Abstract

Dietary iron intake is associated with bone metabolism in human and animals. Previous studies have suggested that iron deficiency diminishes bone formation and causes bone loss in rats, however, the detailed mechanisms remain unclear. To clarify the mechanism of the diminishing bone formation in iron deficiency, we examined the renal 25-hydroxyvitamin D3-1α-hydroxylase (1α-hydroxylase) activity and femoral expression of bone formation-related genes in iron-deficient rats. Male Wistar rats (n = 18) at 3 weeks of age were divided into three groups of six rats each. Two groups of rats were given free access to a control diet or an iron-deficient diet for 4 weeks. Rats in the third group were pair-fed the control diet, calculated as the mean food intake of the iron-deficient group. Following the treatment, compared with the control and pair-fed groups, hemoglobin and liver iron concentrations were significantly lower and heart weight was significantly higher in the iron-deficient group. Serum 1,25-dihydroxyvitamin D3 concentration and renal 1α-hydroxylase activity were significantly lower in the iron-deficient group compared with the control and pair-fed groups. Serum osteocalcin concentration and bone mineral density of the femur were also significantly lower in the iron-deficient group compared with the control and pair-fed groups. Furthermore, iron-deficient diet decreased runt-related transcription factor 2, osteocalcin, and type I collagen mRNA expression in the femur. Our findings indicate that iron deficiency reduces renal 1α-hydroxylase activity, leading to a decreased bone formation in rats.

Highlights

  • Dietary iron intake is associated with bone metabolism in human and animals

  • Serum 1,25-dihydroxyvitamin D3 concentration, renal iron concentration, and renal 1α-hydroxylase activity Serum 1,25-dihydroxyvitamin D3 concentration was significantly lower in the iron-deficient group in comparison with the control and pair-fed groups, and there was no significant difference in the concentration levels between the control and pair-fed groups (Fig. 1)

  • Renal iron concentration and 1α-hydroxylase activity were significantly lower in the iron-deficient group compared with the control and pair-fed groups, and there were no significant differences in these factors between the control and pair-fed groups

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Summary

Introduction

Dietary iron intake is associated with bone metabolism in human and animals. Previous studies have suggested that iron deficiency diminishes bone formation and causes bone loss in rats, the detailed mechanisms remain unclear. Iron deficiency anemia is an important health problem throughout the world, and several researchers have studied the relationships between dietary iron and bone metabolism in human and animals. Iron intake was positively associated with bone mineral density (BMD) in postmenopausal women [1, 2]. Bone mineral content (BMC), BMD, and bone strength were reduced in the iron-deficient rats [3, 4]. Our previous study showed that iron deficiency decreases BMC, BMD, and bone strength in rats, together with diminishing bone formation [7]. We demonstrated that iron deficiency diminishes bone formation rate, which was reflected in a decreased serum 1,25-dihydroxyvitamin D3 concentration in the iron-deficient rats [8]

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