Yamasaki D, Enokida M, Okano T, Hagino H, Teshima R
Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Bone. 2001 Jun;28(6):634-40. doi: 10.1016/s8756-3282(01)00426-4.
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 (17beta-estradiol at 20 microg/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.
我们研究了卵巢切除术（ovx）和雌激素替代疗法（ERT）对胶原诱导性关节炎（CIA）大鼠骨矿物质密度（BMD）和关节炎严重程度的影响。将7个月大的雌性Sprague-Dawley大鼠分为假手术组（n = 8）、CIA组（n = 14）、ovx组（n = 10）、CIA + ovx组（n = 11）和CIA + ovx + ERT组（n = 14）。在这些组中，ovx在第7天进行，ERT（17β-雌二醇，20μg/kg，每周3次）在致敏后第8天开始。每2周进行一次评估，直至致敏后8周，评估关节炎评分和后爪厚度，并通过外周定量计算机断层扫描测量胫骨干骺端和骨干小梁骨和皮质骨的BMD。致敏后所有时间点，CIA + ovx组的关节炎评分最高。致敏后8周，CIA + ovx组的后爪厚度显著高于CIA组（p < 0.05）。CIA + ovx + ERT组的关节炎评分和后爪厚度均低于CIA + ovx组。与CIA组相比，致敏后4、6和8周，CIA + ovx组干骺端小梁骨和皮质骨的BMD均显著降低。在CIA + ovx组中，与0周相比，8周时干骺端小梁骨BMD变化为-34±11%，皮质骨BMD变化为-14±7%。在CIA组中，干骺端小梁骨BMD变化为-7±11%，皮质骨BMD变化为0±7%。干骺端小梁骨和皮质骨丢失的这些差异具有显著性（均p < 0.01）。致敏后6周和8周，CIA + ovx + ERT组的BMD降低显著低于CIA + ovx组。虽然患有CIA的组中骨干的BMD也有所降低，但降低程度小于干骺端。我们得出结论，CIA大鼠的ovx可加重关节炎严重程度和骨质流失，而ERT可抑制关节炎和骨质流失。
