Effects of ovariectomy and estrogen replacement therapy on arthritis and bone mineral density in rats with collagen-induced arthritis

Abstract

We investigated the effects of ovariectomy (ovx) and estrogen replacement therapy (ERT) on bone mineral density (BMD) and arthritis severity in rats with collagen-induced arthritis (CIA). Seven-month-old female Sprague-Dawley rats were separated into a sham group (n = 8), CIA group (n = 14), ovx group (n = 10), CIA + ovx group (n = 11), and CIA + ovx + ERT group (n = 14). In these groups, ovx was performed at 7 days, and ERT (17β-estradiol at 20 μg/kg three times per week) was initiated 8 days after sensitization. Every 2 weeks, until 8 weeks after sensitization, arthritis score and hind paw thickness were evaluated, and BMD of the trabecular and cortical bones in the metaphysis and diaphysis of the tibia were measured by peripheral quantitative computed tomography. The arthritis score was highest in the CIA + ovx group at all timepoints after sensitization. The hind paw thickness was significantly higher in the CIA + ovx group than in the CIA group at 8 weeks after sensitization ( p < 0.05). Both the arthritis score and hind paw thickness were lower in the CIA + ovx + ERT group than in the CIA + ovx group. BMD in the metaphysis was significantly decreased in both the trabecular and cortical bones in the CIA + ovx group compared with those in the CIA group at 4, 6, and 8 weeks after sensitization. In the CIA + ovx group, trabecular BMD was changed by −34 ± 11%, and cortical BMD changed by −14 ± 7% in the metaphysis at 8 weeks compared with those at 0 week. In the CIA group, changes of BMD in the metaphysis were −7 ± 11% in trabecular bone and 0 ± 7% in cortical bone. These differences of trabecular and cortical bone loss in the metaphysis were significant (both p < 0.01). BMD reduction was significantly less in the CIA + ovx + ERT group than in the CIA + ovx group at 6 and 8 weeks after sensitization. Although BMD in the diaphysis was also reduced in the groups with CIA, the degree of reduction was smaller than in the metaphysis. We conclude that ovx in CIA rats could enhance the severity of arthritis and bone loss, and that ERT could suppress arthritis and bone loss.