| 1. |
- Tong, Xiaoyu, et al.
(författare)
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Cortical Bone Histomorphometry in Male Femoral Neck: The Investigation of Age-Association and Regional Differences
- 2015
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 96:4, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- Low bone volume and changes in bone quality or microarchitecture may predispose individuals to fragility fractures. As the dominant component of the human skeleton, cortical bone plays a key role in protecting bones from fracture. However, histological investigations of the underlying structural changes, which might predispose to fracture, have been largely limited to the cancellous bone. The aim of this study was to investigate the age-association and regional differences of histomorphometric properties in the femoral neck cortical bone. Undecalcified histological sections of the femoral neck (n = 20, aged 18-82 years, males) were cut (15 mu m) and stained using modified Masson-Goldner stain. Complete femoral neck images were scanned, and cortical bone boundaries were defined using our previously established method. Cortical bone histomorphometry was performed with low (x50) and high magnification (x100). Most parameters related to cortical width (Mean Ct.Wi, Inferior Ct.Wi, Superior Ct.Wi) were negatively associated with age both before and after adjustment for height. The inferior cortex was the thickest (P < 0.001) and the superior cortex was the thinnest (P < 0.008) of all cortical regions. Both osteonal size and pores area were negatively associated with age. Osteonal area and number were higher in the antero-inferior area (P < 0.002) and infero-posterior area (P = 0.002) compared to the postero-superior area. The Haversian canal area was higher in the infero-posterior area compared to the postero-superior area (P = 0.002). Moreover, porosity was higher in the antero-superior area (P < 0.002), supero-anterior area (P < 0.002) and supero-posterior area (P < 0.002) compared to the infero-anterior area. Eroded endocortical perimeter (E.Pm/Ec.Pm) correlated positively with superior cortical width. This study describes the changes in cortical bone during ageing in healthy males. Further studies are needed to investigate whether these changes explain the increased susceptibility to femoral neck fractures.
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| 2. |
- Tong, Xiaoyu, et al.
(författare)
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Histomorphometric and osteocytic characteristics of cortical bone in male subtrochanteric femoral shaft
- 2017
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Ingår i: Journal of Anatomy. - : Wiley. - 0021-8782. ; 231:5, s. 708-717
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Tidskriftsartikel (refereegranskat)abstract
- The histomorphometric properties of the subtrochanteric femoral region have rarely been investigated. The aim of this study was to investigate the age-associated variations and regional differences of histomorphometric and osteocytic properties in the cortical bone of the subtrochanteric femoral shaft, and the association between osteocytic and histological cortical bone parameters. Undecalcified histological sections of the subtrochanteric femoral shaft were obtained from cadavers (n = 20, aged 18–82 years, males). They were cut and stained using modified Masson-Goldner stain. Histomorphometric parameters of cortical bone were analysed with ×50 and ×100 magnification after identifying cortical bone boundaries using our previously validated method. Within cortical bone areas, only complete osteons with typical concentric lamellae and cement line were selected and measured. Osteocytic parameters of cortical bone were analyzed under phase contrast microscopy and epifluorescence within microscopic fields (0.55 mm2 for each). The cortical widths of the medial and lateral quadrants were significantly higher than other quadrants (P < 0.01). Osteonal area per cortical bone area was lower and cortical porosities were higher in the posterior quadrant than in the other quadrants (P < 0.05). Osteocyte lacunar number per cortical bone area was found higher in the young subjects (≤ 50 years) than in the older ones (> 50 years) both before and after adjustments for body height and weight (P < 0.05). Moreover, significant but low correlations were found between the cortical bone and osteocytic parameters (0.20 ≤ R2 ≤ 0.35, P < 0.05). It can be concluded that in healthy males, the cortical histomorphometric parameters differ between the anatomical regions of the subtrochanteric femoral shaft, and are correlated with the osteocytic parameters from the same site. These findings may be of use when discussing mechanisms that predispose patients to decreasing bone strength.
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| 3. |
- Tong, Xiaoyu, et al.
(författare)
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Iliac crest histomorphometry and skeletal heterogeneity in men
- 2017
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Ingår i: Bone Reports. - : Elsevier BV. - 2352-1872. ; 6, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The cortical characteristics of the iliac crest in male have rarely been investigated with quantitative histomorphometry. Also it is still unknown how cortical microarchitecture may vary between the iliac crest and fractures related sites at the proximal femur. We studied the microarchitecture of both external and internal cortices within the iliac crest, and compared the results with femoral neck and subtrochanteric femoral shaft sites. Methods Undecalcified histological sections of the iliac crest were obtained bicortically from cadavers (n = 20, aged 18–82 years, males). They were cut (7 μm) and stained using modified Masson-Goldner stain. Histomorphometric parameters of cortical bone were analysed with low (× 50) and high (× 100) magnification, after identifying cortical bone boundaries using our previously validated method. Within cortical bone area, only complete osteons with typical concentric lamellae and cement line were selected and measured. Results At the iliac crest, the mean cortical width of external cortex was higher than at the internal cortex (p < 0.001). Also, osteon structural parameters, e.g. mean osteonal perimeter, were higher in the external cortex (p < 0.05). In both external and internal cortices, pore number per cortical bone area was higher in young subjects (≤ 50 years) (p < 0.05) while mean pore perimeter was higher in the old subjects (> 50 years) (p < 0.05). Several cortical parameters (e.g. osteon area per cortical bone area, pore number per cortical area) were the lowest in the femoral neck (p < 0.05). The maximal osteonal diameter and mean wall width were the highest in the external cortex of the iliac crest (p < 0.05), and the mean cortical width, osteon number per cortical area were the highest in the subtrochanteric femoral shaft (p < 0.05). Some osteonal structural parameters (e.g. min osteonal diameter) were significantly positively correlated (0.29 ≤ R2 ≤ 0.45, p < 0.05) between the external iliac crest and the femoral neck. Conclusions This study reveals heterogeneity in cortical microarchitecture between the external and internal iliac crest cortices, as well as between the iliac crest, the femoral neck and the subtrochanteric femoral shaft. Standard iliac crest biopsy does not reflect accurately cortical microarchitecture of other skeletal sites.
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| 4. |
- Tong, Xiao-Yu, et al.
(författare)
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Development of new criteria for cortical bone histomorphometry in femoral neck: intra- and inter-observer reproducibility
- 2015
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Ingår i: Journal of Bone and Mineral Metabolism. - : Springer Science and Business Media LLC. - 0914-8779 .- 1435-5604. ; 33:1, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- Histomorphometry is commonly applied to study bone remodeling. Histological definitions of cortical bone boundaries have not been consistent. In this study, new criteria for specific definition of the transitional zone between the cortical and cancellous bone in the femoral neck were developed. The intra- and inter-observer reproducibility of this method was determined by quantitative histomorphometry and areal overlapping analysis. The undecalcified histological sections of femoral neck specimens (n = 6; from men aged 17-59 years) were processed and scanned to acquire histological images of complete bone sections. Specific criteria were applied to define histological boundaries. "Absolute cortex area" consisted of pure cortical bone tissue only, and was defined mainly based on the size of composite canals and their distance to an additional "guide" boundary (so-called "preliminary cortex boundary," the clear demarcation line of density between compact cortex and sparse trabeculae). Endocortical bone area was defined by recognizing characteristic endocortical structures adjacent to the preliminary cortical boundary. The present results suggested moderate to high reproducibility for low-magnification parameters (e.g., cortical bone area). The coefficient of variation (CV %) ranged from 0.02 to 5.61 in the intra-observer study and from 0.09 to 16.41 in the inter-observer study. However, the intra-observer reproducibility of some high-magnification parameters (e.g., osteoid perimeter/endocortical perimeter) was lower (CV %, 0.33-87.9). The overlapping of three histological areas in repeated analyses revealed highest intra- and inter-observer reproducibility for the absolute cortex area. This study provides specific criteria for the definition of histological boundaries for femoral neck bone specimens, which may aid more precise cortical bone histomorphometry.
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| 5. |
- Väänänen, Sami P, et al.
(författare)
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Automated segmentation of cortical and trabecular bone to generate finite element models for femoral bone mechanics
- 2019
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Ingår i: Medical Engineering & Physics. - : Elsevier BV. - 1873-4030 .- 1350-4533. ; 70:August 2019, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- Finite element (FE) models based on quantitative computed tomography (CT) images are better predictors of bone strength than conventional areal bone mineral density measurements. However, FE models require manual segmentation of the femur, which is not clinically applicable. This study developed a method for automated FE analyses from clinical CT images. Clinical in-vivo CT images of 13 elderly female subjects were collected to evaluate the method. Secondly, proximal cadaver femurs were harvested and imaged with clinical CT (N = 17). Of these femurs, 14 were imaged with µCT and three had earlier been tested experimentally in stance-loading, while collecting surface deformations with digital image correlation. Femurs were segmented from clinical CT images using an automated method, based on the segmentation tool Stradwin. The method automatically distinguishes trabecular and cortical bone, corrects partial volume effect and generates input for FE analysis. The manual and automatic segmentations agreed within about one voxel for in-vivo subjects (0.99 ± 0.23 mm) and cadaver femurs (0.21 ± 0.07 mm). The strains from the FE predictions closely matched with the experimentally measured strains (R2 = 0.89). The method can automatically generate meshes suitable for FE analysis. The method may bring us one step closer to enable clinical usage of patient-specific FE analyses.
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| 6. |
- Dahlberg, Leif E, et al.
(författare)
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A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis
- 2016
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X. ; 34:3, s. 50-445
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the safety of intra-articular sprifermin (primary), and to evaluate systemic exposure, biomarkers, histology, and other cartilage parameters in patients with advanced osteoarthritis (OA).METHODS: This was a first-in-human, double-blind, randomised, placebo-controlled trial of single and multiple ascending doses of sprifermin from 3-300 μg in knee OA patients scheduled for total knee replacement. Patients were randomised 3:1 to sprifermin or placebo, injected into the target knee once or once weekly for 3 weeks, and followed-up for 24 weeks.RESULTS: Fifty-five patients were treated with sprifermin, 25 with single and 30 with multiple doses, 18 received placebo. There was no clear difference between the active and placebo groups in incidence, severity, and nature of reported treatment emergent adverse events. Acute inflammatory reactions were slightly more common with sprifermin 300 μg, but none led to discontinuation. No clear difference was seen between placebo and sprifermin in physician-assessed local tolerability, pain, or swelling in the knee. No meaningful changes over time, or differences between treatment groups, were observed for safety laboratory parameters or ECG. Although individual abnormalities were observed, no patterns were evident suggesting a relation to treatment or potential safety concern. No systemic sprifermin exposure, anti-FGF18 antibodies, or clear-cut effects on systemic biomarkers were detected.CONCLUSIONS: This first clinical trial of sprifermin revealed no serious safety concerns, although larger studies are needed. The possibility of positive effects of intra-articular sprifermin on histological and other cartilage parameters in knee OA also warrant further investigation.
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| 7. |
- Grassi, Lorenzo, et al.
(författare)
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Elucidating failure mechanisms in human femurs during a fall to the side using bilateral digital image correlation
- 2020
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- An improved understanding of the mechanical properties of human femurs is a milestone towards a more accurate assessment of fracture risk. Digital image correlation (DIC) has recently been adopted to provide full-field strain measurements during mechanical testing of femurs. However, it has typically been used to measure strains on the anterior side of the femur, whereas in both single-leg-stance and sideways fall loading conditions, the highest deformations result on the medial and lateral sides of the femoral neck. The goal of this study was to measure full-field deformations simultaneously on the medial and lateral side of the femoral neck in a configuration resembling a fall to the side. Twelve female cadaver femurs were prepared for DIC measurements and tested in sideways fall at 5 mm/s displacement rate. Two pairs of cameras recorded the medial and lateral side of the femoral neck, and deformations were calculated using DIC. The samples exhibited a two-stage failure: first, a compressive collapse on the superolateral side of the femoral neck in conjunction with peak force, followed by complete femoral neck fracture at the force drop following the post-elastic phase. DIC measurements corroborated this observation by reporting no tensile strains above yield limit for the medial side of the neck up to peak force. DIC measurements registered onto the bone micro-architecture showed strain localizations in proximity of cortical pores due to, for instance, blood vessels. This could explain previously reported discrepancies between simulations and experiments in regions rich with large pores, like the superolateral femoral neck.
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| 8. |
- Grassi, Lorenzo, et al.
(författare)
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Experimental Validation Of Finite Element Model For Proximal Composite Femur Using Optical Measurements
- 2013
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Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 21, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- Patient-specific finite element models have been used to predict femur strength and fracture risk in individuals. Validation of the adopted finite element modelling procedure against mechanical testing data is a crucial step when aiming for clinical applications. The majority of the works available in literature used data from strain gages to validate the model, thus having up to 15 experimental measurements. Optical techniques, such as Digital Image Correlation, can help to improve the models by providing a continuous field of deformation data over a femoral surface. The main objective of this study was to validate finite element models of six composite femora against strain data from digital image correlation, obtained during fracture tests performed in quasi-axial loading configuration. The finite element models were obtained from CT scans, by means of a semi-automatic segmentation. The principal strains both during the elastic phase and close to the fracture were compared, and showed a correlation coefficient close to 0.9. In the linear region, the slope and intercept were close to zero and unity, while for the case when fracture load was simulated, the slope decreased somewhat. The accuracy of the obtained results is comparable with the state-of-the-art literature, with the significant improvement of having around 50000 data points for each femur. This large number of measurements allows a more comprehensive validation of the predictions by the finite element models, since thousand of points are tracked along the femoral neck and trochanter region, i.e., the sites that are most critical for femur fracture. Moreover, strain measurement biases due to the strain gage reinforcement effect, were avoided. The combined experimental-numerical approach proved to be ready for application to in-vitro tests of human cadaver femurs, thus helping to develop a suitable mechanistic fracture risk criterion.
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| 9. |
- Grassi, Lorenzo, et al.
(författare)
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Full-field Strain Measurement During Mechanical Testing of the Human Femur at Physiologically Relevant Strain Rates
- 2014
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Ingår i: Journal of Biomechanical Engineering. - : ASME International. - 0148-0731 .- 1528-8951. ; 136:11
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanical properties of human femora is of great importance for the development of a reliable fracture criterion aimed at assessing fracture risk. Earlier ex vivo studies have been conducted by measuring strains on a limited set of locations using strain gauges. Digital Image Correlation (DIC) could instead be used to reconstruct the full-field strain pattern over the surface of the femur. The objective of this study was to measure the full-field strain response of cadaver femora tested at a physiological strain rate up to fracture in a configuration resembling single stance. The three cadaver femora were cleaned from soft tissues, and a white background paint was applied with a random black speckle pattern over the anterior surface. The mechanical tests were conducted up to fracture at a constant displacement rate of 15 mm/s, and two cameras recorded the event at 3000 frames per second. DIC was performed to retrieve the full-field displacement map, from which strains were derived. A low-pass filter was applied over the measured displacements before the crack opened in order to reduce the noise level. The noise levels were assessed using a dedicated control plate. Conversely, no filtering was applied at the frames close to fracture to get the maximum resolution. The specimens showed a linear behavior of the principal strains with respect to the applied force up to fracture. The strain rate was comparable to the values available in literature from in-vivo measurements during daily activities. The cracks opened and fully propagated in less than 1 ms, and small regions with high values of the major principal strains could be spotted just a few frames before the crack opened. This corroborates the hypothesis of a strain-driven fracture mechanism in human bone. The data represents a comprehensive collection of full-field strains, both at physiological load levels and up to fracture. About 10000 measurements were collected for each bone, providing superior spatial resolution compared to ~15 measurements typically collected using strain gauges. These experimental data collection can be further used for validation of numerical models, and for experimental verification of bone constitutive laws and fracture criteria.
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| 10. |
- Grassi, Lorenzo, et al.
(författare)
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How accurately can subject-specific finite element models predict strains and strength of human femora? Investigation using full-field measurements
- 2016
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 49:5, s. 802-806
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Tidskriftsartikel (refereegranskat)abstract
- Subject-specific finite element models have been proposed as a tool to improve fracture risk assessment in individuals. A thorough laboratory validation against experimental data is required before introducing such models in clinical practice. Results from digital image correlation can provide full-field strain distribution over the specimen surface during in vitro test, instead of at a few pre-defined locations as with strain gauges. The aim of this study was to validate finite element models of human femora against experimental data from three cadaver femora, both in terms of femoral strength and of the full-field strain distribution collected with digital image correlation. The results showed a high accuracy between predicted and measured principal strains (R2=0.93, RMSE=10%, 1600 validated data points per specimen). Femoral strength was predicted using a rate dependent material model with specific strain limit values for yield and failure. This provided an accurate prediction (<2% error) for two out of three specimens. In the third specimen, an accidental change in the boundary conditions occurred during the experiment, which compromised the femoral strength validation. The achieved strain accuracy was comparable to that obtained in state-of-the-art studies which validated their prediction accuracy against 10–16 strain gauge measurements. Fracture force was accurately predicted, with the predicted failure location being very close to the experimental fracture rim. Despite the low sample size and the single loading condition tested, the present combined numerical-experimental method showed that finite element models can predict femoral strength by providing a thorough description of the local bone mechanical response.
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| 11. |
- Grassi, Lorenzo, et al.
(författare)
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Prediction of femoral strength using 3D finite element models reconstructed from DXA images: validation against experiments
- 2017
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer Science and Business Media LLC. - 1617-7940 .- 1617-7959. ; 16:3, s. 989-1000
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Tidskriftsartikel (refereegranskat)abstract
- Computed tomography (CT)-based finite element (FE) models may improve the current osteoporosis diagnostics and prediction of fracture risk by providing an estimate for femoral strength. However, the need for a CT scan, as opposed to the conventional use of dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnostics, is considered a major obstacle. The 3D shape and bone mineral density (BMD) distribution of a femur can be reconstructed using a statistical shape and appearance model (SSAM) and the DXA image of the femur. Then, the reconstructed shape and BMD could be used to build FE models to predict bone strength. Since high accuracy is needed in all steps of the analysis, this study aimed at evaluating the ability of a 3D FE model built from one 2D DXA image to predict the strains and fracture load of human femora. Three cadaver femora were retrieved, for which experimental measurements from ex vivo mechanical tests were available. FE models were built using the SSAM-based reconstructions: using only the SSAM-reconstructed shape, only the SSAM-reconstructed BMD distribution, and the full SSAM-based reconstruction (including both shape and BMD distribution). When compared with experimental data, the SSAM-based models predicted accurately principal strains (coefficient of determination >0.83, normalized root-mean-square error <16%) and femoral strength (standard error of the estimate 1215 N). These results were only slightly inferior to those obtained with CT-based FE models, but with the considerable advantage of the models being built from DXA images. In summary, the results support the feasibility of SSAM-based models as a practical tool to introduce FE-based bone strength estimation in the current fracture risk diagnostics.
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| 12. |
- Julkunen, Petro, et al.
(författare)
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A Review of the Combination of Experimental Measurements and Fibril-Reinforced Modeling for Investigation of Articular Cartilage and Chondrocyte Response to Loading
- 2013
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Ingår i: Computational & Mathematical Methods in Medicine. - : Hindawi Limited. - 1748-6718 .- 1748-670X.
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Forskningsöversikt (refereegranskat)abstract
- The function of articular cartilage depends on its structure and composition, sensitively impaired in disease (e. g. osteoarthritis, OA). Responses of chondrocytes to tissue loading are modulated by the structure. Altered cell responses as an effect of OA may regulate cartilage mechanotransduction and cell biosynthesis. To be able to evaluate cell responses and factors affecting the onset and progression of OA, local tissue and cell stresses and strains in cartilage need to be characterized. This is extremely challenging with the presently available experimental techniques and therefore computational modeling is required. Modern models of articular cartilage are inhomogeneous and anisotropic, and they include many aspects of the real tissue structure and composition. In this paper, we provide an overview of the computational applications that have been developed for modeling the mechanics of articular cartilage at the tissue and cellular level. We concentrate on the use of fibril-reinforced models of cartilage. Furthermore, we introduce practical considerations for modeling applications, including also experimental tests that can be combined with the modeling approach. At the end, we discuss the prospects for patient-specific models when aiming to use finite element modeling analysis and evaluation of articular cartilage function, cellular responses, failure points, OA progression, and rehabilitation.
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| 13. |
- Khayyeri, Hanifeh, et al.
(författare)
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A novel semi-automatic hip morphology assessment tool is more accurate than manual radiographic evaluations
- 2020
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Ingår i: Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization. - : Informa UK Limited. - 2168-1163 .- 2168-1171. ; 8:1, s. 76-86
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Tidskriftsartikel (refereegranskat)abstract
- Radiological and pathological characteristics of hip osteoarthritis (OA) is joint-space loss due to degradation of articular cartilage. However, patients with early-stage OA do not yet show any radiological signs, which leaves them without diagnosis and treatment. This study evaluates the potential of a novel tool to identify pre-radiographic OA changes based on hip bone morphology. Two statistical appearance models for femur and pelvis were used to estimate the 3Dmorphology of the hip bones based on planar radiographs from patients. Well-known hip geometrical parameters (n = 22) were computed from patient CT scans (truth), 3D reconstructions (new method) and radiographs (calculated manually). The methods were compared by measuring relative error to truth. The new method was significantly more accurate in calculating hip geometrical parameters than the manual 2D calculations. The proposed approach could also capture rotational parameters like cross-over sign and anterior wall sign (100% correct predictions). The method can successfully reconstruct 3D hip shapes and densities for patients that have not yet developed severe osteoarthritis, and provided higher precision than manual estimations. Thus, it may be used to calculate morphological parameters that are predictors of OA and can become a powerful tool in human hip OA research and diagnostics.
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| 14. |
- Kobrina, Yevgeniya, et al.
(författare)
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Clustering of infrared spectra reveals histological zones in intact articular cartilage
- 2012
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 20:5, s. 460-468
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Articular cartilage (AC) exhibits specific zonal structure that follows the organization of collagen network and concentration of tissue constituents. The aim of this study was to investigate the potential of unsupervised clustering analysis applied to Fourier transform infrared (FIR) microspectroscopy to detect depth-dependent structural and compositional differences in intact AC. Method: Seven rabbit and eight bovine intact patellae AC samples were imaged using FTIR microspectroscopy and normalized raw spectra were clustered using the fuzzy C-means algorithm. Differences in mean spectra of clusters were investigated by quantitative estimation of collagen and proteoglycan (PG) contents, as well as by careful visual investigation of locations of spectral changes. Results: Clustering revealed the typical layered structure of AC in both species. However, more distinct clusters were found for rabbit samples, whereas bovine AC showed more complex layered structure. In both species, clustering structure corresponded with that in polarized light microscopic (PLM) images; however, some differences were also observed. Spectral differences between clusters were identified at the same spectral locations for both species. Estimated PG/collagen ratio decreased significantly from superficial to middle or deep zones, which might explain the difference in clustering results compared to PLM. Conclusion: FTIR microspectroscopy in combination with cluster analysis allows detailed examination of spatial changes in AC. As far as we know, no previous single technique could reveal a layered structure of AC without any a priori information. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 15. |
- Koistinen, Arto P, et al.
(författare)
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Short-term exercise-induced improvements in bone properties are for the most part not maintained during aging in hamsters.
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 51, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise during growth affects composition, structure and mechanical properties of bone. In this study we investigated whether the beneficial effects of exercise during the early growth phase have long-lasting effects or not. Female Syrian golden hamsters (total n=152) were used in this study. Half of the hamsters had access to running wheels during their rapid growth phase (from 1 to 3months of age). The hamsters were sacrificed at the ages of 1, 3, 12, and 15months. The diaphysis of the mineralized humerus was analyzed with microCT and subjected to three-point-bending mechanical testing. The trabecular bone in the tibial metaphysis was also analyzed with microCT. The collagen matrix of the humerus bone was studied by tensile testing after decalcification. The weight of the hamsters as well as the length of the bone and the volumetric bone mineral density (BMDvol) of the humerus was higher in the running group at the early age (3months). Moreover, the mineralized bone showed improved mechanical properties in humerus and had greater trabecular thickness in the subchondral bone of tibia in the runners. However, by the age of 12 and 15months, these differences were equalized with the sedentary group. The tensile strength and Young's modulus of decalcified humerus were higher in the runners at early stage, indicating a stronger collagen network. In tibial metaphysis, trabecular thickness was significantly higher for the runners in the old age groups (12 and 15months). Our study demonstrates that physical exercise during growth improves either directly or indirectly through weight gain bone properties of the hamsters. However, the beneficial effects were for the most part not maintained during aging.
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| 16. |
- Ojanen, Xiaowei, et al.
(författare)
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Differences in acoustic impedance of fresh and embedded human trabecular bone samples - Scanning acoustic microscopy and numerical evaluation
- 2016
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966. ; 140:3, s. 1931-1936
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Tidskriftsartikel (refereegranskat)abstract
- Trabecular bone samples are traditionally embedded and polished for scanning acoustic microscopy (SAM). The effect of sample processing, including dehydration, on the acoustic impedance of bone is unknown. In this study, acoustic impedance of human trabecular bone samples (n = 8) was experimentally assessed before (fresh) and after embedding using SAM and two-dimensional (2-D) finite-difference time domain simulations. Fresh samples were polished with sandpapers of different grit (P1000, P2500, and P4000). Experimental results indicated that acoustic impedance of samples increased significantly after embedding [mean values 3.7 MRayl (fresh), 6.1 MRayl (embedded), p < 0.001]. After polishing with different papers, no significant changes in acoustic impedance were found, even though higher mean values were detected after polishing with finer (P2500 and P4000) papers. A linear correlation (r = 0.854, p < 0.05) was found between the acoustic impedance values of embedded and fresh bone samples polished using P2500 SiC paper. In numerical simulations dehydration increased the acoustic impedance of trabecular bone (38%), whereas changes in surface roughness of bone had a minor effect on the acoustic impedance (-1.56%/0.1 μm). Thereby, the numerical simulations corroborated the experimental findings. In conclusion, acoustic impedance measurement of fresh trabecular bone is possible and may provide realistic material values similar to those of living bone.
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| 17. |
- Pulliainen, Outi, et al.
(författare)
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Poly-L-D-lactic acid scaffold in the repair of porcine knee cartilage lesions.
- 2007
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Ingår i: Tissue engineering. - : Mary Ann Liebert Inc. - 1076-3279 .- 1557-8690. ; 13:6, s. 1347-55
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Tidskriftsartikel (refereegranskat)abstract
- Articular cartilage injuries cause a major clinical problem because of the negligible repair capacity of cartilage. Autologous chondrocyte transplantation is a surgical method developed to repair cartilage lesions. In the operation, cartilage defect is covered with a periosteal patch and the suspension of cultured autologous chondrocytes is injected into the lesion site. The method can form good repair tissue, but new techniques are needed to make the operation easier and to increase the postoperative biomechanical properties of the repair tissue. In this study, we investigated poly-L,D-lactic acid (PLDLA) scaffolds alone or seeded with autologous chondrocytes in the repair of circular 6-mm cartilage lesions in immature porcine knee joints. Spontaneous repair was used as a reference. Histologic evaluation of the repair tissue showed that spontaneous repair exhibited higher scores than either PLDLA scaffold group (with or without seeded chondrocytes). The scaffold material was most often seen embedded in the subchondral bone underneath the defect area, probably because of the hardness of the PLDLA material. However, some of the cell-seeded and nonseeded scaffolds contained cartilaginous tissue, suggesting that invasion of mesenchymal cells inside nonseeded scaffolds had occurred. Hyaluronan deposited in the scaffold had possibly acted as a chemoattractant for the cell recruitment. In conclusion, the PLDLA scaffold material used in this study was obviously mechanically too hard to be used for cartilage repair in immature animals.
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| 18. |
- Turunen, Mikael J., et al.
(författare)
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Bone mineral crystal size and organization vary across mature rat bone cortex
- 2016
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Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1047-8477. ; 195:3, s. 337-344
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Tidskriftsartikel (refereegranskat)abstract
- The macro- and micro-features of bone can be assessed by using imaging methods. However, nano- and molecular features require more detailed characterization, such as use of e.g., vibrational spectroscopy and X-ray scattering. Nano- and molecular features also affect the mechanical competence of bone tissue. The aim of the present study was to reveal the effects of mineralization and its alterations on the mineral crystal scale, by investigating the spatial variation of molecular composition and mineral crystal structure across the cross-section of femur diaphyses in young rats, and healthy and osteoporotic mature rats (N = 5). Fourier transform infrared spectroscopy and scanning small- and wide-angle X-ray scattering (SAXS/WAXS) techniques with high spatial resolution were used at identical locations over the whole cross-section. This allowed quantification of point-by-point information about the spatial distribution of mineral crystal volume. All measured parameters (crystal dimensions, degree of orientation and predominant orientation) varied across the cortex. Specifically, the crystal dimensions were lower in the central cortex than in the endosteal and periosteal regions. Mineral crystal orientation followed the cortical circumference in the periosteal and endosteal regions, but was less well-oriented in the central regions. Central cortex is formed rapidly during development through endochondral ossification. Since rats possess no osteonal remodeling, this bone remains (until old age). Significant linear correlations were observed between the dimensional and organizational parameters, e.g., between crystal length and degree of orientation (R2 = 0.83, p < 0.001). Application of SAXS/WAXS provides valuable information on bone nanostructure and its constituents, effects of diseases and, prospectively, mechanical competence.
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| 19. |
- Turunen, Mikael J., et al.
(författare)
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Composition and microarchitecture of human trabecular bone change with age and differ between anatomical locations
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 54:1, s. 118-125
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Tidskriftsartikel (refereegranskat)abstract
- The microarchitecture of trabecular bone adapts to its mechanical loading environment according to Wolff's law and alters with age. Trabecular bone is a metabolically active tissue, thus, its molecular composition and microarchitecture may vary between anatomical locations as a result of the local mechanical loading environment. No comprehensive comparison of composition and microarchitecture of trabecular bone in different anatomical locations has been conducted. Therefore, the objective of this study was to compare the molecular composition and microarchitecture, evaluated with Fourier transform infrared (FTIR) microspectroscopy and micro-computed tomography (mu CT), respectively, in the femoral neck, greater trochanter and calcaneus of human cadavers. Specimens were harvested from 20 male human cadavers (aged 17-82 years) with no known metabolic bone diseases. Significant differences were found in composition and microarchitecture of trabecular bone between the anatomical locations. Compositional differences were primarily observed between the calcaneus and the proximal femur sites. Mineralization was higher in the greater trochanter than in the calcaneus (+2%, p<0.05) and crystallinity was lowest in the calcaneus (-24%, p<0.05 as compared to the femoral neck). Variation in the composition of trabecular bone within different parts of the proximal femur was only minor. Collagen maturity was significantly lower in greater trochanter than in femoral neck (-8%, p<0.01) and calcaneus (-5%, p<0.05). The greater trochanter possessed a less dense trabecular bone microarchitecture compared to femoral neck or calcaneus. Age related changes were mainly found in the greater trochanter. Significant correlations were found between the composition and microarchitecture of trabecular bone in the greater trochanter and calcaneus, indicating that both composition and microarchitecture alter similarly. This study provides new information about composition and microarchitecture of trabecular bone in different anatomical locations and their alterations with age with respect to the anatomical loading environments. (C) 2013 Elsevier Inc. All rights reserved.
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| 20. |
- Turunen, Mikael J, et al.
(författare)
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Evaluation of composition and mineral structure of callus tissue in rat femoral fracture.
- 2014
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Ingår i: Journal of Biomedical Optics. - 1083-3668. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT. Callus formation is a critical step for successful fracture healing. Little is known about the molecular composition and mineral structure of the newly formed tissue in the callus. The aim was to evaluate the feasibility of small angle x-ray scattering (SAXS) to assess mineral structure of callus and cortical bone and if it could provide complementary information with the compositional analyses from Fourier transform infrared (FTIR) microspectroscopy. Femurs of 12 male Sprague-Dawley rats at 9 weeks of age were fractured and fixed with an intramedullary 1.1 mm K-wire. Fractures were treated with the combinations of bone morphogenetic protein-7 and/or zoledronate. Rats were sacrificed after 6 weeks and both femurs were prepared for FTIR and SAXS analysis. Significant differences were found in the molecular composition and mineral structure between the fracture callus, fracture cortex, and control cortex. The degree of mineralization, collagen maturity, and degree of orientation of the mineral plates were lower in the callus tissue than in the cortices. The results indicate the feasibility of SAXS in the investigation of mineral structure of bone fracture callus and provide complementary information with the composition analyzed with FTIR. Moreover, this study contributes to the limited FTIR and SAXS data in the field.
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| 21. |
- Vaananen, Sami P., et al.
(författare)
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Estimation of 3D rotation of femur in 2D hip radiographs
- 2012
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 45:13, s. 2279-2283
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Tidskriftsartikel (refereegranskat)abstract
- Femoral radiographs are affected by the degree of rotation of the femur with respect to the plane of projection. We aimed to determine the 3D rotation of the proximal femur in 2D radiographs. A 3D Statistical Appearance Model (SAM), which was built from CT images of cadaver proximal femurs (n = 33) was randomly sampled to form a training set of 500 bones. Nineteen clinical CT images were collected for testing. All CT images were rotated to +/- 20 degrees in 2 degrees division around the shaft axis, +/- 10 degrees around medial-lateral axis, and by simultaneous rotation of both axes (+/- 16 degrees and +/- 8 degrees around shaft and medial-lateral axes). In each orientation, a 2D projection was recorded for generating a 2D SAM. The outcome parameters of the 2D SAM were used as input for a linear regression model and an artificial neural network to predict the rotation. The artificial neural network estimated the rotation more accurately than the linear regression. For artificial neural networks the mean errors were 4.0 degrees and 2.0 degrees around the shaft and medial-lateral axes, respectively. For an individual radiograph, the confidence interval of estimation was still relatively large. However, this method has high potential to differentiate the amount of rotations in two image sets. (C) 2012 Elsevier Ltd. All rights reserved.
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| 22. |
- Vaananen, Sami P., et al.
(författare)
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Repeatability of digital image correlation for measurement of surface strains in composite long bones
- 2013
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 46:11, s. 1928-1932
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Tidskriftsartikel (refereegranskat)abstract
- Digital image correlation (DIC) can measure full-field surface strains during mechanical testing of hard and soft tissues. When compared to traditional methods, such as strain gauges, DIC offers larger validation data (similar to 50,000 points) for, e.g., finite element models. Our main aim was to evaluate the repeatability of surface strain measurements with DIC during compressive testing of composite femurs mimicking human bones. We also studied the similarity of the composite femur samples using CT. Composite femurs were chosen as test material to minimize the uncertainties associated with the use of cadaveric tissues and to understand the variability of the DIC measurement itself. Six medium-sized fourth generation composite human proximal femora (Sawbones) were CT imaged and mechanically tested in stance configuration. The force-displacement curves were recorded and the 3D surface strains were measured with DIC on the anterior surface of the femurs. Five femurs fractured at the neck-trochanter junction and one at the site below the minor trochanter. CT image of this bone showed an air cavity at the initial fracture site. All femurs fractured through a sudden brittle crack. The fracture force for the composite bones was 5751 +/- 650 N (mean +/- SD). The maximum von Mises strain during the fractures was 2.4 +/- 0.8%. Noise in one experiment was 5-30 mu epsilon. When applied loads were equalized the variation in strains between the bones was 20-25%, and when the maximum strains were equalized, variation in the other regions was 5-10%. DIC showed that the ability of nominally identical composite bones to bear high strains and loads before fracturing may vary between the samples. (C) 2013 Elsevier Ltd. All rights reserved.
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| 23. |
- Vasara, Anna I., et al.
(författare)
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Arthroscopic cartilage indentation and cartilage lesions of anterior cruciate ligament-deficient knees
- 2005
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Ingår i: AMERICAN JOURNAL OF SPORTS MEDICINE. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 33:3, s. 408-414
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Tidskriftsartikel (refereegranskat)abstract
- The anterior cruciate ligament-deficient knee is prone to osteoarthritis and meniscus lesions. Very little, however, is known about the biomechanical properties of articular cartilage in anterior cruciate ligament-deficient knees. Purpose To evaluate biomechanical and macroscopical cartilage changes in the knee joint with respect to the time after anterior cruciate ligament rupture. Hypothesis Chronic anterior cruciate ligament deficiency induces cartilage softening. Study Design Cross-sectional study; Level of evidence, 3. Methods Cartilage stiffness of 50 patients undergoing anterior cruciate ligament reconstructive surgery because of symptomatic knee instability after chronic anterior cruciate ligament rupture was measured with an arthroscopic indenter device, and the number and size of cartilage lesions were evaluated. Results The cartilage stiffness did not correlate with time from trauma to surgery (r = 0.002, P =. 99), but the number of cartilage lesions in the knee increased when the time from the initial trauma to reconstructive surgery increased (r = 0.356, P =. 011). Indentation values measured on healthy-looking cartilage on damaged joint surfaces were lower than the values measured on healthy joint surfaces (P <. 01 on lateral femoral condyle and on tibial plateaus). Conclusions The number of cartilage lesions increases with increased time after initial trauma. The arthroscopic indenter device is able to detect cartilage softening as the early mechanical sign of degradation not yet visible to the eye.
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| 24. |
- Vasara, Anna I, et al.
(författare)
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Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation.
- 2006
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Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 14:10, s. 1066-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.
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| 25. |
- Vasara, Anna I, et al.
(författare)
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Indentation stiffness of repair tissue after autologous chondrocyte transplantation.
- 2005
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Ingår i: Clinical orthopaedics and related research. - 0009-921X. ; :433, s. 233-42
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Tidskriftsartikel (refereegranskat)abstract
- Our main hypothesis was that indentation stiffness of the repair tissue approaches the values of adjacent cartilage 1 year after autologous chondrocyte transplantation. We also wanted to investigate the differences between osteochondritic lesions and full-thickness lesions. Thirty patients with cartilage lesions were operated on with autologous chondrocyte transplantation. The repair was evaluated arthroscopically, indentation stiffness was measured, and clinical evaluations were done. The stiffness of the repair tissue improved to 62% (mean 2.04 +/- 0.83 N, mean +/- SD) of adjacent cartilage (3.58 +/- 1.04 N). Fifty-three percent of the patients graded their knee as excellent or good and 47% of the patients graded their knee as fair at the followup. In six patients the normalized stiffness was at least 80%, suggesting hyaline-like repair. The indentation stiffness of the osteochondritis dissecans lesion repairs (1.45 +/- 0.46 N; n = 7) was less than that of the nonosteochondritis dissecans lesion repair sites (2.37 +/- 0.72 N; n = 19). Gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) during followup of four patients suggested proteoglycan replenishment, although all grafts showed low indentation values. Low stiffness values may indicate incomplete maturation or predominantly fibrous repair. The indentation analysis showed that the repair tissue stiffness could, in some cases, reach the same level as the adjacent cartilage, but there was a large variation among the grafts.
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| 26. |
- Väänänen, Sami P, et al.
(författare)
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Generation of 3D shape, density, cortical thickness and finite element mesh of proximal femur from a DXA image
- 2015
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Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415. ; 24:1, s. 125-134
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Tidskriftsartikel (refereegranskat)abstract
- Areal bone mineral density (aBMD), as measured by dual-energy X-ray absorptiometry (DXA), predicts hip fracture risk only moderately. Simulation of bone mechanics based on DXA imaging of the proximal femur, may help to improve the prediction accuracy. Therefore, we collected three (1-3) image sets, including CT images and DXA images of 34 proximal cadaver femurs (set1, including 30 males, 4 females), 35 clinical patient CT images of the hip (set 2, including 27 males, 8 females) and both CT and DXA images of clinical patients (set 3, including 12 female patients). All CT images were segmented manually and landmarks were placed on both femurs and pelvises. Two separate statistical appearance models (SAMs) were built using the CT images of the femurs and pelvises in sets 1 and 2, respectively. The 3D shape of the femur was reconstructed from the DXA image by matching the SAMs with the DXA images. The orientation and modes of variation of the SAMs were adjusted to minimize the sum of the absolute differences between the projection of the SAMs and a DXA image. The mesh quality and the location of the SAMs with respect to the manually placed control points on the DXA image were used as additional constraints. Then, finite element (FE) models were built from the reconstructed shapes. Mean point-to-surface distance between the reconstructed shape and CT image was 1.0mm for cadaver femurs in set 1 (leave-one-out test) and 1.4mm for clinical subjects in set 3. The reconstructed volumetric BMD showed a mean absolute difference of 140 and 185mg/cm3 for set 1 and set 3 respectively. The generation of the SAM and the limitation of using only one 2D image were found to be the most significant sources of errors in the shape reconstruction. The noise in the DXA images had only small effect on the accuracy of the shape reconstruction. DXA-based FE simulation was able to explain 85% of the CT-predicted strength of the femur in stance loading. The present method can be used to accurately reconstruct the 3D shape and internal density of the femur from 2D DXA images. This may help to derive new information from clinical DXA images by producing patient-specific FE models for mechanical simulation of femoral bone mechanics.
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