| 1. |
- Grassi, Lorenzo, et al.
(författare)
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Validation of 3d finite element models from simulated Dxa images for Biofidelic simulations of sideways fall impact to the hip
- 2020
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Computed tomography (CT)-derived finite element (FE) models have been proposed as a tool to improve the current clinical assessment of osteoporosis and personalized hip fracture risk by providing an accurate estimate of femoral strength. However, this solution has two main drawbacks, namely: (i) 3D CT images are needed, whereas 2D dual-energy x-ray absorptiometry (DXA) images are more generally available, and (ii) quasi-static femoral strength is predicted as a surrogate for fracture risk, instead of predicting whether a fall would result in a fracture or not. The aim of this study was to combine a biofidelic fall simulation technique, based on 3D computed tomography (CT) data with an algorithm that reconstructs 3D femoral shape and BMD distribution from a 2D DXA image. This approach was evaluated on 11 pelvis-femur constructs for which CT scans, ex vivo sideways fall impact experiments and CT-derived biofidelic FE models were available. Simulated DXA images were used to reconstruct the 3D shape and bone mineral density (BMD) distribution of the left femurs by registering a projection of a statistical shape and appearance model with a genetic optimization algorithm. The 2D-to-3D reconstructed femurs were meshed, and the resulting FE models inserted into a biofidelic FE modeling pipeline for simulating a sideways fall. The median 2D-to-3D reconstruction error was 1.02 mm for the shape and 0.06 g/cm3 for BMD for the 11 specimens. FE models derived from simulated DXAs predicted the outcome of the falls in terms of fracture versus non-fracture with the same accuracy as the CT-derived FE models. This study represents a milestone towards improved assessment of hip fracture risk based on widely available clinical DXA images.
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| 2. |
- Gustafsson, Anna, et al.
(författare)
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Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture
- 2016
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Ingår i: Bone. - : ELSEVIER SCIENCE INC. - 8756-3282 .- 1873-2763. ; 88, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healink. A patient specific finite element model was developed, based on clinical CT images and high resolution CT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% cif the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. (C) 2016 Elsevier Inc. All rights reserved.
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| 3. |
- Kamal, Bushra, et al.
(författare)
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Biomechanical properties of bone in a mouse model of Rett syndrome.
- 2015
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 71, s. 106-114
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Tidskriftsartikel (refereegranskat)abstract
- Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2(stop/y) male mice in which Mecp2 is silenced in all cells and female Mecp2(stop/+) mice in which Mecp2 is silenced in ~50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies.
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| 4. |
- Malo, M K H, et al.
(författare)
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Ultrasound Backscatter Measurements of Intact Human Proximal Femurs - Relationships of ultrasound parameters with tissue structure and mineral density.
- 2014
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 64:Online April 24, 2014, s. 240-245
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Tidskriftsartikel (refereegranskat)abstract
- Ultrasound reflection and backscatter parameters are related to mechanical and structural properties of bone in vitro. However, the potential of ultrasound reflection and backscatter measurements has not been tested with intact human proximal femurs ex vivo. We hypothesize that ultrasound backscatter can be measured from intact femurs and that the measured backscattered signal is associated with cadaver age, bone mineral density (BMD) and trabecular bone microstructure. In this study, human femoral bones of 16 male cadavers (47.0±16.1years, range: 21-77 years) were investigated using pulse-echo ultrasound measurements at the femoral neck in the antero-posterior direction and at the trochanter major in the antero-posterior and latero-medial directions. Recently introduced ultrasound backscatter parameters, independent of cortical thickness, e.g., time slope of apparent integrated backscatter (TSAB) and mean of the backscatter difference technique (MBD) were obtained and compared with the structural properties of trabecular bone samples, extracted from the locations of ultrasound measurements. Moreover, more conventional backscatter parameters, e.g., apparent integrated backscatter (AIB) and frequency slope of apparent integrated backscatter (FSAB) were analysed. Bone mineral density of the intact femurs was evaluated using dual energy X-ray absorptiometry (DXA). AIB and MDB measured from the femoral neck correlated significantly (p<0.01) with the neck BMD (R(2)=0.44 and 0.45), cadaver age (R(2)=0.61 and 0.41) and several structural parameters, e.g., bone volume fraction (R(2)=0.33 and 0.39, p<0.05 and p<0.01), respectively. To conclude, ultrasound backscatter parameters, measured from intact proximal femurs, are significantly related (p<0.05) to trabecular bone structural properties and mineral density.
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| 5. |
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| 6. |
- Mathavan, Neashan, et al.
(författare)
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Investigating the synergistic efficacy of BMP-7 and zoledronate on bone allografts using an open rat osteotomy model.
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 56:2, s. 440-448
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Tidskriftsartikel (refereegranskat)abstract
- Bone grafts are well-established in the treatment of fracture non-unions but union is still not always achieved. Harvesting autograft is associated with donor site morbidity and the available amount of bone is limited. Allograft is more easily obtained and available in greater quantities but lacks the osteoinductive characteristics of autograft. We have previously shown a synergistic effect of bone morphogenetic protein (BMP-7), systemic bisphosphonates and autograft. In the present study we hypothesized that the combination of allograft+BMP-7+systemic ZA is more effective than autograft alone, which is currently the most frequently used aid in augmenting fracture and non-union healing. Femoral osteotomies were performed on 82 male Sprague Dawley rats and fixed with intramedullary K-wires. The rats were randomized into 7 groups: i. saline, ii. autograft, iii. allograft, iv. allograft+BMP-7, v. autograft+zoledronate (ZA), vi. allograft+ZA and vii. allograft+BMP-7+ZA. Autografts were harvested from the contralateral tibia. Allografts were obtained from donor rats and frozen. BMP-7 was administered locally in the form of a putty placed circumferentially around the osteotomy. At 2weeks, the rats were injected with a single dose of either saline or ZA. The rats were sacrificed at 6weeks and the femurs were evaluated using radiography, histology, μCT and three-point bending tests. Complete radiological healing was seen in all rats in the BMP-7 groups. The callus volume was larger and the calluses were denser with allograft+BMP-7+ZA than in all other groups (μCT, p<0.001). Mechanical testing yielded a substantially higher peak force with the allograft+BMP-7+ZA combination than all other groups (p<0.01, p<0.001). This was further reinforced in the 59% increase in the peak force observed in the osteotomized femurs of the allograft+BMP-7+ZA group compared to the control femurs (p<0.01), whereas significant decreases of 22-27% were observed in the saline or bone-graft alone groups (p<0.01, p<0.05). Thus our results suggest that allograft combined with the anabolic effect of BMP-7 and the anti-catabolic effect of zoledronate is more efficient than autograft alone.
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| 7. |
- 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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| 8. |
- Agholme, Fredrik, et al.
(författare)
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The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions
- 2011
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Ingår i: BONE. - : Elsevier Science B.V., Amsterdam.. - 8756-3282. ; 48:5, s. 988-996
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Tidskriftsartikel (refereegranskat)abstract
- The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unclear how it is involved in the mechanical control of bone maintenance. We investigated the response to administration of a Dkk1 neutralizing antibody (Dkk1-ab) in metaphyseal bone under different loading conditions, with or without trauma. In this three part experiment, 120 rats had a screw or bone chamber inserted either unilaterally or bilaterally in the proximal tibia. Mechanical (pull-out) testing, mu CT and histology were used for evaluation. The animals were injected with either 10 mg/kg Dkk1-ab or saline every 14 days for 14, 28, or 42 days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28 days, the pull-out force was increased by over 100%. In cancellous bone, the bone volume fraction was increased by 50%. In some animals, one hind limb was paralyzed with Botulinum toxin A (Botox) to create a mechanically unloaded environment. This did not increase the response to antibody treatment with regard to screw fixation, but in cancellous bone, the bone volume fraction increased by 233%. Thus, the response in unloaded, untraumatized bone was proportionally larger, suggesting that Dkk1 may be up-regulated in unloaded bone. There was also an increase in thickness of the metaphyseal cortex. In bone chambers, the antibody treatment increased the bone volume fraction. The results suggest that antibodies blocking Dkk1 might be used to stimulate bone formation especially during implant fixation, fracture repair, or bone disuse. It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction.
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| 9. |
- Isaksson, Hanna, et al.
(författare)
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Neutron tomographic imaging of bone-implant interface : Comparison with X-ray tomography
- 2017
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 103, s. 295-301
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Tidskriftsartikel (refereegranskat)abstract
- Metal implants, in e.g. joint replacements, are generally considered to be a success. As mechanical stability is important for the longevity of a prosthesis, the biological reaction of the bone to the mechanical loading conditions after implantation and during remodelling determines its fate. The bone reaction at the implant interface can be studied using high-resolution imaging. However, commonly used X-ray imaging suffers from image artefacts in the close proximity of metal implants, which limit the possibility to closely examine the bone at the bone-implant interface. An alternative ex vivo 3D imaging method is offered by neutron tomography. Neutrons interact with matter differently than X-rays; therefore, this study explores if neutron tomography may be used to enrich studies on bone-implant interfaces. A stainless steel screw was implanted in a rat tibia and left to integrate for 6 weeks. After extracting the tibia, the bone-screw construct was imaged using X-ray and neutron tomography at different resolutions. Artefacts were visible in all X-ray images in the close proximity of the implant, which limited the ability to accurately quantify the bone around the implant. In contrast, neutron images were free of metal artefacts, enabling full analysis of the bone-implant interface. Trabecular structural bone parameters were quantified in the metaphyseal bone away from the implant using all imaging modalities. The structural bone parameters were similar for all images except for the lowest resolution neutron images. This study presents the first proof-of-concept that neutron tomographic imaging can be used for ex-vivo evaluation of bone microstructure and that it constitutes a viable, new tool to study the bone-implant interface tissue remodelling.
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| 10. |
- Pierantoni, Maria, et al.
(författare)
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Muscular loading affects the 3D structure of both the mineralized rudiment and growth plate at early stages of bone formation
- 2021
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- Fetal immobilization affects skeletal development and can lead to severe malformations. Still, how mechanical load affects embryonic bone formation is not fully elucidated. This study combines mechanobiology, image analysis and developmental biology, to investigate the structural effects of muscular loading on embryonic long bones. We present a novel approach involving a semi-automatic workflow, to study the spatial and temporal evolutions of both hard and soft tissues in 3D without any contrast agent at micrometrical resolution. Using high-resolution phase-contrast-enhanced X-ray synchrotron microtomography, we compare the humeri of Splotch-delayed embryonic mice lacking skeletal muscles with healthy littermates. The effects of skeletal muscles on bone formation was studied from the first stages of mineral deposition (Theiler Stages 23 and 24) to just before birth (Theiler Stage 27). The results show that muscle activity affects both growth plate and mineralized regions, especially during early embryonic development. When skeletal muscles were absent, there was reduced mineralization, altered tuberosity size and location, and, at early embryonic stages, decreased chondrocyte density, size and elongation compared to littermate controls. The proposed workflow enhances our understanding of mechanobiology of early bone formation and could be implemented for the study of other complex biological tissues.
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