Imperial College London

DrRichardAbel

Faculty of MedicineDepartment of Surgery & Cancer

Senior Lecturer
 
 
 
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Contact

 

richard.abel

 
 
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Location

 

204Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
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71 results found

Stavri R, Tay T, Wiles CC, Di Federico E, Boughton O, Ma S, Karunaratne A, Churchwell JH, Bhattacharya R, Terrill NJ, Cobb JP, Hansen U, Abel RLet al., 2023, A cross-sectional study of bone nanomechanics in hip fracture and aging, Life, Vol: 13, ISSN: 2075-1729

Bone mechanics is well understood at every length scale except the nano-level. We aimed to investigate the relationship between bone nanoscale and tissue-level mechanics experimentally. We tested two hypotheses: (1) nanoscale strains were lower in hip fracture patients versus controls, and (2) nanoscale mineral and fibril strains were inversely correlated with aging and fracture. A cross-sectional sample of trabecular bone sections was prepared from the proximal femora of two human donor groups (aged 44–94 years): an aging non-fracture control group (n = 17) and a hip-fracture group (n = 20). Tissue, fibril, and mineral strain were measured simultaneously using synchrotron X-ray diffraction during tensile load to failure, then compared between groups using unpaired t-tests and correlated with age using Pearson’s correlation. Controls exhibited significantly greater peak tissue, mineral, and fibril strains than the hip fracture (all p < 0.05). Age was associated with a decrease in peak tissue (p = 0.099) and mineral (p = 0.004) strain, but not fibril strain (p = 0.260). Overall, hip fracture and aging were associated with changes in the nanoscale strain that are reflected at the tissue level. Data must be interpreted within the limitations of the observational cross-sectional study design, so we propose two new hypotheses on the importance of nanomechanics. (1) Hip fracture risk is increased by low tissue strain, which can be caused by low collagen or mineral strain. (2) Age-related loss of tissue strain is dependent on the loss of mineral but not fibril strain. Novel insights into bone nano- and tissue-level mechanics could provide a platform for the development of bone health diagnostics and interventions based on failure mechanisms from the nanoscale up.

Journal article

Bonicelli A, Tay T, Cobb JP, Boughton OR, Hansen U, Abel RL, Zioupos Pet al., 2023, Association between nanoscale strains and tissue level nanoindentation properties in age-related hip-fractures, JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, Vol: 138, ISSN: 1751-6161

Journal article

Behforootan S, Thorniley M, Minonzio J-G, Boughton O, Karia M, Bhattacharya R, Hansen U, Cobb J, Abel Ret al., 2022, Can guided wave ultrasound predict bone mechanical properties at the femoral neck in patients undergoing hip arthroplasty?, JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, Vol: 136, ISSN: 1751-6161

Journal article

Abel R, Behforootan S, Boughton O, Hansen U, Cobb J, Huthwaite Pet al., 2021, Ultrasound and Bone Disease: A Systematic Review, World Journal of Surgery and Surgical Research

Journal article

Ma S, Goh EL, Tay T, Wiles C, Boughton O, Churchwell J, Wu Y, Karunaratne A, Bhattacharya R, Terrill N, Cobb J, Hansen U, Abel Ret al., 2020, Nanoscale mechanisms in age-related hip-fractures, Scientific Reports, Vol: 10, Pages: 1-14, ISSN: 2045-2322

Nanoscale mineralized collagen fibrils may be important determinants of whole-bone mechanical properties and contribute to the risk of age-related fractures. In a cross-sectional study nano-and tissue-level mechanics were compared across trabecular sections from the proximal femora of three groups(n=10 each): ageing non-fractured donors (Controls);untreated fracture patients (Fx-Untreated); bisphosphonate-treated fracture patients (Fx-BisTreated).Collagen fibril, mineral and tissue mechanics were measured using synchrotron X-Ray diffraction,of bone sections under load. Mechanical data were compared across groups, and tissue-level data were regressed against nano. Compared to controls fracture patients exhibited significantly lower critical strain, max strain and normalized strength, with lower peak collagen and mineral strain. Bisphosphonate-treated exhibited the lowest properties. In all three groups, peak mineral strain coincided with maximum tissue strength (i.e. ultimate stress), whilst peak fibril strain occurred afterwards(i.e. higher strain). Tissue strain and strength were positively and strongly correlated with peak fibril and mineral strains. Age-related fractures were associated with lower peak fibril and mineral strain irrespective of treatment. Indicating earlier mineral disengagement and the subsequent onset of fibril sliding is one of the key mechanisms leading to fracture. Treatments for fragility should target collagen-mineral interactions to restore nano-scale strain to that of healthy bone.

Journal article

Ajdari N, Tempelaere C, Masouleh MI, Abel R, Delfosse D, Emery R, Dini D, Hansen Uet al., 2020, Hemiarthroplasties: the choice of prosthetic material causes different levels of damage in the articular cartilage, Journal of Shoulder and Elbow Surgery, Vol: 29, Pages: 1019-1029, ISSN: 1058-2746

Background Hemiarthroplasty has clear advantages over alternative procedures and is used in 20% of all shoulder joint replacements. Because of cartilage wear, the clinical outcome of hemiarthroplasty is unreliable and controversial. This paper suggests that the optimal choice of prosthetic material may reduce cartilage degeneration and improve the reliability of the procedure. The specific objectives were to assess 3 materials and assess how the severity of arthritis might affect the choice of prosthetic material. Methods A CoCr alloy, an AL2O3 ceramic, and a polycarbonate urethane polymer (PCU) were mechanically tested against 5 levels of human osteoarthritic cartilage (from intact to severely arthritic, n = 45). A high friction coefficient, a decrease in Young's modulus, an increase in permeability, a decrease in relaxation time, an increase in surface roughness, and a disrupted appearance of the cartilage after testing were used as measures of cartilage damage. The biomaterial that caused minimal cartilage damage was defined as superior. Results The CoCr caused the most damage. This was followed by the AL2O3 ceramic, whereas the PCU caused the least amount of damage. Although the degree of arthritis had an effect on the results, it did not change the trend that CoCr performed worst and PCU the best. Discussion and Conclusion This study indicates that ceramic implants may be a better choice than metals, and the articulating surface should be as smooth as possible. Although our results indicate that the degree of arthritis should not affect the choice of prosthetic material, this suggestion needs to be further investigated.

Journal article

Boughton O, Ma S, Cai X, Yan L, Peralta L, Laugier P, Marrow J, Giuliani F, Hansen U, Abel R, Grimal Q, Cobb Jet al., 2019, Computed tomography porosity and spherical indentation for determining cortical bone millimetre-scale mechanical properties, Scientific Reports, Vol: 9, ISSN: 2045-2322

The cortex of the femoral neck is a key structural element of the human body, yet there is not a reliable metric for predicting the mechanical properties of the bone in this critical region. This study explored the use of a range of non-destructive metrics to measure femoral neck cortical bone stiffness at the millimetre length scale. A range of testing methods and imaging techniques were assessed for their ability to measure or predict the mechanical properties of cortical bone samples obtained from the femoral neck of hip replacement patients. Techniques that can potentially be applied in vivo to measure bone stiffness, including computed tomography (CT), bulk wave ultrasound (BWUS) and indentation, were compared against in vitro techniques, including compression testing, density measurements and resonant ultrasound spectroscopy. Porosity, as measured by micro-CT, correlated with femoral neck cortical bone’s elastic modulus and ultimate compressive strength at the millimetre length scale. Large-tip spherical indentation also correlated with bone mechanical properties at this length scale but to a lesser extent. As the elastic mechanical properties of cortical bone correlated with porosity, we would recommend further development of technologies that can safely measure cortical porosity in vivo.Introduction

Journal article

Zhao S, Arnold M, Ma S, Abel R, Cobb J, Hansen U, Boughton ORet al., 2018, Standardising compression testing for measuring the stiffness of human bone: a systematic review, Bone and Joint Research, Vol: 7, Pages: 524-538, ISSN: 2046-3758

Objectives: The ability to determine human bone stiffness is of clinical relevance in many fields, including bone quality assessment and orthopaedic prosthesis design. Stiffness can be measured using compression testing; an experimental technique commonly used to test bone specimens in vitro. This systematic review aims to determine how best to perform compression testing of human bone. Methods: A keyword search of all English language articles up until December 2017 of compression testing of bone was undertaken in Medline, Embase, PubMed and Scopus databases. Studies using bulk tissue, animal tissue, whole bone or testing techniques other than compression testing were excluded. Results: 4712 abstracts were retrieved with a total of 177 papers included in the analysis. 20 studies directly analysed the compression testing technique to improve the accuracy of the testing technique. Several influencing factors should be considered when testing bone samples in compression. These include the method of data analysis, specimen storage, specimen preparation, testing configuration and loading protocol. Conclusions: Compression testing is a widely used technique for measuring the stiffness of bone but there is a great deal of inter-study variation in experimental techniques across the literature. Based on best evidence from the literature, suggestions for bone compression testing are made in this review, though further studies are needed to help establish standardised bone testing techniques to increase the comparability and reliability of bone stiffness studies.

Journal article

Boughton OR, Ma S, Zhao S, Arnold M, Lewis A, Hansen U, Cobb J, Giuliani F, Abel Ret al., 2018, Measuring bone stiffness using spherical indentation, PLoS ONE, Vol: 13, ISSN: 1932-6203

ObjectivesBone material properties are a major determinant of bone health in older age, both in terms of fracture risk and implant fixation, in orthopaedics and dentistry. Bone is an anisotropic and hierarchical material so its measured material properties depend upon the scale of metric used. The scale used should reflect the clinical problem, whether it is fracture risk, a whole bone problem, or implant stability, at the millimetre-scale. Indentation, an engineering technique involving pressing a hard-tipped material into another material with a known force, may be able to assess bone stiffness at the millimetre-scale (the apparent elastic modulus). We aimed to investigate whether spherical-tip indentation could reliably measure the apparent elastic modulus of human cortical bone.Materials and methodsCortical bone samples were retrieved from the femoral necks of nineteen patients undergoing total hip replacement surgery (10 females, 9 males, mean age: 69 years). The samples underwent indentation using a 1.5 mm diameter, ruby, spherical indenter tip, with sixty indentations per patient sample, across six locations on the bone surfaces, with ten repeated indentations at each of the six locations. The samples then underwent mechanical compression testing. The repeatability of indentation measurements of elastic modulus was assessed using the co-efficient of repeatability and the correlation between the bone elastic modulus measured by indentation and compression testing was analysed by least-squares regression.ResultsIn total, 1140 indentations in total were performed. Indentation was found to be repeatable for indentations performed at the same locations on the bone samples with a mean co-efficient of repeatability of 0.4 GigaPascals (GPa), confidence interval (C.I): 0.33–0.42 GPa. There was variation in the indentation modulus results between different locations on the bone samples (mean co-efficient of repeatability: 3.1 GPa, C.I: 2.2–3.90 GPa). No cle

Journal article

Jin A, Cobb JP, Hansen U, Bhattacharya R, Reinhard C, Vo N, Atwood R, Li J, Abel RLet al., 2017, The effect of long term bisphosphonate therapy on trabecular bone strength and microcrack density, Bone & Joint Research, Vol: 6, Pages: 602-609, ISSN: 2046-3758

ObjectivesBisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding the efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While DEXA scanning may show a gain in bone density the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate for this study), and correlate this with the microarchitecture and density of microcracks in comparison with untreated controls. MethodsTrabecular bone from hip-fracture patients treated with BP (n=10) was compared to naïve fractured (n=14) and non-fractured controls (n=6). Trabecular cores were synchrotron and micro-CT scanned for microstructural analysis including quantification of bone volume fraction, micro-architecture and microcracks, then mechanically tested in compression. ResultsBP bone was 28% lower in strength than untreated hip-fracture bone and 48% lower in strength than and non-fracture control bone (4.6 vs 6.4 vs 8.9 MPa). BP treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12 vs 6.55 vs 5.25 /cm2). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. ConclusionsBP therapy had no detectable mechanical benefit. Instead its use was associated with substantially reduced bone strength. This low strength was probably due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP induced microcrack accumulation may be substantial and long term.

Journal article

Arnold M, Zhao S, Ma S, Giuliani F, Hansen U, Cobb JP, Abel RL, Boughton ORet al., 2017, Microindentation: a tool for measuring cortical bone stiffness? A systematic review, Bone & Joint Research, Vol: 6, Pages: 542-549, ISSN: 2046-3758

Objectives: Microindentation hasthe potential to measuretheelasticity(stiffness)of individualpatients’bone. Bone elasticity plays a crucial role in the press-fit stability of orthopaedic implants.Arming surgeons with accuratebone elasticityinformation may reduce surgical complicationsincluding peri-prosthetic fractures. The question we address with this systematicreview is whether microindentation can accurately measure cortical bone stiffness.Methods: A systematic review of all English language articles using a keyword search was undertaken in Medline, Embase, PubMed, Scopus and Cochrane databases. Studies thatonly used nanoindentation, cancellous boneoranimal tissue were excluded.Results: 1094abstracts were retrieved and 32papers were included in the analysis, 20 of which used reference point indentation and 12of which used traditional depth sensing indentation.There are a number of factors thatmust be taken into account when using microindentation such as tip size, depth and method of analysis.Only two studies validated microindentation againsttraditional mechanical testing techniques. Bothstudies used reference point indentation(RPI) with one showing that RPI parameters correlate well with mechanical testing, butanother suggestedthatthey do not. Conclusion: Microindentation has been used in various studies to assess bone elasticity but only two studies with conflicting results compared microindentation to traditional mechanical testing techniques. Further research,includingmore studies comparingmicroindentationto other mechanical testing methodsare needed,before microindentation can be reliably used to calculate cortical bone stiffness.

Journal article

Ridzwan M, Sukjamsri C, Pal B, van Arkel R, Bell A, Khanna M, Baskaradas A, Abel R, Boughton O, Cobb J, Hansen Uet al., 2017, Femoral fracture type can be predicted from femoral structure: a finite element study validated by digital volume correlation experiments, Journal of Orthopaedic Research, Vol: 36, Pages: 993-1001, ISSN: 1554-527X

Proximal femoral fractures can be categorized into two main types: Neck and intertrochanteric fractures accounting for 53% and 43% of all proximal femoral fractures, respectively. The possibility to predict the type of fracture a specific patient is predisposed to would allow drug and exercise therapies, hip protector design, and prophylactic surgery to be better targeted for this patient rendering fracture preventing strategies more effective. This study hypothesized that the type of fracture is closely related to the patient-specific femoral structure and predictable by finite element (FE) methods. Fourteen femora were DXA scanned, CT scanned, and mechanically tested to fracture. FE-predicted fracture patterns were compared to experimentally observed fracture patterns. Measurements of strain patterns to explain neck and intertrochanteric fracture patterns were performed using a digital volume correlation (DVC) technique and compared to FE-predicted strains and experimentally observed fracture patterns. Although loaded identically, the femora exhibited different fracture types (six neck and eight intertrochanteric fractures). CT-based FE models matched the experimental observations well (86%) demonstrating that the fracture type can be predicted. DVC-measured and FE-predicted strains showed obvious consistency. Neither DXA-based BMD nor any morphologic characteristics such as neck diameter, femoral neck length, or neck shaft angle were associated with fracture type. In conclusion, patient-specific femoral structure correlates with fracture type and FE analyses were able to predict these fracture types. Also, the demonstration of FE and DVC as metrics of the strains in bones may be of substantial clinical value, informing treatment strategies and device selection and design.

Journal article

Agbesi MPK, Borsuk HS, Hunt JN, Maclaine JS, Abel RL, Sykes D, Ramsey AT, Wang Z, Cox JPLet al., 2017, Motion-driven flow in an unusual piscine nasal region, Zoology, Vol: 119, Pages: 500-510, ISSN: 0944-2006

Journal article

Feola AJ, Coudrillier B, Mulvihill J, Geraldes DM, Vo NT, Albon J, Abel RL, Samuels BC, Ethier CRet al., 2017, Deformation of the Lamina Cribrosa and Optic Nerve Due to Changes in Cerebrospinal Fluid Pressure, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 58, Pages: 2070-2078, ISSN: 0146-0404

Journal article

Ma S, Goh EL, Jin A, Bhattacharya R, Boughton O, Patel B, Karunaratne A, Vo NT, Atwood R, Cobb J, Hansen U, Abel Ret al., 2017, Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties, Scientific Reports, Vol: 7, Pages: 1-10, ISSN: 2045-2322

Osteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young’s Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of microstructural integrity and consequently, reduced mechanical strength.

Journal article

Boughton OR, Zhao S, Arnold M, Ma S, Cobb JP, Giuliani F, Hansen U, Abel RLet al., 2017, Measuring bone stiffness using microindentation, British Orthopaedic Research Society (BORS) 2016 Conference, Publisher: British Editorial Society of Bone and Joint Surgery, Pages: 31-31, ISSN: 2049-4416

Conference paper

Ma S, Goh EL, Patel B, Jin A, Boughton O, Cobb J, Hansen U, Abel RLet al., 2016, Are the cracks starting to appear in bisphosphonate therapy?, British Orthopaedic Research Society (BORS) 2016 Conference, Publisher: British Editorial Society of Bone and Joint Surgery, Pages: 53-53, ISSN: 2049-4416

Conference paper

Ma S, Boughton O, Karunaratne A, Jin A, Cobb JP, Hansen U, Abel RLet al., 2016, Synchrotron imaging assessment of bone quality, Clinical Reviews in Bone and Mineral Metabolism, Vol: 14, Pages: 150-160, ISSN: 1559-0119

Bone is a complex hierarchical structure and its principal function is to resist mechanical forces and fracture. Bone strength depends not only on the quantity of bone tissue but also on the shape and hierarchical structure. The hierarchical levels are interrelated, especially the micro-architecture, collagen and mineral components; hence analysis of their speciļ¬c roles in bone strength and stiffness is difficult. Synchrotron imaging technologies including micro-CT and small/wide angle X-Ray scattering/diffraction are becoming increasingly popular for studying bone because the images can resolve deformations in the micro-architecture and collagen-mineral matrix under in situ mechanical loading. Synchrotron cannot be directly applied in-vivo due to the high radiation dose but will allow researchers to carry out systematic multifaceted studies of bone ex-vivo. Identifying characteristics of aging and disease will underpin future efforts to generate novel devices and interventional therapies for assessing and promoting healthy aging. With our own research work as examples, this paper introduces how synchrotron imaging technology can be used with in-situ testing in bone research.

Journal article

Coudrillier B, Campbell IC, Read AT, Geraldes DM, Vo NT, Feola A, Mulvihill J, Albon J, Abel RL, Ethier CRet al., 2016, Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 57, Pages: 2666-2677, ISSN: 0146-0404

Journal article

Symes DR, Najmudin Z, Cole JM, Wood JC, Lopes NC, Poder K, Abel P, Abel RL, Alatabi S, Kneip S, Mecseki K, Winkler M, Foster PS, Norris DP, Teboul L, Johnson S, Szoke-Kovacs Z, Sandholzer M, Botchway S, Gratton S, Hill MA, De Lazzari M, Thomson Jet al., 2016, High-resolution tomographic imaging using coherent hard x-rays from compact laser driven accelerators, Compact EUV & X-ray Light Sources 2016, Publisher: OSA Publishing

Extremely bright coherent femtosecond x-ray pulses are generated in compact laserdriven electron accelerators. Micro-tomography obtained with the Gemini laser indicates the usefulness of these sources in research and clinical applications.

Conference paper

Gill RJ, Smith DB, Raine NE, Bernhardt G, Abel RL, Sykes D, Ahmed F, Pedroso Iet al., 2016, Exploring miniature insect brains using micro-CT scanning techniques, Scientific Reports, Vol: 6, ISSN: 2045-2322

The capacity to explore soft tissue structures in detail is important in understandinganimal physiology and how this determines features such as movement, behaviour and the impactof trauma on regular function. Here we use advances in micro-computed tomography (micro-CT)technology to explore the brain of an important insect pollinator and model organism, thebumblebee (Bombus terrestris). Here we present a method for accurate imaging and exploration 2of insect brains that keeps brain tissue free from trauma and in its natural stereo-geometry, andshowcase our 3D reconstructions and analyses of 19 individual brains at high resolution.Development of this protocol allows relatively rapid and cost effective brain reconstructions,making it an accessible methodology to the wider scientific community. The protocol describes thenecessary steps for sample preparation, tissue staining, micro-CT scanning and 3D reconstruction,followed by a method for image analysis using the freeware SPIERS. These image analysis methodsdescribe how to virtually extract key composite structures from the insect brain, and wedemonstrate the application and precision of this method by calculating structural volumes andinvestigating the allometric relationships between bumblebee brain structures.

Journal article

Cole JM, Wood JC, Lopes NC, Poder K, Abel RL, Alatabi S, Bryant JSJ, Jin A, Kneip S, Mecseki K, Parker S, Symes DR, Sandholzer MA, Mangles SPD, Najmudin Zet al., 2016, Tomography of human trabecular bone with a laser-wakefield driven x-ray source, Plasma Physics and Controlled Fusion, Vol: 58, ISSN: 1361-6587

A laser-wakefield driven x-ray source is used for the radiography of human bone. The betatron motion of accelerated electrons generates x-rays which are hard (critical energy ${{E}_{\text{crit}}}>30$ keV), have small source size (<3 μm) and high average brightness. The x-rays are generated from a helium gas cell which is near-instantly replenishable, and thus the average photon flux is limited by the repetition rate of the driving laser rather than the breakdown of the x-ray source. A tomograph of a human bone sample was recorded with a resolution down to 50 μm. The photon flux was sufficiently high that a radiograph could be taken with each laser shot, and the fact that x-ray beams were produced on 97% of shots minimised failed shots and facilitated full micro-computed tomography in a reasonable time scale of several hours, limited only by the laser repetition rate. The x-ray imaging beamline length (not including the laser) is shorter than that of a synchrotron source due to the high accelerating fields and small source size. Hence this interesting laboratory-based source may one day bridge the gap between small microfocus x-ray tubes and large synchrotron facilities.

Journal article

Langley RE, Kynaston HG, Alhasso AA, Duong T, Paez EM, Jovic G, Scrase CD, Robertson A, Cafferty F, Welland A, Carpenter R, Honeyfield L, Abel RL, Stone M, Parmar MK, Abel PDet al., 2015, A randomised comparison evaluating changes in bone mineral density in advanced prostate cancer: luteinising hormone-releasing hormone agonists versus transdermal oestradiol., European Urology, Vol: 69, Pages: 1016-1025, ISSN: 1421-993X

BACKGROUND: Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. OBJECTIVE: To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). DESIGN, SETTING, AND PARTICIPANTS: Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006-2011; 1:1, thereafter) were recruited into a BMD study (2006-2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. INTERVENTIONS: LHRHa as per local practice, OP (FemSeven 100μg/24h patches). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. RESULTS AND LIMITATIONS: A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was -0.021g/cm(3) for patients randomised to the LHRHa arm (mean percentage change -1.4%) and +0.069g/cm(3) for the OP arm (+6.0%; p<0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa -3.0% and OP +7.9% (p<0.001). CONCLUSIONS: Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial. PATIENT SUMMARY: This study found that prostate cancer patients treated with transdermal oestradiol for ho

Journal article

Shah SIMRANA, Jin ANDI, Wilson HANNAHCP, Abel PAULD, Price PATRICIAM, Hansen ULRICHN, Abel RICHARDLet al., 2015, Novel Computed Tomography-based Metric Reliably Estimates bone Strength, Offering Potentially Meaningful Enhancement in Clinical Fracture Risk Prediction, European Journal of Medicine, Vol: 10, Pages: 214-220, ISSN: 2310-3434

Osteoporosis with resultant fractures is a major global health problem with huge socioeconomicimplications for patients, families and healthcare services. Areal (2D bone mineraldensity (BMD) assessment is commonly used for predicting such fracture risk, but is unreliable,estimating only about 50% of bone strength. By contrast, computed tomography (CT) basedtechniques could provide improved metrics for estimating bone strength such as bone volumefraction (BVF; a 3D volumetric measure of mineralised bone), enabling cheap, safe and reliablestrategies for clinical application, and to help divert resources to patients identified as most likelyto benefit, meeting an unmet need.Here we describe a novel method for measuring BVF at clinical-CT like low-resolution(550µm voxel size). Femoral heads (n=8) were micro-CT scanned ex-vivo. Micro-CT data weredowngraded in resolution from 30µm to 550µm voxel size and BVF calculated at high and lowresolution. Experimental mechanical testing was applied to measure ex vivo bone strength ofsamples. BVF measures collected at high-resolution showed high correlation (correlationcoefficient r2=0.95) with low-resolution data. Low-resolution BVF metrics showed high correlation(r2=0.96) with calculated sample strength. These results demonstrate that measuring BVF at lowresolution is feasible, which also predicts bone strength. Measures of BVF should be useful for clinically estimating bone strength and fracture risk. The method needs to be validated using clinical CT scans.

Journal article

Cole JM, Wood J, Lopes NC, Poder K, Abel RL, Alatabi S, Bryant JSJ, Jin A, Kneip S, Mecseki K, Symes DR, Mangles SPD, Najmudin Zet al., 2015, Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone, Scientific Reports, Vol: 5, ISSN: 2045-2322

A bright μm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 μm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications.

Journal article

Acquaah F, Robson Brown KA, Ahmed F, Jeffery N, Abel RLet al., 2015, Early trabecular development in human vertebrae: overproduction, constructive regression, and refinement, Frontiers in Endocrinology, Vol: 6, ISSN: 1664-2392

Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior–superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant “sculpting” of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabec

Journal article

Campbell IC, Coudrillier B, Mensah J, Abel RL, Ethier CRet al., 2015, Automated segmentation of the lamina cribrosa using Frangi's filter: a novel approach for rapid identification of tissue volume fraction and beam orientation in a trabeculated structure in the eye, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 12, ISSN: 1742-5689

Journal article

Brewer P, Hand SJ, Archer M, Abel RLet al., 2015, New genus of primitive wombat (Vombatidae,Marsupialia) from Miocene deposits in the RiversleighWorld Heritage Area (Queensland, Australia), Palaeontologia Electronica

Journal article

Coudrillier B, Geraldes D, Nghia V, Campbell I, Albon J, Abel R, Ethier Cet al., 2015, Phase-contrast micro-tomography measurements of intraocular pressure-induced deformation of the porcine lamina cribrosa, Biomechanics, Bioengineering and Biotransport Conference 2015

Conference paper

Coudrillier B, Geraldes D, Nghia V, Abel R, Albon J, Campbell I, Ethier Cet al., 2015, A novel micro-computed tomography method to measure IOP-induced deformation of the lamina cribrosa., The Annual Meeting of the Association for Research in Vision and Ophthalmology 2015

Conference paper

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