局部应用唑来膦酸预防股骨头坏死塌陷Prevention of femoral head collapse due to osteonecrosis in rats by local delivery of zoledronate via polylactic-co-glycolic acid
徐小龙;苟文龙;王程;袁雪凌;王玉;彭江;卢世璧;郭全义;汪爱媛;许文静;孟昊业;刘舒云;
摘要(Abstract):
[目的]建立大鼠股骨头骨坏死动物模型,观察以聚乳酸-羟基乙酸共聚物(polylactic-co-glycolic acid,PLGA)为载体,局部应用唑来膦酸(zoledronate acid,ZOL)防止大鼠股骨头骨坏死塌陷的效果。[方法]选用PLGA作为局部应用ZOL的载体,制备含有30μg的ZOL的PLGA棒。取SD雄性大鼠30只,随机分为三组,建立创伤性股骨头骨坏死模型。股骨头钻孔,分别植入含有ZOL的PLGA棒(PLGA-ZOL组),以不含ZOL的PLGA棒(PLGA组)和空置(单纯打孔组)为对照组。6周后将大鼠处死取材,进行X线检查计量股骨头高度比,进行MicroCT扫描,分别计算比较各组的骨矿密度(bone mineral density,BMD)、骨体积分数(bone volume fraction,BVF)、骨小梁厚度(trabecular plate thickness,Tb.Th)和骨小梁间隙(trabecular spacing,Tb.Sp)。扫描后进行HE和Masson三色染色了解各组间组织学改变情况。[结果]与打孔组和PLGA组相比,PLGA-ZOL组中BMD(535.95±15.08,P<0.05),BVF(0.77±0.04,P<0.05)和Tb.Th(0.64±0.05,P<0.05)显著增加,而Tb.sp(0.37±0.06,P<0.05)显著降低,而打孔组和PLGA组并无统计学差异。而且PLGA-ZOL组股骨头有更好的形态,骨小梁保留更完整,新生骨更多。[结论]使用ZOL能够抑制局部骨吸收活动,促进局部骨生成,预防股骨头塌陷。
关键词(KeyWords): 股骨头骨坏死;成骨细胞;破骨细胞;唑来膦酸
基金项目(Foundation): 肢体重要组织损伤组织工程修复重建技术研发,国家863主题项目(编号:2012AA020502);; 肢体重要组织战创伤组织工程再生医学关键技术系列研究,全军十二五重点项目(编号:BWS11J025);; 严重创伤后骨、软骨、神经损伤修复与再生研究,国家973计划项目(编号:2012CB518106)
作者(Author): 徐小龙;苟文龙;王程;袁雪凌;王玉;彭江;卢世璧;郭全义;汪爱媛;许文静;孟昊业;刘舒云;
Email:
DOI:
参考文献(References):
- [1]Little DG,Mc Donald M,Sharpe IT,et al.Zoledronic acid improves femoral head sphericity in a rat model of perthes disease[J].J Orthop Res,2005,4:862-868.
- [2]Catterall A,Pringle J,Byers PD,et al.Perthes disease:is the epiphysial infarction complete[J].J Bone Joint Surg Br,1982,3:276-281.
- [3]Kim HK,Randall TS,Bian H,et al.Ibandronate for prevention of femoral head deformity after ischemic necrosis of the capital femoral epiphysis in immature pigs[J].J Bone Joint Surg Am,2005,3:550-557.
- [4]Kim HK,Su PH.Development of flattening and apparent fragmentation following ischemic necrosis of the capital femoral epiphysis in a piglet model[J].J Bone Joint Surg Am,2002,8:1329-1334.
- [5]Pringle D,Koob TJ,Kim HK.Indentation properties of growing femoral head following ischemic necrosis[J].J Orthop Res,2004,1:122-130.
- [6]陈宜,祝云利,吴海山.非创伤性股骨头坏死的国外研究进展[J].中国矫形外科杂志,2010,3:230-233.
- [7]Kim HK,Sanders M,Athavale S,et al.Local bioavailability and distribution of systemically(parenterally)administered ibandronate in the infarcted femoral head[J].Bone,2006,1:205-212.
- [8]Bellido T,Plotkin LI.Novel actions of bisphosphonates in bone:preservation of osteoblast and osteocyte viability[J].Bone,2011,1:50-55.
- [9]Tenenbaum HC,Torontali M,Sukhu B.Effects of bisphosphonates and inorganic pyrophosphate on osteogenesis in vitro[J].Bone,1992,3:249-255.
- [10]Xu XL,Gou WL,Wang AY,et al.Basic research and clinical applications of bisphosphonates in bone disease:what have we learned over the last 40 years[J].J Transl Med,2013,1:303.
- [11]Gou W,Wang X,Peng J,et al.Controlled delivery of zoledronate improved bone formation locally in vivo[J].PLo S One,2014,3:e91317.
- [12]Kim HK,Morgan-Bagley S,Kostenuik P.RANKL inhibition:a novel strategy to decrease femoral head deformity after ischemic osteonecrosis[J].J Bone Mineral Res,2006,12:1946-1954.
- [13]Nishii T,Sugano N,Miki H,et al.Does alendronate prevent collapse in osteonecrosis of the femoral head[J].Clin Orthop,2006:273-279.
- [14]Amanatullah DF,Strauss EJ,Di Cesare PE.Current management options for osteonecrosis of the femoral head:part 1,diagnosis and nonoperative management[J].Am J Orthop(Belle Mead NJ),2011,9:186-192.
- [15]Agarwala S,Shah S,Joshi VR.The use of alendronate in the treatment of avascular necrosis of the femoral head:follow-up to eight years[J].J Bone Joint Surg Br,2009,8:1013-1018.
- [16]苟文隆,彭江,卢强,等.股骨头骨坏死塌陷机制研究进展[J].中国矫形外科杂志,2014,7:621-624.
- [17]Little DG,Peat RA,Mcevoy A,et al.Zoledronic acid treatment results in retention of femoral head structure after traumatic osteonecrosis in young wistar rats[J].J Bone Mineral Res,2003,11:2016-2022.
- [18]Peled E,Bejar J,Zinman C,et al.Alendronate preserves femoral head shape and height/length ratios in an experimental rat model:a computer-assisted analysis[J].Indian J Orthop,2009,1:22-26.
- [19]Omi H,Kusumi T,Kijima H,et al.Locally administered low-dose alendronate increases bone mineral density during distraction osteogenesis in a rabbit model[J].J Bone Joint Surg Br,2007,7:984-988.