甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成的影响

Effect of parathyroid hormone combined with alendronate on the formation of osteophytes in rats with osteoporotic fractures

目的探讨甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成及骨折愈合的影响。方法 75只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、阿仑膦酸钠组、联合用药组,每组15只,首先行双侧卵巢切除术,术后4周行右侧股骨干骨折髓内固定术,以构建大鼠骨质疏松性骨折动物模型。观察并评估骨折愈合,检测骨痂生物力学和骨密度(bone mineral density,BMD),检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)和骨形成发生蛋白-2(bone morphogenetic protein-2,BMP-2)浓度,观察骨痂形态结构,检测骨痂VEGF表达。结果去势组较假手术组骨折愈合评分、骨痂生物力学强度、骨痂BMD、血清BMP-2和VEGF浓度、骨痂VEGF蛋白表达、骨痂微血管数均显著降低(P<0.05),甲状旁腺素组、阿仑膦酸钠组、联合用药组较去势组上述指标均升高,其中以联合用药组升高最显著(P<0.05)。结论甲状旁腺激素联合阿仑膦酸钠通过介导VEGF,上调BMP-2表达,促进骨质疏松性骨折大鼠骨痂血管形成,增加骨密度,改善生物力学强度及骨组织形态学,加快骨折愈合。

Objective To investigate the effect of parathyroid hormone combined with alendronate on osteophyte formation and fracture healing in rats with osteoporotic fractures. Methods Seventy-five female SD rats were randomly divided into 5 groups: sham operation group, ovariectomized group, parathyroidism group, alendronate group, and combination drug group, with 15 rats in each group, Bilateral ovariectomy was performed. After 4 weeks of the operation, intramedullary fixation of the right femoral shaft was performed to establish the animal model of rat osteoporotic fractures. The fracture healing, biomechanics and bone mineral density(BMD) of the osteophyte were observed. Serum levels of VEGF and BMP-2 were detected. The morphology of the epiphysis was observed. VEGF expression in osteophytes was detected. Results The fracture healing score, osteophyte biomechanical strength, osteophyte BMD, serum BMP-2 and VEGF concentrations, osteophyte VECF protein expression, and epiphyseal microvascular count were significantly lower in the ovariectomized group than those in the sham operation group(P<0.05). The above indicators increased in the parathyroidism group, the alendronate group, and the combination group. Among them, the increase in combination group was the most significant(P<0.05). Conclusion Parathyroid hormone combined with alendronate up-regulates BMP-2 expression, promotes osteophyte angiogenesis in rats with osteoporotic fracture, increases BMD, improves biomechanical strength and bone histomorphology, and accelerates fracture healing via mediation of VEGF.