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Item Open Access The Structural Response of the Human Head to a Vertex Impact(Springer (part of Springer Nature), 2023) Thompson-Bagshaw, D.W.; Quarrington, R.D.; Dwyer, A.M.; Jones, N.R.; Jones, C.F.In experimental models of cervical spine trauma caused by near-vertex head-first impact, a surrogate headform may be substituted for the cadaveric head. To inform headform design and to verify that such substitution is valid, the force-deformation response of the human head with boundary conditions relevant to cervical spine head-first impact models is required. There are currently no biomechanics data that characterize the force-deformation response of the isolated head supported at the occiput and compressed at the vertex by a flat impactor. The effect of impact velocity (1, 2 or 3 m/s) on the response of human heads (N = 22) subjected to vertex impacts, while supported by a rigid occipital mount, was investigated. 1 and 2 m/s impacts elicited force-deformation responses with two linear regions, while 3 m/s impacts resulted in a single linear region and skull base ring fractures. Peak force and stiffness increased from 1 to 2 and 3 m/s. Deformation at peak force and absorbed energy increased from 1 to 2 m/s, but decreased from 2 to 3 m/s. The data reported herein enhances the limited knowledge on the human head's response to a vertex impact, which may allow for validation of surrogate head models in this loading scenario.Item Metadata only Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study(Wiley, 2021) Bliuc, D.; Tran, T.; Adachi, J.D.; Atkins, G.J.; Berger, C.; van den Bergh, J.; Cappai, R.; Eisman, J.A.; van Geel, T.; Geusens, P.; Goltzman, D.; Hanley, D.A.; Josse, R.; Kaiser, S.; Kovacs, C.S.; Langsetmo, L.; Prior, J.C.; Nguyen, T.V.; Solomon, L.B.; Stapledon, C.; et al.Abstract not availableItem Open Access Hip osteoarthritis: A novel network analysis of subchondral trabecular bone structures(Oxford University Press (OUP), 2022) Dorraki, M.; Muratovic, D.; Fouladzadeh, A.; Verjans, J.W.; Allison, A.; Findlay, D.M.; Abbott, D.; Yooseph, S.Hip osteoarthritis (HOA) is a degenerative joint disease that leads to the progressive destruction of subchondral bone and cartilage at the hip joint. Development of effective treatments for HOA remains an open problem, primarily due to the lack of knowledge of its pathogenesis and a typically late-stage diagnosis.We describe a novel network analysis methodology for microcomputed tomography (micro-CT) images of human trabecular bone.We explored differences between the trabecular bone microstructure of femoral heads with and without HOA. Large-scale automated extraction of the network formed by trabecular bone revealed significant network properties not previously reported for bone. Profound differences were discovered, particularly in the proximal third of the femoral head, where HOA networks demonstrated elevated numbers of edges, vertices, and graph components. When further differentiating healthy joint and HOA networks, the latter showed fewer small-world network properties, due to decreased clustering coefficient and increased characteristic path length. Furthermore,we found that HOA networks had reduced length of edges, indicating the formation of compressed trabecular structures. In order to assess our network approach,we developed a deep learningmodel for classifying HOA and control cases, and we fed it with two separate inputs: (i) micro-CT images of the trabecular bone, and (ii) the network extracted from them. The model with plain micro-CT images achieves 74.6% overall accuracy while the trained model with extracted networks attains 96.5% accuracy. We anticipate our findings to be a starting point for a novel description of bone microstructure in HOA, by considering the phenomenon from a graph theory viewpoint.Item Open Access The effect of surgical change to hip geometry on hip biomechanics after primary total hip arthroplasty(Wiley, 2023) Bahl, J.S.; Arnold, J.B.; Saxby, D.J.; Taylor, M.; Solomon, L.B.; Thewlis, D.The aim of this study was to determine the effect of surgical change to the acetabular offset and femoral offset on the abductor muscle and hip contact forces after primary THA using computational methods. Thirty-five patients undergoing primary THA were recruited. Patients underwent a computed tomography scan of their pelvis and hip, and underwent gait analysis pre- and 6-months post-operatively. Surgically induced changes in acetabular and femoral offset were used to inform a musculoskeletal model to estimated abductor muscle and hip joint contact forces. Two experiments were performed: (1) influence of changes in hip geometry on hip biomechanics with preoperative kinematics; and (2) influence of changes in hip geometry on hip biomechanics with postoperative kinematics. Superior and medial placement of the hip centre of rotation during THA was most influential in reducing hip contact forces, predicting 63% of the variance (p<0.001). When comparing the preoperative geometry and kinematics model, with postoperative geometry and kinematics, hip contact forces increased after surgery (0.68 BW, p=0.001). Increasing the abductor lever arm reduced abductor muscle force by 28% (p<0.001) and resultant hip contact force by 17% (0.6 BW, p=0.003), with both preoperative and postoperative kinematics. Failure to increase abductor lever arm increased resultant hip contact force 11% (0.33 BW, p<0.001). In conclusion, increasing the abductor lever arm provides a substantial biomechanical benefit to reduce hip abductor and resultant hip joint contact forces. The magnitude of this effect is equivalent to the average increase in hip contact force seen with improved gait from pre-to post-surgery. This article is protected by copyright. All rights reserved.Item Metadata only A survival model of thoracic contusion spinal cord injury in the domestic pig(Mary Ann Liebert, 2023) Gayen, C.; Bessen, M.; Dorrian, R.; Quarrington, R.; Mulaibrahimovic, A.; O'Hare Doig, R.; Freeman, B.; Leonard, A.; Jones, C.Spinal cord injury (SCI) frequently results in motor, sensory and autonomic dysfunction for which there is currently no cure. Recent preclinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and assist the translation of potential therapeutic interventions. The aim of this study was to characterize two severities of thoracic contusion SCI in female domestic pigs, measuring motor function and spinal cord lesion characteristics, over two weeks post-SCI. A custom instrumented weight drop injury device was used to release a 50 g impactor from 10 cm (n=3) or 20 cm (n=7) onto the exposed dura, to induce a contusion at the T10 thoracic spinal level. Hind limb motor function was assessed at 8 and 13 days post-SCI using a 10-point scale. Volume and extent of lesion-associated signal hyperintensity in T2-weighted magnetic resonance (MR) images was assessed at 3, 7 and 14 days post-injury. Animals were transcardially perfused at 14 days post-SCI and spinal cord tissue was harvested for histological analysis. Bowel function was retained in all animals and transient urinary retention occurred in one animal after catheter removal. All animals displayed hind limb motor deficits. Animals in the 10 cm group demonstrated some stepping and weight bearing and scored a median 2- 3 points higher on the 10-point motor function scale at 8 and 13 days post-SCI, than the 20 cm group. Histological lesion volume was 20 % greater, and 30 % less white matter was spared, in the 20 cm group than in the 10 cm group. The MR signal hyperintensity in the 20 cm injury group had a median cranial-caudal extent approximately 1.5 times greater than the 10 cm injury group at all three time points, and median volumes 1.8, 2.5 and 4.5 times greater at day 3, 7 and 14 post-injury, respectively. Regional differences in axonal injury were observed between groups, with amyloid precursor protein immunoreactivity greatest in the 20 cm group in spinal cord sections adjacent the injury epicenter. This study demonstrated graded injuries in a domestic pig strain, with outcome measures comparable to miniature pig models of contusion SCI. The model provides a vehicle for the study of SCI and potential treatments, particularly where miniature pig strains are not available and/or where small animal models are not appropriate for the research question.Item Metadata only The variation in hip stability measurements between supine and standing radiographs of dysplastic hips(British Editorial Society of Bone and Joint Surgery, 2021) Bhanushali, A.; Chimutengwende-Gordon, N.; Beck, M.; Callary, S.A.; Costi, K.; Howie, D.W.; Solomon, L.B.AIMS: The aims of this study were to compare clinically relevant measurements of hip dysplasia on radiographs taken in the supine and standing position, and to compare Hip2Norm software and Picture Archiving and Communication System (PACS)-derived digital radiological measurements. METHODS: Preoperative supine and standing radiographs of 36 consecutive patients (43 hips) who underwent periacetabular osteotomy surgery were retrospectively analyzed from a single-centre, two-surgeon cohort. Anterior coverage (AC), posterior coverage (PC), lateral centre-edge angle (LCEA), acetabular inclination (AI), sharp angle (SA), pelvic tilt (PT), retroversion index (RI), femoroepiphyseal acetabular roof (FEAR) index, femoroepiphyseal horizontal angle (FEHA), leg length discrepancy (LLD), and pelvic obliquity (PO) were analyzed using both Hip2Norm software and PACS-derived measurements where applicable. RESULTS: Analysis of supine and standing radiographs resulted in significant variation for measurements of PT (p < 0.001) and AC (p = 0.005). The variation in PT correlated with the variation in AC in a limited number of patients (R2 = 0.378; p = 0.012). CONCLUSION: The significant variation in PT and AC between supine and standing radiographs suggests that it may benefit surgeons to have both radiographs when planning surgical correction of hip dysplasia. We also recommend using PACS-derived measurements of AI and SA due to the poor interobserver error on Hip2Norm.Item Metadata only Elevated levels of active Transforming Growth Factor β1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis(Elsevier BV, 2022) Muratovic, D.; Findlay, D.M.; Quarrington, R.D.; Cao, X.; Solomon, L.B.; Atkins, G.J.; Kuliwaba, J.S.Objective
The association between the spatially distributed level of active TGFβ1 in human subchondral bone, and the characteristic structural and cellular parameters of human knee OA, was assessed.Design
Paired subchondral bone samples from 35 OA arthroplasty patients, (15 men and 20 women, aged 69 ± 9 years) were obtained from beneath macroscopically present (CA+) or denuded cartilage (CA-) to determine the concentration of active TGFβ1 (ELISA) and its relationship to bone quality (synchrotron micro-CT), cellularity, and vascularization (histology).Results
Bone samples beneath (CA-) regions had significantly increased concentrations of active TGFβ1 protein (mean difference: 26.4; 95% CI: [3.2, 49.7]), when compared to bone in CA + regions. Trabecular Bone below (CA-) regions had increased bone volume (median difference: 4.3; 96.49% CI: [-1.7, 17.8]), increased trabecular number (1.5 [0.006, 2.6], decreased trabecular separation (-0.05 [-0.1,-0.005]), and increased bone mineral density (394.5 [65.7, 723.3]) comparing to (CA+) regions. Further, (CA-) bone regions showed increased osteocyte density (0.012 [0.006, 0.018]), with larger osteocyte lacunae (39.8 [7.8, 71.7]) that were less spherical (-0.02 [-0.04, -0.003]), and increased bone matrix vascularity (12.4 [0.3, 24.5]) compared to (CA+). In addition, increased levels of active TGFβ1 related to increased bone volume (0.04 [-0.11, 0.9]), while increased OARSI grade associated with lacunar volume (-44.1 [-71.1, -17.2]), and orientation (2.7 [0.8, 4.6]).Conclusion
Increased concentration of active TGFβ1 in the subchondral bone of human knee OA associates spatially with impaired bone quality and disease severity, suggesting that TGFβ1 is a potential therapeutic target to prevent or reduce human OA disease progression.Item Metadata only "Context, content, and system" supporting digital health hub (DHH)-enabled models of care (MoCs) for fragility hip fractures: perspectives of diverse multidisciplinary stakeholders in South Australia from qualitative in-depth interviews(Springer, 2021) Yadav, L.; Gill, T.K.; Taylor, A.; deYoung, J.; Visvanathan, R.; Chehade, M.J.Summary: Combining thematic analysis and a human–computer persuasive systems framework suggests that hip fracture recovery among older people can be enhanced through person-centered digital health hub models of care focused on behavior change education and integrated care. The findings intend to guide settings involving comorbid conditions and low- and middle-income countries in developing innovative digital health solutions. Purpose: The purpose of this study was to understand stakeholders’ perspectives on the development of a digital healthenabled model of care for fragility hip fractures and to map out factors that could influence the design and implementation of such a model. Methods: Qualitative in-depth interviews were conducted with stakeholders from various clinical disciplines, allied health, and computer science. A hybrid process involving thematic analysis of the raw data using inductive coding was the first step. In the second step, the tenets of a theoretical framework (health behavior change supporting systems) were deductively applied to the thematic constructs generated as part of the first step of the analysis. Results: In total, 24 in-depth interviews were conducted with stakeholders. We identified 18 thematic constructs presented under the categories of context, content, and system. Context covered patient characteristics such as frailty, digital literacy, and patient or carer participation, whereas healthcare delivery aspects included the structure and culture of existing practice and the need for innovative holistic models of care. Content outlines the active ingredients and approach in developing a digital health hub, and it highlights the importance of targeted education and behavior change. The system is a complicated matrix crossing different aspects of healthcare and offering a value proposition design through personalization across modes of content delivery. This must foster trust, ensure adequate financing, and support ownership and privacy by establishing appropriate mechanisms for embedding change. Conclusion: The findings from this study provide insights around potential factors related to patients, community support, and healthcare delivery influencing the design and next-stage implementation of a digital health hub model of care for fragility hip fractures.Item Metadata only 3D bioprinting of methylcellulose/gelatin-methacryloyl (MC/GelMA) bioink with high shape integrity(American Chemical Society; ACS Publications, 2020) Rastin, H.; Ormsby, R.T.; Atkins, G.J.; Losic, D.The advent of three-dimensional (3D) bioprinting offers a feasible approach to construct complex structures suitable for tissue regeneration, during which cell-laden materials are dispensed on a substrate according to a predesigned structure. However, the lack of ideal printable bioinks with high shape fidelity and improved biological stability remains a major challenge. In this study, methylcellulose/gelatin-methacryloyl (MC/GelMA) bioink with high shape integrity is presented, which takes advantage of the printability of MC and the permanent photo-cross-linking of GelMA under UV irradiation. Although MC demonstrates good printability at room temperature, the lack of cross-linking ability causes distortion and finally dissociation of printed MC in biological media within a few days. However, UV-cross-linked MC/GelMA bioink remains stable in biological media over a period of several months. The shape integrity of MC/GelMA was systematically characterized in terms of yield stress and complex modulus. Unlike pure MC ink, the MC/GelMA ink demonstrated self-supporting behavior once printed due to the higher complex modulus and yield stress induced by GelMA in the system. Shape integrity of MC/GelMA ink resulted in higher resolution and printability which are evaluated by the successful printing of various 1D, 2D, and 3D constructs. Moreover, human primary osteoblasts encapsulated within the MC/GelMA hydrogel show cell viability of >95%. Overall, this work introduces MC/GelMA bioink with high shape integrity and improved biological stability and highlights the importance of rheological properties and post-cross-linking for fabrication of physiologically scaled tissue implants.Item Metadata only Predicting infections after total joint arthroplasty using a prescription based comorbidity measure(Elsevier, 2015) Inacio, M.C.S.; Pratt, N.L.; Roughead, E.E.; Graves, S.E.This study evaluated the association and predictive ability of co-morbidities measured by RxRisk-V, Elixhauser and Charlson measures and post-total hip (THA) and total knee arthroplasties (TKA) infection. THAs and TKAs (2001–2012) were identified using the Australian Department of Veterans’ Affairs data. Infections within 90 days post-surgery were the study endpoint. Co-morbidities were identified using pharmacy (RxRisk-V) and hospitalization history (Elixhauser, Charlson). Of the 11,848 THAs, 3.1% (N = 364) had infections and out of 18,972 TKAs 3.4% (N = 648). Comorbidity burden and specific conditions were associated with infection likelihood. RxRisk-V performed better than other measures, but none had high predictive ability and differences were small. The best performing infection prediction models resulted when a combination of conditions identified by all measures was used.Item Open Access Evidence for osteocyte-mediated bone-matrix degradation associated with periprosthetic joint infection (PJI)(European Cells & Materials, 2021) Ormsby, R.T.; Zelmer, A.R.; Yang, D.; Gunn, N.J.; Starczak, Y.; Kidd, S.P.; Nelson, R.; Solomon, L.B.; Atkins, G.J.Osteomyelitis associated with periprosthetic joint infection (PJI) signals a chronic infection and the need for revision surgery. An osteomyelitic bone exhibits distinct morphological features, including evidence for osteolysis and an accelerated bone remodelling into poorly organised, poor-quality bone. In addition to immune cells, various bone cell-types have been implicated in the pathology. The present study sought to determine the types of bone-cell activities in human PJI bones. Acetabular biopsies from peri-implant bone from patients undergoing revision total hip replacement (THR) for chronic PJI (with several identified pathogens) as well as control bone from the same patients and from patients undergoing primary THR were analysed. Histological analysis confirmed that PJI bone presented increased osteoclastic activity compared to control bone. Analysis of osteocyte parameters showed no differences in osteocyte lacunar area between the acetabular bone taken from PJI patients or primary THR controls. Analysis of bone matrix composition using Masson's trichrome staining and second-harmonic generation microscopy revealed widespread lack of mature collagen, commonly surrounding osteocytes, in PJI bone. Increased expression of known collagenases, such as matrix metallopeptidase (MMP) 13, MMP1 and cathepsin K (CTSK), was measured in infected bone compared to non-infected bone. Human bone and cultured osteocyte-like cells experimentally exposed to Staphylococcus aureus exhibited strongly upregulated expression of MMP1, MMP3 and MMP13 compared to non-exposed controls. In conclusion, the study identified previously unrecognised bone-matrix changes in PJI caused by multiple organisms deriving from osteocytes. Histological examination of bone collagen composition may provide a useful adjunct diagnostic measure of PJI.Item Metadata only Calcitonin(Elsevier, 2016) Findlay, D.M.; Sexton, P.M.; Martin, T.J.; Jameson, J.L.; De Groot, L.J.; Weir, G.C.Item Metadata only Changes in 24-Hour physical activity patterns and walking gait biomechanics after primary total hip arthroplasty: a 2-year follow-up study(Lippincott, Williams & Wilkins, 2021) Bahl, J.S.; Millar, S.C.; Fraysse, F.; Arnold, J.B.; Taylor, M.; Callary, S.; Solomon, L.B.; Thewlis, D.BACKGROUND: Despite marked improvements in self-reported pain, perceived functional ability, and gait function following primary total hip arthroplasty (THA), it remains unclear whether these improvements translate into improved physical activity and sleep behaviors. The aim of this study was to determine the change in 24-hour activity profile (waking activities and sleep) and laboratory-based gait function from preoperatively to 2 years following the THA. METHODS: Fifty-one patients undergoing primary THA at a single public hospital were recruited. All THAs were performed using a posterior surgical approach with the same prosthesis type. A wrist-worn accelerometer was used to capture 24-hour activity profiles preoperatively and at 1 and 2 years postoperatively. Three-dimensional gait analysis was performed to determine changes in temporospatial and kinematic parameters of the hip and pelvis. RESULTS: Patients showed improvements in all temporospatial and kinematic parameters with time. Preoperatively, patients were sedentary or asleep for a mean time (and standard deviation) of 19.5 ± 2.2 hours per day. This remained unchanged up to 2 years postoperatively (19.6 ± 1.3 hours per day). Sleep efficiency remained suboptimal (<85%) at all time points and was worse at 2 years (77% ± 10%) compared with preoperatively (84% ± 5%). More than one-quarter of the sample were sedentary for >11 hours per day at 1 year (32%) and 2 years (41%), which was greater than the preoperative percentage (21%). Patients accumulated their activity performing light activities; however, patients performed less light activity at 2 years compared with preoperative levels. No significant differences (p = 0.935) were observed for moderate or vigorous activity across time. CONCLUSIONS: Together with improvements in self-reported pain and perceived physical function, patients had significantly improved gait function postoperatively. However, despite the opportunity for patients to be more physically active postoperatively, patients were more sedentary, slept worse, and performed less physical activity at 2 years compared with preoperative levels. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.Item Metadata only Anodized 3D-printed titanium implants with dual micro- and nano-scale topography promote interaction with human osteoblasts and osteocyte-like cells(Wiley, 2017) Gulati, K.; Prideaux, M.; Kogawa, M.; Lima-Marques, L.; Atkins, G.J.; Findlay, D.M.; Losic, D.The success of implantation of materials into bone is governed by effective osseointegration, requiring biocompatibility of the material and the attachment and differentiation of osteoblastic cells. To enhance cellular function in response to the implant surface, micro- and nano-scale topography have been suggested as essential. In this study, we present bone implants based on 3D-printed titanium alloy (Ti6Al4V), with a unique dual topography composed of micron-sized spherical particles and vertically aligned titania nanotubes. The implants were prepared by combination of 3D-printing and anodization processes, which are scalable, simple and cost-effective. The osseointegration properties of fabricated implants, examined using human osteoblasts, showed enhanced adhesion of osteoblasts compared with titanium materials commonly used as orthopaedic implants. Gene expression studies at early (day 7) and late (day 21) stages of culture were consistent with the Ti substrates inducing an osteoblast phenotype conducive to effective osseointegration. These implants with the unique combination of micro- and nano-scale topography are proposed as the new generation of multi-functional bone implants, suitable for addressing many orthopaedic challenges, including implant rejection, poor osseointegration, inflammation, drug delivery and bone healing. Copyright © 2016 John Wiley & Sons, Ltd.Item Metadata only Effect of Dementia on Outcomes After Surgically Treated Hip Fracture in Older Adults(Elsevier, 2021) Jorissen, R.N.; Inacio, M.C.; Cations, M.; Lang, C.; Caughey, G.E.; Crotty, M.Background Hip fractures are associated with increased mortality and functional limitations. However, the effect that dementia has on these outcomes in individuals in aged care settings after fracture is not well established. This study examined the association of dementia with post-hip fracture mortality, permanent residential aged care entry, transition care use, and change in activities of daily living (ADL) needs. Methods A retrospective cohort study using data from the Registry of Senior Australians (2003-2015) was conducted. Individuals with a hip fracture while receiving aged care services were included. Associations of dementia with mortality, risks of transition and permanent care use, and ADL needs progression were estimated using multivariable Cox, Fine-Gray, and logistic regression methods, respectively. Results Of 4771 individuals evaluated, 76% were women, the median age was 86 years (IQR 82-90), and 71% already lived in permanent residential aged care at the time of fracture. Within two years of their hip fracture, 50.4% (95% CI 48.9%-51.8%) of individuals died, 16.2% (95% CI 14.2%-18.2%) entered a transition care program, 59.1% (95% CI 56.5%-61.7%) entered permanent residential aged care, and 32% had greater ADL needs. Dementia was associated with higher risk of two-year mortality (HR = 1.19, 95% CI 1.09-1.30), 90-day entry into permanent care (sHR = 1.96, 95% CI 1.60-2.38), and increased likelihood of ADL limitations (OR = 1.36, 95% CI 1.00-1.85). Minor differences were seen in transition care use by dementia status. Conclusion Dementia is a strong risk factor for mortality after hip fractures in individuals in aged care settings and associated with a high risk of entry into permanent care.Item Metadata only Traumatic subaxial cervical facet subluxation and dislocation: epidemiology, radiographic analyses, and risk factors for spinal cord injury(Elsevier, 2018) Quarrington, R.; Jones, C.; Tcherveniakov, P.; Clark, J.; Sandler, S.; Lee, Y.; Torabiardakani, S.; Costi, J.; Freeman, B.Background Context: Distractive flexion injuries (DFIs) of the subaxial cervical spine are major contributors to spinal cord injury (SCI). Prompt assessment and early intervention of DFIs associated with SCI are crucial to optimize patient outcome; however, neurologic examination of patients with subaxial cervical injury is often difficult, as patients commonly present with reduced levels of consciousness. Therefore, it is important to establish potential associations between injury epidemiology and radiographic features, and neurologic involvement. Purpose: The aims of this study were to describe the epidemiology and radiographic features of DFIs presenting to a major Australian tertiary hospital and to identify those factors predictive of SCI. The agreement and repeatability of radiographic measures of DFI severity were also investigated. Study Design/Setting: This is a combined retrospective case-control and reliability-agreement study. Patient Sample: Two hundred twenty-six patients (median age 40 years [interquartile range = 34]; 72.1% male) who presented with a DFI of the subaxial cervical spine between 2003 and 2013 were reviewed. Outcome Measures: The epidemiology and radiographic features of DFI, and risk factors for SCI were identified. Inter- and intraobserver agreement of radiographic measurements was evaluated. Methods: Medical records, radiographs, and computed tomography and magnetic resonance imaging scans were examined, and the presence of SCI was evaluated. Radiographic images were analyzed by two consultant spinal surgeons, and the degree of vertebral translation, facet apposition, spinal canal occlusion, and spinal cord compression were documented. Multivariable logistic regression models identified epidemiology and radiographic features predictive of SCI. Intraclass correlation coefficients (ICCs) examined inter- and intraobserver agreement of radiographic measurements. Results: The majority of patients (56.2%) sustained a unilateral (51.2%) or a bilateral facet (48.8%) dislocation. The C6–C7 vertebral level was most commonly involved (38.5%). Younger adults were over-represented among motor-vehicle accidents, whereas falls contributed to a majority of DFIs sustained by older adults. Greater vertebral translation, together with lower facet apposition, distinguished facet dislocation from subluxation. Dislocation, bilateral facet injury, reduced Glasgow Coma Scale, spinal canal occlusion, and spinal cord compression were predictive of neurologic deficit. Radiographic measurements demonstrated at least a “moderate” agreement (ICC>0.4), with most demonstrating an “almost perfect” reproducibility. Conclusions: This large-scale cohort investigation of DFIs in the cervical spine describes radiographic features that distinguish facet dislocation from subluxation, and associates highly reproducible anatomical and clinical indices to the occurrence of concomitant SCI.Item Metadata only Age and sex effects on FGF23-mediated response to mild phosphate challenge(Elsevier, 2021) Tippen, S.P.; Noonan, M.L.; Ni, P.; Metzger, C.E.; Swallow, E.A.; Sacks, S.A.; Chen, N.X.; Thompson, W.R.; Prideaux, M.; Atkins, G.J.; Moe, S.M.; Allen, M.R.; White, K.E.Background: During aging, there is a normal and mild loss in kidney function that leads to abnormalities of the kidney-bone metabolic axis. In the setting of increased phosphorus intake, hyperphosphatemia can occur despite increased concentrations of the phosphaturic hormone FGF23. This is likely from decreased expression of the FGF23 co-receptor Klotho (KL) with age; however, the roles of age and sex in the homeostatic responses to mild phosphate challenges remain unclear. Methods: Male and female 16-week and 78-week mice were placed on either normal grain-based chow or casein (higher bioavailable phosphate) diets for 8 weeks. Gene expression, serum biochemistries, micro-computed tomography, and skeletal mechanics were used to assess the impact of mild phosphate challenge on multiple organ systems. Cell culture of differentiated osteoblast/osteocytes was used to test mechanisms driving key outcomes. Results: Aging female mice responded to phosphate challenge by significantly elevating serum intact FGF23 (iFGF23) versus control diet; males did not show this response. Male mice, regardless of age, exhibited higher kidney KL mRNA with similar phosphate levels across both sexes. However, males and females had similar blood phosphate, calcium, and creatinine levels irrespective of age, suggesting that female mice upregulated FGF23 to maintain blood phosphorus, and compromised renal function could not explain the increased serum iFGF23. The 17β-estradiol levels were not different between groups, and in vivo bone steroid receptor (estrogen receptor 1 [Esr1], estrogen receptor 2 [Esr2], androgen receptor [Ar]) expression was not different by age, sex, or diet. Trabecular bone volume was higher in males but decreased with both age and phosphate challenge in both sexes. Cortical porosity increased with age in males but not females. In vitro studies demonstrated that 17β-estradiol treatment upregulated FGF23 and Esr2 mRNAs in a dose-dependent manner. Conclusions: Our study demonstrates that aging female mice upregulate FGF23 to a greater degree during a mild phosphate challenge to maintain blood phosphorus versus young female and young/old male mice, potentially due to direct estradiol effects on osteocytes. Thus, the control of phosphate intake during aging could have modifiable outcomes for FGF23-related phenotypes.Item Metadata only Relationships between tibial articular cartilage, in vivo external joint moments and static alignment in end-stage knee osteoarthritis: a micro-CT study(Wiley, 2022) Rapagna, S.; Roberts, B.C.; Solomon, L.B.; Reynolds, K.J.; Thewlis, D.; Perilli, E.Biomechanical factors (e.g. joint loading) have a significant role in the progression of osteoarthritis (OA). However, some relationships between in vivo joint loading indices and tibial cartilage thickness are conflicting. This study investigated relationships between pre-operative in vivo external knee joint moments and joint alignment with regional tibial cartilage thickness using micro-CT in subjects with end-stage knee OA. Tibial plateaus from 25 patients that underwent knee replacement for OA were micro-CT scanned (17µm/voxel). Prior to surgery, subjects underwent gait analysis to calculate external knee moments. The mechanical axis deviation (MAD) was obtained from pre-operative radiographs. Cartilage thickness (Cart.Th) was analyzed from micro-CT images, in anteromedial, anterolateral, posteromedial and posterolateral subregions of interest. Medial-to-lateral Cart.Th ratios were also explored. Relationships between Cart.Th and joint loading indices were examined using Pearson's correlations. Significant correlations were found between Cart.Th and joint loading indices, positive anteromedially with the first peak knee adduction moment (r= 0.55, p<0.01) and external rotation moment (ERM; r= 0.52, p<0.01), and negative with MAD (r= -0.76, p<0.001). In the lateral regions, these correlations had opposite signs. The medial-to-lateral Cart.Th ratio correlated strongly with ERM (r= 0.63, p=0.001) and MAD (r= -0.75, p<0.001). Joint loading indices correlated with regional cartilage thickness values and their medial-to-lateral ratios in end-stage knee OA subjects, with higher regional loads corresponding to thinner cartilage. These relationships have the opposite sign compared to the subchondral bone microarchitecture found in our previous study on the same specimens, which may suggest a complementary bone-cartilage interplay in response to loading.Item Open Access Differential iron requirements for osteoblast and adipocyte differentiation(Wiley, 2021) Edwards, D.F.; Miller, C.J.; Quintana‐Martinez, A.; Wright, C.S.; Prideaux, M.; Atkins, G.J.; Thompson, W.R.; Clinkenbeard, E.L.Bone marrow mesenchymal progenitor cells are precursors for various cell types including osteoblasts, adipocytes, and chondrocytes. The external environment and signals act to direct the pathway of differentiation. Importantly, situations such as aging and chronic kidney disease display alterations in the balance of osteoblast and adipocyte differentiation, adversely affecting bone integrity. Iron deficiency, which can often occur during aging and chronic kidney disease, is associated with reduced bone density. The purpose of this study was to assess the effects of iron deficiency on the capacity of progenitor cell differentiation pathways. Mouse and human progenitor cells, differentiated under standard osteoblast and adipocyte protocols in the presence of the iron chelator deferoxamine (DFO), were used. Under osteogenic conditions, 5μM DFO significantly impaired expression of critical osteoblast genes, including osteocalcin, type 1 collagen, and dentin matrix protein 1. This led to a reduction in alkaline phosphatase activity and impaired mineralization. Despite prolonged exposure to chronic iron deficiency, cells retained viability as well as normal hypoxic responses with significant increases in transferrin receptor and protein accumulation of hypoxia inducible factor 1α. Similar concentrations of DFO were used when cells were maintained in adipogenic conditions. In contrast to osteoblast differentiation, DFO modestly suppressed adipocyte gene expression of peroxisome-proliferating activated receptor gamma, lipoprotein lipase, and adiponectin at earlier time points with normalization at later stages. Lipid accumulation was also similar in all conditions. These data suggest the critical importance of iron in osteoblast differentiation, and as long as the external stimuli are present, iron deficiency does not impede adipogenesis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Item Metadata only Children's school footwear: The impact of fit on foot function, comfort and jump performance in children aged 8 to 12 years(Elsevier, 2021) Matthias, E.; Banwell, H.A.; Arnold, J.B.Background: There is a common perception that poorly fitting footwear will negatively impact a child’s foot, however, there is limited evidence to support this. Aim: To determine the effect of shoe size on foot motion, perceived footwear comfort and fit during walking, maximal vertical jump height and maximal standing broad jump distance in children aged 8–12 years. Methods: Fourteen participants completed 3D walking gait analysis and jumping tasks in three different sizes of school shoes (one size bigger, fitted for size, one size smaller). In-shoe motion of the hindfoot, midfoot and 1st metatarsophalangeal joint (1st MTPJ) were calculated using a multi-segment kinematic foot model. Physical performance measures were calculated via maximal vertical jump and maximal standing broad jump. Perceived footwear comfort and fit (heel, toes and overall) was assessed using a 100 mm visual analog scale (VAS). Differences were compared between shoe sizes using repeated measures ANOVA, post-hoc tests and effect sizes (Cohen’s d). Results: Compared to the fitted footwear, the smaller sizing restricted hindfoot eversion (−2.5°, p = 0.021, d = 0.82), 1st MTPJ dorsiflexion (−3.9°, p = 0.012, d = 0.54), and compared to the bigger footwear, smaller sizing restricted sagittal plane midfoot range-of-motion during walking (−2.5°, p = 0.047, d = 0.59). The fitted footwear was rated as more comfortable overall with the smaller size rated as too tight in both the heel (mean difference 11.5 mm, p = 0.042, d = 0.58) and toes (mean difference 12.1 mm, p = 0.022, d = 0.59), compared to the fitted size. Vertical and standing broad jump distance were not impacted by footwear size (p = 0.218−0.836). Significance: Footwear that is too small restricts foot motion during walking in children aged 8–12 years. Jump performance was not affected. Children were able to recognise shoes that were not correctly matched to their foot length, reinforcing that comfort is an important part of the fitting process.