[Focused High-Energy Extracorporeal Shock Wave Therapy (ESWT) for Bone healing Disorders of the Forearm and the Hand]. / Hochenergetische, fokussierte extrakorporale Stoßwellentherapie (ESWT) bei Knochenheilungsstörungen von Unterarm und Hand.

BACKGROUND: ESWT is a non-surgical treatment option but can also be used in addition to surgical treatment (stabilisation, freshening, defect filling, removal of discomforting osteosynthesis material) for the treatment of delayed bone healing (DBH) and non-union (NU). Its value as well as influencing factors on the upper extremity have not been adequately quantified so far. PATIENTS AND METHODS: Sixty cases were retrospectively studied after application of focused high-energy ESWT with regard to healing rate and consolidation time. The influence of age, location, time of treatment and treatment prior to and concurrent with ESWT were analysed. RESULTS: In 70% of the cases, healing occurred after a median of 2.4 months (DBH) and 2.8 months (NU). The median age of healed (DBH 44 y., non-union 35 y.) and non-healed (DBH 51 y., NU 37 y.) did not differ significantly. The time between trauma/surgery and ESWT was 4.2 months for DBH in healed and 3.7 months in non-healed without a significant difference, and 27 months for NU in both healed and non-healed. Age and smoking status also had no influence. The healing rate was highest at metacarpal bone/finger/thumb (91%), followed by forearm shaft (88%), epiphysis/metaphysis of the forearm (67%), and, lastly, carpal bones (59%). After conservative pre-treatment, 55% healed, compared with 67% after more than two previous surgeries, 73% without any pre-treatment, and 75% after one previous surgery. Further analysis of surgical pre-treatment showed 85% healing after ORIF alone, 64% without previous surgery, and 57% healing after ORIF with bone grafting/debridement. Intraoperative ESWT combined with bone debridement/transplantation and ORIF resulted in 67% healing, compared with 86% in combination with ORIF alone. ESWT alone or with only minimal measures (removal of osteosynthesis material) led to 70% consolidation. CONCLUSION: ESWT is equally effective at any stage of a bone healing disorder. The principles of stability and filling of bone defects must also be taken into account when using ESWT; then ESWT alone or combined with surgery is equally effective. The negative influence of bone defects/resorption is still detectable even with ESWT. Furthermore, treatment of the scaphoid is more problematic compared with other locations. Previous surgery is not a negative factor, even with osteosynthesis material in situ.

Risk Factors for Nonunion After Nonoperative Treatment for Pediatric Lumbar Spondylolysis: A Retrospective Case-Control Study.

BACKGROUND: Pediatric lumbar spondylolysis, a stress fracture of the lumbar spine, frequently affects young athletes, and nonoperative treatment is often the first choice of management. Because the union rate in lumbar spondylolysis is lower than that in general fatigue fractures, identifying risk factors for nonunion is essential for optimizing treatment. PURPOSE: To determine the risk factors for nonunion after nonoperative treatment of acute pediatric lumbar spondylolysis through multivariate analysis. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: We analyzed 574 pediatric patients (mean age, 14.3 ± 1.9 years) with lumbar spondylolysis who underwent nonoperative treatment between 2015 and 2022. Nonoperative treatment included the elimination of sports activities, bracing, and weekly athletic rehabilitation, with follow-up computed tomography. Patient data, lesion characteristics, sports history, presence of spina bifida occulta at the lamina with a lesion or at the lumbosacral spine excluding the lesion level, and lumbosacral parameters were examined. Differences between the union and nonunion groups were investigated using multivariate analysis to determine the risk factors for nonunion. RESULTS: Of the 574 patients, 81.7% achieved bone union. Multivariate analysis revealed that an L5 lesion and the progression of the main and contralateral lesion stages were significant independent risk factors for nonunion. An L5 lesion had a lower union rate than non-L5 lesions. As the main lesion progressed, the likelihood of nonunion increased significantly, and the progression of the contralateral lesion also showed a similar trend. Spina bifida occulta and lumbosacral parameters were not significant predictors of nonunion in this study. CONCLUSION: We identified the L5 lesion level and the progression of the main and contralateral lesion stages as independent risk factors for nonunion in pediatric lumbar spondylolysis after nonoperative treatment. These findings aid in treatment decision-making. When bone union cannot be expected with nonoperative treatment, symptomatic treatment is required without prolonged external fixation and rest, and without aiming for bone union. Individualized treatment plans are crucial based on identified risk factors.

A case series utilizing bone marrow aspirate concentrate, cancellous bone autograft, platelet-rich plasma and autologous fibrin for the treatment of femur nonunions.

Aim: To assess the efficacy of a bioregenerative scaffold derived from bone marrow aspirate, cancellous bone autograft, platelet-rich plasma and autologous fibrin in treating supracondylar femur nonunions. Methods & materials: Three patients with nonunions following multiple surgical failures underwent bone stabilization and the application of a novel bioregenerative scaffold. x-rays and subjective scales were collected before surgery and at 6, 12 and 24 months post-surgery. Results: All nonunions exhibited healing with sufficient callus formation, as confirmed radiologically. After 6 months, all patients resumed full weight-bearing walking without pain. Statistical analysis showed improvements in all scales compared with pre-surgical values. Conclusion: This method presents itself as an option for treating supracondylar femur nonunions following multiple surgical failures.

What is this summary about? The objective of this case series study was to evaluate the effectiveness of a new biological autologous scaffold, comprised of stem and blood cells along with blood derivatives, in treating challenging cases of supracondylar femur nonunions.What were the results? Three participants underwent the application of this surgical method and were monitored for a period of 2 years. The therapy was well tolerated and deemed safe. Notably, all three patients experienced significant reductions in pain and improvements in functionality. Within a few months, they were able to walk with full weightbearing without pain, and clear indications of progressing toward bone union were evident by the 6 months.What do the results mean? This study demonstrates that the surgical application of autologous blood, cancellous bone and bone marrow, following the described concept and method, is an effective, safe and enduring treatment for femur nonunions. It markedly diminishes pain, enhances leg function and yields statistically significant improvements in quality of life.

Clinical management and innovation in fracture non-union.

INTRODUCTION: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union. AREAS COVERED: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling. EXPERT OPINION: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.

Assessment, Diagnosis and Management Strategies for Forearm Shaft Non-union: A Contemporary Perspective.

Forearm non-union poses a challenge in orthopaedic surgery due to its intricate anatomy and functional significance. This review provides a comprehensive overview of the assessment, diagnosis and management of forearm non-union. Initial evaluation involves a meticulous history, physical examination and imaging studies to identify factors contributing to non-union, including infection. Surgical approaches are discussed, with emphasis on restoring biomechanical stability and promoting bone healing. Treatment options range from autografts to allografts, with considerations for vascularised bone transfers in complex cases. Decision-making strategies are outlined, considering patient-specific factors and individualised treatment plans. Special considerations for specific types of forearm non-unions are addressed, along with postoperative care protocols to optimise healing and functional outcomes. Overall, this review aims to provide clinicians with a comprehensive understanding of forearm non-union management based on current evidence and clinical practice. Level of Evidence: Level V (Therapeutic).

Percutaneous injection of autologous platelet gel accelerate healing in diabetic tibial non union: On going longitudinal study.

INTRODUCTION: In this study the tibial shaft fracture non unions in diabetes mellitus are evaluated with percutaneous autologous platelet gel supplementation to accelerate union are compared with individually matched control group with autologous iliac crest bone marrow aspirate injection. MATERIAL AND METHODS: This present study was carried out on tibial non unions in diabetic patients recruited in an ongoing longitudinal study over a period of 2006 to 2017, treated by one surgeon at one institute, are included in this report. Each of 18 established tibial atrophic, aseptic non unions treated by percutaneous autologous platelets and iliac crest bone marrow aspirate were followed up on regular basis up till 9 months. The healing of non union was assessed clinically by painless full weight bearing and the radiological union was judged by bridging callus formation observed on at least 3 of 4 cortices in anteroposterior and lateral views. RESULTS: Union was observed in 17 (94.4 %) patients of the autologous platelet group. The average time to union was 9.2 weeks (range 8 to 18 weeks) after percutaneous autologous platelet injection (P < 0.0517) .In the control group, union was observed in 14 (77.8 %) patients (P = 0.672). The average time to union following percutaneous bone marrow injection was 11.6 weeks (range 9 to 28 weeks). The proximal 1/3 shaft non union healed comparatively faster than the distal 1/3 shaft tibia (P ≤ 0.0612). No correlation was observed between the comminuted and non comminuted fracture non union (P = 0.789). A significant correlation was noted as regards the non union healing time duration in patients who were on insulin and oral hypoglycemic drugs (P ≤ 0.001) and also about the total duration of diabetes mellitus in years (P ≤ 0.003). CONCLUSION: This investigation showed that percutaneous autologous platelet gel delivery is sufficient method to obtain union in diabetic tibial fracture non unions, which is less invasive procedure than bone marrow injection. The efficacy of this autologous platelets is once again well established and this study reinforced categorically the previously published report by the author.

Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial.

UPDATE: This article was updated on September 4, 2024 because of a previous error, which was discovered after the preliminary version of the article was posted online. In the Note listing the members of the Wrist and Elbow Research Group of Canada, the text that had read "Thomas T. Goetz, MD, FRCSC" now reads "Thomas J. Goetz, MD, FRCSC". BACKGROUND: The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. METHODS: Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. RESULTS: A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). CONCLUSIONS: Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

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?

PURPOSE: 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. METHODS: 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. RESULTS: Our initial search yielded 430 publications, which was screened down to 25 studies. 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. CONCLUSION: 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 OF EVIDENCE: Level III.

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

OBJECTIVE: To 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. METHODS: A 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. RESULTS: All 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. CONCLUSION: Bone 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.

SVF Therapy of Delayed Fracture Union in Patients with Multiple Combat Injury. Case Report.

Delayed union of fractures is one of the most frequent complications in orthopedic practice, especially in polytrauma patients. With the development of new methods of regenerative medicine, including the use of adipose derived stromal cells as a component of the stromal-vascular fraction (SVF), new possibilities for conservative treatment of this problem have emerged. This article presents a clinical case of conservative treatment of delayed union of a radial bone fracture using local SVF injections. In the fracture space, SVF with PRP creates a pool of cells that could differentiate towards surrounding tissue, releases various inducers of tissue growth and, via an indirect chemotactic effect on receptors, mobilizes the body's own resources and creates conditions for angiogenesis and trophism in the injured segment. In the patient with delayed consolidation after SFV-therapy, progress in clinical and radiological dynamics was noted with complete healing within 7 months. The positive clinical result provides a basis for further study and implementation in practice.

Polytherapy versus monotherapy in the treatment of tibial non-unions: a retrospective study.

BACKGROUND: Treating tibial non-unions efficiently presents a challenge for orthopaedic trauma surgeons. The established gold standard involves implanting autologous bone graft with adequate fixation, but the addition of biologicals according to the so-called diamond concept has become increasingly popular in the treatment of non-unions. Previous studies have indicated that polytherapy, which involves implanting mesenchymal stem cells, bioactive factors and osteoconductive scaffolds, can improve bone healing. This study aims to evaluate the efficacy of polytherapy compared with monotherapy in treating tibial non-unions of varying severity. MATERIALS AND METHODS: Data from consecutive tibial non-unions treated between November 2014 and July 2023 were retrospectively analysed. The Non Union Scoring System (NUSS) score before non-union surgery, and the Radiographic Union Score for Tibial fractures (RUST), scored at 1, 3, 6, 9, 12 and 18 months post-surgery, were recorded. Initially, a comparison was made between the polytherapy and monotherapy groups. Subsequently, patients receiving additional surgical non-union treatment were documented, and the frequency of these treatments was tallied for a subsequent per-treatment analysis. RESULTS: A total of 34 patients were included and divided into a polytherapy group (n = 15) and a monotherapy group (n = 19). The polytherapy group demonstrated a higher NUSS score (44 (39, 52) versus 32 (29, 43), P = 0.019, z = -2.347) and a tendency towards a higher success rate (93% versus 68%, P = 0.104) compared with the monotherapy group. For the per-treatment analysis, 44 treatments were divided into the polytherapy per-treatment group (n = 20) and the monotherapy per-treatment group (n = 24). The polytherapy per-treatment group exhibited a higher NUSS score (48 (43, 60) versus 38 (30, 50), P = 0.030, z = -2.173) and a higher success rate (95% versus 58%, P = 0.006) than the monotherapy per-treatment group. Within the monotherapy per-treatment group, the NUSS score displayed excellent predictive performance (AUC = 0.9143). Setting the threshold value at 48, the sensitivity and specificity were 100.0% and 70.0%, respectively. CONCLUSIONS: Polytherapy is more effective than monotherapy for severe tibial non-unions, offering a higher success ratio. The NUSS score supports decision-making in treating tibial non-unions. LEVEL OF EVIDENCE: Level III.

Approach to Tibial Shaft Nonunions: Diagnosis and Management.

The tibia is the most common long bone at risk for nonunion with an annual incidence ranging from 12% to 19%. This topic continues to be an area of research as management techniques constantly evolve. A foundational knowledge of the fundamental concepts, etiology, and risk factors for nonunions is crucial for success. Treatment of tibial shaft nonunions often requires a multidisciplinary effort. This article provides guidance based on the most recent literature that can be used to aid the treating provider in the diagnosis, workup, and management of tibial shaft nonunions.

Are displaced distal clavicle fractures associated with inferior clinical outcomes following nonoperative management? A systematic review.

BACKGROUND: Management of displaced distal clavicle fractures remains a topic of discussion because of notoriously high nonunion rates, but there is little documented in the literature as to what effect this may have on patient-reported function. The aim of this systematic review was to look at nonoperative management following displaced distal clavicle fractures to determine union rates, complications, and patient-reported outcome measures. METHODS: A review of the online databases MEDLINE and Embase was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies that included a cohort of nonoperatively managed displaced distal clavicle fractures and reported on union rate, complications, and patient-reported functional scores were included. RESULTS: Eleven studies were eligible for inclusion (2 randomized controlled trials, 1 prospective noncomparative cohort study, 5 retrospective comparative cohort studies, and 3 case series) with a total of 779 patients included in this review. Average union rate was 63.2% (22.2%-94.4%) in nonoperatively managed patients, compared with 96.3% (87.9%-100%) in operatively managed patients. The Constant-Murley score and Disabilities of the Arm, Shoulder, and Hand questionnaire were the most frequently used outcome measure tools. No study demonstrated any significant difference in any outcome measure when comparing nonoperative with operative treatment. Complication rate (including nonunion) in nonoperatively managed patients was 45.1%, with 11.1% requiring delayed surgery. Average complication rate in the operatively managed groups was 41.2%, with 40.1% requiring a second operation. CONCLUSION: Nonoperative management of displaced distal clavicle fractures results in higher nonunion rates, but shoulder function remains excellent, and risk of complications and delayed surgery are low. Decision making must take into account patient factors and expectations to provide high-quality, individualized care.

A review of scaphoid fracture, treatment outcomes, and consequences.

PURPOSE: Scaphoid fractures are the most common carpal fracture and can lead to severe complications like carpal collapse and osteoarthritis. This study reviewed scaphoid fracture patterns, outcomes, and consequences in conservative and surgical management. METHODS: Sixty-four patients with scaphoid fracture who attended the hand clinic at King Hussein Medical City from January 2022 to December 2022 were included and reviewed regarding the anatomical fracture site, the associated injury, the treatment modality (conservative versus surgical), the healing time, and fracture sequelae such as nonunion and scaphoid nonunion advanced collapse. RESULTS: Most patients were males (62 patients, 96.9%), and most (47, 73.4%) fell within 25 to 40 years. Scaphoid waist fracture was the most common location (40, 52.5%). Most patients (47, 73.4%) received conservative treatment and 17 (26.6%) were fixed acutely. However, nonunion complicated 53 fractures (82.8%). Notably, there were no differences in the union rate or time between cases of scaphoid nonunion treated with vascularized or nonvascularized grafts. Furthermore, there were no variations in union rates among genders, extremities, age, fracture locations, or among smokers. However, a higher union rate was noted in office workers and those who received conservative treatment. CONCLUSION: Nonunions were higher in our study than in the literature, as our department is a referral center for established nonunion cases. For conservative treatment, we recommend aggressive management and follow-up with a clinical and CT scan at three months and early referral of non-united fractures to the hand clinic to avoid the advanced collapse of the scaphoid.

Phase III clinical trial of autologous CD34 + cell transplantation to accelerate fracture nonunion repair.

BACKGROUND: We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients. METHODS: CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded. RESULTS: All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16-6.85); moreover, no safety concerns were observed. CONCLUSIONS: Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion. TRIAL REGISTRATION: UMIN-CTR, UMIN000022814. Registered on 22 June 2016.

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.

Nonunion of conservatively treated humeral shaft fractures is not associated with anatomic location and fracture pattern.

INTRODUCTION: Humeral shaft fractures make up 1-3% of all fractures and are most often treated nonoperatively; rates of union have been suggested to be greater than 85%. It has been postulated that proximal third fractures are more susceptible to nonunion development; however, current evidence is conflicting and presented in small cohorts. It is our hypothesis that anatomic site of fracture and fracture pattern are not associated with development of nonunion. MATERIALS AND METHODS: In a retrospective cohort study, 147 consecutive patients treated nonoperatively for a humeral shaft fracture were assessed for development of nonunion during their treatment course. Their charts were reviewed for demographic and radiographic parameters such as age, sex, current tobacco use, diabetic comorbidity, fracture location, fracture pattern, AO/OTA classification, and need for intervention for nonunion. RESULTS: One hundred and forty-seven patients with 147 nonoperatively treated humeral shaft fractures were eligible for this study and included: 39 distal, 65 middle, and 43 proximal third fractures. One hundred and twenty-six patients healed their fractures by a mean 16 ± 6.4 weeks. Of the 21 patients who developed a nonunion, two were of the distal third, 10 of the middle third, and nine were of the proximal third. In a binomial logistic regression analysis, there were no differences in age, sex, tobacco use, diabetic comorbidity, fracture pattern, anatomic location, and OTA fracture classification between patients in the union and nonunion cohorts. CONCLUSIONS: Fracture pattern and anatomic location of nonoperatively treated humeral shaft fractures were not related to development of fracture nonunion.

Single-cell RNAseq provides insight into altered immune cell populations in human fracture nonunions.

Nonunion describes bone fractures that fail to heal, resulting in the fracture callus failing to fully ossify or, in atrophic cases, not forming altogether. Fracture healing is regulated, in part, by the balance of proinflammatory and anti-inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single-cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (n = 5) or from native bone controls when harvesting autologous bone graft (n = 4). Cells within the samples were isolated and analyzed using the Chromium Single-Cell System (10x Genomics Inc.) and Illumina sequencers. Twenty-three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14 + dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14 + DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human-derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single-cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and/or investigation into therapeutic options.

The perceptions of clinicians using low-intensity pulsed ultrasound (LIPUS) for orthopaedic pathology: A national qualitative study.

INTRODUCTION: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive treatment modality for delayed union or non-union of acute fractures. We aimed to assess the current use of LIPUS at a national level in the United Kingdom, why and how clinicians use it, what treatment protocols are followed, and what the current perceptions are on this technology. METHODOLOGY: Using a detailed online survey compromised of 20 questions delivered to known LIPUS users, we were able to collect qualitative data on indication of use, type of machine used, personal views on the technology, frequency of usage, and treatment protocols. Each question was peer-reviewed to exclude bias. RESULTS: A total of 70 respondents completed the survey. LIPUS was used by most clinicians for cases of non-union (N = 55, 78.5%) and delayed union (N = 51, 72.8%). The majority of respondents personally used a LIPUS device between 1 and 5 times in 12 months (N = 38, 54.3%). Most considered LIPUS a failure after three to six months of treatment without clinical improvement (N = 39, 55.7%). A total of 32 respondents (45.7%) mentioned the need for funding approval before accessing LIPUS technology. Poor revision surgery candidates (N = 48, 68.6%) and atrophic non-union (N = 46, 65.7%) were the most frequently cited reasons for using LIPUS technology as treatment. Most participants (N = 48, 68.6%) considered LIPUS to be cost-effective. Despite most clinicians being comfortable with the use of LIPUS, some respondents did not understand the basic science underpinning the technology nor could explain the need for LIPUS to patients comfortably. CONCLUSION: LIPUS technology may have a significant role to play in the treatment of orthopaedic fracture related pathology. Regular users perceived the technology to be cost-effective and efficacious. Further research should standardize treatment protocols and aim to establish a national LIPUS registry.

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials.

BACKGROUND: Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis. METHODS: A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions. RESULTS: Thirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: - 14.64, - 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk. CONCLUSIONS: Among the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results. TRIAL REGISTRATION: Retrospectively registered.