Influence of femur size and morphology on load transfer in the resurfaced femoral head: A large scale, multi-subject finite element study

Femoral resurfacing has become an increasingly popular procedure, especially for young, active patients. The procedure is known to alter load transfer through the proximal femur and this has been linked with the most commonly observed complication, neck fracture. An intriguing observation noted by registry data and clinical studies is an inverse relationship between implant size and revision rate. While computational analysis has become an established part of biomedical engineering, the majority of work uses a single or small set of bone models, with a single implant size, due to the constraints of time and data availability. Therefore, it has been infeasible to run a study incorporating natural inter-patient variability or the performance of smaller implants could not be meaningfully studied. In previous work a statistical model of the whole femur was used to generate large numbers of unique, realistic, FE-ready femur models describing both geometry and material properties. The current study demonstrates a methodology for virtually implanting and performing stress analysis of cemented femoral resurfacing components, with model specific sizing and orientation. Automated analysis of 400 generated femurs, in both implanted and intact configurations showed the strain changes induced by resurfacing. This produced a statistically meaningful number of results and allowed the examination of outliers. Results showed increased femoral neck strain changes potentially increasing the risk of neck fracture, associated with smaller, less dense femurs and smaller implant sizes; agreeing with clinical observations. The study demonstrates a methodology for more comprehensive analyses, based on populations rather than individuals.     

动力加压髋螺钉对股骨上段生物力学特征性的影响

目的：探讨股骨上端骨折,以动力加压髋螺钉进行骨固定治疗,骨折愈合后,取出动力加压髋螺钉以后的股骨上段与完整的股骨上段的生物力学特性相比较,为临床内固定取出术后功能锻炼的强度提供量化依据。方法：收集8具新鲜尸体股骨标本进行实验应力分析,分别测定完整股骨上段和动力加压髋螺钉取出后股骨上段的力学特性改变。结果：动力加压髋螺钉取出术后股骨上段的力学特性与完整股骨上段的力学特性相比有显著的差异（P＜0．01）。结论：股骨上端骨折如果以动力加压髋螺钉为治疗手段,在骨折愈合取出内固定后,功能锻炼只能控制在慢速步行水平,不能进行奔跑、跳跃等活动,以防止再骨折等并发症的发生。     

7,8,3'-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo

Most sensorineural hearing loss cases occur as a result of hair cell loss, which results in secondary degeneration of spiral ganglion neurons (SGNs). Substantial loss of SGNs reduces the benefit of cochlear implants, which rely on SGNs for transmitting signals to the central auditory centers. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) play essential roles in cochlear development and are required for SGN survival. Here we report that 7,8,3'-trihydroxyflavone (7,8,3'-THF), which is a small molecule agonist of tyrosine receptor kinase B (TrkB), promoted SGN survival with high potency both in vitro and in vivo. The compound protected the SGNs in a TrkB-dependent manner, as its effects on SGNs disappeared when the TrkB was blocked. Application of 7,8,3'-THF in the bulla of conditional connexin26 (cCx26)-null mice dramatically rescued SGNs in the applied ear compared to untreated control cochlea in the same animal. Our findings suggest that 7,8,3'-THF is a promising therapeutic agent protecting the SGNs from degeneration both in vitro and in vivo.     

动力髋螺钉与股骨近端髓内钉治疗老年股骨近端骨折的临床疗效比较

目的:比较动力髋螺钉与股骨近端髓内钉治疗老年股骨近端骨折的临床疗效和安全性。方法:收集我院收治的老年股骨近端骨折患者64例,随机分为DHS组和PFN组,每组各32例。DHS组患者给予动力髋螺钉的固定方式,PFN组给予股骨近端髓内钉的固定方式。手术后对患者的手术切口长度、术中出血量、手术时间、骨折愈合时间、术后并发症以及患者临床疗效进行检测并比较。结果:与治疗前相比,两组患者治疗后的Harris评分均显著下降(P0.05);与DHS组相比,PFN组患者的手术切口长度、术中出血量、手术时间、骨折愈合时间、术后并发症的发生率以及Harris评分均较低(P0.05)。结论:股骨近端髓内钉的固定治疗老年股骨近端骨折的临床疗效较好,安全性更高。     

The proximal femoral nail antirotation (PFNA) in the treatment of proximal femoral fractures

Proximal femoral fractures, especially in elderly persons with osteoporosis, present a challenge for the traumatologist. While the dynamic hip screw (DHS) became the implant of choice for the treatment of stable fractures, the ideal implant for the treatment of unstable fractures remains an issue. In our experience, Proximal Femoral Nail Antirotation (PFNA) is an excellent device for osteosynthesis as it can be easily inserted, it provides angular and rotational stability and allows early weight bearing on the affected limb. Between February 2007 and August 2009, 76 patients underwent the PFNA fixation for proximal femoral fractures (15 men and 61 women). Forty seven fractures were pertrochanteric, 14 subtrochanteric, 2 pathological and 5 ipsilateral trochanteric and diaphyseal fractures whereas in 8 cases the PFNA was used in reosteosynthesis. The mean age of patients was 73.4 years (range 22-91 years). The fractures were reduced on a traction table and the implant was inserted using minimally invasive technique. Four patients developed superficial postoperative wound infection. No cases of implant breakage have been recorded; there was one cut-out; delayed union was noted in three patients. The majority of patients regained their pre-injury mobility status. The PFNA is an excellent implant for stabilisation of both trochanteric and complex combination fractures as well as an exceptional device for reosteosynthesis. It is easily inserted with few intra- and postoperative complications and allows early weight bearing on the affected limb as well as quicker rehabilitation of patients.     

Biomechanical studies and finite element analysis of a bone-implant interface]

In the present study, the fixation system of a femoral medullary nail connection was investigated. In surgical treatment of fractured femurs, the fracture is bridged by a medullary nail that is fixed by interlocking screws in the bone. Bone failure around these screws is the most common complication associated with the treatment of fractures of osteoporotic bone. The present study analyses the stresses present in the region of the implant/bone system. Three-dimensional finite element models were generated, a nonlinear structure analysis performed, and the stresses at material interfaces investigated. The highest concentration of stresses is to be found in the middle of the interlocking screws and the holes drilled in the bone. This is in agreement with the results of experimental investigations.     

PFNA和DHS治疗老年性股骨粗隆间骨折的临床对照研究

目的:探讨PFNA和DHS治疗老年性股骨粗隆间骨折的临床疗效.方法:回顾分析2010年3月至2011年6月间69例行手术治疗的老年性股骨粗隆间骨折的临床资料,其中股骨近端抗旋髓内钉(PFNA)37例(PFNA组),动力髋螺钉(DHS)32例(DHS组);比较两组平均手术时间、术中出血量、术后并发症、治疗费用、骨折愈合时间和髋关节功能.结果:PFNA组平均手术时间和术中出血量均低于DHS组(P＜0.05);术后并发症差别无统计学意义(P＞ 0.05);PFNA组治疗费用高于DHS组(P＜0.05);术后随访时间11-20个月,两组病例均临床愈合,PFNA组优良率高于DHS组(P＜0.05).结论:PFNA与DHS均是治疗老年性股骨粗隆间骨折的较好材料,PFNA更符合生物学特点,具有手术创伤小、固定牢靠、恢复好的优点,但治疗费用较高,临床应用可根据患者病情和经济状况选用.     

A biomechanical comparison of composite femurs and cadaver femurs used in experiments on operated hip fractures

Fourth generation composite femurs (4GCFs, models #3406 and #3403) simulate femurs of males <80 years with good bone quality. Since most hip fractures occur in old women with fragile bones, concern is raised regarding the use of standard 4GCFs in biomechanical experiments. In this study the stability of hip fracture fixations in 4GCFs was compared to human cadaver femurs (HCFs) selected to represent patients with hip fractures.Ten 4GCFs (Sawbones, Pacific Research Laboratories, Inc., Vashon, WA, USA) were compared to 24 HCFs from seven females and five males >60 years. Proximal femur anthropometric measurements were noted. Strain gauge rosettes were attached and femurs were mounted in a hip simulator applying a combined subject-specific axial load and torque. Baseline measurements of resistance to deformation were recorded. Standardized femoral neck fractures were surgically stabilized before the constructs were subjected to 20,000 load-cycles. An optical motion tracking system measured relative movements.Median (95% CI) head fragment migration was 0.8 mm (0.4 to 1.1) in the 4GCF group versus 2.2 mm (1.5 to 4.6) in the cadaver group (p=0.001). This difference in fracture stability could not be explained by observed differences in femoral anthropometry or potential overloading of 4GCFs. 4GCFs failed with fracture-patterns different from those observed in cadavers.To conclude, standard 4GCFs provide unrealistically stable bone-implant constructs and fail with fractures not observed in cadavers. Until a validated osteopenic or osteoporotic composite femur model is provided, standard 4GCFs should only be used when representing the biomechanical properties of young healthy femurs.     

Fracture risk in the femoral hip region: A finite element analysis supported experimental approach

The decrease of bone mineral density (BMD) is a multifactorial bone pathology, commonly referred to as osteoporosis. The subsequent decline of the bone's micro-structural characteristics renders the human skeletal system, and especially the hip, susceptible to fragility fractures. This study represents a systematic attempt to correlate BMD spectrums to the mechanical strength characteristics of the femoral neck and determine a fracture risk indicator based on non-invasive imaging techniques. The BMD of 30 patients' femurs was measured in vivo by Dual-energy X-ray absorptiometry (DXA). As these patients were subjected to total hip replacement, the mechanical strength properties of their femurs' were determined ex-vivo using uniaxial compression experiments. FEA simulations facilitated the correlation of the DXA measurements to the apparent fracture risk, indicating critical strain values during complex loading scenarios.     

Developmental changes in the responsiveness of rat spiral ganglion neurons to neurotrophic factors in dissociated culture: differential responses for survival, neuritogenesis and neuronal morphology

The way that the development of the inner ear innervation is regulated by various neurotrophic factors and/or their combinations at different postnatal developmental stages remains largely unclear. Moreover, survival and neuritogenesis in deafferented adult neurons is important for cochlear implant function. To address these issues, developmental changes in the responsiveness of postnatal rat spiral ganglion neurons (SGNs) to neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were examined by using a dissociated cell culture system. SGNs at postnatal day (P) 0, P5 and P20 (young adult) were cultured with the addition of NT-3, BDNF, or LIF or of a combination of NT-3 and BDNF (N + B) or of NT-3, BDNF and LIF (ALL factors). SGNs were analyzed for three parameters: survival, longest neurite length (LNL) and neuronal morphology. At P0, SGNs required exposure to N + B or ALL factors for enhanced survival and the ALL factors combination showed a synergistic effect much greater than the sum of the individual factors. At P5, SGNs responded to a wider range of treatment conditions for enhanced survival and combinations showed only an additive improvement over individual factors. The survival percentage of untreated SGNs was highest at P20 but combinations of neurotrophic factors were no more effective than individual factors. LNL of each SGN was enhanced by LIF alone or ALL factors at P0 and P5 but was suppressed by NT-3, BDNF and N + B at P5 in a dose-dependent manner. The LNL at P20 was enhanced by ALL factors and suppressed by N + B. Treatment with ALL factors increased the proportion of SGNs that had two or more primary neurites in all age groups. These findings suggest that NT-3, BDNF, LIF and their combinations predominantly support different ontogenetic events at different developmental stages in the innervation of the inner ear.     

Relevance of osteoporosis in women with fracture of the femoral neck.

A prospective study of fractures of the femoral neck was conducted over 12 months in order to ascertain the relevance of generalised osteoporosis as determined by metacarpal morphometry. A series of some 200 women sustaining a fracture of the femoral neck after minor trauma had bone mass measurements similar to those of a control population of normal women, and 16% were not osteoporotic. A history of previous fractures was documented in one third of the women, but this was unrelated to the presence or severity of osteoporosis, although over half of the fractures had occurred within the previous four years. Trochanteric fractures were seen more commonly in severely osteoporotic women (p less than 0.005), whereas cervical fractures predominated in those who were not osteoporotic. These findings support the hypothesis that postural instability is the major determinant for femoral neck fracture and that generalised osteoporosis, rather than being a prerequisite for fracture, merely determines the type of fracture sustained.     

Overexpression of Bcl-2 or Bcl-xL prevents spiral ganglion neuron death and inhibits neurite growth

Spiral ganglion neurons (SGNs) provide afferent innervation to the cochlea and rely on contact with hair cells (HCs) for their survival. Following deafferentation due to hair cell loss, SGNs gradually die. In a rat culture model, we explored the ability of prosurvival members of the Bcl-2 family of proteins to support the survival and neurite outgrowth of SGNs. We found that overexpression of either Bcl-2 or Bcl-xL significantly increases SGN survival in the absence of neurotrophic factors, establishing that the Bcl-2 pathway is sufficient for SGN cell survival and that SGN deprived of trophic support die by an apoptotic mechanism. However, in contrast to observations in central neurons and PC12 cells where Bcl-2 appears to promote neurite growth, both Bcl-2 and Bcl-xL overexpression dramatically inhibit neurite outgrowth in SGNs. This inhibition of neurite growth by Bcl-2 occurs in nearly all SGNs even in the presence of multiple neurotrophic factors implying that Bcl-2 directly inhibits neurite growth rather than simply rescuing a subpopulation of neurons incapable of extending neurites without additional stimuli. Thus, although overexpression of prosurvival members of the Bcl-2 family prevents SGN loss following trophic factor deprivation, the inhibition of neurite growth by these molecules may limit their efficacy for support of auditory nerve maintenance or regeneration following hair cell loss.     

Femoral strength is better predicted by finite element models than QCT and DXA.

Clinicians and patients would benefit if accurate methods of predicting and monitoring bone strength in-vivo were available. A group of 51 human femurs (age range 21-93; 23 females, 28 males) were evaluated for bone density and geometry using quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). Regional bone density and dimensions obtained from QCT and DXA were used to develop statistical models to predict femoral strength ex vivo. The QCT data also formed the basis of a three-dimensional finite element (FE) models to predict structural stiffness. The femurs were separated into two groups; a model training set (n = 25) was used to develop statistical models to predict ultimate load, and a test set (n = 26) was used to validate these models. The main goal of this study was to test the ability of DXA, QCT and FE techniques to predict fracture load non-invasively, in a simple load configuration which produces predominantly femoral neck fractures. The load configuration simulated the single stance phase portion of normal gait; in 87% of the specimens, clinical appearing sub-capital fractures were produced. The training/test study design provided a tool to validate that the predictive models were reliable when used on specimens with "unknown" strength characteristics. The FE method explained at least 20% more of the variance in strength than the DXA models. Planned refinements of the FE technique are expected to further improve these results. Three-dimensional FE models are a promising method for predicting fracture load, and may be useful in monitoring strength changes in vivo.     

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.     

Mortality and morbidity after hip fractures.

OBJECTIVE--To study the mortality and morbidity associated with proximal femoral fractures with reference to fracture type (intracapsular and extracapsular). DESIGN--Consecutive prospective study with 12 month follow ups. SETTING--Two British trauma receiving centres. PATIENTS--1000 consecutive acute proximal femoral fractures (fractured necks of femur) in 972 patients. RESULTS--Significantly higher mortality at one year was seen in patients with extracapsular fractures (188/490; 38%) than in those with intracapsular fractures (147/510; 29%; p < 0.01). Greater morbidity was experienced during the study period by patients with extracapsular fractures, who were less mobile and less independent at the time of their injury. CONCLUSIONS--The rise in average age of presentation with proximal femoral fracture is associated with a persistently high mortality (33%) and morbidity, greater in patients with an extracapsular fracture. Comparison with other studies, principally from outside Britain, is difficult, but despite advancing standards of care the mortality and morbidity of femoral neck fractures remains high, placing an ever increasing burden on the health service.     

Therapeutic potential of neurotrophins for treatment of hearing loss

Degeneration of spiral ganglion neurons (SGNs) and hair cells in the cochlea induced by aging, injury, ototoxic drugs, acoustic trauma, and various diseases is the major cause of hearing loss. Discovery of growth factors that can either prevent SGN and hair-cell death or stimulate hair-cell regeneration would be of great interest. Studies over the past several years have provided evidence that specific neurotrophins are potent survival factors for SGNs and protect these neurons from ototoxic drugs in vitro and in vivo. Current research focuses more on understanding the mechanism of hair-cell regeneration/differentiation and identification of growth factors that can stimulate hair-cell regeneration. SGNs are required to relay the signal to the central nervous system even when a cochlear implant is used to replace hair-cell function or in the case that cochlear sensory epithelium can be stimulated to regenerate new hair cells successfully. Therefore, neurotrophins may have their therapeutic value in prevention and treatment of hearing impairment.     

Fracture mechanics of the femoral neck in a composite bone model: Effects of platen geometry

Load applicator (platen) geometry used for axial load to failure testing of the femoral neck varies between studies and the biomechanical consequences are unknown. The purpose of this study was to determine if load application with a flat versus a conical platen results in differing fracture mechanics. Femurs were aligned in 25° of adduction and an axial compressive force was applied to the femoral heads at a rate of 6 mm/min until failure. Load application with the conical platen resulted in an average ultimate failure load, stiffness, and energy to failure of 9067 N, 4033 N/mm, and 12.12 J, respectively. Load application with the flat platen resulted in a significant (p<0.05) reduction in ultimate failure load (7620 N) and stiffness (2924 N/mm). Energy to failure (12.30 J) was not significantly different (p=0.893). Different fracture patterns were observed for the two platens and the conical platen produced fractures more similar to clinical observations. Use of a flat platen underestimates the strength and stiffness of the femoral neck and inaccurately predicts the associated fracture pattern. These findings must be considered when interpreting the results of prior biomechanical studies on femoral neck fracture and for the development of future femoral neck fracture models.     

PFN与DHS治疗老年不稳定型股骨粗隆下骨折的疗效分析

目的：比较PFN与DHS内固定治疗老年不稳定型股骨粗隆下骨折的预后及评其疗效。方法：2002年1月至2008年1月我科共收治老年不稳定型股骨粗隆下骨折患者129例,男59例,女70例,年龄51～86岁,平均61．7岁。随机选择PFN或DHS内固定,PFN组62例,DHS组67例。比较两组的手术时间、术中出血量、术后第二天CRP值、张力侧出现骨痂时间、骨折愈合时间、Harris评分等6项指标。结果：116例获得13-48个月的随访,平均18．7月,除手术时间及Harris评分无差异外,PFN组在术中出血量、术后第二天CRP值、张力侧出现骨痂时间、骨折平均愈合时间等方面与DHS组比较有显著优势（P〈0．05）。结论：PFN内固定创伤小、术后并发症率较低,可以成为治疗老年不稳定型股骨粗隆下骨折的主要方法。     

Influence of the change in stem length on the load transfer and bone remodelling for a cemented resurfaced femur

The effect of a short-stem femoral resurfacing component on load transfer and potential failure mechanisms has rarely been studied. The stem length has been reduced by approximately 50% as compared to the current long-stem design. Using 3-D FE models of natural and resurfaced femurs, the study is aimed at investigating the influence of a short-stem resurfacing component on load transfer and bone remodelling. Applied loading conditions include normal walking and stair climbing. The mechanical role of the stem along with implant–cement and stem–bone contact conditions was observed to be crucial. Shortening the stem length to half of the current length (long-stem) led to several favourable effects, even though the stress distributions in the implant and the cement were similar in both the cases. The short-stem implant led not only to a more physiological stress distribution but also to bone apposition (increase of 20–70% bone density) in the superior resurfaced head, when the stem–bone contact prevailed. This also led to a reduction in strain concentration in the cancellous bone around the femoral neck–component junction. The normalised peak strain in this region was lower for the short-stem design as compared to that of the long-stem one, thereby reducing the initial risk of neck fracture. The effect of strain shielding (50–75% reduction) was restricted to a small bone volume underlying the cement, which was approximately half of that of the long-stem design. Consequently, bone resorption was considerably less for the short-stem design. The short-stem design offers better prospects than the long-stem resurfacing component.     

Calpain Inhibitor PD150606 Attenuates Glutamate Induced Spiral Ganglion Neuron Apoptosis through Apoptosis Inducing Factor Pathway In Vitro

Objective

This research aimed to investigate whether glutamate induced spiral ganglion neurons (SGNs) apoptosis through apoptosis inducing factor (AIF) pathway. And verify whether PD150606, a calpain inhibitor could prevent apoptosis by inhibiting cleaving and releasing AIF in mitochondrion.

Methods

SGNs of postnatal days 0-3 were harvested and cultured in dishes. 20 mM Glu, the caspase inhibitor Z-VAD-FMK and calpain inhibitor PD150606 were added into cultured dishes separately. We used optical microscope and immunofluoresence staining to observe cell morphology and AIF distribution, RT-PCR and Westernblot to analyse AIF and calpain expression in SGNs. TUNEL assay was used to test cell apoptosis.

Results

Cell morphology and nuclear translocation of AIF were altered in SGNs by 20 mM Glu treated in vitro. The axon of SGN shortened, more apoptosis SGN were observed and the expression of AIF and calpain were up-regulated in Glu-treated group than the normal one (P<0.05). The same experiments were conducted in 20 mM+PD150606 treated group and 20 mM+Z-VAD-FMK group. Obviously AIF were located from cytoplasm to the nuclear and the expressions of AIF and calpain were down-regulated by PD150606 (P<0.05). Positive cells in TUNEL staining decreased after PD150606 treating. However, Z-VAD-FMK had no influence on AIF, calpain expression or cell apoptosis.

Conclusion

The AIF-related apoptosis pathway is involved in the process of Glu-induced SGN injury. Furthermore, the inhibition of calpain can prevent AIF from releasing the nuclear or inducing SGN apoptosis.