ArticlePloS one2016
Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- m6A RNA modifications in neurosystem genes as early markers for osteoporosis with iron accumulation.Molecular biology reports · 2026Article
- The Interplay Between Bone Biology and Iron Metabolism: Molecular Mechanisms and Clinical Implications.Biomedicines · 2026Review
- Ferroptosis in osteoporosis: core mechanisms, cell-specific effects in bone remodelling, and therapeutic perspectives.Frontiers in endocrinology · 2026Review
- Article
- Increased Risk of Fracture Among Patients With Iron Overload: A Population-based Matched Cohort Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Iron and Bone Pathophysiology.Advances in experimental medicine and biology · 2025Review
- Depletion of macrophages and osteoclast precursors mitigates iron overload-mediated bone loss.IUBMB life · 2025Article
- Bone phenotyping of murine hemochromatosis models with deficiencies of Hjv, Alk2, or Alk3: The influence of sex and the bone compartment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- GPX4-mediated bone ferroptosis under mechanical stress decreased bone formation via the YAP-TEAD signalling pathway.Journal of cellular and molecular medicine · 2024Article
- Comparison of the effects of high dietary iron levels on bone microarchitecture responses in the mouse strains 129/Sv and C57BL/6J.Scientific reports · 2024Article
- Risk factors for fractures following liver transplantation: a population-based cohort study.Annals of medicine · 2023Article
- Role of Iron Accumulation in Osteoporosis and the Underlying Mechanisms.Current medical science · 2023Article
- Fighting age-related orthopedic diseases: focusing on ferroptosis.Bone research · 2023Review
- mDIXON-Quant technique diagnostic accuracy for assessing bone mineral density in male adult population.BMC musculoskeletal disorders · 2023Article
- Haemochromatosis revisited.World journal of hepatology · 2022Review
- Adding liver R2* quantification to proton density fat fraction MRI of vertebral bone marrow improves the prediction of osteoporosis.European radiology · 2022Article
- Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload.Journal of cachexia, sarcopenia and muscle · 2022Article
- Identification of Common Pathogenic Pathways Involved in Hemochromatosis Arthritis and Calcium Pyrophosphate Deposition Disease: a Review.Current rheumatology reports · 2022Review
- Association between bone trace elements and osteoporosis in older adults: a cross-sectional study.Therapeutic advances in musculoskeletal disease · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis.
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