Penn State College of Medicine, Department of Orthopaedics and Rehabilitation, Hershey, PA 17033-0850, USA.
Endocr J. 2010;57(5):373-82. doi: 10.1507/endocrj.k09e-349. Epub 2010 Feb 6.
The anabolic effect of intermittent PTH on bone is variable depending on the species studied, duration/mode of administration, and location of skeletal response investigated. We tested the hypothesis low dose, short term, intermittent PTH 1-34 administration is sufficient to enhance bone formation without altering bone resorption. To test our hypothesis, mice were treated intermittently with one of three concentrations of PTH 1-34 (1 microg/kg; low, 10 microg/kg, or 20 microg/kg; high) for three weeks. The skeletal response was identified by quantifying: serum markers of bone turnover, cancellous bone parameters in distal femur, proximal tibia, and lumbar vertebrae by microCT, and number of osteoblasts and osteoclasts in distal femur. Mice receiving 20 microg/kg of PTH 1-34 demonstrated a 30% increase in serum osteocalcin, but no differences in serum calcium, type I collagen teleopeptides, or TRACP 5b. For all bones, microCT analysis suggested mice receiving 20 microg/kg of PTH 1-34 had increased cancellous bone mineral density, trabecular thickness and spacing, but decreased trabecular number. A 60% increase in the number of alkaline phosphatase positive osteoblasts in the distal femur was also observed in tissue sections; however, the number of TRAP positive osteoclasts was not different between test and control groups. While animals administered 10 microg/kg demonstrated similar trends for all bone turnover indices, such alterations were not observed in animals administered PTH 1-34 at 1 microg/kg per day. Thus, PTH 1-34, administered intermittently for three weeks at 20 microg/kg is sufficient to enhance bone formation without enhancing resorption.
间歇 PTH 对骨骼的合成代谢作用因所研究的物种、给药持续时间/方式以及研究的骨骼反应部位而异。我们检验了以下假说：低剂量、短期、间歇 PTH1-34 给药足以增强骨形成而不改变骨吸收。为了检验我们的假说，我们用三种浓度的 PTH1-34（1μg/kg，低剂量；10μg/kg 或 20μg/kg，高剂量）间歇处理小鼠 3 周。通过定量检测血清骨转换标志物、股骨远端、胫骨近端和腰椎的松质骨参数、股骨远端成骨细胞和破骨细胞数量来确定骨骼反应。接受 20μg/kg PTH1-34 的小鼠血清骨钙素增加 30%，但血清钙、I 型胶原 C 端肽或 TRACP5b 无差异。对于所有骨骼，微 CT 分析表明，接受 20μg/kg PTH1-34 的小鼠松质骨骨密度、小梁厚度和间距增加，但小梁数量减少。组织切片中还观察到股骨远端碱性磷酸酶阳性成骨细胞数量增加 60%；然而，实验组和对照组的 TRAP 阳性破骨细胞数量没有差异。接受 10μg/kg PTH1-34 的动物所有骨转换指标均表现出类似趋势，但接受 1μg/kg PTH1-34 的动物未观察到这种变化。因此，间歇 3 周给予 20μg/kg PTH1-34 足以增强骨形成而不增强吸收。
