Effects of ethane-1-hydroxy-1, 1-diphosphonate on cell differentiation, and proteoglycan and calcium metabolism, in the proximal tibia of young rats.

The effects of ethane-1-hydroxy-1, 1-diphosphonate(EHDP) on cell differentiation, and on the metabolism of proteoglycan and calcium in the epiphyseal plate and metaphysis of rats were investigated through histology and autoradiograms of [35S]-sulfate, 45Ca, and [3H]-thymidine. Suppression of bone resorption in the metaphysis due to low dose EHDP administration was associated with a proliferation of osteoclasts with an increased number of nuclei. High dose EHDP induced enlargement of the hypertrophic zone of the epiphyseal plate and suppression of calcification of the cartilage matrix. This change had a significant association not only with the suppression of chondroitin sulfate synthesis and the degradation in the cartilage matrix, but also with the suppression of growth and differentiation of chondrocytes. Calcification was also inhibited in the metaphysis, and growth and differentiation from undifferentiated mesenchymal cells to osteoblasts, osteocytes, and osteoclasts were also suppressed by high dose EHDP.