Local injection of simvastatin affected reconstruction of trabecular bone of condyles of femur of osteoporotic rats

doi:10.3969/j.issn.2095-4344.2013.46.003

Abstract

Abstract:

BACKGROUND: Local injection with simvastatin can induce osteogenesis, significantly increase the bone mineral density and mechanical strength of femoral neck and femoral condyle of rats with osteoporosis and analyze effects of local injection of simvastatin on trabecular bone of the femoral condyle.
OBJECTIVE: To explore the effects of local injection of simvastatin on trabecular bone of the femoral condyle of osteoporotic rats and provide experimental basis for the application of simvastatin in clinical topical treatment of osteoporosis.
METHODS: Eighteen female Sprague-Dawley rats received bilateral ovariotomy at 3 months, and were used to produce rat models of osteoporosis. They were assigned into three groups. Experimental rats received 5 and 10 mg simvastatin by single injection into right femoral cavity. Control rats received blank vector. The rat models were sacrificed at 1 month after injection and specimens were collected. Right femoral condyles were taken out for bone histomorphometric analysis by Micro-CT.
RESULTS AND CONCLUSION: One month post-injection, Micro-CT scanning results revealed that cortical bone thickness, trabecular bone density and connection rate were significantly better in the simvastatin group than those in the control group. Results indicated that single injection of small-dose simvastatin obviously promoted rebuilding of trabecular bone of condyles of femur, improved microstructure of skeleton, strengthened local skeleton, prevented and treated osteoporosis, and provided a further basis for the prevention and treatment of osteoporosis, especially for osteoporotic fractures.

Key words: osteoporosis, ovariectomy, femur, femoral neck fractures, imaging, three-dimensional

CLC Number:

R318

Li Yang, Feng Shi-qing, Yang Ning. Local injection of simvastatin affected reconstruction of trabecular bone of condyles of femur of osteoporotic rats[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(46): 7994-7999.

Figures/Tables 4

References

[1]Stein GS, Lian JB. Molecular mechanisms mediating roliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev. 1993; 14(4):424-442.
[2]Stein EA, Farnier M, Waldstreicher J, et al. Effects of statins on biomarkers of bone metabolism: a randomized trial. Nutr Metab Cardivasc Dis. 2001;11(2):84-87.
[3]Chan MH, Mak TW, Chiu RW, et al. Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolaemia. J Clin Endocrinol Metab. 2001; 86(9):4556-4559.
[4]杨宁,崔岳毅,韩晓光,等. 骨质疏松大鼠股骨内单次注射辛伐他汀强化骨骼的实验研究[J]. 中华骨科杂志,2012,32(5):500-506.
[5]尚庆,刘宗超,鲁晓波,等. 快速制备骨质疏松体外模型的实验研究[J]. 中国修复重建外科杂志,2013,27(3):326-329.
[6]王亮,张志敏,甄相周,等.去势雌性山羊骨质疏松模型的特点[J].中国组织工程研究,2012,16(7):1303,1306.
[7]汪玉海,刘兴炎,白孟海,等. 骨形态发生蛋白对去势大鼠股骨颈骨形态、骨密度和骨生物力学的影响[J]. 中国组织工程研究与临床康复,2007,11(27):5273-5276.
[8]Song C, Guo Z, Ma Q, et al. Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochem Biophys Res Commun. 2003;308(3):458-462.
[9]曾高峰,张志勇,鲁力,等. 多糖干预骨质疏松模型大鼠的作用及机制[J]. 中国组织工程研究,2012,16(50):9471-9478.
[10]王兆杰,杨晋, 王吉博,等. 兔骨质疏松与骨坏死模型骨组织病理变化的比较研究[J]. 中国骨质疏松杂志,2012,18(12): 1082- 1085.
[11]曾天舒,陈璐璐,夏文芳.辛伐他汀促进成骨细胞增殖的实验研究[A].中华医学会第一次全国骨质疏松学术会议论文汇编[C].北京:中华医学会,2001:121.
[12]Christiansen BA,Silva MJ. The effect of varying magnitudes of whole-body vibration on several skeletal sites in mice. Ann Biomed Eng.2006;34(7):1149-1156.
[13]Peter B,Ganthier O,Laib S,et al.Local delivery of bisphosphohate from coated orthopedic implants increases implants mechanieal stability in osteoperotie tats.J Biomed Mater Bes A. 2006;76(1):133-143．
[14]姚新苗,杨林,王靖,等.益骨汤对去势大鼠血清激素水平、骨密度和骨生物力学影响的实验研究[J].中医正骨,2006,18(1):3-4.
[15]Cramer JA,Gold DT,Silverman SL,et al. A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int.2007;18(8):1023-1031.
[16]Barlow DH. Osteoporosis guidelines. Climacteric. 2007;10 Suppl 2:79-82.
[17]赵金东,唐海．骨质疏松症及其骨折的局部治疗[J]．中华骨质疏松和骨矿盐疾病杂志,2010,3(2):137-140．
[18]朱静琳,宋泉生,王晶莹,等．局部植入辛伐他汀修复兔桡骨极限骨缺损的实验研究[J].中国修复重建外科杂志,2010,24(4): 465-471．
[19]Stadelmann VA, Gauthier O, Terrier A, et al. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study. Eur Cell Mater. 2008;16:10-16.
[20]Gallagher AM, Rietbrock S, Olson M, et al. Fracture outcomes related to persistence and compliance with oral bisphosphonates. J Bone Miner Res. 2008;23(10):1569-1575.
[21]Stadelmann VA, Ganthier O, Terrier A, et al. Implants delivering bisphosphonate locally increase periprosthetic bone density in an asteopomtic sheep model.A pilot study. Eur Cell Mater.2008;16(1):10-16．
[22]王晶莹,宋泉生,朱静琳,等．辛伐他汀复合聚乳酸修复颅骨极限缺损的实验研[J].中国微创外科杂志,2009,9(12):1148-1151．
[23]Ho ML, Chen YH, Liao HJ, et al. Simvastatin increases osteoblasts and osteogenic proteins in ovariectomized rats. Eur J Clin Invest. 2009;39(4):296-303.
[24]吴子祥,雷伟,胡蕴玉,等. 局部注射缓释型bBMP对去势绵羊椎体骨骼影响的研究[J].中华骨科杂志,2008,28(1):51-55.
[25]Tanaka A, Ishii Y. Mechanical properties of the femur after injection of calcium phosphate cement containing arbekacin sulfate and polylactic acid in a rat model of experimental osteoporosis. J Orthop Sci. 2002;7(3):370-378.
[26]宋纯理,耕町,贾弘提,等. 辛伐他汀促进骨髓基质细胞的成骨分化[J]. 北京大学学报：医学版,2003,35(5):533-536.
[27]Li X, Song QS, Wang JY, et al. Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ER alpha expression and uterine wet weight in ovariectomized rats. J Bone Miner Metab. 2011;29(4): 396-403.
[28]王慧,罗晓晋,武锋. 辛伐他汀与Bio-Oss骨粉混合物对种植体周围缺损骨重建中破骨细胞的作用[J].中国药物与临床,2013, 13(4):434-436.
[29]张勇妹,丁妍,郭贵宾,等. 接骨七厘片、辛伐他汀对促进骨折愈合的动物实验研究[J]. 实用临床医药杂志,2013,17(5):18-20.
[30]Stewart NA, Chantrey J, Blankley SJ, et al. Predictors of 5 year survival following hip fracture. Injury. 2011;42(11): 1253-1256.