Aims. Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing. Methods. The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series. Results. In all, 94 eligible studies were identified. The clinical and methodological aspects of the studies were too heterogeneous for a meta-analysis to be undertaken. A narrative synthesis examined study characteristics, stem cell methods (source, aspiration, concentration, and application) and outcomes. Conclusion. Insufficient high-quality evidence is available to determine the efficacy of stem cells for fracture healing. The studies were heterogeneous in population, methods, and outcomes. Work to address these issues and establish standards for future research should be undertaken. Cite this article: Bone Joint Open 2020;1-10:628–638

There is conjecture on the optimal timing to administer bisphosphonate therapy following operative fixation of low- trauma hip fractures. Factors include recommendations for early opportunistic commencement of osteoporosis treatment, and clinician concern regarding the effect of bisphosphonates on fracture healing. We performed a systematic review and meta-analysis to determine if early administration of bisphosphonate therapy within the first month post-operatively following proximal femur fracture fixation is associated with delay in fracture healing or rates of delayed or non-union. We included randomised controlled trials examining fracture healing and union rates in adults with proximal femoral fractures undergoing osteosynthesis fixation methods and administered bisphosphonates within one month of operation with a control group. Data was pooled in meta-analyses where possible. The Cochrane Risk of Bias Tool and the GRADE approach were used to assess validity. For the outcome of time to fracture union, meta-analysis of three studies (n= 233) found evidence for earlier average time to union for patients receiving early bisphosphonate intervention (MD = −1.06 weeks, 95% CI −2.01 – −0.12, I. 2. = 8%). There was no evidence from two included studies comprising 718 patients of any difference in rates of delayed union (RR 0.61, 95% CI 0.25–1.46). Meta-analyses did not demonstrate a difference in outcomes of mortality, function, or pain. We provide low-level evidence that there is no reduction in time to healing or delay in bony union for patients receiving bisphosphonates within one month of proximal femur fixation

Olecranon fractures are common injuries representing roughly 5% of pediatric elbow fractures. The traditional surgical management is open reduction and internal fixation with a tension band technique where the pins are buried under the skin and tamped into the triceps. We have used a modification of this technique, where the pins have been left out of the skin to be removed in clinic. The purpose of the current study is to compare the outcomes of surgically treated olecranon fractures using a tension-band technique with buried k-wires (PINS IN) versus percutaneous k-wires (PINS OUT). We performed a retrospective chart review on all pediatric patients (18 years of age or less) with olecranon fractures that were surgically treated at a pediatric academic center between 2015 to present. Fractures were identified using ICD-10 codes and manually identified for those with an isolated olecranon fracture. Patients were excluded if they had polytrauma, metabolic bone disease, were treated non-op or if a non-tension band technique was used (ex: plate/screws). Patients were then divided into 2 groups, olecranon fractures using a tension-band technique with buried k-wires (PINS IN) and with percutaneous k-wires (PINS OUT). In the PINS OUT group, the k-wires were removed in clinic at the surgeon's discretion once adequate fracture healing was identified. The 2 groups were then compared for demographics, time to mobilization, fracture healing, complications and return to OR. A total of 35 patients met inclusion criteria. There were 28 patients in the PINS IN group with an average age of 12.8 years, of which 82% male and 43% fractured their right olecranon. There were 7 patients in the PINS OUT group with an average age of 12.6 years, of which 57% were male and 43% fractured their right olecranon. All patients in both groups were treated with open reduction internal fixation with a tension band-technique. In the PINS IN group, 64% were treated with 2.0 k-wires and various materials for the tension band (82% suture, 18% cerclage wire). In the PINS OUT group, 71% were treated with 2.0 k-wires and all were treated with sutures for the tension band. The PINS IN group were faster to mobilize (3.4 weeks (range 2-5 weeks) vs 5 weeks (range 4-7 weeks) p=0.01) but had a significantly higher complications rate compared to the PINS OUT group (6 vs 0, p =0.0001) and a significantly higher return to OR (71% vs 0%, p=0.0001), mainly for hardware irritation or limited range of motion. All fractures healed in both groups within 7 weeks. Pediatric olecranon fractures treated with a suture tension-band technique and k-wires left percutaneously is a safe and alternative technique compared to the traditional buried k-wires technique. The PINS OUT technique, although needing longer immobilization, could lead to less complications and decreased return to the OR due to irritation and limited ROM

Introduction. The management of fracture-related infection has undergone radical progress following the development of international guidelines. However, there is limited consideration to the realities of healthcare in low-resource environments due to a lack of available evidence in the literature from these settings. Initial antimicrobial suppression to support fracture union is frequently used in low- and middle-income countries despite the lack of published clinical evidence to support its practice. This study aimed to evaluate the outcomes following initial antimicrobial suppression to support fracture union in the management of fracture-related infection. Materials & Methods. A retrospective review of consecutive patients treated with initial antimicrobial suppression to support fracture healing followed by definitive eradication surgery to manage fracture-related infections following intramedullary fixation was performed. Indications for this approach were; a soft tissue envelope not requiring reconstructive surgery, radiographic evidence of stable fixation with adequate alignment, and progression towards fracture union. Results. This approach was associated with successful treatment in 51/55 (93%) patients. Fracture union was achieved in 52/55 (95%) patients with antimicrobial suppression alone. Remission of infection was achieved in 54/55 (98%) patients following definitive infection eradication surgery. Following antibiotic suppression, 6/46 (13%) pathogens isolated from intra-operative samples demonstrated multi-drug resistance. Conclusions. Initial antimicrobial suppression to support fracture healing followed by definitive infection eradication surgery was associated with successful treatment in 93% of patients. The likelihood of remission of infection increases when eradication surgery is performed in a healed bone. This approach was not associated with an increased risk of developing multi-drug-resistant infections compared to contemporary bone infection cohorts in the published literature

Aim. The treatment of fracture-related infections (FRI) focuses on obtaining fracture healing and eradicating infection to prevent osteomyelitis. Treatment guidelines include removal, exchange, or retention of the implants used according to the stability of the fracture and the time from the infection. Infection of a fracture in the process of healing with a stable fixation may be treated with implant retention, debridement, and antibiotics. Nonetheless, the retention of an intramedullary nail is a potential risk factor for failure, and it is recommended to exchange or remove the nail. This surgical approach implies additional life-threatening risks in elderly fragile hip fracture patients. Our study aimed to analyze the results of implant retention for the treatment of infected nails in elderly hip fracture patients. Methods. Our retrospective analysis included patients 65 years of age or older with an acute fracture-related infection treated with implant retention from 2012 to 2020 in 6 Spanish hospitals with a minimum 1-year follow-up. Patients that required open reduction during the initial fracture surgery were excluded. Variables included in our analysis were patient demographics, type of fracture, date of FRI diagnosis, causative microorganism, and outcome. Treatment success was defined as fracture healing with infection eradication without the need for further hospitalization. Results. A total of 48 patients were identified. Eight patients with open reduction were excluded and 11 did not complete a 1-year follow-up. Out of the 29 remaining patients, the mean age was 81.5 years, with a 21:9, female to male ratio. FRI was diagnosed between 10 and 48 days after initial surgery (mean 26 days). Treatment success was achieved in 24 patients (82.7%). Failure was objectivated in polymicrobial infections or infections caused by microorganisms resistant to antibiofilm antibiotics. Seven patients required more than one debridement with a success rate of 57%. Twelve patients had an infection diagnosed after 21 days from the initial surgery and implant retention was successful in all of them. Conclusion. Our results suggest implant retention is a valid therapeutic approach for fracture-related infection in elderly hip fracture patients treated by closed reduction and intramedullary nailing

Introduction. Open fractures are fortunately rare but pose an even greater challenge due to poor soft tissues, in addition to poor bone quality. Co-morbidities and pre-existing medical conditions, in particular, peripheral vascular diseases make them often unsuitable for free flaps. We present our experience in treating severe open fractures of tibia with Acute Intentional Deformation (AID) to close the soft tissues followed by gradual correction of deformity to achieve anatomical alignment of the tibia and fracture healing with Taylor Spatial Frame. Materials and Methods. We treated 4 geriatric (3 female and 1 male) patients with Gustillo-Anderson III B fractures of the tibia between 2017–18. All were unfit to undergo orthoplastic procedures (free flap or local flaps). The age range is 69 yrs to 92 years. Co-morbidities included severe rheumatoid arthritis, multiple sclerosis and heart failure. The procedure involved wound debridement, application of two ring Taylor Spatial Frame, acute deformation of the limb on the table to achieve soft-tissue closure/approximation. Regular neurovascular assessments were performed in the immediate post-operative period to monitor for compartment syndrome and nerve compression symptoms. After 7–10 days of latent period, the frame was gradually manipulated, according to a method we had previously published, to achieve anatomical alignment. The frame was removed in clinic after fracture healing. Results. Time in frame ranged from 1.5 months to 7 months. In one patient (92 yr old with an open fracture of the ankle) hindfoot nail was inserted after soft-tissue closure was achieved at 1.5 months, and frame removed. We achieved complete healing of soft tissue wounds without any input from plastic surgeons in all patients. All fractures healed in anatomical alignment. 3 patients had one episode of superficial pin infection each requiring 5 days of oral antibiotics. None of the patients developed a deep infection. Conclusions. Acute intentional deformation (AID) with Taylor Spatial Frame achieves good closure of soft tissues in physiologically compromised geriatric patients who were deemed unfit for plastic surgery. We also achieved fracture healing in all four cases without any major complications

Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally, fracture callus development is affected by the absence of SP indicating a critical effect of sensory nerve fibers on bone health and regeneration. For α-calcitonin gene-related peptide (α-CGRP)-deficient mice, a profound distortion of bone microarchitecture has also been described. We hypothesize that SP and α-CGRP modulate inflammatory as well as pain-related processes and positively affect bone regeneration during impaired fracture healing under osteoporotic conditions. Therefore, this study investigates the effects of SP and α-CGRP on fracture healing and fracture-related pain processes under conditions of experimental osteoporosis using SP- and α-CGRP-deficient mice and WT controls. We ovariectomized female WT, Tac1−/− and α-CGRP−/− mice (age 10 weeks, all strains on C57Bl/6J background) and set intramedullary fixed femoral fractures in the left femora 28 days later. We analyzed pain threshold (Dynamic Plantar Aesthesiometer Test) and locomotion (recorded at day and night, each for 1 hour, EthoVision®XT, Noldus) at 5, 9, 13, 16 and 21 days after fracture. At each time point, fractured femora were prepared for histochemical analysis of callus tissue composition (alcian blue/sirius red staining). Pain threshold is significantly higher in Tac1−/− mice 13 days after fracture and tends to be higher after 21 days compared to WT controls. In contrast, touch sensibility was similar in α-CGRP−/− mice and WT controls but compared to Tac1−/− mice pain threshold was significantly lower in α-CGRP−/− mice 13 and 16 days and tends to be lower 21 days after fracture. Locomotion of Tac1−/− mice during daylight was by trend higher 9 days after fracture and significantly higher 16 days after fracture whereas nightly locomotion is reduced compared to WT mice. Analysis of locomotion during daylight or night revealed no differences between α-CGRP−/− and WT mice. During early fracture healing phase, 5 and 9 days after fracture, transition of mesenchymal to cartilaginous callus tissue tends to be faster in Tac1−/− mice compared to WT controls whereas no difference was observed during late stage of fracture healing, 13, 16 and 21 days after fracture. In contrast, callus tissue maturation seems to be similar in α-CGRP−/− and WT mice. Our data indicate different effects of SP and α-CGRP on fracture healing under conditions of experimental osteoporosis as a model for impaired bone tissue. Lack of α-CGRP seems to have no effects, but loss of SP affects locomotion throughout osteoporotic fracture healing and fracture-related pain processes during late phases of osteoporotic fracture healing. This indicates a modified role of SP during fracture healing under impaired versus healthy conditions, where SP changed early fracture-related pain processes and had no influence on callus tissue composition

Abstract. Background. Aim of this study is to determine the difference between re-operation rates after conventional Methods of fixation of patella fractures using Metallic implants and novel technique of all suture fixation using Ethibond or fiber tape. Methods. This is a retrospective comparative analysis involving 62 patients who had a transverse patellar fracture and underwent surgery between January 2013 to December 2021. Selected patients were divided, based on different fixation methods used, into four groups - TBW group, CC screw group, Encirclage group and Suture Fixation Group. Patients were followed till bone union was evident on radiographs. Number of patients in Metallic implant group undergoing repeat operation were compared with the patients who underwent patella fracture fixation using all suture technique. Mean and standard deviation (SD) were calculated for all continuous variables. Mean of the two groups was compared using unpaired t-test. Results. TBW was the most common method of fixation used in 41(66.1%) patients. 7 patients each underwent surgery using CC screw, Encirclage +/− TBW, and suture fixation respectively. Bone union was seen in about 85% of patients in all the groups suggesting all treatment modalities lead to good fracture healing. 15 patients(36.6%) of patients in TBW group and 3 patients(42.9%) in encirclage group had implant removal because of hardware-related complications (p<0.001). None of the patient who underwent All suture Fixation underwent re-operation. Conclusion. The results suggest that Suture fixation of patellar fractures is a valid treatment modality giving excellent results with similar bone union rates without any complications

Introduction. Frame configuration for the management of complex tibial fractures is highly variable and is dependent not only on fracture pattern and soft tissue condition but also surgeon preference. The optimal number of rings to use when designing a frame remains uncertain. Traditionally, larger, stiffer constructs with multiple rings per segment were thought to offer optimal conditions for bone healing, however, the concept of reverse dynamisation questions this approach. Materials & Methods. We compared clinical outcomes in 302 consecutive patients with tibial fractures treated in our unit with either a two-ring circular frame or a three-or-more-ring (3+) frame. The primary outcome measure was time spent in frame. Secondary outcomes were the incidence of malunion and the need for further surgical procedures to achieve bone union. The groups were evenly matched for age, co-morbidities, energy of injury mechanism, fracture classification, post-treatment alignment and presence of an open fracture. Results. The mean time in frame was 168 days for the 2-ring group and 200 days for the 3+ rings group (p=0.003). No significant difference was found in the rate of malunion (p=0.428) or the requirement for secondary surgical intervention to achieve union (p=0.363). No significant difference in time in frame was found between individual surgeons. Conclusions. This study finds that 2-ring frame constructs are a reliable option associated with significantly shorter duration of treatment and no increase in rates of adverse outcomes compared with larger, more complex frame configurations. Although this study cannot identify the underlying cause of the difference in treatment time between frame designs, it is possible that differences in mechanical stability lead to a more favourable strain environment for fracture healing in the 2-ring group

It has been previously shown that Low-Magnitude High-Frequency Vibration (LMHFV) is able to enhance ovariectomy-induced osteoporotic fracture healing in rats. Fracture healing begins with the inflammatory stage, and all subsequent stages are regulated by the infiltration of immune cells such as macrophages and the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Therefore, the aim of this study was to investigate the effect of LMFHV treatment on the inflammatory response in osteoporotic fracture healing. In this study, ovariectomy-induced osteoporotic and sham-operated closed-femoral fracture SD-rats were randomized into three groups: sham control (SHAM), ovariectomized control (OVX-C) or ovariectomized vibration (OVX-V) (n=36, n=6 per group per time point). LMHFV (35Hz, 0.3g) was given 20 min/day and 5 days/week to OVX-V group. SHAM operation and ovariectomy were performed at 6-month and closed femoral fracture was performed at 9-month. Callus morphometry was determined by callus width from weekly radiography. Local expressions of inducible nitric oxide synthase (iNOS) (macrophage M1 marker), CD206 (macrophage M2 marker), TNF-α, IL-6 and IL-10 were detected by immunohistochemistry and quantified by colour threshold in ImageJ, assessed at weeks 1 and 2 post-fracture. Significant difference between groups was considered at p≤0.05 by one-way ANOVA. Callus formation was higher in OVX-V than that of OVX-C as shown by callus width at weeks 1 and 2 (p=0.054 and 0.028, respectively). Immunohistochemistry results showed that CD206 positive signal and the M2/M1 ratio which indicates the progression of macrophage polarization were significantly higher in OVX-V rats (p=0.053 and 0.049, respectively) when compared to OVX-C at week 1. Area fraction of TNF-α positive signal was significantly higher in SHAM and OVX-V rats at week 1 (p=0.01 and 0.033, respectively). IL-6 signal was also significantly higher in SHAM and OVX-V groups at week 1 (p=0.004 and 0.029, respectively). IL-10 expression was significantly lower in SHAM and OVX-V groups at week 1 (p=0.013 and 0.05, respectively). Here we have shown that LMHFV treatment promoted the shift from pro-inflammatory stage towards anti-inflammatory stage earlier. It has been reported that the polarization of pro-inflammatory macrophages M1 to anti-inflammatory macrophages M2 was indicative of the endochondral ossification process in the long bone fracture model. Besides, we found that LMHFV treatment enhanced pro-inflammatory markers of TNF-α and IL-6 and suppressed anti-inflammatory marker of IL-10 at week 1, showing that inflammatory response was enhanced at week 1 post-fracture. These inflammatory cytokines involved in fracture healing were shown to coordinate different fracture healing processes such as mesenchymal stem cell recruitment and angiogenesis. Our previous study has demonstrated that ovariectomized rats exhibit lower levels of inflammatory response after fracture creation. Therefore, we report that LMHFV treatment can modulate macrophage polarization from M1 to M2 at an earlier time-point and partly restore the impaired inflammatory response in OVX bones at the early stage of fracture healing that may lead to accelerated healing of osteoporotic fracture as shown by promoted callus formation

Introduction. Non-union is an unfortunate outcome of the fracture healing process for some patients; with an estimated annual incidence of 17.4- 18.9 per 100,00. The management of these patients depicts a significant clinical challenge for surgeons and financial burden to health services. External ultrasound stimulation devices (Exogen. TM. ) have been highlighted as a novel non invasive therapy to achieve union in cases of delayed and non-union. The aim of the current study was to assess the rate of union in patients using Exogen. TM. therapy for delayed fracture union in a district general hospital. Materials & Methods. This is a single centre retrospective continuous cohort study. Patients were identified from a prospective database of all patients prescribed Exogen. TM. therapy between June 2013- September 2021 in a district general hospital. Patient data was collected retrospectively using electronic patient records. Fracture union was assessed both clinically and radiographically and recorded in patient records. Failure of treatment was defined as progression to operative treatment due to lack of progression with ultrasound therapy or established asymptomatic non-union. Patient were excluded from the study if Exogen. TM. therapy was prescribed within 6 weeks of injury. Results. 142 potential patient were identified from the database. 35 patients were excluded from the data set (17 patients due to insufficient data available, 9 lost to follow up, 4 died and 5 excluded due to early application of Exogen. TM. therapy). 58 Patients progressed to union with an average time to union of 41 weeks. 49 cases failed to progress to union, of which 7 cases had conversion to operative management prior to completion of single course of Exogen. TM. therapy and were excluded from all other data review. 12% of cases that failed to unite with ultrasound therapy required multiple operations to establish union. Conclusions. A union rate of 58% was reported by the current study, which is lower than previously published. This likely reflects the heterogenous nature of the patient population and fracture distribution included. However, this is potentially a more reflective union rate for the general population than previously published. There were no adverse events associated with the use of Exogen. TM. therapy in the current study. Therefore supporting its use as a first line management to promote union in delayed fracture union in the general population. Additionally, failure to achieve fracture union with utilisation of Exogen. TM. therapy was associated with risk for requirement of multiple surgeries to achieve union. This could serve as an indicator for surgeon to consider the requirement additional measures at the initial surgical procedure

Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for Macrophage Colony Stimulating Factor 1 (MCSF-1) and Hepatocyte Growth Factor (HGF) (p<0.01). In comparing AS with HEAL patients, 9 cytokines displayed significant differences, including interleukin (IL)-6, Vascular Endothelial Growth Factor A (VEGFA), Matrix Metalloproteinase 1 (MMP-1). Comparison of INF with HEAL patients revealed significantly different expression of 20 cytokines, including. IL-6, IL-18, VEGFA or MMP-1. Conclusions. Our study revealed differences in plasma cytokine profile of blood samples from INF and AS patients. Although no single biomarker is sufficient to differentiate these patients preoperatively in isolation, future multivariant analysis of this cytokine data in combination with clinical characteristics may provide valuable diagnostic insights. Funded by German Social Accident Insurance (FF-FR 0276) and AO Trauma (AR2021_04)

Aim. Silver is known for its excellent antimicrobial activity, including activity against multiresistant strains. The aim of the current study was to analyze the biocompatibility and potential influence on the fracture healing process a silver-coating technology for locking plates compared to silver-free locking plates in a rabbit model. Methods. The implants used in this study were 7-hole titanium locking plates, and plasma electrolytic oxidation (PEO) silver coated equivalents. A total of 24 rabbits were used in this study (12 coated, 12 non-coated). An osteotomy of the midshaft of the humerus was created with an oscillating saw and the humerus stabilized with the 7 hole locking plates with a total of 6 screws. X-rays were taken on day 0, week 2, 4, 6, 8, and 10 for continuous radiographical evaluation of the fracture healing. All animals were euthanized after 10 weeks and further assessment was performed using X-rays, micro-CT, non-destructive four-point bending biomechanical testing and histology. Furthermore, silver concentration was measured in the kidney, liver, spleen and brain. Results. X-rays showed normal undisturbed healing of the osteotomy in all animals without any differences between the two groups over the entire X-ray analysis over 10 weeks (Figure 1). Callus formation was observed up to week 4 to 5 followed by callus remodeling after 6 weeks indicating physiological fracture healing pattern in both the silver and in the silver free group. Micro CT analysis revealed overall tissue (callus and cortical bone) volume as well as tissue density to be comparable between the two groups. Mechanical testing showed comparable stiffness with an average stiffness relative to contralateral bones of 75.7 ± 16.1% in the silver free control group compared to 69.7 ± 18.5% (p-value: 0.46). Histology showed no remarkable difference in the analysis of the healed osteotomy gap or in the surrounding soft tissue area. Silver content was found to be close to baseline values without differences between the two groups. Conclusions. This study shows that the presented antimicrobial silver surface modification for locking plates has a good biocompatibility without any negative influence on the fracture healing processes compared to the silver free control group. This allows for further clinical investigation of this silver technology for locking plates in fracture patients with an elevated infection risk, e.g. in patients with open fractures. For any figures or tables, please contact the authors directly

Fractures of the humeral diaphysis occur in a bimodal distribution and represent 3-5% of all fractures. Presently, the standard treatment of isolated humeral diaphyseal fractures is nonoperative care using splints, braces, and slings. Recent data has questioned the effectiveness of this strategy in ensuring fracture healing and optimal patient function. The primary objective of this randomized controlled trial (RCT) was to assess whether operative treatment of humeral shaft fractures with a plate and screw construct provides a better functional outcome than nonoperative treatment. Secondary objectives compared union rates and both clinical and patient-reported outcomes. Eligible patients with an isolated, closed humeral diaphyseal fracture were randomized to either nonoperative care (initial sugar-tong splint, followed by functional coaptation brace) or open reduction and internal fixation (ORIF; plate and screw construct). The primary outcome measure was the Disability Shoulder, Arm, Hand (DASH) score assessed at 2-, 6-, 16-, 24-, and 52-weeks. Secondary outcomes included the Short Musculoskeletal Functional Assessment (SMFA), the Constant Shoulder Score, range of motion (ROM), and radiographic parameters. Independent samples t-tests and Chi-squared analyses were used to compare treatment groups. The DASH, SMFA, and Constant Score were modelled over time using a multiple variable mixed effects model. A total of 180 patients were randomized, with 168 included in the final analysis. There were 84 patients treated nonoperatively and 84 treated with ORIF. There was no significant difference between the two treatment groups for age (mean = 45.4 years, SD 16.5 for nonoperative group and 41.7, SD 17.2 years for ORIF group; p=0.16), sex (38.1% female in nonoperative group and 39.3% female in ORIF group; p=0.87), body mass index (mean = 27.8, SD 8.7 for nonoperative group and 27.2, SD 6.2 for ORIF group; p=0.64), or smoking status (p=0.74). There was a significant improvement in the DASH scores at 6 weeks in the ORIF group compared to the nonoperative group (mean=33.8, SD 21.2 in the ORIF group vs. mean=56.5, SD=21.1 in the nonoperative group; p < 0 .0001). At 4 months, the DASH scores were also significantly better in the ORIF group (mean=21.6, SD=19.7 in the ORIF group vs. mean=31.6, SD=24.6 in the nonoperative group; p=0.009. However, there was no difference in DASH scores at 12-month follow-up between the groups (mean=8.8,SD=10.9 vs. mean=11.0, SD=16.9 in the nonoperative group; p=0.39). Males had improved DASH scores at all timepoints compared with females. There was significantly quicker time to union (p=0.016) and improved position (p < 0 .001) in the ORIF group. There were 13 (15.5%) nonunions in the nonoperative group and four (4.7%) combined superficial and deep infections in the ORIF group. There were seven radial nerve palsies in the nonoperative group and five (a single iatrogenic) radial nerve palsies in the ORIF group. This large RCT comparing operative and nonoperative treatment of humeral diaphyseal fractures found significantly improved functional outcome scores in patients treated surgically at 6 weeks and 4 months. However, the early functional improvement did not persist at the 12-month follow-up. There was a 15.5% nonunion rate, which required surgical intervention, in the nonoperative group and a similar radial nerve palsy rate between groups

Fractures of the humeral diaphysis occur in a bimodal distribution and represent 3-5% of all fractures. Presently, the standard treatment of isolated humeral diaphyseal fractures is nonoperative care using splints, braces, and slings. Recent data has questioned the effectiveness of this strategy in ensuring fracture healing and optimal patient function. The primary objective of this randomized controlled trial (RCT) was to assess whether operative treatment of humeral shaft fractures with a plate and screw construct provides a better functional outcome than nonoperative treatment. Secondary objectives compared union rates and both clinical and patient-reported outcomes. Eligible patients with an isolated, closed humeral diaphyseal fracture were randomized to either nonoperative care (initial sugar-tong splint, followed by functional coaptation brace) or open reduction and internal fixation (ORIF; plate and screw construct). The primary outcome measure was the Disability Shoulder, Arm, Hand (DASH) score assessed at 2-, 6-, 16-, 24-, and 52-weeks. Secondary outcomes included the Short Musculoskeletal Functional Assessment (SMFA), the Constant Shoulder Score, range of motion (ROM), and radiographic parameters. Independent samples t-tests and Chi-squared analyses were used to compare treatment groups. The DASH, SMFA, and Constant Score were modelled over time using a multiple variable mixed effects model. A total of 180 patients were randomized, with 168 included in the final analysis. There were 84 patients treated nonoperatively and 84 treated with ORIF. There was no significant difference between the two treatment groups for age (mean = 45.4 years, SD 16.5 for nonoperative group and 41.7, SD 17.2 years for ORIF group; p=0.16), sex (38.1% female in nonoperative group and 39.3% female in ORIF group; p=0.87), body mass index (mean = 27.8, SD 8.7 for nonoperative group and 27.2, SD 6.2 for ORIF group; p=0.64), or smoking status (p=0.74). There was a significant improvement in the DASH scores at 6 weeks in the ORIF group compared to the nonoperative group (mean=33.8, SD 21.2 in the ORIF group vs. mean=56.5, SD=21.1 in the nonoperative group; p < 0 .0001). At 4 months, the DASH scores were also significantly better in the ORIF group (mean=21.6, SD=19.7 in the ORIF group vs. mean=31.6, SD=24.6 in the nonoperative group; p=0.009. However, there was no difference in DASH scores at 12-month follow-up between the groups (mean=8.8,SD=10.9 vs. mean=11.0, SD=16.9 in the nonoperative group; p=0.39). Males had improved DASH scores at all timepoints compared with females. There was significantly quicker time to union (p=0.016) and improved position (p < 0 .001) in the ORIF group. There were 13 (15.5%) nonunions in the nonoperative group and four (4.7%) combined superficial and deep infections in the ORIF group. There were seven radial nerve palsies in the nonoperative group and five (a single iatrogenic) radial nerve palsies in the ORIF group. This large RCT comparing operative and nonoperative treatment of humeral diaphyseal fractures found significantly improved functional outcome scores in patients treated surgically at 6 weeks and 4 months. However, the early functional improvement did not persist at the 12-month follow-up. There was a 15.5% nonunion rate, which required surgical intervention, in the nonoperative group and a similar radial nerve palsy rate between groups

Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures

Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient mechanical strength to support the fracture. Microarc oxidation (MAO) is a metal surface coating that reduces corrosion. We hypothesized that Mg pins, with or without MAO, would enhance fracture healing radiologically, mechanically, and histologically, while MAO would decrease degradation of Mg pins. Patellar fracture was performed on forty-eight 18-week-old female New Zealand White rabbits according to established protocol. Briefly, the patella is osteotomized transversely and a tunnel (1.1mm) was drilled longitudinally through the two bone fragments. A pin (1 mm, stainless steel, Mg, or MAO-Mg) was inserted into the tunnel. The reduced construct was stabilized with a figure-of-eight band wire (⊘ 0.6 mm stainless steel wire). Cast immobilization was applied for 6 weeks. The rabbits were euthanized at week 8 and 12 post-operation. Microarchitecture and mechanical properties of the repaired patella were analyzed with microCT and tensile testing respectively. Histological sections of the repaired patella were stained. To evaluate the effect of the MAO treatment on degradation rate of Mg pin, the volume of the Mg pins in the patella was measured with microCT. At week 8, both Mg and Mg-MAO showed higher ratio of bone volume to tissue volume (BV/TV) than the control while there was no significant different between Mg and Mg-MAO. At week 12, Control, Mg, and Mg-MAO groups showed enlarged patella when compared to the normal patella. Tissue volume (TV) and bone volume (BV) of the patella in Mg and Mg-MAO were larger than those in the Control group. However, the Control had higher ratio of bone volume to tissue volume (BV/TV), TV density, and BV density than Mg and Mg-MAO. Tensile testing showed that the mechanical properties of the repaired patella (failure load, stiffness, ultimate strength, and energy-to-failure) of Mg and Mg-MAO were higher than that of the control at both week 8 and week 12. Histological analysis showed that there was significant new bone formation in the Mg and Mg-MAO group compared with the Control group at week 8 and 12. The degradation rate of the MAO-coated Mg pins was significantly slower than those without MAO at week 8 but no significant difference was detected at week 12. Mechanical, microarchitectural, and histological assessments showed that Mg pins, with or without MAO, enhanced fracture healing of the repaired patella compared to the Control. MAO treatment enhanced the corrosion resistance of the Mg pins at the early time point

Age-related fragility fractures are highly correlated with the loss of bone integrity and deteriorated morphology of the osteocytes. Previous studies have reported low-magnitude high-frequency vibration(LMHFV) promotes osteoporotic diaphyseal fracture healing to a greater extent than in age-matched normal fracture healing, yet how osteoporotic fractured bone responds to the mechanical signal has not been explored. As osteocytes are prominent for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance fracture healing in ovariectomized metaphyseal fracture through morphological changes and mineralisation in the osteocyte Lacuno-canalicular Network(LCN). As most osteoporotic fractures occur primarily at the metaphysis, an osteoporotic metaphyseal fracture model was established. A total of 72 six-month old female Sprague-Dawley rats (n=72) were obtained(animal ethical approval ref: 16–037-MIS). Half of the rats underwent bilateral ovariectomy(OVX) and kept for 3 months for osteoporosis induction. Metaphyseal fracture on left distal femur was created by osteotomy and fixed by a plate. Rats were then randomized to (1) OVX+LMHFV(20 mins/day and 5 days/week, 35Hz, 0.3g), (2) OVX control, (3) SHAM+LMHFV, (4) SHAM control. Assessments of morphological structural changes, functional markers of the LCN(Scanning Electron Microscopy, FITC-Imaris, immunohistochemistry), mineralization status(EDX, dynamic histomorphometry) and healing outcomes(X-ray, microCT, mechanical testing) were performed at week 1, 2 and 6 post-fracture. One‐way ANOVA with post-hoc test was performed. Statistical significance was set at p < 0.05. Our results showed LMHFV could significantly enhance the morphology of the LCN. There was a 65.3% increase in dendritic branch points(p=0.03) and 93% increase in canalicular length(p=0.019) in the OVX-LMHFV group at week 2 post-fracture. Besides, a similar trend was also observed in the SHAM+LMHFV group, with a 43.4% increase in branch points and 53% increase in canaliculi length at week 2. A significant increase of E11 and DMP1 was observed in the LMHFV groups, indicating the reconstruction of the LCN. The decreasing sclerostin and increasing FGF23 at week 1 represented the active bone formation phase while the gradual increase at week 6 signified the remodelling phase. Furthermore, Ca/P ratio, mineral apposition rate and bone formation rate were all significantly enhanced in the OVX+LMHFV group. The overall bone mineral density in BV was significantly raised in the OVX+LMHFV group at week 2(p=0.043) and SHAM+LMHFV at week 6(p=0.04). Quantitative analysis of microCT showed BV/TV was significantly increased at week 2 in OVX+LMHFV group(p=0.008) and week 6(p=0.001) in both vibration groups. In addition, biomechanical testing revealed that the OVX+LMHFV group had a significantly higher ultimate load(p=0.03) and stiffness(p=0.02) at week 2. To our best knowledge, this is the first report to illustrate LMHFV could enhance osteocytes' morphology, mineralisation status and healing outcome in a new osteoporotic metaphyseal fracture animal model. Our cumulative data supports that the mechanosensitivity of bone would not impair due to osteoporosis. The revitalized osteocyte LCN and upregulated osteocytic protein markers implied a better connectivity and transduction of signals between osteocytes, which may foster the osteoporotic fracture healing process through an enhanced mineralisation process. This could stimulate further mechanistic investigations with potential translation of LMHFV to our fragility fracture patients

Introduction. Metabolic bone disease encompasses disorders of bone mineralization, abnormal matrix formation or deposition and alteration in osteoblastic and osteoclastic activity. In the paediatric cohort, patients with metabolic bone disease present with pain, fractures and deformities. The aim was to evaluate the use of lateral entry rigid intramedullary nailing in lower limbs in children and adolescents. Materials and Methods. Retrospective review was performed for an 11-year period. Lower limb rigid intramedullary nailing was performed in 27 patients with a total of 63 segments (57 femora, 6 tibiae). Majority of patients had underlying diagnoses of osteogenesis imperfecta or fibrous dysplasia (including McCune Albright disease). Mean age at surgery was 14 years. Indications for surgery included acute fractures, prophylactic stabilisation, previous nonunion and malunion, deformity correction and lengthening via distraction osteogenesis. Results. All fractures healed. Correction of deformity was successfully achieved in all segments. Delayed union occurred in 4 segments in 1 patient and was successfully treated with nail dynamization. Other complications included prominence, cortical penetrance and loosening of locking screws. One patient who had lengthening performed had nonunion and was managed with exchange nailing and adjunctive measures. Conclusions. Rigid intramedullary nailing is very effective in stabilisation and deformity correction of long bones in adolescent patients with pathological bone disease. The technique has low complication rates. We recommend the use of this technique in paediatric units with experience in managing metabolic bone conditions

Introduction. Osteogenesis imperfect (OI) is a geno- and phenotypically heterogeneous group of congenital collagen disorders characterized by fragility and microfractures resulting in long bone deformities. OI can lead to progressive femoral coxa vara from bone and muscular imbalance and continuous microfracture about the proximal femur. If left untreated, patients develop Trendelenburg gait, leg length discrepancy, further stress fracture and acute fracture at the apex of the deformity, impingement and hip joint degeneration. In the OI patient, femoral coxa vara cannot be treated in isolation and consideration must be given to protecting the whole bone with the primary goal of verticalization and improved biomechanical stability to allow early loading, safe standing, re-orientation of the physis and avoidance of untreated sequelae. Implant constructs should therefore be designed to accommodate and protect the whole bone. The normal paediatric femoral neck shaft angle (FNSA) ranges from 135 to 145 degrees. In OI the progressive pathomechanical changes result in FNSA of significantly less than 120 degrees and decreased Hilgenreiner epiphyseal angles (HEA). Proximal femoral valgus osteotomy is considered the standard surgical treatment for coxa vara and multiple surgical techniques have been described, each with their associated complications. In this paper we present the novel technique of controlling femoral version and coronal alignment using a tubular plate and long bone protection with the use of teleoscoping rods. Methodology. After the decision to operate had been made, a CT scan of the femur was performed. A 1:1 scale 3D printed model (AXIAL3D, Belfast, UK) was made from the CT scan to allow for accurate implant templating and osteotomy planning. In all cases a subtrochanteric osteotomy was performed and fixed using a pre-bent 3.5 mm 1/3 tubular plate. The plate was bent to allow one end to be inserted into the proximal femur to act as a blade. A channel into the femoral neck was opened using a flat osteotome. The plate was then tapped into the femoral neck to the predetermined position. The final position needed to allow one of the plate holes to accommodate the growing rod. This had to be determined pre operatively using the 3D printed model and the implants. The femoral canal was reamed, and the growing rod was placed in the femur, passing through the hole in the plate to create a construct that could effectively protect both the femoral neck and the full length of the shaft. The distal part of the plate was then fixed to the shaft using eccentric screws around the nail to complete the construct. Results. Three children ages 5,8 and 13 underwent the procedure. Five coxa vara femurs have undergone this technique with follow-up out to 62 months (41–85 months) from surgery. Improvements in the femoral neck shaft angle (FNSA) were av. 18. o. (10–38. o. ) with pre-op coxa vara FNSA av. 99. o. (range 87–114. o. ) and final FNSA 117. o. (105–125. o. ). Hilgenreiner's epiphyseal angle was improved by av. 29. o. (2–58. o. ). However only one hip was restored to <25. o. In the initial technique employed for 3 hips, the plates were left short in the neck to avoid damaging the physis. This resulted in 2 of 3 hips fracturing through the femoral neck above the plate at approximately 1 year. There were revisions of the 3 hips to longer plates to prevent intra-capsular stress riser. All osteotomies united and both intracapsular fractures healed. No further fractures have occurred within the protected femurs and no other repeat operations have been required. Conclusions. Surgical correction of the OI coxa vara hip is complex. Bone mineral density, multiplanar deformity, a desire to maintain physeal growth and protection of the whole bone all play a role in the surgeon's decision making process. Following modifications, this technique demonstrates a novel method in planning and control of multiplanar proximal femoral deformity, resulting in restoration of the FNSA to a more appropriate anatomical alignment, preventing long bone fracture and improved femoral verticalization in the medium term follow-up