Effect of strontium ranelate on fracture healing in rat tibia

ObjectivesVarious anti-osteoporotic agents are available for clinical use. In contrast to other anti-osteoporotic drugs, strontium ranelate has anti-resorptive and bone-forming effects (dual action). Our objective in the present study is to investigate the efficacy of strontium ranelate (SR) on fracture healing in rat tibia.MethodsForty-two male Wistar rats randomized into two groups (groups 1 and 2, n = 21 for each). Left tibiae of all animals were broken in a closed manner using a manual three-point bending technique through mid-tibia following deep anesthesia with ketamine. The animals in group 1 were fed 25 g/day specially produced food containing 450 mg/kg SR starting from the first post-operative day. Group 2 were given 25 g/day normal food. The animals were sacrificed on the 2nd, 3rd and 4th post-operative weeks (each week 7 animals were sacrificed from each group) and the broken tibiae were removed. The tibiae were examined first radiographically and second, histopathologically.ResultsRadiologically, callus maturity and bone union increased with time in both groups. But no significant differences were found regarding callus maturity and bone union in weekly comparisons (p = 0.52, p = 0.19, p = 0.74).ConclusionsHistopathologically, it was seen that the fractures remarkably healed steadily in both groups on the 2nd, 3rd and 4th post-operative weeks. But no significant differences were found regarding the progression of fracture callus in weekly comparison (p = 1.0, p = 0.52, p = 1.0).In the present study, we were unable to find any beneficial or harmful effects of strontium ranelate on fracture healing.     

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.     

The neuronal regulation of fracture healing: Effects of sciatic nerve resection in rat tibia

The effect of sciatic nerve resection on tibial fracture healing was studied in rats 25 days post-trauma. To prevent differences in loading between sham-operated and nerve-resected animals the fractured limbs were cast-immobilized. On radiograms 8 of 11 fractures in the sham-operated animals showed very little callus formation in contrast to only 1 of 8 fractures in the group with nerve resection. Measured by single-photon absorptiometry, animals with sciatic nerve resection had a higher bone mineral content than the sham-operated animals. However, the mechanical strength in three-point cantilever bending was not better in the nerve-resected rats, implying a defective organization of the large callus. These results suggest neural regulation plays a role in the type of fracture healing, primary or secondary, and in the amount and quality of the callus.     

Effect of nerve injury on fracture healing: Callus formation studied in the rat

In an attempt to determine the effects of peripheral nerve lesions on fracture healing, radiographic, histomorphometric and chemical methods were used to evaluate callus formation in tibial fractures of rats with sciatic denervation. Fracture union by bridging external callus was more rapid in denervated limbs than in controls. By contrast, external calluses of denervated fractures were smaller and less dense and contained less collagenous matrix (hydroxyproline) and minerals (calcium, phosphorus) than controls. The RNA/DNA ratio decreased more rapidly in denervated calluses than in controls. Mineralization of collagenous matrix (estimated from the calcium/hydroxyproline ratio) was not affected by denervation.     

Effect of nerve injury on fracture healing. Callus formation studied in the rat

In an attempt to determine the effects of peripheral nerve lesions on fracture healing, radiographic, histomorphometric and chemical methods were used to evaluate callus formation in tibial fractures of rats with sciatic denervation. Fracture union by bridging external callus was more rapid in denervated limbs than in controls. By contrast, external calluses of denervated fractures were smaller and less dense and contained less collagenous matrix (hydroxyproline) and minerals (calcium, phosphorus) than controls. The RNA/DNA ratio decreased more rapidly in denervated calluses than in controls. Mineralization of collagenous matrix (estimated from the calcium/hydroxyproline ratio) was not affected by denervation.     

Prediction of fracture healing in the tibia by quantitative radionuclide imaging

The uptake of 99mTc-MDP was studied in 73 patients after a tibial fracture. The image obtained five minutes after injection during a period between one and four weeks after fracture was found to be related to the incidence of non-union after six months. A ratio of 1.3 between the uptake at the fracture site and at normal bone adjacent to it predicted non-union in an individual patient with a sensitivity of about 70% and a specificity of 90%.     

影响胫腓骨开放性骨折愈合的多因素分析

[目的]探讨影响胫腓骨开放性骨折愈合的主要因素。[方法]回顾性分析本院从2005年5月～2010年2月5年间收治的81例胫腓骨开放性骨折的病历资料。采用单因素分析患者年龄、性别、致伤原因、合并伤、骨折肢别、骨折分型、从受伤至开始清创的时间、固定方式、软组织修复时机、VSD的应用等10项因素与骨折愈合率的关系,对以上有意义的因素进行二分类的多因素Logistic回归分析。[结果]单因素分析结果,可能影响胫腓骨开放性骨折愈合的因素有致伤原因、骨折分型、从受伤至开始清创的时间及软组织修复时机等4个因素,多因素Lo-gistic回归分析发现致伤原因、骨折分型以及软组织修复时机与胫腓骨开放性骨折愈合独立相关,其他因素没有统计学意义。[结论]高能量损伤是影响胫腓骨开放性骨折愈合的危险因素,胫腓骨开放性骨折的愈合率与骨折分型严重程度有关,早期软组织修复有利于胫腓骨开放性骨折愈合。     

人工合成成骨生长肽促进兔胫骨骨折愈合的实验研究

目的观察人工合成的成骨生长肽(sOGP)经静脉应用对兔胫骨骨折愈合的影响。方法52只新西兰大白兔制成胫骨中段截骨、髓内钉固定骨折模型后,随机分为两组。实验组从术后第1d开始每天注射sOGP0.5μg·kg-1至取材前1d,对照组注射同样剂量的生理盐水。分别于术后第1、2、3、4、6周每组宰杀3～5只,测定血清ALP、BGP;同时取材测定骨折端骨密度、摄X线片后,再行组织学检查和形态分析,观察骨痂的大小及其组成成分的变化;其中术后6周的标本还进行了生物力学测定。结果实验组血清ALP、BGP水平高于对照组。X线片显示两组骨折均愈合,第3、4周实验组外骨痂平均面积比对照组大,3周时为265.44mm2、209.95mm2,4周时为233.10mm2、209.21mm2。第3、4、6周的骨密度实验组均大于对照组,其中第4周的骨密度经F检验两组的差异具有显著性(P<0.05)。组织学形态分析显示第2、3、4周的外骨痂平均面积实验组比对照组大;所有实验组外骨痂中小梁骨占骨痂总面积的百分比均高于对照组,其中第2、4周经F检验两组的差异具有显著性(P<0.05)。第6周骨折端平均最大破坏载荷及最大位移实验组比对照组高,但差异没有显著性(P>0.05)。结论全身应用sOGP对不稳定固定的兔胫骨横断骨折的愈合具有一定的促进作用。     

Influence of haemorrhagic shock on fracture healing

Background The purpose of the study was to evaluate the effect of haemorrhagic shock on the outcome of fracture healing.Material and methods Forty-two male Wistar rats were randomly divided into a control group and a shock group. After producing a tibia fracture we induced shock by creating a blood loss of 12 ml/kg body weight. The rats were isovolumetrically resuscitated with a colloid volume solution. Blood flow was measured by laser Doppler flowmetry. Mechanical properties were tested by three-point bending after 4 weeks.Results The blood flow of the shock group was characterised by no reduction in the distal region and in the soft tissue in the first 24 h, while the flow in the control group was reduced to 39% of the pre-fracture level. Biomechanical testing showed a better fracture healing outcome for the shock group than for the control group in failure load (31/11 N; P=0.06) and flexural rigidity (22,7/4,7 Nmm²; P=0.07).Conclusions In the shock group the restoration of vascularity in the distal region and in the soft tissue in the early healing stages, provoked by the isovolumic resuscitation, led to enhanced fracture healing. In addition, the results indicate that a fast blood supply may generate an improved initial healing process that results in an increased mechanical outcome of bone healing. In general, our findings underline the close interrelation between blood supply and successful fracture healing.This research study was presented at the 2nd Berlin Symposium "Significance of Musculo-Skeletal Soft Tissue on Pre-Operative Planning, Surgery and Healing", Berlin, 13–14 February 2003 (oral presentation)     

临床放疗对骨折愈合的影响

临床上运用放射治疗的部分病例并发有骨质破坏,甚至骨折,放疗对骨折愈合的影响值得关注。该文总结近年相关研究文献,就骨折愈合修复机制、放疗影响骨折修复机制和减小放疗对骨折愈合影响等方面介绍减小放疗不良反应的科研发现及进展。研究证明分次放疗、改变放疗介入时间对减小放疗对骨折愈合影响无显著效果,放疗对骨折愈合有阻碍和削弱作用,容易造成骨折延迟愈合或不愈合。近来研究发现低剂量放疗具有促进组织血液循环和骨折愈合的作用,分次放疗联合氨磷汀(amifostine)能够保护成骨细胞免受电离辐射损害并维持其生理功能。     

Influence of shock waves on fracture healing

During the last decades the influence of physical factors on fracture healing has been widely described. With the use of shock waves for the treatment of urolithiasis, a new mechanical medium has been introduced into medicine. For the first time the influence of shock waves on fracture healing was studied in rats. With fractioned shock-wave treatment (5 times 100 shock waves at 14 or 18 kV) an enhancement in healing could be achieved.     

Bone healing models in rat tibia after different injuries

AIMS: Gradual elaboration of an adequate and efficient multistage method for experimental remodelling of specific wound healing process--bone repair. Comparison of clinical characteristics with the results of microanatomy, histology, electronmicroscopy and computer morphometry. MATERIAL AND METHODS: An investigation of posttraumatic bone repair after internal fracture, excision and cortical perforation was carried out on 142 young adult male Wistar rats.The repair was studied in normal and affected animals (exercises, immobilization, isolation of periost) at 1-42 days after operation. RESULTS: The posttraumatic bone callus development and the related soft tissue repair, likewise the continuous remodelling, is an ordinary process of osteohisto- and organogenese. In trained rats the blood supply and bone formation is increased, whereas in immobilized animals it is inhibited and destroyed (osteoporose, pseudoarthrosis). After the injury some characteristics of bone repair histogenese will be became evident (after the perforation the primary endosteal and secondary periosteal ossification, inhibition of endosteal bone repair after the isolation of periost etc.). CONCLUSION: The posttraumatic bone healing, like embryohistogenese, has similar repair stages in all models of the experiments as well as similar tissue and cell responses (callus formation, its replacement, bone remodelling, etc.). However, the repair process in general (order of chondrous and/or bone callus stages, etc.) is variable and dependent on the mode and degree of injury. The use of bone cortex perforation in wound healing study is more recommendable as compared to internal fracture and excision (possibility of in situ study the periost and callus tissue compartments in bone repair machinery separately).     

Effect of tenoxicam on fracture healing in rat tibiae

BACKGROUND: Nonsteroidal anti-inflammatory drugs have been implicated in the development of delayed unions and nonunion after fractures in animal models. Previous investigations have identified two important factors as determinants of delayed fracture healing: early drug administration and a dose-dependent effect. OBJECTIVE: The purpose of this investigation was to study the effect of tenoxicam, a nonsteroidal anti-inflammatory drug, on the fracture healing process in rat tibiae. METHODS: Fifty-eight Wistar rats were randomly divided in four groups (I, II, III, and IV). Group I (control group, n=12) was given 0.1ml saline solution per day intramuscularly. Groups II (n=12), III (n=12), and IV (n=12) were administered 10mg per kg per day of tenoxicam intramuscularly. Administration of substances was begun on a week before to 48h after the fracturing procedure and continued during the entire experiment. Callus formation was studied histologically and histomorphologically, using light microscopy. In addition, a histologic grading based on the morphologic stage of fracture healing was carried out at 4 weeks, according to the criteria proposed by Allen et al. RESULTS: There was a significant difference in treatment effect between Group I (saline solution) and Groups II, III, and IV (tenoxicam) (P=0.07). Histologically and histomorphologically, there were qualitative and quantitative delay in callus formation at all tenoxicam groups. This was more pronounced the earlier the nonsteroidal anti-inflammatory drug was started, although no significant difference could be detected between Groups II, III, and IV (P>(alpha=10%)). Four weeks after fracture, Group I (n=3) showed complete osseous union, Groups II (n=3) and III (n=3), complete cartilaginous union, and Group IV (n=3), incomplete osseous union, according to Allen et al. By using this rating scale, the difference between control and drug-treated groups was statistically significant (P<0.1). CONCLUSION: Under studied conditions, this investigation shows that administration of tenoxicam intramuscularly delays fracture healing process in rat tibiae. These results suggest the hypothesis that early drug administration may delay bone healing after experimental fractures in animals, although it could not be detected statistically significant.     

Electrical behaviour of the rat's tibia during growth and fracture healing

Summary The electrical behaviour of the exposed tibial surface of young rats has been studied in normal conditions, after fracture and during the repair process. Recordings of potentials were made after all the electrical artefacts (muscle injury potentials) had been neutralized. No significant potential difference was obtained on the exposed bony surface in all the specimens. The results suggest that the currents of the hypothetical bone-generator do not reach the tibial surface. The bioelectrical properties of bone cannot therefore be investigated by an external recording method.

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Résumé Les auteurs ont étudié le comportement électrique des surfaces osseuses tibiales exposées sur de jeunes rats, en condition normale, après fracture et pendant le processus de réparation. L'enregistrement des potentiels a été fait après neutralisation de tous les artefacts électriques (potentiels de lésion musculaire). Aucune différence de potentiel n'a été enregistrée au niveau des surfaces osseuses exposées, dans chacune des conditions.Ces résultats indiquent que les courants de l'hypothétique »g'enérateur osseux« ne parviennent pas à la surface du tibia. Donc aucune méthode d'ènregistrement externe des propriétés bio-éléctriques de l'os n'est possible.

     

骨折类型对掌骨骨折钢板内固定术后骨愈合的影响

[目的] 评价掌骨骨折类型、患者职业与骨折愈合的相关性。[方法] 回顾性分析了104例掌骨关节外骨折，评价指标为愈合时间和愈合的并发症。与评价指标相关的因素为：骨折类型（横形骨折／非横形骨折）、患者类别、软组织损伤情况和钢板类型。[结果] 12例患者发生了骨折愈合问题：横形骨折组8例，非横形骨折组4例，横形骨折比非横形骨折更易发生愈合困难（P=0．01）。两种骨折类型的患者中，手工劳动者比非于工劳动者更易发生骨折愈合的问题（P〈0．01）：优势手骨折、软组织损伤和钢板的类别与骨折愈合问题没有相关性。[结论] 掌骨骨折的愈合与骨折类型、患者职业有相关性。     

Poor muscle coverage delays fracture healing in rats

We undertook this study in rats to ascertain the influence of muscle coverage on tibial fracture healing. 30 rats were randomly assigned to three intervention groups. Following a mid-diaphyseal osteotomy in the left tibia, reamed nailing was performed in all animals. In one group (A), the antero-lateral muscles were detached from the fractured bone, while the anterolateral compartment was excised in another group (B). In the third group (C), the muscle compartment was resected, and the superficial gluteal muscle was mobilized and transposed over the fractured area. Muscle intervention, like that in group A and C, had no effect on the blood flow. The fibular nerve was resected in all the rats. At 4 weeks, we studied the healing bones in each group clinically, radiologically and mechanically. At 4 weeks, radiographs in two planes revealed a clearly visible fracture line in the three experimental groups. Mechanical testing of the healing fractures showed significantly lower bending moment and bending rigidity in group B than in groups A and C. No difference in mechanical characteristics was detected between the healing bones in groups A and C. This animal study indicates that in tibial fractures, an extensive muscle tissue defect may have negative effects on early bone healing.     

Impact of smoking on fracture healing and risk of complications in limb-threatening open tibia fractures

OBJECTIVES: Current data show smoking is associated with a number of complications of the fracture healing process. A concern, however, is the potential confounding effect of covariates associated with smoking. The present study is the first to prospectively examine time to union, as well as major complications of the fracture healing process, while adjusting for potential confounders. SETTING: Eight Level I trauma centers. PATIENTS: Patients with unilateral open tibia fractures were divided into 3 baseline smoking categories: never smoked (n = 81), previous smoker (n = 82), and current smoker (n = 105). OUTCOME MEASURE: Time to fracture healing, diagnosis of infection, and osteomyelitis. METHODS: Survival and logistic analyses were used to study differences in time to fracture healing and the likelihood of developing complications, respectively. Multivariate models were used to adjust for injury severity, treatment variations, and patient characteristics. RESULTS: After adjusting for covariates, current and previous smokers were 37% (P = 0.01) and 32% (P = 0.04) less likely to achieve union than nonsmokers, respectively. Current smokers were more than twice as likely to develop an infection (P = 0.05) and 3.7 times as likely to develop osteomyelitis (P = 0.01). Previous smokers were 2.8 times as likely to develop osteomyelitis (P = 0.07), but were at no greater risk for other types of infection. CONCLUSION: Smoking places the patient at risk for increased time to union and complications. Previous smoking history also appears to increase the risk of osteomyelitis and increased time to union. The results highlight the need for orthopaedic surgeons to encourage their patients to enter a smoking cessation programs.     

The effect of Cox-2 specific inhibition on direct fracture healing in the rabbit tibia

Objective  

The purpose of this study was to evaluate the effect of Cox-2 administration on direct (primary) fracture healing.