RESUMEN
Neck of femur (NOF) fracture is a prevalent fracture type amongst the ageing and osteoporotic populations, commonly requiring total hip replacement (THR) surgery. Increased fracture risk has also been associated with Alzheimer's disease (AD) in the aged. Here, we sought to identify possible relationships between the pathologies of osteoporosis and dementia by analysing bone expression of neurotropic or dementia-related genes in patients undergoing THR surgery for NOF fracture. Femoral bone samples from 66 NOF patients were examined for expression of the neurotropic genes amyloid precursor protein (APP), APP-like protein-2 (APLP2), Beta-Secretase Cleaving Enzyme-1 (BACE1) and nerve growth factor (NGF). Relationships were examined between the expression of these and of bone regulatory genes, systemic factors and bone structural parameters ascertained from plain radiographs. We found strong relative levels of expression and positive correlations between APP, APLP2, BACE1 and NGF levels in NOF bone. Significant correlations were found between APP, APLP2, BACE1 mRNA levels and bone remodelling genes TRAP, RANKL, and the RANKL:OPG mRNA ratio, indicative of potential functional relationships at the time of fracture. Analysis of the whole cohort, as well as non-dementia (n = 53) and dementia (n = 13) subgroups, revealed structural relationships between APP and APLP2 mRNA expression and lateral femoral cortical thickness. These findings suggest that osteoporosis and AD may share common molecular pathways of disease progression, perhaps explaining the common risk factors associated with these diseases. The observation of a potential pathologic role for AD-related genes in bone may also provide alternative treatment strategies for osteoporosis and fracture prevention.
Asunto(s)
Enfermedad de Alzheimer , Fracturas del Cuello Femoral , Anciano , Enfermedad de Alzheimer/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Ácido Aspártico Endopeptidasas , Remodelación Ósea/genética , Hueso Cortical , Fracturas del Cuello Femoral/genética , HumanosRESUMEN
Postoperative weight bearing has the potential to generate fragmental motion of surgically repaired tibial plateau fractures (TPFs), which may contribute to loss of fracture reduction. The effect of loading on the internal distribution of fragmentary displacements is currently unknown. The aim of this study was to determine the internal displacements of surgically repaired split TPFs due to a three-bodyweight load, using large-volume micro-CT imaging and image correlation. Fractures were generated and surgically repaired for two cadaveric specimens. Load was applied to the specimens inside a large-volume micro-CT system and scanned at 0.046 mm isotropic voxel size. Pre- and post-loading images were paired, co-registered, and internal fragmentary displacements quantified. Internal fragmental displacements of the cadaveric bones were compared to in vivo displacements measured in the lateral split fragments of TPFs in a clinical cohort of patients who had similar surgical repair and were prescribed pain tolerated postoperative weight bearing. The split fragments of cadaveric specimens displaced, on average, less than 0.3 mm, consistent with in vivo measurements. Specimen one rotated around the mediolateral axis, while specimen two displaced consistently caudally. Specimen two also had varying displacements along the mediolateral axis where, at the fracture site, the fragment displaced caudally and laterally, while the most lateral edge of the tibial plateau displaced caudally and medially. The methods applied in this study can be used to measure internal fragmental motion within TPFs.