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

We investigated the effects of ovariectomy (ovx) and estrogen replacement t herapy (ERT) on bone mineral density (BMD) and arthritis severity in rats w ith collagen-induced arthritis (CIA). Seven-month-old female Sprague-Dawley rats were separated into a sham group (n = 8), CIA group (n = 24), ovx gro up (n = 10), CIA + ovx group (n = II), and CIA + ovx + ERT group (n = 14). In these groups, ovx was performed at 7 days, and ERT (17 beta -estradiol a t 20 mug/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 hones in the metaphysis and diaphysis of the tibia were measured by peripheral q uantitative 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 gr oup. BMD in the metaphysis was significantly decreased in both the trabecul ar and cortical bones in the CIA + ovxr group compared with those in the CI A group at 4, 6, and 8 weeks after sensitization. In the CIA + ovx group, t rabecular 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 CI A group, changes of BmD in the metaphyis were -7 +/- 11% in trabecular bone and 0 +/- 7% in cortical bone. These differences of trabecular and cortica l bone loss in the metaphysis were significant (both p < 0.01). BMD reducti on vas significantly less in the CIA + ovx + ERT group than in the CIA + ov x group at 6 and 8 weeks after sensitization. Although BMD in the diaphysis was also reduced in the groups crith CW, the degree of reduction was small er than in the metaphysis. We conclude that ovx in CIA rats could enhance t he severity of arthritis and bone loss, and that ERT could suppress arthrit is and bone loss. (C) 2001 by Elsevier Science Inc. All rights reserved.