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Rizzoli R.,University of Geneva | Chapurlat R.D.,University of Lyon | Laroche J.-M.,Toulouse University Hospital Center | Krieg M.A.,CHUV | And 6 more authors.
Osteoporosis International | Year: 2012

Summary Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2 years, in postmenopausal osteoporotic women. Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. Results In the intention-to-treat population (n=83, age: 64± 8 years; lumbar T-score: -2.8±0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P<0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P<0.05 for all above betweengroup differences). Difference for CTh evaluated with a distance transformation method was close to significance (P=0.06). The estimated failure load increased with SrRan (+2.1%, P<0.005), not with alendronate (-0.6%, NS) (between-group difference, P<0.01). Cortical stress was lower with SrRan (P<0.05); both treatments decreased trabecular stress. At distal radius, there was no betweengroup difference other than DCort (P<0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P<0.0001). Both treatments were well tolerated. Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011.

Vilayphiou N.,University of Lyon | Vilayphiou N.,SCANCO Medical AG | Boutroy S.,University of Lyon | Sornay-Rendu E.,University of Lyon | And 2 more authors.
Bone | Year: 2016

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women.The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity.Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r2=0.22 only at the tibia in postmenopausal women.In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia. © 2015 .

Burghardt A.J.,University of California at San Francisco | Buie H.R.,University of Calgary | Laib A.,SCANCO Medical AG | Majumdar S.,University of California at San Francisco | Boyd S.K.,University of Calgary
Bone | Year: 2010

Quantitative cortical microarchitectural end points are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and microarchitecture from HR-pQCT images of the distal radius and tibia.An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia and detect intracortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled data set of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates.The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%, p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23μm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume but not for density or microarchitecture.This study indicates that HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality. © 2010 Elsevier Inc.

Sengle G.,University of Cologne | Tufa S.F.,Shriners Hospital for Children | Sakai L.Y.,Shriners Hospital for Children | Sakai L.Y.,Oregon Health And Science University | And 3 more authors.
Journal of Histochemistry and Cytochemistry | Year: 2013

We present a method in which a precise region of interest within an intact organism is spatially mapped in three dimensions by non-invasive micro-computed X-ray tomography (micro-CT), then further evaluated by light microscopy (LM) and transmission electron microscopy (TEM). Tissues are prepared as if for TEM including osmium fixation, which imparts soft tissue contrast in the micro-CT due to its strong X-ray attenuation. This method may therefore be applied to embedded, archived TEM samples. Upon selection of a two-dimensional (2-D) projection from a region of interest (ROI) within the three-dimensional volume, the epoxyembedded sample is oriented for microtomy so that the sectioning plane is aligned with the micro-CT projection. Registration is verified by overlaying LM images with 2-D micro-CT projections. Structures that are poorly resolved in the micro-CT may be evaluated at TEM resolution by observing the next serial ultrathin section, thereby accessing the same ROI by all three imaging techniques. We compare white adipose tissue within the forelimbs of mice harboring a lipid-altering mutation with their littermate controls. We demonstrate that individual osmium-stained lipid droplets as small as 15 μm and separated by as little as 35 μm may be discerned as separate entities in the micro-CT, validating this to be a high-resolution, non-destructive technique for evaluation of fat content. © The Author(s) 2013.

Blom H.,KTH Royal Institute of Technology | Hassler K.,KTH Royal Institute of Technology | Hassler K.,SCANCO Medical AG | Chmyrov A.,KTH Royal Institute of Technology | Widengren J.,KTH Royal Institute of Technology
International Journal of Molecular Sciences | Year: 2010

Electrostatic interactions between dielectric surfaces and different fluorophores used in ultrasensitive fluorescence microscopy are investigated using objective-based Total Internal Reflection Fluorescence Correlation Spectroscopy (TIR-FCS). The interfacial dynamics of cationic rhodamine 123 and rhodamine 6G, anionic/dianionic fluorescein, zwitterionic rhodamine 110 and neutral ATTO 488 are monitored at various ionic strengths at physiological pH. As analyzed by means of the amplitude and time-evolution of the autocorrelation function, the fluorescent molecules experience electrostatic attraction or repulsion at the glass surface depending on their charges. Influences of the electrostatic interactions are also monitored through the triplet-state population and triplet relaxation time, including the amount of detected fluorescence or the count-rate-per-molecule parameter. These TIR-FCS results provide an increased understanding of how fluorophores are influenced by the microenvironment of a glass surface, and show a promising approach for characterizing electrostatic interactions at interfaces. © 2010 by the authors; licensee Molecular Diversity Preservation International.

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