Currently, between 17% of patients undergoing surgery for adult spinal deformity experience severe instrumentation related problems such as screw pullout or proximal junctional failure necessitating revision surgery. Cables may be used to reinforce pedicle screw fixation as an additive measure or may provide less rigid fixation at the construct end levels in order to prevent junctional level problems. The purpose of this study is to provide insight into the maximum expected load during flexion in UHMWPE cable in constructs intended for correction of adult spine deformity (degenerative scoliosis) in the PoSTuRe first-in-man clinical trial. Following the concept of toppinoff, a new construct is proposed with screw/cable fixation of rods at the lower levels and standalone UHMWPE cables at the upper level (T11). A parametric FE model of the instrumented thoracolumbar spine, which has been previously validated, was used to represent the construct. Pedicle screws are modeled by assigning a rigid tie constraint between the rod and the lamina of the corresponding spinal level. Cables are modeled using linear elastic line elements, fixing the rod to the lamina medially at the cranial laminar end and laterally at the caudal laminar end. A Youngs modulus was assigned such that the stiffness of the line element was the same as that of the cable. An 8 Nm flexion moment was applied to the cranial endplate. The maximum value of the force in the wire (80 N) is found at the T11 (upper) level. At the other levels, forces in the cable are very small because most of the force is carried by the screw (T12) or because the wires are force shielded by the contralateral and adjacent level pedicle screws (L2, L3). The model provides first estimates of the forces that can be expected in the UHMWPE cables in constructs for kyphosis correction during movement. It is expected that this approach can help in defining the number of wires for optimal treatment

Introduction. Adult tendon injuries occur very frequently, but injured tendon heals very slowly and the mechanisms of the slow-healing response to injury are still largely unknown. Currently, the main barrier is our insufficient understanding of the mechanisms responsible for homeostasis, regeneration and repair of adult tendon. This gap in knowledge translates to a lack of experimental models. Therefore, using the combination of state-of-the-art genetic approaches, we have established novel cell biological tools to advance the understanding of tendon biology. Materials and Methods. Adult mouse tendon progenitor lines and Adult mouse tenocyte lines: Primary adult tenocytes were isolated from Achilles tendon in Scleraxis(fl/fl)/Scleraxis-GFP/p21(−/−) mice, then CD90.2- and subsequent Sca1-positive cells were sorted by Flow Cytometry. Then Scleraxis-null progenitor lines were generated by the treatment of those cells with adenovirus-Cre. Adult Scleraxis(+/+) and Scleraxis-null tenocyte lines were also generated from Scleraxis(fl/fl)/Scleraxis-GFP/p21(−/−) mice. To establish Scleraxis-Flag overexpressing tenocyte lines, Scleraxis and Flag-tag fusion-protein expression construct was generated and transfected into Scleraxis-null tenocytes (Scleraxis transgenic mouse strains were provided by Dr Ronen Schweitzer). Scleraxis antibody: DNA coding mouse Scleraxis residues were obtained by PCR, then the recombinant protein was expressed, immunized in rabbits, and an affinity-purified antibody was generated. Results. Established parental progenitor lines highly expressed Sca1 (98.9%), CD90.2 (97.3%), and CD44 (99.8%) and were almost negative for ScxGFP (2.3%). Interestingly, Scleraxis-null progenitors showed significantly increased clonogenicity. Furthermore, when stimulated toward mesenchymal lineages, Scleraxis-null progenitors enhanced differentiation into chondrocytes. Our Scleraxis antibody reacted with lysates from cells expressing Scleraxis-Flag fusion proteins (∼30 kDa), whereas it did not react with Scleraxis-null cells by Western analysis. Immunofluorescence analysis of adult mouse Achilles tendons further confirmed intense Scleraxis protein expression in wild-type tenocytes, whereas considerably decreased expression of Scleraxis was evident in Cre-treated Scleraxis(fl/fl) tenocytes. Discussion. These novel tools will be the promising resources to get an insight into molecular framework for Scleraxis in adult tendons. It is anticipated that the establishment of experimental models using these resources will fill major gaps in the current knowledge of adult tendon biology and will facilitate development of novel strategies to treat adult tendon injury

The modified Hedgehog technique was previously used to reattach pure chondral shear-off fragments in the pediatric knee. In the modified Hedgehog technique, the calcified side of chondral fragments is multiple times incised and trimmed obliquely for an interlocking fit in the defect site. Fibrin glue with or without sutures is subsequently applied to fix the fragment to the defect. This preliminary report further elucidates the potential of the technique by evaluation of its application in young adults using patient reported outcome measures (PROMs) and high-field Magnetic Resonance Imaging (MRI) as outcome measures. Three patients with a femoral cartilage defect (2 medial, 1 lateral), and a concomitant pure chondral corpus liberum were operatively treated by the modified Hedgehog technique. Age at surgery ranged from 20.6–21.2 years, defect size ranged from 3.8–6.0 cm2. Patients were evaluated at three months and one year after surgery by PROMs and 7.0T MRI. PROMs included the Internation Knee Documentation (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale (VAS) questionnaires. 7.0T MRI (Magnetom, Siemens Healthcare, Erlangen, Germany) using a 28-channel proton knee coil (QED, Electrodynamics LLC, Cleveland, OH) included a proton density weighted turbo spin-echo sequence with fat suppression to assess morphological tissue structure andgagCEST imaging to measure the biochemical tissue composition in terms of glycosaminoglycans (GAG). Twelve months after surgery all patients reported no pain and showed full range of motion. While PROMs at three months showed large variability between patients, one year after surgery the scores were consistently improved. Over time, morphological MRI visualized improvements in integration of the cartilage fragment with the surrounding cartilage, which was supported by biochemical MRI showing increased GAG values at the defect edges. Statistics were not applied to the results because of the small sample size. The modified Hedgehog technique in young adults with an acute onset caused by a pure chondral corpus liberum can be considered promising. The improved PROM results over time were supported by 7.0T MRI that visualized improvements in tissue structure and biochemical composition. Inclusion of more patients in future studies would allow statistical analysis and more conclusive results. The etiology of loosening and time between onset of symptoms and surgery for successful graft integration may differ between pediatric and young adult patients and is subject for future studies

The diagnosis and treatment of hip disease in young adults has rapidly evolved over the past ten years. Despite the advancements of improved diagnostic skills and refinement of surgical techniques, the psychosocial impact hip disease has on the young adult has not yet been elucidated. This observational study aimed to characterise the functional and psychosocial characteristics of a group of patients from our young hip clinic. 49 patients responded to a postal questionnaire which included the Oswestry Disability Index (ODI) and Hospital Anxiety and Depression Scale (HADS). Median age was 20 years (range 16-38) with a gender ratio of 2:1 (female: male). The most common diagnoses were Perthes' disease and developmental hip dysplasia. More than half of our patients had moderate to severe pain based on the Visual Analogue Scale (VAS) and at least a moderate disability based on the ODI. Thirty-two percent of patients were classified as having borderline to abnormal levels of depression and 49% of patients were classified as having borderline to abnormal levels of anxiety based on the HADS. Comparison of the ODI with the VAS and HADS anxiety and depression subscales showed a significant positive correlation (p<0.05). Multiple regression showed the ODI to be a significant predictor of the HADS anxiety and depression scores (regression coefficient 0.13, 95% confidence interval 0.06 to 0.21, p<0.05). This study highlights the previously unrecognised psychosocial effects of hip disease in the young adult. A questionnaire which includes HADS may be of particular value in screening for depression and anxiety in young people with physical illness. This study also highlights that collaboration with psychologists and other health care providers may be required to achieve a multidisciplinary approach in managing these patients

Femoral shaft fractures are potentially devastating injuries. Despite this, clinical studies of the biomechanics of this injury are lacking. We aimed to clinically evaluate bone behaviour under high and low energy trauma in paediatric, adult and older patients. Single-centre retrospective study identifying all diaphyseal femoral fractures between Feb 2015-Feb 2017. Peri-prosthetic and pathological fractures were excluded. Patients were subdivided into groups 1 (paediatric, <16yo), 2 (adult, 17–55yo) and 3 (older, >55yo) to reflect immature, peak bone age and osteoporotic bone respectively. Chi-Squared analysis assessed significance of bone age to degree of comminution and fracture pattern. A p-value <0.05 was significant. A total 4130 radiographs were analysed with 206 femoral shaft fractures identified. Forty-three patients were excluded with 163 remaining. Group 1, 2 and 3 included 38, 37 and 88 patients respectively. Mean age 50.8 (SD 32.8) with male-to-female ratio of 1:1.2. Groups 1 and 3 included majority simple fractures (35/38 and 62/88 respectively). Group 2 included more comminuted injuries (33/37). Bone age to degree of comminution proved significant (p<0.05) with a bimodal distribution of simple fractures noted in groups 1 and 3. Energy to fracture was significant in group 2, where a high energy injury was associated with comminution (p<0.05). This study is the first to demonstrate an association between fracture comminution and age. Simple femoral shaft fractures showed a bimodal age distribution in paediatric and older patients regardless of mechanism energy. High energy mechanism trauma was directly related to fracture comminution at peak bone age

Background and purpose of the study. Effective communication between healthcare professionals and patients is key to a successful consultation and is reported to affect both adherence to treatment and outcome. Despite this evidence, research on how best to open consultations is limited and the optimal way, unknown. This study seeks the opinions of physiotherapists on how to open a clinical encounter in an adult musculoskeletal outpatient setting – a topic which has relevance to all clinicians aiming to build rapport with their patients. Methods. Forty clinical encounters between physiotherapists in a primary care setting and patients with back pain were observed and audio-recorded. The clinicians' key questions inviting the patient to discuss their back pain were identified, together with a content analysis of the topics discussed prior to the conversation about their back pain. In 2012, a national survey was undertaken, approaching 34,922 physiotherapists from 3 networks on the interactive website hosted by the professional body, the Chartered Society of Physiotherapy asking participants to rank the data from clinical practice, to determine the preferred way to open a clinical encounter. Results. Form the 40 recorded consultations eleven opening questions were identified. In these encounters fourteen other topics were discussed before the key opening question about back pain. In the national survey, the top 5 openings were identified. Conclusion. Knowing how clinicians and patients communicate, and specifically, how clinical encounters are opened, is important for teaching and professional development to assist clinicians in optimising their non-specific treatment effects. No Conflict of interest. No funding obtained. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting

Summary Statement. This study reports that hMSC can be manipulated in order to engineer a bone organ, characterised by mature osseous and vascular components and capable to recruit, host and maintain functional HSCs. Introduction. Bone tissue engineering strategies are typically based on methods involving adult human Mesenchymal Stromal Cells (hMSC) in a process resembling intramembranous ossification. However, most bones develop and repair through endochondral ossification. In addition, endochondral ossification presents several advantages for regenerative purposes such as osteogenic activity, capability to drive formation of the Hematopoietic Stem Cell (HSC) niche, resistance to hypoxia, intrinsic vasculogenic potential and, consequently, efficiency of engraftment. In this study, we aimed at developing an endochondral bone organ model characterised by functional osseous and hematopoietic compartments by using hMSC. Materials & Methods. Expanded hMSC were seeded onto 8 mm diameter, 2 mm thick collagen sponges (UltrafoamTM, Davol Inc.), cultured for vitro under defined chondrogenic (3 weeks) and hypertrophic (2 weeks) conditions and then implanted ectopically in subcutaneous pouches in nude mice. Consistently with the normal process of bone regeneration, which requires an inflammatory environment, we added IL-1β to the hypertrophic medium and assessed its effect on in vitro mineralization, hypertrophy, extracellular matrix processing and in vivo remodeling/bone formation. Samples were analyzed by histology, IHC, Luminex® assays, ISH for human Alu repeats and µCT. Bone marrow cells, extracted after 12 weeks from the implanted samples were analyzed by flow cytometry and transplanted into lethally irradiated congenic animals to asses functionality of the engrafted bone marrow. Results. In vitro, samples showed a mineralised collar, rich in Collagen I and BSP, and a hypertrophic core, rich in proteoglycans and Collagen X. In vivo, extensive remodeling occurred, with mature vessel ingrowth (CD31+, NG2+, α-SMA+) and osteoclast (TRAP+ and MMP9+ multinucleated cells). Bone formation displayed a peculiar topography: at the periphery of the samples, perichondral bone was formed, corresponding to the in vitro pre-mineralised outer ring; in the core of the samples, endochondral bone was formed, corresponding to the in vitro non-mineralised cartilaginous areas. Human cells could be still detected after 12 weeks in vivo, mainly in the bone in the core of the samples. IL-1β resulted in (i) enhanced MMP13 endogenous activity; (ii) enhanced osteoclasts activity by increased M-CSF levels and RANKL/OPG ratio; (iii) faster vascularization; (iv) larger regions of bone marrow, possibly because of an increased synthesis of SDF1, IL-8, M-CSF and MCP-1. Murine bone marrow cells in the newly generated bone included phenotypically and functionally defined HSC at a comparable frequency than normal bones of the same mice. Discussion/Conclusion. We reported the generation of an ectopic “bone organ” with a size, structure and functionality comparable to native bones by appropriately primed hMSC. The use of hMSC and IL-1β makes this model closer to bone regeneration than to bone development. The work, provides a model useful for fundamental and translational studies on bone development and regeneration, as well as for the modeling of normal and malignant hematopoiesis

Study Purpose

A preliminary study to compare continuous sagittal plane lumbar inter-vertebral kinematics in 10 healthy volunteers in recumbent and weight bearing configurations using quantitative fluoroscopy.

X-Linked Hypophosphataemia (XLH) is a rare, progressive, hereditary phosphate-wasting disorder characterised by excessive activity of fibroblast growth factor 23. The International XLH Registry was established to provide information on the natural history of XLH and impact of treatment on patient outcomes. The cross-sectional orthopaedic data presented are from the first interim analysis. The XLH Registry (NCT03193476) was initiated in August 2017, aims to recruit 1,200 children and adults with XLH, and will run for 10 years. At the time of analysis (Last Patient In: 30/11/2020; Database Lock: 29/03/2021) 579 subjects diagnosed with XLH were enrolled from 81 hospital sites in 16 countries (360 (62.2%) children, 217 (37.5%) adults, and 2 subjects of unknown age). Of subjects with retrospective clinical data available, skeletal deficits were the most frequently self-reported clinical problems for children (223/239, 93.3%) and adults (79/110, 71.8%). Retrospective fracture data were available for 183 subjects (72 children, 111 adults); 50 had a fracture (9 children, 41 adults). In children, fractures tended to occur in tibia/fibula and/or wrist; only adults reported large bone fractures. Joint conditions were noted for 46 subjects (6 children, 40 adults). For adults reporting osteoarthritis, knees (60%), hips (42.5%), and shoulders (22.5%) were the most frequently affected joints. Retrospective orthopaedic surgery data were collected for 151 subjects (52 children, 99 adults). Osteotomy was the most frequent surgery reported (n=108); joint replacements were recorded for adults only. This is the largest set of orthopaedic data from XLH subjects collected to date. Longitudinal information collected during the 10-year Registry duration will generate real-world evidence which will help to inform clinical practice. Authors acknowledge the contribution of all International XLH Registry Steering Committee members

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews

Total knee arthroplasty (TKA) aims to alleviate pain and restore joint biomechanics to an equivalent degree to age-matched peers. Zimmer Biomet's Nexgen TKA was the most common implant in the UK between 2003 and 2016. This study compared the biomechanical outcomes of the Nexgen implant against a cohort of healthy older adults to determine whether knee biomechanics is restored post-TKA. Patients with a primary Nexgen TKA and healthy adults >55 years old with no musculoskeletal deficits or diagnosis of arthritis were recruited locally. Eligible participants attended one research appointment. Bilateral knee range of motion (RoM) was assessed with a goniometer. A motorised arthrometer (GENOUROB) was then used to quantify the anterior-posterior laxity of each knee. Finally, gait patterns were analysed on a treadmill. An 8-camera Vicon motion capture system generated the biomechanical model. Preliminary statistical analyses were performed in SPSS (α = 0.05; required sample size for ongoing study: n=21 per group). The patient cohort (n=21) was older and had a greater BMI than the comparative group (n=13). Patients also had significantly poorer RoM than healthy older adults. However, there were no inter-group differences in knee laxity, walking speed or cadence. Gait kinematics were comparable in the sagittal plane during stance phase. Peak knee flexion during swing phase was lower in the patient group, however (49.0° vs 41.1°). Preliminary results suggest that knee laxity and some spatiotemporal and kinematic parameters of gait are restored in Nexgen TKA patients. While knee RoM remains significantly poorer in the patient cohort, an average RoM of >110° was achieved. This suggests the implant provides sufficient RoM for most activities of daily living. Further improvements to knee kinematics may necessitate additional rehabilitation. Future recruitment drives will concentrate on adults over the age of 70 for improved inter-group comparability

Despite extensive research aimed at improving surgical outcomes of enthesis injuries, re-tears remain a common problem, as the repairs often lead to fibrovascular scar as opposed to a zonal enthesis. Zonal enthesis formation involves anchoring collagen fibers, synthesizing proteoglycan-rich fibrocartilage, and mineralizing this fibrocartilage [1]. During development, the hedgehog signaling pathway promotes the formation and maturation of fibrocartilage within the zonal tendon-to-bone enthesis [1-4]. However, whether this pathway has a similar role in adult zonal tendon-to-bone repair is not known. Therefore, we developed a murine anterior cruciate ligament (ACL) reconstruction model [5] to better understand the zonal tendon-to-bone repair process and perturb key developmental regulators to determine the extent to which they can promote successful repair in the adult. In doing so, we activated the hedgehog signaling pathway both genetically using transgenic mice and pharmacologically via agonist injections. We demonstrated that both treatments improved the formation of zonal attachments and tunnel integration strength [6]. These improved outcomes were due in part to hedgehog signaling's positive role in proliferation of the bone marrow stromal cell (bMSC) progenitor pool and subsequent fibrocartilage production of bMSC progeny cells that form the attachments. These results suggest that, similar to growth and development, hedgehog signaling promotes the production and maturation of fibrocartilage during tendon-to-bone integration in adults. Lastly, we developed localized drug delivery systems to further improve the treatment of these debilitating injuries in future translational studies. Acknowledgements: This work was supported by NIH R01AR076381, R21AR078429, R00AR067283, F31AR079840, T32AR007132, and P30AR069619, in addition to the McCabe Fund Pilot Award at the University of Pennsylvania

Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults. The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker. 49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m. 2. ; e SD 3. At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed. 45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001). In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs. We concluded that the levels of calcium crystals in FAI patients are correlated with joint damage, OA signs and worst post-operative outcome. The presence of calcium crystals in SF of FAI patients might be a potential new biomarker that might help clinicians to make an early diagnosis, evaluate disease progression and monitor treatment response

Adult Spine Deformity (ASD) is a degenerative condition of the adult spine leading to altered spine curvatures and mechanical balance. Computational approaches, like Finite Element (FE) Models have been proposed to explore the etiology or the treatment of ASD, through biomechanical simulations. However, while the personalization of the models is a cornerstone, personalized FE models are cumbersome to generate. To cover this need, we share a virtual cohort of 16807 thoracolumbar spine FE models with different spine morphologies, presented in an online user-interface platform (SpineView). To generate these models, EOS images are used, and 3D surface spine models are reconstructed. Then, a Statistical Shape Model (SSM), is built, to further adapt a FE structured mesh template for both the bone and the soft tissues of the spine, through mesh morphing. Eventually, the SSM deformation fields allow the personalization of the mean structured FE model, leading to generate FE meshes of thoracolumbar spines with different morphologies. Models can be selectively viewed and downloaded through SpineView, according to personalized user requests of specific morphologies characterized by the geometrical parameters: Pelvic Incidence; Pelvic Tilt; Sacral Slope; Lumbar Lordosis; Global Tilt; Cobb Angle; and GAP score. Data quality is assessed using visual aids, correlation analyses, heatmaps, network graphs, Anova and t-tests, and kernel density plots to compare spinopelvic parameter distributions and identify similarities and differences. Mesh quality and ranges of motion have been assessed to evaluate the quality of the FE models. This functional repository is unique to generate virtual patient cohorts in ASD. Acknowledgements: European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828)

Management of ankle arthritis in young patients is challenging. Although ankle arthrodesis gives consistent pain relief, it leads to loss of function and adjacent joint arthritis. Ankle joint distraction (AJD) has been shown to give good outcomes in adults with osteoarthritis or post-traumatic arthritis. The efficacy in children or young adults and those with juvenile idiopathic arthritis is less well evidenced. Clinical notes and radiographs of all patients (n=6) managed with AJD in one tertiary referral centre were retrospectively reviewed. Radiographs were taken pre-surgery, intra-operatively, 1 month following frame removal and at the last follow up, tibiotalar joint space was assessed using ImageJ software. Measurements were taken at the medial, middle and lateral talar dome using frame components as reference. Radiographic data for patients with a good clinical outcome was compared with those who did not. At time of surgery mean age was 16.1 years (12 – 25 years). Mean follow up was 3.4 years (1.5 – 5.9 years). Indications were juvenile idiopathic arthritis (4) post-traumatic (1) and post-infective arthritis (1). Three patients at last follow up had a good clinical outcome. Two patients required revision to arthrodesis (1.3 and 2.4 years following distraction). One patient had spontaneous fusion. One patient required oral antibiotics for pin site infection. Inter-observer reliability was 95%. Mean joint space was 1.17mm (SD = 0.87mm) pre-operatively which increased to 6.72mm (SD = 2.23mm) at the time of distraction and 2.09mm (SD = 1.14mm) at the time of removal. At one-year follow up, mean joint space was 1.96mm (SD = 1.97mm). Outcomes following AJD in this population are variable although significant benefits were demonstrated for 50% of the patients in this series. Radiographic joint space preoperatively did not appear to be associated with need for arthrodesis. Further research in larger groups of young patients is required

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model. Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05. When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice. Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis

Falls in adults are a major problem and can lead to injuries and death. In order to better understand falls and successful recoveries, identifying kinematics, kinetics, and muscle forces during recovery from loss of balance is crucial. To obtain reactive gait patterns, participants must be subjected to unexpected perturbations such as trips and slips. Previous researchers have reported kinetics recovery data following stumbling; however, the muscle force recovery patterns remain unknown. To better target exercises to reduce the risk of falls, we must first understand which muscles, their magnitude, and their coordination patterns, play a role in a successful recovery from a trip and a slip. Additionally, knowing the successful patterns of lower limb function can help with the diagnosis of faulty movements. A total of 20 healthy adults in their twenties with similar athletic backgrounds were perturbed on a split-belt treadmill using Computer-Assisted Rehabilitation Environment (Motkforce Link) at a preset speed of 1.1m/s. Two kinds of perturbations were administered: slip and trip. Slips were simulated by accelerating one belt, whereas trips were simulated by decelerating one belt. Both perturbations had similar intensity and only differed in the direction. Computational modeling was used to obtain lower-limb function during the compensatory step. SPM paired t-test was used to compare differences in recovery strategies between slip and trip through magnitude and patterns of joints. There were no significant differences in joint angles post tripping vs post-slipping. Results of net joint moments showed that compensating for the loss of balance due to tripping required a higher ankle plantarflexion moment than slipping (at 22-52%; 1.2± 0.3vs0.4±0.2, p<0.001). Additionally, larger gluteus maximus (at 40-50%;8.7±3.8vs2.7±1.1N/kg, p=0.001), gluteus medius (at23~33%; 22.6±5.7vs6.8±3.6N/kg, p<0.001) were generated than post-slipping, respectively. These findings suggested that greater GMAX and GMED forces are required post-trip recovery than slip. Future analysis of trip recovery showed the importance of ankle joint in recovering from forward and backward fall. These results can be used as references in remote diagnosis of joint and muscle weakness and assessment of the risk of falls with the use of accelerometers

Abstract. Objectives. The aim of this study was to investigate whether mechanical loading induced by physical activity can reduce risk of sarcopenia in middle-aged adults. Methods. This was a longitudinal study based on a subset of UK Biobank data consisting of 1,918 participants (902 men and 1,016 women, mean age 56 years) who had no sarcopenia at baseline (assessed between 2006 and 2010). The participants were assessed again after 6 years at follow-up, and were categorized into no sarcopenia, probable sarcopenia, or sarcopenia according to the definition and algorithm developed in 2018 by European Working Group on Sarcopenia in Older People (EWGSOP). Physical activity was assessed at a time between baseline and follow-up using 7-day acceleration data obtained from wrist worn accelerometers. Raw acceleration data were then analysed to study the mechanical loading of physical activity at different intensities (i.e. very light, light, moderate-to-vigorous). Multinominal logistic regression was employed to examine the association between the incidence of sarcopenia and physical activity loading, between baseline and follow up, controlled for other factors at baseline including age, gender, BMI, smoking status, intake of alcohol, vitamin D and calcium, history of rheumatoid arthritis, osteoarthritis, secondary osteoporosis, and type 2 diabetes. Results. Among the 1918 participants with no sarcopenia at baseline, 230 (69 men and 161 women) developed probable sarcopenia and 37 (14 men and 23 women) developed sarcopenia at follow-up. Physical activity loading at moderate-to-vigorous intensity was higher in men (p<0.05), while women had higher physical activity loading at very light intensity (p<0.05). No significant difference was found in physical activity loading at light intensity between men and women (p>0.05). Logistic regression models showed that increase in physical activity loading at moderate-to-vigorous intensity significantly reduced the risk of sarcopenia (odds ratio = 0.368, p<0.05), but not probable sarcopenia (odds ratio = 0.974, p>0.05), while loading at light or very light activity intensity were not associated with the risk of sarcopenia or probable sarcopenia (p>0.05). Conclusion. Loading of physical activity at moderate-to-vigorous intensity could reduce risk of sarcopenia in middle-aged adults. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Osteoarthritis (OA) is the most common joint disease, affecting approximately 16% of the adult population worldwide. The chronic inflammation in the joint leads to the breakdown of cartilage, which leads to permanent pain and limitations in everyday life at an early stage of the disease. To date, there is no therapy that can interrupt the inflammatory state or reverse cartilage damage. The PROTO consortium (funded by the EU Horizon Europe program, Grant 101095635) aims to prevent the development of OA by correcting a pathological biomechanical pattern by a digital training intervention and to treat early stage OA with an innovative allogeneic cell therapy

Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and bone inducers, is a potential alternative to conventional treatments. Pre-clinical testing of innovative scaffolds relies on in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs) is required to mimic their crosstalk and molecular cooperation for bone remodelling. To this aim, two composite materials based on type I collagen were developed, containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. Following chemical crosslinking with genipin, the nanostructured materials were tested for 2–3 weeks with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors. The favourable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of bone cells, encouraging a further investigation of the two bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE