Long-term effect of ovary removal on the joints of aged mice

Age-related diseases are medical conditions whose incidence or severity increases with advancing age. Among them, musculoskeletal diseases, like osteoarthritis, are associated with postmenopausal hormonal shifts. Ovariectomy (OVX) is a widely used animal model to mimic the decline of ovarian hormones after menopause. Most preclinical studies rely on ovariectomized young animals, questioning their relevance to faithfully replicate the complexities of the human conditions. This study examines the long-term effects of OVX on motor performance, nociceptive response, and joint morphology in adult mice, all of which are osteoarthritis-related characteristics. Seven-month-old female mice underwent OVX or sham surgery and were monitored longitudinally until 18 months of age. Motor ability was assessed using rotarod and open field tests, pain sensitivity was evaluated via Von Frey testing, and bone integrity was analyzed through micro-computed tomography (µCT). Histological evaluation of articular cartilage was performed using Safranin-O staining. A transient increase in mechanical pain sensitivity was observed between 10 and 13 months post-OVX. Despite this change, OVX did not exacerbate the age-related decline in motor function. µCT revealed reduced bone mineral density in the subchondral cortical and vertebral trabecular bone in OVX mice, without significant changes in trabecular volume. Articular cartilage degeneration was similar in both experimental groups. These findings suggest that hormonal depletion alone may not be sufficient to drive the full osteoarthritic phenotype in aging mice. Importantly, longitudinal studies allow the capture of subtle differences in the aging process.