Søgaard C H, Mosekilde L, Thomsen J S, Richards A, McOsker J E
Department of Cell Biology, University of Aarhus, Denmark.
Bone. 1997 May;20(5):439-49. doi: 10.1016/s8756-3282(97)00020-3.
The aim of this investigation was to compare the effects of sodium fluoride (NaF) and parathyroid hormone (PTH) on ash density and strength in an osteopenic rat model. The study comprised 66 female virgin rats divided into the following 11 groups, each comprising six animals: baseline controls; baseline ovariectomized (ovx); intact controls (5 and 16 weeks), ovx controls (5 and 16 weeks); ovx-treated with PTH (0.02 mg/kg per day, 5 and 16 weeks); ovx treated with NaF (10 mg/kg per day, 5 and 16 weeks); ovx-treated with NaF (1.0 mg/kg per day, 16 weeks). Ovariectomy was performed at 12 weeks of age, 14 weeks prior to start of treatment. Ash density, bone fluoride content, and biomechanical analyses were performed on femoral cortical bone, the right femoral neck, and the sixth lumbar vertebral body. ovx had no effect on cortical bone, whereas the femoral neck displayed a significantly lower bone strength in ovx baseline animals compared with intact baseline rats (p < 0.05). Vertebral ash density was found to be significantly decreased in ovx rats after 5 and 16 weeks (p < 0.05). Treatment with fluoride had little effect on the osteopenic rat skeleton. Cortical ash density was significantly lower than ovx and intact groups in the high-dose-treated rats after 5 (p < 0.01) but not after 16 weeks. High doses of fluoride for 16 weeks induced a significant increase in maximum load and normalized strength in cortical bone when compared with intact animals (p < 0.05), but not at the other bone sites. Cortical bone strength was not different from the ovx animals at either timepoint. In fluoride-treated animals, femoral neck bone strength, vertebral body bone strength, bone quality, and ash density were found to be at about ovx levels and, in the vertebral body, significantly lower than intact animals (p < 0.05, p < 0.01). In contrast, treatment with PTH increased ash density, bone strength, and bone quality to above ovx levels (p < 0.01), and above the level of the intact animals also, although significant values were reached for cortical bone strength only (p < 0.01). Additionally, biomechanical competence and ash density measurements were significantly higher in PTH-treated rats compared with fluoride-treated rats. In conclusion, this study has shown that PTH has a highly anabolic effect and is capable of effectively restoring ovx-induced loss of bone mass and biomechanical competence. In addition, in this osteopenic rat model, PTH proved much more advantageous than treatment with fluoride, which failed to restore the ovx-induced loss of bone strength.
本研究的目的是比较氟化钠(NaF)和甲状旁腺激素(PTH)对骨质疏松大鼠模型骨灰密度和强度的影响。该研究包括66只未生育的雌性大鼠,分为以下11组,每组6只动物:基线对照组;基线卵巢切除组(ovx);完整对照组(5周和16周),ovx对照组(5周和16周);用PTH治疗的ovx组(每天0.02mg/kg,5周和16周);用NaF治疗的ovx组(每天10mg/kg,5周和16周);用NaF治疗的ovx组(每天1.0mg/kg,16周)。卵巢切除术在12周龄时进行,即治疗开始前14周。对股骨皮质骨、右股骨颈和第六腰椎椎体进行骨灰密度、骨氟含量和生物力学分析。ovx对皮质骨无影响,而与完整基线大鼠相比,ovx基线动物的股骨颈骨强度显著降低(p<0.05)。发现ovx大鼠在5周和16周后椎体骨灰密度显著降低(p<0.05)。氟治疗对骨质疏松大鼠骨骼影响不大。高剂量治疗5周后,高剂量治疗组大鼠的皮质骨灰密度显著低于ovx组和完整组(p<0.01),但16周后无此差异。与完整动物相比,高剂量氟治疗16周可使皮质骨的最大负荷显著增加,强度恢复正常(p<0.05),但在其他骨部位则不然。在两个时间点,皮质骨强度与ovx动物无差异。在氟治疗的动物中,发现股骨颈骨强度、椎体骨强度、骨质量和骨灰密度约为ovx水平,且在椎体中显著低于完整动物(p<0.05,p<0.01)。相比之下,PTH治疗可使骨灰密度、骨强度和骨质量增加至高于ovx水平(p<0.01),也高于完整动物水平,尽管仅皮质骨强度达到显著值(p<0.01)。此外,与氟治疗的大鼠相比,PTH治疗的大鼠生物力学性能和骨灰密度测量值显著更高。总之,本研究表明PTH具有高度的合成代谢作用,能够有效恢复ovx诱导的骨量丢失和生物力学性能。此外,在这个骨质疏松大鼠模型中,PTH被证明比氟治疗更具优势,氟治疗未能恢复ovx诱导的骨强度丢失。