Bone Phenotype of Toll-like Receptor 5 Deficient (TLR5KO) Mice and PTH Treated Osteopenic Sheep

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Bone mass and mechanical properties are known to influence risk of fragility fracture. Clinical measures of bone mineral density (BMD) are used to evaluate fracture risk, but patients with obesity have greater risk of fracture than would be expected from BMD. Obesity is a common component of metabolic syndrome. Metabolic syndrome may contribute to the increased risk of fracture associated with obesity. Patients with osteoporosis have low bone mass and increased risk of fracture. Parathyroid hormone (PTH) treatment can be used to reverse the effects of osteoporosis. Here, we looked at mechanical properties of bone in an animal model of metabolic syndrome and an animal model of osteoporosis treated with parathyroid hormone. First, we characterized the cortical bone phenotype of the toll-like receptor 5 deficient mouse (TLR5KO). The TLR5KO mouse is a model of metabolic syndrome with mild levels of adiposity. Metabolic syndrome in TLR5KO mice is caused by alterations to the gut microbiome. Male and female mice 10-55 weeks of age (n = 5-19/ group) were used in this study. Cortical bone geometry and mechanical properties of the mid-diaphysis of the femur were analyzed to characterize the cortical bone phenotype. The femurs were tested in three-point bending to obtain peak moment, bending rigidity and post yield displacement. Peak moment was related to geometry to infer the effect of genotype on tissue material properties. We found that metabolic syndrome was associated with impaired cortical bone tissue material properties in both male and female mice in most ages studied. In summary, metabolic syndrome with only mild adiposity was associated with alterations to bone strength that could not be explained by bone geometry and density, suggesting altered bone tissue material properties. Secondly, we determined the mechanical properties of cancellous bone from osteopenic sheep treated with PTH. Osteopenia was induced in 6-7 year-old sheep through a combination of ovariectomy (OVX) and a diet to induce metabolic acidosis (MA). A year after OVX, the sheep were treated with either vehicle (n = 6) or PTH (n = 7) for a year. Cancellous bone cores were taken from the medial caudal quadrant of the right distal femur for mechanical testing. We found no detectable effect of PTH treatment on mechanical properties of cancellous bone in uniaxial compression.

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Hernandez, Christopher J.

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van der Meulen, Marjolein

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Mechanical Engineering

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M.S., Mechanical Engineering

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Master of Science

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