Wronski T J, Ratkus A M, Thomsen J S, Vulcan Q, Mosekilde L
Department of Physiological Sciences, University of Florida, Gainesville 32610, USA.
J Bone Miner Res. 2001 Aug;16(8):1399-407. doi: 10.1359/jbmr.2001.16.8.1399.
This study was designed to determine whether sequential treatment with basic fibroblast growth factor (bFGF) and parathyroid hormone (PTH) can restore lost cancellous bone mass and strength at a severely osteopenic skeletal site in aged ovariectomized (OVX) rats. Female Sprague-Dawley rats were subjected to sham surgery or ovariectomy at 3 months of age and maintained untreated for the first year after surgery. At 15 months of age, groups of baseline control and OVX rats were killed and catheters were inserted in the jugular veins of all remaining rats. Two groups of OVX rats were injected intravenously (iv) daily with bFGF for 14 days at a dose of 200 microg/kg body weight. At the end of bFGF treatment, one group was killed whereas the other group was subjected to 8 weeks of treatment with synthetic human PTH 1-34 [hPTH(1-34)] consisting of subcutaneous (sc) injections 5 days/week at a dose of 80 microg/kg. Another group of OVX rats was treated iv with vehicle for 2 weeks followed by treatment with PTH alone for 8 weeks. Other groups of sham-operated control rats and OVX rats were treated iv and sc with vehicle alone. The right proximal tibia from each rat was processed undecalcified for quantitative bone histomorphometry and the left proximal tibia was subjected to biomechanical testing. Baseline and vehicle-treated OVX rats were severely osteopenic because their tibial cancellous bone volumes were less than 5% compared with mean values of 20.3% and 15.0% in baseline and vehicle-treated control rats, respectively. Treatment of OVX rats for 2 weeks with bFGF alone did not significantly increase tibial cancellous bone volume but induced marked increases in osteoid volume, osteoblast surface, and osteoid surface. Sequential treatment of aged OVX rats with bFGF and PTH increased tibial cancellous bone volume (15.1%) and load to failure to at least the level of vehicle-treated control rats. Tibial cancellous bone volume (10.8%) and load to failure also were significantly increased by treatment with PTH alone, and these variables were not significantly different from those of OVX rats treated with bFGF + PTH. However, tibial ash density was significantly greater in OVX rats treated sequentially with bFGF and PTH compared with OVX rats treated with PTH alone. Our findings suggest that sequential treatment with bFGF and PTH may be useful for restoration of lost cancellous bone in the severely osteopenic, estrogen-deplete skeleton, but it cannot be concluded with certainty that this sequential treatment has a greater bone restorative effect than treatment with PTH alone.
本研究旨在确定碱性成纤维细胞生长因子（bFGF）和甲状旁腺激素（PTH）序贯治疗能否恢复老年去卵巢（OVX）大鼠严重骨质减少骨骼部位丢失的松质骨量和强度。雌性Sprague-Dawley大鼠在3月龄时接受假手术或卵巢切除术，并在术后第一年不进行治疗。15月龄时，处死基线对照组和OVX大鼠组，将导管插入所有剩余大鼠的颈静脉。两组OVX大鼠每天静脉注射（iv）剂量为200μg/kg体重的bFGF，持续14天。在bFGF治疗结束时，处死一组，而另一组接受8周的合成人PTH 1-34 [hPTH(1-34)]治疗，每周皮下（sc）注射5天，剂量为80μg/kg。另一组OVX大鼠先静脉注射赋形剂2周，然后单独用PTH治疗8周。其他假手术对照组大鼠和OVX大鼠组仅接受静脉和皮下赋形剂治疗。每只大鼠的右胫骨近端进行不脱钙处理，用于定量骨组织形态计量学分析，左胫骨近端进行生物力学测试。基线和赋形剂治疗的OVX大鼠严重骨质减少，因为它们的胫骨松质骨体积分别比基线和赋形剂治疗的对照大鼠的平均值20.3%和15.0%低5%以下。单独用bFGF治疗OVX大鼠2周并未显著增加胫骨松质骨体积，但导致类骨质体积、成骨细胞表面和类骨质表面显著增加。老年OVX大鼠用bFGF和PTH序贯治疗可增加胫骨松质骨体积（15.1%）和破坏载荷，至少达到赋形剂治疗对照大鼠的水平。单独用PTH治疗也显著增加了胫骨松质骨体积（10.8%）和破坏载荷，这些变量与用bFGF + PTH治疗的OVX大鼠无显著差异。然而，与单独用PTH治疗的OVX大鼠相比，用bFGF和PTH序贯治疗的OVX大鼠的胫骨灰密度显著更高。我们的研究结果表明，bFGF和PTH序贯治疗可能有助于恢复严重骨质减少、雌激素缺乏骨骼中丢失的松质骨，但不能确定这种序贯治疗比单独用PTH治疗具有更大的骨修复效果。
