Estradiol-Induced Knee Osteoarthrosis in Ovariectomized Rabbits

Abstract

Experiments in animals have shown that estrogen is chondrodestructive. The existence of 17 beta-estradiol receptor in rabbit chondrocyte and canine cartilage suggests that estrogen is associated with the development of osteoarthrosis (OA). The increased frequency of knee OA in obese postmenopausal women, who are often associated with hyperestrogenism, suggests a link between estradiol and OA. The pathologic changes induced by nine and 12 weeks of intraarticular injection of high doses of estradiol (0.3 mg/kg body weight/day) and low doses of estradiol (0.06 mg/kg body weight/day) into knee joints of ovariectomized rabbits have been examined. In the high-dose group, loss of condyle surface congruity, thinning, fissuring, and fibrillation of the remaining cartilage surface were observed at Week 9. At Week 12, cartilage erosion extended to the calcified layer, exposing the subchondral bone. Scanning electron microscopy (SEM) further revealed numerous pits, which indicated formation of cysts on the cartilage surface. Injection of low dose estradiol, conversely, did not induce significant pathologic changes. The results demonstrated that the direct interaction of estradiol and rabbit cartilage was dose- and duration-dependent. Pathologic changes from the current animal model of knee OA closely resembled those of knee OA in humans. Thus, this model constitutes a potential tool for further studies of the early pathologic changes of OA and the possible prevention of cartilage degeneration by estrogen receptor inhibitors.