Eberhardt A W, Yeager-Jones A, Blair H C
Department Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Endocrinology. 2001 Mar;142(3):1333-40. doi: 10.1210/endo.142.3.8048.
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.
药理浓度的糖皮质激素会导致骨质疏松和无菌性坏死，尤其是在股骨近端。虽然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处理的兔子在骨折或塌陷发生前股骨的骨结构和细胞活性变化。用4微摩尔/千克·天的醋酸甲泼尼龙处理28天的兔子，皮质骨的变化较小。然而，代谢标记显示关节下小梁骨几乎没有骨形成，扫描电子显微镜显示小梁表面有50 - 80%被吸收。因此，骨合成减少和吸收增加参与了骨质流失。虽然有人推测血管变化介导糖皮质激素损伤，但未观察到这种变化，不过组织学变化表明小梁骨受到了损伤。使用激光扫描共聚焦显微镜检测被动四环素吸附来检查基质完整性。在处理过的动物中，而非对照组中，四环素以一种新的层状模式吸附在深入小梁达50 - 200微米的区域。这表明通常不可渗透的基质在这些部位暴露。TUNEL分析表明，基质损伤与处理过的动物关节下小梁骨中的细胞死亡相关。在受影响区域，涉及成骨细胞和骨细胞群体的细胞死亡模式占骨体积的一半，这与凋亡机制一致。在对照骨中检测到少量TUNEL标记的成骨细胞，但未检测到骨细胞。我们得出结论，骨基质通透性的暴露以及与凋亡一致的局部细胞死亡是糖皮质激素诱导的骨损伤中的早期事件。
