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Published byRolf Gregory Modified over 9 years ago
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Bone: Normal Physiology and Response to Injury Wongworawat August 3, 2010
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Structure Cortical vs. Trabecular Woven vs. Lamellar Vascular supply –Nutrient artery—intramedullary –Periosteal –Periarticular plexus
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Extracellular Matrix Mineral: 2/3 –Hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2 Organic –Type I collagen: 90% –Noncollagenous protein: 10% Osteocalcin, most abundant Proteoglycans Others
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Collagen Problems OI: Type I collagen Scurvy: Ascorbic acid dependent prolyl hydroxylase and lysyl hydroxylase Ehlers-Danlos: Lysyl oxidase for crosslinking Urinary detection of turnover: pyridinoline, telopeptide, and hydroxyproline
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Bone Cells Osteoblasts –Receptor for PTH –Roles Form bone Regulate osteoclasts –Lipoprotein receptor-related protein 5 (LRP5) Transmembrane protein for osteoblast proliferation regulation Signaling important for maintenance of bone mass
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Bone Cells Osteoblast differentiation –Stem cell –Mesenchymal stem cell –Osteoprogenitor –Pre-osteoblast –Mature osteoblast –Osteocyte –Cell deth
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Osteoblastic Problems Fibrodysplasia ossificans progressiva –Activating mutation in BMP receptor ACVR1 Cleidocranial dysostosis –Loss of runx 2 gene (formerly CBFA 1) –Runx 2: transcription factor, “master regulator” of osteoblast differentiation
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Osteoclasts Lineage: related to hematopoietic cells, macrophages Receptors –Calcitonin –RANKL, (osteoprotegrin) –Integrin Half-life: 10 days
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Form and Function Remodeling –Trabecular –Cortical Molecular coupling –PTH –RANKL –BMP
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Mechanical Regulation Wolff’s Law
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Mechanical Properties Anisotropic –Stronger in compression than tension Viscoelastic –Higher stiffness and strength at higher loading rates
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Aging Osteoporosis: 2.5 SD < young standard Increase in both inner and outer diamters More anisotropy
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Bone Injury and Repair Osteonecrosis Fracture Fixation Adjunctive therapies
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Osteonecrosis Histo changes 10-14 days after event Empty lacunae MRI findings Bone remodeling: creeping substitution –Vascularization from fibrous tissue –Differentiation of bone cells –Cutting cones –Remodeling
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Fracture Healing External factors –Micromotion: endochondral ossification –Rigid fixation: direct intramembranous ossification
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Fracture Healing Inflammatory response Cell differentiation –sox9 upregulates cartilage genes (col2) –Hypertrophic chondrocytes: type X collagen Ossification Remodeling
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Chondrogenesis Pathology Camptomelic dysplasia: sox9 mutation Cleidocranial dysplasia: runx2 mutation Multiple epiphyseal dysplasia (MED): cartilage oligomeric matrix protein (COMP) Diastrophic dysplasia: sulfate transport protein
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Fixation Biomechanics Intramedullary device Plates –Rigidity: thickness 3 External fixation –Rigidity Pin diameter, number, bone to rod distance, pin group separation, ½ pins separated 45°
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Bone Grafts Osteoconductive Osteoinductive Osteogenic Gold Standard: Autograft
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Allograft Structural Particulate Demineralized
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Minerals and Other Calcium sulfate Tricalcium phosphate ceramics Calcium phosphate cements Polymers
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BMP TGF- β family Bind cell curface receptors –Serine/threonine kinase receptors Phosphorylate SMADs SMADs translocates into nucleus to activate genes for osteoblast differentiation
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Adjunctive Therapies Inductive coupling (magnetic) –Upregulation TGF-β1, FGF-2, BMP Capacitative coupling (electrodes) –Transmembrane calcium translocation –Upregulation of TGF- β1, BMP Ultrasound –Increased TGF- β1, PGE2, PDGF
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