Reversed distal femoral locking plate for failed proximal femoral nail with non-union of proximal femoral fractures.

INTRODUCTION: Failure of proximal femoral fracture managed by proximal femoral nail (PFN) leads to a very difficult situation to handle with conventional techniques, and reversed distal femoral locking compression plate (DF-LCP) is of great benefit in these selective cases. METHODS: Twelve patients with ununited proximal femoral fractures including subtrochanteric fractures with a failed PFN implant were included in the study. All patients with periprosthetic fractures and fractures treated by implants other than PFN were excluded from this study. RESULT: All fractures went into union in an average time of nine months and 15 days with no implant failures. The mean time of re-osteosynthesis after the primary index surgery of PFN was one year eight months. Mean surgical time of re-osteosynthesis was 110 minutes, and average blood loss during surgery was 550 ml. DISCUSSION: The PFM is one of the most commonly used implant for unstable proximal femur fractures. The use of PFN is technically demanding and is associated with high failure rates. Although dynamic compression screw (DCS), proximal femoral locking plate (PF-LCP) and other implants can be used in these failed situations, they are associated with a high complication rate. The reversed DF-LCP is a rescue implant for these complex situations. Apart from anatomical and biomechanical advantages, there are several other clinical benefits of using DF-LCP. CONCLUSION: We conclude that DF-LCP is a potential and safe implant of choice for the management of nonunion associated with failed PFN. It may be considered an implant of choice as rescue from such a complex situation. It offers several anatomical, biomechanical and clinical advantages over other available conventional implants.

CGRP promotes osteogenic differentiation by regulating macrophage M2 polarization through HDAC6/AKAP12 signaling pathway.

Aim: To determine the mechanism of Calcitonin gene-related peptide (CGRP) in bone healing.Materials & methods: Alkaline phosphatase (ALP) activity and inflammatory-factor levels were detected using ELISA. Osteogenic differentiation was assessed using Alizarin red staining technique. The interaction between histone deacetylase 6 (HDAC6) and A-kinase anchoring protein 12 (AKAP12) was investigated through Co- immunoprecipitation.Results: CGRP treatment promoted rat bone marrow-derived macrophages (BMDMs) M2 polarization. CGRP facilitated osteogenic differentiation by enhancing M2 polarization of BMDMs. Mechanistically, CGRP promoted AKAP12 acetylation to activate the extracellular regulated protein kinases pathway by HDAC6 inhibition.Conclusion: CGRP promoted M2 polarization of rat BMDMs and facilitated osteogenic differentiation through the HDAC6/AKAP12/extracellular regulated protein kinases signaling pathway, thereby promoting bone healing.

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Surgical Reconstruction of Canine Nonunion Fractures Using Bone Morphogenetic Protein-2-loaded Alginate Microbeads and Bone Allografts.

BACKGROUND/AIM: Effective treatment of nonunion fractures is challenging as it requires a biological and mechanical environment to promote sufficient osteogenesis. Herein, we present a case series in which we evaluated the clinical efficacy of bone morphogenetic protein-2 (BMP-2)-loaded alginate microbeads and allografts in two dogs with nonunion fractures. CASE REPORT: A 3-year-old, 2.3-kg, spayed female Pomeranian (Case 1) presented with intermittent lameness of the left forelimb after radial and ulnar fracture repair 8 weeks prior. A 4-year-old, 4.8-kg, spayed female Pomeranian (Case 2) was referred for non-weight-bearing lameness of the left hindlimb due to implant failure following left tibial fracture repair. Both dogs had atrophic bone ends and no bridging calluses at the fracture site on radiographs, and were diagnosed with nonviable nonunion fractures of the radius/ulna and tibia, respectively. The surgical approach involved implant removal, debridement, and fracture gap reconstruction. BMP-2 was loaded into alginate microbeads for a prolonged release with bone allograft chips in both cases. In Case 1, bead grafts were applied directly at the fracture site, while in Case 2, they were implanted inside a frozen cortical bone allograft as a scaffold to fill the large gap. Postoperative radiography revealed excessive callus formation, early radiographic bone union, and cortical bone remodeling, in line with improved lameness scores. At the final follow-up, gait was improved and the desired bone length and shape were achieved in both cases. CONCLUSION: Simultaneous use of osteoinductive BMP-2 alginate microbeads and osteoconductive bone allografts yielded functionally and structurally favorable outcomes in canine nonunion fractures, without major complications.

Stem Cells and Their Derivatives: An Implication for the Regeneration of Nonunion Fractures.

Despite advances in biomedical research, fracture nonunion rates have remained stable throughout the years. Long-bone fractures have a high likelihood of nonunion, but the specific biological pathways involved in this severe consequence are unknown. Fractures often heal in an organized sequence, including the production of a hematoma and an early stage of inflammation, the development of a soft callus and hard callus, and eventually the stage of bone remodeling. Deficient healing can result in a persistent bone defect with instability, discomfort, and loss of function. In the treatment of nonunions, mesenchymal stem cells (MSCs) prove to be a promising and safe alternative to the standard therapeutic strategies. Moreover, novel scaffolds are being created in order to use a synergistic biomimetic technique to rapidly generate bone tissue. MSCs respond to acellular biomimetic matrices by regenerating bone. Extracellular vesicles (EVs) derived from MSCs have recently gained interest in the field of musculoskeletal regeneration. Although many of these techniques and technologies are still in the preclinical stage and have not yet been approved for use in humans, novel approaches to accelerate bone healing via MSCs and/or MSC derivatives have the potential to reduce the physical, economic, and social burdens associated with nonhealing fractures and bone defects. In this review, we focus on providing an up-to-date summary of recent scientific studies dealing with the treatment of nonunion fractures in clinical and preclinical settings employing MSC-based therapeutic techniques.

Pediatric Humeral Shaft Fracture Nonunion: A Case Report.

Humeral shaft fractures in the pediatric population are a commonly encountered injury in everyday practice. Most patients with these injuries are treated without surgery and go on to have an uneventful recovery. Nonunion of these injuries in the pediatric population has been reported only once in the literature. This case report follows a 13-year-old female after a seemingly standard transverse humeral shaft fracture. The patient was treated with a fracture brace initially. No signs of healing were noted at the eight-week post-injury follow-up. The family elected for continued conservative management until the patient returned at four months post-injury with persistent gross motion at the fracture site and no healing on radiographs. Laboratory testing did show that she has mild-to-moderate vitamin D deficiency, which was addressed. The patient underwent nonunion treatment with open reduction, internal fixation, and bone grafting. She went on to full union with an uncomplicated postoperative course. This case presents an interesting and unique case presentation. This report shows that, while rare, it is a potential outcome of humeral shaft fractures in the pediatric population. This case also demonstrates that using the standard adult operative technique for nonunion treatment with rigid internal fixation and bone grafting in a pediatric patient will lead to full-bone healing.

Using Teriparatide to Augment Healing in a Humeral Shaft Nonunion: A Case Report.

The occurrence of complications of fracture healing, such as delayed union and nonunion, is well known, but the use of pharmacotherapy for these delayed unions and nonunions has not been explored in detail. The authors describe a case of traumatic humeral shaft fracture successfully treated with once-daily administration of 20mcg of teriparatide for six months. The patient was a 22-year-old male who had been through a road traffic accident. The radiograph of the humerus shaft showed a fracture line and the displaced distal portion of the shaft of the humerus. Based on these features, the patient was diagnosed with a humeral shaft fracture. The patient underwent internal fixation with a dynamic compression plate. However, there were no signs of callus formation even after 12 weeks from the time of internal fixation. The patient was initiated with teriparatide administration and union was achieved after six months of a once-daily administration of teriparatide. Once-daily teriparatide treatment is shown to be beneficial for improving the healing of humeral shaft fractures showing delayed union.

Intercalary Tricortical Iliac Crest Graft for Treatment of Midclavicle Nonunion With Bone Loss: Two Case Reports and Review of Literature.

Several articles support the use of cancellous iliac crest bone grafting in the treatment of clavicle nonunion; however, there is very little literature on the use of tricortical iliac crest grafts in the setting of clavicle nonunion with bone loss. When it has been studied, tricortical grafting has been shown to produce radiologically confirmed union in the clavicle, leaving patients satisfied with the ultimate outcome. We present two cases of clavicle fracture nonunion successfully treated with tricortical interposition bone grafting. In the first case, a 45-year-old female presented with an atrophic left midshaft clavicle fracture nonunion with failed hardware that had undergone two previous attempts at fixation without achieving union. She was treated with a structural interposition iliac crest bone graft with plate fixation and regained full painless function of the arm with radiographic fracture union. In the second case, a 50-year-old male presented after a left midshaft clavicle fracture that had undergone acute stabilization, followed by revision for nonunion that was unsuccessful, resulting in persistent nonunion with bone loss. He was treated with a tricortical iliac crest bone graft and plate fixation. Cultures from the time of surgery did grow Staphylococcus epidermidis and Propionibacterium acnes, and he was treated with intravenous vancomycin for six weeks. The patient's clavicle went on to union and he regained full, painless function by his six-month follow-up visit. These cases demonstrate the use of tricortical interposition bone grafting with compression plating as a viable option for rare instances in which previous surgical intervention has failed to progress a midshaft clavicle fracture to union.

Nonunion of Hoffa Fracture Successfully Treated by Total Knee Arthroplasty: A Case Report.

A Hoffa fracture is a rare type of femoral fracture that is difficult to treat. Nonoperative treatments usually result in failure; hence, in most cases, surgical treatments are essential. Nonunion following Hoffa fracture appears to be relatively uncommon, and there are limited reports in the literature about this type of nonunion. These reports suggest that open reduction and rigid internal fixation is the standard treatment for this type of nonunion. This study reports the case of a 61-year-old male patient who suffered from left lateral Hoffa fracture after falling from a truck bed. At the former hospital, open reduction and internal fixation were performed with plates and screws at 8 days post-injury. Postoperatively, displacement of the lateral proximal fragment was observed, and the patient reported left knee pain. Therefore, a revision open reduction and internal fixation was performed 4 months post-surgery. However, 6 months after the revision surgery, the patient reported instability and pain in the left knee, and subsequent radiography revealed nonunion of the fracture in the lateral condyle. The patient was referred to our hospital for further treatment. Treatment by re-revision open reduction and internal fixation was deemed challenging, and so rotating hinge knee (RHK) arthroplasty was performed as a salvage treatment. At 3 years post-surgery, no significant problems were observed, and the patient could walk without any assistance. The range of motion of the left knee was 0 to 100° without extension lag, and there was no lateral instability. Standard treatment for Hoffa fracture nonunion is commonly anatomical reduction and rigid internal fixation. However, total knee arthroplasty may be a better option for the treatment of Hoffa fracture nonunion in older patients.

Non-union of Conservatively Managed Radial Neck Fractures in Adults: A Systematic Review.

Non-union of radial neck fractures in adults is rare. This review aims to identify factors contributing to the non-union of undisplaced radial neck fractures and assess treatment options and outcomes. Systematic searches of English articles in PubMed, Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were undertaken in September 2021 according to the PRISMA guidelines. The search terms were (fracture) AND (radial neck) AND (non-union OR non-union). Eligible studies reported adults who experienced undisplaced radial neck fractures that went on to non-union without prior surgical intervention. Fifteen case reports/series were included involving 29 non-unions in 27 patients. The largest study included eight patients. There were 11 males (38%) and 18 females (62%). The average age at the time of the presentation was 55 (range: 29-73). In 13 cases, comorbidities were commented on, including association with smoking in 4 (30%), diabetes in 3 (23%), and excessive alcohol in 5 (38%). The average time from injury to a diagnosis of non-union was 6.7 (range: 2-24) months. The average time of follow-up was 28.6 (range:6-84) months. Eight minimally symptomatic or asymptomatic non-unions were managed conservatively without complication. Seventeen symptomatic non-unions were managed operatively. Treatments included open fixation (1), open fixation with bone grafting (1), bone grafting alone (2), arthroplasty (2), radial head resection (2), and unknown surgery (7). Patients managed operatively achieved full or near-full, asymptomatic range of motion at an average of 5.4 (3-12) months postoperatively. Non-union is a rare complication of an adult radial neck fracture, and risk factors may include female gender, smoking, diabetes, and chronic alcohol. Persistence with non-operative management is encouraged as it can resolve symptoms with or without a radiographic union. Operative options range from bone grafting +/- fixation to arthroplasty. On average, the time from injury to the decision made to operate is 6.5 (3-12) months. A comfortable, functional range of motion is possible with all treatment strategies.

Autologous tendon graft for non-union distal clavicle fracture in a patient with chronic kidney disease.

BACKGROUND: Fracture of distal-end accounts for 20% of all clavicle fracture. In the situation of impaired bone healing environment such as chronic kidney disease (CKD), nonunion rates after surgery might increase. In the case where bone healing is unexpected, biological healing with tendon graft could be an alternative method to maintain bone reduction. PRESENTATION OF CASE: A 62-year old male with a history of end-stage CKD presented to the hospital with pain, wound, and deformity on the right shoulder. The patient have had surgery in the past 4 months and resulted in a non-union fracture of the distal third right clavicle. The patient underwent implant removal and continued with coracoclavicular ligament reconstruction with autologous tendon grafts of semitendinosus tendon and mini-plate augmentation. DISCUSSION: The Distal clavicle has a high rate of delayed and nonunion even without the presence of comorbidity. A compromised bone quality frequently leads to failed osteosynthesis in patients with end-stage renal failure. In the advanced stages of kidney disease, problems with a renal clearance of phosphate and low 1ɑ-hydroxylase levels resulting in increased serum phosphate levels and low serum calcium levels. Given these circumstances, we considered the idea to maintain fracture reduction by biologic soft tissue healing of the graft to replace the coracoclavicular ligaments as we can not rely on normal bone strength and healing capacity. CONCLUSION: In the situation where bone healing is unexpected, biological healing with tendon graft may be necessary. The use of autologous tendon graft and mini-plate suture augmentation could help to maintain bone reduction in such environment.

Fracture healing physiology and the quest for therapies for delayed healing and nonunion.

Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses. However, untreated control animals in most of these studies also demonstrate robust structural and biomechanical healing, leaving unclear how these interventions might alter the healing of recalcitrant fractures in humans. This review describes the physiology of fracture healing, with a focus on aspects of natural repair that may be pharmacologically augmented to prevent or treat delayed or nonunion fractures (collectively referred to as DNFs). The agents covered in this review include recombinant BMPs, PTH/PTHrP receptor agonists, activators of Wnt/ß-catenin signaling, and recombinant FGF-2. Agents from these therapeutic classes have undergone extensive preclinical testing and progressed to clinical fracture healing trials. Each can promote bone formation, which is important for the stability of bridged calluses, and some but not all can also promote cartilage formation, which may be critical for the initial bridging and subsequent stabilization of fractures. Appropriately timed stimulation of chondrogenesis and osteogenesis in the fracture callus may be a more effective approach for preventing or treating DNFs compared with stimulation of osteogenesis alone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:213-223, 2017.

Collagen sponge functionalized with chimeric anti-BMP-2 monoclonal antibody mediates repair of nonunion tibia defects in a nonhuman primate model: An exploratory study.

Recombinant human bone morphogenetic protein (BMP)-2 is an FDA-approved therapy for nonunion tibia fracture, though it has a number of biological and practical disadvantages. Our research group has developed a novel tissue engineering strategy termed antibody-mediated osseous regeneration. This entails application of anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMP's to mediate in vivo bone formation. This has been documented in a number of animal models. The present exploratory study sought to investigate the application of antibody-mediated osseous regeneration for repair of nonunion tibia defect in a nonhuman primate model. A 20 mm segmental osteotomy was performed in tibia of 6 Macaca fascicularis and was implanted with absorbable collagen sponge that was functionalized with chimeric anti-BMP-2 or isotype matched control mAb. Cone beam computed tomography (CBCT), histologic and histomorphometric analyses were performed 12 weeks post-operatively. CBCT analyzed by quantitative 3D volumetric analysis revealed that sites implanted with absorbable collagen sponge functionalized with anti-BMP-2 mAb demonstrated numerically higher mineralized tissue (408 ± 127 mm3) compared with sites implanted with isotype matched control mAb (214 ± 81 mm3), though the difference was not statistically significant ( p = 0.09). Histologic and histomorphometric analysis showed de novo bone formation with greater ( p < 0.01) percentage of bone volume in sites implanted with anti-BMP-2 (41.3 ± 4.4%), compared with isotype matched control mAb (14.6 ± 5.6%). Results from the present exploratory study provide evidence for the potential of anti-BMP-2 mAb to mediate repair of a large segmental tibia defects in a nonhuman primate model. Therapeutic antibodies have generally been shown to have great safety and efficacy profile, though their application in tissue engineering has been limited in the past. Following further investigation, anti-BMP-2 mAbs immobilized on appropriate scaffold may have application in repair of large skeletal defects without the need for exogenous growth factors.

Reverse distal femoral locking compression plate a salvage option in nonunion of proximal femoral fractures.

BACKGROUND: When primary fixation of proximal femoral fractures with implants fails, revision osteosynthesis may be challenging. Tracts of previous implants and remaining insufficient bone stock in the proximal femur pose unique problems for the treatment. Intramedullary implants like proximal femoral nail (PFN) or surface implants like Dynamic Condylar Screw (DCS) are few of the described implants for revision surgery. There is no evidence in the literature to choose one implant over the other. We used the reverse distal femur locking compression plate (LCP) of the contralateral side in such cases undergoing revision surgery. This implant has multiple options of fixation in proximal femur and its curvature along the length matches the anterior bow of the femur. We aimed to evaluate the efficacy of this implant in salvage situations. MATERIALS AND METHODS: Twenty patients of failed primary proximal femoral fractures who underwent revision surgery with reverse distal femoral locking plate from February 2009 to November 2012 were included in this retrospective study. There were 18 subtrochanteric fractures and two ipsilateral femoral neck and shaft fractures, which exhibited delayed union or nonunion. The study included 14 males and six females. The mean patient age was 43.6 years (range 22-65 years) and mean followup period was 52.1 months (range 27-72 months). Delayed union was considered when clinical and radiological signs of union failed to progress at the end of four months from initial surgery. RESULTS: All fractures exhibited union without any complications. Union was assessed clinically and radiologically. One case of ipsilateral femoral neck and shaft fracture required bone grafting at the second stage for delayed union of the femoral shaft fracture. CONCLUSIONS: Reverse distal femoral LCP of the contralateral side can be used as a salvage option for failed fixation of proximal femoral fractures exhibiting nonunion.

Dynamic acoustic radiation force retains bone structural and mechanical integrity in a functional disuse osteopenia model.

Disuse osteopenia and bone loss have been extensively reported in long duration space mission and long term bed rest. The pathology of the bone loss is similar to osteoporosis but highly confined to weight bearing bones. The current anabolic and/or anti-resorptive drugs have systemic effects and are costly over extended time, with concerns of long term fracture risk. This study use Low Intensity Pulsed Ultrasound (LIPUS) as a non-invasive acoustic force and anabolic stimulus to countermeasure disuse induced bone loss. Four-month old C57BL/6 mice were randomized into five groups, 1) age-matched (AM), 2) non-suspended sham (NS), 3) non-suspended-LIPUS (NU), 4) suspended sham (SS), and 5) suspended-LIPUS (SU) groups. After four weeks of suspension, µCT analyses showed significant decreases in trabecular bone volume fraction (BV/TV) (-36%, p<0.005), bone tissue mineral density (TMD) (-3%, p<0.05), trabecular thickness (Tb.Th) (-12.5%, p<0.005), and increase in bone surface/bone volume (+BS/BV) (+16%, p<0.005), relative to age-matched (AM). The application of LIPUS for 20 min/day for 5 days/week, significantly increased TMD (+3%, p<0.05), Tb.Th (+6%, p<0.05), and decreased BS/BV (-10%, p<0.005), relative to suspension alone (SS) mice. Histomorphometry analyses showed a breakdown of bone microstructure under disuse conditions consist with µCT results. In comparison to SS mice, LIPUS treated bone showed increased structural integrity with increased bone formation rates at metaphysical endosteal and trabecular surfaces (+0.104±0.07 vs 0.031±0.30 µm(3)/µm(2)/day) relative to SS. Four-point bending mechanical tests of disused SS femurs showed reduced elastic modulus (-53%, p<0.05), yield (-33%, p<0.05) and ultimate strength (-45%, p<0.05) at the femoral diaphysis relative to AM bone. LIPUS stimulation mitigated the adverse effects of disuse on bone elastic modulus (+42%, p<0.05), yield strength (+29%, p<0.05), and ultimate strength (+39%, p<0.05) relative to SS femurs. LIPUS provides the essential mechanical stimulus to retain bone morphological and mechanical integrity in disuse conditions. This study demonstrates LIPUS potential as regional therapeutic agent to countermeasure disuse induced bone loss while maintaining bone's integrity.

Treatment of antebrachial and crural septic nonunion fractures in dogs using circular external skeletal fixation: a retrospective study.

OBJECTIVE: To evaluate the outcome of treatment of antebrachial and crural septic non-union fractures in dogs using circular external skeletal fixation (CESF), and to document the type and frequency of complications associated with this technique. METHODS: The medical records of all dogs with infected antebrachial and crural non-union fractures treated using the methods of Ilizarov at the Department of Animal Pathology of the University of Turin between 2006 and 2011 were retrospectively reviewed. Only dogs in which radiographic and clinical assessment were available at the time of CESF removal were included in the study. RESULTS: Twenty-three dogs met the inclusion criteria. Twenty nonunion fractures treated with CESF healed and three did not. The latter three cases underwent amputation of the affected limb. In the 20 dogs that achieved bone union, six had minor complications and five had major complications. The mid-term outcome was judged to be excellent (n = 11), good (n = 6), fair (n = 2), or poor (n = 4). CONCLUSIONS: The results of this study support the use of CESF for the management of antebrachial and crural septic nonunion fractures in dogs. Union was achieved in the majority of dogs and the complication rate was acceptable, considering the severity of the nonunion fractures that were managed in this fashion.

Existence of mesenchymal stem cellsin sites of atrophic nonunion.

OBJECTIVES: Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest. METHODS: We enrolled five patients with neglected atrophic nonunions of long bones confirmed by clinical examinations and plain radiographs into this study. As much as 10 ml bone marrow aspirate was obtained from both the nonunion site and the iliac crest and cultured for three weeks. Cell numbers were counted using a haemocytometer and vitality of the cells was determined by trypan blue staining. The cells were confirmed as MSCs by evaluating their expression marker (CD 105, CD 73, HLA-DR, CD 34, CD 45, CD 14, and CD 19). Cells number and viability were compared between the nonunion and iliac creat sites. RESULTS: After three weeks, numbers of 6.08×10(6) cells (sd 2.07) and 4.98×10(6) cells (sd 1.15) were obtained from the nonunion site and the iliac crest, respectively, with viability of 87.1% (81.7% to 90.8%) and 89.8% (84.7% to 94.5%), respectively. No differences was found between the two sources of MSCs regarding cells number (p = 0.347) and viability (p = 0.175). CONCLUSIONS: Our findings showed the existence of MSCs in the site of atrophic nonunion, at a similar number and viability to those isolated from the iliac crest.