Abstract
Effects of four kinds of chelating agents, Ca-DTPA (calcium diethylenetriaminepentaacetic acid), Ca-EDTA (calcium ethylenediaminetetraacetic acid), CBMIDA [catechol-3, 6-bis(methyleiminodiacetic acid)] and Zn-DTPA (zinc DTPA), on bone metabolism were examined in beagle dogs by bone histomorphometry and measurement of serum biochemical constituents related to bone metabolism. Ca-DTP, Ca-EDTA or CBMIDA (150μmol/kg) was injected intravenously to dogs for 1 month, respectively. Three doses (30, 150 and 300μmol/kg) of Zn-DTPA were administered orally to dogs for 1 month respectively. All dogs received twice tetracycline hydrochloride infections at an interval of 7 days before the beginning of administration of chelating agents and also twice calcein injections at the same time schedule prior to sacrifices for analyzing bone dynamics. Bone samples were obtained from ilium and undecalcified bone sections were made. Bone histomorphometry of cancellous bone area of ilium was performed using an image analyzer.Bone volume and mean trabecular thickness did not change in any of the groups. Osteoid volume in the CBMIDA group increased (p<0.05). Osteoid volume and mean osteoid thickness in the 150μmol/kg of Zn-DTPA group decreased (p<0.05 and p<0.01). Mineral apposition rate and bone formation rate did not change in any groups except the CBMIDA and 150μmol/kg of Zn-DTPA groups, in which fluorescent bone labeling was absent or obscure, revealing inhibition of bone mineralization.Serum total calcium levels did not change in any of the groups. Serum phosphorus level decreased significantly in the 30μmol/kg dose of Zn-DTPA group (p<0.05). Parathyroid hormone level increased in the 30μmol/kg dose of Zn-DTPA (p<0.05), while it decreased in the 150μmol/kg dose of Zn-DTPA group (p<0.05).The results suggest that the protracted therapy using the above four kinds of chelating agents may incur damages of bone such as decrease of bone volume and inhibition of mineralization.
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