Introduction Fracture healing involves a complex and sequential set of events to restore injured bone to pre-fracture condition stem cells are crucial to the fracture repair process login to view 1 more bullet Fracture stability dictates the type of healing that will occur mechanical stability governs the mechanical strain when the strain is below 2%, primary bone healing will occur when the strain is between 2% and 10%, secondary bone healing will occur Modes of bone healing primary bone healing (strain is < 2%) login to view 3 more bullets secondary bone healing (strain is between 2%-10%) login to view 3 more bullets bone healing may occur as a combination of the above two process depending on the stability throughout the construct Type of Fracture Healing with Treatment Technique Cast treatment Secondary: endochondral ossification External fixation Secondary: endochondral ossification IM nailing Secondary: endochondral ossification Compression plate Primary: Haversian remodeling Secondary Bone Healing Stages of Fracture Healing Inflammation Hematoma forms and provides a source of hematopoietic cells capable of secreting growth factors. Macrophages, neutrophils, and platelets release several cytokines this includes PDGF, TNF-Alpha, TGF-Beta, IL-1,6, 10,12 they may be detected as early as 24 hours post-injury lack of TNF-Alpha (ie. HIV) results in delay of both endochondral/ intramembranous ossification BMPs, fibroblasts and mesenchymal cells migrate to fracture site and granulation tissue forms around fracture ends During fracture healing granulation tissue tolerates the greatest strain before failure Osteoblasts and fibroblasts proliferate Inhibition of COX-2 (ie NSAIDs) causes repression of runx-2/osterix, which are critical for differentiation of osteoblastic cells Repair Primary callus forms within two weeks. If the bone ends are not touching, then bridging soft callus forms. The mechanical environment drives differentiation of either osteoblastic (stable enviroment) or chondryocytic (unstable environment) lineages of cells Endochondral ossification converts soft callus to hard callus (woven bone). Medullary callus also supplements the bridging soft callus Cytokines drive chondocytic differentiation. Cartilage production provides provisional stabilization Type II collagen (cartilage) is produced early in fracture healing and then followed by type I collagen (bone) expression Amount of callus is inversely proportional to extent of immobilization Primary cortical healing occurs with rigid immobilization (ie. compression plating) Endochondral healing with periosteal bridging occurs with closed treatment Remodeling Begins in middle of repair phase and continues long after clinical union Chondrocytes undergo terminal differentiation Complex interplay of signaling pathways including, indian hedgehog (Ihh), parathyroid hormone-related peptide (PTHrP), FGF and BMP These molecules are also involved in terminal differentiation of the appendicular skeleton Type X collagen types is expressed by hypertrophic chondrocytes as the extraarticular matrix undergoes calcification Proteases degrade the extracellular matrix Cartilaginous calcification takes place at the junction between the maturing chondrocytes and newly forming bone Multiple factors are expressed as bone is formed including TGF-Betas, IGFs, osteocalcin, collagen I, V and XI Subsequently, chondrocytes become apoptotic and VEGF production leads to new vessel invasion Newly formed bone (woven bone) is remodeling via organized osteoblastic/osteoclastic activity Shaped through Wolff's law: bone remodels in response to mechanical stress Piezoelectric charges: bone remodels is response to electric charges: compression side is electronegative and stimulates osteoblast formation, tension side is electropostive and simulates osteoclasts Variables that Influence Fracture Healing Internal variables blood supply (most important) login to view 6 more bullets head injury may increase osteogenic response mechanical factors login to view 6 more bullets External variables Low Intensity Pulsed Ultrasound (LIPUS) login to view 7 more bullets bone stimulators login to view 9 more bullets COX-2 login to view 1 more bullet radiation (high dose) login to view 2 more bullets Patient factors diet login to view 12 more bullets diabetes mellitus login to view 5 more bullets nicotine login to view 5 more bullets HIV login to view 6 more bullets medications affecting healing login to view 9 more bullets