Publicação
Characterization and Optimization of Sheep as an Animal Model of Osteoporosis Follow-up of Bone Turnover Markers, Bone Mineral Density and Mechanical Properties and Bone Remodelling After Osteoporosis Induction
| Resumo: | Osteoporosis is a skeleton alteration characterized by a decrease of bone mass and strength, resulting in an increased of bone fragility and consequently fractures. This patology is the most common metabolic disorder, with a prevalence the 200 million of women worldwide affected. Therefore, osteoporosis is a global public health problem associated with a high cost to national health services. The main diagnostic tool is dual X-ray absorptiometry (DXA) or namely bone densitometry. This method allows to monitor bone mineral density (BMD) status, which can be normal, osteopenic, osteoporotic or severe osteoporotic, but not characterizing the early stages of bone loss. Thus, bone turnover markers (BTMs), which can be classified into formation, resorption and osteoclast regulatory protein, are aim of research for decades to assess the early bone remodelling. However, the high biological variability among individuals associated to analytical variability introduced by the different assay techniques is the main limitation to their clinical use due to the difficulty to establish reference ranges for serum and urinary BTM levels. Thereby, the main purpose of this work (Chapter VI) was the characterization and optimization of sheep (Portuguese Serra da Estrela breed) as an animal model of osteoporosis through the follow-up of BTMs during osteoporosis induction, and assess of BMD and mechanical properties and also bone remodelling after osteoporosis induction. In conclusion, biomarkers showed to be reliable in determining bone remodelling. However, the combination method ovariectomy (OVX) and glucocorticoid to induce osteoporosis resulted in limited trabecular alteration in vertebrae. And finally, it was verified that fouth (L4), sixth (L6) and seventh lumbar vertebrae (L7) are the most useful for further studies of vertebral augmentation or spinal fusion. Additionally, a review of the literature (Chapter III) was undertaken to summarize research on the use of sheep and goats as large animal models of human osteoporosis for preclinical and translational studies. The available data established that, the majority of studies is perfomed by isolated ovariectomized (OVX) or combined treatment with glucocorticoids (GCs) in sheep, while goat model present a limited use in these type of studies. With the knowledge acquired about the pathophysiological mechanisms, studies with sheep model should be carried out with greater confidence in obtaining transposable results for humans. A second literature review (Chapter IV) aimed to compile the available information on the use of BTMs in studies on small ruminants, specially highlighting the clinical effectiveness of BTMs in pre-clinical or translational experimental orthopaedic research and reporte a variability influence on BTMs. With a systematic literature search was demonstrated, BTMs are effective to determine the bone remodelling in small ruminants, however, the variability may be a limitation. Posteriorly, another study (Chapter V) aimed to generate a reference range for a bone resorption biomarker, tartrate-resistant acid phosphatase in sheep and validate the already published data. The data represents a useful tool in clinical orthopedic research studies and any variation verified in this marker can be explained by the well-known physiology. In summary, the work presented under the scope of this Thesis consolidates investigation in the field of BTMs in small ruminants and contributed to the characterization of the GCtreated OVX osteoporotic sheep model for pre-clinical and translational studies in orthopaedic research. |
|---|---|
| Autores principais: | Camassa, José Arthur de Abreu |
| Assunto: | osteoporosis sheep model |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Trás-os-Montes e Alto Douro |
| Idioma: | inglês |
| Origem: | Repositório da UTAD |
| Resumo: | Osteoporosis is a skeleton alteration characterized by a decrease of bone mass and strength, resulting in an increased of bone fragility and consequently fractures. This patology is the most common metabolic disorder, with a prevalence the 200 million of women worldwide affected. Therefore, osteoporosis is a global public health problem associated with a high cost to national health services. The main diagnostic tool is dual X-ray absorptiometry (DXA) or namely bone densitometry. This method allows to monitor bone mineral density (BMD) status, which can be normal, osteopenic, osteoporotic or severe osteoporotic, but not characterizing the early stages of bone loss. Thus, bone turnover markers (BTMs), which can be classified into formation, resorption and osteoclast regulatory protein, are aim of research for decades to assess the early bone remodelling. However, the high biological variability among individuals associated to analytical variability introduced by the different assay techniques is the main limitation to their clinical use due to the difficulty to establish reference ranges for serum and urinary BTM levels. Thereby, the main purpose of this work (Chapter VI) was the characterization and optimization of sheep (Portuguese Serra da Estrela breed) as an animal model of osteoporosis through the follow-up of BTMs during osteoporosis induction, and assess of BMD and mechanical properties and also bone remodelling after osteoporosis induction. In conclusion, biomarkers showed to be reliable in determining bone remodelling. However, the combination method ovariectomy (OVX) and glucocorticoid to induce osteoporosis resulted in limited trabecular alteration in vertebrae. And finally, it was verified that fouth (L4), sixth (L6) and seventh lumbar vertebrae (L7) are the most useful for further studies of vertebral augmentation or spinal fusion. Additionally, a review of the literature (Chapter III) was undertaken to summarize research on the use of sheep and goats as large animal models of human osteoporosis for preclinical and translational studies. The available data established that, the majority of studies is perfomed by isolated ovariectomized (OVX) or combined treatment with glucocorticoids (GCs) in sheep, while goat model present a limited use in these type of studies. With the knowledge acquired about the pathophysiological mechanisms, studies with sheep model should be carried out with greater confidence in obtaining transposable results for humans. A second literature review (Chapter IV) aimed to compile the available information on the use of BTMs in studies on small ruminants, specially highlighting the clinical effectiveness of BTMs in pre-clinical or translational experimental orthopaedic research and reporte a variability influence on BTMs. With a systematic literature search was demonstrated, BTMs are effective to determine the bone remodelling in small ruminants, however, the variability may be a limitation. Posteriorly, another study (Chapter V) aimed to generate a reference range for a bone resorption biomarker, tartrate-resistant acid phosphatase in sheep and validate the already published data. The data represents a useful tool in clinical orthopedic research studies and any variation verified in this marker can be explained by the well-known physiology. In summary, the work presented under the scope of this Thesis consolidates investigation in the field of BTMs in small ruminants and contributed to the characterization of the GCtreated OVX osteoporotic sheep model for pre-clinical and translational studies in orthopaedic research. |
|---|