用载有阿仑膦酸盐的磷酸钙骨水泥对骨质疏松症进行局部治疗。

Zhao Jindong, Tang Hai, Wang Jiayang, Li Gang

Department of Orthopedics, the Fifth Hospital of Harbin City, Harbin, Heilongjiang 150040, China.

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Email:

Chin Med J (Engl). 2014;127(22):3906-14.

BACKGROUND

A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures. We term this strategy as the "local treatment of osteoporosis". The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement (CPC) as a novel drug delivery system for local treatment of osteoorosis.

METHODS

An in vitro study was performed using CPC fabricated with different concentrations of alendronate (ALE, 0, 2, 5, 10 weight percent (wt%)). The microstructure, setting time, infrared spectrum, biomechanics, drug release, and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE. An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups: normal, Sham (ovariectomized (OVX) + Sham), CPC with 2% ALE, 5%ALE, and 10% ALE groups. At 4 months after the implantation of the composite, animals were sacrificed and the caudal vertebrae (levels 4-7) were harvested for micro-CT examination and biomechanical testing.

RESULTS

The setting time and strength of CPC was significantly faster and greater than the other groups. The ALE release was sustained over 21 days, and the composite showed good biocompatibility. In micro-CT analysis, compared with the Sham group, there was a significant increase with regard to volumetric bone mineral density (BMD) and trabecular number (Tb.N) in the treated groups (P < 0.05). Trabecular spacing (Tb.Sp) showed a significant increase in the Sham group compared to other groups (P < 0.01). However, trabecular thickness (Tb.Th) showed no significant difference among the groups. In biomechanical testing, the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups.

CONCLUSIONS

The ALE-loaded CPC displayed satisfactory properties in vitro, which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.

背景

一种新的治疗策略是针对骨骼系统中易于发生具有临床意义的骨质疏松性骨折的特定区域。我们将这种策略称为“骨质疏松症的局部治疗”。本研究旨在探讨载阿仑膦酸钠的磷酸钙骨水泥（CPC）作为一种用于骨质疏松症局部治疗的新型药物递送系统的效果。

方法

使用不同浓度阿仑膦酸钠（ALE，0、2、5、10重量百分比（wt%））制备的CPC进行体外研究。测量复合材料的微观结构、凝固时间、红外光谱、生物力学、药物释放和生物相容性，以检测CPC与ALE混合时的变化。还使用30只Sprague-Dawley大鼠进行体内研究，随机分为六组：正常组、假手术组（卵巢切除（OVX）+假手术）、含2% ALE的CPC组、5% ALE组和10% ALE组。复合材料植入4个月后，处死动物，采集尾椎（4-7节）进行显微CT检查和生物力学测试。

结果

CPC的凝固时间和强度明显快于且大于其他组。ALE释放持续21天以上，复合材料表现出良好的生物相容性。在显微CT分析中，与假手术组相比，治疗组的骨体积密度（BMD）和骨小梁数量（Tb.N）显著增加（P<0.05）。与其他组相比，假手术组的骨小梁间距（Tb.Sp）显著增加（P<0.01）。然而，骨小梁厚度（Tb.Th）在各组之间无显著差异。在生物力学测试中，假手术组小梁骨的最大压缩强度和刚度低于实验组。