The inhibitory effects of aluminum and iron on bone formation, in vivo and in vitro study

We studied the effects of Al and Fe on bone metabolism in vivo and in vitro using nitrilotriacetic acid (NTA) as a chelator. We have reported experimental osteopathy in growing rats (6 weeks). In the present study, we used adult Wistar rats (15 weeks). Both Al-NTA (3.0 mg Al/kg) and Fe-NTA (6.0 mg Fe/kg) caused renal insufficiency and osteomalacia. Osteoid volume was 65.79±5.25% in Al-treated rats, 3.97±2.25% in Fe-treated rats and 2.22±0.77% in the control rats. The impairment of bone mineralization was detected in Al- and Fe-treated rats. The osteoidosis induced by Al-NTA in adult rats was much more severe than that in growing rats. Osteomalacia was not induced by Fe-NTA in growing rats, but moderate osteomalacia was induced in adult rats. Therefore, an age-related change of the bone metabolism was suggested. The direct effects of these metals were also examined using an osteoblast-like cell line (HuO9) in vitro. The collagen synthesis was kept constant between Al and Fe concentration of 10−6 and 10−4 M, although ALP activity was decreased by Al and Fe. The results of this study demonstrate that Al- and Fe-NTA have negative effects on bone formation in vivo and in vitro, and that they are useful for experimental models of mineral induced osteomalacia.