1 Bone Pathophysiology and Fractures .ppt

BIOLOGICAL PRINCIPLES OF BONE AND CARTILAGE HEALING PROF. E. KON HUMANITAS UNIVERSITY MILAN HISTOLOGICAL CLASSIFICATION OF THE BONE Lamellar bone: -Characterized by collagen fibers running parallel to one another. -Normal adult bone. Immature bone (non lamellar): -Characterized by disorganized...

BIOLOGICAL PRINCIPLES OF BONE AND CARTILAGE HEALING PROF. E. KON HUMANITAS UNIVERSITY MILAN HISTOLOGICAL CLASSIFICATION OF THE BONE Lamellar bone: -Characterized by collagen fibers running parallel to one another. -Normal adult bone. Immature bone (non lamellar): -Characterized by disorganized collagen fiber bundles running in various directions through the matrix -Present in adults in fracture healing, at the level of osteotendineal and osteo-ligamentous junctions and in pathological conditions (Paget’s disease) LAMELLAR BONE Cortical bone: -Organized in units called osteons (haversian system) -Osteons communicate with the medullary cavity through Volkmann’s canals LAMELLAR BONE Trabecular or spongy bone: -Bone trabeculae are oriented along force lines and lines of load distribution. HAVERSIAN SYSTEM osteocyte Haversian canal osteon Volkmann’s canal BONE COMPOSITION Cells: -Osteoblasts -Osteoclasts -Osteocytes Extracellular matrix: -Organic 35% Collagen (type I) 90% Osteocalcin, osteonectin, proteoglycans, glycosaminoglycans, lipids -Inorganic 65% Primarily hydroxyapatite Ca 5PO4 OSTEOBLASTS ● ● Derive from mesenchymal stem cells They align along bone surface and produce osteoid (unmineralized organic component of bone matrix) OSTEOCYTES ● ● ● Osteocytes are osteoclasts embedded in osteoid, becoming entrapped in lacunae which are connected by canaliculi Interconnected by cellular expansion that project into the canaliculi No clear function, involved in regulation of bone metabolism in response to chemical and physical stress OSTEOCLASTS ● ● ● Derive from hematopoietic stem cells Multinuclear cells in charge of bone resorption and remodeling Function stimulated by activation of PTH receptor BONE HEALING TISSUES INVOLVED IN BONE HEALING ●Cortical bone ●Periosteum ●Bone marrow ●Soft tissues MECHANISMS OF BONE FORMATION ● CUTTING CONES (Bone remodeling) ● PERIOSTEAL OSSIFICATION ● ENDOCHONDRAL OSSIFICATION CUTTING CONES MECHANISM ● ● ● Responsible for bone remodeling Organized with osteoclasts making the head of the cutting cone followed by capillaries and the osteoblasts lay down osteoid to fill the cutting cong This mechanism is in function of mechanical stimuli PERIOSTEAL OSSIFICATION ● ● ● Mechanism by which the bone grows in thickness Osteoblasts differentiate directly from periosteal and preosteoblasts and lay down osteoid No intermediate cartilage ENDOCHONDRAL OSSIFICATION ● ● ● Mechanism through which the bone grows in length Presence of cartilage as intermediate Hypertrophy of chondrocytes determines degeneration and then calcification with vascular invasion and bone production by osteoblasts 15 ENDOCHONDRAL OSSIFICATION • Pericondrium lays down periosteal bone collar • Nutrient artery penetrates the center of the cartilage model • Periosteal bud brings osteoblasts and osteoclasts to the center of the cartilage model • Osteoblasts deposit bone matrix over calcified cartilage forming spongy bone trabeculae • Osteoclasts form medullary cavity CARTILAGE GROWTH PLATE REQUIREMENT S OF BONE FORMATION ADEQUATE BLOOD SUPPLY ADEQUATE MECHANICAL STABILITY 35 ● ● 15 VASCULARIZATION OF THE BONE ● Long bones have 3 sources of blood supply: ○ Intramedullary nutrient artery ○ Periosteal vessels (supply 20% of blood) ○ Metaphyseal vessels (penetrate at the level of the metaphysis) 80% of NUTRIENT INTRAMEDULLARY ARTERY • Normally it supply the majority of blood to the diaphyseal bone (80-85%) • It enters the bone through a foramen and • Gives off many collaterals along the bone PERIOSTEAL VESSELS • Derive from the periosteum which is highly vascularized • They are responsible for 15-20% of total blood supply the cortical part. • In case of damage to the intra-medullary nutritional system they increase a lot the blood supply of the damaged site. METAPHYSEAL VESSELS • Derive from peri-articular vascular structures. • Penetrate at the level of metaphyseal cortical and anastomize with the intra-medullary system. FACTORS INVOLVED IN LOCAL REGULATION OF BONE HEALING  Growth factors and growth factors antagonists  Cytokines  Prostaglandins/leukotrienes  Hormones MAIN GROWTH FACTORS     Transforming growth factor Bone morphogenetic proteins Fibroblast growth factors Platelet-derived growth factors  Insulin-like growth factors CYTOKINES ROLE Cytokine IL-1 TNF-α TNF-β TGF-α TGF-β PDGF IGF-1 IGF-2 FGF Bone Formation + + + -++ ++ +++ +++ +++ Bone Resorption +++ +++ +++ +++ ++ ++ 0 0 0 PROSTAGLANDINS/LEUKOTRIENES • Species-dependent effect • Prostaglandins E – Stimulate bone neo-formation – Inhibit osteoclastic activity • Leukotrienes – Globally stimulate the deposition of bone matrix – Stimulate also selective bone reabsorption HORMONES  Estrogens (stimulate fractures healing with a mechanism of receptors)  Thyroid hormones  Glucocorticoids  PTH  GH (stimulate maturation of bone callus) HISTOLOGICAL CLASSIFICATION OF THE CARTILAGE • Hyaline – Articular surface, nose, trachea, bronchi • Elastic – Auricular, Epiglottis • Fibrocartilage – Epiglottis Articular cartilage A UNIQUE TISSUE • No blood supply • No lymphatic drainage • No neural elements • Chondrocytes are shielded from immunological recognition. • 60 – 80% of human cartilage Chondrocyt es • Chondrocytes are the "cellular manufacturing sites" of cartilage and are responsible for the production and maintenance of the surrounding matrix . Chondroc yte Collagen s • Protein macromolecules that contain characteristic helical amino acid chains. • Provide the tensile strength and form of cartilage • Proteoglycans are attached to the collagen framework. Proteoglyc an • It consist of a core protein, Aggrecan, to which are covalently bound glycosaminoglycan side chains of chondroitin and keratan sulfate. • These charged side chains account for the hydration and resistance to compression of the cartilage matrix. Cartilage Matrix Organization Zones • Superficial (gliding) – cells are horizontal, • Middle (transitional) – cells are crisscross, • Deep (radial) – cells are perpendicular • Calcified cartilage. • Subchondral bone. Articular Cartilage Matrix Organization Zones • Morphologic, biochemical & functional differences between zones based on depth from articular surface. • Superficial – shearing • Deep - compression OA – Articular Cartilage Articular cartilage is the main tissue affected OA results in: •Increased tissue swelling •Change in color •Cartilage fibrillation •Cartilage erosion down to subchondral bone OA – Articular Cartilage A)Normal articular cartilage from 21year old adult (3000X) B)Osteoarthritic cartilage (3000X)