Murata Masakazu, Kumagai Kenji, Miyata Noriaki, Osaki Makoto, Shindo Hiroyuki
Department of Orthopedic Surgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
J Orthop Sci. 2007 May;12(3):289-95. doi: 10.1007/s00776-007-1129-y. Epub 2007 May 31.
High-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks).
A total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups' laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG.
The S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group.
This study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.
大剂量使用类固醇激素与骨坏死的主要风险相关。在本研究中，我们调查了类固醇激素对易中风自发性高血压大鼠/长崎（SHRSP/Ngsks）股骨头骨坏死发生率的影响。
总共71只SHRSP/Ngsks被分为两组：对照组（C组，n = 40）和类固醇激素组（S组，n = 31），在17周龄时给予5毫克（约20毫克/千克）醋酸甲泼尼龙。我们比较了两组的实验室数据、组织学外观、骨坏死发生率以及使用单克隆抗体抗4 - 羟基壬烯醛（anti - 4HNE）和抗8 - 羟基脱氧鸟苷（anti - 8OHdG）进行免疫组织化学分析时氧化应激的表达。
S组总胆固醇升高，高密度脂蛋白、低密度脂蛋白和甘油三酯的量均显著高于C组。组织学检查显示，S组股骨头坏死频率（95.2%）显著高于C组（51.2%）。两组骨坏死的大多数组织学特征表现出相似的典型特征。然而，S组股骨头的骨髓腔中被增多的脂肪细胞占据，且这些脂肪细胞肿胀、部分变性和坏死。免疫组织化学分析显示，S组抗4HNE和抗8OHdG抗体的染色比C组更强。
本研究在很大程度上证实了类固醇激素给药会增加骨髓中脂肪细胞数量的怀疑。还观察到了被认为是骨坏死早期迹象的脂肪变性和坏死。据推测，骨坏死是由骨髓间隔压力负荷伴随的缺血性改变引起的，在骨髓中脂肪变性、坏死和内皮细胞损伤可能与氧化应激同时发生。
