phytoestrogens and Osteoarthritis--Knee

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but that site differences in static and dynamic bone histomorphometry parameters exist, particularly between EMC and osteophyte bone.

Topics: Analysis of Variance; Animals; Bone Remodeling; Disease Models, Animal; Estrogen Antagonists; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Macaca fascicularis; Osteoarthritis, Knee; Osteophyte; Ovariectomy; Phytoestrogens; Postmenopause; Random Allocation; Tibia

The purpose of this study was to determine the effects of long-term estrogen replacement therapy (ERT) on insulin-like growth factor binding protein (IGFBP)-2, IGFBP-3, collagen and proteoglycan levels in the articular cartilage of the knee joint in a well-characterized monkey model of naturally occurring osteoarthritis (OA). A secondary aim was to evaluate the effect of soy phytoestrogen treatment on these articular cartilage components.. Monkeys were ovariectomized and given ERT, soy phytoestrogen treatment or no treatment (control) for 3 years. Ten animals were randomly selected from each of the three groups and the cartilage was dissected from the proximal tibia and distal femur of the knee. Levels of IGFBP-2, IGFBP-3, and total protein were measured in cartilage desorptions, and proteoglycan levels and collagen levels were measured in the cartilage tissue. Sections from the tibial plateau of the opposite knee were immunostained using antibodies directed against IGFBPs and evaluated subjectively.. IGFBP-3 levels were significantly higher, and total protein levels were significantly lower in the cartilage desorption samples from the estrogen-treated animals compared to the control animals. There were no significant differences in IGFBP-2, collagen or proteoglycan levels between the estrogen-treated and control groups. Soy phytoestrogen treatment had no significant effect on the levels of any of the cartilage components that were measured. The staining patterns observed by immunohistochemistry suggested local production of IGFBP-2 and IGFBP-3 by articular cartilage chondrocytes.. Long-term estrogen treatment results in increased IGFBP-3 levels in articular cartilage without a significant change in IGFBP-2, collagen or proteoglycan content, and IGFBP-3 appears to be synthesized by articular cartilage chondrocytes. Long-term soy phytoestrogen treatment did not have a statistically significant effect on the levels of IGFBP-2, IGFBP-3, collagen or proteoglycan.

Topics: Animals; Cartilage, Articular; Collagen; Estrogen Replacement Therapy; Female; Femur; Glycine max; Immunohistochemistry; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Isoflavones; Knee Joint; Macaca fascicularis; Osteoarthritis, Knee; Ovariectomy; Phytoestrogens; Plant Preparations; Proteins; Proteoglycans; Tibia

To determine the effects of long-term estrogen replacement therapy (ERT) on the severity of osteoarthritis (OA) of the knee joint in surgically postmenopausal (bilaterally ovariectomized) female monkeys. A secondary aim was to evaluate the effect of soy phytoestrogen (SPE) treatment on the severity of OA.. Feral adult female cynomolgus macaques were ovariectomized bilaterally and then randomly divided into 3 age- and weight-matched treatment groups. For 3 years, the first group received ERT with conjugated equine estrogens, the second group received SPE, and the third group received no treatment (controls). At necropsy, histologic lesions of OA were graded, and the area and thickness of cartilage and subchondral bone were measured. The data were summarized by principal components analysis, and the resulting factors and individual variables were compared using analysis of variance and analysis of covariance (age and weight as covariates).. Cartilage lesions of OA were significantly less severe in the animals given ERT compared with those in the control group. This treatment effect remained significant when adjusted for age and weight. The factor representing subchondral bone was significantly higher, but the number of osteophytes was lower, in the ERT group compared with the control group. SPE treatment had no significant effect on cartilage or bone lesions of OA.. These results demonstrate that long-term ERT significantly reduces the severity of OA lesions in this animal model.

Topics: Animals; Bone and Bones; Cartilage, Articular; Disease Models, Animal; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Isoflavones; Macaca fascicularis; Osteoarthritis, Knee; Ovariectomy; Phytoestrogens; Plant Preparations; Random Allocation