The Effects on the Femoral Cortex of a 24 Month Treatment Compared to an 18 Month Treatment with Teriparatide: A Multi-Trial Retrospective Analysis.

BACKGROUND: Teriparatide (TPTD) is an anabolic agent indicated for the treatment of severely osteoporotic patients who are at high risk of fragility fractures. The originally approved duration of TPTD treatment in several regions, including Europe, was 18 months. However, studies of areal bone mineral density (aBMD) showed additional benefit when treatment is continued beyond 18 months, and the drug is currently licenced for 24 months. Improvements in cortical structure at the proximal femur have already been shown in patients given TPTD for 24 months using quantitative computed tomography (QCT). Here, we investigate whether cortical and endocortical trabecular changes differ between an 18- and 24-month treatment. METHODS: Since an 18- versus 24-month TPTD study using QCT has not been conducted, we studied combined QCT data from four previous clinical trials. Combined femoral QCT data from three 18-month TPTD studies ('18-month group') were compared with data from a fourth 24-month trial ('24-month group'). Cortical parameters were measured over the entire proximal femur which allowed for a comparison of the mean changes as well as a visual comparison of the colour maps of changes after 18 and 24 months TPTD. RESULTS: For both the combined 18-month group and the 24-month group, overall cortical thickness and endocortical trabecular density increased, while overall cortical bone mineral density decreased. While the changes in the 24-month group were of greater magnitude compared to the 18-month group, the differences were only significant for the endocortical trabecular density (ECTD), corrected for age, weight, femoral neck T-score, total hip T-score and the baseline mean ECTD. CONCLUSION: Although the combination of data from different clinical trials is not optimal, these data support the concept that the duration of TPTD in the 18-24 month phase is of clinical relevance when considering improvement in hip structure.This study was funded by Eli Lilly. TW, GMT, AHG and KESP received research grants from Eli Lilly. KESP is also funded by the Cambridge NIHR Biomedical research Centre. The Evelyn Trust funded GMT. The funders had no role in study design, data analysis or decision to publish, but were involved in collection of data and had the chance to review the manuscript once written.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014772

Mapping Bone Changes at the Proximal Femoral Cortex of Postmenopausal Women in Response to Alendronate and Teriparatide Alone, Combined or Sequentially.

Combining antiresorptive and anabolic drugs for osteoporosis may be a useful strategy to prevent hip fractures. Previous studies comparing the effects of alendronate (ALN) and teriparatide (TPTD) alone, combined or sequentially using quantitative computed tomography (QCT) in postmenopausal women have not distinguished cortical bone mineral density (CBMD) from cortical thickness (CTh) effects, nor assessed the distribution and extent of more localized changes. In this study a validated bone mapping technique was used to examine the cortical and endocortical trabecular changes in the proximal femur resulting from an 18-month course of ALN or TPTD. Using QCT data from a different clinical trial, the global and localized changes seen following a switch to TPTD after an 18-month ALN treatment or adding TPTD to the ALN treatment were compared. Ct.Th increased (4.8%, p < 0.01) and CBMD decreased (-4.5%, p < 0.01) in the TPTD group compared to no significant change in the ALN group. A large Ct.Th increase could be seen for the switch group (2.8%, p < 0.01) compared to a significantly smaller increase for the add group (1.5%, p < 0.01). CBMD decreased significantly for the switch group (-3.9%, p < 0.01) and was significantly different from no significant change in the add group. Ct.Th increases were shown to be significantly greater for the switch group compared to the add group at the load bearing regions. This study provides new insights into the effects of ALN and TPTD combination therapies on the cortex of the proximal femur and supports the hypothesis of an increased bone remodeling by TPTD being mitigated by ALN.This is the accepted manuscript. The final version is available at http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2454/abstract

A groupwise mutual information metric for cost efficient selection of a suitable reference in cardiac computational atlas construction

International audienceComputational atlases based on nonrigid registration have found much use in the medical imaging community. To avoid bias to any single element of the training set, there are two main approaches: using a (random) subject to serve as an initial reference and posteriorly removing bias, and a true groupwise registration with a constraint of zero average transformation for direct computation of the atlas. Major drawbacks are the possible selection of an outlier on one side, and an initialization with an invalid instance on the other. In both cases there is great potential for affecting registration performance, and producing a final average image in which the structure of interest deviates from the central anatomy of the population under study. We propose an inexpensive means of reference selection based on a groupwise correspondence measure, which avoids the selection of an outlier and is independent from the atlas construction approach that follows. Thus, it improves tractability of reference selection and robustness of automated atlas construction. We illustrate the method using a set of 20 cardiac multislice computed tomography volumes

Building a better future: An exploration of beliefs about climate change and perceived need for adaptation within the building industry

Copyright © 2011 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Building and Environment . Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Building and Environment Vol. 46 (2011), DOI: 10.1016/j.buildenv.2010.12.007The present research explored beliefs about climate change among an important yet relatively understudied population: representatives of the building industry. We also assessed the perceived adequacy of current climate-related actions within the industry and the perceived need for developing new practices. The results of a survey administered within a large engineering firm suggest a fairly high level of concern about climate issues within this sector: participants perceived climate change to be an important issue, current practices to be inadequate, and a need to develop new ways of addressing climate change. Despite this, there was notable and consequential variability in how participants thought about climate change. Higher levels of seniority were associated with greater satisfaction with current practices, and the belief that climate change was a natural rather than man-made phenomena was associated with a reduced support for the idea that changes to current practices were necessary. In addition, when thinking about climate relevant actions (whether current practices or the alternatives) participants focussed almost exclusively on mitigation rather than adaptation. The implications of these patterns for innovation around climate change within the building industry are discussed.EPSR

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density.

Funder: NIHR Cambridge BRC; Id: http://dx.doi.org/10.13039/501100018956Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).This research was funded by Amgen and supported by the NIHR Cambridge BRC. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

3D reconstruction of the proximal femur and lumbar vertebrae from dual-energy x-ray absorptiometry for osteoporotic risk assessment

In this thesis a method was developed to reconstruct both the 3D shape and the BMD distribution of bone structures from Dual-energy X-ray Absorptiometry (DXA) images. The method incorporates a statistical model built from a large dataset of Quantitative Computed Tomography (QCT) scans together with a 3D-2D intensity based registration process. The method was evaluated for its ability to reconstruct the proximal femur from a single DXA image. The resulting parameters of the reconstructions were subsequently evaluated for their hip fracture discrimination ability. The reconstruction method was finally extended to the reconstruction of the lumbar vertebrae from anteroposterior and lateral DXA, thereby incorporating a multi-object and multi-view approach. These techniques can potentially improve the fracture risk estimation accuracy over current clinical practice.En esta tesis se desarrolló un método para reconstruir tanto la forma 3D de estructuras óseas como la distribución de la DMO a partir de una sola imagen de DXA. El método incorpora un modelo estadístico construido a partir de una gran base de datos de QCT junto con una técnica de registro 3D-2D basada en intensidades. Se ha evaluado la capacidad del método para reconstruir la parte proximal del fémur a partir de una imagen DXA. Los parámetros resultantes de las reconstrucciones fueron evaluados posteriormente por su capacidad en discriminar una fractura de cadera. Por fin, se extendió el método a la reconstrucción de las vértebras lumbares a partir de DXA anteroposterior y lateral incorporando así un enfoque multi-objeto y multi-vista. Estos técnicas pueden potencialmente mejorar la precisión en la estimación del riesgo de fractura respecto a la estimación que ofrece la práctica clínica actual