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Background: The aim of this study is to search for the predictive value of 3D fat analysis and calculation technique (FACT) and intravoxel incoherent motion (IVIM) parameters in identifying osteoporosis in women. Methods: We enrolled 48 female subjects who underwent 3.0 T MRI, including 3D FACT and IVIM sequences. Bone mineral density (BMD) values and Fracture Risk Assessment (FRAX) scores were obtained. Proton density fat fraction (PDFF) in the bone marrow and the real diffusion (D) value of intervertebral discs were measured on 3D FACT and IVIM images, respectively. Accuracy and bias were assessed by linear regression analysis and Bland–Altman plots. Intraclass correlation coefficients were used to assess the measurements’ reproducibility. Spearman’s rank correlation was applied to explore the correlation. MRI-based parameters were tested for significant differences among the three groups using ANOVA analyses. A receiver operating characteristic (ROC) analysis was performed. Results: The PDFF of the vertebral body showed a negative correlation with BMD (R = −0.393, p = 0.005) and a positive correlation with the FRAX score (R = 0.706, p < 0.001). The D value of intervertebral discs showed a positive correlation with BMD (R = 0.321, p = 0.024) and a negative correlation with the FRAX score (R = −0.334, p = 0.019). The area under the curve values from the ROC analysis showed that the 3D FACT and IVIM sequences could accurately differentiate between normal and osteoporosis (AUC = 0.88 using the PDFF; AUC = 0.77 using the D value). The PDFF value demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 78.6%, 89.5%, 84.6%, and 85.0%, respectively, in its ability to predict osteoporosis. The D value had a sensitivity, specificity, PPV, and NPV of 63.16%, 92.9%, 65.0%, and 77.8%, respectively, for predicting osteoporosis. Conclusions: The 3D FACT- and IVIM-measured PDFF and D values are promising biomarkers in the assessment of bone quality and fracture risk.

Introduction/backgroundOsteoporotic fractures are usually painful. However, data on whether osteoporosis without fracture causes pain are insufficient. This study aims to determine whether osteoporosis without fracture is the cause of pain.MethodologyPatients aged over 18 years who visited the Physical Medicine and Rehabilitation outpatient clinic of a tertiary university hospital for dual-energy X-ray absorptiometry scan and were suitable for dual-energy X-ray absorptiometry scan without a history of fracture were included in the study. Patients with a history of fractures or those with fracture/fracture sequelae on X-rays were excluded. The cervical, lumbar, and thoracic spine and general body pains of the patients were questioned and dual-energy X-ray absorptiometry results were recorded.ResultsThe study was conducted with 139 patients. Lumbar bone mineral density and T score values of the patients were found to be negatively correlated with the numerical rating scale levels of the cervical, thoracic, lumbar spine, and general body pain. Hip total bone mineral density and T score values were also negatively correlated with numerical rating scale scores of the lumbar and thoracic spine and general body pain. When the patients were divided into two groups as those with and without osteoporosis, it was found that the cervical, lumbar, thoracic spine, and general body pain numerical rating scale levels of the patients with osteoporosis were significantly higher than the group without osteoporosis.ConclusionThe results of this study showed that osteoporosis might be associated with pain even though there is no fracture.

Finite element (FE) modelling of a vertebral body (VB) is considered challenging due to the many parameters involved such as element size and type, and material properties. Previous studies have reported how these pa- rameters affect the mechanical behaviour of a VB model; however, most studies just compared results without any specific statistical tool to quantify their influence. The Taguchi Method (TM) has been successfully used in manufacturing and biomechanics to evaluate process parameters and to determine optimum set-up conditions. This study aimed to evaluate the influence of the main finite element modelling parameters on the mechanical behaviour of a VB model using the Taguchi Method. A FE model was developed based on a C2 juvenile porcine vertebral body and three of the most commonly used modelling parameters were evaluated using TM in terms of change in the predicted stiffness in comparison to experimental values: element size, number of different material properties for VB (based on grey-scale bins) and calibration factor for grey-scale to density to Young's Modulus equation. The influence of the combined factors was also assessed. The Taguchi analysis showed that the three factors are independent. The calibration factor is the main contributor, accounting for 97% of the predicted stiff- ness, with the value of 0.03 most closely aligning the numerical and experimental results. Element size accounted for 2% of the predicted stiffness, with 0.75 mm being the optimal, while the number of grey-scale bins influenced the results by less than 1%. Our findings indicate that the calibration factor is the main modelling parameter, with the element size and number of bins accounting for less than 3% of the predicted stiffness. Therefore, calibration of material properties should be done based on a large number of samples to ensure reliable results.

Bone cement is often used, in experimental biomechanics, as a potting agent for vertebral bodies (VB). As a consequence, it is usually included in finite element (FE) models to improve accuracy in boundary condition settings. However, bone cement material properties are typically assigned to these models based on literature data obtained from specimens created under conditions which often differ from those employed for cement end caps. These discrepancies can result in solids with different material properties from those reported. Therefore, this study aimed to analyse the effect of assigning different mechanical properties to bone cement in FE vertebral models. A porcine C2 vertebral body was potted in bone cement end caps, [Formula: see text]CT scanned, and tested in compression. DIC was performed on the anterior surface of the specimen to monitor the displacement. Specimen stiffness was calculated from the load-displacement output of the materials testing machine and from the machine load output and average displacement measured by DIC. Fifteen bone cement cylinders with dimensions similar to the cement end caps were produced and subjected to the same compression protocol as the vertebral specimen and average stiffness and Young moduli were estimated. Two geometrically identical vertebral body FE models were created from the [Formula: see text]CT images, the only difference residing in the values assigned to bone cement material properties: in one model these were obtained from the literature and in the other from the cylindrical cement samples previously tested. The average Youngs modulus of the bone cement cylindrical specimens was 1177 ± 3 MPa, considerably lower than the values reported in the literature. With this value, the FE model predicted a vertebral specimen stiffness 3% lower than that measured experimentally, while when using the value most commonly reported in similar studies, specimen stiffness was overestimated by 150%.

Rationale: Wolf-Hirschhorn Syndrome (WHS) is a rare disorder caused by the loss of the distal part of the short arm of chromosome 4, and has various phenotypes depending on the deletion size. Although many articles report on urinary tract malformations or ophthalmologic abnormalities, there are few descriptions of the skeletal anomalies. This is an extremely rare case of cervical dysplasia in WHS. Patient concerns: A 24-year-old pregnant woman was transferred to our hospital at 21 gestational weeks for intrauterine growth retardation and oligohydramnios and decided to preserve the pregnancy after evaluation. A female was born at full term by normal vaginal delivery, weighing 1791 g. The patient was suspected to have congenital dysplasia of the cervical vertebrae on the routine newborn chest radiograph, and cervical spine magnetic resonance imaging revealed nonossification of the C3 and C4 vertebral bodies. Diagnosis: The newborn had the “Greek warrior helmet” face typical of WHS. A deletion was detected in the distal portion of the short arm of chromosome 4 (p 16.3) by fluorescence in situ hybridization analysis. Interventions: She was hospitalized for nutritional management and congenital anomaly evaluation for a month before being discharged with rehabilitation and antiepileptic drugs. Outcomes: The patient has been readmitted with seizure attacks 5 times to date. At one year of age, she still shows severe head lag and feeding problems. Her last weight was below the 3rd centile. Lessons: Although cervical dysplasia is a rarely reported morphology in WHS, it may provide artefacts for diagnosing WHS as cervical anomalies, unlike facial anomalies or developmental delays, are seldom found in congenital disease.

Research Objective: improvement of transpedicular fixation technique in cases with spine injuries accompanied by vertebral body splintering. Material and Methods. Transpedicular spondylosynthesis was performed in 52 patients aged 18-49 years with comminuted fractures of thoracic and lumbar vertebral bodies. Individual peculiarities of the operation depended on the character of the injury ascertained during the preoperative examination. Standard roentgenography and computer tomography were used. Results. Lasting antalgic effect was observed in 94,2% of the operated patients. In cases with type A3 fractures according to F. Magerl the rate of the surgical correction of the pathologic posttraumatic kyphotic deformity averages 87%. Injuries classified as type A2, B2 or C2 were the indication for transpedicular os-teosynthesis by advanced techniques. Conclusion. Transpedicular spondylosynthesis is one of the effective methods of treatment of patients with comminuted fractures of thoracic and lumbar vertebral bodies, and the choice of carrying out of the procedure depends on the injury character. In cases with comminuted fractures of type A2, B2, C2 it is reasonable to perform transpedicular spondylosynthesis with introduction of the transpedicular screws into the injured vertebral body, and the technique of their use depends on the injury character.

In recent years it has become clear that, mechanistically, biomineralization is a process that has to be actively inhibited as a default state. This inhibition must be released in a rigidly controlled manner in order for mineralization to occur in skeletal elements and teeth. A central aspect of this concept is the tightly controlled balance between phosphate, a constituent of the biomineral hydroxyapatite, and pyrophosphate, a physiochemical inhibitor of mineralization. Here, we provide a detailed analysis of a zebrafish mutant, dragonfish (dgf), which is mutant for ectonucleoside pyrophosphatase/phosphodiesterase 1 (Enpp1), a protein that is crucial for supplying extracellular pyrophosphate. Generalized arterial calcification of infancy (GACI) is a fatal human disease, and the majority of cases are thought to be caused by mutations in ENPP1. Furthermore, some cases of pseudoxanthoma elasticum (PXE) have recently been linked to ENPP1. Similar to humans, we show here that zebrafish enpp1 mutants can develop ectopic calcifications in a variety of soft tissues – most notably in the skin, cartilage elements, the heart, intracranial space and the notochord sheet. Using transgenic reporter lines, we demonstrate that ectopic mineralizations in these tissues occur independently of the expression of typical osteoblast or cartilage markers. Intriguingly, we detect cells expressing the osteoclast markers Trap and CathepsinK at sites of ectopic calcification at time points when osteoclasts are not yet present in wild-type siblings. Treatment with the bisphosphonate etidronate rescues aspects of the dgf phenotype, and we detected deregulated expression of genes that are involved in phosphate homeostasis and mineralization, such as fgf23, npt2a, entpd5 and spp1 (also known as osteopontin). Employing a UAS-GalFF approach, we show that forced expression of enpp1 in blood vessels or the floorplate of mutant embryos is sufficient to rescue the notochord mineralization phenotype. This indicates that enpp1 can exert its function in tissues that are remote from its site of expression.

Computer aided image analysis was applied to elaborate an automatic method of histomorphometric analysis of trabecular bone samples. Transverse sections of decalcified vertebral bodies were examined using optical microscopy and digital image acquisition system. Further analysis was done by means of a general purpose image analysis package. The same algorithm was applied to all the images tested, thus enabling obtainment of objective and repeatable results. High efficiency in measurements and evaluation of parameters not accessible for manual methods makes this method an interesting alternative for classical histomorphometric analysis. The results obtained demonstrated that assessment of bone mineral density is not sufficient for evaluation of compression strength of vertebral bodies. In contrast, mechanical properties correlate well with histomorphometric parameters. As a consequence it was postulated that compression strength of vertebral bodies is controlled by trabecular structure rather than bone mineral density.

Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.

In recent years it has become clear that, mechanistically, biomineralization is a process that has to be actively inhibited as a default state. This inhibition must be released in a rigidly controlled manner in order for mineralization to occur in skeletal elements and teeth. A central aspect of this concept is the tightly controlled balance between phosphate, a constituent of the biomineral hydroxyapatite, and pyrophosphate, a physiochemical inhibitor of mineralization. Here, we provide a detailed analysis of a zebrafish mutant, dragonfish (dgf), which is mutant for ectonucleoside pyrophosphatase/phosphodiesterase 1 (Enpp1), a protein that is crucial for supplying extracellular pyrophosphate. Generalized arterial calcification of infancy (GACI) is a fatal human disease, and the majority of cases are thought to be caused by mutations in ENPP1. Furthermore, some cases of pseudoxanthoma elasticum (PXE) have recently been linked to ENPP1. Similar to humans, we show here that zebrafish enpp1 mutants can develop ectopic calcifications in a variety of soft tissues – most notably in the skin, cartilage elements, the heart, intracranial space and the notochord sheet. Using transgenic reporter lines, we demonstrate that ectopic mineralizations in these tissues occur independently of the expression of typical osteoblast or cartilage markers. Intriguingly, we detect cells expressing the osteoclast markers Trap and CathepsinK at sites of ectopic calcification at time points when osteoclasts are not yet present in wild-type siblings. Treatment with the bisphosphonate etidronate rescues aspects of the dgf phenotype, and we detected deregulated expression of genes that are involved in phosphate homeostasis and mineralization, such as fgf23, npt2a, entpd5 and spp1 (also known as osteopontin). Employing a UAS-GalFF approach, we show that forced expression of enpp1 in blood vessels or the floorplate of mutant embryos is sufficient to rescue the notochord mineralization phenotype. This indicates that enpp1 can exert its function in tissues that are remote from its site of expression.

Vertebral deformities constitute a recurrent problem in farmed teleost fish species. Potential causes of skeletal deformities are associated with genetic, environmental and nutritional factors. Considering nutritional factors, previous studies have shown that nutritional vitamin A (VA) imbalance implied the appearance of vertebral deformities in marine fish larvae; however, information about the effects of VA on bone homeostasis in juveniles is scarce. A study of vertebral bone tissue homeostasis in gilthead sea bream (Sparus aurata) juveniles fed with two dietary VA levels was performed by means of histological (Haematoxylin-Eosin, Alcian blue – PAS, Haematoxylin – VOF and Picrosirius red staining) and histochemical (immunostaining for bone and matrix Gla protein; OC and MGP, respectively) approaches. Fish were fed with two diets containing 2.5 × 104 (control) and 2.3 × 106 (hypervitaminosis A group) IU total VA kg−1 during 6 months. Results showed that gilthead sea bream juveniles were not affected in terms of growth or survival rate by nutritional hypervitaminosis A, whereas the homeostasis of the vertebral bone was altered. Vertebral bodies from the control and VA fed fish showed differences in their morphological and biochemical composition at the growth zone of the vertebral end-plates. Picrosirius red staining revealed that vertebral end-plates and the trabecular bone layer from control and VA fed fish presented different diameter in collagen fibers. In addition, immunohistochemical analysis revealed increased protein levels of MGP and BGP in the notochord from gilthead sea bream juveniles fed hypervitaminosis A. Results suggest that hypervitaminosis A alter bone homeostasis through an accelerated bone mineralization, which might increase mechanical load between adjacent vertebrae and induce vertebral compression/fusion through a bone remodelling process., This work was funded by Ministry of Science and Innovation (MICIIN) of the Spanish government (projects AGL2005-02478, AGL2008-03897-C04-01 and AGL2008-03897-C04-04).

This study evaluated the applicability of the regression method for determining vertebral age developed by Caldas et al. (2007) by testing this method in children from low-income families of the rural zone. The sample comprised cephalometric and hand-wrist radiographs of 76 boys and 64 girls aged 7.0 to 14.9 years living in a medium-sized city in the desert region of the northeastern region of Brazil, with an HDI of 0.678. C3 and C4 vertebrae were traced and measured on cephalometric radiographs to estimate the bone age. The average age, average hand-wrist age and average error estimated for girls and boys were, respectively, 10.62 and 10.44 years, 11.28 and 10.57 years, and 1.42 and 1.18 years. Based on these results, the formula proposed by Caldas et al. (2007) was not applicable to the studied population, and new multiple regression models were developed to obtain the children's vertebral bone age accurately. O objetivo deste estudo foi avaliar a aplicabilidade do método de análise para determinar a idade vertebral proposto por Caldas et al., 2007 em crianças de baixa renda. A amostra se constituiu de radiografias cefalometricas e carpais de 76 meninos e 64 meninas com idade entre 7,0 a 14,9 anos que vivem em zona rural de um município sergipano. Os corpos das vértebras C3 e C4 foram traçadas e mensuradas e em seguida as idades ósseas foram estimadas. A idade media estimada para as meninas foi de 10,62 anos e a idade óssea carpal foi de 11,28 anos; o erro médio de 1,42 anos. A idade media estimada para os meninos foi de 10,44 anos e a idade óssea carpal foi de 10,57 anos com erro médio de 1,18 anos. Baseado nos resultados, o modelo proposto por Caldas et al. (2007) não pode ser aplicada na população estudada, e portanto novos modelos de regressão foram desenvolvidos.

Osteoporosis is a disease characterized by reduced bone strength leading to an increased fracture risk. Current diagnostic best practice involves measuring the bone mineral density (BMD) of a patient using absorptiometric imaging tools. This measurement is compared to a known value in order to compute fracture risk. This assessment of bone quality is based solely on the BMD, which has been shown to make up only a portion of the explanation of bone strength. The extent of BMD's contribution to bone strength is also extensively debated and widely varying in the scientific literature. This thesis work encompasses a preliminary investigation into factors in addition to density that contribute to bone strength. The geometric and material properties of 21 vertebral functional unit specimens were measured using dual energy absorptiometry (DXA), pQCT (peripheral quantitative computed tomography) and HCT (helical computed tomography) techniques. The strength of the functional units was assessed through mechanical testing under compressive loading conditions. These measurements were amalgamated into multiple linear regression models to characterize vertebral strength in terms of a few key variables. The model developed for failure load had a coefficient of determination of 0.725 and indicated that the volume of the vertebral body as well as the cross-sectional area of the cortical region were significant in the explanation of failure load. A model was also developed for stress at failure which indicated that the vertebral body height and cortex concavity were important parameters. The coefficient of determination for this model was 0.871. The goal of this study was to provide a foundation on which further investigation into the explanation of bone strength could be built. Ultimately, a better understanding of the parameters that affect bone strength will provide a basis for more accurate clinical tools for the diagnosis of osteoporosis. Thesis Master of Applied Science (MASc)

In clinical routine, spine pathologies can be most often deduced from the vertebral body shape, position and orientation. Additionally, per-vertebra spatial information could be used in intervention planning and surgical navigation. Especially in vertebral metastasis treatment, MRI is inalienable, and therefore, segmentation methods are developed for spine MRI. Our approach starts with a simple user-assisted initialization Then intensity and edge features are combined for a subsequent hybrid level-set segmentation. We evaluated our method on highly anisotropic clinical routine spine MRI datasets, containing 34 vertebrae, both healthy and pathological. We achieved a 3D Dice coefficient of 84.8% and a mean surface-to-surface distance of 1.29 ± 0.42 mm with regard to a manually created ground truth segmentation. The main advantages of our method are precise segmentation results on clinical routine images within reasonable processing time and with minimal user interaction.