INSERM, U922-LHEA, Faculté de Médecine, 49045, Angers, France.
Osteoporos Int. 2011 Aug;22(8):2313-9. doi: 10.1007/s00198-010-1456-2. Epub 2010 Oct 26.
Genetic hemochromatosis is a cause of osteoporosis; mechanisms leading to iron-related bone loss are not fully characterized. We assessed the bone phenotype of HFE (-/-) male mice, a mouse model of hemochromatosis. They had a phenotype of osteoporosis with low bone mass and alteration of the bone microarchitecture.
Genetic hemochromatosis is a cause of osteoporosis. However, the mechanisms leading to iron-related bone loss are not fully characterized. Recent human data have not supported the hypothesis of hypogonadism involvement. The direct role of iron on bone metabolism has been suggested.
Our aim was to assess the bone phenotype of HFE (-/-) male mice, a mouse model of human hemochromatosis, by using microcomputed tomography and histomorphometry. HFE (-/-) animals were sacrificed at 6 and 12 months and compared to controls.
There was a significant increase in hepatic iron concentration and bone iron content in HFE (-/-) mice. No detectable Perls' staining was found in the controls' trabeculae. Trabecular bone volume (BV/TV) was significantly lower in HFE (-/-) mice at 6 and 12 months compared to the corresponding wild-type mice: 9.88 ± 0.82% vs 12.82 ± 0.61% (p = 0.009) and 7.18 ± 0.68% vs 10.4 ± 0.86% (p = 0.015), respectively. In addition, there was an impairment of the bone microarchitecture in HFE (-/-) mice. Finally, we found a significant increase in the osteoclast number in HFE (-/-) mice: 382.5 ± 36.75 vs 273.4 ± 20.95 ¢/mm(2) (p = 0.004) at 6 months and 363.6 ± 22.35 vs 230.8 ± 18.7 ¢/mm(2) (p = 0.001) at 12 months in HFE (-/-) mice vs controls.
Our data show that HFE (-/-) male mice develop a phenotype of osteoporosis with low bone mass and alteration of the microarchitecture. They suggest that there is a relationship between bone iron overload and the increase of the osteoclast number in these mice. These findings are in accordance with clinical observations in humans exhibiting genetic hemochromatosis and support a role of excess iron in relation to genetic hemochromatosis in the development of osteoporosis in humans.
通过微计算机断层扫描和组织形态计量学评估 HFE（-/-）雄性小鼠（一种人类遗传性血色素沉着症的小鼠模型）的骨骼表型。HFE（-/-）动物在 6 个月和 12 个月时被处死，并与对照组进行比较。
HFE（-/-）小鼠的肝铁浓度和骨铁含量显著增加。在对照组的小梁中未发现可检测到的 Perl 染色。HFE（-/-）小鼠的小梁骨体积（BV/TV）在 6 个月和 12 个月时均显著低于相应的野生型小鼠：9.88±0.82%比 12.82±0.61%（p=0.009）和 7.18±0.68%比 10.4±0.86%（p=0.015）。此外，HFE（-/-）小鼠的骨微结构受损。最后，我们发现 HFE（-/-）小鼠的破骨细胞数量显著增加：382.5±36.75 个/毫米 2 比 273.4±20.95 个/毫米 2（p=0.004），在 6 个月时和 363.6±22.35 个/毫米 2 比 230.8±18.7 个/毫米 2（p=0.001），在 12 个月时在 HFE（-/-）小鼠与对照组之间。
我们的数据表明，HFE（-/-）雄性小鼠表现出低骨量和微结构改变的骨质疏松表型。它们表明，骨铁过载与这些小鼠中破骨细胞数量的增加之间存在关系。这些发现与表现出遗传性血色素沉着症的人类的临床观察结果一致，并支持过量铁与遗传性血色素沉着症之间的关系在人类骨质疏松症的发展中的作用。
