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

 目的 研究骨质疏松骨骼局部注射辛伐他汀刺激成骨的效果, 探索疏松骨骼局部给药预 防脆性骨折的治疗方法。 方法36 只3 月龄雌性SD 大鼠双侧卵巢切除后加低钙饮食3个月, 制备大鼠 骨质疏松模型。实验大鼠随机分为3 组, 每组12 只, 分别在实验大鼠的左侧股骨髓腔内单次注射辛伐 他汀溶液5 mg、10 mg, 对照组单纯注射空白载体。分别在术后1 个月及术后5 个月每组随机处死半数 大鼠(n=6)并取材。双能X 线骨密度仪测定骨密度、Micro-CT扫描并定量分析骨组织形态改变、骨生物 力学测试研究骨骼力学性能的变化。 结果 辛伐他汀局部注射后1 个月和5 个月, 辛伐他汀注射组的 骨密度、骨微结构参数如骨皮质厚度、骨小梁密度及连接率明显优于对照组, 股骨髁及股骨颈的力学性 能明显高于对照组。单次注射辛伐他汀的局部骨强化效果至少持续5 个月, 对照组骨量则持续丢失, 力 学性能持续降低。 结论 疏松骨骼单次注射小剂量辛伐他汀可强效而持久地促进皮质骨形成及骨小梁 改建, 改善骨骼微结构, 增加骨密度及骨强度, 可作为强化局部、防治骨质疏松骨折的新选择。     

骨质疏松大鼠尾椎局部单次注射辛伐他汀强化骨骼的实验研究

目的 研究骨质疏松大鼠尾椎局部注射辛伐他汀刺激成骨的效果，探索疏松椎体局部给药，重 点强化，预防脆性骨折的治疗方法。方法 36只3月龄雌性SD大鼠双侧卵巢切除后加低钙饮食3 个月，制备大鼠骨质疏松模型。实验大鼠随机分为3组，每组12只，分别在实验大鼠的第5、6、7尾椎 内（C5-C7)单次注射空白载体、辛伐他汀溶液1mg、2mg。分别在术后12天及24天每组随机处死半数大鼠（n=6 )并取材。Micro-CT扫描并定量分析骨组织形态改变、骨生物力学测试研究骨骼力学性能的变化。结果 辛伐他汀局部注射后仅12天辛伐他汀注射组骨微结构参数如骨皮质厚度、骨小梁 密度及连接率明显优于对照组，椎体力学性能明显高于对照组，术后24天效果依然明显。结论 骨质疏松大鼠尾椎单次注射小剂量辛伐他汀（1mg与2 mg)可快速、强效地促进皮质骨形成及骨小梁改 建，改善骨骼微结构，提高骨强度，可作为强化局部、防治椎体骨质疏松骨折的新选择。     

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

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%(P0.01);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。     

辛伐他汀对绝经伴血脂代谢异常女性跟骨骨密度的影响

目的 研究辛伐他汀对绝经后伴血脂代谢异常女性跟骨骨密度的影响。方法 分析885名绝经后口服辛伐他汀治疗血脂代谢异常（TC>5.18mmol/L 或 LDL-C> 3.37mmol/L）女性的跟骨骨密度,并依据T值分为骨质正常、骨量减少、骨质疏松。结果 治疗前跟骨骨密度为305.3± 59.2 mg/cm2,骨质正常、骨量减少、骨质疏松的人数分别为115、446、324,口服辛伐他汀（20mg/d）治疗3月后骨密度为309.7±56.3 mg/cm2,骨质正常、骨量减少、骨质疏松的人数为117、459、319,12月后跟骨骨密度为312.5±60.9 mg/cm2,骨质正常、骨量减少、骨质疏松的人数为122、460、303。结论 绝经后伴血脂代谢异常女性应用辛伐他汀（20mg/d）治疗12个月后跟骨骨密度增高,但对骨质疏松患病风险无影响。     

PMMA提高椎体钉固定强度的体外实验研究

[目的]探讨骨水泥(PMMA)强化后椎体钉穿透单侧椎体固定的可行性。[方法]选用新鲜成人尸体标本32个,按骨密度分为骨质正常组和骨质疏松组分别进行实验。实验组为骨水泥(PMMA)强化后椎体钉穿单侧椎体皮质固定;对照组为无骨水泥强化,椎体钉穿透双侧椎体皮质固定。应用螺钉拔出实验,记录螺钉最大拔出力。[结果]在骨质正常组中,PMMA组和对照组拉出力分别为1758.42±32.63N和843.25±65.35N,增加109%±33%。在骨质疏松组中,PMMA组和对照组拉出力分别为811.19±188.58N和374.21±77.66N,增加122%±56%。差异有显著性P<0.01。[结论]应用PMMA固化椎体钉,减少手术并发症是可行的。     

经皮注射外源性BMP和DCN治疗骨不连的实验研究

目的 经皮注射外源性骨形态发生蛋白(BMP)和核心蛋白多糖(DCN),观察单独应用和联合应用两种因子治疗骨不连的效果.方法 选10只新西兰大白兔,制作骨不连动物模型,将10只兔的20条桡骨随机分成4组,具体分组情况如下:1)BMP-2组;2)BMP-2+DCN组;3)DCN组;4)空白组.通过影像学、生物力学及组织学检测比较骨不连接区的成骨效果.结果 X线检查骨不连区有骨吸收、断端硬化、髓腔封闭及少量不规则骨痂.外源性注射成骨因子4周后,镜下观察BMP-2+DCN组的骨不连接区组织成骨较其他3组明显.影像学观察注射BMP-2组和BMP-2+DCN组肢体骨折区成骨量明显增多,DCN组和空白组则较少.生物力学检测,空白组与DCN组的压缩刚度及最大负荷无显著差异,但均低于BMP-2组与BMP-2+DCN组;BMP-2+DCN组的刚度与最大负荷均明显优于其他3组(P＜0.05).结论 BMP-2复合纤维蛋白胶具有较好的骨诱导作用,可作为BMP-2理想的载体之一.骨不连接区联合应用BMP和DCN局部注射治疗较单独应用BMP的效果明显,能促进骨不连接区陈旧性组织成骨,单独使用DCN效果不明显.     

咖啡酸苯乙酯对雌性骨质疏松小鼠的实验研究

：目的采用骨生物力学、骨密度测定方法综合评价咖啡酸苯乙酯（Caffeic acid phenethyl ester CAPE)对去势小鼠骨质疏松影响的实验研究。方法取96只12周龄C57BL/6J雌性小鼠随机分16 组,（每组6只）。分别研究CAPE预防骨质疏松部分：1周假手术组（sham PBS组）、去势组（ovx PBS 组）;4 周、7 周的 sham PBS 组、ovx PBS 组、ovx CAPE(0. 5 mg/kg)组、cmc CAPE( 1 mg/kg)组。CAPE 治 疗骨质疏松部分:7周sham空白组和ovx空白组;造模7周后腹腔注射药物4周,包括11周sham PBS 组、ovx PBS 组、ovx CAPE (0.5 mg/kg)组、ovx CAPE(1 mg/kg)组。96 只小鼠均用 0.5% 的戊巴比妥 0.3 ml腹腔注射麻醉,5分钟后心脏采血,采用ELISA方法检测血清中雌激素水平。并对小鼠的双侧 肱骨、脊柱进行取材,取双侧肱骨进行三点弯曲实验,采用美国HOLOGIC骨密度仪分析小鼠脊柱骨 密度变化。结果（1)血清中雌激素水平检测发现,所有ovx组雌激素较sham组显著降低（P<0. 05) ? (2)骨密度：预防部分4周ovx组的脊柱骨密度值较sham组、OVx0. 5mg组及ovxlmg组明显降 低（P <0. 05)。（3)生物力学：预防部分1周、4周与治疗部分7周、11周ovx组较sham组、ovxO. 5mg 组、ovxlmg组的最大破坏应力指标显著降低（P<0.05)。结论咖啡酸苯乙酯能明显改善去势骨质 疏松小鼠骨的力学性能,增加去势骨质疏松小鼠的骨密度,抑制骨吸收,从而达到预防和治疗骨质疏 松的作用。     

骨密度对椎弓根螺钉系统内固定影响的临床研究

目的　研究骨密度对椎弓根内固定系统稳定性和临床疗效的影响。方法　回顾总结1 998年 6月到 2 0 0 1年 7月在我科实施腰椎椎间植骨、经椎弓根内固定资料完整的病例 65例 ,内容包括骨密度与椎弓根螺钉松动发生率、固定节段椎间隙高度、植骨融合率、主观满意率和客观疗效之间的关系。随访 1年～ 4年 2个月 ,平均 2年 6个月。结果　椎弓根螺钉松动患者的骨密度为 (0 796±0 1 67)g/cm2 ,无螺钉松动患者的骨密度为 (0 953± 0 1 85)g/cm2 ,两者之间差异有显著性 (P <0 0 1 ) ;两组患者之间的固定节段椎间隙高度 (P <0 0 5)、植骨融合率 (P <0 0 0 1 )、主现满意率 (P <0 0 1 )和客观疗效 (P <0 0 0 1 )之间也差异有显著性。结论　对于行腰椎椎间植骨、经椎弓根内固定的患者 ,骨密度是影响螺钉松动和临床疗效的重要因素。术前采用双能X线吸收骨密度仪 (DEXA)客观定量测定骨密度可为椎弓根螺钉系统的有效应用提供依据 ,术前骨密度低于 (0 796± 0 1 67)g/cm2 的患者螺钉松动的发生率显著增加     

CPC提高椎体钉固定强度的体外实验研究

目的探讨磷酸钙骨水泥(calcium phosphate cement,CPC)强化骨质疏松椎体钉后穿透单侧椎体皮质固定的可行性。方法选用新鲜成人尸体胸腰段骨质疏松标本24个,实验组为骨水泥(PMMA)和磷酸钙骨水泥灌注后椎体钉穿透单侧椎体皮质固定;对照组为无骨水泥强化,螺钉穿透双侧椎体皮质固定。应用螺钉拔出实验,记录螺钉最大拔出力并观察椎体破坏形态。结果三组拉出力值PMMA组(811.19±188.58N)、CPC组(541.89±101.44N)、对照组(374.21±77.66N)差异有显著性,P<0.01。分别增加122%±56%和50%±37%。对照组(8例)螺钉拔出破坏时均为螺钉抽出,在8例PMMA强化椎体中所有椎体均有不同程度骨折。而在8例CPC强化椎体中仅1例发生椎体骨折。结论应用CPC强化骨质疏松椎体钉简化手术步骤、增加手术安全性是可行的。     

嗅鞘细胞移植对坐骨神经切断后神经元的作用

目的研究嗅鞘细胞(olfactory ensheathing cells,OECs)移植对周围神经切断后脊髓及神经节内神经元的保护作用。方法SD大鼠55只,随机分为3个组:空白组5只、实验组及对照组各25只。行右侧坐骨神经切断,近端断端行肌肉内包埋,实验组和对照组分别予OECs及细胞培养液,空白组暴露神经后不作任何处理。术后1、2、3、7和14d,分批处死,行组织学观察及TUNEL标记观察神经元的改变。结果空白组术后14d均无阳性变化。大鼠坐骨神经切断后,脊髓及神经节内均有神经元凋亡发生。术后1、2、3d实验组细胞存活率分别为98.4%±6.5%、97.6%±6.5%及95.2%±6.7%,对照组分别为97.8%±6.7%、97.4%±6.4%及94.3%±6.8%,比较差异无统计学意义(P>0.05);7、14d实验组细胞存活率分别为92.4%±8.9%、87.7%±9.4%,较对照组87.4%±8.6%、83.4%±8.5%高,差异有统计学意义(P<0.05)。术后1、2d实验组及对照组脊髓前角运动神经元无细胞凋亡;3、7、14d实验组脊髓前角运动神经元凋亡指数分别为1.2±0.8、1.4±0.6及4.1±1.3,较对照组2.1±1.1、3.1±1.1、6.1±1.8低,差异有统计学意义(P<0.05)。术后1、2、3d神经节内细胞无凋亡;7d实验组神经节内的凋亡指数2.10±0.32,较对照组4.40±0.56低,差异有统计学意义(P<0.05);14d实验组神经节内的凋亡指数4.3±1.80与对照组6.70±2.50比较,差异无统计学意义(P>0.05)。结论周围神经损伤后脊髓及神经节内神经元有神经元凋亡发生,OECs移植对神经元凋亡有保护作用。     

Strontium ranelate treatment enhances hydroxyapatite‐coated titanium screws fixation in osteoporotic rats

Increased bone turnover with excessive bone resorption and decreased bone formation is known to impair implant fixation. Strontium ranelate is well known as an effective antiosteoporotic agent by its dual effect of antiresorbing and bone‐forming activity. This study was designed to evaluate the effect of systemic strontium ranelate (SR) treatment on fixation of hydroxyapatite (HA)‐coated titanium screws in ovariectomized (OVX) rats. Twelve weeks after being OVX (n = 30) or sham (n = 10) operated, 40 female Sprague–Dawley rats received unilateral implants in the proximal tibiae. The OVX rats were randomly divided into the following groups: OVX, OVX + SR_L (“_L” refers to low SR dose of 500 mg/kg/day), OVX + SR_H (“_H” refers to high SR dose of 1000 mg/kg/day).Twelve weeks after treatment, bone blocks with implants were evaluated with micro‐CT and biomechanical push‐out tests. Compared to OVX animals, SR treatment increased the bone volume ratio by 51.5% and 1.1‐fold, the percentage osteointegration by 1.0‐fold and 1.9‐fold in micro‐CT evaluation, and the maximal force by 1.9‐fold and 3.3‐fold in biomechanical push‐out test, for the low and high dose of SR, respectively. Significant correlation between micro‐CT and biomechanical properties demonstrated that trabecular parameters played an important role in predicting the biomechanical properties of implant fixation. Our findings suggest that SR treatment can dose‐dependently improve HA‐coated screw fixation in OVX rats and facilitate the stability of the implant in the osteoporotic bone. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:578–582, 2010     

Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats

Summary

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR

Introduction

This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.

Methods

Sixty female Sprague–Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX?+?Veh), ALN (OVX?+?ALN), SR (OVX?+?SR), and ZOL (OVX?+?ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.

Results

ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P?<?0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P?<?0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P?<?0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).

Conclusions

In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.     

Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats

The aim of this study was to evaluate the effects and explore the mechanism of a local injection of a single dose of simvastatin as a strategy to strengthen target bone. Simvastatin was injected into the femurs (5 or 10 mg) or caudal vertebrae (1 or 2 mg) of ovariectomized rats, with an equal volume of vehicle injected as a control. Bone mineral density (BMD), bone microstructure and strength were evaluated at 1 and 5 months post-injection for the femurs and at 12 days post-injection for the vertebrae. Bone mass, adipocyte numbers and Runx2 expression were also examined using histology and immunohistochemistry. Compared with controls, simvastatin significantly increased BMD, bone volume fraction (BV/TV), improved bone microstructural parameters and bone strength in the femurs at both time points (all P < 0.01). Simvastatin-treated femurs contained fewer adipocytes and a higher Runx2 expression. For the caudal vertebrae, simvastatin significantly improved BV/TV, bone microstructures, and bone strength (all P < 0.01) as compared with controls. In conclusion, local injection of a single dose of simvastatin induces early onset and long-lasting bone augmentation in osteoporotic bone, significantly improving BMD, and bone microstructure and biomechanical strength. Simvastatin induces Runx2 expression, which may function to induce osteogenesis and inhibit adipogenesis as an underlying mechanism to augment bone mass.     

Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats

Osseointegration is vital to avoid long‐time implants loosening after implantation surgery. This study investigated the effect of low‐magnitude high‐frequency (LMHF) loading via whole body vibration on bone‐implant osseointegration in osteoporotic rats, and a comparison was made between LMHF vibration and alendronate on their effects. Thirty rats were ovariectomized to induce osteoporosis, and then treated with LMHF vibration (VIB) or alendronate (ALN) or a control treatment (OVX). Another 10 rats underwent sham operation to establish Sham control group. Prior to treatment, hydroxyapatite (HA)‐coated titanium implants were inserted into proximal tibiae bilaterally. Both LMHF vibration and alendronate treatment lasted for 8 weeks. Histomorphometrical assess showed that both group VIB, ALN and Sham significantly increased bone‐to‐implant contact and peri‐implant bone fraction (p < 0.05) when compared with group OVX. Nevertheless the bone‐to‐implant contact and peri‐implant bone fraction of group VIB were inferior to group ALN and Sham (p < 0.05). Biomechanical tests also revealed similar results in maximum push out force and interfacial shear strength. Accordingly, it is concluded that LMHF loading via whole body vibration enhances bone‐to‐implant osseointegration in ovariectomized rats, but its effectiveness is weaker than alendronate. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:733–739, 2012     

Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits

One main problem associated with alveolar bone augmentation in implant dentistry is resorption of grafted bone, which may be further compromised by systemic skeletal disorders such as osteoporosis. Zoledronate acid (ZOL) is the most potent bisphosphonate to treat osteoporosis and therefore it is hypothesized to be able to invert the negative effect of osteoporosis on osseointegration and fixation of dental implants in autologous bone grafts. In this study, 56 rabbits received bilateral ovariectomy (OVX) (40 rabbits) or sham operation (16 rabbits). Three months later, 8 animals from each group were sacrificed for bone mineral density (BMD) examination. Then the remaining animals underwent bilateral autologous iliac bone grafting with simultaneous implantation of titanium implants in tibiae and were divided into 5 groups (n = 8): Sham, OVX, Loc-ZOL (local treatment), Sys-ZOL (systemic treatment) and Loc + Sys-ZOL (local plus systemic) group. At 3 months after implantation, all animals were sacrificed and specimens were harvested for examinations. Both BMD and histological examinations of femurs showed osteoporotic changes after ovariectomy, while systemic treatment with ZOL restored mineralized bone. Micro-CT examination demonstrated that OVX group showed significant decrease of mineralized bone and implant-bone contact when compared with sham control, whereas both systemic and local treatments of ZOL significantly increased mineralized bone and implant-bone contact in ovariectomized animals. However, the best effects were observed in Loc + Sys-ZOL group (combined use of ZOL) and most of bone indices were similar to (IBCR, p > 0.05) or higher than (BV/TV, Conn.D and Tb.N) (p < 0.01) those of the sham group, except Tb.Th, which was still significantly lower (p < 0.01), and Tb.Sp, which was further decreased (p < 0.01). The aforementioned effects were also confirmed by histomorphometric analysis of bone indices on implant-bone contact and mineralized bone. In addition, biomechanical testing further supported the beneficial effect of ZOL treatment and maximal removal torque of titanium implants was observed in Loc + Sys-ZOL group. In conclusion, our study suggests that both systemic and local treatments with ZOL can invert negative effect of osteoporosis and promote osseointegration and fixation of dental implants in autologous bone grafts under osteoporotic condition. Combined systemic and local use of ZOL exerts best effects when compared to their single use.     

Osseointegration of porous titanium and tantalum implants in ovariectomized rabbits: A biomechanical study

BACKGROUNDToday, biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty. Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant, and their ability to withstand functional loads.AIMTo compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits.METHODSThe study was performed in 50 female California rabbits divided into non-ovariectomized (non-OVX) and ovariectomized groups (OVX) at 6 mo of age. Rabbits were sacrificed 8 wk after the implantation of four biomaterials [TTM, CONCELOC, Zimmer Biomet''s Trabecular Metal (TANTALUM), and ATLANT] in a 5-mm diameter defect created in the left femur. A biomechanical evaluation of the femur was carried out by testing implant breakout force. The force was gradually increased until complete detachment of the implant from the bone occurred.RESULTSThe breakout force needed for implant detachment was significantly higher in the non-OVX group, compared with the OVX group for all implants (TANTALUM, 194.7 ± 6.1 N vs 181.3 ± 2.8 N; P = 0.005; CONCELOC, 190.8 ± 3.6 N vs 180.9 ± 6.6 N; P = 0.019; TTM, 186.3 ± 1.8 N vs 172.0 N ± 11.0 N; P = 0.043; and ATLANT, 104.9 ± 7.0 N vs 78.9 N ± 4.5 N; P = 0.001). In the OVX group, The breakout forces in TANTALUM, TTM, and CONCELOC did not differ significantly (P = 0.066). The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC, and by 2.2 compared with TTM (P = 0.001). In the non-OVX group, the breakout force for ATLANT was significantly different from all other implants, with a reduction in fixation strength by a factor of 1.9 (P = 0.001).CONCLUSIONTANTALUM, TTM, and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone. ATLANT had significantly decreased osseointegration (P = 0.001) in healthy and in osteoporotic bone.     

Osteogene Aktivität BMP-3-beschichteter Titanprüfkörper unterschiedlicher Oberflächenbeschaffenheit im orthotopen Lager des Riesenkaninchens

INTRODUCTION: The successful combination of osteoinductive factors with current materials used in both endoprosthetics and implantology improves bony ingrowth and long-term stability of the chosen implants. The aim of the present experimental animal study was to clarify in what way faster bony integration can be achieved through additional BMP-3-coating of titanium test implants of different surface textures (hydroxy-apatite-coated or corundum-blasted). METHODS: Thirty of 60 cylindrical titanium test implants with a hydroxy-apatite or corundum-blasted surface were coated with 230 microg porcine, high-purified BMP-3-precipitate per implant to check their osteoinductive potential in a bioassay. In each case a BMP-3-coated and an uncoated control-device were implanted with a gap formation of 1 mm into the femoral part of the patellofemoral joint of the right and left leg of 30 adult giant rabbits. Serial saw slices of all explanted specimens were prepared, and the osseous integration of the implant and time-dependent bone neoformation were analyzed microscopically and histomorphometrically 14, 35, and 56 days after implantation. RESULTS: Coating of TiAl4V6-test devices with BMP-3 led in both groups after gap implantation to an improved osseointegration, that was histomorphological and histomorphometrical verifiable. Statistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of new formed bone of the BMP-3-coated corundum-blasted or hydroxy-apatite-coated TiAl4V6 test devices compared to the non-coated controls of the same type (P < 0.01). Light microscopy demonstrated osseointegration without connective tissue membrane around the surface of the implants after 2, 5, and 8 weeks. Better osseointegration was achieved in the hydroxy-apatite-coated implants than in the corundum-blasted implants. CONCLUSIONS: Our results indicate that composite metal implants, as used in endoprosthetics and implantology, are suitable carriers for BMP-3 and improved fixation of the implants can be achieved.     

The bisphosphonate ibandronate improves implant integration in osteopenic ovariectomized rats

Osteoporosis is known to impair the process of implant osseointegration. Bisphosphonates are drugs that inhibit osteoclast-mediated bone resorption and normalize the high rate of bone turnover that characterizes this disease. Consequently, there is a rationale for using bisphosphonates to enhance the early stabilization of implants in subjects with low bone mass. In this study, 84 rats received titanium-only or hydroxyapatite (HA)-coated titanium femoral implants, 3 months after being ovariectomized (OVX) or sham operated. They were then treated for 4 weeks. The OVX rats were randomly assigned to daily subcutaneous injections of either saline or the bisphosphonate ibandronate (at a dose of 1 microg/kg or 25 microg/kg), while the sham-operated animals received saline throughout. The 1 microg/kg or 25 microg/kg ibandronate doses are considered translatable to doses used to treat osteoporosis and metastatic bone disease (MBD), respectively, in rats, and roughly reflect those used in humans. At the end of the treatment period, bone mineral density (BMD) at the lumbar spine increased in both of the ibandronate-treated groups when compared with the OVX control animals and to a level similar to that of the sham-operated control group. Osseointegration, determined by histomorphometric analysis and expressed as percentage of osseointegration implant surface (OIS), did not differ between groups for the titanium-only implants. For the HA-coated implants, however, OIS was 113.5% and 185% higher in the groups receiving 1 microg/kg or 25 microg/kg ibandronate, respectively, relative to the OVX controls. In turn, the OIS of the HA-coated implants was 56.5% lower in the OVX control group than in the sham control group. These findings clearly demonstrate that OVX-induced osteopenia impairs the osseointegration of HA-coated titanium implants and that ibandronate, administered at doses analogous to those used to clinically treat osteoporosis and MBD, counters this harmful effect. Ibandronate may, therefore, have a role in improving the osseointegration of implants in patients with osteoporosis and MBD.     

Intermittent administration of human parathyroid hormone (1–34) increases new bone formation on the interface of hydroxyapatitecoated titanium rods implanted into ovariectomized rat femora

Background  As hydroxyapatite (HA) has good osteoconductive properties, HA is used as coating material for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Parathyroid hormone (PTH) is known to have anabolic effects on bone formation. Intermittent administration of PTH increases both cancellous and cortical bone mass. The aim of this study was to confirm the effect of the fixation strength of HA-coated implants in the osteoporotic condition with a mechanical test and a bone histomorphometric method. Methods  Female Sprague-Dawley rats were used for this study. Four weeks after ovariectomy (OVX) or sham surgery, HA-coated titanium rods were inserted into the distal femoral canal (Sham+HA group and OVX+HA group). PTH was administered immediately after the implantation of the HAcoated rods (OVX+HA+P group). We measured the shear strength at the bone-implant interface by a push-out test and the newly formed bone volume on the implant (BV.Im) by bone histomorphometry at 2 and 4 weeks after implantation. Results  The bone-implant shear strength in the OVX+HA group was significantly lower than that in the Sham+HA group at 2 weeks after implantation of the rods. In the OVX+HA+P group, the strength was significantly higher than that in the other groups. Similarly, at 4 weeks, statistically significant differences were confirmed in the bone-implant shear strength among the Sham+HA group, the OVX+HA group, and the OVX+HA+P group. BV.Im in the OVX+HA group was significantly lower than that in the Sham+HA group at 2 weeks after implantation. BV.Im was significantly higher in the OVX+HA+P group than that in the OVX+HA group. However, there was no difference in BV.Im between the Sham+HA group and the OVX+HA+P group. At 4 weeks after implantation, BV.Im was significantly lower in the OVX+HA group than that in the other groups, but no difference was found between the Sham+HA group and the OVX+HA+P group. Conclusions  Intermittent administration of PTH has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition. This finding suggests that PTH administration is useful to improve the initial fixation of HA-coated implants even in osteoporotic patients.