LIGHT MICROSCOPIC AND ULTRASTRUCTURAL OBSERVATIONS ON THE SHORT-TERM EFFECTS OF ETHYLENE-1-HYDROXY-1, 1-DIPHOSPHONATE (EHDP) ON RAT TIBIA EPIPHYSIS

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Abstract
Ethylene-1-hydroxy-1, 1-diphosphonate (EHDP) was administered i.p. to 1-day old rats at a concentration of 30 and 40 mg/kg body weight per injection. Two groups of animals received 4 doses, respectively, over a 44 h-period and a 3rd group received 2 high doses with a 15 h interval, the total amounts corresponding to 30, 40 and 20 mg EHDP/kg body wt. Animals in the 1st 2 groups showed increased width of the hypertrophic zone as compared with normal controls and lack of calcified septa within the zone of provisional calcification. In the calcification zone, persistent atypical chondrocytes were present, and in the septa there was a large number of matrix vesicles which hardly ever contained crystals. The ground substance of these septa contained fine precipitates, probably representing proteoglycan complexes which were not seen normally in this zone. In the 3rd group, the septa of the calcification zone were calcified and the hypertrophic zone was not clearly widened. In the metaphysis, remnants of cartilage or osteoid were observed as islands covered with osteoblast-like cells which showed signs both of collagen and apatite formation, the latter evidenced by the appearance of crystals within the matrix vesicles. The complex effects observed in calcifying cartilage after administration of high doses of EHDP in vivo may not be restricted solely to the stage of crystal formation.