Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose
Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose
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DOI：
10.1080/01926230490462138
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发表时间：
2004-07-01
影响因子：
1.5
通讯作者：
Sato, M
中科院分区：
文献类型：
--
作者：
Vahle, JL;Long, GG;Sato, M
在雌性F344大鼠中进行了一项长期研究，以确定剂量、给药持续时间和开始给药时的年龄对特立帕肽[rhPTH[1-34]]诱导的骨增殖性病变发生率的相对重要性。给药组包括不同的剂量组合（0、5或30 μ g/kg/d）、给药持续时间（6、20或24个月）和开始给药时的年龄（2或6个月大）。主要终点是骨肿瘤的发生率以及通过定量计算机断层扫描和组织形态学评价的对骨量和结构的影响。以30 μ g/kg剂量给药20或24个月的大鼠骨肿瘤（骨瘤、成骨细胞瘤和骨肉瘤）发生率显著增加。当在6月龄时开始5 μ g/kg治疗并持续6或20个月（高达寿命的70%）时，未发现肿瘤。该治疗方案定义了肿瘤形成的“无效”剂量，但仍导致骨量显著增加。这些结果表明，治疗持续时间和给药剂量是特立帕肽诱导大鼠骨肿瘤的最重要因素。
A long-term study was conducted in female F344 rats to determine the relative importance of dose, treatment duration, and age at initiation of treatment on the incidence of teriparatide [rhPTH[1-34)]-induced bone proliferative lesions. Treatment groups consisted of different combinations of dose (0, 5, or 30 mug/kg/d), treatment duration (6, 20, or 24 months) and age at initiation of treatment ( 2 or 6 months of age). The primary endpoints were the incidence of bone neoplasms and effects on bone mass and structure as evaluated by quantitative computed tomography and histomorphometery. Significant increases in the incidence of bone tumors (osteoma, osteoblastoma, and osteosarcoma) occurred in rats treated with 30 mug/kg for 20 or 24 months. No neoplasms were found when the 5 mug/kg treatment was initiated at 6 months of age and continued for either 6 or 20 months ( up to 70% of life span). This treatment regimen defined a "no-effect" dose for neoplasm formation that nevertheless resulted in substantial increases in bone mass. These results demonstrate that treatment duration and administered dose are the most important factors in the teriparatide-induced bone tumors in rats.