Defranco D J, Lian J B, Glowacki J
Department of Orthodontics, Harvard School of Dental Medicine.
Endocrinology. 1992 Jul;131(1):114-21. doi: 10.1210/endo.131.1.1611989.
Prolonged glucocorticoid excess is associated with bone loss. Among the contributory factors are glucocorticoids' suppression of bone formation and stimulation of bone resorption. In this study, the effects of glucocorticoids on bone resorption were evaluated in a rodent model. Subcutaneous implants of devitalized mineralized bone particles (BPs) elicit the recruitment of progenitor cells and their differentiation to osteoclasts which resorb the BPs. The effects of glucocorticoids on both the recruitment and the activity of cells induced by normal BPs were distinguished based upon when treatment was initiated. When treatment with hydrocortisone or dexamethasone was initiated at the time of BP implantation, the recruitment of bone-resorbing cells was impaired and a subsequent decrease in BP resorption was found. On the other hand, when treatment was initiated on day 7, glucocorticoids increased osteoclastic resorption and tartrate-resistant acid phosphatase activity. We also tested hydrocortisone's effect to stimulate the activity of cells associated with osteocalcin-deficient BPs. As previously reported, BPs deficient in osteocalcin were poorly resorbed as a result of decreased formation and activity of osteoclasts. Hydrocortisone had an even more pronounced effect in stimulating the low level resorption of the osteocalcin-deficient BP implants than of the normal BP implants. These findings show differential effects of glucocorticoids on two aspects of bone resorption: they inhibit the recruitment and/or differentiation of bone-resorbing cells, but they stimulate the activity of existing osteoclastic cells. The ability of glucocorticoids to increase resorption of normal bone and to overcome resistance to resorption of osteocalcin-deficient bone suggests an important regulatory effect of glucocorticoids in the activation of osteoclasts to increase bone resorption.
长期糖皮质激素过量与骨质流失有关。促成因素包括糖皮质激素对骨形成的抑制和对骨吸收的刺激。在本研究中，在啮齿动物模型中评估了糖皮质激素对骨吸收的影响。皮下植入失活的矿化骨颗粒（BPs）会引发祖细胞的募集及其向破骨细胞的分化，破骨细胞会吸收BPs。根据治疗开始的时间，区分了糖皮质激素对正常BPs诱导的细胞募集和活性的影响。当在植入BPs时开始用氢化可的松或地塞米松治疗时，骨吸收细胞的募集受到损害，随后发现BPs吸收减少。另一方面，当在第7天开始治疗时，糖皮质激素增加了破骨细胞的吸收和抗酒石酸酸性磷酸酶活性。我们还测试了氢化可的松刺激与骨钙素缺乏的BPs相关细胞活性的作用。如先前报道，由于破骨细胞形成和活性降低，骨钙素缺乏的BPs吸收不良。氢化可的松在刺激骨钙素缺乏的BP植入物的低水平吸收方面比正常BP植入物具有更明显的作用。这些发现表明糖皮质激素对骨吸收的两个方面有不同的影响：它们抑制骨吸收细胞的募集和/或分化，但刺激现有破骨细胞的活性。糖皮质激素增加正常骨吸收并克服对骨钙素缺乏骨吸收的抗性的能力表明糖皮质激素在激活破骨细胞以增加骨吸收方面具有重要的调节作用。
