Intact Femur Research Articles

Evidence for Overgrowth after Midfemoral Fracture via Increased RNA for Mitosis

Middiaphyseal femoral fractures in children and young rats stimulate linear femoral growth, a phenomenon commonly attributed to increased vascularity. To test for changes in mRNA expression of genes related to blood vessels, nerve fibers, cartilage, bone, and cell metabolism, we measured mRNA gene expression for all known rat genes in the physis at various times after diaphyseal fracture. Female Sprague-Dawley rats, 4 weeks of age at surgery, were subjected to a unilateral, simple, transverse, middiaphyseal femoral fracture stabilized with an intramedullary rod. At 0 (intact), 0.1, 0.4, 1, 2, 3, 4, and 6 weeks after fracture, the femoral head with the proximal physis was collected from fractured and intact femora. The RNA was extracted, processed to biotinlabeled cRNA, and hybridized to Affymetrix Rat 230 2.0 GeneChip microarrays. Transcripts from fracture-induced lengthening of the injured femora were compared to those of the intact contralateral femur. In the proximal physis, transcripts related to blood vessels and cartilage formation were down-regulated by fracture. Transcripts related to bone remodeling, nerve axon elongation, cell division, and protein synthesis were up-regulated by fracture. The data support increased mitotic activity in the physis after a midshaft fracture and not increased vascularity.

High Concentrations of Pamidronate in Bone Weaken the Mechanical Properties of Intact Femora in a Rat Model

PurposeBisphosphonates have been used to treat osteoporosis for more than ten years. However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture or osteonecrosis of the jaw, have been recently reported in the literature. We investigated the relationships among the mechanical properties of the intact rat femur as well as healing fracture calluses and the intraosseous concentration of pamidronate (ICP), after long-term administration of pamidronate in a rat osteoporosis model.Materials and MethodsWe performed bilateral ovariectomy in 25 3-month-old female Sprague-Dawley rats. Beginning three months after ovariectomy, disodium pamidronate (0.5mg/kg) was injected every month. After the six-month administration period, the left femoral shaft was fractured using the closed fracture technique. Five weeks after fracture, 23 rats were euthanized and both femora were removed. We checked the mechanical properties of the intact (right) and fractured (left) femora using a three-point bending technique. Intraosseous concentration of pamidronate was checked by high-performance liquid chromatography.ResultsThe mean ICP was 61.8 ± 15.7ng/mg of bone. High ICP decreased the ultimate load to failure, stiffness, and ultimate stress of the intact femora (p = 0.015, 0.027, 0.039, respectively). There was a tendency to decrease the ultimate load to failure in the healing callus when the ICP increased (p = 0.183). High ICP decreased the bone mineral density of the femoral head (p = 0.005).ConclusionHigh concentrations of pamidronate in intact bone decreased the bone mineral density and weakened the mechanical strength of the rat femora. The mechanical strength of the early healing callus was not correlated with concentration of pamidronate in the bone.

Experimental validation of intact and implanted distal femur finite element models

Four finite element (FE) models of intact and distal femur of knee replacements were validated relative to measured bone strains. FE models of linear tetrahedrons were used. Femoral replacements with cemented stemless, cemented and noncemented femoral stems of the PFC Sigma Modular Knee System were analyzed. Bone strains were recorded at ten locations on the cortex. The magnitude of the FE bone strains corresponded to the mean measured strains, with an overall agreement of 10%. Linear regression between the FE and mean experimental strains produced slopes between 0.94 and 1.06 and R 2 values between 0.92 and 0.99. RSME values were less than 12%. The FE models were able to adequately replicate the mechanical behavior of distal femur reconstructions.

Structural Bone Allograft Combined with Genetically Engineered Mesenchymal Stem Cells as a Novel Platform for Bone Tissue Engineering

The presence of live periosteal progenitor cells on the surface of bone autografts confers better healing than devitalized allograft. We have previously demonstrated in a murine 4 mm segmental femoral bone-grafting model that live periosteum produces robust endochondral and intramembraneous bone formation that is essential for effective healing and neovascularization of structural bone grafts. To the end of engineering a live pseudo-periosteum that could induce a similar response onto devitalized bone allograft, we seeded a mesenchymal stem cell line stably transfected with human bone morphogenic protein-2/beta-galactosidase (C9) onto devitalized bone allografts or onto a membranous small intestinal submucosa scaffold that was wrapped around the allograft. Histology showed that C9-coated allografts displayed early cartilaginous tissue formation at day 7. By 6 and 9 weeks, a new cortical shell was found bridging the segmental defect that united the host bones. Biomechanical testing showed that C9-coated allografts displayed torsional strength and stiffness equivalent to intact femurs at 6 weeks and superior to live isografts at 9 weeks. Volumetric and histomorphometric micro-computed tomography analyses demonstrated a 2-fold increase in new bone formation around C9-coated allografts, which resulted in a substantial increase in polar moment of inertia (pMOI) due to the formation of new cortical shell around the allografts. Positive correlations between biomechanics and new bone volume and pMOI were found, suggesting that the biomechanical function of the grafted femur relates to both morphological parameters. C9-coated allograft also exhibited slower resorption of the graft cortex at 9 weeks than live isograft. Both new bone formation and the persistent allograft likely contributed to the improved biomechanics of C9-coated allograft. Taken together, we propose a novel strategy to combine structural bone allograft with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering.

Bildwandlergestützte Vermeidung einer Torsionsabweichung zur Gegenseite bei der Oberschenkelmarknagelung

The problem of preventing malrotation after closed intramedullary nailing of femoral shaft fractures has not been solved yet. As clinical tests and radiologic criteria for intraoperative use provide little accuracy, the theoretical basis for a C-arm-based measurement of the femoral antetorsion was analysed. The directions of femoral neck axis and condylar axis can be identified by the radiologic views "knee joint, lateral view" and "hip joint, axial view". The rotation of the C-arm in relation to a horizontal axis to achieve these views can be measured in degrees. Theoretically, the difference between these rotation angles could be used to calculate the antetorsion. Intact plastic femora (Sawbone) and a femoral shaft fracture model were used to research optical and geometrical phenomena that influence a direct measuring technique. Several geometrical phenomena were observed, making direct measurement with arithmetic corrective factors not recommendable. For practical reasons, a data table was created, correlating the difference between the two C-arm angles with true antetorsion. In an interobserver trial with 18 trauma surgeons, the method proved to achieve high accuracy with a maximum interobserver variation of 5 degrees. The method is easily reproducible, reliable and can be recommended to every surgeon. Due to the wide range of physiological antetorsion angles in different individuals, fair results can be expected controlling the rotation with standard value tables, and excellent results can be expected using bilateral measurement.

Genetic network and pathway analysis of differentially expressed proteins during critical cellular events in fracture repair

Bone repair consists of inflammation, intramembranous ossification, chondrogenesis, endochondral ossification, and remodeling. To better understand the translational regulation of these distinct but interrelated cellular events, we used the second generation of BD Clontechtrade mark Antibody Microarray to dissect and functionally characterize proteins differentially expressed between intact and fractured rat femur at each of these cellular events. Genetic network analysis showed that proteins differentially expressed within a given cellular event tend to be physically or functionally correlated. Seventeen such interacting networks were established over five cellular events that were most frequently associated with cell cycle, cell death, cell-to-cell signaling and interaction, and cell growth and proliferation. Eighteen molecular pathways were significantly enriched during the bone repair process, of which ERK/MAPK, NF-kB, PDGF, and T-cell receptor signaling pathways were significant during three or more cellular events. The analyses revealed dynamic temporal expression patterns and cellular-event-specific functions. The inflammation event on Day 1 was characteristic of the cell cycle-related molecular changes. The relative quiet stage of intramembranous ossification on Day 4 and the molecularly most active stage of chondrogenesis on Day 7 were featured by coordinated cell death and cell-proliferation signals. Endochondral ossification on Day 14 experienced a clear transition from the molecular/cellular function to the physiological system development/function. The osteoclast-mediated remodeling on Day 28 was highlighted by the integrin signaling pathway. The distinct changes in protein expression during these cellular events provide a molecular basis for developing cellular event-targeted therapeutic strategy to accelerate bone healing.

Feasibility of a percutaneous technique for repairing proximal femora with simulated metastatic lesions

Fracture of the proximal femur due to metastatic disease is a significant cause of morbidity and mortality among breast cancer patients. Prophylactic surgical fixation is advised for patients at risk of fracture and typically involves placement of an orthopaedic implant. We propose that some proximal femora with metastases can be repaired by removing the lesion and filling the resulting defect with bone cement (polymethylmethacrylate), a procedure that could be performed percutaneously without the use of hardware. We studied the strengths of 12 matched pairs of cadaveric proximal femora under single-limb stance loading. One femur from each pair remained intact, while a simulated metastatic lesion, measuring approximately 75% of the neck diameter, was burred into the neck of the contralateral femur. The defects were repaired using a procedure similar to the one proposed. Femoral strength was measured via mechanical testing to failure. The strengths of the repaired femora averaged 94.7% of the strength of their respective contralateral intact femur (standard deviation, 8.7%). These findings suggest that the proposed procedure may be useful for some patients with metastases in the femoral neck. If the proximal femur could be safely repaired using the proposed technique in place of conventional surgical fixation, the patient would benefit from a shorter and less invasive surgical procedure, less pain and discomfort, greatly reduced recovery time, and a shorter hospital stay—all at a much lower cost.

The effect of necrotic lesion size and rotational degree on the stress reduction in transtrochanteric rotational osteotomy for femoral head osteonecrosis – a three-dimensional finite-element simulation

The prospect for success in the efficacy of osteotomy for precollapse stage of femoral head osteonecrosis depends on the ability to predict reliably the stress changes derived from specific osteotomies. A three-dimensional finite-element analysis was thus designed to compute necrotic femoral head stress changes with different extent of necrocrosis that accompany anterior or posterior rotational osteotomies. Computed tomography images of a standard composite femur were used to create the three-dimensional finite-element intact femur model. Based on the intact model, 27 models simulating three different levels of necrotic region together with nine different rotational osteotomies were created. The von Mises stress distributions of each model were analyzed and compared for a loading condition simulating single-legged stance. (1) The stress reduction in anterior rotational osteotomy is more effective as compared to that of the posterior rotational osteotomy for various necrotic lesion sizes. (2) Von Mises stress on the necrotic zone decreased with increasing rotational angle. The decreasing rate was higher for the femoral head with a narrow lesion. (3) Femoral head with a wider necrotic lesion had a higher risk for developing collapse due to high local stress on the surface of necrotic region; whereas the necrotic region tended to expand in size instead of collapse for femoral head with a narrow lesion due to high local stress on the interface between necrotic region and healthy bone. Transtrochanteric rotational osteotomy is a technically demanding procedure and associated with high complication risks, a more scrupulous planning including the finite-element analysis should be considered before doing surgery in clinical subjects.

Bone remodelling inside a cemented resurfaced femoral head

Although the short-term performance of modern resurfacing hip arthroplasty is impressive, the long-term performance is still unknown. It is hypothesised that bone remodelling and the resulting changes in stress/strain distribution within the resurfaced femur influence the risk of fixation failure. Three-dimensional finite element models and adaptive bone remodelling algorithms have been used to predict long-term changes in bone density following cemented femoral head resurfacing. Applied loading conditions include normal walking and stair climbing. The remodelling simulation was validated by comparing the results of an analysis of a proximal femur implanted with a Charnley femoral component with known clinical data in terms of bone density adaptations. Resurfacing caused a reduction of strain of 20-70% in the bone underlying the implant as compared to the intact femur, immediately post operative. Elevated strains, ranging between 0.50 and 0.80% strain, were generated post-operatively around the proximal femoral neck regions, indicating a potential risk of neck fracture. However, this strain concentration was considerably reduced after bone remodelling. After remodelling, bone resorption of 60-90% was observed in the bone underlying the implant. Reduction in bone density of 5-47% occurred in the lateral femoral head. Bone apposition was observed in the proximal-medial cortex, around the inferior edge of the implant. Hardly any changes in bone density occurred in the distal neck or the femoral diaphysis. Although resurfacing has produced encouraging clinical results, bone remodelling within the femoral head might be a concern for long-term fixation. Regions of strain concentration at the head-neck junction, which may increase the initial risk of femoral neck fracture, are reduced with bone remodelling. In order to reduce this risk of femoral neck fracture, patients should avoid activities which induce high loading of the hip during the early rehabilitation period after surgery.

Tetrahedral versus hexahedral finite elements in numerical modelling of the proximal femur

The objective of this study was to evaluate and compare tetrahedral and hexahedral finite element meshes of simplified and realistic proximal intact femur geometries. Theoretical expressions of stresses and strains were derived for the simplified model of the femur. For the analysis of the realistic geometry of the proximal femur, a CAD model of the third generation composite femur (Pacific Research Labs, Vashion Island, WA) was used and simulations were performed with Hyperworks ® (Altair Engineering, Inc., Troy, MI) finite element analysis software. Convergence tests with hexahedral (8- and 20-node brick-elements) and tetrahedral (4- and 10-node tetrahedrons) elements were analysed by comparing the periosteal von Mises stresses and principal strains at a selected point of the femur. The numerical periosteal strains were also compared with experimental ones to determine the accuracy of the finite elements. Overall, we concluded, for the simplified femur, that tetrahedral linear element allowed results more closely to theoretical ones, but hexahedral quadratic elements seem to be more stable and less influenced to the degree of refinement (NDOF) of the mesh. It was not possible to correlate these findings with those observed for the realistic proximal femur simulations where no significant differences were seen using refined meshes, with more than NDOF = 20 000 for hexahedral elements.

DIRECT PERCUTANEOUS GENE DELIVERY TO ENHANCE HEALING OF SEGMENTAL BONE DEFECTS

Background: Healing of segmental bone defects can be induced experimentally with genetically modified osteoprogenitor cells, an ex vivo strategy that requires two operative interventions and substantial cost. Direct transfer of osteogenic genes offers an alternative, clinically expeditious, cost-effective approach. We evaluated its potential in a well-established, critical-size, rat femoral defect model. Methods: A critical-size defect was created in the right femur of forty-eight skeletally mature Sprague-Dawley rats. After twenty-four hours, each defect received a single, intralesional, percutaneous injection of adenovirus carrying bone morphogenetic protein-2 (Ad.BMP-2) or luciferase cDNA (Ad.luc) or it remained untreated. Healing was monitored with weekly radiographs. At eight weeks, the rats were killed and the femora were evaluated with dual-energy x-ray absorptiometry, micro-computed tomography, histological analysis, histomorphometry, and torsional mechanical testing. Results: Radiographically, 75% of the Ad.BMP-2-treated femora showed osseous union. Bone mineral content was similar between the Ad.BMP-2-treated femora (0.045 ± 0.020 g) and the contralateral, intact femora (0.047 ± 0.003 g). Histologically, 50% of the Ad.BMP-2-treated defects were bridged by lamellar, trabecular bone; the other 50% contained islands of cartilage. The control (Ad.luc-treated) defects were filled with fibrous tissue. Histomorphometry demonstrated a large difference in osteogenesis between the Ad.BMP-2 group (mean bone area, 3.25 ± 0.67 mm2) and the controls (mean bone area, 0.65 ± 0.67 mm2). By eight weeks, the Ad.BMP-2-treated femora had approximately one-fourth of the strength (mean, 0.07 ± 0.04 Nm) and stiffness (mean, 0.5 ± 0.4 Nm/rad) of the contralateral femora (0.3 ± 0.08 Nm and 2.0 ± 0.5 Nm/rad, respectively). Conclusions: A single, percutaneous, intralesional injection of Ad.BMP-2 induces healing of critical-size femoral bone defects in rats within eight weeks. At this time, the repair tissue is predominantly trabecular bone, has normal bone mineral content, and has gained mechanical strength. Clinical Relevance: Direct administration of adenovirus carrying BMP-2 could provide a straightforward and cost-effective treatment for large osseous defects with adequate surrounding soft-tissue support. This local in vivo genetherapy approach avoids the cost and complexity of ex vivo methods that require artificial scaffolds and autologous cell culture.

Direct Percutaneous Gene Delivery to Enhance Healing of Segmental Bone Defects

Healing of segmental bone defects can be induced experimentally with genetically modified osteoprogenitor cells, an ex vivo strategy that requires two operative interventions and substantial cost. Direct transfer of osteogenic genes offers an alternative, clinically expeditious, cost-effective approach. We evaluated its potential in a well-established, critical-size, rat femoral defect model. A critical-size defect was created in the right femur of forty-eight skeletally mature Sprague-Dawley rats. After twenty-four hours, each defect received a single, intralesional, percutaneous injection of adenovirus carrying bone morphogenetic protein-2 (Ad.BMP-2) or luciferase cDNA (Ad.luc) or it remained untreated. Healing was monitored with weekly radiographs. At eight weeks, the rats were killed and the femora were evaluated with dual-energy x-ray absorptiometry, micro-computed tomography, histological analysis, histomorphometry, and torsional mechanical testing. Radiographically, 75% of the Ad.BMP-2-treated femora showed osseous union. Bone mineral content was similar between the Ad.BMP-2-treated femora (0.045 +/- 0.020 g) and the contralateral, intact femora (0.047 +/- 0.003 g). Histologically, 50% of the Ad.BMP-2-treated defects were bridged by lamellar, trabecular bone; the other 50% contained islands of cartilage. The control (Ad.luc-treated) defects were filled with fibrous tissue. Histomorphometry demonstrated a large difference in osteogenesis between the Ad.BMP-2 group (mean bone area, 3.25 +/- 0.67 mm(2)) and the controls (mean bone area, 0.65 +/- 0.67 mm(2)). By eight weeks, the Ad.BMP-2-treated femora had approximately one-fourth of the strength (mean, 0.07 +/- 0.04 Nm) and stiffness (mean, 0.5 +/- 0.4 Nm/rad) of the contralateral femora (0.3 +/- 0.08 Nm and 2.0 +/- 0.5 Nm/rad, respectively). A single, percutaneous, intralesional injection of Ad.BMP-2 induces healing of critical-size femoral bone defects in rats within eight weeks. At this time, the repair tissue is predominantly trabecular bone, has normal bone mineral content, and has gained mechanical strength.

Effects of frequency-dependent attenuation and velocity dispersion on in vitro ultrasound velocity measurements in intact human femur specimens

Numerous studies have shown that ultrasonic velocity measured in bone provides a good assessment of osteoporotic fracture risk. However, a lack of standardization of signal processing techniques used to compute the speed of sound (SOS) complicates the comparison between data obtained with different commercial devices. In this study, 38 intact femurs were tested using a through-transmission technique and SOS determined using different techniques. The resulting difference in measured SOS was determined as functions of the attenuation and the velocity dispersion. A numerical simulation was used to explain how attenuation and dispersion impact two different SOS measurements (group velocity, velocity based on the first zero crossing of the signal). A new method aimed at compensating for attenuation was devised and led to a significant reduction in the difference between SOS obtained with both signal processing techniques. A comparison between SOS and X-ray density measurements indicated that the best correlation was reached for SOS based on the first zero crossing apparently because it used a marker located in the early part of the signal and was less sensitive to multipath interference. The conclusion is that first zero crossing velocity may be preferred to group velocity for ultrasonic assessment at this potential fracture site.

Reamed Femoral Nailing in Sheep: Does Irrigation and Aspiration of Intramedullary Contents Alter the Systemic Response?

Reaming of the femoral canal has been demonstrated to introduce intramedullary contents into the circulation with subsequent pulmonary embolization. The aim of this study was to investigate whether this effect can be minimized by use of a reamer system that provides simultaneous irrigation and aspiration of intramedullary contents. A unilateral lung contusion was created and intramedullary femoral nailing was subsequently performed in eighteen female skeletally mature Merino sheep. The animals were divided into three groups, of six animals each, to receive one of three types of treatment: reamed femoral nailing; reaming, irrigation, and aspiration; and unreamed femoral nailing. Blood samples were obtained and a bronchoalveolar lavage was performed at baseline, immediately after creation of the lung contusion, immediately after intramedullary nailing, and at four hours after surgery. Pulmonary permeability, polymorphonuclear leukocyte activity, and systemic hemostatic response were measured. Lung specimens were obtained for histological evaluation. At baseline and immediately after creation of the lung contusion, endothelial permeability was comparable among the three groups. At four hours postoperatively, pulmonary permeability was significantly higher in the group treated with reamed femoral nailing (urea/protein ratio; 256.7) than in the group treated with reaming, irrigation, and aspiration (urea/protein ratio, 91.5) and the group treated with unreamed femoral nailing (urea/protein, 110.64) (p < 0.05). The stimulatory capacity of the polymorphonuclear leukocytes was significantly decreased (p < 0.05) only in the group treated with reamed femoral nailing; the other two groups had no significant decrease postoperatively (p > 0.05). The D-dimer level at four hours postoperatively was significantly higher in the group treated with reamed femoral nailing than it was in the other two groups (p < 0.05). Histological examination showed that the grades of edema and polymorphonuclear leukocyte diapedesis were also highest in the group treated with reamed femoral nailing. It appears that, in the presence of a unilateral pulmonary injury, the systemic effects of intramedullary reaming of an intact femur can be minimized with use of a modified reamer design that simultaneously irrigates the canal and removes debris. Additional clinical validation of this reaming system is necessary.

Recombinant human BMP‐7 effectively prevents non‐union in both young and old rats

The purpose of this study was to evaluate the influence of age on the effectiveness of rhBMP-7 treatment in a fracture with severe periosteal damage that is known to result in non-union formation. Closed stabilized femur fractures were produced in 3-month-old and 18-month-old rats. The fracture site was exposed and 2 mm of the periosteum cauterized circumferentially to impair normal fracture healing. The cauterized fracture site was immediately treated with either 100 microg rhBMP-7 (BMP-7 group), or with 25 microL of vehicle alone (control group). Fracture healing was evaluated with radiographs taken at 3 and 6 weeks. Animals were sacrificed at 3 and 6 weeks and specimens subjected to biomechanical and histological evaluation. In both age groups, none of the control animals healed throughout the 6 weeks experimental duration. All of the rhBMP-7-treated 3-month-old animals were radiographically healed at 3 weeks. In comparison, only 56% (9/16) of the rhBMP-7-treated 18-month-old animals were radiographically healed at 3 weeks. At 6 weeks, however, all of the 18-month-old rhBMP-7-treated animals had healed. Histology revealed slower healing in the 18-month-old animals. Treatment with rhBMP-7 significantly increased all of the biomechanical properties in both age groups. In the 3-month-old animals the mechanical strength approached that of the intact femur at 3 weeks, while in the 18-month-old animals this did not occur until 6 weeks. In conclusion, rhBMP-7 can effectively stimulate fracture repair in both young (3-month-old) and old (18-month-old) rats. However, the effect of rhBMP-7 on the rate of fracture healing is greater in young rats compared to old rats.

Potential of Superparamagnetic Iron Oxide in the Differential Diagnosis of Metastasis and Inflammation in Bone Marrow

The utility of ferucarbotran for the diagnosis of bone metastases was investigated using tumor-implanted rabbits. The potential of ferucarbotran in the differential diagnosis of metastasis and inflammation was also investigated. Twelve rabbits were divided into 2 groups (tumor and inflammation groups). Six rabbits of tumor group were inoculated with VX2 tumor cell suspension, and the 6 rabbits of the inflammation group were inoculated with 10% croton oil in the bone marrow of the right femur. All rabbits were imaged using a clinical MRI system. Signal intensity in the bone marrow of the right femur was measured in each rabbit before and after the intravenous injection of 8 micromol Fe/kg of ferucarbotran. As a control, the signal intensity in the bone marrow of the left femur (the normal, intact femur) was measured in each rabbit. The change in signal intensity of each group was compared statistically. After MRI imaging, the femora were removed, and sections were prepared for microscopic examination. Signal intensity in the right femur of the tumor group did not change after injection, although that of the inflammation group and the control group decreased. In the histologic findings, tumors were widely spread in the right femur of the tumor group. The infiltration of pseudoeosinocytes was induced in the right femur of the inflammation group. This animal study showed that ferucarbotran was useful to detect bone marrow tumors. In addition, ferucarbotran may have potential in the differential diagnosis of bone metastasis and some kinds of inflammation.

In vitro speed of sound measurement at intact human femur specimens

Quantitative ultrasound has been recognized as a useful tool for fracture risk prediction. Current measurement techniques are limited to peripheral skeletal sites. Our objective was to demonstrate the in vitro feasibility of ultrasonic velocity measurements on human proximal femur and to investigate the relationship between velocity and bone mineral density (BMD). Sound velocity images were computed from 2-D scans performed on 38 excised human femurs in transmission at 0.5 MHz. Different regions-of-interest were investigated. Dual x-ray absorptiometry scans have been achieved for BMD measurements in site-matched regions. Our study demonstrates the feasibility of ultrasonic velocity measurements at the hip with reasonable precision (coefficient of variation of 0.3%). The best prediction of BMD was reached in the intertrochanter region (r 2 = 0.91, p < 10 −4), with a residual error of 0.06 g/cm 2 (10%). Because BMD measured at the femur is the best predictor of hip fracture risk, the highly significant correlation and small residual error found in this study suggest that speed of sound measurement at the femur might be a good candidate for hip fracture risk prediction. (E-mail: Frederic.padilla@lip.bhdc.jussieu.fr)

Deletion of iNOS gene impairs mouse fracture healing

Nitric oxide (NO) is a signaling molecule synthesized from l-arginine by nitric oxide synthases (NOSs). NOS isoforms are either constitutive (endothelial NOS [eNOS] and neuronal NOS [nNOS]) or inducible NOS (iNOS). Previously, our group has reported that NO is expressed during and modulates fracture healing. In this study, we evaluated the specific contribution of iNOS to fracture healing by using iNOS gene therapy in iNOS-deficient mice. Twelve-week-old female wild-type mice and iNOS-KO mice had a right femoral midshaft osteotomy fixed with an intramedullary 0.5-mm-diameter needle. A gelatine sponge was implanted across the fracture site. The gelatine sponge received either Ad5-CMViNOS (in iNOS-deficient mice; n = 16) or Ad5-CMVempty (in wild-type mice; n = 15, and iNOS-deficient mice; n = 15) at a dose of 10 7 pfu. Mice were sacrificed at day 14, and their right and left hind limbs were harvested. Cross-sectional area (CSA) was determined by measuring the callus diameter across the mediolateral and anteroposterior plane using a vernier caliper. Specimens were loaded to failure torsionally in a biaxial INSTRON testing system, and maximum torque, torsional stiffness, and maximal and total energy were determined. Deletion of the iNOS gene decreased the total and maximum energy absorption of the healing femoral fracture by 30% and by 70% ( P < 0.01), respectively, in comparison to the wild-type mice. This reduction in energy absorption was reversed by iNOScDNA administration via adenovirus vector. Furthermore, iNOScDNA caused an increase in torsional failure by 20% ( P = 0.01) in comparison to iNOS(−/−) mice that did not receive the iNOScDNA. There were no significant differences in the biomechanical properties of intact femora. These data indicate that iNOS is important in mouse fracture healing. However, the clinical utility of NOS gene therapy to enhance fracture healing will need further evaluation.

Transphyseal Bioabsorbable Screws Cause Temporary Growth Retardation in Rabbit Femur

A self-reinforced bioabsorbable poly-L-lactide/polyglycolide (SR-PLGA) 80/20 screw 2.0 mm in diameter was implanted transphyseally across the distal growth plate of the right femur in 24 immature rabbits. Radiologic evaluation revealed a mean shortening of 3.1 mm at 3 weeks, 11.1 mm at 6 weeks, 9.3 mm at 24 weeks, 9.0 mm at 48 weeks, and 12.6 mm at 72 weeks compared with the intact contralateral femur. In 13 control rabbits, drilling without screw placement did not cause any statistically significant femoral shortening. Therefore, the transphyseal SR-PLGA 80/20 screw caused growth retardation for 6 weeks postoperatively, after which the normal growth tendency was recovered until the growth plate was closed. The duration of temporary growth retardation correlated with that of strength retention of the SR-PLGA 80/20 copolymer. These findings suggest that SR-PLGA 80/20 screws can be applied in transphyseal bone fixation. The use of bioabsorbable screws for temporary epiphysiodesis seems attractive but requires further study.

MECHANICAL EFFECTS OF THE EXTENDED TROCHANTERIC OSTEOTOMY

Background: The extended trochanteric osteotomy was introduced as a safe and effective exposure technique for revision hip surgery; however, intraoperative iatrogenic femoral fractures have been reported. This study examined the effects of the extended trochanteric osteotomy on the torsional strength of the femur with use of cadaver bones. We hypothesized that repair of the osteotomy fragment would restore the torsional strength to that of an intact femur and that an osteotomized femur containing a well-fixed stem would have the same torsional strength as an intact femur with a stem. Methods: Fifty-eight cadaveric human femora were divided into five groups, according to the repair technique, to examine the effects of the extended trochanteric osteotomy: intact, osteotomy, repaired osteotomy, implant, and implant-repaired osteotomy. Osteotomy fragments were reattached with use of three double-looped 18-gauge wires. A femoral stem was cemented into the last two groups. Specimens were tested mechanically in rotation until failure. Rotational properties were compared with one-way analysis of variance followed by post hoc pairwise comparisons. Linear regression analysis was performed for bone mineral density and torsional strength. Results: Torque to failure was reduced by 73% for the specimens in the osteotomy group compared with the intact group (p < 0.0001). Repair of the osteotomy did not improve torque to failure (p > 0.99). Femora in the implant-repaired osteotomy group displayed significantly improved torque-to-failure values compared with the specimens in the osteotomy and repaired osteotomy groups (p < 0.0001). However, the strength of the femora in the implant-repaired osteotomy group remained significantly less than that of the specimens in the implant group (p < 0.007). A significant linear relationship was observed between bone mineral density and torque to failure for femora in the intact (p < 0.006), osteotomy (p < 0.002), and repaired osteotomy (p < 0.001) groups. Conclusions: The extended trochanteric osteotomy reduces torsional strength by 73% even when the osteotomy fragment is repaired. Bone mineral density directly affects absolute femoral strength in this model. Clinical Relevance: In this in vitro cadaver study, the extended trochanteric osteotomy resulted in a significant reduction of torsional strength and energy required for fracture. Femoral stem insertion with osteotomy repair significantly improved torsional strength; however, this construct remained significantly weaker than that of a femur that had an implant without an osteotomy. This finding suggests that postoperative rehabilitation protocols should be even more restrictive with regard to weight-bearing and the use of abduction braces after revisions with use of an extended trochanteric osteotomy than after revisions that do not require an extended trochanteric osteotomy.