Ishikawa K, Ohira T, Sakata H
Toxicol Appl Pharmacol. 1984 Sep 30;75(3):423-36. doi: 10.1016/0041-008x(84)90179-0.
Halopredone diacetate, which is a new synthetic corticosteroid drug showing local retention, and methylprednisolone acetate in common clinical use were injected into the knee joints of adult rabbits to compare the effects of the two drugs on the articular cartilage. The dosage of one injection was 1.75 mg (H-1 group) and 8.75 mg (H-5 group) for halopredone diacetate and 1.4 mg (M-1 group) and 7.0 mg (M-5 group) for methylprednisolone acetate. The drugs were injected into the right knee joint once a week, 12 times in total. One week after the last injection, the steroid crystals remaining in the knee joint were observed in all rabbits in the H-1 and H-5 groups. White deposits were seen locally on a part of the cartilage in all the rabbits in the H-1, H-5, and M-5 groups but not in the M-1 group. These white deposits were observed as cystic lesions by light microscopy and contained abundant hydroxyapatite. Other histologic findings in the articular cartilage included fissure, hypocellularity, and a decrease of proteoglycan in each group. However, no distinct difference was noted between the H-1 group and the M-1 group as regards the histological-histochemical grades of the cartilage on the medial tibial condyle or in the electron microscopic findings of the cartilage on the medial femoral condyle. The same was true for the H-5 and M-5 groups. These results show that repeated intraarticular injections of these two drugs cause severe cartilage lesions to the same degree, except for the intracartilaginous white deposits of rabbit knees.
将具有局部滞留性的新型合成皮质类固醇药物二醋酸卤泼尼龙和临床常用的醋酸甲泼尼龙注入成年兔膝关节,以比较两种药物对关节软骨的影响。二醋酸卤泼尼龙一次注射剂量为1.75mg(H - 1组)和8.75mg(H - 5组),醋酸甲泼尼龙一次注射剂量为1.4mg(M - 1组)和7.0mg(M - 5组)。每周向右侧膝关节注射一次药物,共注射12次。最后一次注射后一周,在H - 1组和H - 5组的所有兔子膝关节中观察到残留的类固醇晶体。在H - 1组、H - 5组和M - 5组的所有兔子中,部分软骨局部可见白色沉积物,而M - 1组未见。通过光学显微镜观察,这些白色沉积物呈囊性病变,含有丰富的羟基磷灰石。关节软骨的其他组织学表现包括每组均有裂隙、细胞减少和蛋白聚糖减少。然而,在内侧胫骨髁软骨的组织学 - 组织化学分级或内侧股骨髁软骨的电子显微镜检查结果方面,H - 1组和M - 1组之间未发现明显差异。H - 5组和M - 5组也是如此。这些结果表明,除兔膝关节软骨内白色沉积物外,这两种药物反复关节内注射会导致同等程度的严重软骨损伤。