Iron Deficiency Negatively Affects Bone Quality and Microarchitecture in Weanling Male Sprague Dawley Rats

Abstract

The objective of this study was to examine the effects of severe iron restriction on bone microarchitecture and begin to characterize the mechanism by which this occurs. Weanling Sprague Dawley rats were assigned to one of three dietary treatments for 35 days: severe iron restriction (< 3 mg Fe/kg diet), control (50 mg Fe/kg diet), or pair-fed control diet to the level of intake of the iron restricted animals. Analysis of bone mineral density (BMD) and microarchitecture were obtained by DXA and microcomputed tomography (CT) in both the tibia and spine. RNA was extracted from the femur and used to synthesize cDNA for quantitative real-time polymerase chain reactions (qPCR).Iron deficiency was confirmed by the expression of transferrin receptor mRNA in bone marrow cells (3.6-fold higher in iron-restricted animals, p<0.05). BMD (-12%) and bone microarchitecture of spines from animals receiving both levels of iron restriction were decreased (p<0.05), whereas no changes were observed in the tibia. Trabecular number and thickness were significantly decreased (p<0.001) coupled with an increase in trabecular separation in the spine. mRNA expression analysis revealed significant down-regulation of key osteogenic factors including Runx2, osterix, and bone morphogenetic protein-2 (BMP-2). Our findings indicate that iron deficiency negatively impact the differentiation and maturation of mesenchymal stem cells into osteoblasts, based on the observed decrease in expression of BMP-2, Runx2, and osterix. Thus, our results demonstrate that severe iron deficiency during a period of rapid growth is very likely a risk factor for osteoporosis, and future research regarding the mechanism by which this occurs is warranted.