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Fracture healing is a complex process requiring mechanical stability, an osteoconductive matrix, and osteoinductive and osteogenic biology. This intricate process is easily disrupted by various patient factors such as chronic disease and lifestyle. As the medical complexity and age of patients with fractures continue to increase, the importance of developing relevant experimental models is becoming paramount in preclinical research. The objective of this review is to describe the most common small animal models of systemically impaired fracture healing used in the orthopedic literature including osteoporosis, diabetes mellitus, smoking, alcohol use, obesity, and ageing. This review will provide orthopedic researchers with a summary of current models of systemically impaired fracture healing used in small animals and present an overview of the methods of induction for each condition., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

The assessment of fracture healing is an imperative and fundamental clinical aspect within orthopaedics. Despite that, there have historically been non-reliable methods utilized to assess for fracture union and nonunion. In recent years, a number of radiographic assessment tools such as the Radiographic Union Score for Tibial fractures (RUST) and Radiographic Union Score for Hip fracture (RUSH) have been developed in order to improve the reliability of fracture assessment for union. These scores have not only increased the reliability of assessments but have also provided thresholds to aid in predicting nonunion as well as union. The nonunion risk determination (NURD) Score was also created to prognosticate these clinical presentations. With the large burdens of cost, lower quality of life and morbidity associated with fracture nonunion, these evaluation methods have provided orthopaedic surgeons with an improved ability to predict nonunion and assist in the management of patients. This review outlines the development, reliability testing as well as biomechanical validity testing associated with these scoring systems., Competing Interests: Declaration of Competing Interest Yousif Atwan: None. Emil Schemitsch: Acumed, LLC: Paid consultant Alexion: Paid consultant Amgen Co: Paid consultant Canadian Orthopaedic Association: Board or committee member DePuy, A Johnson & Johnson Company: Other financial or material support Hip Society: Board or committee member International Society for Fracture Repair: Board or committee member ITS: Paid consultant Journal of Orthopaedic Trauma: Editorial or governing board Orthopaedic Trauma Association: Board or committee member Orthopaedic Trauma Association International: Editorial or governing board Osteosynthesis and Trauma Care Foundation: Board or committee member Pentopharm: Paid consultant Sanofi-Aventis: Paid consultant Saunders/Mosby-Elsevier: Publishing royalties, financial or material support Smith & Nephew: Other financial or material support; Paid consultant; Research support Springer: Publishing royalties, financial or material support Stryker: IP royalties; Other financial or material support; Paid consultant Zimmer: Other financial or material support; Paid consultant., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: This study was designed to measure early postoperative outcomes of plate vs. nail fixation for humeral shaft fractures., Patients and Methods: Patients ≥18 years who underwent plate or nail fixation for low-energy humeral shaft fractures between 2005-2016 were identified from the National Surgical Quality Improvement Program (NSQIP). Multivariable regression was used to compare postoperative outcomes using propensity score adjustment to account for differences between fixation groups. Variables included in the propensity score were age, American Society of Anesthesiologists (ASA) class, hypertension, steroid use, cancer, functional status, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and sex., Results: Plate fixation was used in 1418 patients (70.6%), while nail fixation was used in 591 (29.4%). Patients undergoing nail fixation were more likely to be older, have a higher American Society of Anesthesiologists (ASA) class, and have comorbidities. Mean operative time was statistically longer in the plate fixation group (130 +/-62 min vs. 102 +/-54 min). After propensity score adjustment, type of fixation was not a significant predictor of major or minor complications, length of stay, or readmission. However, nail fixation was a significant predictor of mortality following propensity score adjustment (OR 3.15, 95% Confidence interval 1.26-7.85)., Conclusion: Patients undergoing intramedullary nail fixation tended to be older patients with more comorbidities, suggesting that surgeons are selecting nail fixation in patients who may not be ideal surgical candidates. Although LOS, complications, and readmission rates were higher in the nail group, this difference was not statistically significant following propensity score adjustment. However, nail fixation remained an independent predictor of 30-day mortality following adjustment. This suggests that nail fixation may not be a safer surgical option in patients with multiple medical co-morbidities and low-energy humeral shaft fractures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is a significant burden of disease associated with infected fractures, and their management is challenging. Prevention of infection after musculoskeletal trauma is essential because treatment of an established infection continues to be a major obstacle. Despite the need for evidence-based decision making, there is a lack of consensus around strategies for prevention and surgical management of the infected fracture. The current evidence for the prevention of the infected fracture is reviewed here with a focus on evidence for antibiotic therapy and debridement, the induced membrane technique, management of soft-tissue defects, patient optimization, and adjuncts to prevent infection.

Background: The Radiographic Union Score for Tibial fractures (RUST) and the modified version of the system, mRUST, are popular standards for assessing fracture-healing progress with use of radiographs. To our knowledge, this is the first study to experimentally validate the ability of RUST and mRUST to accurately assess bone-healing progression with use of both micro-computed tomography (micro-CT) scanning and biomechanical testing., Methods: Adult male rats (n = 29) underwent osteotomy with a midshaft fracture gap repaired with use of a polyetheretherketone plate. Anteroposterior and lateral radiographs were made of the repaired femora prior to rat death at end points of 5, 6, 7, 8, 9, and 17 weeks, and 2 fellowship-trained orthopaedic trauma surgeons independently assigned RUST and mRUST scores to repaired femora. The repaired and intact contralateral femora were then dissected. Bones underwent dissection, micro-CT scanning, and biomechanical torsion testing at the end points., Results: RUST scores ranged from 5 to 12 and mRUST scores ranged from 5 to 16. Intraclass correlation coefficients (ICCs) were 0.89 (95% confidence interval [CI]: 0.78 to 0.94) for RUST and 0.86 (95% CI: 0.74 to 0.93) for mRUST, which fall within the "almost perfect agreement" category for ICCs. Spearman rank correlation coefficients (RS) showed correlation of RUST (RS range, 0.456 to 0.818) and mRUST (RS range, 0.519 to 0.862) with micro-CT measurements of mineralized callus volume (BV), total callus volume (TV), and BV/TV ratio, but less so with bone mineral density (BMD). Additionally, RUST (RS range, 0.524 to 0.863) and mRUST (RS range, 0.434 to 0.850) were correlated with some biomechanical properties. A RUST score of 10 or an mRUST score of 15 may be considered the threshold above which a plated bone is "healed" because, at these scores, 120% or 140% of failure torque, respectively, was achieved by the repaired femora as compared with the intact contralateral femora., Conclusions: RUST and mRUST both show strong statistical correlations with micro-CT and biomechanical parameters., Clinical Relevance: RUST and mRUST scoring systems provide clinicians with validated, reliable, and available tools to assess the progress of fracture-healing.

Proximal humerus, humeral shaft, and distal humerus fractures are all common adult fractures, and often occur in older patients. While the treatment of proximal humerus fractures remains controversial, certain fractures benefit from plate fixation such as fracture-dislocations and head-split fractures. When plate fixation is chosen, anatomic reduction and restoration of the medial calcar are important for successful results. Further research is required to minimize complications and determine the optimal surgical candidates for plate fixation. Humeral shaft fractures are generally treated non-operatively. However, certain shaft fractures warrant plate fixation, such as open fractures, those with associated forearm fractures, and those in poly-trauma patients. Choice of surgical approach and plate depends on the location and type of the fracture. The majority of intra-articular distal humerus fractures should be treated with plate fixation. Dual plating is generally accepted as the gold standard treatment, while the optimal surgical approach and plate configuration requires more research., (© 2018 Elsevier Ltd. All rights reserved.)

This article summarizes presentations of a symposium on bone health-related hot topics of the 2016 Basic Science Focus Forum. Taken together, these topics emphasize the critical importance of bone health in fracture management, the systemic factors that influence fracture healing, and the need to focus on issues other than simply the technical aspects of fracture repair.

Objective: The purpose of this study was to review the rates of adverse healing outcomes following surgical fixation of lower extremity fractures in diabetic patients and matched controls., Materials and Methods: Searches of PubMed, MEDLINE, CINAHL and Embase were performed for studies published between the date of database inception and July 6, 2015. Patient characteristics and the incidence of adverse healing outcomes (nonunion, malunion, delayed union, infection and reoperation) were extracted from each study. The occurrence of each fracture healing complication was pooled and analyzed for comparisons between diabetic and non-diabetic patients. An odds ratio with a 95% confidence interval for each healing outcome was calculated between the diabetic and non-diabetic groups., Results: Diabetes was found to significantly increase rates of malunion, infection and reoperation in patients with surgically treated lower extremity fractures. In addition, when only peripheral lower extremity fractures (i.e. below the knee) were examined, diabetes significantly increased the rates of nonunion., Conclusion: Diabetes substantially alters bone metabolism and soft tissue healing, posing a risk of adverse fracture healing and other complications. This systematic review provides evidence that the presence of diabetes significantly increases the risks of infection, malunion, nonunion and re-operation across a wide variety of surgically treated lower extremity fractures. This study provides prognostic information for clinicians and may aid in guiding treatment for this population., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Treating fracture nonunion with endothelial progenitor cells (EPCs) is a promising approach. Nevertheless, the effect of different EPC-related cell populations remains unclear. In this study, we compared the therapeutic potential of early (E-EPCs) and late EPCs (L-EPCs)., Methods: Male Fischer 344 rats were used for cell isolation and in vivo experiments. Bone marrow-derived E-EPCs and L-EPCs were kept in culture for seven to ten days and four weeks, respectively. For each treatment group, we seeded one million cells on a gelatin scaffold before implantation in a segmental defect created in a rat femur; control animals received a cell-free scaffold. Bone healing was monitored via radiographs for up to ten weeks after surgery. In vitro, secretion of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2 was quantified by ELISA for both cell populations. Tube formation assays were also performed., Results: Final radiographs showed complete (four out of five rats) or partial (one out of five rats) union with E-EPC treatment. In contrast, complete healing was achieved in only one of five animals after L-EPC implantation, while control treatment resulted in nonunion in all animals. In vitro, E-EPCs released more VEGF, but less BMP-2 than L-EPCs. In addition, L-EPCs formed longer and more mature tubules on basement membrane matrix than E-EPCs. However, co-culture with primary osteoblasts stimulated tubulogenesis of E-EPCs while inhibiting that of L-EPCs., Conclusions: We demonstrated that bone marrow-derived E-EPCs are a better alternative than L-EPCs for treatment of nonunion. We hypothesize that the expression profile of E-EPCs and their adaptation to the local environment contribute to superior bone healing.

Objectives: The purpose of this study was to characterize demographics, healing time, and complications of a large series of operatively treated atypical femur fractures., Design: Retrospective multicenter review., Setting: Seventeen academic medical centers., Patients: Bisphosphonate-related fractures as defined by American Society of Bone and Mineral Research. Fractures had to be followed for at least 6 months or to union or revision., Intervention: Operative treatment of bisphosphonate-related fracture., Main Outcome Measurements: Union time and complications of treatment, as well as information about the contralateral limb., Results: There were 179 patients, average age 72, average body mass index 27.2. Average follow-up was 17 months. Twenty-one percent had a previous history of fragility fracture; 34% had prodromal pain. Most (88%) lived independently before injury. Thirty-one percent had radiographic changes suggesting stress reaction. Surgical fixation was with cephalomedullary nail (51%), IM nail (48%), or plate (1%). Complications included death (4), PE (3), and wound infection (6). Twenty (12%) patients underwent revision at an average of 11 months. Excluding revisions, average union time was 5.2 months. For revisions, union occurred at an average of 10.2 months after intervention. No association was identified between discontinuation of bisphosphonates and union time (P = 0.5) or need for revision (P = 0.7). Twenty-one percent sustained contralateral femur fractures; 32% of these had pain and 59% had stress reaction before contralateral fracture., Conclusions: In this series, surgery had a 12% failure rate and delayed average time to union. Twenty-one percent developed contralateral femur fractures within 2 years, underscoring the need to evaluate the contralateral extremity., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Introduction: Recombinant Human Bone Morphogenetic Protein-7 (rhBMP-7) has been shown to promote fracture healing in both clinical studies and basic science models, however, there is little information from large-scale studies of its use for human nonunion. The purpose of this study was to determine the safety and efficacy of rhBMP-7 in the treatment of atrophic human long-bone nonunions in the upper extremity., Patients and Methods: This was a single center, retrospective, longitudinal cohort study of patients treated with compression plating and the application of rhBMP-7 in isolation to a long-bone nonunion. Patients over sixteen years of age with an atrophic, aseptic nonunion of a humerus, radius, ulna or clavicle were eligible for inclusion., Results: We identified seventy eligible patients who were treated with rhBMP-7 for a long-bone nonunion between July 1997 and April 2012. The mean age of the patients at the time of treatment with rhBMP-7 was 50.7 years (range, 20-92 years). Five patients were lost to follow-up prior to definitive clinical or radiographic union. During the one-year post-operative period fifty-six patients had achieved union and two patients developed a stable fibrous union after the index procedure. Two patients had early implant failure and five patients had persistent nonunion. Thus, the union rate following initial surgery was 89% (58/65) and four of the five nonunion patients went on to heal following revision open reduction and internal fixation., Conclusion: We found that the application of rhBMP-7 for upper extremity nonunion was an effective method (89% union rate) of treating this challenging pathology. Additionally, if not initially successful, further reconstruction was not compromised by rhBMP-7 use., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Assessment of fracture union is a critical concept in clinical orthopaedics; however, there is no established "gold standard" for fracture healing. This review provides an overview of the problems related to the assessment of fracture healing, examines currently available tools to determine union, discusses the role of functional outcomes in the assessment of fracture healing, and finally evaluates healing outcome measures as they pertain to fracture trials. Because there is no universally accepted method to determine fracture healing, orthopaedic surgeons must rely on a range of tools that can include: radiographic assessment, mechanical assessment, serologic markers, and clinical evaluation (including functional outcomes). When used in conjunction, these tools can help to improve the sensitivity and specificity of determining fracture union. This is furthermore relevant when conducting fracture healing trials, for which there is little consensus between surgeons or the Food and Drug Administration as to optimal study endpoints. Such studies should therefore include a composite outcome measure consisting of radiographic and functional assessments to increase the quality and consistency of fracture healing trials.

Objective: To determine the reliability of the Radiographic Union Scale for Tibia (RUST) score and a new modified RUST score in quantifying healing and to define a value for radiographic union in a large series of metadiaphyseal fractures treated with plates or intramedullary nails., Design: Healing was evaluated using 2 methods: (1) evaluation of interrater agreement in a series of radiographs and (2) analysis of prospectively gathered data from 2 previous large multicenter trials to define thresholds for radiographic union., Intervention: Part 1: 12 orthopedic trauma surgeons evaluated a series of radiographs of 27 distal femur fractures treated with either plate or retrograde nail fixation at various stages of healing in random order using a modified RUST score. For each radiographic set, the reviewer indicated if the fracture was radiographically healed. Part 2: The radiographic results of 2 multicenter randomized trials comparing plate versus nail fixation of 81 distal femur and 46 proximal tibia fractures were reviewed. Orthopaedic surgeons at 24 trauma centers scored radiographs at 3, 6, and 12 months postoperatively using the modified RUST score above. Additionally, investigators indicated if the fracture was healed or not healed., Main Outcome Measures: The intraclass correlation coefficient (ICC) with 95% confidence intervals was determined for each cortex, the standard and modified RUST score, and the assignment of union for part 1 data. The RUST and modified RUST that defined "union" were determined for both parts of the study., Results: ICC: The modified RUST score demonstrated slightly higher ICCs than the standard RUST (0.68 vs. 0.63). Nails had substantial agreement, whereas plates had moderate agreement using both modified and standard RUST (0.74 and 0.67 vs. 0.59 and 0.53)., Union: The average standard and modified RUST at union among all fractures was 8.5 and 11.4. Nails had higher standard and modified RUST scores than plates at union. The ICC for union was 0.53 (nails: 0.58; plates: 0.51), which indicates moderate agreement. However, the majority of reviewers assigned union for a standard RUST of 9 and a modified RUST of 11, and >90% considered a score of 10 on the RUST and 13 on the modified RUST united., Conclusions: The ICC for the modified RUST is slightly higher than the standard RUST in metadiaphyseal fractures and had substantial agreement. The ICC for the assessment of union was moderate agreement; however, definite union would be 10 and 13 with over 90% of reviewers assigning union. These are the first data-driven estimates of radiographic union for these scores.

Background: The role of low-intensity pulsed ultrasound (LIPUS) in the management of fractures remains controversial. The purpose of this study was to assess the feasibility of a definitive trial to determine the effect of LIPUS on functional and clinical outcomes in tibial fractures managed operatively., Methods: We conducted a multicenter, concealed, blinded randomized trial of 51 skeletally mature adults with operatively managed tibial fractures who were treated with either LIPUS or a sham device. All participating centers were located in Canada and site investigators were orthopedic surgeons specializing in trauma surgery. The goals of our pilot study were to determine recruitment rates in individual centers, investigators' ability to adhere to study protocol and data collection procedures, our ability to achieve close to 100% follow-up rates, and the degree to which patients were compliant with treatment. Patients were followed for one year and a committee (blinded to allocation) adjudicated all outcomes. The committee adjudicators were experienced (10 or more years in practice) orthopedic surgeons with formal research training, specializing in trauma surgery., Results: Our overall rate of recruitment was approximately 0.8 patients per center per month and site investigators successfully adhered to the study protocol and procedures. Our rate of follow-up at one year was 84%. Patient compliance, measured by an internal timer in the study devices, revealed that 39 (76%) of the patients were fully compliant and 12 (24%) demonstrated a greater than 50% compliance. Based on patient feedback regarding excessive questionnaire burden, we conducted an analysis using data from another tibial fracture trial that revealed the Short Musculoskeletal Function Assessment (SMFA) dysfunction index offered no important advantages over the SF-36 Physical Component Summary (PCS) score. No device-related adverse events were reported., Conclusions: Our pilot study identified key issues that might have rendered a definitive trial unfeasible. By modifying our protocol to address these challenges we have enhanced the feasibility of a definitive trial to explore the effect of LIPUS on tibial fracture healing., Trial Registration: The TRUST definitive trial was registered at ClinicalTrials.gov on 21 April 2008 (identifier: NCT00667849).

Purpose: Endothelial progenitor cells (EPCs) represent a population of novel precursor cells with known ability to participate in angiogenesis. Our previous studies have shown that local EPC therapy significantly increased angiogenesis and osteogenesis to promote fracture healing in an animal bone defect model. However, the cellular and molecular mechanisms by which EPC therapy promotes fracture healing remain largely unknown. The purpose of this study was to quantify local bone morphogenetic protein (BMP-2) expression after EPC therapy for a rat segmental bone defect, in hopes of further defining the potential mechanisms by which EPCs promote fracture healing., Method: EPCs were isolated from the bone marrow of syngeneic rats and cultured ex vivo for 7-10 days before transfer to the bone defect. A total of 56 rats were studied. The treatment group received 1 × 10 EPCs on a gelfoam scaffold at the bone defect, and control animals received gelfoam/saline only. Before euthanasia, radiographs of the femur were performed. Animals were euthanized at 1, 2, 3, and 10 weeks, and specimens from the fracture gap area were collected, pulverized, and total messenger RNA (mRNA) was extracted. BMP-2 mRNA was measured by reverse transcriptase-polymerase chain reaction and quantified by VisionWorksLS. All measurements were performed in triplicate., Results: All EPC-treated bone defects healed radiographically by 10 weeks, whereas control-treated defects developed a nonunion. The expression of BMP-2 mRNA was significantly elevated in EPC-treated defects relative to controls at week 1 (EPC, 0.59 ± 0.10; control, 0.31 ± 0.08; P = 0.05), week 2 (EPC, 0.40 ± 0.06; control, 0.23 ± 0.04; P = 0.04), and week 3 (EPC, 0.33 ± 0.06; control, 0.18 ± 0.03; P = 0.04), but not at week 10 (EPC, 0.31 ± 0.06; control, 0.21 ± 0.04, P = 0.15). The highest mean expression of BMP-2 in EPC-treated defects was observed at 1 week, with a progressive decline in BMP-2 expression noted thereafter., Conclusions: These findings demonstrate that EPC-treated bone defects demonstrate both radiographic healing and elevated expression of BMP-2 relative to control-treated defects. These results provide further insight into the potential mechanisms by which EPC therapy may promote fracture healing and provide further evidence to suggest that the trophic actions of EPC therapy may be a critical factor in their contribution to fracture healing.

Background: Prediction of negative postoperative outcomes after long-bone fracture treatment may help to optimize patient care. We recently completed the Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT), a large, multicenter trial of reamed and unreamed intramedullary nailing of tibial shaft fractures in 1226 patients. Using the SPRINT data, we conducted an investigation of baseline and surgical factors to determine any associations with an increased risk of adverse events within one year of intramedullary nailing., Methods: Using multivariable logistic regression analysis, we investigated fifteen baseline and surgical factors for any associations with an increased risk of negative outcomes., Results: There was an increased risk of negative events in patients with a high-energy mechanism of injury (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.05 to 2.35), a stainless steel compared with a titanium nail (OR = 1.52; 95% CI, 1.10 to 2.13), a fracture gap (OR = 2.40; 95% CI, 1.47 to 3.94), and full weight-bearing status after surgery (OR = 1.63; 95% CI, 1.00 to 2.64). There was no increased risk with the use of nonsteroidal anti-inflammatory agents, late or early time to surgery, or smoking status. Open fractures had a higher risk of events among patients treated with reamed nailing (OR = 3.26; 95% CI, 2.01 to 5.28) but not in patients treated with unreamed nailing (OR = 1.50; 95% CI, 0.92 to 2.47). Patients with open fractures who had wound management either without any additional procedures or with delayed primary closure had a decreased risk of events compared with patients who required subsequent, more complex reconstruction (OR = 0.18 [95% CI, 0.09 to 0.35] and 0.29 [95% CI, 0.14 to 0.62], respectively)., Conclusions: We identified several baseline fracture and surgical characteristics that may increase the risk of adverse events in patients with tibial shaft fractures. Surgeons should consider the predictors identified in our analysis to inform patients treated for tibial shaft fractures., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Purpose: The purpose of this article was to analyze the results of studies in the literature, which evaluated the use of endothelial progenitor cells (EPCs) as a cell-based tissue engineering strategy., Methods: EPCs have been successfully used in regenerative medicine to augment neovascularization in patients after myocardial infarction and limb ischemia. EPCs' important role as vasculogenic progenitors presents them as a potential source for cell-based therapies to promote bone healing., Results: EPCs have been shown to have prominent effects in promoting bone regeneration in several animal models. Evidence indicates that EPCs promote bone regeneration by stimulating both angiogenesis and osteogenesis through a differentiation process toward endothelial cell lineage and formation of osteoblasts. Moreover, EPCs increase vascularization and osteogenesis by increased secretion of growth factors and cytokines through paracrine mechanisms., Conclusion: EPCs offer the potential to emerge as a new strategy among other cell-based therapies to promote bone regeneration. Further investigations and human trials are required to address current questions with regard to biology and mechanisms of action of EPCs in bone tissue engineering.

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 × 10(6) 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.

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.

The objective of this study was to evaluate the effects of local endothelial progenitor cell (EPC) therapy on bone regeneration in a rat model. A segmental bone defect (5 mm) was created in the femur and fixed with a mini-plate. There were two groups: EPC-treated (N = 28) and control (N = 28). Seven animals were sacrificed from each group at 1, 2, 3, and 10 weeks postoperatively. Healing of the defect was evaluated with radiographic, histological, and quantitative micro-computed tomography (micro-CT) scans. Radiographically, mean scores of the EPC and control groups were, respectively, 1.16-0.61 (p < 0.05) at 1 week, 2.53-1.54 (p < 0.05) at 2 weeks, and 4.58-2.35 at 3 weeks (p < 0.05). At 10 weeks, all the animals in the EPC-treated group had complete union (7/7), but in the control group none achieved union (0/7). Histological evaluation revealed that specimens from EPC-treated animals had abundant new bone and vessel formation compared to that in controls. Micro-CT assessment of the samples from the animals sacrificed at 10 weeks (N = 14) showed significantly improved parameters of bone volume (36.58-10.57, p = 0.000), bone volume density (0.26-0.17, p = 0.000), model index -2.22-2.79, p = 0.000), trabecular number (1.28-0.91, p = 0.063), trabecular thickness (0.21-0.15, p = 0.001), trabecular spacing (0.63-1.07, p = 0.022), bone surface (353.75-152.08, p = 0.000), and bone surface to bone volume ratio (9.54-14.24, p = 0.004) for the EPC group compared to control, respectively. In conclusion, local EPC therapy significantly enhanced bone regeneration in a segmental defect model in rat femur diaphysis., (Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Low-intensity pulsed ultrasound (LIPUS) is a relatively new technique for the acceleration of fracture healing in fresh fractures and nonunions. It has a frequency of 1.5 MHz, a signal burst width of 200 micros, a signal repetition frequency of 1 kHz, and an intensity of 30 mW/cm2. In 1994 and 1997, two milestone double-blind randomized controlled trials revealed the benefits of LIPUS for the acceleration of fracture healing in the tibia and radius. They showed that LIPUS accelerated the fracture healing rate from 24% to 42% for fresh fractures. Some literature, however, has shown no positive effects. The beneficial effect of acceleration of fracture healing by LIPUS is considered to be larger in the group of patients or fractures with potentially negative factors for fracture healing. The incidence of delayed union and nonunion is 5% to 10% of all fractures. For delayed union and nonunion, the overall success rate of LIPUS therapy is approximately 67% (humerus), 90% (radius/radius-ulna), 82% (femur), and 87% (tibia/tibia-fibula). LIPUS likely has the ability to enhance maturation of the callus in distraction osteogenesis and reduce the healing index. The critical role of LIPUS for fracture healing is still unknown because of the heterogeneity of results in clinical trials for fresh fractures and the lack of controlled trials for delayed unions and nonunions.

Background: : The objective was to evaluate the newly developed Radiographic Union Score for Tibial fractures (RUST). Because there is no "gold standard," it was hypothesized that the RUST score would provide substantial improvements compared with previous scores presented in the literature., Methods: : Forty-five sets of X-rays of tibial shaft fractures treated with intramedullary fixation were selected. Seven orthopedic reviewers independently scored bony union using RUST. Radiographs were reassessed at 9 weeks. Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) measured agreement., Results: : Overall agreement was substantial (ICC, 0.86; 95% CI, 0.79-0.91). There was improved reliability among traumatologists compared with others (ICC = 0.86, 0.81, and 0.83, respectively). Overall intraobserver reliability was also substantial (ICC, 0.88; 95% CI, 0.80-0.96)., Conclusions: : The RUST score exhibits substantial improvements in reliability from previously published scores and produces equally reproducible results among a variety of orthopedic specialties and experience levels. Because no "gold standards" currently exist against which RUST can be compared, this study provides only the initial step in the score's full validation for use in a clinical context.

The measurement of clinical outcomes in trauma research is often problematic in that it is subjective and currently no feasible gold standard evaluation is available. Consequently, observed trial results are partly dependent on which outcome measure is used. Precise and useful estimates of treatment effects can only be obtained when using reliable, valid, and responsive instruments for measuring fracture healing. This overview outlines the concept of the validation of outcome measures and provides a summary of available and frequently used instruments in orthopaedic clinical trials. Outcome instruments can be divided into assessments by the clinician and assessments by the patient. Clinician-assessed measures are frequently used in routine practice but have often not been validated before their use in research. They include clinical and radiographic assessments. In contrast, patient-assessed measures have been designed specifically for investigational purposes and measure health on various domains. Some of them have been validated extensively. Critically evaluating established clinician-based assessments and integrating those found to be valid with patient-assessed outcomes into a composite measure of fracture healing constitute major future challenges.

Traumatic bone defects and nonunion represent a significant source of morbidity and socioeconomic burden in trauma patients. The treatment of these conditions is currently hampered by inadequate therapies. This has prompted a new era of investigation into biologic therapies for augmenting fracture healing. Within this body of research, gene therapy has arisen as a novel and effective method of delivering therapeutic proteins at a site of desired bone regeneration. Gene therapy has shown tremendous potential in preclinical studies of fracture healing, but to date, no clinical trials have occurred. This article reviews the scientific basis for gene therapy in fracture healing, provides an overview of important preclinical studies that have been performed to date, and discusses the current barriers and future directions of gene therapy as it applies to fracture healing.

Selecting the most appropriate outcome measures can be especially burdensome in trials studying fracture healing, because the process of fracture healing is subjective and without a gold standard. Although a wide variety of radiographic modalities are available, plain radiography remains the most common approach for healing assessment. Radiographic criteria, however, do not correlate well with fracture strength and stiffness. Additional challenges include a lack of consensus in what radiographic measures are most appropriate in the assessment of healing. In this article, we provide an overview of the most commonly used radiographic and clinical criteria for defining fracture healing. The validity and reliability of alternative approaches is also discussed.

The management of open fractures continues to be complicated by high rates of treatment failure and significant patient disability and dissatisfaction. The use of bone morphogenetic proteins (BMPs) in the treatment of open fractures has been assessed by a number of different clinical trials, both in the acute management of open fractures and in the delayed reconstruction of bone defects secondary to open fracture. This review describes the scientific basis for the use of BMPs in open fractures, reviews the current evidence for their use in open fractures, provides grades of recommendation for the different uses of BMPs in open fractures, and identifies important areas for additional research., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0 x 10(6) fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n = 9); control groups were treated with fibroblasts (Group 2) (n = 7), or saline (Group 3) (n = 7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p < 0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits.

Objective: We aimed to: 1). compare rates of in vitro bone formation following reamed and nonreamed intramedullary fixation in a murine model of femoral fracture healing; and 2). examine whether antibodies to insulin-like growth factor (IGF) I, IGF II, or indomethacin (an inhibitor of the inflammatory process) affect bone formation following intramedullary reaming., Design: Experimental study., Participants: Twenty-four C57 black mice were randomized to two groups: reamed ( = 12), and nonreamed intramedullary nail insertion ( = 12)., Intervention: In the reamed group, the femoral canals were successively reamed with 30-, 27-, 25-, and 23-gauge stainless steel pins and stabilized with a 27-gauge pin. In mice randomized to the nonreamed group, a 27-gauge pin was inserted. An external three-point bending force created a midshaft transverse femoral fracture. Seven days postsurgery, each mouse was killed, and the right femur was removed. Following pin removal, the callus was minced, the bone marrow was removed, and both were ultracentrifuged at 1200 rpm for 5 minutes. The supernatent was cocultured with 3-day-old murine calvarial cells in culture media. At day 5 of culture, reamed plasma and calvarial cell cocultures were exposed to either 1.0 micro g/mL of anti-IGF I, 1.0 micro g/mL of anti-IGF II, 2 micro M indomethacin, or served as controls (calvarial cells only). The cells were cultured for a total of 21 days., Main Outcome Measurements: The number of bone nodules was quantified by light microscopy., Results: Reamed pin insertion resulted in 4.1-fold and 8.9-fold increases in the mean number of bone nodules compared to pins inserted without reaming and controls, respectively (399 +/- 40.0 vs. 97.0 +/- 21.0, < 0.001). The positive effect of intramedullary reaming on bone nodule formation was reversed with the administration of antibodies to IGF I and IGF II. The addition of anti-IGF I or anti-IGF II to calvarial, or osteoblastlike, cells treated with supernatent from the callus and bone marrow of mice with prior intramedullary reaming resulted in significant declines in the mean number of bone nodules ( < 0.001). Specifically, treatment of osteoblastlike cells with anti-IGF I or anti-IGF II resulted in 7.0-fold and 5.4-fold declines in mean bone nodule formation compared to cells without such treatment., Conclusions: Intramedullary reaming prior to pin insertion resulted in a significantly greater number of bone nodules than pin insertion only. Antibodies to IGF I, IGF II, and indomethacin reversed the stimulatory effect of reaming on bone nodule formation, suggesting their role in modulating the course of fracture healing following intramedullary reaming.

Background: The assessment of fracture healing is both a clinically relevant and frequently used outcome measure following lower extremity trauma. However, it remains uncertain whether there is a consensus in the assessment of fracture healing among orthopaedic surgeons. Variability in the assessment of healing may have important implications in surgeons' decisions to intervene when they perceive fracture healing is slow to progress., Objective: To identify surgeons' approaches in the assessment of tibial fracture healing and the definitions of a delayed union, nonunion, and malunion among orthopaedic surgeons., Study Design: Cross-sectional survey of 577 orthopaedic surgeons., Methods: Focus groups, key informants, and sampling to redundancy strategies were used to develop a survey to examine surgeons' opinions in the assessment of tibial shaft fractures. Surgeons were asked how often the following variables were used in the assessment of fracture healing: (a) callus size; (b) cortical continuity; (c) progressive loss of fracture line; (d) pain with weight bearing; and (e) pain to palpation at the fracture site. Further, surgeons were asked to provide a time point beyond which a delayed union becomes a nonunion. Finally, surgeons specified their limits of acceptable fracture alignment (translation, shortening, rotation, varus/valgus, and procurvatum/recurvatum). The survey was pilot tested for clarity and content validity. This survey was mailed to 577 orthopaedic surgeons who were members of the Orthopaedic Trauma Association, American Academy of Orthopaedic Surgeons, and European-AO International-affiliated trauma centers., Results: Responses were obtained from 444 surgeons (response rate 77%). For each variable, the proportion of surgeons who always used the criterion ranged from 39.7% to 45.4%, and those who occasionally or never used the criterion ranged from 20.7% to 26.9%. Surgeons' definitions of delayed union ranged from 1 to 8 months, whereas definitions of nonunion ranged from 2 to 12 months. There was also variability in definitions of fracture malunion. Acceptable degrees of fracture shortening and translation ranged from less than 5 mm to greater than 15 mm. Surgeons' definitions of acceptable angular malunions (rotational, varus/valgus, and procurvatum/recurvatum) ranged from less than 5 degrees to 20 degrees., Conclusions: There is a lack of consensus in the assessment of fracture healing in tibial shaft fractures among orthopaedic surgeons. Varying definitions of nonunion and malunion may influence the decision to intervene in an effort to promote fracture healing and/or realign the fracture.

Objectives: To evaluate the effect of both high-pressure pulsatile lavage and bulb syringe irrigation on the biomechanical parameters of fracture healing using an in vivo open noncontaminated diaphyseal femoral fracture model in rats., Background: The utility of high-pressure pulsatile lavage irrigation on soft tissue debridement has been extrapolated to a similar perceived benefit in the debridement of bone. However, there have been several reports of a possible deleterious effect that high-pressure pulsatile lavage may have on bone architecture, intramedullary bacterial and contaminant seeding, and fracture healing. Although a previous in vivo histologic study suggests damage to bone architecture and impairment of early bone formation, it remains unclear whether these microscopic findings translate to a detectable decline in the biomechanical strength of the healing fracture. To our knowledge, there have been no reports of the in vivo effects high-pressure pulsatile lavage on fracture healing in open diaphyseal fractures., Materials and Methods: Using sterile technique, standard open transverse mid-shaft femur fractures were created in thirty-six rats randomized into three groups: a control group underwent retrograde intramedullary pinning only; a bulb syringe irrigation group and a high-pressure pulsatile lavage group underwent identical procedures as the control group, except that the osteotomy site was irrigated with bulb syringe irrigation and high-pressure pulsatile lavage, respectively, before insertion of the intramedullary pin. Six rats from each group were killed at three weeks and six weeks, and the femora was mechanically tested in bending., Results: Mechanical testing of the thirty-six femora revealed that the peak bending force (17.7 +/- 10.2 N) and stiffness (21.2 +/- 5.1 N/mm) of the healing fracture in the high-pressure irrigation group were significantly lower at three weeks when compared with the control (peak force, 28.1 +/- 5.9 N; stiffness, 31.4 +/- 5.8 N/mm) and the bulb syringe (peak force, 27.7 +/- 3.3 N; stiffness, 23.6 +/- 4.5 N/mm) irrigation groups (p < 0.05). The 37 percent lower peak bending force and 32 percent lower stiffness in the high-pressure pulsatile lavage group after three weeks of fracture healing were not present in the femora tested at six weeks. The high-pressure pulsatile lavage group did reveal a trend toward a lower peak bending force and stiffness after six weeks of fracture healing when compared with the control and bulb syringe irrigation groups, but the differences were not statistically significant at the 95 percent level., Conclusions: The use of high-pressure pulsatile lavage in open noncontaminated diaphyseal femur fractures in rats has a significant negative impact on the mechanical strength of the fracture callous during the early phases (three weeks) of fracture healing. However, it appears that the early deleterious effect of high-pressure pulsatile irrigation is not apparent in the late phases (six weeks) of fracture healing. Further study is required to evaluate the effect of high-pressure pulsatile lavage on fracture healing in the presence of wound contamination, fracture comminution, and soft tissue damage., Clinical Significance: The findings of this study suggest that selective use of high-pressure irrigation in the management of open fractures appears warranted. In situations in which high-pressure lavage may be deleterious to bone healing, alternative strategies that optimize bacterial removal from soft tissues while preserving bone architecture will need to be investigated.

Background: Extremity fractures are common, and most are managed operatively; however, despite successful reduction, up to half of patients report persistent post-surgical pain. Furthermore, psychological factors such as stress, distress, anxiety, depression, catastrophizing, and fear-avoidance behaviors have been associated with the development of chronic pain. The purpose of this pilot study was to examine the feasibility of a randomized controlled trial to determine the effect of in-person cognitive behavioral therapy (CBT) vs. usual care on persistent post-surgical pain among patients with a surgically managed extremity fracture. Methods: Eligible patients were randomized to either in-person CBT or usual care. We used four criteria to judge the composite measure of feasibility: 1) successful implementation of CBT at each clinical site, 2) 40 patients recruited within 6 months, 3) treatment compliance in a minimum 36 of 40 participants (90%), and 4) 32 of 40 participants (80%) achieving follow-up at one year. The primary clinical outcome was persistent post-surgical pain at one year after surgery. Results: Only two of the four participating sites were able to implement the CBT regimen due to difficulties with identifying certified therapists who had the capacity to accommodate additional patients into their schedule within the required timeframe (i.e., 8 weeks of their fracture). Given the challenges associated with CBT implementation, only one site was able to actively recruit patients. This site screened 86 patients and enrolled 3 patients (3.5%) over a period of three months. Participants were unable to comply with the in-person CBT, with no participants attending an in-person CBT session. Follow-up at one year could not be assessed as the pilot study was stopped early, three months into the study, due to failure to achieve the other three feasibility criteria. Conclusion: Our pilot trial failed to demonstrate the feasibility of a trial of in-person CBT versus usual care to prevent persistent pain after surgical repair of traumatic long-bone fractures and re-enforces the importance of establishing feasibility before embarking on definitive trials. Protocol modifications to address the identified barriers include the delivery of our intervention as a therapist-guided, remote CBT program. Trial registration: ClinicalTrials.gov (Identifier NCT03196258); Registered June 22, 2017, https://clinicaltrials.gov/ct2/show/NCT03196258 [ABSTRACT FROM AUTHOR]

• This review paper summarizes the results of English language literature biomechanically focused on acetabular fracture fixation methods. • It is necessary to standardized mechanical experimental method for biomechanical testing of the pelvis fracture. • The effect of fracture micromotion for optimal stability and early healing in pelvis and acetabular fractures is unknown. • More complicated acetabular fracture types that, such as posterior wall/posterior column complex fractures and transverse/posterior wall complex fractures, need to be addressed in a biomechanical research setting. Acetabular fractures are known as one of the most frequent types of pelvic fractures with growing frequency among elderly people. Because of this, it is important to establish the methods of repair that will produce optimal outcomes for fracture healing and joint remobilization. Open reduction and internal fixation are considered as the "gold standard" of acetabular fracture repair; however, to the best of authors' knowledge, there is no systematic review comparing different repair methods from biomechanical point of view. As such, in this review paper, we summarize the results of English language literature biomechanically focused on acetabular fracture fixation methods in the last thirty years with the aim to create a reference for clinical decision making. The selected literature within the review is broken down into categories based on type of fracture, i.e., simple or complex, and then further grouped based on fracture line orientation. Clinical recommendations and future research possibilities are also provided. [ABSTRACT FROM AUTHOR]

Background: Romosozumab is an antibody that binds and inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. A double-blinded, randomized, phase-2, dose-finding trial was performed to evaluate the effect of romosozumab on the radiographic and clinical outcomes of surgical fixation of tibial diaphyseal fractures.Methods: Patients (18 to 82 years old) were randomized 3:1:1:1:1:1:1:1:1:1 to a placebo or 1 of 9 romosozumab treatment groups. Patients received subcutaneous injections of romosozumab or the placebo postoperatively on day 1 and weeks 2, 6, and 12. The primary outcome was the time to radiographic evidence of healing ("radiographic healing") analyzed after the week-24 assessments had been completed for all patients.Results: A total of 402 patients were randomized: 299 to the romosozumab group and 103 to the placebo group. The median time to radiographic healing (the primary outcome) ranged from 14.4 to 18.6 weeks in the romosozumab groups and was 16.4 weeks (95% confidence interval [CI]: 14.6 to 18.0 weeks) in the placebo group, which was not a significant difference. There was also no significant difference in the median time to clinical healing, no relationship between romosozumab dose/frequency and unplanned revision surgery, and no apparent treatment benefit in terms of physical function. The safety and tolerability profile of romosozumab was comparable with that of the placebo.Conclusions: Romosozumab did not accelerate tibial fracture-healing in this patient population. Additional studies of patients at higher risk for delayed healing are needed to explore the potential of romosozumab to accelerate tibial fracture-healing.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Romosozumab is a bone-forming antibody that increases bone formation and decreases bone resorption. We conducted a double-blinded, randomized, phase-2, dose-finding trial to evaluate the effect of romosozumab on the clinical outcomes of open reduction and internal fixation of intertrochanteric or femoral neck hip fractures.Methods: Patients (55 to 94 years old) were randomized 2:3:3:3 to receive 3 subcutaneous injections of romosozumab (70, 140, or 210 mg) or a placebo postoperatively on day 1 and weeks 2, 6, and 12. The primary end point was the difference in the mean timed "Up & Go" (TUG) score over weeks 6 to 20 for romosozumab versus placebo. Additional end points included the time to radiographic evidence of healing and the score on the Radiographic Union Scale for Hip (RUSH).Results: A total of 332 patients were randomized: 243 to receive romosozumab (70 mg, n = 60; 140 mg, n = 93; and 210 mg, n = 90) and 89 to receive a placebo. Although TUG scores improved during the study, they did not differ significantly between the romosozumab and placebo groups over weeks 6 to 20 (p = 0.198). The median time to radiographic evidence of healing was 16.4 to 16.9 weeks across treatment groups. The RUSH scores improved over time across treatment groups but did not differ significantly between the romosozumab and placebo groups. The overall safety and tolerability profile of romosozumab was comparable with that of the placebo.Conclusions: Romosozumab did not improve the fracture-healing-related clinical and radiographic outcomes in the study population.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

This investigation assessed the biomechanical performance of the metal plate and bone strut technique for fixing recalcitrant nonunions of femur midshaft segmental defects, which has not been systematically done before. A finite element (FE) model was developed and then validated by experiments with the femur in 15 deg of adduction at a subclinical hip force of 1 kN. Then, FE analysis was done with the femur in 15 deg of adduction at a hip force of 3 kN representing about 4 x body weight for a 75 kg person to examine clinically relevant cases, such as an intact femur plus 8 different combinations of a lateral metal plate of fixed length, a medial bone strut of varying length, and varying numbers and locations of screws to secure the plate and strut around a midshaft defect. Using the traditional “high stiffness” femur-implant construct criterion, the repair technique using both a lateral plate and a medial strut fixed with the maximum possible number of screws would be the most desirable since it had the highest stiffness (1948 N/mm); moreover, this produced a peak femur cortical Von Mises stress (92 MPa) which was below the ultimate tensile strength of cortical bone. Conversely, using the more modern “low stiffness” femur-implant construct criterion, the repair technique using only a lateral plate but no medial strut provided the lowest stiffness (606 N/mm), which could potentially permit more in-line interfragmentary motion (i.e., perpendicular to the fracture gap, but in the direction of the femur shaft long axis) to enhance callus formation for secondary-type fracture healing; however, this also generated a peak femur cortical Von Mises stress (171 MPa) which was above the ultimate tensile strength of cortical bone. [ABSTRACT FROM AUTHOR]

B Correction: Trials 23, 894 (2022) b B https://doi.org/10.1186/s13063-022-06835-3 b Following publication of the original article [[1]], the authors identified an error in the authorship. Reference 1 Busse J. Cognitive Behavioural Therapy to Optimize Post-Operative Fracture Recovery (COPE): protocol for a randomized controlled trial. [Extracted from the article]

Introduction: The induced membrane technique (IMT) is a two-stage surgical procedure used to treat fracture nonunion and bone defects. Although there is an increasing number of animal studies investigating the IMT, few have examined the outcomes of bone healing after a second stage grafting procedure. This study aimed at comparing two bone grafting procedures, as part of the IMT, in order to establish a rat model providing consistent healing outcomes.Methods: In male Fischer 344 rats, we created a 5 mm defect in the right femur, stabilized the bone with a plate and screws, and inserted a polymethylmethacrylate spacer into the defect. Four weeks later, the spacer was removed. Bone graft was harvested from a donor rat and placed into the defect, followed by membrane and wound closure. Experiments were conducted in two groups. In group 1 (n = 11), the bone graft contained a variable amount of cortical and cancellous bone, the time from donor euthanasia to grafting was up to 240 min, and one donor rat provided graft for 5-6 recipients. In group 2 (n = 12), we reduced the contribution of cortical bone to the graft, included bone marrow, and kept donor euthanasia to grafting time under 150 min. One donor was used per 3-4 recipients. The volume of graft per recipient and all other elements of the protocol were the same across groups. Bone healing at 12 weeks post grafting was compared radiographically by two orthopaedic surgeons in a blinded fashion, based on union status and a modified Lane & Sandhu score.Results: Healing rates improved from 36.4% in Group 1 to 91.6% in Group 2. There was a significant relationship between the methods and resulting union status (p = 0.004). The odds of achieving full union were significantly higher in group 2 compared to group 1 (odds ratio=19.25, 95% confidence interval [1.77-209.55]; p = 0.009). The average radiographic score was also significantly higher in group 2 (p = 0.005).Conclusion: The revised bone grafting method significantly improved the healing outcomes and contributed to establishing a consistent rat model of the IMT. This model can benefit preclinical investigations by allowing for reliable and clinically-relevant comparisons. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of periprosthetic femoral fractures around total hip arthroplasties is increasing. Fractures around a stable implant stem (Vancouver type B1) are among the most common of these fractures. Various fixation strategies for Vancouver type B1 periprosthetic fractures have been reported in the literature; however, little high-level evidence exists. This study was designed to determine the current management strategies and opinions among orthopaedic surgeons treating Vancouver type B1 periprosthetic femoral fractures, and to evaluate the need for a large prospective randomized controlled trial for the management of these injuries.Methods: Orthopaedic surgeon members of the Orthopaedic Trauma Association (OTA), the Canadian Orthopaedic Association (COA), and the Hip Society were invited to participate in a 51-item web-based survey surrounding the management of periprosthetic femoral fractures around total hip replacements, as well as the perceived need for future research in this area. Responses were summarized using proportions, and further stratified by practice type, case volume, surgeon age, and fellowship training.Results: For Vancouver type B1 fractures, open reduction and internal fixation (ORIF) with locked plating was favoured slightly over ORIF with cable plating ± cortical strut allograft (51.1% versus 45.5%). When compared to cable plating with cortical strut allograft, respondents believed that isolated locked plating resulted in lower nonunion and reoperation rates, but similar infection and malunion rates. Subgroup analyses revealed that practice type, surgeon age, case volume, and fellowship training influenced surgeons' management of periprosthetic femoral fractures and beliefs regarding complications. There is high demand for a large prospective randomized controlled trial for Vancouver type B1 fracture fixation.Conclusions: Consensus surrounding the management of Vancouver type B1 periprosthetic femoral fractures is lacking, and there is a perceived need among orthopaedic surgeons for a large prospective randomized controlled trial in order to define the optimal management of these injuries. [ABSTRACT FROM AUTHOR]

Abstract: A large body of research has investigated the use of growth factors for bone regeneration, as a potential alternative to autogenous bone grafting. The bone morphogenetic proteins (BMPs) represent the most extensively investigated growth factors to date, as potential therapeutic agents for bone regeneration. Despite decades of research, the ideal growth factor or combination of growth factors for bone regeneration remains undefined. This article reviews the current available evidence for the application of growth factors for bone regeneration, with a focus on the clinical evidence for BMP use. Emerging pre-clinical and clinical evidence for growth factors other than the BMPs is also discussed. [Copyright &y& Elsevier]

Even the best-designed, randomized controlled trials suffer when patients are lost to follow-up. Incomplete follow-up biases the results of a trial when patients who drop out are different from those who complete follow-up. This is exaggerated further when there are differential dropout rates between study groups. Previous randomized controlled trials in orthopedic trauma have reported up to 28% loss to follow-up. Only by striving to achieve a 0% loss to follow-up rate can we be certain that this type of bias does not affect our results. In our ongoing multicenter, randomized controlled trial comparing reamed and nonreamed intramedullary nailing of tibial shaft fractures, we have implemented several innovative strategies to minimize loss to follow-up. The exclusion criteria and consent process are designed to minimize losses. Study staff are carefully trained in communication and negotiation with patients. Additionally, a central methods center monitors all patient follow-up and aids in finding lost patients. Through these primary, secondary, and tertiary interventions, we have achieved 94% complete 1-year follow-up for the first 440 patients enrolled in the trial. Eleven patients withdrew consent, and we are unable to locate 17 patients. We have successfully minimized the loss to follow-up rate in our trial by incorporating innovative prevention and retention strategies into its design and conduct. Through planning, organization, and committing time and resources to minimizing loss to follow-up, other orthopedic trauma trials can hope to achieve the same high rates of follow-up. [Copyright &y& Elsevier]