周围神经系统对骨折愈合影响的实验研究

目的研究周围神经系统在骨折愈合早、中期所起的作用。方法将大鼠一侧下肢制成失神经胫骨骨折模型,对侧制成正常神经支配骨折模型。骨折后15d、30d处死大鼠,取双侧胫骨,拍X线片、测定生物力学强度,制备不脱钙切片,进行骨计量学观察。结果X线片显示失神经组骨痂形成量明显增多(P<0.01),但抗弯强度降低(P<0.05)。骨计量学显示,失神经组矿化骨小梁宽度明显减小(P<0.05),类骨质宽度增加,破骨细胞指数及骨吸收表面明显增大(P<0.05),成骨细胞指数及骨形成表面两组无差别。动态参数显示失神经组矿化沉积率明显变小(P<0.05),类骨质成熟时间延长(P<0.05)。结论周围神经在骨折愈合早、中期起重要的调节作用,完整神经支配是骨折愈合所必需的。     

神经切除对骨形态发生蛋白异位诱导成骨的影响

[目的]通过rhBMP-2异位诱导成骨模型，观察坐骨神经和股神经切除对骨再生的影响，探讨神经支配在骨再生中的作用以及失神经所致骨折骨痂增大的部分机制。[方法]1CR小鼠36只随机分为实验组和对照组。行右侧股后部肌袋模型，实验组行右侧坐骨神经和股神经切除后植入含0．125mgrhBMP-2胶原复合物。对照组仅进行神经暴露后植入等量rhBMP-2胶原复合物。于术后7、14、21d取材，行湿重测量、放射学、生化检测、组织学观察和形态计量分析以及破骨细胞TRAP染色。[结果]湿重检测显示实验组组织块湿重明显大于对照组。X线检测实验组成骨范围较对照组明显增大，成骨组织密度不及对照组。生化检测结果显示术后第7d实验组AKP含量明显高于对照组，术后第14d，实验组钙含量高于对照组，术后21d，实验组钙、磷含量均低于对照组。组织学观察显示实验组成骨范围大于对照组，成骨后期破骨细胞活跃，骨小梁稀疏。组织形态计量分析显示实验组术后21d破骨细胞相对数增多，骨小梁体积密度、平均宽度均低于对照组。TRAP染色显示实验组破骨细胞明显较对照组活跃。[结论]在外源性BMP-2异位诱导过程中，神经切除引起骨诱导早期成骨活动的增加，在成骨中后期失神经导致破骨细胞活动增强引起骨小梁的稀疏和骨密度的降低，提示神经支配可能通过直接或间接的方式影响骨再生活动。     

感觉/运动神经切断影响大鼠骨折愈合的实验研究

[目的]通过建立切断组成大鼠坐骨神经的不同成分、联合胫骨骨折的动物模型,来研究感觉/运动神经损伤对骨折愈合的影响,并进一步探讨周围神经系统对骨组织的生理作用。[方法]Wistar大鼠90只平均分为3组：对照组,运动神经（前根）切断组,感觉神经（后根）切断组,选择性切断一侧L4～6神经根。所有大鼠于神经根暴露侧/切断侧胫骨造成横行骨折,髓钉固定。30d后取大鼠双侧胫骨,测患侧胫骨近端骨密度、在影像学资料上测量患侧骨痂宽度及健侧胫骨相应位置的皮质宽度、取所有大鼠双侧胫骨行湿重称量、骨痂组织学切片观察、双侧胫骨行生物力学拉伸测试。所得结果均以患侧数据除以相应健侧数据得出一相对数,以相对数数据进行统计分析。[结果]患侧胫骨近端骨密度无显著差异（P〉0.05）;检测项目示神经切断组骨折处骨痂形成多,力学强度差,骨痂成熟度差（P〈0.05）,以感觉神经（后根）切断组尤甚（P〈0.05）[结论]感觉神经纤维对骨折愈合的影响较运动神经纤维显著;完整的神经支配是正常骨折愈合的必要条件。     

中枢神经损伤对大鼠股骨骨折愈合影响观察

摘要：[目的] 观察中枢神经损伤后大鼠股骨骨折愈合速度和骨痂量的变化，分析中枢神经损伤对大鼠股骨骨折愈合速度影响的机制。[方法] 54只雄性Wistar大鼠随机分成3组，（1）脑外伤合并股骨骨折组18只；（2）脊髓损伤合并股骨骨折18只；（3）单纯股骨骨折18只。术后7、14、28d分批处死动物，大体体积测量骨痂，X线片评分，并做HE染色比较。[结果] 脑外伤组，脊髓损伤组形成骨痂体积、X线片评分高于单纯股骨骨折组，差异有显著性（P〈0．05）。HE染色结果显示脑外伤组、脊髓损伤组骨折愈合速度较单纯骨折组加快。[结论] 中枢神经损伤后大鼠骨折愈合加速，骨痂量增多，中枢神经损伤后引起骨痂量和骨折愈合速度的改变，表明中枢神经损伤对骨折愈合有促进作用。     

不同神经损伤对骨折前期愈合影响的实验研究

目的：研究脊髓和周围神经损伤对骨折前期修复的影响。方法：将实验大鼠分成3组，一组为T10脊髓横断伴股骨骨折，另两组分别为周围神经切断伴股骨骨折组和单纯股骨骨折组。骨折后2周和4周摄股骨X线片，4周处死大鼠行骨痂细胞和组织学检查。结果：骨折后2周3组均未出现明显骨痂，术后4周测量x线片骨痂大小显示周围神经切断组骨痂最多，其次分别为对照组和脊髓损伤组。组织学显示周围神经切断组骨痂量多，并有明显的皮质骨桥接断端，但其中类骨质较多，骨钙的沉积相对较少，而且骨痂缺乏血管和正常的骨小梁结构，骨化重建不够理想；而脊髓损伤组骨痂则表现为欠成熟，细胞种类多，分布紊乱，少部分仍处于纤维修复阶段。对照组的组织学改变介于两者之间，但其骨小梁结构良好而且骨钙沉着明显。结论：不同类型神经损伤对骨折愈合前期有着不同的影响。失周围神经支配对骨折修复有一定的加速作用，而脊髓损伤则延缓了骨折前期愈合，其发生机理仍需进一步研究。     

高能震波对骨痂中骨形成蛋白表达的影响

目的 观察高能震波（ＨＥＳＷ）对骨痂中骨形成蛋白（ＢＭＰ）表达的影响，探讨其促进骨折愈合的机理。方法 手术造成家兔双侧胫骨中段标准骨折模型，对一侧胫骨骨折部施以ＨＥＳＷ，另一侧为对照组，术后每周进行Ｘ线及组织学检查，并取骨痂组织切片用ＢＭＰ抗体进行免疫组化染色（ＳＡＢＣ法（）。结果 实验组骨痂中ＢＭＰ表达强度在第２－４周时明在于对照组（Ｐ〈０．０１），且Ｘ线摄片及组织学观察均显示实验组骨折愈合时间     

骨折周围骨痂移植治疗骨不愈合的形态学观察

目的　观察骨不愈合采用骨折断端周围自体骨痂移植治疗的效果。方法　新西兰兔 42只 ,双侧桡骨中段模拟骨折 ,观察至明显骨痂生长随机分配实验Ⅰ组 36只 ,实验Ⅱ组 6只 ,随机选择一侧髂骨切取部分全层骨和双侧骨折处周围骨痂备用 ,并建立 1 0cm骨缺损的标准不愈合模型。实验Ⅰ组 ,左桡骨移植骨痂为A组 ,右桡骨移植髂骨为B组 ,术后分别于 2、 4、 6、9、 12、 15周各处死 6只兔并取标本作X线摄片和图像分析、标本大体观察 ,组织切片检查。实验Ⅱ组 ,左桡骨移植髂骨为C组 ,右桡骨空白对照为D组 ,术后定期X线摄片检查。结果　①术后 15周 ,A、B、C组全部完成骨不愈合的修复 ;②D组无一例骨不愈合完整修复 ;③A、B组修复骨不愈合的病理过程相仿 ,首先是桥梁骨痂和连接骨痂形成 ,而后是成熟骨板期 ,最后是塑形期 ,但修复进程在实验 9周存在明显差异 (P <0 0 5 ) ,A组优于B组。结论　骨折周围骨痂和髂骨都是较为理想的骨移植材料 ,在治疗骨不愈合过程中 ,骨痂移植在早期有加速骨缺损修复的趋势。     

戊酸雌二醇对去势大鼠骨折愈合影响的实验研究

目的 探讨戊酸雌二醇在骨质疏松性骨折愈合过程中的作用,为绝经后骨质疏松性骨折的治疗提供理论依据.方法 选用6月龄雌性Sprague-Dawley(SD)大鼠54只,实验分为SHAM组(假手术组)、OVX组(去势组)、补佳乐组.除SHAM组外,其余各组均切除双侧卵巢建立骨质疏松动物模型.去势后8周各组行右股骨骨折建立骨折模型,同时补佳乐组按0.104(mg·kg-1·d-1)灌胃.3组均在骨折后第2、4、6、8周处死大鼠后行放射学观察骨痂变化,骨痂HE染色及成骨细胞、破骨细胞计数.结果 ①放射学:OVX组骨痂密度影低,8周时OVX组骨折线仍然存在,SHAM组和补佳乐组骨折线模糊甚至消失.②骨痂组织学:OVX组骨小梁表面破骨细胞明显增多,成骨细胞也较多,呈骨高转换状态.8周时骨小梁变细、中断,软骨成分仍较多,软骨性骨痂向骨性骨痂转化缓慢;SHAM组和补佳乐组随骨折愈合骨小梁逐渐增加成熟,小梁骨粗大,排列紧密,骨小梁表面成骨细胞体积大,胞浆丰富,破骨细胞减少.③成骨、破骨细胞指数:2、4周OVX组破骨细胞指数大于补佳乐组和SHAM组.成骨细胞指数在3组间差异无显著性.结论 戊酸雌二醇对于促进绝经后骨质疏松性骨折早期愈合有效.     

骨折周围骨痂移植治疗骨不愈合的形态学观察

目的 观察骨不愈合采用骨折断端周围自体骨痂移植治疗的效果。方法 新西兰兔42只,双侧桡骨中段模拟骨折,考察至明显骨痂生长随机分配实验I组36只,实验Ⅱ组6只,随机选择一侧髂骨切取部分全层骨和双侧骨折处周围骨痂备用,并建立1．0cm骨缺损的标准不愈合模型。实验Ⅰ组,左桡骨移植骨痂为A组,右桡骨移植髂骨为B组,术后分别为2、4、6、9、12、15周各处死6只兔并取标本作X线摄片和图像分析、标本大体观察,组织切片检查。实验组Ⅱ组,左桡骨移植髂骨为C组,右桡骨空白对照为D组,术后定期X线摄片检查。结果 ①术后15周,A、B、C组全部完成骨不愈合的修复;②D组无一例骨不愈合完整修复;③A、B组修复骨不愈合的病理过程相仿,首先是桥梁骨痂和连续骨痂形成,而后是成熟骨板期,最后是塑形期,但修复进程在实验9周存在明显差异（P＜0．05）,A组优B组。结论 骨折周围骨痂和髂骨都是较为理想的骨移植材料,在治疗骨不愈合过程中,骨痂移植在早期有加速骨缺损修复的趋势。     

唑来膦酸联合胰岛素促进2型糖尿病并发雌激素缺乏大鼠骨折早期愈合

目的探讨唑来膦酸联合胰岛素对于2型糖尿病并发雌激素缺乏大鼠早期骨折愈合的影响。方法 32只雌性SD大鼠随机分为CF、DOF、DOFI和DOFIZ 4组。除CF组外,其余3组建立2型糖尿病并发雌激素缺乏动物模型,其中DOFI组和DOFIZ组分别给予单独胰岛素或联合唑来膦酸治疗,骨折后3周取材。通过对骨痂X线片、Micro-CT、番红O-固绿染色、TRAP阳性破骨细胞密度、OCN和Caspase-3的表达进行分析,评价单独应用胰岛素或联合唑来膦酸对其早期骨折愈合的影响。结果DOF组骨痂的骨折愈合X线评分、Tb.N、BV/TV、骨性骨痂面积比和OCN表达均显著低于CF组(P0.05),Th.Sp、TRAP阳性破骨细胞密度和Caspase-3表达均显著高于CF组(P0.05)。胰岛素干预后,DOFI组以上各受损指标中除了Th.Sp外均得到显著改善(P0.05)。联合唑来膦酸干预后,DOFIZ组骨痂面积、Tb.N、BV/TV和骨性骨痂面积比显著高于DOFI组(P0.05),Th.Sp和TRAP阳性破骨细胞密度显著低于DOFI组(P0.05)。结论胰岛素联合早期单剂量唑来膦酸干预可促进2型糖尿病并发雌激素缺乏大鼠骨折早期愈合。     

Traumatic late dissociation of the polyethylene articulating surface in a total knee arthroplasty--a case report

Clodronate was administered daily 28 days before and after an experimental tibial fracture in 35 male rats, and the effect on fracture healing and posttraumatic bone loss was studied. 5 groups were tested. The clodronate/clodronate group received clodronate in daily doses of 10 mg/ kg body weight for 28 days before being subjected to a standardized fracture of the right tibia, and during the fracture healing period of 28 days. The clodronate/ saline group received clodronate before fracture and saline during the healing period. The saline/ clodronate group received saline before and clodronate after fracture. The saline/saline group received saline only, while the control group served as unfractured, untreated controls. After 28 days of fracture healing, the tibias were evaluated with dual energy x-ray absorptiometry, and tested mechanically in a 3-point ventral bending test. Bone mineral content and bone mineral density were approximately 30% higher in the groups receiving clodronate during the experiment, compared to the untreated groups. The weight and cross-sectional area of the fracture callus were equal in all groups. Whether clodronate was administered before the fracture, after the fracture or both, did not affect the bone mineral. Ultimate bending moment, energy absorption, stiffness and deflection were not significantly different between the groups. Our findings suggest that clodronate increases bone mineral both when given before and after a tibial shaft fracture, without affecting fracture healing at 28 days.     

Standardization of tibial fractures in the rat.

The influence of the fracture level on the biomechanical properties of healing rat tibial fractures has not been investigated so far, despite the widespread use of rats in fracture healing studies. Fractures were produced in four different zones in the right rat tibia and immobilized with a K-wire. A fifth group of rats was not fractured. After 40 days of healing the fractures and the non-fractured bones were tested in three-point bending. A distinct correlation was found between fracture level and mechanical parameters: maximum load, maximum stiffness, and maximum stress decreased the more distal the fracture was located. In the non-fractured bones, maximum load and maximum stress were constant in all four zones tested, whereas energy absorption increased in the distal part of the tibia. No influence of the healing fracture was found on the contralateral, non-fractured tibia, compared with the animals left undisturbed, and the mechanical properties of the right and the left tibia were found to be symmetrical in terms of mean values. Four different methods of determining the area moment of inertia were investigated, and the simple method of approximating the cross section to an elliptical annulus was found to correlate well with the area moment of inertia, determined from computer tracings of bone slices prepared from the test specimens after the bending test. The computer tracings were corrected for the compression of the specimens caused by the mechanical test.     

闭合性胫骨骨折兔模型的建立与评估

目的：探讨改良设计的三点弯曲骨折装置用于建立闭合性胫骨骨折兔模型的效果。方法：选取6月龄SPF级健康雄性新西兰兔40只,体质量2.5~3.0 kg,制备闭合性胫骨骨折兔模型,并于术后6周进行模型验证。预造模组5只,造模前未行临时外固定,后以改良设计三点弯曲骨折装置进行骨折;正式造模组35只,造模前行穿针及夹板外固定,后以改良设计三点弯曲骨折装置进行骨折。于术后2 h及4、6周行影像学、组织病理学评估骨折模型情况及愈合进程。结果：造模后2 h,预造模组呈不同程度的斜行骨折且断端明显移位;正式造模组除1只粉碎性骨折,2只弯曲蝶形骨折,2只未显示明显骨折线外,其余均呈简单横行及斜行骨折,断端无明显移位。根据判定标准,模型成功率为85.71%。造模后4周,实验兔固定针及夹板位置良好,骨折对位对线良好,骨折线已模糊不清,骨折端周围可见大量连续骨痂生长,骨痂密度较高。造模后6周,镜下见骨折处大量粗大的新生骨小梁,边缘成骨细胞附着并见少量巨噬细胞,膜内成骨区域为编织骨阶段,骨折处髓腔已部分再通,骨痂处于吸收塑性阶段,可见大量破骨细胞。X线显示骨折线几乎消失,髓腔部分已通,周围见外骨痂减少,骨痂处于塑形期,骨皮质连续。提示骨折模型呈二期愈合。结论：改良三点弯曲骨折装置可建立稳定的闭合性胫骨骨折兔模型,且操作简便,符合骨折愈合相关基础研究对闭合性骨折模型的要求。     

失神经及制动后兔肱骨骨密度与生物力学性能的对比研究

目的 对比分析失神经和制动后兔肱骨生物力学特性及骨密度的改变。方法 将54只新西兰兔随机分成正常组、失神经组和制动组,每组设置4周、8周和12周三个取材时间点。每组18只兔子,每个时间点6只兔子。正常组不做任何处理,失神经组兔子完全离断右侧上肢臂丛神经,制动组采用石膏与石膏托对右上肢进行牢靠的固定。主要检测指标:在造模后4周、8周和12周时取出兔右侧肱骨进行检测,称量肱骨的湿重,三点弯曲试验测定骨力学特性,双能X线骨密度仪检测骨密度,HE染色观察骨组织细微结构。结果 失神经和制动组的骨密度在造模后均低于同时间的正常组（P＜0.05）。失神经组肱骨骨密度与制动组相比虽有所降低,但差异不具有统计学意义（P＞0.05）。失神经组与制动组相比,失神经组的最大负荷、弯曲强度在造模后各个时间点都低于制动组,但只有到第12周时差异才具有显著性（P＜0.05）。失神经和制动组的右侧肱骨湿重随着时间的延长逐渐降低。但失神经组肱骨湿重与制动组相比差异不具有统计学意义（P＞0.05）。与正常组骨组织形态学相比,失神经组和制动组均出现骨小梁变细,小梁之间出现明显断裂,出现大量空泡状结构。结论 失神经和制动均可造成严重的骨质疏松。就两者造成的骨质疏松程度上来说,失神经对骨质力学性能的影响较制动更为严重。力学载荷的降低在导致骨质疏松的过程中起到了更为重要的作用。     

Callus formation and fixation rigidity: a fracture model in rats.

To produce different amounts of callus in rats, we devised a procedure to fix leg fractures using intramedullary nails that differ in bending rigidity. We inserted a silicone cannula into the intact diaphysis of the tibia of rats that had already been killed and then fractured the tibia by a three-point bending technique. The fracture was stabilised by insertion of either a stainless-steel or polypropylene nail into the silicone cannula. Biomechanical testing showed that the initial stiffness of the fractures differed between the two nail types by a factor of 16. In vivo, 16 Wistar rats were operated on by the same technique to study the formation of callus. Four weeks after fracture, the size of the callus differed significantly between the steel-nailed and polypropylene-nailed fractures. In conclusion, mechanically differing internal fixation devices led to different callus responses in rats when all other factors were kept equal.     

Mechanical stimulation by external application of cyclic tensile strains does not effectively enhance bone healing

OBJECTIVE: To determine whether an externally induced interfragmentary movement enhances the healing process of a fracture under flexible fixation. DESIGN: Randomized, prospective in vivo animal study with control group. Twenty-four skeletally mature Merino sheep were randomly assigned to six groups of four animals, which received cyclic interfragmentary movements of 0.2 and 0.8 millimeters and stimulation frequencies of 1, 5, and 10 Hertz, respectively. Twelve animals did not receive any externally applied stimulation and served as a control group. SETTING: Unrestricted stall activity with weight bearing reduced by tenotomy of the Achilles tendon. INTERVENTIONS: Osteotomy of the tibial diaphysis with three-millimeter gap width fixed with a six-pin, monolateral, double-bar external fixator. Interfragmentary movement of the osteotomy gap was externally induced by a motor-driven actuator unit. Five hundred cycles inducing nonuniform tensile strains within the gap were performed each day. MAIN OUTCOME MEASUREMENTS: Nine weeks after surgery, the animals were killed, and bone mineral density and callus cross-sectional area were measured with quantitative computed tomography. Callus projectional area was assessed by radiographs, and mechanical stability was determined with a three-point bending test. RESULTS: External stimulation with nonuniform cyclic tensile strains did slightly affect but not significantly enhance the fracture healing process. Varying the stimulation frequency had no influence on the healing process. The stimulation with 0.8 millimeter displacement magnitude resulted in a larger periosteal callus, but a decreased bone mineral density compared with the 0.2-millimeter displacement magnitude. The stimulation had no significant influence on the mechanical properties of the healing bone. CONCLUSIONS: Induced cyclic tensile strains did not produce a relevant enhancement of bone healing under flexible fixation.     

Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rats

BACKGROUND: The question of whether fracture healing and mechanical properties of the callus are influenced by osteoporosis (OP) is still not settled. We therefore studied this issue in vitamin D-depleted ovariectomized (OVX) rats, an OP model previously shown to induce weakening of the femoral neck, and thus thought to be closer to the human condition than the classic OVX rat model. METHODS: 72 female Wistar rats were randomized into two groups: ovariectomy and vitamin D-deficient diet (Ovx-D group) or sham operation and normal rat chow (Sham group). After 12 weeks, a closed tibial midshaft fracture was performed on the right side and fixed with an intramedullary nail. Bone loss and callus formation were monitored with DXA; serum levels of estradiol and vitamin D3 were measured and histomorphometric analyses were performed. Mechanical properties of callus, tibia, femoral shaft, and femoral neck were examined in 3-point cantilever bending 6 weeks after fracture. RESULTS: The Ovx-D group showed reduced BMD in the spine and femoral neck, and reduced trabecular bone volume in the femoral head. There were no differences in BMD and mechanical properties of callus between the groups. Except for reduced stiffness of the right femoral neck in the Ovx-D group (p = 0.02), no differences in the mechanical strength of long bones were detected. INTERPRETATION: Our results suggest that the systemic effects of estrogen and vitamin D deficiency are not crucial for fracture healing or mechanical properties of the callus.     

Intact fibula improves fracture healing in a rat tibia osteotomy model.

Rat tibia fractures are often used in fracture healing studies. Usually the fracture is stabilized with an intramedullary pin, which provides bending stiffness, but little torsional stiffness. The objective of this research was to determine the in vitro torsional rigidity of an osteotomized tibia with and without the fibula, and to determine if this difference influences the healing process in vivo. In vitro eleven rat tibias received an osteotomy, were stabilized with an intramedullary pin, and were tested in internal rotation to determine the torsional rigidity. The fibula was then manually broken and the torsional rigidity measured again. In vivo 18 rats received a tibial osteotomy, eight of which had an additional fractured fibula. After three weeks, the rats were sacrificed and the tibias were analyzed. Bone density in the fracture callus was measured with qCT. Bending rigidity and maximum breaking moment were determined in three-point bending. In vitro testing demonstrated that the torsional rigidity with an intact fibula was nearly two times higher than when the fibula was fractured. Though the torsional rigidity was still small in comparison with an intact bone, it resulted in a significantly different healing process in vivo. Rats with intact fibulas had significantly higher bone mineral density, bending rigidity, and maximum breaking moment compared to rats with a fractured fibula. These results indicate that torsional stability considerably affects the healing process. In a fracture model, it is critical to characterize the mechanical environment of the fracture.     

Effect of COX-2-specific inhibition on fracture-healing in the rat femur

BACKGROUND: Nonsteroidal anti-inflammatory medications have been shown to delay fracture-healing. COX-2-specific inhibitors such as celecoxib have recently been approved for human use. Our goal was to determine, mechanically, histologically, morphologically, and radiographically, whether COX-2-specific inhibition affects bone-healing. METHODS: A nondisplaced unilateral fracture was created in the right femur of fifty-seven adult male rats. Rats were given no drug, indomethacin (1 mg/kg/day), or celecoxib (3 mg/kg/day) daily, starting on postoperative day 1. Fractures were analyzed at four, eight, and twelve weeks after creation of the fracture. Callus and bridging bone formation was assessed radiographically. The amounts of fibrous tissue, cartilage, woven bone, and mature bone formation were determined histologically. Morphological changes were assessed to determine fibrous healing, callus formation, and bone-remodeling. Callus strength and stiffness were assessed biomechanically with three-point bending tests. RESULTS: At four weeks, only the indomethacin group showed biomechanical and radiographic evidence of delayed healing. Although femora from rats treated with celecoxib appeared to have more fibrous tissue than those from untreated rats at four and eight weeks, radiographic signs of callus formation, mechanical strength, and stiffness did not differ significantly between the groups. By twelve weeks, there were no significant differences among the three groups. CONCLUSIONS: Postoperative administration of celecoxib, a COX-2-specific inhibitor, did not delay healing as seen at twelve weeks following fracture in adult rat femora. At four and eight weeks, fibrous healing predominated in the celecoxib group as compared with the findings in the untreated group; however, mechanical strength and radiographic signs of healing were not significantly inhibited. Clinical Relevance: Many orthopaedists rely on narcotic analgesia for postfracture and postoperative pain, despite deleterious side effects and morbidity. Traditional nonsteroidal anti-inflammatory medications have been shown to delay fracture union. This effect may be smaller with COX-2-specific inhibitors.     

Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing.

The aim of this study was to investigate the effect of a moderate soft tissue trauma to the course of fracture healing in a standardized animal model. Thirty-eight Wistar rats were randomly divided into a fracture group (F, n = 19) and a group with a fracture and a soft tissue trauma (F + STT, n = 19). The fracture and the soft tissue trauma were created using an impact device with a standardized energy. All fractures were stabilized by two Kirschner wires. Three rats were measured for blood flow and sacrificed at days 1, 3, 7, and 14, and seven rats at day 28, from both groups. A three-point bending test was performed on the healed tibia after 28 days. During the first 24 h there was a reduction in blood flow, which was more pronounced in the F + STT group than in the F group. From histological sections, the shape of the callus formation, as well as the tissue distribution of newly formed bone, fibrous cartilage and fibrous connective tissue were determined. Distinctly more periosteal new bone formed and a larger callus formed at days 3 and 7 in group F compared to group F + STT. However, by days 14 and 28, the ossification and overall callus size no longer showed differences between the two groups. A fast recovery of blood flow and callus formation took place in the F + STT group, which led to similar histological and biomechanical results in fracture healing observed after 28 days between the two groups.