背景:双膦酸盐可以提高骨密度、抑制骨吸收的作用已被临床所证实,但其对于骨骼基质结构的影响研究较少。目的:实验通过观察双膦酸盐类药物——阿仑膦酸钠对骨结构及骨基质代谢的影响,探讨阿仑膦酸钠改善骨质量、提高骨强度的骨基质调控机制。方法:实验建立去卵巢大鼠模型,用阿仑膦酸钠进行干预,同时设置模型组和假手术组进行对照。运用骨骼影像学、骨组织病理学和骨生物力学检测技术与酶联免疫吸附法观察阿仑膦酸钠对骨丢失大鼠骨密度、骨代谢、骨生物力学性能和骨结构的影响。结果与结论:药物干预后4,8,12周,阿仑膦酸钠组骨密度均高于模型组(P〈0.05h药物干预8周后,与模型组相比,阿仑膦酸钠组骨代谢指标尿脱氧吡啶诺啉,血清I型胶原羧基端前肽水平均降低(P〈0.05),腰椎和股骨的最大载荷、最大压强、模量以及I型胶原不同交联形式的尿毗啶啉/脱氧吡啶啉值均增高(P〈0.05)。结果证实,阿仑膦酸钠能够对抗因雌激素缺乏导致大鼠骨量的丢失,提高生物力学性能,改善骨基质结构,同时恢复因去卵巢所导致的I型胶原交联组分的改变。
BACKGROUND: Bisphosphonates that can increase bone density and inhibit bone resorption have been clinically confirmed, but the structure of the bone matrix has been less studied OBJECTIVE: To observe the effects of alendronate on bone structure and bone matrix metabolism, and then to investigate the controlling mechanism by which alendronate improves bone mass and increase bone intensity. METHODS: An ovariectomized rat model was prepared and intervened with alendronate as treatment group. Model and sham-surgery groups were set as controls. Alendronate effects on bone mineral density, bone metabolism, bone biomechanics, and bone structure were observed in bone loss rats using bone imaging, bone tissue pathology and biomechanical test and enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: Alendronate intervention could fight against bone loss as compared with model group at weeks 4, 8, and 12 after treatment (P 〈 0.05). Compared with the model group, the expression of urinary deoxypyridinoline and serum carboxyterminal propeptide of type I procollagen was decreased significantly after alendronate intervention (P 〈 0.05); the maximal load, maximal pressure and modelus on the lumbar vertebrae and femur were increased as well as ratio of urinary pyridinoline/deoxypyridinoline of type 1 procollagen (P 〈 0.05). These findings suggest that alendronate intervention can inhibit bone loss in rats induced by estrogen deficiency, increase biomechanical properties, improve bone matrix structure, and meanwhile, recover the 1 collagen crosslinking component due to ovariectomy.