PREVENTION OF BONE LOSS BY PERCUTANEOUS ESTRADIOL IMPLANTS IN OVARIECTOMIZED RATS

This study was conducted to investigate whether hydroxyapatite (HAP) i s appropriate as a percutaneous drug carrier for estradiol (E2) for th e suppression of bone loss. Ten-week-old female Sprague-Dawley rats we re subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-H AP disks containing low, medium or high doses of estradiol (50, 250, o r 500 mu g E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. Al l rats were sacrificed 90 days after surgery. At the end of the experi ment, bone mineral density of the lumbar spine was measured by dual en ergy X-ray absorption, and serum E2 was assayed by radioimmunoassay. T he bone mineral density of OVX and HAP-treated OVX rats decreased by 1 8% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 mu g E2/rat, respectively. The i n vitro release of E2 from E2-HAP devices was determined by an HPLC me thod. Estradiol release from the HAP devices followed almost a zero-or der kinetics. Estradiol remained intact in E2-HAP implants for up to s ix months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the sp ine of OVX rats in a dose-dependent manner. (C) 1995 John Wiley & Sons , Inc.