SKELETAL CHANGES IN RATS RECEIVING ESTRADIOL BENZOATE AS INDICATED BY HISTOLOGICAL STUDIES AND DETERMINATIONS OF BONE ASH, SERUM CALCIUM AND PHOSPHATASE1

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Abstract
More than 200 rats, from 30-650 days of age, were given subcut. injs. of estradiol benzoate over intervals of time varying from 17-125 days. The effects on the skeleton were studied by means of histological, x-ray, and chemical technics. The latter included detns. of total bone ash, % bone ash, bone phosphatase, serum phosphatase, and serum Ca and Mg. The paired feeding technic was used in certain exps. Histological changes, consisting of an increase in density at the growing end of the bones, became detectable in young rats as early as 17 days after the beginning of treatment with estrogen. Estrogen apparently caused a decrease in normal destruction of bony trabeculae just beneath the cartilage shaft junction. There was also some increase in osteoblastic activity at the cartilage shaft junction, but not elsewhere. This increased the density of the epiphyses and apparently accounted for the increase in conc. of ash in the whole bone. The total amt. of bone was reduced owing to decreased growth in length. The skeletal changes were greater in [female][female] than in [male][male]. Skeletal changes were very slight in rats if estrogen adm. was not begun until adulthood was reached. The responsiveness of the skeleton to estrogen seemed dependent upon an active anabolic state in the bone. Serum Ca was slightly raised in rats undergoing skeletal changes. Serum Mg apparently rose but the data were not conclusive. Serum phosphatase was depressed in rats undergoing skeletal changes. Bone phosphatase was raised during the first few wks. but later it showed no difference from normal.