Basics of fracture healing of bones.pptx
- 1. Basics of fracture healing Dr. Syed Wajahat Kamal
- 2. Objectives •Bone Composition •Bone Types •Bone Healing •Stages of Fracture Healing •Factors that affect Bone Healing
- 3. Bone Composition • Cells • Osteocytes • Osteoblasts • Osteoclasts • Extracellular Matrix • Organic Portion (35%) • Collagen Type 1 90% • Osteocalcin, Osteonectin • Proteoglycans, glycosaminoglycans • Inorganic Portion (65%) • Calcium Hydroxyapatite • Calcium Phosphate Normal Cortex. Courtesy of Andrew Rosenberg, MD
- 4. OsteoBlasts • Derives from undifferentiated Mesenchymal Stem Cells • RunX2 directs mesenchymal cells to osteoblast lineage • Line the surface of bone and produce osteoid • Functions: • Form Bone • Regulate osteoclastic activity • Osteoblasts produce Type 1 collagen, RANKL, and Osteoprotegrin • Osteoblasts are activated by intermittent PTH levels • Inhibited by tumor necrosis Factor (TNF-α) Courtesy of Andrew Rosenberg, MD
- 5. Osteocytes • About 90% of cells in the mature skeleton • Osteocytes live in lacunae • Previous osteoblasts that get surrounded by the new formed matrix • Control extracellular calcium and phosphorus concentration • Stimulated by calcitonin • Inhibited by PTH Electron microscope picture of osteocyte. Courtesy of Andrew Rosenberg, MD
- 6. Osteoclasts • Derived from Hematopoietic stem cell (monocyte precursor cells) • Multinucleated cells • Function to resorb bone and release calcium • Parathyroid Hormone stimulates receptors on osteoblasts that activate osteoclasts • Found in bone resorption craters called Howship Lacunae • Uses ruffled borders which increases surface area • Produces hydrogen ions through carbonic anhydrase • The lower pH increases the solubility of hydroxyapatite crystals
- 7. Osteon • Basic unit of bone • Consists of • Lamella- extracellular matrix made up of collagen fibers. Parallel to each other • Osteocytes in their lacunae • Vessels in the center in the Haversian Canal
- 8. Extracellular Matrix • Organic Components • Collagen- mostly Type 1 Collagen which provides tensile strength • Proteoglycans • Matrix proteins • Osteocalcin-most abundant noncollagenous protein • Growth Factors • Cytokines • Inorganic Components • Calcium hydroxyapatite • Calcium Phosphate
- 9. Types of bone •Lamellar • Collagen fibers are arranged in parallel layers • Normal adult bone • Cortical • Cancellous •Woven • Collagen fibers are oriented randomly • Seen in remodeling bone or ligament/tendon insertion • Pathological conditions Cancellous Bone Cortical Bone Courtesy of Andrew Rosenberg, MD
- 10. Lamellar Bone • Stress Oriented formation – highly organized • Consists of Osteons and Interstitial lamellae (fibrils between osteons) • Osteons communicate through Volkmann’s canals • Cortical Bone • Constitutes 80 % of bone • Slow turnover rate • Cancellous Bone • Spongy or Trabecular bone • Higher turnover rate • Less dense than cortical bone Above- Lamellar bone with osteocytes. Left-Osteons Courtesy of Andrew Rosenberg, MD
- 11. Woven Bone • Immature or Pathologic Bone • Random orientation of collagen • Has more osteocytes • Not stress oriented • Weaker Fracture with Reactive Woven Bone Courtesy of Andrew Rosenberg, MD
- 12. Mechanism of Bone Formation •Bone Remodeling • Wolff’s Law • Bone will adapt according to the stress or load it endures • Longitudinal Load will increase density of bone • Compressive forces inhibit growth • Tensile forces stimulates growth •Types of Bone Formation • Appositional • Intramembranous (Periosteal) Bone Formation • Endochondral Bone Formation
- 13. Appositional Ossification • Increase in diameter of bone by osteon formation on existing bone • Osteoblasts align on existing bone surface and lay down new bone • Periosteal bone increases in width • Bone formation phase of bone remodeling • Seen as bone grows in diameter and strength secondary to stress • Remodeling due to forces on the bone
- 14. Intramembranous Bone Formation • Mostly seen in flat bones like cranium and clavicle • Osteoblasts differentiate directly from preosteoblasts and lay down osteoid • There is no cartilage precursor • Direct bone healing Courtesy of Andrew Rosenberg, MD
- 15. Endochondral Bone Formation • Seen in embryonic bone formation, growth plates, and fracture callus • Cartilaginous matrix is laid down osteoprogenitor cells come to the area through vascular system- Osteoclasts resorb the cartilage Osteoblasts make bone • The Chondrocytes hypertrophy, degenerate and calcify • Vascular Invasion of the cartilage occurs followed by ossification • Bone Grows in Length • Indirect bone healing
- 16. Stages of Fracture Healing •Inflammatory Phase •Repair • Early Callus Phase • Mature Callus Phase •Remodeling Phase
- 17. Inflammatory Phase • Begins as soon as fracture occurs when a hematoma forms • It lasts about 3-4 days • Proinflammatory markers are released into the area • IL-1, IL-6, TNF alpha • This attracts cells like fibroblasts, mesenchymal cells and osteoprogenitor cells Fracture with hematoma. Courtesy of Andrew Rosenberg, MD
- 18. Early Callus Phase • Starts a few days after fracture and lasts weeks • Vascularization into the area takes place • Mesenchymal Cells in the area differentiate into Chondrocytes • Cartilage Callus is formed and provides initial mechanical stability Image from Rockwood and Green’s Fractures in Adults. Fig 4-3
- 19. Mature Callus Phase • Cartilaginous Matrix is mineralized • Cartilage is degraded • Bone is laid done as woven bone through endochondral ossification • Fracture is considered healed in this stage Image from Rockwood and Green’s Fractures in Adults. Fig 4-4.
- 20. Remodeling Phase • Happens several months after fracture • Woven Bone becomes Lamellar bone • Previous shape of bone begins to be formed through Wolff’s Law • This phase can continue for a year or more • Fracture healing is complete when marrow space is reconstituted
- 21. Primary (direct) healing Cutting Cones • Primary method of bone remodeling • Osteoclasts are in the front of the cone and remove the disorganized woven bone • Osteoblasts trail behind to lay down new bone • Blood vessel is in the center of the core Image from Rockwood and Green’s Fractures in Adults Fig 4-6.
- 22. Clinical Fracture Healing • Direct (Primary) Bone Healing • Cutting Cones • Absolute Stability • Rigid Fixation • No callus formation • Indirect (Secondary) Bone Healing • Endochondral Ossification • Relative Stability • Comminution • Callus Formation A. Patient treated with fracture brace using secondary bone healing B. Patient with Compression plating and primary bone healing. A. B.
- 23. Direct (Primary) Bone Healing • There is no motion at the fracture site • Cutting cone crosses the fracture site • Contact healing- there is direct contact between the two fracture ends which allows for healing to start with lamellar bone formation • Gap Healing- if < 200-500 microns woven bone that is formed can be remodeled into lamellar bone • Examples: Compression Plating, lag screws and neutralization plate
- 24. Indirect (Secondary) Bone Healing • Some motion at the fracture site • Relative Stability • Endochondral Ossification • Comminution • Example: Intramedullary nail, Casting/bracing, Bridge plating Right femoral shaft fracture treated with IMN. Post OP 1 month, 8 months, 12 months.
- 25. • Stability and blood supply are the two most important factors in fracture healing • Long Bones Receive blood from three sources • Nutrient artery system (endosteal system) , supplies 2/3rd of bone • Metaphyseal-epiphyseal system • Periosteal system, supplied 1/3rd of bone • Direction of blood flow is usually centrifugal endosteal towards periosteal. Reverse in fracture.
- 26. Stem cells differentiation • Stem cells differentiate into osteoblasts or chondroblasts. They come from the vasculature of the periosteum and endosteum. • Pericytes become osteoblasts in low strain and high oxygen environment and become chondrocytes in moderate strain and moderate vascularity • When strain is reduced at the fracture site by stabilization of soft callus formation, then endothelial cells migrate there in response to VEGF • VEGF is released by chondrocytes and osteoblasts
- 27. Factors affecting Healing Biological • Comorbidities • Nutritional Status • Cigarette Smoking • Hormones • Growth Factors • NSAIDs Mechanical • Soft Tissue Attachments • Stability • High vs low energy mechanism • Extent of bone loss
- 28. Biological Factors: Comorbidities/Behavioral • Comorbidities • Diabetes- associated with collagen defects • Vascular Disease- decreased blood flow to fracture site • Nutritional Status • Poor protein intake/ Albumin and prealbumin • Vit D deficiency • Cigarette Smoking • Inhibits osteoblasts • Causes Vasoconstriction decreasing blood flow to fracture site
- 29. Biological Factors: Hormones • Growth Hormone: Increases gut absorption of calcium, Increases callus volume • Calcitonin: Secreted from parafollicular cells in thyroid, Inhibits osteoclasts, decreases serum calcium levels • PTH: Chief cells of parathyroid gland, stimulates osteoclasts, intermittent pulses stimulate osteoblasts • Corticosteroids: Decrease gut absorption of calcium, Inhibits collagen synthesis and osteoblast effectiveness
- 30. Biological Factors: Growth Factors • Bone Morphogentic Protiens (BMP): Stimulates bone formation by increasing differentiation of mesenchymal cells into osteoblasts. • Transforming growth factor Beta (TGF-β): Stimulates mesenchymal cells to produce type II collagen and proteoglycans, stimulate osteoblasts to make collagen • Insulin like Growth Factor 2 (IGF-2): Stimulates collagen I formation, cartilage matrix synthesis and bone formation • Platelet-derived growth factor (PDGF): Attract inflammatory cells to fracture sites
- 31. Mechanical Factors Soft tissue • Periosteal Stripping • Disruption of local blood supply • Decrease ability of angiogenesis • Decrease formation of soft callus or bone formation • Interposition of fat or soft tissue in fracture site • Increase fracture gap • Inability to build upon a scaffold
- 32. Mechanical Factors Energy of injury • High Energy • GSW • Crush Injury • Motor Cycle or Motor Vehicle Accident • More soft tissue injury and greater risk of nonunion • Low Energy • Fall from Standing Height • Twisting Injury • Less soft tissue damage Nondisplaced Lateral Tibial Plateau Fracture Mangled foot and open pilon from a Motorcycle Crash
- 33. Mechanical Factors Stability • Absolute stability • No movement between fracture fragments • Anatomic Reduction of Fracture • Intermembranous Ossification • Relative Stability • Controlled motion between fracture fragments • Restoration of length, alignment, and rotation • Endochondral Ossification • Instability • Gross movement at the fracture site • Cannot make callus or increase stability due to constant motion • Leads to nonunion Stability Spectrum From left to right: Unstable, Casting, External fixation, Intramedullary Nail, and Plate fixation
- 34. Failure of Stability Instability Results in Nonunion Not Enough Stability Results in Hardware failure and nonunion
- 35. Absolute Stability • Articular Fractures • Pilon • Tibial Plateau • Distal Humerus • Anatomic Reductions • Fibular Fractures • Humeral Shaft • Radial and Ulnar Shafts Injury Xray Open Pilon Fracture and Post Op Xray about 12mo Injury Xray Both Bone Forearm fracture and Post Op Xray 6 mo
- 36. Relative Stability • High Comminution • Long Bone Fractures • Tibia Midshaft Fractures • Femur Midshaft Fractures • Metaphyseal fractures • Distal Femur Fractures • Proximal Femur fractures Injury Xray and Post Op 12 months Injury Xray and Post op 6 months
- 37. Summary • Two main types of bone cells are osteoblasts and osteoclasts • Two main pathways of bone healing are intramembranous and endochondral ossification • There are many molecules that play a part and effect bone healing • Stability of the fracture and blood flow to the region are the most important factors in having a successfully healed fracture
Editor's Notes
- #3: Normal cortex
- #5: Osteocytes with cannuculi-
- #7: Figure 1-12 The hierarchical structure of bone is demonstrated. At the lowest level of organization, the ratio of mineral crystals to collagen fibrils determines the elastic modulus of the combined material. At the next level, the fiber orientation is important in determining the difference in strength of bone in different directions. At the final level, the lamella of bone fibers form haversian systems that, particularly in cortical bone, are oriented in the direction of the major loads the bone must support.
- #10: Cortical bone with interstitial lamella osteon
- #11: Fracture with reactive woven bone
- #12: Mechanotransduction: Mechanical forces are turned into biological signals through cellular signaling and promote osteoblasts or osteoclasts. When the osteocytes feel a load they communicate with other cells Longitudinal load will increase strength and density. The bone will remodel to make it stronger and better resist the load. This can make bones thicker. Weight bearing exercises to increase bone density and osteoporosis. If there is no load then this results in decreased density, osteopenia in the bones, ex. Astronaut in space or person not placing weight on an injured limb.
- #18: Figure 4-3 Early repair of a diaphyseal fracture of a long bone. A: Drawing showing organization of the hematoma, early woven bone formation in the subperiosteal regions, and cartilage formation in other areas. Periosteal cells contribute to healing this type of injury. If the fracture is rigidly immobilized or if it occurs primarily through cancellous bone and the cancellous surfaces lie in close apposition, there will be little evidence of fracture callus. B: Photomicrograph of a fractured rat femur 9 days after injury showing cartilage and bone formation in the subperiosteal regions. (Reprinted from: Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. 1998;335(suppl):S7–S21, with permission.)
- #19: Figure 4-4 Progressive fracture healing by fracture callus. A: Drawing showing woven or fiber bone bridging the fracture gap and uniting the fracture fragments. Cartilage remains in the regions most distant from ingrowing capillary buds. In many instances, the capillaries are surrounded by new bone. Vessels revascularize the cortical bone at the fracture site. B: Photomicrograph of a fractured rat femur 21 days after injury showing fracture callus uniting the fracture fragments. (Reprinted from: Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res. 1998;335(suppl):S7–S21, with permission.)
- #21: Figure 4-6 Primary bone healing utilizes an osteoclastic cutting cone crossing the fracture gap (I) followed by bone reconstitution by the trailing osteoblasts (II, III).
- #28: Castillo RC, et al: Impact of smoking on fracture healing and risk of complications in limb-threatening open tibia fractures. J Orthop Trauma 2005; 19: pp. 151-157