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ABSTRACT: The appearance of a forefoot push-off mechanism in the hominin lineage has been difficult to identify, partially because researchers disagree over the use of the external skeletal morphology to differentiate metatarsophalangeal joint functional differences in extant great apes and humans. In this study, we approach the problem by quantifying properties of internal bone architecture that may reflect different loading patterns in metatarsophalangeal joints in humans and great apes. High-resolution x-ray computed tomography data were collected for first and second metatarsal heads of Homo sapiens (n = 26), Pan paniscus (n = 17), Pan troglodytes (n = 19), Gorilla gorilla (n = 16), and Pongo pygmaeus (n = 20). Trabecular bone fabric structure was analyzed in three regions of each metatarsal head. While bone volume fraction did not significantly differentiate human and great ape trabecular bone structure, human metatarsal heads generally show significantly more anisotropic trabecular bone architectures, especially in the dorsal regions compared to the corresponding areas of the great ape metatarsal heads. The differences in anisotropy between humans and great apes support the hypothesis that trabecular architecture in the dorsal regions of the human metatarsals are indicative of a forefoot habitually used for propulsion during gait. This study provides a potential route for predicting forefoot function and gait in fossil hominins from metatarsal head trabecular bone architecture.
Journal of Human Evolution 08/2010; 59(2):202-13. · 3.64 Impact Factor
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ABSTRACT: Multiple myeloma (MM) is an incurable B-cell neoplasia in which progressive skeletal lesions are a characteristic feature. Earlier we established an animal model for human MM in the immune-deficient RAG2(-/-)gammac(-/-) mouse, in which the growth of luciferase-transduced MM cells was visualized using noninvasive bioluminescence imaging (BLI). This model appeared well suited to study disease progression and response to therapy by identifying the location of various foci of MM tumor growth scattered throughout the skeleton and at subsequent time points the quantitative assessment of the tumor load by using BLI. We report here on the corresponding high-resolution X-ray micro-computed tomographic (micro-CT) analysis to study skeletal defects in the mice with full-blown MM. Several anatomical derangements were observed, including abnormalities in geometry and morphology, asymmetrical bone structures, decreased overall density in the remaining bone, loss of trabecular bone mass, destruction of the inner microarchitecture, as well as cortical perforations. Using the combination of BLI, micro-CT imaging, and immune-histopathological techniques, we found a high correlation between the micro-CT-identified lesions, exact tumor location, and infiltration leading to structural lesions and local bone deformation. This confirms that this animal model strongly resembles human MM and has the potential for studying the biology of MM growth and for preclinical testing of novel therapies for MM and for repair of MM-induced bone lesions.
Calcified Tissue International 10/2009; 85(5):434-43. · 2.38 Impact Factor
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ABSTRACT: Glucocorticoids (GCs) are widely used in medicine for treatment of chronic diseases. Especially in children, prolonged treatment causes growth retardation and early onset of osteoporosis. Human parathyroid hormone (PTH) has an anabolic effect on bone when administrated intermittently. The aim of the present study was to examine whether a combined therapy of dexamethasone (DEX) and PTH could prevent the detrimental effects of GC on cortical and trabecular bone in the femur and vertebrae of growing mice. Three-week-old female FVB mice were treated with control, DEX, PTH, or a combination of DEX and PTH by daily subcutaneous injections. After 4 weeks, animals were killed and the femur and L5 vertebra were isolated. Cortical and trabecular bone parameters and relative calcium density were measured by high-resolution X-ray micro-computed tomography (micro-CT). In the femur, PTH can reverse the effects of DEX on bone volume to control. However, it cannot reverse the undermineralization, which most likely is a strong contributor to bone fragility. In the vertebra, PTH improves bone volume to some extent but does not restore the values to normal. It augments the negative effect of DEX on mineralization. We conclude that the detrimental effects of DEX in the growing skeleton cannot be prevented by simultaneous PTH treatment.
Calcified Tissue International 10/2009; 85(6):530-7. · 2.38 Impact Factor
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ABSTRACT: Hyperphosphataemia is a risk factor for arterial calcification contributing to the high cardiovascular mortality in patients with chronic kidney disease. Calcium-based phosphate binders can induce hypercalcaemia and are associated with progression of vascular calcification. Therefore, the effect of lanthanum carbonate, a non-calcium phosphate binder, on the development of vascular calcification was investigated in uraemic rats.
Chronic renal failure (CRF) was induced by feeding rats an adenine-enriched diet for 4 weeks. After 2 weeks, 1% or 2% lanthanum carbonate was added to the diet for 6 weeks. Calcification in the aorta, carotid and femoral arteries was evaluated histomorphometrically, biochemically and by ex vivo micro-CT. Chondro-/osteogenic conversion of vascular smooth muscle cells was also analysed in the rat aorta.
Treatment with 1% lanthanum carbonate (1% La) did not reduce vascular calcification, but in the 2% lanthanum carbonate (2% La) group vascular calcium content and area% Von Kossa positivity were decreased compared with control CRF rats. The aortic calcified volume measured with ex vivo micro-CT was significantly reduced in rats treated with 2% La. Although calcification was inhibited by treatment with 2% La, the chondrocyte transcription factor sox-9 was abundantly expressed in the aorta.
Treatment of CRF rats with 2% La reduces the development of vascular calcification by adequate phosphate binding resulting in a decreased supply of phosphate as a substrate for vascular calcification.
Nephrology Dialysis Transplantation 02/2009; 24(6):1790-9. · 3.40 Impact Factor
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ABSTRACT: Chronic renal failure (CRF) is associated with a 10- to 20-fold increase in cardiovascular risk. Vascular calcification is a prominent feature of cardiovascular disease in patients with end-stage renal failure and contributes to the excess mortality in this population. In this study, we explored in vivo X-ray microtomography (micro-CT) as a tool to detect and follow-up vascular calcifications in the aorta of living rats with adenine-induced CRF.
With in vivo micro-CT, calcification of the aorta in uremic rats was clearly discernible on transversal virtual cross-sections. Micro-CT findings correlated well with tissue calcium content and histology. Repetitive scans in animals with light, moderate, and severe vascular calcification showed good reproducibility with minimal interference of motion artifacts. Moreover, both calcified volume and area could be quantified with this method.
In vivo micro-CT scanning is a sensitive method to detect vascular calcifications in CRF rats, allowing follow-up and quantification of the development, and potential reversal during treatment, of vascular calcifications in living animals.
Arteriosclerosis Thrombosis and Vascular Biology 10/2006; 26(9):2110-6. · 6.37 Impact Factor
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ABSTRACT: Bone augmentation underneath an occlusive titanium membrane is evaluated in most cases by means of serial histological sections and histomorphometry. Micro-computed tomography (micro-CT) is a less invasive and dynamic technique to measure bone volume in animals of a size that fits into the gantry. The aim of the present study was to evaluate whether the latter approach could match histomorphometry to assess bone augmentation under a titanium membrane.
Pre-formed titanium cups were placed on the skull of 16 rabbits. Bone formation underneath the cups was allowed to occur for 12 weeks. The amount of bone volume assessed by micro-CT was expressed as a numerical unit. One unit volume corresponds to 0.043 mm3. The measurements reveal the volume of bone-like tissue under the membrane, with the same density as that of the original rabbit skull bone. Histological sections were cut along the same plane as the one used for the micro-CT images. The total bone surface was assessed by a digital image system in double-stained undecalcified histological sections and related to the maximum available surface of the titanium cups, which was on average 1366 mm2.
The amount of total bone surface found under the titanium membrane varied between 40 and 163 mm2. Measured by micro-CT, the bone detected ranged from 3.7 to 396 numerical units. A highly significant (P<0.001) correlation was found between the total bone volume measured in conventional serial histological sections and by the micro-CT technique (r2=0.72).
The total bone volume measured underneath a membrane using the micro-CT when compared with histological sections remained within a 16% error. This is because of the scattering effect of the metallic membrane and the impossibility to distinguish newly formed bone from the original skull bone on the micro-CT images.
Clinical Oral Implants Research 12/2005; 16(6):708-14. · 2.51 Impact Factor
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ABSTRACT: High resolution micro-CT images are often corrupted by ring artefacts, prohibiting quantitative analysis and hampering post processing. Removing or at least significantly reducing such artefacts is indispensable. However, since micro-CT systems are pushed to the extremes in the quest for the ultimate spatial resolution, ring artefacts can hardly be avoided. Moreover, as opposed to clinical CT systems, conventional correction schemes such as flat-field correction do not lead to satisfactory results. Therefore, in this note a simple but efficient and fast post processing method is proposed that effectively reduces ring artefacts in reconstructed micro-CT images.
Physics in Medicine and Biology 08/2004; 49(14):N247-53. · 2.83 Impact Factor
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ABSTRACT: High resolution micro-CT images are often corrupted by ring artifacts, prohibiting quantitative analysis and hampering post processing. Removing, or at least significantly reducing such artifacts is indispensable. However, since micro-CT systems are pushed to the extremes in the quest for the ultimate spatial resolution, ring artifacts can hardly be avoided. Moreover, as opposed to clinical CT systems, conventional correction schemes such as flat-field correction do not lead to satisfactory results. Therefore, in this paper, a simple but e#cient and fast post processing method is proposed that e#ectively reduces ring artifacts in reconstructed -CT images.
07/2004;
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ABSTRACT: The appearance of a forefoot push-off mechanism in the hominin lineage has been difficult to identify, partially because researchers disagree over the use of the external skeletal morphology to differentiate metatarsophalangeal joint functional differences in extant great apes and humans. In this study, we approach the problem by quantifying properties of internal bone architecture that may reflect different loading patterns in metatarsophalangeal joints in humans and great apes. High-resolution x-ray computed tomography data were collected for first and second metatarsal heads of Homo sapiens (n = 26), Pan paniscus (n = 17), Pan troglodytes (n = 19), Gorilla gorilla (n = 16), and Pongo pygmaeus (n = 20). Trabecular bone fabric structure was analyzed in three regions of each metatarsal head. While bone volume fraction did not significantly differentiate human and great ape trabecular bone structure, human metatarsal heads generally show significantly more anisotropic trabecular bone architectures, especially in the dorsal regions compared to the corresponding areas of the great ape metatarsal heads. The differences in anisotropy between humans and great apes support the hypothesis that trabecular architecture in the dorsal regions of the human metatarsals are indicative of a forefoot habitually used for propulsion during gait. This study provides a potential route for predicting forefoot function and gait in fossil hominins from metatarsal head trabecular bone architecture.
Journal of Human Evolution.
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