Immunosuppressive therapy is considered as one of the factors inducing to the onset of osteoporosis after organ transplantation. Chronic immunosuppressive therapy after transplantation is required for organ transplant patients, and it is important to prevent the occurrence of osteoporotic fractures to maintain the quality of life in patients. In this study, we examined the effects of cyclosporine and tacrolimus on bone metabolism in rats. Five-week-old male Wistar rats were treated orally with 15 mg/kg cyclosporine or 1.5 mg/kg tacrolimus daily for 4 weeks. Each of cyclosporine and tacrolimus significantly reduced the bone strength of the femoral mid-diaphysis and bone mineral density of the tibia and femur. Bone histomorphometry showed that the administration of both drugs resulted in a decrease in bone volume, number and thickness of trabeculae, and an increase in trabecular separation. Bone formation parameters such as osteoid volume, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate significantly increased in the cyclosporine-treated group. Bone resorption parameters such as eroded surface, osteoclast surface, and osteoclast number significantly increased in both the cyclosporine- and the tacrolimus- treated groups. These results showed that cyclosporine increases both bone formation and bone resorption, leading to a high-turnover bone loss, and that tacrolimus increases bone resorption without affecting bone formation, leading to bone loss.

中文翻译：

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钙调神经磷酸酶抑制剂环孢素和他克莫司对大鼠骨代谢的影响。

免疫抑制疗法被认为是引起器官移植后骨质疏松症发作的因素之一。器官移植患者需要进行移植后的慢性免疫抑制治疗，对于预防骨质疏松性骨折的发生以维持患者的生活质量很重要。在这项研究中，我们检查了环孢素和他克莫司对大鼠骨代谢的影响。对五周大的雄性Wistar大鼠每天口服15 mg / kg环孢素或1.5 mg / kg他克莫司治疗4周。环孢素和他克莫司均显着降低了股骨中骨干的骨强度以及胫骨和股骨的骨矿物质密度。骨组织形态计量学表明，两种药物的使用都会导致小梁的骨体积，数量和厚度减少，并增加小梁分离。环孢素治疗组的骨形成参数，如类骨质体积，成骨细胞表面，矿化表面，矿物质沉积率和骨形成率显着增加。在环孢素治疗组和他克莫司治疗组中，骨吸收参数（例如侵蚀表面，破骨细胞表面和破骨细胞数量）均显着增加。这些结果表明，环孢菌素增加了骨形成和骨吸收，导致高周转骨质流失，而他克莫司增加了骨吸收而不影响骨形成，导致骨质流失。环孢素治疗组的骨形成率显着增加。在环孢素治疗组和他克莫司治疗组中，骨吸收参数（例如侵蚀表面，破骨细胞表面和破骨细胞数量）均显着增加。这些结果表明，环孢菌素增加了骨形成和骨吸收，导致高周转骨质流失，而他克莫司增加了骨吸收而不影响骨形成，导致骨质流失。环孢素治疗组的骨形成率显着增加。在环孢素治疗组和他克莫司治疗组中，骨吸收参数（例如侵蚀表面，破骨细胞表面和破骨细胞数量）均显着增加。这些结果表明，环孢菌素增加了骨形成和骨吸收，从而导致高周转骨质流失，而他克莫司增加了骨吸收而不影响骨形成，导致骨质流失。