Patrick Chabrand

Fracture following lower limb lengthening in children: a series of 58 patients.

INTRODUCTION Fracture is one of the main complications following external fixator removal used in cases of progressive lower limb lengthening; rates as high as 50% are found in the literature. The aim of this study was to determine the factors influencing this complication. MATERIALS AND METHODS One hundred and eleven cases of lower limb lengthening were performed in 58 patients (40 femurs and 71 tibias). The mean age at surgery was 10.1years old. Lengthening was performed in all cases with an external fixator alone, associated in 39.6% of cases with intramedullary nailing. The patients were divided into three groups according to disease etiology (congenital, achondroplasia and other). The fractures were classified according to the Simpson classification. RESULTS Twenty fractures were recorded (18%). Sixteen fractures were found in patients with congenital disease, four with achondroplasia and none in the group of other etiologies. The fracture was more often in the femur (27.5%) than in the tibia (12.7%). DISCUSSION The rate of fracture is influenced by different factors depending on the etiology of disease. In congenital diseases, the fracture rate is higher when there is lengthening of more than 15% of the initial length and a delay between surgery and the beginning of lengthening of less than 7days. In patients with achondroplasia, the influence of a relative percentage of lengthening is less important than in those with congenital disease. However, to avoid fractures, lengthening should not be started in children under the age of nine. Moreover, lengthening should begin at least 7days after the fixator has been placed. TYPE OF STUDY Retrospective. LEVEL OF EVIDENCE Level IV.

Ratio between mature and immature enzymatic cross-links correlates with post-yield cortical bone behavior: An insight into greenstick fractures of the child fibula

As a determinant of skeletal fragility, the organic matrix is responsible for the post-yield and creep behavior of bone and for its toughness, while the mineral apatite acts on stiffness. Specific to the fibula and ulna in children, greenstick fractures show a plastic in vivo mechanical behavior before bone fracture. During growth, the immature form of collagen enzymatic cross-links gradually decreases, to be replaced by the mature form until adolescence, subsequently remaining constant throughout adult life. However, the link between the cortical bone organic matrix and greenstick fractures in children remains to be explored. Here, we sought to determine: 1) whether plastic bending fractures can occur in vitro, by testing cortical bone samples from childrens fibula and 2) whether the post-yield behavior (ωp plastic energy) of cortical bone before fracture is related to total quantity of the collagen matrix, or to the quantity of mature and immature enzymatic cross-links and the quantity of non-enzymatic cross-links. We used a two-step approach; first, a 3-point microbending device tested 22 fibula machined bone samples from 7 children and 3 elderly adults until fracture. Second, biochemical analysis by HPLC was performed on the sample fragments. When pooling two groups of donors, children and elderly adults, results show a rank correlation between total energy dissipated before fracture and age and a linear correlation between plastic energy dissipated before fracture and ratio of immature/mature cross-links. A collagen matrix with more immature cross-links (i.e. a higher immature/mature cross-link ratio) is more likely to plastically deform before fracture. We conclude that this ratio in the sub-nanostructure of the organic matrix in cortical bone from the fibula may go some way towards explaining the variance in post-yield behavior. From a clinical point of view, therefore, our results provide a potential explanation of the presence of greenstick fractures in children.

Radiographic bone texture analysis is correlated with 3D microarchitecture in the femoral head, and improves the estimation of the femoral neck fracture risk when combined with bone mineral density

PURPOSE Femoral neck fracture is a major public health problem in elderly persons, representing the main source of osteoporosis-related mortality and morbidity. In this study, we aimed at comparing radiographic texture analysis with three-dimensional (3D) microarchitecture in human femurs, and at evaluating whether bone texture analysis improved the assessment of the femoral neck fracture risk other than that obtainable by bone mineral density (BMD). MATERIALS AND METHODS Thirteen osteoporotic femoral heads from patients who fractured their femoral neck and twelve non-fractured femoral heads from osteoarthritic patients were studied using respectively (1) a new high-resolution digital X-ray device (BMA™, D3A Medical Systems) allowing for bone texture analysis with fractal parameter Hmean, and (2) a micro-computed tomograph (CT) for 3D microarchitecture. BMD was measured postoperatively by DXA in all patients in the contralateral femur. RESULTS In these femoral heads, we found that fractal parameter Hmean was correlated with 3D microarchitecture parameters: bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp) and fractal dimension (FD) respectively (p<0.05). Then, fractal parameter Hmean was significantly lower in the femoral heads from the fractured group than from the non-fractured group (p<0.01). Finally, multiple regression analysis showed that combining bone texture analysis and total hip BMD significantly improved the estimation of the femoral neck fracture risk from adjusted r(2)=0.46 to adjusted r(2)=0.67 (p<0.05). CONCLUSION Radiographic bone texture analysis was correlated with 3D microarchitecture parameters in the femoral head, provided accurate discrimination between the femoral heads from the fractured and non-fractured groups, and significantly improved the estimation of the femoral neck fracture risk when combined with BMD.

Computed tomography, histological and ultrasonic measurements of adolescent scoliotic rib hump geometrical and material properties

In Adolescent Idiopathic Scoliosis (AIS), numerical models can enhance orthopaedic or surgical treatments and provide reliable insights into the mechanism of progression. Computational methods require knowledge of relevant parameters, such as the specific geometrical or material properties of the AIS rib, about which there is currently a lack of information. The aim of our study was to determine the geometrical and material properties (Youngs modulus [E] and Poissons ratio [ν]) for AIS rib bones. Twelve ribs extracted during gibbectomy on 15 and 17 year old girls were tested using computed tomography (CT) scanner, histology and ultrasonic scanner. The mean porosity (± standard deviation (SD)) is 1.35 (±0.52)% and the mean (±SD) bone mineral density is 2188 (±19)mmHA/cc. The cortical part of the AIS rib hump is found to be thicker than physiological values in the literature. To mimic the rib hump for an AIS girl, our results suggest that ribs should be modeled as hollow circular cylinders with a 10.40 (±1.02)mm external radius and 7.56mm (±0.75) internal radius, and material properties with a mean E of 14.9GPa (±2.6) and a mean ν of 0.26 (±0.08).

Influence of the optical system and anatomic points on computer-assisted total knee arthroplasty

BACKGROUND For over a decade, computer-assisted orthopaedic surgery for total knee arthroplasty has been accepted as ensuring accurate implant alignment in the coronal plane. HYPOTHESIS We hypothesised that lack of accuracy in skeletal landmark identification during the acquisition phase and/or measurement variability of the infrared optical system may limit the validity of the numerical information used to guide the surgical procedure. METHODS We built a geometric model of a navigation system, with no preoperative image acquisition, to simulate the stages of the acquisition process. Random positions of each optical reflector center and anatomic acquisition point were generated within a sphere of predefined diameter. Based on the virtual geometric model and navigation process, we obtained 30,000 simulations using the Monte Carlo statistical method then computed the variability of the anatomic reference frames used to guide the bone cuts. Rotational variability (α, β, γ) of the femoral and tibial landmarks reflected implant positioning errors in flexion-extension, valgus-varus, and rotation, respectively. RESULTS Taking into account the uncertainties pertaining to the 3D infrared optical measurement system and to anatomic point acquisition, the femoral and tibial landmarks exhibited maximal alpha (flexion-extension), beta (valgus-varus), and gamma (axial rotation) errors of 1.65° (0.9°); 1.51° (0,98°), and 2.37° (3.84°), respectively. Variability of the infrared optical measurement system had no significant influence on femoro-tibial alignment angles. CONCLUSION The results of a Monte Carlo simulation indicate a certain level of vulnerability of navigation systems for guiding position in rotation, contrasting with robustness for guiding sagittal and coronal alignments. LEVEL OF EVIDENCE Level IV.

COMPUTATIONAL MODEL COMBINED WITH IN VITRO EXPERIMENTS TO ANALYSE MECHANOTRANSDUCTION DURING MESENCHYMAL STEM CELL ADHESION

The shape that stem cells reach at the end of adhesion process influences their differentiation. Rearrangement of cytoskeleton and modification of intracellular tension may activate mechanotransduction pathways controlling cell commitment. In the present study, the mechanical signals involved in cell adhesion were computed in in vitro stem cells of different shapes using a single cell model, the so-called Cytoskeleton Divided Medium (CDM) model. In the CDM model, the filamentous cytoskeleton and nucleoskeleton networks were represented as a mechanical system of multiple tensile and compressive interactions between the nodes of a divided medium. The results showed that intracellular tonus, focal adhesion forces as well as nuclear deformation increased with cell spreading. The cell model was also implemented to simulate the adhesion process of a cell that spreads on protein-coated substrate by emitting filopodia and creating new distant focal adhesion points. As a result, the cell model predicted cytoskeleton reorganisation and reinforcement during cell spreading. The present model quantitatively computed the evolution of certain elements of mechanotransduction and may be a powerful tool for understanding cell mechanobiology and designing biomaterials with specific surface properties to control cell adhesion and differentiation.

Radiographical texture analysis improves the prediction of vertebral fracture: an ex vivo biomechanical study.

Study Design. Compression biomechanical tests using fresh cadaveric thoracolumbar motion segments. Objective. The purpose of this study was to determine if the combination of bone texture parameters using bone microarchitecture, and bone mineral density (BMD) measurement by dual-energy x-ray absorptiometry provided a better prediction of vertebral fracture than BMD evaluation alone. Summary of Background Data. Bone strength is routinely evaluated using BMD, as measured by dual-energy x-ray absorptiometry. Currently, there is an ongoing debate about the strengths and limitations of bone densitometry in clinical practice. To assess the fracture risk properly, other factors are important to be taken into account such as the macro- and microarchitecture of the bone. Recently, a new high-resolution x-ray device with direct digitization, named bone microarchitecture (BMA, D3A Medical Systems), has been developed to provide a better precision of texture parameters than those previously obtained on digitized films. Methods. Twenty-seven 3-level thoracolumbar motion segments (T11, T12, L1, and L2, L3, L4) of excised spines, obtained at the Anatomy Department of Marseille, were studied using bone microarchitecture to estimate 3 textural parameters: fractal parameter Hmean, co-occurrence matrix, and run-length matrix, dual-energy x-ray absorptiometry to measure BMD, and mechanical compression tests to failure. All specimens were examined by computed tomography before and after compression. The prediction of the vertebral failure load was evaluated using multiple regression analyses. Results. Twenty-seven vertebral fractures were observed with a mean failure load of 2636.3 N (standard deviation, 996 N). Fractal parameter Hmean, co-occurrence matrix, and run-length matrix were each significantly correlated with BMD (P< 0.01) and bone strength (P< 0.01). Combining bone texture parameters and BMD significantly improved the fracture load prediction from adjusted r2 = 0.701 to adjusted r2 = 0.806 (P< 0.01). Conclusion. In these excised vertebrae, the combination of bone texture parameters with BMD demonstrated a better performance in the failure load prediction than that of BMD alone. Level of Evidence: N/A

Characterisation of the difference in fracture mechanics between children and adult cortical bone

Clinical literature describes a specific type of children bone fracture, known as “greenstick facture” which is never encountered for adult bone. Concerning children bone, there is a tremendous lack of mechanical references. Indeed, the few studies which explored the mechanical characteristics of growing process in bone dealt with samples close to cancerous cells [1], or with samples from cadavers [2]. These studies gave dispersive results and did not provide insights to the two different kinds of fracture (i.e. brittle for mature bone and plastic for growing bone). Part of the answer could lie in the evolution of the biochemical composition of cortical bone; indeed, Bala et al. [3] have shown that the elasticity depends on the mineral part of the bone matrix and the plasticity on the organic part (collagen 1). This organic part of cortical bone seems to differ between adult and children. Saito et al. [4] have shown that the main non enzymatic crosslinks in mature bone (PYD+DPD) are different from those of growing bone (DHLNL+HLNL). It seems to us that the difference between plastic growing bone fractures and brittle adult bone fractures could be explained by this difference in the non enzymatic collagen crosslinking. We performed three point microbending tests on children and adult bone to evaluate the mechanical Young’s modulus (Em) and the plastic strain energy (ωp). The results are in agreement with the clinical observations. The goal of this study is to explain these differences in mechanical behaviour between children and adult bone by using a biochemical analysis of the organic part quantifying the composition of the collagen.

Computational Tension Mapping of Adherent Cells Based on Actin Imaging.

Forces transiting through the cytoskeleton are known to play a role in adherent cell activity. Up to now few approaches haves been able to determine theses intracellular forces. We thus developed a computational mechanical model based on a reconstruction of the cytoskeleton of an adherent cell from fluorescence staining of the actin network and focal adhesions (FA). Our custom made algorithm converted the 2D image of an actin network into a map of contractile interactions inside a 2D node grid, each node representing a group of pixels. We assumed that actin filaments observed under fluorescence microscopy, appear brighter when thicker, we thus presumed that nodes corresponding to pixels with higher actin density were linked by stiffer interactions. This enabled us to create a system of heterogeneous interactions which represent the spatial organization of the contractile actin network. The contractility of this interaction system was then adapted to match the level of force the cell truly exerted on focal adhesions; forces on focal adhesions were estimated from their vinculin expressed size. This enabled the model to compute consistent mechanical forces transiting throughout the cell. After computation, we applied a graphical approach on the original actin image, which enabled us to calculate tension forces throughout the cell, or in a particular region or even in single stress fibers. It also enabled us to study different scenarios which may indicate the mechanical role of other cytoskeletal components such as microtubules. For instance, our results stated that the ratio between intra and extra cellular compression is inversely proportional to intracellular tension.

In silico CDM model sheds light on force transmission in cell from focal adhesions to nucleus

Cell adhesion is crucial for many types of cell, conditioning differentiation, proliferation, and protein synthesis. As a mechanical process, cell adhesion involves forces exerted by the cytoskeleton and transmitted by focal adhesions to extracellular matrix. These forces constitute signals that infer specific biological responses. Therefore, analyzing mechanotransduction during cell adhesion could lead to a better understanding of the mechanobiology of adherent cells. For instance this may explain how, the shape of adherent stem cells influences their differentiation or how the stiffness of the extracellular matrix affects adhesion strength. To assess the mechanical signals involved in cell adhesion, we computed intracellular forces using the Cytoskeleton Divided Medium model in endothelial cells adherent on micropost arrays of different stiffnesses. For each cell, focal adhesion location and forces measured by micropost deflection were used as an input for the model. The cytoskeleton and the nucleoskeleton were computed as systems of multiple tensile and compressive interactions. At the end of computation, the systems respected mechanical equilibrium while exerting the exact same traction force intensities on focal adhesions as the observed cell. The results indicate that not only the level of adhesion forces, but also the shape of the cell has an influence on intracellular tension and on nucleus strain. The combination of experimental micropost technology with the present CDM model constitutes a tool able to estimate the intracellular forces.