Mosekilde L, Thomsen J S, McOsker J E
Department of Cell Biology, University of Aarhus, Denmark.
Bone. 1997 May;20(5):429-37. doi: 10.1016/s8756-3282(97)00024-0.
The aim of the study was to assess the biomechanical effects of short-term PTH treatment and withdrawal on bone mass and strength in an aged, osteopenic, ovariectomized (ovx) rat model. Additionally, the effect of sequential therapy with PTH and the bisphosphonate, risedronate, the effect of longterm PTH monotherapy, and the effect of long-term risedronate monotherapy were assessed. 96 4-month-old rats were randomized into nine groups. Eight groups were ovariectomized and one group was sham operated. 12 months after surgery, treatment regimens were initiated (OW) and were continued for either 2 weeks (2 W) or 12 weeks (12 W). The treatment regimens were as follows: (1) baseline ovx (OW); (2) ovx-saline (2 W); (3) ovx-PTH 1-34 (2 W); (4) intact-saline (12 W); (5) ovx-saline (12 W); (6) ovx-risedronate (12 W); (7) ovx-PTH 1-34 (12 W); (8) ovx-PTH 1-34 (2 W), followed by pause (10 W); and (9) ovx-PTH 1-34 (2 W), accompanied by risedronate (12 W). The effect of therapy (endpoint) was measured at three skeletal sites: vertebral bodies; femoral cortical bone; and femoral necks. The results revealed an anabolic, time-dependent effect of PTH 1-34 at all skeletal sites. No loss of anabolic effect was observed 10 weeks after discontinuation of 2 week PTH treatment in this rat model. Risedronate given in sequential therapy with PTH produced no significant effect on biomechanical properties at any skeletal sites when compared with 2 week PTH followed by a 10 week pause. However, when risedronate was given alone, a positive effect was seen at the vertebral site after a 12 week treatment. On the basis of this study with short-term PTH treatment of aged, osteopenic, ovariectomized rats, there seemed to be a significant effect of PTH on the biomechanical properties and no loss of effect even 10 weeks after PTH withdrawal.
本研究的目的是评估短期甲状旁腺激素(PTH)治疗及停药对老年骨质疏松性卵巢切除(ovx)大鼠模型骨量和骨强度的生物力学影响。此外,还评估了PTH与双膦酸盐利塞膦酸盐序贯治疗的效果、长期PTH单一疗法的效果以及长期利塞膦酸盐单一疗法的效果。将96只4月龄大鼠随机分为9组。8组进行卵巢切除术,1组进行假手术。术后12个月开始治疗方案(OW),持续2周(2W)或12周(12W)。治疗方案如下:(1)基线ovx(OW);(2)ovx-生理盐水(2W);(3)ovx-PTH 1-34(2W);(4)完整-生理盐水(12W);(5)ovx-生理盐水(12W);(6)ovx-利塞膦酸盐(12W);(7)ovx-PTH 1-34(12W);(8)ovx-PTH 1-34(2W),随后停药(10W);(9)ovx-PTH 1-34(2W),同时给予利塞膦酸盐(12W)。在三个骨骼部位测量治疗效果(终点):椎体;股骨皮质骨;和股骨颈。结果显示,PTH 1-34在所有骨骼部位均有合成代谢的、时间依赖性的作用。在该大鼠模型中,2周PTH治疗停药10周后未观察到合成代谢作用的丧失。与2周PTH治疗后停药10周相比,PTH与利塞膦酸盐序贯治疗对任何骨骼部位的生物力学特性均无显著影响。然而,单独给予利塞膦酸盐时,12周治疗后在椎体部位观察到积极效果。基于对老年骨质疏松性卵巢切除大鼠进行短期PTH治疗的这项研究,PTH对生物力学特性似乎有显著影响,甚至在PTH停药10周后效果也未丧失。