LncRNA MAGI2-AS3 promotes fracture healing through downregulation of miR-223-3p.

BACKGROUND: Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study investigated the molecular mechanism and regulatory significance of lncRNA MAGI2-AS3 (MAGI2-AS3) in fracture healing. METHODS: Serum levels of MAGI2-AS3 in patients with normal and delayed fracture healing were verified by RT-qPCR assays. The predictive efficacy of MAGI2-AS3 for delayed fracture healing was analyzed by ROC curve. Osteogenic markers were quantified by RT-qPCR assays. MC3T3-E1 cell viability was detected using CCK-8 assay, and flow cytometry was utilized to measure cell apoptosis. The dual-luciferase reporter gene assay was used to determine the targeted binding between MAGI2-AS3 and miR-223-3p. RESULTS: Serum MAGI2-AS3 expression was decreased in patients with delayed fracture healing compared with patients with normal healing. Elevated MAGI2-AS3 resulted in an upregulation of the proliferative capacity of MC3T3-E1 cells and a decrease in mortality, along with increased levels of both osteogenic markers. However, after transfection silencing MAGI2-AS3, the trend was reversed. Additionally, miR-223-3p was the downstream target of MAGI2-AS3 and was controlled by MAGI2-AS3. miR-223-3p mimic reversed the promoting effects of MAGI2-AS3 overexpression on osteogenic marker levels and cell growth, and induced cell apoptosis. CONCLUSION: The upregulation of MAGI2-AS3 may expedite the healing of fracture patients by targeting miR-223-3p, offering a novel biomarker for diagnosing patients with delayed healing.

Factors contributing to non-union amongst dentate mandibular fractures treated by load-sharing miniplate osteosynthesis: a case-control study.

The stability provided by load-sharing miniplate osteosynthesis (LSMO) in dentate mandibular fractures (DMF) is usually adequate for bony healing. Non-union following LSMO is an uncommon complication. We aimed to determine the incidence and identify contributing factors, if any, of non-union amongst DMFs that have undergone LSMO. This retrospective case-control study with an allocation ratio of 1:3 includes cases of non-union DMF following LSMO and controls with healed DMF following LSMO over a five-year period. Relevant sociodemographic data, mandibular fracture characteristics, and treatment variables were collected for both groups. Of the 381 patients who underwent LSMO for DMFs, 12 cases of non-union were identified. The control group included 36 patients with uncomplicated healing. A significant association was observed between non-union and teeth in the line of fracture, postoperative infections, and time from injury to LSMO. The odds ratio with chronic alcohol usage was 1.4. Vigilant follow up of patients with chronic alcohol use, those with teeth in the fracture line, and adherence to LSMO principles may help to minimise the non-union complication.

Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing.

BACKGROUND: Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. METHODS: 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. RESULTS: Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. CONCLUSIONS: LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.

Modified and alternative bone cements can improve the induced membrane: Critical size bone defect model in rat femur.

BACKGROUND: As a two-stage surgical procedure, Masquelet's technique has been used to care for critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity. METHODS: Thirty-five male rats were included in five groups: plain polymethyl methacrylate (PMMA), estrogen-impregnated PMMA (E+PMMA), bone chip added PMMA (BC+PMMA), hydroxyapatite-coated PMMA (HA) and calcium phosphate cement (CPC). The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-ß), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically. RESULTS: Serum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P = 0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P = 0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86 ± 1.57, 4.71 ± 0.76, and 6.57 ± 1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14 ± 0.70 and 1.86 ± 0.69, respectively) (P < 0.0001). Significant increases in TGF-ß and VEGF expressions were observed in E+PMMA and CPC groups (P = 0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P < 0.0001). CONCLUSIONS: The modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-ß and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement.

A comparative study of volar locking-plate fixation with corticocancellous and pure cancellous bone grafts for scaphoid nonunion with dorsal intercalated segmental instability secondary to scaphoid humpback deformity.

INTRODUCTION: Bone grafts for scaphoid nonunion with deformity include cortcicocancellous or pure cancellous bone grafts. This study compared the outcomes between two types of bone grafts when employing a volar locking-plate in patients with scaphoid nonunion with dorsal intercalated segmental instability (DISI). PATIENTS AND METHODS: This retrospective study included 34 patients with scaphoid nonunion and DISI due to humpback deformity treated between March 2017 and January 2022. Two types of bone grafts were obtained from iliac crest. Twenty of the corticocancellous (CC) group underwent a wedge-shaped graft, while 14 patients of the pure cancellous (C-only) group received graft chips. In both groups, a 1.5-mm anatomically pre-contoured locking plate was used for fixation. Radiographic evaluations included the union rate and carpal alignment including scapholunate angle (SLA), radiolunate angle (RLA), intrascaphoid angle (ISA) and scaphoid height to length ratio (HLR). Clinical assessments encompassed wrist range-of-motion, grip strength, and patient-reported outcomes. RESULTS: Nineteen of the 20 patients in the CC group and 12 of the 14 patients in the C-only group respectively, achieving osseous union. The mean follow-up period in CC group was 14.7 (range, 12 ∼ 24) months and that in C-only group was 12.6 (range, 12 ∼ 15) months. Postoperatively, there were no significant intergroup differences of radiographic parameters including SLA (CC; 49.9° ± 6.7° vs. C-only; 48.9° ± 3.5°, P = 0.676), RLA (1.7° ± 6.4° vs. 2.4° ± 3.3°, P = 0.74), ISA (36° ± 7.5° vs. 36.6° ± 12.2°, P = 0.881), and HLR (0.54 ± 0.09 vs. 0.53 ± 0.05, P = 0.587). Clinical outcomes, including the flexion-extension arc (137° ± 30° vs. 158° ± 33°, P = 0.122), grip strength (93.4 % ± 15.4% vs. 99.5 % ± 16.7 %, P = 0.39), Quick Disabilities of the Arm, Shoulder, and Hand scores (11.2 ± 8.3 vs. 12.5 ± 7.7, P = 0.74) and Mayo Wrist Scores (81.2 ± 13.1 vs. 89 ± 11.4, P = 0.242) also showed no significant intergroup differences. CONCLUSIONS: Volar locking-plate fixation with pure cancellous bone grafts achieved outcomes comparable to those achieved with corticocancellous bone grafts in scaphoid nonunion with deformity, possibly due to the biomechanical advantages of the volar plate to provide structural supports.

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.

Technology Behind Cell Therapy Augmentation of Fracture Healing: Concentrated Bone Marrow Aspirate.

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.

Open Reduction and Internal Fixation for Supination-External Rotation Type IV Ankle Fractures by Means of Anterolateral and Posterolateral Approaches.

BACKGROUND: The present study aimed to analyze and compare the efficacy of the anterolateral and posterolateral approaches for surgical treatment of supination-external rotation type IV ankle fractures. METHODS: This retrospective study enrolled 60 patients (60 feet) with supination-external rotation type IV ankle fractures, including 30 patients (30 feet) treated by means of the anterolateral approach and 30 patients (30 feet) treated by means of the posterolateral approach. Postoperative clinical efficacy was compared between the groups based on operation time, intraoperative blood loss, postoperative complications, fracture healing time, visual analog scale scores, Short Form-36 Health Survey scores, and American Orthopedic Foot and Ankle Society scores. Comparisons between the two groups were performed using independent-samples t tests and analyses of variance. Intragroup differences were compared using paired t tests, and the χ2 test was used to compare categorical variables. RESULTS: All 60 included patients completed follow-up ranging from 12 to 18 months (mean duration, 14.8 ± 3.5 months). Although baseline characteristics were similar in the two groups, there were significant differences in operation time (86.73 ± 17.44 min versus 111.23 ± 10.05 min; P < .001) and intraoperative blood loss (112.60 ± 25.05 mL versus 149.47 ± 44.30 mL; P < .001). Although fracture healing time (10.90 ± 0.66 weeks versus 11.27 ± 0.94 weeks; P = .087) was shorter in the anterolateral group than in the posterolateral group, the difference was not significant. Postoperative complications occurred in one and three patients in the anterolateral and posterolateral approach groups, respectively. Visual analog scale scores were significantly lower in the anterolateral group than in the posterolateral group (1.43 ± 0.50 versus 1.83 ± 0.75; P = .019), although there was no significant difference in Short Form-36 Health Survey scores between the groups (73.63 ± 4.07 versus 72.70 ± 4.04; P = .377). However, American Orthopedic Foot and Ankle Society scores were higher in the anterolateral group than in the posterolateral group (80.43 ± 4.32 versus 75.43 ± 11.32; P = .030). CONCLUSIONS: Both the anterolateral and posterolateral approaches can achieve good results in the treatment of supination-external rotation type IV ankle fractures. Compared with the posterolateral approach, the anterolateral approach is advantageous for the treatment of supination-external rotation type IV ankle fractures given its safety and ability to reduce trauma, clear field of view revealed, and allow for exploration and repair of the inferior tibiofibular anterior syndesmosis within the same incision.

Cellular therapies for bone repair: current insights.

Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.

Favourable outcome in survivors of CPR-related chest wall injuries.

BACKGROUND: There is a lack of studies focusing on long-term chest function after chest wall injury due to cardiopulmonary resuscitation (CPR). The purpose of this cross-sectional study was to investigate long-term pain, lung function, physical function, and fracture healing after manual or mechanical CPR and in patients with and without flail chest. METHODS: Patients experiencing out-of-hospital cardiac arrest between 2013 and 2020 and transported to Sahlgrenska University Hospital were identified. Survivors who had undergone a computed tomography (CT) showing chest wall injury were contacted. Thirty-five patients answered a questionnaire regarding pain, physical function, and quality of life and 25 also attended a clinical examination to measure the respiratory and physical functions 3.9 (SD 1.7, min 2-max 8) years after the CPR. In addition, 22 patients underwent an additional CT scan to evaluate fracture healing. RESULTS: The initial CT showed bilateral rib fractures in all but one patient and sternum fracture in 69 %. At the time of the follow-up none of the patients had persistent pain, however, two patients were experiencing local discomfort in the chest wall. Lung function and thoracic expansion were significantly lower compared to reference values (FVC 14 %, FEV1 18 %, PEF 10 % and thoracic expansion 63 %) (p < 0.05). Three of the patients had remaining unhealed injuries. Patients who had received mechanical CPR in additional to manual CPR had a lower peak expiratory flow (80 vs 98 % of predicted values) (p=0.030) =0.030) and those having flail chest had less range of motion in the thoracic spine (84 vs 127 % of predicted) (p = 0.019) otherwise the results were similar between the groups. CONCLUSION: None of the survivors had long-term pain after CPR-related chest wall injuries. Despite decreased lower lung function and thoracic expansion, most patients had no limitations in physical mobility. Only minor differences were seen after manual vs. mechanical CPR or with and without flail chest.

Management of non-union of rib fractures secondary to trauma: A scoping review.

OBJECTIVE: Rib fracture non-union is an uncommon complication of traumatic rib fractures. Our objective was to perform a scoping review of the literature for the management of rib fracture non-union. This included analysis of the variations in surgical technique, complications experienced, and reported outcomes. METHODS: We conducted a scoping review and searched databases (MEDLINE, CINAHL, and Embase). We performed abstract and full-text screening, and abstracted data related to pre-operative assessment, surgical technique, complications, and reported outcome measures. RESULTS: We included 29 articles of which 19 were case reports and 10 were case series. The data quality was generally heterogeneous. The studies included 229 patients and the commonest symptoms of rib fracture non-union included chest pain, clicking, dyspnea and deformities. The patients underwent surgical management of rib fracture non-union (excluding first rib fractures) using various techniques. The majority used surgical stabilization of rib fracture with or without a graft. The reported outcomes were inconsistent between studies, but showed high rates of union (>94 %), reduction in reported VAS scores, and improved return to work when included. Implant failure occurred in 10 % of the 229 total patients reported in our studies, the re-operation rate was 13 %, and the overall complication rate was 27 %. CONCLUSION: Surgical management of rib fracture non-union often involving locking plates and screws with or without a graft has been shown in several case reports and series as an effective treatment with acceptable implant failure and complication rates. Surgical management is therefore a viable option for symptomatic patients. Further research is required to determine optimal management strategies that further reduce surgical complications for these patients.

Metatarsal Fractures.

Metatarsal fractures are some of the most common fractures reported in the human body. Recent advances in surgical techniques and fixation have helped facilitate healing and improved outcomes for our patients. The treatment goals of metatarsal fractures are to maintain the metatarsal parabola, sagittal position of the metatarsal heads, and a congruent metatarsophalangeal joint. Most of these injuries can be treated nonoperatively, but displaced fractures require surgical intervention to preserve normal gait biomechanics.

The validation of computed tomography derived radiodensity measurements of bone healing using histopathology.

BACKGROUND: The early identification of delayed bone healing or a non-union is vital for prompt treatment and superior patient outcomes. Current techniques rely heavily on operator skill for interpretation and hence their reliability and repeatability may be inconsistent. This study assessed the application of computed tomography (CT) derived densiometric measurements as a quantitative tool for the assessment of bone healing. METHODS: This prospective, longitudinal, method comparison study was performed using a recognised sheep tibial ostectomy model. Secondary bone healing was assessed at 2, 4, 6, and 8 weeks after the ostectomy was performed. CT densiometric measures of bone healing (Hounsfield units) were taken of the cis, trans, cranial and caudal cortices relative to the bone plate, with histological measurements (percentage of ossification) sourced from the same areas. Cis cortical densiometric data points were excluded from analysis due to significant beam hardening artefact from the bone plate (P < 0.001). A univariable linear regression was performed on the remaining data using averaged radiodensity (independent variable) and histomorphometric (dependent variable) measurements. RESULTS: The two measurements were significantly correlated (R2 = 0.623, P = 0.020) with a clear positive trend identified. CONCLUSION: This study suggests that radiodensity measurements may be a useful diagnostic and management tool for the monitoring of indirect bone healing.

Size and fixation options of dorsoulnar fragments in distal radius fractures.

PURPOSE: This study aimed to investigate the influence of size and fixation options of dorsoulnar fragments on the clinical outcomes of distal radius fractures (DRFs). METHODS: This retrospective analysis was performed on 94 patients with DFR accompanied by dorsoulnar fragments, spanning the period from October 2018 to November 2022. Mean follow-up was 15.5 (range, 12-20) months. Patients were divided into small- (<5 %, n = 28), middle- (5-15 %, n = 50), and large- (>15 %, n = 16) sized groups according to articular involvement of dorsoulnar fragments determined by three-dimensional (3D) computed tomography (CT) modeling. Subdivision also took place for the presence of postoperative fragment displacement (>2 mm) and fixation methods including volar locking plate (VLP), VLP combined with dorsal hollow compression screw (VDS), and VLP combined with dorsal low-profile mini plate (VDP). The radiographic parameters (volar tilt, radial inclination, and radial height) and functional outcome measures of wrist range of motion, wrist function (DASH, PRWE), and wrist pain (VAS) were evaluated and compared between groups. RESULTS: Fracture healing was observed in all patients at final follow-up. No instances of dorsoulnar fragment displacement were observed in patients undergoing VDS and VDP treatment and the incidence of the dorsoulnar fragment displacement was 35 % (n = 8) in small-sized group, 21 % (n = 7) in middle-sized group, and 7 % (n = 1) in large-sized group when patients were treated with VLP. In small-sized group, no significant differences were found between patients with and without dorsoulnar fragment displacement in dorsiflexion restriction (10.6 ± 2.8°, 9.1 ± 2.3°, P = 0.159), pronosupination restriction (9.6 ± 2.1°, 8.6 ± 1.7°, P = 0.188), DASH (11.5 ± 4.1, 10.7 ± 3.2, P = 0.562), PRWE (11.9 ± 4.2, 10.6 ± 3.6, P = 0.425), and VAS (1.1 ± 1.1, 0.9 ± 1.0, P = 0.528). In middle-sized combined with large-sized group, the functional outcome measures of dorsiflexion restriction (12.5 ± 3.7°, 9.8 ± 2.9°, P = 0.022), DASH (14.6 ± 5.2, 11.4 ± 3.7, P = 0.030), and PRWE (15.0 ± 4.5, 11.3 ± 3.9, P = 0.016) were superior in patients without dorsoulnar fragment displacement. In patients treated with VLPs, no significant differences were found in dorsiflexion restriction (9.8 ± 2.5°, 10.8 ± 3.5°, 9.4 ± 2.5°, P = 0.299), pronosupination restriction (9.2 ± 1.9°, 10.1 ± 2.8°, 8.9 ± 1.5°, P = 0.200), DASH (11.1 ± 3.5, 12.9 ± 4.3, 11.1 ± 3.6, P = 0.162), PRWE (11.1 ± 3.9, 12.8 ± 4.2, 10.8 ± 3.9, P = 0.188), and VAS (1.0 ± 1.0, 1.4 ± 1.1, 0.9 ± 0.9, P = 0.151) between small-sized, middle-sized, and large-sized groups. In middle-sized group, no significant differences were found in dorsiflexion restriction (10.8 ± 3.5°, 9.4 ± 2.2°, 9.4 ± 2.4°, P = 0.316); pronosupination restriction (10.1 ± 2.8°, 8.8 ± 1.9°, 9.0 ± 2.5°, P = 0.314), DASH (12.9 ± 4.3, 10.3 ± 3.7, 10.5 ± 3.7, P = 0.133), PRWE (12.8 ± 4.2, 10.4 ± 3.8, 10.6 ± 4.1, P = 0.199), and VAS (1.4 ± 1.1, 0.8 ± 0.7, 1.0 ± 1.1, P = 0.201) between subgroups of VLP, VDS, and VDP. No significant differences were found in radiographic parameters between all groups compared. CONCLUSION: This study indicated that the strict reduction and fixation of a dorsoulnar fragment might be not essential when its articular involvement was less than 5 %. The volar locking plate (VLP) fixation was commonly effective in treating distal radius fractures accompanied by a dorsoulnar fragment involving over 15 % of the articular surface. Additionally, the use of an additional dorsal hollow compression screw or a dorsal low-profile mini plate can get good wrist function in the early-term follow-up when the dorsoulnar fragment involve 5-15 % of the articular surface.

Fixation of Proximal Tibial Fractures with Intramedullary Nail and Immediate Weightbearing: A Beneficial Alternative.

Newer intramedullary (IM) nails have become another option in the fixation of proximal tibia fractures. There is limited data on the successful use of these implants in intra-articular and extra-articular fractures of the proximal tibia, and no studies assessing the ability of these implants to maintain alignment with early weight bearing. Our objective was to determine whether immediate weight bearing after IM fixation, with or without supplemental plate or screw fixation, of proximal third tibial fractures (OTA/AO 41A-C) results in a change in alignment prior to union. 35 patients with 39 proximal tibia fractures from 2015 to 2020, all treated with IM nailing with or without supplemental plate or screw fixation, all made weight-bearing as tolerated following surgery, were included. The main outcomes were change in medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) from initial post-operative films to final follow up. 12 fractures were OTA/AO 41 type A, 14 were type B, and 13 were type C. Mean initial MPTA was 87.0 +/-2.53 degrees, while mean initial PPTA was 79.6 +/- 3.50 degrees. The mean change in MPTA was 0.048 +/- 2.8 degrees (P=0.92), and mean change in PPTA was 0.264 +/- 3.67 degrees. 92.3% of fractures had normal final coronal plane alignment, with MPTA between 85.0 and 90.0 degrees. 89.7% of fractures had normal final sagittal plane alignment, with PPTA between 77.0 and 84.0 degrees. No patients required reoperation for malalignment. In OTA/AO type 41 fractures, immediate weight bearing after IM nail fixation, with or without supplemental plate or screw fixation when indicated, leads to minimal change in final coronal or sagittal alignment, and was well tolerated in most patients. [authors blinded for review].

Comparison of femoral neck shortening after femoral neck system and cannulated cancellous screw fixation for displaced femoral neck fractures in young adults.

BACKGROUND: The purpose of this study was to compare the outcomes of femoral neck shortening between the femoral neck system (FNS) and the cannulated cancellous screws (CCS) for displaced femoral neck fractures in young adults PATIENTS AND METHODS: In this retrospective analysis, 225 patients aged 18-65 years with displaced femoral neck fracture were divided into two groups according to internal fixation: 135 patients in the FNS group and 90 patients in the CCS group. The length of hospital stay, duration of surgery, intraoperative blood loss, quality of reduction, extent of femoral neck shortening, incidence of femoral neck shortening, femoral neck shortening at each follow-up visit, Harris hip score (HHS), reoperation, and complications were compared between the two groups. RESULTS: The median follow-up time was 28.2 (26.0, 31.2) months in the FNS group and 30.2 (26.3, 34.7) months in the CCS group. The follow-up time, age, sex distribution, body mass index (BMI), mechanism of injury, injured side, length of hospital stay, time from injury to surgery, and fracture classification were similar between the groups. Duration of surgery was longer in the FNS group (65.0 (55.0, 87.0) min versus 55.0 (50.0, 65.0) min, P<0.001); intraoperative blood loss was greater in the FNS group (50.0 (20.0, 60.0) ml versus 20.0 (10.0, 35.0) ml, P<0.001). Femoral neck shortening was 2.4 (1.0, 4.5) mm in the FNS group versus 0.6 (0.0, 2.6) mm in the CCS group at 1 month postoperatively (P<0.001); 3.7 (1.8, 6.4) mm in the FNS group versus 1.2 (0.6, 3.8) mm in the CCS group at 3 months (P<0.001); 4.1(2.4, 7.7) mm in the FNS group versus 2.3 (1.1, 4.4) mm in the CCS group at 6 months (P<0.001); 4.2 (2.6, 7.7) mm in the FNS group versus 2.6 (1.3, 4.6) mm in the CCS group at 12 months (P<0.001); and 4.5 (2.8, 8.0) mm in the FNS group versus 2.8 (1.5, 4.8) mm in the CCS group at 18 months (P<0.001). The two groups showed no significant differences in HHS, reoperation, and reduction quality. CONCLUSION: Compared to CCS, FNS is deficient in preventing femoral neck shortening. Future research should focus on improving FNS in terms of preventing femoral neck shortening.

Increased ß2-adrenergic signaling promotes fracture healing through callus neovascularization in mice.

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the ß2-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine. In a murine model of femoral osteotomy combined with cortical impact brain injury, TBI was associated with ADRB2-dependent enhanced fracture healing compared with osteotomy alone. In the unfractured 12-week-old mouse skeleton, ADRB2 was required for TBI-induced decrease in bone formation and increased bone resorption. Adult 30-week-old mice had higher bone concentrations of norepinephrine, and ADRB2 expression was associated with decreased bone volume in the unfractured skeleton and better fracture healing in the injured skeleton. Norepinephrine stimulated expression of vascular endothelial growth factor A and calcitonin gene-related peptide-α (αCGRP) in periosteal cells through ADRB2, promoting formation of osteogenic type-H vessels in the fracture callus. Both ADRB2 and αCGRP were required for the beneficial effect of TBI on bone repair. Adult mice deficient in ADRB2 without TBI developed fracture nonunion despite high bone formation in uninjured bone. Blocking ADRB2 with propranolol impaired fracture healing in mice, whereas the ADRB2 agonist formoterol promoted fracture healing by regulating callus neovascularization. A retrospective cohort analysis of 72 patients with long bone fractures indicated improved callus formation in 36 patients treated with intravenous norepinephrine. These findings suggest that ADRB2 is a potential therapeutic target for promoting bone healing.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.