Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid- treated rabbits.
Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid- treated rabbits.
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DOI：
10.1210/endo.142.3.8048
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发表时间：
2001-03
期刊：
影响因子：
4.8
通讯作者：
Alan W. Eberhardt;Angela Yeager-Jones;Harry C. Blair
中科院分区：
文献类型：
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作者：
Alan W. Eberhardt;Angela Yeager-Jones;Harry C. Blair
药理浓度的糖皮质激素可引起骨质疏松和无菌性坏死，尤其是在股骨近端。已经提出了几种机制，但主要事件尚不清楚。我们研究了糖皮质激素治疗的兔股骨在骨折或塌陷发生前的骨结构和细胞活性的变化。在用4 μ mol/kg.day醋酸甲泼尼龙治疗28天的兔子中，皮质骨的变化很小。然而，代谢标记显示关节下骨小梁中几乎不存在骨形成，扫描电子显微镜显示骨小梁表面有50-80%的吸收。因此，骨合成减少和骨吸收增加与骨丢失有关。血管变化，这已被假设为介导糖皮质激素损伤，没有看到，但组织学变化表明，骨小梁受损。使用激光扫描共聚焦显微镜检查基质完整性以检测被动四环素吸附。在治疗组动物中，四环素以一种新的层状模式吸附在50- 200 μ m的区域，深入骨小梁，而对照组动物则不然。这表明，通常不透水的基质在这些地点暴露在外。TUNEL检测显示，基质损伤与治疗动物关节下骨小梁细胞死亡相关。涉及成骨细胞和骨细胞群的细胞死亡模式在受影响区域中占骨体积的一半，并且与凋亡机制一致。在对照骨中检测到少量TUNEL标记的成骨细胞，但没有骨细胞。我们的结论是骨基质通透性的暴露和与细胞凋亡一致的区域细胞死亡是糖皮质激素诱导的骨损伤的早期事件。
Glucocorticoids at pharmacological concentrations cause osteoporosis and aseptic necrosis, particularly in the proximal femur. Several mechanisms have been proposed, but the primary events are not clear. We studied changes in the bone structure and cellular activity in femora of glucocorticoid-treated rabbits before the occurrence of fracture or collapse. In rabbits treated 28 days with 4 micromol/kg.day of methylprednisolone acetate, changes in the cortical bone were minor. However, metabolic labeling showed that bone formation was virtually absent in the subarticular trabecular bone, and scanning electron microscopy showed resorption of 50-80% of the trabecular surface. Thus, reduction in bone synthesis and increased resorption were involved in bone loss. Vascular changes, which have been hypothesized to mediate glucocorticoid damage, were not seen, but histological changes suggested that trabecular bone was damaged. Matrix integrity was examined using laser scanning confocal microscopy to detect passive tetracycline adsorption. In treated animals, but not controls, tetracycline was adsorbed, in a novel lamellar pattern, in 50--200 microm regions extending deep into trabeculae. This showed that the matrix, which is normally impervious, was exposed at these sites. TUNEL assays showed that matrix damage correlated with cell death in the subarticular trabecular bone of treated animals. The pattern of cell death involving cohorts of osteoblasts and osteocytes comprised up to half of the bone volume in affected regions and is consistent with an apoptotic mechanism. Small numbers of TUNEL-labeled osteoblasts, but no osteocytes, were detected in control bone. We conclude that exposure of bone matrix permeability and that regional cell death consistent with apoptosis is an early event in glucocorticoid-induced bone damage.