阿仑膦酸钠和鲑鱼降钙素对骨质疏松骨床中假体骨整合影响的对比研究

目的探讨阿仑膦酸钠(ALO)和鲑鱼降钙素(CT)两种药物促进假体骨整合作用效果的差异,为临床药物的选择应用提供参考。方法将40只雌性SD大鼠随机分为四组(A,B,C,D组),每组10只。切除B、C、D组大鼠卵巢建立骨质疏松(OP)模型(骨密度降幅20%),A组行假手术做为对照。随后在大鼠的胫骨平台植入羟基磷灰石假体,术后C、D组分别给予皮下注射CT(5IU/kg/d)和口服ALO(7mg/kg/w)各12周,A、B组做药物干预的对照组。所有大鼠在处死前,行体内荧光染色。处死后取带假体的胫骨制备成薄片,运用骨组织计量学检测手段,观察假体周围的骨量和测量假体的骨结合率。结果(1)ALO和CT两者均能促进假体周围成骨,增加骨量,显著提高骨-假体界面骨结合率至63.7%和45.7%,较OVX组骨整合比率分别提高近1～2倍,但阿仑膦酸钠促进假体周围成骨与促进骨整合较鲑鱼降钙素作用更为显著(P0.05),骨结合率增加18%;(2)阿仑膦酸钠和鲑鱼降钙素组大鼠腰椎BMD均提高,分别从(0.081±0.009)g/cm2和(0.078±0.009)g/cm2提至(0.116±0.008)g/cm2和(0.109±0.010)g/cm2。而且,阿仑膦酸钠的效果较降钙素更为明显。结论骨质疏松条件下,全身给予阿仑膦酸钠和鲑鱼降钙素均可增强假体周围成骨及骨量,有效促进假体的骨整合,但与鲑鱼降钙素相比,阿仑膦酸钠作用更为明显。     

阿仑膦酸钠不同给药时间间隔对磨损颗粒诱导的假体周围骨溶解影响

目的 观察阿仑膦酸钠不同给药时间间隔对磨损颗粒诱导假体周围骨溶解的影响,为临床应用阿仑膦酸钠预防人工关节假体周围骨溶解提供理论依据。方法 雄性SD大鼠12只,经膝关节将钛合金假体及混合磨损颗粒植入胫骨近端（双侧）,随机分成实验Ⅰ组和实验Ⅱ组,每组6只,术后分别每日1次空腹阿仑膦酸钠（0．1m∥kg）灌胃和每周1次空腹阿仑膦酸钠（0．7mg／kg）灌胃,持续6周。术后12周处死取材,进行组织学观察及组织形态计量学测定。结果 实验Ⅰ组和实验Ⅱ组假体柄周围纤维界膜均较薄,细胞成分少,假体周围新生骨与假体间可见有直接接触,对假体支撑作用良好。假体周围界膜厚度及面积的形态计量学检测发现,两组间差异无显著性。结论阿仑膦酸钠预防磨损颗粒诱导的假体周围骨溶解时,每周给药1次与每日给药1次可产生同样的效果。     

阿伦膦酸钠防治人工关节松动的实验研究

目的：评价二膦酸盐阿伦膦酸钠在防治人工关节松动中的作用。方法：36只SD大鼠右膝置入自制人工关节假体,建立人工关节松动的动物模型,分成3组：阴性对照组,阳性对照组和实验组。阴性对照组关节腔内注射磷酸缓冲液与鼠血清混合液,阳性对照组关节腔内注射10^10/ml关节磨屑（超高分子聚乙烯颗粒）,实验组关节腔内注射10^10/ml关节磨屑同时用阿伦膦酸钠灌胃（每日1mg/kg）。术后12周,处死各组动物行组织切片对比观察假体周围骨溶解情况。体外分离培养人外周血单个核细胞并分成5组,A组为单核细胞组,B组为单核细胞和关节磨屑混合培养组,C组为单核细胞和关节磨屑混合培养加入10^-4mol/L阿伦膦酸钠,D组单核细胞和关节磨屑混合培养加入10^-5mol/L阿伦膦酸钠,E组为单核细胞和关节磨屑混合培养加入10^-6mol/L阿伦膦酸钠,检测各组单个核细胞分泌溶骨因子的情况。结果：关节磨屑可引起假体周围骨溶解,刺激单个核细胞分泌溶骨因子,阿伦膦酸钠可阻止这种作用。结论：阿伦膦酸钠可有效防止关节磨屑诱导的人工关节松动,有望用于临床。     

阿仑膦酸钠局部释放对假体周围骨溶解的抑制作用

目的 通过阿仑膦酸钠(ALN)复合羟基磷灰石(HA)涂层假体,检测局部释放的ALN对骨溶解的抑制作用. 方法 选择18只雌性新西兰大白兔,随机均分为实验组、阳性对照组和空白对照组,三组均于左侧胫骨平台处向胫骨髓腔竖直植入HA涂层假体.在植入前,实验组于HA涂层表面复合ALN 5 mg,且实验组和阳性对照组涂层表面均匀涂抹25μg超高相对分子质量聚乙烯颗粒,空白对照组不做处理.术后12周取左侧胫骨行骨组织形态学、生物力学以及影像学测馈,检测ALN体外释放周期,并评估抗骨溶解效果. 结果 与对照组相比,实验组的骨皮质厚度(+9.26%)、假体生物力学固定强度(极限抗剪强度:+36.42%、表观抗剪刚度:+37.79%、总能量吸收值:+30.00%)、骨-假体接触率(+44.40%)、假体周围骨体积分数(+16.07%)、骨矿化水平(钙盐沉积岛平均而积:+598.86%、钙盐沉积岛面积分数:+650.11%)和假体周围骨密度(+62.05%)均明显增高,差异有统计学意义(P<0.05);反映成骨细胞活性的各项参数(类骨质表面:+33.53%、类骨质厚度:+49.60%、骨形成速率:+91.62%、松质骨骨矿沉积率:+48.04%、皮质骨骨矿沉积率:+60.42%)也有不同程度的增高,差异有统计学意义(P<0.05). 结论 非多孔HA涂层假体复合ALN的局部释放可以明显抑制超高相对分子质量聚乙烯颗粒诱导的假体周围骨溶解,ALN在预防磨屑诱导的假体周围骨溶解过程中能够增强成骨细胞活性.     

骨水泥型Ⅰ期全髋关节置换术后假体周围骨质丢失的早期研究

[目的]研究人工全髋关节置换术(THR)后假体周围的骨质丢失及假体松动的防治方法。[结果]89例骨水泥型Ⅰ期全髋关节置换的患者,分成2组,观察组47例,术后每日服用阿仑膦酸钠10 mg+钙剂600 mg;对照组42例,术后每天服用600 mg钙剂。随访12个月,测定假体周围骨矿密度及骨代谢生化指标。[结果]假体周围相同区域BMD降低不明显或升高。在股骨近端(prRO I),对照组的BMD平均降低(21.2±5.2)%,而观察组平均升高(4.2±2.6)%(P<0.05)。在随访期末两组间全假体周围(totRO I)平均BMD对照组下降了(12.1±6.2)%,而观察组升高了(2.6±1.4)%,差别有统计学意义(P<0.05)。观察组BGP明显升高(P<0.05),而对照组ACP升高(P<0.05)。[结论]阿伦膦酸钠可明显降低骨水泥型Ⅰ期全髋置换术后骨质丢失,改善骨骼对假体的支撑作用,可能会预防或延缓假体松动。     

阿仑膦酸钠对人工关节假体周围骨长入的影响

目的观察阿仑膦酸钠对人工关节假体周围骨长入的影响。方法SD雄性大鼠16只,双侧胫骨上端经膝关节植入定制钛合金假体,随机分成对照组和实验组,对照组术后每日空腹生理盐水灌胃;实验组术后每日空腹阿仑膦酸钠灌胃,剂量0.1 mg/(kg.d),持续6周。术后12周处死取材,进行组织学观察及组织形态计量学测定。结果组织学观察发现,对照组假体周围由新生骨、类骨质和纤维界膜构成。纤维界膜较厚,与新生骨或类骨质间界限清晰。实验组假体周围纤维界膜薄且稀少,新生骨与假体界面多为直接接触,有些部位新生骨与假体界面完全整合。组织形态计量学测定发现,对照组假体周围界膜的厚度和面积均明显大于实验组,差异有显著性(P<0.05)。结论阿仑膦酸钠经胃肠给药可能对钛合金人工关节假体周围骨长入有一定的促进作用。     

阿仑膦酸钠/磷酸钙骨水泥释放体系结构及体外释放规律的研究

目的 制备不同浓度的阿仑膦酸钠/磷酸钙骨水泥释放体系,观察阿仑膦酸钠对磷酸钙骨水泥结构的影响及复合释放体系体外释放的规律.方法 分别制备1wt％、3wt％和5wt％的载阿仑膦酸钠磷酸钙骨水泥释放体系,分别采用傅氏转换红外线光谱分析仪、扫描电子显微镜和高效液相色谱仪研究载阿仑膦酸钠磷酸钙骨水泥的结构和药物体外释放规律.结果 阿仑膦酸钠的载入没有改变磷酸钙骨水泥相成分的官能团;扫描电镜下各实验组微观结构相似,均呈珊瑚样状结晶体相互交织成网状结构;各组药物在同一时间点释放量(％)的差异无统计学意义(P＞0.05),各组药物的释放均分为48 h前的突释阶段和48 h后的缓释阶段,符合Higuchi机制扩散释放模型.结论 阿仑膦酸钠的载入对磷酸钙骨水泥的晶体结构基本没有影响,且在磷酸钙骨水泥释放体系中能够持续、稳定的释放.     

阿仑膦酸钠预防非骨水泥型假体周围早期骨丢失的临床研究

目的 探讨阿仑膦酸盐对非骨水泥型人工假体周围早期骨量的影响.方法 50例患者随机分为对照组和治疗组,术后1周对照组予以口服钙尔奇D1片,治疗组予以固邦10mg＋钙尔奇D片.连续服用3周.休息2周.5周为1疗程,连续5个疗程.分别于术后7天、3个月、6个月行假体周围骨密度（DEXA）检测.结果 50例病例中,45例获得完整随访.术后3个月、6个月假体周围骨量（ROI1区和ROI7区）对照组与治疗组相比有显著性差异（P＜0.01）.结论 阿仑膦酸钠能有效预防假体周围早期骨量减少.     

不同剂量阿仑膦酸钠对磨损颗粒诱导假体周围骨溶解的影响

目的观察不同剂量阿仑膦酸钠对磨损颗粒诱导假体周围骨溶解的影响，确定其合适剂量.方法雄性SD大鼠24只，经膝关节将钛合金假体及混合磨损颗粒植入胫骨近端（双侧），随机分为对照组和实验Ⅰ、Ⅱ、Ⅲ组，每组6只，术后对照组每日空腹生理盐水2ml灌胃；实验Ⅰ、Ⅱ、Ⅲ组每日空腹阿仑膦酸钠灌胃，剂量分别为0．01、0．1、1mg／（kg·d），持续6周.术后12周处死取材，进行组织学观察及组织形态计量学测定.结果对照组和实验Ⅰ组假体柄周围纤维界膜厚，细胞成分多，与纤维界膜连接处新生骨边缘呈虫蚀状，新生骨对假体的支撑作用较差；实验Ⅱ、Ⅲ组假体柄周围纤维界膜较薄，新生骨与假体间可见有直接接触，对假体有良好的支撑作用.假体周围界膜厚度及面积的形态计量学检测并经统计学分析显示：对照组与实验Ⅰ组、实验Ⅱ与Ⅲ组间差异无显著性（P〉0．05），对照组和实验Ⅰ组分别与实验Ⅱ组和实验Ⅲ组间差异有显著性（P〈0．05）.结论以阿仑膦酸钠预防磨损颗粒诱导的假体周围骨溶解时，最适合剂量为0．1mg／（kg·d）.     

阿仑膦酸钠对骨质疏松性大鼠钛合金假体骨整合影响的实验研究

[目的]观察阿仑磷酸钠对骨质疏松大鼠假体骨整合的影响。[方法]SD雌性大鼠39只,双侧胫骨结节处垂直骨面置入定制钛合金假体,随机分为正常组、对照组、治疗组(每组13只),正常组不做任何处理;对照组和治疗组8周后行双侧切除卵巢建立骨质疏松模型。骨质疏松模型建成后,对照组术后每周空腹生理盐水灌胃;治疗组术后每周空腹阿仑膦酸钠灌胃,剂量1 mg/(kg/周),持续8周。灌胃结束后处死取材,进行组织学观察及组织形态计量学测定。[结果]组织学观察发现,正常组假体周围纤维界膜薄且稀少,新生骨与假体界面为直接接触,大部位新生骨与假体界面完全整合。对照组假体周围由新生骨、类骨质和纤维界膜构成。纤维界膜较厚,与新生骨或类骨质间界限清晰。治疗组假体周围纤维界膜薄且稀少,新生骨与假体界面多为直接接触,有些部位新生骨与假体界面完全整合。组织形态计量学测定发现,治疗组假体周围界膜的厚度和面积均明显大于对照组,差异有统计学意义(P<0.05)。[结论]阿仑膦酸钠经胃肠给药对骨质疏松大鼠假体骨整合有一定的促进作用。     

The effects of local and systemic alendronate delivery on wear debris‐induced osteolysis in vivo

We investigated the effects of locally and systemically administered alendronate on wear debris‐induced osteolysis in vivo. Endotoxin‐free titanium particles were injected into rabbit femurs, prior to insertion of a nonweight‐bearing polymethylmethacrylate plug into the distal femur canal. Then the particles were repeatedly injected into the knee 2, 4, and 6 weeks after the implantation. Alendronate was incorporated at three different concentrations (0.1, 0.5, and 1.0 wt %) into bone cement for local delivery. For systemic delivery, alendronate was subcutaneously injected (1.0 mg/kg/week) 1 week after the implantation and then once a week until sacrifice. Eight weeks postoperatively, there was significant evidence of osteolysis surrounding the plug in the control group compared with markedly blocked osteolysis in the 0.5 wt % and the 1.0 wt % groups, and the systemic group. There was a concentration‐dependent effect of alendronate‐loaded bone cement on the improvement of peri‐prosthetic bone stock. Notably, no significant differences were found between the 0.5 wt % and the systemic group in peri‐prosthetic bone stock and implant fixation. Collectively, although the biological efficacy after the systemic delivery of alendronate was slightly higher than that in the local treatment groups, alendronate‐loaded bone cement may be therapeutically effective in inhibiting titanium particle‐induced osteolysis in vivo. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:893–899, 2010     

Inhibition of particulate debris-induced osteolysis by alendronate in a rat model.

A rat model was used to study the efficacy of alendronate therapy in inhibition of particle-induced periprosthetic osteolysis. A prosthesis was simulated by inserting a cylindrical polymethylmethacrylate plug into the distal femur of 24 rats allowing the plug to communicate with the joint space. Intra-articular injections of irregularly-shaped ultra-high molecular weight polyethylene particles of 20-200 pm in diameter were administered at 2-week intervals. The rats were randomized into two groups (n=12 each). Group A rats received twice weekly subcutaneous injections of alendronate sodium while group B rats received injections of saline vehicle only. At 10 weeks all rats were sacrificed. The distal femurs were harvested and axial sections were prepared for histologic analysis. Each section was graded on a scale of 1-4, quantifying the degree of osteolysis surrounding the polymethylmethacrylate plug. Microscopic examination showed a significant (P<.0001) difference in the amount of periprosthetic bone. Femurs from group A treated with alendronate demonstrated mostly normal or near-normal periprosthetic trabeculations, whereas femurs from group B treated with saline showed extensive bone resorption. There was no qualitative difference in the inflammatory cellular response between the groups. This study established the ability of alendronate to inhibit the osteoclastic-mediated osteolysis around joint implants.     

阿仑膦酸钠对假体周围骨溶解中OPG及RANKL的影响

目的 探讨阿仑膦酸钠对聚乙烯颗粒诱导假体周围骨溶解中OPG及RANKL影响.方法 将钛金属棒植入新西兰大白兔左侧股骨内,每2周向左膝关节内注射聚乙烯颗粒,使用随机数字表随机分成实验组和对照组,各6只.实验组给予阿仑膦酸钠灌胃,而对照组给予等量的0.9％的氯化钠溶液灌胃.12周后处死动物,取出假体周围界膜组织,用ELIS...     

大颗粒聚乙烯对人工关节假体周围组织影响的实验研究

目的　制作松动人工关节的动物模型 ,了解大颗粒聚乙烯对实验动物人工关节假体周围骨组织的影响 ,并初步探讨其作用机制。　方法　选用健康新西兰白兔 2 0只 ,雌雄各半 ,体重 2 .3～ 2 .7kg。从两侧膝关节向股骨置入钴 -铬 -钼棒 ,分别于术后 2、4、6、8及 10周向一侧膝关节腔内注射聚乙烯微粒 (直径 10 0 μm)悬液 1.5 ml(实验侧 ) ,向另一侧膝关节腔内注射生理盐水 1.5 ml(对照侧 )。术后第 10周摄双下肢 X线片 ,了解假体周围是否有骨溶解和假体松动。术后第 12周处死动物。取 13只兔检查聚乙烯颗粒在关节囊分布情况 ,假体有否松动 ,周围有无新骨及界膜形成 ;取5只兔双侧股骨、膝关节囊作组织学检查 (实验过程中有 2只动物死亡 )。　结果　 1肉眼观察 :实验侧有 4侧金属假体被新生骨组织覆盖 ,9侧被纤维膜覆盖 ;对照侧有 11侧金属假体被新生骨组织覆盖 ,2侧被纤维膜覆盖 ,差异有统计学意义(P<0 .0 5 )。2 X线片观察 :假体位于股骨髓腔远端 ,其周围未见明显新生骨组织和骨溶解征像。3组织学观察 :实验侧关节囊见大量异物颗粒被成纤维细胞和多核巨细胞包绕 ,假体近端髓腔周围见成纤维细胞和纤维组织或新生骨组织形成 ,未见异物颗粒和多核巨细胞 ,靠近关节面部分见异物颗粒被成纤维细胞和多核巨细胞包绕     

Alendronate enhances antibiotic-impregnated bone grafts in the treatment of osteomyelitis

Bisphosphonates are systemic drugs. There is limited knowledge about their effects when applied locally and in osteomyelitis treatment. A prospective longitudinal randomised controlled study was designed in rat tibia to test the efficacy of local or systemically administered bisphosphonates for controlling the osteolytic reactions and possible effects on local infection control. Tibial osteomyelitis was induced in 72 Wistar albino rats with Staphylococcus aureus ATCC 25923 strain. Débridement was performed on all rats in all groups. No other treatment was given to the control group. Treatment groups received "plain bone grafts", "vancomycin-loaded bone grafts", "vancomycin-loaded bone grafts+systemic alendronate", "alendronate-impregnated bone grafts" and "vancomycin+alendronate-impregnated grafts". Study results were evaluated by swab cultures, radiology, quantitative computed tomography, dual-energy X-ray absorptiometry (DEXA) and histopathology. S. aureus was eradicated in groups II and IV by the sixth week. Diaphyseal widening, bone deformation, diaphyseal widening and osteolysis scores were significantly lower (p < 0.05), and bone mineral content, density measurements and DEXA scores were significantly higher (p = 0.001) with alendronate administration. Histology revealed marked osteoblastic activity. Local alendronate interfered with local infection control. Even though local alendronate at the given dose has stronger effects, the possible effects on the local inflammatory process needs to be clarified.     

Effects of alendronate on particle-induced osteolysis in a rat model

BACKGROUND: Particle-induced osteolysis is currently a major problem affecting the long-term survivorship of total joint replacements. Alendronate is a third-generation bisphosphonate that blocks osteoclastic bone resorption. The objective of this study was to determine whether alendronate could prevent particle-induced osteolysis or restore (reverse) bone loss in established osteolysis. METHODS: A rat model of particle-induced osteolysis was used. A specially designed polyethylene implant was placed in the proximal part of the right tibia of seventy-two animals. Following four weeks of healing, the animals were randomized into control groups, a prevention group, or a treatment group. In the prevention group, animals received intra-articular injections of high-density polyethylene particles (mean size, 2 m; all <10 m) at four, six, and eight weeks postoperatively. Alendronate (0.01 mg/kg/day) was administered concomitantly through an implantable pump from the fourth week through the tenth week. In the treatment group, animals were also exposed to polyethylene particles at four, six, and eight weeks, to establish bone loss, but they received alendronate subsequently, from the tenth week through the sixteenth week, to treat the bone loss. Positive (particle-only) and negative (saline-solution-only) control groups were assessed as well. Tissues were harvested at ten weeks in the prevention group and at sixteen weeks in the treatment group. Histological analyses and histomorphometric determinations of the periprosthetic bone volume were carried out. RESULTS: Histological examination showed a rim of new bone (neocortex) around the implant in the untreated and saline-solution-treated control animals (no polyethylene particles). Treatment with saline solution (no polyethylene particles) did not affect periprosthetic bone. Animals exposed to polyethylene particles had bone loss. In those that received alendronate, the bone loss was either prevented or reversed, and the quantity of neocortical and trabecular bone was increased compared with that of the controls. Alendronate effectively preserved periprosthetic bone in both the prevention and treatment groups. In the prevention arm, the mean periprosthetic bone volume of the neocortex and the surrounding trabecular bone, as determined with histomorphometry, was 21.5% +/- 6.5% in the saline-solution-treated controls (no particles), 13.1% +/- 5.9% in the particle-treated animals, and 32.6% +/- 6.4% in the alendronate-treated animals (p < 0.001). In the treatment arm, the mean periprosthetic bone volume was 27.2% +/- 5.6% in the saline-solution-treated controls, 17.7% +/- 6.2% in the particle-treated animals, and 30.2% +/- 5.9% in the alendronate-treated animals (p = 0.002). CONCLUSIONS: In our model, the intra-articular injection of polyethylene particles caused substantial bone loss around a loaded implant. Alendronate effectively prevented and treated the particle-induced periprosthetic bone loss.     

Effect of local delivery of alendronate on bone formation in bioactive glass grafting in rats.

OBJECTIVE: The aim of this study was to investigate whether local delivery of alendronate could improve bone formation after bioactive glass grafting in rat mandible. STUDY DESIGN: Twenty-six male Sprague-Dawley rats were divided into control and experimental groups (13 rats/group). A surgical defect was created on the angle of mandible of each animal. In the experimental group, a bioactive glass soaked with the alendronate solution was placed in the bone defect, and in the control group the bioactive glass soaked with saline was used. All animals were killed after 4 weeks. The number of osteoclasts and the amount of new bone formation were evaluated and compared. RESULTS: Four weeks after surgery, the experimental group had significantly more bone formation than the control groups (P < .05). However, no statistically significant difference was found between the groups when the numbers of osteoclasts were compared. CONCLUSION: Histologic results showed that a single dose of local delivery of alendronate improves bone formation. However, further studies are required to elucidate the effect of local delivery of alendronate on bone formation in humans.     

Local administration of alendronate reduced peri‐tunnel bone loss and promoted graft‐bone tunnel healing with minimal systemic effect on bone in contralateral knee

Continued systemic administration of alendronate was reported to reduce peri‐tunnel bone resorption and promoted graft‐bone tunnel healing at the early stage post‐anterior cruciate ligament (ACL) reconstruction. However, systemic increase in bone mineral density (BMD) in the contralateral intact knee was observed. We tested if single local administration of alendronate into the bone tunnel during ACL reconstruction could achieve similar benefits yet without the systemic effect on bone. Seventy‐two rats with unilateral ACL reconstruction were divided into three groups: saline, low‐dose (6 μg/kg) and mid‐dose (60 μg/kg) alendronate. For local administration, alendronate was applied to the bone tunnels for 2 min before graft insertion and repair. At weeks 2 and 6, the reconstructed complex was harvested for high‐resolution computed tomography (vivaCT) imaging followed by biomechanical test or histology. Our results showed that local administration of low‐dose alendronate showed comparable benefits on the reduction of peri‐tunnel bone loss, enhancement of bone tunnel mineralization, tunnel graft integrity, graft osteointegration and mechanical strength of the reconstructed complex at early stage post‐reconstruction, yet with minimal systemic effect on mineralized tissue at the contralateral intact knee. A single local administration of alendronate at the low‐dose therefore might be used to promote early tunnel graft healing post‐reconstruction. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1897–1906, 2013