Kishi T, Hagino H, Kishimoto H, Nagashima H
Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Bone. 1998 May;22(5):515-22. doi: 10.1016/s8756-3282(98)00045-3.
This study was undertaken to examine bone responses to human parathyroid hormone (hPTH) at various skeletal sites. Forty 6-month-old female Wistar rats were divided into four groups, and bilateral ovariectomy (ovx) was performed in three of the four groups (n=30). The other group (n=10) received sham surgery (sham). Four weeks after the ovx, hPTH(1-34) administration was started. The ovx rats received 5 microg/kg per day of PTH (PTH-5; n=10), 10 microg/kg per day of PTH (PTH-10; n=10), or vehicle (PTH-v; n=10), three times a week for 24 weeks. Thereafter, PTH was withdrawn for 16 weeks followed by readministration at the same dosage for 8 weeks. The bone mineral content (BMC) at the whole skeleton and the bone mineral density (BMD) at the lumbar vertebrae, caudal vertebrae, distal femur, diaphysis of the femur, proximal tibia, and skull were longitudinally measured by dual-energy x-ray absorptiometry (DXA) at 4-week intervals during the experimental period. Thirteen rats that died during the experimental period were excluded from the analysis. As a result, the whole skeleton showed an increase in BMC during the PTH administration, whereas no withdrawal or readministration effects were observed. The metaphysis showed a highly sensitive bone response, while the lumbar vertebrae and diaphysis showed a moderate magnitude of changes in bone mass during the PTH administration. The skull and the caudal vertebrae did not show sensitive responses to PTH. After withdrawal, the BMD was markedly decreased at the sites that showed marked increases in BMD after PTH administration. The PTH readministration increased the BMD again at the sites that showed sensitive responses after the initial administration. Strength tests were also performed when the readministration was completed. The ultimate loads for the femur and vertebral body in the PTH-treated groups were significantly higher than those in the vehicle-treated group. In conclusion, the response to PTH in ovx rats varied among skeletal sites; withdrawal-related decreases were marked at the sites showing marked increases in bone mass related to PTH administration, and PTH readministration may be sufficiently effective.
本研究旨在检测不同骨骼部位对人甲状旁腺激素（hPTH）的骨反应。40只6月龄雌性Wistar大鼠被分为四组，四组中的三组（n = 30）进行双侧卵巢切除术（ovx）。另一组（n = 10）接受假手术（sham）。卵巢切除术后4周开始给予hPTH(1 - 34)。卵巢切除的大鼠每天接受5μg/kg的PTH（PTH - 5；n = 10）、10μg/kg的PTH（PTH - 10；n = 10）或赋形剂（PTH - v；n = 10），每周三次，共24周。此后，停用PTH 16周，然后以相同剂量重新给药8周。在实验期间，每隔4周用双能X线吸收法（DXA）纵向测量全骨骼的骨矿物质含量（BMC）以及腰椎、尾椎、股骨远端、股骨干、胫骨近端和颅骨的骨矿物质密度（BMD）。将实验期间死亡的13只大鼠排除在分析之外。结果显示，在给予PTH期间全骨骼的BMC增加，而未观察到停药或重新给药的影响。干骺端显示出高度敏感的骨反应，而在给予PTH期间腰椎和骨干的骨量有中等程度的变化。颅骨和尾椎对PTH未显示出敏感反应。停药后，在给予PTH后BMD显著增加的部位，BMD明显降低。重新给予PTH后，在初次给药后显示出敏感反应的部位，BMD再次升高。在重新给药完成后也进行了强度测试。PTH治疗组的股骨和椎体的极限载荷显著高于赋形剂治疗组。总之，卵巢切除大鼠对PTH的反应在不同骨骼部位有所不同；在与PTH给药相关的骨量显著增加的部位，停药相关的降低很明显，并且重新给予PTH可能足够有效。
