Turner Russell T, Lotinun Sutada, Hefferan Theresa E, Morey-Holton Emily
Dept. of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97333, USA.
J Appl Physiol (1985). 2006 Sep;101(3):881-6. doi: 10.1152/japplphysiol.01622.2005. Epub 2006 May 4.
Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 microg.kg(-1).day(-1)) of human PTH(1-34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.
甲状旁腺激素（PTH）间歇性治疗可增加后肢去负荷（HLU）大鼠的骨形成并预防骨质流失。然而，PTH的作用机制尚不完全清楚。为了探究负重与PTH之间可能的相互作用，我们用人类治疗剂量（1μg·kg⁻¹·天⁻¹）的人PTH(1-34)（hPTH）对6月龄的负重和HLU大鼠进行治疗。分别在胫腓骨融合处近端的骨干和近端干骺端测量胫骨的皮质骨和松质骨形成。两周的后肢去负荷导致两个骨骼部位的骨形成速率显著降低，而仅在松质骨部位进行PTH治疗可预防这种降低。相比之下，PTH治疗增加了负重大鼠的皮质骨和松质骨形成。双向方差分析显示，hPTH和HLU对两个骨骼部位所有骨形成的组织形态计量学指标[矿物质沉积率（MAR）、双标记周长（dLPm）和骨形成率（BFR）]具有独立且相反的作用。负重和hPTH对皮质部位dLPm和BFR的骨合成作用是相加的，对松质骨部位MAR的作用也是如此。相比之下，负重和hPTH导致皮质骨MAR以及松质骨dLPm和BFR协同增加。我们得出结论，负重和PTH协同作用以增加骨形成，通过导致成骨细胞数量和活性指标在特定部位的相加和协同增加，这表明针对骨质减少骨骼部位的负重运动可能会提高PTH治疗骨质疏松症的疗效。
