Dietary iron supplementation reverses the effects of iron deficiency on bone formation markers in iron-deficient rats

Abstract

Iron plays important roles in bone health as it is required as a cofactor for renal 25-hydroxyvitamin D-1α-hydroxylase, which is involved in the production of 1,25-dihydroxyvitamin D₃ (active vitamin D), and regulates the expression of proteins involved bone formation. Herein, we investigated the effects of dietary iron supplementation on bone formation in iron-deficient rats. Male Wistar rats were fed a control (n = 12) or iron-deficient diet (n = 18) for 30 days, after which 6 rats in the iron-deficient group were switched to the control diet for 14 days. At the end of the 30-day period, hemoglobin, liver iron, serum 1,25-dihydroxyvitamin D₃, and serum osteocalcin concentrations, and femoral bone mineral density (BMD) were found to be significantly lower in iron-deficient rats than that in control rats. Following dietary iron supplementation, hemoglobin and liver iron concentrations elevated significantly in iron-deficient rats; however, they were not restored to the normal levels. Additionally, dietary iron supplementation increased serum 1,25-dihydroxyvitamin D₃ and osteocalcin concentrations and femoral mRNA expression of Bglap and Col1a1 in iron-deficient rats, which were downregulated by iron deficiency, to levels similar to that in control rats. However, femoral BMD was not recovered with dietary iron supplementation. These results suggest that iron deficiency-induced downregulation of bone formation can potentially be reversed by dietary iron supplementation. Furthermore, elevated serum 1,25-dihydroxyvitamin D₃ concentrations due to dietary iron supplementation could be responsible for increased expression of bone formation markers in iron-deficient rats.