Effects of estrogen replacement therapy on bone turnover in subchondral bone and epiphyseal metaphyseal cancellous bone of ovariectomized cynomolgus monkeys

Abstract

ERT decreases the severity of OA in OVX cynomolgus monkeys. We show that bone formation is greater in subchondral bone compared with epiphyseal/ metaphyseal cancellous bone of the proximal tibia in these animals and that ERT decreases bone formation in both sites. ERT may decrease the risk of OA by decreasing bone formation in the SC bone. Introduction: Estrogen replacement therapy (ERT) decreases the risk of osteoporosis and osteoarthritis (OA) in postmenopausal women and has been shown to have direct effects on cells of the bone and cartilage. The effects of ERT have been studied extensively in cancellous bone, but subchondral (SC) bone directly beneath the articular cartilage has not been specifically evaluated. Materials and Methods: Adult feral female cynomolgus monkeys were bilaterally ovariectomized (OVX) to simulate menopause; treated with ERT, soy phytoestrogens (SPE), or no hormones (OVX control group) for 3 years; and labeled with calcein before necropsy. At necropsy, the proximal tibias of 20 randomly selected animals from each treatment group were embedded in bioplastic and sectioned. Areas and labels were measured in a carefully defined region of the SC bone and epiphyseal/ metaphyseal cancellous (EMC) bone, and derived dynamic and static indices were compared between the SC and EMC bone and among the three treatment groups. Student's t-tests and ANOVA were used to compare the data. Results and Conclusions: In both the SC and EMC bone, most of the values for the dynamic indices were highest in the OVX control group, intermediate in the SPE group, and lowest in the ERT group. The mineralizing surface, double-labeled surface, and bone formation rate (surface referent) were significantly higher in the SC bone compared with the EMC bone in the OVX control group. The trabecular bone volume was higher in the SPE-treated group compared with the OVX control group. In conclusion, the bone turnover indices were higher in the SC bone compared with the EMC bone, and ERT decreased these indices in both sites. In addition, SPE was protective against loss of bone volume. © 2004 American Society for Bone and Mineral Research.