Parâmetros ósseos para avaliação de baixa densidade mineral óssea e risco de fratura por osteoporose em TCFC de mulheres na pós-menopausa

Tese (doutorado) — Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Odontologia, Programa de Pós-Graduação em em Odontologia, 2022.O presente trabalho teve como objetivo principal analisar parâmetros ósseos mandibulares para avaliação de osteoporose e do risco de fratura em mulheres na pós-menopausa, por meio de tomografia computadorizada de feixe cônico (TCFC). A amostra final foi composta por 103 pacientes, sendo 52 com densidade mineral óssea (DMO) normal e 51 com diagnóstico densitométrico de osteoporose. A mensuração dos índices radiomorfométricos e da dimensão fractal foi realizada no programa ImageJ. O primeiro artigo avaliou qualitativamente e quantitativamente a cortical mandibular, com o estabelecimento de um novo índice denominado índice mandibular tridimensional para osteoporose (3D MOI). Este índice foi significativamente diferente entre mulheres na pós-menopausa com osteoporose e com DMO normal. Mulheres idosas, com a cortical inferior da mandíbula com espessura inferior a 2,75mm na TCFC e classificadas como C3 devem ser investigadas para osteoporose. O segundo artigo avaliou o parâmetro trabecular dimensão fractal em dois sítios distintos (mandíbula e segunda vértebra cervical). Apesar dos valores de dimensão fractal na mandíbula terem sido menores nos pacientes com osteoporose quando comparados aos das mulheres com DMO normal, a análise não apresentou boa reprodutibilidade e acurácia para predizer o diagnóstico densitométrico. Por fim, o terceiro artigo analisou a relação entre a densidade mineral óssea (DXA), o risco de fratura calculado pela ferramenta FRAX e dados de microarquitetura óssea. Neste último estudo, dados de microarquitetura óssea (MAO) foram analisadas pelo programa CT Analyzer, com a seleção de um volume de interesse nas regiões de segunda vértebra cervical e anteriormente ao forame mentual. As análises foram realizadas em TCFCs de 100 mulheres na pós-menopausa e, destas, 46 também responderam à ferramenta FRAX. O parâmetro número de trabéculas correlacionou-se com os dados densitométricos e com o FRAX em ambos os sítios de interesse. A área abaixo da curva foi de 0.732 para predizer o alto risco de fratura no quadril considerando o ponto de corte do FRAX brasileiro de 3%. Na coluna vertebral, o parâmetro espessura das trabéculas e a anisotropia também se correlacionaram com a DMO e com o FRAX. Como conclusão final destes estudos, a TCFC demonstrou acurácia para predizer o diagnóstico densitométrico de osteoporose, com base em um novo índice tridimensional baseado na análise da cortical mandibular, conforme descrito no primeiro artigo. Por outro lado, a análise da dimensão fractal não demonstrou boa acurácia e reprodutibilidade para a mesma finalidade, conforme evidenciado no artigo 2. Já os parâmetros trabeculares, avaliados de forma tridimensional, como o número e a espessura das trabéculas e anisotropia apresentaram correlação com os resultados do DXA e com o FRAX. O parâmetro número de trabéculas apresentou potencial para predizer o risco de fratura baseado nos pontos de corte do FRAX.The present work aimed to analyze mandibular bone parameters for evaluating osteoporosis and fracture risk in postmenopausal women, by means of Cone-Beam Computed Tomography (CBCT). The final sample consisted of 103 patients, 52 with normal BMD and 51 with osteoporosis. The measurement of radiomorphometric indices and fractal dimension was performed using ImageJ software. The first article qualitatively and quantitatively evaluated the mandibular cortical bone. A composite CBCT-driven index (3D MOI) was established and demonstrated to be significantly different between postmenopausal women with normal BMD and those with osteoporosis. Elderly women with inferior mandibular cortical thickness lower than 2.75 mm on CBCT and classified as C3 should be investigated for osteoporosis. The second article calculated fractal dimension in two different sites (mandible and second cervical vertebra). Although the fractal dimension values in the mandible were lower in patients with osteoporosis when compared to those of women with normal BMD, the analysis did not present good reproducibility and accuracy to predict the densitometric diagnosis. Finally, the last article aimed to analyze the relationship between bone mineral density (DXA results), fracture risk calculated by FRAX tool and bone microarchitecture data. In the third study, bone microarchitecture data were analyzed by the CT Analyzer program, with the selection of two volume of interests in the regions of the second cervical vertebra and anterior to the mental foramen. The analyses were performed on CBCT scans of 100 postmenopausal women and, from these, 46 also responded to the FRAX tool. The bone parameter number of trabeculae correlated with densitometric data and with FRAX at both sites of interest. The trabecular number assessed in the mandible showed the most promising results in comparison to the other variables, since it presented a strong inverse correlation both for hip fractures and major osteoporotic fractures. The area under the curve value was 0.732 for predicting high hip fracture risk by using the Brazilian FRAX cut-off. In the spine, bone parameter trabecular thickness and anisotropy also correlated with BMD and FRAX. As a final conclusion of the three studies, CBCT showed accuracy to predict the densitometric diagnosis of osteoporosis, based on a new cortical index (3D MOI), as described in the first article. On the other hand, the analysis of fractal dimension did not demonstrate good accuracy and reproducibility for the same purpose, as shown in article 2. Some 3D trabecular parameters, such as the number and thickness of trabeculae and anisotropy were correlated with DXA and FRAX results, and the trabecular number at the mandibular site may be further investigated as potential tool to predict fracture risk, as shown in article 3

Early diagnosis of medication related osteonecrosis of the jaw (MRONJ)

La osteonecrosis de la mandíbula relacionada a la mediación (MRONJ) es un efecto secundario adverso al uso de drogas antirresortivas o antiangiogénicas. Una vez que la necrosis ósea ha avanzado de manera tal que el hueso se encuentra expuesto a la cavidad oral, el tratamiento es dificultoso y puede terminar en la resección del hueso afectando, resultando una solución de continuidad en el maxilar afectado. Se considera una condición irreversible, y por lo tanto los esfuerzos deben estar dirigidos a su prevención, tanto antes como después del inicio de la terapia farmacológica. Los métodos de diagnóstico complementarios, como la radiografía panorámica o la tomografía computada de haz cónico (CBCT) son herramientas muy útiles que permiten un diagnóstico temprano de MRONJ.Medication-related osteonecrosis of the jaw (MRONJ) is an adverse side effect of the use of antiresorptive or antiangiogenic drugs. Once the bone necrosis has progressed and the bone is exposed to the oral cavity, treatment is difficult and may end in resection of the affected bone, resulting in a continuity solution in the affected jaw. It is considere dan irreversible condition, and therefore efforts should be directed at its prevention, both before and after the start of drug therapy. Complementary diagnostic methods such as panoramic radiograph or conebeam computed tomography (CBCT) are very usefull tolos that enable early diagnosis of MRONJ.Fil: Avendaño, María Eugenia. Universidad Nacional de Cuyo. Facultad de OdontologíaFil: Poletto, Adriana. Universidad Nacional de Cuyo. Facultad de OdontologíaFil: Zeni, Susana. Universidad de Buenos Aire

Patient specific finite volume modeling for intraosseous PMMA cement flow simulation in vertebral cancellous bone

Ph.DDOCTOR OF PHILOSOPH

Osteoporosis Screening: Applied Methods and Technological Trends

Bones are continuously remodeled (resorbed and regenerated) to allow fracture healing and skeleton adaptation to stress. When excessive resorption occurs, bone microstructure is deteriorated, leading to osteoporosis. At early stages, osteoporosis usually has no symptoms; most people are diagnosed when a fracture occurs due to disease severity. To prevent fractures, technologies have been developed to identify high risk population eligible to treatment. Fracture risk has been assessed by analyzing the interaction of different energy stimulus with bone tissues as well as by statistical models that evaluate multiple clinical risk factors. The most applied methods are Dual-energy X-ray Absorptiometry and Fracture Risk Assessment tool. As they present some limitations, other technologies have been proposed for such purpose. A survey of the currently applied and emerging methods is here presented in order to provide a scenario of the technological challenges and trends to diagnose osteoporosis

Micro-CT yields high image quality in human fetal post-mortem imaging despite maceration

Background Current clinical post-mortem imaging techniques do not provide sufficiently high-resolution imaging for smaller fetuses after pregnancy loss. Post-mortem micro-CT is a non-invasive technique that can deliver high diagnostic accuracy for these smaller fetuses. The purpose of the study is to identify the main predictors of image quality for human fetal post-mortem micro-CT imaging. Methods Human fetuses were imaged using micro-CT following potassium tri-iodide tissue preparation, and axial head and chest views were assessed for image quality on a Likert scale by two blinded radiologists. Simple and multivariable linear regression models were performed with demographic details, iodination, tissue maceration score and imaging parameters as predictor variables. Results 258 fetuses were assessed, with median weight 41.7 g (2.6–350 g) and mean gestational age 16 weeks (11–24 weeks). A high image quality score (> 6.5) was achieved in 95% of micro-CT studies, higher for the head (median = 9) than chest (median = 8.5) imaging. The strongest negative predictors of image quality were increasing maceration and body weight (p < 0.001), with number of projections being the best positive imaging predictor. Conclusions High micro-CT image quality score is achievable following early pregnancy loss despite fetal maceration, particularly in smaller fetuses where conventional autopsy may be particularly challenging. These findings will help establish clinical micro-CT imaging services, addressing the need for less invasive fetal autopsy methods

The development of a small animal model for assessing the 3D implications of loading on bone microarchitecture

It is well established that bone is capable of adapting to changes in its environment; however, little is known regarding how environmental stimuli, specifically loading, are associated with the internal 3D microarchitecture of cortical bone. The aim of this thesis was to develop a small animal model that can be used to experimentally test hypotheses regarding bone adaptation. High resolution micro-CT was validated and employed as a novel method for the visualization and quantification of rat cortical bone microarchitecture in 3D. The use of this imaging method allowed for the measurement of primary vascular canal orientation in 3D, which had never been achieved before. Using this measure along with an immobilization model for unloading allowed me to test how loading is associated with the orientation of these vascular canals. Normally ambulating rat bones (from 10 female rats) had a canal structure that was 9.9° more longitudinal than their immobilized counterparts. This finding that loading has an effect on primary canal orientation brought to light the need to induce remodeling and therefore, secondary vascular canals, in the rat to increase its novelty as a model for looking at bone adaptation. Remodeling was induced by increasing the calcium demands of female rats, either through a calcium restricted diet (n=2) or pregnancy and lactation coupled with a calcium restricted diet (n=2). Mean cortical thickness for the calcium restricted rats and the pregnant and lactating rats that were on a calcium restricted diet were 622 µm and 419 µm, respectively. The mean BMU count for calcium restricted rats seemed to be higher than that of the pregnant and lactating rats; however, the calcium restricted rats seemed to have a lower BMU density. Once this full-scale study is executed the rat will provide a more representative model for studying human bone adaptation

The Effects of Aging and Tooth Loss to the Microstructure of the Mandible in South Africans

Thesis (PhD (Anatomy))--University of Pretoria, 2022.The mandible plays a crucial role in many biological functions (especially mastication, swallowing and speech) and its efficiency to perform these functions depends on its intactness. Aging and tooth loss are biological processes that may compromise the normal functioning of the mandible by changing its morphology. While many studies address the macroscopic mandibular variations, there is a paucity regarding its microstructure. The aim was to investigate microstructural mandibular changes, with reference to the macrostructure, with advancing age and across various tooth loss patterns in South Africans. As the reasons why individuals are differently affected (extent, rate) by senescence or tooth loss are unclear, the influence of other biological factors (sex, ancestry) was also considered. Using micro-focus X-ray Computed Tomography (micro-CT) scans of 333 mandibles, external dimensions, and inner parameters, namely the cortical thickness (CtTh) and cortical density (approximated by histomorphometric parameters, BV/TV) were measured. To assess whether the mandible ages in the same way and rate as the rest of the skeleton, a comparison of mandibular and femoral cortical BV/TV, using a micro-CT subsample of 68 individuals, was included. A comprehensive assessment of the mandibular morphology and cortical microstructure of fully dentate individuals highlighted that the smaller the alveolar height is, the thicker and denser the cortical bone. An inner cortical asymmetry between basal, buccal, and lingual areas was described for CtTh, but was absent for BV/TV. Sexual dimorphism and ancestral variations were confirmed for the external distances and CtTh, but not for BV/TV. With tooth loss, a general decrease in external distances (aggravated by edentulism), CtTh and BV/TV was observed, except at the midline where the lingual CtTh increased with edentulism. Sexual dimorphism and ancestral variations of the external dimensions and CtTh were emphasised in edentulous mandibles. The cortical density decreased with aging, corroborating the general decline in bone mass of the skeleton, as noted in the femur. By contrasting the effects of tooth loss and aging, it was concluded that both external distances and CtTh were mainly influenced by tooth loss and not age, whereas the cortical bone density displayed an age-related decrease independent of tooth loss. To ascertain the applicability of the findings in a dental setting, where Cone-Beam Computed Tomography (CBCT) is commonly used, measurements were performed on 24 mandibles scanned by both CBCT and micro-CT (considered as the reference). The accuracy and repeatability of CBCT was confirmed for large-scale measurements, and CtTh in a lesser manner, whereas results were uncertain for BV/TV, revealing a distinct lack of reliability. In conclusion, this thesis inferred the precise role of aging and tooth loss, but also sex and ancestry, on the variations of the mandibular macro- and microstructure. Not only does knowledge and understanding of these changes have implications in dentistry fields, as cortical thickness and density are essential for many dental procedures; but also in biological anthropology, in which the microstructure of extant human mandibles gives valuable insights into intra- and interspecific variations (e.g., sexual dimorphism), or functional considerations (mastication, diet) of archaeological/fossil specimens.AnatomyPhD (Anatomy)Unrestricte

The quantification of pregnancy-induced bone mineral mobilisation in the maternal appendicular skeleton with novel peripheral quantitative computed tomography (pQCT) techniques.

The quantification of pregnancy-induced bone mineral mobilisation in the maternal appendicular skeleton with novel peripheral quantitative computed tomography (pQCT) techniques. Adaptations in maternal calcium (Ca) economy occur during pregnancy to meet fetal demand and by birth a typical new-born contains 25-30g Ca. At the individual-level if Ca is mobilised it is important to identify where this occurs to identify any potential impact on fracture risk. At present, pregnancy is not considered a risk factor for osteoporosis but data are few. Trabecular bone is more metabolically active than cortical bone in part due to its structure, orientation and much greater surface area. During lactation, studies have consistently reported significant transient bone mineral mobilisation from trabecular-rich axial sites such as the hip and spine, while newer peripheral quantitative computed tomography (pQCT) techniques have found trabecular microarchitectural change in the appendicular skeleton also. My primary objective was to explore whether a similar pregnancy-induced bone mineral mobilisation could be observed in two distinct cohorts of pregnant women using novel pQCT techniques from mid- to late-pregnancy. These techniques provide non-invasive measurements of bone density, mass, geometry, distribution and strength at the radius and tibia. This thesis aims to determine: whether pregnancy-induced changes occur in a) the trabecular compartment, b) the cortical compartment, c) any potential predictors of a) and b); d) to explore the correlation and agreement of pQCT techniques in-vivo. Single-slice and high-resolution (HR) pQCT data were used to characterise maternal appendicular skeletal change during pregnancy in two studies in contrasting populations: 1) a resource poor subsistence farming Sub-Saharan African community with an habitually low Ca intake and high parity; 2) an affluent Cambridge based population, where Ca intake is higher but parity much lower. In The Gambia, existing pQCT data obtained at 14 and 30 weeks of pregnancy from women (n=811), aged 18-45 and accustomed to low habitual Ca intake, were analysed. In Cambridge, UK, I designed a study where pregnant women (n=53) and non-pregnant non-lactating (NPNL, n=37) controls aged 30-45 years were scanned with pQCT and HRpQCT at 14 and 36 weeks. These data were modelled to explore the maternal response to pregnancy in these distinct populations. Contrary to my primary hypothesis there was no evidence of trabecular bone mobilisation in Gambian women, however in contrast in the UK study a -0.5 SD decrease in trabecular vBMD was observed. In The Gambia total vBMD did not change at the radius or tibia, while in Cambridge both techniques detected decreases in total vBMD at the distal tibia. Changes in cortical bone were documented during pregnancy in both populations. In Gambian women small but significant increases in cortical vBMD and BMC were observed at the radius and tibia. In Cambridge at the tibia HRpQCT showed a decrease in cortical vBMD and cortical thickness with an increase in cortical porosity. There were fewer pregnancy-induced changes at the radius but at the cortical- rich diaphysis cortical thickness decreased and endosteal circumference increased. No consistent predictors of these changes were found in either population. These data from two contrasting populations show a “one size fits all” approach cannot be applied to the maternal skeletal response to pregnancy. In Gambian women with a habitually low Ca intake we have observed the conservation of bone mineral in the appendicular skeleton into the third trimester. In contrast in the Cambridge women evidence of trabecular and cortical mobilisation was observed at the distal tibia. At the radius changes were confined to the cortical-rich proximal radius and supported endosteal resorption during pregnancy. These data suggest that the maternal skeleton is a significant source of fetal Ca in a population accustomed to higher dietary Ca intakes. Further work is needed to determine what this mobilisation means at the individual level and to determine if the mobilised bone mineral is restored postpartum or whether there are lasting consequences for the woman’s bone health