Lane N E, Thompson J M, Strewler G J, Kinney J H
Department of Medicine, University of California at San Francisco, USA.
J Bone Miner Res. 1995 Oct;10(10):1470-7. doi: 10.1002/jbmr.5650101007.
Previous studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1-34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three-dimensional (3D) ex vivo in situ morphometry by X-ray tomographic methods (XTM). Six-month-old retired Sprague-Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post-OVX, a prePTH-treatment OVX groups was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1-34) at 4, 40, or 400 microg/kg of body weight (BW)/day and were sacrificed on day 84 post-OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1-34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p<0.05). The trabecular bone volume was equal to or greater than the Sham-operated animals in both hPTH(1-34) 40 and 400 microg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the S ham-operated group at day 84 post-OVX and did not increase with any of the hPTH(1-34) treatments. Intermittent hPTH(1-34) treatment is osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabeculae. Human PTH(1-34) did not re-establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re-establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis.
以往的研究已确定，间歇性甲状旁腺激素（PTH）治疗可增加骨质减少动物模型的骨量并改善生物力学强度。本研究的目的是，通过X射线断层扫描方法（XTM）进行三维（3D）离体原位形态测定，以确定间歇性人甲状旁腺激素（hPTH[1-34]）治疗是否会增加已建立骨质减少大鼠模型的小梁骨体积和连通性。使用6个月大的退役Sprague-Dawley繁殖大鼠。30只动物接受卵巢切除术（OVX），6只进行假手术。在OVX术后第56天，处死一组OVX术前治疗组。其余OVX动物随机分为四组，每组6只，每7天注射5次，连续28天，分别注射载体或hPTH(1-34)，剂量为4、40或400μg/kg体重（BW）/天，并在OVX术后第84天处死。处死时，采集左胫骨近端进行XTM扫描。与接受载体治疗的去卵巢动物相比，中高剂量的hPTH(1-34)显著增加了小梁骨体积和小梁厚度（p<0.05）。在hPTH(1-34) 40和400μg/kg BW治疗组中，小梁骨体积等于或大于假手术动物。与假手术组相比，OVX术后第84天小梁骨连通性下降了近50%，且在任何hPTH(1-34)治疗下均未增加。间歇性hPTH(1-34)治疗可使骨质减少的OVX大鼠通过增厚现有小梁将小梁骨体积增加至对照水平或更高。当50%的小梁连通性丧失后开始治疗时，人PTH(1-34)并未重新建立连通性。我们假设，要重新建立小梁连通性，必须在小梁之间形成显著距离之前进行治疗干预。需要进一步研究以反驳或证实我们的假设。
