Ono Yuichi, Miyakoshi Naohisa, Kasukawa Yuji, Imai Yuuki, Nagasawa Hiroyuki, Tsuchie Hiroyuki, Akagawa Manabu, Nagahata Itsuki, Yuasa Yusuke, Sato Chiaki, Kawatani Masahito, Shimada Yoichi
Department of Orthopedic Surgery, Akita University Graduate School of Medicine.
Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University Graduate School of Medicine.
Biomed Res. 2019;40(5):197-205. doi: 10.2220/biomedres.40.197.
We investigated the effects of ibandronate, a bisphosphonate; eldecalcitol, an active vitamin D3 analogue; and combination treatment with both agents on secondary osteoporosis and arthritis using rats with adjuvant-induced arthritis. Arthritis was induced in 8-week-old male Lewis rats. Rats were randomized into four treatment groups and an untreated normal control group: ibandronate, eldecalcitol, ibandronate + eldecalcitol, vehicle, and control. Paw thickness was measured to evaluate arthritis. Joint destruction was evaluated histomorphometrically by the ankle joint stained with Fast Green and safranin O. The femur and lumbar spine were scanned using dual-energy X-ray absorptiometry, and the distal femur was scanned using micro-computed tomography for bone mineral density (BMD) and trabecular microstructural evaluations. Ibandronate and/or eldecalcitol increased BMD in both the lumbar vertebrae and femur and improved several microstructural parameters (bone volume/total volume, structure model index, trabecular number, and trabecular separation of the distal femur). In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters, including BMD and bone volume. However, ibandronate and/or eldecalcitol did not inhibit arthritis and joint destruction. Combination treatment with ibandronate and eldecalcitol may be effective for secondary osteoporosis associated with arthritis.
我们使用佐剂诱导性关节炎大鼠模型,研究了双膦酸盐类药物伊班膦酸钠、活性维生素D3类似物 eldecalcitol 以及二者联合治疗对继发性骨质疏松和关节炎的影响。在8周龄雄性 Lewis 大鼠中诱导关节炎。将大鼠随机分为四个治疗组和一个未治疗的正常对照组:伊班膦酸钠组、 eldecalcitol 组、伊班膦酸钠 + eldecalcitol 联合组、赋形剂组和对照组。测量爪厚度以评估关节炎。通过用固绿和番红O染色的踝关节进行组织形态计量学评估关节破坏情况。使用双能X线吸收法扫描股骨和腰椎,使用显微计算机断层扫描扫描股骨远端以评估骨密度(BMD)和小梁微结构。伊班膦酸钠和/或 eldecalcitol 增加了腰椎和股骨的骨密度,并改善了几个微结构参数(骨体积/总体积、结构模型指数、小梁数量和股骨远端的小梁间距)。此外,与单一治疗相比,联合治疗对包括骨密度和骨体积在内的大多数小梁参数有相加作用。然而,伊班膦酸钠和/或 eldecalcitol 并未抑制关节炎和关节破坏。伊班膦酸钠和 eldecalcitol 联合治疗可能对与关节炎相关的继发性骨质疏松有效。