Bone Healing/Nonunions/Malunions (Student Copy) 2024 PDF

Bone Healing/Nonunions/ Malunions Sean T. Grambart DPM FACFAS, D.ABFAS Associate Dean of Clinical Affairs, DMU-CPMS Director of Research, CPMS Attending, IMMC Foot and Ankle Surgical Residency, Des Moines IA AO Fellow - Dresden, Germany Past-President, ACFAS 1 1 Objectives Differentiate Differentiat...

Bone Healing/Nonunions/ Malunions Sean T. Grambart DPM FACFAS, D.ABFAS Associate Dean of Clinical Affairs, DMU-CPMS Director of Research, CPMS Attending, IMMC Foot and Ankle Surgical Residency, Des Moines IA AO Fellow - Dresden, Germany Past-President, ACFAS 1 1 Objectives Differentiate Differentiate between delayed, nonunion and malunion Identify Identify the evaluation of patients with bone healing problems Demonstrate knowledge of biophysical Demonstrate principles and indications behind the various types of bone stimulators Recognize types of bone grafts and indications for grafting Recognize 2 Bone Healing 3 Types of Bone Healing Direct/Primary ‘Absolute Stability’ of bony surfaces Close contact of less than 0.15 mm Minimal interfragmentary strains of less than 2% Compression lag screw or compression plating 4 Types of Bone Healing Secondary/Callus ‘Relative Stability’ of bony surfaces Fracture hematoma formation Inflammation Cellular proliferation and differentiation and Remodeling 5 Factors for Osseous Healing Cellular environment Growth factors Diamond Concept Bone matrix Mechanical stability 6 Bone Healing “Diamond Concept” There is no other section to understand more critically than the etiology of nonunion of bone because this is a major determinant of treatment. If one knows the cause of nonunion, one can give proper treatment. As discussed above, nonunion is a multifactorial pathologic process. Patient, biology, fracture type, surgeon, and clinical factors all merit consideration in treatment. The recommendation is to optimize each of these factors going forward with treatment. The major patient factor in nonunion is the blood supply. When the bone has a decrease in blood supply, it can not heal. This can occur with poor nutrition and smoking The study by Steen et al. has shown the most important risk factors involved in the nonunion of bone are smoking and diabetes. These factors are important in predicting patient-specific risk factors for nonunion and helps to determine the best surgical treatment and may allow a more aggressive surgical plan to prevent non-union. 7 Diamond Concept 8 Osteoinductive Mediators Vascular endothelial growth factor (VEGF) also play Platelet-derived growth factor (PDGF) Fibroblast growth factor (FGF) Insulin-like growth factor (IGF) Transforming growth factor beta (TGFβ) Bone morphogenic protein (BMP)-2, 4, 6 and 7 Initial bleeding following fracture initiates the coagulation cascade; this leads to development of a fracture haematoma. This contains platelets and macrophages, which release a series of cytokines (cell signalling molecules) of different types, stimulating a cascade of events to initiate healing. Metalloproteinases and angiogenic factors such as vascular endothelial growth factor (VEGF) also play an important role in the overall bone repair process [1,34, 35]. However, the most important mediators releasedhaving a direct effect on progenitor cells to undergo the process of mitogenesis and osteoblastic differentiation include plateletderived growth factor (PDGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF) and transforming growth factor beta (TGFβ) proteins, which include bone morphogenic protein (BMP)-2, 4, 6 and 7 9 Diamond Concept 10 Osteogenic Cells Committed osteoprogenitor cells (periosteum) Undifferentiated multipotent stem cells (MSCs) (bone marrow) Proliferation and differentiation of MSCs, leading to simultaneous hard and soft callus formation Critical in guiding this process are the BMPs 21 Osteogenic cells, which comprise both committed osteoprogenitor cells from the periosteum as well as undifferentiated multipotent stem cells (MSCs) from bone marrow and endothelial progenitor cells, are also activated according to the local fracture environment in the haematoma Higher oxygen tension at periosteal surfaces distal to the fracture site, as well as other factors, encourages preferential MSC differentiation into osteoblasts. In the peripheral (cortical) zone, osteocalcin initiates periosteal osteoblasts to produce type 1 collagen, leading to intramembranous ossification (hard callus). In central (medullary) zones, MSCs develop into chondrocytes, initially laying down type 2 collagen (soft callus) known as endochondral ossification; 11 Diamond Concept 12 Osteoconductive Matrix Extracellular matrix Scaffold and promoting migration and adhesion of osteoinductive and osteogenic cells to the fracture site With good apposition of bone, necrotic bone at the fracture site serves this purpose If there is insufficient ‘natural’ scaffold, then autograft and/or allograft demineralised bone matrix (DBM) 13 Diamond Concept 14 Nonunion A fracture that is a minimum of 9 months post occurrence and is not healed and has not shown radiographic progression for 3 months Orthopaedic Advisory Panel: Food & Drug Administration, 1986 Fracture that, in the opinion of the treating physician, has no possibility of healing without further intervention 3 Non-union has been defined in various ways, with a 55% disagreement amongst clinicians on timing nonunion is a complex orthopedic problem that is multifactorial, and clinicians need to entertain multiple modalities as therapeutic interventions. One must review radiographs to determine if there is evidence of fracture healing demonstrated by cortical bridging of the fracture lines. Also, clinical markers of healing must be evaluated, evidenced by a resolution of pain with weight-bearing with no movement at the fracture site. Patient comorbidities require evaluation to determine 15 Delayed Union Fracture that shows slower progression to healing than anticipated and it’s at risk of non-union without further intervention Shows healing progress over time 16 Malunion Term used to indicate that osseous healing has occurred, but that it has healed in less than an optimal position 17 Etiology of Nonunion There is no other section to understand more critically than the etiology of nonunion of bone because this is a major determinant of treatment. If one knows the cause of nonunion, one can give proper treatment. As discussed above, nonunion is a multifactorial pathologic process. Patient, biology, fracture type, surgeon, and clinical factors all merit consideration in treatment. The recommendation is to optimize each of these factors going forward with treatment. The major patient factor in nonunion is the blood supply. When the bone has a decrease in blood supply, it can not heal. This can occur with poor nutrition and smoking The study by Steen et al. has shown the most important risk factors involved in the nonunion of bone are smoking and diabetes. These factors are important in predicting patient-specific risk factors for nonunion and helps to determine the best surgical treatment and may allow a more aggressive surgical plan to prevent non-union. 18 Diamond Concept If vascular supply or fracture haematoma is compromised or lost, there is a higher risk of non-union, as insufficient osteoinductive and osteogenic cells will be available at the fracture site to initiate osteogenesis, remodelling and healing [2, 45]. The chance of this significantly increases in high-energy and open fractures, or in primary surgical repair where the fracture biology, periosteum and soft tissue envelope are not respected [24, 51]. Periosteum, as well as providing critical blood supply, also has unique regenerative potential 19 Risk Factors for Nonunion 20 Nicotine Use Decreases peripheral oxygen tension Dampens peripheral blood flow Well documented difficulties in wound healing in patients who smoke Increased risk of NONUNION Overall 15% higher 4x Greater Risk 31 21 Types of Nonunion Hypertrophic Nonunion Atrophic Nonunion Oligotrophic Septic Nonunion Pseusoarthrosis 22 Hypertrophic Nonunion Shown by radiographically abundant callus formation There is no bridging bone, and the ends are not united There is adequate blood supply and biology but inadequate stability 23 Type of Hypertrophic Nonunions Elephant’s Foot Horse’s Huff 8 24 Atrophic Nonunion Evidenced by radiographically absent callus Poor biology Lack of blood supply Inadequate fixation? Inadequate joint preparation? 25 Types of Atrophic Nonunion Torsion wedge Comminuted fracture nonunion, necrotic intermediate fragment Defect Atrophic nonreactive 26 Oligotrophic Nonunion Combination of atrophic and hypertrophic in that there is incomplete callus formation 27 Septic Nonunion Reduction in blood flow from organisms consuming the nutrition to healthy bone Decreases the new bone formation 28 Pseudoarthrosis Typically has adequate vascularity Excessive motion/ instability False joint forms over significant time Sufficient biology but so much mechanical instability that the body is “tricked” into thinking there should be a joint there à likely need to reset the whole system 29 Mechanical Stability In the presence of appropriate growth factors… Combination of compression/ distraction encourages osteoblasts For ossification to occur, the fracture gap must have reduced to an appropriate level Ideally less than 2 mm Anything gap > 6 mm, little callus is seen to form Evidence suggests that cells are able to sense the surrounding mechanical environment, through electrochemical signals generated by fluid shift Based on studies of cells in culture, cellular development has been shown to be greatly influenced by local mechanics, with the mechanical and physiological environment impacting significantly upon subsequent lineage differentiation of multi-potent mesenchymal stem cells. Axial micromotion seems to stimulate fracture healing in the early stages Too much motion increases differentiation down the soft tissue lineage pathway predominates, leading to delayed or non-union 30 Patient Work-Up History Open versus closed Surgery (Type, Fixation) Smoker Diabetes Vascular disease Vitamin D NSAIDs Steroids Physical Pain Sinus tracts Drainage Movement 30 Due to several factors contributing to the nonunion of bone, it is important to evaluate all aspects of the patient's history so these factors can be optimized. Ask about injury mechanisms (open vs. closed), type of surgical treatments (plate and screw versus intramedullary nailing). One must evaluate patients' medical history for risk factors including nutritional status, diabetes, smoking, vascular disease, vitamin D status, renal sufficiency, and use of NSAIDs or steroids. One must evaluate fracture type on radiographs and/or CT (comminution, segmental, infection). Clinically, one must ask the patient if he/she is having pain at the fracture site with weight-bearing or ambulation. The physical exam should evaluate signs of infection like draining sinus tracts or purulence at the incision. It should include the neurovascular exam and the status of the soft tissues. 31 Infection Nonunion should be considered infected until proven otherwise Dramatic association between deep infection and nonunion Debridement, debridement, debridement Multiple cultures. Identify the bacteria Infectious disease consult is helpful Infected bone requires stability to resolve infection May achieve union in the presence of infection with appropriate treatment 32 Patient Work-Up Lab Work Up Rule-Out Infection WBC with Diff ESR CRP CMP Vit D Levels Imaging Callus Formation Fixation CT Scan?? 33 Due to several factors contributing to the nonunion of bone, it is important to evaluate all aspects of the patient's history so these factors can be optimized. Ask about injury mechanisms (open vs. closed), type of surgical treatments (plate and screw versus intramedullary nailing). One must evaluate patients' medical history for risk factors including nutritional status, diabetes, smoking, vascular disease, vitamin D status, renal sufficiency, and use of NSAIDs or steroids. One must evaluate fracture type on radiographs and/or CT (comminution, segmental, infection). Clinically, one must ask the patient if he/she is having pain at the fracture site with weight-bearing or ambulation. The physical exam should evaluate signs of infection like draining sinus tracts or purulence at the incision. It should include the neurovascular exam and the status of the soft tissues. 33 Treatment Communication Non-operative Operative 34 Non-Operative Treatment Electrical stimulation Ultrasound Extracorporeal shock wave therapy Immoblization 35 Electrical Stimulation Applied mechanical stress on bone generates electrical potentials Compression = electronegative potentials = bone formation Tension = electropositive potentials = bone resorption Basic science suggests e-stim upregulates TGF-β and BMP’s suggesting osteoinduction 36 Contraindications for Electrical Stimulation Synovial pseudoarthrosis Electric stimulation does not addressassociated problems of angulation, malrotation and shortening – deformity!! 37 Ultrasound Piezoelectric transducer generates an acoustic pressure wave Some evidence to show faster healing in fresh fractures Evidence is moderate to poor in quality with conflicting results 38 Extracorporeal Shock Wave Therapy (ESWT) Single impulse acoustic wave with a high amplitude and short wavelength Microtrauma induced in bone thought to stimulate neovascularization and cell differentiation 39 Operative Treatment Autogenous bone graft Debridement and hardware removal Plate osteosynthesis Intramedullary nailing External fixation Bone marrow aspirate Allograft bone Demineralized bone matrix BMP’s Platelet concentrates 40 Autologous Bone Graft Considered the “gold standard” Osteoinductive - proteins and other factors promoting vascular ingrowth and healing Osteogenic – contains viable osteoblasts, progenitor cells, mesenchymal stem cells Osteoconductive - contains a scaffolding for which new bone growth can occur 41 Operative Strategy Define nonunion type Hyper-, oligo-, atrophic, or pseudarthrosis Nonunion location – diaphysis vs metaphysis Infected vs Aseptic Deformity? Patient/host factors Goals and expectations 42 Case Studies - Stop Recording 43 Summary 44