Treatment Of Long Bone Nonunion Research Articles

Bone marrow aspirate and bone marrow aspirate concentrate: Does the literature support use in long-bone nonunion and provide new insights into mechanism of action?

To assess the use of bone marrow aspirate (BM) and bone marrow aspirate concentrate (BMAC) in the treatment of long-bone nonunion and to understand mechanism of action. A systematic review of PubMed and EBSCOHost was completed to identify studies that investigated the use of BM or BMAC for the diagnosis of delayed union and/or nonunion of long-bone fractures. Studies of isolated bone marrow-mesenchymal stem cells (BM-MSCs) and use in non-long-bone fractures were excluded. Statistical analysis was confounded by heterogeneous fracture fixation methods, treatment history, and scaffold use. Our initial search yielded 430publications, which was screened down to 25studies. Successful treatment in aseptic nonunion was reported at 79-100% (BM) and 50-100% (BMAC). Septic nonunion rates were slightly better at 73-100% (BM) and 83.3-100% (BMAC). 18/24 studies report union rates > 80%. One study reports successful treatment of septic nonunion with BMAC and no antibiotics. A separate study reported a significant reduction in autograft reinfection rate when combined with BMAC (P = 0.009). Major adverse events include two deep infections at injection site and one case of heterotopic ossification. Most studies note transient mild donor site discomfort and potential injection site discomfort attributed to needle size. The current literature pertaining to use of BM/BMAC for nonunion is extremely heterogeneous in terms of patient population and concomitant treatment modalities. While results are promising for use of BM/BMAC with other gold standard treatment methodologies, the literature requires additional Level I data to clarify the impact of role BM/BMAC in treating nonunion when used alone and in combination with other modalities. Level III.

Efficacy and safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with autologous bone for the treatment of long bone nonunion: A report of a prospective case series

IntroductionRecombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection. Materials and MethodsThis was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies. ResultsOf the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed. ConclusionBMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients.

Comparison of reamer irrigator aspirator (RIA) suspension versus bone marrow aspirate concentrate (BMC) for percutaneous treatment of long bone nonunions—A preclinical canine model

ObjectiveTo compare the bone healing effects of percutaneously delivered bone marrow aspirate concentrate (BMC) versus reamer irrigator aspirator (RIA) suspension in a validated preclinical canine ulnar nonunion model. We hypothesized that BMC would be superior to RIA in inducing bone formation across a nonunion site after percutaneous application. The null hypothesis was that BMC and RIA would be equivalent. MethodsA bilateral ulnar nonunion model (n= 6; 3 matched pairs) was created. Eight weeks after segmental ulnar ostectomy, RIA from the ipsilateral femur and BMC from the proximal humerus were harvested and percutaneously administered into either the left or right ulnar defect. The same volume (3 ml) of RIA suspension and BMC were applied on each side. Eight weeks after treatment, the dogs were euthanized, and the nonunions were evaluated using radiographic, biomechanical, and histologic assessments. ResultsAll dogs survived for the intended study duration, formed radiographic nonunions 8 weeks after segmental ulnar ostectomy, and underwent the assigned percutaneous treatment. Radiographic and macroscopic assessments of bone healing at the defect sites revealed superior bridging-callous formation in BMC-treated nonunions. Histologic analyses revealed greater amount of bony bridging and callous formation in the BMC group. Biomechanical testing of the treated nonunions did not reveal any significant differences. ConclusionBone marrow aspirate concentrate (BMC) had important advantages over Reamer Irrigator Aspirator (RIA) suspension for percutaneous augmentation of bone healing in a validated preclinical canine ulnar nonunion model based on clinically relevant radiographic and histologic measures of bone formation.

Erratum

Journal of Tissue Engineering and Regenerative MedicineVolume 16, Issue 8 p. 771-771 ERRATUMFree Access Erratum This article corrects the following: Erratum Volume 16Issue 8Journal of Tissue Engineering and Regenerative Medicine pages: 771-771 First Published online: August 5, 2022 Correction(s) for this article Erratum Volume 16Issue 8Journal of Tissue Engineering and Regenerative Medicine pages: 771-771 First Published online: August 5, 2022 First published: 05 August 2022 https://doi.org/10.1002/term.3336AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat In the article entitled “Minimally invasive treatment of long bone non-unions with bone marrow concentrate, demineralized bone matrix and platelet-rich fibrin in 38 patients” (Cevolani et al., 2021), one of the co-authors’ first name and surname appeared in the wrong order. His name has been corrected as follows: Costantino Errani (Cevolani et al., 2021). REFERENCE Cevolani, L., Bianchi, G., Errani, C., Staals, E., Lucarelli, E., Spazzoli, B., Frisoni, T., & Donati, D. M. (2021). Minimally invasive treatment of long bone non-unions with bone marrow concentrate, demineralized bone matrix and platelet-rich fibrin in 38 patients. Journal of Tissue Engineering and Regenerative Medicine, 15(10), 831– 840. https://doi.org/10.1002/term.3231 Volume16, Issue8August 2022Pages 771-771 ReferencesRelatedInformation

Cortical allograft strut augmented with platelet-rich plasma for the treatment of long bone non-union in lower limb- a pilot study

BackgroundThe autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb.MethodThis study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up.ResultsFourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18–56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication.ConclusionCortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use.

Preliminary outcomes of the combination of demineralized bone matrix and platelet Rich plasma in the treatment of long bone non-unions

BackgroundA variety of bone graft substitutes have been introduced into the treatment of bone non-unions. However, clinical outcomes from current evidences are various and conflicting. This study aimed to present the preliminary outcomes of a treatment protocol in which the combination of demineralized bone matrix (DBM) and platelet rich plasma (PRP) was used as a bone graft substitute for long bone non-unions.MethodsData of this retrospective study were reviewed and collected from a consecutive case series involving 43 patients who presented with a long bone non-union and were treated in our department from October 2018 to May 2019. The combination of DMB and PRP was applied as a bone defect filler in 16 patients, whilst the other 27 patients were treated with iliac bone autografting. Patients’ demographics, postoperative complications and the result of bone union were compared and evaluated.ResultsThe demographic data between the two groups were comparable. No significant difference was found with regard to the incidence of postoperative complications. No graft rejection, heterotopic ossification or other complications were noted. The distribution of bony healing time was rather scattered but did not differ significantly between the groups (7.533 ± 3.357 months vs. 6.625 ± 2.516 months; P=0.341). Union was identified radiographically in 15 of 16 patients in the DBM+PRP group and in 24 of 27 patients in autograft group.ConclusionsThe present study identified that low incidence of postoperative complications and satisfactory bony healing rate could be achieved in the treatment of long bone non-unions augmented with the combination of DBM and PRP. Although these findings might indicate the promising future of this treatment protocol, larger and higher quality studies should also be executed to assess its routine use.

Effect of Bone Morphogenetic Protein-2 in the Treatment of Long Bone Non-Unions.

Background: Delayed fracture healing continues to cause significant patient morbidity and an economic burden to society. Biological stimulation of non-unions includes application of recombinant bone morphogenetic protein-2 (rhBMP-2). However, rhBMP-2 use continues to be a matter of controversy as literature shows scarce evidence for treatment effectiveness. Questions: The objective of this study was to evaluate the effectiveness of rhBMP-2 treatment on long bone non-unions measuring union rate and time to union. Furthermore, we assess risk factors for treatment failure. Methods and patients: A total of 91 patients with non-unions of long bones were treated with rhBMP-2 (n = 72) or standard care without BMP (n = 19) at our institution. Patient characteristics, comorbidities, nicotine consumption, and complications were recorded. Bone healing was assessed by plane X-rays and clinical examination. Patients were followed up with for 24 months. Results: Overall, there was significantly faster bone healing after rhBMP-2 application compared to the no-BMP group (p < 0.001; HR = 2.78; 95% CI 1.4–5.6). Union rates differed significantly between rhBMP-2 compared to the no-BMP group (89% vs. 47%; p < 0.001). At the humerus, there was neither a significantly higher union rate in the rhBMP-2 (83%) compared to the no-BMP group (50%) (p = 0.26; n = 12) nor a faster bone healing with a median time of 9 months in both groups (HR = 2.01; 95% CI 0.49–8.61; p = 0.315). The 33 femora treated using rhBMP-2 healed significantly faster than 9 femora in the no-BMP group (HR = 2.93; 95% CI 1.00–8.4; p = 0.023) with significant differences in union rate with 85% and 44%, respectively (p = 0.022). Regarding tibia non-unions, 25 out of 27 (93%) healed with a median of 9 months after rhBMP-2 application with no significant difference in the no-BMP group (33%) in time to union (p = 0.097) but a significantly higher union rate (p = 0.039). There was no effect of comorbidities, age, sex, soft tissue damage, or nicotine use on time to union, union rate, or secondary interventions. Conclusion: Consistent with the literature, overall, significantly higher union rates with reduced time to union were achieved after rhBMP-2 application. Femoral and tibial non-unions in particular seem to profit from rhBMP-2 application.

Long-term patient-related quality of life after successfully treated aseptic non-unions of the long bones

BackgroundNon-union after fracture depicts a devastating complication in trauma surgery and studies assessing patient-reported outcome measures after stable bone consolidation are rare. Therefore, we aimed to evaluate the long-term impact of aseptic long bone non-union on the patients’ physical health state and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of long bone non-union was assessed. MethodsSixty-one patients with aseptic long bone non-union surgically treated in our department between November 2009 and March 2019 with achieved bone consolidation were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data. ResultsWith a minimum follow-up time of one year after the last surgery (mean 4.7 ± 2.7 years) the mean physical health component score of the SF-36 was 38.9 ± 13.7 and the mean mental health component score of the SF-36 was 49.0 ± 5.9, indicating lower quality of life compared to German normative values of 48.4 ± 9.4 (p < .001) and 50.9 ± 8.8 (p = 1.61), respectively. The mean EQ-5D index value reached 0.827 ± 0.18 with an EQ-5D VAS rating of 64.4 ± 21.5 compared to scores of 0.922 (p < .001) and 72.9 ± 1.1 (p < .001) obtained from an age-matched reference population. Mean scores of the ISR did not reveal significant psychological symptom burden in any scale, while an individual analysis showed moderate to severe impairments in 11.5% of the patients in total. ConclusionEven 4.7 years on average after surgically successful treatment of aseptic long bone non-union, patients still report significant lower quality of life in comparison to normative data. Future clinical studies on non-unions should focus on patient-related outcome measures. Newly emerging treatment strategies and interdisciplinary approaches should be implemented to improve the overall quality of life of non-union patients.

Autologous platelet injection in the treatment of long bone nonunion: A prospective interventional study

Introduction: Union of fracture is a complex process involving many systemic as well as local factors. Disturbance in any of these factors may lead to failure of process of union. This non-union is associated with increased morbidity, pain and functional disability. Autologous platelet injection at local site has been reported to be one of the effective measures in managing the cases of fracture of long bones complicated by non-union. We conducted this prospective study to know the effectiveness of autologous platelet injection at the fracture site in cases of fracture of long bones complicated by non-union. Materials and Methods: This was a prospective interventional study comprising of 30 cases of fracture of long bones complicated by non-union. The patients were included in this study on the basis of a predefined inclusion and exclusion criteria. The patients with established nonunion after fracture femur, tibia, humerus, radius and ulna were included in this study. Patients who were treated either by, by internal fixation, bone grafting or conservatively were added in this study. Imaging was done by X-rays and if needed by computerized tomography. Imaging was done till definite evidence of union was obtained. Results: Out of 30 cases there were 18 males and 12 females with a M:F ratio of 0.66. The most common bones involved were femur (60%), tibia (16.67%) and humerus (16.67%). Combined fractures of Radius and Ulna were seen in 3 (10 %) patients. The mechanism of injury was Road traffic accidents (66.66%) followed by direct blow and fall from height. All patients initially were treated conservatively or by surgery depending upon type of fractures. Non-union of fractures were treated by autologous platelet injection. All fractures showed radiological evidence of union within 4 months of treatment. Conclusion: Autologous platelet injection at local site is an effective management strategy in patients of fracture of long bones complicated by non-union. A non-infected site is the pre-requisite of this treatment.

Minimally invasive plate augmentation in the treatment of long-bone non-unions.

Exchange nailing is most acceptable for treating hypertrophic non-union of the long bones, requiring the removal of previously fixed implant. However, its main effect of mechanical stabilization is controversial in non-isthmal area. We hypothesized that minimally invasive plate augmentation over the non-union site may have a better option, without the need of bone grafting or removing pre-existing implants. Seventeen patients with hypertrophic non-union of the long bones between 2010 and 2014 on radiography who previously underwent intramedullary (IM) nailing or plate osteosynthesis for long-bone fractures were included. A locking compression plate was inserted with at least three mono- or bicortical screws at each proximal and distal segment. Broken or loosened interlocking screws of IM nail were simultaneously re-fixed. Fracture site exposure, pre-fixed implant removal, and bone grafting were not performed. We investigated whether union occurred and analyzed functional outcomes and complications. Eleven femoral and six tibial non-unions were prospectively included. In the pre-existing implants, 13 nails and 4 plates were found. All cases achieved union at a mean 22.7weeks. One case of superficial infection was managed with oral antibiotics. Deep infection or implant failure did not occur. Minimally invasive plate augmentation can achieve additional stability and promote healing of hypertrophic non-union of the long bones. When indicated, this technique is the least invasive alternative to exchange nailing and reduces surgical risks in the treatment of diaphyseal non-union.

Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7.

AIMTo present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of nonunions.METHODSBone morphogenetic proteins (BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients (80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent joints were also carried out. Factors related to the patient (age, gender), the nonunion (location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure (graft and fixation type, amount of rhBMP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ2 test was performed.RESULTSEighty point nine percent of the nonunions treated with rhBMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients (17.8%) and it was apparent in the routine radiological evaluation of the nonunion site, in a mean time of 5.5 mo after the rhBMP-7 application (range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhBMP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient’s gender was the only important factor for the development of heterotopic ossification (P = 0.007).CONCLUSIONHeterotopic ossification after the use of rhBMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.

Human autologous mesenchymal stem cells with extracorporeal shock wave therapy for nonunion of long bones.

Background:Currently, the available treatments for long bone nonunion (LBN) are removing of focus of infection, bone marrow transplantation as well as Ilizarov methods etc. Due to a high percentage of failures, the treatments are complex and debated. To develop an effective method for the treatment of LBN, we explored the use of human autologous bone mesenchymal stems cells (hBMSCs) along with extracorporeal shock wave therapy (ESWT).Materials and Methods:Sixty three patients of LBN were subjected to ESWT treatment and were divided into hBMSCs transplantation group (Group A, 32 cases) and simple ESWT treatment group (Group B, 31 cases).Results:The patients were evaluated for 12 months after treatment. In Group A, 14 patients were healed and 13 showed an improvement, with fracture healing rate 84.4%. In Group B, eight patients were healed and 13 showed an improvement, with fracture healing rate 67.7%. The healing rates of the two groups exhibited a significant difference (P < 0.05). There was no significant difference for the callus formation after 3 months treatment (P > 0.05). However, the callus formation in Group A was significantly higher than that in the Group B after treatment for 6, 9, and 12 months (P < 0.05).Conclusion:Autologous bone mesenchymal stems cell transplantation with ESWT can effectively promote the healing of long bone nonunions.

Failed treatment of long bone nonunions with low intensity pulsed ultrasound.

IntroductionThe use of low intensity pulsed ultrasound (LIPUS) in the treatment of nonunions is still controversial. The present study is concerned with whether this procedure has a clinical use and which cofactors influence its therapeutic results.MethodsIn this prospective, single institution, observational study, data from October 2010 to October 2013 from 61 nonunions in 60 patients treated with EXOGEN® LIPUS therapy were analysed. The average age was 45.4 ± 9.81 (18–63) years. Treatment was primarily done on long bones of the lower extremity (75.4 %). All 61 nonunions were examined after treatment, and the rate of healing as well as functional and subjective results were evaluated. Based on clinical and radiological findings, patients were divided into two groups: G1—successful treatment; and G2—unsuccessful treatment. Groups were compared to one another to identify possible factors influencing treatment.ResultsTwenty (32.8 %) patients showed bone consolidation with an average time of healing of 5.3 (2–7) months. In patients without successful treatment, who underwent revision surgery instead, full weight bearing took on average 3.7 months longer, and they were able to return to work 6.8 months later. Most of the treated patients (70.5 %) reported no improvement in pain. In G2, 12 (29.3 %) patients suffered in their previous history from osteitis; in G1 there were only two patients (10 %) (p = 0.012). There were further significant differences in the age of the fracture, the type of osteosynthesis, the gap size, as well as the NUSS score.ConclusionDespite patients being chosen strictly according to EXOGEN® indications, only a small number of patients with nonunions who underwent LIPUS therapy experienced successful treatment (32.8 %). Overall, its use resulted in a clear delay in the time of treatment, so that according to our results, the use of LIPUS should be seen critically in long bone nonunions and use should be made on a case-by-case basis.

Low intensity pulsed ultrasound in the treatment of long bone nonunions: Evaluation of cytokine expression as a tool for objectifying nonunion therapy

BackgroundNonunion is one of the most common complications in bone healing. After several clinical studies, the effect of low intensity pulsed ultrasound (LIPUS) in the treatment of nonunions remains unclear because of the difficulty in evaluating its effect on bone healing. In former studies, the analysis of serum cytokine expression patterns over time has proven to be an objective method for showing the bone healing process and evaluating nonunion therapies. This study evaluates LIPUS as a treatment option for patients with nonunions based on the analysis of serum cytokine expression. MethodsIn this prospective, single institution study, venous blood samples from 23 patients were taken from October 2012 to October 2013 before starting LIPUS therapy and at the end of week 1 and 2 and after 1, 2, and 3 months. Patients attended clinical and radiological follow-up examinations at the same intervals. After treating all patients according to the LIPUS therapy protocol, we divided them into two groups: Group 1 consisted of patients with healing at the nonunion site, and Group 2 consisted of patients with failed nonunion therapy. We measured transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), and basic fibroblastic growth factor (bFGF) at all time-points. ResultsThe TGF-β1 serum concentration increased from the pre-treatment value to 1 week within the unsuccessful group. Otherwise, no significant differences between groups in measured cytokines during LIPUS therapy could be detected. ConclusionOur findings suggest that LIPUS does not lead to a significant increase in cytokine levels in patients with nonunions. It is likely that “successful” treatment can be attributed to spontaneous healing. Our results suggest that LIPUS is not a proper treatment for long bone nonunions.

Long bone non-unions treated with the diamond concept: a case series of 64 patients.

The aim of this retrospective study with prospectively documented data was to report the clinical results of treatment of long bone non-unions using the "diamond concept". Over a 4-year period, patients that presented with a long bone non-union and were managed with the diamond conceptual framework of bone repair were evaluated. Exclusion criteria were hypertrophic, pathological, and infected non-unions. Fixation was revised as it was indicated whilst biological enhancement included the implantation of RIA graft, BMP-7 and concentrated bone marrow aspirate. Data recorded included patient demographics, initial fracture pattern and type of stabilisation, number of previous interventions, time to reoperation, time to union and functional outcome. Painless full weight bearing defined clinical union. Radiological union was defined as the presence of mature callous bridging to at least 3 bone cortices. The minimum follow up was 12 months (range 12-32). In total 64 patients (34 males) with a mean age of 45 years (17-83) were evaluated. Anatomical distribution of non-unions included the femur (54.68%), tibia (34.38%), humerus (4.68%), radius (3.13%) and clavicle (3.13%). The median number of previous interventions was 1 (range 1-5). The majority of patients (82.62%) underwent revision of fixation whereas only bone grafting was performed 9.38% of patients. Three patients developed superficial wound infection (one was MRSA), 1 had deep vein thrombosis and 1 developed heterotopic bone formation. Union was successful in 63/64 (98.4%) non-unions at a mean time of 6 months (range 3-12). All patients were mobilising pain free and returned to their daily living activities at the final follow up. The application of the "diamond concept" in this cohort of patients was associated with a high union rate by providing an optimal mechanical and biological environment. Such an approach should be considered in the surgeon's armamentarium particularly in such cases where difficulty of bone repair is foreseen.

Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study.

Fracture union is a complex biological process, which depends upon several systemic and local factors. Disturbance of any of these factors may lead to nonunion of the fracture. These nonunions have a huge impact on quality of life as well as socioeconomical aspects. The platelets on activation release a number of growth factors and differentiation factors, which play important role in fracture healing. This study aimed to look for efficacy of platelet-rich plasma in the treatment of established fracture nonunions of long bones. A total of 94 patients with established nonunion of long bone (35 tibia, 30 femur, 11 humerus, 4 radius, 12 ulna, 2 with both radius and ulna) were included in this study. We injected 15-20 ml of autologous platelet-rich plasma (>2,000,000 platelets/μl) under image intensifier at each nonunion site. The fracture union was evaluated clinically and radiologically regularly at monthly interval till 4 months. Eighty-two patients had their fracture united at the end of 4 months. Thirty-four patients showed bridging trabeculae on X-rays at the end of 2 months, while 41 patients showed bridging trabeculae at the end of third month. Twelve patients did not show any attempt of union at 4 months and were labeled as failure of treatment. There were no complications. Platelet-rich plasma is a safe and effective treatment for the treatment of nonunions. More studies are needed to look into molecular mechanism of this fracture healing acceleration by platelet-rich plasma.

Biological Methods to Enhance Bone Healing and Fracture Repair

This article looks into normal physiological fracture healing with special emphasis on the diamond concept. A precise definition of nonunion of long bones is described. Most often inadequate fixation (too rigid or too loose) is the reason for nonunion in long bone fractures. Because a critical bone defect cannot be bridged, it may lead directly or indirectly (lack of fixation) to nonunion. Individual inadequate local biological characteristics are also often found to be the cause; poor soft tissue coverage as well as a lack of periosteum and muscle or fascia or skin defects can lead to compromised vascularity in situ. Systemic factors are now much more recognized, e.g., smoking, diabetes, and cachexia, as well as the limited impact of some medications, e.g., nonsteroidal anti-inflammatory drugs and steroids. Today's mode of treatment for nonunion is approached in this article, and suggestions for appropriate treatment of long bone nonunion is presented.

Bone marrow injection in treatment of long bone nonunion

Objectives The goal of this study was to report the role of bone marrow injection in treatment of nonunited long bones fractures and to evaluate the relationship between bony union and bone marrow. Background Bone marrow injection has been used for the management of fracture nonunion since a long period of time. The main advantages for this technique are: it can be used in patient unfit for open grafting, is safe, uses osteogenic cells, has no complications in graft site, and can prevent nonunion development. Other advantages include: it is simple, quick, inexpensive, and causes minimal surgical trauma. Patients and methods From November 2009 to February 2013, 20 patients, 16 male patients and four female patients, mean age 36.5 years, suffering from nonunited lower limb fractures were treated in the Orthopedic Department, El-Menoufiya University Hospital by bone marrow injection in site of fracture nonunion. Results Of the 20 patients who had bone marrow injection for nonunion, 16 (80%) patients achieved union and four (20%) patients failed to achieve union. Of the four patients who were not healed, one patient had received three bone marrow injections, whereas three patients had received four bone marrow injections. Conclusion In our study, the patient's age and smoking were inversely proportional to healing after bone marrow injection. In addition, patients who had closed fracture at the time of initial injury achieved union more than patients who had open fracture at the time of initial injury.

Long bone nonunions treated with autologous concentrated bone marrow-derived cells combined with dried bone allograft

Nowadays the treatment of long bone nonunion continues to be one of the most complex and debated topics due to the large number of failures. For several years, in the relevant literature three factors have been considered essential in the healing process: growth factors and hormones, osteoprogenitor cells (mesenchymal stem cells), and extracellular matrix. The mechanical stability of the fracture site is considered the fourth element of the "Diamond concept theory." The aim of our study was to evaluate the validity of biological adjuvants of mechanical synthesis allowing a faster healing process of nonunions. We dealt with 19 patients with long bone nonunion. All patients have been treated with concentrated mesenchymal stem cells without bone autologous transplant. We used the Extracell BMC-marrow aspirate protocol of Regen Lab. The radiographic parameters taken into account for the diagnosis of successful healing were the presence of a bridge callus, obliteration of the fracture line and bone cortical continuity. Clinically, the pain was investigated with VAS score (visual analogue scale), where zero means no pain and 10 the worst possible pain. Radiographic investigation shows complete healing in 78.9 % (15 cases) with an average time to healing of 6.5 months (minimum healing time 80 days) corresponding also in complete remission of clinical symptoms. The use of growth factors and autologous mesenchymal stem cells through the enforcement of system for tissue regeneration is a valid and innovative biotechnology technique for the treatment long bone nonunions.

Augmentative locking compression plate fixation for the management of long bone nonunion after intramedullary nailing

Intramedullary nailing is widely used in the treatment of long bone fractures. But some patients suffer from nonunion after receiving intramedullary nailing. This paper investigates the methods and effects of locking compression plate (LCP) in the treatment of long bone nonunion after intramedullary nailing. A total of 6 patients (4 males, 2 females) with long bone nonunion were enrolled. All these patients had previously undergone intramedullary nailing for fractures of long bones (4 femurs, 2 tibiae). The average time from injury to LCP treatment was 12.2months. The locking compression plate was applied over the intramedullary nail, and unicortical purchase achieved with locking head screws due to underlying nails. Autologous bone grafting was done in all cases. Six patients were followed up for 12-20months (mean 14.2months). X-ray imaging showed bone callus at the broken ends of the fracture at 3-7 (mean 4.5)months after surgery. All patients did not have any complications such as infection, breaking or loosening of the LCPs. LCP can be used for the treatment of long bone nonunion after intramedullary nailing for its convenience, minimal invasion and curative effect.