Yamane Itsuro, Hagino Hiroshi, Okano Toru, Enokida Makoto, Yamasaki Daisuke, Teshima Ryota
Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Arthritis Rheum. 2003 Jun;48(6):1732-41. doi: 10.1002/art.10987.
To study the effect of minodronic acid (ONO-5920) on bone loss and arthritis in rats with collagen-induced arthritis (CIA) treated according to 2 different schedules.
Four groups of female Sprague-Dawley rats (7 months old) were studied: rats without CIA treated with vehicle (controls), CIA rats treated with vehicle (CIA-V), CIA rats treated therapeutically with minodronic acid (CIA-T), and CIA rats treated prophylactically with minodronic acid (CIA-P). Minodronic acid was administered orally at 0.2 mg/kg 3 times a week, beginning 2 weeks after initial sensitization in the CIA-T rats and beginning the day after initial sensitization in the CIA-P rats. Bone mineral density (BMD) was measured by peripheral quantitative computed tomography in the proximal metaphysis and diaphysis of the tibia every 2 weeks until week 8, when the rats were killed. The BMD and bone microstructure of the excised femur were evaluated by dual x-ray absorptiometry and microfocal computed tomography, respectively. Histomorphometry of the proximal tibia was also performed.
In CIA-P rats, the incidence of arthritis and the severity of posterior limb swelling were reduced early after sensitization, and the decrease in BMD was prevented throughout the observation period. Bone and joint destruction evaluated by radiography of the foot was reduced in CIA-P rats. The eroded surface was reduced and the microstructure was maintained in CIA-P rats compared with CIA-V rats. The mineral apposition and bone formation rates were not reduced in the CIA-P rats. In CIA-T rats, however, the inflammation was not suppressed and the inhibitory effect on bone loss was smaller than that in CIA-P rats.
Minodronic acid suppressed the decrease in BMD and the deterioration of the bone microstructure caused by arthritis. Prophylactic administration of minodronic acid had a preventive effect on arthritis at the early stage, although not throughout the observation period.
研究氨基双膦酸（ONO - 5920）按照两种不同给药方案治疗胶原诱导性关节炎（CIA）大鼠时对骨质流失和关节炎的影响。
对四组7月龄雌性斯普拉格 - 道利大鼠进行研究：未患CIA且用赋形剂处理的大鼠（对照组）、患CIA且用赋形剂处理的大鼠（CIA - V）、患CIA且用氨基双膦酸进行治疗的大鼠（CIA - T）以及患CIA且用氨基双膦酸进行预防的大鼠（CIA - P）。氨基双膦酸以0.2mg/kg的剂量每周口服3次，在CIA - T组大鼠初次致敏后2周开始给药，在CIA - P组大鼠初次致敏后次日开始给药。每2周通过外周定量计算机断层扫描测量胫骨近端干骺端和骨干的骨密度（BMD），直至第8周处死大鼠。分别通过双能X线吸收法和微焦点计算机断层扫描评估切除的股骨的BMD和骨微结构。还对胫骨近端进行了组织形态计量学分析。
在CIA - P组大鼠中，致敏后早期关节炎的发病率和后肢肿胀的严重程度降低，并且在整个观察期内BMD的降低得到预防。通过足部X线摄影评估的骨和关节破坏在CIA - P组大鼠中减少。与CIA - V组大鼠相比，CIA - P组大鼠的侵蚀表面减少且微结构得以维持。CIA - P组大鼠的矿物质沉积和骨形成率未降低。然而，在CIA - T组大鼠中，炎症未得到抑制，并且对骨质流失的抑制作用小于CIA - P组大鼠。
氨基双膦酸抑制了由关节炎引起的BMD降低和骨微结构恶化。氨基双膦酸的预防性给药在早期对关节炎有预防作用，尽管在整个观察期内并非如此。
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