Effect of 16,16-dimethyl prostaglandin E2 methyl ester on weanling rat skeleton: daily and systemic administration

The effects of 0, 0.3, 1.0, and 3.0 mg of 16,16-dimethyl prostaglandin E2 methyl ester (Di-M-PGE2) per kilogram per day administered subcutaneously for 21 days to fluorescent-labeled weanling rats were studied, by single-photon absorptiometric and static and dynamic histomorphometric techniques, to determine possible alterations in growth and mineralized tissue mass and their mechanisms of response. Specimens of femurs, proximal tibia, and tibial shaft were analyzed. Di-M-PGE2 caused a reduction in bone elongation and a dramatic accumulation in metaphyseal trabecular hard tissue mass. At high doses, the growth cartilage exhibited reduced thickness and degenerative cell size and cell production rate. The increased metaphyseal trabecular hard tissue mass was restricted to the secondary spongiosa region and was observed at all dose levels. The metaphysis was further characterized by an increase in bone and calcified cartilage cores, a marked elevation in osteoblast and osteoclast numbers, in osteoblast-to-osteoclast ratios, and in ratios of differentiated cells to osteoprogenitor cells. These findings were consistent with the interpretations that Di-M-PGE2 depressed bone elongation by delaying the division and maturation of growth plate chondrocytes; stimulated the differentiation of osteoblasts and osteoclasts, thus generating more differentiated bone cells but suppressing their activities; and increased metaphyseal trabecular hard tissue by creating an imbalance in osteoblasts over osteoclasts and suppressing hard tissue resorption.