Aaron Nauth

Heterotopic Ossification in Orthopaedic Trauma

Summary: Heterotopic ossification (HO) can be defined as the pathologic formation of bone in extraskeletal tissues. There has been a substantial amount of recent research on the pathophysiology, prophylaxis, and treatment of HO and traumatic conditions associated with the development of HO. This research has advanced our understanding of this disease and helped to clarify evidence-based approaches to both the prophylaxis and treatment of HO. This article reviews the literature on these topics with a focus on their application in orthopaedic trauma.

Growth factors: beyond bone morphogenetic proteins.

The current landscape of growth factors in orthopaedic trauma is dominated by the BMPs, as they are the most extensively studied growth factors in clinical applications pertaining to orthopaedic trauma. Despite this, their application and indications for use in trauma remain controversial. This article highlights a number of selected growth factors, other than BMPs, that are currently being investigated in orthopaedic trauma applications. These growth factors have shown significant promise in preclinical and early clinical investigation.

Managing bone defects.

The management of bone defects caused by trauma and nonunion continues to represent a substantial clinical challenge in the management of orthopaedic trauma patients. A variety of treatment options have been described and reported in the literature. The relative rarity of these injuries means that high level, comparative evidence to guide their management is sparse. As such, treatment decisions must be based on knowledge of the available evidence, contemporary fracture management principles, and consideration of patient and surgeon factors. This article reviews the available evidence for the different treatment options available for the management of bone defects.

Systematic review of the treatment of periprosthetic distal femur fractures.

Objectives: To systematically review and compare nonoperative and operative treatments for the management of periprosthetic distal femur fractures adjacent to total knee arthroplasties. Specific operative interventions compared included locked plating, retrograde intramedullary nailing (RIMN), and conventional (nonlocked) plating. Where possible, data were pooled to arrive at summary estimates of treatment effect [odds ratios (ORs) with associated 95% confidence intervals (CIs)]. Methods: A comprehensive database search (via Pubmed, Medline, Cochrane Database, and the Orthopaedic Trauma Association database) was completed, yielding 44 eligible studies with a total of 719 fractures for analysis. Pertinent outcomes including malunion, nonunion, and the need for secondary surgical procedures were compared statistically. Results: Both locked plating and RIMN demonstrated significant advantages over nonoperative treatment. Some advantages were also observed when locked plating and RIMN were compared with conventional (nonlocked) plates. Comparison of locked plating and RIMN showed no significant differences with regard to nonunion rates (OR = 0.39, 95% CI = 0.13–1.15; P = 0.09) or rate of secondary surgical procedures (OR = 0.65, 95% CI = 0.31–1.35; P = 0.25). However, RIMN demonstrated a significantly higher malunion rate when compared with locked plating (OR = 2.37, 95% CI = 1.17–4.81; P = 0.02). Conclusions: Locked plating and RIMN offer significant advantages over nonoperative treatment and conventional (nonlocked) plating techniques in the management of periprosthetic femur fractures above total knee arthroplasties. Locked plating demonstrated a trend toward increased nonunion rates when compared with RIMN. Malunion was significantly higher with RIMN compared with locked plating.

Endothelial progenitor cells for fracture healing: a microcomputed tomography and biomechanical analysis.

Purpose: Local treatment of segmental bone defects with ex vivo expanded endothelial progenitor cells (EPCs) has been shown to increase osteogenesis and callus formation in rat femur diaphyseal defects. The purpose of this study was to evaluate the effects of local EPC therapy on the microarchitecture and biomechanical properties of a segmental bone defect in a rat model. Methods: Five-millimeter segmental defects were created in the femora of 14 Fisher 344 rats and stabilized with miniplates. The treatment group (n = 7) received 1 × 106 EPCs, seeded on a Gelfoam scaffold, locally at the site of the bone defect, and control animals (n = 7) received Gelfoam and saline only. Animals were euthanized 10 weeks after the procedure and new bone formation was assessed with radiographs, microcomputed tomography and biomechanical testing. Results: Radiographically, all the animals in the EPC-treated group healed with bridging callus formation, whereas animals in the control group developed nonunion of the defect. Microcomputed tomography assessment demonstrated significantly superior bone formation in the EPC-treated group versus the control group for all parameters tested (P = 0.013-0.000). Biomechanical testing revealed that the EPC-treated group had significantly higher torsional strength (P = 0.000) and stiffness (P = 0.000) when compared with the control group. Conclusion: The results of this study suggest that local EPC therapy significantly enhances fracture healing in a segmental defect model in a rat femur. EPC therapy results in superior radiographic bone formation and healing when compared with appropriate controls.

Periprosthetic distal femur fractures: current concepts.

Periprosthetic fractures of the distal femur most commonly present as fragility fractures associated with relatively minor trauma. These injuries are often complicated by osteopenia of the distal femur secondary to stress shielding or osteolysis. Effective management of periprosthetic fractures of the distal femur requires knowledge of both fracture fixation techniques and revision arthroplasty. This article reviews the treatment options for these challenging fractures with a particular focus on the management of displaced fractures with a stable prosthesis.

Surgical fixation of Vancouver type B1 periprosthetic femur fractures: a systematic review.

Objectives: Vancouver type B1 periprosthetic femur fractures occur around a stable implant and are typically treated with open reduction and internal fixation (ORIF). Different fixation techniques are described in the literature, and there is a lack of consensus regarding the best operative fixation strategy. The purpose of this investigation was to systematically review and compare the most commonly used fixation strategies for these fractures. Data Sources: A database search was performed using PubMed, MEDLINE, and Cochrane databases to identify studies published in English language from 1985 to 2013. Study Selection: Articles with a minimum of 5 patients with type B1 periprosthetic femur fractures and containing outcome data regarding nonunion, malunion, infection, and reoperation rate were included. Data Extraction: Studies were analyzed and categorized into 4 groups: group 1: ORIF with cortical strut allografts alone, group 2: ORIF with cable plate/compression plates alone, group 3: ORIF with cable plate/compression plates and cortical strut allograft, group 4: ORIF with locking plates alone. Individual patient outcomes were extracted for each study and pooled for each of the 4 groups. Data analysis was performed comparing rates of nonunion, malunion, hardware failure, infection, and reoperation. Data Synthesis: Data were analyzed using Review Manager and SAS 9.3. Conclusions: In total, 333 patients identified with an overall rate of 5% nonunion, 6% malunion, 5% infection, 4% hardware failure, 9% reoperation, and 15% total complications. When comparing outcomes for different modes of fixation, compared with cable plate/compression plate systems, locking plates had a significantly higher rate of nonunion (3% vs. 9% P = 0.02) and a trend toward a higher rate of hardware failure (2% vs. 7%, P = 0.07). There are limitations to this study, and further investigation with high-quality randomized controlled trials is needed to effectively compare treatment strategies.

Expression of VEGF gene isoforms in a rat segmental bone defect model treated with EPCs

Objectives: Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. Vascular endothelial growth factor (VEGF) has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological, biomechanical, and micro-CT evaluations. Although EPCs have demonstrated effectiveness in animal models of fracture healing, the mechanism by which EPCs enhance fracture healing remains unclear. We hypothesized a possible paracrine mechanism of action, where the secretion of growth factors critical to the processes of fracture healing (such as VEGF), is responsible for the positive effects of EPC therapy. The purpose of this study was to evaluate VEGF gene expression after local EPC therapy for a rat segmental bone defect. Methods: Rat bone marrow–derived EPCs were isolated by the Ficoll-paque gradient centrifuge technique. The EPCs were cultured for 7–10 days in endothelial cell growth medium with supplements and collected for treatment of the rat segmental bone defect. EPCs were identified by immunocytochemistry staining with primary antibodies for CD34, CD133, fetal liver kinase-1, and Von Willebrand factor. A total of 56 rats were studied. A 5-mL segmental bone defect was created in the middle one-third of each femur followed by miniplate fixation. The treatment group received 1 × 106 EPCs locally at the bone defect on a gelfoam scaffold and control animals received the gelfoam scaffold only. Seven control and 7 EPC-treated rats were included in each group at 1, 2, 3, and 10 weeks. The animals were sacrificed at the end of the treatment period, and specimens from the fracture gap area were collected and immediately frozen. Rat VEGF mRNA was measured by reverse-transcriptase-polymerase chain reaction and quantified by VisionWorksLS. All measurements were performed in triplicate. Results: Cultured EPCs at 1 week showed positive staining for CD34, CD133, fetal liver kinase-1, and Von Willebrand factor markers. The EPC group had a greater VEGF expression than the control group at weeks 1, 2, and 3, but not at week 10. Three VEGF isoforms were detected in this rat model: VEGF120, VEGF164, and VEGF188. VEGF120 and VEGF164 levels peaked at 2 weeks, whereas VEGF188 levels peaked at 3 weeks. All 3 VEGF isoform levels were low at 10 weeks. Discussion and Conclusions: EPC-based therapy for a segmental bone defect results in increased VEGF expression during the early period of fracture repair. In addition, the specific VEGF isoform may be a key regulator of the bone healing process. These findings demonstrate that EPCs may promote fracture healing by increasing VEGF levels and thus stimulating angiogenesis, a process that is essential for early callus formation and bone regeneration.

Stem cell therapies in orthopaedic trauma

Summary: Stem cells offer great promise to help understand the normal mechanisms of tissue renewal, regeneration, and repair, and also for development of cell-based therapies to treat patients after tissue injury. Most adult tissues contain stem cells and progenitor cells that contribute to homeostasis, remodeling, and repair. Multiple stem and progenitor cell populations in bone are found in the marrow, the endosteum, and the periosteum. They contribute to the fracture healing process after injury and are an important component in tissue engineering approaches for bone repair. This review focuses on current concepts in stem cell biology related to fracture healing and bone tissue regeneration, as well as current strategies and limitations for clinical cell-based therapies.

Bone grafting: Sourcing, timing, strategies, and alternatives

Summary: Acute fractures, nonunions, and nonunions with bone defects or osteomyelitis often need bone graft to facilitate union. There are several factors to consider when it is determined that a bone graft is needed. These factors include the source of the bone graft (autograft vs. allograft), proper timing for placement of the bone graft, strategies to avoid further complications (particularly in the setting of osteomyelitis), and with the development of a variety of bone graft substitutes, whether alternatives to autograft are available and appropriate for the task at hand. Autograft bone has commonly been referred to as the “gold standard” of bone grafts, against which the efficacy of other grafts has been measured. The best timing for when to place a bone graft or substitute is also somewhat controversial, particularly after an open fracture or a potentially contaminated bed. The treatment of infected nonunions, particularly those that require a graft to facilitate healing, can be quite challenging. Typically, the infection is completely eradicated before placement of a bone graft, but achieving a sterile bed and the timing of a bone graft require strategic thinking and planning. This review outlines the benefits of autografts, the most suitable sites for harvesting bone grafts, the timing of bone graft procedures, the potential risks and benefits of grafting in the face of infection, and the currently available bone graft extenders.