Effects on early estrogen replacement therapy in stability of ovariectomized rat bones. A biomechanical and radiological study on the tibia plateau

Postmenopausal osteoporosis leads to a significant increase in bone fragili ty. In this study we used the rat tibia plateau fracture model to investiga te the efficiency of estrogen replacement therapy (ERT) to mitigate the pos t-ovariectomy decrease in fracture load. A total of 73 virgin Sprague Dawley rats had been ovariectomized and 26 ani mals underwent sham operation. The ovariectomized animals were either untre ated (n=35) or treated with estrogen injections (10 mug/kg per day 3 days a week until sacrifice), starting treatment at either 0, 5, 8, or 13 days po st surgery. Before starting ERT and at 50 days post surgery, the trabecular structure o f the right proximal tibial metaphysis of each animal was imaged non-invasi vely using high resolution X-ray topography. The animals were then sacrific ed and the right knee from each animal was harvested and mounted into a ser vo-hydraulic materials testing system so that the distal femoral condyle co uld be forced into the proximal tibial plateau until fracture occurred. The failure load (F) of the ovariectomized group without estrogen administrati on was significantly less than that for the sham group. The mean stiffness (K) of the ovariectomized group was 22 percent less than that of the sham g roup, though this difference did not reach statistical significance. Across ail groups, the failure load and stiffness were significantly correl ated with the trabecular bone volume. Our data suggest that prompt ERT can increase the fracture load a nd stiffness of trabecular bone by allowing bo ne formation to continue in previously activated bone remodeling units whil e suppressing the production of new remodeling units. This may be the mecha nism by which estrogen and other antiresorptive agents increase bone mass, and thereby reduce the risk of osteoporotic fractures in postmenopausal wom en.