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/en.142.3.1333
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发表时间：
2001-03-01
期刊：
影响因子：
4.8
通讯作者：
Blair, HC
中科院分区：
文献类型：
--
作者：
Eberhardt, AW;Yeager-Jones, A;Blair, HC
药理学浓度的糖皮质激素会导致骨质疏松和无菌性坏死，特别是在股骨近端。已经提出了几种机制，但主要事件尚不清楚。我们研究了经过糖皮质激素治疗的兔子在发生骨折或塌陷之前股骨骨结构和细胞活性的变化。在用4μmol/kg天的醋酸甲泼尼龙治疗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实际上不存在骨形成，扫描电子显微镜显示小梁表面 50-80% 发生吸收。因此，骨合成的减少和骨吸收的增加与骨丢失有关。没有观察到血管变化（被假设介导糖皮质激素损伤），但组织学变化表明骨小梁受损。使用激光扫描共焦显微镜检查基质完整性以检测被动四环素吸附。在接受治疗的动物（而非对照组）中，四环素以一种新颖的层状模式被吸附在 50-200 个区域，深入延伸到小梁中。这表明通常不渗透的基质在这些部位暴露出来。 TUNEL 分析表明，基质损伤与治疗动物关节下骨小梁中的细胞死亡相关。涉及成骨细胞和骨细胞群的细胞死亡模式占受影响区域骨体积的一半，并且与细胞凋亡机制一致。在对照骨中检测到少量 TUNEL 标记的成骨细胞，但没有检测到骨细胞。我们得出的结论是，骨基质渗透性的暴露以及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 mu mol/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 mum 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 hone. We conclude that exposure of hone matrix permeability and that regional cell death consistent with apoptosis is an early event in glucocorticoid-induced bone damage.