Zalavras Charalampos, Shah Swapnil, Birnbaum Mark J, Frenkel Baruch
Department of Orthopaedic Surgery, Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Crit Rev Eukaryot Gene Expr. 2003;13(2-4):221-35.
Bone disease is a side effect of concern regarding chronic glucocorticoid (GC) administration. Most GC-treated patients exhibit a process of bone loss, frequently leading to osteoporosis, with increased fracture risk, especially in spinal vertebrae. Some GC-treated patients will develop osteonecrosis, a disease with distinct clinical and histopathological features, most often occurring underneath the articular surface of the femoral head. Remarkably, both of these GC-induced bone diseases are associated with osteoblast and osteocyte apoptosis, which is emerging as a potential primary pathogenic mechanism. Here, we review the evidence for osteoblast and osteocyte apoptosis in GC-induced bone disease and highlight current debates: (1) With recent reports describing the antiapoptotic effect of GCs in some in vitro osteoblast models, and with the known adverse effects of GCs on osteoblast cell cycle and differentiation, could the in vivo osteoblast apoptosis be an indirect rather than a direct effect of GCs? (2) What is the pathogenic relationship between GC-induced osteoporosis and osteonecrosis? Could the latter be a mere manifestation of the former? and (3) How does apoptosis fit into the traditional concept of ischemia as a key etiology in osteonecrosis? Regardless of the answers, recent studies with cells, animals, and humans point out bone cell apoptosis as a potential target in the design of treatment for GC-induced bone disease.
骨病是长期使用糖皮质激素（GC）治疗时令人担忧的一种副作用。大多数接受GC治疗的患者都经历骨质流失过程，常导致骨质疏松，骨折风险增加，尤其是在脊椎部位。一些接受GC治疗的患者会发生骨坏死，这是一种具有独特临床和组织病理学特征的疾病，最常发生在股骨头关节面下方。值得注意的是，这两种GC诱导的骨病都与成骨细胞和骨细胞凋亡有关，而凋亡正成为一种潜在的主要致病机制。在此，我们综述GC诱导骨病中关于成骨细胞和骨细胞凋亡的证据，并强调当前的争议点：（1）近期有报道描述了GC在一些体外成骨细胞模型中的抗凋亡作用，且已知GC对成骨细胞细胞周期和分化有不良影响，那么体内成骨细胞凋亡可能是GC的间接而非直接作用吗？（2）GC诱导的骨质疏松症和骨坏死之间的致病关系是什么？后者仅仅是前者的一种表现形式吗？以及（3）在骨坏死中，凋亡如何与作为关键病因的传统缺血概念相契合？无论答案如何，近期对细胞､动物和人类的研究指出，骨细胞凋亡是设计GC诱导骨病治疗方法的一个潜在靶点。
