不同类型骨水泥对椎旁转移瘤细胞毒作用的实验研究
摘要
目的
探讨磷酸钙骨水泥(CPC)和聚甲基丙烯酸甲酯骨水泥(PMMA)对实验兔椎旁转移瘤的细胞毒作用,研究动物椎旁转移瘤模型代替脊柱肿瘤模型进行实验研究的可行性。
材料及方法
1. CT定位下经皮穿刺瘤块推送法建立实验兔VX2椎旁转移瘤模型。15天后MRI检查模型建立情况。2.模型兔随机分为3组:①对照组:模型兔无任何处理。②PMMA组:模型兔肿瘤内注入PMMA骨水泥。③CPC组:模型兔肿瘤内注入CPC骨水泥。3.对照组不做处理,CPC组及PMMA组在CT定位下向椎旁转移瘤中心分别注入CPC或PMMA骨水泥1.0ml。骨水泥注入后每组分别于1天、7天、14天后处死5只荷瘤兔,取出肿瘤组织,10%甲醛固定。标本切取两部分:骨水泥表面肿瘤组织、骨水泥远端肿瘤组织(对照组取肿瘤中心和边缘),经冲洗、脱水、透明、包埋、制成蜡块后切片。4.①骨水泥注入后每天观察动物生理状态;②HE染色法观察骨水泥表面及边缘肿瘤细胞形态变化及坏死情况;③TUNEL细胞原位凋亡检测,观察肿瘤细胞凋亡并计算凋亡指数,所得数据采用SPSS13.0统计软件包行统计学分析。
结果
①模型动物均能很好的耐受手术,骨水泥注入后成团状,无明显的渗漏。术后实验动物无明显的生理不适,无精神萎靡、嗜睡、拒食等现象;②HE染色结果显示PMMA组术后骨水泥表面肿瘤细胞发生不同程度的坏死,细胞出现典型的核浓缩、核分裂、核溶解、胞浆溶解红染,在坏死的肿瘤组织中可见少许残存的肿瘤细胞,尤以骨水泥远端较多见,7天及14天后骨水泥表面肿瘤细胞较第1天有明显增生,边缘及周边肿瘤细胞增生活跃;对照组和CPC组各时间段均显示骨水泥表面和边缘肿瘤组织增生活跃;③TUNEL细胞原位凋亡检测结果显示:各时间点内PMMA组骨水泥表面肿瘤细胞凋亡较周边多,治疗后第1天差异较为明显,以后逐渐减少。对照组和CPC组骨水泥表面及周边细胞凋亡不明显。PMMA组各时间点骨水泥表面及周边肿瘤细胞凋亡较对照组和CPC组明显增加,两者比较有统计学意义(P<0.05)。CPC组和对照组则无明显差异,两者比较无统计学意义(P>0.05)。
结论
PMMA具细胞毒性,对活体肿瘤细胞具有一定的杀伤作用,CPC则没有明显的肿瘤杀伤作用。实验兔椎旁转移瘤模型建立比较容易,可能作为动物脊柱肿瘤模型进行有关实验研究。
Objective
To investigate the anti-tumor effect of two kinds of bone cements(CPC and PMMA) in rabbit paravertebral metastatic tumors. To research the feasibility of the paravertebral me-tastatic tumor model to replace the spine tumor model.
Methods and methods
1. Transplantable tumor model were constructed by paracentesis under the CT guiding. The rabbits were checked after 15 days by MRI. 2. The rabbit models were randomly divided into 3 groups: Control Group-nothing was injected with the rabbits, PMMA Group-PMMA 1 ml was injected to the center of the tumor, CPC Group-CPC 1 ml was injected to the center of the tumor. 3. The rabbits were executed at 1d、7d and 14d after bone cement were injected. The tissues of tumor were washed、dehydrated、permeabilized、embeded and cut into section after tumor tissue dissection. 4.①The model rabbits were observed every day after operation;②The morphological change and necrosis of tumor cells near and away from the bone cements were observed by HE stain③Apoptotic feature and apoptotic rate were analyzed by TUNEL apoptosis measurement. The data were statistically analyzed by SPSS13.0 statistical bag.
Results
①All model animals can tolerate the operation well. Bone cement was agglomerate in tumor, and was not found cement leakage. Physiological discomfort, psychical dispirited, drowsiness and fastidium were not observed after operation on rabbits;②HE stain results suggested that there was typical nuclei concentration、nuclei cleavage、nuclei dissolution and necrosis of tumor cells near the PMMA bone cements. Few of tumor cells could found in necrosis tissues. Until at 7 days and 14 days after operation, the tumor cells near bone cement were significantly proliferated. But tumor cells significantly proliferated were found on control group and CPC group at all time.③TUNEL apoptosis examination showed that PMMA could induce apoptosis on tumor cells near bone cements,and the PMMA’s apoptotic effect was reduced gradually. At the different time after treatment, the apoptosis index (AI, %) of tumor tissue in the PMMA group was higher than that of in control group and CPC group. The difference of apoptosis index PMMA group compared with other two group has statistical significance (p<0.001). There is no statistical signifi-cance of CPC group and control group (p>0.001).
Conclusion:
The results suggest that PMMA has a significantly cytotoxic and anti-tumor effect, and CPC haven’t the effect. The method establishing rabbit paravertebral metastatic tumor model is easy, which can replace the spine tumor model partially.
探讨磷酸钙骨水泥(CPC)和聚甲基丙烯酸甲酯骨水泥(PMMA)对实验兔椎旁转移瘤的细胞毒作用,研究动物椎旁转移瘤模型代替脊柱肿瘤模型进行实验研究的可行性。
材料及方法
1. CT定位下经皮穿刺瘤块推送法建立实验兔VX2椎旁转移瘤模型。15天后MRI检查模型建立情况。2.模型兔随机分为3组:①对照组:模型兔无任何处理。②PMMA组:模型兔肿瘤内注入PMMA骨水泥。③CPC组:模型兔肿瘤内注入CPC骨水泥。3.对照组不做处理,CPC组及PMMA组在CT定位下向椎旁转移瘤中心分别注入CPC或PMMA骨水泥1.0ml。骨水泥注入后每组分别于1天、7天、14天后处死5只荷瘤兔,取出肿瘤组织,10%甲醛固定。标本切取两部分:骨水泥表面肿瘤组织、骨水泥远端肿瘤组织(对照组取肿瘤中心和边缘),经冲洗、脱水、透明、包埋、制成蜡块后切片。4.①骨水泥注入后每天观察动物生理状态;②HE染色法观察骨水泥表面及边缘肿瘤细胞形态变化及坏死情况;③TUNEL细胞原位凋亡检测,观察肿瘤细胞凋亡并计算凋亡指数,所得数据采用SPSS13.0统计软件包行统计学分析。
结果
①模型动物均能很好的耐受手术,骨水泥注入后成团状,无明显的渗漏。术后实验动物无明显的生理不适,无精神萎靡、嗜睡、拒食等现象;②HE染色结果显示PMMA组术后骨水泥表面肿瘤细胞发生不同程度的坏死,细胞出现典型的核浓缩、核分裂、核溶解、胞浆溶解红染,在坏死的肿瘤组织中可见少许残存的肿瘤细胞,尤以骨水泥远端较多见,7天及14天后骨水泥表面肿瘤细胞较第1天有明显增生,边缘及周边肿瘤细胞增生活跃;对照组和CPC组各时间段均显示骨水泥表面和边缘肿瘤组织增生活跃;③TUNEL细胞原位凋亡检测结果显示:各时间点内PMMA组骨水泥表面肿瘤细胞凋亡较周边多,治疗后第1天差异较为明显,以后逐渐减少。对照组和CPC组骨水泥表面及周边细胞凋亡不明显。PMMA组各时间点骨水泥表面及周边肿瘤细胞凋亡较对照组和CPC组明显增加,两者比较有统计学意义(P<0.05)。CPC组和对照组则无明显差异,两者比较无统计学意义(P>0.05)。
结论
PMMA具细胞毒性,对活体肿瘤细胞具有一定的杀伤作用,CPC则没有明显的肿瘤杀伤作用。实验兔椎旁转移瘤模型建立比较容易,可能作为动物脊柱肿瘤模型进行有关实验研究。
Objective
To investigate the anti-tumor effect of two kinds of bone cements(CPC and PMMA) in rabbit paravertebral metastatic tumors. To research the feasibility of the paravertebral me-tastatic tumor model to replace the spine tumor model.
Methods and methods
1. Transplantable tumor model were constructed by paracentesis under the CT guiding. The rabbits were checked after 15 days by MRI. 2. The rabbit models were randomly divided into 3 groups: Control Group-nothing was injected with the rabbits, PMMA Group-PMMA 1 ml was injected to the center of the tumor, CPC Group-CPC 1 ml was injected to the center of the tumor. 3. The rabbits were executed at 1d、7d and 14d after bone cement were injected. The tissues of tumor were washed、dehydrated、permeabilized、embeded and cut into section after tumor tissue dissection. 4.①The model rabbits were observed every day after operation;②The morphological change and necrosis of tumor cells near and away from the bone cements were observed by HE stain③Apoptotic feature and apoptotic rate were analyzed by TUNEL apoptosis measurement. The data were statistically analyzed by SPSS13.0 statistical bag.
Results
①All model animals can tolerate the operation well. Bone cement was agglomerate in tumor, and was not found cement leakage. Physiological discomfort, psychical dispirited, drowsiness and fastidium were not observed after operation on rabbits;②HE stain results suggested that there was typical nuclei concentration、nuclei cleavage、nuclei dissolution and necrosis of tumor cells near the PMMA bone cements. Few of tumor cells could found in necrosis tissues. Until at 7 days and 14 days after operation, the tumor cells near bone cement were significantly proliferated. But tumor cells significantly proliferated were found on control group and CPC group at all time.③TUNEL apoptosis examination showed that PMMA could induce apoptosis on tumor cells near bone cements,and the PMMA’s apoptotic effect was reduced gradually. At the different time after treatment, the apoptosis index (AI, %) of tumor tissue in the PMMA group was higher than that of in control group and CPC group. The difference of apoptosis index PMMA group compared with other two group has statistical significance (p<0.001). There is no statistical signifi-cance of CPC group and control group (p>0.001).
Conclusion:
The results suggest that PMMA has a significantly cytotoxic and anti-tumor effect, and CPC haven’t the effect. The method establishing rabbit paravertebral metastatic tumor model is easy, which can replace the spine tumor model partially.
引文
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1. Galibert P, Deramond H, Rosat P, Le Gars D. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie, 1987, 33: 166-168.
2. Galibert P, Deramond H, Rosat P, et al. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie 1987,33:166-168.
3. Galibert P, Deramond H, Percutaneous acrylic vertebroplasty as a treatment of verte-bral angioma as well as painful and debilitating diseases.Chirurgie,1990,116:326-334.
4. Cotton A, Deramond H, Cortet B, et al. Preoperative percutancous injection of methyl methacrylate and N-buty cyanoacrylate intervertebral hemangiomas. AJNR Am JNeuroradiol,1996,17(1):137-142.
5. Ide C, Gangi A, Rimmelin A, et al. Vertebral haemangiomas with spinal cord compres-sion: the place of preoperative percutaneous vertebroplasty with methyl methacrylate. Neuroradiology 1996,38(6):585-589.
6. Dean JR, Ison KT, Gishen P.The strengthening effect of percutaneous vertebroplasty. Clin Radiol, 2000,55:471-476.
7. Cotton A, Boutry N, Cortet B, et al. Percutaneous vertebroplasty: state of the art.Radiographics, 1998,18(2):311-320;discussion 320-323.
8. Dufresne AC, Brunet E, Sola-Martinez MT, et al. Percutaneous vertebroplasty of the cervico-thoracic junction using an anterior route.Technique and results.Report of nine case. J Neuroradiol, 1998,25(2):123-128.
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18. Radin EL, Rubin CT, Thrasher EL, et al. Thermal aspects of self-curing polymethyl-methacrylate [J]. J Bone Joint Surg (Am),1975,57(4):380-391.
19. Tohmeh AG, Mathis JM, Fenton DC, et al. Biomechanical efficacy of unipedicular versus bipedicular vertebroplasty for the management of osteoporotic compression fractures [J]. Spine, 1999,24 (17):1772-1776.
20. Deramond H, Wright NT, Belkof SM. Assessment of bone viability after heat trauma:a histologica1. histochemical and vital microscopic study in the rabbit [J]. Scand J Plast Reconstr Surg, 1984;l8:261-8.
21. Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive me-thylme-thacrylate fractures and osteoporosis [J]. J Bone Joint surg(Am), 1995,67(7):1094-1097.
22. Ledlie JT, Renfro M. Balloon kyphoplasty. one-year outcomes in vertebral body height restoration, chronic pain, and activity levels [J]. J Neurosurg,2003,98 (1 Suppl):36-421.
23. Lieberman IH, Dudeney S, Reinhardt MK, et al. Initial outcome and efficacy of“kyphoplasty”in the treatment of painful osteoporotic vertebral compression frac-tures[J].Spine,2001,26(14):1631-1638.
24. Constantz BR, Barr BM, Ison IC, et al. Histological, chemical, and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites. J Biomed Mater Res, 1998,43:451-461.
25. Cortet B, Cotton A, Boutry N, et al. Percutaneous vertebroplasty in patients with oste-olytic metastases or multiple myeloma. Rev Rhum Engl Ed, 1997,64(3):177-83.
26. Bai Bo, Jazrawi LM , Kum mer FJ, et al. The use of an injectable,biodegradablw cal-cium phosphate bone substitute forthe prophylactic augm entation ofsoteoporotic ver-tebrae and the m anagem entofvertebral compression fractures [J]. Spine,1999, 24:1521-1526
27. Harris NH, Miller AJ, Bourne R, et al.Proceedings: experimental investigation of fat embolism after the use of acry lic cement in orthopaedic surgery [J].J Bone Joint Surg (Br), 1975,57(2):245-246.
28. Phillips H, Cole Pv, Lettin AW. Cadiovascular effects of implanted acrylic bone ce-ment [J]. BMJ,1971,3(772):460-461.
29. Dahl OE, Garvik LJ, Lyberg TL. Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro. Acta Orthop Scand,1994,65:147-153.
30. Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive me-thylme-thacrylate fractures and osteoporosis [J]. J Bone Joint surg(Am),1995, 67(7):1094-1097.
31. Weill A, Chiras J, Simon JM, et al. Spinal metastases:indications for and results of percuteneous injection of acrylic surgical cement. Radiology,1996,199(1):241-247 .
32. Verlaan JJ, Oner FC, Verbout AJ, et al .A biomenchanical analysis of intravertebral pressures during vertebroplasty of cadaveric spines with and without simulated me-tastaes. Spine.2003,28(14):1534-1539.
33. Dahl OE, Cardiorespiratory and vascular dysfunction related to major reconstructive orthopedic surgery. Acta Orthop Scand.1997 Dec,68(6):607-614.
34. Belkoff SM, Mathis JM, Erbe EM, et al. Biomechanical evaluation of a new bone ce-ment for use in vertebroplasty [J]. Spine, 2000, 25 (9):1061-1064.
35. Yerby SA, Toh E, McLain RF, Rexision of failed pedicle screws using hydroxyapatite cement:a biomechanical analysis [J]. Spine,1998,23(15):1657-1661.
36. Ripamonti U, Crooks J, Kirkbride AN. Sintered poroushy-droxya patites with in trin-sicosteo inductive activity: geometric induction of bone formation. South African Journal of Science, 1999:95(8):335.
37. Yoshikawa T, Ohgushi H, Tamai S. Immediate bone forming capability of prefabri-cated osteogenic hydroxya-patite. J Biomed Mater Res, 1996;32:481.
38. Cunin G, Boissonnet H, Petite H, et al. Experimental vertebrplasty using osteoconduc-tive granular material [J].Spine,2000,25(9):1070-1076.
39. Brown WE. Chow LC. A new calcium phosphate watersetting cement//Brown PW. Cements research progress. Wasterville, Ohio: American Ceramic Society,1986: 352-379.
40.周馨,郑昌琼,王方瑚等.骨水泥及磷酸钙生物活性骨水泥[J].硅酸盐通报,l998,l7(5):33-38.
41. Niedhart C. Maus U. Redmann E, et a1. In vivo resting of a new in situsetting betatri-calcium phosphate cement for OSSEOUS reconstruction. J Biomed Mater Res 2001;55(4):530-537.
42.赵晓伟.自制磷酸钙骨水泥分子生物相容性初探.济宁医学院学报. 2007.30(2):l20-l2l.
43. Belkoff SM, Mathis JM, Jasper LE, et al. The biomechanics of vertebraphlasty: the effect of cement volume on mechanical behavior [J].Spine, 2001,26(14)1537-1541.
44.林立波,曾维权.磷酸钙骨水泥的研究进展综述[J].中国修复重建外科杂志,1998, 123: 169-172.
45. Knaack D, Goad EB, Aiolova M, et al. Resorbable calcium phosphate bone substitute [J].J Biomed Mater Res, 1998,43(4):399-409.
46. Xu HH, Quinn JB. Whisker-reinforced bioactive composites containing calcium phosphatecement fillers: efects of fillers ratio and surface treatments on mechanical properties [J]. J Biomed Mater Res, 2001,2:165-174.
47. Bigi A, Bracci B, Panzavolta SEfect of added gelatin on the properties of calcium phosphate cement. Biomaterials [J]. 2004,25:2893-2899.
48. Pan Z, Jiang P, Fan Q, et a1. Mechanical and biocompatible influences of chitosan fi-ber andgelatin on calcium phosphate cement [J]. J Biomed Mater Res B Appl Bioma-ter,2006,20:378-381.
49. Wang X, Ye J, Wang Y, et a1. Self-setting properties of a beta-dicalcium silicate rein-forcedcaleium phosphate cement [J]. J Biomed Mater Res B Appl Biomater, 2006,31:134-139.
50. Leroux L, Hatim Z, Freche M, et a1. Effects of Various Adjuvants(Lactic Acid, Glyc-erol, and Chitosan)on the Injectability ofa Calcium Phosphate Cement [J]. Bone, 1999,25(2):3l-34.
51. Fernandez E, Sarda S, Hamcereneu M, et a1. Hish-strength apatitie cement by modifi-cation with superplastieizers[J]. Biomaterials,2005,15:2289-2296.
52. Cherng A, Takagi S, Chow LC, et a1. Effects of hydroxyproply methylcellulose and other gelling agents on the handling properties of calcium phosphate cement[J]. Jour-nal of Biomedical Materials Research,1999,50:273-274.
53. Xu HHK, Quinn JB. Calcium phosphate cement containing resorbable fibles for short -rerm reinforcement and macroporosity. Biomatefials,2002,23(1):193.
54. Blom EJ, Klein Nulend J, Kliend CP, et al. Transforming growth factor-batel incorpo-rated during setting in calcium phosphate cement stimulates bone cell differentiation in vitro. J Biomed Mater Res,2000,50(1):67.
55. Kroese-Deutman HC, Ruhe PQ, Spanwen PH, et a1. Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement im-plants inserted at an ectopic site inrabbits[J]. Biomaterials, 2005,10:l131-1138.
56. Joosten U, Joist A, Gosheger G, et a1. Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of staphylococcus anreus induced chronic osteomye-litis[J]. Biomaterials, 2005, 25:525l-5258.
57.张进军,李兵仓,陈青等,磷酸钙骨水泥承载头孢哌酮钠后对其理化特性的影响[J],生物医学工程学杂志,2000,17(4):400-402.
58.杨晓彤,吴波以,黄文铎.含硫酸妥布霉素的磷酸钙骨水泥对外伤性骨髓炎作用的观察.创伤外科杂志[J],2001,3:31-33.
59.苗军,王继芳,郝利波等.磷酸钙骨水泥复合去甲万古霉素后理化性质改变及药物释放规律的研究.中华创伤骨科杂志,2004.6:648-656.
60. Tahara Y, Ishii Y. Apafite cement containing cis-diamminedichloroplatinum implanted in rabbit femur for sustained release of the anticancer drug and bone forma-tion [J]. J Orthop Sci,2001,6:556-561.
61.孙诚,张贵祥等,兔VX2肿瘤对表阿霉素骨水泥介入治疗反应的(31)P MRS监测.中国医学影像学杂志,2000-05-024.
62.陆军,张贵祥等,CT引导下PVP携带化疗药物治疗脊柱转移瘤.第四军医大学学报,2002-24-026.
63. Miyamoto Y, Ishikawa K, Takechi M, et al. Basic properties of calcium phosphate cement containing atelo-collagen in its liquid or pow der phases [J]. B iomaterials, 1998,19(7-9):707-715.
64. Perry A, Mahar A, Massie J, et al. Biomechanical evaluationof kyphoplasty with cal-cium sulfate cement in a cadaveric osteoporotic vertebral compression fracture model [J].Spine J,2005,5(5):489-493.
2. Galibert P, Deramond H, Percutaneous acrylic vertebroplasty as a treatment of verte-bral angioma as well as painful and debilitating diseases.Chirurgie,1990,116:326-334.
3. Cotton A, Deramond H, Cortet B, et al. Preoperative percutancous injection of methyl methacrylate and N-butyl cyanoacrylate intervertebral hemangiomas. AJNR Am J Neuroradiol, 1996,17(1):137-142.
4. Ide C, Gangi A, Rimmelin A, et al. Vertebral haemangiomas with spinal cord compres-sion:the place of preoperative percutaneous vertebroplasty with methyl methacrylate. Neuroradiology 1996,38(6):585-9.
5. Dean JR, Ison KT, Gishen P. The strengthening effect of percutaneous vertebroplasty. Clin Radiol, 2000,55:471-476.
6. Cotton A,Boutry N, Cortet B, et al. Percutaneous vertebroplasty:state of the art. Ra-diographics,1998,18(2):311-20;discussion 320-323.
7. Dufresne AC, Brunet E, Sola-Martinez MT, et al. Percutaneous vertebroplasty of the cervico-thoracic junction using an anterior route.Technique and results.Report of nine case. J Neuroradiol,1998,25(2):123-128.
8. Weill A, Chiras J, Simon JM, et al. Spinal metastases:indications for and results of percuteneous injection of acrylic surgical cement. Radiology,1996,199(1):241-247 .
9. Cortet B, Cotton A, Boutry N, et al. Percutaneous vertebroplasty in patients with oste-olytic metastases or multiple myeloma. Rev Rhum Engl Ed, 1997,64(3):177-83.
10. Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive methyl-methacrylate on failures of fixation and function in patients with intertrochanteric frac-tures and osteoporosis [J]. J Bone Joint Surg (Am),1985,67(7):1094-107.
11. McAfee PC, Bohlman HH, Ducker T, et al. Failure of stabilization of the spine withmethylmethacrylate: a retrospective analysis of twenty-four cases[J]. J Bone Joint Surg (Am),1986,68(8):1145-1157.
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13. Ushio Y, Posner R, Posner JB, Shapiro WR. Experimental spinal cord compression by epidural neoplasm. Neurology. 1977,27(5):422-429.
14. Galibert P, Deramond H, Rosat P, Le Gars D. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplty. Neurochirurgie, 1987, 33:166- 168.
15. Harris NH, Miller AJ, Bourne R, et al. Proceedings: experimental investigation of fat embolism after the use of acry lic cement in orthopaedic surgery [J]. J Bone Joint Surg (Br),1975,57(2):245-246.
16. Phillips H, Cole Pv, Lettin AW. Cadiovascular effects of implanted acrylic bone ce-ment [J]. BMJ, 1971, 3(772):460-461.
17. Dahl OE, Garvik LJ, Lyberg TL. Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro. Acta Orthop Scand, 1994 ,65 :147-153.
18. Deramond H,Wright NT, Belkof SM.Assessment of bone viability after heat trauma: a histologica1. histochemical and vital microscopic study in the rabbit [J]. Scand J Plast Reconstr Surg, 1984, l8:261-8.
19. Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive me-thylme-thacrylate fractures and osteoporosis [J]. J Bone Joint surg(Am), 1995, 67(7): 1094-1097.
20. Ledlie JT, Renfro M. Balloon kyphoplasty. one-year outcomes in vertebral body height restoration, chronic pain, and activity levels [J]. J Neurosurg, 2003,98 (1 Suppl):36-421.
21. Lieberman IH, Dudeney S, Reinhardt MK, et al. Initial outcome and efficacy of ky-phoplasty in the treatment of painful osteoporotic vertebral compression fractures [J].Spine, 2001, 26(14):1631-1638.
22. Constantz BR, Barr BM, Ison IC, et al. Histological chemical and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites. J Biomed Mater Res, 1998, 43:451-461.
23. Higashi S, Ohsumi T, Ozumi K, et al. Evaluation of cytotoxicity of calcium phosphate cement consisting of alpha-tricalcium phosphate and dicalcium phosphate dehydrate. Dent Mater J, 1998, 17:186-194.
24. Costantino PD, Friedman CD, Jones K, et al. Experimental hydroxyapatite cement dranioplasty. Plast Reconstrr Surg, 1992, 90:174-185.
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1. Galibert P, Deramond H, Rosat P, Le Gars D. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie, 1987, 33: 166-168.
2. Galibert P, Deramond H, Rosat P, et al. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie 1987,33:166-168.
3. Galibert P, Deramond H, Percutaneous acrylic vertebroplasty as a treatment of verte-bral angioma as well as painful and debilitating diseases.Chirurgie,1990,116:326-334.
4. Cotton A, Deramond H, Cortet B, et al. Preoperative percutancous injection of methyl methacrylate and N-buty cyanoacrylate intervertebral hemangiomas. AJNR Am JNeuroradiol,1996,17(1):137-142.
5. Ide C, Gangi A, Rimmelin A, et al. Vertebral haemangiomas with spinal cord compres-sion: the place of preoperative percutaneous vertebroplasty with methyl methacrylate. Neuroradiology 1996,38(6):585-589.
6. Dean JR, Ison KT, Gishen P.The strengthening effect of percutaneous vertebroplasty. Clin Radiol, 2000,55:471-476.
7. Cotton A, Boutry N, Cortet B, et al. Percutaneous vertebroplasty: state of the art.Radiographics, 1998,18(2):311-320;discussion 320-323.
8. Dufresne AC, Brunet E, Sola-Martinez MT, et al. Percutaneous vertebroplasty of the cervico-thoracic junction using an anterior route.Technique and results.Report of nine case. J Neuroradiol, 1998,25(2):123-128.
9. Weill A, Chiras J, Simon JM, et al. Spinal metastases:indications for and results of percuteneous injection of acrylic surgical cement .Radiology, 1996,199(1):241-247
10. Kelekis A, Lovblad K, Mehdizade A, et a1. Pelvic osteoplasty in osteolytic metastases: technical approach under fluoroscopic guidanceand and early clinical results. Journal Cardi0vascular&Interventional Radiology, 2005,16:81-88.
11. Harry JA, Brennan D, Eustace S, et a1. Percutaneous cementoplasty of acetabular bone metastasis Surg. R Coil Surg Edinb Irel, 2003,1:48-59.
12. Fujita T, Inoue T, Morii H, et al. Effect of an intermittent Weekly dose of human pa-rathyroid hormone(1-34)on osteoporosis: a randomized double-masked prospective study using three dose levels. Osteoporos Int,1999,9:296-306
13. Pfutzner A, Flacke F, Pohl R, et al. Pilot study with technosphere/PTH(1-34)a new approach for effective pulmonary delivery ofparathyroid hormone(1-34). Horm Metab Res, 2003,35;319-323.
14. Cranney A, Papaioannou A, Zytaruk N, et a1. Parathyroid hormone for the treatment of osteoporosis: a systematic review.CM AJ,2006,175:52-59.
15. Brixen. Teriparatide (biosynthetic human parathyroid hormone 1-34):A new paradigm in the treatment of osteoporosis. Basic Clin Pharmacol Toxicol,2004,94:260-270.
16. Heini PF, Berlemann U, Kaufmann M, et al. Augmentation of mechanical properties in osteoprotic vertebral bones-a biome-chanical investigation of vertebroplasty effi-cacy with different bone cements [J]. Eur Spine J, 2001,10(2):164-171.
17. Lu WW, Cheung KMC, Li YW, et al. Bioactive bone cement as a principal fixture for spinal burst fracture:A in vitro biome-chanical and morphological study [J].Spine,2001,26(24):2684-2690.
18. Radin EL, Rubin CT, Thrasher EL, et al. Thermal aspects of self-curing polymethyl-methacrylate [J]. J Bone Joint Surg (Am),1975,57(4):380-391.
19. Tohmeh AG, Mathis JM, Fenton DC, et al. Biomechanical efficacy of unipedicular versus bipedicular vertebroplasty for the management of osteoporotic compression fractures [J]. Spine, 1999,24 (17):1772-1776.
20. Deramond H, Wright NT, Belkof SM. Assessment of bone viability after heat trauma:a histologica1. histochemical and vital microscopic study in the rabbit [J]. Scand J Plast Reconstr Surg, 1984;l8:261-8.
21. Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive me-thylme-thacrylate fractures and osteoporosis [J]. J Bone Joint surg(Am), 1995,67(7):1094-1097.
22. Ledlie JT, Renfro M. Balloon kyphoplasty. one-year outcomes in vertebral body height restoration, chronic pain, and activity levels [J]. J Neurosurg,2003,98 (1 Suppl):36-421.
23. Lieberman IH, Dudeney S, Reinhardt MK, et al. Initial outcome and efficacy of“kyphoplasty”in the treatment of painful osteoporotic vertebral compression frac-tures[J].Spine,2001,26(14):1631-1638.
24. Constantz BR, Barr BM, Ison IC, et al. Histological, chemical, and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites. J Biomed Mater Res, 1998,43:451-461.
25. Cortet B, Cotton A, Boutry N, et al. Percutaneous vertebroplasty in patients with oste-olytic metastases or multiple myeloma. Rev Rhum Engl Ed, 1997,64(3):177-83.
26. Bai Bo, Jazrawi LM , Kum mer FJ, et al. The use of an injectable,biodegradablw cal-cium phosphate bone substitute forthe prophylactic augm entation ofsoteoporotic ver-tebrae and the m anagem entofvertebral compression fractures [J]. Spine,1999, 24:1521-1526
27. Harris NH, Miller AJ, Bourne R, et al.Proceedings: experimental investigation of fat embolism after the use of acry lic cement in orthopaedic surgery [J].J Bone Joint Surg (Br), 1975,57(2):245-246.
28. Phillips H, Cole Pv, Lettin AW. Cadiovascular effects of implanted acrylic bone ce-ment [J]. BMJ,1971,3(772):460-461.
29. Dahl OE, Garvik LJ, Lyberg TL. Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro. Acta Orthop Scand,1994,65:147-153.
30. Bartucci EJ, Gonzalez MH, Cooperman DR, et al. The effect of adjunctive me-thylme-thacrylate fractures and osteoporosis [J]. J Bone Joint surg(Am),1995, 67(7):1094-1097.
31. Weill A, Chiras J, Simon JM, et al. Spinal metastases:indications for and results of percuteneous injection of acrylic surgical cement. Radiology,1996,199(1):241-247 .
32. Verlaan JJ, Oner FC, Verbout AJ, et al .A biomenchanical analysis of intravertebral pressures during vertebroplasty of cadaveric spines with and without simulated me-tastaes. Spine.2003,28(14):1534-1539.
33. Dahl OE, Cardiorespiratory and vascular dysfunction related to major reconstructive orthopedic surgery. Acta Orthop Scand.1997 Dec,68(6):607-614.
34. Belkoff SM, Mathis JM, Erbe EM, et al. Biomechanical evaluation of a new bone ce-ment for use in vertebroplasty [J]. Spine, 2000, 25 (9):1061-1064.
35. Yerby SA, Toh E, McLain RF, Rexision of failed pedicle screws using hydroxyapatite cement:a biomechanical analysis [J]. Spine,1998,23(15):1657-1661.
36. Ripamonti U, Crooks J, Kirkbride AN. Sintered poroushy-droxya patites with in trin-sicosteo inductive activity: geometric induction of bone formation. South African Journal of Science, 1999:95(8):335.
37. Yoshikawa T, Ohgushi H, Tamai S. Immediate bone forming capability of prefabri-cated osteogenic hydroxya-patite. J Biomed Mater Res, 1996;32:481.
38. Cunin G, Boissonnet H, Petite H, et al. Experimental vertebrplasty using osteoconduc-tive granular material [J].Spine,2000,25(9):1070-1076.
39. Brown WE. Chow LC. A new calcium phosphate watersetting cement//Brown PW. Cements research progress. Wasterville, Ohio: American Ceramic Society,1986: 352-379.
40.周馨,郑昌琼,王方瑚等.骨水泥及磷酸钙生物活性骨水泥[J].硅酸盐通报,l998,l7(5):33-38.
41. Niedhart C. Maus U. Redmann E, et a1. In vivo resting of a new in situsetting betatri-calcium phosphate cement for OSSEOUS reconstruction. J Biomed Mater Res 2001;55(4):530-537.
42.赵晓伟.自制磷酸钙骨水泥分子生物相容性初探.济宁医学院学报. 2007.30(2):l20-l2l.
43. Belkoff SM, Mathis JM, Jasper LE, et al. The biomechanics of vertebraphlasty: the effect of cement volume on mechanical behavior [J].Spine, 2001,26(14)1537-1541.
44.林立波,曾维权.磷酸钙骨水泥的研究进展综述[J].中国修复重建外科杂志,1998, 123: 169-172.
45. Knaack D, Goad EB, Aiolova M, et al. Resorbable calcium phosphate bone substitute [J].J Biomed Mater Res, 1998,43(4):399-409.
46. Xu HH, Quinn JB. Whisker-reinforced bioactive composites containing calcium phosphatecement fillers: efects of fillers ratio and surface treatments on mechanical properties [J]. J Biomed Mater Res, 2001,2:165-174.
47. Bigi A, Bracci B, Panzavolta SEfect of added gelatin on the properties of calcium phosphate cement. Biomaterials [J]. 2004,25:2893-2899.
48. Pan Z, Jiang P, Fan Q, et a1. Mechanical and biocompatible influences of chitosan fi-ber andgelatin on calcium phosphate cement [J]. J Biomed Mater Res B Appl Bioma-ter,2006,20:378-381.
49. Wang X, Ye J, Wang Y, et a1. Self-setting properties of a beta-dicalcium silicate rein-forcedcaleium phosphate cement [J]. J Biomed Mater Res B Appl Biomater, 2006,31:134-139.
50. Leroux L, Hatim Z, Freche M, et a1. Effects of Various Adjuvants(Lactic Acid, Glyc-erol, and Chitosan)on the Injectability ofa Calcium Phosphate Cement [J]. Bone, 1999,25(2):3l-34.
51. Fernandez E, Sarda S, Hamcereneu M, et a1. Hish-strength apatitie cement by modifi-cation with superplastieizers[J]. Biomaterials,2005,15:2289-2296.
52. Cherng A, Takagi S, Chow LC, et a1. Effects of hydroxyproply methylcellulose and other gelling agents on the handling properties of calcium phosphate cement[J]. Jour-nal of Biomedical Materials Research,1999,50:273-274.
53. Xu HHK, Quinn JB. Calcium phosphate cement containing resorbable fibles for short -rerm reinforcement and macroporosity. Biomatefials,2002,23(1):193.
54. Blom EJ, Klein Nulend J, Kliend CP, et al. Transforming growth factor-batel incorpo-rated during setting in calcium phosphate cement stimulates bone cell differentiation in vitro. J Biomed Mater Res,2000,50(1):67.
55. Kroese-Deutman HC, Ruhe PQ, Spanwen PH, et a1. Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement im-plants inserted at an ectopic site inrabbits[J]. Biomaterials, 2005,10:l131-1138.
56. Joosten U, Joist A, Gosheger G, et a1. Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of staphylococcus anreus induced chronic osteomye-litis[J]. Biomaterials, 2005, 25:525l-5258.
57.张进军,李兵仓,陈青等,磷酸钙骨水泥承载头孢哌酮钠后对其理化特性的影响[J],生物医学工程学杂志,2000,17(4):400-402.
58.杨晓彤,吴波以,黄文铎.含硫酸妥布霉素的磷酸钙骨水泥对外伤性骨髓炎作用的观察.创伤外科杂志[J],2001,3:31-33.
59.苗军,王继芳,郝利波等.磷酸钙骨水泥复合去甲万古霉素后理化性质改变及药物释放规律的研究.中华创伤骨科杂志,2004.6:648-656.
60. Tahara Y, Ishii Y. Apafite cement containing cis-diamminedichloroplatinum implanted in rabbit femur for sustained release of the anticancer drug and bone forma-tion [J]. J Orthop Sci,2001,6:556-561.
61.孙诚,张贵祥等,兔VX2肿瘤对表阿霉素骨水泥介入治疗反应的(31)P MRS监测.中国医学影像学杂志,2000-05-024.
62.陆军,张贵祥等,CT引导下PVP携带化疗药物治疗脊柱转移瘤.第四军医大学学报,2002-24-026.
63. Miyamoto Y, Ishikawa K, Takechi M, et al. Basic properties of calcium phosphate cement containing atelo-collagen in its liquid or pow der phases [J]. B iomaterials, 1998,19(7-9):707-715.
64. Perry A, Mahar A, Massie J, et al. Biomechanical evaluationof kyphoplasty with cal-cium sulfate cement in a cadaveric osteoporotic vertebral compression fracture model [J].Spine J,2005,5(5):489-493.