The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of Glucocorticoids
The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of Glucocorticoids
复制标题
DOI：
10.1002/art.22976
复制
发表时间：
2007-11-01
影响因子：
--
通讯作者：
Lane, Nancy E.
中科院分区：
文献类型：
--
作者：
Balooch, Guive;Yao, Wei;Lane, Nancy E.
Objective.糖皮质激素（GC）会改变骨强度，因此接受这些药物治疗的患者发生脆性相关骨折的几率很高。本研究的目的是评估同时使用GC（泼尼松龙）和利塞膦酸盐（一种氨基二膦酸盐）治疗是否可以预防GC诱导的骨强度降低，在GC诱导的骨丢失的小鼠模型和临床研究中招募的患者中。我们评估了单独使用泼尼松龙颗粒、GC加利塞膦酸钠或单独使用安慰剂治疗的小鼠，以及从接受GC加安慰剂或GC加利塞膦酸钠治疗1年的患者中获得的髂嵴活检标本。我们使用同步加速器X射线断层扫描、弹性模量映射、透射电子显微镜和小角度X射线散射技术，在纳米尺度到宏观尺度上测量了骨的质量、结构、物理和材料特性（接受治疗）。GC治疗降低了骨小梁的骨量、微结构、骨矿化程度和骨小梁内的弹性模量。在小鼠和人骨中，GC和利塞膦酸钠的同时治疗防止了骨小梁结构的恶化，降低了矿化程度，并保留了骨小梁内的弹性模量。此外，与单独使用GCs治疗相比，利塞膦酸盐联合GCs治疗小鼠似乎可以保持骨晶体方向。利塞膦酸钠阻止了GC引起的骨矿物质和材料性质的局部变化，这可能最终改善骨强度。
Objective. Glucocorticoids (GCs) alter bone strength such that patients receiving these medications have a high rate of fragility-related fractures. The purpose of this study was to assess whether concurrent treatment with GCs (prednisolone) and risedronate (an aminobisphosphonate) would prevent the reduction in bone strength induced by GCs, in a mouse model of GC-induced bone loss and in patients enrolled in a clinical study.Methods. We evaluated mice treated with prednisolone pellets alone, GCs plus risedronate, or placebo alone and iliac crest biopsy specimens obtained from patients who were treated with GCs plus placebo or GCs plus risedronate for 1 year. We measured the mass, architecture, and physical and material properties of bone (subject to therapeutic treatments) at nanoscale to macroscopic dimensions, using synchrotron x-ray tomography, elastic modulus mapping, transmission electron microscopy, and small-angle x-ray scattering techniques.Results. GC treatment reduced trabecular bone mass, microarchitecture, and the degree of bone mineralization and elastic modulus within the trabeculae. Concurrent treatment with GCs and risedronate prevented the deterioration of trabecular bone architecture, reduced the degree of mineralization, and preserved elastic modulus within the trabeculae, in both mouse and human bone. In addition, treatment with risedronate plus GCs in mice appeared to preserve bone crystal orientation, compared with treatment with GCs alone.Conclusion. Risedronate prevented the localized changes in mineral and material properties of bone induced by GCs, which may ultimately improve bone strength.