, we generated transgenic mice overexpressing the peptide specifically in this tissue.
View Article and Find Full Text PDFEndocrine
September 2025
Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.