Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
These results demonstrate that long-term ERT significantly reduces the severity of OA lesions in this animal model.
Ham
Kimberley D
KD
Dpartment of Veterinary Pathology, College of Veterinary Medicine, University of Minnesota, St. Paul, 55108, USA. hamx0012@tc.umn.edu
Loeser
Richard F
RF
Lindgren
Bruce R
BR
Carlson
Cathy S
CS
D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D004195:Disease Models, Animal; D015914:Estrogen Replacement Therapy; D004968:Estrogens, Non-Steroidal / Q000627:therapeutic use; D005260:Female; D007529:Isoflavones; D008252:Macaca fascicularis; D020370:Osteoarthritis, Knee / Q000473:pathology*; D010052:Ovariectomy; D048789:Phytoestrogens; D028321:Plant Preparations; D011897:Random Allocation
D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations