Experimental and probabilistic analysis of distal femoral periprosthetic fracture: a comparison of locking plate and intramedullary nail fixation. Part B: probabilistic investigation

The following is Part B of a two-part study. Part A evaluated, biomechanically, intramedullary (IM) nails versus locking plates for fixation of an extra-articular, metaphyseal wedge fracture in synthetic osteoporotic bone. Part B of this study introduces deterministic finite element (FE) models of each construct type in synthetic osteoporotic bone and investigates the probability of periprosthetic fracture of the locking plate compared with the retrograde IM nail using Monte Carlo simulation. Deterministic FE models of the fractured femur implanted with IM nail and locking plate, respectively, were developed and validated using experimental data presented in Part A of this study. The models were validated by comparing the load-displacement curve of the experimental data with the load-displacement curve of the FE simulation with a root-mean square error of less than 3?mm. The validated FE models were then modified by defining the cortical and cancellous bone modulus of elasticity as uncertain variables that could be assumed to vary randomly. Monte Carlo simulation was used to evaluate the probability of fracture (POF) of each fixation. The POF represents the cumulative probability that the predicted shear stresses in the cortical bone will exceed the expected shear strength of the cortical bone. This investigation provides information regarding the significance of post-operative damage accumulation on the POF of the implanted bones when the two fixations are used. The probabilistic analysis found the locking plate fixation to have a higher POF than the IM nail fixation under the applied loading conditions (locking plate 21.8% versus IM nail 0.019%).     

Bone remodelling analysis of a bovine femur for a veterinary implant design

The response of bovine bone to the presence of an implant is analysed with the aim of simulating bone remodelling in a developing model of a polymeric intramedullary interlocking nail for veterinary use. A 3-D finite element model of the femur diaphysis is built based on computed tomography images and using a CAD-based modelling pipeline. The bone remodelling process after the surgery is analysed and compared with the healthy bone. The remodelling law assumes that bone adapts to the mechanical environment. For the analyses a consistent set of loads is determined for the bovine walk cycle. The remodelling results reproduce the morphologic features of bone and provide evidence of the difference on the bone behaviour when comparing metallic and polymeric nails. Our findings indicate that an intramedullary polymeric nail has the advantage over the metallic one of improving long-term bone healing and possibly avoiding the need of the implant removal.     

逆行交锁髓内钉联合单侧骨皮质锁定钢板固定治疗股骨髁上骨不连

目的:探讨逆行交锁髓内钉联合单侧骨皮质钢板固定治疗股骨髁上骨不连的临床疗效。方法:对25例股骨髁上骨不连,均采用逆行交锁髓内钉联合单侧骨皮质钢板固定加自体髂骨植骨治疗。结果:25例获12～24个月随访,平均12个月。4～8个月内均获骨性愈合。结论:应用逆行交锁髓内钉联合单侧骨皮质钢板固定后骨折端可获得坚强内固定,手术操作简便、安全,可早期进行膝关节和股四头肌功能锻炼,是一种治疗股骨髁上骨不连的有效方法。     

Predicting the external formation of a bone fracture callus: an optimisation approach

The formation of a fracture callus in vivo tends to form in a structurally efficient manner distributing tissues where mechanical stimulus persists. Therefore, it is proposed that the formation of a fracture callus can be modelled in silico by way of an optimisation algorithm. This was tested by generating a finite element model of a transversal bone fracture embedded in a large tissue domain which was subjected to axial, bending and torsional loads. It was found that the relative fragment motion induced a compressive strain field in the early callus tissue which could be utilised to simulate the formation of external callus structures through an iterative optimisation process of tissue maintenance and removal. The phenomenological results showed a high level of congruence with in vivo healing patterns found in the literature. Consequently, the proposed strategy shows potential as a means of predicting spatial bone healing phenomena for pre-clinical testing.     

Predicting the external formation of a bone fracture callus: an optimisation approach

The formation of a fracture callus in vivo tends to form in a structurally efficient manner distributing tissues where mechanical stimulus persists. Therefore, it is proposed that the formation of a fracture callus can be modelled in silico by way of an optimisation algorithm. This was tested by generating a finite element model of a transversal bone fracture embedded in a large tissue domain which was subjected to axial, bending and torsional loads. It was found that the relative fragment motion induced a compressive strain field in the early callus tissue which could be utilised to simulate the formation of external callus structures through an iterative optimisation process of tissue maintenance and removal. The phenomenological results showed a high level of congruence with in vivo healing patterns found in the literature. Consequently, the proposed strategy shows potential as a means of predicting spatial bone healing phenomena for pre-clinical testing.     

Experimental and probabilistic analysis of distal femoral periprosthetic fracture: a comparison of locking plate and intramedullary nail fixation. Part A: experimental investigation

The following is a two-part study. Part A evaluates biomechanically intramedullary (IM) nails vs. locking plates for fixation of femoral fractures in osteoporotic bone. Part B of this study introduces a deterministic finite element model of each construct type and investigates the probability of periprosthetic fracture of the locking plate compared with the retrograde IM nail using Monte Carlo simulation. For Part A, an extra-articular, metaphyseal wedge fracture pattern was created in 11 osteoporotic fourth-generation composite femurs. Fixation was performed with a locking plate or a retrograde IM nail. Axial, torsion and bending cyclic loading to simulate post-operative damage accumulation were performed followed by ramped load to failure. Locking plates proved to be more stable (using stiffness as the determining factor) in osteoporotic bone as observed under low load cycle conditions. However, some of these advantages were offset by a greater incidence of sudden periprosthetic fracture observed under ramped loading conditions. Cadaveric, osteoporotic femurs included as a case study also exhibited periprosthetic fracture, but failure was accompanied by catastrophic comminution of the cortex. Periprosthetic failure at the implant end including bone comminution is difficult to salvage with revision fixation. The weakened trabecular matrix and thinned cortex of osteoporotic bone may increase the incidence of periprosthetic fracture. It is, therefore, essential for the surgeon to consider all possible loading scenarios when recommending an ideal implant for the osteoporotic patient.     

The role of interfragmentary strain on the rate of bone healing—A new interpretation and mathematical model

It is postulated that there is a causal relationship between mechanical stimulus and the rate of bone healing post fracture. However, despite numerous experimental studies in the literature, no quantifiable relationship has been proposed. It is hypothesized in the present study that the temporal rate of bone fracture healing, measured in terms of callus stiffening per week, can be described mathematically based on the relative motions between bone fragments at the initial stage of the healing process. To test this, a comparative reanalysis of experimental data found in the literature was conducted. These individual data sets described a relationship between an initial intermittently applied peak interfragmentary strain and the change in interfragmentary motion or the increase in callus stiffness over time. The data were converted into a relative increase in stiffness, which normalised the results and reduced inter-study variability. The rates of healing for the various initial strains were compared, and based on this a mathematical phenomenological model was derived. Error analyses were then performed, which showed a high level of congruence between the in-vivo and simulated rates of healing. The results of the comparative analysis revealed that there is a positive correlation between the rate of callus stiffening and interfragmentary strain. Finally, the proposed model has shown for the first time that a quantifiable cause–and–effect relationship exists between the rate of bone healing and mechanical stimulus.     

Mineral and matrix contributions to rigidity in fracture healing

The purpose of this study was to investigate the relationships among selected properties of fracture callus: bending rigidity, tissue density, mineral density, matrix density and mineral-to-matrix ratio. The experimental model was an osteotomized canine radius in which the development of the fracture callus was modified by electrical stimulation with various levels of direct current. This resulted in a range of values for the selected properties of the callus, determined post mortem at 7 weeks after osteotomy. We found that the rigidity (R) of the bone-callus combination obeyed relationships of the form R = axb, where x is the tissue density, mineral density, matrix density or the mineral-to-matrix ratio of the repair tissue. These are analogous to power-law relationships found in studies of compact and cancellous bone. The results suggest that fracture callus at 7 weeks after osteotomy in canine radius behaves more like immature compact bone than cancellous bone in its mechanical and physicochemical properties. The present study demonstrates the feasibility of developing non-invasive in vivo densitometric methods to monitor fracture healing, since models may be developed that can predict mechanical properties from densitometric data. Further studies are needed to develop a refined model based on experimental data on the mechanical and physicochemical properties and microstructure of fracture callus at different stages of healing.     

甲真菌病患者甲微生物群分析

目的研究甲真菌病患者甲微生物群的构成,为进一步阐明甲真菌病的发病机制提供线索。方法本研究共纳入47例甲真菌病患者及7例健康志愿者。取患者病甲的甲屑进行真菌镜检及培养鉴定;提取患者病甲、患者对侧健甲及健康人甲的DNA,对真菌rDNA ITS区及细菌16S rDNA V3-V4区PCR扩增,分析微生物群构成,并进行α多样性、β多样性、Simper分析及Spearman相关性分析。结果甲真菌病患者病甲的微生物群构成与对侧健甲及健康人甲存在差异。患者病甲的真菌菌群的丰富度高于对侧健甲。患者对侧健甲细菌菌群的多样性高于病甲及健康人甲,且患者对侧健甲细菌菌群的构成与患甲和健康人甲均有部分重叠。结论患者对侧健甲的细菌菌群构成具有由健康人甲向患者病甲转变的趋势。且在患者病甲的微生物群中,某些真菌和细菌菌属可能具有相关性。     

The influence of mechanical stimulus on the pattern of tissue differentiation in a long bone fracture--an FEM study

2D, coronal plane, finite elements models (FEMs) were developed from orthogonal radiographs of a diaphyseal tibial fracture and its reparative tissue at four different time points during healing. Each callus was separated into regions of common tissue histology by computerised radiographic analysis. Starting point values of tissue material properties from the literature were refined by the model to simulate exactly the mechanical behaviour of the subject's callus and bone during loading. This was achieved by matching measured inter-fragmentary displacements with calculated inter-fragmentary forces. Stress and strain distributions in the callus and bone were calculated from peak inter-fragmentary displacements measured during natural walking activity, and were correlated with the subsequently observed pattern of tissue differentiation and maturation of the callus. The growth and stiffening of the external callus progressively reduced the inter-fragmentary gap strain. Partial maturation of the gap tissue was apparent only one week before fixator removal. Principal stresses in the callus were compared with 'yield stresses' in corresponding tissue from the literature. This indicated the presence of stress concentrations medial and lateral to the fracture gap, which probably caused tissue damage during normal activity levels. Tissue damage may also have precipitated partial structural failure of the callus, both of which were believed to have delayed healing during the middle third of the fixation period. Had the fixation device provided greater inter-fragmentary support during early healing, this may have prevented callus failure and the consequent delay in healing. A further benefit of this would have been the reduction of the initially high intra-gap tissue strains to a magnitude more conducive to earlier maturation of the bridging tissue that united the bone.     

Predicting the external formation of callus tissues in oblique bone fractures: idealised and clinical case studies

It is proposed that the external asymmetric formation of callus tissues that forms naturally about an oblique bone fracture can be predicted computationally. We present an analysis of callus formation for two cases of bone fracture healing: idealised and subject-specific oblique bone fractures. Plane strain finite element (FE) models of the oblique fractures were generated to calculate the compressive strain field experienced by the immature callus tissues due to interfragmentary motion. The external formations of the calluses were phenomenologically simulated using an optimisation style algorithm that iteratively removes tissue that experiences low strains from a large domain. The resultant simulated spatial formation of the healing tissues for the two bone fracture cases showed that the calluses tended to form at an angle equivalent to the angle of the oblique fracture line. The computational results qualitatively correlated with the callus formations found in vivo. Consequently, the proposed methods show potential as a means of predicting callus formation in pre-clinical testing.     

Evaluation of residual stresses due to bone callus growth: a computational study

Mechanical environment in callus is determinant for the evolution of bone healing. However, recent mechanobiological computational works have underestimated the effect that growth exerts on the mechanical environment of callus. In the present work, we computationally evaluate the significance of growth-induced stresses, commonly called residual stresses, in callus. We construct a mechanobiological model of a callus in the metatarsus of a sheep in two different stages: one week and four weeks after fracture. The magnitude of stresses generated during callus growth is compared with the magnitude of stresses when only external loads are applied to the callus. We predict that residual stresses are relevant in some areas, mainly located at the periosteal side far from the fracture gap. Therefore, the inclusion of these residual stresses could represent a significant impact on the callus growth and predict a different evolution of biological processes occurring during bone healing.     

A 3D computational simulation of fracture callus formation: influence of the stiffness of the external fixator

The stiffness of the external fixation highly influences the fracture healing pattern. In this work we study this aspect by means of a finite element model of a simple transverse mid-diaphyseal fracture of an ovine metatarsus fixed with a bilateral external fixator. In order to simulate the regenerative process, a previously developed mechanobiological model of bone fracture healing was implemented in three dimensions. This model is able to simulate tissue differentiation, bone regeneration, and callus growth. A physiological load of 500 N was applied and three different stiffnesses of the external fixator were simulated (2300, 1725, and 1150 N/mm). The interfragmentary strain and load sharing mechanism between bone and the external fixator were compared to those recorded in previous experimental works. The effects of the stiffness on the callus shape and tissue distributions in the fracture site were also analyzed. We predicted that a lower stiffness of the fixator delays fracture healing and causes a larger callus, in correspondence to well-documented clinical observations.     

Hydration of human nails investigated by NIR-FT-Raman spectroscopy.

The human nail, although it is usually stable against outer influences, becomes soft and flexible after soaking in water. Frequent washing increases brittleness of nails. Hydration of nails is thought to be the most important factor influencing the physical properties of nails and possibly acts through changes in keratin structure. Here NIR-FT-Raman has been used to examine molecular structural changes of intact moisten nails. Raman spectra were obtained both in vitro from nail samples and in vivo before and after soaking in water. The water uptake of normal nail samples during the first 15 min was reflected in the increasing intensity ratio of the nu(OH)/nu(CH(2)) bands. A saturating effect appeared soon after 10 min which is explained by a defined water holding capacity. R(nu) representation of the low frequency range of the Raman spectra showed that mainly bound water is found both in dry and in wet nails. This implies water-protein interaction. Protein backbone vibration at 932 cm(-1) indicating alpha-helical proteins increased in intensity in the wet nails. The nu(S-S) which is sensitive to changes in conformation of proteins showed a 4% higher intensity. Additional protein-water interactions could lead to a slight change of the dihedral angle of the C-S-S-C bonds and to geometric changes in coiling behavior of the alpha-helical protein. Suggesting a separation between matrix proteins and fiber proteins giving them a greater freedom of flexibility. The in vivo spectra detected from the distal part of the nail resembled spectra in vitro. Raman spectra of the proximal part of the nail showed that it was fully saturated with water. The proximal part of the nail did not show changes in water content and protein structure during nail moisturizing in the Raman spectra. Our results suggest that the softening of the nail following hydration may be due to changed matrix protein molecular structure induced by water.     

The analysis of the unstable tibia fracture treatment applying internal stabilization method

The study included 51 patients with tibia fractures, who underwent percutaneous bone reposition and stabilization with unrimed tibial locking nail. The results obtained using this method were compared with those obtained by standard fracture treatment where flat and anatomic plates were applied (n = 64). In patients who had osteosynthetic material implanted percutaneously (using unrimed tibial locking nail) there was no incidence of post surgical osteitis or any pseudarthrosis. The healing callus of the fracture was of lesser quality and spindle shaped, suggesting that fracture stabilization using this method was less efficient. In patients with fractures stabilized by the open method using flat and anatomic plates (n = 64), we noticed 3.1% (n = 2) cases of osteitis and 4.7% (n = 3) cases of pseudarthrosis. Due to lesser incidence of postoperative osteitis, our method of choice in tibia fractures would be percutaneous stabilization with unrimed tibial locking nail. However, this treatment method has its disadvantages, too. Fracture callus is of lesser quality and it is spindle shaped. Furthermore, there are problems with adequate percutaneous reposition in some cases, as well as necessity for radiological checking.     

Trabecular bone fracture healing simulation with finite element analysis and fuzzy logic

Trabecular bone fractures heal through intramembraneous ossification. This process differs from diaphyseal fracture healing in that the trabecular marrow provides a rich vascular supply to the healing bone, there is very little callus formation, woven bone forms directly without a cartilage intermediary, and the woven bone is remodelled to form trabecular bone. Previous studies have used numerical methods to simulate diaphyseal fracture healing or bone remodelling, however not trabecular fracture healing, which involves both tissue differentiation and trabecular formation. The objective of this study was to determine if intramembraneous bone formation and remodelling during trabecular bone fracture healing could be simulated using the same mechanobiological principles as those proposed for diaphyseal fracture healing. Using finite element analysis and the fuzzy logic for diaphyseal healing, the model simulated formation of woven bone in the fracture gap and subsequent remodelling of the bone to form trabecular bone. We also demonstrated that the trabecular structure is dependent on the applied loading conditions. A single model that can simulate bone healing and remodelling may prove to be a useful tool in predicting musculoskeletal tissue differentiation in different vascular and mechanical environments.     

Effects of mechanical loading patterns,bone graft,and proximity to periosteum on bone defect healing

The goal of this study is to elucidate whether mechanobiological factors, including mechanical loading patterns, presence of bone graft, and proximity to the periosteum, correlate to de novo tissue generation and healing in critical sized long bone defects, which are enveloped by periosteum in situ and are bridged at 16 weeks, in sheep femora. Quantitative histomorphometric measures of defect cross sections show that, along the axis least able to resist bending loads (minor centroidal axis, CA), bone laid down in the first two weeks after surgery exhibits more mineralization albeit less total area compared to bone along the axis most able to resist bending loads (major CA). Similarly, areas of the cross section along the minor CA show a higher degree of perfusion albeit less total area of perfusion compared to bone along the major CA. Furthermore, proximity to the periosteal niche, in conjunction with the presence of bone graft and predominant loading patterns, relates significantly to the radial distribution of early bone apposition and perfusion of bone at 16 weeks after surgery (linear regression with R²>0.80). In the absence of graft, early bone density is relatively evenly distributed in the defect zone, as is the intensity of perfused tissue. As measured by a steeper average slope in intensity of fluorochrome (new bone) distribution between the periosteum and the IM nail, the presence of bone graft retards initial bone formation in the defect zone and is associated with less evenly distributed tissue perfusion (steeper slope) persisting 16 weeks after surgery. Finally, although the mean area of bone resorption is not significantly different within or between groups defined by the presence of graft and/or mechanical loading patterns in the defect zone, the mean area of infilling resorption spaces is significantly higher in areas of the defect zone least able to resist bending (minor CA) but is not significantly related to the presence of bone graft. To our knowledge, the use of the major and minor centroidal axes to relate prevailing mechanical loading patterns to area and density of early bone generation in bone defects has not been reported prior to this study and may provide a new means to assess structure–function relationships in de novo bone generation and healing of bone defects.     

Beneficial effects of moderate,early loading and adverse effects of delayed or excessive loading on bone healing

Fracture healing involves the differentiation and proliferation of cells in the callus and the synthesis and degradation of connective, cartilage and bone tissue. These processes are initiated and tightly regulated by growth factors and by the mechanical environment in the callus. In this work we incorporated the effects of mechanical stimulation on cell differentiation and ossification into a previously developed temporal-spatial model of growth factor mediated fracture healing. In particular, the stimulatory and inhibitory effects of dilatational and deviatoric strains were modeled. This predictive model was then calibrated and validated using well-defined in vivo experiments from the literature. As in the experiments, the results of the model demonstrated the beneficial and adverse effects of moderate and excessive loading, respectively, as well as the negative effects of delaying mechanical stimulation of rigidly fixed calluses. In addition, the model examined loading conditions and time points beyond those used in the experiments, providing a more complete and mechanistic characterization of the effects of loading in the biological tissue response associated with fracture healing.     

DEXA对骨髓炎骨缺损治疗中骨痂密度的评价

目的：探讨DEXA对骨髓炎骨缺损治疗中骨痂密度的评价及意义。方法：严格按照纳入排除标准,选取21例骨髓炎清创后伴大段皮质骨缺损一期植骨的病人。术后4,6,8,10个月后对骨折端骨痂行双能X线骨密度仪检测,并进行X摄片以及Enneking评分,从而明确植骨区愈合骨痂的密度变化趋势,骨愈合情况以及症状改善情况。结果：（1）X线摄片结果显示：4个月后：骨缺损区依然清晰可见,内有少量稀疏骨痂通过,少量外骨痂形成。6个月后：植骨区内骨痂含量明显增多,且外骨痂膨大。8个月：缺损区模糊,有较致密骨痂生成,且外骨痂逐渐减少。10个月：植骨区骨痂更加致密,且部份髓腔再通。（2）Enneking评分：患者术后第10个月功能恢复情况评估正常功能20例,20分以下的患者1例。（3）BMD测定：骨折端的骨密度及骨密度比率随时间延长而增加,植骨10个月后患侧的骨密度已可基本上达到正常对照侧的骨密度水平。结论：双能X线骨密度测量从一定程度上反映出骨痂的力学强度特性。在感染性骨缺损治疗中可以作为检测植骨区的恢复情况的参考。     

DLS 5.0 - The Biomechanical Effects of Dynamic Locking Screws

Introduction

Indirect reduction of dia-/metaphyseal fractures with minimally invasive implant application bridges the fracture zone in order to protect the soft-tissue and blood supply. The goal of this fixation strategy is to allow stable motion at the fracture site to achieve indirect bone healing with callus formation. However, concerns have arisen that the high axial stiffness and eccentric position of locked plating constructs may suppress interfragmentary motion and callus formation, particularly under the plate. The reason for this is an asymmetric fracture movement. The biological need for sufficient callus formation and secondary bone healing is three-dimensional micro movement in the fracture zone. The DLS was designed to allow for increased fracture site motion. The purpose of the current study was to determine the biomechanical effect of the DLS_5.0.

Methods

Twelve surrogate bone models were used for analyzing the characteristics of the DLS_5.0. The axial stiffness and the interfragmentary motion of locked plating constructs with DLS were compared to conventional constructs with Locking Head Screws (LS_5.0). A quasi-static axial load of 0 to 2.5 kN was applied. Relative motion was measured.

Results

The dynamic system showed a biphasic axial stiffness distribution and provided a significant reduction of the initial axial stiffness of 74.4%. Additionally, the interfragmentary motion at the near cortex increased significantly from 0.033 mm to 0.210 mm (at 200N).

Conclusions

The DLS may ultimately be an improvement over the angular stable plate osteosynthesis. The advantages of the angular stability are not only preserved but even supplemented by a dynamic element which leads to homogenous fracture movement and to a potentially uniform callus distribution.