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PubMed1992

GLOBIC: a very fast microcomputer program for fingerprinting, characterization and comparison of long nucleotide sequences.

This paper describes the program GLOBIC, which compares, characterizes and fingerprints even 0.1 Mbase sequences in a few minutes with the aid of an IBM-AT microcomputer. Instead of the nucleotide sequences themselves, GLOBIC compares the local nucleotide or short oligonucleotide compositions. GLOBIC presents two-dimensional maps of contour lines depicting the similarity of two different sequences, a sequence compared to itself, to its complementary sequence or to a random sequence. A vocabulary is presented to translate the typical patterns appearing in the two-dimensional maps into their meanings as relationships between the compared sequences. The application of GLOBIC is demonstrated using several examples from the genomic nucleotide sequences of bacteriophage T7, adenovirus type-2 and Epstein-Barr virus.

Adenoviridae↗
PubMed1998

Use of microcomputed tomography scanning as a new technique for the evaluation of membranous bone.

Previous basic bone studies in cranial bone biology and bone grafting have used calipers, volume displacement, and cephalometric tracings to measure membranous bone and to infer fundamental properties of cranial bone. These tools have limited accuracy and reproducibility. Histomorphometry has also been used in the quantitative analysis of cranial bone; however, two-dimensional histology is unable to capture a precise representation of the three-dimensional structure of bone. For the first time, we have used the advanced technology of three-dimensional microcomputed tomographic (micro-CT) scanning as a highly accurate and automated tool to precisely measure changes in bone stereology, volume and projection, and microarchitecture in the evaluation of membranous bone. The advantages of this technology are numerous and include the rapid and nondestructive three-dimensional analysis of bone microstructure at resolutions between 10 and 75 microns. Measures of "connectivity" in three dimensions and the architectural parameter of "anisotropy" are available through micro-CT imaging but can only be inferred through two-dimensional histological series. We successfully imaged two full-thickness cranial bone specimens and one cancellous iliac bone graft. The images demonstrate a similarity between the two membranous specimens and a marked difference in comparison with the endochondral graft. These differences are borne out by mathematical analysis, and their significance is discussed. The utility of micro-CT in the evaluation of membranous bone was displayed by its ability to rapidly calculate differences in bone stereology and to quantitatively measure morphological changes at an ultrastructural level. We believe the benefits of this system will prove to be extremely useful for investigations into the basic biology of membranous bone, bone grafts, and craniofacial interfaces, and we encourage its use by other scientific investigators in the field of craniofacial surgery as they strive for more scientifically rigorous tools to understand the basic biology of membranous bone.

Animals↗
PubMed1989

A microcomputer program for coding external cause of injury.

The publication of Injury in America emphasized a renewed interest in the scientific study of trauma. Collection and analysis of population-based data were viewed as necessary prerequisites for the establishment and evaluation of injury prevention programs. While it was noted that there is an existing broad-based gathering of injury mortality information, it was also made clear that there is a paucity of systematically collected morbidity data. A fundamental step toward correcting this deficiency is to identify and adopt a uniform system for coding causes of injury morbidity that is compatible with the large body of mortality data currently being collected. This paper describes a microcomputer-based program, which is intended to aid in the selection of External Cause of Injury Codes (E-codes). It is designed for coding both fatal and nonfatal injury causes and is appropriate for use in the hospital setting. The system is a modification of the one currently used for coding all injury deaths in the United States.

Humans↗
PubMed2006

Analysis of change patterns of microcomputed tomography 3-dimensional bone parameters as a high-throughput tool to evaluate antiosteoporotic effects of agents at an early stage of ovariectomy-induced osteoporosis in mice.

OBJECTIVES: The purposes of this study were to develop an osteoporosis model in a short period of 2 weeks after ovariectomy in mice and to investigate whether analysis of microcomputed tomography (muCT) 3-dimensional bone parameters could provide useful information on the mechanism of action of antiosteoporotic agents. MATERIALS AND METHODS: Mice were ovariectomized (OVX) or sham-operated, and the OVX mice were treated daily with 17beta-estradiol (E2), parathyroid hormone (PTH[1-34]), raloxifene, rolipram, or vehicle for 2 weeks. On day 14 post-OVX, the left femur bones were removed and then the distal metaphyseal bone was analyzed by both muCT and histomorphometry. RESULTS: The trabecular bone volume, thickness, number, and connectivity significantly decreased and the number of osteoclasts increased in OVX mice. Treatment of OVX animals with each of the 4 antiosteoporotic agents significantly increased the bone volume and improved the bone architecture. However, the improvement of trabecular thickness in the rolipram-treated group and that of cortical thickness in the PTH(1-34)-treated group were the most marked, whereas the improvement of connectivity in the rolipram-treated group was the least among the drug-treated groups. These different improving effects of agents on the bone parameters reflect the differential effects of these agents on bone formation and bone resorption. CONCLUSIONS: This study demonstrated the feasibility of evaluating the effect of the antiosteoporotic agents within 2 weeks after ovariectomy in mice. The muCT analysis may serve as a valuable tool, specifically in a high-throughput pharmacological screening test, offering useful information regarding the effects of test compounds on both bone resorption and formation.

Animals↗
PubMed2006

Assessment of bone union/nonunion in an experimental model using microcomputed technology.

BACKGROUND: High-resolution microcomputed tomography (microCT) is one of the most recent technical developments to visualize and quantify primarily cancellous bone. Regarding bone formation, microCT is becoming increasingly important, although its reliability has not yet been evaluated. Our study had two goals: to develop a reproducible nonunion model and to determine the efficacy of microCT for the assessment of bone healing in this model. METHODS: The designed fracture model in the rat simulates secondary fracture healing. After plate fixation to the femur, diaphysis transverse middiaphyseal osteotomy was performed with a reciprocating saw, resulting in a 0.38-mm gap with a defect of bone and periosteum corresponding to the thickness of the blade. Proximally and distally to this gap, the periosteum was preserved. Thus, three separate zones were defined: proximal femur diaphysis with periosteum, gap, and distal femur diaphysis with periosteum. In the nonunion group (NM group), a model of impaired bone healing (nonunion), silicone foil was wrapped around the femur diaphysis to block any influence from surrounding tissue. Coverage of the bone repair site by thigh muscles was designed for a model of bone union (M group). Four weeks postoperatively, callus formation was determined by conventional anterior-posterior and lateral plain radiographs. Ten weeks later, a second x-ray series was done as the clinical standard evaluation method. Afterward, specimens were harvested for microCT examination (two-dimensional and three-dimensional [3D]). Biomechanical testing was carried out to determine fracture healing. RESULTS: Our model is highly reproducible and results in bone nonunion in five out of six cases (83.3%). In determining fracture site, plain radiographs the least reliable method in comparison to the biomechanical testing which is the most accurate reference method. In contrast, microCT (the 3D reconstruction) showed significant correlation (r = 1) to the results assessed by biomechanical testing, whereas microCT was correct in 100%. We found bone healing in five out of six animals in the M group verified by microCT (in accordance to biomechanical data). In the M group, significantly enhanced bone formation (50%) (p = 0.008) was observed within the osteotomy site (i.e. within the gap), but there was no difference in periosteal bone formation between the groups proximally and distally to the gap. Interestingly, we did not find statistically significant differences in mineralization. CONCLUSION: We conclude that microCT with 3D reconstruction is the optimal method diagnostic tool in fracture healing, especially in nonunion. Furthermore, direct coverage of the fracture site by muscle flaps results in a mineralized enhanced bone formation within the osteotomy site (i.e. within the gap). Skeletal muscle coverage hypothetically might have osteogenic augmentation potential, thus being able to prevent pseudoarthrosis.

Animals↗
PubMed2000

Microcomputed tomography of kidneys following chronic bile duct ligation.

BACKGROUND: In hepatic cirrhosis, renal sodium and water retention can occur prior to decreases in renal blood flow (RBF). This may be explained in part by redistribution of the intrarenal microcirculation toward the juxtamedullary nephrons. To appreciate this three-dimensional spatial redistribution better, we examined the intrarenal microcirculatory changes using microcomputed tomography (micro-CT) in rats subjected to chronic bile duct ligation (CBDL). METHODS: Six kidneys from control rats and eight kidneys from rats that had undergone CBDL for 21 days were perfusion fixed in situ at physiological pressure, perfused with silicon-based Microfil containing lead chromate, embedded in plastic, and scanned by micro-CT. The microvasculature in the reconstructed three-dimensional renal images was studied using computerized image-analysis techniques. To determine the physiological condition of the rats, parallel experiments were conducted on six control and six CBDL rats to measure mean arterial pressure (MAP), RBF, glomerular filtration rate (GFR), urine flow (UF) rate, and sodium excretion by conventional methods. RESULTS: The percentage of vasculature in the renal cortex from CBDL rats was significantly decreased (10.8 +/- 0.4% vs. 16.8 +/- 2.7% control values). However, the vascular volume fractions of the medullary tissues were not significantly altered. There were no significant differences in the number of glomeruli between groups (36,430 +/- 1908 CBDLs, 36,609 +/- 3167 controls). The CBDL rats had a similar GFR than the controls but a reduced MAP, RBF, UF, and sodium excretion. CONCLUSIONS: The results indicate that after CBDL, there is a selective decrease in cortical vascular filling, which may contribute to the salt and water retention that accompanies cirrhosis.

Animals↗
PubMed1991

Population analysis on the microcomputer: a system of software packages.

"This paper describes a system of versatile software packages that has been developed by the author for population analysis on IBM-compatible microcomputers using PC or MS DOS. The series includes programs for the production of life tables, the analysis of spatial patterns and temporal trends in mortality, population projections, stationary-state population simulations and demographic planning, cohort survival estimates of net migration, and the analysis of migration matrices. Each of the programs in the series is discussed in terms of its principal analytical features, associated conceptual and methodological issues, and potential applications. The programs are intended for use both as basic research and planning tools and as instructional aids in university-level-courses. The programs and related documentation are available on a set of four 360K diskettes." (SUMMARY IN FRE)

Cohort Studies↗
PubMed1981

Direct assessment of depression by microcomputer. A feasibility study.

A self-rating depression questionnaire based on the Hamilton Depression Questionnaire was given directly by a microcomputer to 43 controls and 125 depressed patients. Scores obtained from the two groups differed very significantly; choosing an appropriate cut-off point, the computer-delivered questionnaire accurately detected the presence of depression. The severity of depression in the patients, as indicated by their scores, correlated significantly with assessments of severity by qualified clinicians. Patients commented favourably on the procedure, and the medical and nursing staff found it instructive and helpful. The use of this technique appears practicable and further evaluation is in progress.

Computers↗
PubMed2005

Effect of microcomputed tomography voxel size on the finite element model accuracy for human cancellous bone.

The level of structural detail that can be acquired and incorporated in a finite element (FE) analysis might greatly influence the results of microcomputed tomography (microCT)-based FE simulations, especially when relatively large bones, such as whole vertebrae, are of concern. We evaluated the effect of scanning and reconstruction voxel size on the microCT-based FE analyses of human cancellous tissue samples for fixed- and free-end boundary conditions using different combinations of scan/reconstruction voxel size. We found that the bone volume fraction (BV/TV) did not differ considerably between images scanned at 21 and 50 microm and reconstructed at 21, 50, or 110 microm (-0.5% to 7.8% change from the 21/21 microm case). For the images scanned and reconstructed at 110 microm, however, there was a large increase in BV/TV compared to the 21/21 microm case (58.7%). Fixed-end boundary conditions resulted in 1.8% [coefficient of variation (COV)] to 14.6% (E) difference from the free-end case. Dependence of model output parameters on scanning and reconstruction voxel size was similar between free- and fixed-end simulations. Up to 26%, 30%, 17.8%, and 32.3% difference in modulus (E), and average (VMExp), standard deviation (VMSD) and coefficient of variation (COV) of von Mises stresses, respectively, was observed between the 21/21 microm case and other scan/reconstruction combinations within the same (free or fixed) simulation group. Observed differences were largely attributable to scanning resolution, although reconstruction resolution also contributed significantly at the largest voxel sizes. All 21/21 microm results (taken as the gold standard) could be predicted from the 21/50 (r2adj= 0.91-0.99;p<0.001), 21/110 (r2adj =0.58-0.99;p<0.02) and 50/50 results (r2adj=0.61-0.97;p<0.02). While BV/TV, VMSD, and VMExp/sigma(z) from the 21/21 could be predicted by those from the 50/110 (r2adj =0.63-0.93;p<0.02) and 110/110 (r2adj =0.41-0.77;p<0.05) simulations as well, prediction of E, VMExp, and COV became marginally significant (0.04<p<0.13) at 50/110 and nonsignificant at 110/110 (0.21<p<0.70). In conclusion, calculation of cancellous bone modulus, mean trabecular stress, and other parameters are subject to large errors at 110/110 microm voxel size. However, enough microstructural details for studying bone volume fraction, trabecular shear stress scatter, and trabecular shear stress amplification (VMExp/sigma(z)) can be resolved using a 21/110 microm, 50/110 microm, and 110/110 microm voxels for both free- and fixed-end constraints.

Absorptiometry, Photon↗
PubMed2003

Fundamental image quality limits for microcomputed tomography in small animals.

Small-animal imaging has become increasingly more important as transgenic and knockout mice are produced to model human diseases. One imaging technique that has emerged is microcomputed tomography (micro-CT). For live-animal imaging, the precision in the images will be determined by the x-ray dose given to the animal. As a result, we propose a simple method to predict the noise performance of an x-ray micro-CT system as a function of dose and image resolution. An ideal, quantum-noise limited micro-CT scanner, assumed to have perfect resolution and ideal efficiency, was modeled. Using a simplified model, the coefficient of variation (COV) of the linear attenuation coefficient was calculated for a range of entrance doses and isotropic voxel sizes. COV calculations were performed for the ideal case and with simulated imperfections in efficiency and resolution. Our model was validated in phantom studies and mouse images were acquired with a specimen scanner to illustrate the results. A simplified model of noise propagation in the case of isotropic resolution indicates that the COV in the linear attenuation coefficient is proportional to (dose)(-1/2) and to the (isotropic voxel size)(-2) in the reconstructed volume. Therefore an improvement in the precision can be achieved only by increasing the isotropic voxel size (thereby decreasing the resolution of the image) or by increasing the x-ray dose. For the ideal scanner, a COV of 1% in the linear attenuation coefficient for an image of a mouse exposed to 0.25 Gy is obtained with a minimum isotropic voxel size of 135 microm. However, the same COV is achieved at a dose of 5.0 Gy with a 65 microm isotropic voxel size. Conversely, for a 68 mm diameter rat, a COV of 1% obtained from an image at 5.0 Gy would require an isotropic voxel size of 100 microm. These results indicate that short-term, potentially lethal, effects of ionizing radiation will limit high-resolution live animal imaging. As improvements in detector technology allow the resolution to improve, by decreasing the detector element size to tens of microns or less, high quality images will be limited by the x-ray dose administered. For the highest quality images, these doses will approach the lethal dose or LD50 for the animals. Approaching the lethal dose will affect the way experiments are planned, and may reduce opportunities for experiments involving imaging the same animal over time. Dose considerations will become much more important for live small-animal imaging as the limits of resolution are tested.

Animals↗
PubMed2006

Comparison of synchrotron radiation and conventional x-ray microcomputed tomography for assessing trabecular bone microarchitecture of human femoral heads.

Microcomputed tomography (microCT) produces three-dimensional (3D) images of trabecular bone. We compared conventional microCT (CmicroCT) with a polychromatic x-ray cone beam to synchrotron radiation (SR) microCT with a monochromatic parallel beam for assessing trabecular bone microarchitecture of 14 subchondral femoral head specimens from patients with osteoarthritis (n=10) or osteoporosis (n=4). SRmicroCT images with a voxel size of 10.13 microm were reconstructed from 900 2D radiographic projections (angular step, 0.2 degrees). CmicroCT images with a voxel size of 10.77 microm were reconstructed from 205, 413, and 825 projections obtained using angular steps of 0.9 degrees, 0.45 degrees, and 0.23 degrees, respectively. A single threshold was used to binarize the images. We computed bone volume/ tissue volume (BV/TV), bone surface/bone volume (BS/BV), trabecular number (Tb.N), trabecular thickness (Tb.Th and Tb.Th*), trabecular spacing (Tb.Sp), degree of anisotropy (DA), and Euler density. With the 0.9 degrees angular step, all CmicroCT values were significantly different from SRmicroCT values. With the 0.23 degrees and 0.45 degrees rotation steps, BV/TV, Tb.Th, and BS/BV by CmicroCT differed significantly from the values by SRmicroCT. The error due to slice matching (visual site matching +/- 10 slices) was within 1% for most parameters. Compared to SRmicroCT, BV/TV, Tb.Sp, and Tb.Th by CmicroCT were underestimated, whereas Tb.N and Tb. Th* were overestimated. A Bland and Altman plot showed no bias for Tb.N or DA. Bias was -0.8 +/- 1.0%, +5.0 +/- 1.1 microm, -5.9 +/- 6.3 microm, and -5.7 +/- 29.1 microm for BV/TV, Tb.Th*, Tb.Th, and Tb.Sp, respectively, and the differences did not vary over the range of values. Although systematic differences were noted between SRmicroCT and CmicroCT values, correlations between the techniques were high and the differences would probably not change the discrimination between study groups. CmicroCT provides a reliable 3D assessment of human defatted bone when working at the 0.23 degrees or 0.45 degrees rotation step; the 0.9 degrees rotation step may be insufficiently accurate for morphological bone analysis.

Femur Head↗
PubMed2005

Microcomputed tomography and histology of a fragmented medial coronoid process in a 20-week-old golden retriever.

A 20-week-old male golden retriever, which was not lame and showed no clinical signs of a fragmented medial coronoid process (FCP), was euthanased for another study and perfused intravenously with formaldehyde. Gross dissection revealed no abnormalities within the right elbow joint. The medial coronoid process was excised, embedded in methylmethacrylate, scanned in a microcomputed tomography (microCT) scanner and sectioned for histology. The microCT scans revealed a dense trabecular bone structure, much denser than in other dogs of similar age, which was considered to be responsible for the sclerosis visible at the base of the coronoid process in radiographs. Three-dimensional reconstructions indicated that there was a small step within the subchondral bone, extending from the apex towards the radial notch. Histology revealed a necrotic lesion between locally thickened articular cartilage and the subchondral bone, characteristic of osteochondrosis.

Animals↗
PubMed1979

On-line analysis of intracellular electrophysiological data using a microcomputer system.

Automated analysis of intracellular action potentials from cardiac Purkinje fibers was implemented using a microcomputer system. A dual sampling rate was used during analog-to-digital conversion of action potentials recorded from stimulated fibers. The rapid phase of depolarization was sampled at 42.55 kHz. The repolarization and the diastolic phases were sampled at 1 kHz. The resting potential, action potential amplitude, conduction time, action potential duration measured at 50% and at 90% of repolarization, and the maximum upstroke velocity were obtained on-line. The digital form of the action potential was stored on cassette tape and a table containing the various measurements was assembled during the experiment. In unstimulated fibers, the time interval between consecutive action potentials was measured on-line along with the maximum diastolic potential, the action potential overshoot, and the slope of the diastolic depolarization.

Action Potentials↗
PubMed2006

Relations between radiograph texture analysis and microcomputed tomography in two rat models of bone metastases.

AIMS: Osteolytic (Walker 256, W256) and osteoblastic (MatLyLu, MLL) metastases were induced to investigate their effect on bone architecture by microcomputed tomography (microCT) and texture analysis of radiographs. METHODS: Fischer and Copenhagen rats received an intracardiac injection with W256/MLL cells, respectively. Femur and tibia radiographs were analyzed by texture analysis with run lengths and fractal algorithms. Microarchitecture was analyzed on primary and secondary spongiosa by microCT. RESULTS: W256 and MLL induced a decrease of trabecular bone mass, a disconnection of trabeculae and an increased conversion of plates into pillars. On radiographs and 3-dimensional models of W256 rats, a disappearance of the primary spongiosa was observed. On radiographs and 3-dimensional models of MLL rats, osteolytic lesions were observed as disseminated dark areas. Run length and fractal analyses were altered in both metastases. CONCLUSION: W256 and MLL cells induced two different patterns of osteolysis. Texture analysis of radiographs is a useful technique to explore trabecular bone changes.

Animals↗
PubMed1979

Applications of microcomputer technology to cytophotometry.

Lack of appropriate software support for microprocessor program development has previously limited the applications of such technology in the field of microspectrophotometry. This paper describes our use of a Vickers M86 integrating microdensitometer coupled through a custom-designed interface circuit to a Processor Technology SOL III microcomputer. W e have developed a series of interactive, user-oriented programs for DNA-Feulgen cytophotometry with this instrument to allow automatic storage of data in files on floppy disks and instant retrieval of sets of measurements for statistical processing. The same data files can also be used to generate graphic displays in the form of bar histograms or plots of linear regressions on a video monitor and to produce hardcopy output of data files and graphic displays through the use of a high speed DIABLO printer.

Animals↗
PubMed2001

The prospects of estimating trabecular bone tissue properties from the combination of ultrasound, dual-energy X-ray absorptiometry, microcomputed tomography, and microfinite element analysis.

Osteoporosis commonly is assessed by bone quantity, using bone mineral density (BMD) measurements from dual-energy X-ray absorptiometry (DXA). However, such a measure gives neither information about the integrity of the trabecular architecture nor about the mechanical properties of the constituting trabeculae. We investigated the feasibility of deriving the elastic modulus of the trabeculae (the tissue modulus) from computer simulation of mechanical testing by microfinite element analysis (muFEA) in combination with measurements of ultrasound speed of sound (SOS) and BMD measurements. This approach was tested on 15 postmortem bovine bone cubes. The apparent elastic modulus of the specimens was estimated from SOS measurements in combination with BMD. Then the trabecular morphology was reconstructed using microcomputed tomography (muCT). From the reconstruction a mesh for muFEA was derived, used to simulate mechanical testing. The tissue modulus was found by correlating the apparent moduli of the specimens as assessed by ultrasound with the ones as determined with muFEA. A mean tissue modulus of 4.5 GPa (SD, 0.69) was found. When adjusting the muFEA-determined elastic moduli of the entire specimens with their calculated tissue modulus, an overall correlation of R2 = 96% with ultrasound-predicted values was obtained. We conclude that the apparent elastic stiffness characteristics as determined from ultrasound correlate linearly with those from muFEA. From both methods in combination, the elastic stiffness of the mineralized tissue can be determined as an estimator for mechanical tissue quality. This method can already be used for biopsy specimens, and potentially could be applicable in vivo as well, when clinical CT or magnetic resonance imaging (MRI) tools with adequate resolution reach the market. In this way, mechanical bone quality could be estimated more accurately in clinical practice.

Absorptiometry, Photon↗
PubMed2002

Three-dimensional-line skeleton graph analysis of high-resolution magnetic resonance images: a validation study from 34-microm-resolution microcomputed tomography.

The resolution achievable in vivo by magnetic resonance imaging (MRI) techniques is not sufficient to depict precisely individual trabeculae and, thus, does not permit the quantification of the "true" trabecular bone morphology and topology. Nevertheless, the characterization of the "apparent" trabecular bone network derived from high-resolution MR images (MRIs) and their potential to provide information in addition to bone mineral density (BMD) alone has been established in studies of osteoporosis. The aim of this work was to show the ability of the three-dimensional-line skeleton graph analysis (3D-LSGA) to characterize high-resolution MRIs of trabecular bone structure. Fifteen trabecular bone samples of the distal radius were imaged using the high-resolution MRI (156 x 156 x 300 microm3) and microcomputed tomography (microCT; 34 x 34 x 34 microm3). After thresholding, the 3D skeleton graph of each binary image was obtained. To remove the assimilated-noise branches of the skeleton graph and smooth this skeleton graph before it was analyzed, we defined a smoothing length criterion (l(c)), such that all "termini" branches having a length lower than l(c) were removed. Local topological and morphological LSGA measurements were performed from MRIs and microCT images of the same samples. The correlations between these two sets of measurements were dependent on the smoothing criterion l(c), reaching R2 = 0.85 for topological measurements and R2 = 0.57-0.64 for morphological measurements. 3D-LSGA technique could be applied to in vivo high-resolution MRIs of trabecular bone structure, giving an indirect characterization of the microtrabecular bone network.

Adult↗
PubMed2002

Risedronate preserves trabecular architecture and increases bone strength in vertebra of ovariectomized minipigs as measured by three-dimensional microcomputed tomography.

Risedronate reduces the risk of new vertebral fractures up to 70% within 1 year of treatment in patients with osteoporosis. Both increases in bone mass and preservation of bone architecture are thought to contribute to antifracture effects. Our objectives were to determine the effects of risedronate on trabecular bone mass and architecture and to determine the relative contributions of mass and architecture to strength in the vertebra of ovariectomized (OVX) minipigs. The minipigs were OVX at 18 months of age and were treated daily for 18 months with either vehicle or risedronate at doses of 0.5 mg/kg per day or 2.5 mg/kg per day. The three-dimensional (3D) bone architecture of the L4 vertebral cores of Sinclair S1 minipigs was evaluated by 3D microcomputed tomography (muCT). Compared with the OVX control, the vertebral bone volume (bone volume/tissue volume [BV/TV]) was higher in both treated groups (p < 0.05). The architectural changes were more significant at the 2.5-mg/kg dose and were more prevalent at the cranial-caudal ends compared with the midsection. At the higher dose, the trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity were higher, and marrow star volume (Ma.St.V) and trabecular separation (Tb.Sp) were lower (p < 0.05). The trabecular separation variation index (TSVI), a new measure to approximate structural variations, was smaller in the 2.5-mg/kg-treated group (p < 0.05). In this group, a significant preservation of trabeculae orthogonal to the cranial-caudal axis was confirmed by a decrease in the degree of anisotropy (DA) and an increase in the percent Cross-strut (% Cross-strut; p < 0.05). Both normalized maximum load (strength) and normalized stiffness of the same vertebral cores were higher in the 2.5-mg/kg risedronate group compared with the OVX group (p < 0.05). BV/TV alone could explain 76% of the variability of the bone strength. The combination of bone volume and architectural variables explained >90% of the strength. The study showed that risedronate preserved trabecular architecture in the vertebra of OVX minipigs, and that bone strength is tightly coupled to bone mass and architecture.

Animals↗