EFFECTS OF LY-117018 HCL ON BONE REMODELING AND MINERAL DENSITY IN THE OOPHORECTOMIZED RAT

OBJECTIVE: LY-117018 HCl is a recently developed, selective estrogen r eceptor modulator and an analog of raloxifene. Its mode of action on t he skeleton is similar to that of estrogens, although it does not have the same side effects. The aim of the current study was to compare th e effects produced by the administration of 17 alpha-ethinyl estradiol (0.1 mg/kg/day) and LY-117018 HCl (1 mg/kg/day) on bone remodeling, b one mineral density, and body and uterus weight in sham-operated and o ophorectomized rats (experimental model of postmenopausal osteoporosis ). STUDY DESIGN: Twelve-week-old female Wistar rats were used. Treatme nt was given for 3 months after oophorectomy or sham operation, Bone m ineral density was determined in the lumbar spine (L2, L3, and L4) and in the left femur with use of a Hologic QDR 1000 (S/N 277) densitomet er. Bone remodeling was estimated with use of the formation markers os teocalcin (bone gla protein) and alkaline phosphatase and the resorpti on markers type I collagen carboxyterminal telopeptide and tartrate-re sistant acid phosphatase. RESULTS AND CONCLUSIONS: The newly developed derivative of raloxifene, LY-117018 HCl, offsets the reduction in bon e mineral density and the accompanying increase in bone remodeling mar kers observed in oophorectomized rats compared with control animals. 1 7 alpha-Ethinyl estradiol also prevents the loss of bone mass attribut ed to oophorectomy, but this is accompanied by an increase in body mas s and a greater increase in uterus weight than that observed after tre atment with LY-117018 HCl.