Estrogen dose required to maintain parathyroid hormone mediated bone gain in osteopenic ovariectomized rats is probably higher than in preventive treatment with estrogen

Successful prevention of bone loss in ovariectomized rats with 17 beta-estradiol (E2) at 10 micrograms/kg/d has been reported. Here we show that E2 dose twice that much is not enough to maintain PTH(1-34) mediated bone gain. Three-month-old female Wistar rats were ovariectomized and fed with regular rodent chow and water ad libitum. Three months later they were divided into 9 groups (5-8 per group) and treated cyclically with PTH(1-34) (20 micrograms/kg/d sc, 5d/w for 3w) and E2 (20 micrograms/kg/d sc, 5d/w for 4w). There were also a baseline group and five vehicle control groups. Cancellous bone volume (Cn.BV/TV) of distal femoral metaphyses was measured by computer-aided histomorphometry on trichrome stained thin sections, and 24-hour fasted urine was analyzed for pyridinoline/creatinine (PYR/CREA) by immunoassay. Histomorphometric results showed that PTH(1-34) progressively increased Cn.BV/TV but E2 failed to maintain them. Urinary PYR/CREA results showed that E2-treated groups had lower values. We conclude that E2 dose > 20 micrograms/kg/d is required to maintain the PTH mediated bone gain.