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.

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.

Addition of shock wave therapy to nail dynamization increases the chance of long-bone non-union healing.

BACKGROUND: Long-bone non-unions after intramedullary nailing can be treated by nail dynamization or focused high-energy extracorporal shock wave therapy (fESWT). The objective of this study was to assess the effect of the combination therapy of nail dynamization and fESWT on long-bone non-unions. MATERIALS AND METHODS: 49 patients with long-bone non-unions (femur and tibia) after nailing were treated with nail dynamization (group D, n = 15), fESWT (group S, n = 17) or nail dynamization in addition to fESWT (group DS, n = 17). Patients were followed up for 6 months retrospectively. Furthermore, age, sex, Non-Union Scoring System (NUSS) score, time intervals from primary and last surgery until intervention and smoking status were analysed for their correlations to bone union. RESULTS: Union rates were 60% for group D, 64.7% for group S and 88.2% for group DS, with a significant difference between group D and DS (p = 0.024). Successful treatment was correlated with high age (OR 1.131; 95% CI 1.009-1.268; p = 0.034), female gender (OR 0.009; 95% CI 0.000-0.89; p = 0.039), low NUSS score (OR 0.839; 95% CI 0.717-0.081; p = 0.028) and negative smoking status (OR 86.018; 95% CI 3.051-2425.038; p = 0.009). CONCLUSIONS: Data from the present study indicate that the combination therapy of nail dynamization and fESWT leads to a higher union rate than dynamization or fESWT alone. LEVEL OF EVIDENCE: Level 3.

An early cost analysis of magnetic bone growth stimulation in England.

BACKGROUND: Fracture nonunions impact on morbidity and health care costs and are associated with substantial pain, reduced mobility, prolonged morbidity, and a lower quality of life. CMF OrthoLogic 1000 (OL1000) is a bone growth stimulator used to promote fracture healing potentially reducing the need for surgical intervention. A cost analysis comparing CMF OL1000 versus surgical care for patients with nonunion tibial fractures was conducted. METHODS: A Markov model was developed to compare the difference in costs between CMF OL1000 versus surgical care within the English National Health Service over a 2-year time horizon. The effectiveness of CMF OL1000 was based on recently published registry data. Cost data were derived from published sources and national cost databases. Sensitivity and scenario analyses were conducted. RESULTS: The use of CMF OL1000 is estimated to lead to cost-savings of £1,104 per patient, a reduction in average healing time of 2.1 months and a relative risk of infection of 0.19 compared to immediate surgical intervention (standard of care). The results of the model are robust to most changes in input parameters and scenarios considered. CONCLUSIONS: This early analysis shows cost-savings for CMF OL1000 compared with surgical intervention for individuals with nonunion tibial fractures.

High-energy extracorporeal shockwave therapy in humeral delayed and non-unions.

INTRODUCTION: Within the last few decades, focused high-energy extracorporeal shockwave therapy (ESWT) has proven to be an effective alternative to standard of care revision surgery in delayed healing fractures or manifest non-unions in various anatomical regions. MATERIALS AND METHODS: A retrospective multi-variant analysis of an open prospective, single-armed clinical study was conducted. Patients receiving focused high-energy ESWT for a delayed healing or an apparent non-union of a humeral fracture between January 1999 and December 2015 at a single trauma center were included in the study. Bony healing was defined as cortical continuity in three of four cortices and pain-free force loading and evaluated using CT scans and clinical examination at three- and six-month follow-ups after ESWT. RESULTS: A total of 236 patients were included. N = 93 (43.8%) showed bony consolidation three months after ESWT and n = 105 (52.5%) after six months. Sub-group analysis showed significantly better healing for the proximal metaphyseal humerus (66.7% after six months, n = 42) compared to the diaphyseal region (48.1%, n = 133) and distal metaphyseal humerus (48.1%, n = 25). Regression analysis indicated significantly increased healing rates for patients of younger ages (p = 0.001) and a fracture diastasis of less than 5 mm (p = 0.002). CONCLUSION: The findings of this study indicate that ESWT can be considered as a treatment option for a well-selected patient population despite the lower healing rates compared to other anatomical regions.

Platelet-Rich Plasma, Mesenchymal Stem Cell, and Non-metallic Suture-Based Fixation Technique in a Patellar Fracture Nonunion: A Technical Note and Systematic Review.

BACKGROUD: We performed a systematic review on the management of patellar fracture nonunion and report a novel suture-based non-metallic fixation technique associated with platelet-rich plasma and mesenchymal stem cell injections in the management of this injury. METHODS: A systematic search was performed up to August 2020 in PubMed and Scopus electronic databases of scholarly articles evaluating different surgical techniques used for nonunion of patellar fractures, with no restrictions on language or year of publication. Furthermore, we describe our novel non-metallic suture fixation technique and a patient in whom this technique was applied. RESULTS: A total of 9 articles were included in the systematic review. Tension band wiring was the most commonly used procedure (62.7%). Nonoperative procedures (8.1%) resulted in nonunion in all patients. The most common complication after open reduction and internal fixation was infection (7.8%). Our patient at the latest follow-up reported full functional recovery and full extension and flexion of the affected knee with no pain and subjectively normal strength. CONCLUSIONS: The management of patella nonunions is still a challenge. The technique reported here can be used in patellar fracture nonunion, as well as in primary patellar fractures.

Rat model of an autologous cancellous bone graft.

Autologous cancellous bone (ACB) grafting is the "gold standard" treatment for delayed bone union. However, small animal models for such grafts are lacking. Here, we developed an ACB graft rat model. Anatomical information regarding the iliac structure was recorded from five rat cadavers (10 ilia). Additionally, 5 and 25 rats were used as controls and ACB graft models, respectively. A defect was created in rat femurs and filled with ACB. Post-graft neo-osteogenic potential was assessed by radiographic evaluation and histological analysis. Iliac bone harvesting yielded the maximum amount of cancellous bone with minimal invasiveness, considering the position of parailiac nerves and vessels. The mean volume of cancellous bone per rat separated from the cortical bone was 73.8 ± 5.5 mm3. Bone union was evident in all ACB graft groups at 8 weeks, and new bone volume significantly increased every 2 weeks (P < 0.001). Histological analysis demonstrated the ability of ACB grafts to act as a scaffold and promote bone union in the defect. In conclusion, we established a stable rat model of ACB grafts by harvesting the iliac bone. This model can aid in investigating ACB grafts and development of novel therapies for bone injury.

Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute.

Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague-Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by µ-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.

Minimally invasive treatment of long bone non-unions with bone marrow concentrate, demineralized bone matrix and platelet-rich fibrin in 38 patients.

To determine the efficacy of percutaneous injection of autologous bone marrow concentrated (BMC), demineralized bone matrix (DBM), and platelet rich fibrin (PRF) in the treatment of long bone non-unions. From January 2011 to January 2018 patients with non-union of the lower limbs who were on the waiting list for open grafting with established tibial or femoral non-union and minimal deformity were eligible to participate in this study. Patients were treated with a single percutaneous injection of DBM, BMC and PRF. Our study group comprised 38 patients (26 males and 12 females; mean age 39, range 18 to 65). Non-unions were located in the femur (18 cases) and in the tibia (20 cases). Clinical and imaging follow-up ranged from 4 to 60 months (mean 20 months). Bone union occurred in 30 out of 38 patients (79%) in an average of 7 months (range 3 to 12) and all healed patients had full weight bearing after 9 months on average (range 6 to 12) from injection. In 19 cases the osteosynthesis was removed 12 months on average (range 3 to 36) from surgery. One patient developed infection at the non-union site after treatment. Percutaneous injection of DBM, BMC, and PRF is an effective treatment for long-bone non-unions. This technique allows the bone to heal with a minimally invasive approach and with a hospitalization of 2 days. Key elements of bone regeneration consist of a combination of biological and biomechanical therapeutic approach.

Adolescent mid-shaft clavicular fracture displacement does not predict nonunion or inferior functional outcome at long-term follow-up.

AIMS: The aim of this study was to define the complications and long-term outcome following adolescent mid-shaft clavicular fracture. METHODS: We retrospectively reviewed a consecutive series of 677 adolescent fractures in 671 patients presenting to our region (age 13 to 17 years) over a ten-year period (2009 to 2019). Long-term patient-reported outcomes (abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score and EuroQol five-dimension three-level (EQ-5D-3L) quality of life score) were undertaken at a mean of 6.4 years (1.2 to 11.3) following injury in severely displaced mid-shaft fractures (Edinburgh 2B) and angulated mid-shaft fractures (Edinburgh 2A2) at a minimum of one year post-injury. The median patient age was 14.8 years (interquartile range (IQR) 14.0 to 15.7) and 89% were male (n = 594/671). RESULTS: The majority of fractures were mid-shaft (n = 606) with angulation (Edinburgh 2A2, n = 241/606, 39.8%) or displacement (Edinburgh 2B1/2, n = 263/606, 43.4%). Only 7% of the displaced mid-shaft fractures underwent acute fixation (n = 18/263). The incidence of refracture over ten years following nonoperative management of mid-shaft fractures was 3.2% (n = 19/588) and all united without surgery. Fracture type, severity of angulation, or displacement were not associated with refracture. One nonunion occurred following nonoperative management in a displaced mid-shaft fracture (0.4%, n = 1/245). Of the angulated fractures, 61 had angulation > 30°, of which 68.9% (n = 42/61) completed outcome scores with a median QuickDASH of 0.0 (IQR 0.0 to 0.6), EQ-5D-3L 1.0 (1.0 to 1.0), and 98% satisfaction with shoulder function. For the displaced fractures, 127 had displacement beyond one cortical width of bone for which completed outcome scores were provided in 72.4% (n = 92/127). Of these 15 had undergone acute fixation. Following nonoperative treatment, the median QuickDASH was 0.0 (IQR 0.0 to 2.3), EQ-5D-3L 1.0 (1.0 to 1.0), and satisfaction with shoulder function was 95%. There were no significant differences in the patients' demography or functional outcomes between operative and nonoperative treatments. CONCLUSION: Nonoperative management of adolescent mid-shaft clavicle fractures results in excellent functional outcomes at long-term follow-up. Nonunion is exceptionally rare following nonoperative management and the relative indications for surgical intervention in adults do not appear to be applicable to adolescents. Cite this article: Bone Joint J 2021;103-B(5):951-957.

Neither operative nor nonoperative approach is superior for treating displaced midshaft clavicle fractures: a partially blinded randomized controlled clinical trial.

AIMS: To compare the functionality of adults with displaced mid-shaft clavicular fractures treated either operatively or nonoperatively and to compare the relative risk of nonunion and reoperation between the two groups. METHODS: Based on specific eligibility criteria, 120 adults (median age 37.5 years (interquartile range (18 to 61)) and 84% males (n = 101)) diagnosed with an acute displaced mid-shaft fracture were recruited, and randomized to either the operative (n = 60) or nonoperative (n = 60) treatment group. This randomized controlled, partially blinded trial followed patients for 12 months following initial treatment. Functionality was assessed by the Constant score (CS) (assessor blinded to treatment) and Disability of the Arm, Shoulder and Hand (DASH) score. Clinical and radiological evaluation, and review of patient files for complications and reoperations, were added as secondary outcomes. RESULTS: At 12 months, 87.5% of patients (n = 105) were available for analysis. The two groups were well balanced based on demographic and fracture-related characteristics. At six weeks of follow-up a significant difference in DASH score (p < 0.001) was found in favour of operative treatment. The functionality at 12 months of follow-up based on CS and DASH was excellent in both groups (CS > 90 points and DASH < 10 points) with no significant difference (p = 0.277 for DASH and p = 0.184 for CS) between the two groups. The risk of symptomatic nonunion was significantly higher in the nonoperative group (p = 0.014), with a relative risk of 9.47 (95% confidence interval (CI) 1.26 to 71.53) in this group compared to the operative group. The number-needed-to-treat to avoid one symptomatic nonunion was 6.2. Initial treatment and age were factors significantly associated with nonunion in a logistic analysis. There were 26% in both groups (n = 14 in operative group and n = 15 in nonoperative group) who required secondary surgery, with most indications in the nonoperative group mandatory due to nonunion compared to most relative indications in the operative group requiring intervention due to implant irritation. CONCLUSION: Superiority was not identified with either an all-operative or all-nonoperative approach. The functionality at short term (within six weeks) seems igreater following operative treatment but was not found at one year. The risk of nonunion is significantly higher with nonoperative treatment. However, an all-operative approach to lower the nonunion risk may result in unnecessary surgery and is not recommended. Cite this article: Bone Joint J 2021;103-B(4):762-768.

Percutaneous injection of platelet-rich plasma to treat atrophic nonunion after internal fixation of ulnar fracture: a case report.

Non-union is a serious postoperative complication of fracture. Early detection and intervention can avoid revision surgery. Platelet-rich plasma releases many active tissue factors and has potential to promote fracture healing. Percutaneous injection of platelet-rich plasma at the fracture site may avoid surgical treatment when non-union occurs. We present a case of atrophic non-union of an ulna fracture treated conservatively with percutaneous injection of platelet-rich plasma.

Early systemic immune biomarkers predict bone regeneration after trauma.

Severe traumatic injuries are a widespread and challenging clinical problem, and yet the factors that drive successful healing and restoration of function are still not well understood. One recently identified risk factor for poor healing outcomes is a dysregulated immune response following injury. In a preclinical model of orthopedic trauma, we demonstrate that distinct systemic immune profiles are correlated with impaired bone regeneration. Most notably, elevated blood levels of myeloid-derived suppressor cells (MDSCs) and the immunosuppressive cytokine interleukin-10 (IL-10) are negatively correlated with functional bone regeneration as early as 1 wk posttreatment. Nonlinear multivariate regression also implicated these two factors as the most influential in predictive computational models. These results support a significant relationship between early systemic immune responses to trauma and subsequent local bone regeneration and indicate that elevated circulating levels of MDSCs and IL-10 may be predictive of poor functional healing outcomes and represent novel targets for immunotherapeutic intervention.