RESUMO
PURPOSE OF REVIEW: This review surveys recent literature related to cortical bone fracture mechanics and its application towards understanding bone fragility and hip fractures. RECENT FINDINGS: Current clinical tools for hip fracture risk assessment have been shown to be insensitive in some cases of elevated fracture risk leading to the question of what other factors account for fracture risk. The emergence of cortical bone fracture mechanics has thrown light on other factors at the tissue level that are important to bone fracture resistance and therefore assessment of fracture risk. Recent cortical bone fracture toughness studies have shown contributions from the microstructure and composition towards cortical bone fracture resistance. A key component currently overlooked in the clinical evaluation of fracture risk is the importance of the organic phase and water to irreversible deformation mechanisms that enhance the fracture resistance of cortical bone. Despite recent findings, there is an incomplete understanding of which mechanisms lead to the diminished contribution of the organic phase and water to the fracture toughness in aging and bone-degrading diseases. Notably, studies of the fracture resistance of cortical bone from the hip (specifically the femoral neck) are few, and those that exist are mostly consistent with studies of bone tissue from the femoral diaphysis. Cortical bone fracture mechanics highlights that there are multiple determinants of bone quality and therefore fracture risk and its assessment. There is still much more to learn concerning the tissue-level mechanisms of bone fragility. An improved understanding of these mechanisms will allow for the development of better diagnostic tools and therapeutic measures for bone fragility and fracture.
Assuntos
Doenças Ósseas , Fraturas do Quadril , Humanos , Densidade Óssea , Fraturas do Quadril/epidemiologia , Colo do Fêmur , Água , Medição de RiscoRESUMO
Chordoma is a rare primary bone cancer with limited treatment options. Surgical resection followed by radiotherapy has proven effective; however, when, in 30-40% of patients, tumours recur and metastasize, a high level of resistance to chemotherapies leaves these patients with a dearth of treatment options. Recent work published in the Journal of Pathology by Scheipl et al describing a focused compound drug screen highlights the significance of epidermal growth factor receptor (EGFR) signalling in chordoma, and shows potential for EGFR inhibitors as a way forward for developing an effective treatment for chordoma. Importantly, combining EGFR inhibitors with a MET inhibitor induces a synergistic effect on growth inhibition of resistant chordoma cells, highlighting the significance of combined EGFR and MET inhibitors as a potential avenue to defeat chemoresistance in chordoma patients. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Cordoma/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Antineoplásicos/farmacologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Reino UnidoRESUMO
Environmental reclamation of Canada's oil sands tailings ponds is among the single largest water treatment challenges globally. The toxicity of oil sands process-affected water (OSPW) has been associated with its dissolved organics, a complex mixture of naphthenic acid fraction components (NAFCs). Here, we evaluated solar treatment with buoyant photocatalysts (BPCs) as a passive advanced oxidation process (P-AOP) for OSPW remediation. Photocatalysis fully degraded naphthenic acids (NAs) and acid extractable organics (AEO) in 3 different OSPW samples. However, classical NAs and AEO, traditionally considered among the principal toxicants in OSPW, were not correlated with OSPW toxicity herein. Instead, nontarget petroleomic analysis revealed that low-polarity organosulfur compounds, composing <10% of the total AEO, apparently accounted for the majority of waters' toxicity to fish, as described by a model of tissue partitioning. These findings have implications for OSPW release, for which a less extensive but more selective treatment may be required than previously expected.
RESUMO
Cortical bone tissue, primarily composed of collagen, hydroxyapatite, and water, is a strong and tough natural, structural biomaterial. The integrity of the collagenous phase (native triple helix vs. damaged/denatured coil) has previously been correlated via various means, including hydrothermal isometric tension testing and FTIR and Raman spectroscopy, with the capability of cortical bone to undergo stable fracture. Collagen is a relatively stable protein, requiring around 70 J/g to thermally denature its native triple helix structure, through the melting of hydrogen bonds. It is widely thought that bone collagen molecules denature (unravel) during fracture, acting as a molecular-scale mechanical toughening mechanism, but this has not been empirically demonstrated to date. A new technology, fluorescently-labeled collagen hybridizing peptides (F-CHP), enables imaging that specifically detects denatured collagen. This provides an opportunity to empirically test whether bone collagen molecules do denature during bone fracture. Here, F-CHP was used to stain fracture surfaces produced by transverse Mode-I fracture of chevron-notched bovine and human cortical bone beams. The fracture surfaces demonstrated increased staining, above the level of rigorous paired controls, and the staining directly correlated with the work-to-fracture (WFx) of bovine bone beams. This increased denaturation signal was also constrained to a rough textured region visible on the fracture surface, which is known to correspond with stable tearing. Similar staining was also detected on the fracture surfaces of human cortical bone. Increased staining was not detected on the fracture surfaces of specimens that were dehydrated prior to fracture, suggesting a role for water in the denaturation process. This study provides the first empirical evidence of bone collagen denaturation resulting from cortical bone fracture and extends our understanding of this mechanism towards the mechanical performance of cortical bone.