JOURNAL OF BONE AND MINERAL RESEARCH Volume 5, Number 11, zyxwvutsrqpon 1990 Mary Ann Liebert, Inc., Publishers zyxwvutsrqpo Effects of Progesterone on Postovariectomy Bone Loss in Aged Rats E.I. BARENGOLTS,' H.F. GAJARDO,' T. J. ROSOL,' J.J. D'ANZA,' M. PENA,' J. BOTSIS,3 and S.C. KUKREJA' ABSTRACT The effects of progesterone on oophorectomy-induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham-operated controls (SHAM); zyx (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX zyxwvu + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats. These reductions did not occur in OVX rats treated with PROG. There was no difference in the bone composition between the control and progesterone-treated rats. Vertebral bone histomorphometry showed increased bone resorption as well as increased bone formation parameters in OVX rats. Proges- terone treatment inhibited the increased resorption indices, but the bone formation remained elevated. The results indicate that progesterone therapy prevents the postovariectomy bone loss in aged rats. The protec- tive effect of progesterone is mediated by inhibition of bone resorption while maintaining the increased bone formation. These findings suggest that progesterone alone may be a valuable agent for management of post- menopausal osteoporosis. INTRODUCTION HE IMPORTANCE OF OVARIAN ESTROGEN ir,, bone mineral T homeostasis has been clearly demonstrated in animal models" zyxwvutsrq z, as well as in patients with osteopenia." Estro- gen (E,) treatment prevents the postovariectomy (OVX) bone IOSS.'~-~' The effects of progesterone (F'ROG) on this bone loss are less clear, however.I9) Snow and Anderson demonstrated that medroxyprogesterone stimulated bone formation in spayed Beagle dams."') Animal studies of progesterone effects on mineral metabolism are few and controversial. Aitken et al. showed that, by histomor- phometry, progesterone prevented osteopenia in young oophorectomized rats but estrogen had no significant ef- fect on bone loss."" On the other hand, in the study by Barbagallo et al. bone mineral loss was prevented by either progesterone or estrogen but the combination of these drugs had no effect on bone mineral Recently, ovariectomized aged rats have been used as a model for postmenopausal osteoporosis.'" 14) In the present study we evaluated the effects of progesterone on ovariectomy-in- duced bone loss in aged rats. MATERIALS AND METHODS zyx Animals Female rats (9 months old, retired breeders) were ob- tained from Sprague-Dawley Breeding Laboratories (In- dianapolis, IN). The animals were housed in the animal fa- cility for an additional 3 months, so that they were 12 months old at the start of the study. The animals were as- signed to three groups: (1) sham-operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). Bilateral ovariectomy was performed under ketamine anesthesia (100 mg/kg IP) via an abdominal approach. In the sham- operated animals abdominal incision was made and ovaries ~ ~~~ 'Department of Medicine, VA West Side Medical Center, and University of Illinois College of Medicine, Chicago, IL 60612. 'Department of Pathobiology, College of Veterinary Medicine, Ohio State University, Columbus, OH 43210. 'Department of Civil Engineering, Mechanics and Metallurgy, College of Engineering, University of Illinois, Chicago. IL 60680. 1143