Intact Femur Research Articles

Preoperative virtual reduction reduces femoral malrotation in the treatment of bilateral femoral shaft fractures.

In bilateral femoral shaft fractures, significant malrotation (>15°) occurs in about 40 % of cases after intramedullary nailing. Most of the methods that provide rotational control during surgery are based on a comparison to the intact femur and, thus, not applicable for bilateral fractures. In this study, we evaluated if preoperative virtual reduction can help improving rotational alignment in patients with bilateral femoral shaft fractures. Seven patients with bilateral femoral shaft fractures were initially treated with external fixation of both femurs. After obtaining a CT scan of both legs, the fractures were reduced virtually using the software program VoXim®, and the amount and direction of rotational correction were calculated. Subsequently, the patients were treated by antegrade femoral nailing and rotation was corrected to the preoperatively calculated amount. After external fixation, the mean rotational difference between both legs was 15.0° ± 10.2°. Four out of seven patients had a significant malrotation over 15°. Following virtual reduction, the mean rotational difference between both legs was 2.1° ± 1.2°. After intramedullary nailing, no case of malrotation occurred and the mean rotational difference was 6.1° ± 2.8°. Preoperative virtual reduction allows determining the pretraumatic femoral antetorsion and provided useful information for the definitive treatment of bilateral femoral shaft fractures. We believe that this procedure is worth being implemented in the clinical workflow to avoid malrotation after intramedullary nailing.

Bone Health Collaborative Fracture Prevention Platform: New Tools That Will Enable the Rapid Implementation of a Fracture Liaison Service Program Focused on Provider Performance, Quality Improvement, Care Coordination and Community

The phases of fracture healing have been well characterized. However, the exact source and genetic profile of the skeletal progenitors that participate in bone repair is somewhat unclear. Sox9 expression in skeletal elements precedes bone and cartilage formation and a Sox9+ cell type is retained in the adult periosteum. We hypothesized that Sox9+ periosteal cells are multipotent skeletal progenitors normally participating in fracture repair.To test this hypothesis we used tamoxifen (TM)-mediated lineage tracing of Sox9+ cells in Sox9CreErt2:Td-Tomato mice. Intact femora were analyzed with immunostaining and RNA sequencing to evaluate the skeletal distribution and gene expression profile of Td-Tomato positive, Sox9-descendent cells in the adult femur. To assess the role of Td-tomato + cells in the fracture healing process, mice underwent a closed mid-diaphyseal femoral fracture. Fractured hind limbs were analyzed by X-ray, histology and immuno-staining at 3, 9 or 56 days post-fracture.In the intact adult mouse femur, Td-Tomato-labeled cells were observed in the primary spongiosa, periosteum and endosteum. RNA sequencing showed that Td-Tomato positive periosteal cells were co-enriched for Sox9 transcripts, and mRNAs for osteoblast and chondrocyte specific genes. In a femoral fracture model, we showed that pre-labeled Td-Tomato positive descendent cells were mobilized during the early stages of bone repair (day 3 post-op) contributing to the fracture repair process by differentiating into chondrocytes, osteoblasts and osteocytes.A Sox9+ skeletal progenitor population resides in the adult periosteum. Fate tracing studies show that descendants of the Sox9+ periosteal progenitors give rise to chondrocytes, osteoblasts and mature cortical osteocytes in repair of the fractured femur. To our knowledge this is the first report of a reparative Sox9+ progenitor population in the periosteum of the adult long bone. Taken together with developmental studies, our data suggest a broad role for Sox9+ osteochondroprogenitors in development and repair of the mammalian skeleton.

Evaluating the distance between the femoral tunnel centers in anatomic double-bundle anterior cruciate ligament reconstruction using a computer simulation.

PurposeWe aimed to clarify the distance between the anteromedial (AM) bundle and posterolateral (PL) bundle tunnel-aperture centers by simulating the anatomical femoral tunnel placement during double-bundle anterior cruciate ligament reconstruction using 3-D computer-aided design models of the knee, in order to discuss the risk of tunnel overlap. Relationships between the AM to PL center distance, body height, and sex difference were also analyzed.Patients and methodsThe positions of the AM and PL tunnel centers were defined based on previous studies using the quadrant method, and were superimposed anatomically onto the 3-D computer-aided design knee models from 68 intact femurs. The distance between the tunnel centers was measured using the 3-D DICOM software package. The correlation between the AM–PL distance and the subject’s body height was assessed, and a cutoff height value for a higher risk of overlap of the AM and PL tunnel apertures was identified.ResultsThe distance between the AM and PL centers was 10.2±0.6 mm in males and 9.4±0.5 mm in females (P<0.01). The AM–PL center distance demonstrated good correlation with body height in both males (r=0.66, P<0.01) and females (r=0.63, P<0.01). When 9 mm was defined as the critical distance between the tunnel centers to preserve a 2 mm bony bridge between the two tunnels, the cutoff value was calculated to be a height of 160 cm in males and 155 cm in females.ConclusionWhen AM and PL tunnels were placed anatomically in simulated double-bundle anterior cruciate ligament reconstruction, the distance between the two tunnel centers showed a strong positive correlation with body height. In cases with relatively short stature, the AM and PL tunnel apertures are considered to be at a higher risk of overlap when surgeons choose the double-bundle technique.

Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage.

Mechanical factors play a critical role in the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. We undertook this study to test the hypothesis that type VI collagen is necessary for mechanotransduction in articular cartilage by determining the effects of type VI collagen knockout on the activation of the mechano-osmosensitive, calcium-permeable channel TRPV4 (transient receptor potential vanilloid channel 4) as well as on osmotically induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties. Confocal laser scanning microscopy was used to image TRPV4-mediated calcium signaling and osmotically induced cell swelling in intact femora from 2- and 9-month-old wild-type (WT) and type VI collagen-deficient (Col6a1(-/-)) mice. Immunofluorescence-guided atomic force microscopy was used to map PCM mechanical properties based on the presence of perlecan. Hypo-osmotic stress-induced TRPV4-mediated calcium signaling was increased in Col6a1(-/-) mice relative to WT controls at 2 months. Col6a1(-/-) mice exhibited significantly increased osmotically induced cell swelling and decreased PCM moduli relative to WT controls at both ages. In contrast to our original hypothesis, type VI collagen was not required for TRPV4-mediated Ca(2+) signaling; however, knockout of type VI collagen altered the mechanical properties of the PCM, which in turn increased the extent of cell swelling and osmotically induced TRPV4 signaling in an age-dependent manner. These findings emphasize the role of the PCM as a transducer of mechanical and physicochemical signals, and they suggest that alterations in PCM properties, as may occur with aging or osteoarthritis, can influence mechanotransduction via TRPV4 or other ion channels.

Important tips and numbers on using the cortical step and diameter difference sign in assessing femoral rotation – Should we abandon the technique?

Rotational malalignment during femoral nailing is common despite having various intraoperative assessment methods. The cortical step sign and diameter difference sign (CSSDDS) is commonly used because of convenience, yet it lack proper scientific scrutiny and is thought to be error prone.Using a software algorithm, cross-sectional dimensions were obtained from CT scans of 22 intact adult femurs at the proximal, mid and distal diaphysis. With multiple simulated scenarios the sensitivity of CSSDDS was comprehensively determined at all possible C-arm positions.At rotation, cortical width changed most significantly around the thick linea aspera and femoral diameter changed most significantly at the sagittal plane. At 15 degrees of rotation and with the linea aspera in view, CSSDDS thresholds of 0.3mm, 0.6mm and 1mm had sensitivities of 98.8%, 93.1% and 73.8%. With the linea aspera masked behind the femur and out of view, the sensitivities significantly deteriorated to 96.4%, 77.1% and 44.1% respectively.CSSDDS is sufficiently sensitive only when strict rules are followed. It is imperative that the operator position the image intensifier in lateral view under proper magnification so that steps of less than 0.6mm around the linea aspera may be appreciated.

Femoral Neck Anteversion: Estimation in Bones of South Indian Origin and Clinical Significance

ObjectiveTo determine the average angle of Femoral Neck Anteversion (FNA) in bones of South Indian population.Methods: One hundred and fifty intact dry femur bones belonging to 78 males (63 Right &amp; 15 Left) and 72 females (36 Right and 36 Left) were chosen for the study. The FNA, angle between a transverse line that passes through bicondylar plane of the distal end of femur and an imaginary line passing through the center of femoral head and neck were evaluated by Kingsley Olmsted method and the results statistically analyzed.Results: The mean FNA of the bones observed was 12.860+ 7.380. The mean measurements in the male and female bones was 14.110+ 6.190 and 11.50+ 8.320. It was observed that in 58% of bones the FNA was 11‐200, in 24% it was 0‐ 100, in 12% it was 21‐ 300 and in 9% bones the femoral neck was retroverted.ConclusionThe cause for variation in measurement of FNA can be multifactorial and has important implications in arthroplasties and evaluation of pathology of hip. The values of the present study add to the data on FNA as it is known to increase in conditions like Perthe's disease, cerebral palsy, postural defects etc and is known to decrease in toing out and rickety chondrodystrophy.

Synchronization of calcium sulphate cement degradation and new bone formation is improved by external mechanical regulation.

A major challenge faced in the bone materials of weight-bearing without internal fixture support is the mismatch of material degradation and new bone formation, leading to weakening or even failure of the overall bony structure. This study demonstrated in the rat femur model that calcium sulphate cement degradation and new bone formation could be better synchronized by external mechanical force. An ascending force in line with calcium sulphate cement degradation could achieve bone healing in 37 days with ultimate load to failure of 87.00 ± 7.30 N, similar to that of intact femur (80.46 ± 2.79 N, p = 0.369). In contrast, the healing process under either a constant force or no force illustrated significant residual defect volumes of 1.47 ± 0.44 and 4.08 ± 0.89 mm(3) (p < 0.001), and weaker ultimate loads to failure of 69.56 ± 4.74 and 59.17 ± 7.48 N, respectively (p < 0.001). Our results suggest that the mechanical regulation approach deserves further investigation and may potentially offer a clinical strategy to improve synchronization.

A Biomechanical Comparison of Two Intramedullary Implants for Subtrochanteric Fracture in Two Healing Stages: A Finite Element Analysis.

Background. The biomechanical effect of two implants, namely, proximal femoral nail antirotation for Asia (PFNA-II) and Expert Asian Femoral Nail (A2FN), for treating subtrochanteric fracture during healing stages, is still unclear. Methods. A 3D finite element model of an intact femur was constructed and validated. The fractured and postoperative models were accordingly produced. The postoperative models were loaded with the peak joint forces during gait for the soft and hard callus stages. The effects of stress distribution on the implants, femoral head and callus, and the deformation of the proximal femur were examined. Results. Both implants showed similar biomechanical effect in two healing stages. As the healing duration increased, the von Mises stress of two implants and the tensile stress of the femoral head decreased, whereas the compressive stress of the femoral head increased. However, the PFNA-II operation resulted in higher stress on the implant, lower stress on the proximal femur, and lower compressive stress and higher tensile stress on the callus than A2FN operation. Conclusions. The A2FN implant may provide a biomechanically superior construct for subtrochanteric fracture healing. However, the upper screw of the A2FN implant may be more likely to be loose in the healing process.

Fracture healing in mice lacking Pten in osteoblasts: a micro-computed tomography image-based analysis of the mechanical properties of the femur

In the United States, approximately eight million osseous fractures are reported annually, of which 5–10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks increased in femurs from Pten osteoblast conditional knock-out mice (Pten-CKO) compared to wild-type mice (WT) of the same genetic strain as measured by an increase in mechanical stiffness and failure load in four-point bending tests. Preceding mechanical testing, each femur was imaged using a Skyscan 1172 micro-computed tomography (μCT) scanner (Skyscan, Kontich, Belgium). The present study used µCT image-based analysis to test the hypothesis that the increased femoral fracture force and stiffness in Pten-CKO were due to greater section properties with the same effective material properties as that of the WT. The second moment of area and section modulus were computed in ImageJ 1.46 (National Institutes of Health) and used to predict the effective flexural modulus and the stress at failure for fourteen pairs of intact and callus WT and twelve pairs of intact and callus Pten-CKO femurs. For callus and intact femurs, the failure stress and tissue mineral density of the Pten-CKO and WT were not different; however, the section properties of the Pten-CKO were more than twice as large 28 days post-fracture. It was therefore concluded, when the gene Pten was conditionally knocked-out in osteoblasts, the resulting increased bending stiffness and force to fracture were due to increased section properties.

On optimization of a composite bone plate using the selective stress shielding approach

Bone fracture plates are used to stabilize fractures while allowing for adequate compressive force on the fracture ends. Yet the high stiffness of conventional bone plates significantly reduces compression at the fracture site, and can lead to subsequent bone loss upon healing. Fibre-reinforced composite bone plates have been introduced to address this drawback. However, no studies have optimized their configurations to fulfill the requirements of proper healing. In the present study, classical laminate theory and the finite element method were employed for optimization of a composite bone plate. A hybrid composite made of carbon fibre/epoxy with a flax/epoxy core, which was introduced previously, was optimized by varying the laminate stacking sequence and the contribution of each material, in order to minimize the axial stiffness and maximize the torsional stiffness for a given range of bending stiffness. The initial 14×414 possible configurations were reduced to 13 after applying various design criteria. A comprehensive finite element model, validated against a previous experimental study, was used to evaluate the mechanical performance of each composite configuration in terms of its fracture stability, load sharing, and strength in transverse and oblique Vancouver B1 fracture configurations at immediately post-operative, post-operative, and healed bone stages. It was found that a carbon fibre/epoxy plate with an axial stiffness of 4.6MN, and bending and torsional stiffness of 13 and 14N·m2, respectively, showed an overall superiority compared with other laminate configurations. It increased the compressive force at the fracture site up to 14% when compared to a conventional metallic plate, and maintained fracture stability by ensuring the fracture fragments’ relative motions were comparable to those found during metallic plate fixation. The healed stage results revealed that implantation of the titanium plate caused a 40.3% reduction in bone stiffness, while the composite plate lowered the stiffness by 32.9% as compared to the intact femur. This study proposed a number of guidelines for the design of composite bone plates. The findings suggest that a composite bone plate could be customized to allow for moderate compressive force on the fracture ends, while remaining relatively rigid in bending and torsion and strong enough to withstand external loads when a fracture gap is present. The results indicate that the proposed composite bone plate could be a potential candidate for bone fracture plate applications.

Systemic administration of sclerostin monoclonal antibody accelerates fracture healing in the femoral osteotomy model of young rats.

Genetic studies have demonstrated that sclerostin was a key negative regulator of bone formation. Sclerostin monoclonal antibody (Scl-Ab) treatment enhanced bone healing in experimental fracture healing. The purpose was to investigate the effects of systemic Scl-Ab administration on open fracture healing in young rats. Unilateral femoral fractures were generated in eight-week-old Sprague-Dawley rats. Rats were treated with vehicle or Scl-Ab for 6weeks. Fracture healing was evaluated by western blotting, immunohistochemistry, histology, radiography, micro-CT, and biomechanical testing. In addition, the bone mass of intact femur was also evaluated by micro-CT. The results showed that, at 1 and 2weeks after fracture, proliferating cell nuclear antigen (PCNA) score and bone morphogenetic protein-2 (BMP-2) expression in the Scl-Ab group were significantly increased compared with the control group. A decrease in cartilage in the Scl-Ab group was also observed after fracture, and this was accompanied by more rapider fracture healing. At 4 and 6weeks, there were significant increases in bone mass and mechanical properties in the calluses from Scl-Ab group compared with control group. In addition, Scl-Ab treatment also showed significant anabolic effects in intact femur. In conclusion, systemic Scl-Ab administration has a significant enhancement in a rat femoral osteotomy model. These results support the therapeutic potential of Scl-Ab as a noninvasive strategy to enhance open fracture healing.

Effects of stemmed and nonstemmed hip replacement on stress distribution of proximal femur and implant.

BackgroundDespite improvements in shape, material, and coating for hip stem, both stress shielding and aseptic loosening have been the major drawbacks of stemmed hip arthroplasty. Some nonstemmed systems were developed to avoid rasping off the intramedullary canal and evacuating the bone marrow due to stem insertion.MethodsIn this study, the finite-element models of one intact, one stemmed, and two nonstemmed femora with minimal removal of the healthy neck were investigated to evaluate their biomechanical effects. The resurfacing (ball-shaped) and fitting (neck-shaped) systems were respectively selected as the representative of the ready- and custom-made nonstemmed implants. The stress distribution and interface micromotion were selected as the comparison indices.ResultsThe results showed that stress distributions of the two nonstemmed femora are consistently more similar to the intact femur than the stemmed one. Around the proximal femur, the stem definitely induces the stress-shielding phenomenon of its counterparts. The fitting system with the anatomy-shaped cup can make intimate contact with the neck cortex and reduce the bone-cup micromotion and the implant stress. Comparatively, the reamed femoral head provides weaker support to the resurfacing cup causing higher interfacial micromotion.ConclusionsThe reserved femoral neck could act as the load-transferring medium from the acetabular cup, femoral neck, to the diaphysial bone, thus depressing the stress-shielding effect below the neck region. If the hip-cup construct can be definitely stabilized, the nonstemmed design could be an alternative of hip arthroplasty for the younger or the specific patients with the disease limited only to the femoral head.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-312) contains supplementary material, which is available to authorized users.

Mechanical properties and in vivo performance of load-bearing fiber-reinforced composite intramedullary nails with improved torsional strength

Fiber-reinforced composites (FRC) could be feasible materials for fracture fixation devices if the mechanical properties of the composites are congruent with the local structural properties of bone. In a recently developed FRC implant, bisphenol A dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) resin was reinforced with unidirectional E-glass fibers. The addition of a braided glass fiber sleeving to the unidirectional fibers increased the torsional strength (99.5MPa) of the FRC implants at the expense of the flexural strength (602.0MPa). The flexural modulus was 15.3GPa. Two types of FRC intramedullary nails were prepared; first type was FRC as such, second type was FRC with a surface layer of bioactive glass (BG) granules. Experimental oblong subtrochanteric defect was created in 14 rabbits. The defect, which reduced the torsional strength of the bones by 66%, was fixed with an FRC intramedullary nail of either type. The contralateral intact femur served as the control. This model simulated surgical stabilization of bone metastasis. After 12 weeks of follow-up, the femurs were harvested and analyzed by torsional testing, micro-CT and hard tissue histology. Healed undisplaced peri-implant fractures were noticed in half of the animals irrespective of the type of FRC implant. Torsional testing showed no significant differences between the implantation groups. The torsional strength of the bones stabilized by either type of FRC implant was 83% of that of the contralateral femurs. In histological analysis, no implant debris and no adverse tissue reactions were observed. While the mechanical properties of the modified FRCs were suboptimal, the FRC intramedullary nails supported the femurs without structural failure, even in the cases of peri-implant fractures.

Biomechanical assessment of composite versus metallic intramedullary nailing system in femoral shaft fractures: A finite element study

BackgroundIntramedullary nails are the primary choice for treating long bone fractures. However, complications following nail surgery including non-union, delayed union, and fracture of the bone or the implant still exist. Reducing nail stiffness while still maintaining sufficient stability seems to be the ideal solution to overcome the abovementioned complications. MethodsIn this study, a new hybrid concept for nails made of carbon fibers/flax/epoxy was developed in order to reduce stress shielding. The mechanical performance of this new implant in terms of fracture stability and load sharing was assessed using a comprehensive non-linear FE model. This model considers several mechanical factors in nine fracture configurations at immediately post-operative, and in the healed bone stages. ResultsPost-operative results showed that the hybrid composite nail increases the average normal force at the fracture site by 319.23N (P<0.05), and the mean stress in the vicinity of fracture by 2.11MPa (P<0.05) at 45% gait cycle, while only 0.33mm and 0.39mm (P<0.05) increases in the fracture opening and the fragments' shear movement were observed. The healed bone results revealed that implantation of the titanium nail caused 20.2% reduction in bone stiffness, while the composite nail lowered the stiffness by 11.8% as compared to an intact femur. InterpretationOur results suggest that the composite nail can provide a preferred mechanical environment for healing, particularly in transverse shaft fractures. This may help bioengineers better understand the biomechanics of fracture healing, and aid in the design of effective implants.

Ultrasound backscatter measurements of intact human proximal femurs—Relationships of ultrasound parameters with tissue structure and mineral density

Ultrasound reflection and backscatter parameters are related to the mechanical and structural properties of bone in vitro. However, the potential of ultrasound reflection and backscatter measurements has not been tested with intact human proximal femurs ex vivo. We hypothesize that ultrasound backscatter can be measured from intact femurs and that the measured backscattered signal is associated with cadaver age, bone mineral density (BMD) and trabecular bone microstructure. In this study, human femoral bones of 16 male cadavers (47.0±16.1years, range: 21–77years) were investigated using pulse-echo ultrasound measurements at the femoral neck in the antero-posterior direction and at the trochanter major in the anteroposterior and lateromedial directions. Recently introduced ultrasound backscatter parameters, independent of cortical thickness, e.g., time slope of apparent integrated backscatter (TSAB) and mean of the backscatter difference technique (MBD) were obtained and compared with the structural properties of trabecular bone samples, extracted from the locations of ultrasound measurements. Moreover, more conventional backscatter parameters, e.g., apparent integrated backscatter (AIB) and frequency slope of apparent integrated backscatter (FSAB) were analyzed. Bone mineral density of the intact femurs was evaluated using dual energy X-ray absorptiometry (DXA). AIB and MDB measured from the femoral neck correlated significantly (p<0.01) with the neck BMD (R2=0.44 and 0.45), cadaver age (R2=0.61 and 0.41) and several structural parameters, e.g., bone volume fraction (R2=0.33 and 0.39, p<0.05 and p<0.01), respectively. To conclude, ultrasound backscatter parameters, measured from intact proximal femurs, are significantly related (p<0.05) to structural properties and mineral density of trabecular bone.

Bone regeneration is not affected by medullary canal size in four different mouse strains after marrow ablation (922.16)

It is well established that mouse strains exhibit different bone phenotypes, however, there is limited data on intramembranous bone regeneration post‐injury challenge in different mouse strains. Here, we determined if intramembranous bone regeneration differed in four wild‐type inbred mouse strains in response to marrow ablation and if bone geometry (medullary canal size) impacted the bone regeneration response. Mechanical femur ablation was performed in 27‐33 week old females of four mouse strains (FVB/N, C3H/He, C57Bl/6, BALB/C). Animals were euthanized 3 weeks post‐ablation; all bone within the medullary canal of the ablated and intact femurs as well as medullary area at the midshaft of the intact femur was analyzed by µCT. In ablated femurs, mean BV/TV showed clear quantitative differences among the four strains (p = 0.002, 1‐way ANOVA). FVB/N (p = 0.007) and C3H/He (p = 0.002) mice had approximately a 4‐fold increase in BV/TV compared to BALB/C mice. Medullary area varied among the four strains (p &lt; 0.001, 1‐way ANOVA). The BV/TV of the regenerated bone was not correlated with the size of the medullary canal. Our results suggest that genetic differences among mouse strains contribute to the bone regeneration response independent of bone geometry. We identified relatively good (FVB/N and C3H) and poor (BALB/C) bone regeneration mouse strains. This differential bone regenerative response to injury was not affected by bone geometry, specifically medullary canal size.

The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness

Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4−/− littermates at 8 and 20weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4−/− mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4−/− mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness.

Computerized Navigation for Length and Rotation Control in Femoral Fractures

Operative treatment of femoral fractures yields a predictably high union rate, but residual malrotation and leg length discrepancy remain a clinically significant problem. The aim of this study was to determine the safety and efficacy of using computerized navigation in controlling the length and rotation in femoral fracture surgery. Prospective consecutive case series of 16 skeletally mature patients with femoral fractures undergoing surgical fixation; 14 were fixed with intramedullary nails and 2 with plates. An Academic Level I trauma center. Computerized navigation was used to determine the length and rotation of the operated extremity as compared with the intact healthy contralateral side. All patients underwent postoperative computed tomography scanogram for determining the length and rotation. All fractures healed. Mean rotational difference between the treated and nontreated sides was 3.45 degrees (range, 0-7.7 degrees). Mean length difference between the 2 extremities as calculated by the computed tomography scan was 5.83 mm (range, 0-13 mm). Additional operative time required for computerized navigation was measured in 2 of the cases and totaled ∼30-35 min/case. Computerized navigation was accurate and precise at restoring femoral length and rotation during femoral fracture fixation when the intact contralateral femur was used for reference. Further, large-scale randomized studies are required. Additionally, improvements aimed at decreasing operative time and improving user interface of these systems are recommended. Therapeutic level IV. See instructions for authors for a complete description of the levels of evidence.

Integrin α1β1 participates in chondrocyte transduction of osmotic stress

Background/purposeThe goal of this study was to determine the role of the collagen binding receptor integrin α1β1 in regulating osmotically induced [Ca2+]i transients in chondrocytes. MethodThe [Ca2+]i transient response of chondrocytes to osmotic stress was measured using real-time confocal microscopy. Chondrocytes from wildtype and integrin α1-null mice were imaged ex vivo (in the cartilage of intact murine femora) and in vitro (isolated from the matrix, attached to glass coverslips). Immunocytochemistry was performed to detect the presence of the osmosensor, transient receptor potential vanilloid-4 (TRPV4), and the agonist GSK1016790A (GSK101) was used to test for its functionality on chondrocytes from wildtype and integrin α1-null mice. Results/interpretationDeletion of the integrin α1 subunit inhibited the ability of chondrocytes to respond to a hypo-osmotic stress with [Ca2+]i transients ex vivo and in vitro. The percentage of chondrocytes responding ex vivo was smaller than in vitro and of the cells that responded, more single [Ca2+]i transients were observed ex vivo compared to in vitro. Immunocytochemistry confirmed the presence of TRPV4 on wildtype and integrin α1-null chondrocytes, however application of GSK101 revealed that TRPV4 could be activated on wildtype but not integrin α1-null chondrocytes. Integrin α1β1 is a key participant in chondrocyte transduction of a hypo-osmotic stress. Furthermore, the mechanism by which integrin α1β1 influences osmotransduction is independent of matrix binding, but likely dependent on the chondrocyte osmosensor TRPV4.

Biomechanical analysis of impending femoral neck fractures: The role of percutaneous cement augmentation for osteolytic lesions

BackgroundManagement of impending pathologic femoral neck fractures includes internal fixation, arthroplasty and megaprostheses. The study aim was to determine the augmentative effect of cement injection for minimally invasive treatment of femoral neck lesions. MethodsTwenty-seven cadaveric femora received a simulated osteolytic lesion previously shown to decrease the femur's failure load by 50%. Specimens were allocated to three groups of nine and loaded to failure in simulated single-leg stance: (1) percutaneous cementation + internal fixation (PCIF); (2) percutaneous cementation (PC); and (3) internal fixation (IF). Lesion-only and augmented finite element models were virtually loaded and stresses were queried adjacent to the lesion. FindingsPCIF resulted in the largest failure load though the increase was not significantly greater than the PC or IF groups. Inspection of the PC and PCIF specimens indicated that the generation of a cement column that spanned the superior and inferior cortices of the femoral neck increased failure loads significantly. Finite element analysis indicated that IF and PCIF constructs decreased the stress adjacent to the lesion to intact femur levels. Cementation without superior-to-inferior femoral neck cortical contact did not restore proximal femoral stress toward the intact condition. InterpretationInternal fixation alone and internal fixation with or without cementation produce similar levels of mechanical augmentation in femora containing a high-risk lesion of impending fracture. A cement injection technique that produces a cement column contacting the superior and inferior femoral neck cortices confers the highest degree of biomechanical stability, should percutaneous cementation alone be performed.