椎体内单次注射辛伐他汀对骨质疏松小型猪腰椎椎体骨质和椎弓根螺钉内固定稳定性的影响

The effect of intraosseous injection of simvastatin into the lumbar vertebrae on vertebral bone microstructure and stability of pedicle screw in osteoporotic miniature pigs

中文关键词:  辛伐他汀  骨内注射  骨质疏松  椎弓根螺钉  稳定性  小型猪

英文关键词:Simvastatin  Intraosseous injection  Osteoporosis  Pedicle screw  Stability  Miniature pigs

中文摘要:

  【摘要】 目的：探讨椎体内注射辛伐他汀/泊洛沙姆407温敏型智能水凝胶对骨质疏松小型猪腰椎骨质和椎弓根螺钉内固定稳定性的影响。方法：9只健康成年雌性广西巴马小型猪，行双侧卵巢切除术，术后低钙饮食18个月，双侧卵巢切除后18个月小型猪腰椎骨密度（bone mineral density，BMD）较切除前降低了25.23%，即骨质疏松模型建立成功。每只骨质疏松小型猪采取自身对照，将3个腰椎（L4~L6）进行随机分组，在椎体左侧钉道内单次注射载辛伐他汀0、0.5、1.0mg的水凝胶，并分别在两侧置入钛合金椎弓根螺钉。3个月后处死，取出每只小型猪的椎体（L4~L6），剔除椎体周围软组织，在各椎间盘处离断，游离成单个椎体，用双能X线骨密度仪检测BMD，行Micro-CT扫描并定量分析骨小梁微结构及骨整合率，内固定螺钉轴向拔出实验，不脱钙骨组织学观察。结果：辛伐他汀0.5mg、1mg组椎体与给药前相比，BMD分别增加了32.12％和28.16％，辛伐他汀0.5mg、1mg组椎体与辛伐他汀0mg组相比，BMD分别增加了31.25%和31.09%（P均<0.01）；辛伐他汀0.5mg、1mg组与辛伐他汀0mg组相比，相对骨体积（BV/TV，%）分别增加了47.49%和43.42%，骨小梁数量（Tb.N）分别增加了49.23%和39.01%，骨小梁厚度（Tb.Th）分别增加了66.09%和54.28%，骨小梁间隙（Tb.Sp）分别降低了55.85%和52.80%，骨整合率分别增加了46.54%和42.63%（P均<0.01）；辛伐他汀0.5mg与1mg组的最大轴向拔出力（Fmax）与辛伐他汀0mg组相比，分别增加了45.75%和51.53%（P<0.01）；组织学观察发现辛伐他汀0.5mg、1mg组螺钉周围骨小梁明显增多，钉骨接触面积明显增大。结论：骨质疏松小型猪腰椎椎体内单次注射低剂量辛伐他汀可促进骨形成，增加骨密度，改善骨骼微结构，增加骨整合率，显著提高椎弓根螺钉在骨质疏松椎体中的稳定性。

英文摘要:

  【Abstract】 Objectives: To study the effect of intraosseous injection of simvastatin/poloxamer 407 gel into the lumbar vertebrae on vertebral bone microstructure and stability of pedicle screw in osteoporotic miniature pigs. Methods: Nine female mature Guangxi BA-MA miniature pigs received bilateral ovariectomy(OVX) and feeded with the calcium-restricted diet in order to establish the model of osteoporosis. The bone mineral density(BMD) of pig lumbar was examined before the bilateral OVX and 18 months after the bilateral OVX, the BMD decreased by 25.23%, which could be used as the successful establishment of osteoporotic pig. Three lumbar vertebrae(L4-L6) in each miniature pig were divided into three groups randomly after the establishment of osteoporotic pig. Blank vector(0mg), 0.5mg, 1mg simvastatin was once injected into the left side of pilot hole on the lumbar vertebrae(L4-L6) of experimental pigs. After the injection, titanium alloy pedicle screw was inserted through the pilot hole bilaterally. All animals were sacrificed and lumbar vertebrae(L4-L6) were harvested at 3 months after the injection, respectively. All the lumbar vertebrae were disarticulated and dissected free of soft tissue to yield individual vertebra. The samples were collected for BMD, bone microstructure and biomechanical pull-out test analysis by using dual energy X-ray absorptiometry(DXA), micro-computed tomography(Micro-CT) and the Bionix Servohydraulic Test System. BMD, bone microstructural parameters and the maximum pull-out strength were recorded. Results: Compared with pre-treatment, BMD of SIM 0.5mg and 1.0mg increased by 32.12% and 28.16%, respectively, compared with SIM 0mg, BMD of SIM 0.5mg and 1.0mg increased by 31.25% and 31.09%(all P＜0.01), respectively. Compared with SIM 0mg, SIM 0.5mg and 1.0mg significantly increased BV/TV by 47.49% and 43.42%, Tb.N by 49.23% and 39.01%, Tb.Th by 66.09% and 54.28%, %OI by 46.54% and 42.63%, decreased Tb.Sp by 55.85% and 52.80%(all P＜0.01), respectively. Compared with SIM 0mg, the pull-out strength of SIM 0.5mg and SIM 1.0mg significantly increased by 45.75% and 51.53%(both P＜0.01). Histological test found large amount of peri-implant trabecular bone in the single, local simvastatin injection groups and screw-bone interfaces increased. Conclusions: Single intraosseous injection of simvastatin/poloxamer 407 gel into the lumbar vertebrae can stimulate bone formation, which can increase the BMD and also improve bone microstructure, finally enhances strength of pedicle screw in osteoporotic miniature pigs.