Kabata T, Kubo T, Matsumoto T, Hirata T, Fujioka M, Takahashi K A, Yagishita S, Kobayashi M, Tomita K
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
Rheumatology (Oxford). 2005 Oct;44(10):1233-7. doi: 10.1093/rheumatology/keh721. Epub 2005 Jun 21.
To clarify the initial onset time of osteonecrosis after the start of steroid treatment and its relation to the onset of abnormal lipid metabolism.
Animal models were prepared by administering methylprednisolone to rabbits using five different steroid regimens.
A single, acute ischaemic event suggested by the frequency, size or number of necrotic foci within the proximal femur was not different among the groups. Histological evidence of osteonecrosis first occurred 1-2 weeks after initial steroid administration. At the same time there were significantly abnormal elevations in serum lipids, which persisted for between 1 and 2 weeks after the initial corticoid treatment. Triglycerides, total cholesterol and free fatty acids were markedly elevated in all groups; these lipid abnormalities were significantly present in the rabbits with osteonecrosis but not in the rabbits without osteonecrosis.
This study shows that (i) osteonecrosis appears in rabbits shortly after corticoids are first administered, and (ii) osteonecrosis in rabbits is chronologically associated with the onset of hyperlipaemia and increased free fatty acids. This supports the occurrence of intraosseous fat embolism as a cause of osteonecrosis.
明确类固醇治疗开始后骨坏死的初始发病时间及其与脂质代谢异常发病的关系。
采用五种不同的类固醇给药方案给兔子注射甲基泼尼松龙制备动物模型。
股骨近端坏死灶的频率、大小或数量提示的单一急性缺血事件在各组之间并无差异。骨坏死的组织学证据在首次给予类固醇后1 - 2周首次出现。与此同时,血清脂质显著异常升高,在初始皮质类固醇治疗后持续1至2周。所有组的甘油三酯、总胆固醇和游离脂肪酸均显著升高;这些脂质异常在患有骨坏死的兔子中显著存在,但在没有骨坏死的兔子中不存在。
本研究表明,(i)在首次给予皮质类固醇后不久兔子就出现骨坏死,(ii)兔子的骨坏死在时间上与高脂血症和游离脂肪酸增加的发病相关。这支持骨内脂肪栓塞作为骨坏死病因的发生。