Effect of dichloromethane diphosphonate on calcium homeostatic mechanisms in pregnant cows

The administration of 4 mg/kg/day of dichloromethane diphosphonate (Cl2MDP) subcutaneously to pregnant cows fed a low-calcium diet significantly reduced bone resorption as indicated by microradiographic evaluation of endosteal surfaces of cross sections of ribs. Plasma parathyroid hormone levels were similar between Cl2MDP-treated and control cows prepartum, during EDTA infusions, and near parturition. Ultrastructurally, chief cells of the parathyroid glands of both groups of cows were in the active stage of the secretory cycle. The chronically stimulated chief cell from cows administered Cl2MDP had a large cytoplasmic area containing many lipofuscin granules and lysosomal bodies and a few secretory granules near the large Golgi apparatus or aligned along the plasma membrane. Uptake of calcium 45 by the duodenal mucosa incubated in vitro was greater in Cl2MDP-treated cows compared to control cows. The administration of Cl2MDP significantly reduced rapidly mobilization calcium reserves. Following an intravenous EDTA infusion and the spontaneous calcium drain associated with parturition and the beginning of lactation, Cl2MDP-treated cows developed severe hypocalcemia. The rapid mobilization of calcium reserves in cows administered Cl2MDP prepartum was impaired mainly because of diminished resorption of bone despite adequate parathyroid hormone secretion in response to severe postpartal or EDTA-induced hypocalcemia.