Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)). Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO. 4. and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO. 4. to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA. Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality. Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases

Background. Fracture of an osteoporotic vertebral body reduces vertebral stiffness and decompresses the nucleus in the adjacent intervertebral disc. This leads to high compressive stresses acting on the annulus and neural arch. Altered load-sharing at the fractured level may influence loading of neighbouring vertebrae, increasing the risk of a fracture ‘cascade’. Vertebroplasty has been shown to normalise load-bearing by fractured vertebrae but it may increase the risk of adjacent level fracture. The aim of this study was to determine the effects of fracture and subsequent vertebroplasty on the loading of neighbouring (non-augmented) vertebrae. Methods. Fourteen pairs of three-vertebra cadaver spine specimens (67-92 yr) were loaded to induce fracture. One of each pair underwent vertebroplasty with PMMA, the other with a resin (Cortoss). Specimens were then creep loaded at 1.0kN for 1hr. In 17 specimens where the upper or lower vertebra fractured, compressive stress distributions were measured in the disc between adjacent non-fractured vertebrae by pulling a pressure transducer through the disc whilst under 1.0kN load. These ‘stress profiles’ were obtained at each stage of the experiment (in flexion and extension) in order to quantify intradiscal pressure (IDP), the size of stress concentrations in the posterior annulus (SP) and compressive load-bearing by anterior (FA) and posterior (FP) halves of the vertebral body and by the neural arch (FN). Results. No differences were found between Cortoss and PMMA so all data were pooled. Following fracture, IDP fell by 26% in extension (P=0.004) and SP increased by more than 200% in flexion (P=0.01). FA decreased from 55% to 36% of the applied load in flexion (P=0.002) and from 36% to 27% in extension (P=0.002). FN increased from 17% to 31% in flexion (P=0.006) and from 22% to 37% in extension (P=0.008). Vertebroplasty reduced stress concentrations in the disc and restored load-bearing towards pre-fracture values. Conclusion. Vertebral fracture transfers compressive load from the anterior vertebral body to the posterior vertebral body and neural arch of adjacent (non-fractured) vertebrae. Vertebroplasty largely restores normal load-sharing at both the augmented and adjacent levels and in doing so may help reduce the risk of a spinal fracture cascade

Introduction. Vertebral osteoporotic fracture increases both elastic and time-dependent ('creep') deformations of the fractured vertebral body during subsequent loading. The accelerated rate of creep deformation is especially marked in central and anterior regions of the vertebral body where bone mineral density is lowest. In life, subsequent loading of damaged vertebrae may cause anterior wedging of the vertebral body which could contribute to the development of kyphotic deformity. The aim of this study was to determine whether gradual creep deformations of damaged vertebrae can be reduced by vertebroplasty. Methods. Fourteen pairs of spine specimens, each comprising three vertebrae and the intervening soft tissue, were obtained from cadavers aged 67-92 yr. Specimens were loaded in combined bending and compression until one of the vertebral bodies was damaged. Damaged vertebrae were then augmented so that one of each pair underwent vertebroplasty with polymethylmethacrylate cement, the other with a resin (Cortoss). A 1kN compressive force was applied for 1 hr before fracture, after fracture, and after vertebroplasty, while creep deformation was measured in anterior, middle and posterior regions of each vertebral body, using a MacReflex optical tracking system. Results. Cement type had little influence on creep deformation, so data from all 28 specimens were pooled. After fracture, creep in the anterior vertebral body increased from 4,513 (STD 4766) to 54,107 (STD 54,845) microstrains (P<0.001), and creep in the central region of the vertebral body increased from 885 (STD 5,169) to 34,378 (STD 40,762) microstrain (P<0.001). (10,000 microstrains = 1% deformation.) Following vertebroplasty, creep deformations were reduced by 61% (P=0.002) and 66% (P=0.006) in anterior and central regions respectively. Conclusion. Creep deformations of the anterior and central regions of vertebral bodies increase markedly as a result of fracture but are then reduced by vertebroplasty. In life, vertebroplasty could help to slow or prevent the gradual development of kyphotic deformity following vertebral osteoporotic fracture, as well as increase vertebral stiffness and strength

Introduction. Senile kyphosis arises from anterior ‘wedge’ deformity of thoracolumbar vertebrae, often in the absence of trauma. It is difficult to reproduce these deformities in cadaveric spines, because a vertebral endplate usually fails first. We hypothesise that endplate fracture concentrates sufficient loading on to the anterior cortex that a wedge deformity develops subsequently under physiological repetitive loading. Methods. Thirty-four cadaveric thoracolumbar “motion segments,” aged 70–97 yrs, were overloaded in combined bending and compression. Physiologically-reasonable cyclic loading was then applied, at progressively higher loads, for up to 2 hrs. Before and after fracture, and again after cyclic loading the distribution of compressive loading on the vertebral body was assessed from recordings of compressive stress along the sagittal mid-plane of the adjacent intervertebral disc. Vertebral deformity was assessed from radiographs at the beginning and end of testing. Results. Initial overload usually fractured a vertebral endplate, at 2.31 kN (STD 0.85). There was minimal anterior wedging, but pressure in the nucleus of the adjacent disc was reduced by 65.2% on average, and relatively elevated in the annulus and neural arch. Subsequent cyclic loading then caused anterior wedge deformity of the vertebral body, with the height of the anterior and posterior cortex decreasing by 34.3% (13.2) and 12.7% (7.5) respectively, and wedge angle increasing from 5.0° (3.76) to 11.4° (3.93) (all p<0.001). Discussion and Conclusion. Our hypothesis is supported: initial minor damage facilitates progressive anterior wedge deformity by transferring compressive loading on to the anterior cortex. Detecting initial endplate damage is important to minimise subsequent vertebral deformity in patients with osteoporosis. 256 words (250 excluding section headings) Acknowledgements Funding was provided by a Royal College of Surgeons of England Research Fellowship and by the Gloucestershire Arthritis Trust

Introduction. Vertebroplasty helps to restore mechanical function to a fractured vertebra. We investigated how the distribution of injected cement benefits both fractured and neighbouring vertebrae. Methods. Nine pairs of three-vertebra cadaver spine specimens (aged 67–90 yr) were compressed to induce fracture. One of each pair underwent vertebroplasty with PMMA, the other with a resin (Cortoss). Specimens were then creep-loaded at 1.0kN for 1hr. Before and after vertebroplasty, compressive stiffness was determined, and stress profilometry was performed by pulling a pressure-transducer through each disc whilst under 1.0kN load. Profiles indicated intradiscal pressure (IDP) and compressive load-bearing by the neural arch (F. N. ) at both disc levels. Micro-CT was used to quantify cement fill in the anterior and posterior halves of each augmented vertebral body, and also in the region immediately adjacent to the fractured endplate. Results. Fracture reduced stiffness and IDP, and increased F. N. Following vertebroplasty, anterior fill was greater for Cortoss (30%) than PMMA (17%) (P<0.01). With Cortoss, increased posterior fill was associated with a greater restoration of IDP in the adjacent disc (P<0.05). Furthermore, specimen stiffness increased in proportion to cement fill adjacent to the fractured end-plate. With PMMA, increased anterior fill caused a greater reduction in F. N. in the non-adjacent disc (P<0.05), whereas increased posterior fill and increased fill adjacent to the fracture caused a greater restoration of IDP in the adjacent disc (P<0.05). Conclusion. Cement distribution varied between the two cements. However, increased filling immediately adjacent to the fractured endplate was linked most consistently to improved mechanical function. Conflicts of Interest. None. Source of Funding. This work was funded by Action Medical Research. Vertebroplasty materials were provided by Stryker and by Orthovita. We can confirm that this abstract has not been published previously in whole or substantial part, and the findings have not been presented previously at a national meeting

The use of antifibrinolytic drugs and many other agents have a critical importance in bleeding control. Tranexamic acid [4- (aminomethyl) cyclohexanecarboxylic acid] is a synthetic amino acid lysine derivative with antifibrinolytic activity in humans. There are many studies in the literature that show that it is effective and effective both systemically and locally in spinal surgery. However, all of these studies have investigated the effects of topical tranexamic acid on bleeding and its effect on fusion has not been investigated yet. Aim of this study is to investigate the effect of topical tranexamic acid on fusion using macroscopic, radiologic and microscopic techniques.

After approve of ethics committee with the protocol number 19/2019 for 28 Wistar Albino rats underwent intertransvers fusion. All rats were randomized into four (4) groups, using sealed envelopes. Local tranexamic acid (Transamin® 100 mg/ml, Teva İlaç, İstanbul) doses was determined based on previously conducted studies; 1mg/kg (D1 group), 10mg/kg (D10 group), 100 mg/kg (D100 group) and no tranexamic acid (D0 group). At the end of 8^th weeks all rats were evaluated with manuel palpation, mammography and histopathologic analysis. Radiographic examination was performed two times to evaluate the intra and inter observer differences. 2 rats in-group D0 died after the radiographic examination.

Assessment of fusion with manual palpation revealed that use of local 1mg / kg tranexamic acid had no effect on fusion (p=0.32), however with increasing doses of tranexamic acid had negative effect on fusion (p=0.002). On radiologic examination, spearman's rho correlation coefficient was found to be moderate in the first evaluation (r=0.46) and high in second evaluation (r=0.61). Radiological examination revealed that the control group was the best in fusion (p=0.007), and that tranexamic acid affected fusion adversely, independent of dosage (p=0.27). Among the groups in histopathologic examination, no statistical difference was found (p=0.134).

Local administration of tranexamic acid affects the intertransverse fusion adversely depending on the dosage macroscopically and it also affects fusion adversely independent of the dosage radiologically and histopathologically.

Summary Statement

Paraspinal muscle contain higher proportion of slow-twich fibers. The fixation of the rat tail induced transition of muscle fiber types in the paravertebral muscles characterised by the decrease in the proportion of the slow type myosin heavy chain.

Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them. Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05). One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases

Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft. 13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4). It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study

Introduction. Patients (2.7M in EU) with positive cancer prognosis frequently develop metastases (≈1M) in their remaining lifetime. In 30-70% cases, metastases affect the spine, reducing the strength of the affected vertebrae. Fractures occur in ≈30% patients. Clinicians must choose between leaving the patient exposed to a high fracture risk (with dramatic consequences) and operating to stabilise the spine (exposing patients to unnecessary surgeries). Currently, surgeons rely on their sole experience. This often results in to under- or over-treatment. The standard-of-care are scoring systems (e.g. Spine Instability Neoplastic Score) based on medical images, with little consideration of the spine biomechanics, and of the structure of the vertebrae involved. Such scoring systems fail to provide clear indications in ≈60% patients. Method. The HEU-funded METASTRA project is implemented by biomechanicians, modellers, clinicians, experts in verification, validation, uncertainty quantification and certification from 15 partners across Europe. METASTRA aims to improve the stratification of patients with vertebral metastases evaluating their risk of fracture by developing dedicated reliable computational models based on Explainable Artificial Intelligence (AI) and on personalised Physiology-based biomechanical (VPH) models. Result. The METASTRA-AI model is expected to be able to stratify most patients with limited effort end cost, based on parameters extracted semi-automatically from the medical files and images. The cases which are not reliably stratified through the AI model, are examined through a more detailed and personalised biomechanical VPH model. These METASTRA numerical tools are trained through an unprecedentedly large multicentric retrospective study (2000 cases) and validated against biomechanical ex vivo experiments (120 specimens). Conclusion. The METASTRA decision support system is tested in a multicentric prospective observational study (200 patients). The METASTRA approach is expected to cut down the indeterminate diagnoses from the current 60% down to 20% of cases. METASTRA project funded by the European Union, HEU topic HLTH-2022-12-01, grant 101080135

The COVID-19 pandemic necessitated a pivot to online learning for many traditional, hands-on subjects such as anatomy. This, coupled with the increase in online education programmes, and the reduction of time students spend in anatomy dissection rooms, has highlighted a real need for innovative and accessible learning tools. This study describes the development of a novel 3-dimensional (3D), interactive anatomy teaching tool using structured light scanning (SLS) technology. This technique allows the 3D shape and texture of an object to be captured and displayed online, where it can be viewed and manipulated in real-time. Human bones of the upper limb, vertebrae and whole skulls were digitised using SLS using Einscan Pro2X/H scanners. The resulting meshes were then post-processed to add the captured textures and to remove any extraneous information. The final models were uploaded into Sketchfab where they were orientated, lit and annotated. To gather opinion on these models as effective teaching tools, surveys were completed by anatomy students (n=35) and anatomy educators (n=8). Data was collected using a Likert scale response, as well as free text answers to gather qualitative information. 3D scans of the scapula, humerus, radius, ulna, vertebrae and skull were successfully produced by SLS. Interactive models were produced via scan data in Sketchfab and successfully annotated to provide labelled 3D models for examination. 94% of survey respondents agreed that the interactive models were easy to use (n=35, 31% agree and 63% strongly agree) and 97% agreed that the 3D interactive models were more useful than 2D images for learning bony anatomy (n=35; 26% agree and 71% strongly agree). This initial study has demonstrated a suitable proof-of-concept for SLS technology as a useful technique for producing 3D interactive online tools for learning and teaching bony anatomy. Current studies are focussed on determining the SLS accuracy and the ability of SLS to capture soft tissue/joints. We believe that this tool will be a useful technique for generating online 3D interactive models to study orthopaedic anatomy

Abstract. OBJECTIVES. Bone health deterioration is a major public health issue. General guidelines for the limitation of bone loss prescribe a healthy lifestyle and a minimum level of physical activity. However, there is no specific recommendation regarding targeted activities that can effectively maintain lumbar spine bone health. To provide a better understanding of such influencing activities, a new predictive modelling framework was developed to study bone remodelling under various loading conditions. METHODS. The approach is based on a full-body subject-specific musculoskeletal model [1] combined with structural finite element models of the lumbar vertebrae. Using activities recorded with the subject, musculoskeletal simulations provide physiological loading conditions to the finite element models which simulate bone remodelling using a strain-driven optimisation algorithm [2]. With a combination of daily living activities representative of a healthy lifestyle including locomotion activities (walking, stair ascent and descent, sitting down and standing up) and spine-focused activities involving twisting and reaching, this modelling framework generates a healthy bone architecture in the lumbar vertebrae. The influence of spine-focused tasks was studied by adapting healthy vertebrae to an altered loading scenario where only locomotion activities were performed. RESULTS. The spine-focused activities were responsible for 57% of the overall bone mechanical stimulus of the five lumbar vertebrae. Cortical bone maintenance was more influenced by these activities in the superior vertebrae than in the inferior ones, with a stimulus degradation of 74% in L1 against 24% in L5 when adapted to the altered loading scenario. Trabecular bone stimulus degradation varied between 53% and 68%. CONCLUSION. The study suggests that locomotion activities are insufficient to maintain lumbar spine bone health. When appropriate, larger spine movements should be recommended as part of the minimum daily physical activities. 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

Complications after spinal fusion surgery are common, with implant loosening occurring in up to 50% of osteoporotic patients. Pedicle screw fixation strength reduces as a result of decreased trabecular bone density, whereas sublaminar wiring is less affected by these changes. Therefore, pedicle screw augmentation with radiopaque sublaminar wires (made with Dyneema Purity® Radiapque fibers, DSM Biomedical, Geleen, the Netherlands) may improve fixation strength. Furthermore, sublaminar tape could result in a gradual motion transition to distribute stress over multiple levels and thereby reduce implant loosening. The objective of this study is to test this hypothesis in a novel experimental setup in which a cantilever bending moment is applied to individual human vertebrae. Thirty-eight human cadaver vertebrae were stratified into four different groups: ultra-high molecular weight polyethylene sublaminar tape (ST), pedicle screw (PS), metal sublaminar wire (SW) and pedicle screw reinforced with sublaminar tape (PS+ST). The vertebrae were individually embedded in resin, and a cantilever bending moment was applied bilaterally through the spinal rods using a universal material testing machine. This cantilever bending setup closely resembles the loading of fixators at transitional levels of spinal instrumentation. The pull-out strength of the ST (3563 ± 476N) was not significantly different compared to PS, SW or PS+ST. The PS+ST group had a significantly higher pull-out strength (4522 ± 826N) compared to PS (2678 ± 292N) as well as SW (2931 ± 250N). The higher failure strength of PS + ST compared to PS indicates that PS augmentation with ST may be an effective measure to reduce the incidence of screw pullout, even in osteoporotic vertebrae. Moreover, the lower stiffness of sublaminar fixation techniques and the absence of damage to the cortices in the ST group suggest that ST as a stand-alone fixation technique in adult spinal deformity surgery may also be clinically feasible and offer clinical benefits

Abstract. Objectives. A damaged vertebral body can exhibit accelerated ‘creep’ under constant load, leading to progressive vertebral deformity. However, the risk of this happening is not easy to predict in clinical practice. The present cadaveric study aimed to identify morphometric measurements in a damaged vertebral body that can predict a susceptibility to accelerated creep. Methods. Mechanical testing of 28 human spinal motion segments (three vertebrae and intervening soft tissues) showed how the rate of creep of a damaged vertebral body increases with increasing “damage intensity” in its trabecular bone. Damage intensity was calculated from vertebral body residual strain following initial compressive overload. The calculations used additional data from 27 small samples of vertebral trabecular bone, which examined the relationship between trabecular bone damage intensity and residual strain. Results. Calculations from trabecular bone samples showed a strong non-linear relationship between residual strain and trabecular bone damage intensity (R. 2. = 0.78, P < 0.001). In damaged vertebral bodies, damage intensity as calculated from residual strain was then related to vertebral creep rate (R. 2. = 0.39, P = 0.001). This procedure enabled accelerated vertebral body creep to be predicted from morphological changes (residual strains) in the damaged vertebral body. Conclusion. These findings suggest that morphometric measurements obtained from fractured vertebrae can be used to quantify vertebral damage intensity and hence to predict progressive vertebral deformity

This study aimed to characterise the microarchitecture of bone in different species of animal leading to the development of a physiologically relevant 3D printed cellular model of trabecular (Tb) and cortical bone (CB). Using high resolution micro-computed tomography (μ-CT) bone samples from multiple species were scanned and analysed before creating in silico models for 3D printing. Biologically relevant printing materials with physical characteristics similar to that of in vivo bone will be selected and tested for printability. Porcine and murine bone samples were scanned using μ-CT, with a resolution of 4.60 μM for murine and 11 μM for porcine and reconstructed to determine the architectural properties of both Tb and CB independently. A region of interest, 1 mm in height, will be used to generate an in-silico 3D model with dimensions (10 mm. 3. ) and suitable resolution before being translated into printable G code using CAD assisted software. A 1 mm section of each bone was analysed, to determine the differences in the microarchitecture with the intent of setting a benchmark for the developmental 3D in vitro model to be comparable against. In contrast, porcine caudal vertebrae (PCV) have an increased volume due to the size of the bone sample. Interestingly, BV/TR for Tb is similar between species in all samples except murine femur. Murine tibia and PCV have a similar Tb. number and thickness, however different SMI shape and separation. μ-CT scanning and analysis permits tessellation of the 3D output which will lead to the generation of an in silico printable model. Biomaterials are currently under optimisation to allow printability and shape integrity to reflect the morphological and physiological properties of bone

Compressive fracture of osteoporotic vertebrae has been one of the most important health problems in aged societies because severely injured spin might be a reason of bedridden for elderly people. Osteoporosis has been widely assessed by averaged bone mineral density of vertebrae measured using DEXA, however, BMD sometimes does not reflect the strength of vertebrae. CT imaged based finite element method (CT-FEM) has been applied to evaluate the strength of vertebrae based on the biomechanics theory and approved by a part of the highly advanced medical treatment in Japan. In the present study, compressive strength of more than 100 vertebrae were evaluated using CT-FEM, and the correlation between BMD and the strength was thoroughly investigated. It was found that some vertebrae with high BMD could have low strength which may cause fracture easily. Thus, a controversial point of the BMD based diagnosis of osteoporosis was clearly indicated. In this invited talk, some basic theories of CT-FEM and fracture assessment and some key results from the recent study will be presented

Introduction. This research aims to enhance the control of intricate musculoskeletal spine models, a critical tool for comprehending both healthy and pathological spinal conditions. State-of-the-art musculoskeletal spine models incorporate segments for all vertebra, each possessing 3 degrees-of-freedom (DOF). Manually defining the posture with this amount of DOFs presents a significant challenge. The prevalent method of equally distributing the spine's overall rotation among the vertebrae often proves to be an inadequate assumption, particularly when dealing with the entire spine. Method. We have engineered a comprehensive non-linear spine rhythm and the requisite tools for its implementation in widely utilized musculoskeletal modelling software (1). The rhythm controls lateral bending, axial rotation, and flexion/extension. The mathematical and implementation details of the rhythm are beyond this abstract, but it's noteworthy that the implementation accommodates non-linear rhythms. This means, for example, that one set of rhythm coefficients is used for flexion and another for extension. The rhythm coefficients, which distinguish the movement along the spine, were derived from a review of spine literature. The values for spine and vertebra range-of-motion (ROM) vary significantly in published studies, and no complete dataset was found in any single study. Consequently, the rhythm presented here is a composite, designed to provide the most consistent and average set of rhythm coefficients. Result. The novel spine rhythm simplifies the control of detailed spine models, accommodating varying amounts of input data. It allows for the specification of only the overall motion or the posture at a more detailed level (i.e., lumbar, thoracic, neck). The tools and rhythm coefficients are publicly available on GitHub. Conclusion. The innovative spine rhythm enhances the usability of cutting-edge spine models. For flexion/extension of the spine, it introduces a non-linear rhythm, exhibiting distinct behaviour between flexion and extension - a feature not previously observed in musculoskeletal spine models. 1) The AnyBody Modeling System

Introduction. Low back pain (LBP) is a worldwide leading cause of disability. This preclinical study evaluated the safety of a combined advanced therapy medicinal product developed during the European iPSpine project (#825925) consisting of mesendoderm progenitor cells (MEPC), derived from human induced pluripotent stem cells, in combination with a synthetic poly(N-isopropylacrylamide) hydrogel (NPgel) in an ovine intervertebral disc degeneration (IDD) model. Method. IDD was induced through nucleotomy in 4 adult sheep, 5 lumbar discs each (n=20). After 5 weeks, 3 alternating discs were treated with NPgel (n=6) or NPgel+MEPC (n=6). Before sacrifice, animals were subjected to: MRI of lumbar spines (disc height and Pfirmann grading); blood sampling (hematological, biochemical, metabolic and lymphocyte/monocytes immunological). After 3 months the sheep were sacrificed. The spines were processed for: macroscopic morphology (Thompson grading), microscopic morphology (Histological grading), and glycosaminoglycan content (GAG, DMMB Assay). Furthermore, at sacrifice biodistribution of human MEPC was assessed by Alu-sequences quantification (qPCR) from three tissue samples of heart, liver, spleen, brain, lungs, and kidneys, and PBMCs collected to assess activation of systemic immune cells. To each evaluation, appropriate statistical analysis was applied. Result. Flow cytometry showed no induction of systemic activation of T cells or monocytes. Alu quantification did not give detection of any cells in any organ. Disc height index was slightly increased in discs treated with NPgel+MEPC. Pfirmann's and Thompson's classification showed that treatment with NPgel or NPgel+MEPC gave no adverse reactions. Histological grading showed similar degeneration in vertebrae treated with NPgel+MEPC or with NPgel alone. The amount of GAG was significantly increased in the nucleus pulposus following treatment with NPgel+MEPC compared to NPgel alone, in which a decrease was observed compared to untreated discs in both nucleus pulposus and annulus fibrosus. Conclusion. This study showed the safety of both NPgel+MEPC and NPgel treatments

Introduction. In daily clinical practice, progression of spinal fusion is typically monitored during clinical follow-up using conventional radiography and Computed Tomography scans. However, recent research has demonstrated the potential of implant load monitoring to assess posterolateral spinal fusion in an in-vivo sheep model. The question arises to whether such a strain sensing system could be used to monitor bone fusion following lumbar interbody fusion surgery, where the intervertebral space is supported by a cage. Therefore, the aim of this study was to test human cadaveric lumbar spines in two states: after a transforaminal lumbar interbody fusion (TLIF) procedure combined with a pedicle-screw-rod-construct (PSR) and subsequently after simulating bone fusion. The study hypothesized that the load on the posterior instrumentation decreases as the segment stiffens due to simulated fusion. Method. A TLIF procedure with PSR was performed on eight human cadaveric spines at level L4-L5. Strain sensors were attached bilaterally to the rods to derive implant load changes during unconstrained flexion-extension (FE), lateral bending (LB) and axial rotation (AR) loads up to ±7.5Nm. The specimens were retested after simulating bone fusion between vertebrae L4-L5. In addition, the range of motion (ROM) was measured during each loading mode. Result. The ROM decreased in the simulated bone fusion state in all loading directions (p≤0.002). In both states, the measured strain on the posterior instrumentation was highest during LB motion. Furthermore, the sensors detected a significant decrease in the load induced rod strain (p≤0.002) between TLIF+PSR and simulated bone fusion state in LB. Conclusion. Implant load measured via rod strain sensors can be used to monitor the progression of fusion after a TLIF procedure when measured during LB of the lumbar spine. However, further research is needed to investigate the influence of daily loading scenarios expected in-vivo on the overall change in implant load

Introduction. Pedicle screw loosening in posterior instrumentation of thoracolumbar spine occurs up to 60% in osteoporotic patients. These complications may be alleviated using more flexible implant materials and novel designs that could be optimized with reliable computational modeling. This study aimed to develop and validate non-linear homogenized finite element (hFE) simulations to predict pedicle screw toggling. Method. Ten cadaveric vertebral bodies (L1-L5) from two female and three male elderly donors were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT, Scanco Medical) and instrumented with pedicle screws made of carbon fiber-reinforced polyether-etherketone (CF/PEEK). Sample-specific 3D-printed guides ensured standardized instrumentation, embedding, and loading procedures. The samples were biomechanically tested to failure in a toggling setup using an electrodynamic testing machine (Acumen, MTS) applying a quasi-static cyclic testing protocol of three ramps with exponentially increasing peak (1, 2 and 4 mm) and constant valley displacements. Implant-bone kinematics were assessed with a stereographic 3D motion tracking camera system (Aramis SRX, GOM). hFE models with non-linear, homogenized bone material properties including a strain-based damage criterion were developed based on intact HR-pQCT and instrumented 3D C-arm scans. The experimental loading conditions were imposed, the maximum load per cycle was calculated and compared to the experimental results. HR-pQCT-based bone volume fraction (BV/TV) around the screws was correlated with the experimental peak forces at each displacement level. Result. The nonlinear hFE models accurately (slope = 1.07, intercept = 0.2 N) and precisely (R. 2. = 0.84) predicted the experimental peak forces at each displacement level. BV/TV alone was a weak predictor (R. 2. <0.31). Conclusion. The hFE models enable fast design iterations aiming to reduce the risk of screw loosening in low-density vertebrae. Improved flexible implant designs are expected to contribute to reduced complication rates in osteoporotic patients