Prediction of the pathological fracture risk during stance and fall-loading configurations for metastases in the proximal femur, using a computed tomography-based finite element method.

BACKGROUND: It is important to assess the fracture risk associated with metastasis in the proximal femur. The study aimed to clarify the effect of tumor location on the risk of pathological fracture of the proximal femur and investigate the fracture risk not only in the stance-loading configuration (SC), but also in the fall-loading configuration (FC) using a computed tomography (CT)-based finite element (FE) method based on a simulated metastatic model. METHODS: The axial CT scans of the proximal femora of non-osteoporotic healthy men (n = 4; age range, 42-48 years) and osteoporotic post-menopausal women (n = 4; age range, 69-78 years) were obtained with a calibration phantom, from which the three-dimensional FE models were constructed. A single 15-mm-diameter spherical void simulating a tumor was created at various locations from the neck to subtrochanteric level. Nonlinear FE analyses were performed. RESULTS: The mean predicted fracture loads without spherical voids in the SC were 7700 N in men and 4370 N in women. With the void at the medial femoral neck and in the region anteromedial to lesser trochanter, the mean predicted fracture load significantly reduced to 51.3% and 59.4% in men and 34.1% and 64.5% in women, respectively. The mean predicted fracture loads without a spherical void in the FC were 2500 N in men and 1862 N in women. With the void at the medial and posterior femoral neck, the predicted fracture load was significantly reduced to 65.7% and 79.7% in men and 48.3% and 65.4% in women, respectively. CONCLUSIONS: These results showed that the risk of pathologic fracture was quite high in both the SC and FC when the lytic lesion existed along the principal compressive trabecular trajectory or posterior neck. Prophylactic intervention should be considered for metastases at these locations.

The effect of cartilage degeneration on ultrasound speed in human articular cartilage.

OBJECTIVES: We investigated the effect of cartilage degeneration on ultrasound speed in human articular cartilage in vitro. METHODS: Ultrasound speed was calculated by the time-of-flight method for 22 femoral condyle osteochondral blocks obtained from osteoarthritis patients. In parallel, histological evaluation of specimens was performed using the modified Mankin and OARSI scores. RESULTS: The mean ultrasound speed was 1757 ± 109 m/s. Ultrasound speed showed significant negative correlation with OARSI score, and a decreasing tendency with high Mankin scores. Good correlation was found between the optically measured and the calculated cartilage thickness. CONCLUSION: Our results show that articular cartilage degeneration has relatively little influence on ultrasound speed. In addition, morphological evaluation of articular cartilage using a preset value of ultrasound speed seems to offer relatively accurate results.

Prediction of proximal femur strength by a quantitative computed tomography-based finite element method--Creation of predicted strength data of the proximal femur according to age range in a normal population.

OBJECTIVE: The objective of this study was to investigate the factors that affect the predicted bone strength of proximal femur in Japanese population. METHODS: Participants (552 men and 273 women) in a health checkup program with computed tomography (CT) at the University of Tokyo Hospital were enrolled in this study. Three-dimensional finite element models of the proximal femur were constructed from CT data of the participants with simultaneous scans of a calibration phantom containing hydroxyapatite rods. Multiple regression analysis was performed to analyze the relationship between the predicted bone strength and clinical factors. RESULTS: Average predicted strength of proximal femur was lower in women than in men in all age ranges. Predicted bone strength in women under both stance and fall configurations significantly decreased with age, and that in men had the tendency to decrease with age. Body weight positively affected the predicted bone strength in both men and women. CONCLUSIONS: This is the first cross-sectional analysis of the predicted bone strength of the proximal femur in Japanese population of wide age range. Age and body weight critically affected bone strength of proximal femur determined by quantitative CT-based finite element method, in particular in women, under both stance and fall configurations.

Reliability and Validity of Caregivers' Fear of Falling Index When Caring for Home-Based Rehabilitation Patients With Fall-Related Fractures.

OBJECTIVE: To evaluate the reliability and validity of this new measure, called the caregivers' fear of falling index (CFFI). METHODS: The study surveyed home-based rehabilitation patients with fall-related fracture, and their primary caregivers. The characteristics of these patients were evaluated, and the caregivers were surveyed using the CFFI and Falls Efficacy Scale-International (FES-I). The reliability of the CFFI was assessed using item-total correlation, while the validity of the CFFI was evaluated through correlation coefficients calculated between the CFFI and the FES-I. RESULTS: The participants were 51 patient-caregiver pairs. The internal consistency of the CFFI showed an alpha coefficient of 0.904. No items were excluded in the corrected item-total correlations. The CFFI showed a moderate correlation with FES-I (r=0.432, p=0.002). CONCLUSION: This study found the CFFI to be a reliable and valid tool for measuring the primary caregivers' fear. The CFFI may be a useful tool for healthcare professionals to identify and supporting these primary caregivers.

Association between Caregivers' Fear of Post-fracture Patients Falling and a Decline in Patients' Activities.

Objectives: To evaluate caregivers' fear of post-fracture patients falling, we previously developed the Caregivers' Fear of Falling Index (CFFI). In this study, we investigated the relationship between patient performance in activities of daily living (ADLs) and CFFI. Methods: We surveyed 55 patients receiving home-visit rehabilitation after fall-related fracture and their primary caregivers. Participants (patient and caregiver pair) were divided into two groups based on patient performance in basic ADLs (BADLs) and instrumental ADLs (IADLs). ROC analysis was conducted to assess the usefulness of CFFI and Falls Efficacy Scale-International (FES-I) in determining declines in performance in BADLs and IADLs. Multivariate logistic regression analysis was performed to examine the association between CFFI and declining performance in BADLs and IADLs. Results: ROC analysis showed that CFFI exhibited a higher accuracy than FES-I (AUC: 0.73 in BADLs, 0.77 in IADLs) as an indicator of reduced ADL performance. Multivariate logistic analysis adjusted for age, sex, and physical function showed that CFFI was associated with a decline in patients' performance in IADLs (odds ratio, 0.92; 95% confidence interval, 0.85-0.99). Conclusions: Caregivers' fear of post-fracture patients falling was associated with a decline in patients' performance in IADLs. These findings may serve as a guide for supporting caregivers of post-fracture patients.

Effect of low-intensity pulsed ultrasound stimulation on gap healing in a rabbit osteotomy model evaluated by quantitative micro-computed tomography-based cross-sectional moment of inertia.

BACKGROUND: It has been previously demonstrated that low-intensity pulsed ultrasound stimulation (LIPUS) enhances formation of the medullary canal and cortex in a gap-healing model of the tibia in rabbits, shortens the time required for remodeling, and enhances mineralization of the callus. In the current study, the mechanical integrity of these models was confirmed. In order to do this, the cross-sectional moment of inertia (CSMI) obtained from quantitative micro-computed tomography scans was calculated, and a comparison was made with a four-point bending test. METHODS: This parameter can be analyzed in any direction, and three directions were selected in order to adopt an XYZ coordinate (X and Y for bending; Z for torsion). RESULTS: The present results demonstrated that LIPUS improved earlier restoration of bending stiffness at the healing site. In addition, LIPUS was effective not only in the ultrasound-irradiated plane, but also in the other two planes. CONCLUSIONS: CSMI may provide the structural as well as compositional determinants to assess fracture healing and would be very useful to replace the mechanical testing.

Proposal of index to evaluate caregivers' fear of care recipient falls.

This study aimed to identify evaluation items that can be used to create an index to evaluate caregivers' fear of care recipient falls. A three-round Delphi method was conducted with medical professionals engaged in discharge support for patients with fall-related fractures. In the first round, a working group brainstormed evaluation items. In the second and third rounds, opinions of medical professionals were quantified and evaluation items were refined. The Delphi method showed convergence of opinion with Kendall's W of 0.561 in the third round. Of the 109 evaluation items pooled in the first round, the consensus was reached on the importance of 19 items and one more item was additionally included. The 20 items may be useful for creating an index that sensitively measures caregivers' fear of care recipient falls.

[Prediction of bone strength using a quantitative computed tomography based finite element method].

Clinically available methods for estimating bone strength include bone densitometry techniques such as dual energy X-ray absorptiometry and quantitative computed tomography, and other diagnostic imaging procedures such as radiographic imaging. These techniques evaluate regional bone density and morphology, which are partly related to fracture risk, but are of limited value for quantifying structural strength. Therefore, it is necessary to develop a noninvasive method for accurate quantitative structural analysis that incorporates information on both morphology and bone density in a three-dimensional distribution. Computed tomography-based finite element method (CT/FEM), which incorporates information on both the three-dimensional architecture and bone density distribution, could possibly achieve precise assessment of the strength of the bone. We focused on a CT/FEM to quantify structural strength, developing a nonlinear CT/FEM to achieve accurate assessment of strength in the proximal femur and lumbar vertebrae. Here, we describe the CT/FEM.

Comparison of ultrasound speed in articular cartilage measured by different time-of-flight methods.

The purpose of this study was to investigate whether different time-of-flight (TOF) methods including amplitude-related methods, which determine tissue borders from the reflected wave itself, and the cross-correlation method, which requires reference signals to determine borders, influence speed of sound (SOS) values for articular cartilage. Left femoral condyle samples from a 6-month-old pig and a 3-year-old pig were used. Radiofrequency signals from the cartilage surface and cartilage-bone interface were acquired using the ultrasound transducer for nine points in each sample. TOF was calculated by three amplitude-related methods (peak amplitude, peak envelope, signal phase) and a cross-correlation method. Cartilage thickness was measured microscopically, and SOS was calculated at each point. Mean (± standard deviation) SOSs in cartilage from the 9-point measurement by the four TOF methods were 1488 ± 51, 1488 ± 48, 1487 ± 54, and 1466 ± 51 m/s (for peak amplitude, peak envelope, signal phase, and cross-correlation methods, respectively) for the 6-month-old pig, and 1709 ± 107, 1717 ± 104, 1713 ± 105, and 1695 ± 138 m/s, respectively, for the 3-year-old pig. Paired t testing identified no significant differences between the amplitude-related methods and the cross-correlation method, although SOS values yielded by the amplitude-related methods tended to be higher than those from the cross-correlation method. These results suggest that amplitude-related methods of TOF measurement and the cross-correlation method are equivalently applicable to articular cartilage SOS measurement when a wave is clearly reflected from cartilage. TOF methods should thus be considered in studies on SOS measurement.

Gamma-crosslinked collagen gel without fibrils: analysis of structure and heat stability.

This paper reports an analysis of the structure and heat stability of two different collagen gels: conventional collagen gel (neutral gel) and gel without collagen fibrils (acidic gel), previously reported. We performed differential scanning calorimetry (DSC), observations by scanning electron microscope (SEM), observations by atomic force microscope (AFM), and small angle X-ray scattering (SAXS). Collagen fibrils were clearly observed in the neutral gel but not in the acidic gel by both SEM and AFM. A clear endothermic peak was observed at 53-55 degrees Celsius, representing disassembly of collagens in collagen fibrils in the neutral gel but not in the acidic gel. Only a small broad endothermic peak, at 35-43 degrees Celsius, representing the deformation of the triple helical structure of collagen, was observed in the acidic gel. The SAXS pattern also suggested that the neutral gel had a more heterogeneous structure than the acidic gel. The experimental results described here are compatible with the model proposed in a previous paper, and indicate more clearly that the acidic gel has no collagen fibrils and has a different molecular assembly state of Type I collagen than the neutral gel.

A new method for evaluation of fracture healing by echo tracking.

Assessment of bone healing on radiographs depends on the volume and radio-opacity of callus at the healing site, but is not necessarily objective, and there are differences of judgment among observers. To overcome this disadvantage, a clinical system was developed to quantify the stiffness of healing fractures of the tibia in patients by the echo tracking (ET) method in a manner similar to a three-point bending test. The purpose of this study was to ensure that the ET system could clinically assess the progress, delay or arrest of healing. The fibular head and the lateral malleolus were supported. A 7.5-MHz ultrasound probe was placed on the proximal and distal fragments and a load of 25 N was applied. Five tracking points were set along the long axis of the ultrasound probe at intervals of 10 mm. With a multiple ET system, two probes measured the displacement of five tracking points on each of the proximal and distal fragments of the tibia, thereby detecting the bending of the two fragments generated by the load. ET angle was defined as the sum of the inclinations of the proximal and distal fragments. Eight tibial fractures in seven patients treated by a cast or internal fixation were measured over time. In patients with radiographically normal healing, the bending angle decreased exponentially over time. However, in patients with nonunion, the angle remained the same over time. It was demonstrated that the ET method could be clinically applicable to evaluate fracture healing as a versatile, quantitative and noninvasive technique.

Prediction of strength and strain of the proximal femur by a CT-based finite element method.

Hip fractures are the most serious complication of osteoporosis and have been recognized as a major public health problem. In elderly persons, hip fractures occur as a result of increased fragility of the proximal femur due to osteoporosis. It is essential to precisely quantify the strength of the proximal femur in order to estimate the fracture risk and plan preventive interventions. CT-based finite element analysis could possibly achieve precise assessment of the strength of the proximal femur. The purpose of this study was to create a simulation model that could accurately predict the strength and surface strains of the proximal femur using a CT-based finite element method and to verify the accuracy of our model by load testing using fresh frozen cadaver specimens. Eleven right femora were collected. The axial CT scans of the proximal femora were obtained with a calibration phantom, from which the 3D finite element models were constructed. Materially nonlinear finite element analyses were performed. The yield and fracture loads were calculated, while the sites where elements failed and the distributions of the principal strains were determined. The strain gauges were attached to the proximal femoral surfaces. A quasi-static compression test of each femur was conducted. The yield loads, fracture loads and principal strains of the prediction significantly correlated with those measured (r=0.941, 0.979, 0.963). Finite element analysis showed that the solid elements and shell elements in undergoing compressive failure were at the same subcapital region as the experimental fracture site.

Patterning cultured cells by visible light illumination with photosensitizers.

We showed that PC12 cells and 3T3 cells cultured in dishes were killed by illumination with visible white light from a halogen lamp at 7 x 10(4) lx for 5 min in the presence of either 10 microM hematoporphyrin or 2 microM methylene blue as a photosensitizer. This simple technique, based on the photodynamic reaction via generation of reactive oxygen species can be applicable for patterning cultured cells.

Gamma-cross-linked nonfibrillar collagen gel as a scaffold for osteogenic differentiation of mesenchymal stem cells.

We fabricated a transparent nonfibrillar collagen gel using gamma irradiation (5 kGy) and cultured rat mesenchymal stem cells (MSCs) on both the gamma-irradiated collagen gel and on unirradiated fibrillar collagen gel. Cells attached well and proliferated with high viability on the surface of both gels. The cells cultured on the gamma-irradiated nonfibrillar gel had a unique elongated shape and adhered to each other in culture. After 21 days of culture in dexamethasone-containing culture medium, the contents of bone-specific osteocalcin and calcium on the gamma-irradiated nonfibrillar gel were 1.4 and 1.9 times higher than those on fibrillar collagen gel, respectively. These data show that osteogenic differentiation of MSCs was promoted more efficiently on the gamma-cross-linked nonfibrillar gel than on the fibrillar gel and demonstrate the potential of the gamma-irradiated collagen gel for use in bone tissue engineering.

Surgical tool alignment guidance by drawing two cross-sectional laser-beam planes.

Conventional surgical navigation requires for surgeons to move their sight and conscious off the surgical field when checking surgical tool's positions shown on the display panel. Since that takes high risks of surgical exposure possibilities to the patient's body, we propose a novel method for guiding surgical tool position and orientation directly in the surgical field by a laser beam. In our navigation procedure, two cross-sectional planar laser beams are emitted from the two laser devices attached onto both sides of an optical localizer, and show surgical tool's entry position on the patient's body surface and its orientation on the side face of the surgical tool. In the experiments, our method gave the surgeons precise and accurate surgical tool adjusting and showed the feasibility to apply to both of open and percutaneous surgeries.

Measurement of mechanical properties on gap healing in a rabbit osteotomy model until the remodeling stage.

BACKGROUND: The most important issue in the assessment of fracture healing is to acquire information about the restoration of the mechanical integrity of bone. Many researchers have attempted to monitor stiffness either directly or indirectly for the purpose of assessing strength, as strength has been impossible to assess directly in clinical practice. The purpose of this study was thus to determine the relationship between bending stiffness and strength using mechanical testing at different times during the healing process. METHODS: Unilateral, transverse, mid-tibial osteotomies with a 2-mm gap were performed in 28 rabbits. The osteotomy site was stabilized using a double-bar external fixator. The animals were divided into four groups (n=7/group/time point; 4, 6, 8 and 12 weeks). A series of images from micro-computed tomography of the gap was evaluated to detect the stage of fracture healing and a 4-point bending test was performed to measure stiffness and strength. Relative stiffness and strength values were also acquired from calculation of ratios relative to those of the non-osteotomized contralateral bones. FINDINGS: Formation of cortex and medullary canal at the gap was seen in the 12-week group and would represent the remodeling stage. In addition, the relationship between stiffness and strength remained almost linear until at least 12 weeks. However, stiffness recovered much more rapidly than strength. INTERPRETATION: Strength was not fully restored until the later stages of fracture healing. However, the current study demonstrated that stiffness could be monitored as a surrogate marker of strength until at least the remodeling stage.

Measurement of articular cartilage thickness using a three-dimensional image reconstructed from B-mode ultrasonography mechanical scans feasibility study by comparison with MRI-derived data.

The present study aimed to develop a method to measure three-dimensional (3-D) thickness of cartilage (Tc) at the femoral condyle using B-mode ultrasonography (US) and to clarify the feasibility of US in clinical evaluations of articular cartilage by comparing the results with 3-D measurement values using magnetic resonance imaging (MRI) and assessing repeatability. The medial surface of the right knees of two healthy male volunteers (age, 37 and 59 years) and the knees on affected side of three male patients with osteoarthritis (OA) (age, 73, 81 and 83 years) were scanned using B-mode US with the knee flexed at 120°. The range of the angle of probe rotation for the arm was 0-80° and B-mode images (total, 101 images) were acquired every 0.8°. MRI of the knees was also performed using the double echo steady-state sequence. Both US and MRI images were used to create 3-D models of medial femoral condyle articular cartilage. Tc was determined at points 1 mm apart from one another in the US model (Tc-US) and MRI model (Tc-MRI). Tc-US was compared with Tc-MRI and the repeatability of Tc-US was assessed by mean Tc in the specific region of interest of the femoral condyle. Tc-US correlated significantly with Tc-MRI both in volunteers and in OA patients (p < 0.0001 each) and coefficients of correlation were 0.976 and 0.964 for volunteers and OA patients, respectively. The coefficient of variance for mean Tc-US was 4.90%. Our results show that 3-D US measurements of femoral cartilage are reproducible and correlate strongly with MRI measurements.

Evaluation of the accuracy of articular cartilage thickness measurement by B-mode ultrasonography with conventional imaging and real-time spatial compound ultrasonography imaging.

The present study aimed to quantify the thickness of articular cartilage (Tc) in vitro using both conventional and real-time spatial compound B-mode ultrasonography (US) with a clinically used transducer and to evaluate the accuracy of measurement by comparing the results with values obtained microscopically. Femoral condyle samples were obtained from a 6-month-old pig and a 3-year-old pig. B-mode US images with conventional imaging and real-time spatial compound imaging (RTSCI) of osteochondral blocks were acquired. Tc determined using US (Tc-US) was measured from line data parallel to US beam direction acquired from B-mode images with an objective method for determining cartilage surface and bone-cartilage interfaces at the peak brightness values. Tc was also determined under microscopy (Tc-optical) using the corresponding points from US measurement. Tc-US was compared with Tc-optical to assess accuracy. Tc-US correlated significantly with Tc in both conventional imaging and RTSCI (r = 0.961, 0.976, respectively). Bland-Altman plots showed mean differences between Tc-optical and Tc-US were -0.0073 mm and 0.0139 mm with standard deviations of 0.171 mm and 0.131 mm for conventional imaging and RTSCI, respectively. Our results show that Tc-US measurement using B-mode US allows accurate measurement of Tc. Considering correlation coefficients between Tc-US and Tc-optical, RTSCI US may offer higher accuracy for measuring Tc than conventional methods when an objective tissue border determination algorithm is used, even though both showed good accuracy in our study.

In vitro osteogenic differentiation of HOS cells on two types of collagen gels.

HOS cell is a model strain of human osteoblasts derived from human osteosarcoma. We cultured the HOS cells on both the conventional collagen gel (neutral gel), and the gamma-crosslinked collagen gel without collagen fibrils (acidic gel). The shape of HOS cells on the neutral gel was similar to that on the culture dish. However, HOS cells on acidic gel had an elongated shape and attached each other to form a mesh-like pattern. The cells attached to the surface of both gels but scarcely penetrated their depths. We measured the biochemical markers for osteogenic differentiation in the HOS cells cultured on both the neutral gel and the acidic gel. The expressions of alkaline phosphatase and osteocalcin were detected in the HOS cells on both types of collagen gel. Deposition of the calcium also occurred on both gels although it was higher in the neutral gel than the acidic one. These results indicate the importance of collagen for the differentiation of HOS cells, but it is not dependent on the molecular structure (fibril formation) of collagen.

Prediction of vertebral strength under loading conditions occurring in activities of daily living using a computed tomography-based nonlinear finite element method.

STUDY DESIGN: A clinical study on osteoporotic vertebral strength in daily living using a computed tomography (CT)-based nonlinear finite element (FE) model. OBJECTIVE: To evaluate the differences in predicted fracture strength of osteoporotic vertebral bodies among the different loading conditions that are occurring in the activities of daily living. SUMMARY OF BACKGROUND DATA: FE model has been reported to predict vertebral strength in uniaxial loading, but forward bending load plays an important role in osteoporotic vertebral fractures. METHODS: Strengths of the second lumbar vertebra in 41 female patients with postmenopausal osteoporosis were analyzed using a nonlinear CT-based FE method. Three different loading conditions were adopted uniaxial compression, forward bending, and erect standing. The same boundary condition was used for all loading conditions. Predicted strengths under forward bending and erect standing were compared with that under uniaxial compression and differences in strength were statistically analyzed. RESULTS: The regression equation relating strength under uniaxial compression to that under erect standing was expressed as y = 0.8912x + 19.332 (R = 0.9522), whereas the equation relating uniaxial compression to forward bending was y = 0.7033x + 55.071 (R = 0.8342). Both relationships were significant, but the correlation between forward bending and uniaxial compression was not strong, while strength was lower under forward bending than under uniaxial compression according to the Friedman multiple comparison test (P = 0.00017). CONCLUSION: Strength under forward bending correlated significantly to that under uniaxial compression, but the correlation was not strong. Therefore, in osteoporotic patients, both uniaxial compression and forward bending should be assessed to evaluate fracture risk in daily living using a CT-based FE method.