Objective: Estrogens are suggested to play a role in the development of osteoarthritis as indicated by the increased prevalence in women after menopause. We studied whether deletion of the estrogen receptor (ER) alpha, beta, or both in female mice results in cartilage damage, osteophytosis, and changes in subchondral bone of skeletally mature animals.Methods: We studied knee joints of 6-month-old female ER alpha-/-, ER beta-/-, and (double) ER alpha-/-beta-/- mice and their wild type (wt) littermates. The presence and size of osteophytes and osteoarthritic changes in cartilage were analyzed using histology. Changes in subchondral plate and trabecular bone were studied using micro-CT.Results: In ER alpha-/-beta-/- mice, we observed an increase in number and/or size of osteophytes and thinning of the lateral subchondral plate. However, cartilage damage was not different from wt. In ER alpha-/- or ER beta-/- mice, no significant differences in cartilage damage score, osteophyte formation, or subchondral plate thickness were found.The bone volume fraction of the epiphyseal trabecular bone was unchanged in ER alpha-/- mice, increased in ER beta-/- mice, and decreased in ER alpha-/-beta-/- mice.Conclusions: We conclude that deletion of both ERs leads to increased osteophytosis, but deletion of one or both ERs does not lead to overt cartilage damage in 6-month-old mice. (c) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.