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Article ; Online: Buds of new bone formation within the Femoral Head of Hip Fracture Patients Coincide with Zones of Low Osteocyte Sclerostin.

Sano, Hiroshige / Whitmarsh, Tristan / Skingle, Linda / Shimakura, Taketoshi / Yamamoto, Noriaki / Compston, Juliet E / Takahashi, Hideaki E / Poole, Kenneth E S

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2023 Volume 38, Issue 11, Page(s) 1603–1611

Abstract: Romosozumab treatment reduces the rate of hip fractures and increases hip bone density, increasing bone formation by inhibiting sclerostin protein. We studied the normal pattern of bone formation and osteocyte expression in the human proximal femur ... ...

Abstract	Romosozumab treatment reduces the rate of hip fractures and increases hip bone density, increasing bone formation by inhibiting sclerostin protein. We studied the normal pattern of bone formation and osteocyte expression in the human proximal femur because it is relevant to both antisclerostin treatment effects and fracture. Having visualized and quantified buds of new bone formation in trabeculae, we hypothesized that they would coincide with areas of (a) higher mechanical stress and (b) low sclerostin expression by osteocytes. In patients with hip fracture, we visualized each bud of active modeling-based formation (forming minimodeling structure [FMiS]) in trabecular cores taken from different parts of the femoral head. Trabecular bone structure was also measured with high-resolution imaging. More buds of new bone formation (by volume) were present in the higher stress superomedial zone (FMiS density, N.FMiS/T.Ar) than lower stress superolateral (p < 0.05), and inferomedial (p < 0.001) regions. There were fewer sclerostin expressing osteocytes close to or within FMiS. FMiS density correlated with greater amount, thickness, number, and connectivity of trabeculae (bone volume BV/TV, r = 0.65, p < 0.0001; bone surface BS/TV, r = 0.47, p < 0.01; trabecular thickness Tb.Th, r = 0.55, p < 0.001; trabecular number Tb.N, r = 0.47, p < 0.01; and connectivity density Conn.D, r = 0.40, p < 0.05) and lower trabecular separation (Tb.Sp, r = -0.56, p < 0.001). These results demonstrate modeling-based bone formation in femoral trabeculae from patients with hip fracture as a potential therapeutic target to enhance bone structure. © 2023 American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Humans ; Bone Density ; Femur Head ; Hip Fractures/diagnostic imaging ; Osteocytes ; Osteogenesis
Chemical Substances	SOST protein, human
Language	English
Publishing date	2023-09-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4898
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Article ; Online: 3-D joint space mapping at the ankle from weight-bearing CT: reproducibility, repeatability, and challenges for standardisation.

Turmezei, Tom D / Malhotra, Karan / MacKay, James W / Gee, Andrew H / Treece, Graham M / Poole, Kenneth E S / Welck, Matthew J

European radiology

2023 Volume 33, Issue 11, Page(s) 8333–8342

Abstract: Objectives: We present a 3-D approach to joint space width (JSW) measurement across the ankle from weight-bearing CT (WBCT) to demonstrate inter-operator reproducibility, test-retest repeatability, and how differences in angulation affect ankle JSW ... ...

Abstract	Objectives: We present a 3-D approach to joint space width (JSW) measurement across the ankle from weight-bearing CT (WBCT) to demonstrate inter-operator reproducibility, test-retest repeatability, and how differences in angulation affect ankle JSW distribution. Methods: One side from repeat WBCT imaging of both feet and ankles was analysed from 23 individuals as part of their routine clinical care pathway. Joint space mapping was performed at four facets across the talus: talonavicular, talar dome and medial gutter (dome-medial), lateral gutter, and posterior subtalar. Inter-operator reproducibility was calculated for two users, while test-retest repeatability was calculated by comparing the two visits, both presented as Bland-Altman statistics. Statistical parametric mapping determined any significant relationships between talocrural joint space angulation and 3-D JSW distribution. Results: The average ± standard deviation interval between imaging was 74.0 ± 29.6 days. Surface averaged bias ± limits of agreement were similar for reproducibility and repeatability, the latter being: talonavicular 0.01 ± 0.26 mm, dome-medial 0.00 ± 0.28 mm, lateral gutter - 0.02 ± 0.40 mm, and posterior subtalar 0.02 ± 0.34 mm. Results are presented as 3-D distribution maps, with optimum test-retest repeatability reaching a smallest detectable difference of ± 0.15 mm. Conclusions: Joint space mapping is a robust approach to 3-D quantification of JSW measurement, inter-operator reproducibility, and test-retest repeatability at the ankle, with sensitivity reaching a best value of ± 0.15 mm. Standardised imaging protocols and optimised metal artefact reduction will be needed to further understand the clinical value of these 3-D measures derived from WBCT. Clinical relevance statement: Weight-bearing computed tomography is an increasingly important tool in the clinical assessment of orthopaedic ankle disorders. This paper establishes the performance of measuring 3-D joint space width using this technology, which is an important surrogate marker for severity of osteoarthritis. Key points: • Joint space width values and error metrics from across the ankle measured from weight-bearing CT can be presented as 3-D maps that show topographic variation. • The best sensitivity for detecting meaningful change in 3-D joint space width at the ankle was ± 0.15 mm, a value less than the isotropic imaging voxel dimensions. • Standardised imaging protocols and optimised metal artefact reduction will be needed to understand the clinical value of 3-D measures from weight-bearing CT.
MeSH term(s)	Humans ; Ankle/diagnostic imaging ; Ankle Joint/diagnostic imaging ; Reproducibility of Results ; Tomography, X-Ray Computed/methods ; Weight-Bearing
Language	English
Publishing date	2023-05-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-023-09718-6
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Article ; Online: Phosphaturic Mesenchymal Tumor of the Ankle: A Case Report and Review of the Literature.

Jones, Oliver / Murphy, Suzanne H / Poole, Kenneth E S / Watkins, A James / Durrani, Amer J

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons

2021 Volume 61, Issue 1, Page(s) 185–188

Abstract: We report the case of a phosphaturic mesenchymal tumor of the ankle; an extremely rare lesion that causes osteomalacia via paraneoplastic renal phosphate wasting. A 41-year-old man was referred to plastic surgery with a swelling over the anterior ankle, ... ...

Abstract	We report the case of a phosphaturic mesenchymal tumor of the ankle; an extremely rare lesion that causes osteomalacia via paraneoplastic renal phosphate wasting. A 41-year-old man was referred to plastic surgery with a swelling over the anterior ankle, which had been increasing in size for 1 year. Focused ultrasound assessment was inconclusive, but excision biopsy demonstrated features in keeping with a phosphaturic mesenchymal tumor. Evidence of tumor-induced osteomalacia was subsequently identified on review of historical biochemistry. The patient was followed-up for 1 year with normalization of serum phosphate. In this case report, we present a discussion of the differential diagnosis for foot and ankle soft tissue lesions, and a review of the literature regarding the diagnosis and management of these tumors. Accurate identification of any soft tissue lesion on clinical examination alone is extremely challenging and excision biopsy should be considered in cases of diagnostic uncertainty.
MeSH term(s)	Adult ; Ankle/diagnostic imaging ; Humans ; Hypophosphatemia ; Male ; Mesenchymoma/diagnosis ; Mesenchymoma/diagnostic imaging ; Neoplasms, Connective Tissue/diagnostic imaging ; Neoplasms, Connective Tissue/surgery ; Osteomalacia ; Paraneoplastic Syndromes
Language	English
Publishing date	2021-07-27
Publishing country	United States
Document type	Case Reports ; Review
ZDB-ID	1146972-9
ISSN	1542-2224 ; 1067-2516
ISSN (online)	1542-2224
ISSN	1067-2516
DOI	10.1053/j.jfas.2021.07.019
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Article ; Online: PHOENIX (Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays)

Lee Shepstone / Jane Fleming / Stephen K Kaptoge / Emma Clark / Adam P Wagner / Kenneth E S Poole / Daniel D G Chappell / Thomas D Turmezei / Karen Willoughby

BMJ Open, Vol 12, Iss

protocol for a randomised, multicentre feasibility study

2022 Volume 5

Keywords	Medicine ; R
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PHOENIX (Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays): protocol for a randomised, multicentre feasibility study.

Poole, Kenneth E S / Chappell, Daniel D G / Clark, Emma / Fleming, Jane / Shepstone, Lee / Turmezei, Thomas D / Wagner, Adam P / Willoughby, Karen / Kaptoge, Stephen K

BMJ open

2022 Volume 12, Issue 5, Page(s) e050343

Abstract: Introduction: Two million out of the UK's 5 million routine diagnostic CT scans performed each year incorporate the thoracolumbar spine or pelvic region. Up to one-third reveal undiagnosed osteoporosis or vertebral fractures. We developed an ... ...

Abstract	Introduction: Two million out of the UK's 5 million routine diagnostic CT scans performed each year incorporate the thoracolumbar spine or pelvic region. Up to one-third reveal undiagnosed osteoporosis or vertebral fractures. We developed an intervention, Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays ('PHOENIX'), to facilitate early detection and management of osteoporosis in people attending hospitals for CT scans. Methods and analysis: A multicentre, randomised, pragmatic feasibility study. From the general CT-attending population, women aged ≥65 years and men aged ≥75 years attending for CT scans are invited to participate, via a novel consent form incorporating Fracture Risk Assessment (FRAX) questions. Those at increased 10-year risk (within the amber or red zones of the UK FRAX graphical outputs for further action) are block randomised (1:1:1) to (1) PHOENIX intervention, (2) active control or (3) usual care. The PHOENIX intervention comprises (i) retrieving the CT scans using the NHS Image Exchange Portal, (ii) Mindways QCT Pro software analysis of CT hip and spine none density with CT vertebral fracture assessment, (iii) sending the participants' general practitioner (GP) a clinical report including diagnosis, necessary investigations and recommended treatment. Baseline CT scans from groups 2 and 3 are assessed with the PHOENIX intervention only at study end. Assuming 25% attrition, the study is powered to find a predicted superior osteoporosis treatment rate with PHOENIX (20%) vs 16% among patients whose GPs were sent the FRAX questionnaire only (active control) and 5% in the usual care group. Five hospitals are participating to determine feasibility. The co-primary feasibility outcome measures are (a) ability to randomise 375 patients within 10 months and (b) retention of 75% of survivors, completing their 1-year bone health outcome questionnaire. Secondary 1-year outcomes include osteoporosis/vertebral fracture identification rates and osteoporosis treatment rates. Stakeholder acceptability and economic aspects are evaluated. Ethics and dissemination: Approved by committee (National Research Ethics Service) East of England (EE) as REF/19/EE/0176. Dissemination will be through the Royal Osteoporosis Society (to patients and public) as well as to clinician peers via national and international bone/rheumatology scientific and clinical meetings. Trial registration number: ISRCTN14722819.
MeSH term(s)	Aged ; Feasibility Studies ; Female ; Humans ; Male ; Multicenter Studies as Topic ; Osteoporosis/diagnostic imaging ; Osteoporotic Fractures/diagnostic imaging ; Osteoporotic Fractures/prevention & control ; Randomized Controlled Trials as Topic ; Spinal Fractures ; Tomography, X-Ray Computed ; X-Rays
Language	English
Publishing date	2022-05-24
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-050343
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Article: Digital health interventions for osteoporosis and post-fragility fracture care.

Gupta, Amit / Maslen, Christina / Vindlacheruvu, Madhavi / Abel, Richard L / Bhattacharya, Pinaki / Bromiley, Paul A / Clark, Emma M / Compston, Juliet E / Crabtree, Nicola / Gregory, Jennifer S / Kariki, Eleni P / Harvey, Nicholas C / McCloskey, Eugene / Ward, Kate A / Poole, Kenneth E S

Therapeutic advances in musculoskeletal disease

2022 Volume 14, Page(s) 1759720X221083523

Abstract: The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture ... ...

Abstract	The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such services might benefit from technologies that enhance automation. The term 'Digital Health' covers a variety of different tools including clinical decision support systems, electronic medical record tools, patient decision aids, patient apps, education tools, and novel artificial intelligence (AI) algorithms. Within the scope of this review are AI solutions that use algorithms within health system registries to target interventions. Clinician-targeted, patient-targeted, or system-targeted digital health interventions could be used to improve management and prevent fragility fractures. This review was commissioned by The Royal Osteoporosis Society and Bone Research Academy during the production of the 2020 Research Roadmap (https://theros.org.uk), with the intention of identifying gaps where targeted research funding could lead to improved patient health. We explore potential uses of digital technology in the general management of osteoporosis. Evidence suggests that digital technologies can support multidisciplinary teams to provide the best possible patient care based on current evidence and to support patients in self-management. However, robust randomised controlled studies are still needed to assess the effectiveness and cost-effectiveness of these technologies.
Language	English
Publishing date	2022-03-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2516075-8
ISSN	1759-7218 ; 1759-720X
ISSN (online)	1759-7218
ISSN	1759-720X
DOI	10.1177/1759720X221083523
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Article ; Online: An exploratory study into measuring the cortical bone thickness from CT in the presence of metal implants.

Whitmarsh, Tristan / Treece, Graham M / Gee, Andrew H / Poole, Kenneth E S

International journal of computer assisted radiology and surgery

2017 Volume 12, Issue 12, Page(s) 2079–2086

Abstract: Purpose: The aim of this study was to develop and evaluate a method for measuring the cortical bone thickness from computed tomography (CT) scans with metallic implants and to assess the benefits of metal artefact removal software.: Methods: A ... ...

Abstract	Purpose: The aim of this study was to develop and evaluate a method for measuring the cortical bone thickness from computed tomography (CT) scans with metallic implants and to assess the benefits of metal artefact removal software. Methods: A previously validated technique based on the fitting of a cortical model was modified to also model metal structures when required. Cortical thickness measurements were taken over intact bone segments and compared with the corresponding contralateral bone segment. The evaluation dataset includes post-operative CT scans of a unipolar hemi-arthroplasty, a dynamic hip screw fixation, a bipolar hemi-arthroplasty, a fixation with cannulated screws and a total hip arthroplasty. All CT scans were analysed before and after processing with metal artefact removal software. Results: Cortical thickness validity and accuracy were improved through the use of a modified metalwork-optimised model and metal artefact removal software. For the proximal femoral segments of the aforementioned cases, the cortical thickness was measured with a mean absolute error of 0.55, 0.39, 0.46, 0.53 and 0.69 mm. The hemi-pelvis produced thickness errors of 0.51, 0.52, 0.52, 0.47 and 0.67 mm, respectively. Conclusions: The proposed method was shown to measure cortical bone thickness in the presence of metalwork at a sub-millimetre accuracy. This new technique might be helpful in assessing fracture healing near implants or fixation devices, and improve the evaluation of periprosthetic bone after hip replacement surgery.
MeSH term(s)	Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Artifacts ; Bone Screws ; Cortical Bone/diagnostic imaging ; Female ; Femur ; Humans ; Male ; Multidetector Computed Tomography/methods
Language	English
Publishing date	2017-02-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2365628-1
ISSN	1861-6429 ; 1861-6410
ISSN (online)	1861-6429
ISSN	1861-6410
DOI	10.1007/s11548-017-1539-z
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Article: Opportunistic diagnosis of osteoporosis, fragile bone strength and vertebral fractures from routine CT scans; a review of approved technology systems and pathways to implementation.

Aggarwal, Veena / Maslen, Christina / Abel, Richard L / Bhattacharya, Pinaki / Bromiley, Paul A / Clark, Emma M / Compston, Juliet E / Crabtree, Nicola / Gregory, Jennifer S / Kariki, Eleni P / Harvey, Nicholas C / Ward, Kate A / Poole, Kenneth E S

Therapeutic advances in musculoskeletal disease

2021 Volume 13, Page(s) 1759720X211024029

Abstract: Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, ...

Abstract	Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fractures in the United Kingdom (UK) in 2017 (costing £4.5 billion), a figure set to increase 30% by 2030. One way to improve both vertebral fracture identification and the diagnosis of osteoporosis is to assess a patient's spine or hips during routine computed tomography (CT) scans. Patients attend routine CT for diagnosis and monitoring of various medical conditions, but the skeleton can be overlooked as radiologists concentrate on the primary reason for scanning. More than half a million CT scans done each year in the National Health Service (NHS) could potentially be screened for osteoporosis (increasing 5% annually). If CT-based screening became embedded in practice, then the technique could have a positive clinical impact in the identification of fragility fracture and/or low bone density. Several companies have developed software methods to diagnose osteoporosis/fragile bone strength and/or identify vertebral fractures in CT datasets, using various methods that include image processing, computational modelling, artificial intelligence and biomechanical engineering concepts. Technology to evaluate Hounsfield units is used to calculate bone density, but not necessarily bone strength. In this rapid evidence review, we summarise the current literature underpinning approved technologies for opportunistic screening of routine CT images to identify fractures, bone density or strength information. We highlight how other new software technologies have become embedded in NHS clinical practice (having overcome barriers to implementation) and highlight how the novel osteoporosis technologies could follow suit. We define the key unanswered questions where further research is needed to enable the adoption of these technologies for maximal patient benefit.
Language	English
Publishing date	2021-07-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2516075-8
ISSN	1759-7218 ; 1759-720X
ISSN (online)	1759-7218
ISSN	1759-720X
DOI	10.1177/1759720X211024029
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Article ; Online: Quantitative Three-dimensional Assessment of Knee Joint Space Width from Weight-bearing CT.

Turmezei, Tom D / B Low, Samantha / Rupret, Simon / Treece, Graham M / Gee, Andrew H / MacKay, James W / Lynch, John A / Poole, Kenneth E S / Segal, Neil A

Radiology

2021 Volume 299, Issue 3, Page(s) 649–659

Abstract: Background Imaging of structural disease in osteoarthritis has traditionally relied on MRI and radiography. Joint space mapping (JSM) can be used to quantitatively map joint space width (JSW) in three dimensions from CT images. Purpose To demonstrate the ...

Abstract	Background Imaging of structural disease in osteoarthritis has traditionally relied on MRI and radiography. Joint space mapping (JSM) can be used to quantitatively map joint space width (JSW) in three dimensions from CT images. Purpose To demonstrate the reproducibility, repeatability, and feasibility of JSM of the knee using weight-bearing CT images. Materials and Methods Two convenience samples of weight-bearing CT images of left and right knees with radiographic Kellgren-Lawrence grades (KLGs) less than or equal to 2 were acquired from 2014 to 2018 and were analyzed retrospectively with JSM to deliver three-dimensional JSW maps. For reproducibility, images of three sets of knees were used for novice training, and then the JSM output was compared against an expert's assessment. JSM was also performed on 2-week follow-up images in the second cohort, yielding three-dimensional JSW difference maps for repeatability. Statistical parametric mapping was performed on all knee imaging data (KLG, 0-4) to show the feasibility of a surface-based analysis in three dimensions. Results Reproducibility (in 20 individuals; mean age, 58 years ± 7 [standard deviation]; mean body mass index, 28 kg/m
MeSH term(s)	Feasibility Studies ; Female ; Humans ; Imaging, Three-Dimensional/methods ; Male ; Middle Aged ; Osteoarthritis, Knee/diagnostic imaging ; Reproducibility of Results ; Retrospective Studies ; Tomography, X-Ray Computed/methods ; Weight-Bearing
Language	English
Publishing date	2021-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	80324-8
ISSN	1527-1315 ; 0033-8419
ISSN (online)	1527-1315
ISSN	0033-8419
DOI	10.1148/radiol.2021203928
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Article ; Online: Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.

Hartley, April / Hardcastle, Sarah A / Frysz, Monika / Parkinson, Jon / Paternoster, Lavinia / McCloskey, Eugene / Poole, Kenneth E S / Javaid, Muhammad K / Aye, Mo / Moss, Katie / Williams, Martin / Tobias, Jon H / Gregson, Celia L

Arthritis research & therapy

2021 Volume 23, Issue 1, Page(s) 4

Abstract: ... hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis ...

Abstract	Background: Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes. Methods: We analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering. Results: Of 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM β Conclusions: HBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation.
MeSH term(s)	Bone Density ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/diagnostic imaging ; Osteoarthritis, Knee ; Osteophyte/diagnostic imaging ; Prospective Studies
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-020-02371-0
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