Estrogen replacement therapy and osteoarthritis in cynomolgus monkeys.

摘要

Osteoarthritis (OA) is a degenerative joint disease that most commonly affects the knees, hips, hands and spine in humans. Several epidemiologic studies have shown that women are at an increased risk for developing OA after menopause, and that estrogen replacement therapy (ERT) may decrease that risk. The goal of this project was to address this issue using an animal model of naturally occurring OA. Surgically postmenopausal (ovariectomized) cynomolgus monkeys were given ERT, soy phytoestrogens (SPE) or no treatment (control group) for 3 years. Histological sections from the knee joints were graded and measured to evaluate disease severity among the three groups. In addition, articular cartilage from the opposite knee was evaluated biochemically to evaluate cartilage components that may be affected by estrogen. Finally, because changes in bone are important in OA, histomorphometric indices of bone turnover were evaluated in the proximal tibia.; The results of the histological study demonstrated that the OA lesions in cartilage were significantly increased in the control group compared to the ERT group, suggesting that estrogen is protective against cartilage lesions of OA. There were no significant differences between the SPE-treated group and the other two groups.; There was a significantly higher level of insulin-like growth factor binding protein (IGFBP)-3 in the articular cartilage of the ERT group compared to the control group, and a higher level of total protein was extracted from the cartilage of the control group compared to the ERT group. There were no significant differences in the levels of IGFBP-2, proteoglycan or collagen among the three groups. Indices of bone turnover were significantly higher in the control animals compared to the ERT animals. In addition, indices of bone turnover were increased in the subchondral bone compared to epipyseal/metapyseal cancellous (EMC) bone in all three groups.; In conclusion, these results indicate that ERT protects against articular cartilage lesions of OA by an unknown mechanism that may involve the upregulation of IGFBP-3 in this surgically postmenopausal monkey model. In addition, the bone turnover activity is increased the subchondral bone compared to the EMC bone, and this appears to be accentuated by estrogen deficiency.