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Bone: Normal Physiology and Response to Injury

Bone: Normal Physiology and Response to Injury. Wongworawat August 3, 2010. Structure. Cortical vs. Trabecular Woven vs. Lamellar Vascular supply Nutrient artery—intramedullary Periosteal Periarticular plexus. Extracellular Matrix. Mineral: 2/3 Hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2

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Bone: Normal Physiology and Response to Injury

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  1. Bone: Normal Physiology and Response to Injury Wongworawat August 3, 2010

  2. Structure • Cortical vs. Trabecular • Woven vs. Lamellar • Vascular supply • Nutrient artery—intramedullary • Periosteal • Periarticular plexus

  3. Extracellular Matrix • Mineral: 2/3 • Hydroxyapatite Ca10(PO4)6(OH)2 • Organic • Type I collagen: 90% • Noncollagenous protein: 10% • Osteocalcin, most abundant • Proteoglycans • Others

  4. 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

  5. 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

  6. Bone Cells • Osteoblast differentiation • Stem cell • Mesenchymal stem cell • Osteoprogenitor • Pre-osteoblast • Mature osteoblast • Osteocyte • Cell deth

  7. 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

  8. Osteoclasts • Lineage: related to hematopoietic cells, macrophages • Receptors • Calcitonin • RANKL, (osteoprotegrin) • Integrin • Half-life: 10 days

  9. Form and Function • Remodeling • Trabecular • Cortical • Molecular coupling • PTH • RANKL • BMP

  10. Mechanical Regulation • Wolff’s Law

  11. Mechanical Properties • Anisotropic • Stronger in compression than tension • Viscoelastic • Higher stiffness and strength at higher loading rates

  12. Aging • Osteoporosis: 2.5 SD < young standard • Increase in both inner and outer diamters • More anisotropy

  13. Bone Injury and Repair • Osteonecrosis • Fracture • Fixation • Adjunctive therapies

  14. 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

  15. Fracture Healing • External factors • Micromotion: endochondral ossification • Rigid fixation: direct intramembranous ossification

  16. Fracture Healing • Inflammatory response • Cell differentiation • sox9 upregulates cartilage genes (col2) • Hypertrophic chondrocytes: type X collagen • Ossification • Remodeling

  17. Chondrogenesis Pathology • Camptomelic dysplasia: sox9 mutation • Cleidocranial dysplasia: runx2 mutation • Multiple epiphyseal dysplasia (MED): cartilage oligomeric matrix protein (COMP) • Diastrophic dysplasia: sulfate transport protein

  18. Fixation Biomechanics • Intramedullary device • Plates • Rigidity: thickness3 • External fixation • Rigidity • Pin diameter, number, bone to rod distance, pin group separation, ½ pins separated 45°

  19. Bone Grafts • Osteoconductive • Osteoinductive • Osteogenic • Gold Standard: Autograft

  20. Allograft • Structural • Particulate • Demineralized

  21. Minerals and Other • Calcium sulfate • Tricalcium phosphate ceramics • Calcium phosphate cements • Polymers

  22. BMP • TGF- β family • Bind cell curface receptors • Serine/threonine kinase receptors • Phosphorylate SMADs • SMADs translocates into nucleus to activate genes for osteoblast differentiation

  23. 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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