Cegieła Urszula, Folwarczna Joanna, Pytlik Maria, Janiec Waldemar
Department of Pharmacology, Silesian Medical University, Jagiellońska 4, PL 41-200 Sosnowiec, Poland.
Pol J Pharmacol. 2004 May-Jun;56(3):327-36.
In the course of tumor metastases into bones, the process of resorption is intensified both as a result of direct influence of tumor cells on normal bone cells, and as a result of bone cell stimulation by cytokines and growth factors, which leads to pathological remodeling of osseous tissue and, in majority of cases, to the development of systemic hypercalcemia. Clinical observations and in vitro research show that also cytostatic drugs may disturb remodeling of bone tissue and cause osteopenia, mostly as a result of their direct effect on osteoblasts. The aim of this study was to investigate in vivo the effect of etoposide on the processes of bone tissue remodeling in rats by assessing macrometric and histomorphometric parameters, as well as mechanical properties of the femur. The tests were carried out on male Wistar rats of initial body mass between 280-310 g, which were divided into three groups (n = 8): I--control group of rats, which were given 0.9% NaCl solution every 7 days (C group), II--rats which were administered etoposide at the dose of 25 mg/kg p.o. every 7 days (E-25 group), III--rats which were given etoposide at one dose of 50 mg/kg i.v. (E-50 group). The experiment lasted 4 weeks. At the end of the experiment, the animals were killed by spinal cord displacement and the following values were determined: the mass, mineral and calcium content in the tested bones, length and diameter of long bones, transverse cross-section surface of tibial cortical bone and marrow cavity, transverse growth of the tibia and width of periosteal and endosteal osteoid in the tibia, as well as the width of osseous trabeculae, the width of epiphysial cartilage and mechanical properties of the femur. The tests showed that etoposide administered every 7 days at the dose of 25 mg/kg p.o. or at one dose of 50 mg/kg i.v. over the period of 28 days, disturbed osseous tissue remodeling processes in rats as a result of impeding the process of bone formation, which led to the impairment of the process of mineralization, weakening mechanical endurance of the femur, and to the development of osteopenia.
在肿瘤转移至骨骼的过程中，吸收过程会因肿瘤细胞对正常骨细胞的直接影响以及细胞因子和生长因子对骨细胞的刺激而加剧，这会导致骨组织的病理重塑，并且在大多数情况下会引发全身性高钙血症。临床观察和体外研究表明，细胞毒性药物也可能干扰骨组织的重塑并导致骨质减少，这主要是由于它们对成骨细胞的直接作用。本研究的目的是通过评估大鼠的宏观和组织形态学参数以及股骨的力学性能，在体内研究依托泊苷对大鼠骨组织重塑过程的影响。对初始体重在280 - 310克之间的雄性Wistar大鼠进行实验，将其分为三组（n = 8）：I组——对照组大鼠，每7天给予0.9%氯化钠溶液（C组）；II组——大鼠口服剂量为25毫克/千克依托泊苷，每7天给药一次（E - 25组）；III组——大鼠静脉注射一次剂量为50毫克/千克的依托泊苷（E - 50组）。实验持续4周。实验结束时，通过脊髓移位处死动物，并测定以下数值：受试骨骼的质量、矿物质和钙含量、长骨的长度和直径、胫骨皮质骨和骨髓腔的横截面积、胫骨的横向生长以及胫骨骨膜和骨内膜类骨质的宽度，以及骨小梁宽度、骨骺软骨宽度和股骨的力学性能。测试表明，在28天内每7天口服25毫克/千克剂量的依托泊苷或静脉注射一次50毫克/千克剂量的依托泊苷，会干扰大鼠的骨组织重塑过程，原因是阻碍了骨形成过程，这导致矿化过程受损、股骨力学耐力减弱以及骨质减少的发生。
