| 1. |
- Grassi, Lorenzo, et al.
(författare)
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3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort
- 2023
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Ingår i: Journal of Bone and Mineral Research. - : John Wiley & Sons. - 0884-0431 .- 1523-4681. ; 38:9, s. 1258-1267
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Tidskriftsartikel (refereegranskat)abstract
- Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed amethod to reconstruct the 3D hip anatomy froma 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a populationbased cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120men with a hip fracture (<10 years frombaseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, Delta AUROC = 0.06) and fallers (Delta AUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.
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| 2. |
- Le Cann, Sophie, et al.
(författare)
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Investigating the mechanical characteristics of bone-metal implant interface using in situ synchrotron tomographic imaging
- 2019
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 6:JAN
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Tidskriftsartikel (refereegranskat)abstract
- Long-term stability of endosseous implants depends on successful bone formation, ingrowth and adaptation to the implant. Specifically, it will define the mechanical properties of the newly formed bone-implant interface. 3D imaging during mechanical loading tests (in situ loading) can improve the understanding of the local processes leading to bone damage and failure. In this study, titanium screws were implanted into rat tibiae and were allowed to integrate for 4 weeks with or without the addition of the growth factor Bone Morphogenetic Protein and the bisphosphonate Zoledronic Acid. Samples were subjected to in situ pullout using high-resolution synchrotron x-ray tomography at the Tomcat beamline (SLS, PSI, Switzerland) at 30 keV with 25 ms exposure time, resulting in a total acquisition time of 45 s per scan, with a 3.6 μm isotropic voxel size. Using a custom-made loading device positioned inside the beamline, screws were pulled out with 0.05 mm increment, acquiring multiple scans until rupture of the sample. The in situ loading protocol was adapted to ensure short imaging time, which enabled multiple samples to be tested with short loading steps, while keeping the total testing time low and reducing dose deposition. Higher trabecular bone content was quantified in the surrounding of the screw in the treated groups, which correlated with increased mechanical strength and stiffness. Differences in screw implantation, such as contact between threads and cortex as well as minor tilt of the screw were also correlated to the mechanical parameters. In situ loading enabled the investigation of crack propagation during the pullout, highlighting the mechanical behavior of the interface. Three typical crack types were observed: (1) rupture at the interface of trabecular and cortical bone tissues, close to the screw, (2) large crack inside the cortex connected to the implant, and (3) first failure away from the screw with cracks propagating toward the screw-bone interface. Mechanical properties of in vivo integrated bone-metal screws rely on a combination of multiple parameters that are difficult to identify and separate one from the other.
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| 3. |
- Belfrage, Ola, et al.
(författare)
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Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.
- 2012
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 13:Dec.,05
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. METHODS: Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml) for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml) was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg) systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV) of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. RESULTS: In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007). In all groups receiving zoledronic acid, the BV/TV was higher compared to control. CONCLUSIONS: This study found a strong inhibitory effect on bone resorption by bisphosphonates but also a limited inhibition of the ingrowth of new bone. Local treatment at surgery resulted in stronger inhibition of both resorption and bone formation compared to systemic treatment.
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| 4. |
- Bosemark, Per, et al.
(författare)
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Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength
- 2013
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 84:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Bone morphogenic proteins (BMPs) can be used in non-unions to replace autograft. BMPs induce osteoblasts and (less well known) also osteoclasts, which can in turn be controlled by a bisphosphonate. In the present study, our aim was to improve the biological effect of autologous bone graft by adding an anabolic BMP, with or without bisphosphonates, in an open-fracture model prone to non-union. Methods Rat femurs were osteotomized and fixed with an intramedullary K-wire. Autograft was placed at the osteotomy, mixed with either saline or BMP-7. After 2 weeks, the rats had a single injection of saline or of a bisphosphonate (zoledronate). The rats were killed after 6 weeks and the femurs were evaluated by radiography, micro-CT, histology, and 3-point bending test. Results All fractures healed. The callus volume was doubled in the BMP-treated femurs (p < 0.01) and increased almost 4-fold in the femurs treated with both BMP and systemic zoledronate (p < 0.01) compared to autograft. In mechanical testing, the autograft group reached approximately half the strength of the contralateral, non-osteotomized femur (p < 0.001). By adding BMP to the autograft, the strength was doubled (p < 0.001) and with both BMP and systemic zoledronate, the strength was increased 4-fold (p < 0.001) compared to autograft alone. Interpretation The combination of BMP and bisphosphonate as an adjunct to autograft is superior to autograft alone or combined with BMP. The combination may prove valuable in the treatment of non-unions.
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| 5. |
- Bosemark, Per, et al.
(författare)
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Influence of systemic bisphosphonate treatment on mechanical properties of BMP-induced calluses in a rat fracture model: Comparison of three-point bending and twisting test.
- 2014
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 32:5, s. 721-726
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Tidskriftsartikel (refereegranskat)abstract
- The combination of autograft, BMP and bisphosphonate has been shown to produce strong calluses. In this study, without autograft we investigate the effect of bisphosphonate treatment on BMP-induced calluses, both in bending and in rotation. Sprague-Dawley rats (n = 42) underwent femoral osteotomy and BMP-7 treatment. At 2 weeks an injection of saline or bisphosphonate was administered. The animals were sacrificed after 6 weeks. Both femurs were tested in either three-point bending or twisting. All femurs healed. BMP + bisphosphonate-treatment led to larger calluses (p < 0.05) and in three-point bending, higher ultimate force (p < 0.01) and greater stiffness (p < 0.05) than BMP alone. The BMP + bisphosphonate group was nearly 60% stronger than controls, while the BMP group did not reach the strength (p < 0.05) nor stiffness (p < 0.01) of the controls. In the twisting test, similar trends were found but less pronounced. Three-point bending produced transverse callus associated fractures, whereas the twisting test produced spiral fractures, located in the structurally weaker distal femur. BMP + bisphosphonate-treatment produces calluses that are mechanically superior to calluses induced by BMP alone, when tested both in three-point bending and in twisting. For the mechanical evaluation of pharmacologically enhanced calluses with breaking strengths exceeding the native bone, the bending test is recommended. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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| 6. |
- Bosemark, Per, et al.
(författare)
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The Masquelet Induced Membrane Technique with BMP and a Synthetic Scaffold Can Heal a Rat Femoral Critical Size Defect.
- 2015
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 33:4, s. 488-495
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Tidskriftsartikel (refereegranskat)abstract
- Long bone defects can be managed by the induced membrane technique together with autologous bone graft. However, graft harvest is associated with donor site morbidity. This study investigates if a tricalcium phosphate hydroxyapatite scaffold can be used alone or in combination with bone active drugs to improve healing. Sprague Dawley rats (n = 40) were randomized into four groups. (A) scaffold, (B) BMP-7, (C) BMP-7 + scaffold, and (D) BMP-7 + scaffold + systemic bisphosphonate at 2 weeks. Locked femoral nailing was followed by 6 mm segment removal and implantation of an epoxy spacer. At 4 weeks, the spacers were removed and the defects grafted. Eleven weeks later, the bones were explanted for evaluation with radiography, manual assessment, micro-CT, histology, and Fourier Transform Infrared spectroscopy (FTIR). Isolated scaffolds (A) did not heal any defects, whereas the other treatments led to healing in 7/10 (B), 10/10 (C), and 9/10 (D) rats. Group D had greater volume of highly mineralized bone (p < 0.01) and higher bone volume fraction (p < 0.01) compared to all other groups. A synthetic scaffold + BMP-7 combined with a bisphosphonate improved the callus properties in a rat femoral critical size defect, compared to both BMP-7 and scaffold alone or the two combined. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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| 7. |
- Dejea, Hector, et al.
(författare)
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In Situ Loading and Time-Resolved Synchrotron-Based Phase Contrast Tomography for the Mechanical Investigation of Connective Knee Tissues : A Proof-of-Concept Study
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Ingår i: Advanced Science. - 2198-3844.
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Tidskriftsartikel (refereegranskat)abstract
- Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time-resolved synchrotron-based X-ray phase-contrast tomography (SR-PhC-µCT) allows to capture the tissue dynamics. This proof-of-concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR-PhC-µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress–relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases.
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| 8. |
- Finnilä, Mikko A J, et al.
(författare)
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Mineral Crystal Thickness in Calcified Cartilage and Subchondral Bone in Healthy and Osteoarthritic Human Knees
- 2022
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 37:9, s. 1700-1710
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage.
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| 9. |
- Grassi, Lorenzo, et al.
(författare)
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3d Finite Element Models Reconstructed From 2d Dxa Images Improve Hip Fracture Prediction Compared to Areal Bmd in Mros Sweden Cohort
- 2023
-
Ingår i: Journal of Bone and Mineral Research. - 1523-4681. ; 38:9, s. 1258-1267
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Tidskriftsartikel (refereegranskat)abstract
- Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (MrOS Sweden). We defined two sub-cohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and 2 controls to each hip fracture case, matched by age, height, and body mass index; (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperform aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.
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| 10. |
- Gustafsson, Anna, et al.
(författare)
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Linking multiscale deformation to microstructure in cortical bone using in situ loading, digital image correlation and synchrotron X-ray scattering
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 69, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of fragility fractures is expected to increase in the near future due to an aging population. Therefore, improved tools for fracture prediction are required to treat and prevent these injuries efficiently. For such tools to succeed, a better understanding of the deformation mechanisms in bone over different length scales is needed. In this study, an experimental setup including mechanical tensile testing in combination with digital image correlation (DIC) and small/wide angle X-ray scattering (SAXS/WAXS) was used to study deformation at multiple length scales in bovine cortical bone. Furthermore, micro-CT imaging provided detailed information about tissue microstructure. The combination of these techniques enabled measurements of local deformations at the tissue- and nanoscales. The orientation of the microstructure relative to the tensile loading was found to influence the strain magnitude on all length scales. Strains in the collagen fibers were 2-3 times as high as the strains found in the mineral crystals for samples with microstructure oriented parallel to the loading. The local tissue strain at fracture was found to be around 0.5%, independent of tissue orientation. However, the maximum force and the irregularity of the crack path were higher when the load was applied parallel to the tissue orientation. This study clearly shows the potential of combining these different experimental techniques concurrently with mechanical testing to gain a better understanding of bone damage and fracture over multiple length scales in cortical bone. Statement of Significance: To understand the pathophysiology of bone, it is important to improve our knowledge about the deformation and fracture mechanisms in bone. In this study, we combine several recently available experimental techniques with mechanical loading to investigate the deformation mechanisms in compact bone tissue on several length scales simultaneously. The experimental setup included mechanical tensile testing in combination with digital image correlation, microCT imaging, and small/wide angle X-ray scattering.The combination of techniques enabled measurements of local deformations at the tissue- and nanoscales. The study clearly shows the potential of combining different experimental techniques concurrently with mechanical testing to gain a better understanding of structure-property-function relationships in bone tissue.
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