Relationship between iron overload and osteopenia in ethanol-fed rats

Some observations suggest that iron overload may directly affect bone metabolism, leading to osteopenia. Objective: To analyze the relationship between bone iron overload and bone metabolism, including trabecular bone mass, osteocalcin, insulin-like growth factor-1 (IGF-1) and parathormone, in ethanol and/or 2% protein-fed rats. Method: Adult male Sprague-Dawley rats were divided into 4 groups. The control rats received the Lieber-DeCarli control diet (Dyets Inc, Bethlehem, PA, USA), containing 18% protein and 1 kcal/ml; a second group was fed an isocaloric, 36% ethanol-containing diet; the third one was fed an isocaloric, 2% protein-containing diet; and the fourth group was fed an isocaloric diet containing 2% protein and 36% ethanol. After sacrifice (5 weeks later), trabecular bone mass (TBM) and osteoid area were histomorphometrically assessed, bone and liver iron were determined by flame atomic absorption spectrophotometry, and serum osteocalcin, insulin- like growth factor-1 (IGF-1), and PTH, by radioimmuno-analysis. Results: Ethanol-fed rats showed decreased TBM and increased liver iron (especially when protein deficiency was also present), and significant relationships were found both between bone iron and liver iron and TBM. Bone iron was also inversely related to osteocalcin. Multivariate analysis showed that trabecular bone mass was independently related to liver iron and albumin, in this order, whereas osteoid was related to liver iron and bone iron, in this order. Conclusion: Our results suggest that bone iron and liver iron overload are related to decreased bone mass and decreased bone synthesis in rats fed the Lieber-de Carli ethanol and/or protein-deficient diets.